Abstractbook

AL02 integral role in the pathophysiology of PTH and CGRP Hypersensitivity to Calcitonin Gene-Related Peptide in antagonism might provide a novel mechanism-based Post-Traumatic Headache attributed to Mild treatment option for PTH. Traumatic Brain Injury: A Randomized Clinical Trial. H. Ashina1, A. Iljazi1, H. Al-Khazali1, C. Christensen1, F. Amin1, M. Ashina1, H. Schytz1 1Danish Headache Center, Neurology, Glostrup, AL05 Denmark A randomised, placebo controlled, double blind trial of the effect of the GLP-1 receptor agonist Exenatide Question: Does CGRP induce headache exacerbations on intracranial pressure in Idiopathic Intracranial with migraine-like features in patients with persistent Hypertension (IIH: Pressure Trial). post-traumatic headache (PTH) attributed to mild J. Mitchell1, J. Walker1, H. Lyons1, K. Brock2, V. Vijay1, A. traumatic brain injury (TBI). Yiangou1, Z. Alimajstorovic1, O. Grech1, G. Tsermoulas3, S. Mollan4, A. Sinclair1 Design: A randomized, double-blind, placebo- 1University of Birmingham, Metabolic Neurology, controlled, 2-way crossover study. Analyses were Birmingham, United Kingdom intention-to-treat. Inclusion criteria were diagnosis of 2University of Birmingham, Institute of Cancer and persistent PTH, mild TBI at least 12 months prior to Genomic Sciences, Birmingham, United Kingdom study inclusion, and age between 18 and 65 years. 3University Hospitals Birmingham NHS Foundation Exclusion criteria were any history of primary headache Trust, Department of Neurosurgery, Birmingham, disorder (except infrequent tension-type headache), United Kingdom any history of whiplash injury or more than one TBI, 4University Hospitals Birmingham NHS Foundation pregnant or nursing women, cardiovascular or Trust, Department of Ophthalmology, Birmingham, cerebrovascular disease, pre-trauma psychiatric United Kingdom disease, and medication-overuse headache. Objectives: Assessing the biological effect of a Interventions: Thirty patients with persistent PTH Glucagon-like Peptide 1 receptor(GLP-1R) agonist on received intravenous infusion of 1.5 µg/min of CGRP or intracranial pressure (ICP) in Idiopathic Intracranial placebo over 20 min on 2 study days. Hypertension(IIH).

Main Outcomes and Measures: Difference in incidence Background: Pre-clinical data demonstrates the ability of headache exacerbation with migraine-like features of Exenatide, a GLP-1R agonist, to reduce CSF secretion and difference in area under the curve (AUC) for and ICP. Existing GLP-1R agonists therapies are widely headache intensity scores (0-12 h). used to treat obesity and diabetes(but do not cause hypoglycaemia). Results: Of 34 patients assessed for eligibility, 30 patients were included in the analysis. The mean age Methods: Randomised, placebo controlled, double- was 37 years (SD, 11 years; range, 20 – 59 years), and blind physiology trial of Exenatide in women with the mean weight was 73 kg (range, 50 – 110 kg). active IIH(lumbar puncture pressure >25 cmCSF and Twenty-one of 30 participants (70%) developed papilloedema). headache exacerbation with migraine-like features Telemetric, intraparenchymal ICP monitors were after CGRP compared to six participants (20%) after implanted to enable gold standard, long-term ICP placebo (P < 0.001). The baseline corrected AUC for monitoring(Raumedic p-Tel, Helmbrechts, Germany). headache intensity was significantly larger after CGRP Participants were randomised 1:1 to receive compared to placebo (AUC0-12 h, P < 0.001). The median Exenatide(10mcg twice daily sub-cutaneous) or time to peak headache intensity was 120 min (range: placebo for 12 weeks. ICP and weight were recorded 20 – 660 min) after CGRP and 300 min (range: 10 – 600 over a 24-hour baseline visit, at 2 weeks and 12 weeks. min) after placebo (P = 0.509). Monthly headache diaries were completed at baseline and 8-12weeks. No other ICP modulating drugs were Conclusions: PTH patients exhibit hypersensitivity to taken during the study. CGRP infusion which suggests that CGRP plays an

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Results: Of the 16 participants recruited 15 were ± 1.40 ng/ml, n=10) showed significantly reduced tear randomised and completed the study: age 29.5±9.5, fluid CGRP levels compared to CH patients with no BMI 38.1±6.2 kg/m2, ICP 23.5 ±3.9 mmHg(30.6 cmCSF). intake of acute medication (p=0.022), and their tear All ICP implants were well tolerated and enabled fluid CGRP levels were not significantly different from successful ICP quantification after drug dosing. At healthy controls (p=0.484). No significant difference in baseline participants had median(IQR) Frisen grade tear fluid CGRP levels between episodic 2(1) papilloedema, perimetric mean deviation - (1.48±1.68ng/ml) and chronic CH patients (1.60±1.63 1.76±1.93dB, headache severity 4.64±1.79(numeric ng/ml, p=0.535) was detected. In constrast to these rating scale 0-10) and monthly headache days results in tear fluid samples, there were no significant 17.3±8.19. The primary outcomes(ICP at 2.5hrs, 24hrs differences in plasma CGRP levels between groups. and 12 weeks) are presented at EHF Berlin 2020. Conclusion: To the best of our knowledge, this study Conclusions: We report the first human study to assess shows for the first time that CH patients (chronic or the biological effect of the GLP-1 agonist exenatide on episodic within bout) have increased CGRP levels in ICP in IIH utilising highly accurate implantable tear fluid compared to healthy subjects, which are telemetric ICP monitors. ICP telemetric monitoring was reduced to control levels after intake of a triptan. safe and well tolerated and provides new insights into Detection of CGRP in tear fluid is non-invasive, and drug effects on ICP. New therapies for ICP modulation likely allows a more direct access to CGRP released in IIH are a significant un-met need in this population from the trigeminal nerve than plasma sampling. with escalating incidence.

AL07 AL06 Quantification of facial microvascular blood flow in Calcitonin gene-related peptide levels in tear fluid are cluster headache using laser speckle contrast imager: elevated in cluster headache patients compared to Differences between episodic and chronic cluster healthy controls headache K. Kamm1, R. Ruscheweyh1, A. Straube1 A. Andreou1,2, M. Murphy2, B. Hill2, R. 1University Hospital of Munich, Neurology, Munich, AbuukarAbdullahi1, A. Al-Kaisy3, G. Lambru2 Germany 1King's College London, Headache Research, Wolfson CARD, Institute of Psychiatry, Psychology & Background: Calcitonin gene-related peptide (CGRP) Neuroscience, , London, United Kingdom released from trigeminal nerve fibres indicates 2Guy's and St thomas' NHS Foundation Trust, Headache trigeminal activation and has a key role in cluster Centre, London, United Kingdom headache pathophysiology. The trigeminal nerve 3Guy's and St thomas' NHS Foundation Trust, Pain directly innervates the eye. In this study, we compared Management and Neuromodulation Centre, London, CGRP in tear fluid of cluster headache (CH) patients United Kingdom and healthy controls. Aim: To evaluate facial microcirculatory changes, as an Methods: CGRP concentrations in tear fluid and indicator of autonomic system dysregulation using a plasma of 16 episodic (within bout) and 11 chronic CH laser speckle contrast imager interictally in episodic patients and 48 controls were assessed using ELISA. (ECH) in- and outside a bout and in chronic cluster headache (CCH) patients. Results: CH patients without use of triptans in the last 48h (1.78±1.57ng/ml, n=17) showed significantly Methods: Changes in facial blood flow blinded to the higher tear fluid CGRP levels compared to healthy side of the headache were measured in consecutive controls (0.75±0.80ng/ml, p=0.001). High CGRP levels 114 cluster patients (CCH: N=54; ECH: N=60). The mean in CH patients were independent of the recent perfusion rate of both ipsilateral and contralateral occurence of a CH attack (no attack in last 48h: trigeminal territories were calculated. Mann-Whitney 1.95±1.65 ng/ml, n=8; attack in last 48h: 1.63±1.59 test was used for within group comparisons and ng/ml, n=9, p=0.82) as long as no acute medication was Pearson’s correlation was applied for measuring the used. CH patients with triptan use in the last 48h (0.84 association between variables. 3

Results: Nine patients were excluded because of side month post-treatment follow-up (PTFU) period. Safety alternating attacks. In the ECH group in bout, there was outcomes included adverse events, discontinuations, an increased microcirculation on the ipsilateral V1-V2 laboratory values, vital signs, ECG, & suicidality ratings trigeminal territories compared to the corresponding (Columbia Suicide Severity Rating Scale [C-SSRS]). contralateral territories (N=27; V1: 19±2.8%, P<0.001; V2: 20.1±4.2%, P<0.001). The cluster side could be Results: 237 patients entered CGAM, 230 completed predicted in 25/27 patients by the operator (r=0.85, DBL phase, 229 entered OLE (116 PBO, 113 GMB), 152 P<0.001). In contrast, ECH patients outside a bout had (66%) completed OLE, & 148 (65%) completed all study no significant differences in blood flow between the phases. In total, 233 patients received ≥1 dose of GMB, ipsilateral and contralateral sides (N=29; P≥0.53). with a mean exposure to GMB of 341 days. GMB- Amongst CCH, 16/49 had decreased, and 33/49 had treated patients were mostly male (73%), with a mean increased microvascular blood flow in the ipsilateral V1 age of 45 (±11) years. 22% reported history of suicidal and V2 regions. The cluster side could not be predicted ideation. 4% reported history of suicidal behavior. No in CCH (r=0.05, P=0.7). Among all patients, ipsilateral deaths were reported in CGAM. 185 patients (79%) microvascular blood flow increase correlated reported treatment-emergent adverse events (TEAEs), significantly with the time (days) since the last cluster 23 (9.9%) reported serious AEs (SAEs), & 18 (7.7%) attack (r=0.23, P=0.02). discontinued due to an AE. Cluster headache was the only SAE reported by >1 patient (n=3). The most Conclusions: Laser speckle contrast imager can detect common TEAEs (>10%) were nasopharyngitis (n=41; microcirculatory facial changes in CH. Microvascular 18%) & injection site pain (n=33; 14%). Most TEAEs blood flow imaging of the face may be able to predict were mild (24%) or moderate (42%). 27% of patients the cluster side in bout and to correlate autonomic had injection site-related TEAEs (including pain), & 14 activation with the time since last attack in ECH (6.01%) reported ≥1 likely hypersensitivity event. 15 patients, but not in CCH. Differences between ECH and patients (6.5%) reported suicidal ideation, 11 of whom CCH may suggest different degree of peripheral had previous history of suicidal ideation. 1 patient with autonomic imbalance possibly due to differential a history of suicidal behavior had a non-fatal attempt involvement of certain central autonomic regulatory during the OLE & an aborted attempt during the PTFU. circuits. There were no new safety findings compared to the PBO-controlled treatment period in laboratory values, vital signs, or ECGs.

AL08 Conclusions: GMB 300mg monthly had a favorable Safety and tolerability of galcanezumab in patients safety/tolerability profile with up to 15 months of with chronic cluster headache with up to 15 months treatment of galcanezumab treatment M. J. Láinez1, J. Schoenen2, C. Stroud3, J. Bardos3, M. Bangs3, P. Kemmer3, R. Wenzel3, D. Kuruppu3, J. M. Martinez3, T. M. Oakes3 AL09 1University Clinic Hospital, Neurology, Valencia, Spain REFRACTORY CHRONIC MIGRAINE: COULD IT BE 2Université de Liège Faculté de Médecine, Citadelle IDIOPATHIC INTRACRANIAL HYPERTENSION? DATA Hospital, Liege, Belgium FROM A TERTIARY HEADACHE CENTER 3Eli Lilly and Company, Indianapolis, United States E. Colangeli1, R. Ornello1, F. Gabriele1, C. Scarpato1, C. Tiseo1, I. Frattale1, E. De Matteis1, S. Sacco1 Question: To assess the safety/tolerability of 1University of L'Aquila, Neuroscience Section, galcanezumab (GMB) in patients with chronic cluster Department of Applied Clinical Sciences and headache (CCH) with up to 15 months of treatment Biotechnology, L'Aquila, Italy

Methods: CGAM was a Ph3 randomized, double-blind, Background: Idiopathic intracranial hypertension (IIH) PBO-controlled study of GMB in adult patients with is a chronic condition characterized by raised CCH. Patients received monthly injections during a 3- intracranial pressure (ICP) in the absence of a known month double-blind (DBL) period followed by an etiology [1]. We aimed to investigate the prevalence of optional 12-month open-label extension (OLE) & a 4- 4

IIH in patients with chronic migraine unresponsive to Figure 1 medical treatment.

Methods: We included consecutive patients, referring within a 3-month period to our headache center and who met ICHD diagnostic criteria for chronic migraine (CM) and had failed at least 4 classes of previous preventive treatments. Those patients entered a diagnostic path including 1) brain MRI with magnetic resonance venography (MRV); 2) fundus oculi examination and 3) lumbar cerebrospinal fluid (CSF) opening pressure measurement (reserved to patients with at least 3 imaging signs of IIH, including perioptic nerve sheath distention, vertical buckling of optic nerve, globe flattening, asymmetric transverse sinuses, and empty sella).

Results: Over the study period, 19 patients met the criteria to enter the IIH diagnostic path. They were all women, with a median age of 54 years (interquartile AL10 range 21-71). The prevalence of overweight or obesity Noninvasive Evaluation of Intracranial Compliance in Spontaneous Intracranial Hypotension: Case series was 10.5%. Ten (52.6%) of them had failed treatment 1 1 2 2 with onabotulinumtoxinA treatment failure and 8 M. N. P. Souza , G. Kubota , S. Wayhs , C. Hayashi , G. Vilela2, S. Lima2, I. Fortini1, M. Calderaro1 (42.1%) treatment with erenumab. All patients had 1 fundus oculi examination which was normal. Nine Hospital das Clínicas, University of São Paulo, Neurology, Headache Medicine, São Paulo, Brazil (47.4%) patients performed had MRI with MRV; for the 2 other patients the exam is scheduled but not yet Brain4care, São Paulo, Brazil performed. At brain MRI, 3 patients had features of possible IIH. Lumbar puncture was performed in 2 of Background: Spontaneous intracranial hypotension them while 1 refused the exam. Both patients had an (SIH) is a treatable cause of orthostatic headache. The increase in the CSF pressure which was of 30 and 33 best diagnostic approach remains uncertain. This study mmHg respectively. aims to present results of a novel noninvasive method for evaluation of intracranial compliance in four cases of diagnosed SIH. BRAIN4CARE® is a noninvasive device Conclusion: IIH may be one possible explanation which developed to evaluate intracranial compliance, and may contribute to drug failure in patients with CM. Further data are needed to understand validated for intracranial hypertension. appropriateness and timing MRI with MRV and CSF pressure measurement in patients with CM. Methods: Patients with confirmed diagnosis of SIH were evaluated in orthostatic and dorsal decubitus. [1] Sina F et al. Migraine headache in patients with IIH. The monitoring reveals a curve of 2 phases (P1 and P2), corresponding respectively to systolic and diastolic Neurol Int. 2017;9(3):7280. intracranial repercussion. Compliance was inferred by measure of time to peak (TTP) and mean P2/P1 ratio (mP2/P1).

Results: Case 1: 42-year-old woman with orthostatic headache and brain MRI presenting indirect signs of intracranial hypotension. The mP2/ was 1,778 in decubitus and 1,371 in orthostasis. TTP in decubitus was 0,266s and 0,226s in orthostasis. Case 2: 39-year- old woman with orthostatic headache and brain MRI presenting indirect signs of intracranial hypotension.

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The mP2/P1 was 1,228 in decubitus and 1,103 in Neurovent P-tel device) on one visit. Cohort 2 were orthostasis. TTP in decubitus was 0,259s and 0,268s in evaluated at baseline, 3, 12 and 24 months and orthostasis. Case 3: A 37-year-old woman with underwent lumbar puncture assessment of ICP. The orthostatic headache and brain MRI with indirect signs OCT protocol included peripapillary retinal nerve fibre of intracranial hypotension. The mP2/P1 was 0,383 in layer (RNFL), optic nerve head and macular volume decubitus and 1,288sin orthostasis. TTP in decubitus scans (SPECTRALIS, Heidelberg Engineering). All scans was 0,08s and 0,236s in orthostasis. Case 4: A 47-year- were validated for quality and re-segmented manually old man with orthostatic headache and negative MRI. when required. SIH was confirmed by dynamic CT myelography. The mP2/P1 was 1,141 in decubitus and 1,16 in orthostasis. Results: 104 patients were recruited (cohort 1: n=15; TTP in decubitus was 0,277s and 0,224s in orthostasis. cohort 2: n=89). Amongst cohort 1, the range of OCT protocols were evaluated and optic nerve head central Conclusion: The mP2/P1 above 1,2 is suggestive of thickness (CT) was found to be most closely associated reduced compliance. Considering that all cases with ICP (p = 0.03; r = 0.56) and superior to the current presented alterations in the measured curves, we standard of care scan (RNFL). Subsequently, cohort 2 hypothesize that the distinct pattern of intracranial confirmed the correlation between CT and ICP compliance, as evaluated by this noninvasive device, longitudinally (at 12 and 24 months). Finally, bootstrap may help to improve the diagnosis of this SIH. surrogacy analysis noted a positive association between treatment effects in CT and ICP at all time points. At 12 months, an increase in CT of 50µm predicted an increase in ICP of 5 cmCSF. AL11 Critical appraisal of outcome measures in Idiopathic Conclusions: OCT optic nerve head CT reproducibly Intracranial Hypertension and surrogate outcomes for correlates with ICP and surrogacy analysis Intracranial Pressure demonstrates its ability to predict ICP changes. OCT V. Vijay1, J. Mitchell1, E. Bilton1, A. Yiangou1, Z. scanning is widely utilised internationally; our data Alimajstorovic1, O. Grech1, K. Brock2, P. Nightingale3, S. suggests that it has the utility to not only monitor Mollan 4, A. Sinclair1,4 papilloedema but also non-invasively predict ICP in IIH. 1University of Birmingham, Institute of Metabolism and Systems Research, Birmingham, United Kingdom 2University of Birmingham, Cancer Research UK Clinical Trials Unit, Birmingham, United Kingdom AL12 3University of Birmingham, NIHR/Wellcome Trust Two-Hour Infusion of Vasoactive Intestinal Clinical Research Facility, Birmingham, United Kingdom Polypeptide Promotes Delayed Headache and 4University Hospitals Birmingham, Birmingham Neuro- Extracranial Vasodilation in Healthy Participants Ophthalmology Unit, Birmingham, United Kingdom L. Pellesi1, M. Al-Mahdi Al-Karagholi1, B. A. Chaudhry1, F. M. Amin1, M. Ashina1 Question: Intracranial pressure (ICP) elevation is the 1Danish Headache Center, Department of Neurology, defining feature of Idiopathic Intracranial Hypertension Copenhagen, Denmark (IIH) and a key measure of disease activity. Currently, ICP is quantified through invasive procedures, with an Question: VIP and the PACAPs (i.e. PACAP27 and unmet need for non-invasive biomarkers. ICP manifests PACAP38) are related in structure and function, but as papilloedema which can be quantified by optical they show differences in vasodilating- and headache- coherence tomography (OCT) scanning. We inducing properties. Intravenous infusion of PACAP27 hypothesised that OCT could act as a surrogate or PACAP38, but not VIP, induces a long-lasting dilation measure of ICP. of cranial arteries and delayed headache. Whether a long-lasting cranial vasodilation is a contributing factor Methods: Active IIH patients (papilloedema and ICP > of headache is yet unexplored. 25 cm CSF) were recruited and underwent ICP measurement and OCT scanning (with automated Methods: In a double-blinded, placebo-controlled, perimetry) on the same day. Cohort 1 utilised crossover study in 12 healthy volunteers, cranial continuous sitting telemetric ICP monitoring (Raumedic arteries, occurrence of headache and the 6

parasympathetic system were examined before, during Figure 2 and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve (AUC) for the superficial temporal artery (STA) diameter and headache intensity scores, as well as headache incidence, between VIP and placebo.

Results: The STA diameter was significantly larger on the VIP day compared to placebo (p < 0.001) and the dilation lasted for three hours (Figure 1). The incidence of headache was higher (p = 0.003) on the VIP day compared to the placebo day. The difference in headache intensity scores was evident in the post- infusion period (p = 0.009), but not in the infusion period (p = 0.059) (Figure 2). Cranial parasympathetic activity, measured through the production of tears, was higher during VIP compared to placebo (p = 0.033).

Conclusions: Continuous intravenous infusion of VIP over 2 h induced a long-lasting cranial vasodilation, activation of the cranial parasympathetic system and a AL13 delayed headache in healthy volunteers. Adrenomedullin induces migraine-like attacks in patients with migraine without aura 1 1 1 Figure 1 H. Ghanizada , M. A. Al-Karagholi , N. Arngrim , M. 1 2 2 Mørch-Rasmussen , C. S. Walker , D. L. Hay , M. ASHINA1 1Danish Headache Center, Neurology, Glostrup, Denmark 2University of Auckland, School of Biological Sciences and Centre for Brain Research, Auckland, New Zealand

Adrenomedullin is a potent vasodilator peptide that is structurally related to calcitonin gene-related peptide (CGRP) and amylin. Basic and clinical evidence implicates CGRP hypersensitivity in migraine, but considerable gaps remain in our understanding of migraine pathogenesis. The similarities between the CGRP family peptides and their over-lapping receptor pharmacology warrants further elucidation of the potential role of each family member in migraine. Here, we investigated the role of adrenomedullin in migraine.

We conducted a randomized, double-blind, crossover, placebo-controlled study on 20 migraine without aura patients using intravenous infusion of human adrenomedullin (19.9 picomol/kg/min) or placebo (saline) over 20 minutes on two separate days with a washout period of one week. The main outcome of the study was defined as a difference in migraine incidence (0–12 h).

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Eleven patients (55%) developed migraine attacks after oxidative phosphorylation and maximal respiratory adrenomedullin infusion, compared to only three capacity, with and without the prior addition of the (15%) after placebo (P= 0.039). The area under the fatty acid conjugate octanoyl-carnitine was assessed in curve for headache score (0-12 hours) was increased non-permeabilised slices using Oroboros O2k after adrenomedullin compared with placebo (P= oxygraphy. 0.035). Results: Our initial data indicate that mitochondrial Our data implicate adrenomedullin in migraine integrity was not disrupted in KCl- or KCl+ slices and pathophysiology. This suggests that adrenomedullin that basal respiration remains unchanged. However, and its receptors are novel therapeutic targets for we observe elevation in oxidative capacity derived migraine treatment. However, we cannot discount the from complex I and II which is maintained when we possibility that adrenomedullin may be acting through evaluate maximal rates of uncoupled respiration (22.78 the canonical CGRP receptor. vs. 26.97 pmol O2/mg-1/s-1), independent of substrate sources.

Conclusions: Here we show that a CSD in an acute AL14 brain slice can, at least transiently, elevate Investigation of mitochondrial respiratory function in mitochondrial oxidative capacity initiated from a brain slice model of cortical spreading depression. complex I and II. The mechanisms that account for O. Grech1, D. Fulton2, Z. Alimajstorovic1, S. Heising1, D. these observations require further definition. These Cartwright1, G. C. Faas3, A. C. Charles3, A. Sinclair1,4,5, G. data may begin to suggest that CSD induced G. Lavery1,4 disturbances in metabolic energy metabolism that 1University of Birmingham, Institute of Metabolism and contribute to migraine may be amenable to Systems Research, Birmingham, United Kingdom nutraceutical and nutrient intervention as an 2University of Birmingham, Institute of Inflammation adjunctive therapy. and Ageing, Birmingham, United Kingdom 3University of California Los Angeles, Department of Neurology, Los Angeles, United States 4Birmingham Health Partners, Centre for AL15 Endocrinology, Diabetes and Metabolism, Birmingham, Resting State Functional Connectivity Changes of the United Kingdom Hypothalamus in Migraine Patients: A Cross-Sectional 5University Hospitals Birmingham NHS Foundation and Longitudinal Study Trust, Queen Elizabeth Hospital, Department of R. Messina1, M. A. Rocca1, P. Valsasina2, P. Misci2, M. Neurology, Birmingham, United Kingdom Filippi1 1IRCCS Sas Raffaele Scientific Institute, Neuroimaging Background: Cortical Spreading Depression (CSD) - a Research Unit and Neurology Unit, milano, Italy propagating wave of depolarisation across the cerebral 2IRCCS Sas Raffaele Scientific Institute, Neuroimaging cortex - is proposed to activate trigeminal nerve Research Unit, milano, Italy afferents, that contribute to migraine headache. In vivo models of CSD are associated with disturbances in Question: The aim of our study was to explore cross- neuronal and glial cell oxidative capacity and sectional and longitudinal resting state functional mitochondrial function, the extent of which may connectivity (RS FC) changes of the hypothalamus in contribute to migraine severity and duration. Here we patients with migraine. begin to elucidate the metabolic consequences of CSD in an acute mouse brain slice system by first Methods: Using a 3.0 Tesla scanner, RS functional conducting high-resolution respirometry to profile magnetic resonance imaging (MRI) and 3D T1-weighted mitochondrial function. scans were acquired from 92 headache-free episodic migraine patients and 73 controls. Twenty-three Methods: CSD was induced following application of 1ul migraineurs and 23 controls were reexamined after a 2M KCl (KCl+ vs. control- KCl-) to cortical regions of mean follow-up (FU) of 4 years. RS FC analysis was acute brain slices (from C57BL6). 10 minutes after CSD performed using a seed-region correlation approach induction mitochondrial complex I+II mediated and SPM12. 8

Results: At baseline, compared to controls, possible peculiarities in migraine, we analysed the migraineurs showed a decreased RS FC between the difference in gene expression between the superior right and left hypothalamus and the right cerebellum, occipital gyrus (which harbours V3a) and the rest of the left parahippocampus and bilateral orbitofrontal cortex brain. (OFC). The left hypothalamus had also a decreased RS FC with the left middle frontal gyrus. While, the right Materials and methods: We performed a differential hypothalamus had a decreased RS FC with the right search of gene expression between the left superior inferior temporal gyrus, lingual gyrus and left calcarine occipital gyrus (lSOG) and the rest of the cerebral cortex. At baseline, the decreased RS FC between the cortex using the Allen Brain Institute Human RNA micro right hypothalamus and the ipsilateral lingual gyrus array atlas/database. This database includes 500 correlated with higher migraine attack frequency (r=- samples per hemisphere extracted from the brain of 6 0.4, p<0.05, FWE corrected). After 4 years, migraine different donors with no known history of neurologic patients developed an increased FC between the or neuropsychiatric disorders. For each sample, >62000 hypothalamus and the OFC, bilaterally, while RS FC gene probes were tested. Here, only differences in between the right hypothalamus and the ipsilateral gene expression (higher or lower in the lSOG with lingual gyrus decreased. RS FC between the right respect to the rest of the cortex) with a p≤1x10^-10 hypothalamus and the ipsilateral OFC correlated with significance threshold are reported. lower migraine attack frequency at year 4 (r=-0.6, p<0.001, uncorrected). Results: In the left superior occipital gyrus expression of MET (member of the receptor tyrosine kinase Conclusion: During the interictal phase, the family), SLC17A6 (vesicular glutamate transporter), and hypothalamus modulates the activity of pain and visual KCNS1 (potassium voltage-gated channel modifier processing areas in migraine patients. The recurrent subfamily S Member 1) genes was augmented experience of migraine attacks might disrupt the compared to the rest of the cerebral cortex. functional interaction between the hypothalamus and Conversely, SPHKAP (sphingosine kinase type 1 high-order visual processing areas. An increased RS FC interacting protein), GABRQ (GABA receptor type A, between the hypothalamus and brain areas belonging theta subunit), and KCNG1 (potassium voltage-gated to the descending pain-inhibitory pathway might channel modifier subfamily S Member 1) gene reduce migraine attack frequency over time. expression levels were reduced.

Conclusions: Differences in gene expression between the left superior occipital gyrus and the rest of the AL16 cortex include genes whose products are involved in Gene expression in the cortical region that harbours neuronal excitability (SLC17A6, KCNS1, KCNG1, and V3a and its possible implications with migraine GABRQ), synaptogenesis (MET), and cell metabolism M. Lisicki1, M. Carpinella1, G. Coppola2, E. Ruiz (SPHKAP via its interaction with c-AMP-dependent Romagnoli3, M. Manise4, A. Maertens de Noordhout4, protein kinase). The possible significance of this D. Conci1, J. Schoenen4 particular gene expression profile for migraine 1Conci Carpinella Institute, Headache Dept. / pathogenesis and therapy remains to be determined. Neuroscience Unit, Córdoba, Argentina 2 Sapienza University of Rome Polo Pontino, Department of Medico-Surgical Sciences and Biotechnologies, Latina, Italy 3Italian Hospital of Buenos Aires, Neuroradiology, Buenos Aires, Argentina 4University of Liège, Neurology / Headache Research Unit, Liège, Belgium

Introduction: Several imaging studies have pinpointed a particular area in the visual cortex, namely V3a, which might play a central role in migraine. In order to better characterize this area, and determine its 9

AL17 criteria that define a core syndrome probably caused Migraine with brainstem aura: defining the core by brainstem dysfunction. syndrome N. Yamani1, J. Olesen2 1Tehran University of Medical Sciences, Neurology, Tehran, Iran AL18 2University of Copenhagen, Danish Headache Center, Acute Treatment Optimization Influences Disability Copenhagen, Denmark and Quality of Life in Migraine: Results of the ObserVational Survey of the Epidemiology, tReatment Background: Although Migraine with brainstem aura and Care Of MigrainE (OVERCOME) Study (MBA) has been known for many years, its diagnosis D. Buse1, A. Kovacik2, R. Nicholson 2, E. Doty 2, A. Araujo and even its existence are still a matter of debate. 2, S. Ashina 3, M. Reed 4, R. Shapiro 5, Y. Kim2, R. Lipton 1 Previous studies demonstrated that current diagnostic 1Albert Einstein College of Medicine, Department of criteria for migraine with brainstem aura are too open Neurology, Bronx, United States and brainstem symptoms may originate within the 2Eli Lilly and Company, Indianapolis, United States cortex and not in the brainstem. 3Beth Israel Deaconess Medical Center, Department of Neurology and Department of Anesthesia, Critical Care Aims: The aims of the present study were to analyze and Pain Medicine, and Harvard Medical School, whether aura from the brainstem exists, how prevalent Boston, United States such a core syndrome is, to analyze if current 4Vedanta Research, LLC, Chapel Hill, United States diagnostic criteria define such a core syndrome and, if 5Larner College of Medicine, The University of necessary, to develop new diagnostic criteria that Vermont, Department of Neurological Sciences, define only the core syndrome. Burlington, United States

Methods: We analyzed all cases with MBA in the Objective: Assess the influence of acute treatment literature described in detail, clinical cases from the optimization and migraine related disability and health Danish Headache Center(DHC) and our very large related quality of life (HRQoL) across monthly Migraine sample of telephoneinterviewed cases with migraine Headache Day (MHD) categories from the OVERCOME with aura. study.

Results: Out of 79 MBA cases described in detail in the Background: Acute treatments for migraine attacks are literature, 44 fulfilled the diagnostic criteria for MBA of considered optimized when they resolve pain and the International Classification of Headache Disorders, restore function. Optimized acute treatment should be 3rd edition (ICHD-3) and most were convincing. In the associated with less disability and better HRQoL in DHC after face-to-face interview, neurological people with migraine. examination and imaging, only 4 MBA out of 293 (1.25%) with migraine with aura were found Design/methods: OVERCOME is a web-based survey corresponding to 0,04% or less in the general conducted in a representative US sample. The current population. Our telephone-interviewed cohort sample, collected in 2019, included 20,041 people included 1781 subjects with a diagnosis of migraine meeting ICHD-3 criteria for migraine who completed with aura. 228 of these fulfilled the diagnostic criteria measures of acute treatment optimization (Migraine for MBA of the ICHD-3. Thus, using interview diagnosis Treatment Optimization Questionnaire [mTOQ]), according to current diagnostic criteria, far too many disability (Migraine Disability Assessment Scale get the MBA diagnosis. Therefore, we developed [MIDAS], and HRQoL (Migraine-Specific Quality of Life stricter diagnostic criteria in an attempt to include only Questionnaire, Role Function – Restrictive subscale those rare cases who really have aura originating from [MSQ-RFR]). This analysis examined the relationship the brainstem. between mTOQ, MIDAS, and MSQ-RFR across MHDs per month categories (0-3, 4-7, 8-14, ≥15 MHDs). One- Conclusion: Migraine with brainstem aura does exist way ANOVA or Chi-square test, stratified by MHD but it is very rare. Existing diagnostic criteria are too category, evaluated differences between mTOQ groups unspecific, but it was possible to develop tighter (p<.05).

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Results: For the whole cohort, mean (SD) age was 42.5 in this cross-sectional study. All participants underwent (14.9) years, 74.9% were female, and 72.1% were non- an individualized OA paradigm consisting of three- Hispanic white. Among the 3,938 respondents with 4-7 stimulus offset trials and three constant temperature MHDs per month, 60.1% with very poor treatment trials examined at both, a trigeminal and an extra- optimization had severe MIDAS disability as opposed trigeminal test site. Items from the quantitative to only 19.5% with maximum treatment optimization sensory testing protocol were additionally included. (p<.001). In this group, those with very poor treatment optimization had significantly lower MSQ-RFR scores, Results: In contrast to the extra-trigeminal area (Figure Mean=32.0 (SD 22.8) relative to those with maximum 1), a reduced offset analgesia response was shown in treatment optimization, Mean=63.4 (SD 20.7) (p<.001). the trigeminal area in patients with migraine compared Significant differences in MIDAS and MSQ-RFR by to healthy controls (p<0.01, MD: 13.7, 95%CI: 3.8; treatment optimization were observed across all other 23.6). Statistically significant differences between the MHD cohorts (i.e. 0-3, 8-14, ≥15; all p<.001). trigeminal area and the extra-trigeminal area were neither observed in healthy controls nor in patients Conclusion: When acute migraine treatment is with migraine (p>0.05). Mechanical detection, optimized, people with migraine report lower levels of mechanical pain threshold, warm detection and heat disability and better health related quality of life. pain threshold showed no significant differences between groups or test sites (p>0.05).

Conclusion: In summary, patients with episodic AL19 migraine in the headache free interval exhibited Offset analgesia - somatotopic endogenous pain somatotopically specific differences in endogenous modulation in migraine pain modulation. T. Szilszay1,2, W. Adamczyk1,3, G. Carvalho4,2, A. May2, K. Lüdtke1,2 Figure 1 1University of Lübeck, Orthopaedic and Trauma Surgery, Academic Physiotherapy, Lübeck, Germany 2University Medical Center Hamburg-Eppendorf, Department of Systems Neuroscience, Hamburg, Germany 3The Jerzy Kukuczka Academy of Physical Education, Laboratory of Pain Research, Katowice, Poland 4University of São Paulo, Department of Health of Sciences, São Paulo, Brazil

Background: The complex mechanisms underlying migraine are not entirely understood. It has been suggested that descending endogenous pain modulation is an important contributing factor, although research is controversial. A frequently used method to quantify the inhibitory pain modulation system is offset analgesia (OA), defined as a disproportionally large decrease in pain perception in response to a small decrease of painful stimulation. The aim of this study is to evaluate the OA response in patients with migraine and healthy controls, measured at the forehead (trigeminal, V1) and forearm (extra- trigeminal).

Methods: Patients with episodic migraine during the headache free interval (n=26) and age and sex matched headache-free controls (n=26) were included 11

AL20 Headache relief was obtained in 666/1207 subjects Systematic review and meta-analysis on the use of (55.1%, 95%CI: 52.3-57.9%), compared with active opioids in the acute treatment of migraine comparators 506/794 (63.7 (95%CI: 60.3-67%), OR 1.42 D. García-Azorín1, S. Benemei2, A. Negro3, î Guerrero (95% CI: 1.18-1.71). Headache freedom and adverse Peral1, S. Ashina4, P. Martelletti5 events occurred in 279/883 (31.6%, 95% CI: 28.6- 1Hospital Clínico Universitario de Valladolid, Headache 34.7%) and in 964/1299 (74.2%, 95%CI: 71.7-76.5%) of Unit, Valladolid, Spain patients treated with opioids respectively. 2Careggi University Hospital, Headache Center, Florence, Italy Conclusions: Evidence supporting use of opioids for 3Sapienza University of Rome, Regional Referral migraine attack was scarce and with poor quality. Headache Centre, department of clinical and molecular Active comparators provided better results and medicine, Rome, Italy adverse events occurred in 2/3 of patients using 4Harvard Medical School, Beth Israel Deaconess opioids. Medical Center, Boston, BIDMC Comprehensive Headache Center, Department of Neurology and Anesthesia, Critical Care and Pain Medicine, Boston, United States AL21 5Sant'Andrea University Hospital, Sapienza University, The Disease Burden of Episodic and Chronic Migraine Department of Clinical and Molecular Medicine, Rome, in France, Spain and the United Kingdom Italy S. Díaz-Insa1, S. Santos2, H. Benhaddi3, L. Lee4, P. J. Goadsby5 Question: Use of opioids in headache disorders is 1Hospital Universitari i Politècnic La Fe, Valencia, Spain contradictive and evidence supporting their use is 2Hospital Clínico Universitario Lozano Blesa, Zaragoza, scarce. We aimed to systematically review studies Spain evaluating the use of opioids for the acute treatment 3TEVA Pharma, Wilrijk, Belgium of migraine. 4Kantar, San Mateo, CA, United States 5NIHR-Wellcome Trust King’s Clinical Research Facility, Methods: Systematic review and meta-analysis. We King’s College London, London, United Kingdom included controlled studies in migraine patients that treated at least one migraine attack with an opioid Question: Migraine is a disabling disease affecting 14% derivate. Studies were excluded if research was not of the population worldwide. The burden of disease original, preclinical, if addressed pharmacokinetics or extends to all aspects of life and is higher for tolerability or if headache was not migraine. The individuals who have failed preventive treatment. Real- screened databases were PubMed, Embase, world data were collected on patients with episodic Clinicaltrials.gov and Cochrane. We present categorical migraine (EM) and chronic migraine (CM) who had data as frequency and percentage and continuous data failed ≥2 preventive treatments in the UK, France, and as median and inter-quartile range (IQR). Spain, with a focus here on health-related quality-of- life (HRQoL) outcomes. Results: We identified 688 records, 42 articles were assessed for eligibility and 30 were included in the Methods: A cross-sectional, web-based survey was analysis, counting for 2445 participants. The studied conducted among eligible patients with EM and CM in drugs were meperidine (8), codeine (7), butorphanol the UK, France, and Spain. HRQoL was assessed using (5), tramadol (2), dextropropoxyphene (2), fentanyl (2), the Migraine Disability Assessment (MIDAS) and hydromorphone (1), morphine (1), nalbuphine (1) and EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire pethidine (1). 17 studies analysed opioids in (assessed for health "today" and during most recent combination with other analgesics, including 7/8 migraine headache). Descriptive statistics were meperidine studies and 7/7 codeine studies. calculated at the country level and qualitatively Comparator was placebo in 11 studies (35.5%) and compared across countries. other drugs in 19 (61.3%). Mean JADAD score of studies was 1.03 (1.9). Median sample size was 46.5 Results: Patients (n=316) were included from the UK patients [IQR: 26.5-134.2]. Most frequent primary (n=106; 80 EM), France (n=105; 80 EM), and Spain endpoint was pain relief, in 24 studies (77.4%). (n=106; 80 EM). Of the CM patients, 63% were female, 12

while of the EM patients, 48% were female. CM patients experienced greater migraine disability versus EM patients (median MIDAS score, 30 vs 12). For their most recent migraine, CM patients reported lower health status than EM patients, based on the EQ-5D-5L visual analog scale score (median, 40 vs 60) and total index score (median, 0.35 vs 0.52). Among EM patients, MIDAS scores were highest in Spain (median, 19) followed by France (13) and the UK (8). EQ-5D-5L index scores for most recent migraine were comparable across countries (median, UK, 0.57; Spain, 0.55; France, 0.41).

Conclusions: Results reveal substantial migraine disability among patients who have failed previous preventive therapies and that unmet needs may be greater in certain countries.

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P01 7 Bladder Dysfunction K 1 A 1 Possible effects, adverse and side-effects of Ketamine, a NMDA receptor antagonist in resistant chronic 8 Stomachache K 0 A 12 migraine- cohort observation 1994-2019- pilot data M. Nicolodi1, M. S. Pinnaro1, A. Torrini1, V. Sandoval1, 9 Gut dysfunction K 7 A 19 P. L. Del Bianco1, R. Conigliaro1,2, F. Sicuteri1,2 1Foundation Prevention Therapy of Primary Pain and 10 Confusion K 82 A 29 Headache, Research, Firenze, Italy 2 Hospital Humanitas Gradenigo, Neurology, Torino, 11 Hallucination Psychotic Reactions K 2 A 0 Italy 12 Somnolence K 82 A 53 Background Aim: In 1994 we published a coltrolled study on ketamine in migraine. Positive results led a 13 Dizziness K 82 A 53 prospective observation concerning effects/side- effects of this uncompetitive antagonist within NMDA 14 Sleep Disturbances K 1 A 0 receptor channel, relevant in plasticity of chronic pain 15 Mood (Hamilton D) Amelioration K 66 A35 Method: Dose 0.1mg/Kg/i.m 4 times/day. Out of 6020 volunteers 4.700 chronic migraine patients (2111; 1112 16 Mood Worsening K 2 A2 males, age 35.7+16.3SD) resistant to therapies were enrolled. Exclusions organic diseases, addiction history. Clustering by sex 3,6,8-12 ketamine adverse-effects, A parallel observation was made on a matched group male female ratio was 3:10. Side-effects appear chiefly (A n=2010) choosing to re-test amitriptiline 25 mg i.m. in 35-45 aged; n14 in under 25, n16 in over 60

Plan 15days run-in, 7-days in hospital R/L-ketamine or Cost-Benefit: Patients’s cost during first 24 months K amitriptyline IM injection. Follow-up lasted 52 weeks E2150+890, A 4730E+734 at minimum. Hence 1 prevention therapy unused before was given. Observations performed in Benefit K+748E+679 vs A –2370E+787 agreement with Helsinki Declaration 2013. Conclusion: Ketamine likely had not heavy side-effects, Effects: Decrease of migraine/days versus baseline: prevalent in females, and may improve sufferers’ life- Ketamine group (K)-67.05+6.8SD vs group A- quality 17.6+10.9SD p>00001 post-treatment and during entire follow-up. Relapses in K group: 3 after 1, 25 after

3 years.

Side effects

1 Discontinuations due to adverse events K 0 A0

2 Moderate withdrawal K2 A0 resolution 10 days

3 Sexual performances increase/flow chart K 69 A0

4 Blood pressure Decrease K 39 Increase 6A

5 Hearth rate changes ECG 1 K 12 A

6 Nausea and Vomiting K 27 30 A

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P02 Results: 59% of patients chose an MBS that Patient-identified most bothersome symptom in corresponded with the predefined list; 41% specified patients with chronic migraine: an analysis of their own option. Combining the predefined and PROMISE-2 recoded "other" options, MBS included light sensitivity R. B. Lipton1, D. W. Dodick2, J. Ailani3, P. Winner4, N. A. (18.7%), nausea/vomiting (together or separately, Hindiyeh5, J. Hirman6, S. Snapinn7, L. Mehta8, R. Cady8 15.1%), pain with activity (13.7%), sound sensitivity 1Albert Einstein College of Medicine, Department of (7.3%), cognitive disruption (4.1%), fatigue (2.4%), and Neurology, Bronx, NY, United States mood changes (1.5%). New symptoms from the 2Mayo Clinic, Phoenix, AZ, United States "other" list included pain (12.4%) and headache 3Department of Neurology, Georgetown University (11.2%), throbbing/pulsation (4.7%), multiple Hospital, Washington, DC, United States symptoms (2.5%), smell sensitivity (0.9%), vision 4Palm Beach Headache Center, West Palm Beach, FL, impact (0.7%), aura (0.7%), and pressure/tightness United States; Neurology Research Institute Palm (0.7%), among others. Beach, West Palm Beach, FL, USA; Premiere Research Institute, West Palm Beach, FL, United States; Palm Conclusions: Results demonstrate that migraine is Beach Neurology, West Palm Beach, FL, United States; associated with numerous symptoms that are most Nova Southeastern University, Fort Lauderdale, FL, bothersome to patients beyond the ICHD-3 defining United States symptoms. ~25% of MBS identified in PROMISE-2 are 5Stanford University School of Medicine , Stanford, CA, not included in ICHD-3 diagnostic classification for United States migraine. Future efforts should endeavor to capture a 6Pacific Northwest Statistical Consulting, Inc., broader range of MBS in individuals with migraine in Woodinville, WA, United States order to enhance doctor-patient communication and 7Employed by Lundbeck Seattle Biopharmaceuticals, customize treatment goals. Inc. (FKA Alder BioPharmaceuticals, Inc.) at time of abstract preparation; currently contracting with Lundbeck Seattle Biopharmaceuticals, Inc. , Bothell, WA, United States P03 8Lundbeck Seattle BioPharmaceuticals, Inc., Bothell, ERENUMAB IN CHRONIC MIGRAINE: EFFICACY AND WA, United States RESPONSE PREDICTORS FROM AN ITALIAN MULTICENTRIC OBSERVATIONAL STUDY. Background: In addition to headache, migraine R. Rao1, F. Schiano di Cola2, S. Caratozzolo2, E. encompasses a variety of autonomic, cognitive, and Venturelli3, U. Balducci4, V. Sidoti4, E. Pari5, C. Costanzi5, sensory symptoms. Allowing patients to self-identify a A. di Summa6, G. J. Sixt6, E. D'Adda5, P. Liberini1, A. most bothersome symptom (MBS) without limitation Padovani2 can provide a unique patient-centered approach for 1ASST Spedali Civili Brescia, Brescia, Italy identifying and measuring migraine-associated 2Università degli Studi di Brescia - ASST Spedali Civili di symptoms that matter most to an individual. This Brescia, Brescia, Italy analysis assesses patient-identified MBS in patients 3ASST Papa Giovanni XXIII, Bergamo, Italy with chronic migraine (CM) enrolled in PROMISE-2. 4ASST Franciacorta, Chiari, Italy 5ASST Crema, Crema, Italy Methods: PROMISE-2 (NCT02974153) was a double- 6Azienda Sanitaria dell’Alto Adige, Bolzano, Italy blind, randomized, placebo-controlled trial evaluating eptinezumab for preventive treatment of CM. At Introduction: Randomized, placebo-controlled trials screening, patients verbally described the MBS demonstrated erenumab safety and efficacy in the associated with their migraine, which were categorized prevention of Chronic Migraine (CM). Real life clinical by the investigator into a predefined list of 8 symptoms data is still missing, especially regarding response or an "other" option with free-text description. MBS predictors. categorized as "other" were recoded to the predefined list or to new symptom classes. MBS was pooled across Methods: An observational multicentre study was treatment arms (N=1072). performed involving six italian hospitals. Patients were treated with erenumab 70 mg every four weeks. If no clinical response was observed after 12 weeks, a dose 15

increase to 140 mg was attempted. Data about Figure 1 outcome and baseline clinical and demographic characteristics, i.e. age, gender, education, body mass index, migraine localization, disease duration, triptans response, medication overuse, allodynia, psychiatric and autoimmune disorders, previous prophylaxes, hormonal therapies, shift work and add-on therapies, were collected. Clinical follow-up was performed up to 24 weeks.

Results: Eighty-six consecutive patients were enrolled (67 female, 19 male). Mean disease duration at baseline was 10.9 (±7.2) years, with a mean age of 48.2 (±8.3) years. Medication overuse was documented in 77 patients (89.5%). On average, patients had already failed at least 5 previous prophylactic therapies. Patients were classified according to the percentage of P04 headache days reduction as non-responders (<30%), Exploring the boundaries between episodic and partial-responders (<50%) and responders (>50%) at chronic migraine: Results from the CaMEO Study week 4, 12 and 24 of treatment (see Figure 1). At week R. B. Lipton1, M. L. Reed2, K. M. Fanning2, D. C. Buse1, P. 24, psychiatric comorbidities (mood disorders) and J. Goadsby3, J. Olesen4, D. W. Dodick5, A. Manack antidepressant add-on therapies (amitriptyline and Adams6 serotonin reuptake inhibitors) were more frequent in 1Albert Einstein College of Medicine, Bronx, NY, United non-responders compared to responders States (respectively p<0.001; p=0.02). 2Vedanta Research, Chapel Hill, NC, United States 3King’s College, London, United Kingdom Conclusion: Our data confirm erenumab efficacy in CM 4Copenhagen University, Copenhagen, Denmark prophylaxis, with nearly 80% of patients documenting 5Mayo Clinic, Phoenix, AZ, United States a significant response at week 24. However, psychiatric 6Allergan plc, Irvine, CA, United States comorbidities were found to negatively impact its efficacy. Such evidence will need to be further Background: Differences in migraine burden between validated as it might have a significant effect on people with high-frequency episodic migraine (HFEM) patients selection. and low-frequency chronic migraine (LFCM) have not been well characterized. We evaluated migraine Figure1: responders rate at 4, 12 and 24 weeks of burden across monthly headache day (MHD) treatment. subgroups in the web-based Chronic Migraine Epidemiology and Outcomes (CaMEO) Study population.

Methods: Eligible respondents who met modified International Classification of Headache Disorders, 3rd edition criteria for migraine answered web-based survey questions on demographics, headache features; disability, interictal burden, and depression. Four subgroups were defined based on self-reported MHDs: low-frequency episodic migraine (LFEM; 0-7), HFEM (8- 14), LFCM (15-23), and high-frequency chronic migraine (HFCM; ≥24). Trends by MHDs were assessed by the linear-by-linear association test and 2-sided chi statistics.

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Results: Data were provided by 16,789 respondents the percentage of patients who converted to Episodic (13,473 LFEM, 1840 HFEM, 1035 LFCM, and 441 Migraine (EM). HFCM). Of the respondents in the 4 MHD subgroups, 12.8%, 51.9%, 66.3%, and 70.1%, respectively, had Results: 54 patients received at least one Erenumab severe disability (grade 4) based on the Migraine dose and 31 patients (11 males; 20 females) were Disability Assessment Scale. Severe scores (≥5) on the evaluated after 3 doses (12 weeks). Mean previous Migraine Interictal Burden Scale were reported by number of failed preventive treatments was 19.2%, 38.2%, 46.7%, and 58.3% of respondents in the 13.94±2.97 (9.42±2.68 pharmacological; 4.52±1.91 4 subgroups, respectively. Depression (score of ≥10 on non-pharmacological). After 12 weeks there was a the 9-item Patient Health Questionnaire) occurred in >50% response rate in 45.2% (14/31) and a >75% 27.6%, 47.3%, 54.9%, and 60.8% of respondents in the response rate in 9.7% (3/31) respectively. Monthly 4 MHD subgroups, respectively. All changes were migraine days decreased from baseline 23.70±5.31 to statistically significant for the linear-by-linear 15.03±7.84 (p<0.0001) and monthly analgesic intake association test (P<0.001). decreased from baseline 37.35±20.03 to 20.52±16.24 (p<0.0001). At last follow up (12 weeks), 16/31 (52%) Discussion: These data indicate substantial overlap in patients were clinically converted from CM with MOH these measures of burden and depression among to EM. There were few reported side effects and no CaMEO respondents with HFEM (8-14 MHDs) and serious adverse event. those with LFCM (15-23 MHDs). Treatment needs of patients with HFEM may be similar to those with LFCM, Conclusions: Our real-life results confirmed efficacy of adding doubt to the rigid boundary between EM and Erenumab also in very severe CM with MOH cohort CM at 15 MHDs. after 12 weeks with no serious safety issues. Furthermore, half of the patients converted to episodic migraine, although longer follow-up will be needed to evaluate long-term results. P05 Erenumab in highly refractory Chronic Migraine patients with Medication Overuse Headache: a single centre real-life study. P06 U. Pensato1, V. Favoni1, A. Pascazio1, M. Benini1, G. M. Ketogenic diet in pediatric patients with chronic Asioli1, E. Merli1, C. Calabrò1, P. Cortelli1, G. Pierangeli1, migraine S. Cevoli1 R. Moavero1,2, D. Elia1, L. Papetti1, M. A. N. Ferilli1, F. 1IRCCS Scienze Neurologiche di Bologna, Neurology, Ursitti1, S. Tarantino1, C. Dionisi Vici1, F. Vigevano1, M. Bologna, Italy Valeriani1 1Bambino Gesù Children's Hospital , Rome, Italy Question: Erenumab has proven its efficacy and safety 2Tor Vergata University of Rome, Systems Medicine in Chronic Migraine (CM) patients in randomized Department, Rome, Italy control trial, but few studies have investigated its efficacy in highly refractory CM patients with Objectives: Aim of this study was to evaluate efficacy, Medication Overuse Headache (MOH). safety and feasibility of ketogenic diet (KD) in children and adolescents with chronic migraine (CM). Methods: In our Tertiary Headache Centre, we selected consecutive patients with a diagnosis of CM Materials and Methods: We prospectively enrolled with MOH who received Erenumab monthly. We patients aged 10-18 years with CM unresponsive to included only patients who had failed at least 10 previous prophylactic treatments or that refused other pharmacological and non-pharmacological commonly therapies. A biochemical screening was performed to used preventive treatments for CM. Furthermore, all exclude inborn errors of metabolism. KD was then included patients failed to respond to botulinum toxin, introduced at 1:1 ratio. Biochemical analysis were the only approved preventive treatment for CM. We repeated at 1 week, 1 and 3 months of treatment. evaluated changes in monthly migraine days, monthly Daily ketones and glucose measurements at home analgesic intake and >50%, >75% responder rates at were required. Results. We enrolled 16 patients (3M, week 12 compared to baseline. At last, we evaluated 13F) to start KD. Among them 8 decided not to initiate 17

KD mainly due to concerns about dietary restrictions (PREEMPT) protocol bilaterally across 7 different and difficult compliance. Therefore, KD was initiated in injection areas (every 12 weeks): procerus 5-units, 8 patients (1M, 7 F – age 11-18 years). In 3 patients KD frontalis 10 units, temporalis 20 units, occipitalis 20 was withdrawn in the first 3 months of treatment due units, cervical paraspinals, 20 units, and trapezius 25. to inefficacy. In one case KD determined a partial benefit, but the patient had an onset of bowel Results: From January 2018 to today, 11 patients have inflammatory disease and KD was withdrawn. In 2 received OBT-A (mean age 15 ± 4.5; 7 females and 4 patients, after an initial response headaches appeared males). To date, one patient has performed only one again, and although at a lower frequency and intensity administration and therefore it is not possible to define than before KD, both patients decided to stop KD due the response to treatment. Of the remaining 9 to unsatisfactory pros/cons ratio after 4 and 5 months patients, one patient discontinued treatment after 4 of treatment. One patient was lost to follow-up, and administration for no benefit. Three patients one patient is still under treatment after 4 months, discontinued therapy due to lack of tolerance for with reduction of headache frequency. injection therapy. The remaining patients performed at least 3 toxin injections and presented a benefit. In Discussion: In our headache center we experienced particular, 4 patients presented a reduction in the difficulties in enrolling patients for KD, mainly due to number of attacks and in the response to the drugs for concerns about palatibility. In patients enrolled we the attack. For 2 of the 4 patients, a reduction in the observed a partial efficacy in 50% of cases. However, monthly frequency of attacks of more than 50% was benefits were transient in 2 of them, and were not observed. No patients presented major side effects. considered sufficient to justify such a dietary regimen according to our patients. Conclusions: The preliminary results of our study show that OBT-A in pediatric patients with migraine is not Conclusion: According to our experience, although KD always tolerated as consequence of the modality of has a potential to treat chronic migraine, it requires a injection. This represents the main cause of non- significant effort to patients and their families, making adherence to treatment in our sample. Patients who it a hardly feasible option in childhood and received at least three toxin administrations adolescence. experienced headache improvement. OBT-A therapy should be considered in pediatric patients with chronic migraine refractory to conventional drugs.

P07 Longitudinal evaluation of tolerability of Onabotulinumtoxin A in pediatric chronic migraine. P08 L. Papetti1, C. Ruscitto2, G. Sforza2, F. Ursitti1, M. A. N. Erenumab in Refractory Chronic Migraine patients: Ferilli1, R. Moavero1,2, S. Tarantino1, M. Valeriani1 Real-life results from an Italian tertiary Headache 1IRCSS Bambino Gesù, Neuroscience, rome, Italy Center 2Torvergata University of Rome, Child Neurology Unit, V. Favoni1, U. Pensato1, A. Pascazio1, M. Benini1, G. M. Systems Medicine Department, Rome, Italy Asioli1, E. Merli1, C. Calabrò1, P. Cortelli1, G. Pierangeli1, S. Cevoli2 Introduction: The use of onabotulinumtoxin A (OBT-A) 1IRCCS Istituto delle Scienze Neurologiche di Bologna, in the pediatric migraine has not been evaluated for Italy, Department of Biomedical and NeuroMotor chronic migraine in a longitudinal study. The aim of this Sciences (DiBiNeM), Alma Mater Studiorum - study was to verify drug tolerance in pediatric migraine University of Bologna Italy. , Bologna, Italy patients. 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy Methods: For the treatment with OBT-A , patients with chronic migraine according to ICHD 3 criteria’s were Question: Randomized controlled trials have proven selected from January 2018 to date. Patients must the efficacy and safety of erenumab as preventive have failed at least two conventional drug treatments. treatment in chronic migraine (CM).The aim of the OBT-A injections were injected similarly to the Phase study is to evaluate the effectiveness and the safety of III Research Evaluating Migraine Prophylaxis erenumab in refractory CM patients in real-life. 18

Methods: Between May 2019 and January 2020, all P09 eligible consecutive CM patients received erenumab 70 Sustained Clinical Benefits Following mg subcutaneously once every 4 weeks in our Tertiary OnabotulinumtoxinA Treatment in Patients With Headache Center. Erenumab was increased to 140 mg Chronic Migraine: A Post Hoc Analysis of the Pooled at week 8 in poor-responders and non-responders. We PREEMPT Studies evaluated changes in monthly migraine days, monthly D. W. Dodick1, H. C. Diener2, S. D. Silberstein3, L. analgesic intake and >50%, >75% responder rates at Yedigarova4, R. B. Lipton5 week 8 and 12 compared to baseline. 1Mayo Clinic, Phoenix, AZ, United States 2University of Duisburg-Essen, Essen, Germany Results: 115 patients (88 females, 27 males; mean age 3Thomas Jefferson University, Philadelphia, PA, United 50.23±9.35) received at least one erenumab dose. States Mean previous failed pharmacologic preventive 4Allergan plc, Irvine, CA, United States treatments was 7.23 and mean previous failed non- 5Albert Einstein College of Medicine, Bronx, NY, United pharmacologic preventive treatments was 3.32. States 95/115 (83%) patients received at least 2 doses. At week 8, there was a >50% response rate in 31.6% Background: We evaluated the sustained benefits of (30/95) and a >75% response rate in 10.5% (10/95), onabotulinumtoxinA treatment in patients with chronic respectively. Monthly migraine days decreased from migraine (CM) through 56 weeks. baseline 23.03±5.19 to 15.36±7.92 (p<0.0001) and monthly analgesic intake decreased from baseline Methods: Post hoc analysis of pooled data from the 35.02.±25.49 to 18.53±13.91 (p<0.0001). 65/115 (57%) 24-week, placebo-controlled PREEMPT (NCT00156910, patients received at least 3 doses. At week 12, there NCT00168428) clinical trials, including the 32-week was a >50% response rate in 35% (23/65) and a >75% open-label phase, during which all patients received response rate in 9% (6/65), respectively. Monthly onabotulinumtoxinA. The proportions of patients migraine days decreased from baseline 32.34±5.77 to treated with onabotulinumtoxinA who achieved 14.45±7.14 (p<0.0001) and monthly analgesic intake clinically meaningful improvement at week 24 (primary decreased from baseline 29.60±19.23 to 18.20±15.34 endpoint; double-blind period) in headache day (p<0.0001). Only one patient discontinue treatment reductions (≥50% or ≥75% from baseline) and 6-item due to ineffectiveness. There were few reported side Headache Impact Test score (HIT-6; ≥5-point effects. No serious adverse event were reported. improvement) were calculated. A sustained responder was defined as a patient who experienced clinically Conclusions: Our real-life results confirmed a meaningful improvement at week 24 that continued significant rate of reduced migraine days on erenumab through 56 weeks of treatment. Only patients who with good safety and tolerability in a cohort of severe achieved a clinically meaningful change at week 24 and CM patients with multiple preventive treatment had ≥1 available assessment after 24 weeks were failure. included in this analysis.

Results: A total of 1384 patients were randomized to onabotulinumtoxinA (n=688) or placebo (n=696) in the PREEMPT trials; only those treated with onabotulinumtoxinA were included in this analysis. At week 24, 254/539 (47%) patients experienced a ≥50% reduction in headache days; 163 of the 254 (64%) sustained benefits for the remaining 32 weeks of the study. A ≥75% reduction in headache days was experienced by 123/539 (23%) patients at week 24, and 69 of the 123 (56%) sustained the reduction for the remaining 32 weeks of the study. At week 24, 248/599 (41%) patients experienced a clinically meaningful improvement on HIT-6; 169 of the 248 (68%) sustained benefits over the remaining 32 weeks.

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Discussion: In the PREEMPT trials, a majority of Discussion: In our study we have shown that the drugs patients treated with onabotulinumtoxinA experienced for acute attack are not very effective in patients with clinically meaningful improvements at week 24 that CM and that some patients do not respond to any were sustained throughout the entire 56-week acute treatment. treatment period with regard to headache days and headache impact.  1) Headache Classification Committee of the International Headache Society (IHS) . The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018; 38: 1– P10 211. Does symptomatic treatment help children and  2) Arruda M, Bigal M. Migraine and migraine adolescents with chronic migraine? subtypes in preadolescent children: association M. A. N. Ferilli1, L. Papetti1, F. Ursitti1, R. Moavero2,1, S. with school performance. Neurology Tarantino1, G. Sforza1, F. Vigevano1, M. Valeriani3,1 2012;79:1881–1888. 1Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy, Neurology, Roma, Italy 2Tor Vergata University of Rome, Italy, 2. Child Neurology and Psychiatry Unit, Roma, Italy P11 3Aalborg University, Aalborg, Denmark, Center for Healthcare resource utilization and health-related Sensory Motor Interaction , Aalborg, Denmark quality of life in adult patients with chronic migraine: Results from the PREDICT study Background and aim: Chronic migraine (CM) is defined G. Boudreau1, I. Finkelstein2, C. Graboski3, M. Ong- in the third edition of the International Classification of Lam4, S. Christie5, K. Sommer6, M. Bhogal7, G. Headache Disorders (ICHD-3) as the presence of Davidovic7, W. J. Becker8 headaches on 15 days or more in a month, at least 8 1Centre Hospitalier Universitaire de Montréal (CHUM), days showing the migraine phenotype, for more than 3 Montréal, QC, Canada months (1). CM affects from 0.6% to 1.8% of children 2Toronto Headache & Pain Clinic, Toronto, ON, Canada and adolescents (2) and determines a huge decrease of 3Island Health, Brentwood Bay, BC, Canada the quality of life. Aim of this study is to analyze the 4St. Paul Hospital, Vancouver, BC, Canada type of symptomatic drugs used and their efficacy for 5University of Ottawa, Ottawa, ON, Canada the treatment of acute migraine attacks in pediatric 6Allergan plc, Marlow, Buckinghamshire, United patients with chronic migraine. Kingdom 7Allergan plc, Markham, ON, Canada Methods: We conducted a retrospective and 8University of Calgary, Calgary, AB, Canada prospective study by selecting pediatric patients diagnosed with CM in our Department. We Background: This analysis evaluates outcomes administered a questionnaire to the parents of all our including HRU, HRQoL, and safety in Canadian patients pediatric patients with CM according to ICHD-3; with CM treated with onabotulinumtoxinA from the questions were focused on symtomatic drugs used for PREDICT (NCT02502123) study. acute migraine attacks and their effectiveness. Methods: PREDICT was a 2-year, Canadian, single-arm, Results: For the final analysis we considered 25 open-label, multicenter, post-authorization, prospec- patients with CM. No patient responded to the initial tive study in adults naïve to botulinum toxin(s) for CM. therapy with acetaminophen and only 12% improved OnabotulinumtoxinA was administered per the with ibuprofen. Thirty six percent of patients had relief Canadian product monograph. The primary endpoint with second-line NSAIDs drugs like ketoprofen, was mean change in MSQ at treatment 4 vs baseline. indomethacin, naproxen. Twenty-eight percent of HRU data were collected at baseline and at each patients did not respond to more than three drugs and treatment session. 24% were resistant to all acute treatments. All patients underwent prophylaxis therapy (amitriptyline, Results: A total of 184 enrolled participants received topiramate, flunarizine). ≥1 onabotulinumtoxinA treatment. Patients were, on average, aged 45 years, Caucasian, and 85% female; 20

60% had a family history of migraine. Statistically migraine (EM, N=30) and CM-MO (N=27), to significant improvements from baseline were observed investigate their role in reduction of headache in MSQ domains after treatment 4 and at the final frequency. CM-MO group was tested at baseline and 2 study visit, all P<0.0001 and exceeding minimal months after detoxification. important differences. At baseline, 96.2% of patients reported an HA-related visit to an HCP, and 17.9% Results: Baseline levels of CGRP and microRNAs were reported an HA-related visit to an ER or urgent care significantly higher in CM-MO subjects compared with clinic, both of which decreased to 76.8% and 8.4% at EM patients. All the CM-MO subjects completed the final study visit (2 years), respectively. HA-related successfully the detoxification and were overuse-free hospital admissions were reported by 3.8% of patients at 2 months. During the follow-up we recorded an at baseline and only 1.4% at the final study visit. At overall 50% decrease in headache days/month baseline, 37.5% of patients reported HA-related reduction (26.23±5.24 vs 13.4±10). When stratifying diagnostic testing; this decreased to 9.9% at the final the CM-MO group after detoxification in EM and CM, study visit. The most common diagnostic tests were based on the mean headache number days during the blood tests, MRIs, and CAT/CT scans. A total of 168 2-month follow-up (<15 or >15), in the EM (n= 15) TEAEs were reported by 41.8% of patients; of those, 38 group, we found that both CGRP and microRNAs levels were considered treatment related in 12.0% of were significantly reduced as compared to baseline patients. Six serious TEAEs were reported in 2.2% of values. By contrast, in the CM group (n= 12) we only patients; none was considered treatment related. No observed a decrease in microRNAs, while CGRP plasma new safety signals were identified. levels did not differ from baseline.

Discussion: Real-world findings from the PREDICT Conclusions: Increased CGRP plasma levels are study demonstrate that treatment with associated to migraine severity, whereas miR-34a-5p onabotulinumtoxinA in the Canadian population is and miR-382-5p changes are a consequence of MO. associated with improvements in health-related quality of life and reductions in HRU.

P13 The use of the Severity of Dependence Scale to the P12 severity of analgesics dependence: An Italian study CGRP plasma levels and peripheral expression of S. Bottiroli1,2, G. Sances2, R. De Icco2,3, M. Allena2, E. specific microRNAs in chronic migraine with Guaschino2, C. Tassorelli2,3 medication‐overuse: changes induced by 1University Giustino Fortunato, Pavia, Italy detoxification 2IRCCS Mondino Foundation, Pavia, Italy R. Greco1, C. Demartini1, A. M. Zanaboni1,2, E. 3University of Pavia, Pavia, Italy Tumelero1, R. De Icco1, G. Sances1, M. Allena1, C. Tassorelli1,2 Objective: To test the severity of analgesics 1IRCCS Mondino Foundation, Pavia, Italy dependence in chronic migraine using the Italian 2University of Pavia, Pavia, Italy version of the Severity of Dependence Scale (SDS).

Introduction: Chronic migraine (CM) is frequently Methods: Four hundred and eighteen patients with associated to symptomatic medication overuse (MO) chronic migraine (CM) (mean age: 46.9±12.5) recruited but the mechanisms underlying the development of at the Mondino Foundation served as the participants. MO remain unknown. Calcitonin gene related peptide The SDS is a self-completion 5-item instrument to (CGRP) is involved in sensitization phenomena and assess the compulsive dimension of medication likely, in migraine chronification. MicroRNA expression dependence on a 4-point Likert scale ranging from 0 to patterns may useful as disease biomarkers and for 3. The diagnose for formal substance dependence predicting individual risks of chronic pain. based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) was used as Methods: We evaluated CGRP plasma levels and the comparative measure. expression of miR-34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with episodic 21

Results: Seventy-three percent of CM were classified treatment visit. HRU data, including family doctor or as DSM-IV substance dependent (i.e., SD group) (mean specialist visits, inpatient acute treatment, acute age: 48.9±11.0) and 27% did not receive this diagnose treatment for headache, acupuncture, technical (i.e., NSD group) (mean age: 42.0±12.5). SD and NSD investigations (CT, MRI, X-ray, ECG, ultrasound), and groups differed in most of the clinical variables (e.g., use of nonpharmacologic remedies, were collected at number of previous relapses, drug doses per month, baseline (occurrence within prior 3 months) and at 6, months of chronic headache), in which SD patients 12, 18, and 24 months (events since prior visit). resulted as more severely affected. SD patients had significantly higher scores in SDS (mean: 7.5±2.8, Results: Of 641 enrolled patients, 633 received ≥1 p<.001) questionnaire in comparison to NSD ones onabotulinumtoxinA dose. Patients were, on average, (mean: 6.3±2.9). SD group had also higher scores that aged 45 years, 85% were female, and 60% (n=377) NSD group in all SDS items (ps<.001) except for item 3. were from Germany. German patients had an average Higher SDS scores (OR 1.135, 95% CI 1.015–1.271, of 18.9 monthly headache days at baseline, with p=.027), together with higher number of drug doses reductions observed at all follow-up visits (range: 11.3– per month (OR 1.033, 95% CI 1.009–1.058, p=.007) and 6.0). At baseline, 41.7% and 61.7% of patients saw a of relapses after previous detoxification programs (OR family doctor or specialist with the number of visits 14.566, 95% CI 5.188–40.894, p<.001) resulted as declining throughout follow-up (ranges: 18.3%–9.2%, prognostic factors in predicting substance dependence. family doctor; 9.5%–4.6%, specialist). Inpatient acute This logistic regression model was statistically treatment declined from 6.4% of patients at baseline significant, χ2(7) = 109.561, p < .001 and it explained to a range of 0.8%–0.0% with continued treatment. 43.2% of the variance in the presence of substance Acute treatment for headache and acupuncture dependence and correctly classified 80.8 % of cases. declined from 71.2% and 14.5% at baseline to ranges of 69.2%–55.4% and 2.2%–0.0%, respectively. Conclusion: Our results show that the SDS Technical investigations and use of remedies decreased questionnaire is a good instrument for detecting from 19.7% and 30.6% at baseline to ranges of 1.6%– medication overuse and dependency-like behavior in 0.0% and 15.4%–4.6%, respectively. persons with chronic headache. Discussion: In German REPOSE participants, onabotulinumtoxinA treatment for CM is associated with reduced monthly headache days and decreased P14 HRU. Due to drop-outs, a population of responders Real-life use of onabotulinumtoxinA for symptom remained in later months of the study. relief in patients with chronic migraine: REPOSE study German population K. Kollewe1, C. Gaul2, A. Gendolla3, K. Sommer4 1Hannover Medical School, Hanover, Germany P15 2Migraine and Headache Clinic, Königstein, Germany Migraine patients with and without medication 3Praxis fur Neurologie, Essen, Germany overuse headache and dependency rate 4Allergan plc, Marlow, Buckinghamshire, United P. Merbaum1, G. Tabeeva1 Kingdom 1Sechenov University, Neurology, Moscow, Russian Federation Background: In Germany, chronic migraine (CM) has been associated with substantial disability and Main objective: Patients with medication overuse increased healthcare resource utilization (HRU) and headache (MOH) are likely to have predisposition to costs. abuse development but there are restricted evidence based data about their tendency to have dependence Methods: REPOSE, a 2-year, prospective, noninter- behavior. The main objective of this study was to ventional, observational, open-label study, described determine how medication overuse correlates with real-world use of onabotulinumtoxinA in adults with dependency in migraine patients. CM. Patients received onabotulinumtoxinA ~every 12 weeks. Patient-estimated mean headache-day Patients and Methods: The study included 30 patients frequency in the last month was collected at each with migraine with and without MOH, mean age is 22

40.6±21,1 years. Definite diagnosis of migraine and Figure 2 MOH were based on 2018 international classification of headache disorder 3 (ICHD3) criteria. All patients were asked about their abuse history and filled in the Leeds dependence questionnaire (LDQ), Dependence Personality questionnaire (DPQ) and Severity of Dependence scale (SDS). Statistical analysis was performed using Exel data analysis.

Results: The results showed there is a statistically significant difference between LDQ (p=0,05) and SDS (p=0,016) results in the group of migraine patients with and without MOH (Fig. 1 and 2). Patients with medication overuse have higher scale at both tests. Interestingly, both groups have reported near the same index of alcohol or drug abuse in their family history or indicated the substance abuse themselves.

Conclusion: The study results showed that patient with migraine and medication overuse headache seem to have higher dependency rate than migraine patients without MOH that may affect their ability to withdrawal. Further investigation with long-term observation of withdrawal therapy efficiency should be performed.

Figure 1

P16 Erenumab in chronic migraine patients with prior non-successful onabotulinumtoxinA therapy: a multicentre retrospective observational study B. Raffaelli1, R. Kalantzis1, J. Mecklenburg1, L. H. Overeem1, L. Neeb1, A. Gendolla2, U. Reuter1 1Charité - Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany 2Praxis Gendolla, Essen, Germany

Background: German authorities approve migraine prevention with the CGRP-receptor antibody erenumab only in treatment-refractory patients who previously did not have therapeutic success with at least five oral prophylactics or have contraindications to such. In this real-world analysis we assessed treatment response to erenumab in patients with chronic migraine (CM) who failed five oral prophylactics and, in addition, onabotulinumtoxinA (BoNTA).

Methods: We analysed retrospective data of 139 CM patients with at least one injection of erenumab from two German headache centres. Patients previously did 23

not respond sufficiently or had contraindications to ß- Methods: 8 patients diagnosed with MOH and without blockers, flunarizine, topiramate, amitryptilin, and anamnestic evidence of known sleep disturbances valproic acid, and additionally BoNTA. Headache and were admitted to undergo a two night migraine frequency, headache severity, acute non- polysomnography before starting a standard 5 days specific medication and triptan intake were assessed in detoxification therapy with intravenous fluid and the four-week period before erenumab initiation and paracetamol administration. Another sleep study was over the course of the twelve-week treatment. performed the night after detoxification therapy completion. Migraine Disability Assessment (MIDAS), Results: From the first injection onwards erenumab Epworth Sleepiness Scale (ESS), Pittsburgh Sleep (starting dose 70 mg) led to a significant reduction of Quality Index (PSQI), Hamilton Anxiety Scale (HAM-A) monthly headache days (-3.7 ± 5.5 in weeks 1-4, -4.7 ± and Beck Depression Inventory II (BDI-II) were 5.9 in weeks 9-12, p<0.001 for both). Monthly migraine administered before and after detoxification therapy. days, days with severe headache, days with acute Sleep recordings were score for both macro- and medication and triptan intake were reduced over time. microstructure variables, with specific attention to the Half of patients (51.11%) had a >30% reduction of indexes of sleep fragmentation. monthly headache days in weeks 9-12. Only 4.3% of patients terminated erenumab treatment due to side Results and discussion: Compared to predetoxification, effects. a significative reduction of HAM-A (t test p=0.013; Wilcoxon test p=0.027) was observed. Regarding sleep, Conclusion: In this refractory CM population, indexes of sleep fragmentation were reduced: Cyclic erenumab showed efficacy in a real-word setting Alternating Pattern (CAP) rate (p=0.017; p=0.025), CAP similar to data from clinical trials in less severely rate A1 (p=0.009; p=0.025), CAP index A1 (p=0.011; affected patients with up to four unsuccessful p=0.012) and CAP index A2 (p=0.026; P=0.017). therapeutic attempts. Tolerability was good and no safety issues emerged. Erenumab is a treatment option These data indicate a partial sleep stabilization with for CM patients who failed all first-line preventives in sleep quality improvement in patients affected by addition to BoNTA. MOH after painkilling-drug withdrawal, showing a relation between this kind of headache and sleep characteristic. The amelioration of sleep pattern is accompanied by a reduction of anxiety levels at HAM- P17 A. Both could play a role in the compliance to Reduction of sleep fragmentation and of anxiety withdrawal procedure. levels after withdrawal of acute painkilling drugs in medication overuse headache

Valente M, Bevilacqua F, Garbo R, Pez S, Gigli GL Clinical Neurology, University of Udine, Udine, Italy M. Valente1, F. Bevilacqua1, R. Garbo1, S. Pez1, G. L. Gigli1 1Neurological Clinic University of Udine, Udine, Italy

Introduction: Increasing evidence is pointing at a relationship between headache and sleep disturbances, with probably a bidirectional influence. Few studies about this relationship are present, mainly performed in some types of primary headaches. However little is known about sleep quality in patient suffering from medication-overuse headache (MOH).

Objectives: In this study we aim to evaluate sleep characteristics in this subgroup of patients and their modification after acute painkilling drugs withdrawal. 24

P18 Conclusion: In pts with EM or CM and documented Efficacy of Fremanezumab in Patients With Episodic inadequate response to 2-4 classes of migraine and Chronic Migraine And Inadequate Response to 2- preventive medications, fremanezumab significantly 4 Classes of Migraine Preventive Medication by reduced the number of MMDs and HDs and improved Therapeutic Class With Inadequate Response Due to response rates compared with PBO, regardless of prior Lack of Efficacy: Results of the International, therapeutic class of medication with inadequate Multicenter Phase 3b FOCUS Study response due to lack of efficacy. L. Pazdera1, J. M. Cohen2, X. Ning2, L. J. Krasenbaum2, R. Yang2, M. Seminerio2 Figure 1 1Vestra Clinics, Rychnov nad Kněžnou, Czech Republic 2Teva Pharmaceutical Industries, West Chester, PA, United States

Question: Fremanezumab has demonstrated efficacy for migraine prevention in adults with episodic (EM) or chronic migraine (CM) and documented inadequate response to 2-4 migraine preventive medication classes in the FOCUS study. This analysis evaluated efficacy of fremanezumab in that study by prior therapeutic class in patients (pts) with inadequate response due to lack of efficacy for ≥1 prior preventive medication.

Methods: In the 12-week, double-blind period of FOCUS, pts were randomized (1:1:1) to quarterly P19 fremanezumab (Month 1/2/3: 675mg/placebo Early Efficacy of Fremanezumab in Patients With (PBO)/PBO), monthly fremanezumab (Month 1/2/3: Episodic and Chronic Migraine and Inadequate 675mg (CM), 225mg (EM)/225mg/225mg), or matched Response to 2-4 Classes of Migraine Preventive PBO. Efficacy at 12 weeks was assessed by prior Medications Due to Lack of Efficacy: Results of the therapeutic class (angiotensin II receptor antagonists, International, Multicenter Phase 3b FOCUS Study anticonvulsants, beta-blockers, calcium channel A. J. Starling1, V. Ramirez-Campos2, R. Yang2, J. M. blockers, onabotulinumtoxinA, tricyclic Cohen2, M. Galic3, X. Ning2, K. Carr2, C. Treppendahl4 antidepressants, valproic acid) with inadequate 1Department of Neurology, May Clinic, Scottsdale, AZ, response due to lack of efficacy using changes from United States baseline (BL) in monthly average migraine days 2Teva Pharmaceutical Industries, West Chester, PA, (MMDs), changes from BL in headache days of at least United States moderate severity (HDs), and proportion of pts 3Teva Pharmaceuticals, Amsterdam, Netherlands achieving ≥50% reduction in monthly migraine days. 4The Headache Center, Ridgeland, MS, United States Results: Overall, 741 of 838 randomized pts had Question: Fremanezumab, a fully-humanized inadequate response to different prior preventive monoclonal antibody (IgG2Δa) that selectively targets migraine medication classes due to a lack of efficacy. calcitonin gene-related peptide (CGRP), has proven Across all prior preventive medication classes, changes efficacy for migraine prevention in adults. This analysis from BL in MMDs and HDs over 12 weeks were of the FOCUS study, which included patients (pts) with significantly greater with fremanezumab vs PBO episodic or chronic migraine (EM or CM) that had (P<0.05; Table). For all classes of preventive reported inadequate response to 2-4 classes of medications, proportions of pts with ≥50% reduction in migraine preventive medications, evaluated early MMDs were significantly greater with quarterly (27- efficacy of fremanezumab in pts with inadequate 39%) and monthly (23-42%) fremanezumab vs PBO (3- response to ≥1 preventive medication due to lack of 12%; P<0.05; Table). efficacy prior to the clinical trial.

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Methods: In the 12-week, double-blind period, pts P20 were randomized (1:1:1) to quarterly (qtly) Correlation between the tolerability to fremanezumab (Month 1/2/3: onabotulinumtoxinA administration and the presence 675mg/placebo(PBO)/PBO), monthly (mtly) of adverse events: A prospective cohort study. fremanezumab (Month 1/2/3: 675mg (CM), 225mg A. Sierra Mencia1, M. Gutierrez Sanchez1, B. Martinez (EM)/225mg/225mg), or matched PBO. Efficacy Rodriguez1, D. Gil Contreras1, A. L. Guerrero Peral1, B. outcomes evaluated over the first 4 weeks in pts with Talavera de la Esperanza1, D. García-Azorín1 inadequate response to ≥1 prior migraine preventive 1Hospital Clinico Universitario de Valladolid, Neurology, medication due to lack of efficacy were changes from Valladolid, Spain baseline (BL) in mtly average migraine days (MDs) and headache days of at least moderate severity (HDs), and Background: OnabotulinumtoxinA (onabotA) proportions of pts with ≥50% reduction in mean mtly treatment for chronic migraine (CM) requires the MDs. infiltration of 25 craniocervical points and 6 trapezius sites. Most of described adverse events (AE) are local. Results: Of 838 pts randomized, 741 demonstrated In this study we aim to analyse if tolerability to inadequate response to prior preventive migraine onabotA administration is associated with a higher medication classes due to lack of efficacy. Changes frequency of AE. from BL in mtly average MDs over 4 weeks were significantly greater with qtly and mtly fremanezumab, Methods: Prospective cohort study including all respectively, vs PBO in this population (LSMD vs PBO: consecutive CM patients underwent onabotA −3.5 and −3.5; P<0.0001). Changes from BL in HDs were administration for the first time after prior failure of at also significantly greater with fremanezumab vs PBO least two oral preventatives. We analysed headache (LSMD: qtly, −3.0; mtly, −3.3; P<0.0001). Over weeks 1- intensity at the moment of onabotA administration 4, the proportion of pts with ≥50% reduction in MDs and tolerability to the procedure in a 0-10 numeric was significantly greater with qtly and mtly rating scale from 0: worst to 10: best. We fremanezumab vs PBO (Table). systematically contacted patients afterwards and assessed AE occurrence, both spontaneously reported Conclusion: In pts with EM or CM and documented and by systematic approach. We describe frequency inadequate response to 2-4 classes of migraine and percentage and mean and standard deviation or preventive medications due to lack of efficacy, median and interquartile range. fremanezumab rapidly reduced the number of MDs and HDs and improved 50% responder rates vs PBO Results: We included 105 patients, 97.6% female, aged within the first 4 weeks. 44.1 (10.3). At the moment of infiltration, 75 of them (71.4%) were experiencing headache, with a mean Figure 1 intensity of 4.88/10. Tolerability to onabotA administration was 8.25/10 [6.8-9.2] in median.

Adverse events were described by 74 patients (70.5%), none of them severe. Described AE were headache in 33 (31.4%), aesthetic 27 (25.7%), cervical stiffness in 11 (19.5%) muscular pain in 9 (8.6%), and ptosis in 4 cases (3.8%). Overall frequency of AE was not associated with a higher intensity of headache at the moment of administration (3.6 vs. 3.1, p=0.4) or with a better tolerability (7.7 vs. 7.7, p=0.8). Concerning individual AE, only intensity of headache in the moment of infiltration was higher in patients that experienced ptosis (6.5 vs 3.37, p=0.03) and in patients with muscular pain (5.0 vs. 3.3, p=0.04).

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Conclusion: Most of our patients were experiencing monthly fremanezumab vs PBO across all classes of headache at the moment of their first onabotA preventive medication (Table). Proportions of pts with administration. Tolerability was rated good. AE ≥50% response were numerically higher with occurrence was not associated neither with a higher fremanezumab vs PBO from wk 1 through 4 across all headache intensity nor with a worse tolerability, medication classes. At wk 4, response rates were except for ptosis and muscular pain. significantly greater with monthly fremanezumab (35%-53%) vs PBO (12%-33%; all P<0.05) across all medication classes, except calcium channel blockers (45% vs 33%; Table). P21 Early Efficacy of Fremanezumab in Episodic and Conclusion: In pts with documented past inadequate Chronic Migraine in Patients Who Had Failed response due to lack of efficacy to ≥1 prior migraine Preventive Medication: Lack of Previous Efficacy preventive medication, fremanezumab reduced Based on Therapeutic Class Prior to the International, numbers of MMDs and HDs and improved response Multicenter Phase 3b FOCUS Study rates vs PBO, regardless of prior therapeutic class of J. Lewis Brandes1,2, J. M. Cohen3, X. Ning3, L. J. preventive medication. Krasenbaum3, R. Yang3, M. Seminerio3 1Nashville Neuroscience Group, Nashville, TN, United Figure 1 States 2Vanderbilt University, Nashville, TN, United States 3Teva Pharmaceutical Industries, West Chester, PA, United States

Question: Fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), has demonstrated efficacy in adults with episodic (EM) or chronic migraine (CM), with documented previous inadequate responses to 2-4 classes of migraine preventive medications. This analysis evaluated early efficacy for fremanezumab in the FOCUS study by therapeutic class in patients (pts) with inadequate P22 response to ≥1 prior preventive medication due to lack Safety of Fremanezumab in Patients With Episodic of efficacy. and Chronic Migraine and Inadequate Response to 2-4 Classes of Migraine Preventive Medication Due to Methods: In the 12-week (wk), double-blind, placebo Poor Tolerability: Results of the International, (PBO)-controlled study, pts were randomized (1:1:1) to Multicenter Phase 3b FOCUS Study 1 2 2 2 quarterly fremanezumab (Month 1/2/3: S. J. Nahas , J. M. Cohen , Y. Kessler , X. Ning , R. 2 2 3 675mg/PBO/PBO), monthly fremanezumab (Month Yang , K. Carr , D. Kudrow 1 1/2/3: 675mg(CM), 225mg(EM)/225mg/225mg), or Jefferson Headache Center, Thomas Jefferson matched monthly PBO. Efficacy by prior therapeutic University, Philadelphia, PA, United States 2 class was evaluated over 4 wks based on changes from Teva Pharmaceutical Industries, West Chester, PA, baseline (BL) in monthly average migraine days United States 3 (MMDs), changes from BL in headache days of at least California Medical Clinic for Headache, Santa Monica, moderate severity (HDs), and proportions of pts with CA, United States ≥50% response (≥50% reduction in MMDs). Question: Fremanezumab, a fully-humanized Results: Of 838 pts randomized, 741 demonstrated monoclonal antibody (IgG2Δa) that selectively targets inadequate response to prior preventive migraine calcitonin gene-related peptide (CGRP), has medication classes due to lack of efficacy. During the demonstrated efficacy and favorable safety and first 4 wks of FOCUS, changes from BL in MMDs and tolerability as preventive treatment for migraine in HDs were significantly greater with both quarterly and adults. This analysis of the FOCUS study, which 27

evaluated efficacy and safety of fremanezumab in Figure 1 patients (pts) with episodic or chronic migraine (EM or CM) and inadequate response (due to lack of efficacy, poor tolerability, or contraindication or unsuitability for the patient) to 2-4 prior migraine preventive medication classes, assessed the safety of fremanezumab in pts with inadequate response to ≥1 prior preventive medication due to poor tolerability.

Methods: The 12-week, double-blind, placebo (PBO)- controlled FOCUS study randomized (1:1:1) pts to quarterly fremanezumab (Month 1/2/3: 675mg/PBO/PBO), monthly fremanezumab (Month 1/2/3: 675mg (CM), 225mg (EM)/225mg/225mg), or matched PBO. Safety was assessed during double-blind treatment by adverse events (AEs), AEs leading to discontinuation, and serious AEs (SAEs).

Results: Of 838 pts randomized, 448 had inadequate P23 response to ≥1 prior migraine preventive medication Efficacy of Fremanezumab in Patients with Migraine due to poor tolerability. AEs were reported for similar and Documented Inadequate Response to 3 or 4 proportions of pts across treatment groups (Table). Migraine Preventive Medication Classes and The most common AEs were injection-site erythema, Medication Overuse in the International, Multicenter, injection-site induration, nasopharyngitis, and Randomized, Placebo-controlled FOCUS Study 1 2 2 2 insomnia. Two pts each in the fremanezumab groups L. Pazdera , X. Ning , V. Ramirez-Campos , R. Yang , K. 2 2 (<1%) and PBO group (1%) had AEs leading to Carr , J. M. Cohen 1 discontinuation. SAEs occurred in <1% in both Vestra Clinics, Rychnov nad Kněžnou, Czech Republic 2 fremanezumab and PBO groups, and no SAE occurred Teva Pharmaceutical Industries, West Chester, PA, in >1 pt. These results are consistent with the safety United States profile of fremanezumab in the overall population of the FOCUS study. Question: Fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets Conclusion: In pts with inadequate response to 2-4 calcitonin gene-related peptide (CGRP), has prior migraine preventive medication classes, with demonstrated efficacy as a preventive treatment in inadequate response to ≥1 of those preventive patients with episodic (EM) or chronic migraine (CM) medications due to poor tolerability, fremanezumab and documented inadequate response to 2-4 prior demonstrated similar, low incidences of AEs, AEs migraine preventive medication classes in the FOCUS leading to discontinuation, and SAEs compared with study. The primary endpoint (change from baseline PBO. (BL) in monthly average migraine days (MMDs)) for the FOCUS study was evaluated in different subgroups of patients (pts) with difficult-to-treat migraine.

Methods: During the 12-week, double-blind period (DBP), pts were randomized (1:1:1) to monthly fremanezumab (Months 1/2/3: 675mg(CM), 225mg(EM)/225mg/225mg), quarterly fremanezumab (Months 1/2/3: 675mg/placebo(PBO)/PBO), or matched PBO. Changes from BL in MMDs were evaluated in subgroups with inadequate response to ≥3 migraine preventive medication classes, inadequate response to ≥3 medication classes and acute medication overuse at BL, inadequate response to ≥3

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medication classes and ≥8 days of acute medication P24 use at BL, and inadequate response to ≥4 medication Efficacy of Fremanezumab in Subjects With Migraine classes. and Prior Inadequate Response to Valproic Acid, Topiramate, or OnabotulinumtoxinA in the Open- Results: Of 838 pts randomized, 420 had inadequate label Period of the International, Multicenter, response to ≥3 medication classes, 229 had inadequate Randomized, Placebo-controlled FOCUS Study response to ≥3 medication classes and acute A. J. Nagy1, X. Ning2, M. Galic3, J. M. Cohen2, R. Yang2, medication overuse at BL, 327 had inadequate M. Seminerio2, L. Mechtler4 response to ≥3 medication classes and ≥8 days of acute 1Nevada Headache Institute, Las Vegas, NV, United medication use at BL, and 155 had inadequate States response to ≥4 medication classes. MMDs were 2Teva Pharmaceutical Industries, West Chester, PA, significantly reduced with fremanezumab vs PBO in the United States overall FOCUS population; reductions in MMDs in 3Teva Pharmaceuticals, Amsterdam, Netherlands subgroups with inadequate response to ≥3 and ≥4 4Dent Neurologic Institute, Buffalo, NY, United States medication classes and overuse of acute medication were comparable or greater than in the overall Question: In the double-blind period (DBP) of the population (Figure). FOCUS study, fremanezumab demonstrated efficacy as a preventive treatment in subjects with episodic or Conclusion: In pts with difficult-to-treat migraine, chronic migraine (EM/CM) and documented including inadequate response to ≥3 and ≥4 inadequate response to 2-4 prior migraine preventive medication classes and overuse of acute medication, medication classes. In the open-label extension (OLE), fremanezumab treatment resulted in substantial efficacy in subjects with inadequate response to reductions in MMDs, comparable to the overall FOCUS valproic acid (VPA), topiramate, or population. onabotulinumtoxinA was evaluated.

Figure 1 Methods: This phase 3b study included a 12-week DBP and 12-week OLE. In the DBP, subjects were randomized (1:1:1) to subcutaneous (SC) quarterly fremanezumab (months 1/2/3: 675mg/placebo/placebo), monthly fremanezumab (months 1/2/3: 675mg(CM), 225mg(EM)/225mg/225mg), or matched placebo. After completing the DBP, subjects entered the OLE and received monthly fremanezumab (225mg) for 3 months. During the OLE, changes from baseline (BL) in monthly average migraine days (MMDs) in subjects with prior inadequate response to valproic acid, topiramate, or onabotulinumtoxinA and ≥1 other prior migraine preventive medication class were evaluated and compared by double-blind randomization group (DB group).

Results: Of 838 subjects randomized, 807 entered the OLE. Among subjects with prior inadequate response to VPA (n=247) and VPA and 2-3 other preventive medication classes (n=157), subjects experienced reductions from BL in MMDs over the 12-week OLE of −3.9 to −6.0 days across DB groups (Table 1). The proportion of subjects achieving ≥50% reduction in MMDs was higher in both fremanezumab DB groups than the placebo DB group (Table 1). Among subjects with prior inadequate response to topiramate (n=590) 29

or onabotulinumtoxinA (n=218), change from BL in fremanezumab in patients with EM or CM and MMDs were −3.9 to −5.2 days across the DB groups inadequate response to ≥1 prior migraine preventive (Table 2). Similar reductions in MMDs had been medication in a 1-year extension of the 3-month HALO observed during the DBP with fremanezumab studies or inadequate response to 2-4 prior migraine treatment. preventive medication classes in the open-label extension (OLE) period of the FOCUS study. Conclusions: Treatment with fremanezumab over up to 6 months (DBP and OLE) was effective in providing Methods: In the 1-year extension study, monthly or sustained reductions in MMDs. quarterly fremanezumab treatment was maintained; patients who previously received placebo were Figure 1 randomized 1:1 to monthly or quarterly fremanezumab. In the FOCUS OLE, all patients completing the 3-month, double-blind period (DBP) entered the OLE and received 3 monthly doses of fremanezumab (225mg). Efficacy outcomes included changes from baseline in the monthly average number of migraine days (MMDs) and headache days of at least moderate severity (HDs) and the proportion of patients responding with ≥50% reduction in MMDs.

Results: Of 1890 patients enrolled in the 1-year Figure 2 extension study, 700 had inadequate response to ≥1 preventive medication. In the FOCUS study, 559 patients with documented inadequate response to 2-4 classes of prior preventive treatment were randomized to fremanezumab in the DBP, and 543 continued receiving fremanezumab in the OLE. Fremanezumab treatment for 6 to 12 months resulted in reductions in the MMDs and HDs (Table). Approximately half or more of patients achieved clinically meaningful (≥50%) reduction in the MMDs (Table).

P25 Conclusion: Across multiple different study Long-Term Efficacy of Fremanezumab in Patients With populations with inadequate response to prior Episodic Migraine and Chronic Migraine Who Failed treatment, fremanezumab was efficacious over up to 6 At Least One Prior Migraine Preventive Medication: months (FOCUS DBP and OLE) or up to 15 months (3- Results From 6- and 12-Month Studies month HALO studies and 1-year extension study). C. Dougherty1, X. Ning2, J. M. Cohen2, R. Yang2, V. Ramirez-Campos2, M. Seminerio2, S. D. Silberstein3 1Department of Neurology, MedStar Georgetown University Hospital, Washington, D.C., United States 2Teva Pharmaceutical Industries, West Chester, PA, United States 3Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA, United States

Question: Fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), has demonstrated efficacy for the preventive treatment of episodic migraine (EM) and chronic migraine (CM). This analysis evaluated efficacy outcomes for

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Figure 1 (22,4%) of the visits. The odds ratio of recurrency to the ED in the same period with ≥1 visit with opioid prescription was 4,07 (IC95%: 3,23 - 5,11, p<0,001).

Conclusion: In this study, we observed a high prevalence of opioids prescribed for acute migraine treatment in the ED. Patients who received opioids at least in one visit presented a higher risk of recurrence in the same period. As a transversal retrospective study, it is not possible to imply a causal relation. Nevertheless, we hypothesize that educational programs for the ED staff and better acute treatment protocols may reduce the inadequate use of opioids, P26 with a positive impact on recurrent migraine patients. Opioids use for acute migraine treatment and the risk of recurrent visit to the Emergency Department in a Figure 1 tertiary Hospital in Brazil M. N. P. Souza1,2, G. Kubota1,2, A. P. D. Oliveira3, L. S. Zambon3, M. R. Jordão3, M. Calderaro1,2 1Hospital das Clínicas, University of São Paulo, Neurology, Headache Medicine, São Paulo, Brazil 2Hospital Samaritano, Neurology, São Paulo, Brazil 3Hospital Samaritano, São Paulo, Brazil

Background: Current migraine acute treatment guidelines emphasize the importance of avoiding opioids as the first option. The excessive use of opioids has shown to impose further disability for this population, but it is still present in up to 35% of acute treatments registred in North America. However, the prevalence of opioid use for migraine treatment in

Brazil is still unknown. P27 Objective: To evaluate the prevalence of opioid use for A Multicenter Cooperative REgistry for Load and acute migraine treatment and correlation with Management of MEdicAtion OveruSE Headache recurrency to the Emergency Department (ED) at a H. Park1, S. J. Cho2 Tertiary Hospital in São Paulo, Brazil. 1Inje University Ilsan Paik Hospital, Inje University College of Medicine, Neurology, Goyang, South Korea Methods: Observational retrospective longitudinal 2Hallym University Dongtan Sacred Heart Hospital, evaluation of patients admitted in the ED, with Neurology, Hwaseong, South Korea migraine diagnoses, from January 1st, 2018 to December 31st, 2019. Demographical and clinical Background: Medication overuse headache (MOH) is a aspects were evaluated. Patients who recurred to the disabling chronic headache disorder which is ED with migraine were compared with nonrecurrent developed with frequent usage of analgesics for patients regarding the opioids use. control of primary headache disorders. Prevention and management of MOH can significantly relieved the Results: a total of 3775 visits due to migraine were burden of migraine because impact of migraine is registered in the period, with 80,3% being women, 53% closely related to those of MOH. However, there are aged between 30-40 years-old. Opioids were used for several controversies about MOH such as diagnostic acute treatment in 524 (13,9%) of the visits. criteria, the threshold of overuse of medications, etc. Investigation with neuroimaging was performed in 846

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Method: A Multicenter Cooperative REgistry for Load Results: We included 250 patients, 217 (86.8%) and Management of MEdicAtion OveruSE Headache female). Mean age was 42.1±10.1 years, with (RELEASE) is a cross-sectional observation study. We 23.3±11.6 years of migraine and 34.8±45.1 months of are going to prospectively enroll the patients who use chronic migraine in mean. At baseline, they multiple or migraine-specific drugs for acute or experienced 23.4±5.6 headache days per month, taking symptomatic treatment of headache 10 or more times symptomatic medications 17.6±7.8 days per month, per month or simple analgesics 15 or more times per fulfilling 194 (77.6%) patients medication overuse month during last month or who meet the diagnostic headache criteria. After 3 administrations 154 (61.6%) criteria of MOH by diagnostic criteria of The patients had a 50% response and 76 (30.4%) a 75% International Classification of Headache Disorders, 3rd response. Mean reduction in headache days was edition. Severe headache day and headache-free day 11.4±9.7 and mean reduction in symptomatic will be assessed. The protocol included the clinical medication days was 8.2±10.2. Every 0.53 headache manifestation, headache days, medication days for days that patients had at baseline (95% CI: 0.33-0.73, recent 3 months, associated symptoms, comorbid p<0.001), one more headache day was reduced after illness, overused medication, and underlying primary three onabotA sessions (Figure 1). After adjusting for headache disorders of MOH. The projected sample size time of migraine, time of chronic migraine, number of is 500. The diagnostic criteria of MOH, clinical subtypes symptomatic medication days, frequency of MOH, sex of MOH will be compared. and age, results remained statistically significant (0.59 days, 95% CI: 0.33-0.81, p<0.001). Conclusion: RELEASE will provide the clue for solving the controversies about MOH. Conclusion: In our sample, the higher the frequency at baseline, the higher the reduction in headache days per month after three onabotA sessions. Response to onabotA might vary depending on the frequency of P28 headache days at baseline. THE HIGHER THE HEADACHE FREQUENCY, THE BETTER THE RESPONSE TO ONABOTULINUMTOXINA IN Figure 1 PATIENTS WITH CHRONIC MIGRAINE D. García-Azorín1, M. Gutierrez-Sánchez1, î Sierra- Mencía1, D. Gil Contreras1, B. Martínez1, î Guerrero Peral1 1Hospital Clínico Universitario de Valladolid, Headache Unit, Valladolid, Spain

Question: Response to prophylactic treatment in chronic migraine (CM) patients is not homogeneous. Magnitude of response might vary depending on the frequency of headache at baseline. We aim to analyze if patients with higher frequency of headache days per month at baseline respond differently to onabotulinumtoxinA (onabotA).

Methods: Prospective cohort study including patients with CM with prior failure to two preventive drugs. OnabotA was administered following PREEMPT protocol quarterly and analyzed results of the first three procedures. We conducted a linear regression analyzing if a higher frequency of headache days at baseline was associated with a higher reduction of headache days evaluated after three onabotA sessions and we adjusted for the main confounders that could influence the response. 32

P29 duration, and gender) against 8 used with classic The clinical utility of a pragmatic criterion for criteria. The prediction rate was higher for CR and NR assessing the response of chronic migraine to than PR (55% and 56% vs. 27, p<0.001). preventive therapy and its predictors in a cohort of 403 patients. Conclusions: The pragmatic criterion allowed to better A. Viganò1, E. Simoncelli2, B. Petolicchio2, I. Maestrini2, predict the outcome of patients with CM, using only M. Toscano2,3, M. Puma2, R. De Sanctis4, M. Alessiani2,5, the basic parameters, regardless of the preventive V. Di Piero2 therapy used. 1IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy 2Sapienza - University of Rome, Human Neurosciences, 1. Tassorelli C. Cephalalgia. 2018 Apr;38(5):815-832. Rome, Italy 3Fatebenefratelli Hospital, Neurology, Rome, Italy 4Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy P30 5Campus Bio-Medico University , Neurology, Rome, Evaluation of anxiety –depressive disturbances and Italy headache related disability in patients with chronic and episodic migraine. Background: Evaluating the response to a prophylactic C. Rustamova1,2, M. Yakubova1,2 drug in chronic migraine (CM) is challenging. While an 1Tashkent Medical Academy, Neurology, Tashkent, episodic migraineurs that halves the number of Uzbekistan headache days usually represents a success, a CM 2Tashkent Medical Academy, neurology, Tashkent, patient, with the same result, remains chronic. We Uzbekistan tested a simple alternative pragmatic criterion to evaluate improvement and its ability to identify Background and objectives: Anxiety-depressive outcome predictors. disorders frequently accompany migraine and impact negatively on patient’s academic performance. Most Methods: We collected data from CM patients patients with migraine, especially with chronic form (including those with medication overuse – MOH) who report their ability to function severely impaired. Our have attended our headache clinic in the past 7 years. study was aimed to assess the depression and anxiety They should have successfully completed at least one and to determine the headache related disability of prophylaxis treatment cycle and have had a patients with both chronic and episodic migraine. reevaluation after 4 months. Depending on the number of headache days per month, we pragmatically Materials and methods: We examined 130 patients defined the CM patients as Complete- (CR <4), Partial- with migraine (men - 24 (18.5%) and women - 106 (PR <15) and No-responder (NR> 15). We compared (81.5%) aged from 22 to 46 years, average age them with the classic criteria used in the CM guidelines 35.17±0.95) at the Tashkent Medical Academy in [1]. We used baseline parameters to assess clinical neurology department. The hospital anxiety and outcome predictability with the Discriminant Function depression scale (HADS) was used for determining Analysis (DFA). depression and anxiety disorders, while headache related disability was measured using the Migraine Results: We recruited 403 CM patients (341 F, mean Disability Assessment (MIDAS) Questionnaire in age 45.24 ±15.97), 167 had MOH and 96 migraine with patients with chronic migraine, comparing with aura. They were treated with amitriptyline (N=125), episodic form. flunarizine (N=83), topiramate (N=80), valproate (N=60), or onabotulinumtoxinA (N=55). Pragmatic Results: Among 130 patients 48 (36.9%) had chronic criteria identified 148 CR, 119 PR and 135 NR; while migraine(CM), while 82 (63.1%) had episodic classic criteria 261 CR, 39 PR and 100 NR. The correct migraine(EM). According to the hospital scale of rate of outcome prediction was higher with pragmatic anxiety and depression, depression and anxiety were criteria (35.5%, Lambda:0.69; F=6.19, p<0.001) than more pronounced in CM than in EM (63% vs 37%, classic criteria (18%, Lambda:0.69, F=3.82, p<0.001), p<0.0001). According to MIDAS Questionnaire, the with 5 predictors (i.e. number of baseline headache, patients with chronic migraine had more total number of previous preventive lines, HIT-6, headache 33

headache days over 3 months (53.3 vs 13.5, 155 units were administrated in 31 fixed-sites as fixed p<0.005),missed more days of work or school ( 6.6 vs dose injections following the PREEMPT injection and 2.2,p< 0.006), had more reduced effectiveness days at dose paradigm. The frequency of her recurrent work or school(12.7 vs 5.1,p<0.0001),missed more transient vertigo was reduced 3 weeks after the first days of housework( 16.9 vs 3.5, p<0.0005),and missed injection and disappeared after the second injection of more days of family, social activities(7.3 vs the onabotulinum toxin A. Her headache frequency 5.0,p<0.0001).The patients who had CM was more was also reduced to once a month. She re-visited the likely to be in MIDAS grade 4 than in EM(65.6% vs clinic 8 months later with increased frequency of 42.5%,p<0.005),expressing the severe disability in dizziness and headache (more than 10 times a month these patients. with 5 days of crystal clear day). Her symptoms were disappeared again one month after the onabotulinum Conclusion: The patients with CM demonstrate toxin A therapy. remarkable impairment of their daily activities and severely burdened by their headache syndrome and Conclusion: Disappearance of recurrent transient had severe depression and anxiety. Complex treatment vertigo in chronic vestibular migraine by the measures are needed to decline disability, psychiatric onabotulinumtoxin A therapy highlights the need for a symptoms in patients with migraine. confirmation of the efficacy of this preventive treatment strategy in this situation.

Figure 1 P31 Frequent Severe Vertigo Abolished by the Onabotulinum toxin A therapy in Patient with Chronic Migraine: A Case Report G. S. Kim1, H. K. Park1 1Inje University Ilsan Paik Hospital, Neurology, Goyang, South Korea

Background: Although onabotulinum toxin A therapy has been approved for the prevention of headache in chronic migraine, the effect of onabotulinum toxin A on migraine-associated dizziness or vertigo has not been evaluated yet. Here we report a case of chronic vestibular migraine whose dizziness and vertigo had been abolished by onabotulinum toxin A therapy. P32 Chronic Headache Prevalence and Helicobacter pylori Case: A 53 year-old female presented to our Infection in Outpatients emergency department. She felt cloudiness inside her N. Ninashvili1,2, M. Shavdia1, N. Chakvetadze2, K. head and stuffiness of air. Just after standing up to Tchaava1, N. Gegeshidze1 open the window, we fell down on the floor with head 1Tbilisi State Medical University, Tbilisi, Georgia trauma. She was diagnosed as probable orthostatic 2National Center for Disease Control and Public Health, intolerance. Three month later, she experienced Tbilisi, Georgia similar event. The findings of cardiac tests were unremarkable. During the follow-up, she had reported Introduction: Chronic pain is a public health priority frequent dizziness and vertigo lasting for few seconds and the main cause of primary care referral worldwide. to minutes 3 to 4 times a week which was not Acute and chronic headaches are among prevailed pain associated with any particular circumstance such as conditions. Cross-sectional survey aimed to study dehydration or body position. She also reported that prevalence of chronic pain and its impact on health- she has headache which do not bother her daily life. related quality of life (HRCoL). However, the headache turned out to be a chronic migraine with medication overuse headache. Without any oral preventive medications, onabotulinum toxin A 34

Methods: Cross-sectional survey enrolled 280 Results: Surgical neurostimulation, depending on the randomly selected outpatients >18 in 2017. IASP pain location of the electric pulse, is divided into and SF-36 questionnaires along with numeric pain scale neurostimulation of peripheral nerves, their distal were employed. branches and roots, and neurostimulation of neuronal structures of the spinal cord and brain: stimulation of Results: Chronic pain prevalence was 27% (95% CI deep brain structures and stimulation of the motor 22.15% - 35.65%, P<0.005). Headache dominated cortex. The following methods are used: among the study subjects (30%), followed by low back electrostimulation of the occipital nerves, pain (23.3%). 93.3% of the study subjects suffered of electrostimulation of the pterygopal ganglion, and severe pain when visiting to family physician and over electrostimulation of deep brain structures, in 40.0% - during the past 5 years and more. Due to particular the posterior hypothalamus. All these unrelieved pain every forth patient had to refer to methods are minimally invasive, since they do not family physician 2-8 times per year. Chronic pain had a require large surgical incisions, are limited to minimal serious impact on HRCoL, in particular on work ability blood loss and, most importantly, carry a minimal and everyday activity (rs=-0.593 p=0.005), sleep (rs=- potential risk of possible complications, unlike "large" 0.393 p=0.001). Disease history revealed that the vast operations. Some researchers have shown that 60% of majority of patients along with headache suffered with patients managed to achieve complete relief from chronic gastrointestinal (GI) symptoms. Previous headaches, and in General, 80% of patients received a seroprevalence prevalence studies on Helicobacter good response to stimulation. pylori infection in adults >18 and children of ages 3-16 revealed that 72% of adults and 38.4% of children were Conclusion: If the patient has a refractory chronic positive to the infection and the vast majority of them migraine, neurostimulation can be used. It is the task were symptomatic. Abdominal pain and headache of the neurosurgeon to analyze the criteria for were more frequent symptoms recurring once and selecting patients for neurostimulation and to select three times per week accordingly. Symptoms scores the individual, most appropriate variant of exposure. varied by age and the Clevelend system. Implantation of the device must be performed by a qualified team of neurosurgeons who know the Conclusions: Prevalence of Chronic headache is high in technique of implanting invasive devices for outpatients. Based on the results of the studies it is neurostimulation. If these conditions are met, high- most likely that chronic headache in adults is related to tech neurostimulation methods offer prospects for childhood exposure to H. pylori infection, however significantly improving the quality of life for patients considering disadvantages of cross-sectional surveys with severe chronic migraine that are resistant to other observational studies are required to be conducted to types of treatment. ascertain causative relationship between headache and H. pylori infection in the country population.

P34 SURGERY AS AN ALTERNATIVE AND EFFECTIVE P33 METHOD OF TREATMENT CHRONIC MIGRAINE NEUROSTIMULATION AS ONE OF THE MOST A. Gusev1, M. Kurnukhina1 EFFECTIVE METHODS OF TREATMENT OF CHRONIC 1First Pavlov State Medical University of St. Petersburg, MIGRAINE neurosurgery, St. Petersburg, Russian Federation M. Kurnukhina1, A. Gusev1 1First Pavlov State Medical University of St.Petersburg, Background: Every year 3 % of migraine patients with Neurosurgery, Saint-Petersburg, Russian Federation episodic migraine attacks without aura or migraine with aura progress in the form of increased attacks and Background: The high prevalence of chronic migraine the development of chronic migraine. Refractory and the significant difficulties associated with its migraine is one of the most severe variants of treatment have made it necessary to constantly search migraine. The frequency of this type migraine increases for and improve methods of its treatment. every year. For the treatment of refractory migraine, a Neurostimulation is one of the modern methods of modern treatment method such as surgical treatment treatment of chronic migraine. can be used. 35

Results: The main principle of this method is the predictors and compared patients with anxiety, trigger point deactivation (decompression of one or depression and SD to those without. more nerves in the head and neck, which can lead to migraines). For decompression, the supraorbital and Results: Among 112 patients, 34 (30.4%) had chronic subvertebral nerves in the forehead, zygomatic and migraine (CM) while 68 (69.6%) had episodic migraine auriculotemporal nerves in the temple area, and (EM). Depression, anxiety and sleep disturbances were occipital nerves can be used. Surgical treatment of more common in CH than in EH (58 % vs. 32 %, p < migraine may cause complications. However, the 0.0001). Patients with CM had more serious clinical frequency of these complications is insignificant and is and very poor QOL than patients with EM. The mainly manifested in the early postoperative period in strongest predictor of the MSQoL score in all patients the form of local edema, difficulty in healing the with migraine was the BDI score (β=0.382,p < 0.001), wound, and pain caused by nerve injury. The average followed by the ISI score (β = 0.324, p = 0.005), BAI recovery time for a patient after surgery is 14-21 days. score (β = 0.212, p < 0.001). Next came female gender According to some studies, after 5 years of surgical (β = 0.184, p < 0.001), headache intensity (β = 0.166; p treatment 88% of patients reported a decrease in the < 0.001), and attack duration (β = 0.148; p = 0.001). frequency and severity of migraine pain, and 29% BDI, ISI BAI scores and headache features (intensity showed a complete regression of chronic migraine. The and duration) had a direct effect on the QOL. positive results of surgical treatment include a reduction in treatment costs for such patients by Conclusion: Sleep disturbances and psychiatric almost 4 thousand dollars per patient per year. comorbidities such as depression and anxiety have a significant effect on quality of life in patients with EH Conclusion: Surgery is an alternative and effective and CH. Improved complex treatment approaches are method of treatment chronic migraine. However, this needed to decrease disability on the personal and method of treatment requires careful monitoring of social level in these patients. patient selection criteria.

Due to its high efficiency and significant improvement in the quality of life of patients with severe chronic P36 migraine who are resistant to other types of treatment, Body mass index and its association with episodic and migraine surgery should become a more commonly chronic migraine used method of treatment. K. Abdurakhmonova1, G. Rakhimbaeva1 1Mrs, Tashkent, Uzbekistan

Objective: This study was carried out to evaluate the P35 relationship between body mass index (BMI) and Effects of depression, anxiety and sleep disturbances episodic and chronic migraine. Because, obesity can be on the quality of life in patients with episodic and a risk factor for the transformation of episodic chronic migraine migraine (EM) to chronic migraine (CM). K. Abdurakhmonova1, G. Rakhimbaeva1 1Mrs, Tashkent, Uzbekistan Materials and methods: We included 112 patients (78.6 % women) who diagnosed with EM(65.1%) and Background: Episodic and especially chronic headaches CM(34.9%). We used the following formula: BMI are associated with depression, anxiety and sleep (kg/m2) = weight (kg) / height (m2) to measure to BMI. disturbances, and have significant negative impact on The patients were divided into 4 categories on the health-related quality of life (QOL). basis of BMI underweight (<18.5 kg/m2); normal weight (18.5 to <25 kg/m2); overweight (25 to <30 Methods: We included 112 patients (78.6 % women) kg/m2); obese (≥30 kg/m2). who completed self-report questionnaires including the Beck Depression Inventory (BDI), Beck Anxiety Results: Among the migraineurs, the proportions of Inventory (BAI), Migraine-Specific Quality of Life obese and overweight patients were higher in the CM (MSQoL) and Insomnia Severity Index (ISI). We used group than in the EM group, with the difference in the multiple regression analyses to establish QOL 36

percent of overweight patients being significant (EM and 1% of respondents are healthcare professionals. vs. CM: 14.6% vs. 34.8%; p < 0.005). The results Treatment analysis showed that only 20% of patients showed that BMI was linked with CM (p = 0.005). follow physician’s recommendations, others seek Relative to normal weight, the odds ratios for advice from friends and pharmacists or in the Internet. overweight and obesity were 3.26 (95% CI, 1.21–8.78) Regarding abortive drugs for migraine, based on 485 and 26.83 (95% CI, 2.84–278.4) in CM patients. In our respondents answers, non-steroidal anti-inflammatory study, underweight and normal weight had no drugs derived from propionic acid (ibuprofen as a association with EM and CM. monotherapy or in combinations), tryptans, and derivatives of salicylic acid and pyrazolones are used in Conclusion: Obesity and overweight plays an crucial 33%, 15%, and 12% of cases, respectively. role in the chronification of migraine. The effect of loss of weight can help to manage migraine disorder. Conclusion: Data analysis demonstrated that many people with migraine did not seek for medical advise, receive inadequate diagnosis and treatment which results in aggravation and chronization of the disease P37 Factors of migraine chronization: data from a medical and social online survey N. Kovalchuk1 P38 1First Moscow State Medical University, Moscow, Stress management efficacy in the treatment of Russian Federation chronic headache and comorbid immune disorders. A. Prishchepa1,2, A. Danilov1 Background: Previous studies demonstrated a very 1I.M. Sechenov First Moscow State Medical University high prevalence of chronic headache and medication of the Ministry of Health of the Russian Federation overuse headache in Russia, probably due to lack of (Sechenov University), Department of Neurology countrywide adequate medical care for headache. (Institute of professional education), Moscow, Russian Federation Aim: The purpose of this study was to analyze 2The Psychotherapy and Neurology Center "Stoic", treatment of patients with migraine and the Moscow, Russian Federation prevalence of self-treatment in a population of patients seen at Sechenov State Medical University. Introduction: Neuroimmunological disturbances accompanied by chronic stress are not only an Materials and Methods: Current data were obtained important element in headache (HA) pathogenesis, but from online medical and social survey in social can be risk factors of HA transformation into a chronic networks (Instagram, Vkontakte, Facebook, and form, atypical HA course and drug resistance. In this Telegram) and via a QR code placed at Sechenov case stress management can be alternative to drug University Clinic of Neurology. therapy without its side effects.

Results: By the time of the analysis, 1561 respondents Study objective was to evaluate the complex stress aged from 14 to 65 years (Mo=30-39 years) have taken management (SM) program efficacy in patients with part in the survey, 912 of them met the criteria of chronic migraine (CM) and chronic tention type migraine, 876 respondents were female and 36 headache (CTTH). respondents were male. In this cohort 21% of respondents did not seek medical care for headache, Methods: 44 patients with CTTH (n=22) and CM (n=22) among the ones who consulted a physician 33.2% were were stratified into two groups. The complex SM diagnosed with vegetative-vascular dystonia, 8% and program in the main group included biofeedback, self- 16.4% were diagnosed with tension headache and help techniques, lifestyle modification and art therapy; migraine, respectively, and 21.4% had unspecified patients in the control group received a standart drug diagnosis at the first visit. According to our data, 83% therapy (DT) (amitriptylin 50 mg, topiramat 100 mg). of patients are not regularly followed up by a The examination scheme included clinical and neurologist, 16% consult a physician 1-2 times a year, neurological examination, psychological stress evaluation and immunological tests. 37

Results: A decrease in HA freaquency and intensity was P39 found in both groups (p<0.001). But after SM patients Analysis of the Efficacy and Safety of 210 refractory demostrated signicantly lower stress level migraine patients treated with erenumab in a (p=0.000018) and pain catastrofizing (p=0.000281), and personalized managed access program in Spain significantly higher stress resistance compared to the R. Belvis1, M. Sanchez del Rio2, P. Irimia3, A. Alpuente4, DT group (p=0.000412). Normalization of the immune C. Gonzalez-Oria5, A. Cano6, J. Viguera7, B. Sanchez8, F. activity namely a decrese in the number of patients J. Molina9, I. Beltran10, A. Oterino11, E. Cuadrado- with diagnosed immune supression (from 54,5% (n=12) Godía12, A. Gomez Camello13, M. Alberte-Woodward14, to 13,6% (n=3) (p=0.006835) was determined only in th C. Jurado15, B. Oms16, D. Ezpeleta17, J. Diaz De Teran18, SM group (Figure 1). After SM treatment immune tests N. Morollon19, G. Latorre20, R. Leira21, S. Santos22 revealed a significantly lower number of abnormalities 1Hospital de la Santa Creu I Sant Pau. Universitat in content auto-antibodies compared to those after DT Autonoma de Barcelona, Headache Unit. Department (p=0.000098). of Neurology, Barcelona, Spain 2Clinica Unversitaria de Navarra, Neurology, Madrid, Conclusion: Improvement of HA qualitative and Spain quantitative parameters after the SM treatment is 3Clinica Universitaria de Navarra, Neurology, comparable to that after the DT, while the SM effect Pamplona, Spain on the psychological and immunological states is 4Vall D´Hebron University Hospital, Neurology, significantly higher. The qualities that ensure the SM Barcelona, Spain efficacy in HA treatment are high patient's compliance, 5Hospital Universitario Virgen del Rocio, Neurology, high level of patient's social activity and Sevilla, Spain immunosupression based on laboratory data. 6Hospital de Mataro, Neurology, Barcelona, Spain 7Hospital Virgen de la Macarena, Neurology, Sevilla, Figure 1 Spain 8Hospital Quironsalud, Neurology, Zaragoza, Spain 9Hospital Universitario Son Espases, Neurology, Palma de Mallorca, Spain 10Hospital General Universitario de Alicante, Neurology, Alicante, Spain 11Hospital Universitario Marques de Valdecilla, Neurology, Santander, Spain 12Parc de Salut Mar, Imim (Institut Hospital Del Mar D'investigacions Mèdiques),Universitat Pompeu Fabra, Neurology, Barcelona, Spain 13Hospital Universitario San Cecilio, Neurology, Granada, Spain 14Hospital Lucus Augusti, Neurology, Lugo, Spain 15Hospital Universitario Reina Sofia, Neurology, Córdoba, Spain 16Hospital Dos De Maig, Neurology, Barcelona, Spain 17Hospital Quironsalud, Neurology, Madrid, Spain 18Hospital Universitario La Paz, Neurology, Madrid, Spain 19Hospital Universitario Dexeus, Neurology, Barcelona, Spain 20Hospital Universitario de Fuenlabrada, Neurology, Madrid, Spain 21Hospital Universitario de Santiago De Compostela, Neurology, Santiago de Compostela, Spain 22Hospital Universitario Lozano Blesa, Neurology, Zaragoza, Spain

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Introduction: Erenumab was approved in Europe for P40 the preventive treatment of migraine in patients with Epidemiology of headache in a Mexican Tertiary-care ≥4 monthly migraine days (MMD). In Spain, Novartis center started a personalized managed access program which R. Garcia1, R. Carrera1, J. Hernandez1 allowed neurologists to treat patients before official 1Mexican Institute of Social Security, Neurology, reimbursement. The Headache Study Group of the Mexico city, Mexico Spanish Neurological Society created a registry to monitor real-world safety and efficacy, inviting Question: To establish the proportion of primary headache specialists around the country. headaches (PH), secondary headaches (SH) and other headaches (OH) in Mexican population at the Patients and methods: Patients fulfilled ICHD3 criteria emergency department. of migraine and ≥4MMD. Sociodemographic and clinical data were registered as well as MMD, headache Methods: We carried out an observational, case series, frequency (MHD), prior and concomitant preventive descriptive, and retrospective study in the Neurology treatment, analgesic overuse, years of migraine service at Speciality Hospital of National Medical duration, adverse events (AEs), and PROs: HIT6, Center XXI Century. Information was collected from MIDAS, and PGIC. A >50% reduction of MMD after 3 patients with headache from January to June 2019, months was considered as responder rate. obtaining the frequency of PH, SH and OH.

Results: We included 210 patients from 22 hospitals Results: 76 patients with headache were included; (February-to-November 2019), 86.7% women, mean 40.7% (31) had a PH, of which 67.7%(21) was tension- age: 46.4 years-old, and with 26.3 years mean migraine type headache (TTH), 25.8%(8) was migraine, and duration. Most patients (89.5%) had chronic migraine 6.4%(2) was trigeminal autonomic cephalalgias; 44.7% with a mean evolution of 8.6years. 70% overused (34) had SH, of which 23.5%(8) was secondary to analgesics, and 17.1% had aura. Average of prior arterial hypertension, 14.7%(5) secondary to preventives failure was >7 (onabotA was used by respiratory tract infections, 8.8%(3) secondary to 95.2%). MMD: 16.4, MHD: 22.4, MIDAS: 98.9p., HIT-6: neoplasms, 8.8%(3) secondary to head trauma, 8.8%(3) 68p. Erenumab initial doses: 70mg(67.6%), secondary to vascular etiologies; 14.7% (11) had OH, of 140mg(32.4%). Simultaneous oral preventives:60.5%, which 100% (11) was trigeminal neuralgia. and simultaneous onabotA:27.6%. Conclusions: Headache is one of the main reasons for Responder rate was 37.1% and the mean reduction of consultation in neurology, with a prevalence in adults MMD was -6.28 and MHD:-8.6. Regarding PROs: up to 47%1. From PH, the most frequent is TTH with a MIDAS:-35p., HIT6:-11.6p., PIGC: 4.7p. Predictors of prevalence of 46%2. SH constitutes up to 10% of the good response were: low HIT6 score(p=0.01), few prior total headaches attended in the emergency preventives(p=0.026), absence of analgesic department3. Neuralgias has a prevalence of 1.5% in overuse(p=0.039), and simultaneous OnabotA some populations4. Our study shows a greater treatment(p=0.001). Percentage of AEs:20%, but only 4 proportion of SH than PH due to arterial hypertension of them were severe(0.9%) and induced a commonly, however it is still more frequent TTH above discontinuation. Constipation was the more frequent all headaches. Further studies are needed for getting AE(8.1%). exact prevalence.

Conclusion: In real-life, in a personalized managed References: 1Gómez M, y cols. Cefalea: más que un access program, erenumab shows good efficacy and a simple dolor. Revista Mexicana de Neurociencia. favourable safety profile in migraine prevention in our 2015;16(6)41-53. cohort of refractory patients 2Jensen R, et al. Epidemiology and comorbidity of headache. Lancet Neurol. 2008;7:354-61.

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3Perkins A, et al. When to worry about headache; Head work was to study the impact of obesity on migraine pain as a clue to intracranial disease. Postgrad Med. clinical presentation, burden, and treatment outcome 1995;98:197-208. among a sample of Egyptian migraineurs.

4Liang X, et al. Characteristics of primary stabbing Methods: This was a prospective study conducted on headache in a tertiary neurological clinic in China. Pain 52 migraine patients attending the headache clinic at Medicine, 2014;15:871-875. Alexandria University hospital in Egypt. Demographic, clinical and migraine burden data were collected from Figure 1 all patients at baseline visits. The migraine burden assessed using depression anxiety stress score-21 (DASS21), migraine disability assessment score (MIDAS), the activity of daily living (ADL), headache days per month, days with analgesics use, days with triptans/ergots use, days of absenteeism and healthcare visits. After 3 months of prophylaxis, patients were reassessed for migraine frequency, severity, DASS-21, MIDAS, and patient-reported satisfaction. A comparison was made between obese (Body mass index (BMI)≥30) and non-obese patients (BMI<30) as regards all baseline and follow-up data.

Results: Of 52 patients recruited, 80.8% were females, 46.2% were obese and 54% had chronic migraine. The mean age of patients was 35.2±12.5 years. Obese patients were more likely to have migraine with aura (4.2% versus 3.6%, p=0.012), a shorter duration to progression to the chronic stage (5.96±6.47 years versus 14.94±10.01 years, p=0.008), and to have their headaches precipitated by menstruation (45.8% versus 14.3%, p=0.014) and odors (29.8% versus 7.1%) than non-obese. There was no statistically significant difference between the 2 groups as regards the migraine burden variables studied (p>0.05). On follow- up, obese patients tended to have higher DASS-21

scores (21.79±14.68 versus 12.61±45, p=0.02).

Conclusion: Obesity has an impact on the clinical presentation of migraine and on the treatment P41 outcome in Egypt. The Impact Of Obesity On Migraine Clinical Presentation And Treatment Response Among A Sample Of Egyptian Patients M. M. Hamdy1, N. M. Nasreldine1, A. Fawzy1, E. Hamdy1 1Faculty of Medicine, Alexandria University, Egypt, Department of Neurology and Psychiatry , Alexandria, Egypt

Question: Both migraine and obesity are prevalent among Egyptians, and there is a lack of data about the impact of obesity on migraine in Egypt. The aim of this

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P42 Conclusion: Gender and marital status can affect The Impact Of Sociodemographic Characteristics On migraine disability scores, depression scores and Migraine Burden In Egypt anxiety scores among Egyptian migraineurs. M. M. Hamdy1, N. M. Nasreldine1, A. Fawzy1, E. Hamdy1 1Faculty of Medicine, Alexandria University, Egypt, Department of Neurology and Psychiatry , Alexandria, P43 Egypt The Relationship between Pain Catastrophizing Level, Extreme Sensory Processing Patterns and Headache Question: Migraine is prevalent among the Egyptian Severity among Adolescents with Migraine population, and is associated with a considerable J. Genizi1, A. Halevy2, M. Schertz2,3, K. Osman1, N. negative impact on the activity of daily living and the Assaf1, I. Segal1, I. Srugo 1, A. Kessel1, B. Engel-Yeger1,4 patients’ quality of life. The objective of this research 1Bnai Zion Medical Center, Pediatric Neurology, Haifa, was to study the impact of different socio- Israel demographic variables on migraine burden in a sample 2Schneider Children's Medical Center, Petach Tikva, of Egyptian migraineurs. Petach Tikva, Israel 3Child Development and Pediatric Neurology Service, Methods: This was a cross-sectional study conducted Meuhedet-Northern Region, , Haifa, Israel on migraine patients attending the headache clinic at 4University of Haifa, Occupational Therapy Alexandria University hospital in Egypt. The burden of Department, , Haifa, Israel migraine was evaluated via assessing the migraine frequency, severity, days with analgesic use, days with Objective: To evaluate the relationship between pain triptan/ergot use, absenteeism days, healthcare visits catastrophizing level, sensory processing patterns, and number during the past 3 months, activity of daily headache severity among adolescents with episodic living (ADL) impairment and self-filled depression migraine. anxiety stress score (DASS-21) and migraine disability assessment score (MIDAS). Background: Catastrophizing about pain is a critical variable in how we understand adjustment to pain and Results: Of 125 recruited patients, 80% were females has a unique contribution in predicting pain intensity. and 73.6% were urban citizens. The mean age of all Recent reports found that migraine is also related to patients was 34.35±14.09 years. About half of the enhanced sensory sensitivity. However, the sample (51.2%) had chronic migraine, and 5.6% had relationship between pain severity, pain migraine with aura. Of all the studied demographic catastrophizing level and sensory sensitivity requires variables, only gender and marital status had a greater study especially among adolescents. significant impact on the migraine burden. Females tended to have longer headache duration (13.6±17.6 Methods: Participants were 92 adolescents aged 13-18 versus 5.5±6.6 hours, p=0.003). They also had years, 40 with episodic migraine and 52 healthy significantly higher MIDAS scores (72.3±89.7 versus controls. All participants completed the Short Sensory 10.5±13.7, p=0.015) and DASS-21 scores (29.5±17.5 Profile (SSP), and the Pain Catastrophizing Scale for versus 20.8±15.4, p=0.010). Marital status was also children (PCS-C). The migraine groups also completed significantly correlated with the DASS-21. The DASS-21 the PedMIDAS. scores were significantly higher among divorced (32.8±17.83) and married patients (30.44±18.88) than Results: Adolescents with migraine had significantly single patients (22.15±12.65) (p=0.05). There was no higher pain catastrophizing level than healthy controls, significant correlation between the remaining as seen in enhanced rumination (p ≤ 0.001) and sociodemographic variables (i.e. residency, educational helplessness (p ≤ 0.05). They also had significantly level, employment state, work stress, and work hours) lower tendency to seek sensory input than healthy and migraine burden parameters. controls. Elevated rumination and helplessness correlated with higher migraine pain severity. Tendency to avoid sensory input predicted the migraine related disability level.

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Conclusions: Sensory processing difficulties are Conclusions: The system of feedback in families is common among adolescents with episodic migraine. formed incorrectly, most often manifests itself in the Sensory avoidance may be related to pain experience, form of disharmonious education strategies. An and pain catastrophizing and disability level. important component of helping parents of children with autism is the interaction between them and a team involved in family-based rehabilitation.

P44 Psychoemotional distress in parents of patients with Childhood Autism: a cohort study. P45 T. Voloshyn1 The impact of headaches and related factors on 1Institute of Medical Rehabilitation, Neurology, mothers raising young children Truskavets, Ukraine H. Kawasaki1, M. Kawasaki1, S. Yamasaki1, M. Nishiyama2, P. D’Angelo3, T. IKI4 Question: Childhood Autism is one of the fastest 1Hiroshima University, School and Public Health spreading diseases worldwide. Treatment of these Nursing, Hiroshima, Japan patients should not be singly related to patients 2Hiroshima Bunkyo University, Hiroshima, Japan themselves. Prolonged emotional stress experienced 3D’Angelo Clinic, Hiroshima, Japan by the parents forms certain features of their 4Kansai University of Nursing and Health Sciences, personality, such as increased sensitivity and anxiety, AWAJI, Japan insecurity, internal contradictions. Such an emotional state, coupled with anxiety, uncertainty in itself, in Purpose: This study explored the symptoms of turn, adversely affects the emotional and personal mothers’ headache and how it affects infant childcare. development of the child. The social demand of parents of autistic children for a qualitative and timely Background: The Mothers may not be able to rest examination, diagnosis, systematic medical and when experiencing headaches, because childcare is psychological and pedagogical assistance does not dependent upon the child’s needs, Children with always correspond to the reality. mothers in poor physical condition may also be prone to abuse. Further, babysitting is uncommon in Japan. Methods: 402 parents of patients with Childhood Many consider it socially unacceptable and Autism examined (F84.0) (mean age 32,7 y., range 20 economically questionable among non-working to 47 y.) using Autism Spectrum Questionnaire(ASQ), mothers It is therefore necessary to clarify how Family Quality of Life Survey(FQoLS-2006), Analysis of headaches affect these mothers and explore the Family Relations-Eidemiller version (AFR), Internet background to the issue. Addiction Test(IAT), General Health Questionnaire(GHQ-28). Methods: This study examined headache presence, anger, the parenting environment, temperament, and Results: Intra-family relationships examination fatigue. Fatigue was divided into drowsiness, revealed 5 major problem: the conflict between irritability, head discomfort, frustration, and eye spouses in the area of education (71.4±22.5 points), discomfort. Respondents were divided into two groups the expansion of the sphere of parental feelings (headache/non-headache). Analysis used chi-square (67.7±20.2), hyperprotective strategy of upbringing and Mann-Whitney U tests. (59.8±25.6), underdevelopment of parental feelings (59.1±23.3), projection on a child of their own Results: Of the 105 total respondents, 82 were undesirable qualities (51.6±22.4). Parents showed unemployed, while 50 used childcare services more significant signs of anxiety, decreased mood, social than once per week, and 45 respondents (43.7%) had dysfunction, for example, the level of depressive headaches. Mothers experiencing headaches averaged experiences was 18.9±4.2, the general health level was 6.2 hours of sleep per night (minimum of 3), while 12.2±3.9. There was a steady decline in the quality of those without headaches averaged 6.4 hours life of the patient's family: the average FQoLS score (minimum of 5). Mothers experiencing headaches also was 3.4±1.7. had heightened senses of time urgency and less

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frequent use of services. Sleep time was associated P48 with urgency. Recurrent Headache in Indian Adolescents in New Delhi public school. Discussion: Headaches pose problems for mothers of P. Kumar1, V. Sharma1 young children. Approximately half of this study’s 1 Shri Maha maya vaishnav devi mandir research respondents experienced headaches. institute, Department of applied sciences, New Delhi, Countermeasures include controlling time urgency, India ensuring proper sleep, finding refreshment, and painkillers. Many Japanese mothers worry about Objective: To analyze the epidemiology and affecting breast milk, while expectant mothers may be characteristics of primary recurrent headaches in concerned about the fetus. Thus, proper medical Indian adolescents in New Delhi public school. guidance is needed when using headache medications. Methods: This cross sectional study was conducted in three urban public schools in New Delhi, India. Adolescents of 8th to 12th grades were included and P46 they were given a questionnaire in their classrooms in Poverty leading to headache the presence of at least one of the authors, who M. J. Mwambu1 assisted them in filling it. They were asked to provide 1Jajaz in Christ, Kampala, Uganda responses based on most severe recurrent headache they had experienced rather than the more frequent Information on the prevalence and health burden of one. Diagnosis was based upon the information headache in Africa is scanty. Earlier studies in the contained in questionnaire, however, where it was 1970s suggested that migraine was a rare condition in inadequate, those subjects were approached the African. This may have been due to an telephonically. Statistical analysis was done with the underdiagnosis because in less educated and rural help of SPSS v. 11.0. Descriptive analysis, Chi-Square African communities headache is considered a test, Fisher’s Exact test, and independent sample"t" relatively trivial condition compared to other more test were run. basic and demanding socio-economic problems. More recent community-based studies put the prevalence Results: We studied 2457 adolescents (boys: girls rates of migraine between 3%–6.9%. The one-year 1.6:1). 58.5% adolescents reported recurrent prevalence of chronic tension-type headache in one headaches in past one year. Migraine was the most African study was 1.7%. A review of the published prevalent (19.2%) headache followed by unspecified literature reveal that cluster headache is extremely (15.9%) and tension type headache (11%). Family rare in the African. The clinical features of migraine in history of headache was more common in adolescents the African are similar to those described among with headache (p < 0.001) compared to those without Caucasians. However classical migraine appears to be headache. Average age of headache onset was 11.33 yr rare in the African. Hot climate particularly exposure to (10.72 yr in girls vs. 11.75 years in boys; p < 0.001). the sun and physical and emotional stress were found 37.1% adolescents complained of progression of to be the most common trigger factor for migraine headache since its onset. A significantly higher attacks. Few African migraineurs use specific proportion of girls suffered headache (p=0.018), medications. The majority opt for traditional and particularly migraine, than boys. However, other herbal therapies. It is to be emphasized that there is a characteristics of headache were not dependent upon big need to undertake well planned epidemiological gender. Headache was more prevalent in higher studies on headache in African populations using the grades. International Headache Society Criteria with particular emphasis on health facility utilization and sickness Conclusion: Primary recurrent headaches are prevalent absence from work in Indian adolescents and migraine is comparatively the most prevalent type of headache. Female gender and increasing age is associated with higher chances to have headache, particularly migraine. It progresses in

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approximately one third of sufferers and aura increases Conclusion: Majority of Nepalese people lack the chances of worsening of headache. knowledge of migraine and are also reluctant to visit physician for treatment. Migraine awareness programs should be taken seriously by government with better plans and policy making. P49 Migraine knowledge and awareness among Nepalese Population: still in infancy R. Ojha1, N. Guragain1, R. Karn1 P50 1Tribhuvan University Teaching Hospital, Neurology, INFLUENCE OF MIGRAINE AND BAD SELF-RATED Kathmandu, Nepal HEALTH ON PUBLIC HEALTH AND INTEGRATIVE MEDICINE SERVICES USE IN SLOVENIA Question: Migraine is one of the common disabling M. Zaletel1, M. Popit1, L. Kragelj-Zaletel2, B. Žvan1 neurological disorders worldwide. But is still not well 1University Clical Centre Ljubljana, Department of studied among Nepalese population. How is the Vascular Neurology, Ljubljana, Slovenia awareness regarding Migraine among Nepalese 2University of Ljubljana, Medical Faculty, Ljubljana, population? Slovenia

Methods: It is a clinical survey done in 50 non-migraine Self-rated health (SRH) is a subjective experience of patients family members(NMFM) presented to health and a measure of health-related quality of life. Neurology outpatient clinic of Tribhuvan University SRH acts as a predictor for use of hospital services. It is Teaching Hospital, Kathmandu, Nepal, on the day of not known whether migraine is associated with bad World Brain Day, July 22, 2019 SRH (bSRH) and independently affects public health services and integrative health praxis in Slovenia. Results: Mean age of the studied people was 34.38 ±11.39 years with male 33 (66%) and female 17 (34%). We used the European Health Interview Survey (EHIS). Majority of the patients were from Kathmandu: 31 It was conducted from August to December 2014. Our (62%), eastern Nepal: 8 (16%) and western Nepal: 11 target population was the population of all residents in (22%). Migraine was present in 30 ( 60%), out of which Slovenia.The initial sample size was 11.000, the 3 had daily headache, 13 had 1-2 episode per week, 10 response rate was 62%. had 1-2 episodes per month and 4 had 1-2 episodes per year. Only 2 out of 30 NMFM were The multivariate model consisting of pulmonary taking prophylactic medicines for it in some part of diseases, cardiovascular diseases, arthrosis, allergies, their life, remaining were just taking any headache urinary tract diseases, mood disorders, carcinoma, abortive medications from nearby pharmacy. Triggers migraine, age and gender, showed an independent were sunlight in 7, Stress in 5, delayed meal in 1, association of migraine with bSHR (p<0.001: OR=1,95; multiple factors in 8 and unknown in 9. 13 out of 30 95%CI 1,50 – 2,53). Variables related to bSHR, except NMFM (43.3%) had experienced severe headache in migraine, were gathered into variable disease load their life. 34 NMFM had heard of term migraine (DL). Multivariate analysis of hospitalization in the last whereas rest 26 hadn't heard about it. Among 34 12 months, appeared significant for bSHR (p<0.001), DL NMFM, 6 NMFM couldn't explain anything about (p<0.001) and age (p=0.001) but not with migraine migraine, 13 NMFM think it is a repetitive severe (p=0,356). Visits to a specialist were significant for headache, 5 NMFM think it is a one sided shifting type migraine (p=0.005), bSHR (p<0.001), DL (p<0.001) and of headache, 4 NMFM think it is headache with nausea age (p<0.001). The emergency unit visit in the last 12 and visual symptoms, 2 NMFM think it is stress related months was significant for bSHR (p<0.001), DL headache and 4 NMFM think it is psychiatric illness. (p<0.001) and age (p<0.001) and borderline for Regarding disability grading of various diseases: migraine (p=0.059). The acupuncture utilization was 15 NMFM think that Migraine is the most disabling significant for migraine (p=0.002) and borderline for DL disease below age of 50, whereas 25 think (p=0.052) but not for bSHR (p=276) and age (p=0.545). hypertension, Diabetes by 8 and Tuberculosis by 2. Psychotherapy showed significant association for migraine (p=0.004), and DL, bSRH, age (p<0.001).

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Homeopathy was not significant for migraine (p=0.087) was in the majority (55.1%) of respondents in 1st group. and bSRH (p=0.376). In the 2nd group, patients with primary headache prevailed (88%), migraine was diagnosed in 32.2%, Patients with bSRH use public services more with frequent attacks in 38.3% patients, secondary frequently, but they do not use integrative medicine headache was diagnosed in 11.2 %.MIDAS score was praxis. However, migraine patients are frequent users significantly lower in the 1st group (23.8±10.6) than in of integrative medicine praxis. Patients with both bSHR the 2nd(42.8±20.5),p<0.005. and migraine seem to be frequent users of both public services and integrative praxis. Conclusions: Migraine in the structure of cephalalgias is more common among patients in a specialized pain clinic, which may be associated with more severe descriptors of the disease, as well as insufficient P51 diagnostic efficiency in primary health care. The prevalence of migraine among patients at primary care clinic and specialized pain clinic References: 1Steiner, T.J., Jensen, R., Katsarava, Z. J E. Malenkova1, L. Medvedeva1, O. Zagorulko1, G. Headache Pain 2019 Shevtsova2 1Petrovsky National Research Centre of Surgery, Pain 2. Medvedeva, Zagorulko, Clin. Experiment. Surg. Department, Moscow, Russian Federation Petrovsky J. N3 2016. 2First Moscow State Medical University, Moscow, Russian Federation

Question: Migraine is prevalent over the world,but P52 despite clear diagnostic criteria, it remains an actual Migraine-related disability and co-morbid depression problem [1].The aim was to assess the negotiability of among migraineurs in Ethiopia: a cross-sectional patients with headache in an outpatient neurologist of study primary care(1st group - 1341 respondents) and a B. Ayele1, Y. Yifru1 neurologist in a specialized clinic for the study and 1Addis Ababa University, Neurology, Addis Ababa, treatment of pain(2nd group - 1296 people) from 2017 Ethiopia to 2018. Background: Migraine headache is a neurologic Methods: The diagnosis of headache was by the disorder which mainly affects younger and productive International Classification of Headache Disorders, 3rd segment of population. Migraine not only causes pain; edition, beta version (ICHD‐3b)migraine criteria.At the but also affects quality of life in terms of low initial treatment, patients filled out a questionnaire productivity and economic loss. The main aim of this developed at the Russian Pain Clinic [2]. We analyzed study was to examine migraine-related disability, co- gender, age, nature and duration of headache and morbid depression, and relationship between the two. seizure frequency, and the impact on daily activity according to the Migraine Disability Assessment Methods: A cross-sectional study was conducted (MIDAS) scale. among migraineurs who visited two neurology referral clinics. The study was conducted between June 1st Results: Women prevailed among the patients of both 2016 to December 30th 2016. Migraine disability group(63.3% in the 1st group and 67.2% in the 2nd). assessment score [MIDAS] and patient health The average age was 57±14.5 and 54.9±12.7,and the questionnaire [PHQ-9] were used to assess disability disease duration was 9.6±2.7 and 7.8±1.9 years in the and depression, respectively. 1st and 2nd groups, respectively. Results: A total of 70 patients participated in the study. Primary headache was diagnosed in 44.9% of the 1st Fifty-three (74.3%) of our study participants were group, with migraine in 11.1% of them, with frequent women. Fifty one (72.9%) study participants were attacks (more than 5 per month) in every second between age group 20–40 years. Migraine without patient with migraine (55.2%). Secondary headache aura was the most common subtype (70%); migraine

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with aura accounted for the other 28.6%. The mean (± Results: The total study cohort was 16,495 employed SD) headache frequency and intensity was 23.4 ± 14.9 participants; 556 in the migraine cohort (mean age: days and 7.4 ± 1.2 respectively. Major depressive 39.5 years; women: 81.6%) and 15,939 (mean age: 40.7 disorder was common in this group (41.4%). The mean years; women: 44.6%) in the non-migraine cohort. MIDAS and PHQ-9 scores were 46.7 ± 30 and 9.2 ± 4.4 After PS matching, the annualized societal burden was respectively. More than two-thirds (74.3%) of our significantly higher for patients with migraine (total participants had severe disability. We found a and subgroups) versus non-migraine, mean difference: statistically significant correlation between migraine- total migraine, $3392; AMO, $7859; stigmatized-risk, related disability and co morbid depression among our $5031 (Table 1a). The annual work absenteeism was participants(r = 0.318, p-value = 0.007). significantly higher for migraine (overall and subgroups) versus non-migraine, mean difference in Conclusion: The positive correlation observed between work absenteeism (days): overall migraine, 2.77; AMO, migraine-related disability and co-morbid depression 4.25; stigmatized-risk, 4.75. In "education, health, and warrant routine screening and treatment of disability social services" (overall: $1.7 billion) and and depression in migraineurs; In addition, the "manufacturing" (overall: $849 million) industry observed high degree of disability among our categories, patients with migraine were estimated to participants may indicate sub optimal treatment of contribute ~13% of total indirect costs (Table 1b). these patients. Conclusion: Migraine is associated with substantially higher annualized societal cost, including higher loss in annual work absenteeism versus patients without P53 migraine; which is notably higher for specific Economic impact of migraine in employed adult subgroups and industries. patients with migraine from the United States: Results from the Medical Expenditure Panel Survey Figure 1 (MEPS) S. Joshi1, J. H. Ford2, W. Ye2, J. S. Andrews2, R. Bhandari3, R. Okonkwo 2, D. Nelson2 1DENT Neurologic Institute, New York, United States 2Eli Lilly and Company, Indianapolis, United States 3Eli Lilly Services India Private Limited, Bangalore, India

Objective: Migraine poses a high financial burden in patients with migraine versus non-migraine. This study evaluated the annual societal burden (direct + indirect costs) associated with migraine versus non-migraine among employed adults.

Method: Data from the household component of MEPS panel data between 2012-2014, in patients with a migraine diagnosis (ICD-9 346) and non-migraine, ages 18-65 years and who were employed during the whole panel, were included. Continuous and categorical variables were summarized using descriptive statistics applying survey sample weights. Additionally, comparisons among total migraine cohort and two identified migraine subgroups, acute medication overuse (AMO; pre-defined threshold indicative of insufficient treatment) and stigmatized- risk (concurrent anxiety and/or depression), versus non-migraine were conducted using propensity scores (PS) matching. 46

Figure 2 TJ dysfunction in the form of limitation or increase in range of motion was detected in 35 (39.3%) examined patients.

All patients with CH underwent manual therapy. After treatment in 48 (53.9%) patients, H ceased to bother, 33 (37.1%) noted a decrease in the intensity and frequency of H attacks.

Conclusions: Thus, a comprehensive clinical examination with an analysis of the H nature, associated pain symptoms, clinically significant neurological symptoms and syndromes, MD, X-ray examination, duplex scanning of the brachiocephalic arteries, in patients with CH made it possible to

identify concomitant diseases, pathological changes in the spine, pathobiomechanical disorders affecting the course of H, complicating their pathophysiological P54 mechanisms of the formation of clinical manifestations Factors influencing the course of cervicogenic head of the disease. The effectiveness of manual therapy in pain, effectiveness of manual therapy patients with CH has been shown. A. Borisenko1, S. Likhavhev1, V. Vashchylin1 1Republican Research and Clinical Center of Neurology and Neurosurgery, Minsk, Belarus P55 Introduction: Headache (H) occurs in patients with The importance of considering the patient’s and vascular diseases of the brain, migraine, tension treating physician’s view to generate comprehensive headache, cervicogenic headache (CH), und unbiased real-world evidence data 1 2 3 4 temporomandibular joint (TJ) pathology, myofascial K. Schuh , C. Gaul , A. Straube , P. Stude , H. Israel- 5 1 pain syndrome, fibromyalgia, Barre-Lew syndrome. CH Willner , M. Koch 1 occurs in 15-20% of cases in patients with chronic H. Novartis Pharma GmbH, Nuremberg, Germany 2 Medication for CH is often not effective enough. Klinik, Neurologie, Königstein, Germany 3Klinik, Neurologie, München, Germany 4 Methods: We observed 89 patients with CH. The Neurologische Praxis, Bochum, Germany 5 diagnosis of CH was made on the basis of diagnostic Klinik, Neurologie, Berlin, Germany criteria ICHD - 3. Background: Real-world evidence (RWE) can be Results: All patients showed restriction of active and collected from different perspectives: the patients’ and passive movements in the cervical spine, functional treating physicians’ perspectives. Here, we describe disorders of mobility in the cranio-vertebral region, the importance of considering both views as a way of myofascial trigger points in the muscles of the neck gathering a comprehensive overview of real-life and shoulder girdle in an amount of 3 to 12. therapeutic effects. Dysfunction of the TJ was detected in 36 (40, 4%) examined. Somatoform disorders were observed in 15 Methods: Between July and December 2019, two (16.9%) patients. independent online surveys were conducted in Germany to collect data from a) migraine patients According to the radiography of the cervical spine, regarding their experience with erenumab (PERISCOPE) degenerative changes of varying severity were and b) migraine-treating physicians regarding their detected in all examined, instability of the vertebral- therapy decisions and observations upon erenumab motor segments was determined in 19 (21.3%), Kimerli treatment (TELESCOPE). Results were compared anomaly was diagnosed in 31 (34.8%) patients. regarding the overall therapy outcome, changes in

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quality of life and influence of quality of life Results: The preliminary results showed there is a parameters. statistically significant relationship between onset of migraine and age of menarche (p=0.042). The onset of Results: The interim analyses of PERISCOPE (90 migraine after menarche were observed to be more erenumab patients) and TELESCOPE (30 physicians prevalent in groups with early menarche (<12 years) overseeing 354 erenumab patients) showed that 75% and timely menarche (12-13 years; p=0,0078 and of all physicians already detected improvement after p=0,00719). In the late menarche (>13 years) group, the first injection (1 month), but only 49% of patients onset of migraine do not significantly differ, migraine is reported a response after their first treatment. less often associated with menstruation (p=0,022). In Likewise, patients and physicians weighted quality of addition, late menarche is associated with less than 14 life parameters differently. Nevertheless, both patients days with migraine per month (p=0.00097). The data and physicians reported a reduction of ~7 migraine also indicate an increase in the number of triggers for days per month after 3 months of treatment. At EAN, menstrual-associated attacks (p=0,001). the comparison of both full data sets will be presented including 155 erenumab patients (PERISCOPE) and 45 Conclusion: The study results showed some physicians/522 erenumab patients (TELESCOPE). relationship between onset of migraine and age of menarche, more rare association with menstruation in Conclusion: These analyses highlight the potential the late menarche groupe. It is possible to assume that differences and overlaps in respect to patients’ and the presence of menstrual-associated attacks increase physicians’ perspectives of therapeutic outcomes the risk of chronic migraine due to significant increase under erenumab treatment. As both interviewed in the number of exogenous and endogenous triggers. populations have a limited view on treatment outcome, only considering both sides will generate comprehensive real-world evidence for treatment options. P57 Different impacts of migraine-associated features on disability and psychiatric comorbidities in patients with migraine without aura P56 N. Imai1, Y. Matsumori2 Age of menarche and clinical features of migraine 1Japanese Red Cross Shizuoka Hospital, Department of E. Kiryanova1, G. Tabeeva1 Neurology, Shizuoka, Japan 1I.M. Sechenov First Moscow State Medical University 2Sendai Headache and Neurology clinic, Sendai, Japan (Sechenov University), neurology, Moscow, Russian Federation Background: Several studies have suggested that associated features are related to migraine disability Main objective: There is a higher risk of migraine in the and psychiatric comorbidities. However, the early menarche group, but there are restricted differences in the impact of each associated feature on evidence based data about the clinical features of migraine disability or psychiatric comorbidities have migraine in connection with age of menarche. The not been studied in detail. This study aimed to explore main objective of this study was to determine how whether these associated features have different menarche affects the clinical features of migraine. impacts on migraine disability or psychiatric comorbidities. Patients and Methods: The study included 42 women with mean age of 32.9±8,99 years. Definite diagnosis of Methods: In this multicentre prospective cohort study, migraine was based on 2018 international classification we compared the impact of associated features on of headache disorder 3 (ICHD3) criteria and confirmed disability or psychiatric comorbidities. Associated by a neurologist. Characteristics of age of menarche, features included nausea, vomiting, photophobia, triggers were collected. Statistical analysis was phonophobia, and osmophobia. Migraine disabilities performed using statistical package R (binominal test, and psychiatric comorbidities were determined by the Fisher exact test). Headache Impact Test (HIT-6), Visual Analogue Scale (VAS), Allodynia Symptom Checklist (ASC), Generalized

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Anxiety Disorder 7-item (GAD-7), and Patient Health Figure 1 Questionnaire-9 (PHQ-9).

Results: We evaluated 978 patients with migraine without aura (mean age, 32.8 ± 13.9 years; 72 % female) in this study. HIT-6, VAS, and ASC were significantly correlated with all associated features, while GDA-7 and PHQ-9 were significantly correlated with all associated features but vomiting. In a multivariate logistic regression analysis, nausea, photophobia, and phonophobia were independent positive predictors of higher HIT-6 scores; nausea, vomiting, photophobia, and phonophobia were independent positive predictors of higher VAS; and photophobia, phonophobia, and osmophobia were independent positive predictors of ASC. Nausea and osmophobia were independent positive predictors of GDA-7, and vomiting was an independent negative predictor of GDA-7. Nausea was an independent positive predictor of PHQ-9.

Discussion: Our results suggest that nausea, vomiting, photophobia, phonophobia, and osmophobia have different impacts on migraine disabilities and psychiatric comorbidities. These results may be helpful for the management of migraine without aura.

P58 Functional approach to headaches and migraines A. Lurye1 1Lurye Clinic, Medical, Almaty, Kazakhstan

During the practical clinical practice with the patients with different types of the encephalopathy results allowing to examine the reasons and nature of the headaches of another angle have been drawn. Dealing with the problem of the encephalopathy the special importance of this disease as one of the special significance for causing the headaches gas emerged. As well as the liquid features were considered as the influencing dimension for causing encephalopathy and migraine-like headaches.

Key words: clinical practice, encephalopathy treatment, headache, nature of headaches, headaches causes, encephalopathy as the reason for headaches, liquid characteristics, migraine-like headaches.

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P59 P60 Neuro - psychological analysis of patients with severe Analysis report of psycho-emotional condition in 32 types of migrain in Uzbekistan region patients with primary headache in uzbekistan D. Akmaljonova1, A. Sabirova1, B. Rahimov2 A. Sabirova1, D. Akmaljonova1, M. Ergasheva1, B. 1Tashkent Medical Academy, Neurology, Tashkent, Rahimov1,2 Uzbekistan 1Tashkent Medical Academy, Neurology, Tashkent, 2Tashkent Medical Academy, Neuropsychology, Uzbekistan Tashkent, Uzbekistan 2Tashkent Medical Academy, Neuropsychology, Tashkent, Uzbekistan The Aim of this study was to examine the neuro- psychological condition of patients with migraine. Objective: Migraine is the second most common headache within the fetus, and 73% of the population Materials and Methods: The study included in the in the past years reported that 27% of the patients main group of 18 patients with an established who had a disability during the course of the disease diagnosis of migraine. 12 women and 6 men. The had to undergo regular exercise. That is why the average age of 27±6,5. The control group of 8 healthy psychological factors and temperament in migraine is people. The average age of 25±3,5. To install the stress interested by medical psychologist. was used scale of psychological distress PSM-25, as well as to determine the "Evaluation of mental nerve Purpose: Examination of psychoemocyanal disorders in tension". primary headache

Results: This study has shown, according to the scale of Material and Methods: The study was conducted in 32 psychological distress PSM-25 in the study group a high patients with migraine, of which 18 were female, 9 level of stress was observed in 12 (66.7%) patients were male and 5 were children. At the age of 25±15.5. (average score 127±4,5), the average stress level in 6 SUNG testi and Spilberger-Khanin scales were used to (33.4%) (average score 113±8,6). At the same time at detect depression. this category of patients according the assessment of mental nerve tension excessive "extensive" stress was Result: The results of the study show that among 32 observed in 13 patients (72.2%) - more than half of the patients by SUNG test had moderate depression 8 patients; moderate "intensity" of mental stress patients, in 21 patients with high levels of depression observed in 3 (16.7%). In comparison with the control and moderate depression in 3 patients. By Spilberger- group, where the average stress level was observed in Khanin scale 29 patients with elevated personalized 2 (25%) patients; 6 patients a high level of stress anxiety were diagnosed with 29 patients and 19 of resistance. Mental nerve tension was not observed in them were jeopardized with anecdotal reactions in 13 any of the probationer (ρ≥0,01). patients with moderate risk.

Conclusion: The main role of the formation of a weak Conclusion: The high risk of high levels of depression in stress in patients with migraine plays mental stress. In migraine patients is a high and moderate level of turn, the level of stress in the body which arrives may individual concern and jeopardy concern that patients be the determining factor in reducing the quality of life with migraine may be a factor that can reduce the in patients with migraine. quality of life.

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P61 P62 Is Headache control overemphasized? An innovative Long-term improvement in migraine outcomes behavior headache therapy for primary headaches: a following participation in an employer-provided randomized controlled trial of efficacy disease management program V. Vasiliou1, E. Karademas2, S. Papacostas3, Y. L. Schaetz1, T. Rimner2, P. Pathak3, J. Fang4, D. Christou3, M. Karekla4 Chandrasekhar5, L. Vandervoort5, J. Mueller1, P. S. 1University College Cork, School of Applied Psychology, Sandor6, A. R. Gantenbein6 Cork, Ireland 1Novartis Pharma AG, Basel, Switzerland 2University of Crete, Psychology, Rethymnon, Greece 2Medgate, Basel, Switzerland 3Cyprus Institution of Neurology & Genetics, Neurology 3Novartis, Dublin, Ireland Clinic B, Nicosia, Cyprus 4Novartis Pharmaceuticals Corporation, East Hanover, 4University of Cyprus, Psychology, Nicosia, Cyprus NJ, United States 5Healint Pte Ltd., Singapore, Singapore Preventing headache episodes via avoidance of triggers 6RehaClinic Group, Department of Neurology, is the main behavioral treatment suggestion for University Hospital Zurich, Zurich, Switzerland headache management. However, overemphasizing avoidance and control of headache triggers may result Introduction: Earlier published data showed that a 6- in increasing trigger potency (Welch et al., 2001), month education and support program, offered as restricting lifestyle (Foote et al., 2015), and complimentary service within a corporate wellness exacerbating and maintaining pain perception (Martin program, significantly reduced migraine-related & McLeod, 2009). New behavior headache treatment disability and promoted disease management among approaches, focusing on minimizing behavioral employees. This analysis further assessed how this avoidance and maximizing acceptance to head pain impact sustained at 3 months after program responses, such as Acceptance and Commitment completion. Therapy (ACT; Hayes et al., 2011), can increase functioning and lower disability (Dindo et al, 2015). Methods: Data from 141 participants who consented, There is limited evidence for the efficacy of ACT for were analyzed. Participants received six monthly headache management and preliminary studies are sessions of individualized telecoaching from a afflicted with methodological limitations (Smitherman specialized nurse supported by a specially developed et al., 2015). This is the first study, examining in a smartphone application. At 3 months after program randomized clinical trial (NCT02734992), whether an completion, participants were evaluated again on ACT-based group intervention, compared to wait-list Migraine Disability Assessment (MIDAS), Patient control, decreases disability, distress, medical Activation Measure (PAM), and an exit survey was also utilization, and improves functioning and quality of life administered to collect their feedback on the program. in patients with primary headache. 94 primary headache patients (84% women; Mage=43 years; Results: 79 out of 141 participants completed the 6- 87.35% migraine diagnosis) were randomized into two month program while 28 were still in the program but groups (47 participants in each). Assessments had not reached month 6, others dropped out either occurred: before, immediately after, and at 3-months due to no further interest, lost to follow up or other following treatment end. Only the ACT group was health reasons. Of these 79, 42 participants were re- additionally assessed at 6- and 12-months follow-up. evaluated at 3 months after program completion. The Results (intent to treat analyses) showed substantial total mean MIDAS and the PAM scores had improved improvements in favor of ACT compared to control, on from baseline during coaching and the effect sustained disability, quality of life, functional status, and and further improved at month 9 (table). A total of depression at 3-months follow-up (all ps < .05). At a 3- 62% of the 42 participants who participated in the exit month follow-up, 63% of ACT participants were survey reported feeling "much improved" or "very classified as clinically improved in headache-related much improved" compared to baseline on the Patient disability and 65% in quality of life (vs. 37% & 35% in Global Impression of Change scale. When prompted for control; ps <.01). Findings can have translational value, self-reported progress towards migraine goals and how showing how alternative to control or avoidance the program helped them to optimize their migraine treatment approaches, can lead to long-term benefits management, 64% and 81% responded in favor of the for patients. program. 51

Conclusions: The employer-sponsored disease Aggregate headache days in one year were translated management program provided a better to losses in paid and unpaid productive hours based on understanding of migraine and promoted methods and estimates of presenteeism and absenteeism along with approaches to improved management combining other socioeconomic parameters. Paid hours lost were medical and lifestyle options leading to significant distributed across the industry sectors. In this way, an improvements that sustained beyond the intervention age-, gender- and industry sector specific monetary supporting prolonged effectiveness of such programs. value was calculated for paid hours lost. Unpaid hours lost were valued by assigning the unpaid activities to Figure 1 their nearest market substitute. In a last step, value- added multipliers derived from input-output tables were used to calculate the economic value chain effects.

Results: A total of 15.5 million persons (20 years or older) suffer from migraine in Germany. Our analysis shows that 60% of those have 4 or less headache days per month, while patients suffering chronic migraine (15+ headache days per month) account for 5.4% of the adult migraine population. Females bear 65% of P63 the total 836 million headache days per year. The The Socioeconomic Burden of Migraine: An Evaluation socioeconomic losses due to those headaches amount of Productivity Losses due to Migraine-Headaches to €100.4 billion (€6,493 on average per patient) in one Based on a Population Study in Germany year. A. H. Seddik1, J. C. Branner1, D. A. Ostwald1,2, Z. Katsarava3,4,5,6, S. Schramm7,8, M. Bierbaum9 Conclusion: In addition to time losses in paid work, 1WifOR institute, Health economics, Darmstadt, migraine causes substantial socioeconomic losses to Germany unpaid work activities due to its disproportionate 2Graduate School of the Faculty for Leadership & prevalence among females. Economic value chain Management at Steinbeis University, Berlin, Germany effects provide a novel perspective on losses beyond a 3Evangelical Hospital Unna, Unna, Germany patient"s time loss. Overall the elements of 4University of Duisburg-Essen, Department of socioeconomic burden provide a strong rationale that Neurology, Essen, Germany innovative migraine therapies could be of high value to 5EVEX Medical Corporation, Tbilisi, Georgia society. 6IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation

7Institute for Medical Informatics, Biometry and Epidemiology, Essen, Germany P64 8University Hospital Essen, Essen, Germany The increasing importance of a dedicated nurse team 9Novartis Pharma GmbH, Market access, Nuremberg, in headache research Germany M. Bianchi1, L. Gracardi1, S. Lunghi1, V. Tosca1, G. Sances1, C. Tassorelli1,2 Background: This study estimates the socioeconomic 1Istituto Neurologico Nazionale Casimiro Mondino, impact of migraine headaches on paid and unpaid Pavia, Italy work productivity in the adult German population in 2University of Pavia, Pavia, Italy one year. Objectives: The role of the headache nurses within the Methods: We used data on headache frequency (days activities of a headache center is becoming increasily per month) from a longitudinal population-based important, even more so in those structures where study. Prevalence estimates of migraine were derived care and research are institutional activities. A long from the Global Burden of Disease Collaborative experience as clinical research nurses (RNs) has Network. Demography data were derived from official prompted dynamically changes in the supporting role statistics in 2017. within the research team. We illustrate the experience 52

of a nurse team to share experience and ideas and to P65 foster innovation and best practices with other centers Clinical characteristics of patients and healthcare and colleagues. resource utilisation in European centres with and without dedicated headache clinic: Real-world Methods: We have analyzed retrospectively the evidence from the multinational BECOME study support activities performed by the headache nurses P. Pozo-Rosich1, D. Watson2, P. Martelletti3, C. Lucas4, team with specific attention to the need to C. Gaul5, S. Ritter6, J. Snellman7 add/remove tasks over time and/or to quantify 1Headache Unit, Neurology Department, Vall d’Hebron relevant changes of time dedicated to different tasks. University Hospital, Barcelona, and Headache and We also focused our attention on the initiatives taken Neurological Pain Research Group, Vall d’Hebron to optimize the management and wellbeing of patients Institute of Research (VHIR), Universitat Autònoma de and improve their active involvement and satisfaction. Barcelona, Barcelona, Spain 2Hamilton Medical Group, Aberdeen, Scotland, United Results: Over the years, activities increased in number Kingdom and type, spreading to multiple domains, such as 3Department of Clinical and Molecular Medicine, protocol development, organizational activities, Sapienza University of Rome, and Sant’Andrea resources and supplies, collecting and storing Hospital, Rome, Italy document, patient recruiting and follow-up, safety 4Pain Clinic, Service de Neurochirurgie, Hôpital reporting, tissue and sample collection, processing and Salengro, CHU de Lille, Lille Cedex, France mailing, triage of complaints, training of health care 5Migraine and Headache Clinic Königstein, Königstein professionals. In particular, the time spent with im Taunus, Germany patients to read and understand the informed consent 6Novartis Pharmaceuticals Corporation, East Hanover, (IC) is mainly appreciated by them. NJ, United States 7Novartis Pharma AG, Basel, Switzerland Conclusions: Being clinical RNs entails a large amount of responsibilities in the outcome of studies and in the Question: There is limited European data on migraine quality of care delivered to patients. To perform the burden in patients with prior prophylactic treatment role at best, the clinical RNs require a large repertoire failures (PPTF). Here we report the impact of migraine of clinical expertise, organizational skill and capability on healthcare resource utilisation (HRU) among to critically evaluate problems and dynamically search patients visiting centres with (DHC) and without for the possible solutions. An expert and well trained dedicated headache clinics (WHC) from the BECOME research nurse team is pivotal for the conduction and study. completion of clinical studies in the field of headache and greatly contributes to the patient’s involvement Methods: BECOME was a prospective, non- and satisfaction. interventional study conducted in two parts; part 2 examined the burden of migraine and HRU in DHC and WHC in patients with ≥1 PPTF and ≥4 monthly migraine days (MMD) through analysis of patient reported outcome questionnaires.

Results: Overall, 2402 patients in Part 2 were grouped according to centre (DHC and WHC) and patient status (new-to-centre/follow-up) (Table 1). DHC had a slightly larger new-to-centre patient pool vs WHC. Here we present data for follow-up patients. DHC had higher proportion of patients with ≥4 PPTF vs WHC (19.7% vs 9.6%). Similarly, proportion of patients with ≥8 and ≥15 MMD was higher in DHC vs WHC. A high proportion of patients from both types of centres reported neurologist visits followed by general practitioners, in the past 3 months. More emergency room (ER) visits, medication-overuse headache (MOH) and 53

hospitalisations due to migraine in the past year were P66 reported by patients in DHC vs WHC. In contrast, MRI Migraine Diagnosis by Integrating Ceramide scans for exclusion of secondary causes were more Biomarker Concentration Checking and von common in WHC vs DHC (23.3% vs 19.3%), possibly Willebrand Factor Biomarker Activity (vWF) with reflecting that less headache-experienced doctors may Diagnostic Criteria based on the Voremide Algorithm. request more scans. R. Fajar1 1Yogyakarta State University, Computational Biology Conclusion: While data suggest generally similar and Medicine, Sleman, Indonesia patient pools at DHC and WHC, some differences were observed. DHC had more new-to-centre patients than Migraine is a fairly common condition globally and 10% WHC, possibly owing to referrals, and a higher of patients with headaches experience migraines. proportion of refractory patients and patients with ≥8 Migraine becomes a serious problem because it can MMDs. In addition, DHC had more patients with MOH reduce the quality of life of patients and increase the and hospitalisations, probably due to a larger chronic risk of heart disease. However, there are currently high migraine population. enough migraine misdiagnosis rates so patients don't get proper treatment. The large number of Figure 1 misdiagnoses currently showing clinical diagnosis through history taking with ICHD-2 criteria is not enough to diagnose migraine. For this reason, we propose a Voremide algorithm design solution; a migraine diagnosis algorithm by integrating ceramide biomarker concentration check and von Willebrand Factor (vWF) biomarker activity with ICHD-2 diagnostic criteria. The method used is a literature review by analyzing the information available to be synthesized into a more accurate migraine diagnosis solution. Based on migraine pathophysiology, the authors obtain ceramide biomass and vWF which are potentially used for migraine diagnosis. Ceramide molecules have decreased concentration in migraine due to increased ceramide catabolism in the body of migraine sufferers, while vWF has increased activity along with endothelial dysfunction that occurs in migraine patients. Through data calculation, it is known that the sensitivity- specificity of ceramide and vWF activity are 90.5%- 65.6% and 30%-93%, respectively. Based on these results, the authors propose the Voremide algorithm with the stages of headache examination through history taking according to ICHD-2 criteria, followed by ceramide examination, then examination of vWF activity. This algorithm has the advantage of a more objective diagnosis, can be done in the interictal phase and can overcome the obstacle of doctor-patient communication. But improvements are still needed such as the development of more efficient measurement tools and testing the effectiveness of the algorithm through replication of research on a wider sample and a more diverse population.

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P68 the possible effects exerted by natural selection in the Natural selection and migraine prevalence past. M. Lisicki1, E. Marucco 2, M. Carpinella1, M. Manise3, A. Maertens de Noordhout3, D. Conci1, J. Schoenen3 1Conci Carpinella Institute, Headache Dept. / Neuroscience Unit, Córdoba, Argentina P69 2Ferreyra Institute, Neurobiology, Córdoba, Argentina Diagnostic and Therapeutic management of migraine 3University of Liège, Neurology / Headache Research in an Emergency Department: our experience Unit, Liège, Belgium F. J. Cabello Murgui1, M. Payá Montes1, C. Nieves Castellanos1, S. Díaz Insa1 Background: The law of natural selection suggests that, 1Hospital Universitari i Politècnic La Fe, Valencia, Spain in populations, favourable phenotypes are likely to be preserved while disadvantageous traits are Introduction: Migraine is one of the most frequent progressively depurated. Although migraine entails a causes of medical attendance in every Emergency considerable personal and societal burden nowadays, Department (ED). However, there is a high variability in it has been suggested that some features of this the way it is managed and treated. An in depth disorder might have constituted an evolutionary analysis of certain cases could provide us with advantage in the past. These allegedly once favourable important insights for improvements in this area. features seem difficult to dissipate, as the prevalence rates of migraine remain constant or even augment. In Objectives: To describe the diagnostic and therapeutic this study we evaluated whether this phenomenon management of migraine during the acute phase in an could be linked to a reduced influence of natural ED. selection in modern times. In order to do so, we evaluated the correlation between the biological state Methods: We made a retrospective and transversal index (a measure of the impact of natural selection on study in which demographic data as well as data populations) and migraine prevalence worldwide. related to diagnostic and therapeutic management has been registered. We selected patients who were Materials and methods: Prevalence estimates of assessed with a diagnosis of migraine, aura with migraine were collected from available epidemiological migraine, aura without migraine or migranous studies in various countries and correlated with their headache, from October to December 2018 in Hospital corresponding biological state index. Biological state La Fe (a tertiary hospital) and a related primary care indexes are calculated by combining age-specific death center ED. Pregnant women have been excluded from frequency with age-specific reproductive loss. this study having been reviewed in subsequent group.

Results: Data from thirty-eight countries were Results: The criterion has been applied to 181 patients included. Mean migraine prevalence was 13.23 ± 6.46. (79% women; 21% men) from 5 to 83 years. 88 Migraine prevalence negatively correlated with the patients have a personal history of migraine (33% of biological state index (r = -0.49, R square 0.24; them being treated with preventive treatments at the p=0.002). moment of attendance).

Discussion: These results indicate that migraine 43.1% of the patients have required additional tests, prevalence decreases as the influence of natural the most frequent being blood tests (41;22.7%) and selection increases. Evolutionary pressure may not only head CT scans (38;21%). 6.1% were evaluated by a be linked with the number of individuals affected by neurologist during attendance. migraine, but it may also have affected their genetic profile, as well as the phenotype they exhibit. Indeed, 112 patients (61.9%) were treated. A partial or geographical dispersion of genes associated with complete response to treatment was registered in 107 migraine has recently been demonstrated. In order to (59.1%) of them. The most commonly used treatments understand the heterogeneity of this disease between were Paracetamol/NSAID (44%), antidopaminergic subjects and populations nowadays, one must consider drugs (25%), opioids (5%) and oxygen (7%). 5% of the patients have been treated with triptans.

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Conclusions: Our data shows the inter-professional mean frequency of crisis was lower 13.6 days. variability in diagnostic-therapeutic management of Conclusion: We need to understand better the impact patients with migraine in our ED. We propose a of treating anxiety in patients with headache protocol to improve the management as care is not comorbidity because so we can to obtain best always adjusted to the existing guidelines and treatment for each disorder. Effective drugs and recommendations. behavioral therapies are available to have good results and less crisis of migraine.

P70 Migraine comorbidity with anxiety disorder, a study P71 in Regional Hospital Durres, Albania Headache Prevalence and Distribution in a E. Harizi (Shemsi)1, F. Domi2, K. Shemsi3, E. Shemsi4 Population-Based Study of Older Adults in Albania 1Regional Hospital Durres, Neurology, Durres, Albania I. Alimehmeti1, E. Reka2, A. Gezhilli2, A. Kuqo3, J. 2Regional Hospital Durres, Emergency, Durres, Albania Kruja3,2 3University of Medicine Tirana, Faculty of medicine, 1Faculty of Medicine, UMT, Department of Family and Tirana, Albania Occupational Health, Tirana, Albania 4University ZKM, Faculty of medicine, Tirana, Albania 2Faculty of Medicine, UMT, Neurology, Tirana, Albania 3UHC Mother Teresa, Neurology, Tirana, Albania Objective: Many migraine patients often suffer from symptoms of anxiety. Patient with migraine have more Our aim was to assess headache prevalence and possibility for symptoms of anxiety then patients distribution in a population-based study of older adults without migraine. About 50 % of patients with in Tirana, capital of Albania. migraine have anxiety. Maybe this comorbidity between migraine and anxiety is because of brain Methods: All residents of one district of Tirana, aged chemicals involved of serotonin and some hormone 59+ where enrolled in the study. A door-to-door changes in woman, that can stimulate both conditions. examination was performed by neurology specialists Symptoms of anxiety are most common in patients and residents after obtaining informed consent. The with chronic migraine, more then 15 days a month. In validated headache survey employed had formerly these patients headache treatments don’t get well shown a high sensitivity (92%) and specificity (83%) when anxiety is not treated. These patients have less when confronted to senior neurology examination and response to headache medications and have more former medical records. Moreover, demographics and relapse. Physical symptoms such fatigue, trouble data for diabetes, hypertension and other neurological concentrating, appetite, and sleep changes are very disorders were obtained. common in these patient. Results: A total of 1206 persons (mean age 70.8±7.7 Methods: In our study we have seen 400 patients with years old), of which 649 (53.8%) females were migraine in ambulatory policlinic in Regional Hospital enrolled. Headache prevalence resulted 27.3%. Out of Durres in year 2017. 330 (82.5 %)patients were female 329 older adults with headache, 200 (60.8%) referred and 70 (27.5%) male. From all patients 208 (52 %) have to suffer from headache two or more days per month, migraine accompanied with anxiety disorder (180 76 (23.1%) referred that headache led to loss of work female (86.5%)and 28 male (13.5%)). Middle age of and/or leisure activities and 68 (20.7%) presented patients with migraine and anxiety was 32.6 years and medical records with formerly diagnosed headache. for patients without anxiety was 38.1 year. All patients Females were younger than males (70.2±7.7 vs. of migraine and anxiety had preventive therapy with 71.5±7.7 years old, p=0.002), had higher headache amytriptiline 25 mg per day for a group of them, and prevalence (31.1% vs. 23.6%, p=0.004), higher escitalopram 20 md per day for others (for long time prevalence of >2 lost days per month (20.4% vs. 12.6%, treatment 6 – 12 months). p <0.001) and higher prevalence of work and/or leisure activities impairment (8.0% vs. 4.6%, p=0.017). Results: The mean frequency of crisis in patients with Headache was not significantly correlated with other anxiety was 15.4 days and without anxiety 4.3 days a diagnosis. However, in multivariate logistic regression month. After treatment of anxiety for one year the analysis, the mini mental state examination (MMSE) 56

was positively associated with headache (OR 1.118, significant underestimation of the prevalence of 95%CI 1.026-1,219, p=0.011), even after adjusting for migraine in the population. education, marital and employment/retirement status.

Conclusion: In our population-based study headache we found that more than 1 out of 4 older adults P73 suffered from headache. Importantly, only 1 out of 5 Characteristics of Headache Education during headache older patients were formerly diagnosed with Residency of Neurology in European Countries. A headache, depicting this nosology as an overlooked survey of the EAN-RRFS National Representative one. Network study D. García-Azorín1, M. van der Meulen2, N. N. Kleineberg3, V. Carvalho4, V. Kosta5, G. di Liberto6, L. Klingelhöfer7, L. Cuffaro8, P. Irimia9, R. Jensen10 P72 1Hospital Clínico Universitario de Valladolid, Headache Migraine prevalence among Russian neurologists Unit, Valladolid, Spain K. Skorobogatykh1, J. Azimova1 2Erasmus MC Cancer Institute, University Medical 1University Headache Clinic, Moscow, Russian Center Rotterdam, Department of Neuro-Oncology, Federation Rotterdam, Germany 3Faculty of Medicine and University Hospital of Migraine is one of the most prevalent diseases. In Cologne, University of Cologne, Germany. Institute of Western countries, the prevalence of migraine is about Neuroscience and Medicine (INM-3), Research Centre 12-15%, in Russia - 20,8%. Previous studies show a Jülich, Germany, Department of Neurology, Cologne, higher prevalence of migraine among neurologists - up Germany to 65.9%. In present study, we estimated the 4ULS Matosinhos/Hospital de Pedro Hispano, prevalence of migraine among Russian neurologists. Department of Neurology, Matosinhos, Portugal 5University of Split School of Medicine, Department of Materials and methods: The study was conducted Neurology, Split, Croatia during continued medical education lectures on 6Department of Clinical Neurosciences, University headache. A total of 9 groups of neurologists were Hospital of Lausanne, University of Lausanne, interviewed in 7 cities of Russia. The number of Switzerland., Division of Neurology, Laussanne, neurologists in each group varied from 17 to 111 Switzerland people. A total of 317 neurologists were interviewed. 7Klinik und Poliklinik für Neurologie Technische One question was asked: "Have you ever had migraine Universität Dresden, Department of Neurology, attacks in your life?" with answer options "Yes" and Dresden, Germany "No". 8Università degli Studi di Palermo, Palermo, Department of Neurology, Palermo, Italy Results: Of the total pool of respondents, 152 (47.9%) 9Clínica Universitaria de Navarra, Headache Unit, replied that they had migraine attacks in their lives. Pamplona, Spain The lifetime migraine prevalence among respondents 10Rigshospitalet Glostrup, Danish Headache Center, in different cities ranged from 41 to 56%. A total of 165 University of Copenhagen, Danish Headache Center, neurologists (52.1%) surveyed responded that they had Copenhaguen, Denmark no migraine attacks throughout their lives. Question: In 2011, the World Health Organization Conclusions: This study confirms the results of pointed that the lack of headache education is the key previous studies, indicating that migraine is more factor in hampering good management of headache. common in neurologists than in the general We aim to analyse headache education across population. Given that this group of respondents has European countries. professional experience in migraine diagnosis, the accuracy of such a study may be higher than in the Methods: We used an online questionnaire, with 23 general population study. This may indicate a topics about headache education during med school and within the neurology residency programmes. This survey was spread among the National Representatives 57

within the Residents and Research Fellows Section of P74 the European Academy of Neurology and we were able Prevalence of psychological symtoms in migraine to obtain data from 24 European countries. They were teenagers with and without aura asked whether there are specific headache rotations in A. Yusupov1, B. Nabiyev1, U. Shamsiyeva1 the residency training programme and to provide to 1Tashkent Medical Akademy, Neurology, Tashkent, what extend several aspects are learned during the Uzbekistan residency training. Background: The occurrence of psychological Results: Nineteen out of 24 participating countries symptoms in teenage migraine patients are still state to have a national headache society (79.2%), debated. The present study aims to evaluate the whilst three of these have a section for junior members prevalence of psychological symtoms among teenage (15.8%). Headache disorders were covered during migraine patients with (MwA) and without aura medical school in all countries, with a median (IQR) of (MwoA). 3 hours lecture (2-10). Methods: 122 migraine patients aged 13-19 years were During residency, a headache rotation was mandatory enrolled in the study and were divided into two in 11 countries (45.8%), and optional in 19 (79.2%). groups: 61 patients with aura and 61 patients without During headache rotations, median (IQR) number of aura.All patients were examined during headache first visit patients seen per week without supervision period in Tashkent Medical Akademy. Patients was estimated as 5 (0-10), and with supervision 10 (5- completed Beck Depression Inventory (BDI), Beck 15). In total, 50% of patients are seen with supervision Anxiety Inventory (BAI), Self-version of Apathy during headache rotations (IQR: 32-70%). Evaluation Scale (AES-S) and Insomnia Severity Index (ISI). Associations between migraine and psychological During residency training, regardless of specific symptoms prevalence were investigated by using rotations, residents are expected to do first and follow- multiple regression. up visits on headache patients in 16 countries (66.7%), anaesthetic blockades or botulinum toxin injection in Results: Among 122 patients, migraineurs with aura 15 countries (62.5%), prescribe acute and prophylactic reported greater prevalence of anxiety,apathy, medication, each in 16 countries (66.7%). Figure 1 depression, reduced quality of sleep compared to shows insingth about the acquired skills during migraineurs without aura (68% vs. 32%, p<0.001). residency. Fewer MwoA had anxiety (16.4% vs. 27.8%, p = 0.002), depression (4.9% vs. 16.4%, p = 0.007),apathy (8.2% vs. Conclusion: There is a strong variability concerning 16.4%, p=0.006) and sleep disturbances (18% vs. headache education between the different European 40.9%, p=0.002) compared to those MwA. countries. Currently, headache education is mandatory in just a minority of European countries. Conclusions: The prevalence of anxiety, depression, apathy and sleep disturbances was lower among Figure 1 teenage migrainers without aura compared to those with aura,especially sleep disturbances was significantly more common in patients with aura overall.

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P75 P76 Association between Migraine and Other Cochlear Evaluation of headache service quality indicators in Disorders In students: Cross-sectional study. primary care in Europe N. Ibrohimova1, Y. Musayeva1, F. Qarshiboyev2 B. Lenz1, Z. Katsarava1, R. Gil-Gouveia2, G. Karelis3, B. 1Tashkent Medical Academy, Neurology, Tashkent, Kaynarkaya4, L. Meksa3, E. Oliveira5, F. Palavra5,6, I. Uzbekistan Rosendo5,7, M. Sahin8, B. Silva5,9, S. Turkmen10, I. 2Tashkent Medical Academy, Otorhinolarynglogy, Varsberga-Apsite3, Y. Ziya11, L. Zvaune3, T. J. Steiner12 Tashkent, Uzbekistan 1Evangelical Hospital Unna, Neurology, Unna, Germany 2Hospital da Luz Headache Center, Lisboa, Portugal Background: Migraines are one of the most serious 3Riga East Clinical University Hospital, Neurology and illnesses. It is still unknown whether a migraine may Neurosurgery Department, Headach Unit, Riga, Latvia raise the risk of cochlear disorders, even though a 4Kagithane Yahya Kemal ASM, Istanbul, Turkey migraine does not appear concurrently with cochlear 5University of Coimbra, Faculty of Medicine, Coimbra, disorders. Portugal 6Centre for Child Development Hospital Pediatrico, Aim: To study the association between migraine and Neuropediatrics Unit, Coimbra, Portugal Cochlear disorders (Tinnitus, sensorineural hearing 7Family Health Unit "Coimbra Centro", Coimbra, impairment or sudden deafness) in a cross-sectional Portugal study among students. 8Kartal 10 Nolu ASM, Istanbul, Turkey 9Family Health Unit "Pulsar", Coimbra, Portugal Methods: Cross-sectional study include 2615 10Bagcilar Yildiztepe ASM, Istanbul, Turkey participants where study in a Tashkent Medical 11Esenler Havaalani ASM, Istanbul, Turkey Academy and Uzbekistan National University. Health, 12Norwegian University of Science and Technology, personal lifestyle, bad habits, migraine symptoms as Trondheim, Norway well as tinnitus and sudden deafness were recorded in a standardized questionnaire based on self-reports. Background / Aim: Headache service quality indicators The research was used logistic regression models to have been developed, and tested in specialist care, in a analyze the association between the students’ collaboration between Lifting The Burden (LTB) and the migraine and cochlear disorders. European Headache Federation (EHF). This study began the evaluation of these indicators in primary care in Results: Migraine was determined in the 788 patients Europe. during questionnaire, 580 were women and 205 were men, and the mean age was 20 years (standard Methods: We included 28 primary-care clinics in deviation 2.9 years). An association was evaluated Germany (4), Turkey (4), Latvia (5) and Portugal (15). between students’ migraine and cochlear disorders To apply the indicators, we interviewed 112 doctors, after adjustment for confounding variables. Tinnitus 90 nurses and medical assistants, 70 secretaries, 27 was found by 8.1% of participants with migraine, 3.1% service managers and 496 patients, and we evaluated of patients sensorineural hearing impairment (sudden 675 chart records. Enquiries were in 9 domains: deafness) with migraine. The adjusted odd ratios of diagnosis, individualized management, referral tinnitus were 1.81 (95% confidence interval, 1.29-2.41), pathways, patients’ education and reassurance, 0.98 (95% confidence interval 1.25-2.18) for convenience and comfort, patients’ satisfaction, equity sensorineural hearing impairment. and efficiency of headache care, outcome assessment and safety. Conclusion: Our research determined an association between migraine and cochlear disorders among Results: Application of the quality indicators proved to students, which was strongest for the subgroup be feasible and practical. We found that a substantial migraine with tinnitus. proportion of patients (eg, about 30% in Portugal) did not receive specific headache diagnoses but, rather, non-specific ICD codes such as R51 ("headache"). That this led to non-specific and inadequate treatments was evidenced in Germany. Almost everywhere, histories of headache, especially temporal profiles, were assessed 59

inaccurately. Headache-related disability and quality of analogic visual scale(AVS) was 8.4. They have been on life were not part of routine clinical enquiry. Headache an average on 7 preventive therapies, 100% incluiding diaries and calendars were not in use. Waiting times onabotulinumtoxinA. The average score for MIDAS, were too long (eg, about 60 minutes in Germany). HIT6 and HAD scales were 108.6, 68.8 and 20 points Nevertheless, 80% of patients expressed satisfaction respectively. After 3 months, 65%patients reduced with their care. their hadache days/month and 18% achieved 50% reduction, the mean score in AVS reduced in 1.7points. Conclusion: Our study in four European countries, the The average score for MIDAS, HIT6 and HAD scales first evaluating headache service quality indicators in were 79.7, 62,4 and 16.8 points respectively. At date primary care, showed them to be feasible and we have available 6-month evaluation of 44 practical. This was the key finding. It also uncovered patients,32(77.2%) reduced their headache days and severe deficits leading to suboptimal treatment, and 19(43.2%) achieved 50% reduction, with a mean demonstrated that patients’ satisfaction is not a good reduction in AVS score in 2.3 points and an average indicator of service quality. score for MIDAS, HIT6 and HAD scales of 92, 63 and 16 points respectively. From the 54patients that initially were on erenumab70mg, 22 were increased to 140mg and 3 were moved to galcanezumab.21(25%) patients P79 reported adverse effects, the most frequent being Experience of the use of calcitonin gene-related constipation and pseudo-fly symptoms.In peptide pathway antibodies as migraine preventive conclusion,CGRP pathway mAbs represent a promising therapies in andalusian population. A multicenter therapy in the prevention of migraine with the study. consequent impact on quality of life. R. Lamas Pérez1, F. J. Viguera Romero2, C. Jurado Cobo3, A. Gómez Camello4, J. Pelegrina Molina5, M. D. Jiménez Hernández1, C. González Oria1 1University Hospital Virgen del Rocío, Neurology, P80 Seville, Spain Rapid referral for headache management from 2University Hospital Virgen Macarena, Neurology, Emergency Department to Headache Centre: four Seville, Spain years data 3Reina Sofía Hospital, Neurology, Córdoba, Spain A. Negro1, V. Spuntarelli1, P. Martelletti1 4San Cecilio Hospital, Neurology, Granada, Spain 1Sapienza University of Rome, Department of Clinical 5Vithas Hospital, Neurology, Granada, Spain and Molecular Medicine, Rome, Italy

Evidence about the pivotal role of calcitonin gene- Background: Headache is one of the most common related peptide(CGRP) in migraine physiopathology is reason for medical consultation to emergency undeniable. For that reason, monoclonal department (ED). Inappropriate use of ED for non- antibodies(mAbs) that antagonize the CGRP-pathway urgent conditions is a problem in terms of crowding has been developed for migraine prevention. To date, emergency facilities, unnecessary testing and in Spain we have 2 of them available: treatment, increased medical bills, burden on medical galcanezumab(targets the CGRP peptide) and service providers and weaker patient-primary care erenumab(targets the CGRP receptor). We aim to provider relationships. The aim of this study was to analyze the efficacy and security of their use in our analyzed the different steps of the ED management of clinical practice.We have developed a prospective patients with headache to detect those deficiencies descriptive study with the data obtained from clinical that can be overcome by a prompt referral to a interviews, headache diaries, disability headache clinic. scales(MIDAS,HIT6) and anxiety-depression scale(HAD).We included 84 patients, 63(75%)women Methods: The study is a retrospective analysis of the with a mean age of 48.3years and a mean time from electronic medical records (EMRs) of patients migraine onset of 30.3years.49(58.3%)suffered from discharged from an academic ED between 1 January chronic migraine and 15(17.85%) from high-frecuency 2015 and 31 December 2018 and referred to the episodic migraine. The average of headache tertiary level headache centre of the same hospital. days/months was 18.7 and the mean pain score in We analyzed all the aspects related to the permanence 60

in ED and we also assessed if there was a concordance Figure 1 between ED diagnosis and ours.

Results: Among our sample of 244 patients, 76.2% were admitted as green tag, 75% underwent a head computed tomography, 19.3% received neurological consultation, 43% did not receive any pharmacological treatment and 62.7% still had headache at discharge. Length in ED stay was associated with the complaint of the first aura ever (p = 0.014) and if patients received consultations (p < 0.001). Concordance analysis shown a significant moderate agreement only for the diagnosis of migraine and only between triage and headache centre.

Conclusions: The majority of patients who went to the ED complaining of headache received the same therapy regardless of their diagnosis and in many cases the headache had not yet resolved at the time of discharge. Given the several shortcomings of ED management of headaches, a rapid referral to the headache centre is of primary importance to help the patient obtain a definite diagnosis and adequate treatment.

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Figure 2 with (32.31%) of them having continuous and (67.69%) of them with no continuous headache. 32 (45.07%) of them had headaches half of them lasted for 1-2 hours and the other half lasted more than 10 hours per day. The most common location for the headache was both sides (23.02%) followed by the fore head (22.22%). The most common characteristic of headache was pulsating (48.48%) followed by pressure like (37.88%).

Conclusion: There is a high prevalence rate of headache among medical students with migraine as the most common cause of headache.

Discussion: This high rate of headache may be due to the stressful life medical students have due to high load of study materials and exams, and therefor it should be furthure investigated to determine the causes of it.

P81 P82 Prevalence, clinical characteristics of headache in Evaluating the quality of life of patients with migraine medical students at Alzaiem Alazhari university in according to the received therapy 1 1 2020,Khartoum, Sudan Z. Akbarkhodjaeva , F. Saidvaliev 1 R. Tofaha Alhusseini 1,2, M. Alfatih Abdoalgadir1, M. Tashkent Medical Academy, Neurology, Tashkent, Ibrahim1,2, A. Idriss1 Uzbekistan 1alzaiem alazhari university, medicine, khartoum bahri, Sudan Aim of the study was to evaluating the quality of life of 2Daoud research group, neurology, khartoum, Sudan patients with migraine according to the received therapy. Introduction: Headache is one of the most common disorders of the nervous system. Headache simply Materials and methods: We observed 110 patients (78 means pain in the head. The (WHO) reports that -male, 32-male) with diagnosis of migraine in the age almost half of the adults worldwide will experience range of 18- 45. All patients were divided in two groups headache in any time at any given year. according to received therapy: 1st group patients – treatment with triptans only, 2nd group- non triptans Objectives: To determine the prevalence rate and treatment of migraine. We used MIDAS (Migraine clinical characteristics of headache among medical Disability Assessment Scale) to evaluate the quality of students in Alzaiem Alazhari university in Khartoum life of patients in both groups on the 1st month, 3rd state, Sudan in 2020. and 6th months after treatment started.

Methodology: A descriptive cross sectional study using Results: The leading factor in all patients was intense a 41 items questionnaire was introduced to 71 medical pain syndrome, however, migraine was also students from alzaeim alazhari university in the period accompanied by related symptoms, which are also from January 1st to 15th of February. significantly affect performance. 80% of patients had from moderate to severe pain, 70% - nausea, photo Results: Out of the 71 respondents 35 (49.3%) were and phonophobia, more than 60% needed bed rest. Male and 36 (50.7%) were female while most of them More than 72% of patients considered their activity of were in the (21-24) age group by (69.01%). Most of the daily living limited due to migraine. In first group of participants responded that they headaches (74.65%) patients all related symptoms decreased after first

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month of treatment to 15%, after third month to 27% Results: We have developed the first version of the (MIDAS mean score- 9) and after six month to 50 % applications. This version has been validated in (MIDAS mean score -5). In patients of second group consultation with real patients and neurologists. there were no significant changes after first month Applying the TAM methodology, the first results are treatment, after third month reduction of symptoms good. We have measured perceived utility, perceived was 17% (MIDAS mean score was -15) and after six ease of use, social norms, facilitating conditions and month - 21% (MIDAS mean score-11). intention to use. The results for both groups are greater than 7 out of 10 in all the measured areas. Conclusion: Early evaluating of migraine diagnosis and starting treatment with triptans will significantly Conclusions: We present a process improvement and decrease pain and related symptoms, and improve optimization project for the diagnosis and treatment of quality of life of patients. headaches. A scalable and flexible system, which is connected to regional health information systems. This system will add value: to patients improving their disease, to professionals helping in clinical decision P83 making, to the scientific community providing real data Smart migraine: A platform for headache assistance for research, and to the healthcare system in: process and clinical research. management, resource optimization and satisfaction of R. Lamas1, G. A. Escobar Rodríguez1, J. Moreno Conde1, end users. M. Millán1, L. Muñoz1, J. Arriola1, R. Pérez Esteban1, M. D. Jiménez Hernández1, C. González Oria1 1HU Virgen del Rocio, Neurology, Sevilla, Spain P85 Objective: Migraine is a prevalent and disability Analysis of the decrease in daily activity in migraine headache. It usually affects young people and M. Sanoyeva1, M. Gulova1, M. Avezova1 produces a high cost for society. On the other hand, 1Bukhara State Medical Institute, Neurology, Bukhara, the acceptance of mobile technology (mainly Uzbekistan smartphones) is growing and applications are increasingly used by the population. We present a Analysis the decrease the working capacity, project to improve headache assistance and clinical assessment of severity condition of patients with research with innovative elements. complicated forms of migraine. Surveyed 160 patients: 78(48.8%)–with migraine status, 82(51.3%)–with Material and methods: A multidisciplinary team chronic migraine. We used MIDAS, ID-migraine, three- (doctors and engineers) carries out this project with dimensional pain scales, facial pain scale(FPS). In the following characteristics, using iterative and migraine status were noted–68(87.2%) patients with incremental methodologies: nausea, 58(74.4%) patients with vomiting; phonophobia and photophobia were concomitant  - An application to empower patients by symptoms of this group. In 68(87.2%) patients were obtaining clinical information and education observed working capacity and daily activity within a  - A Headache Consultation Tool for the few days. In chronic migraine 76(90.2%) patients management of the patient, the process and complained of nausea, 49(59.8%) patients of vomiting, the disease itself (includes digitization with 76(92.7%) patients suffered by phonophobia, devices). 43(52.4%) by photophobia, 72(87.8%) patients by  - A research tool for the generation of working capacity and daily activity. In migraine knowledge with data from different sources paroxysms noted anxiety, restlessness and depression; (including wearables). the post-crisis period characterized by lethargy, feeling of heaviness and fatigue, drowsiness, whith the period To validate the platform, the TAM (Technology of working capacity and daily activity. 1st degree Acceptance Model) methodology has been used with severity was noted in 7.7% patients with migraine patients and neurologists. status and 11.0% patients with chronic migraine, intensity of headaches was insignificant on the VRS scale, 1–3 l/gr of NRS, no pain on VAS and 1–2points on 63

FPS, daily activity—minimal reduction. Second degree Methods: This was a multicenter, randomized, double- was observed about in 10% patients for both groups, blind, placebo-controlled trial enrolling patients with intensity of headaches was moderately to VRS, NRS 4– episodic cluster headache according to the diagnostic 6 l/gr, VAS–no pain, FPS–3points, daily activity is criteria of the International Headache Society. Patients insignificant. Half of the patients with migraine status received 100 mg oral prednisone for five days then and chronic migraine identified 3rd degree of severity. tapered by 20 mg every three days or placebo in Intensity of headaches was acute – VRS, 7–10 l/gr-NRS, parallel to an increasing dose of verapamil starting with acute headache–VAS, 4 points-FPS, daily activity was 40 mg three times per day. The primary endpoint was expressed. Fourth degree of severity watched only in the mean number of cluster headache attacks within migraine status (18.0%); headaches was intensive-VRS, the first week during treatment with prednisone 7–10 l/gr-NRS, acute headache-VAS, 5points-FPS, daily compared to placebo. Key secondary endpoints were activity was to large extent. Thus, Migraine, in the reduction of attacks by more than 50%, as well as presence of complicated forms, leads to a sharp complete cessation of attacks after one week. Quality decrease of working ability, which was an important of life, depression and safety were also assessed. economic and medico-social importance. Results: In total, 118 patients between 18 to 65 years were enrolled in the study (53 prednisone, 56 placebo). Prednisone reduced the mean number of cluster P86 headache attacks by 25.3% (-2.43 attacks [95% CI -4.83 Prednisone in Short-term Prevention of Episodic -0.03]) within the first week compared to placebo Cluster Headache (prednisone: 7.1 attacks (SD: 6.5, 95%CI 5.3 8.9); M. Obermann1,2, S. Nägel3, C. Gaul4, P. Storch5, A. placebo: 9.5 attacks (SD: 6.0, 95%CI 7.9 11.2], p=0.02)). Böger6, T. Kraya7, J. P. Jansen8, A. Straube9, T. Seventeen patients in the prednisone group (34.7%) Freilinger10, H. Kaube11, T. P. Jürgens12, H. C. Diener2, Z. reported complete cessation of attacks after one week Katsarava2,13, D. Holle2 compared to four patients (7.4%) with placebo. Attack 1Asklepios Hospitals Schildautal, Center for Neurology, reduction of at least 50% within the first week was Seesen, Germany reported by 25 (49%) patients receiving prednisone 2University of Duisburg-Essen, Department of compared to 8 (14.5%) receiving placebo. No relevant Neurology, Essen, Germany side effects were observed in relation to prednisone 3University of Halle, Department of Neurology, Halle, treatment. Germany 4Migraine and Headache Clinic, Königstein, Germany Conclusions: Oral prednisone was superior to placebo 5University of Jena, Department of Neurology, Jena, in reducing the frequency of attacks at an early stage. Germany Prednisone is an effective short-term prevention for 6DRK Hospital Kassel, Kassel, Germany episodic cluster headache that should be used to 7St. Georg Hospital, Department of Neurology, Leipzig, attenuate the early cluster episode until long-term Germany prevention becomes effective. 8Pain Center Berlin, Berlin, Germany 9 Ludwig Maximilian University, Department of Neurology, Munich, Germany 10Hospital Passau, Department of Neurology, Passau, Germany 11Neurology and Headache Center Munich, Munich, Germany 12University of Rostock, Department of Neurology, Rostock, Germany 13Evangelic Hospital Unna, Department of Neurology, Unna, Germany

Question: To test the efficacy of oral prednisone in short term prevention of episodic cluster headache.

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P87 P89 Clinical factors influencing the impact of cluster Clinical phenotypes and responsiveness to headaches from a prospective multicenter study sumatriptan in cluster headache S. J. Cho1, J. H. Sohn2, J. W. Park3, M. J. Lee4, P. W. L. Giani1, A. Proietti Cecchini1, A. Astengo1, G. Lauria Chung5, M. K. Chu6, B. K. Kim7 Pinter1, M. Leone1 1Hallym University Dongtan Sacred Heart Hospital, 1IRCCS Carlo Besta Neurological Institute, Neurology, Hwaseong, South Korea Neuroalgology Unit, Milano, Italy 2Hallym University Chuncheon Sacred Heart Hospital, Neurology, Chuncheon, South Korea Question: About 25% of patients with cluster headache 3Uijeongbu St.Mary’s Hospital, Neurology, Uijeongbu, (CH) do not respond to subcutaneous sumatriptan South Korea (SS)1. Reasons are unknown. We looked for clinical 4Samsung Medical Center, Sungkyunkwan University markers associated with resistance to SS in CH. School of Medicine, Neurology, Seoul, South Korea 5Kangbuk Samsung Hospital, Sungkyunkwan University Methods: We retrospectively investigated clinical School of Medicine, Neurology, Seoul, South Korea records of patients of the Headache Centre of 6Severance hospital, Yonsei Univeristy College of the Besta Neurological Institute, Milan, a tertiary Medicine, Neurology, Seoul, South Korea national referral center for CH, with a diagnosis of CH, 7Eulji Hospital, Neurology, Seoul, South Korea as per the ICHD-32, visited from January 1st, 2015 to May 31st, 2019. We compared Responders (R), defined Question: Although many patients with cluster as patients currently pain-free/almost pain-free 15 headaches (CH) are disabled by their condition, few minutes after SS, to Non-Responders (NR) for: age at studies have examined this in detail. We investigated onset and at last visit, sex, disease length, episodic vs the extent of headache impact of CH and the clinical chronic CH, site of pain, spontaneous attack duration, factors associated with a severe impact of CH. attack frequency, presence of autonomic signs, restlessness/agitation, headache side. In SPSS v21.0 we Methods: This cross-sectional, multicenter used Student's T-test or Mann-Whitney's U-test for observational study prospectively collected continuous variables, Χ2 or Fisher's exact test for demographic and clinical questionnaire data from 224 categorical variables. Differences were considered consecutive patients with CH. We assessed headache significant for two-tailed p˂.05. impact using the six-item Headache Impact Test (HIT-6) and evaluated the factors associated with the impact Results: Of 277 CH patients, 71 were excluded from of CH. Participants with a HIT-6 score ≥ 60 were analysis: 63 had never tried SS, the response of 8 classified into a severe impact group. wasn’t stated. Of the remaining 206 patients (mean age 45.6, 16% females, 48% chronic, median disease Result: The majority (190, 84.8%) of the participants length 13 years), 187 (91%) were R, 19 (9%) were NR. were classified into the severe impact group. These In NR attacks were longer (median 100 [IQR 60-120] vs patients were characterized by younger age, earlier 60 [38-90] minutes, p=.028) and more frequent (4/day onset of CH, longer duration of each headache attack, [2.5-5] vs 3/day [2-4], p=.024). No other differences higher pain intensity, more cranial autonomic were observed. symptoms, a higher proportion of depression or anxiety, higher score of stress, and lower score of Conclusions: When attacks are of longer duration, non- quality of life. The anxiety (OR = 1.19, 95% CI: 1.08- 5HT1B/D-related mechanisms seem to take place. 1.31, p = 0.006), higher pain intensity (OR = 1.06, 95% Further studies correlating response to therapies and CI: 1.02–1.10, p = 0.002), and age (OR = 0.99, 95% CI: clinical phenotypes will help understanding the 0.99–1.00, p = 0.008) were significant predictors for pathophysiology of craniofacial pain disorders. severe impact in CH patients. 1. The Sumatriptan Cluster Headache Study Group. Conclusion: According to the HIT-6 results, most of the Treatment of Acute Cluster Headache CH patients were significantly affected by CH. As well with Sumatriptan. N Engl J Med 1991; 325:322-326 as pain intensity, anxiety and age modulated CH’s impact on their lives.

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2 .Headache Classification (IHS). The International beginning of treatment with topiramate 75 mg/day, Classification of Headache Disorders, 3rd followed by replacement with lamotrigine 75 mg/day, edition. Cephalalgia 2018, Vol. 38(1) 1–211 headaches regressed. Cabergoline 0.5 mg 1/2 tab. once a week was added to the therapy, in 4 months, Figure 1 prolactin levels returned to normal, the period of administration of dopamine agonists did not result in more frequent headache attacks and did not provoke them. Conclusion. SUNCT is a rare pathology, pathogenesis of which is not clear yet. Therefore, clinicians should pay attention to the history of symptoms associated with neoplasms in the pituitary gland, perform magnetic resonance imaging of the brain, and screening for hormonal imbalances in the blood serum.

P90 Figure 1 Secondary SUNCT syndrome and hyperprolactinemia: a new case T. Makeeva1, D. Khutorov 2, M. Koreshkina3 1Medical center "New Medical Technologies", Voronezh, Russian Federation 2The Nikiforov Russian Center of Emergency and Radiation Medicine, St.Petersburg, Russian Federation 3Headache centre Ltd. AVA-Peter, St.Petersburg, Russian Federation

Introduction: Pathophysiology of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) remains unclear. Several cases of the secondary SUNCT syndrome were described in patients with neoplasms of the pituitary gland, mainly prolactinomas, with Figure 2 elevated blood serum prolactin level. In some cases, even microadenomas could lead to SUNCT attacks, so it suggests that these pains may be induced not only by a mechanical pressure of the tumor, but also by activation of neuroendocrine pathways. Dopamine affects secretion of prolactin from the anterior pituitary gland. A change in the headache phenotype after administration of dopamine agonists was noted, which suggests that headache syndromes may be a result of changes in the dopamine-prolactin axis, and it is quite possible that specific neuroendocrine pathways, including the dopamine-prolactin axis, are also able to activate SUNCT pathophysiology. Results. We have described a new case of SUNCT in a patient with Rathke's cleft cyst (benign non tumor mass) (8 × 8 × 3 mm, 3 × 3 × 2 mm in magnetic resonance imaging) with persistent hyperprolactinemia, with a prolactin level of 2,180 mIU/ml (normal range: 102-496 mIU/ml) at the beginning of the headaches. Her general somatic and neurological status were normal. After the

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P91 solely responsible for attack induction. In light of the The effect of pituitary adenylate cyclase-activating recent development of a selective PACAP antibody for peptide-38 and vasoactive intestinal peptide in cluster testing in migraine prevention, our findings support headache the rationale of testing this antibody in cluster A. L. Vollesen1, A. Snoer1, B. Chaudry1, A. S. Pedersen1, headache prevention. A. Hagedorn Jespersen1, J. Hoffmann2, R. Højland Jensen1, M. Ashina1 1Danish Headache Center, Glostrup, Denmark 2Basic and Clinical Neuroscience, Institute of P93 Psychiatry, Psychology and Neuroscience, King's Great occipital nerve steroid injections in cluster College London, London, United Kingdom headache. E. Merli1,2, G. Asioli1,2, V. Favoni1,2, G. Giannini1,2, D. Question: Previously reported increases in serum Mascarella1,2, S. Cevoli1, G. Pierangeli1,2 levels of vasodilating neuropeptides pituitary 1IRCCS - Istituto delle Scienze Neurologiche di Bologna, adenylate cyclase-activating peptide-38 (PACAP38) and Bologna, Italy vasoactive intestinal peptide (VIP) during attacks of 2University of Bologna, Department of Biomedical and cluster headache could indicate an involvement in Neuromotor Sciences, Bologna, Italy cluster headache attack initiation. We investigated the attack-inducing effects of PACAP38 and VIP in cluster Background: Peripheral nerve blocks have been headache, hypothesizing that PACAP38, but not VIP, investigated as transitional treatment in cluster would induce cluster-like attacks in episodic active headache (CH), with different agents and number of phase and chronic cluster headache patients. treatments used. We examined the effectiveness and safety of 3 injections of Greater Occipital Nerve (GON) Method: In a double-blind crossover study, 14 episodic with long-acting steroid in episodic and chronic CH. cluster headache in active phase, 15 episodic cluster headache in remission phase and 15 chronic cluster Methods: Between November 2017 and December headache patients were randomly allocated to receive 2019, we consecutively enrolled 57 patients, without intravenous infusion of PACAP38 (10 pmol/kg/min) or contraindications to steroid treatment, who accessed VIP (8 pmol/kg/min) over 20 min on two study days to our Headache Centre for CH. Our group was separated by at least seven days. We recorded composed by 47 episodic CH patients during cluster headache intensity, incidence of cluster-like attacks, period and 10 chronic CH ones. We performed 3 cranial autonomic symptoms and vital signs using a injections of slow-release methylprednisolone 60 mg in questionnaire (0-90 min). suboccipital area on alternate days. Primary outcome was the complete absence of CH attacks at one month Results: In episodic cluster headache active phase, from the injections. Secondary outcome was the PACAP38 induced cluster-like attacks in 6/14 patients reduction of at least 50% of daily attacks. (median time to onset 35 min (range: 10-50 min)) and VIP induced cluster-like attacks in 5/14 patients Results: 34 patients (59%) were attacks free at one (median time to onset 70 min (range: 20-90 min)) (p = month, reaching the primary outcome. In the non- 1.000). In chronic cluster headache PACAP38 and VIP responders patients the daily frequency of attacks both induced cluster-like attacks in 7/15 patients decreased from a median of 2 (IQR:1-3) to 1 (IQR: 0.3- (median time to onset after PACAP38 was 50 min 2) (p=0.001), and 15 out of 23 patients (65%) reached (range 20-70) and after VIP was 30 min (range 10-50 the secondary outcome. The intensity decreased from min)) (p = 0.765). In episodic cluster headache a median of 8 (IQR: 7-9) to 7 (IQR: 5-8) (p<0.004). remission phase neither PACAP38 nor VIP induced any cluster-like attacks. We find no significant difference in responsiveness rate in chronic patients compared to episodic ones. Conclusions: Contrary to our hypothesis, attack induction was roughly equal by PACAP38 and VIP in No serious adverse events were reported: 34 patients episodic active phase and chronic cluster headache (60%) had mild adverse events; neck stiffness/pain was patients which speaks against the PAC1-receptor as the most common.

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Conclusions: 59% of patients were attacks free at one many investigators have reported beneficial effects of month after GON injection and a reduction of at least oral or parenteral corticosteroid in the treatment of 50% of daily attacks was found in 65% of patients who CH. In the absence of definitive trial data, the choice of still complained attacks. To our knowledge, this is the corticosteroid regimen for CH can be extrapolated largest sample of patients investigated with this from the limited published reports only. The quality of protocol. Our findings suggest that suboccipital the evidence in support of the use of corticosteroids methylprednisolone injections may have an important for CH is low, especially in the pediatric age; the role as transitional CH management due to its safe and evidence provides a clear signal of therapeutic benefit rapid effectiveness. for corticosteroids in pediatric CH.

Figure 1

P94 High-dose intravenous methylprednisolone for treatment of cluster headache. F. Ursitti1, L. Papetti1, M. A. N. Ferilli1, G. Sforza1, R. Moavero1, M. Valeriani1 1Ospedale Pediatrico Bambino Gesù, Neurology, Roma, Italy

Background and Objectives: Cluster headache (CH) is a trigeminal autonomic headache with severe, unilateral headache attacks of orbital, supraorbital or temporal pain accompanied by ipsilateral autonomic symptoms and signs. The mean age of onset is in the late third decade. Only few cases of childhood-onset (<14 years) CH have been reported in the literature. We report two cases of CH with onset at childhood, treated with intravenous methylprednisolone with benefit.

Methods and Results: The first case is a 15-year-old girl (onset at 12 years), with unilateral pain localized in the orbital region associated with conjunctival injection, ipsilateral nasal obstruction and hyperemia of the left face. She was treated with Verapamil and Carbolithium with little benefit. Subsequently she has been performed blockage of the spheno-palatine ganglion, without benefit. For recrudescence of symptoms, she was treated with methylprednisolone i.v. for 5 days, with improvement. The second case is a 14-years-old boy (onset at 12 years), with episodes characterized by severe intensity pain located in the frontal and temporal region with conjunctival injection. Verapamil was started with partial response, interrupted for atrioventricular block. He was treated with methylprednisolone i.v. for 5 days, with control of the attacks.

Conclusion: According to the criteria of the International Classification of Headache Disorders (ICHD-3), our patients should be considered as chronic CH, with drug-resistence form. In the last 50 years, 68

Figure 2 P95 Characteristics of pre-cluster symptoms in cluster headache: a cross-sectional multicenter study S. Cho1,2, S. J. Cho3, J. Y. Ahn4, M. K. Chu5, J. M. Chung6, P. W. Chung7, B. S. Kim8, D. Kim9, J. M. Kim9, M. J. Lee10, H. S. Moon7, K. Oh11, J. W. Park12, J. H. Sohn13, C. S. Chung10,4, B. K. Kim1,4 1Nowon Eulji Medical Center, Neurology, Seoul, South Korea 2Samsung Medical Center , Neurology, Seoul, South Korea 3Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, South Korea 4 Seoul Medical Center, Seoul, South Korea 5Severance Hospital, Seoul, South Korea 6Inje University College of Medicine, Seoul, South Korea 7Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea 8Bundang Jesaeng General Hospital, Daejin Medical Center, Seongnam, South Korea 9Chungnam National University College of Medicine, Daejeon, South Korea 10Samsung Medical Center, Seoul, South Korea 11Korea University College of Medicine, Seoul, South Korea 12Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, South Korea 13Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, South Korea

Background: In cluster headache, pre-cluster periods preceding the onset of cluster bout by days to weeks have not been well studied. In this study, we investigated characteristics of pre-cluster symptoms in patients with cluster headache.

Methods: In this multi-center study, 118 cluster headache patients (3 first-onset, 111 episodic and 4 chronic cluster headache) were recruited between October 2018 and December 2019. Patients were interviewed by investigators and underwent a structured questionnaire. Patients were asked about presence of 20 pre-cluster symptoms. Patients were also asked about pre-attack symptoms before cluster headache attacks. We performed univariable and multivariable logistic regression analyses to evaluate the factors associated with presence of pre-cluster symptoms.

Results: Pre-cluster symptoms were reported in 28.8% of our cluster headache patients. When present, pre- 69

cluster symptoms occurred at a median of 7 days with standard parameter (see table). We observed a (range 1 to 30) before the onset of cluster bout. reduction of >50% of attacks after 6 treatments in 3 Among patients with pre-cluster symptoms, 79.4% had patients; in 4 of these the effect was nearly complete. pain symptoms. Patients with pre-cluster symptoms In one patient, instead treatment was ineffective. No had higher prevalence of pre-attack symptoms and side effects were reported. more multi pre-attack symptoms than patients without pre-cluster symptoms (pp<0.045, respectively). In RFp of occipital nerves should deserve more attention univariable and multivariable logistic regression as a neuromodulation therapy in cluster headache. analysis to assess the predictor of presence of pre- cluster symptom, the presence of pre-attack symptom 1 Kelderman T, Vanschoenbeek G, Crombez E, was associated (OR=10.8, p=0.002). Paemeleire K, Safety and efficacy of percutaneous pulsed radiofrequency treatment at the C1–C2 level in Conclusions: Pre-cluster symptoms were reported in chronic cluster headache: a retrospective analysis of 21 almost one-third of cluster headache patients. Our cases Acta Neurologica Belgica 2019 results suggest that pre-cluster symptoms are https://doi.org/10.1007/s13760-019-01203-6 associated with pre-attack symptoms, which may help understand of cluster headache pathophysiology and Figure 1 early treatment strategies.

P96 Pulsed radiofrequency on occipital nerves in cluster headache: a case series

M. Valente1, E. Belgrado1, G. L. Gigli1 1Neurological Clinic University of Udine, Udine, Italy

Cluster Headache (CH) is a debilitating disease, particularly in the chronic form or when resistant to standard therapies.

Pulsed Radiofrequency was tried in the past in CH patients, mainly on SPG ganglion. Recently it was administered on C1-C2 roots1 (which are the main roots of the Greater and Lesser occipital nerves), with mixed but interesting results. However, these P97 structures are deeper and more difficult to target than Analysis of variants in NOS genes in relation to Cluster occipital nerves which run superficially in the posterior headache and predisposing factors scalp and are easily accessed. C. Ran1, C. Fourier1, J. M. Michalska1, C. Sjöstrand2,3, E. Waldenlind2,3, A. Steinberg2,3, A. Carmine Belin1 We report a case series of four patients (2 with Chronic 1Karolinska Institutet, Dept. of Neuroscience, CH, 2 with Episodic CH) treated with Pulsed Stockholm, Sweden Radiofrequency (RFp) of Greater and Lesser occipital 2Karolinska Institutet, Dept. of Clinical Neuroscience, nerves. One patient was resistant to all classic Stockholm, Sweden therapies, while two more patients tried at least 3 3Karolinska University Hospital, Dept. of Neurology, drugs responding only to steroids, the last one was Stockholm, Sweden resistant to verapamil. One patient was treated three times for different clusters, and one more patient was Cluster headache (CH) is a severe primary headache treated twice during the same cluster. The other two characterized by excruciatingly painful attacks of patients were treated once for a total of 7 treatments. unilateral headache. The pathophysiology includes Procedures were carried out using a Cosman device 70

activation of the autonomic-trigeminal reflex with headache, there is an increasing number of cases in the CGRP release, vasodilation and inflammation. Nitric literature describing secondary SUNCT syndrome. oxide (NO) is a vasodilating molecule, with an extremely short half-life, and consequently difficult to Materials and methods: A literature review was measure, which is present in the affected tissues and conducted using PubMed and Google Scholar online has been suggested to be involved in CH. databases. All the works were searched using the terms SUNCT, secondary SUNCT and associated SUNCT In this study we analysed the frequency of seven from 1991 to 2020. An additional manual search was common genetic variants in the three genes encoding also performed by links in the articles found. NO synthase (NOS) enzymes; inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal (nNOS). NOS Results: 80 patients with secondary SUNCT were enzymes catalyse the reaction producing NO from L- identified: 29 women (36.3%) and 51 men (63.4%); arginine. We screened over 500 CH patients and 500 median age was 47.4 ± 16.5 years. The diagnosis met healthy control subjects from Sweden using TaqMan® the criteria for secondary headache according to ICHD- chemistry on an Applied Biosystems 7500 qPCR system 3. In 35 patients (44%), the secondary SUNCT was and then analysed the allele and genotype frequencies caused by cerebrovascular disorders, in the with respect to CH diagnosis. vast majority – by neurovascular compression (30 patients). In 21 patients (26%), the secondary SUNCT Preliminary data suggests that these genetic variants was associated with brain tumors, most often – with a are not associated with CH in the Swedish population. pituitary adenoma (15 patients). In 16 cases (20%), the The minor allele of rs2779249 in iNOS was more secondary SUNCT was associated with neuroinfection, common in the patient group than in controls (p=0.05), more often – of viral etiology (11 patients), in 4 cases but this association does not remain significant after (5%) - with CNS demyelinating diseases, in 2 cases correction for multiple testing. Subgroup analysis (2.5%) - with craniocerebral trauma, and in other 2 dividing patients in groups using tobacco suggests that cases (2.5%) - with congenital anomalies of the skull. the same genetic variant, rs2779249, is more common in CH patients who have used or are currently using Conclusions: In patients with suspected SUNCT tobacco. As nicotine is known to have a syndrome, secondary causes should be ruled out first. vasoconstrictive effect, we will perform similar Careful collection of complaints, disease anamnesis, subgroup analysis on other parameters known to affect assessment of concomitant pathology and its the regulation of blood vessel constriction, for example relationship with the resulting headache are analysing patients with high caffeine consumption or necessary. Neuroimaging is also necessary in order to who report alcohol as a trigger factor for CH attacks. rule out organic damage to the brain: neoplasms, congenital malformations, vascular pathology, demyelinating diseases and neuroinfections.

P98 Secondary SUNCT Syndrome: Literature Review D. Khutorov1, T. Makeeva2, D. Korobkova3 P101 1Nikiforov Russian Center of Emergency and Radiation The clinical profile of cluster headache in Iranian Medicine, Headache center, Saint-Petersburg, Russian patients in southern region of Iran Federation A. Ghabeli Juibary1 2Medical Center “New Medical Technologies”, 1Shiraz University of Medical Sciences, Neurology, Headache center, Voronezh, Russian Federation Marvdasht, Iran 3University Headache Clinic, Moscow, Russian Federation Question: What is the clinical profile of cluster headache in patients in southern region of Iran? Introduction: Recurrent short-lasting unilateral neuralgiform headache attacks with conjunctival Methods: The classification and clinical characteristics injection and tearing (SUNCT) are a rare clinical of 36 consecutive patients with cluster headache (34 disease. SUNCT pathophysiology remains unclear. males, 2 females; mean age, 30.9 ± 8.7 years) visited at Although this disease is one of the primary types of 71

a referral hospital and private office: April 2017 to treatment in cluster headache (CH) . The aim of this January 2020 were analyzed. observational prospective study is to evaluate the effectiveness and safety of repeated suboccipital Results: Patients came from 4 different provinces of injections with methylprednisolone in Chronic CH Iran. Mean age at onset of cluster headache was (CCH). 23.7 ± 10.9 years. Only 6 patients(16%) had previously been diagnosed with cluster headache. Mean time to Methods: We consecutively enrolled all patients diagnosis from first presentation was 6.2 ± 4.1 years accessed to our Headache Centre for CCH without (range, 0–21 years). Chronic cluster headache was contraindication to steroid treatment. Patients observed in only 5 patients (13.88%). The most underwent to three injections in suboccipital area of commonly reported site of cluster headache was slow-release methylprednisolone 60mg on alternate retroorbital region (69.44%), followed by temporal days. Primary outcome was the complete absence of region (55.5%), forehead (33.3%), vertex (27.7%) and CH attacks at one month from the occipital (16.6%). Lacrimation was the most injections. Secondary outcome was the reduction of at consistently autonomic symptom (83.3%). In acute least 50% of daily attacks. attacks phase, 72.2% of patients experienced nausea, and 36.1% reported photophobia and 40.8% reported Results: A total of 12 patients were enrolled, between sonophobia. In addition, 80.5% reported restlessness November, 2017 and February, 2019. Four patients during acute attacks. None of patients experienced (36%) were attacks free at one month, reaching the visual or other types of aura before start of attacks. We primary outcome. In the 6 non-responders patients (1 found that 38.3% of patients had <1 cluster period and were lost to follow up before one month visit) the daily 35.8% for 1–2 cluster periods per year with these frequency of attacks decreased from a median of 2.0 periods occurring less frequently during the spring in (IQR: 1.3-2.8) to 1.0 (IQR: 0.3-1.8), and 3 (43%) reached comparison with other seasons in the year. Cluster the secondary outcome. No serious adverse events duration was 1–2 months in 38.8% of patients. During were reported: 5 patients had mild adverse events; periods, 80.5% had 1–2 attacks per day, and 33.3% neck stiffness/pain was the most common. reported cluster attacks ranging in time span from 1 h to less than 2.5 h. The duration of attacks were 1.5 (1– Conclusion: In our sample, at one month after GON 2.35) hours for males and 1.5 (1-3.1) for females injection, the 36% of patients were attacks free and the respectively. 43% of non-responders showed a reduction of at least 50% of daily attacks. Our preliminary findings Conclusion: In Comparison to Western patients, suggested that suboccipital methylprednisolone Iranian patients showed a relatively low prevalence of injections may have an important role in CCH chronic cluster headaches, pain sites mainly focused on management due to its rapid and good effectiveness. areas distributed by the first division of the trigeminal Effectiveness of this infiltration protocol need to be nerve, a higher frequency of restlessness and absent confirmed in larger and controlled studies. aura before cluster attacks.

P103 P102 Sussac is one of the rare syndromes in neurology but Suboccipital steroid injections for treatment in it’s another differential diagnosis of subacute chronic cluster headache: an observational headache. prospective study S. Zamanian 1,2, E. Pourakbar 2 G. M. Asioli1, E. Merli1, V. Favoni1, C. Calabrò1, S. 1Neurology , Mashhad, Iran Cevoli2, G. Pierangeli1,2 2Mashhad university of medical sciences ,, Neurology , 1University of Bologna, Bologna, Italy Mashhad, Iran 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy Case presentation: Index patient was 36 year-old male who was admitted in Our hospital because of headache Background: Greater Occipital Nerve (GON) injections and weakness.He complained sabacute headache with with corticosteroids can be used for transitional vometing and left hemiparesia from 4 days ago. Some 72

symptom and sing added after admitted that Figure 2 include;cognetive change,cloudy vision,dysarthria and hearing loss.He was previously healthy and had no remarkable medical history.We preformed MRI and LP to evaluate any brian or central nervous system lesions.The MRI scan showed T2- weighted ,area around the periventricular region,in white matter and in the central corpus callosum(Linear defects”spokes”in the central fibers the CC).The LP revealed high protein level(250) but no OCB and IGg index.PRVEP test showed prolonged latency of bilateral P100 waves .An audiogram showed SSNHL in left side.Fundus examination and Fluorescein angiography of the left eye showed Ischemic retina with sings of branch retinal artery obstraction.The patient was treated with anti platelet agent and intravenous P104 prednisolone 1gr/kg for 5 days fallowed by oral steroid Intracranial tuberculoma is rare but important cause tapering five months after treatment.BCVA recovered of chronic headache. in the left eye and a mild residual auditory defect E. Pourakbar1, S. Zamanian 1 remained ,but no remaining headache or left 1Mashhad university of medical sciences, Neurology , hemiparesia were observed. Conclusion: Sussac is one Mashhad, Iran of the rare syndromes in neurology . usually the begin with a subacute and persistent headache especially in Case presentation: Index patient was 24 years old the middle of year, but this syndrome is not often female who was admitted in our hospital because of diagnosed .Diagnosis and proper treatment can resistance headache ,intermittent fever,cough from 2 prevent complications. months ago with a progressive course.She complained chronic compressive headache and constitutional Figure 1 symptoms.She was previously healthy and had no remarkable medical history.On general examination she had oral temperature of 38ć ,neck stiffness and lymphadenopathy were not detected in physical examination.No obvious abnormalities were detected in lung but in heart she had systolic murmur 2/6 LSB.Foundoscopy showed mild bilateral papilledema. Cranial nerves were intact.We preformed MRI and LP to evaluate any brain or central nervous system lesion.The MRI scan showed T2-weighted similar lesions were highly intense and some of the lesions were enhancemented.MRS examination of the brian lesions demonstrated no compatible with tumor mass,no increased choline peak but increased lactate to choline ratio and decreased NAA.The Lp revealed CSF pressure was 300 mm H2O ,glucose 45 mg/dl,Pr 55 mg/dl,RBC and WBC 0, and CSF smear culture were negative.ESR 12 mm in 1 hour.CBC diff were normal.The CXR showed faint reticulonodular infiltrate and mild hilar or mediastinal andenopathy.Chest CT scan was reported Three in bud pattern.Abdomen and pelvic CT scan were showed multiple hypointense foci in liver .TB PCR was positive in BAL.PPD test was

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negative.The patient was immediately treated with P105 anti -TB drugs Yoga Nasal irrigations in the treatment of chronic tension type headache: Randomised waitlist Discussion: Tuberculosis is still a leading cause of death controlled trial amonge the infectious diseases.Brain tuberculomas N. Sharma1,2, P. John 3, S. Sharma2, J. Joshi1 that develop into pus-filled and indicate poor defenes 1Yog-Kulam , London, United Kingdom mechanisms.Tuberculoma is rare and it is variety of 2NMP Medical Research Institute, Jaipur, India presentation and nonspecific symptoms like mild to 3Rajasthan University , Jaipur, India moderate resistance headache or other focal neurological deficit.The should be supported by finding Background: To evaluate the effectiveness of Saline such as history of fever,high ESR,PPD (+).MRI is Nasal Irrigation (SNI) followed by yoga practices on reportedly superior to CT for diagnosis of brain patients with chronic tension-type headache reducing tuberculomas.Lung CT scan indicating the centrilobular pain and disability. nodules and branching linear opacities.The current case made complete recovery on Anti-TB Methods: Ninety eight patients with diagnosed chronic treatment.Patients usually do not need the fallow up tension-type headache were recruited from two after completion of therapy if sings or symptoms do neurology clinics. Study was approved by the not recur. Institutional Review Board and all participants gave informed written consent. After a week of run-in Figure 1 period, baseline assessments were taken. Participants were randomly allocated to intervention (n=49) and wait list control (n=49). SNI was given by qualified, experienced yoga therapist twice a week for 6-weeks. Each practice was followed by Kapalbhati and Bhastrika Pranayam (yoga breathing) for 10 mins. Headache frequency, severity and duration was assessed by headache diary, and Disability with Headache Impact Test (HIT-6). All outcomes were measured at baseline, and at the end of the 6-week intervention.

Results: Comparing two groups, results showed statistically significant differences (p < 0.000) in all the measures.. Within-group comparisons showed no

significant improvement in waitlist control group

whereas frequency, severity and disability score

reduced significantly in Yoga group (p<0.0001) along Figure 2 with duration of pain (p<0.05).

Conclusions: The study findings suggest that saline nasal irritation followed by yoga practices in patients with chronic tension-type headache is effective and safe reducing headache and disability.

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P106 Efficacy of Mechanism-Based Manual Physical Figure 1 Therapy in Treatment of Adults with Cervicogenic Headache- a Randomized Clinical Trial S. K. Paramasivam1,2, C. S. Kumar2 1Academy of Orthopaedic Manual Physical Therapists (AOMPT), Bethel Medical Mission Group,, Physiotherapy, Bengaluru, India 2Bethel Medical Mission Group,, Physiotherapy, Bengaluru, India

Background: Cervicogenic Headache (CGH) is a specific cervical spine disorder with unilateral headache with/without ipsilateral neck pain, reproduced on movement testing and palpation of cervical spine. Conservative treatment of CGH using Physical Therapy

(PT) incorporated electrical/thermal modalities, exercises and manual therapy. Pain management in Figure 2 physical therapy shifted from a symptom-based or syndrome-based approach to a mechanism-based classification (MBC) paradigm that involved subgrouping of patients into either of five mechanisms (cognitive-affective CA, Central sensitization CS, Sympathetically mediated pain SMP, peripheral sensitization PS, and nociceptive N, and applying the suitably indicated specific interventions. The objective of this study was to evaluate the efficacy of MBC-based physical therapy in treatment of people with CGH.

Method: Observer-blinded parallel-arm randomized clinical trial was conducted on 26 adults (12 male, 14 female), with medically diagnosed unilateral symptoms of non-acute (> 3 weeks) CGH (12 right, 8 left, 6 bilateral) who were randomly assigned to receive standard care physical therapy alone (N=12) or in combination with MBC-based PT (N=14) treated for 45 mins per session, 3 sessions per week, for total P107 3weeks. Pre-post outcome measurements included What could be lurking behind a vague headache? 1 1 1 2 Numerical pain rating scale (NPRS) for pain intensity, J. I. Sinelli , I. Cristea , C. Toader , D. M. Boghi 1 Cervical flexion-rotation test (CFRT) measured using The National Institute of Neurology and Neurovascular goniometry in degrees, and Headache Disability Index Diseases, Neurology 2, Bucharest, Romania 2 (HDI) questionnaire, were analysed using students’ t- Saint Pantelimon Hospital, Bucharest, Romania test at 95% confidence interval using SPSS 22.0 for Windows. A 78-year old woman arrives to the emergency room complaining of a tensional headache and vertigo that Results: Both groups had statistically significant (p had been bothering her for the last few months. Neither the pain nor the vertigo had been progressive, while the pain only slightly subsided with OTC painkillers and NSAIDS. The patient history uncovered that the patient was being treated high blood pressure and glaucoma in both eyes for years, while the only pathological finding on the neurological exam was

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significant deafness in both ears. All of these could was 12.1 ± 1.04 points, against the background of have been likely causes of her headache and vertigo. treatment 6.01 ± 0.63 (p≤0.001), depression - 11.2 ± When the patient mentioned that a previous cerebral 1.24 and 2.9 ± 0, 95, respectively (p≤0,001). In the CT showed a right-sided lesion, we decided to repeat. group of patients using only drug therapy, nine (19.5%) It revealed 2 hypodense lesions on the right parietal developed tension headache. lobe and the right side of the cerebellum. An MRI with contrast solution was then recommended, which Conclusion: The use of portable PENS contributes to finally confirmed what was causing the headaches and reduce the intensity of headache in patients with vertigo: an ischemic stroke on the right PICA, which chronic hepatitis B, as well as prevent the development was months old, and an ischemic stroke with of strong tension headache. Furthermore, hemorrhagic transformation on the right MCA. Percutaneous electrical nerve stimulation appears to be a useful complementary therapy to analgesic and antimigraine drugs for the short-term management of headache P108 Assessment of an application per-cutaneous electrical nerve stimulation in patients with chronic tension headache P109 M. Salokhiddinov1, F. Umarov1 Evaluation of the Acute Effects of Orthopedic 1Tashkent Medical Academy, Neuroscience, Tashkent, Manipulative Treatment on pain and cervicothoracic Uzbekistan angle in Cervicogenic Headache A. CAKIR1, N. YAGCI2 Question: Tension-type headache (TTH) occurs in 35– 1Fizyosifa Wellness Center, Denizli, Turkey 78% of population; it is most frequent among all types 2Pamukkale University, School of Physiotherapy and of headaches and more common in women. Presently, Rehabilitation, Denizli, Turkey per-cutaneous electric nerve stimulation (PENS) has become increasingly popular as alternative and Introduction and Aim: Many treatment modalities complementary therapies, showing positive preventive have been used in cervicogenic headache. Current properties in acute and chronic migraine. scientific evidence supports the role of manual therapies in the management of cervicogenic Methods: The study involved 85 patients treated headache, but the results are still conflicting. The aim between 2014 and 2016 at the 1st Republic Clinics of this study was to evaluate of the acute effects of under the Ministry of the Health of Uzbekistan. The orthopedic manipulative therapy (OMT) on pain and patients were divided into two groups. The first group cervicothoracic angle in patients with cervicogenic included 39 patients who received only drug therapy headache. for six months. The second group consisted of 47 patients using, as recommended drugs and portable Methods: In our study, total of 23 patients (Female: 19 PENS Male: 4) aged between 25-64 years who were diagnosed with cervicogenic headache were included Results: The study showed that in the first group, the in this study. The severity of headache was measured assessment of the intensity of headache - 5.4 ± 0.54 by Visual Analogue Scale (VAS;10cm). In order to points during the initial examination; 6.3 ± 0.61 points determine the change in cervical spine posture of at the second admission (p≤0.001). At the same time, patients "cervicothoracic angle" measurement was according to the scales of anxiety and depression, performed by taking pictures over mobile phone during treatment was 11.2 ± 1.05 points, against the application. ACCP CORE 2 posture measurement used background of treatment 9.01 ± 0.86 (p≤0.001), as the application posture program. All measurements depression - 8.9 ± 1.28 and 8.9 ± 1 , 02, respectively were repeated before and immediately after (p≤0.001). In the second group, the level of headache treatment. In one treatment session as OMT; cervical intensity is 6.1 ± 0.50 points during the initial myofascial release, cervicothoracic fascia mobilization, examination; 1.8 ± 0.39 points on the second trigger point massage, and cervical manipulation of the admission (p≤0.001). At the same time, according to segment with dysfunction were performed by the the scales of anxiety and depression, during treatment physiotherapist. 76

Results: The average age of patients participating in Discussion: On the first onset of headache with sexual the study were found to be 43.52±11.64 years. After activity a detailed neuroimaging investigation is one-session treatment, a significant decrease was mandatory to exclude secondary causes (mainly found in headaches of the patients compared to the subarachnoid hemorrhage and arterial dissection). pre-treatment (p=0.0001). There was a significant Primary headache attributed to sexual activity is decrease in the cervicothoracic angles (decrease of usually bilateral, diffuse or occipitally localized and not anterior cervical tilt) after treatment (p=0.0001). associated with disturbance of consciousness, vomiting, visual, sensory or motor symptoms. Usually Conclusion: The result of our study showed that the starts as a dull pain and suddenly becomes intense at application of OMT techniques in the treatment of orgasm. It may last just a few minutes, or in more cervicogenic headache is effective in reducing pain severe cases, hours to a day. Its pathogenesis is poorly severity and improving cervicothoracic angle in the understood and has usually a self-limiting course. acute period. We think that the effects of non-invasive Short-term prophylaxis with indomethacin 25–100 mg treatments such as OMT techniques of health 1–2h before intercourse is recommended. For professionals should be investigated more extensively persisting or longer-lasting symptoms beta-blockers and long term in the treatment of cervicogenic (propranolol 120–240 mg/day) and diltiazem 180 headache mg/day are recommended as prophylactic therapy.

References: The International Classification of Headache Disorders, 3rd edition (beta version). P110 Cephalalgia: an international journal of headache. Primary headache associated with sexual activity: A 2013;33:629-808. case series of 7 patients I. Spanou1, A. Bougea1, S. Xirou1, G. Liakakis1, K. Rizonaki1, E. Anagnostou1, E. Kararizou1 1National and Kapodistrian University of Athens, 1st P111 Department of Neurology, Eginition hospital, Athens, The need for otoscopy before invasive or Greece neuroimaging modalities in the work-up of indeterminate headaches in children Background: Primary headache associated with sexual O. Komolafe1, A. Adebowale2, A. Adeyemo3, M. activity is an uncommon, but probably under- Asaleye1, I. Ogunbameru4 diagnosed and under-reported headache. 1Obafemi Awolowo University Teaching Hospital, Radiology, Ile-Ife, Nigeria Methods: We present a case series of 7 patients with 2Obafemi Awolowo University Teaching Hospital, primary headache associated with sexual activity. Neurology, Ile-Ife, Nigeria 3Obafemi Awolowo University Teaching Hospital, Results: All patients (4 males/3 females) experienced Otorhinolaryngology, Ile-Ife, Nigeria at least two episodes of a sudden onset headache of 4Obafemi Awolowo University Teaching Hospital, bilateral and diffuse localization during orgasm with Neurosurgery, Ile-Ife, Nigeria their partners. The intensity was severe for the first 5– 15 min and gradually abated, with a total duration of Background: The management of children with approximately 2 hours. Nausea and persistent headaches of indeterminate cause can be phono/photophobia were absent. All males and 1 distressing for the patients, parents and physicians female also described similar episodes during alike. Thus, exhaustive protocols for evaluating these masturbation. Secondary causes have been excluded headaches is crucial, so that prompt relief may be to all patients. Six patients received short-term achieved. prophylaxis with indomethacin 1–2 h before intercourse and one with more persisting symptoms We report a secondary cause of headaches in the received propranolol as a prophylactic therapy, all young that was not found in medical literature. finally with favorable outcomes. Case report: A 10-year-old boy was referred for neuroimaging on account of distressing frontal 77

headaches of increasing severity. A detailed headache Figure 1 history was negative for causes of primary headaches. Hence, secondary causes were sought. General physical and neurological examinations were unremarkable.

On pre- and post-contrast computed tomography imaging, both cerebral hemispheres, the cerebellum, brain stem, sinuses, pituitary fossa and vascular anatomy were all preserved. However, impacted within the bony portions of the external auditory canals bilaterally were solitary, non-enhancing lesions of calcific density (Hounsfield unit ~216). Both external auditory canals were otherwise preserved in diameter (for age) and course. He was subsequently referred for otorhinolaryngological evaluation.

At otoscopy, lamellated, hard wax was found impacted within the external auditory canals and removed, with the patient enjoying immediate and sustained relief from his chronic headaches.

Conclusion: Indeterminate headaches in children that warrant further investigation are currently worked-up with laboratory studies, lumbar puncture, electroencephalography and, or neuroimaging.

As cerumen impaction is not listed as a cause of headaches in literature, otoscopy is not performed in standard headache work-up protocols. To further best P112 practices when assessing for headaches of TYPE OF HEADACHE AT ONSET AND SEVERITY OF indeterminate cause in children, we make REVERSIBLE CEREBRAL VASOCONSTRICTION recommendation for routine otoscopy – to rule out SYNDROME. cerumen impaction headaches, before unnecessary K. Lange1, C. Burcin2, J. Mawet2, C. Roos2, A. Ducros1 recourse to invasive or neuroimaging modalities. 1University Hospital Montpellier, Neurology, Montpellier, France Keywords: Children, Headache, Cerumen Impaction, 2Lariboisière Hospital, Neurology, Paris, France Otoscopy Background and Aim: In a recent Italian study, 30% of patients with reversible cerebral vasoconstriction syndrome (RCVS) presented without typical thunderclap headache (TCH), and had a tendency to present more severe forms of RCVS than patients with TCH (Caria et al., Cephalalgia 2019). We aimed to analyze the severity of RCVS in patients with and without TCH at onset.

Methods: In our cohort of 173 French patients with RCVS, we compared patients with and without TCH at onset regarding rates of any radiological lesions on imaging, any neurological complications (namely

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persistent focal deficit, seizures, dissections and brain possible confounding factors of this association, the lesions); and the functional outcome by the modified regression models were extended with age, gender, Rankin Scale (mRS) at 3, 6 and 12 months. bruxism, stress, depression and somatic complaints.

Results: As compared to the 142 patients with TCH at Results: Of the included patients (n=203), 67.5% onset, the 31 patients without TCH had significantly experienced headaches. In the subsample of patients more radiological lesions (64.5% versus 33%, p=0.001, with a painful TMD (n=58), the prevalence of self- OR 3.7 [1.6-8.3]) and neurological complications reported headaches increased to 82.8%. The (64.5% versus 34%, p=0.002, OR 3.6 [CI 1.6-8.0]), while associations found between self-reported headache the functional outcome was not different (median mRS and 1) painful TMD(OR 3.0; 95%CI 1.4-6.4) and 2) score at 3, 6 and 12 months: 0). function-related TMD(OR 0.5; 95%CI 0.3-0.9), were confounded by the presence of somatic complaints. Conclusion: Absence of TCH at onset might predict a For probable migraine, both somatic complaints and higher risk of complications in RCVS. Our results bruxism confounded the initial association found with warrant further studies in order to provide better painful TMD. pathophysiological understanding and clinical management of patients with RCVS. Discussion: The confounding variables somatic complaints and parafunctions imply there is a central working mechanism overlapping TMD and headache. Healthcare providers should not look at these P113 disorders separately but at the bigger picture to The association between headaches and appreciate the complex nature of the diagnostic and temporomandibular disorders is confounded by therapeutic process. bruxism and somatic complaints: a retrospective medical file study. Conclusion: The association between headaches and H. van der Meer1,2,3,4, C. Speksnijder3, R. Engelbert2, F. temporomandibular disorders is confounded by Lobbezoo1, M. Nijhuis - van der Sanden4, C. Visscher1 bruxism and somatic complaints. 1Academic Center for Dentistry Amsterdam, Orofacial Pain and Dysfunction, Amsterdam, Netherlands 2University of Applied Sciences Amsterdam, Faculty of Health, Amsterdam, Netherlands P116 3University Medical Center Utrecht, Department of Headache and cerebral hemodynamics in children Oral-Maxillofacial Surgery, Prosthodontics and Special with consequences of transferred Dental Care, Utrecht, Netherlands meningoencephalitis 4Radboud University Medical Center, Research N. Maxamatjanova1, G. Ishankhodjayeva1 Institute for Health Sciences, IQ healthcare, Nijmegen, 1Tashkent medical academy, Neurological diseases, Netherlands Tashkent, Uzbekistan

Aim of investigation: The objective of this study was to One of the most common causes of headaches in study the presence of possible confounders of the childhood is cerebrospinal fluid disturbances, which association between temporomandibular disorders are leading in the clinical picture of the effects of viral (TMD) and headaches in a patient population from a meningoencephalitis. TMD and Orofacial Pain Clinic. The purpose of the study was to study the state of Methods: Several subtypes of headaches were cerebral vascular tone and blood flow in children with diagnosed: self-reported headache, migraine, tension- the consequences of transferred meningoencephalitis. type headache and headache attributed to TMD. The presence of TMD was subdivided into two subtypes: Materials and research methods: 56 children were painful TMD and function-related TMD. The examined with the consequences of the transferred associations between the subtypes of TMD and the meningoencephalitis with hypertension syndrome. All three headaches were evaluated by single regression models. Subsequently, to study the influence of 79

patients underwent clinical neurological, Patients and Methods: The study was conducted as a dopplerographic examination, brain MRI. single center, cohort prospective study which included 252 patients (105 men and 147 women), average age Results and discussions: Complaints were constant or of 47.3 ± 15.0 years, in which lumbar puncture (LP) was regular headaches of varying severity, aggravated by performed with traumatic needles of different caliber tilting the head or changing the position of the body, (20G vs. 18G, p=0,167). often accompanied by nausea and vomiting, dizziness, restless sleep, irritability. A neurological examination Results: PDPH was reported in 133 (52.8%) patients. In revealed pain at the exit points of the FMN, a positive the studied group, 82 (32.5%) patients had CH. Patients symptom of Danzig-Kunakov, oculomotor disorders, with CH were more likely to have PDPH (p=0.003). The nystagmus. individual clinical type of CH did not have an effect on the incidence of PDPH (p=0.128). Patients with PDPH The method of transcranial Doppler ultrasonography and CH had a clinical deterioration of CH after three, determined the blood flow velocity and the ripple six and twelve months of LP in terms of higher days per index (Gosling), which reflects the elastic properties of months and/or incomplete efficacy of performed the artery. In 47% of the examined children with therapy regarding baseline values (p=0.047, p=0.027, hypertension syndrome, the Gosling index was 0.91- p=0.030, respectively). Multivariate analysis confirmed 1.15, which corresponds to 12-15 mm Hg. and is the direct association of female sex and duration of CH considered conditionally increased intracranial and worsening of CH after twelve months of LP (OR pressure. In 53% of the examined children, the Gosling 4,785 [95% CI: 1,248-14,322], p=0,033; OR 1,788 [95% index was in the range of 1.16-1.5, corresponding to CI: 1,332-1,988], p=0,032). 15-20 mm Hg. and considered severely increased intracranial pressure. All children showed a decrease in Conclusion: The presented results can be significant for the linear velocity of blood flow. A correlation was the prediction of PDPH occurrence in patients having observed between the severity of clinical and CH and for the prediction/prevention of clinical neurological manifestations and Doppler data. worsening of CH in patients having PDPH.

Conclusions: Thus, dopplerography of cerebral vessels Keywords: Postdural puncture headache, chronic may be a criterion for assessing the severity of headache intracranial pressure.

P118 P117 Erenumab for Post-Meningitic Headache Postdural puncture headache, but not lumbar K. Arca1, M. Grill1, R. Halker Singh1 puncture itself, leads to the clinical worsening of 1Mayo Clinic, Neurology, Scottsdale, United States previous chronic headache. One year follow up study. S. Ljubisavljevic1, J. Zidverc Trajkovic2, M. Objective: CGRP antagonists are new migraine Ljubisavljevic3 therapies, but have not been evaluated in secondary 1Clinical Center of Nis, Nis, Serbia, Clinic for Neurology, headache disorders. We report a case of persistent Nis, Serbia post-meningitic headache that responded to 2Clinical Center of Serbia, Clinic for Neurology, erenumab. Belgrade, Serbia 3Clinical Center of Nis, Center for Mental Health Case: In May 2015, A 44 year-old woman with episodic protection, Nis, Serbia migraine presented with severe, holocephalic headache that progressed over 3 days, preceded by Objective: The incidence of postdural puncture low-grade fever. The headache was associated with headache (PDPH)in relation to the pre-existing chronic photophobia, phonophobia, nausea, neck pain, and headache (CH) was assessed as well as the effects of was phenotypically distinct from her typical migraine. PDPHon the clinical course of CH (days with headache CSF was positive for Varicella Zoster Virus PCR. She was per months, duration of attacks, efficacy of therapy) three, six and twelve months after PDPH. 80

treated with intravenous acyclovir followed by oral P119 valacyclovir. Headache phenotype in idiopathic intracranial hypertension is predominantly migraine-like: She continued to have LPs for frequent headache Characteristics from the Idiopathic Intracranial exacerbations, often with CSF pleocytosis but negative Hypertension Weight Trial (IIH:WT) viral studies (Figure 1). In 2018, she was started B. Wakerley1, J. Mitchell2,3, R. Ottridge4, A. Yiangou2,3, on erenumab 70 mg, which decreased headache Z. Alimajstorovic 2,3, V. Vijay 2,5, T. Matthews 6, A. frequency to 1-2 days/month. She had a recurrent Ansons 7, S. Hickman8, J. Benzimra9, M. Lawden10, B. severe headache exacerbation in August 2019 for Davies11, O. Grech 2,3, N. Ives 4, S. Patel 4, R. Woolley 4, which she self-administered an extra injection of C. Rick 12, R. Singhal 5, A. Tahrani2, S. Mollan 2,6, A. erenumab 70 mg with ensuing headache resolution. Sinclair 2,3 CSF at that time was normal. 1Gloucestershire Royal Hospital, Department of Neurology, Gloucester, United Kingdom Conclusion: Pain symptoms in meningitis result from 2University of Birmingham, Institute of Metabolism and trigeminal nerve innervation of meninges, which is Systems Research, Birmingham, United Kingdom accompanied by CGRP release. CGRP levels are 3University Hospitals Birmingham, Department of elevated in patients with acute bacterial meningitis. In Neurology, Birmingham, United Kingdom animal models, rapid treatment with triptans after CSF 4University of Birmingham, Birmingham Clinical Trials bacterial inoculation reduced the amount of CGRP Unit, Birmingham, United Kingdom released from perivascular nerve fibers; similar 5University Hospitals Birmingham, Upper GI and mechanisms are likely at play in viral meningitis. The Minimally Invasive Unit, Birmingham, United Kingdom trigeminovascular system may also be involved, as 6University Hospitals Birmingham, Neuro- CGRP is a potent vasodilator and hyperemia has been Ophthalmology Unit, Birmingham, United Kingdom described in both CNS inflammation and migraine. We 7Manchester University NHS Foundation Trust, conclude that the meningeal activation triggered by Manchester Royal Eye Hospital, Manchester, United aseptic meningitis enhances peripheral and central Kingdom sensitization via CGRP, thereby resulting in headaches 8Sheffield Teaching Hospitals NHS Foundation Trust, of a migrainous phenotype, with the potential to Department of Neurology, Sheffield, United Kingdom respond to CGRP antagonists. Further studies exploring 9Royal Devon and Exeter NHS Foundation Trust, the use of these drugs in post-meningitis headache Department of Ophthalmology, Exeter, United should be considered. Kingdom 10Leicester General Hospital, Department of Neurology, Figure 1 Leicester, United Kingdom 11University Hospital North Midlands, Department of Neurology, Stoke, United Kingdom 12University of Nottingham, Nottingham Clinical Trials Unit, Nottingham, United Kingdom

Question: Headache is the most common and disabling feature in idiopathic intracranial hypertension (IIH). Headache is driven by raised intracranial pressure and the characteristics have historically been thought to be unique to IIH. Here we report the headache phenotype in a large cohort of active IIH patients.

Methods: Baseline headache characteristics were assessed in patients recruited to the IIH Weight Trial (IIH:WT) clinicaltrials.gov identifier: NCT02124486. A standardised history, diary and phenotyping (ICHD 2b criteria) were performed, and reviewed by physicians from the Headache Centre at University Hospital Birmingham, UK. 81

Results: 66 females with active IIH were recruited, all dyslipidaemia, obesity and obstructive sleep apnoea with papilloedema. Mean age was 32 years (range 20- syndrome, presented at the emergence department 53), mean body mass index 43.9 kg/m2 (range 35.3 - with an explosive, holocranial headache, maximum 63.3). Mean baseline lumbar puncture (LP) opening from the begging, lasting for 1 hour, with no photo- pressure was 34.7 cmCSF (range 25.5 - 46.5) at phonophobia, nausea or vomit. He was agitated and enrolment. 98% reported headache. 86% described a sudoretic, but denied other symptoms including chest migraine-like phenotype of which 70% were chronic pain. There was no previous history of headache. migraine and 40% reported aura. Mean headache Neurologic examination was unremarkable. Brain and frequency 22.2±7.8 days per month and severity angio-CT did not show any abnormality. EKG revealed 5.0±2.0 (numerical rating sale 0-10). Medication- ST elevation on lateral derivations and ST depression overuse headache was present in 35%. Previous on inferior derivations and high-sensitivity troponin I migraine was reported in 68% and of these, 53% (hsTNI) was elevated (2078.4ng/L), suggesting anterior migraine had started before the age of 18 years. Only cardiac wall AMI. Prompt coronary angiography 27% were taking headache preventatives. Headache excluded large vessel occlusion. Posteriorly, headache impact test-6 disability score was 65±7.3. We also returned, patient developed pulmonary oedema and noted a significant but weak correlation between hsTNI was 93067ng/L. Bed-side echocardiogram headache severity and LP pressure at baseline (r=0.28 showed moderate decreased of left ventricular p=0.024). function. Patient was admitted at coronary intensive care unit with suspected myocarditis. Later cardiac MRI Conclusions: Chronic migraine, many with aura, is the was consistent with AMI of probable embolic origin. At commonest phenotype in active IIH. The high 9-months follow-up, patient remained headache-free, proportion with medication overuse headache and low echocardiogram showed mild left ventricular numbers receiving headache preventative therapy dysfunction. suggest sub-optimal management of headache in IIH. Specific therapeutics for IIH headaches is an urgent Conclusion: Cardiac Cephalgia may be difficult to need for this patient group. The phenotypic features diagnose, especially when there is no chest pain. This suggest that migraine treatment strategies might be striking case should prompt us to add a cardiac worthy of evaluation in IIH. screening (EKG + hsTNI ± echocargiogram) in patient with new onset headache and multiple vascular risk factors in order to avoid misdiagnosis, once treatment differs largely from common headaches. P120 Cardiac cephalgia: an uncommon headache to be aware of! A. F. Jorge1, P. Faustino1, A. C. Lima1, F. Moreira1,2, I. P121 Luzeiro1,2 Clinical characteristics of idiopathic cerebrospinal 1Centro Hospitalar e Universitário de Coimbra, fluid leak developped with thunderclap headache: for Neurology, Coimbra, Portugal an early diagnosis 2Faculty of Medicine, Coimbra University, Coimbra, Y. Nakazato1, K. Ikeda1, K. Ota1, M. Takashi1, K. Portugal Kawasaki1, T. Fukuoka1, A. Tanaka2, N. Tamura1, T. Yamamoto1 Introduction: Cardiac Cephalgia is a rare but serious 1Saitama Medical University, Neurology, Saitama, cause of secondary headaches. It is defined by the Japan ICHD-3 as a migraine-like headache, occurring during 2Tottori Medical Center, Department of Neurology, an episode of myocardial ischaemia. Although, it Tottori, Japan usually presents associated with angina pectoris, this may not occur in 30% of the cases, mainly in acute Introduction: Thunderclap headache (TH) is an initial myocardial infarction (AMI). We present a case of an sign of neurologic emergency diseases such as AMI presenting with headache. subarachnoid hemorrhage, vertebral artery dissection, or idiopathic cerebrospinal fluid leak (ICFL). Brain CT Clinical-case: A 58-year-old male, with previous history and/or MRI are usually performed urgently. When of diabetes mellitus type 2, hypertension, there is no abnormality, cerebrospinal fluid study, MR 82

angiography are performed additionally. The purpose Question: Idiopathic intracranial hypertension (IIH) is a of this study is to find the useful clinical symptoms and rare disabling condition characterised by chronic examinations for early diagnosis of ICFL which headaches alongside other symptoms such as visual developped with TH. loss(2). Quantitative reports of headache in IIH show that it affects quality of life (SF-36); causes disability Method: Thirty-two cases of ICFL developped with TH (HIT-6), is daily in most (86%)(4–6) and is an unmet (included six our cases and 24 reported cases) were need in IIH(3). The qualitative lived experience of the investigated retrospectively. We investigated the impact of headache in people with IIH is under details of their headache, checked the initial brain reported. CT/MRI, cerebrospinal fluid, site of cerebrospinal fluid leakage, and enhanced brain MRI. Question - What is the lived experience of headache in the words of people with IIH? Result: Headache has occurred in occipital region in 18 cases, in the whole head in 8 cases. Orthostatic Methods: This study was an anonymous online survey headache was worsened during clinical course in 12 using Survey MonkeyTM. The survey was emailed to cases. There were nuchal rigidity in 9 cases. Twenty members of the national charity for people with IIH three of 24 cases revealed normal findings in initial (IIH UK) and shared on their national and regional brain imaging. Four cases of 23 cases showed normal social media sites (Facebook). The survey asked: In one pressure of cerebrospinal fluid. The site of sentence explain how IIH headache has cerebrospinal fluid leakage were detected in 20 cases impacted/changed your life. How does it make you by vertebral MRI; cervical leak (10 cases), thoracic leak feel? (7 cases), lumbar leak (3 cases). Enhanced brain MRI was performed from three days to seven weeks later of Results: 512 people responded to the survey in one the disease onset in 24 cases; diffuse dural week. In November 2019 IIH UK had 445 members and enhancement were found in 23 cases and subdural over 2,000 unique visitors to its Facebook pages. hygroma/hematoma in 11 cases. Common words from responses were used to create a graphic (Figure 1) using WordleTM. Thematic analysis Discussion: ICFL should be considered in cases of a TH of participant comments identified themes in the data in occipital region. The enhanced MRI is useful for (changes in participation, mood and well-being, wider detection of ICFL. When there were no abnormality by symptoms and the overwhelming, debilitating nature initial brain imaging and examinations in a case of TH, of headache. enhanced brain MRI should be performed early. The cervical and thoracic MRI is useful for detection of a "It has completely changed my life over the past few leakage site. Attention is necessary for symptom years, it effects my work, my social life, everything" deterioration after an examination of lumbar puncture, since subdural hygroma/hematoma is not rare in "It makes me feel worthless and like a failure and chronic stage. suicidal, I'm a shadow of the person I once was."

"IIH headache is miserable and lonely. Nobody understands how debilitating it is. P122 Describing the impact of headache in the words of Figure 1. Visual representation of common people with Idiopathic Intracranial Hypertension – A descriptors of the impact of headache in IIH. qualitative social media study. 1 1 2 2 A. Denton , S. Williamson , O. Grech , S. Mollan , A. Conclusions: This survey shows the breadth and depth 2 Sinclair of the impact of headache in IIH. Current measures do 1 Idiopathic Intracranial Hypertension UK , Patient not capture all elements of resultant disability. Further Charity, Exeter, United Kingdom qualitative research is needed to explore the lived 2 University of Birmingham, Institute of Metabolism and experience of IIH to ensure that disability is not Systems Research, Birmingham, United Kingdom underestimated in this complex condition.

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Figure 1 with IHS criteria of CTH with, finding painful trigger point in physical examination and no contraindication for massage after written inform consent, enrolled to this study. They will be randomized to intervention or comparator group by block randomization method, then they receiving acceptable treatment of CTH with tablet Nortriptyline 10 mg daily for comparison or trigger point massage. Massage the trigger points in 8 different points for 1 min in circle direction and 3 times a day for 30 days performed. Participants report severity, frequency, duration of headaches and number of analgesic drugs in diary during week 1 and week 4. Then data based on dairy were analyzed. Minimal clinical important difference according to HIS guide line considered 30 % decrease in headache severity. Primary outcome was headache severity change assessed by mean Visual Analogue Scale (VAS) score (from 0 that indicate no pain to 10 that indicate severe pain) change in week 4 from the baseline. Secondary outcomes were change in headache duration, frequency and number of analgesic consumption. This trial has been registered in ClinicalTrials.gov (NCT04232046) and Mazandaran University of Medical Sciences was the source of funding.

Results: Trigger point massage decreased headache severity 45% vs 67.5% in comparator group (RR = 0.66 with 95%CI = 0.44-0.99 ; NNT =5,95% CI =2.29- 75.48, p=0.04,dcohen =- 0.41].

Conclusion: Trigger point massage is inferior in comparison to Nortriptyline for treatment of CTH.

P123 Efficacy of Trigger Points Massage in Severity of Chronic Tension Headache: An Unmasked, P124 Randomized, Controlled Trial Investigation of Eating Disorder and Psychiatric A. Sharifi-Razavi1, E. Sharifi-Razavi2, M. Tabarestani1 Comorbidity in Idiopathic Intracranial Hypertension 1Mazandaran University of Medical Science, Neurology, î Ulukan1, U. Çıkrıkçılı2, M. Sezgin1, E. Berberoğlu2, E. Sari, Iran Ekizoğlu1, E. Kocasoy Orhan1, B. Yücel2, B. Baykan1 2Segal Psychotherapy and Counseling Clinic, Sari, Iran 1Istanbul Faculty of Medicine, Istanbul University, Department of Neurology, Istanbul, Turkey Question: The present study tended to show trigger 2Istanbul Faculty of Medicine, Istanbul University, point massage is not inferior to standard drug Department of Psychiatry, Istanbul, Turkey treatment in patients with chronic tension headache (CTH). Objective: Obesity-related inflammation is among the recommended mechanisms in idiopathic intracranial Methods: This was a randomized, parallel, unmasked, hypertension (IIH) whose pathophysiology is still controlled study with active comparator group, on CTH unknown and effect of losing weight in treatment has patients referred to educational Clinic in Sari, Iran been proven by evidence-based research. In this study, (2016-2019). 80 patients (age between 18 to 60 years) it was aimed to investigate the association of 84

psychiatric comorbidities, specifically eating disorders Despite the prevalence is rare, NDPH considered (ED), with IIH process. important because it is persistent and often refractory to treatment and accompanied with disability and Method: Thirty patients with a diagnosis of IIH psychiatric comorbidities. according to Friedman criteria and age, gender, education and socioeconomic status matched 24 Objectives: The objective of this structured review is to controls were included to the study. Demographic describe existing data of NDPH and expand the data, family history and disease characteristics were knowledge to better understand this enigmatic recorded. Psychiatric evaluation of the participants was disorder. made according to DSM-5 diagnostic criteria. Beck Depression and Anxiety Inventories, Eating Disorder Methods: We performed PubMed and EMBASE search Diagnostic Scale (EDDS), Eating Attitudes Test (EAT-26), using the search terms "new daily persistent The Body Parts Dissatisfaction Scale were applied to headache" and "NDPH". all participants. Results: NDPH presents with sudden onset headache Result: The mean BMI of the patients was 33.3±7.16 which continues without remitting within 24 hours. kg/m2. Forty percent of IIH were diagnosed with Headache characteristics might resemble tension-type adjustment disorder with depressed and anxious headache or migraine or both. Prevalence of NDPH mood, major depression, obsessive-compulsive estimated to be 0.03% to 0.1% in the general personality disorder or social anxiety disorder. The population and it may occur more often in children and average score was 2.1±1.1 for IIH group and adolescents than in adults. Proinflammatory cytokines 1.2±1.2 for controls in EDDS; the difference was and cervicogenic problems might play role in its significant (p=.001). There was a significant difference development, however, the exact pathogenic (p=.004) in IIH group (21.9±8.4) compared to controls mechanism is anonymous. No specific treatment (16.1±8.1) in EAT-26. Three patients were diagnosed as strategy described for treatment of NDPH on the basis binge eating disorder and one case was defined as of clinical evidence, and it probably is best to treat "other specified feeding or eating disorder". In the control group no psychiatric pathology including ED There is no well-defined strategy for treatment of were detected. NDPH based on clinical evidence and it seems best to treat NDPH based upon the prominent headache Conclusion: Our results show that ED is frequent in IIH phenotype. A few treatment regimens have been used compared to controls, and suggest that it may have a in the literature with mixed results. However, even contributing role in the pathogenesis of the disease. aggressive treatment is ineffective or only partially Eating behavior must be questioned carefully for every effective. IIH patient to optimize the management. High prevalence of other psychiatric comorbidities affecting Conclusion: All aspects of NDPH discussed in this patient cooperation should also be considered for the review need further study. NDPH remains poorly treatment approaches. understood but very burdensome for the individual without any efficient therapy.

P125 New daily persistent headache: a systematic review on an enigmatic disorder N. Yamani1, J. Olesen2 1Tehran University of Medical Sciences, Neurology, Tehran, Iran 2University of Copenhagen, Danish Headache Center, Copenhagen, Denmark

Background: New daily persistent headache (NDPH) recognized as one type of primary headache disorders. 85

P126 Figure 1 Features of New daily persistent headache in a pediatric cohort. L. Papetti1, G. Sforza2, S. Tarantino1, F. Ursitti1, M. A. N. Ferilli1, R. Moavero1,2, M. Valeriani1 1IRCSS Bambino Gesù, Neuroscience, rome, Italy 2Torvergata University of Rome, Child Neurology Unit, Systems Medicine Department, Rome, Italy

Introduction: Our aim was to investigate the clinical features of primary new daily persistent headache (NDPH) in a cohort of pediatric patients. Figure 2 Methods: We retrospectively reviewed the charts of patients attending the Headache Centre of Bambino Gesú Children from the last ten years with history of persistent daily headache. The ICHD-III criteria were used for diagnosis. Statistical analysis was conducted by SPPS version 22.0 and χ2 test was used to study possible correlations between: - NDPH and population features (age and sex); - NDPH and headache qualitative features; - NDPH and response to prophylactic therapies.

Results: We included 380 patients with CPH (68% female, 32% male, age between 0 and 18 years). The frequency of NDPH was 15% (49/380). The frequency of NDPH was similar in females (57%) and males (43%) (p>0.05) and it tends to have low frequency in very young children less than 10 years of age. Features of pain resembles more frequently migraine headache rather than tensive headache (62% vs 38%) However we found a low frequency of nausea and vomiting in the NADPH population (28.6% vs 48.2%, p<0.05). We found that 75% of patients have an onset of the symptoms in the winter months (November-February), respect the remaining months of the year when the incidence is very low (p<0.05). Our results show that 58% of NDPH patients received a prophylactic therapy and the most used drug was amitriptyline. Positive response to therapy (reduction of attacks by at least 50% in a month) was detected in 30.6% of patients, while no outcome data were obtained from 63.3% of cases.

Conclusions: NDPH can be very disabling and correlate with seasonal factors. Considering also the long duration that the headache can have, it is recommended to undertake a prophylaxis treatment. Amitriptyline could be an effective choice in this type of headache.

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P127 Metabolite profiles also showed diagnostic value in IIH. Proton nuclear magnetic resonance spectroscopy- A receiver operating characteristic curve produced based metabolomic analysis has diagnostic potential using the 12 differential serum metabolites had an in Idiopathic Intracranial Hypertension and sheds light area under curve of 0.85 (95% confidence interval on disease processes 0.74-0.93). S. Y. Seneviratne1, Z. Alimajstorovic1, A. Yiangou1,2, J. Mitchell1,2, V. Vijay1,2, O. Grech1, S. P. Mollan3, C. Discussion and Conclusion: Our results establish that Ludwig4, A. Sinclair1,2,3 metabolic disturbances, predominant in CSF but also 1University of Birmingham, UK, Metabolic Neurology, manifesting in serum and urine, are present in IIH. This Institute of Metabolism and Systems Research, College suggests that IIH is not merely a disease of the brain of Medical and Dental Sciences, Birmingham, United and optic nerve but, a condition with significant global Kingdom metabolic dysregulation. 2University Hospitals Birmingham NHS Foundation Trust, Department of Neurology, Birmingham, United Based on our results, developing a serum-based Kingdom diagnostic tool could be valuable in IIH (important as 3Queen Elizabeth Hospital, University Hospitals there is a 40% diagnostic error rate). Future research Birmingham, Birmingham Neuro-Ophthalmology, into this metabolic signature in IIH may shed light on Birmingham, United Kingdom disease aetiology. 4University of Birmingham, UK, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, Birmingham, United Kingdom P128 Background: Idiopathic intracranial hypertension (IIH) Primary stabbing headache in children and predominantly affects young, obese women and is adolescents: is it a migraine precursor? characterised by high intracranial pressure (ICP) M. Valeriani1, F. Ursitti1, M. A. N. Ferilli1, R. Moavero1,2, causing severe, debilitating headaches and a risk of S. Tarantino1, G. Sforza1,2, C. Ruscitto1,2, F. Vigevano1, L. permanent blindness. The pathogenesis of IIH remains Papetti1 poorly understood however, recent evidence suggests 1Ospedale Bambino Gesù, Neuroscience and IIH likely involves systemic metabolic perturbations. Neurorehabilitation, Roma, Italy 2Tor Vergata University, Child Neurology Unit, Systems Aims and Methods: Our primary objective was to Medicine Department, Rome, Italy determine if systemic metabolic disturbances are evident in IIH. Proton nuclear magnetic resonance In pediatric age, primary stabbing headache (PSH) is an spectroscopy was used to perform untargeted, uncommon, but not rare, primary headache. The aims quantitative metabolomic profiling of cerebrospinal of our prospective study were to describe the clinical fluid (CSF), serum and urine samples from active IIH characteristics of the pediatrric PSH and to investigate patients (n=84) and controls (n=20), matched for age, whether in young subjects PSH is related to more gender and body mass index. common primary headaches. Nineteen consecutive patients with PSH, diagnosed according to the ICHD-III Results: 23 of 47 CSF metabolites, 12 of 45 serum criteria, were recruited. There were 13 girls and 6 boys, metabolites and 9 of 52 urine metabolites detected aged from 4 to 16 years (mean age: 9.9±3.4 years). In significantly differed in concentration between IIH our patients, pain had different locations, but it usually patients and controls. CSF Acetate was significantly involved the bilateral fronto-temporal region. Four higher in IIH patients than controls (p<0.01) and patients failed to identify a precise pain location. Stabs showed a significant positive correlation with were very short, usually lasting less than 1 minute. headache frequency (p<0.01) and severity (p=0.03). Only in one patient, each attack included several stabs Serum Pyruvate was significantly lower in IIH patients and lasted around 20 minutes. Pain intensity was than controls (p<0.01) and showed a significant usually judged to be mild to moderate. Strong pain negative correlation with ICP (p=0.02). intensity was referred only by 2 patients. Eight out of 19 patients presented with associated symptoms, such as photophobia (5), phonophobia (6), and nausea (3). Migraine was associated with PSH in 5 patients and 87

tension-type headache (TTH) in one. Episodic including 52 questions assessing management of TN. syndromes which may be associated with migraine, Participants were asked to describe freely which were such as infantile colic, motion sickness, limb pain, their first-choice drugs in the treatment of TN during recurrent abdominal pain, and vertigos, were referred pregnancy or breastfeeding and how often did they by 13 patients. In our pediatric case series, PSH clinical avoid each therapy. We present the data as frequency features were very similar to those described in and percentage. adulthood. However, while in adults PSH is frequently associated with migraine and TTH (Hagler et al., 2014), Results: One hundred and six participants completed only 32% of our young patients referred another the survey, 48.1% of them female and aged 43.2±10.46 primary headache. It is noteworthy that around 70% of years in mean. They reported to consult a mean our PSH patients had a clinical history of episodic monthly number of 6.84±6.87 (range: 1-40) TN syndromes. These elements suggest that in pediatric patients. Participants mentioned 14 different drugs as age PSH can represent an age-related phenotype of the first choice TN therapies for pregnant TN patients. The migrainous syndrome which will turn later into a more most frequently mentioned first choice therapy was typical migraine. Longitudinal studies in which pediatric pimozide in 21 cases (19.8%), followed by lamotrigine PSH patients are followed for several years will be in 16 (15.1%), eslicarbazepine in 11 (10.4%), anesthetic needed to confirm this hypothesis. blockades and clonazepam in 7 cases (7.7%). Figure 1 shows the listed therapies. Valproic acid was avoided by 95 (89.6%) of participants, phenytoin was avoided by 62 (58.5%), topiramate by 46 (43.4%), and P129 carbamazepine by 42 (39.6%) The least avoided Management of Trigeminal Neuralgia during therapy were anesthetic blockades, just by 2 pregnancy and breastfeeding: Results from a survey responders (1.9%). including 106 Spanish Neurologists. A. Mínguez-Olaondo1,2, D. García-Azorín3, N. Morollón Conclusions: There was no consensus about the first Sánchez-Mateos4, A. Gago-Veiga5, M. Torres-Ferrús6, P. choice TN treatment during pregnancy. Pimozide was Irimia2, A. L. Guerrero3, S. Santos-Lasaosa7 more frequently mentioned than others. Poor quality 1Hospital Universitario Donostia, Neurology, Donostia- evidence supports its use during pregnancy or San Sebastián, Spain childbearing. Anesthetic blockades were considered, 2Clínica Universidad de Navarra, Neurology, Navarra, probably due to safety reasons and immediate effect. Spain The need for protocols in this patient profile is evident 3Hospital Clínico Universitario de Valladolid, Neurology, given the heterogeneity of the care practice. Valladolid, Spain 4 Hospital de la Santa Creu i Sant Pau, Neurology, Figure 1. Preferred TN treatment during pregnancy Barcelona, Spain 5Hospital de La Princesa, Neurology, Madrid, Spain 6Hospital Universitario Valle de Hebron, Neurology, Barcelona, Spain 7Hospital Clínico Universitario Lozano Blesa, Neurology, Zaragoza, Spain

Background: Pregnant patients have been excluded from most of the clinical trials about trigeminal Neuralgia (TN) and many of the used drugs have known teratogenic effects. Its management will be more complex due to those therapeutic limitations. We aim to evaluate how Spanish neurologists deal with TN during pregnancy.

Methods: We invited all the neurologists ascribed to the Spanish Society of Neurology (SSN) and the Headache Study Group of the SSN to complete a survey 88

Figure 1 antiepileptic drugs and the others did not need preventive treatment.

Conclusions: The EF has particular characteristics that allow it to be differentiated from other headaches and neuralgias. Meningioma and mild head injury may be found in some cases. Since the pathophysiology of this type of pain is unknown, a possible link needs further research.

Figure 1

P130 Clinical characterization of Epicrania Fugax: a case series A. Jaimes Sánchez1, J. L. Hernández Alfonso2, J. P131 Rodríguez Vico1 Intracranial hypertension and systemic lupus 1Hospital Universitario Fundación Jiménez Díaz, erythematosus Headache Unit, Department of Neurology, Madrid, D. Turki1, S. Sakka1, S. Sallem1, S. Daoud1, N. Farhat1, Spain M. Damak1, C. Mhiri1 2 Hospital Universitario Fundación Jiménez Díaz, 1Habib Bourguiba Hospital, Neurology, Sfax, Tunisia Department of Neurology, Madrid, Spain Introduction: Idiopathic intracranial hypertension (IH) Objectives: To describe the clinical characteristics of a occurs most commonly in obese women of case series of patients with Epicrania Fugax (EF) reproductive age group. It has been reported associated to general diseases, like systemic lupus Methods: Retrospective analysis of 10 patients with EF erythematosus (SLE) to describe the manifestations, diagnosed in a Headache Unit in a tertiary hospital. treatments and outcomes of Idiopathic intracranial hypertension in patients with SLE. Results: There were seven women and three men. The mean age was 76,1 years (SD 18,1). The pain was Methods: We report an observation of a patient with always described as a brief electric shock-like. It lupus complicated by IH. followed a fixed trajectory across different dermatomes in all the cases (Fig A). One patient Observation: A 40 years old woman, without presented two variants of pain, each one with a overweight, was followed for a SLE with skin and different path, one in zig-zag and the other one linear arthritic involvement and nephrotic syndrome. Two (Fig A. 2). The pain was bilateral in one patient (Fig A. years after the onset of the renal complication of SLE, 9). Only two cases had triggers. None of the patients the patient present a headache with blurred vision. A had accompanying autonomic features. Three patients bilateral papillar oedema was discovered, revealing an had migraine comorbidity. One case was associated IH. Neuroimaging and cerebrospinal fluid (CSF) analysis with an ipsilateral meningioma and another one with a were normal, except for increased intracranial pressure mild head injury. Four patients responded to

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(24 cmH 2 0). The evacuation of 15 mL of CSF and high separately. All statistical tests were corrected for dose steroid therapy allowed symptoms regression. multiple testing (Benjamin-Hochberg method).

Discussion/Conclusion: Some cases of IH associated to Results: Comparing IIH to control samples we SLE with nephritis have been reported in literature. identified 21 differential metabolites in the serum with Young women are more frequently involved with in a significant fold change >2 (p <0.05). In the CSF there half of cases a diffuse proliferative glomerulonephritis. were 4 differential metabolites with a significant fold SLE has to be searched as an etiology of IH, in change >2 (p <0.05). A number of organic acids were particular in non-obese patients and when nephritis is overrepresented in these metabolites and were associated. Steroids should be considered as a first-line present in both serum and CSF. Pathway analysis treatment. suggested altered systemic glycolysis in IIH.

Conclusions: These results support IIH being a systemic metabolic disease, not merely a pathology of the brain P132 and optic nerve. The relative paucity of differential The systemic and CNS metabolite profile in IIH using metabolites in the CSF and their role in CSF dynamics is untargeted mass spectrometry analysis. of particular interest. The metabolite profiles require Z. Alimajstorovic1, J. Mitchell1, A. Yiangou1, L. Najdekr2, further mechanistic evaluation for potential disease A. Jankevics2, G. Lloyd2, V. Vijay1, O. Grech1, R. biomarkers and therapeutic targets. Ottridge1, S. Mollan3, W. Dunn2, A. Sinclair1 1University of Birmingham, College of medical and dental sciences, Birmingham, United Kingdom 2University of Birmingham, School of Biosciences, P133 Birmingham, United Kingdom Persistent idiopathic facial pain: Guidelines to the 3University hospitals birmingham, Birmingham Neuro- general practitioners Ophthalmology Unit, Birmingham, United Kingdom L. Melek1 1Alexandria University, Oral and Maxillofacial Surgery, Question: Idiopathic intracranial hypertension (IIH) is a Alexandria, Egypt disease characterised by raised intracranial pressure (ICP). IIH occurs predominantly in women with Persistent idiopathic facial pain (PIFP), previously called obesity; however the underlying pathogenesis is not "atypical facial pain", is a diagnostic entity that fully understood [1]. Evidence is mounting to suggest describes chronic facial pain without evidence of that IIH is a systemic metabolic disease with patients structural or other specific causes of pain. Most of the noted to have truncal adiposity correlating closely with data clearly indicate that PIFP is a rare disorder. It is degree of ICP elevation [2] and a unique profile of more common in women, and the mean age of onset is systemic and cerebrospinal fluid (CSF) androgen excess in the mid forties. Careful interdisciplinary [3]. collaboration is needed to establish the diagnosis and management of persistent idiopathic facial pain (PIFP). We aimed to utilise unbiased liquid chromatography- The diagnostic criteria for PIFP include the presence of mass spectrometry (LCMS) analysis to define the daily or near daily pain that is initially confined but may systemic and CSF metabolite profile in IIH compared to subsequently spread, which cannot be attributed to controls that could inform on underlying disease any pathological process. So, the diagnosis of PIFP is mechanisms. mainly done by exclusion of other disorders.

Methods: Samples were collected from IIH patients References: (n=65 serum and n=63 cerebrospinal fluid (CSF)) all with active disease (lumbar puncture pressure >25 1. R. Benoliel, C. Gaul, Persistent idiopathic facial pain, cmCSF and Frisén papilloedema grade ≥1) on the day Cephalalgia 37(7) (2017) 680-691. of sample collection. Healthy controls with obesity were matched for age, gender and BMI (n=20). LCMS 2. S. Maarbjerg, F. Wolfram, T.B. Heinskou, P. Rochat, was performed applying two assays to profile water- A. Gozalov, J. Brennum, J. Olesen, L. Bendtsen, soluble metabolites and lipids (non-polar metabolites) 90

Persistent idiopathic facial pain - a prospective or XeominTM, Merz Pharmaceuticals, Germany). Mean systematic study of clinical characteristics and dosage of BoNT/A used were 35.7 U. All patients were neuroanatomical findings at 3.0 Tesla MRI, Cephalalgia evaluated by using VAS scale and Patient Global 27 (2016) 27 Impression of Change (PGIC) at baseline and 5 weeks after injection. 3. S. Headache Classification Committee of the International Headache, The International Results: 5 weeks after injection, all patients Classification of Headache Disorders, 3rd edition (beta experienced a significant reduction of VAS (mean version), Cephalalgia 33(9) (2013) 629-808. improvement: 60.8%) and PGIC scores compared to baseline. Benefit persisted over subsequent weeks and booster treatments. No significant adverse effect was reported. P134 BOTULINUM NEUROTOXIN (BoNT) injection for Conclusions: BoNT injection appears to be a safe and refractory trigeminal neuralgia: a case series from a effective treatment for refractory TN type 2. RCTs are single center. needed in order to confirm our results. Valente M, Lettieri C, Gigli GL Department of Neurosciences, University Hospital, Udine, Italy M. Valente1, C. Lettieri1, G. L. Gigli1 P135 1Neurological Clinic University of Udine, Udine, Italy Results from a pilot randomized controlled trial of a community-based mindfulness-based stress reduction Introduction: Classical trigeminal neuralgia (TN) can be intervention versus usual care for moderate-to-severe distinguished in TN pure paroxysmal and TN with migraine headache concomitant continuous facial pain (ICHD, 2013). A. Pressman1, A. Jacobson1, H. Law1, R. Stahl2, A. Botulinum neurotoxin (BoNT) injection is Scott1, M. Goodreau1, S. Sudat1, A. Avins3 recommended as third line therapy for peripheral 1Sutter Health, Research, Walnut Creek, United States neuropathic pain. 2Insights, Santa Cruz, United States 3Kaiser Permanente, Research, Oakland, United States Possible mechanisms of action of BoNT in neuropathic pain include: inhibition of pain mediators release in Question: Does Mindfulness-Based Stress Reduction peripheral nerve terminal, dorsal root ganglia, and (MBSR), for moderate-to-severe migraine result in spinal cord neuron, thereby reducing inflammatory better outcomes than usual care(UC)? response and preventing development of peripheral and central sensitization. Reduction in pain frequency Methods: This study, set in California, was a two-arm, and visual analogue scale (VAS) after BoNT in TN has parallel-comparison, randomized controlled pilot trial. been reported in three RCTs and in three prospective, Feasibility outcomes included ability and time required open, case series. All patients suffered from classical to recruit 60 participants (> 18 in a 6-week period), and trigeminal neuralgia purely paroxysmal. Based on adherence to the MBSR treatment (attending at least 5 pathophysiology of peripheral neuropathic pain and of the 8 classroom sessions). Headache outcomes possible mechanism of action of BoNT, we included change in headache days and anxiety after 4 hypothesized that toxin injections could be effective months (4M). The MBSR arm was an eight-week also on classical trigeminal neuralgia with concomitant community-based MBSR class plus UC, and the control continuous facial pain (former TN type 2 or atypical group was UC alone. TN). We present our experience with BoNT treatment in this type of TN. Results: We successfully recruited 66 participants for this trial within the allotted time (Figure), with 15 Materials and Methods: we describe 7 MRI negative (23%) withdrawals at 4M. Adherence was good; 26 patients who have been suffering from refractory (76%) attended 5+ classes. In post-treatment classical TN with persistent background facial pain for qualitative interviews, of the 26 participants who several years. They were successfully treated completed MBSR, all spoke positively about their subcutaneously with BoNT/A (BotoxTM, Allergan, USA 91

experience, and 6 (23%) reported an improvement in P136 migraine symptoms. Headache days decreased by an Rates and predictors of relapse in medication overuse average of 0.8 in the MBSR group and increased by 0.8 headache: a clinic-based study from China. in the UC group. 4 (17%) of MBSR patients had a 50% D. Zhao1 reduction in headache days compared with only 1 (4%) 1the First Medical Centre, Chinese PLA General of the UC. Moderate-to-severe anxiety in the MBSR Hospital, Department of Neurology, Beijing, China group decreased from 28% at baseline (BL) to 5% at 4M while the UC group had minimal change (19% at BL Objective:This study aims to further assess the rates and 18% at 4M). and risk factors for relapse in medication overuse headache patients in China. Conclusions: Although the study was not powered for effectiveness, we observed positive trends in several Methods: The patients were admitted to neurology key migraine outcomes, and gained insight into which outpatient clinics at Chinese PLA General Hospital measures are likely to be influenced by MBSR. We (primarily for headache) and diagnosed with learned about the intermittent nature of the medication overuse headache. They responded well to recruitment process, refined our dropout estimates, 2 months of preventive treatment and completed a 1- and learned about adherence. To our knowledge, this year consultation. General information was collected, is the first pragmatic trial of MBSR for migraine in the including demographic characteristics (age, height, U.S., and it provides an excellent background for the weight and education level), the clinical features of the design and implementation of fully-powered trials to headache and the use of pain relievers (type, determine the effectiveness of MBSR for reducing frequency and duration). Differences in each factor headache frequency for patients with moderate-to- between the group with relapse and the group without severe migraine relapse were analyzed by the chi-square test or Wilcoxon test. Variables with a p<0.05 were included Figure 1 as independent variables in nonconditional logistic regression analysis.

Results: In total, 129 patients were recruited for this retrospective study. The relapse rate of the medication overuse headache patients at the 1-year follow-up was 24.8%. The relapse rate was significantly higher in the patients with migraine (29/97, 29.9%) than in the patients with tension-type headache (3/32, 9.4%) and in the patients with low education levels (middle school or lower) (24/77, 31.6%) than in those with high education levels (high school or higher) (8/52, 15.4%). Nonconditional logistic regression analysis showed that the type of primary headache was an independent risk factor for medication overuse headache relapse (odds ratio, 3.719, p=0.044).

Conclusions: The relapse rate of medication overuse headache patients at the 1-year follow-up was 24.8% in China. The type of primary headache is an independent risk factor for medication overuse headache relapse, and patients with migraine as the primary headache are more prone to relapse.

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P137 P138 Experience with botulinum toxin in the treatment of Headache and HIV in sub-Saharan Africa: a cross chronic post-traumatic headache sectional study at the DREAM Centre, Malawi B. Böhringer1 M. Leone1, L. Giani1, M. Mwazangati2, D. Uluduz3, T. 1BGU-Murnau, Painmanagement, Murnau, Germany Şaşmaz4, M. Kamponda2, V. Tolno2, G. Guidotti5, M. C. Marazzi5, T. J. Steiner6 Question: Chronic post-traumatic headaches are listed 1The Foundation of the Carlo Besta Neurological first among secondary headaches and are often Institute, IRCCS, Neuroalgology Unit, Milano, Italy difficult to treat. 2DREAM Program, Blantyre, Malawi 3Cerrahpaşa School of Medicine, Istanbul, Turkey They usually show up as tension headaches, less often 4Mersin University School of Medicine, Mersin, Turkey than migraine or cluster headaches. The chronification 5DREAM Program, Rome, Italy rate is 10-20%. 6Global Campaign against Headache, Lifting The Burden, London, United Kingdom Can chronic post-traumatic headache be affected by a therapy with botulinum toxin? Question: About 26 million HIV+ people live in sub- Saharan Africa (SSA). Are the prevalence and burden of Methods: In accordance with the injection schedule for common headache disorders magnified in this the treatment of chronic migraines, treatment with population with other health problems, or rendered botulinum toxin was carried out in 8 patients (7 men, 1 less important by the gravity of the latter? We aim to woman) with chronic post-traumatic daily headaches. answer this question, and present here the pilot enquiry. Treatment was started with 155 U BoNT-A and the BoNT dose could be increased to 195 U according to Methods: We conducted the study in collaboration the follow-the-pain principle. There was a repeat after with the DREAM (Disease Relief through Excellent and 12 and 24 weeks. Advanced Means) programme. DREAM, now active in 12 SSA countries, has provided health services to The clinical follow-up was carried out after 12, 24 and prevent and treat HIV/AIDS since 2002, following 36 weeks. >500,000 HIV+ patients1. At the DREAM Centre in Blantyre, Malawi, we administered a structured Results: In a prospective clinical observational study, questionnaire to consecutively attending HIV+ patients between January 2016 and October 2018, 8 patients aged 6-65 years who had been followed for at least 1 with post-traumatic daily headaches were included in year and gave their consent. the treatment study with BoNT (botulinum toxin). Results: Of 515 patients invited, all under antiretroviral Headache intensity and duration could be positively treatment, 15 (2.9%) declined. Among the 500 influenced in 7 of 8 patients with post-traumatic daily participants (mean age 34.2 [±13.0] years, 359 [71.8%] headache (improvement more than 30%). female), viral load was undetectable in 420 (84.0%). The 1-year prevalence of any headache was 402 In the e-poster, the individual follow-up regarding (80.6%), of any headache on ≥15 days/month 19 quantitative and qualitative intensities are shown. (3.8%), and of headache on ≥15 days/month with medication overuse (probable MOH) 4 (0.8%). Lost Conclusions: Botulinum toxin is a promising option in time from work or school because of headache the treatment of chronic post-traumatic headache averaged 0.6±1.8 days/month; lost time from household work was 0.9±2.7 days/month. Fewer than one third (160; 32.1%) had sought professional advice for headache in the last year.

Conclusions: Headache remains a health problem among HIV+ patients in SSA, imposing additional burden. The continuing study will characterize this in

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greater detail and highlight how headache disorders Finally, we collected clinical data and tested genetic should be included among other chronic disorders status of proband’s siblings. diagnosed and managed within the DREAM programme2. Results: Patient"s feature was suggestive for hyperostosis. Thus, neuroimaging studies displayed 1.Mancinelli S et al. Who will be lost? Identifying cranio-tubular hyperostosis, which particularly patients at risk of loss to follow-up in Malawi. The involved the skull, with multiple cranial nerve DREAM Program Experience. HIV Med 2017 18(8):573 entrapment in cranial foraminal and altered structure 2.Leone M et al. What headache services in sub- of upper airways. Moreover, neuroimaging findings Saharan Africa? The DREAM program as possible and CSF monitoring gave evidence of IH and model. Cephalalgia 2019 39(10):1339 polysomnography revealed an obstructive sleep apnea (OSA). Genetic test detected the p.Gln24X mutation in homozygous state in the proband and in heterozygous state in his family. P139 Headache due to intracranial hypertension secondary Conclusion: This is the first Italian family with to sleep apnea in hyperostosis sclerosteosis. We also described the presence of L. Rapisarda1, G. Demonte1, C. Bombardieri2, F. intracranial hypertension due to OSAS in a patient with Roccia3, M. Gagliardi4, G. Annesi4, R. Procopio4, A. sclerosteosis. We hypothesize that OSAS is due to Gambardella5, F. Bono1 abnormal structure of the patient’s splanchnocranium 1A.O.U. Mater Domini, Neurology Unit, Center of as consequence of the hyperostosis of the skull. Headache and Intracranial Pressure Disorders, Therefore, it is advisable to investigate the ventilator Catanzaro, Italy disturbances secondary to a structural bone alteration 2A.O.U. Mater Domini, Institute of Neuroradiology, in these patients, as it might cause IH. In conclusion Catanzaro, Italy this finding expands the clinical spectrum of 3A.O.U. Mater Domini, Institute of Rehabilitative hyperostosis. cardiology, Department of medical sciences, Catanzaro, Italy 4National Research Council, Institute of Molecular Bioimaging and Physiology, Catanzaro, Italy P142 5Magna Graecia University, Institute of Neurology, Harlequin syndrome as a rare complication of cervical Catanzaro, Italy artery dissection L. Kalashnikova1, M. Gubanova1, A. Belopasova1, L. Question: Hyperostosis is an uncommon cause of Dobrynina1 severe headache secondary to progressive bone- 1Research Center of Neurology, 3rd Neurological overgrowth in the skull. We aim to describe the clinical Department, Moscow, Russian Federation presentation and the ventilatory disturbances, imaging evaluation, treatment and genetic evaluation in the Introduction: Cervical artery dissection (CeAD) is the first Italian family with sclerosteosis. common cause of ischemic stroke (IS) in young adults and one of the causes of secondary headache. Methods: We described a 36-years-old Italian man Harlequin syndrome (HS) is a rare condition in which with a history of refractory headache, nocturnal one half of the face fails to flush and sweat due to snoring, multiple cranial nerve palsy and peculiar facial damage of the sympathetic fibers on the ipsilateral dysmorphism. The patient performed an accurate side. neuroimaging study with cranial CT, brain MRI, MR venography and a 1-hour CSF pressure monitoring Aim: To describe a case of Harlequin syndrome through lumbar spinal needle to assess the presence of associated with ipsilateral headache and Horner intracranial hypertension (IH). Moreover, it was also syndrome in the setting of internal carotid artery performed a nocturnal polysomnography to evaluate dissection. the presence of sleep apnea. It was also performed genetic analysis looking for SOST gene mutations.

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Clinical observation: Patient L. at the age of 43 years Figure 2 with complaints of intense headache in the right frontal area and pain at the angle of the lower jaw on the right. A few weeks later, she also reported separate episodes of distinct left sided facial flushing triggered by heat, exertion or emotion as evidenced by a photo that she provided (Fig.1). The photo clearly demonstrates the distinct line of demarcation down the middle of her forehead. On exam, she had right sided miosis, ptosis. The were no lesions on brain MRI. Right internal carotid artery dissection was verified by MRI (T1 fat saturation) (Fig.2) and MR angiography.

Typically, the unilateral increased discoloration focuses the attention on that side as abnormal; however, the underlying sympathetic neural injury occurs on the P143 non-flushed side of the face. Headache, but not obesity, is a risk factor for hypertension caused by obstructive sleep apnea The strictly left-sided facial flushing that occurred with S. Khamsai1, K. Sawanyawisuth1 exertion and loss of sweating on the right, non-flushed 1Khonkaen university, Medicine, Khonkaen, Thailand side of the face, suggestive for sympathetic dysfunction on the right and consistent with Harlequin Background: Obstructive sleep apnea (OSA) has been syndrome. known to be a secondary cause of hypertension by the JNC 7 since 2003. The prevalence of OSA in Conclusion: HS is a disorder of the autonomic nervous hypertension is ranged from 30-80%. There is limited system. Ipsilateral sympathetic fiber injury can be the data on risk factors of OSA with hypertensive patients. underlying etiology due to internal carotid artery This study aimed to evaluate clinical predictors of dissection; appropriate examination is important to obstructive sleep apnea (OSA) in hypertensive patients. rule these conditions out. Clinicians should consider the point that HS could occur as a first sign of some Methods: This study was a cross-sectional study and serious conditions. conducted at hypertension clinic, Srinagarind Hospital, Khon Kaen University, Thailand. We enrolled all Figure 1 hypertensive patients treated at the clinic. The definition of OSA as a cause of hypertension is defined by presence of apnea-hypopnea index of more than 5 events/hour by polysomnography and no other identifiable causes of hypertension. Prevalence of OSA in hypertensive patients was calculated. Risk factors for OSA in hypertensive patients were also studied by using multivariate logistic regression analysis.

Results: There were 726 hypertensive patients treated at the clinic. Of those, 324 patients (44.63%) were diagnosed as OSA. Approximately one-third of patients with and without OSA were randomly studied; 106 OSA patients and 147 non-OSA patients. There were 4 independent factors associated with OSA induced hypertension age, sex, history of snoring, and history of headache. Headache had an adjusted odds ratio (95% confidence interval) of 3.58 (1.51, 8.48).

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Conclusion: The independent predictors for OSA in P145 hypertension were age, sex, history of snoring, and Sentinel headache before transient ischemic attacks history of morning headache but not obesity. and ischemic stroke E. R. Lebedeva1, A. V. Ushenin1, N. M. Gurary2, D. V. Gilev3, J. Olesen4 1the Ural State Medical University, International P144 Headache Center "Europe-Asia", Yekaterinburg, Headaches during pregnancy: Management Protocols Russian Federation within the Emergency Department 2MU "New Hospital", Neurology, Yekaterinburg, M. Payá Montes1, S. Diaz Insa1, C. Nieves Castellanos1, Russian Federation F. J. Cabello Murgui1 3the Graduate school of Economics and Management, 1Hospital La Fe, Neurología, Valencia, Spain the Ural Federal University, Department of Econometrics and Statistics, Yekaterinburg, Russian Introduction: Despite headaches being a frequent Federation reason for medical consultation within women of 4Danish Headache Center, Department of Neurology, reproductive age there is limited information available Rigshospitalet-Glostrup, University of Copenhagen, during pregnancy. In the present study, we will analyze Neurology, Copenhagen, Denmark the management of this particular pathology within the emergency department context in order to assess Objective: There are no previous studies of sentinel the need for a protocol of action. headache in transient ischemic attacks (TIA) and no previous controlled studies of sentinel headache in Methods: A retrospective study of patients within the ischemic stroke. The purpose of the present study was emergency department with the diagnosis of to evaluate the presence of such headache and its headaches took place between April 2018 and April characteristics as compared to a simultaneous control 2019. The following variables were assessed: point of group. care, treatment given, further tests, neurologist assessment requirement and discharge treatments. Methods: Eligible patients with TIA (n=120, mean age 56.1, 45% males) had focal brain or retinal ischemia Results: 61 patients were surveyed; 58% received point with resolution of symptoms within 24 hours without of care within general emergency department with presence of new infarction on MRI with DWI (n=112) or 42% remaining in obstetric emergencies. Only 50.8% of CT (n=8). Eligible patients with stroke (n=550, mean women received treatment related to headaches. age 63.1, 54% males) had first-ever acute ischemic Paracetamol was used in 54.8% of cases, metamizol in stroke with presence of new infarction on MRI with 41.9%, NAIDs and pethidine in 6.4% and with oxygen DWI (n=469) or on CT (n=81). As a control group we therapy in the final 16.1%. No triptans, corticosteroids studied in parallel patients (n=192, mean age 58.7, 36% or lidocaine were administered within the surveyed males) who were admitted to the emergency room sample. without acute neurological deficits or serious neurological or somatic disorders. All these patients In 10 out of 31 women the same drug as previously were extensively interviewed soon after admission received was prescribed. 28 patients showed using validated neurologist conducted semi-structured improvement with 10 cases needing neurologist interview forms. evaluation. One woman was admitted to hospital. 10 cases return to emergency department because of lack Results: We defined sentinel headache as a new type of pain control. of headache or a previous kind of headache with altered characteristics (severe intensity, increased Conclusion: Headache treatment in the emergency frequency, absence of effect of drugs) within seven department during pregnancy is suboptimal. As our days before TIA or stroke. Totally 22 patients (18.3%) study suggests, a protocol that collects different had sentinel headache within the last week before TIA therapeutic options for the treatment of pregnant and 81 patients (14.7%) had sentinel headache within women as well as indicated complementary follow up the last week before stroke. Only two patients (1.0%) tests and neurology evaluation is required. had headache with altered characteristics before admission (p<0.0001). Attacks of arrythmia during 96

seven days before stroke were significantly associated Conclusion Dialysis -induced headache seems to be the with sentinel headache (p=0.04, OR 2.3; 95% CI 1.1- most prevalent headache (and not be related with 4.8). coexisting primary headache) among patient undergoing Hemodialysis. Recognizing it is important in Conclusions: A new type of headache and a previous order to prevent it and improve the quality of life of kind of headache with altered characteristics during patient under this treatment. one week before TIA and stroke are significantly more prevalent than in controls. Such sentinel headache should prompt urgent examination for stroke prevention. P147 Headache and the sporadic form of meningioangiomatosis P. Řehulka1, M. Hermanová2, M. Brázdil1,3 P146 1St. Anne’s University Hospital and Faculty of Medicine, Dialysis – induced headache Masaryk University, Department of Neurology, Brno, P. Djamandi1, L. Shehaj2, H. Gorica1, N. Mitrollari1, M. Czech Republic Rroji2, J. Kruja1,3 2St. Anne’s University Hospital and Faculty of Medicine, 1UHC Mother Teresa, Neurology, Tirana, Albania Masaryk University, First Department of Pathological 2UHC Mother Teresa, Nephrology, Tirana, Albania Anatomy, Brno, Czech Republic 3Faculty of Medicine, UMT, Neurology, Tirana, Albania 3CEITEC - Central European Institute of Technology, Masaryk University, Behavioral and Social Introduction: Dialysis -induced headache (ICHD-3; Neuroscience Research Group, Brno, Czech Republic 10.2) is one of the most frequent acute complications of Hemodialysis. It is thought to be related with Meningioangiomatosis is a rare, chronic, benign lesion amount of water and some electrolyte shift. of the meninges and adjacent cortices characterized by focal vascular and cellular proliferation. Sporadic form Aim: To detect Dialysis - induced headache in patient of meningioangiomatosis (not associated with undergoing dialysis. Investigating its features, it is neurofibromatosis type 2) often causes epilepsy. important in order to prevent it and improve the Moreover, cases with headache have been reported. quality of life of patient under this treatment. However, there is scarce evidence to establish whether meningioangiomatosis might be considered as a Methodology: In this study we investigate the causative disorder of secondary headache. We present characteristics of headache occurring during the the case of 59-year-old woman who underwent hemodialysis. Sixty-eight patients, (35 female) with epilepsy surgery and a sporadic form of chronic renal failure on regular dialysis for at least 12 meningioangiomatosis in the right temporal lobe was months, in the Hemodialysis unit of UHC "Mother proven. Our aim is to describe the clinical phenotype of Theresa" participated. The dialysis solution contained headache prior and after the epilepsy surgery. bicarbonate for all participants. All patients received the same questionnaire and patient diagnosed with primary headache were excluded. P148 Results: We found 41% (28 patients) meeting criteria Characterization of persistent headache attributed to for Dialysis- induced headache. The differences of past stroke 1 1 1 1 urea values and mean systolic blood pressure pre- A. Rêgo , F. Bernardo , R. Pinheiro , S. Delgado , E. 1 and post - dialysis were statistically significant. Parreira 1Hospital Prof. Doutor Fernando Fonseca, Neurology, The most prevalent features of dialysis induced Lisboa, Portugal headache were temporal location, pulsatile quality, mild to moderate severity and lasting < 3.5 hours. Question: Persistent headache attributed to past stroke (PHAPS) is a controversial entity, recently included in the new ICHD-3 classification despite being

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described only in retrospective studies. Does it really P149 exist? The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) baseline characteristics: a multicentre, Methods: We selected all patients with headache randomised controlled trial assessing bariatric surgery associated with acute stroke (HAAS) from a versus a community weight loss programme prospective, single-center registry of all patients with S. Mollan1, J. Mitchell2, R. Ottridge3, A. Yiangou2, V. acute stroke admitted to a Neurology ward between Vijay2, Z. Alimajstorovic2, R. Woolley3, S. Patel3, N. Ives3, November 2018 and December 2019. We analysed T. Matthews1, B. Wakerley4, A. Ansons5, S. Hickman6, J. demographic, clinical and neuroimaging data. We Benzimra7, M. Lawden8, B. Davies9, C. Rick10, R. assessed the follow-up with a phone call questionnaire Singhal11, A. Tahrani2,11, A. Sinclair2 at 3 months. 1University Hospitals Birmigham NHS foundation trust, Neuro-Ophthalmology, Birmingham, United Kingdom Results: Among 122 patients with acute stroke from 2University of Birmingham, Institute of Metabolism and the registry, only 28 patients (23.0%) had HAAS. From Systems Research, Birmingham, United Kingdom these, only 19 patients answered the 3-month follow- 3University of Birmingham, Birmingham Clinical Trials up questionnaire (67.9%) and were included in this Unit, Birmingham, United Kingdom study. Median age was 59 years (IIQ 46-76) and there 4Gloucestershire Royal Hospital, Neurology, was a male predominance (63.2%). Pain localization Gloucester, United Kingdom was more frequently anterior and bilateral and when 5Manchester University NHS Foundation Trust, unilateral it was not typically ipsilateral to stroke. Pain Manchester Royal Eye Hospital, Manchester, United was usually mild to moderate in all cases. The majority Kingdom (73.7%) had less than two episodes a month. Only 3 6Sheffield Teaching Hospitals NHS Foundation Trust, patients referred highly frequent episodes of 15 days a Neurology, Sheffield, United Kingdom month. Eight patients (42.1%) were pain free at the 3- 7Royal Devon and Exeter NHS Foundation Trust, West month follow-up. Of the 11 patients (57.9%) that had of England Eye Unit, Exeter, United Kingdom persistent headache at the 3-month follow-up, 7 8Leicester General Hospital, Neurology, Leicester, (63.6%) clearly suffered from previous chronic United Kingdom headaches (PCH). However, they all mentioned a 9Royal Stoke University Hospital, Dept. of Neurology & different kind of headache. From the 4 patients Midlands Regional Headache clinic, Stoke-on-Trent, without a previously known headache history, 3 had United Kingdom other reasons for a secondary headache and reported 10University of Nottingham, Nottingham Clinical Trials conflicting information regarding the existence of a Unit, Nottingham, United Kingdom PCH. 11University Hospitals Birmingham NHS Foundation Trust, Upper GI and Minimally Invasive Unit, Conclusion: In this study, only 11 out of 122 stroke Birmingham, United Kingdom patients (9.0%) referred persistent headache at the 3- month follow-up. The majority had a PCH, although Background: Weight loss is an important modifiable with a change of the usual pattern of headache. Only risk factor in Idiopathic Intracranial Hypertension one patient with persistent headache at the 3-month (IIH)1,2. The aim is to report the clinical and visual follow-up did not have a clear PCH history. This study features in the IIH Weight Trial (IIH:WT). may question the existence of PHAPS. Methods: IIH:WT was a prospective, multi-centre, open-label, parallel group, randomised controlled trial. Individuals with active IIH, defined according to the modified IIH criteria3, were randomised to a bariatric surgery pathway or to a commercial weight management programme (Weight Watchers) (1:1). IIH symptoms; quality of life (SF-36); visual function (logMAR visual acuity, Humphrey Visual Field (HVF) perimetric mean deviation (PMD)); and papilloedema measured by optical coherence tomography (OCT) and Frisén classification grading were collected. They were 98

grouped by PMD (Mild >-2dB; Moderate -2 to -7dB and secondary causes have been described to date. severe <-7dB). Lamotrigine is one of the most effective drug used in this type of headache. Results: 66 women were enrolled with a mean (standard deviation (SD)) age of 32.0 (7.8) years. The Methods: A 67 years old woman started in 2008 to mean (SD) body mass index of 43.9 (7.0) kg/m2. have left facial paroxysmal episodes of electrical pain Headache was the most common current symptom and was diagnosed as trigeminal neuralgia. She (95%), pulse synchronous tinnitus occurred in 74% and received treatment with high doses carbamazepine 73% reported visual loss. The mean (SD) PMD in the and oxcabamazepine with poor improvement. She was worst eye was -3.6 (3.7) dB, (range -0.2 to -19.8 dB). treated with surgery (Mullan technique) twice in 2012 Patients with mild visual loss (36.4%) had less and 2013, with no response. In a MR study in 2016, an papilloedema, headache disability and a shorter aneurism of cavernous portion of left ICA was found duration of IIH, compared to those with moderate (figure), and was considered the cause of the (53.0%) or severe (10.6%) visual loss. There was a trigeminal neuralgia. It was embolized in September stepwise reduction in quality of life between the 2019 because a growth up. One month after the groups from mild to severe visual loss. embolization, she continued having episodes.

Conclusions and relevance: Patients within IIH:WT Result: Patient was attended in our Headache Unit. represent the full clinical spectrum of those with mild She described episodes lasting 5-10 seconds, of to severe visual loss, unlike previously published trials. electrical pain moving in a vertical linear trajectory They had typical symptoms, however compared to the from the left forehead to the left upper lip. Pain was literature had a higher portion of patients reporting accompanied with lacrimation. No triggers were headache and visual loss. described. She has a frequency of 20 paroxysms a day. During the 12 years of evolution, pain episodes always References: maintained the same characteristics. Because of the linear trajectory following from V1 to V2 dermatomes, 1. Mollan SP, et al.J Neurol Neurosurg Psychiatry. she was diagnosed of facial EF secondary to an 2018; 89(10): 1088–100. aneurism of ICA and we started treatment with 2. Mollan SP, et al.J Neurol Neurosurg Psychiatry. lamotrigine 150 mg a day, achieving a reduction of 2016; 87(9): 982–92. >50% in pain paroxysms. 3. Friedman DI, et al. Neurology 2013; 81:1159- 1165. Conclusion: This is a new case of a secondary EF and the first case of facial EF described. This case also shows the importance of the correct diagnosis of EF in order to choose the best possible treatment. In our P150 case, we think that a delayed effect of the FACIAL EPICRANIA FUGAX SECONDARY TO AN embolization and the election of lamotrigine, never ANEURISM IN INTERNAL CAROTID ARTERY: A NEW used previously in this patient, led to a significant SYMPTOMATIC CASE improvement. M. Gutierrez1, J. Galvan2, M. Schuller2, M. Galdamez2, A. Sierra Mencia1, A. L. Guerrero Peral1, D. García- Azorín1 1Hospital Clinico Universitario de Valladolid, Neurology, P151 Valladolid, Spain PREVALENCE OF HEADACHES IN PATIENTS WITH 2Hospital Clinico Universitario de Valladolid, EPILEPSY IN UZBEKISTAN Interventional Neurorradiology, Valladolid, Spain D. Daminov1 1Tashkent Medical, Neurology, Tashkent, Uzbekistan Background: Epicrania fugax (EF) is a primary headache consisting of paroxysmal episodes of pain, which Background: Epilepsy and headaches are common radiate in a lineal or zigzag trajectory crossing different episodic and paroxysmal neurological disorders and dermatomes of the cranial region. Only three relationship between this disorders still is poorly understood. 99

Purpose: The goal of this study was to estimate the P152 frequency of headache occurrence in adult patients Usefulness of Transcranial Color Doppler in the with epilepsy, to determine the temporal association diagnosis of Reversible Cerebral Vasoconstriction of epileptic and migraine attacks. Syndrome R. Oliveira1,2, P. Batista2,3, N. Inacio2, R. Gil-Gouveia1,2 Materials and methods: In this study we investigated 1Hospital da Luz, Headache Center , Lisboa, Portugal 110 patients with confirmed diagnosis of epilepsy. The 2Hospital da Luz, Neurology, Lisboa, Portugal group consisted of 40 (36%)male and 70 (64%) female 3Centro Hospitalar Lisboa Norte, Vascular Surgery, patients. The age of the patients varied from 14 to 55 Lisboa, Portugal years. Criteria for the diagnosis of epilepsy were based on clinical symptoms and electroencephalographic Introduction: Reversible cerebral vasoconstriction findings (EEG), (MRI) The time of headache onset in syndrome(RCVS) diagnosis is based on the occurrence relation to the epileptic attack was defined of thunderclap headache(THC) without subarachnoid as:preictal;ictal; postictal; interictal. hemorrhage(SHA) supported by brain imaging and angiographic findings. Results: In a group of patients with epilepsy, migraines and epilepsy were diagnosed in 30 (27.27%) 10 of them Objective: To establish the validity of transcranial color were diagnosed migraine with aura, 25 (22.76%) doppler(TCD) in supporting the diagnosis of RCVS patients had epilepsy and other non-migraine headaches, while epilepsy without headaches was Methods: All patients with the diagnosis of TCH found in 55 (50%) patients. Out of the total number of without SHA of our neurology and headache center in patients suffering from epilepsy and migraines, 80% the last 10 years were identified through an were females. Out of the total of 110 patients, 80 anonymized database search. Of these, we identified (72.7%) had a generalized type of seizure (with or patients with clinical diagnosis RCVS, defined by ICHD- without focal onset) and partial seizures were found in 3 criteria and cerebral vasospasm, detected by TCD. 30 (27.27%) patients. Temporal association of epileptic and migraine attacks was found in 60 (54.5%) out of Results: Twenty-nine patients (89.7% female, 110 patients with epilepsy and migraines. 25 of them 42.9±11.1 years) were enrolled, 21.4% with (22.76%) had preictal migraines while in 35 (31.8%) cardiovascular risk factors. A causative factor for RCVS patients migraines occurred postictally. was identified in 16 patients(55%) including drugs, valsalva maneuvers and sexual activity. Complications Conclusion: The results of this study indicate that the occurred in 5 patients (17.2%), such as delayed prevalence of headaches associated with one third cerebral ischemia, seizures, high convexity SAH and patients with epilepsy, while the prevalence of persistent hemiparesis. Initial TCD was conducted a migraines in the same group was two times low. median duration of 15(7-23) days after headache Preictal migraine headaches occurred significantly onset. Initial mean MCA flow velocity(VMCA) was more often than other non-migraine headaches, but 135.7± 17.0 cm/sec and mean maximum VMCA was postictal migraine headaches occurred significantly less 138.3± 17.2. Vasospasm was mild in 21 patients (72%) often than other, non-migraine headaches. and moderate in 8 (28%). Complete normalization of the flow velocity occurred in a median duration of 41(30-70) days after headache onset and 24(11-47) days after initial TCD. Recurrence of RCVS occurred in three patients (10.3%). TCD had a sensitivity of 74% and a specificity of 66.7% in the diagnosis of RCVS, with a positive predictive value of 90.2%.

Conclusion: TCD may be a useful tool in the identification of vasospasm, supporting the diagnosis of RCVS in patients presenting with TCH without SHA.

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P153 P154 Headache following cerebrovascular events and Pericranial nerve block in patients with headache correlation of cardiovascular biomarkers/ risk factors difficult to treat: an option in a emergent country. with primary and secondary headache disorders R. Dominguez-Moreno1, F. A. Vega-Boada2 K. Kaltseis1, L. Domig1, S. Komarek1, F. Frank1, M. 1Instituto Nacional de Ciencias Médicas y Nutrición Knoflach1, G. Brössner1 "Salvador Zubiran", Neurology and Neuropsychiatry, 1Medical University Innsbruck , Neurology, Innsbruck, Ciudad de Mexico, Mexico Austria 2Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran", Neurology and Psychiatry, Ciudad Background: Migraine is a neurovascular disorder that de Mexico, Mexico affects about 15% of the general population, mainly women. A link between migraine and ischemic stroke Objective: To describe the use of pericranial nerve has been well established over the past decades, block in patients wiht primary headache and orofacial particularly for women who suffer from migraine with pain who failed or no tolerate oral preventive aura. The reasons that drive this solid association are treatments. poorly understood and possibly multifactorial, but a better understanding would have enormous clinical Methods: we perform pericranial nerve block (greater- implications. lesser occipital nerves, supraorbital and supratrochlear nerves) using lidocaine 2% in patients with difficult to Objectives: Our aim is to take a structured lifetime treat headache, including chronic migraine. headache history of stroke patients to compare primary headaches prior the cerebrovascular event Results: Was 20 patients who were blocked, 16(76.2%) and secondary headaches following the event and the were woman, median age was 53.4 + 15.1 years-old, changes in the primary headaches, respectively. The the headaches frecuency was: chronic migraine 52.4%, main focus will be on migraine with/ without aura. We type tensional 9.5% and occipital neuralgia 9.5%. the will analyze if those patients have a specific intensity of pain was 8.7 + 1.3 in VAS, the median cardiovascular profile and whether there exists a duration of headahe was 12 years, the median correlation of the migraine subtypes with specific risk headache-days per month was 15-25. Lidocaine 2% factors and/ or biomarkers. was use at median dose of 6 mls, 71.4% of patients has a inmediat response to disminution of pain to 0-3 in Methods: Between 2014 and 2018, the STROKE-CARD VAS. The general response rate is 76.2% and we are trial was conducted and more than 2000 patients after activately recruiting, the duration of effect is in acute ischemic stroke or TIA were prospectively evaluation. enrolled. Numerous baseline characteristics and various disease markers characterizing cardiovascular Discusion: the response rate is high and early in risk for each individuum were collected. In the Follow- patients with difficult to treat headaches, but the up study of this trial, we will also include a structured duration of effect is going to be determined headache interview for each participant comprising a lifetime history of primary and secondary headache Conclusion: Pericranial nerve block is cheap, easy to prior and post the cardiovascular event. Characteristics perform, safe treatment to patients who present of headaches are collected using a headache difficult to treat headache and who don´t have other questionnaire enabling headache classification alternative treatmen like neuroestimulators or according to the International Headache Society onabotulin toxin A. criteria. We expect approximately 1000-1200 participants in the Follow-up Study, of which 150-200 are estimated to suffer from migraine.

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P155 3Frishberg B, Rosenberg J, Matchar D, et al. Evidence- Neurological manifestations as the best predictor of based guidelines in the primary care setting: abnormalities in tomography in Mexican patients neuroimaging in patients with nonacute headache. Am attended by emergency headache Acad Neurol. 2000. R. Garcia1, J. Hernandez1, R. Carrera1 1Mexican Institute of Social Security, Neurology, 4Francis M. Neuroimaging in Headache Disorders. J Mexico City, Mexico Headache Pain Manache. 2017;2(1).

Question: To identify the probability of an abnormal computed tomography (ACT) in Mexican patients with abnormal neurological examination (ANE). P156 Presence of Headache in Multiple Sclerosis Patients Methods: We carried out an observational, case series, receiving B-cell depleting therapies compared to analytical, and retrospective study in the Neurology placebo: A Systematical Review Approach. service at Speciality Hospital of National Medical T. Mavridis1, N. Papagiannakis1, M. Breza1, A. Center XXI Century. Information was collected from Laskaratos2, D. D. Mitsikostas1 urgently requested interconsultations of patients with 1Eginition Hospital, 1st Neurology Department, Athens, headache from January to June 2019, obtaining red Greece flags (RF) and CT, performing Chi-square. 2National and Kapodistrian University of Athens, Medical School, Athens, Greece Results: 46 patients with RF were treated; of this group, 15.2% (7) had an ANE, with 42.4% (3) of ACT Introduction: Patients with Multiple Sclerosis (MS) and neoplasms being the main cause. Of the remaining have an increased incidence of headache, whereas the 84.7% (39) with another RF, 5.1% (2) had ACT, finding mechanism and the various co-factors are poorly neoplasm and sinusitis. We found an OR 13.87 with understood. Among them, MS therapies are 95% CI 1.759-109.4439 (p 0.019). considered to play a role. Nonetheless, there is not enough data that corelates MS therapies with Conclusions: Headache is one of the main reasons for headache. consultation in neurology. Secondary headaches constitute up to 10% of the total headaches attended Objectives: The aim of the present study is to conduct in the emergency department1, for which there are RF a systematic review of the current literature on the that indicate the need for neuroimaging2. An ANE is identification of any possible association between B- more likely to be associated with abnormalities in cell therapies for MS and increased headache neuroimaging3; in spite of MRI has greater sensitivity incidence. than CT, in cases of subarachnoid hemorrhage, bone abnormalities and hydrocephalus, CT is preferred4. This Methods: Systematic literature search was conducted study shows in our population a greater probability of using PubMed/MEDLINE database and clinicaltrials.gov finding ACT in patients with ANE than with others RF, searching for articles and clinical trials of B-cell with neoplasms as main etiology; however, further therapies for MS (i.e. ofatumumab, ocrelizumab, studies are required. rituximab, cladribine) investigating a role in the increased incidence of headache in MS patients References: PRISMA guidelines for systematic reviews were applied. Double blinded clinical trials were assessed as 1Perkins A, Ondo W. When to worry about headache; eligible studies to level down and balance the nocebo Head pain as a clue to intracranial disease. Postgrad response. A random effects model was fitted with the Med. 1995;98:197-208. extracted data from the eligible studies.

2Phu T, Remmers A, Winther H, et al. Red and orange Results: In total 12 randomized-control trials were flags for secondary headaches in clinical practice. included in this study. The pooled relative risk of Neurology. 2019;92:134-144. headaches in MS patients receiving B-cell depleting therapies is 1.12 (95% CI 0.96 – 1.31; p-value = 0.14)

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compared to placebo. Headache was present in 18% of its hypoplasia was revealed in 3 patients (6%), only patients in the intervention group, and in 16% of vertebral arteries (VA) deformity, in one cases, one- patients in the control group. Heterogeneity score was sided in combination with asymmetry of blood flow in I2 = 24.75%. the internal carotid arteria (ICA)

Conclusion: Although headache is a very common Conclusions: Thus, in the group of patients without symptom among MS patients receiving B-cell depleting cephalic syndrome, but with anomalies of cerebral therapies, its incidence is comparable with patients vessels, hemodynamically significant changes in VA receiving placebo. Further analysis of each drug, as were observed, while pathological tortuosities and well as analysis of clinical trials regarding different underdeveloped ICA, although present, were therapeutic mechanisms is needed to extract safer hemodynamically insignificant in relation to cerebral conclusions. blood circulation

P157 P158 Evaluation of anomalies of cerebral vessels in patients αCGRP induced changes in cerebral and systemic without cephalic syndrome circulation; a TCD study M. Salokhiddinov1, F. Umarov1 D. Visočnik1, M. Zaletel1, M. Zupan1, B. Žvan1 1Tashkent Medical Academy, Neuroscience, Tashkent, 1Universit Clinical Centre of Ljubljana, Departmnet of Uzbekistan Vascular Neurology, Ljubljana, Slovenia

Question: The number of patients suffering from There is a growing interest in the role of calcitonin chronic headache accompanied by dizziness and gene-related peptide (CGRP) in migraine. It is not clear cephalic ringing is gradually increasing. whether intravascular αCGRP induce changes in Pathophysiology of migraine has been commonly cerebral and systemic hemodynamic. We explored the explained by trigeminovascular theory, although recent influence of αGRP intravenous infusion on studies have suggested that the cause of the migraine hemodynamic factors using transcranial Doppler (TCD). stems from cortical hyperexcitability. We hypothesize that αCGRP intravenous infusion might have significant intravascular effects on cerebral Methods: The study involved 50 patients treated in and systemic vessels. 2nd Clinics of Tashkent Medical Academy between 2015-2017 years. Anomalies of cerebral vessels Hemodynamic effects of αCGRP infusion were studied without cephalic syndrome were examined. Clinical- in twenty healthy subjects . TCD was used to measure neurologic, neurological imaging (MSCT with mean arterial velocity in the left middle cerebral artery angiography, DS ACS) was performed (vm MCA ) and in the right posterior cerebral artery (vm PCA ). At the same time we measured mean Results: The study showed that 50 (100%) patients arterial pressure (MAP) and heart rate (HR) by with anomalies of cerebral vessels without cephalic plethysmography. Partial pressure at the end of expiry syndrome were examined. Among them, women are (Et-CO2) was detected by infrared capnometer. TCD 15 (30%), men are 35 (70%). The main complaints of Multi-Dop X4 software was used to calculate vm MCA these patients were systemic dizziness in 43 (86%) and vm PCA, MAP, HR and Et-CO2 in defined time cases, nausea and vomiting in 9 (18%), and hearing loss intervals before, during and after αCGRP infusion. was also observed in two patients. It should be noted that 2 (4%) healthy individuals were identified during We found out that intravenous infusion of αCGRP the recruitment of the control group, without significantly decrease vm MCA (p<0.001) and vm PCA complaints and deviations in the neurological status. In (p < 0.001). MAP was also significantly decreased (p < which, in one case, the deformation of the vertebral 0.001), but HR significantly increased (p<0.001). Et-CO2 artery in another of its hypoplasia is disturbed. Thus, significantly decreased during αCGRP (p=0.030). We these two anomalies of the vertebral arteries were found a significant positive relationship between vm diagnostic findings. In general, in 43 (86%) cases, the MCA and vm PCA (p<0.001). However, the combination of deformation of vertebral arteries with relationships between MAP and vm MCA (p=0.744) and 103

MAP and vm PCA (p=0.081) were not significant. The Conclusion: This study shows that cortical stimulation relationship between Et-CO2 and vm MCA was can evoke headache. The hypothesis of a meningeal significant (p=0.001) and positive as well as between activation seems unlikely when pain is bilateral or Et-CO2 and vm PCA (p=0.043). Relations between Et- contralateral to stimulation. Headache could represent CO2 and MAP and Et-CO2 and HR were negative but a somatosensory or an interoceptive sensation significant (p=0.043 and p=0.007). triggered by cortical stimulation. These results suggest the implication of insulo-limbic regions in some focal We have concluded that αCGRP induces significant and epileptic seizures and also bring insight in some non- measurable changes in cerebral and systemic epileptic headache pathophysiology. circulation. It might cause vasodilatation of MCA and PCA. Et-CO2 lowering during α-CGRP infusion might be compensatory effect to αCGRP. P160 Sumatriptan does not antagonize CGRP induced symptoms in healthy volunteers P159 K. Falkenberg1, H. Bjerg1, N. Yamani1, J. Olesen1 Is stimulation of the Human cortex able to provoke 1Rigshospitalet Glostrup, Neurology, Danish Headache headache? A stereo-electroencephalography (SEEG) Center, Glostrup, Denmark study G. Demarquay1, E. Hotolean1, F. Mauguiere1, L. Objective: Previous attempts to develop a pragmatic Mazzola1 human model for testing new anti-migraine drugs, 1Neurological Hospital Lyon, Bron, France have failed. Calcitonin gene-related peptide (CGRP) induces a mild headache in healthy volunteers and Question: It is commonly admitted that cortical migraine-like headache in migraine patients. Thus stimulations do not produce headache. First studies CGRP seems ideal for a model for drug testing. The performed in the middle of the 20th century identified objective of the study was to test the effect of dura mater, venous sinuses, meningeal and pial sumatriptan against CGRP induced symptoms to arteries -but not the brain parenchyma- as pain- validate the CGRP model for drug testing. sensitive intracranial structures. However, headache has been occasionally reported in patients with drug Methods: Thirty healthy volunteers received a 2h resistant epilepsy undergoing stereo- infusion of CGRP on two separate days. The electroencephalography (SEEG) stimulations. participants were pre-treated with sumatriptan one day and with placebo the other day in a randomized Methods: The aim of our study was to investigate double-blind cross-over fashion. During the infusion, a whether headache can be triggered by cortical questionnaire about headache and side effects was stimulations using intracerebral electrodes implanted administered. Vital signs, dermal blood flow and in all cerebral lobes and might be related to specific diameter of peripheral arteries were monitored during brain areas. Data were gathered from 16050 the infusion. Participants filled out a questionnaire at stimulation sites collected in 266 patients who home until 12h after the infusion start. Primary underwent a SEEG as part of a pre-surgical assessment endpoints are difference between the sumatriptan day of their pharmaco-resistant focal epilepsy. and the placebo day in area under the headache score curve(AUC) 0-2h and in headache intensity 2h after Results: Headache was induced in 1.3% of cortical infusion start. stimulations. Pain was more frequently described as bilateral (42.31%) than ipsilateral (16.83%) or Results: CGRP induced headache in 86% of the contralateral (14.42%) to the stimulated hemisphere. participants on the sumatriptan day and in 96% of the Headache was more frequently elicited during participants on the placebo day. There was no stimulation of the insulo-limbic regions such as the difference in AUC headache,0-2h between the days anterior and medial cingulate gyrus, the mesial part of (p=0.794). There was a statistically significant decrease temporal lobe, and the insula. in mean atrial pressure over time on both days (p<0.001) and a statistically significant increase in heart rate over time on both days (p<0.001). The diameter of 104

peripheral arteries increased statistically significant on the insertion of all imaginable ranges of filaments. both days (p<0.001). Thus, it is applicable to data derived in any species.

Conclusion: Sumatriptan does not influence headache Conclusion: We advocate the use of this algorithm in score, accompanying symptoms or other symptoms order to minimise inaccuracies and to improve internal induced by CGRP. The 2h CGRP infusion causes a wide and external reproducibility. range of side-effects and does not induce more headache than the usual 20 minutes infusion. Thus, the Figure 1 long infusion of CGRP in healthy volunteers is not a valid or pragmatic model for testing new anti-migraine drugs.

P162 Von Frey testing revisited – provision of an online algorithm for improved accuracy of 50% thresholds S. L. Christensen1, R. B. Hansen2, M. A. Storm1, J. Olesen1, M. Ossipov3, T. F. Hansen1, J. Izarzugaza4, F. Porreca3, D. M. Kristensen1 1Danish Headache Center, Glostrup, Denmark Figure 2 2University of Copenhagen, Copenhagen, Denmark 3University of Arizona, Arizona, United States 4Novo Nordisk, Copenhagen, Denmark

Question: In the pain field, it is essential to quantify nociceptive responses. The response to the application of von Frey filaments to the skin measures tactile sensitivity and is a surrogate marker of allodynia in states of peripheral and/or central sensitization. The method is widely used across species within the pain field. However, uncertainties exist regarding the appropriate method for analysing obtained data. Therefore, there is a need for refinement of the calculations that transform raw data to quantifiable data.

Methods: Here, we briefly review the fundamentals behind von Frey testing using the standard up-down method and the associated statistics and show how different parameters of the statistical equation influence the calculated 50% threshold results. We discuss how to obtain the most accurate estimations in a given experimental setting.

Results: To enhance accuracy and reproducibility across laboratories, we present an easy to use algorithm that calculates 50% thresholds based on the exact filaments and their interval using math beyond the traditional methods. This tool is available for free to the everyday user of von Frey filaments and allows

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P163 P164 Non-invasive vagus nerve stimulation selectively Classification of Eye Condition based on modulates trigeminal pain processing Electroencephalogram Signals using Extreme Learning K. P. Peng1, A. May1 Machines Algorithm (ELM) 1Universitätsklinikum Hamburg Eppendorf, Institut für R. Fajar1 Systemische Neurowissenschaften , Hamburg, 1Yogyakarta State University, Computational Biology Germany and Medicine, Sleman, Indonesia

Background: Recent evidence suggests non-invasive Electroencephalography or EEG signals is a biosignal vagus nerve stimulation (nVNS) serves as an effective that is rife in current research topics. EEG signals have acute treatment for migraine and episodic cluster many benefits such as the detection of epilepsy, sleep headache. However, nVNS is no "pain killer" and has no disorders, or input in a computer application. One effect on somatic pain. The mechanism of how nVNS input that can be detected based on EEG signals is the treats acute headache attacks is not yet clear. state of the eye. However, to be used as input in an application a classification with adequate performance Hypothesis: We hypothesized that nVNS specifically is required. Therefore a study was conducted in which modulates the pain processing in the trigeminal one method of learning Artificial Neural Networks, regions but not the rest of the body and that this Extreme Learning Machine (ELM) will be implemented specificity can be demonstrated using quantitative to classify eye conditions based on EEG signals. The sensory test (QST). dataset used to train and test the model is an eye-state dataset donated by Oliver Roesler combined with a Method: The study used a randomized, single-blind, dataset from the University of California repository sham-controlled, crossover design. Fifteen healthy website, IrvineI (UCI). There are seven corpus which participants were recruited and QST parameters consist of EEG recording done to four different people, including mechanical pain threshold (MPT), wind-up then one corpus is added, which is a combination of all ratio (WUR), heat/cold pain threshold (HPT/CPT), other corpus. From the test results it was concluded electrical pain threshold (EPT), and suprathreshold that ELM can be used for the classification of eye stimulation (5x EPT) were measured over the V1 conditions with an accuracy of 97.95% with training dermatome and the forearm. QST parameters before time of only 0.81 seconds if each data is used and after the nVNS were compared. separately, whereas the merging of the whole dataset only reaches an accuracy of 78.94% with 5.71 seconds Results: After the verum nVNS, MPT was increased training time. By getting a model with good accuracy exclusively over the V1 dermatome (log MPT, 1.7 ± 0.3 with training time that tends to be fast, the ELM vs. 1.5 ± 0.2, p<0.001) but not the forearm. No algorithm can be utilized as a Brain-computer Interface differences were found regarding HPT, CPT, WUR, EPT by previously conducting training based on the or 5x EPT. Sham nVNS was not associated with person's EEG signal with a short amount of time to differences in QST parameters. build the model. However, because the model of 1 person cannot be used for different people, then for Conclusion: nVNS resulted in an increase of MPT in the each different person who uses the system, the V1 dermatome but not the forearm, suggesting a retraining process is necessary. specific connection between vagus input and trigeminal nociceptive processing. Further studies are necessary to investigate why nVNS modulates cephalic pain but not extracephalic pain disorders.

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P167 P168 Transcytosis in primary endothelial cell cultures and a Detailed expression analysis of 5-hydroxytryptamine possible relation to the 5-HT2B receptor in connection and 5-HT1B/1D/1F receptors in the trigeminal system. to migraine pathogenesis J. Edvinsson1,2, K. A. Haanes1, K. Warfvinge1,3, M. J. Nicke1 Sheykhzade2, L. Edvinsson1,3 1Ruhr-Universität, Tierphysiologie (animal physiology), 1University of Copenhagen, Department of Clinical Bochum, Germany Experimental Research, Copenhagen, Denmark 2University of Copenhagen, Department of Drug Design Questions: Trigeminal afferents ensures the and Pharmacology, Copenhagen, Denmark nociceptive transmission within the dural tissue and 3Lund University, Department of Clinical Sciences, are modulators in the theory of neurogenic Lund, Sweden inflammation (NI). Substance P and CGRP are released from these afferents. Consequently, vasodilation and Background: 5-hydroxytryptamine (5-HT) and its 5- increased permeability of meningeal blood vessels can HT1B/1D/1F receptors have key roles in migraine attacks. be observed. This facilitate the release of blood-bourne Their selective agonists 5-HT1B/1D (triptans) and 5-HT1F proteins into perivascular tissue, (plasma protein receptor agonists (ditans) are molecules which can extravasation; PPE) a common indicator for migraine abort acute migraine attacks but their detailed site(s) attacks. mCPP, a partial agonist of 5-HT2B/2C receptors of action are still only partly known. Triptans are strong lead to NI and increased PPE in the dura mater in mice vasoconstrictors of intracranial arteries while ditan of our hypoxic migraine mouse model. The receptor activation does not induce intracranial endothelium of blood vessels plays an important role vasoconstriction. Furthermore, 5-HT1B/1D receptors in the regulation of molecular transport between blood have been shown in trigeminal ganglion neurons to co- and perivascular tissue. Electron microscopic localize CGRP and can reduce the release of CGRP in experiments indicate that transcytosis is the main human migraine attacks and experimentally. pathway for proteins to enter perivascular tissue (Hunfeld et al.). To investigate the processes behind Purpose: The present study was designed to examine PPE and transcytosis in vitro on cellular level, we the localization of 5-HT and 5-HT1B/1D/1F receptors in the established a primary cell culture of murine dural trigeminal system to elucidate possible site(s) of these endothelial cells (PDEC) in normoxic and hypoxic molecules co-localization with the CGRP system. culture conditions. Methods: With specific immunohistochemistry we Methods: 1)Magnetic-activated cell sorting. evaluated the localization of 5-HT and 5-HT1B/1D/1F 2)Comparison of expressionlevel via qPCR and western receptors in the trigeminal system (ganglion and nerve blot. 3) Transcytosis Assays. Results: Caveolin-1 as well fibers) and possible co-localization of CASPR, CGRP and as the 5-HT2B receptor are found to be located on RAMP1. We also used ELISA to investigate potassium PDEC. ICCs of caveolin-1 and BSA-FITC in PDEC show stimulated release of CGRP in dissected TG. This promising results for further investigations of release was further investigated using 5-HT agonists transcytosis mechanisms in vitro. Sumatriptan and Lasmiditan.

Conclusion: regulation of transcytosis markers occurs Results: 5-HT immunoreactivity was extensive in the in PDEC, which indicate a changed regulation of TG and localized to both types of neurons. Specific molecular transport mechanisms in oxygen-deficient antibodies against 5-HT1B/1D/1F receptors demonstrated situations in vitro. Therefore, pharmacological blocking localization to various populations of TG neurons and of transcytotic mechanisms could be a possible nerve fibers. Interestingly, the 5-HT1D expression was approach for the development of migraine by far most extensive, followed by 5-HT1B and lastly 5- prophylactics. References:Hunfeld, A., et al. "Hypoxia HT1F receptor IR. Specific selective agonists were found facilitates neurogenic dural plasma protein to inhibit the potassium-induced CGRP release in the extravasation in mice: a novel animal model for trigeminal system (ganglion or dura mater). migraine pathophysiology", Scientific Reports, vol. 5, no. 1, pp. 1–12 [Online]. DOI: 10.1038/srep17845. Conclusion: The 5-HT1B/1D/1F receptors localized to the neurons and the nerve fibers, though at different

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levels, and selective agonists inhibited CGRP release. significantly affect K+-evoked CGRP release from either Notably the Aδ-fibers contained 5-HT1D receptor also at isolated trigeminal ganglia or dura mater, but oxytocin the nodes of Ranvier, putatively indicative of site of directly constricted cranial arteries in vitro. action. Conclusion: The oxytocin system is not limited to the hypothalamus but there is for the first time a demonstration of a rich distribution in the trigeminal P169 ganglion. Although the mechanisms still need The role of oxytocin and the oxytocin receptor in the elucidation, circulating oxytocin likely acts on receptors trigeminal system. in the trigeminal ganglia to affect pain transmission. K. A. Haanes1, K. Warfvinge1, D. Krause2, J. These effects may help explain hormonal influences in Edvinsson1,3, L. Edvinsson1,4 migraine and offer a novel target for treatment. 1Rigshospitalet Glostrup, Clinical Experimental Research, Glostrup, Denmark 2University of California at Irvine, Department of Pharmaceutical Sciences , Irvine, United States P170 3University of Copenhagen, Department of Drug Design Pituitary adenylate cyclase-activating peptide and and Pharmacology, Copenhagen, Denmark calcitonin gene-related peptide in the 4Lund University, Division of Experimental Vascular trigeminovascular system – two separate signalling Research, Lund, Sweden systems J. Edvinsson1,2, A. S. Grell1, K. Warfvinge1, M. Background: Recent imaging studies have pointed Sheykhzade2, L. Edvinsson1,3, K. A. Haanes3 towards the hypothalamus as a possible locus minors 1Rigshospitalet Glostrup, Clinical Experimental for the start of migraine attacks and this region is also Research, Glostrup, Denmark a key site for hormonal influences. Oxytocin has been 2University of Copenhagen, Department of Drug Design thought of one such hormone with its hypothalamic and Pharmacology, Copenhagen, Denmark localization in the magnocellular nuclei localization. 3Lund University, Division of Experimental Vascular Even though oxytocin has been shown to have Research, Lund, Sweden numerous functions in the body, the role of oxytocin and its receptors in primary headaches is still unclear. Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion (TG). One Purpose: Our main goal was to study if oxytocin and its such signalling molecule is the pituitary adenylate receptor (OTR) are located in the trigeminal sensory cyclase-activating peptide (PACAP). Along with system and may modify trigeminal ganglion activities calcitonin gene-related peptide (CGRP), PACAP of calcitonin gene-related peptide (CGRP). signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Methods: With specific antibodies and sensitive immunocytochemistry we have evaluated the Objective: The present study was designed to localization of oxytocin and OTR in the trigeminal investigate the relationship between PACAP-38 and system and used a specific ELISA to the effect of CGRP, currently the two most significant migraine- oxytocin on CGRP release (by high K+). This was related peptides. combined with arterial wire myograph Methods: We used ELISA to investigate potassium Results: Oxytocin receptor mRNA was detected in rat stimulated release of PACAP and CGRP using a hemi- trigeminal ganglia and receptor protein was localized in skull model. This analysis was combined with qPCR and numerous neurons, primarily larger cells and thick immunohistochemistry to study the expression of axons (A∂ sensory fibers). Double PACAP and CGRP receptors and ligands. immunohistochemistry revealed only a small number of neurons expressing both oxytocin receptors and Results: Both PACAP and CGRP are released from the CGRP. Oxytocin immunofluorescence was observed in TG, but only CGRP from dura mater. There was a weak satellite glial cells; however, oxytocin mRNA was below correlation between the stimulated releases of the two detection in the ganglia. Oxytocin (10 µM) did not 108

neuropeptides in TG. PACAP-38 immunoreactivity was plot slope did not differ from unity (pA2 10.02±0.33). detected occasionally alone and in a subpopulation of Earlier studies using olcegepant and atogepant also neurons in the TG that also store CGRP. The receptor showed a Schild plot slope <1 in HCA, while the slope subtype PAC1 was primarily expressed in the satellite for olcegepant in HMA did not differ from unity. glial cells (SGCs) which envelope the neurons in the TG. Telcagepant and ubrogepant in HCA resulted in Schild PAC1 receptor immunoreactivity occurred in some of plot slopes equal to unity. Remarkably, olcegepant, the neuronal processes inside the Aδ-fibres and in the atogepant and rimegepant, with a Schild plot slope <1 outermost layer of the myelin sheath that covers the in HCA, were all >1 log unit more potent in HMA than Aδ-fibres. in HCA, while telcagepant, ubrogepant and erenumab showed similar (<1 log difference) potency in both Conclusion: There does not appear to be strong tissues. similarities between the release of PACAP and CGRP. This clearly questions whether a migraine therapy Conclusion: For CGRP receptor antagonists with a aimed at the PACAP signalling system would be as Schild plot slope <1 in HCA, the potency difference successful as the CGRP system targeted treatments. between HCA and HMA seems larger than for antagonists yielding a Schild plot slope equal to unity in HCA. As a Schild plot slope <1 may point to the involvement of multiple receptors, it is important to P171 further identify the receptors involved in the relaxation Blocking the CGRP receptor: differences across human to CGRP in HCA, which may enhance improved vascular beds cardiovascular safety of future antimigraine drugs. T. de Vries1, A. van den Bogaerdt2, A. H. J. Danser1, A. Maassen van den Brink1 1Erasmus MC, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, P172 Rotterdam, Netherlands Estrogen receptors α, β and GPER in the rat trigeminal 2ETB-BISLIFE, Heart Valve Department, Beverwijk, system; sex difference and co-localization with CGRP. Netherlands A. Maddahi1, L. Edvinssson1, K. Warfvinge1 1University hospital, Clinical experimentell research, Objective: Multiple drugs targeting the calcitonin Copenhagen, Denmark gene-related peptide (CGRP) receptor have been developed for migraine treatment. We studied the Aim: The role of the presence of estrogen receptors in effect of rimegepant on CGRP-induced relaxation in the trigeminovascular system suggests that trigeminal human isolated blood vessels. Results were compared neurons are sensitive to variations in the levels of the with earlier studies using atogepant, olcegepant, estrogen hormone. With a set of specific antibodies telcagepant, ubrogepant and the monoclonal antibody towards the estrogen receptors we set out to examine erenumab. the localization of estrogen receptors in trigeminal ganglion (TG). Methods: Concentration-response curves to CGRP were constructed in human coronary artery (HCA) and Methods: Single or double immunohistochemistry human middle meningeal artery (HMA) segments, were applied on frozen sections of male and female rat incubated with or without rimegepant (1 nM - 1 µM). trigeminal ganglia using primary antibodies against Schild plots were constructed and pA2 or pKb values CGRP, RAMP1, estrogen receptors α, β and GPER. The were calculated to determine the potency of number of estrogen receptors immunoreactive rimegepant in both tissues. neurons in male and female TG were calculated.

Results: In both HCA and HMA, rimegepant shifted the Results: ERα was exclusively found in the nuclei of concentration-response curve to CGRP. For HCA, the neurons and in most satellite glial cells (SGC). ERβ was Schild plot slope was significantly smaller than unity. found in the cytoplasm of TG neurons. The staining Thus, individual pKb values were calculated to estimate pattern resembles that of the Golgi apparatus. GPER the potency (1 nM: 9.74±0.05, 10 nM: 9.25±0.15, 100 was found in the neuronal cytoplasm and on the cell nM: 8.71±0.16, 1 µM: 8.43±0.25). For HMA, the Schild surface, putatively related to a receptor role. 109

Double immunohistochemistry for estrogen receptors episodic and chronic migraineurs had significantly and CGRP or RAMP1 showed no co-localization for ERα higher median levels of TNF-α (0.24, 0.95, and 1.90 pg/ and CGRP or RAMP1. On the other hand, we found that ml, respectively; P value < 0.001). Also, we observed a ERβ and CGRP were stored in the same organelle (Golgi positive association between the TNF-α levels and the apparatus) and also there was co-expression of ERβ odds of having migraine after considering gender, age, and RAMP1 in the cytoplasm of TG neuron. Further, body mass index, and dietary intakes of energy, there was no co-localization of GPER and CGRP in the carbohydrate, protein, fat, and mono and poly TG neurons. unsaturated fatty acids in the multivariable regression models (OR = 2.15; 95% CI 1.31–3.52; P value < 0.001). The number of immunoreactive neurons in male and However, no significant association was demonstrated female TG were calculated: 32% of the male and 59% between migraine and serum CRP (OR = 2.91; 95% CI of the female neurons expressed ERα, 34% of the male 0.87–9.78; P value = 0.08). and 72% of the female neurons expressed ERβ, 48% of the male and 65% of the female neurons expressed Conclusions: These findings supported that GPER. inflammatory state could be related to the pathogenesis of migraine and it can thus be suggested Discussion: Thus, the results suggest that estrogen that this effect might be beyond migraine progression. receptors are differentially related to CGRP pathway, Further detailed studies are needed to investigate the suggesting interaction with the biology of CGRP in the importance of these findings in the pathogenesis of trigeminal system. In addition, there appears to be migraine headache. more immunoreactive cells in females compared to males; this might support the well-known gender Figure 1 difference in migraine.

P173 Does inflammatory cytokines involve in migraine pathogenesis? F. Martami1, S. Razeghi Jahromi2, M. Togha1, Z. Ghorbani1, M. Seifishahpar2, A. Saidpour2 1Teheran university of medical scinces, headache department, Teheran, Iran 2Shahid beheshti university of medical sciences, Nutrition, Teheran, Iran

Question: Is there significant association between migraine pathogenesis and pro-inflammatory cytokines level?

Methods: In this case-control research, 43 migraine patients (23 chronic and 20 episodic migraineurs) and 40 age-sex-matched headache-free controls were studied. Demographic, dietary, and anthropometric data, headache characteristics, and serum C-reactive proteins (CRP) and tumor necrosis factor-alpha (TNF-α) assessments were collected.

Results: The mean ± SD age of the case and control groups were 36.98 ± 9.91 and 34.84 ± 9.75 years respectively. Compared to control subjects, both

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Figure 2 (SIF), 40 mM potassium chloride (KCl), 100 µM bradykinin 1% ethanol (vehicle) and 100 µm capsaicin.

Results: Twenty-five neurons with input from the frontal dura mater and with responses to chemical stimulation of the sinus were identified. Some of these neurons had additional receptive fields in the parietal dura and most of them in the face. Administration of SIF, KCl and ethanol onto the exposed sinus area was not followed by significant changes in activity. Application of bradykinin provoked a cluster of action potentials in 20 neurons after a latency of 11-40 s and capsaicin led to an increase in activity in 23 neurons after a latency of 7-35 s.

Conclusion: Second-order neurons are localized in the spinal trigeminal nucleus responding to stimulation of the cranial dura mater and paranasal sinuses. Inflammatory mediators such as bradykinin are effective in activating nociceptive input from the sinuses. Trigeminal afferents innervating cranial dura mater and sinuses may form collaterals or converge to spinal trigeminal neurons. Such convergence could

explain the genesis, exacerbations and perpetuation of P174 headaches due to disorders of paranasal sinuses. Responses of spinal trigeminal neurons to noxious stimulation of paranasal sinuses – a rat model of rhinosinusitis headache M. Koch1, K. Messlinger1 P175 1Friedrich-Alexander-University Erlangen-Nürnberg, Antagonism of TRPA1 channels reverts chronic Institute of Physiology and Pathophysiology, Erlangen, migraine pain in an animal model 1 1 1 1,2 Germany C. Demartini , R. Greco , I. Casini , A. M. Zanaboni , C. Nativi3, C. Tassorelli1,2 1 Question: Disorders of the paranasal sinuses can IRCCS Mondino Foundation, Pavia, Italy 2 cause headache (ICHD-3-11.5). The underlying University of Pavia, Pavia, Italy 3 pathophysiology is poorly known, inasmuch the University of Florence, Florence, Italy generation of headaches is thought to be associated with the activation of intracranial afferents. In a rat Several migraine triggers have been reported to model we characterized spinal trigeminal neurons activate/sensitize transient receptor potential ankyrin looking for convergent nociceptive input from the dura 1 (TRPA1) channels, whose activation in the trigeminal mater and paranasal sinuses as a possible basis for nociceptive fibers leads to the release of vasoactive sinus headache generation in man. neuropeptides. Thus, pharmacological blockade of TRPA1 channels may prove beneficial in the treatment Methods: In isoflurane anaesthetized rats extracellular of migraine pain. In this study, we evaluated the ability recordings were made from second-order neurons in of the TRPA1 antagonist ADM_12 to modulate the spinal trigeminal nucleus with afferent input from trigeminal hyperalgesia in the animal model of chronic the exposed frontal or parietal dura mater. The dura migraine, based on intermittent administration of mater and various facial receptive fields were mapped nitroglycerin (NTG). Adult male rats were treated with and the exposed paranasal sinus area was stimulated a single injection of ADM_12 (30mg/kg, i.p.) or vehicle by sequential application of synthetic interstitial fluid 24 hours after the fifth injection of NTG (5mg/kg, i.p., every 2 days over a 9-day period) and then underwent orofacial formalin test 1 hour later. ADM_12 treatment 111

significantly reduced NTG-induced hyperalgesic evaluated after precontraction with 30 mM KCl, and response; this effect was associated with a significant concentration-response curves were constructed to reduction of mRNA expression of genes coding for obtain the pEC50. neuropeptides (CGRP and SP) and inflammatory mediators (cytokines, iNOS) in specific regions involved Results: Both in HCA and HMMA α-CGRP, AM and in migraine pain transmission. These findings show that pramlintide induced concentration-dependent ADM_12 is able to revert experimental chronic relaxation responses that were similar between HCA migraine pain and that TRPA1 channels may act not (mean pEC50 values of 8.51±0.08, 6.67±0.23 and only in the nociceptive process but also on 6.66±0.26, respectively) and HMMA (mean pEC50 inflammatory pathways. values 8.22±0.15, 6.04±0.18 and 5.15±0.46, respectively). In both tissues, the vasodilatory responses by AM and pramlintide were less potent than those induced by α-CGRP. P176 Vasodilatory effects of CGRP receptor agonists in Conclusion: Our results suggest that the vasodilatory isolated human coronary and middle meningeal responses induced by α-CGRP and AM in both HCA and arteries HMMA may be explained by interaction with the E. Rivera-Mancilla1, E. Rubio-Beltrán1, T. de Vries1, A. canonical CGRP receptor. Further research should Vincent2, A. van den Bogaerdt3, A. H. J. Danser4, A. elucidate whether responses to pramlintide are also Maassen van den Brink1 mediated via this receptor, or via additional 1Erasmus University Medical Center, Department of mechanisms, and whether the same receptors are Internal Medicine, Division of Vascular Medicine and involved in both tissues. Pharmacology, Rotterdam, Netherlands 2Erasmus University Medical Center, Department of Neurosurgery, Rotterdam, Netherlands 3ETB-BISLIFE, Heart Valve Department, Beverwijk, P177 Netherlands White matter lesions in migraine: news and 4Erasmus MC, Department of Internal Medicine, challenges` Division of Vascular Medicine and Pharmacology, S. SHAAFI1 Rotterdam, Netherlands 1Tabriz university of medical science, Neurology, tabriz, Iran Background and aim: Calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and amylin (AMY) are Introduction: Between 12-47% of patients with structurally related peptides mediating vasorelaxation migraine have white matter lesions. Bashir et al (2014) via CGRP-, AM- and/or AMY1-receptors. CGRP plays an separated out three types of structural changes in the important role in pathophysiology of migraine, and its brains of persons with migraine-- white matter effects could be mediated through CGRP receptors or abnormalities, infarct-like lesions, and shrinkage. distinct CGRP‐responsive receptors. On this basis, the present study was designed to investigate the Aims: In this review we discuss new concepts in white vasodilatory effects of CGRP, AM and pramlintide (a matter lesions in migraine. stable AMY analogue) in human isolated coronary (HCA) and middle meningeal arteries (HMMA). Methods: Three electronic database (MEDLINE, PUBMED and Cochrane) were searched for valid Methods: For this purpose, HCA (males n=4 [aged 58±4 studies (from Jan2010-SEP2019) reporting on white years] and females n=6 [aged 50±5 years]) were matter lesions in migraine .Valid articles, full-text was obtained from "beating hearts" organ donors who died obtained and their quality was assessed, using the of non-cardiac disorders, and HMMA QUIPS checklist. (males n=6 [aged 57±2 years] and females n=1 [aged 70 years]) were removed from dura mater of patients Results: All agree that these lesions in children are not undergoing neurosurgical procedures. Both in HCA and progressive or associated with neurological HMMA, the vasodilatory responses to α-CGRP, AM and deterioration. White matter hyper intensities were pramlintide (0.1 nM–1 µM, half logarithmic steps) were significant more frequent in migraine with aura than 112

those without aura. The number of white matter hyper double-dummy, cross-over design, on two separate intensities increases significantly with increase study days, by proton magnetic resonance intensity of pain during attack. increase intensity of spectroscopy and pseudo-continuous arterial spin nausea, disability, tolerability during attack and age. labeling at 3T. Headache characteristics were recorded Resistance to treatment, Age, presence of aura, until 24 hours after drug administrations. nausea, disability during attack, and severity of headache and duration of migraine are considered a Results: Twenty-six patients were scanned during risk factor for development of white matter migraine, yielding a total of 41 attacks. Cerebral blood hyperintensities. also shows statistically significant flow increased in the dorsolateral pons, ipsilateral to difference in increase number of WMHs.(Mohamed the pain side during attacks, compared to outside Negm.et.al) Hui Xie et al (2018) reported WMHs can attacks (13.6%, p=0.009). Glutamate levels in the same predict unfavorable migraine prognosis. Furthermore, area remained unchanged during attacks (p=0.873), WMHs may have a closer association with age than while total creatine levels increased (3.5%, p=0.041). migraine features.oted WMHs can predict unfavorable migraine prognosis. Furthermore, WMHs may have a Conclusions: Dorsolateral pontine activation during closer association with age than migraine features. An migraine was not associated with higher glutamate inherited condition called CADASIL should be levels. However, the concurrently increased total suspected in migraine patients with a prolonged typical creatine levels may suggest an altered energy aura and white matter lesions. Mitochondrial metabolism, which should be investigated in future myopathy, antiphospholipid antibodies, SLE, and MS studies to elucidate the role of pons in acute migraine. should also be considered in this situation. CONCLUSION: According to this fact that migraine is a common headache and probably with a genetic predisposition and white matter lesions also are seen P179 about 43 % of migraine patients good model Multi-frequency Analysis of Neuromagnetic activity multicentric cohort studies should be designed to between Open Eyes and Closed Eyes at Resting state response unresolved issues about these correlations. of Migraine S. Saifuddin1 1Jansons Medical Centre, Ophthalmology, Dubai, United Arab Emirates P178 Glutamate levels and perfusion in pons during Objective: The objective of the study was to migraine attacks: a 3 tesla MRI study using proton characterise the difference of neuromagnetic brain spectroscopy and arterial spin labeling activities from low to high frequency ranges between S. Younis1, C. E. Christensen1, M. B. Vestergaard1, U. open eyes and closed eyes at resting state of migraine Lindberg1, D. Tolnai1, O. B. Paulson1, H. B. W. Larsson1, A. Hougaard1, M. Ashina1 Methods: 24 subjects suffering from migraine and 1Danish Headache Center, Glostrup, Denmark gender matched with age of less than 24 years healthy controls using magnetoelecephalography (MEG) Question: Migraine is a complex disorder, involving System, recording at a sample rate of 6000 Hz. Subjects peripheral and central brain structures, where were asked to keep eyes open for 2 minutes and eyes mechanisms and site of attack initiation is an closed for 2 minutes. Activities were localised with unresolved puzzle. While abnormal pontine neuronal accumulated source imaging method in 9 frequency activation during migraine attacks has been reported, bands- which included delta (1-4 Hz), theta (4-8 Hz), exact implication of this finding is unknown. Evidence alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-55 suggests an important role of glutamate in migraine, Hz), high-gamma (65 -90 Hz ), ripple (90 to 200 Hz), hgh which implies a possible association of the pontine frequency oscillations ( VHFOs -1,000 -2,000 Hz). hyperactivity to increase in glutamate levels. Magnetic source power was quantified for each group

Methods: Migraine without aura patients were Results: Compared with eye-open, eyes-closed was scanned during attacks after calcitonin gene-related associated with significant increase of alpha and beta peptide and sildenafil in a double-blind, randomized, 113

activities and was aslo associated with significant our patients before and after administration of the decrease of delta and theta in both migraine and CGRP-mAb erenumab 70 mg. control groups. Results: The study was completed by n=27 patients. Compared with eyes closed, eyes-opened was Our main finding is that the administration of associated with signifcant increase of source power in erenumab modulates the activation of a specific brain ripple, HFOs and VHFs in migraine group but not in the network following trigeminal nociceptive input, which control groups. includes the thalamus, the insular cortex, and the secondary somatosensory cortex. This effect is not Conclusion: The resuts showed that migraine subjects driven by a lesser pain experience or changes in pain had altered brain activities in multiple frequency bands unpleasantness due to erenumab, since pain and during eyes-open and eyes-closed states as compared unpleasantness ratings were equal in both sessions and with controls. The significant increases in high taking them as confounders had no influence on the frequency brain activities at eyes open status in results. When contrasting responders (n=9) and non- migraine might be related to migraine headache responders (n=8) the above-mentioned matrix does attacks, whcih could explain why some migraine not distinguish between groups, but we found a subjects like to stay in dark to keep eyes closed. significant reduction of hypothalamic activation after Though the underlying mechanisms remain unclear, it erenumab injection in responders only. This was might be associated with aberrant visaul processing or confirmed when using the absolute headache days as a aberrant resting state activtion. The findings may regressor (n=17). facilitate the development of new therapeutic stretegies in migraine treatmner in future. Conclusion: Our data suggest that erenumab has at least additional central effects in regions directly Keywords: Migraine - Closed eyes - Open eyes - involved in migraine pathophysiology. Whether this is Aberrant visual processing due to secondary changes following peripheral modulation of sensory input or indeed represents a direct central mode of action remains to be elucidated.

P181 Erenumab modulates hypothalamic processing in migraine patients P182 C. Ziegeler1, J. Mehnert1, K. Asmussen1, A. May1 Investigation of sumatriptan and ketorolac 1University Medical Center Hamburg-Eppendorf, trometamol in the human experimental model of Systems Neuroscience, Hamburg, Germany headache. H. Ghanizada1, M. A. Al-Karagholi1, N. Arngrim1, M. Question: The hypothalamus and midbrain/brainstem Mørch-Rasmussen1, M. Metcalf-Clausen1, H. B. networks are generally considered to be relevant Larsson2, F. M. Amin1, M. ASHINA1 central structures of migraine pathophysiology. The 1Danish Headache Center, Neurology, Glostrup, recent introduction of monoclonal antibodies to the Denmark calcitonin gene-related peptide (CGRP) and its receptor 2Functional Imaging, Clinical Physiology, Nuclear (CGRP-mAb) for the treatment of migraine heralds a Medicine and PET, Glostrup, Denmark new treatment era. Since CGRP-mAb do not cross the blood-brain barrier, mainly peripheral sites of action Pituitary adenylate cyclase-activating polypeptide-38 are discussed. We hypothesized that in line with our (PACAP38) induces headache in healthy volunteers. We current understanding of migraine as a brain disorder, investigated the headache preventive effect of CGRP-mAb may in fact also exhibit central effects. sumatriptan and ketorolac in healthy volunteers. In additon, we explored contribution of vascular Methods: We conducted an event-related fMRI study mechanisms to PACAP38-induced headache using high on migraine patients (n=27), using a well-established resolution magnetic resonance angiography. trigeminal nociceptive study paradigm and examined Thirty-four healthy volunteers were divided in two groups (A and B) and received infusion of PACAP38 (10 114

picomol/kg/min) over 20 min. Group A was pretreated Methods: This double-blinded, sham-controlled study with sumatriptan (4 mg/mL) or ketorolac (30 mg/mL) enrolled 48 subjects and measured headache severity, before infusion of PACAP38. Group B received infusion frequency [headache days/month, number of total and of sumatriptan or ketorolac as post-treatment 90 min mild/moderate/severe attacks/month], functional after infusion of PACAP38. In both experiments, we state and serum levels of inflammatory markers [inter- used a randomized, double-blind, cross-over design. ictal] using immunoassays at baseline and after 2 We recorded headache characteristics and months of nVNS compared to suitably matched circumference of extra-intracerebral arteries. controls.

We found no difference in attenuation of PACAP38- Results: No differences were observed at baseline and induced headache in group A, pretreated with after 2 months for headache severity, total sumatriptan or ketorolac (p=0.297). There was no attacks/month, headache days/month and functional difference between sumatriptan and ketorolac in outcome [sleep, mood, disability] between verum and PACAP38-induced circumference change (AUCBaseline- sham nVNS. Number of severe attacks/month 110 min) of MMA (p=0.227), STA (p=0.795) and MCA decreased in the nVNS group (fig.1). Inflammatory IL- (p=0.356). In group B, post-treatment with ketorolac 1β was elevated significantly in the sham group reduced PACAP38-headache compared to sumatriptan compared to nVNS, while anti-inflammatory IL-10 were (p<0.001). Post-treatment with sumatriptan significantly higher at baseline in both groups significantly reduced the circumference of STA compared to healthy controls, but not at 2 months (p=0.039) and MMA (p=0.015) but not of MCA follow-up [p<0.05]. High-mobility group box - 1, IL-6, (p=0.981) compared to ketorolac. In an explorative tumor-necrosis factor-α, leptin, adiponectin, ghrelin analysis, we found that pre-treatment with remained unchanged (fig. 2). No correlation was found sumatriptan reduced PACAP38-induced headache. between IL-1β and IL-10 and the numbers of severe attacks/month. In conclusion, post-treatment with ketorolac was more effective in attenuating PACAP38-induced headache Conclusions: Cervical nVNS significantly declined the compared to sumatriptan. Ketorolac exerted its effect number of severe attacks/month. IL-1β levels [inter- without affecting PACAP38-induced arterial dilation, ictal] were higher in sham-treated migraine patients whereas sumatriptan post-treatment attenuated compared to verum nVNS, Pro- [IL-6, HMGB-1, TNF-α, PACAP38-induced dilation of MMA and STA. Pre- leptin] and anti-inflammatory [IL-10, adiponectin, treatment with sumatriptan attenuated PACAP38- ghrelin] mediators did not differ statistically. Profiling induced headache without affecting PACAP38-induced of neuroinflammatory pathways in migraine patients arterial dilation. remains experimental confounded by intra-/inter- individual variables deserving systematic biobank- based research.

P183 Figure 2. IL-1β [pg/ml], IL-6 [pg/ml], TNF-α [pg/ml] and Inter-ictal assay of circulating peripheral IL-10 [pg/ml] at baseline and follow-up after 2 months. neuroinflammatory mediators in migraine patients IL-10 was significantly lower in healthy controls treated with non-invasive cervical vagus nerve compared to migraineurs and IL-1β significantly stimulation increased in the sham nVNS compared to nVNS. I. Lendvai1, T. Kinfe2 1Klinikum Nordwest, Neurology, Frankfurt, Germany 2Friedrich-Alexander University (FAU), Neurosurgery, Division Functional Neurosugery and Stereotaxy, Erlangen, Germany

Question: To evalaute peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

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Figure 1 unpaired t-test and regression analyses with Benjamin- Hochberg correction. MIDAS, NRS, HADS were used to clarify the quality of pain and associated psychopathology.

Results. ↑FC were between Salience Network (SN) and SensoriMotor Network (SMN), SN and Default Mode Network (DMN) and also within DMN. ↓FC were between SN and Dorsal Attention Network (DAN) and also within DAN. Regression analyses represent ↓FC between SN and FrontoParietal Network (FPN) connected with depression level (HADS) and years of Figure 2 illness.

Conclusion: We developed the model of migraine pathophysiology based on FC alterations according to Triple Network Theory [2]. Repeating headache put on the disfunction of reward and anti-reward systems [3] forming the pathological circle which consequence of the interaction underlying centralization of pain and sensitization of nociceptive pathways (SN-DMN and SN-DAN atypical FC). On the background of decreased pain threshold, the importance of nociceptive stimuli increases (SN-SMN ↑FC). So patients in the interictal period exist in a waiting state for a pain stimulus. Disbalance in the reward system due to chronic headache is reflected in affective disorders (↑FC within DMN and ↓FC between SN and FPN) and a decreased attention (↓FC within DAN) what is P184 confirmed by questionnaires results. A common ground for pain and affective disorders among migraine patients according to internetwork 1)doi:10.1089/brain.2012.0073 functional connectivity alterations K. Markin1, A. Trufanov1 2)doi:10.1016/j.tics.2011.08.003 1S.M. Kirov Military Medical Academy, Neurology, Saint-Petersburg, Russian Federation 3)doi:10.1016/j.neubiorev.2016.05.033

Resting-state functional magnetic resonance imaging (RS-fMRI) allows to identify atypical functional connectivity (FC) of various brain networks associated with the pathogenesis of migraine.

Aim: to explore the pathogenesis of migraine and concomitant psychopathology in the aspect of internetwork functional connectivity alterations.

Methods and patients: 25 patients (22 women; 36,56±9,83) with chronic migraine and 25 matched healthy controls underwent RS-fMRI during the interictal phase. Postprocessing and secondary analysis were performed using CONN 18b [1] basing on

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Figure 1 candidates for migraine, using the headache and migraine provoking agent, cilostazol. Previous studies have used sumatriptan tablets as the validating drug, but they were not sufficiently effective. In this study we test the effect of subcutaneous sumatriptan on cilostazol induced headache in patients with migraine without aura.

Method: Thirty patients with migraine without aura received 200mg cilostazol on two different study days. The induced headache was treated with subcutaneous sumatriptan in a randomized, double-blind cross-over design. The patients filled out a self-reported headache questionnaire until 12 hours after cilostazol.

Results: All 30 patients experienced headache (range 3-10) on both study days and in 73% on the sumatriptan day and in 77% on the placebo day, the headache fulfilled the criteria for a migraine-like attack. Sumatriptan injection reduced the headache score 2h after treatment (p=0.003). The difference between headache intensity on the sumatriptan day and the placebo day was significant at both 2h (p=0.01) and 4h (p=0.0007) after treatment.

Conclusion: Subcutaneous sumatriptan reduces Figure 2 cilostazol induced headache in migraine patients. The cilostazol model may be useful as a tool to test the potential of new anti-migraine drugs.

P186 Cervical muscle strength in episodic and chronic migraine: a controlled study. L. Florencio1, C. Pinheiro2, T. Will-Lemos2, M. Rocha2, T. Martins2, F. Dach2, C. Fernández-de-las-Peñas1, A. Oliveira2, D. Bevilaqua-Grossi2 1Universidad Rey Juan Carlos, Madri, Spain 2University of São Paulo, Ribeirão Preto, Brazil

Question: do patients with episodic or chronic migraine present cervical muscle weakness? P185 Subcutaneous sumatriptan reduces cilostazol induced Methods: Cervical muscle isometric force was headache in migraine patients measured in 32 women without headache with a mean 1 1 1 K. Falkenberg , H. Bjerg , J. Olesen age of 31.5 years old (SD=9.3); 40 women with episodic 1 Rigshospitalet Glostrup, Neurology, Danish Headache migraine, mean age of 32.5 (SD=8.8) and 6.8 days with Center, Glostrup, Denmark headache per month (SD=3.2) and; 31 women with chronic migraine, mean age 34.6 (SD=9.9) and a mean Objectives: The authors have previously tried to headache frequency of 24.2 (SD=5.6). Migraine develop a model for the testing of novel drug

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diagnosis followed the third edition of the P187 International Headache Society criteria. Force was Assessing sensitization of trigeminal-cervical complex measured by the Multi Cervical Rehabilitation Unit in different phases of the migraine cycle and in during maximal isometric contractions sustained by chronic migraine 3seconds in flexion and extension. The presence of S. Di Antonio1, M. Castaldo1, C. Finocchi2, P. Torelli3, L. pain in the neck or in the head during contractions Arendt-Nielsen1 were recorded. Statistical analyses were performed by 1Aalborg University, Center of Neuroplasticity and Pain, the ANOVA and the Chi-square test with a significant SMI ®, Department of Health Science and Technology, level of 0.05. The study was approved by the local School of Medicine, Aalborg University, Aalborg, ethics committee (12145/2016). Denmark, , Aalborg, Denmark 2Ospedale Policlinico San Martino-IRCCS, Ospedale Results: Episodic migraine group demonstrated lower Policlinico San Martino-IRCCS, Genova, Italy normalized force in flexion (1.0 N/kg; SD=0.36) and in 3Headache Center, Unit of Neurology, Department of extension (1.52N/kg; SD=0.57) when compared to Medicine and Surgery, University of Parma, Parma, control group (Flexion: 1.19 N/kg; SD=0.46; Extension: Italy 1.94N/kg; SD= 0.71) (p<0.05). Chronic migraine group did not differ from controls and episodic migraine Background: Studies assessing abnormality in pain presenting a mean normalized force of 1.06 N/kg (SD= perception in chronic migraine and episodic migraine 0.43) for flexion and 1.70 N/kg (SD=0.54) for extension. patients in different phases show inconclusive results. Greater prevalence of pain report during contractions In this study, we assess pressure pain thresholds in were observed for migraine groups during flexion trigeminal and cervical areas and test for possible (p<0.001) and extension (p=0.001) (Figure 1). differences between chronic migraine and episodic migraine without aura during the different phases of Conclusion: Weakness of the cervical flexors and migraine manifestations. extensors when the isometric force is measured in a sitting position were observed only for the episodic Methods: In this multicenter, cross-sectional, migraine group. Greater prevalence of neck and head observational study patients with chronic and episodic pain reports was observed for migraine groups, migraine without aura and a control group including especially during the flexion contractions. healthy subjects were included. The age of both groups is 18-65. A therapist blinded to the diagnosis assessed Figure 1. Frequency of pain report (%) during the the pressure pain thresholds in temporal and cervical maximal isometric voluntary contraction (MIVC) in areas. The headache characteristics were recorded in flexion and in extension. daily updated diaries that were retrospectively assessed in order to include migraine patients in the Figure 1 different phases. Multivariate analysis of variance was used to analyse differences between groups.

Results: The total numbers of subjects were 116: 25 control; 22 interictal, 25 preictal, 19 ictal, 11 postictal episodic migraine; 14 chronic migraine. There was a significant group difference in pressure pain thresholds over temporalis (F (5, 110) = 4,60; p < 0,01) and neck (F (5, 110) = 6,46; p < 0,001). Post hoc analysis shows that all migraine patients had reduced pressure pain threshold over the cervical area compared with controls (p<0.05) but with no difference between migraine groups. In the temporal area, all migraine patients except preictal migraine (p> 0,05) had reduced pressure pain threshold compared with controls (p<0.05) with no difference between migraine groups.

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Conclusion: Patients with migraine, independently of P188 the chronicity or the phase, present reduced pressure The effects of Vitamin D3 supplementation on TGF-β pain threshold in cervical and trigeminal areas as signs and IL-17 Serum Levels in migraineurs: Post hoc of increase sensitization of trigeminal cervical complex. analysis of a randomized clinical trial The only exception is in the preictal phase, in which M. Togha1, Z. Ghorbani 1, P. Rafiee1, S. Razeghi signs mechanical hypoalgesia were found in the Jahromi1, M. Djalali1, M. Mahmoudi1 trigeminal area. 1Teheran university of medical sciences , Teheran, Iran

Figure 1 Introduction: Although the exact mechanism involved in migraine pathogenesis remained uncertain, different researches have been developed to address the role of neuro-inflammation and immune dysfunction. Therefore, considering the immune protective roles of vitamin D3, we aimed to investigate the effects of daily administration of 2000IU D3 supplements on serum status of immune markers in migraine patients.

Methods and materials: Eighty episodic migraineurs who randomly assigned into two equal groups to receive either vitamin D3 2000IU/d or placebo for 12- week were enrolled in this placebo-controlled, double blind trial included. Serum concentrations of Figure 2 transforming growth factorbeta(TGF-β) and interleukin(IL)-17 were evaluated at baseline and after the trial via ELISA method.

Results: Applying ANCOVA adjusted for baseline levels and confounding variables, it was found that serum level of TGF-β was significantly higher in vitamin D group (adjusted mean:1665.50 ng/L) than the placebo group (1361.90 ng/L) after the experiment (P: 0.012); whereas. IL-17 serum level was significantly reduced in the intervention group (37.84ng/L) comparing to the controls (70.09ng/L P:0.039). The Pearson correlation analysis revealed significant positive correlation between changes in serum 25-hydroxy-vitamin D and TGF-β changes(r=−0.306, P:0.008);while no significant correlations were noted between serum 25-hydroxy- vitamin D and IL-17 changes throughout the study.

Conclusion: Based on the results of this study, it was revealed that 12-week vitamin D3 supplementation (2000 IU/day) could enhance TGF-β level and suppress IL-17 concentration in episodic migraine patients. It was also observed that with increasing serum 25- hydroxy-vitamin D levels serum TGF-β concentration tended to increase throughout the trial. Although these findings are promising regarding immune protective effects of vitamin D in migraineurs, it is needed to be extended and corroborated in further well-designed trials.

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P190 well as sildenafil. We propose that intradural Intradural artery dilation during experimentally vasculature is affected by migraine-driven activation of induced migraine attacks trigeminal afferents during migraine attacks. C. E. Christensen1, S. Younis1, U. Lindberg2, P. de Koning3, D. Tolnai4, O. Paulson5, H. Larsson2, F. Amin1, M. Ashina1 1Rigshospitalet – Glostrup, Danish Headache Center, P191 Glostrup, Denmark Increased Neck Muscle Stiffness in Migraine Patients 2Rigshospitalet – Glostrup, Functional Imaging Unit, with Ictal Neck Pain: a Shear Wave Elastography Glostrup, Denmark Study 3Leiden University Medical Center, Dept of Radiology, J. Hvedstrup1, L. T. Kolding1, M. Ashina1, H. W. Schytz1 Leiden, Netherlands 1Danish Headache Center, Department of Neurology, 4Rigshospitalet – Glostrup, Dept of Radiology, Glostrup, Rigshospitalet Glostrup, Glostrup, Denmark Denmark 5Rigshospitalet, Neurobiology Research Unit, Question: Whether migraine patients with ictal neck Copenhagen, Denmark pain have stiffer neck muscles interictally compared with patients without ictal neck pain and controls. Objective: To examine changes in circumference of the intradural middle meningeal artery during Methods: This was a cross-sectional study investigating experimentally induced attacks of migraine without neck muscle stiffness, pressure pain thresholds and aura. neck pain symptoms in 100 migraine patients recruited from a tertiary headache center and 46 controls. Methods: Thirty-four patients with migraine without aura were given sildenafil and calcitonin gene-related Results: Patients with ictal neck pain had increased peptide on two separate study days in double-blind mean neck muscle stiffness interictally compared to crossover fashion. Patients were scanned with 3.0 tesla both migraine patients without ictal neck pain (P = MR angiography before administration of either 0.018) and controls (P = 0.036). Muscle stiffness was sildenafil or calcitonin gene-related peptide and negatively correlated with pressure pain thresholds in scanned again 6 hours later during induced attacks of the neck in migraine patients with ictal neck pain (r = - migraine. Main outcome was circumference of the 0.292, P = 0.042). There were no differences in mean intradural segment of the middle meningeal artery pressure pain thresholds between migraine subgroups. with comparisons between baseline and migraine attack in patients who suffered attacks at the second Conclusions: Migraine patients with ictal neck pain scan. The middle cerebral and superficial temporal have stiffer neck muscles interictally compared with artery were also examined. migraine patients without ictal neck pain and controls. The similar pressure pain thresholds between migraine Results: Fourteen patients had a migraine attack patients indicate similar sensitization in these groups. during the second scan after both study drugs and 11 The increased stiffness could be due to local alterations had a migraine after either one or the other, resulting in the neck muscles. in a total of 39 attacks included in the final analysis. Mean circumference of the intradural middle meningeal artery at baseline was 3.18 mm with an increase of 0.11 mm during attacks (p=0.005), corresponding to a relative dilation of 3.6% [95% CI: 1.4 to 5.7 %]. Middle cerebral artery dilated by 9.4 % [95% CI: 7.1 to 11.7 %] and superficial temporal artery by 2.3 % [95% CI: 0.2 to 4.4 %].

Interpretation: The intradural middle meningeal artery and the middle cerebral artery are dilated during migraine induced by calcitonin gene-related peptide as

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P192 and upper cervical spine (r= 0,32 with p(one-tailed)< Correlation between sensitization of trigeminal- 0,05) cervical complex and functionality of deep cervical flexor muscles during the interictal period in patients Conclusion: Subjects with episodic migraine have with episodic migraine. increased muscle pressure pain sensitization and S. Di Antonio1, M. Castaldo 1, C. Finocchi2, P. Torelli3, L. dysfunction of the deep cervical flexor muscles. Arendt-Nielsen1 Increased level of sensitization is correlated with a 1Aalborg University, Center of Neuroplasticity and Pain, lower functionality of cervical muscles SMI ®, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Figure 1 Denmark, , Aalborg, Denmark 2Ospedale Policlinico San Martino-IRCCS, Ospedale Policlinico San Martino-IRCCS, Genova, Italy 3Headache Center, Unit of Neurology, Department of Medicine and Surgery, University of Parma, Parma, Italy

Background: Despite migraine is characterized by increase sensitization of trigeminal-cervical complex and impairment of deep cervical-flexor muscles, their relationships have never been studied. The aims of this study were to assess 1) if cervical-flexor muscles dysfunction is present in the interictal period and 2) if Figure 2 cervical-flexor muscles and sensitization are correlated

Methods: In this multicenter, cross-sectional, observational study we included patients with episodic migraine without aura during the interictal phase and a control group including healthy subjects. The age of both groups is 18-65. A therapist blinded to the diagnosis assessed: 1) pressure pain thresholds in temporal area and four points in the upper cervical spine; 2) craniocervical flexion test (activation pressure score was calculated). The differences between groups were established using t-test for data normally distributed and Mann-Whitney test for data not normally distributed. Any correlation between these variables was analyzed using Spearman’s correlation coefficient (SPSS 24)

Results: We included 23 subjects for each group. Patients with migraine had significant lower pressure pain threshold over temporal area (Mean= 198,93 ± 87,79 kPa vs 281,09 ± 122,16 kPa; t(44) = 2,61, p<0,05) and upper cervical spine (Mean= 818,58 ± 304,02 kPa vs 1106,42 ± 492,19 kPa; t(44) = 2,39, p<0,05) compared to control. They also had lower activation pressure score value (Median= 22 mmHg vs 30 mmHg; U= 64,50, z= -4,35, p<0,001) compared to control. There was a significant positive correlation between activation pressure score and pressure pain threshold over temporal area (r= 0,35 with p(one-tailed)< 0,01) 121

P193 PEA levels significantly increased only in GTN+ patients Spinal sensitization and circulating levels of at T-MIG-1h (p=0.031 vs baseline). AEA levels endocannabinoid and non-endocannabinoid lipid significantly increased in all subjects at T-120/T-1h mediators during experimentally-induced migraine (p=0.035 vs baseline), without differences between attacks groups. R. De Icco1,2, R. Greco3, C. Demartini3, A. M. Zanaboni2,3, A. Reggiani4, N. Realini4, M. Allena1, D. We did not find any correlations between Martinelli1,2, V. Grillo1, G. Sances1, C. Tassorelli1,2 neurophysiological parameters and levels of lipid 1IRCCS Mondino Foundation , Headache Science mediators. Centre, Pavia, Italy 2University of Pavia, Department of Brain and GTN facilitates spinal nociceptive modulation and is Behavioral Sciences, Pavia, Italy associated to an increase in circulating PEA levels in the 3IRCCS Mondino Foundation, Laboratory of subjects who develop a migraine. This latter response Neurophysiology of Integrative Autonomic Systems, likely represents a compensatory anti- Pavia, Italy inflammatory/analgesic mechanism. 4Istituto Italiano di Tecnologia, Department of Drug Discovery and Development, Genova, Italy

Migraine subjects experience a derangement of the P194 nociceptive system control as the disease progresses. Visual feedback to modulate pain perception: what The endocannabinoids system may modulate the effects in chronic migraine patients? nociceptive pathways. Here we evaluated the S. Bottiroli1,2, M. Matamala-Gomez3, G. Sances2, M. nociceptive spinal modulation together with Allena2, G. Sandrini2,4, R. De Icco2,4, E. Guaschino2, C. anandamide (AEA) and palmitoylethanolamide (PEA) Tassorelli2,4 circulating levels in patients with episodic migraine 1University Giustino Fortunato, Pavia, Italy that were exposed to glyceryl trinitrate (GTN) as a 2IRCCS Mondino Foundation, Pavia, Italy migraine-provocative test. 3Università of Milano-Bicocca, Milan, Italy 4University of Pavia, Pavia, Italy We enrolled 24 patients (33.0±8.1 years, 22 female) and 19 healthy controls (HC - 29.5±9.3, 15 female). In Objective: Visual feedback interventions allow the the subjects with a positive provocation test (GTN+), dynamic modification of the virtual body that is nociceptive withdrawal reflex and AEA and PEA plasma perceived as one’s own and provide positive and levels were recorded at baseline, at the timing when relaxing feedback to patients. The present study is the migraine-like headache reached an intensity of 5 aimed to investigate whether the exposure to different on a 0-10 nociceptive rating scale (T-MIG), and after 1 visual stimulating conditions may modulate pain hour (T-MIG-1h). In patients with a negative perception in chronic migraine patients. provocation test (MIG-) and in HC, nociceptive withdrawal reflex and AEA and PEA plasma levels were Methods: To this aim, 35 female chronic migraine recorded at baseline and at 30 (T30), 60 (T-60) and 120 patients (mean age: 46.39 ± 10.77) recruited at the (T-120) minutes after GTN administration IRCCS C. Mondino Foundation were enrolled. In this 1x4 within-subjects study design, all chronic migraine Thirteen patients (52.2%) had a GTN+ response. The patients were first evaluated on personal, clinical, latency of migraine onset was 59.9±49.7 minutes. GTN psychological variables, level of pain (VAS) and body induced spinal sensitization in both GTN+ and GTN- image perception at the baseline. During the patients, detectable as a decrease in temporal experimental session, subjects were then randomly summation thresholds (p=0.001 and 0.016, exposed to 4 different types of visual stimulus respectively). Only in the GTN+ patients we detected a conditions (facial expressions): positive, neutral, significant decrease of single stimulus reflex threshold, negative and control. After the observation of each particularly at the T-MIG timepoint (p=0.049). visual condition, subjective perception of pain and the level of identification with each visual stimulus was assessed.

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Results: A repeated measure analyses and the 11Hospital Universitario Virgen de las Nieves, following multiple comparisons by using the Scheffe Department of Otolaryngology, Granada, Spain test showed a significant difference in pain decrease between the positive (32.4±31.0) and the negative Introduction: Vestibular Migraine (VM) and Meniere (38.6±29.7) facial expressions (z=-4.46, p<0.001), or the Disease (MD) are episodic vestibular syndromes with a positive (32.4±31.0) and the neutral (37.2±28.36) facial high symptom overlap, that can be clinically expression (z=3.41, p=0.009), used a control condition. indistinguishable in the earlier stages of disease. Spearman"s correlation test showed a positive Moreover, VM patients respond to antimigraine drugs, relationship between the negative affective state of which suggests a shared disease mechanism with the patients at baseline (15.5±6.8) and the pain ratings migraine. Two subtypes of MD have been described reported during the experimental session (rs=0.32, regarding the patient"s basal levels of IL-1β (high or p=0.05). low), which suggests different disease mechanisms. So, due to the clinical resemblance between these Conclusion: Our results show that a positive visual diseases we proposed to study the cytokine profile of feedback is a stimulus strong enough to modulate MD, VM and Migraine to differentiate these patients. subjective pain perception via the mediation of empathy mechanisms for positive emotions. Our study Materials and Methods: We carried out gene paves the way to the integration of conventional expression microarrays of peripheral blood therapy with new cognitive behavioral training based mononuclear cells (PBMC) of 7 MD patients, 6 VM on the adoption of visual feedback to further control patients and 5 healthy controls and measured the pain perception. levels of 14 cytokines and 11 chemokines in 129 MD patients, 82 VM patients and 66 healthy controls through ELISA-multiplex. Additionally, we measured the levels of CCL18 in 156 MD patients, 74 VM P195 patients, 22 Migraine patients, and 34 healthy controls Role of pro-inflammatory cytokines in the differential by ELISA. diagnosis of Vestibular Migraine, Meniere Disease and Migraine Results: The gene expression profile in PBMCs showed M. Flook Pereira1,2, E. Martinez1,2, A. Gallego- significant differences in MD patients with high and Martinez1,2, E. Martin-Sanz3, M. Rossi-Izquierdo4, J. C. low basal levels of IL- 1β, VM patients and healthy Amor-Dorado5, A. Soto-Varela6, A. I. Martins7, A. controls. We determined by Logistic Regression that IL- Batuecas-Caletrio8, P. Perez-Carpena9, L. Frejo10, J. A. 1β, CCL3, CCL22 and CXCL1 levels can be used to Lopez-Escamez1,11,2 differentiate VM patients from MD patients (area 1GENYO, Granada, Spain under the curve=0.99), suggesting a high diagnostic 2IBS.Granada, Granada, Spain value in patients with symptom overlap. Levels of 3Hospital Universitario de Getafe, Department of CCL18 were higher in Migraine patients than in the Otolaryngology, Getafe, Spain other groups. 4- Hospital Universitario Lucus Augusti, Department of Otolaryngology, Lugo, Spain Conclusion: A cytokine panel including IL- 1β, CCL3, 5 Hospital Universitario Can Misses, Department of CCL22, and CXCL1 could be used as diagnostic panel for Otolaryngology, Ibiza, Spain the differential diagnosis of VM and MD. CCL18 levels 6 Complexo Hospitalario Universitario, Division of may allow to distinguish VM from Migraine. Otoneurology, Santiago de Compostela, Spain 7 Centro Hospitalar e Universitário De Coimbra, Funding: This work was supported by PI17/1644 Grant Neurology, Coimbra, Portugal from ISCIII by FEDER Funds from the EU. Marisa Flook is 8 - Hospital Universitario Salamanca, Department of funded by FI18/00228 from ISCIII. Otolaryngology, Salamanca, Spain 9 Hospital Universitario San Cecilio, Department of Otolarynogology, Granada, Spain 10The Feinstein Institute for Medical Research, Otolaryngology-Pedriatics/Orthopeadics, New York, United States

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P197 Conclusions: We found a decreased neuropeptide Is peripheral neuropeptide release reduced in women action in PCOS women with comorbid migraine – a with migraine? Preliminary results from a cross- finding that contributes to the idea that altered actions sectional study in patients with polycystic ovary of neuropeptides, also in the periphery, may be syndrome associated with migraine pathophysiology. A decreased L. Al-Hassany1, B. K. T. Zick1,2, A. H. J. Danser1, J. S. action of these neuropeptides might be involved in the Laven3, M. J. H. Wermer2, G. M. Terwindt2, A. Maassen increased CV risk in female migraineurs, as the van den Brink1 neuropeptide CGRP is proposed to exhibit 1Erasmus University Medical Center, Division of cardioprotective effects in CV diseases. Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, Netherlands 2Leiden University Medical Center, Department of Neurology, Leiden, Netherlands P198 3Erasmus University Medical Center, Division of Calcitonin Gene-Related Peptide (CGRP) plasma levels Reproductive Endocrinology and Infertility, in patients with migraine and endometriosis Department of Obstetrics and Gynaecology, B. Raffaelli1, L. H. Overeem1, J. Mecklenburg1, M. D. Rotterdam, Netherlands Hofacker1, C. P. Nowak2, L. Neeb1, S. Mechsner3, U. Reuter1 Objective: Both migraine and the endocrine disorder 1Charité - Universitätsmedizin Berlin, Department of Polycystic Ovary Syndrome (PCOS) are associated with Neurology, Berlin, Germany increased cardiovascular risk. The underlying 2Charité Universitätsmedizin Berlin, Institute of mechanism might be related to CGRP or other Biometry and Clinical Epidemiology , Berlin, Germany neuropeptides. We studied the contribution of 3Charité Universitätsmedizin Berlin, Department of neuropeptide release to peripheral microvascular Gynecology, Berlin, Germany function (PMVF) in women suffering from PCOS, with and without migraine. Background: Endometriosis and migraine are pain disorders with epidemiological similarities. CGRP plays Methods: PMVF of migraineurs and non-migraineurs a crucial role in the pathogenesis of both migraine and with PCOS (40-60 years) was assessed cross-sectionally endometriosis-related pain. We aimed to compare by two measurements: (I) the EndoPat and (II) a study CGRP plasma levels at different times of menstrual of Local Thermal Hyperemia (LTH) of the skin of the cycle in patients with migraine and endometriosis, volar forearm under control conditions and after patients with either migraine or endometriosis, and inhibition of neuronal axon reflex by EMLA cream healthy controls. application. The dermal blood flow response to LTH is characterized by a first peak mediated by neuropeptide Methods: We recruited episodic migraine patients release, followed by a plateau phase where nitric oxide from our headache center, and patients with a is mainly involved. laparoscopically confirmed endometriosis from specialized endometriosis centers. All patients and Results: We included 50 women with PCOS (mean age controls had a regular menstrual cycle. A baseline 50.3±2.9 years) and of which 40% had comorbid assessment included anamnestic features, clinical migraine. The EndoPat showed no difference in the history, and disease-related quality of life (Headache Reactive Hyperemia Index scores between migraineurs Impact Test-6 and Endometriosis Health Profile-30). and non-migraineurs (log transformed scores 0.698 We collected peripheral blood samples at day 2 ±2 (d2) and 0.660 respectively; 95% CI of the difference [-0.126 of menstrual cycle (i.e. during menstruation) and at – 0.202]; p=0.641) and both scores fell within the day 15 ±2 (d15). CGRP levels were analyzed with a normal range. In contrast, LTH measurements showed commercial enzyme immunoassay kit (Bertin a lower neuropeptide peak in the control condition in Bioreagent). Groups were compared using migraineurs (p=0.023). Inhibition by EMLA cream nonparametric multiple contrast test procedures. resulted in a higher Area Under the Curve (AUC) of the total heating response relative to the AUC in the Preliminary results: We included 124 participants (31 control condition in women with PCOS and migraine with migraine, 30 with endometriosis, 31 with migraine (95% CI [1.359 – 31.163]; p=0.033). and endometriosis, and 32 healthy controls). Groups 124

did not differ in age or key migraine and endometriosis 2157 subjects recruited from Manchester and characteristics. Patients with migraine and Budapest were included to our cross-sectional study. endometriosis reported a greater impact of 27.8% showed migraine according to the ID-Migraine endometriosis-related pain on their quality of life questionnaire. Stress factors were assessed by a compared to patients with endometriosis only shortened version of Childhood Trauma Questionnaire, (p=0.004). Patients with migraine and endometriosis List of Threatening Experiences and our validated revealed higher CGRP plasma levels at d2 than at d15. background questionnaire to capture financial The difference between d2 and d15 was significantly difficulties. Logistic regression models were used to higher in patents with both diseases than in healthy test the main effect of rs10462028 and the SNP x stress controls (p=0.003). factors interaction effects on migraine in the total population and both subsamples. All models were Conclusion: Migraine patients with a comorbid adjusted for gender, age, population, and possible endometriosis show menstrual cycle-dependent confounding effects of lifetime bipolar disorder and changes in CGRP plasma levels, with higher depression were also tested. concentrations during menstruation. This suggests a common epidemiological background of both diseases Rs10462028 showed no genetic main effect on with a prominent role of CGRP in comorbid patients. migraine. From the included stress factors, only financial difficulties showed a significant interaction effect with rs10462028 (p=0.006 in recessive model) on migraine. This result survived correction for lifetime P199 bipolar and unipolar depression, and was replicated in CLOCK gene and migraine: the role of stress both subsamples, although, only a trend effect was D. Baksa1,2, X. Gonda3,4,5, N. Eszlari1,3, P. Petschner1,5, G. reached after Bonferroni-correction. Bagdy1,3,5, G. Juhasz1,3,5 1Semmelweis University, Department of Our exploratory study suggests that variations in the Pharmacodynamics, Faculty of Pharmacy, Budapest, CLOCK gene might influence the risk of migraine in Hungary interaction with a chronic stress factor, namely 2Semmelweis University, SE-NAP2 Genetic Brain perceived financial difficulties. Thus, financial stress Imaging Migraine Research Group, Hungarian Brain may affect migraine by altering circadian rhythms. Research Program, Budapest, Hungary 3Semmelweis University, NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Budapest, Hungary P200 4Semmelweis University, Department of Psychiatry and Pressure Pain Threshold in the trigeminocervical Psychotherapy, Budapest, Hungary complex muscles in chronic migraine: preliminary 5Semmelweis University, Hungarian Academy of data of a cross-sectional observational study Sciences, MTA-SE Neuropsychopharmacology and M. Deodato1,2,3, P. Manganotti1, L. D'Accunto1,3, A. Neurochemistry Research Group, Budapest, Hungary Granato1,3 1univeristy of Trieste, Department of Medical, Surgical The polygenic nature of migraine is known, and and Health Sciences, University of Trieste, Trieste, Italy environmental factors – especially stress – are also 2university of Trieste, Department of Life Sciences, important in migraine pathogenesis, but there is a University of Trieste, Trieste, Italy significant lack of gene x environmental studies of 3Azienda Sanitaria Universitaria Giuliano Isontina, migraine. Previous studies also suggested roles for Trieste, Italy circadian factors in migraine, however, circadian genes have not been tested in association with migraine. For Objective: Aim of the study is to compare the Pressure our study we selected a tagSNP of CLOCK gene, Pain Threshold (PPT) in 5 muscles of the rs10462028 which has been previously associated with trigeminocervical area with one muscle of the lag, in bipolar disorder, a comorbid disease of migraine. Our patients with chronic migraine (CM). goal was to test the SNP’s main effect and its interaction with various stress factors on migraine. Methods: Patients with CM (ICDH-3 criteria) with diffuse and bilateral headache were enrolled in the 125

Headache Centre of Trieste. The PPT assessment was P202 based on the Guidelines of the Andersen systematic Association of CLOCK rs1801260 polymorphisms in review (2015). The algometer was used over trapezius, patients with chronic migraine and sleep disorder levator scapula, temporalis, suboccipitalis and middle H. Genc1, A. Ozge2, G. Orekici Temel3, I. O. Barlas4, N. scalene bilaterally. Each muscle was assessed with 3 Oksuz2 consecutive measures intervals of one minute each. 1SBU Van Education and Research Hospital, Neurology, The evaluations were applied when the patients were Van, Turkey pain free from at least 48 hours. Data were compared 2Mersin University Medical Faculty, Neurology, Mersin, with the PPT over the tensor fascia lata muscle. Data Turkey were analyzed with GraphPad InStat 3.06. 3University of Mersin, Department of Biostatistics and Medical Informatics, Mersin, Turkey Results: 27 patients were enrolled (22F/5M; mean age 4University of Mersin, Department of Medical Biology 51.9±13.1 years). The mean PPT of the and Genetics, Mersin, Turkey trigeminocervical muscles is reported in the figure. All the mean trigeminocervical muscles PPT were Backgrounds and aims: Many studies have found a significantly lower than the thresholds of the tensor significant relationship between migraine and sleep fascia lata muscle. The higher differences were found disorders. Genetic analysis of circadian phenotypes in the temporal and suboccipital muscles (temporalis may be helpful in understanding sleep disorders right vs tensor fascia lata right, p=<0.001; temporalis associated with migraine. CLOCK rs1801260 right vs tensor fascia lata left, p=<0.001; temporalis left polymorphisms have been previously shown to be vs tensor fascia lata right, p=<0.001; temporalis left vs associated with regulation of the circadian rhythm. Our tensor fascia lata left, p=<0.001; suboccipitalis right vs aim in this study is to evaluate the relationship of tensor fascia lata right, p=<0.001; suboccipitalis right vs CLOCK rs1801260 gene with chronic migraine and tensor fascia lata left, p=<0.001; suboccipitalis left vs sleep disorders and ss far as we know, the association tensor fascia lata right, p=<0.001; suboccipitalis left vs between CLOCK rs1801260 gene and migraine has not tensor fascia lata left, p=<0.001). No significant been investigated before. differences were found between the right and left sides in each of the muscles of the trigemicocervical Methods: Volunteer individuals aged 18-75 were area. included in the study in three groups. Each group was made up of 50 people. The first group; It was created Conclusions: all the trigeminocervical complex muscles from patients diagnosed with chronic migraine. The analyzed, mostly temporalis and sub-occipitalis, are sleep disorders of patients were evaluated by Epworth sensitive in patients with CM in non-algic phase. sleep scale and Pittsburgh Sleep Quality Scales (PSQI). The second group was formed from the first degree Figure 1 relatives that without headache and sleep disturbance of the patients. Finally, the third group was formed from the spouse or other volunteers who did not have headache and sleep disturbance and who did not have blood relation of the patients. Genotyping was performed for the CLOCK rs1801260 gene.

Results: The average age of patients and control groups was 39.6 (± 13.5) and 86 (57.3%) were women(Table 1). All patients with migraine had PSQI≥5. Again, in 14 (28%) of migraine patients, increased daytime sleepiness was detected. Among the patients and control groups, female gender and those with O blood group; there was a statistically significant difference in terms of CLOCK polymorphism. No statistically significant difference was found between migraine patients with psychiatric complaints and control groups(Table 2). 126

Conclusion: In this study, in women patients or P203 patients that have O antigen, when the G allele of the Distinctive association of single nucleotide CLOCK rs1801260 gene appears like a indirect factor polymorphism 1911A>G in the TRPV1 receptor gene that increases the risk of chronic migraine and sleep with episodic and chronic migraine: the absence of disorders, the A allele also appears like a indirect GG genotype as possible biomarker of migraine protective factor. chronification risk A. Yakubova1, Y. Davidyuk1, R. Giniatullin1,2, A. Disclosure: This study was supported by Mersin Rizvanov1 University Faculty of Medicine, Individual Research 1Institute of Fundamental Medicine and Biology, Kazan Project (IRP) (Project No: 2018-2-AP4-2932). Federal University, Kazan, Russian Federation 2A.I.Virtanen Institute for Molecular Sciences, Figure 1 University of Eastern Finland, Kuopio, Finland

Background: Transient receptor potential vanilloid type 1 (TRPV1) receptors activated by heat and capsaicin are expressed in trigeminal nociceptive neurons and implicated in the generation of migraine pain. Genetic studies suggested that single nucleotide polymorphism (SNP) 1911A>G (rs8065080), leading to amino acid substitution Ile585Val, in the TRPV1 gene affects functional activity of TRPV1 receptors and is involved in different pain conditions. However, this SNP has not been tested in migraine patients. Figure 2 Objective: To investigate genetic factors of migraine susceptibility we evaluated frequency distribution of AA, AG and GG variants of SNP 1911A>G in the TRPV1 gene in patients of two subtypes of migraine based on attack frequency, i.e. episodic and chronic migraine, compared to healthy controls.

Methods: The study included 38 patients diagnosed with migraine (22 episodic and 16 chronic) and 50 healthy individuals as a control group. DNA from peripheral blood was used to test TRPV1 SNP using allele-specific PCR combined with gel electrophoresis.

Results: The genotype frequency distribution in episodic migraine patients was comparable with that in controls (AA 32%, AG 54%, GG 14% and AA 34%, AG 46%, GG 20%, respectively) but the contribution of still presenting GG variant was relatively reduced. Opposite, in chronic migraine the distribution differed significantly (p<0.05): the AA genotype nearly doubly increased, whereas the GG variant was completely absent, AA 69%, AG 31%, GG 0% (Fig.1).

Conclusions: This is first indications for a distinctive genotype frequency distribution of TRPV1 1911A>G in chronic migraine patients compared to episodic migraine patients and controls. Our data confirm a

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different predisposition to chronic pain in migraine and Patients and Methods: The study included 343 give a prerequisite for a new look at the nature of individuals: 170 migraine patients and 173 controls. chronification of migraine pain, proposing that the HRMA and Sanger sequencing were used for absence of GG genotype may be considered as genotyping. potential biomarker of migraine chronification risk. Results: AA genotype of c.56G>A SCN2A was found only in migraine patients. Patients with c.328T>C Figure 1 KCNK18 mutation had increased risk of developing migraine before the age of 18. Moreover, individuals with AA/TC haplotype of KCNK18 had higher attack frequency than those with AA/TT (p<0.05). . The c.3053A>G TRPA1 polymorphism was more common in patients with migraine onset before the age of 15 (p<0.05), while c.31-1811C>T STX1A and c.3199G>A SCN1A before the age of 10 (p<0.01). T allele of c.31- 1811C>T STX1A was more frequent in MA patients than MO (p<0.05) Interestingly, meta-analysis showed significant association of c.31-1811C>T STX1A polymorphism with migraine overall (OR=1.22, p=0.0086), MA and MO.

Conclusions: Both polymorphisms and mutations in genes encoded ion channels or proteins regulating P204 their functioning may increase the risk of migraine and Analysis of genetic variants in SCN1A, SCN2A, correlate with clinical features of disease such as age of KCNK18, TRPA1 and STX1A in migraine onset and attack frequency. M. Kowalska1, M. Prendecki1, M. Kapelusiak-Pielok2, T. Grzelak3, U. Łagan-Jędrzejczyk1,2, M. Wiszniewska4,5, W. Kozubski2, J. Dorszewska1 1Poznan University od Medical Sciences, Laboratory of P205 Neurobiology Department of Neurology, Poznan, Alterations in the upper trapezius muscle in migraine Poland patients assessed by quantitative magnetic resonance 2Poznan University od Medical Sciences, Chair and imaging using T2 mapping. Department of Neurology, Poznan, Poland M. V. Bonfert1, P. Schandelmaier1, D. Weidlich2, D. 3Poznan University od Medical Sciences, Department of Karampinos2, C. Börner1, G. Urban1, H. Koenig1, M. N. Physiology, Poznan, Poland Landgraf1, T. Baum3, F. Heinen1, N. Sollmann3 4Stanislaw Staszic University of Applied Sciences in Pila, 1Ludwig-Maximilians-University, Department for Faculty of Health Care, Piła, Poland Pediatric Neurology, Munich, Germany 5Specialistic Hospital in Pila, Department of Neurology, 2Technical Unversity Munich, Department of Diagnostic Piła, Poland and Interventional Radiology, Munich, Germany 3Technical Unversity Munich, Department of Diagnostic Question: Migraine is one of the most common and Interventional Neuroradiology, Munich, Germany neurological disorders and affects 11% of population. It may be considered as a channelopathy. The Questions: Migraine often is associated with pain in dysregulation of ion functioning due to genetic the neck-shoulder region (NSR), playing a crucial role in changes may activate the trigeminovascular system the central-peripheral pathophysiological loops and induce migraine attack both migraine with aura conceptualized as trigemino-cervical complex (TCC). (MA) and without aura (MO). The aim of the study was Quantitative magnetic resonance imaging (MRI) using to analyze the following variants of genes encoding ion T2 mapping can be applied to non-invasively assess the channels and associated protein: c.3199G>A SCN1A, characteristics of skeletal muscle tissue. In this pilot c.56G>A SCN2A, c.28A>G and c.328T>C KCNK18, study, the question is addressed if T2 values are c.3053A>G TRPA1, c.31-1811C>T STX1A in migraine increased in migraine patients (MP). patients. 128

Methods: 41 subjects (35 females, 22.9±2.7 years) association remain unclear. We aimed to assess the participated in this prospective study including 22 MP impact of RLS on migraine features. (ICHD 3 diagnosis) and 19 healthy controls (HC; no primary headache disorder). The NSR of the Methods: We included consecutive patients with participants was scanned on a 3-Tesla MRI (Ingenia migraine referring to our tertiary Headache Center. For Elition, Philips Healthcare), acquiring a three- each patient, we recorded sex, age, and vascular risk dimensional T2-prepared turbo spin echo (TSE) factors, together with migraine characteristics sequence to generate T2 maps. T2 maps were then including frequency, aura, and age at onset. Each used to manually segment the upper trapezius muscles patient underwent a transcranial Doppler examination (TM) of both sides by enclosing the muscle volume to detect RLS in basal conditions and under Valsalva with manually placed regions of interest (ROIs). The maneuver. We quantified RLS as absent (no bubbles), mean T2 values were extracted, averaged for both mild (<10 bubbles), moderate (10-20 bubbles), or sides, and compared between MP and HC (unpaired t- severe (shower effect). We performed Spearman’s test). correlation tests among the collected variables.

Results: MRI including ROI placement and extraction of Results: We included 78 subjects, 87.2% were female, T2 values was feasible in all subjects, with a scanning with a median age of 45 (IQR 34-50) years and a time of ~15 min. Mean T2 values of the TM were median age at migraine onset of 18 (IQR 14-25) years. 30.1±1.1 ms (range: 28.4-32.0 ms) in HC and 31.1±1.0 36 patients had RLS, which was mild in 15, moderate in ms (range: 29.6-32.7 ms) in MP, with a statistical 10 and severe in 11. We did not find any difference in significance between groups (p = 0.0056). migraine characteristics (migraine type, presence of aura, frequency of attacks severity of attacks, age at Conclusion: Higher T2 values among MP when migraine onset) according to RLS presence and compared to HC may reflect an imaging-based severity. Only, in patients with CM there was a trend correlate of oedematous changes of the TM, likely towards a negative correlation between age at consistent with the concept of muscle involvement in migraine onset and monthly frequency (R= -0.225; the pathophysiology of migraine according to the TCC. P=0.071). Given the small sample size current mean T2 values do not allow for a subject-specific diagnosis; however, Conclusion: According to our data, RLS is highly with a larger sample size the T2 value may prove to be prevalent in patients with migraine. However, RLS does a valuable non-invasive, MRI-based biomarker for the not seem to affect migraine characteristics. Advanced muscular involvement in migraine, also potentially functional studies are needed to clarify the role of RLS enabling follow-up evaluations after muscle-focused in migraine. interventions.

P207 P206 Genetically mediated risk factors for migraine with Contribution of right-to-left shunt to migraine aura features I. Maryenko1 I. FRATTALE1, R. ORNELLO1, V. CAPONNETTO1, F. 1Republican Research and Clinical Center of Neurology PISTOIA1, P. CERRONE1, C. TISEO1, A. SPLENDIANI1, S. and Neurosurgery Minsk, Republic of Belarus, SACCO1 neurology, Minsk, Belarus 1UNIVERSITY OF L'AQUILA, Department of Applied Clinical Sciences and Biotechnology , L'AQUILA, Italy Introduction: The studies have shown that there is a link between genetically mediated 5-HT metabolism Background: Migraine is associated with a higher and migraine pathogenesis. prevalence of right-to-left shunt (RLS) compared with the general population. However, the nature of this Objective: To establish a link of 5-HTTLPR functional association remain elusive. RLS may trigger some polymorphism and migraine with aura. migraine attacks but the exact nature of this

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Materials and methods: 58 patients with migraine 4Guy's and St Thomas' NHS Foundation Trust, The Pain were examined, and were divided into 2 subgroups: Managment and Neuromodulation Centre, London, patients with migraine without aura, n=33, age 35 [28; United Kingdom 42], patients with migraine with aura, n=25, age 33 [26; 5Guy's and St Thomas' NHS Foundation Trust, 40]. The control group consisted of 19 healthy persons. Headache Centre , London, United Kingdom

Results: The genotype of 5-HTTPR differed statistically Background: The premonitory phase of migraine significantly (p<0,001) in the main and control groups. reflects the initiation of the migraine attack and It was found that the S/S genotype of the 5-HTTPR hypothalamic dysfunction has been implicated in it. gene is associated with the development of migraine Infusion of glyceryl trinitrate (GTN) have been shown with aura, the detection rate is statistically significantly to trigger migraine attacks and hypothalamic higher in patients with aura compared to patients with dysfunction during the premonitory phase. We have migraine without aura and the control group (criterion previously shown in a rodent model of migraine that χ2, p=0,011 and p=0,008, respectively). A characteristic GTN can induce early changes in hypothalamic genetic feature of migraine without aura is the neuronal firing. This study aims to investigate early detection of the L/L genotype of the 5-HTTPR gene, transcriptional responses to GTN-infusion in mice while the frequency of its detection is statistically hypothalamus in order to elucidate the mechanisms significantly higher in migraine with aura compared involved in the initiation of migraine attacks. with patients with migraine without aura and the control group (criterion χ2, p=0.025 and p=0.041, Methods: Mice were anaesthetized and infused respectively). The relative risk of migraine with aura in intracarotidly with GTN (4 µg/mL; 6µL/min) or vehicle the presence of the S/S genotype of the 5-HTTPR gene for 20 min, followed by a 30 min post-infusion period, is 2,80% [1,75-3,85] compared to the control group, prior to the collection of the hypothalamus for and 2,31% [1,42-3,21] compared to the subgroup of microarray analysis. Expression patterns of selected patients with migraine without aura. The relative risk genes were confirmed by quantitative real-time PCR. of developing migraine without aura in the presence of Pathways analysis was carried out using the database the L/L genotype of the 5-HTTPR gene is 3,44% [2,03- for annotation, visualization and integrated discovery 4,85] compared to the control group, and 4,05% [2,65- (DAVID) Bioinformatics Resource. 5,45] compared to the subgroup of migraine patients with aura. Results: Differences in gene expression were detected in a total of 45037 genes between treatments, and of Conclusions: This 5-HT transcription polymorphism those 864 were significantly different (P <0.05), with affects a different response to 5-HT agonist drugs such 517 genes being upregulated and 347 genes being as tryptans. downregulated post-GTN infusion. The DAVID analysis demonstrated enrichment of pathways pointing towards an increase in immune response, signal transduction, and neurodevelopment, but also in more P208 migraine pathophysiology related pathways, such as in Micro-array analysis of the hypothalamus in the nitro- circadian rhythm and metabolism pathways, and in glycerine animal model of migraine – Investigating pathways involved in the detection of mechanical pain. the migraine premonitory phase R. Abuukar Abdullahi1, D. Chambers 2, G. Williams3, T. Conclusion: GTN infusion in mice provokes early Takahashi1, B. Okine1, A. Al-Kaisy4, G. Lambru5, A. P activation of the hypothalamus and enrichment of Andreou 1,5 several neuronal pathways. Of them, pathways related 1King's College, The Headache Research Lab, Wolfson to migraine pathophysiology, such as circadian rhythm, Centre for Age Related Diseases, London, United metabolism and mechanical pain pathways were Kingdom significantly altered. Future in-depth studies of these 2King's College, Genomics Drug Discovery Unit, pathways will increase our understanding of migraine Wolfson Centre for Age Related Diseases, London, pathogenesis. United Kingdom 3 King's College, Bioinformatics, Wolfson Centre for Age Related Diseases, London, United Kingdom 130

P209 prefrontal cortex, right hippocampus and the posterior Thalamo-cortical networks in migraine: a pilot study cerebellum (lobules VI, IX and VIIIb). using advanced fMRI techniques in experimentally- induced attacks These findings reveal that during the NTG-induced D. Martinelli1, G. Castellazzi2,3, R. De Icco1, A. Bacila4, F. migraine attack the whole brain FC changes Palesi5, G. Salvini2, M. Allena6, E. Guaschino6, G. systematically, involving areas well known for their Sances6, A. Pichiecchio4, C. AM Gandini Wheeler- roles in pain modulation and migraine generation. The Kingshott2,5,7, C. Tassorelli1 NTG model applied to advanced fMRI approach 1IRCCS Fondazione Mondino / Pavia University, provides further support to the idea of migraine as a Headache Science Center / Dept of Brain and cyclical functional disorder where the brainstem pain- Behavioural Sciences, Pavia, Italy modulating circuitry and hypothalamus have a leading 2IRCCS Fondazione Mondino, Brain MRI 3T Center, role in the premonitory phase, while the thalamus Pavia, Italy plays a more relevant role in the full-blown phase for 3Pavia University, Dept of Electrical, Computer and its involvement in cortical processing of both sensory Biomedical Engineering, Pavia, Italy and cognitive information. 4IRCCS Fondazione Mondino, Neuroradiology unit, Pavia, Italy Figure 1 5Pavia University, Dept of Brain and Behavioural Sciences, Pavia, Italy 6IRCCS Fondazione Mondino, Headache Science Center, Pavia, Italy 7UCL Institute of Neurology, NMR Research Unit, Dept of Neuroinflammation, London, United Kingdom

Resting state functional magnetic resonance imaging (rs-fMRI) has depicted cyclical functional connectivity changes during the ictal and inter-ictal phase of the migraine attack. In this pilot study, FC changes during nitroglycerin (NTG) induced migraine attacks were assessed. To this end, 5 subjects with episodic migraine (EM) without aura (3M-2F, 33±6.5 years) were enrolled. NTG-triggered a spontaneous-like migraine attack in the subjects.

They underwent 4 rs-fMRI scan repetitions during different phases of the attack (baseline, prodromal, full blown, recovery phase) with a 3T Skyra Siemens MR scanner. Subjects’ rs-fMRI data were analysed with a P211 seed-based correlation analysis (SCA). According to the Multidisciplinary expert consensus for vestibular pain field literature, left and right thalamic areas were migraine individually selected as seed region for the SCA. X. Qi1 1The Sixth Medical Center, Chinese PLA General Results proved that the thalamic areas show significant Hospital, Neurology, Beijing, China altered functional coupling within themselves and several areas involved in the pain circuits, including the dorsolateral prefrontal cortex, anterior cingulum, The patients with Vestibular migraine（VM） may brainstem, hippocampus and hypothalamus during the need neurological, emergency or otorhino- prodromal phase, reaching the maximal alteration (i.e. laryngological services, and the disorder is often reduced functional correlation) during the full blown misdiagnosed with posterior circulation ischemia or phase (Fig.1). Interestingly, the right thalamus showed TIA, peripheral vestibular vertigo, Meniere’s disease significant increased functional correlation with the (MD), and multiple (lacunar) cerebral infarctions. So multidisciplinary expert consensus about VM is 131

needed. Now Chinese multidisciplinary expert Figure 1 consensus as follow:

1. Vestibular migraine is a common disorder with familiar predisposition, and characterized by recurrence of episodic dizziness or vertigo, which may be accompanied by nausea and vomiting, with or without headaches.

2. VM is one of the most common disorders causing vertigo, with a female preponderance. Some female patients with migraine headaches may transform to VM during their menopausal period.

3. The pathogenesis of VM is multiple.

4. VM present mainly with vertigo/dizziness, and the mean age of first presentation is older than that of migraine. Stress, fatigue, anxiety and lack of sleep may trigger the attack of VM.

5. Asking family history of migraine headache and VM P212 should also be emphasized. The Migraine Landscape on YouTube: An Analysis of YouTube as a Source of Information on Migraine 6. VM lacks specific signs. transient signs may occur. H. Saffi 1, T. P. Do1, J. M. Hansen2, D. W. Dodick3, M. Ashina1 7. MRI imaging and other ancillary findings for VM are 1Danish Headache Center, Department of Neurology nonspecific, however, they are necessary for the Rigshospitalet Glostrup Faculty of Health and Medical differential diagnosis with other disorders. Sciences, University of Copenhagen Valdemar Hansen Vej 5, DK-2600 Glostrup, Denmark, Glostrup, Denmark 8. The diagnostic criteria for VM requires 5 or more 2National Knowledge Center for Headache, Glostrup, episodes of moderate to severe vestibular attacks. For Denmark 3 patients with definite family history of migraine Mayo Clinic, Department of Neurology, Scottsdale, AZ, headache or previous migraine headache attacks, who United States present with the first episode of vestibular vertigo, VM should be considered. The diagnosis and differential Introduction: Health information is one of the most diagnosis flowchart for VM is helpful. frequently searched topics on the Internet. YouTube is the most widely used video hosting website in the world and it is the second most popular website in the world after Google, however, the quality and reliability of this information is unknown. The aim of this study is to evaluate the content and distribution of the most popular videos on YouTube about migraine.

Methods: We searched for migraine-related videos on the online video hosting resource YouTube (http://www.youtube.com). Two authors screened the titles and video descriptions independently for all videos with a view count of ≥10,000 views. For each video we recorded descriptive data, the source/author and the primary purpose/content.

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Results: We identified 351 videos for further analysis. consisting of 35 acute and 42 preventive treatments. In total, there was more than three days of content For acute treatments, pharmacological options were viewed more than 163 million times. Only 9% of these more frequently recommended, whereas non- videos were authored by healthcare professionals. The pharmacological options were more frequent among majority (44%) of videos focused on complementary preventive treatments. Evaluation of the consumer and alternative medicine. health information using the DISCERN tool showed that non-governmental organizations had the highest mean Discussion: Patients seeking information online are in total score. general not trained to evaluate the veracity of this information. Nonetheless, video-sharing media can be Conclusions: The Internet is a major source for health an important way to publish effective interventions information, including migraine treatment. This about health and pathophysiology. Peer-reviewed provides a democratic, accessible and popular venue information on migraine mechanisms and treatment is for dissemination of evidence-based health needed to provide the best available evidence for the information. public and patients. Ideally, a professional society or foundation such as the International Headache Society with the leading experts in the world, would develop, curate, and distribute content that is appropriate for P214 patients of all ages and geographies. Translation and validation of a German ID MigraineTM version as migraine screening tool A. Thiele1, S. Strauß1, A. Angermaier1, R. Fleischmann1 1University Medicine Greifswald, Department of P213 Neurology, Greifswald, Germany Googling migraine: A study of Google as an information resource of migraine management Question: Migraine is a highly prevalent neurological R. Bojazar1, T. P. Do1, J. M. Hansen2, D. W. Dodick3, M. disease that affects patients’ daily activities, Ashina1 psychosocial and work life, leading to loss of 1Danish Headache Center, Department of Neurology, productivity and substantial health care costs. Rigshospitalet Glostrup Faculty of Health and Medical Nevertheless, migraineurs are underrecognized and Sciences, University of Copenhagen, Glostrup, undertreated. Screening tools allowing for their easy Denmark recognition would thus have a significant potential to 2National Knowledge Center for Headache, Glostrup, ameliorate the burden. The ID MigraineTM is a 3-item Denmark screening tool for use in non-specialised settings 3Mayo Clinic, Department of Neurology, Scottsdale, AZ, including primary care. We aimed to translate and United States validate a German ID MigraineTM.

Introduction: Health information is one of the most Methods: The original English version was translated frequently searched topics on the Internet. In this using the multi-stage validated FACIT-translation study, we evaluated the content of the highest indexed methodology. In line with the French ID MigraineTM, Google search results related to migraine we added a fourth aura item. 105 patients (80 female, management. 46.5±17.2 years of age) visiting an outpatient headache clinic filled in the screening tool and were then Methods: We identified the five most used search diagnosed by a headache specialist, blinded to the terms related to migraine management via Google screening result, according to ICHD-3 criteria. Trends. We entered each search term into Google's Sensitivity, specificity and predictors of false search engine and retrieved the search results from positive/negative rates were estimated through ROC the first three sites from each search query. We analyses and binary logistic regression. stratified the recommended treatment options and evaluated the websites using the DISCERN tool. Results: 79 patients (75%) were clinically diagnosed with migraine, 21 patients (20%) had a chronic Results: In total, 73 unique websites recommended a migraine. Sensitivity/specificity of the 3-item German total 77 different migraine treatment options, ID MigraineTM were 99%/68% using a cut-off of 2 133

points and 72%/86% using a cut-off of 3 points, for LFEM, 2.4±1.0 for HFEM, 9.6±5.0 for CM which, respectively. Including the fourth item, according to the Catalan average hourly wage, resulted sensitivity/specificity were 99%/41% using a cut-off of in a global productivity loss for the hospital of 2 points and 79%/86% using a cut-off of 3 points, 28,283.20€/month (7,920€ CM; 2,246.2€ HFEM; respectively. Neither attack frequency, disease 18,117.0€ LFEM). Healthcare resource utilization: duration, patient age or gender were predictive of false 28.4%(135/476) had gone to the emergency room at positives or negatives. Yet, migraineurs without nausea least once for their headache in the last year. Only or vomiting during attacks were overrepresented 13.2%(63/476) had currently a medical follow-up for among false negatives. The aura question identified 18 headache, while 39.7%(189/476) did not, although out of 20 patients with migraine with aura. considered that could benefit from it.

Conclusions: The German version of the ID Conclusion: Although healthcare professionals have MigraineTM is a valid and efficient screening tool to greater knowledge on health issues, our hospital identify migraineurs, even in a challenging population workplace cohort shows underdiagnoses, of a specialised headache clinic. undertreatment and significant working impact of migraine, resulting in economic loss due to reduced productivity and healthcare resource utilization. These results support the need for stronger strategies to face P215 the personal, social and economic burden of migraine Working and economic impact of migraine in a at workplace hospital workplace cohort E. Caronna1,2, V. J. Gallardo1, A. Alpuente1,2, M. Torres- Ferrus1,2, P. Pozo-Rosich1,2 1Vall d’Hebron Research Institute, Barcelona, Spain P216 2Vall d’Hebron Hospital, Headache Unit, Barcelona, A longitudinal study assessing the natural course of Spain Visual Snow Syndrome M. Graber1, A. Scutelnic1, P. Goadsby2, C. Schankin1 Objective: To assess working and economic impact of 1Inselspital, Bern University Hospital, Department of migraine in a workplace cohort of a Spanish tertiary Neurology, Bern, Switzerland hospital. 2King's College London, NIHR-Wellcome Trust King's CRF, London, United Kingdom Methods: Cross-sectional analysis of a cohort of employees working in a tertiary hospital. A web Question: Patients with "visual snow syndrome" (VSS) questionnaire was sent to all current 7517 employees, suffer from a continuous visual disturbance of TV collecting demographic data, characteristics and snow-like flickering dots in the entire visual field (visual working impact of headache (WPAI) as well as data on snow, VS) with additional symptoms. The question we healthcare resource utilization. addressed was how the natural course of the disorder develops over eight years. Results: 672 employees participated: 81.7% women; mean age 41.1±12.2 years; 33.3% nurses, 23.0% Methods: In this longitudinal study, 78 patients with physicians; 84.5% had graduate or higher studies. confirmed VSS, including normal ophthalmologic Headache type: 70.8%(476/672) fulfilled criteria for exams, were followed from November 2011 to migraine or probable migraine, 15.2% (102/672) for December 2019. Assessment of the clinical course was tension-type headache, while 14.0%(94/672) reported performed by a semi-structured telephone interview. no headache. 76.9%(366/476) had low-frequency episodic migraine (LFEM), 12.6%(60/476) high- Results: For the follow up interview, forty of 78 (51%) frequency episodic migraine (HFEM) and patients were reached at a mean follow up time of 10.5%(50/476) chronic migraine (CM). Treatment: 83.6 ± 4.5 months. Less patients rated VS itself as the 91.2%(438/476) denied being on preventive treatment most disturbing symptom when compared to 2011 in the last year and 8.6%(41/476) were overusing acute (40% in 2019 vs 72.5% in 2011, p=0.001); instead, medication. Working and economic impact: working patients suffered more from floaters and palinopsia. time lost due to headache was 3.0±0.8 hours/month Two of 40 (5%) reported the onset of additional visual 134

symptoms, which were tunnel vision and light flashes. transformed). Odds ratios (OR), β-estimates and 95% In 14 of 40 patients (35%) new treatment was initiated. confidence intervals (95%CI) were estimated using Of those, six (42%) were somewhat helpful: multinomial logistic and linear regression models to lamotrigine, diet/vitamin supplements/probiotics, analyze the association between HA status (ref. oHA) lorazepam, cinnarizine, polarized glasses, chiropractic and CAC at t0, adjusted for sex, age, BMI, education, treatment. Three patients experienced new visual smoking, physical activity and systolic blood pressure. migraine aura without headache, and one had new migraine headache during follow up (total prevalence Results: Of 2990 participants (51% women, 45-75 aura 35%, migraine 47.5%). Compared to 2011 there years) most participants had oHA (42%), 9% had M+, was no significant difference in anxiety and depression 23% M- and 27% nHA. Migraine participants were measured by the PHQ-8 and the GAD-7 questionnaire. more often female, younger and had lower CAC scores (M+: 72% women, 57.3±6.9 years, CAC (median: 1.3; 0- Conclusion: In VSS symptoms can persist over 8 years 100: 80%); M-: 68%, 56.8±7.0 years, CAC (2.6; 81%); without spontaneous resolution. Visual snow itself oHA: 48%, 58.0±7.3 years, CAC (10.1; 74%); nHA: 35%, might get less bothersome over time. Rarely new visual 60.7±7.2 years, CAC (27.8; 66%). There was no symptoms can develop. association between HA status and CAC in the fully adjusted models (M+: OR 1.1[95%CI 0.8;1.6], β -0.1[- 0.3;0.2]; M-: OR 1.1[0.8; 1.4]; β -0.1[-0.2; 0.2]; nHA: OR 1.0[0.8;1.2], β 0[-0.2;0.2]). P217 Migraine with and without aura and coronary artery Conclusions: In this cross-sectional evaluation migraine calcification -Results of the Heinz Nixdorf Recall was not associated with CAC, regardless of aura status. Study- CAC cannot explain the discussed relationship between S. Schramm1, D. Myszkowski1, K. H. Jöckel1, R. Erbel1, B. migraine and CHD. Schmidt1, N. Lehmann1, Z. Katsarava2,3,4, S. Moebus1 1University of Duisburg-Essen, University Hospital Essen, Institute for Medical Informatics, Biometry and Epidemiology, Essen, Germany P218 2Evangelical Hospital Unna, Department of Neurology, Is migraine with and without aura a risk factor for Unna, Germany stroke? -Sex-specific results of the longitudinal 3EVEX Medical Corporation, Tbilisi, Georgia population-based Heinz Nixdorf Recall Study- 4Sechenov University Moscow, Moscow, Russian S. Schramm1, C. E. Wagner1, K. H. Jöckel1, Z. Federation Katsarava2,3,4, S. Moebus1 1University of Duisburg-Essen, University Hospital Introduction: The relationship between migraine and Essen, Institute for Medical Informatics, Biometry and coronary heart disease (CHD) remains controversial. Epidemiology, Essen, Germany The aim of the study was to investigate the cross- 2Evangelical Hospital Unna, Department of Neurology, sectional association between lifetime migraine with Unna, Germany (M+) and without aura (M-) and coronary artery 3EVEX Medical Corporation, Tbilisi, Georgia calcification (CAC). 4Sechenov University Moscow, Moscow, Russian Federation Methods: From 4814 participants of the population- based Heinz Nixdorf Recall Study at baseline [t0, 2000- Introduction: Studies report an increased risk of stroke 2003]) we excluded 1726 due to missing information for migraineurs with aura (M+). The association of on headache (HA) and/or CAC. CAC was measured by migraine without aura (M-) and stroke is controversial. computer tomography at t0. At the 10-year follow-up The aim is to investigate the association between M+ the participants were asked about HA and migraine and M- and stroke. symptoms ever experienced in their lives. According to modified criteria of the International Headache Society Methods: We analyzed 3074 participants (51% women, 2004, we classified HA as M+, M-, other HA (oHA) ever 45-75 years at baseline [t0, 2000-2003]) of the in life and never HA (nHA). We applied the CAC score longitudinal population-based Heinz Nixdorf Recall dichotomously (>100 vs. 0-100) and continuously (log- Study with information about lifetime migraine status 135

at 10-year follow-up. According to modified criterial of Methods: Migren patients (n=55) and healthy control the International Headache Society 2004 we classified patients (n=35) were included in the study. Headache headache (HA) in M+, M-, other HA (oHA) and never characteristics, localization, duration, frequency, and HA (nHA). Prevalent and incident strokes were severity of headache attacks were questioned. assessed. Outcome was the first stroke, exposure the Headache types were diagnosed according to ICHD-3. HA-type (ref.: nHA). Hazard ratios (HRs) and 95% Visual Analog Scale (VAS) and confidence intervals [95%CI] were estimated by Cox Migraine Disability Assessment Questionnaire (MIDAS) regression (using the age of 15 years as starting point), were applied. Serum vitamin D was measured for all adjusting for BMI, sport, smoking, systolic blood patients and controls using enzyme-linked pressure and diabetes at t0. immunosorbent assay (ELISA).

Results: M+ was reported by 8.7% participants (73% Results: 55 patients (n=40 females, n=15 males) were women, 57±7 years), 23% M- (68% women, 57±7 included in the study. The mean age was 37.3 ± 10.97 years), 42% oHA (48% women, 58±7 years), 27% nHA years. Patients with migraine had significantly lower (35%, 61±7 years). 135 participants (62% men) vitamin D level in comparison to controls (P-value reported strokes. We observed a younger mean age <0.01). There was no relationship between vitamin D (±SD) of incident stroke in participants with migraine serum level with headache frequency, duration, and compared to oHA and nHA (women: M+ 49±21 years, localization (P-value >0.05). The incidence of M- 63±12 years, oHA 65±12 years, nHA 66±8 years; phonophobia/photophobia, nausea, vomiting, aura men: M+ 59±12 years, M- 58±12 years, oHA 63±11 and allodynia were similar in migraineurs with vitamin years, nHA 68±9 years). Strokes occurred most often in D deficiency than those with normal vitamin D (P-value women and men with M+ (women: M+ 6.3%, M- 3.3%, >0.05). There was a statistically significant negative oHA 2.4%, nHA 2.8%; men: M+ 9.7%, M- 6.7%, oHA correlation between vitamin D serum level and 3.1%, nHA 7.6%). We observed a strong association VAS/MIDAS score (P-value =0.002 and 0.03). between M+ and stroke in women (adjusted HR[95%CI]; 2.9[1.2;7.0]), and oHA and stroke in men Conclusion: Patients with migraine had significant (0.5[0.3;0.9]). All other results showed no distinguished vitamin D deficiency compared to healthy controls. effects (women: M- 1.3[0.5;3.0], oHA 0.9[0.4;2.2]; Deficiency significantly associated with severity of men: M+ 1.4[0.6;3.2], M- 1.2[0.7;2.3]). headache attacks and migraine-related disability.

Conclusions: In our study stroke occurred in younger Key words: Migraine, Vitamin D, MIDAS, VAS age in participants with migraine and there was an association between M+ and stroke in women. For men the results were ambiguous. P221 Sporadic Hemiplegic Migraine: A case report S. Shaafi1 P219 1Tabriz University of Medical Science, Neurology, The association between serum vitamin D level and Tabriz, Iran migraine headache: a case-control study F. Eren1, A. Demir1 We report 28 years old with headache history who was 1Unversity of Health Sciences, Konya Training and admitted in neurology ward with acute right Research Hospital, Neurology, Konya, Turkey hemiparesis and mild right central hemi facial weakness.Her past medical and familial histpry were Question: Vitamin D levels in migraine have shown negative. She underwent work up for stroke in young different results in many studies. But, it has been adult. Her clinical presentation was moderate to severe detected that the frequency, severity and duration of headache with nausea and vomiting, normal headache may decrease with vitamin D supplements. fundoscopy, no cervical redor meningeal signs, mild We performed this cross-sectional clinical-based study right central hemi facial weakness and right in order to determine the association between serum hemiplegia.Cardiovascualr exam was normal. Systemic vitamin D level and characteristics of migraine exam also was without abnormality. Her routine lab headache. tests, CSF analysis, brain CT scan, vasculitic tests were 136

normal. Echocardiography (routine and Trans (10) position of left hand; and (11) position of right esophageal) and cardiology consult were normal. Brain hand. MRI T1-weighted showed left hemispheric edema.D WI showed no abnormality; She was treated with Results: We identified 305 relevant portrayals for Naproxen, Metoclopramide, Acetazolamide.And after analysis on the 283 images included. The images of 24 hr. her hard focal signs were resolved and she people with migraine were predominately female discharged after one week without any neurologic (82%), of adult age (90%), white (64%) and with an signs and with verapamil, acetazolamide and ectomorph body type (86%). The eyes were closed in amitriptyline for prevention of migraine type most of the portrayals (82%). The hands were on both headaches. Hemiplegic migraine is a rare subtype of temporal regions at the same time in half of the migraine with aura, characterized by the presence of portrayals (49%). motor weakness as aura manifestation. A hemiplegic migraine can run in the family (familial hemiplegic Conclusions: The demographics in terms of gender, migraine) or can occur sporadically in one individual race and age reflect large population studies of (sporadic hemiplegic migraine). Sporadic Hemiplegic migraine, however, we are concerned about the Migraine occurs only in one individual without a family stereotypical depiction of "acute pain behavior" (i.e. connection. The unilateral weakness may switch sides eye closed, hands on temples) on these images as this between or during attacks. The symptoms usually is inconsistent with the actual presentations of people occur over 20 to 30 minutes, although rarely, aura with migraine in our clinical experience. This disparity symptoms and motor weakness can develop acutely may both derive from, and further contribute to, social and can mimic a stroke. stigmatization and lack of public and employer validation of migraine-related disability. We suggest A migraine is a common disorder occurring in 15% to that future efforts in migraine advocacy should focus 20% of the population. Hemiplegic migraine is a rare on an accurate representation of people with migraine condition, with a reported prevalence of 0.01%. A in mass media. study done in Denmark indicated the prevalence of sporadic hemiplegic migraine is 0.002% and familial Figure 1 hemiplegic migraine is 0.003%. Women are 3 times more likely to be affected.

P222 The Stereotypical Image of a Person with Migraine According to Mass Media K. Gvantseladze1, T. P. Do2, J. M. Hansen2, R. E. Shapiro3, M. Ashina2 1Caucasus Medical Center, Tbilisi, Georgia 2Danish Headache Center, Glostrup, Denmark 3Larner College of Medicine, Vermont, United States

Question: How are people with migraine portrayed in mass media?

Methods: Using the search term "migraine", we retrieved the 200 highest-indexed images of people with migraine from each of the two popular image- searching websites, Shutterstock and Google Images. For each included image, we analyzed different attributes including (1) gender; (2) age; (3) race; (4) body type; (5) posture; (6) extent of eye closure; (7) clothing attire; (8) environment/setting; (9) lighting; 137

P223 P224 Body weigh, psychological factors and migraine Healthcare Resource Utilization and Economic Burden severity in children and adolescents of Migraine in the United Kingdom, France, and Spain: S. Tarantino1, L. Papetti1, A. Di Stefano1, V. Messina1, F. Results of a Real-world Study Ursitti1, M. A. N. Ferilli1, G. Sfoza1,2, R. Moavero1,2, F. P. Irimia1, H. Benhaddi2, F. Morand3, F. Maurel3, M. Vigevano1, S. Gentile1, M. Valeriani1,3 Lanteri-Minet4, P. J. Goadsby5 1 Bambino Gesù Hospital, Neuroscience, Rome, Italy 1Clínica Universidad de Navarra, Pamplona, Spain 2Child Neurology and Psychiatry Unit, Tor Vergata 2TEVA Pharma, Wilrijk, Belgium University of Rome, Rome, Italy 3IQVIA, Courbevoie, France 3Center for Sensory-Motor Interaction, Aalborg 4Pain Department, CHU Nice, FHU InovPain Côte Azur University, Aalborg, Italy University, Nice, France 5NIHR-Wellcome Trust King’s Clinical Research Facility, Background: Studies exploring the association King’s College London, London, United Kingdom between body weight and migraine severity in children and adolescents are lacking. Data on the possible Question: Migraine is a leading cause of disability and association between body weight, psychological impacts most aspects of life. This longitudinal, factors and migraine severity in pediatric populations retrospective study evaluated epidemiology, are sparse. We aimed to explore the relationship pharmacologic management, resource utilization, and between weight and migraine frequency and to treatment costs (medications/consultations/diagnostic analyze the role of body weight on psychological tests) for patients with episodic migraine (EM; <15- symptoms in children patients suffering from migraine. days/month, last 3-months) and chronic migraine (CM) Methods One hundred and eleven patients with in the UK, France, and Spain. migraine were evaluated (47 boys, 64 girls; mean age =11.7; ± 2.4). They were divided in 2 groups according Methods: The patient cohort, from a representative to headache attack frequency: 1) high frequency (from panel of electronic medical records, included adults weekly to daily episodes) and 2) low frequency with a record of migraine diagnosis or specific patients (≤3 episodes per month). According to their treatment from April 2016 to March 2017. Patients Body Mass Index Percentiles, patients were divided in were stratified, with triptan usage as a surrogate for “Normal weight” (percentile ≥ 5 and < 85), migraine, by migraine classification (EM/CM). Patients “Overweight” (percentile ≥ 85 and < 95) and “Obese” were followed for 1-year after first recorded migraine (percentile ≥ 95). Given the low frequencies of obese diagnosis or specific migraine treatment. subjects, overweight and obese groups were collapsed in the same category. The psychological profile was Results: This study included 42,439 patients in the UK assessed by SAFA Anxiety and Depression scales. (EM, 96%), 31,250 in France (EM, 88%), and 10,577 in Results. Fifty-four patients were normal weight Spain (EM, 82%). In the UK, France, and Spain, 15.7%, (49.6%), while 56 (50.4%) were overweight. The 10.1%, and 2.7% of all patients, respectively, received overweight subjects showed higher frequency of acute and preventive treatments. During follow-up, CM headaches (64.7%; p patients had more mean migraine-related consultations with general practitioners than EM patients in the UK (13.9 vs 4.6), Spain (15.0 vs 5.7), and France (4.2 vs 2.5); proportions with ≥1 migraine- related diagnostic test were higher for CM versus EM patients in the UK (12.1% vs 7.2%) and France (25.1% vs 18.7%), but not Spain (10.7% vs 9.8%). Mean quarterly treatment costs (payer's perspective) were higher in CM versus EM patients in the UK (434.3€ vs 104.3€), France (155.7€ vs 40.8€), and Spain (986.8€ vs 111.5€).

Conclusions: Migraine is associated with substantial healthcare and economic burden, with higher resource

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utilization and treatment costs among CM versus EM percentage of meteosensitive patients in both groups. patients in the UK, France, and Spain. Migraine attacks had a negative impact on the QoL.

P225 P226 Weather impact on migraine in Latvia Typical aura without headache with atypical L. Smeltere1,2, A. Petrinina1, R. Erts1 differential diagnosis 1University of Latvia, Faculty of Medicine, Riga, Latvia E. Kiryanova1, G. Tabeeva1 2Health centre 4, Headache consulting office, Riga, 1I.M. Sechenov First Moscow State Medical University Latvia (Sechenov University), neurology, Moscow, Russian Federation Introduction: Many migraine patients claim that weather changes trigger their headaches. However, Main objective: Typical aura without headache occurs research data are contradictory. in 4% patients, and may take place in 38% of patients with migraine with aura. Objectives: The possible correlation between weather parameters and headache frequency and intensity was Patients and Methods: We present a case of patient investigated and the quality of life (QoL) of SG and CG with isolated TAWH. compared. Results: A 53-year-old man 5 years ago described Materials and Methods: The study of 100 patients recurrent episodes of visual blurring with bright with migraine (study group, SG) and 100 individuals colorful zigzag lines, centrally that gradually progressed with no migraine (control group, CG) was conducted. peripherally in both visual fields for 15-20 min. The Statistical analysis was performed of 82 and 80 episodes occurred 1-2 times a month and were respectively. Statistical significance level was expressed accompanied by palynopsia. Visual phenomena are as p-value<0.05. To analyze outpatient record data, triggered by bright light and emotional stress. 5 years headache diary and questionnaire were used. The ago ophthalmologist diagnosed vitreochorioretinal intensity (VAS) and pain frequency were correlated peripheral dystrophy of the retina with OU ruptures. A with temperature, humidity, atmospheric pressure, the peripheral restrictive laser coagulation of the retina OU number of sun-hours within a 12 hour span in was performed without any dynamics. An extensive November. ophthalmological examination is held annually. Neurological examination was normal. Brain magnetic Results: The headache frequency and intensity showed resonance imaging (MRI) revealed a small non- a weak correlation with various weather conditions. SG enhancing lesions, pituitary microadenoma 3x3 mm. revealed more headache days at lower atmospheric ACTH, somatomedin-S, TSH, T4, cortisol, prolactin, LH, pressure (r=0.2) and higher humidity (r=0.25). There FSH, testosterone, estrogen, DHEA-S, blood tests, was a tendency of headache to be worse on dry (φ=51- homocysteine are normal. Brain magnetic resonance 70%) or sunny days (>4h). In CG, pain of other angiography (MRA) revealed a left-side posterior localization occurred more often on humid (r=0.49; arterial trifurcation. EEG (after sleep deprivation): no φ=90-97%) or warm days (r=0.31; t=+10ºC), being pathological changes were detected. Visual evoked more intense at lower atmospheric pressure. Small potentials - hyperexcitability of the visual cortex. percentage of patients in SG (8.5%; n=7) and in CG (5%; n=4) had an average correlation to the weather Discussion: TAWH is a diagnosis of exclusion. Visual conditions, which can be considered as meteosensitive. evoked potentials can play a major role in the SG more often marked their QoL as very poor differential diagnosis of retinal pathology. There is no compared to CG. growth, no hormonal activity of the pituitary microadenoma (incidentaloma). Conclusions: There was no obvious relationship between any weather condition and intensity or Written, informed consent for publication was frequency of headache in SG. There was a small obtained from the patient.

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P227 gynecological pathology and perimenstrual attacks in all 3 cycles. Features of menstrual association of migraine E. Kiryanova1, G. Tabeeva1 1I.M. Sechenov First Moscow State Medical University (Sechenov University), neurology, Moscow, Russian P228 Federation Visual Snow Syndrome: Quantification of symptoms over time Background: Migraine is a chronic disease that M. Graber1, A. Scutelnic1, P. Goadsby2, C. Schankin1 occupies a leading position of years lived with disability 1Inselspital, Bern University Hospital, Neurology, Bern, for women of reproductive age. Switzerland 2NIHR-Wellcome Trust King’s CRF, King’s College , Aim: To determine the differences between a Neurology, London, United Kingdom persistent menstrual association (MA) and the appearance of MA in patients who have not noted it Question: Patients with "visual snow" (VS) describe a before with а history of perimenstrual migraine attacks persistent disturbance in the entire visual field for at least 6 months. resembling the "static" or "snow" of a badly-tuned analogue television. Here, we addressed the question Methods: The study included 44 women of how the severity of VS develops over time. reproductive age with migraine (mean age 32.9 ± 9.13 years). MA degree: 1 - attacks within –2 to +3 days Methods: In 2019, 78 patients with definite VS of the menstrual cycle in all 3 cycles of 3 (n=13), 2 - in syndrome who had taken part in a previous interview 1-3 cycles of 3 (n=18); control - 0 cycles of 3 (n=26). in 2011 were re-contacted. We assessed the Duration of MA: 1 - constant association with distraction created by VS, density of VS dots, velocity, menstruation, 2 - the appearance in the dynamics of noticeability, and other characteristics by using ordinal the disease (1:1). The number of migraine triggers, a scales. change in perimenstrual migraine pain (increase in duration / intensity), and comorbid pathology were Results: Interviews could be conducted in 40 of 78 noted. Statistical processing was carried out in the R (51%) patients. Mean follow up time was 83.6 ±4.5 program; the exact Fisher test and analysis of variance months. Distraction created by VS improved in 10/40 were used to determine the p-level of significance. (25%), but it worsened in 6/40 (15%). The VS dots got more dense in 7/40 (17.5%), whereas they got less Preliminary results: 40.9% of patients noted a dense in 5/40 (12.5%). The frequency of VS flickering connection between migraine attacks and increased in 10% (4/40) and decreased in 10% (4/40). menstruation. Permanent MA is associated with a VS was perceived on more surfaces in 4/40 (10%) and change of perimenstrual migraine pain (p = 0.0014), an on less surfaces in 2/40 (5%). Color and size of VS dots, increase in the number of days with migraine per duration of symptoms and influence of different month (p = 0.0019) and the number of triggers (p = lightning conditions on VS were stable. 0.0051), there is no reliable connection with gynecological and other pathology, perimenstrual Conclusion: The majority of patients reported a stable attacks in all 3 cycles. The appearance of MA in the course VS parameters. One forth reported less dynamics of the disease is associated with the distraction created by VS. presence of gynecological pathology (p = 0,032) and perimenstrual attacks in all 3 cycles (p = 0,000).

Discussion: Most likely, permanent menstrual association is a risk factor for migraine transformation, associated with a change of perimenstrual migraine pain and increasing the number of triggers. The appearance of menstrual association in the dynamics of the disease is associated with the presence of

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P229 Conclusion: We strongly recommend the Portuguese The impact of migraine on patients' quality of life version of MIDAS to measure the impact of migraine in P. Ferreira1,2, A. Jorge3, M. Lopes3, B. Silva1, I. Luzeiro3,4 patients’ QoL. 1Coimbra University, Centre for Health Studies and Research , Coimbra, Portugal 2University of Coimbra, Faculty of Economics, Coimbra, Portugal P231 3Coimbra University Hospital, Neurology Department, Neck pain disability is related to the frequency of Coimbra, Portugal migraine attacks and the presence of aura 4University of Coimbra, Faculty of Medicine, Coimbra, C. Ferreira Pinheiro1, L. Lima Florencio2, A. Siriani de Portugal Oliveira1, J. Pradela1, M. Rodrigues Rocha1, J. Carolina Silva Marçal1, C. Fernández-de-Las-Peñas2, F. Dach3, D. Question: Migraine is an episodic primary headache Bevilaqua-Grossi1 syndrome, affecting worldwide 1 in 10 patients. It’s 1Ribeirao Preto Medical School of University of São mainly accounted because of pain, with all its spectrum Paulo, Health Sciences, Ribeirão Preto, Brazil of manifestation and impact in a social, familial and 2Universidad Rey Juan Carlos, Madrid, Spain professional level, profoundly affecting patient quality 3Ribeirao Preto Medical School of University of Sao of life (QoL). A useful tool to measure this disability is Paulo, Neurosciences and Behavioral Sciences, Ribeirão the Migraine Disability Assessment Scale (MIDAS). It Preto, Brazil has been proven simple to use, consistent, highly reliable and correlated with physicians’ clinical Question: Migraine is associated with cervical judgment. MIDAS has not yet been validated in dysfunction,[1] and the chronicity of migraine is Portugal. The aim of this study is twofold: to validate it related to a greater neck pain disability.[2] However, it in Portuguese, and to measure the impact of migraine is unknown if other forms of migraine, such as on patients' Qol, as well as to determine its migraine with aura, is also related to more severe characteristics. levels of disability. Our aim was to compare the severity of neck pain disability among patients with Methods: As a translated version already existed, the migraine with and without aura and chronic migraine. first phase encompassed a clinical revision and a Methods: Sixty-two women with migraine were cognitive debriefing with 10 patients. The study was assessed and divided into 3 groups: Episodic migraine conducted in a Neurology Department of a central without aura (MoA, n=18, age 32.3; SD 9.3), episodic hospital and the studied population consisted of adult migraine with aura (MA, n=17, age 32.8; SD 8.8) and patients, able to read/write Portuguese and with chronic migraine (CM, n=26, age 34.1; SD 9.8). They chronic and episodic migraine consultation or were diagnosed by a neurologist according to the third hospitalization. edition of the International Headache Society classification. All participants completed the Neck Results: A sample of 86 patients, 87.1% female, with a Disability Index questionnaire and the severity of mean age of 44.3 years participated in this study. A disability was registered. The groups were compared large percentage (67.1%) were in a prophylactic for the severity of disability using Chi-square test treatment, the intensity of pain reached 7.5 in a 0-10 (p<.05). scale, 45.8% were classified by MIDAS as having a severe disability, and 27.0% and 14.1% showed, Results: No differences were observed for age, respectively, moderate or severe anxiety and migraine onset and migraine intensity (p>0.05). The depression. Their QoL showed an average score of 81 distribution of neck disability severity was different in a 0-100 scale. One-week test-retest on 30 patients among groups (x² = 21.89, p=.001). Up to 33% of MoA showed high reliability (ICC=0.817). Construct validity group had no disability, while on MA and CM groups was tested by comparing MIDAS scores with patients’ the frequency was 0% and 7.7%, respectively. The MA characteristics. In general, MIDAS did not show to be and CM groups also showed a higher proportion of determined by patient’s sociodemographics. Testing individuals with moderate disability than the MoA criterion validity MIDAS showed to be correlated with group (MoA 5.6%, MA 52.9%, MC 38.5%) (Table 1). HADS depression scale (0.568) and with QoL EQ-5D-5L Conclusion: Disability due to neck pain is highly (0.689). prevalent in individuals with migraine. However, on 141

those patients with aura and high frequency of attacks, 0.001). When compared to frequency and duration of the neck disability is presented on higher severity headaches no significant differences were revealed levels. between overweight and obese patients (P = 0.148 and 0.718, respectively). There was a significant higher 1. Luedtke K, Starke W, May A. Musculoskeletal total MIDAS score in patients with 30 ≤ BMI than those dysfunction in migraine patients. Cephalalgia. with 25 ≤ BMI < 30 (P < 0.001). 2018 Apr 22;38(5):865–75. 2. Florencio LL, Chaves TC, Carvalho GF, Conclusion: To conclude, this study showed that Gonçalves MC, Casimiro ECB, Dach F, et al. migraineurs with higher BMI experienced higher Neck pain disability is related to the frequency headache frequency, duration and higher disability of migraine attacks: a cross-sectional study. score. Although the differentiation of migraine Headache. 2014;54(7):1203–10. characteristics revealed that obese migraineurs were almost the same as overweight ones, the differences Figure 1 between normal weight and overweight patients were noticeable.

P234 Migraine activity strongly associated with myofascial pain, posture and Flammer syndrome R. Bubnov1,2, O. Golubnitschaja3 1Clinical hospital `Pheophania`, Ultrasound, Kyiv, Ukraine 2Zabolotny institute of microbiology and virology, NAS of Ukraine, Interferon, Kyiv, Ukraine P233 3Friedrich-Wilhelms University of Bonn, Predictive, Body Mass Index and its Association with Preventive and Personalised (3P) Medicine, Characteristics of Migraine Department of Radiation Oncology, Bonn, Germany K. Abdurakhmonova1, G. Rakhimbaeva1 1Mrs, Tashkent, Uzbekistan Introduction: Dry needling (DN) of MTrP (MTrP) under ultrasound (US) guidance is prioritized method for Background: Migraine and obesity are highly treatment myofascial pain and postural imbalance. We widespread disorders in the population. This study was hypothesize that muscle posture might have crucial carried out to assess the association with body mass effect on migraine; additionally to mechanical stimuli index (BMI) and disability, frequency and duration of cumulative signaling of hypoxic MTrPs, stress can headaches in patients with migraine. shorten periods of relapse. This effect likely more expressed in specific constitutional characteristics like Materials and methods: This study conducted at Flammer syndrome (FS) phenotype. Tashkent Medical Academy (TMA) in Tashkent, Uzbekistan. The study included 64 patients (73.4 % The aim was to study associations of myofascial pain, women) who diagnosed with migraine. We used the altered posture, activity of MTrP and FS phenotype following formula: BMI (kg/m2) = weight (kg) / height with migraine activity. (m2) to measure to BMI. They were divided into three groups (18.5 ≤ BMI< 25(normal weight), 25 ≤ BMI < Materials: We included 12 patients with cases of 30(overweight) and 30 ≤ BMI (obese)). Disability chronic headache (10 females, aged 25–48 y.o.). We evaluated using the Migraine Disability Assessment retrospectively precisely analyzed course of disease, (MIDAS) questionnaire. measured BMI and received responses on FS phenotype questionnaire. All patients underwent Results: Normal-weight patients had a significantly general exam, MRI, precise physical tests, extensive lower frequency of headaches, duration of attacks and functional multiparameter neuromuscular US. Then total MIDAS scores than overweight migraineurs (P < patients received DN of detected MTrPs under US 142

guidance by R. Bubnov to elicit LTR and/or `needle males. Girls in general were more likely to report more grasp`. Outcome assessments were performed multi-modal migraine compared to boys. They according to VAS and patients diary reports. The total consistently reported higher levels of photophobia and follow-up period was 6-12 months. phonophobia. One reason why MA may be more prevalent in girls is due to sex hormones. Mouse Results: Myofascial pain was diagnosed in all patients, models have previously shown that increased migraines in 9 individuals, 7 patients demonstrated FS oestrogen levels predispose the brain to cortical phenotype (13-15/15 positive responses to spreading depressions, the pathophysiological questionnaire); one patients had anomaly of cervical mechanism underlying migraine aura. This corresponds spine. DN resulted immediately in decreasing with reports of increase MA prevalence in high headache and migraine attacks. We detected oestrogen states (such as the first and second decreases migraine activity in all cases. We noted more trimesters of pregnancy). In terms of clinical evidence, expressed MTrP hypovascular pattern, higher MA prevalence has been shown to increase in girls sensitivity, excessive responses (LTR over 60 sec, after the onset of puberty. Migraine in boys was more `needle grasp` over 30 min) in lean individuals with FS strongly associated with nausea and vomiting. The phenotype and with high activity of migraine. current prevailing hypothesis is that these symptoms are due to chronic dopaminergic hypofunction leading Conclusion: Trigger points inactivation is crucial for to dopamine hypersensitivity. This may be a reason migraine treatment. Cumulative effect from active why dopamine receptor antagonists can be used I the MTrPs evoke ischemic systemic signaling and altered treatment of migraine. can increase activity of migraine. Reciprocally intensive migraine pain can provoke MTrPs relapse and damage Conclusion: This paper highlights the clear differences of posture. in the characteristics of migraines experienced by male and female children. It showed that girls tended to suffer MA whilst boys suffered from migraine with associated features such as vomiting and nausea. P235 Identifying Differences in the Characteristics of Paediatric Migraine between Male and Female Children P236 H. Pai1 High-velocity low-amplitude chiropractic intervention 1King's College London, Medicine, London, United on a cervical area combined to pharmaceutical Kingdom treatment for adults with chronic refractory migraine: double-blinded randomized controlled trial Aims: The purpose of this review was to identify T. Voloshyn1, V. Kozyavkin1, L. Shestopalova1 gender differences in the characteristics of Paediatric 1Institute of Medical Rehabilitation, Neurology, Migraine and to offer potential explanations. Migraine Truskavets, Ukraine is the most common cause of primary headache in children. The sex difference in age-related migraine Question: There is a huge amount of treatment incidence has been well documented. It is known that approaches for treatment of patients suffering chronic after the onset of adolescence there is an increase in migraine attacks. Generally 2 main kinds of treatment the number of girls who suffer migraine. The influence exist: psychopharmaceutical and psychological. of sex on other aspects of migraine is less well known. Because of insufficiency of their effectiveness there is an urgent need to search for novel therapies to cure Methods: We systematically searched the literature in this malady. electronic databases to cover the period of January 1 1990 and 31 December 2018. Methods: Double-blinded randomized controlled trial. 120 patients examined using 11-point Headache Pain Results and discussion: The papers reviewed Scale before and 2 hours post intervention. 41% males, highlighted that Paediatric Migraine with Aura (MA) 59% females, mean age — 26 years 4months. Patients was much more prevalent in females compared to averaged 9.8±4.7 headache attack days per month, mean headache attack severity on 11-point headache 143

scale was 6.4±3.9. Divided in 4 groups: 31 in control, 33 Methods: A computer-based literature search was in intervention group 1, 26 in intervention group 2 and conducted on MEDLINE and the US National Institutes 30 in intervention group 3. Intervention group 1 — of Health Clinical Trials Registry for phase 3 NSAIDS+triptans+recommendations on lifestyle randomized-controlled trials of galcanezumab in change; Intervention group 2 — high-velocity low- migraine prevention. The primary outcome was the amplitude chiropractic intervention on a cervical area; mean change in monthly migraine headache days Intervention group 3 — NSAIDS+triptans+high-velocity (MHDs). The proportions of patients who reported at low-amplitude chiropractic intervention on a cervical least one adverse event (AE), at least one serious AE or area. withdrew from the study were used as safety outcomes. Results: The pairwise difference for pain severity was significant for intervention groups 1 and 3 (p < 0.01) Results: Three trials were included in the meta- and nominally significant for group 2 (p < 0.05). There analysis. Migraine preventive treatment with was more relief in pain severity for intervention group subcutaneous galcanezumab, at both 120mg and 3 (2.1±1.5) in comparison to groups 2 (2.9±2.0) and 1 240mg dosages, was associated with a significantly (2.5±1.7), (p < 0.05). The incidence of adverse events greater reduction in the mean number of monthly was low and appeared comparable MHD vs. placebo (120mg MD= -1,98 95% CI = -2,33 to - between intervention groups and control group. 1,63; p <0.0001) or (240 mg MD= -1,86 95% CI = -2,2 to -1,53 p <0.0001). Galcanezumab was found to be more Conclusions: Blockages in cervical area of the efficacious in all key secondary outcomes as well. spine may cause more severe and prolongued chronic Regarding safety, most of the adverse events were migraine attacks. Removal of them using high-velocity mild to moderate while drop-out rates and serious low-amplitude chiropractic intervention may be more adverse events were low. beneficial in comparison to using solely pharmaceutical remedies. Although translating insights from research Conclusions: Galcanezumab is an efficacious and well- data into daily clinical practice is not an easy task. It tolerated preventive treatment for migraine. Larger takes a huge effort in terms of medical staff' education clinical trials with longer follow-up periods need to be as well as clarifying benefits to patients and healthcare conducted in order to provide more safety data of the professionals. above-mentioned drug

P237 Galcanezumab in migraine prevention: a systematic review and meta-analysis of randomized controlled trials P. Gklinos1, D. D. Mitsikostas2 1KAT General Hospital of Athens, Neurology Department, Athens, Greece 2Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, First Neurology Department, Athens, Greece

Background: Galcanezumab along with other three monoclonal antibodies targeting the calcitonin gene related peptide (CGRP) pathway represent the latest and the unique disease-specific and mechanism-based treatments for the prophylaxis of migraine.

Objective: To provide a pooled safety and efficacy analysis of all phase 3 randomized-controlled trials of galcanezumab, in the preventive therapy of migraine. 144

Figure 1 Figure 2

P238 Treatment response to Erenumab in refractory migraine patients 1 1 2 2 R. Messina , I. Cetta , S. Guerrieri , B. Colombo , M. 1 Filippi 1 IRCCS Sas Raffaele Scientific Institute, Neuroimaging Research Unit and Neurology Unit, milano, Italy 2IRCCS Sas Raffaele Scientific Institute, Neurology Unit, milano, Italy

Question: Aim of our study was to investigate real-life efficacy and safety of erenumab in refractory migraine patients.

Methods: Patients received erenumab 70 mg monthly for 3 months. At month 3 (M3), the dose of erenumab was increased to 140 mg following patients’ response. Changes in monthly migraine days (MMD), intake of acute medications, 50% responders rate, Headache Impact Test (HIT-6) and Allodynia Symptom

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Checklist (ASC-12) scores were assessed at M3 and Responsiveness lower than 35% to sumatriptan and after 6 months of treatment (M6). ibuprofen. Exemption from systemic diseases, abuse substances’consumption. Plan: single blind, random Results: Fifty-eight patients with a mean age of 51 allocation to 5 groups. Each treatment tested 4 were enrolled in the study. The MMD at baseline was times/volunteer. Rescue ibuprofen 200 mg 19 (SD 8.0). Forty-one patients had chronic migraine and 44 patients had medication overuse headache Results: December 2019 90 patients from each (MOH). Before starting erenumab, patients have tried treatment group completed the observation. an average of 5 preventives (range: 1-10). Seventeen patients received erenumab 140 mg at M6. The MMD Effects: Mean VAS (0-10 scale) Migraine Pain was reduced by 3.9 at M3 and by 5.0 at M6 (p<0.001). The number of days of acute medication intake was A10.0+0SD vs6.1+2.47 SD p>0.0002 reduced by 3.6 at M3 and by 5.3 at M6 (p<0.001). At M6, a 50% or greater reduction in the MMD was B 9.9+0.3SD vs7.4+2.3 SD p>0.0007 achieved for 39% of patients. Mean HIT-6 and ASC-12 scores were reduced by 7.4 (p=0.002) and 2.9 (p=0.03), C 9.9+0.9SD vs0.9+3.8 SD p>0.00001 respectively, at M6. MOH was not confirmed in 29% of patients at M6. Twenty-five percent of patients had D 9.9+1.1SD vs1.7+3.6 SD p>0.00001 side effects. E 9.9+0.3SD vs 8.8+0.8 SD p>0.7 NS Conclusion: Six-month treatment of Erenumab is effective in reducing migraine severity and patients’ Headache relief at 2hr C,D maximum benefit 6hr C,D disability in refractory migraine in a daily-life setting. No rescue hr: 32hr post-dose C, D, 13hr A,B

Pain-freedom post-dose after 24 hr: 74.4 C,D 46.6% , P239 46.4 % A,B respectively. Acute Treatment of Migraine with Fixed Combination of Decarboxylated THC-CBD versus Decarboxylated Side-Effects THC-CBC, Minor Cannabinoids and Terpenes– Pilot data 1-Decrease: Asthenia Beich and Brown test p>0.001 B M. Nicolodi1, M. S. Pinnaro1 n=20 1Foundation Prevention Therapy of Primary Pain and Headache, Research, Firenze, Italy 2-Drowsiness: A n=11, B n=29, E n=1 Aim: End-point 1: to compare acute anti-migraine 3-Memory failure: n=7 C Randt Memory Battery effect and central side-effects of decarboxylated versus non decarboxylated combinations of THC- 4-Dysthimia Relief: N=80D, 71E (p>0.005 vs baseline (Cannabidiol)CBD with terpenes and minor Hamilton/D) cannabinoids represented by: A) fixed combination of 6%THC-8% cannabidiolCBD 200 mg Romano Hazecamp oil B) decarboxylated preparation A 200 mg + 6 mg Conclusion: Minor cannabinoids increase pain relief terpenes oil 0,6% (myrcene 3 mg, limonene 3 mg C) and terpenes induce entourage effect. Headache relief preparation A 200 mg+ 98%CBD mg 1.5 D) preparation seems lacking if THC under 0,01%. Terpenes seem to A 200mg+99,5%(cannabigerol) CBG 1.5 mg + terpenes relieve dysthymia. oil 6 mg E) terpenes oil 6 mg +cannabis oil whereTHC under 0,01% (HPLC). End point 2: to compare side- effects of the 5 combinations.

Method: Observation started on September 2016. Enrolled volunteers 705 migraine sufferers (322 males, 383 females mean age 31.3+5.3SD). Inclusion: 146

P240 P241 Anticonvulsants as a prevention therapy in pediatric Improvement in function after lasmiditan treatment: patients with migraine Post-hoc analysis of pooled data from Phase 3 studies I. Zaitcev1, S. Likhachev1, S. Kulikova1, S. Belaya1, O. T. Smith1, A. Hake2, E. Nery2, S. Rathmann2, B. Gleb1, M. Savchenko1, R. Popko1 Matthews2, S. Dowsett2, E. Doty2 1Republican Research and Clinical Center of Neurology 1StudyMetrix Research, St Peters, United States and Neurosurgery, Department of Neurology, Minslk, 2Eli Lilly and Company, Indianapolis, United States Belarus Migraine is associated with substantial functional Question: Beta-adrenergic blocking agents are most impairment and affects many aspects of daily life. common drugs for prevention therapy in adults with Lasmiditan is a selective serotonin 5-HT1F receptor migraine. Anticonvulsants and tricyclic antidepressants agonist approved by the FDA for the acute treatment are also used. The application of beta-adrenergic of migraine. Using data from two randomized, double- blocking agents for prevention therapy in pediatric blind, placebo-controlled, Phase 3 trials, SAMURAI and patients is limited due to side effects – hypotension, SPARTAN, we assessed the effects of lasmiditan on bradycardia, insomnia. Treatment with tricyclic migraine-related functional disability over time for up antidepressants can often cause such side effects as to 48 hours (h) post dose. Migraine-related functional weakness, sleepiness and headache that lead to low disability was assessed at multiple time points after the patience compliance. We want to describe our patient took study drug by asking them to rate how experience of application of anticonvulsants for much the migraine interfered with normal activities treatment pediatric patients with migraine. (not at all, mild interference, marked interference, or need complete bed rest). Freedom from migraine- Results: The study sample consisted of 38 pediatric related functional disability was defined as having patients: 28 (73,7%) girls and 10 (26,3%) boys. Median disability "not at all" at a given time point. Pooled data age was 15,4 years, median migraine onset age was from SAMURAI and SPARTAN were analyzed using the 10,9 years. 27 (71%) had family history of migraine. intention-to-treat (ITT) population. Denominators for Medium frequency of migraine attacks was 3±0,7 per calculating migraine-related functional disability %’s month. 22 (57,9%) patients had migraine with optic were patient counts for the ITT population in each aura, 3 (7,9%) suffered from migraine-hemiplegia and treatment arm. At any timepoint, if responses were 13 (34,2%) had migraine without aura. 8 (21%) patients not available they were considered missing. For had a history of unsuccessful prevention therapy: 5 patients who took a 2nd dose, data after the 2h time with propranolol and 3 with amitriptyline. Before point were also considered missing. For statistical treatment all patient underwent brain MRI and EEG: testing, missing data were combined with the "any there were found no abnormalities of brain, also EGG interference" group. Significantly more patients who did not revealed any epileptic activity. All patients had received lasmiditan at any dose reported freedom a normal neurological examination between migraine from migraine-related functional disability at every attacks. Topiramate was prescribed to 31 patients (26 timepoint from 2h post dose and this difference girls and 5 boys), valproic acid was prescribed to 7 persisted to 48h (Figure 1). Significant differences from patients (2 girls and 5 boys). During 3 month of placebo in freedom from migraine-related functional treatment 9 (26,7%) patients became attack free: 7 disability commenced at 1h post dose for lasmiditan girls and 2 boys. Also in the study sample medium 200mg, 1.5h for lasmiditan 100mg and 2h for attack frequency decreased by 60%: from 3±0,7 to lasmiditan 50mg. In conclusion, all doses of lasmiditan 1,2±0,9 attack per month, p=0,0001. There were any resulted in significant improvement in migraine-related side effects that would require discontinuation of functional disability that persisted to 48h. treatment with anticonvulsants. Only 2 cases of light weight loss were obtained in patients treated with Figure 1: Interference with normal activities over time, topiramate. by treatment group - SAMURAI and SPARTAN data pooled Conclusion: Anticonvulsants are an effective and well tolerated option for prevention treatment in pediatric patients with migraine.

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Figure 1 analysis confirms that the percentage of patients with a migraine on Day 1 after eptinezumab administration measures onset of full preventive effect.

Design/Methods: PROMISE-1 (NCT02559895) and PROMISE-2 (NCT02974153) were double-blind, randomized, placebo-controlled trials evaluating eptinezumab for migraine prevention. Testing of treatment effect on Day 1 after dosing was pre- specified and alpha-controlled for both studies. A post hoc closed testing procedure analyzing the percentage of patients experiencing a migraine was used on progressively smaller time intervals beginning with the primary time point (Weeks 1-12; Days 1-84). After every interval demonstrating statistical significance (p≤0.05), the interval decreased by 1 day (Days 1-83,

Days 1-82, etc.) and treatment effect was tested again.

At the first point where statistical significance was not achieved, the procedure was stopped and the onset of P242 preventive efficacy was declared as the end day of the Eptinezumab demonstrated migraine preventive prior interval. efficacy on day 1 after dosing: closed testing analysis from PROMISE-1 and PROMISE-2 Results: Patients who received eptinezumab 100mg, D. W. Dodick1, C. Gottschalk2, S. J. Tepper3, D. I. 300mg, or placebo in PROMISE-1 (100mg, n=221; Friedman4, R. Cady5, J. Smith5, J. Hirman6, S. Snapinn7 300mg, n=222; placebo, n=222) or PROMISE-2 (100mg, 1Mayo Clinic, Phoenix, AZ, United States n=356; 300mg, n=350; placebo, n=366) were included. 2Division of Headache Medicine, Department of For both studies and both doses, all tests from Day 84 Neurology, Yale University, New Haven, CT, United to Day 1 alone achieved nominal significance (p<0.05), States indicating that eptinezumab was effective beginning 3Dartmouth-Hitchcock Medical Center, Lebanon, NH, Day 1 after dosing. United States 4Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Conclusions: This novel closed testing analysis suggests Dallas, TX, United States the onset of a migraine preventive effect of 5Lundbeck Seattle BioPharmaceuticals, Inc., Bothell, intravenous eptinezumab occurs on the day following WA, United States the initial dose. This response was sustained for 12 6Pacific Northwest Statistical Consulting, Inc., weeks following the initial dose. Woodinville, WA, United States 7Employed by Lundbeck Seattle Biopharmaceuticals, Inc. (FKA Alder BioPharmaceuticals, Inc.) at time of abstract preparation; currently contracting with Lundbeck Seattle Biopharmaceuticals, Inc. , Bothell, WA, United States

Background: Traditional options for migraine prevention can require up to 6 months of treatment to demonstrate clinical benefit. Eptinezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, has 100% bioavailability following intravenous administration and has demonstrated ≥50% reductions in the percent of patients with a migraine on the day after dosing. This

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P243 with 50.7% of placebo patients. Rates of MOH levels Eptinezumab treatment reduced acute headache were generally consistent across the study with medication use with corresponding reduction in eptinezumab treatment, and fewer eptinezumab- migraine frequency in patients with chronic migraine treated patients were at MOH levels than placebo and medication-overuse headache in PROMISE-2 patients across all time points (Wks21-24: 100mg H. C. Diener1, M. J. Marmura2, R. P. Cowan3, S. J. 31.5%; 300mg 25.6%; placebo 36.9%). Half the Tepper4, M. L. Diamond5, A. Starling6, J. Hirman7, L. eptinezumab population was below MOH levels during Mehta8, T. Brevig9, B. Sperling9, E. Brunner10, R. Cady8 all 6 study months (100mg 50.5%; 300mg 49.5%), vs 1Institute for Medical Informatics, Biometry and 27.1% with placebo. In ≥50% migraine responders over Epidemiology, Medical Faculty of the University Wks1-4, 74.0% (100mg), 76.7% (300mg), and 58.9% Duisburg-Essen, Essen, Germany (placebo) simultaneously achieved ≥50% reduction in 2Jefferson Headache Center, Thomas Jefferson total medication days; and 86.5%, 86.6%, and 77.6% in University Hospitals, Philadelphia, PA, United States triptan days. 3Department of Neurology and Neurological Sciences, Stanford University Headache and Facial Pain Program, Palo Alto, CA, United States 4Geisel School of Medicine at Dartmouth, Hanover, NH, P244 United States Eptinezumab Reduced Acute Medication Use in 5Diamond Headache Clinic, Chicago, IL, United States Patients with Chronic Migraine and Medication- 6Mayo Clinic, Phoenix, AZ, United States Overuse Headache: Subgroup Analysis of PROMISE-2 7Pacific Northwest Statistical Consulting, Inc., M. J. Marmura1, H. C. Diener2, J. Hirman3, R. Cady4, T. Woodinville, WA, United States Brevig5, E. Brunner6, L. Mehta4 8Lundbeck Seattle BioPharmaceuticals, Inc., Bothell, 1Jefferson Headache Center, Thomas Jefferson WA, United States University Hospitals, Philadelphia, PA, United States 9H. Lundbeck A/S, Copenhagen, Denmark 2Institute for Medical Informatics, Biometry and 10Lundbeck LLC , Deerfield, IL, United States Epidemiology, Medical Faculty of the University Duisburg-Essen, Essen, Germany Objective: Eptinezumab is a CGRP-inhibitor 3Pacific Northwest Statistical Consulting, Inc., monoclonal antibody for migraine prevention. This Woodinville, WA, United States subgroup analysis evaluated the impact of 4Lundbeck Seattle BioPharmaceuticals, Inc., Bothell, eptinezumab on levels of acute headache medication WA, United States use in patients diagnosed with chronic migraine (CM) 5H. Lundbeck A/S, Copenhagen, Denmark and medication-overuse headache (MOH) in PROMISE- 6Lundbeck LLC , Deerfield, IL, United States 2. Objective: Eptinezumab is a monoclonal antibody that Methods: PROMISE-2 randomized patients with CM to inhibits CGRP for the prevention of migraine. The 2 doses of eptinezumab 100mg, 300mg, or placebo objective of this analysis was to evaluate the impact of administered intravenously at baseline and Wk12. eptinezumab on acute headache medication use in MOH was diagnosed at screening based on 3 months patients enrolled in the pivotal PROMISE-2 clinical trial of medication history and ICHD-3b criteria. Analyses who were diagnosed with chronic migraine (CM) and include percentage of patients using acute medication medication-overuse headache (MOH). at MOH levels (defined using ICHD-3b) for each study month (4-wk interval), number of study months below Methods: In PROMISE-2, patients with CM were MOH levels of acute medication use, and reduction in randomized to eptinezumab 100mg, 300mg, or acute medication use stratified by migraine responder placebo for 2 intravenous doses administered every 12 status. weeks. MOH was diagnosed by trained investigators at screening based on 3 months of medication history and Results: MOH was diagnosed in 431 of 1072 patients in alignment with ICHD-3b criteria. Endpoints included (40.2%) treated in PROMISE-2 (100mg n=139; 300mg days/month of any acute medication use (days of ≥1 n=147; placebo n=145). During Wks1-4, 28.5% (100mg) medication class), total acute medication use and 33.3% (300mg) of eptinezumab-treated patients days/month (sum of days for each medication class), were using acute medication at MOH levels compared and days/month with triptan use over Weeks 1-12 and 149

13-24. Classes of acute medication included triptan, Trained investigators diagnosed MOH at screening ergot, opioid, simple analgesic, and combination based on 3 months of medication history and ICHD-3b analgesic. criteria. Endpoints included change from baseline in monthly migraine days (MMDs) and ≥50% and ≥75% Results: Of 1072 patients treated in PROMISE-2, 431 migraine responder rates over Weeks 1-12 and 13-24. (40.2%) were diagnosed with MOH (100mg, n=139; In addition, during Days 1-7, the percentage of patients 300mg, n=147; placebo, n=145). During the 28-day experiencing migraine was calculated. baseline period, the mean days of any acute medication use was ~16.4, total acute medication use Results: Of 1072 patients with CM treated, 431 (40.2%) was ~20.4, and triptan use was ~8.9 across treatment were diagnosed with MOH (100mg, n=139; 300mg, arms. Over Weeks 1-12, mean days/month of any n=147; placebo, n=145). During the 28-day baseline acute medication use was 8.8 (100mg), 9.9 (300mg), period, MOH patients experienced 16.7 migraine days and 11.8 (placebo); total acute medication use was (each arm). Over Weeks 1-12, eptinezumab-treated 10.8, 12.2, and 14.8; and triptan use was 4.3, 4.4, and patients experienced greater reductions from baseline 6.4. Similar or lower rates were observed over Weeks in MMDs than placebo patients (100mg, -8.2; 300mg, - 13-24. 8.5; placebo, -5.2). About twice as many eptinezumab- treated patients were ≥50% (60.4%; 61.9%; 34.5%) or Conclusions: In patients diagnosed with CM and MOH, ≥75% migraine responders (27.3%; 29.9%; 14.5%). eptinezumab treatment reduced acute headache Similar results were observed during Weeks 13-24. The medication use. percentage of patients experiencing migraine on Days 1 through 7 was lower with eptinezumab than placebo (baseline: ~59.7% across groups; Day 1: 27.8%; 30.1%; 45.5%). P245 Eptinezumab Reduced the Frequency of Migraine Conclusions: Eptinezumab is efficacious in patients Days in Patients with Chronic Migraine and diagnosed with CM and MOH, with greater reductions Medication-Overuse Headache: Subgroup Analysis of in migraine days compared with placebo at week 12, PROMISE-2 and with effect as early as Day 1 and sustained through H. C. Diener1, M. J. Marmura2, J. Hirman3, L. Mehta4, T. 24 weeks. Brevig5, E. Brunner6, R. Cady4 1Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty of the University Duisburg-Essen, Essen, Germany 2Jefferson Headache Center, Thomas Jefferson University Hospitals, Philadelphia, PA, United States 3Pacific Northwest Statistical Consulting, Inc., Woodinville, WA, United States 4Lundbeck Seattle BioPharmaceuticals, Inc., Bothell, WA, United States 5H. Lundbeck A/S, Copenhagen, Denmark 6Lundbeck LLC , Deerfield, IL, United States

Objective: Eptinezumab is a monoclonal antibody that inhibits CGRP for the prevention of migraine. This analysis evaluated the impact of eptinezumab on migraine frequency in patients with chronic migraine (CM) and medication-overuse headache (MOH) in the pivotal PROMISE-2 study.

Methods: PROMISE-2 randomized patients with CM to eptinezumab 100mg, 300mg, or placebo for 2 intravenous doses administered every 12 weeks. 150

P246 with placebo. Changes from baseline in HIT-6 total Eptinezumab Improved Patient-Reported Outcomes score at Weeks 4 and 24 were greater with in Patients with Chronic Migraine and Medication- eptinezumab than placebo. At Week 4, 43.8% (100mg), Overuse Headache: Subgroup Analysis of PROMISE-2 62.3% (300mg), and 35.4% (placebo) of patients H. C. Diener1, M. J. Marmura2, R. P. Cowan3, M. L. indicated "much improved" or "very much improved" Diamond4, S. J. Tepper5, A. Starling6, J. Hirman7, L. on the PGIC, and 42.6%, 58.6%, and 28.5% indicated Mehta8, T. Brevig9, B. Sperling9, E. Brunner10, R. Cady8 "much improved" or "very much improved" regarding 1Institute for Medical Informatics, Biometry and their MBS. Results at Weeks 12 and 24 were similar to Epidemiology, Medical Faculty of the University Week 4 (Week 24 PGIC: 57.4%, 64.3%, 37.4%; Week 24 Duisburg-Essen, Essen, Germany MBS: 58.1%, 65.0%, 35.1%). 2Jefferson Headache Center, Thomas Jefferson University Hospitals, Philadelphia, PA, United States Conclusions: In patients with a dual diagnosis of CM 3Department of Neurology and Neurological Sciences, and MOH, eptinezumab treatment resulted in clinically Stanford University Headache and Facial Pain Program, meaningful improvements in headache-related impact. Palo Alto, CA, United States Eptinezumab-treated patients indicated greater 4Diamond Headache Clinic, Chicago, IL, United States improvements in disease status and patient-identified 5Geisel School of Medicine at Dartmouth, Hanover, NH, MBS as early as Week 4 and throughout 24 weeks of United States treatment than placebo patients. 6Mayo Clinic, Phoenix, AZ, United States 7Pacific Northwest Statistical Consulting, Inc., Woodinville, WA, United States 8Lundbeck Seattle BioPharmaceuticals, Inc., Bothell, P247 WA, United States Relative contribution of early-onset efficacy with 9H. Lundbeck A/S, Copenhagen, Denmark eptinezumab to change in headache-related life 10Lundbeck LLC , Deerfield, IL, United States impact in patients with chronic migraine R. J. Wirth1, J. S. McGinley1, R. B. Lipton2, J. Hirman3, H. Objectives: Eptinezumab is a monoclonal antibody for Thomson4, R. Horblyuk5, S. Kymes6, R. Cady4 migraine prevention. This analysis assessed the impact 1Vector Psychometric Group, LLC, Chapel Hill, NC, of eptinezumab on patient-reported outcomes (PROs) United States in patients diagnosed with chronic migraine (CM) and 2Albert Einstein College of Medicine , Bronx, NY, United medication-overuse headache (MOH). States 3Pacific Northwest Statistical Consulting, Inc., Methods: This analysis included patients with CM and Woodinville, WA, United States MOH (diagnosed at screening based on ICHD-3β and 3 4Lundbeck Seattle BioPharmaceuticals, Inc., Bothell, months of medical history) who were treated in the WA, United States PROMISE-2 study. Patients were randomized to 5AESARA, Inc.,, Chapel Hill, NC, United States eptinezumab 100mg, 300mg, or placebo, administered 6H. Lundbeck A/S, Copenhagen, Denmark intravenously at baseline and Week 12. PROs included the 6-item Headache Impact Test (HIT-6), patient Objectives: Eptinezumab, an intravenously global impression of change (PGIC), and patient- administered preventive migraine therapy, is identified most bothersome symptom (MBS). PROs characterized by rapid onset and sustained benefits. were captured at Weeks 4, 12, and 24, with HIT-6 also Prior studies have demonstrated that eptinezumab captured at baseline. treatment reduces monthly migraine days (MMDs), improves patient-identified most bothersome Results: 431 patients (40.2% of total PROMISE-2 symptom (MBS), and lessens headache-related life population) diagnosed with MOH were included impact through 24 wks. This analysis evaluated the (100mg n=139; 300mg n=147; placebo n=145). At degree to which early-onset treatment reductions in baseline, ~87.5% of patients had severe life impact both MMDs and patient-identified MBS predict long- based on HIT-6 total score. At Weeks 4 and 24, the term improvement in headache-related life impact as percentage of patients with severe life impact was measured by the Headache Impact Test (HIT-6). reduced to 50.7% and 39.5%, respectively, with 100mg, to 39.0% and 38.6% with 300mg, vs 61.1% and 65.6% 151

Methods: PROMISE-2, a parallel-group, double-blind, P248 randomized, placebo (pbo)-controlled study, evaluated The possibilities of combined using of physical the efficacy and safety of eptinezumab in patients with therapy and kinesiotaping for correction of myofascial chronic migraine (N=1072). Patients were randomized syndrome in patients with migraine. to eptinezumab 100mg, 300mg, or pbo. For this M. Mozheiko1, I. Maryenko1, S. Likhachev1 analysis, MMDs were treated as continuous; MBS had 1Republican research and clinical centre of neurology a binary response scale (1=much improved or very and neurosurgery, neurological, Minsk, Belarus much improved, 0=minimally improved or worse). Structural equation modeling tested the indirect Question: There were noted a comorbidity of migraine effects of treatment on Wk24 HIT-6 total scores (MG) with myofascial syndrome (MS), the role of MS in through MMDs and MBS, which were modeled using the chronization of MG, as well as the negative impact autoregressive time structures (Figure). on the life quality and patient’s condition in the attack- free interval period. The aim was to evaluate the Results: Results showed that MMDs and MBS effectiveness in combined using of physical therapy mediated the relationship between treatment and (PT) and kinesiotaping (KT) in patients with MG for Wk24 HIT-6 scores (Figure). Relative to pbo, both correction of MS. 100mg and 300mg predicted improved MMDs and MBS at Wk4, which carried through Wk20 and Methods: Were examined 20 females with MG (ICD-3 predicted reduced headache impact at Wk24. The beta, 2013), 5 of them are chronic migraine (HM) and indirect treatment effects on headache impact through 15 are episodic syndromes associated with MG. The MBS (standardized specific indirect effects: 100mg vs average age was 42 ±5.8 years. There was used the KT pbo = –.14, p<.001; 300mg vs pbo = –.20, p<.001) were technique of muscular correction to influence the approximately 2x the magnitude of those through trigger points (TP) of trapezoidal and splenius muscle MMDs (standardized specific indirect effects: 100mg vs of neck. Y-strips of KT were fixed on the thoracic region pbo = –.07, p<.001; 300mg vs pbo = –.09, p<.001). paravertebral (Th I-II) and focused to the nape of the neck (tension 0-15%). The I-strip was fixed on the Conclusions: While early-onset efficacy in both patient- trapezoid muscle horizontally (tension 20%). KT was identified MBS and MMDs mediated the relationship applied for 6 days, 3 approaches. Each patient was through which eptinezumab improved HIT-6 scores, trained of PT complex for strengthening and stretching there is evidence that MBS may have a stronger the muscles of the cervical and thoracic regions. The contribution. effectiveness was evaluated by functional testing of the cervical spine region (CSR), headache (HA) intensity Figure 1 by using the visual-analog scale "VAS".

Results: There were found significant differences in the assessment of the HA intensity by the "VAS" (before 6.9±1.4 points, after-2.7±1.4 points), p<0,05. After daily using of the KT and PT complex, all patients showed a lack of density and tension in the MS area of the trapezius muscle, and a decrease in the severity of pain in MS zone of the splenius muscle of neck.Lateroflexia of CSR was changed: before application 41.5°±1.8 - right, 40.8°±1.9 - left; after 42.6°±1.3 - right and 41.8°±1.5 left.

Conclusions: There was evaluated the method of MS correction by combined using of KT and PT in patients with MG. The combined using of KT and PT allows to regulate muscle tone, reduce local pain and tension in the MS area, and may be prevent the HA paroxysms in MG.

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P249 kg to < 30 kg and 30 kg to < 45 kg) while matching Pediatric Dose Selection for Fremanezumab (AJOVY) exposure in adults at the effective dose of 225 mg sc Phase 3 Migraine Studies using Pharmacokinetic Data monthly. from a Pediatric Phase 1 Study and a Population Pharmacokinetic Model and Simulation Approach Conclusions: Fremanezumab 120 mg sc monthly is the O. Cohen-Barak1, A. Radivojevic2, A. Jones3, J. Fiedler- recommended dose for pediatric patients weighing < Kelly 3, M. Gillespie 4, M. Brennan 4, D. Gutman 1, M. 45 kg and no further stratification below 45 kg is Rasamoelisolo 4, P. Loupe 5, L. Rabinovich-Guilatt 1, M. warranted. Levi 4 1Teva Pharmaceutical Industries, Netanya, Israel Figure 1 2IntiGrowth, East Hanover NJ, United States 3Cognigen Corporation, Buffalo NY, United States 4Teva Pharmaceutical Industries, West Chester PA, United States 5Teva Pharmaceutical Industries, New Orleans LA, United States

Question: The relationship between fremanezumab exposure and body weight supported use of the approved migraine adult dose of 225 mg monthly for pediatric patients weighing ≥ 45 kg. As part of the pediatric phase 3 program for fremanezumab, the dose for patients weighing < 45 kg was determined using a pharmacokinetic (PK) modeling and simulation-based evaluation strategy.

Method: The previously developed adult population PK model was updated and refined using a Phase 1 PK study in pediatric patients (6 to 11 years old). The 16- P250 week study included two weight groups of male and Galcanezumab in Patients with Treatment-Resistant female patients: 17 kg to < 30 kg, n = 6 and ≥30 kg to < Migraine: Results from the Open-Label Phase of the 45 kg, n = 9. A single 75 mg dose of fremanezumab was CONQUER Phase 3 Trial administered via subcutaneous (sc) injection into the H. C. Detke1, U. Reuter2, C. Lucas3, D. Dolezil4, A. L. abdomen. Six PK samples per patient were collected. A Hand5, A. Tockhorn-Heidenreich1, C. Stroud1, S. K. virtual population of 2400 pediatric patients (6 to 17 Aurora1 years of age) was generated and used along with the 1Eli Lilly and Company, Indianapolis, United States final pediatric PK model estimates to simulate 2Charité Universitötsmedizin Berlin, Neurology, Berlin, concentration-time profiles for monthly sc doses Germany ranging from 60 to 225 mg. The simulated pediatric 3Hôpital Salengro, CHRU de Lille, Lille, France exposure measures were then compared to simulated 4DADO Medical, Prague, Czech Republic exposure measures in the adult population receiving 5IQVIA, Biostatistics, Durham, NC, United States fremanezumab 225 mg sc monthly. Question: This study assessed 6-month efficacy and Results: The final PK parameter estimates using the safety of galcanezumab in patients with treatment- phase 1 pediatric data were comparable to the resistant migraine. previously developed adult population PK model. Based on the simulated exposures for pediatric Methods: During double-blind treatment (Months 1-3), patients weighing < 45 kg, a monthly dose of 120 mg sc 462 patients (18-75 years) with episodic or chronic is predicted to match exposure with the approved migraine and 2-4 previous migraine preventive adult dose of 225 mg sc monthly (Fig 1). The medication category failures were randomised 1:1 to distribution of exposure in pediatric patients was injections of placebo or galcanezumab 120mg/month nearly identical in the two body weight categories (17 153

(with 240-mg loading dose). After completing double- of depressive comorbid disorder in chronic migraine blind treatment, patients could enter an open-label (CM). extension (OLE; Months 4-6), in which all patients received galcanezumab 120mg/month. The primary Materials and methods: The treatment was carried out endpoint was mean change from baseline in number of for 15 patients with CM with concomitant symptoms of monthly migraine headache days. Key secondary depression using the "Neuro-MS" apparatus endpoints included response rate (≥50% reduction in (Neurosoft, Ivanovo, Russian Federation). The average monthly migraine headache days) and mean change in age was 39.5 + -9.9 years (all patients were right- Migraine-Specific Quality of Life Questionnaire Role handed). An annular coil was located above the left Function-Restrictive domain score (MSQ-RFR). hemisphere in the dorsolateral prefrontal cortex. Stimulation parameters: frequency - 20 Hz, session - 10 Results: Of 451 patients who completed double-blind trains, duration of the train - 5 seconds, the interval treatment, 449 entered the OLE, with 432 (96%) between trains - 20 seconds. The treatment was 10 completing. From a baseline of approximately 13 sessions. Patients filled out questionnaires before and monthly migraine headache days, the mean decrease after treatment: a headache impact test (HIT-6) and a at Month 6 was >5 days. Beck depression scale with a score above 14.

At Month 6, approximately 54% of patients met the Results: 9 patients were found to have mild depression ≥50% response criterion. Of the 87 galcanezumab- according to the Beck Scale before rTMS treatment treated patients with ≥50% response at double-blind (average score 16 [14; 17]), after treatment the treatment end, 52% maintained that response average score was 13 [11; 14], and moderate throughout OLE. Mean MSQ-RFR scores improved from depression in 6 examined patients (average score 24 baseline (score=45) to Month 6 by approximately 27 [22; 27]), after treatment: 19 [17; 20]) (p<0.05). The points on a 100-point scale. average HIT-6 index in the examined group of patients was 64 [62; 65] before rTMS treatment , which Treatment-emergent adverse events occurring in >2% corresponds to a severe impact on daily activity. At the of patients were nasopharyngitis (4%), injection-site same time, 11 patients (73.3%) had a severe effect, 3 pain (4%), and injection-site erythema (3%). Five patients (20%) had a significant effect, and 1 patient patients (1%) discontinued due to an adverse event. (6.7%) had a moderate effect. After treatment: the There were no clinically meaningful changes in any average HIT-6 index was 52 [50; 54] - a moderate effect safety parameters. on daily activity (p <0.05).

Conclusions: Galcanezumab was effective, safe, and Conclusions: The data obtained show that the use of well tolerated during the CONQUER open-label high-frequency rTMS over the area of the dorsolateral extension in patients with treatment-resistant prefrontal cortex on the left in right-handers can migraine. significantly reduce the clinical manifestations of depression and improve the quality of life of patients with CM. Further research is needed on a larger number of patients in order to select the optimal rTMS P251 parameters for CM with a comorbid state in the form The effect of high-frequency rhythmic transcranial of depression. magnetic stimulation on depression in chronic migraine V. Hleb1, T. Charnukha1, S. Likhachev1 1Republican research and clinical center of neurology and neurosurgery, Consultative-polyclinical, Minsk, Belarus

Aim: Study of the effect of high-frequency rhythmic transcranial magnetic stimulation (rTMS) on the course

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P252 P253 Real-world evidence data characterizing the use of First data collection on the use of prophylactic the monoclonal antibody Erenumab in daily clinical migraine treatments including the monoclonal routine in Germany from the treating physicians antibody Erenumab focused on the patient’s personal perspective experience M. Koch1, A. Straube2, P. Stude3, C. Gaul4, K. Schuh1 C. Gaul1, H. Israel-Willner2, K. Schuh 3, M. Koch3 1Novartis Pharma GmbH, Nuremberg, Germany 1Klinik, Neurologie, Königstein, Germany 2Klinik, Neurologie, München, Germany 2Klinik, Neurologie, Berlin, Germany 3Neurologische Praxis, Bochum, Germany 3Novartis Pharma GmbH, Nuremberg, Germany 4Klinik, Neurologie, Königstein, Germany Background: The perspective of patients regarding a Background/Aim: Erenumab, the first-in-class fully new therapeutic option is not systematically captured. human monoclonal antibody against the CGRP Quality of life including daily activity, time with the receptor, has demonstrated efficacy and safety in family and the wellbeing of the patient are deciding clinical studies. This data collection now aims to collect factors in migraine management. Thus, it is imperative first real-world data by characterizing the use of to understand the patients’ perspective on treatment erenumab in clinical practice from the point of view of with erenumab, a fully human monoclonal antibody treating physicians in Germany. targeting the CGRP receptor, available since November 2018 in Germany. Methods: Data from 70 headache centers across Germany has been collected by an online survey from Methods: From July 2019 to December 2019, an online July-December 2019. First, the use of erenumab is survey of German patients diagnosed with migraine characterized from the treating physician’s perspective collected details regarding their disease and with regards to therapy decision, patient profiles and experience with migraine therapies. Patients who had quality of life of the patients. Second, each center been on erenumab for at least three months were documented 10-20 individual episodic and chronic further asked about their treatment outcome and migraine patients who had already completed 3 impact on their lives. months of treatment with erenumab for their treatment effects and satisfaction with outcome. Results: An interim analysis covered 19740 migraine patients of which 39% had prior prophylactic Results: An interim analysis of 109 patients showed treatment and 37% are using non-pharmaceutical that on average there was a reduction of 8 migraine treatments. The analysis included 91 erenumab days under erenumab therapy. Physicians reported patients with a mean of 18 years disease duration. that 75% of their patients already had a response after These erenumab patients have tried 6.1 different the first injection. Based on observations during pharmacologic prophylactic therapies on average. 85% patient visits, physicians noted that 80% of the patients of erenumab-patients stated that they can cope better felt a reduction of intensity of migraine attacks and in with daily activities, 83% have fewer days lost to general, they rated 80% of the patients as "much migraine since therapy initiation and 47% could already improved" and "very much improved" on the global feel an improvement of their migraine symptoms after impression score. The full data set including >700 the first injection. For EAN congress, the full data set of erenumab patients will be available for EAN congress. >20,000 migraine patients will be presented.

Conclusion: The TELESCOPE study provides real world Conclusion: PERISCOPE provides us the first real world data for erenumab in Germany regarding treatment data of German patients treated with erenumab and routines, typical patient profiles and the effect on daily shows that patients" benefit from erenumab treatment functioning and quality of life, both outcomes with with regard to improvement of quality of life and great impact on migraine patients. reduction of migraine specific symptoms.

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P254 P255 The effect of zinc supplementation on migraine OnabotulinumtoxinA Treatment Improved Health- treatment: a double-blind randomized placebo- related Quality of Life in Adults with Chronic controlled clinical trial Migraine: Results from a Prospective, Observational F. Khorvash1, G. Askari1, H. Ahmadi1 Study (PREDICT) 1Isfahan University Of Medical Sciences, Isfahan, Iran G. Boudreau1, I. Finkelstein2, C. Graboski3, M. Ong4, S. Christie5, K. Sommer6, M. Bhogal7, G. Davidovic7, W. Background: There is evidence linking the zinc Becker8 deficiency to migraine headaches. We aimed to 1Centre Hospitalier Universitaire de Montréal (CHUM), examine the effect of zinc supplementation on the Montreal, Canada characteristics of migraine attacks in patients with 2Toronto Headache & Pain Clinic, Toronto, Canada migraine. 3Island Health, Brentwood Bay, Canada 4St Paul Hospital, Vancouver, Canada Methods: This randomized clinical trial was conducted 5University of Ottawa, Neurology, Ottawa, Canada on 80 patients with migraine. Patients were 6Allergan plc, Marlow, United Kingdom randomly assigned to receive either zinc sulfate (220 7Allergan plc, Markham, Canada mg/d zinc sulfate) or placebo (lactose) for 8 weeks. 8University of Calgary, Calgary, Canada Anthropometric measures, serum zinc concentrations, and characteristics of migraine attacks (headache Question: PREDICT aimed to assess long-term health- severity, frequency and duration of attacks, and related quality of life (HRQOL) in Canadian adults with headache daily result) were assessed at the beginning chronic migraine (CM) treated with and end of the trial. onabotulinumtoxinA (onabotA).

Results: Compared with the placebo, zinc Methods: Canadian, multicentre, prospective, supplementation resulted in a significant reduction in observational study (NCT02502123) in adults naïve to headache severity (-1.75 ± 1.79 vs. -0.80 ± 1.57; P= onabotA for CM. OnabotA (155-195U recommended) 0.01) and attacks frequency (-2.55 ± 4.32 vs. -0.42 ± was administered every ~12 weeks over 2 years (7 4.24; P= 0.02). However, the observed reduction for cycles), per the Canadian product monograph. Primary headache severity became statistically non-significant endpoint: mean change in Migraine-Specific Quality of when the analysis was adjusted for potential Life (MSQ) Tx4 vs. baseline. Secondary endpoints: confounders and baseline values of headache severity. onabotA treatment utilization (each cycle), headache Other characteristics of migraine attacks including days (daily headache diary), and physician (baseline, duration of attacks and headache daily result were not Tx4, and final visit)/patient (each cycle) satisfaction. altered following zinc supplementation either before Unless noted, data presented as mean(SD); number of or after controlling for covariates. patients (n).

Conclusion: Zinc supplementation had a beneficial Results: 184 participants (average 45 years, effect on the frequency of migraine attacks in migraine predominantly female [84.8%] and Caucasian [94.6%]) patients. Additional well-designed clinical trials with a received ≥1 onabotA treatment. Mean dose of long period of intervention and different dosages of onabotA per treatment cycle was 171(18) U; treatment zinc are required. interval 13.2(1.8) weeks. At baseline, patients reported 20.9(6.7) headache days/month, which decreased over time (range: -3.5[6.3] at Tx1 [n=184] to -6.5[6.6] at Tx4 [n=150]; all timepoints versus baseline, p<0.0001). Significant increases in MSQ post-Tx4 (n=150; restrictive: 21.5[24.3], preventive: 19.5[24.7], emotional: 22.9[32.9]) were observed versus baseline, exceeding minimal important differences (all, p<0.0001). Following onabotA treatment, most physicians rated patients as improved (Tx4: 96.6%, final visit: 86.9%) and majority of patients were satisfied (range: 55.1% [Tx2] to 85.8% [Tx7]). 77 patients 156

(41.8%) reported 168 treatment emergent adverse months. In patients with chronic migraine the effect events (TEAEs), with 38 TEAEs in 22 patients (12.0%) lasted up to 3-4 months, in patients with migraine considered treatment-related. 4 patients (2.2%) stroke up to 7-8 months. According to the verbal rating reported 6 serious TEAEs, none were considered scale the intensity of headaches in attack period after treatment-related. No new safety signals identified. Dysport injections was evaluated in the 1st group as 0- 1 score, in the 2nd group as 1-2 points. Conclusions: Real-world data from PREDICT demonstrate that onabotA treatment for CM reduced Conclusion: Our study shows that patients well headache days and improved HRQOL, with high tolerated in treatment with botulinum toxin type A. For physician and patient satisfaction. practitioners who regularly meet with the problem of chronic headache, the drug of BTA is a new valuable method of treatment for patients with moderate and severe pain syndromes. P256 Using BOTULINUM TOXIN A (DYSPORT) as a principal approach to therapy of complicated forms of migraine in Uzbekistan P257 D. Tairova1, A. Sabirova1, A. Kadirov1 Effects of Galcanezumab On Acute Medication Use 1Tashkent Medical Academy, Neurology, Tashkent, and Health Care Resource Utilization in Patients With Uzbekistan Treatment-Resistant Migraine: Results From a Randomized, Double Blind, Placebo-Controlled Objective: Botulinum toxin is a protein that is a Clinical Trial (CONQUER) potential neurotoxin which is produced by anaerobic A. Ambrosini1, E. Estemalik2, J. Pascual3, M. Rettiganti4, bacteria Clostridium botulinum. For headache relief C. Stroud4, K. Day4, J. Ford4 and treatment in complicated forms of migraine has 1Headache Clinic IRCCS Neuromed, Pozzilli, Italy been administered the drug "Dysport" in m.processus, 2Cleveland Clinic Lerner College of Medicine, Cleveland, bilaterally in mm.frontalis, corrugator supercilii, United States temporalis and occipitalis. 3University Hospital Marqués de Valdecilla and IDIVAL, Santander, Spain The Aim of this study was to investigate using Dystort 4Eli Lilly and Company, Indianapolis, United States for treatment of migrane in Uzbekistan. Question: Acute headache medication use (AHM) and Methods: We have done injections in "fixed points" health care resource utilization (HCRU) in patients with depending on the localization and intensity of the protocol-defined treatment-resistant migraine treated headache. 50 patients were selected: 29 with chronic with galcanezumab (GMB). migraine and 21 with migraine status. Methods: In the 3-month double-blind (DB) study Results: In verbal rating scale patients with chronic phase, patients with episodic or chronic migraine and migraine headache was estimated on average about 2- 2-4 migraine preventive category failures due to lack of 3 points and at the time of the attack 4 points while effectiveness or safety/tolerability, received GMB migraine status. Patients in 1st group differed by 120 mg/month (following initial 240 mg loading dose) constant head heaviness and periodically strengthens or placebo (PBO); an optional 3-month open-label (OL) hemicrania attacks, decreased ability to work, marked GMB treatment followed. AHM was self-reported daily emotional instability, insomnia and duration of with eDiary and paper-forms. HCRU was reported at headaches lasted up to 1 week. Patients in the second baseline (retrospectively for previous 6 months) and at group mentioned suffering from pain during attack, monthly visits. patients could not lift the head from the pillow, photophobia and phonophobia, the attacks lasted up Results: Of the 462 patients (GMB n=232, PBO n=230), to 3 days. After dysport administration the pain has baseline mean (±SD) days/month of AHM was 12.3 been removed within 7-10 minutes right after the (±6.0); 44.8% had AHM overuse. The percentage of injection and the effect was held for an average 6-7 patients reporting migraine-specific HCRU at baseline in the GMB and PBO groups were respectively: 40% 157

and 50% healthcare-professional visits (HCP), 6% and 14 bacterial strains or placebo once a day, which had a 5% emergency-room (ER) visits, and in each, 2% completely similar appearance. hospitalizations. LS mean reductions from baseline in the mean number of days/month with AHM in the DB Results: After a 10-week intervention, among episodic was greater for the GMB group (3.9 to 4.5 days) migraineurs the mean frequency of migraine attacks compared to PBO (0.4 to 1.0 days) in each of the first 3 significantly reduced in the probiotic group compare to months; change difference, -3.1 to -3.5, p<0.001 at the placebo group. A significant reduction was also each month during Months 1-3. During the OL, evident in the migraine severity. Episodic migraine reductions from baseline ranged -4.7 to -5.3 days; prior sufferers who received the probiotic also showed PBO group reductions were comparable to that significant reduction in abortive drug usage per week observed in GMB. During the DB, reductions from compare to baseline, while there was no significant baseline of migraine-specific HCP (per 100 person- changes within the placebo group. In chronic migraine years) were numerically greater with GMB than PBO patients, after an 8-week intervention, the mean (-215.5 vs -155.3); during OL, the prior PBO group frequency of migraine attacks significantly reduced in reductions (-212.9) were similar to GMB (-222.6). For the probiotic compared to the placebo group. In both groups, migraine-specific ER visits were <13 and contrast to the placebo, probiotic supplementation hospitalizations were <2 per 100 person-years during significantly decreased the severity, duration of attacks the DB and OL. and the number of abortive drugs taken per day, in chronic migraine patients. We failed to detect any Conclusion: GMB-treated patients with treatment- significant differences in the serum levels of resistant migraine had clinically meaningful reductions inflammatory markers at the end of the study either in in days with AHM and numerically greater reductions chronic or in episodic cases. The effect of probiotic on in migraine-specific HCP. migraine characteristics after considering potential confounders in ANCOVA model, were shown in figure 1 and 2.

P258 Conclusion: 14-strain probiotic mixture could be an The effects of a multispecies probiotic supplement on effective and beneficial supplement to improve inflammatory markers and episodic and chronic migraine headache in both chronic and episodic migraine characteristics: A randomized double-blind migraine headaches. Further research is required to controlled trial confirm our observations. F. Martami1, M. Togha1, M. Seifishahpar2, Z. Ghorbani1, H. Ansari3, T. Karimi3, S. Razeghi Jahromi2 Figure 1 1Teheran university of medical scinces, headache department, Teheran, Iran 2Shahid beheshti university of medical sciences, Nutrition, Teheran, Iran 3university of california, california, United States

Question: Does supplementation with a 14-strain probiotic mixture improve episodic and chronic migraine characteristics?

Methods: A total of 50 episodic and 50 chronic patients were recruited for this trial.Episodic and chronic migraine was diagnosed by the neurologist according to the ICHD III beta criteria. Patients were randomly allocated to group A or B in a 1:1 ratio for the chronic and the episodic group, separately. All subjects received two capsules of multispecies probiotic product (2×109 CFU/capsule) that contained

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Figure 2 and then GLADIATOR. Due to the post-hoc nature of these analyses, no formal statistical testing was performed.

An LTN dose increase/decrease in GLADIATOR resulted in a numerically greater/lower percentage of patients with pain freedom at 2 hours; for example, from 30% (SAMURAI/SPARTAN LTN 100mg) to 36% (GLADIATOR LTN 200mg). An increase in the percentage of patients reporting ≥1 TEAE was observed for those patients who increased their dose from 50mg to 100 or 200mg, but not for 100mg to 200mg (Figure).

In conclusion, increasing the dose may result in improvement in efficacy (pain freedom at 2 hours) and an increase in adverse event reporting. P259 Effect of a change in lasmiditan dose on drug efficacy Figure: Two-hour pain freedom and TEAEs by dose and safety: Phase 3 study findings group in SAMURAI/SPARTAN and then GLADIATOR D. Clemow1, H. Hochstetler 1, S. Rathmann1, M. Peres1, J. Ailani2 Figure 1 1Eli Lilly and Company, Indianapolis, United States 2MedStar Georgetown Headache Center, Washington DC, United States

Lasmiditan (LTN) is a selective serotonin 5-HT1F receptor agonist recently approved for acute treatment of migraine. SAMURAI and SPARTAN were prospective, double-blind, single-attack studies in which patients with migraine were randomized to LTN 50mg (SPARTAN only), 100mg, or 200mg or to placebo. GLADIATOR was an open-label study enrolling patients who had completed either SAMURAI or SPARTAN; patients were re-randomized to LTN 100mg or 200mg; the study was designed to evaluate the safety and efficacy of LTN for the intermittent, acute treatment of migraine attacks for up to 1 year. To help provide insights for clinicians in choosing the most appropriate P260 dose for a patient, we assessed the effects of a change Coadministration of Single Therapeutic Oral Doses of in LTN dose on drug efficacy and safety using data from Atogepant and Sumatriptan Produces No Clinically the Phase 3 studies, SAMURAI, SPARTAN, and Relevant Drug-Drug Interactions GLADIATOR. R. Boinpally1, A. Jakate1, M. Butler1, A. Periclou1 1Allergan plc, Madison, United States Efficacy and safety were assessed based on LTN dose in SAMURAI/SPARTAN and subsequent dose in Background: Single-center, open-label, randomized, GLADIATOR (Figure). We assessed efficacy based on phase 1, pharmacokinetic (PK) study of the potential the percentage of patients who were pain free at 2 for drug-drug interaction (DDI) between atogepant and hours post first dose for first attack and safety based sumatriptan. on the percentage of patients with at least one treatment-emergent adverse event (TEAE) within 48 Methods: Healthy adults (N=30) were randomized to 1 hours of first dose for first attack in SAMURA/SPARTAN of 6 sequences and received 3 single-dose oral

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treatments: atogepant 60 mg, sumatriptan 100 mg, Figure 1 and coadministration. This 3-way crossover design included study drug administration on days 1, 8, and 15; a 7-d washout period; and a safety visit 30 d after last treatment. Pre- and post-dose blood samples were used to evaluate the potential for PK DDI as the primary endpoint. Geometric mean ratios and 90% CIs were calculated for area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax). Safety and tolerability were also evaluated.

Results: Of 30 participants enrolled, 27 (90%) completed the study. For atogepant, median time to maximum plasma concentration (Tmax) was delayed by 1.5 h when coadministered with sumatriptan vs administration alone, while mean apparent terminal half-life (T½) was generally similar (Table). Comparison of the geometric least squares means showed that atogepant Cmax was 22% lower after coadministration vs administration alone. Atogepant AUC0-t and AUC0-∞ were both lower by 5% when coadministered with sumatriptan. For sumatriptan, median Tmax and T½ were similar when administered alone or coadministered. There was no significant change in sumatriptan Cmax P261 (5% reduction), AUC0-t (2% increase), or AUC0-∞ (2% Benefits of Long-Term OnabotulinumtoxinA increase) after coadministration vs administration Treatment in Chronic Migraine: Results from the alone. Incidence of treatment-emergent AEs was low COMPEL Study and all were mild in severity. A. Blumenfeld1, L. Luo2, L. Yedigarova3, R. Lipton4 1Headache Center of Southern California, Carlsbad, Discussion: Atogepant mean Cmax was reduced by 22% United States when coadministered with sumatriptan, while AUC was 2Allergan plc, Madison, United States unchanged. Systemic exposure to sumatriptan was 3Allergan plc, Irvine, United States unchanged when coadministered with atogepant. 4Albert Einstein College of Medicine, Bronx, United Coadministration of atogepant with sumatriptan was States safe and well tolerated, with no safety concerns identified. Background: "Conversion" and "reversion" have been utilized to describe headache day reductions beneath the threshold for chronic migraine (CM) diagnosis (15 monthly headache days [MHDs]). Our aim was to determine the proportion of individuals with CM that achieved

Methods: COMPEL is a multicenter, prospective, open- label, 108-week study (NCT01516892) examining adults with CM receiving 155 U of onabotulinumtoxinA every 12 weeks. The proportion of participants that achieved

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Results: Of the 716 participants, 373 (52.1%) treated individuals versus placebo achieved <15 MHDs completed the 2-year study. An increasing proportion last month DB (66.7%[n=459/688] vs. of onabotulinumtoxinA-treated individuals achieved 59.1%[n=411/696], p=0.003), any 3 consecutive months DB (63.5%[n=437/688] vs. 54.2%[n=377/696], Conclusions: In COMPEL, a high proportion of p<0.001), and/or treatment-controlled CM individuals at each timepoint achieved treatment- (56.1%[n=386/688] vs. 49.1%[n=342/696], p=0.010), controlled CM throughout the 2-year study. A and had lower mean MHDs(SD) last month DB (7.2[4.1] reduction in MHDs to vs. 7.9[4.1], p=0.013), any 3 consecutive months DB (8.6[3.6] vs. 9.0[3.5], p=0.083), and/or treatment- controlled CM (6.8[3.6] vs. 7.4[3.4], p=0.017). In onabotA-treated, 81.1%(n=558/688) achieved <15 P262 MHDs last month OL (mean MHDs[SD]:5.6[4.3]), Sustained Benefits of OnabotulinumtoxinA Treatment 79.4%(n=546/688) any 3 consecutive months entire in Chronic Migraine: Results from a PREEMPT Pooled study (8.1[4.1]), and/or 60.9%(n=419/688) sustained Analysis treatment-controlled CM (5.0[3.4]). S. Silberstein1, H. C. Diener2, D. Dodick3, L. Luo4, L. Yedigarova5, R. Lipton6 Conclusions: In PREEMPT, a high proportion of 1Thomas Jefferson University, Philadelphia, United onabotA-treated individuals achieved sustained States treatment-controlled CM for the entire observed open- 2University of Duisburg-Essen, Essen, Germany label phase. 3Mayo Clinic, Phoenix, United States 4Allergan plc, Madison, United States 5Allergan plc, Irvine, United States 6Albert Einstein College of Medicine, Bronx, United P263 States Pregnancy Outcomes Following Exposure to OnabotulinumtoxinA Update – 29 Years of Safety Background: Determine proportion of individuals with Observation chronic migraine (CM) that achieved <15 monthly M. Brin1,2, A. Adams1, L. Parker1, A. Ukah1, L. Radulian3, headache days (MHDs) following continuous L. Yedigarova1, I. Yushmanova1 onabotulinumtoxinA (onabotA) treatment. 1Allergan plc, Irvine, United States 2University of California, Irvine, Irvine, United States Methods: Modified last observation carried forward 3Allergan plc, Bucharest, Romania (mLOCF) data from PREEMPT (24-wk, 2 onabotA cycle, randomized, double-blind [DB] placebo-controlled Question: A previous publication of pregnancy phase, followed by 32-wk, 3 onabotA cycle, open-label outcomes in onabotulinumtoxinA-exposed mothers [OL] phase) were pooled for analysis. To assess MHD (Brin et al., 2016) demonstrated prevalence of fetal reductions (<15), several time periods were analyzed: defects (2.7%; 3/110, 95%CI:0.6-8.0%) comparable to 1) end DB (21-24wks) or OL (53-56wks); 2) any 3 general population. Present study provides a consecutive months DB (1-24wks) or entire study (1- cumulative 29-year update. 56wks); 3) all months end DB (13-24wks; termed "treatment-controlled CM") or entire OL (25-56wks; Methods: Allergan Global Safety Database searched termed "sustained treatment-controlled CM"). (1/1/1990-12/31/2018) for onabotulinumtoxinA Proportion of participants (DB: onabotA vs. placebo; administration before/during pregnancy for various OL: onabotA only) achieving each classification, with indications, including migraine. A conservative mean MHDs, presented as exploratory post-hoc approach was taken to minimize reporting bias; only analyses with Bonferroni correction (significance prospective cases included (live births and unknown p≤0.008). birth types [ie, live vs. fetal loss]). Any undetermined abnormal birth outcome classified as major birth Results: 1384 participants randomized to onabotA defect. (n=688) or placebo (n=696) in DB; most continued to OL (n=607 onabotA/onabotA, n=629 Results: Of 914 pregnancies, 400 (43.8%) eligible with placebo/onabotA). A higher proportion of onabotA- known outcomes. Maternal age known in 217 cases, 161

45.2% were ≥35 years. Most frequent indications: Figure 2 cosmetic (30.3%), migraine/headache (25.8%), and movement disorders (10.5%). Dose information (243 cases): 32.5% <50U, 11.1% 50U to <100U, 39.9% 100U to <200U, and 16.5% ≥200U. 196 prospective cases (198 fetuses) - 152 (76.8%) live births, 44 (22.2%) abortions (32 spontaneous, 12 elective), 2 (1.0%) unknown birth types. 148 (97.4%) normal live births, 4 live births with abnormal outcomes, and 2 unknowns with abnormal outcomes (minor fetal malformation and undetermined abnormality/possibly hole in heart). 6 abnormal birth outcomes (2 unknowns): 2 major birth defects (1 live and 1 unknown), 3 minor fetal malformations (2 live and 1 unknown), and 1 birth complication (live). Prevalence rates: 3.9% (6/154, 95%CI:1.8-8.2%) for overall fetal defects (2 unknowns) and 1.3% (2/154, 95%CI:0.4-4.6%) for major fetal defects (1 unknown; 2-4% in general population). P264 Conclusions: A 29-year retrospective analysis of safety How and when does the effect of onabotulinumtoxin in onabotulinumtoxinA-exposed mothers, which A wear off over the treatment cycle in chronic included ~26% of women with migraine, demonstrated migraine? The WEOX study: a retrospective analysis that prevalence rates of abnormal birth outcomes of headache diaries were within/below those reported in the general R. Ruscheweyh1, A. Gryglas-Dworak2, I. Frattale3, L. population, with no new safety signals identified. Nina4, R. Ornello3, S. Sacco3, C. Stark5, M. Torres Ferrus6, B. Athwal7, P. Pozo-Rosich6 Figure 1 1Klinikum der LMU München, Neurology, München, Germany 2Silesian University of Wroclaw, Neurology, Wroclaw, Poland 3University of L’Aquila, Department of Applied Clinical Sciences and Biotechnology, L'Aquila, Italy 4Sechenov University, Institute for Professional Education, Department of Neurology, Moscow, Russian Federation 5Austin Health, Department of Neurology, Heidelberg, Australia 6Vall d’Hebron University Hospital, Department of Neurology, Barcelona, Spain 7Royal Free Hospital, Department of Neurology, London, United Kingdom

Treatment of chronic migraine (CM) with onabotulinumtoxin A (OnabotA) is evidence-based, effective and used throughout the world. According to the PREEMPT protocol, treatment should be administered every 3 months. However, some patients complain that the effect of OnabotA falls short of 3 months.

We retrospectively analysed headache diaries from 6 headache centres worldwide (located in Germany,

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Poland, Russia, Italy, Spain, Australia) to determine if Figure 1 CM patients successfully treated with OnabotA show wear-off of the treatment effect within 3 months (13 weeks) after the injection.

A total of 112 CM patients with a ≥30% response to OnabotA and a complete headache diary for 13 weeks after OnabotA treatment were included (age 45 ± 12 years, 82% female, headache days/month before OnabotA 24 ± 6). Weeks 5 to 8 after OnabotA treatment were considered as the period of maximum treatment effect.

Headache days/week were significantly higher in weeks 12 (p=0.009) and 13 (p<0.001) compared with weeks 5 to 8 after injection, demonstrating significant wear-off of the OnabotA effect (see Fig.). Similarly, P265 acute medication days/week significantly increased in Vitamin D Supplementation might be effective in week 12 (p=0.027) and 13 (p<0.001). At individual migraine prophylaxis probably through attenuating level, 57 patients (51%) showed wear-off in weeks 12 CGRP levels: A randomized double-blind placebo- and 13 (increase in headache days/week of ≥30% controlled trial. compared to weeks 5 to 8) and 28 patients (25%) Z. Ghorbani1, P. Rafiee1, A. fotouhi1, S. Haghighi1, R. showed wear-off already by weeks 10 and 11. Age, sex, Rasekh Magham1, Z. S. Ahmadi 1, M. Djalali1, M. OnabotA dose or cycle number (1 to 4), or the Zareei1, S. Razeghi Jahromi1, S. Shahemi1, M. headache centre attended did not predict individual Mahmoudi1, M. togha1 wear-off. However, patients with a better response to 1Teheran university of medical sciences, Teheran, Iran OnabotA in weeks 5-8 had a larger wear-off (Spearman’s rho=0.52, p<0.001). Background: Emerging evidence showed a negative association between headaches frequency and vitamin These data show that on average the OnabotA effect in D concentrations. Thus, it seems there is still a need for CM significantly wears off from week 12 after more researches to clarify the mechanisms by which treatment. 25% of the patients experience wear-off this vitamin exerts anti-migraine effects. even at weeks 10 and 11. This is likely to negatively affect quality of life of CM patients under OnabotA Methods: The present study was conducted as a 16- treatment. The best way to counteract wear-off week randomized double-blind placebo-controlled trial remains to be determined. on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000IU/d or placebo. The characteristics of migraine headache were documented applying a paper-based 30-day headache diary. Also, serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method.

Results: The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99

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hour/attack), less severe headaches (5.47, Visual and ≥1 PPTF in the previous 5 years. Part 2 assessed analog scale) and lower analgesics use/month (2.85) migraine-related HRU. than placebo group (6.43, 18.32, 6.38 and 4.87 respectively) (P values< 0.05). Moreover, after Results: In Part 2, 2419 patients were analysed. Three controlling for baseline levels, and other variables months prior to Visit 1, 58% of overall population using ANCOVA, CGRP level was appeared to be consulted a neurologist (highest: Croatia [98.9%]; UK significantly lower following vitamin D [96.1%]) and 32.0% consulted a primary care physician supplementation (153.260 ng/L) than the patients in (highest: Belgium [58.9%]; Croatia [55.8%])(Figure). In the placebo arm (188.35 ng/L) (P value= 0.022). the year prior to Visit 1, 21.2% of patients visited the emergency department (ED) for headache/migraine, Conclusion: According to the current findings, vitamin with marked differences observed across participating D supplementation may potentially improve migraine countries (mean[SD] number of ED visits or headache characteristics probably through attenuating investigations was 3.0 [5.5]). Proportion of patients CGRP levels. visiting ED and average number of ED visits/patient (mean[SD]) were high in Slovenia (44.8%; 3.0 [2.1]), Spain (39.4%; 4.5 [8.3]) and Greece (31.4%; 4.1 [5.5]) and lowest in Bulgaria (4.3%; 1.0 [0.0]) and Sweden P266 (7.2%; 1.5 [1.3]). CT and MRI scans were performed to Healthcare resource use among migraine patients exclude other possible neurological causes of headache who have failed previous prophylactic treatments: in 11.6% and 20.4% of the patients, respectively Findings from the BECOME study (highest: Slovenia [41.4%]; Croatia [33.7%]). The P. Martelletti1, C. Lucas2, C. Gaul3, D. P. B. Watson4, P. average proportion of patients with at least 1 inpatient Pozo-Rosich5,6, S. Ritter7, J. Snellman8 admission due to headache/migraine was 8.4% 1Sapienza University of Rome, Sant'Andrea Hospital, (highest: Belgium [14.4%]; UK [13.3%]). Department of Clinical and Molecular Medicine, Rome, Italy Conclusions: Analysis of HRU reveals differences in 2Service de Neurochirurgie, Hôpital Salengro, CHU de healthcare systems and migraine management among Lille, Lille Cedex, Pain Clinic, Lille, France participating countries. High HRU was observed 3Migraine and Headache Clinic Königstein, Königstein regardless of healthcare system, indicating a need for im Taunus, Hesse, Germany improved treatment options for difficult-to-treat 4Hamilton Medical Group, Aberdeen, United Kingdom migraine patients with PPTF. 5Vall d'Hebron University Hospital, Headache Unit, Neurology Department, Barcelona, Spain Figure 1 6VHIR, Universitat Autonoma de Barcelona, Headache Research Group, Barcelona, Spain 7Novartis Pharmaceuticals Corporation, East Hanover, United States 8Novartis Pharma AG, Basel, Switzerland

Aim: Limited European data are available on healthcare resource use (HRU) in migraine patients with prior prophylactic treatment failure (PPTF). We report the HRU in migraine patients visiting headache specialised centres in 17 European countries and Israel from the BECOME study.

Methods: BECOME was an observational study conducted in two concurrent parts, Part 1:cumulative hospital data; Part 2 (patient-level data). Part 2 included adult patients attending headache centres as outpatients/inpatients with ≥4 monthly migraine days

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P267 reported treatment-related adverse events; one Ubrogepant is Effective in the Acute Treatment of considered serious (exacerbation of sinus tachycardia). Migraine with Mild Pain R. Lipton1, D. Dodick2, P. Goadsby3, R. Burstein4, A. Conclusion: Treating migraine patients with Adams5, J. Lai6, S. Yu6, M. Finnegan6, J. Trugman6 ubrogepant early, when headaches are mild rather 1Albert Einstein College of Medicine, Montefiore than moderate/severe increases the likelihood of Headache Center, Bronx, United States rendering them free of pain and associated symptoms. 2Mayo Clinic, Phoenix, United States 3NIHR-Wellcome Trust King’s Clinical Research Facility, London, United Kingdom 4Harvard Medical School, Beth Israel Deaconess P268 Medical Center, Boston, United States The new combination of ibuprofen and caffeine in 5Allergan plc, Irvine, United States self-treatment of headache and migraine – Results 6Allergan plc, Madison, United States from a consumer survey in German community pharmacies Objective: Ubrogepant, approved for the acute H. Gräter1, A. Lampert1, T. Weiser1 treatment of migraine in adults with/without aura, 1Sanofi-Aventis Deutschland GmbH, Frankfurt am demonstrated efficacy in treating migraine with Main, Germany moderate/severe pain. Clinical guidance recommends treatment when pain is mild, a strategy studied herein Question: The combination of ibuprofen and caffeine is for ubrogepant. indicated for the treatment of acute moderate pain in adults. How do patients use the new combination and Methods: Phase 3, open-label, 52-week extension trial perceive its effectiveness and tolerability under real- (NCT02873221). Adults with migraine with/without life conditions? aura, randomized 1:1:1 to usual care, or in blinded fashion to ubrogepant-50mg or -100mg, treated up to Methods: From February to June 2019, customers who 8 migraine attacks of any pain severity every 4 weeks. purchased Thomapyrin Tension Duo (ibuprofen 400mg Efficacy measures, collected only for ubrogepant, and caffeine 100mg, FDC) in German community included 2-hour pain freedom and absence of pharmacies were asked to complete a questionnaire to migraine-associated symptoms. Data were analyzed by investigate their pain and perceived treatment effects. first treated attack and all treated attacks (averaged The survey was carried out anonymously. for each participant and then across participants; individuals weighted equally). Results: Of 1124 participants, 65.4% reported to use the product to treat headache (commonly considered Results: Data for 21,454 treated attacks (n=808 as tension-type headache), 14.2% to treat migraine, participants) are included. Across all treated attacks, 9.8% to treat other types of pain, 7.6% reported pain freedom was achieved in a higher proportion of combinations of different types of pain, and 3% had attacks treated with mild vs moderate/severe pain for incomplete or missing data. Headache (60.8%) or ubrogepant-50mg (39% vs 19%;p<.0001) and migraine (56.9%) were often accompanied by neck ubrogepant-100mg (43% vs 21%;p<.0001). Absence of and/or shoulder pain. Migraine patients reported a photophobia was achieved in an average of 55% vs higher baseline pain (mean ± SD: 7.3±1.5 on a scale 34% (both doses;p<.0001) of attacks with mild vs from 0=no pain to 10=worst pain) than headache moderate/severe pain, respectively. Absence of patients (5.9±1.7). Within 2h, 64.2% of headache and phonophobia was achieved in an average of 64% vs 37.5% of migraine patients reported to be pain-free 42% (ubrogepant-50mg;p<.0001) and 70% vs 45% and 92% of headache and 84.9% of migraine patients (ubrogepant-100mg;p<.0001) of attacks with mild vs perceived at least 50% pain reduction. Perceived onset moderate/severe pain, respectively. Absence of nausea of pain relief was fast (ca. 35% within 15 min, 76% was achieved in an average of 83% vs 67% within 30 min). Compared to recently used ibuprofen- (ubrogepant-50mg;p<.0001) and 82% vs 68% lysinate, 94.1% of headache patients perceived the FDC (ubrogepant-100mg;p<.0001) of attacks with mild vs at least as effective or even more effective (31.4%). moderate/severe pain, respectively. First treated Most headache patients (92.4%) perceived the onset of attack data were similar. Overall, 10% of participants action of the FDC at least as fast as or even faster 165

(38%) than ibuprofen-lysinate. Overall, 95.5% of Discussion: As expected, satisfaction was lower in RCTs headache and 85% of migraine patients rated the than in PB studies (e.g. due to selection bias based on perceived effectiveness as good or very good and treatment experience and the unblinded design of the 97.5% (for tolerability: 97.5% and 95.6%). latter). ASA and ibuprofen scored less favorable than APC in RCTs, as well as in PB studies. Since patients use Conclusion: Under real-life conditions headache and their favorite product in the PB studies, equally high migraine patients perceive a high treatment satisfaction rates would be expected. However, satisfaction with the new combination of ibuprofen satisfaction was different, i.e. lowest with ibuprofen and caffeine. and highest with APC. A PB study with the combination of ibuprofen plus caffeine showed satisfaction in 85% Funding: This study was funded by Sanofi-Aventis of migraine patients giving reason to speculate that Deutschland GmbH. also in RCTs this combination will be superior to the above-mentioned treatments [10].

Figure 1 P269 Patient satisfaction in randomized controlled trials (RCTs) and pharmacy based (PB) studies investigating ASA, ibuprofen, and the combination ASA, paracetamol and caffeine (APC) for the treatment of acute migraine H. Gräter1, A. Lampert1, T. Weiser1 1Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany

Introduction: OTC analgesics are first-line therapy for treating acute migraine [1]. For differentiation, patients’ perspective on treatment may be useful. We compared patient ratings of treatment satisfaction between RCTs and PB studies investigating the same active ingredients.

Methods: Studies were included when they contained data on patient-reported satisfaction measured on four- or five-point verbal rating scales. For RCTs, percentages of the top two categories ("excellent/good" or "very good/good") were calculated for verum and placebo (PLA). Treatment benefit (delta) was verum minus PLA.

Results: Data were found for effervescent ASA (3 RCTs, 1 PB study; [2-5]), ibuprofen (1 RCT, 1 PB study [2,6]), and APC (4 RCTs, 1 PB study [7-9]). In RCTs, 40.3% of patients were satisfied with ASA (PLA: 22.4%, delta: 17.9%), 38.2% with ibuprofen (PLA: 16.7%; delta: 21.5%), and 59.3% with APC (PLA: 22.9%; delta: 36.4%). Patient satisfaction was higher in the PB studies: ASA: 76.8%; ibuprofen: 75.6%; APC: 93%. See figure for details.

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P270 82.2% (continuing erenumab) and 90.2% (initiating Sustained efficacy and safety of erenumab in patients erenumab) of patients reported adverse events (AEs) in with episodic migraine who failed 2–4 prior OLTP. The most frequently reported AEs/100 patient- preventive treatments: 2-year interim results of the years during OLTP were nasopharyngitis (33.9), LIBERTY open-label extension study influenza (10.3), and back pain (6.6). No deaths were U. Reuter1, P. J. Goadsby2, M. Lanteri-Minet3,4, T. reported.Conclusions:Long-term treatment with Stites5, S. Wen5, N. Tenenbaum5, M. D. Ferrari6, S. erenumab showed sustained reductions in migraine Pandhi7 frequency in EM patients with 2–4 PPTF both in 1Charité Universitätsmedizin Berlin, Department of patients continuously treated with erenumab and Neurology, Berlin, Germany those initiating erenumab during the OLTP. Erenumab 2NIHR-Wellcome Trust, King’s Clinical Research Facility, was well tolerated with no new safety signals. King’s College London, London, United Kingdom 3CHU Nice, Pain Department, Nice, France Figure 1 4Université Côte d'Azur, Nice, France 5Novartis Pharmaceutical Corporation, East Hanover, United States 6Leiden University Medical Center, Department of Neurology, Leiden, Netherlands 7Novartis Pharma AG, Basel, Switzerland

Aim: The LIBERTY study (NCT03096834) demonstrated efficacy of erenumab 140mg in episodic migraine (EM) patients with 2–4 prior preventive treatment failures (PPTF). We assessed the efficacy and safety of erenumab at Week 112 of the 3-year open-label treatment phase (OLTP) of the LIBERTY study.

Methods: Patients completing the 12-week double- blind treatment phase (DBTP) of the LIBERTY study (N=240) initially randomised to placebo and erenumab 140mg (1:1) were enrolled into the OLTP to receive OL treatment with monthly erenumab 140mg for 3 years. Outcomes measured included proportion of patients P271 who achieved ≥50%/≥75%/100% reduction from the Effect of erenumab on monthly migraine days and DBTP baseline in monthly migraine days (MMD), monthly migraine attacks in patients with episodic change from the DBTP baseline in MMD, Headache migraine 1 1 2 3 Impact Test total score, Migraine Physical Function P. Tfelt-Hansen , M. Ashina , H. C. Diener , S. Ritter , G. 4 4 5 Impact Diary (Everyday Activities and Physical Paiva Da Silva Lima , S. Rasmussen , R. Zielman 1 Impairment) scores and safety. University of Copenhagen, Danish Headache Center,Department of Neurology, Glostrup, Denmark 2 Results: Detailed results are presented in Table 1. Both Institute for Medical Informatics, Medical Faculty of patients groups: on continuous erenumab and those the University Duisburg-Essen, Essen, Germany 3 who initiated erenumab in the OLTP, demonstrated Novartis Pharmaceuticals Corporation, East Hanover, improvement through 2 years of treatment similar to New Jersey, United States 4 what was reported at 1 year. The responder rates refer Amgen Inc, Thousand Oaks, California, United States 5 to a cross sectional interindividual observation and not Novartis Pharma AG, Basel, Switzerland a longitudinal intraindividual responder rate. The change in MMD from DBTP baseline in the overall Question: Erenumab (in the US, erenumab-aooe) is a group sustained over 2 years (1 year [52 weeks]: fully human monoclonal antibody against the canonical −3.7[4.1]; 2 year [112 weeks]: −4.2[5.0]). The median calcitonin gene-related peptide (CGRP) receptor that (Q1, Q3) erenumab exposure (during OLTP) was 106 has demonstrated efficacy in monthly migraine day (103.8, 106.1) weeks. Nearly 86.3% (overall group), (MMD) reduction for both episodic (EM) and chronic 167

migraine. The decrease of MMD observed in current Figure 1 randomised, controlled trials (RCTs) of EM with CGRP related antibodies could theoretically be due to a decrease in monthly migraine attacks (MMAs) and/or to a shortening of the duration of the migraine attacks. The objective of this analysis was to evaluate the effect of erenumab on the MMA frequency in patients with EM.

Methods: We conducted an analysis of data from STRIVE (ClinicalTrials.gov NCT02456740), a randomised, double-blind, placebo-controlled, Phase 3 study of erenumab in patients with EM (N=955). Outcome measures assessed were the change from baseline to the last 3 months (Months 4, 5, and 6) for MMD and MMA and the proportion of subjects who achieved ≥50% reduction in mean MMDs and MMA from baseline. Using the efficacy analysis set, analyses P272 were conducted which were either pre-specified Interictal burden of migraine: correlations with other exploratory or post-hoc (≥50% reduction in mean MMA measures of migraine burden and effects of from baseline). galcanezumab migraine-preventive treatment R. B. Lipton1, D. Buse1, C. Sandoe2, J. Ford3, A. L. Hand4, 3 3 3 Results: Mean MMD at baseline was 8.3 days and J. Jedynak , M. Port , H. C. Detke 1 decreased by [least square mean (LSM),%]; 1.8 (22%), Albert Einstein College of Medicine of Yeshiva 3.2 (39%) and 3.7 (44%) days, respectively, with University, Neurology, Bronx, NY, United States 2 placebo, erenumab 70 mg and 140 mg. Mean MMA for Women’s College Hospital Centre for Headache, placebo and erenumab 70 mg/ 140 mg was 5.1 and Toronto, ON, Canada 3 5.2, respectively, at baseline. MMA [LSM (%)] Eli Lilly and Company, Indianapolis, United States 4 decreased by 1.3 (26%), 2.0 (40%) and 2.2 (43%) with IQVIA, Biostatistics, Durham, NC, United States placebo, erenumab 70 mg and 140 mg, respectively. The proportion of patients achieving a ≥50% reduction Question: Typical migraine clinical trial endpoints from baseline of MMD and MMA were similar assess only ictal burden. What is the nature of (Table).Conclusion:The current analysis of a large RCT interictal burden in migraine, and does treatment with with erenumab suggests that the MMD and MMA galcanezumab (GMB) reduce it? decrease in parallel. These results strongly support the preventive effect of erenumab as shown by the Methods: Adult patients (N=462) with episodic or decrease in both MMD and MMA. The results cannot, chronic migraine who experienced failure of 2-4 prior however, be extrapolated to other CGRP monoclonal preventive medication categories in the past 10 years antibodies, or oral gepants for migraine prophylaxis. were randomized 1:1 to 3 months of double-blind treatment with placebo (PBO) or GMB 120mg. Primary endpoint was mean change from baseline in number of monthly migraine headache days. Migraine Interictal Burden Scale-4 (MIBS-4) measured burden of migraine on non-headache days over the past 4 weeks (0=no burden, 1-2=mild, 3-4=moderate, 5-12=severe). Migraine Disability Assessment (MIDAS), Migraine- Specific Quality of Life Questionnaire v.2 (MSQ), Patient Global Impression of Severity (PGI-S), and symptoms of depression (Patient Health Questionaire- 9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder Scale [GAD-7]) were assessed. We evaluated the relationship between MIBS-4 and these outcome

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measures using Spearman’s rank correlation coefficient Results: All clinical parameters showed a significant for total population at baseline. improvement already at month 1 (T1) of treatment (p<0.001): monthly days of headache (baseline: 25.3+ Results: At baseline, MIBS-4 was moderately 9.2SD, T1: 17.1+8.7), monthly acute medication doses correlated with PHQ-9 (r=.55) and MSQ total (r=-.53) (baseline: 34.4+30.8; T1: 14.2+18.6), days of drug but showed low correlation (│r│=.3 to <.5) with GAD-7, intake (baseline:20.8+9.7; T1:9.5+8.0). Ongoing MIDAS, and PGI-S, and negligible correlation (│r│<.3) observations confirm long-term efficacy (p<0.001 in 19 with monthly migraine headache days. After 3 months, patients at T10). Indeed at month 3 (T3) "50% from mean baseline of 13.2 monthly migraine responders" were 51.2% ) and at month 10 were headache days, GMB patients improved by 4.4 days vs 68.4%. Super-responders (i.e. 75% responders) were 1.3 days for PBO (p<.0001). From mean baseline MIBS- 17.9% at T3 and 31.6% at T10.Disability and health 4 score of 5.5, GMB patients improved by 1.8 points vs status improved accordingly (p< 0.001) during the 0.8 points for PBO (p<.0001). same period. Only mild side effects were reported, mainly worsening or new onset of constipation (23% Conclusions: In addition to reducing ictal burden, GMB after the first treatment). treatment significantly reduces interictal burden of migraine as measured by MIBS-4. The lack of strong Conclusions: These findings provide a long-term real- correlation between MIBS-4 and other trial outcomes life experience with erenumab on a cohort of difficult- supports previous validation work and suggests that to-treat chronic migraine patients, showing that the interictal burden in migraine is a distinct effect of the drug induces a relevant improvement on multiple disease that is not fully captured by other constructs. indicators of effectiveness and is well tolerated. The clinical improvement was detected already after one month of treatment and it was often maintained over the long-term observation period. P273 Real-life experience with erenumab in chronic Figure 1 migraine and medication overuse headache in a tertiary Headache Center. G. Vaghi1,2, G. Fiamingo3,2, R. De Icco3,2, E. Guaschino3, S. Bottiroli4,3, V. Bitetto3,2, M. Allena3, N. Ghiotto3, C. Tassorelli3,2, G. Sances 3 1IRCCS Fondazione Mondino, Pavia, Italy, Headache Science Center, Pavia, Italy 2University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy 3IRCCS Mondino Foundation, Headache Science Center, Pavia, Italy 4University of Benevento, Faculty of Law, Benevento, Italy

Purpose: To present real-life long-term clinical data regarding the anti-CGRP monoclonal antibody Erenumab, in patients with chronic migraine (CM) and medication overuse headache (MOH).

Methods: Erenumab (70 or 140-mg dose) was administered to 82 patients (F59, M23, mean age: 49.5+9.9SD) with CM and MOH who had already failed at least two preventive therapies. We collected changes in monthly migraine days, acute medication intake, quality of life, migraine-related disability and global health status using standardized questionnaires. 169

Figure 2 Results: Significant improvement was observed in the three studied groups. The Level of serum serotonin significantly elevated in G3 than in both G1 and G2.Pain intensity decreased in the three studied groups immediately post treatment and three months later with no significant differences between the groups. A significant decrease in the frequency of the attacks was detected three months post treatment in the three studied groups.

Conclusion: Low-frequency rTMS over occipital cortex is effective in improving migraine headache with no additional benefit when compared to manipulative therapy alone, in the treatment of migraine headaches in adults. Serotonin is an objective and accurate method to assess the severity of migraine headache. P274 Influence of Transcranial Magnetic Stimulation in Management of Migraine Headache H. Elhabashy1, M. Eltamawy1, M. Darweesh1, A. P275 Elhomran1 Suppression of menstrual related migraine attack 1Cairo University, Clinical neurophysiology, Cairo, Egypt severity by pyridoxine, thiamine, and cyanocobalamin: A quasi-experimental within-subject Introduction: Migraine is a common primary headache design disorder with no underlying identifiable pathological M. Togha1,2, R. Rahmanzadeh1,2, S. Nematgorgani1,3, Z. cause. It affects 11% of the total adult population Yari1,3, S. Razeghi Jahromi1,3, F. Refaeian1,2 creating a significant socio-economic burden on 1Neuroscience Institute, Teheran, Iran society. Transcranial magnetic stimulation (TMS) is 2Teheran university of medical sciences, Teheran, Iran non-invasive tool, alter the excitability of the cerebral 3National Nutrition and Food Shahid Beheshti cortex. University of Medical Sciences, Teheran, Iran

Objectives: To investigate the effect of low-frequency Background: B-group vitamins can potentially rTMS over occipital lobe in the management of contribute to migraine prophylaxis through various migraine headache. mechanisms. We conducted a quasi-experimental study to assess the efficacy and tolerability of a Methodology: Thirty patients with migraine were combination of vitamins B1, B6 and B12 (Neurobion) participated in the study. The patients were assigned for prophylaxis of menstruation related migraine into three equal groups. Group one (G1) received 100 attacks. pulses of low frequency rTMS (1Hz) , 90% of motor threshold for twelve sessions over the occipital lope. Methods: Women diagnosed with menstrual related Group two (G2) Which received a designed physical migraine, both chronic and episodic headache, were therapy program and sham rTMS. Group three (G3) enrolled. Patients had begun Neurobion therapy at one which received the same designed physical therapy week before menstruation cycle and repeated the program and rTMS. Pain intensity of headache was injection for three consecutive months, each ampoule, assessed by visual analogue scale pre, immediately containing 100 mg of vitamin B1 and B6 and 1000 μg of post treatment and after three months of post vitamin B12. Neurobion was used as add-on therapy treatment. Level of serum serotonin was measured pre for patients who receive different but the same and immediately post treatment. The frequency of prophylactic therapy during the last two months headache attacks was assessed pre and post three before the start of the study. The outcome parameter months. examined was menstrual related migraine attacks severity on the ten-point visual analog scale.

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Results: Three hundred eighty-three patients (chronic Methods: This was a prospective, real world, open migraine: n= 169 and episodic migraine: n= 214) were label cohort study over 9 months in the United included in the final analysis. Patients received Kingdom (UK). Adult females with confirmed diagnosis treatment with a combination of vitamins B1, B6 and of IIH now in ocular remission (papilloedema now B12 with positive results. Mean menstrual related resolved) with CM-like headaches and failure of ≥3 migraine attacks’ intensity was reduced from 6.7 on preventative medications received 70mg of Erenumab the VAS to 3.2 (P<0.001) in patients with chronic 4-weekly. Clinical assessment was 3-monthly (dose migraine. Mean menstrual related migraine attacks’ adjustment/discontinuation). The primary endpoint severity was also reduced from 7.2 to 3.7 in patients was mean change in monthly migraine days (MMD) with episodic migraine (P<0.001). There was no from baseline (30-day pre-treatment period) compared significant difference in the reduction of headache to 6 months. severity between the two groups of migraineurs (P = 0.985). Results: Study included 55 patients with mean±SD age 35.3±9 years. The mean duration of CM-like headaches Conclusion: Neurotropic vitamins including pyridoxine, was 10.4±8.4 years with mean 3.7±0.9 preventative thiamine, and cyanocobalamin yielded significant treatment failures. Mean baseline MMD was 16.1±4.7 reductions in menstrual related migraine attacks’ and monthly headache days (MHD) was 29±2.3. MMD severity. Neurobion as a combination of B1, B6 and reduced significantly at 6 months by 10.3±4.8 (P < .001) B12 vitamins seems to be well tolerated and beneficial and MHD reduced by 10.6±8.7 (P < .001). Crystal clear as an adjuvant in treatment and prophylaxis of days increased by 10.5±9 (P < .001), headache severity menstrual related migraine attacks. Further large trials (scale 0-10) fell by 1.4±1.7 (P < .001) and monthly with long-term follow-up will be required to confirm analgesic days reduced by 3.9±8.3 (P = .001). Results our results. were consistent at 3 and 9 months. Headache impact test-6 (HIT-6) score and quality of life (SF-36) significantly improved (P < .001 and P < .05 respectively) at 6 months. Sensitivity analysis revealed P276 similar results for patients that had migraine diagnosis An open-label prospective study of the real-world use prior to IIH (52%) or medication overuse headache of Erenumab for the treatment of chronic migraine in (48%) and without. patients with idiopathic intracranial hypertension in ocular remission. Conclusion: This prospective real world open-label A. Yiangou1,2,3, J. Mitchell1,2,3, V. Vijay1,2,3, P. Thomas2, study of Erenumab in IIH patients with CM-like C. Fisher2, J. Edwards2, Z. Alimajstorovic1,3, O. Grech1,3, headaches in whom their papilloedema had resolved, G. Lavery1,3, S. Mollan4, A. Sinclair1,2,3 provides evidence for the efficacy of Erenumab for the 1University of Birmingham, Institute of Metabolism and treatment of headache in this population. This study Systems Research, Metabolic Neurology, Birmingham, provides important mechanistic insights suggesting United Kingdom that CGRP is likely a key modulator driving headache in 2University Hospitals Birmingham NHS Foundation patients with IIH in ocular remission. Trust, Department of Neurology, Birmingham, United Kingdom 3Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom 4University Hospitals Birmingham NHS Foundation Trust, Birmingham Neuro-Ophthalmology Unit, Ophthalmology Department, Birmingham, United Kingdom

Question: Headache is an unmet need in idiopathic intracranial hypertension (IIH). Is Erenumab effective at preventing chronic migraine (CM)-like headaches in patients with IIH in ocular remission? 171

P277 Conclusion: Through the assessment of a range of The PEARL Study Protocol: A Pan-European effectiveness outcomes and patient-reported Prospective Observational Study of Fremanezumab measures in clinical practice, PEARL will generate Effectiveness in Patients with Chronic or Episodic precious information about real-world effectiveness, Migraine in the Real World treatment adherence, and treatment persistence of M. Ashina1, F. Mohammad Amin1,2, P. Kokturk3, J. fremanezumab in patients with EM and CM. Cohen3, M. Konings3, C. Tassorelli4,5, D. D. Mitsikostas6 1Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup, Denmark 2Faculty of Health and Medical Sciences, University of P278 Copenhagen, Copenhagen, Denmark Health-Related Quality of Life Outcomes With 3Teva Pharmaceuticals, Amsterdam, Netherlands Fremanezumab in Patients With Episodic and Chronic 4Headache Science Center, IRCCS Mondino Foundation, Migraine and Documented Inadequate Response to 2- Pavia, Italy 4 Classes of Migraine Preventive Medications: Open- 5Department of Brain and Behavioral Sciences, label Extension of the FOCUS Phase 3b Study University of Pavia, Pavia, Italy L. Mechtler1, X. Ning2, V. Ramirez-Campos2, J. M. 6National & Kapodistrian University of Athens, Athens, Cohen2, R. Yang2 Greece 1Dent Neurologic Institute, Buffalo, NY, United States 2Teva Pharmaceutical Industries, West Chester, PA, Question: Migraine is a common but highly disabling United States disease, and adherence to traditional migraine preventive treatment is low. Fremanezumab is a fully- Question: Fremanezumab, a fully-humanized humanized monoclonal antibody (IgG2Δa) that monoclonal antibody (IgG2Δa) that selectively targets selectively targets calcitonin gene-related peptide calcitonin gene-related peptide (CGRP), has (CGRP) and has been approved in the US and EU for demonstrated efficacy as a preventive treatment in the preventive treatment of migraine in adults. The adult patients (pts) with chronic migraine (CM) or PEARL study aims to provide real-world evidence of episodic migraine (EM) and documented inadequate fremanezumab treatment outcomes in European response to 2-4 prior migraine preventive medication clinical practice in patients with episodic migraine (EM) classes in the 12-week double-blind period (DBP) of the or chronic migraine (CM). FOCUS trial. In addition, significant improvements were observed in migraine-specific and overall health status Methods: PEARL is a 36-month (12-month recruitment during the DBP for fremanezumab vs placebo (PBO). To and 24-month follow-up), multicenter, pan-European, determine if these effects are sustained, health-related prospective, observational study conducted in adults quality of life (HRQoL) outcomes were evaluated with EM (≥4 migraine days per month) or CM (≥ 15 during the 12-week open-label extension (OLE) of the headache days per month, of which ≥8 meet migraine FOCUS study. criteria) in real-world clinical practice. The primary endpoint is the proportion of patients reaching ≥50% Methods: Pts were initially randomized (1:1:1) to reduction in monthly average number of migraine days quarterly fremanezumab (Month 1/2/3: during the 6-month period after the first dose of study 675mg/PBO/PBO), monthly fremanezumab (Month drug. Secondary effectiveness endpoints include 1/2/3: 675mg (CM), 225mg (EM)/225mg/225mg), or changes from baseline in monthly average number of matched monthly PBO for the DBP. All pts completing migraine days, disability scores, and monthly average the DBP entered the OLE and received 3 monthly doses number of days of acute headache medication use. of fremanezumab (225mg). Mean changes from Adherence and persistence with fremanezumab baseline in the migraine-specific quality of life (MSQOL) treatment over the 24-month follow-up, as well as and EuroQol-5 Dimension (EQ-5D-5L) questionnaires reasons for and outcomes of fremanezumab cessation were measured at the end of the DBP and at the end of and re-initiation, will also be examined. the OLE.

Results: The study is planned to be conducted in Results: Of 838 pts randomized, 807 completed the approximately 100 centers in 11 European countries, DBP and entered the OLE; 772 pts completed the OLE. with an estimated sample size of 850 patients. Scores for all 3 domains of the MSQOL showed 172

continued improvement during the OLE across the adults. The FOCUS study of fremanezumab was the double-blind PBO, quarterly fremanezumab, and first and largest study of a migraine preventive monthly fremanezumab randomization groups (Table). treatment in adults with both CM and EM with Health status, as measured by the EQ-5D-5L, also documented inadequate response to 2-4 classes of improved after the DBP with positive mean (SD) migraine preventive medications. This post hoc changes at the end of OLE treatment for all double- analysis evaluated efficacy within the first week of blind treatment groups (Table). study treatment.

Conclusion: In pts with EM and CM and inadequate Methods: Patients were randomized (1:1:1) to response to 2-4 prior classes of migraine preventive quarterly fremanezumab (Month 1: 675 mg; Months 2 medications, open-label administration of and 3: placebo), monthly fremanezumab (Month 1: fremanezumab maintained improvements in HRQoL, as CM, 675 mg; EM, 225 mg; Months 2 and 3: 225 mg), or measured by both disease-specific and general quality matched monthly placebo for 12 weeks. Proportions of of life questionnaires. patients with migraine days during the first 7 days of treatment were evaluated in all groups. Figure 1 Results: 838 patients were randomized. Significantly fewer patients in the overall population had a migraine day with fremanezumab (quarterly, 32% and monthly, 36%) vs placebo (46%) on Day 2 and on each day through Day 7 (all P ≤0.011). In patients with CM (n = 509), significantly fewer patients had a migraine day with fremanezumab (quarterly, 41% and monthly, 43%) vs placebo (57%) on Day 2 and on each day through Day 7 (all P <0.05).

Conclusion: Fremanezumab demonstrated very early P279 onset of action, with a significantly larger proportion of Very Early Onset of Action of Fremanezumab in patients receiving fremanezumab reporting no Patients With Migraine and Documented Inadequate migraine attacks within 24 hours and daily through Day Response to 2-4 Classes of Migraine Preventive 7 compared with those receiving placebo. Medications: Results of the International, Fremanezumab rapidly reduced the number of Multicenter, Randomized, Placebo-controlled FOCUS migraine days in the first week of treatment in patients Study with EM and CM with documented inadequate J. Brandes1,2, V. Ramirez-Campos3, R. Yang3, J. M. response to 2-4 classes of migraine preventive Cohen3, M. Galic4, X. Ning3, C. Treppendahl5 medications. 1Nashville Neuroscience Group, Nashville, TN, United States 2Department of Neurology, Vanderbilt University, Nashville, TN, United States 3Teva Pharmaceutical Industries, West Chester, PA, United States 4Teva Pharmaceuticals, Amsterdam, Netherlands 5The Headache Center, Ridgeland, MS, United States

Question: Preventive treatments for episodic (EM) and chronic migraine (CM) have been associated with slow onset of action. Fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), has proven efficacy for the preventive treatment of migraine in

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P281 Discussion: For CM pts with documented inadequate Efficacy of Fremanezumab by Prior Number of response to 2, 3, or 4 classes of migraine preventive Preventive Treatments With Inadequate Response in medications, clinically meaningful response rates were Patients With Episodic Migraine and Chronic significantly greater with fremanezumab compared Migraine: Results of the International, Multicenter with PBO. Similar results were observed in EM pts. Phase 3b FOCUS Study L. Pazdera1, J. M. Cohen2, X. Ning2, V. Ramirez– Campos2, R. Yang2 1Vestra Clinics, Rychnov nad Kněžnou, Czech Republic P282 2Teva Pharmaceutical Industries, West Chester, PA, Patient Satisfaction With Fremanezumab During the United States Open-label Period of the Phase 3b FOCUS Study in Patients With Episodic and Chronic Migraine and Objective: Fremanezumab has demonstrated efficacy Documented Inadequate Response to 2-4 Classes of as a preventive treatment for episodic or chronic Migraine Preventive Medications migraine (EM or CM) in adults with inadequate L. Mechtler1, X. Ning2, V. Ramirez-Campos2, J. M. response to 2-4 prior classes of migraine preventive Cohen2, R. Yang2 medications in the FOCUS study. This analysis 1Dent Neurologic Institute, Buffalo, NY, United States evaluated response rates (≥50% reduction in monthly 2Teva Pharmaceutical Industries, West Chester, PA, average migraine days) for fremanezumab by migraine United States classification (EM or CM) and number of prior migraine preventive medication classes with inadequate Objective: Fremanezumab, a fully-humanized response (2, 3, or 4). monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), has Methods: During the 12-week, double-blind period, demonstrated efficacy for the preventive treatment of patients (pts) were randomized (1:1:1) to quarterly migraine in adults with chronic migraine (CM) or fremanezumab (Month 1/2/3: 675 episodic migraine (EM) and documented inadequate mg/placebo(PBO)/PBO), monthly fremanezumab response to 2-4 prior classes of migraine preventive (Month 1/2/3: 675 mg (CM), 225 mg (EM)/225 mg/225 medications in the double-blind period (DBP) of the mg), or matched monthly PBO. FOCUS trial. Proportions of patients (pts) who were considered responders and nonresponders on the Results: Of 838 pts randomized, 61% had CM, 39% had patient global impression of change (PGIC) were EM, and 50%, 32%, and 18% had inadequate response evaluated during the 12-week DBP and 12-week open- to 2, 3, and 4 prior preventive medications, label extension (OLE) of the FOCUS study. respectively. The proportions of pts with CM who achieved ≥50% reductions in migraine days were Methods: Pts were initially randomized (1:1:1) to significantly greater with quarterly and monthly quarterly fremanezumab (Month 1/2/3: 675 fremanezumab, respectively, vs PBO among pts with mg/placebo (PBO)/PBO), monthly fremanezumab inadequate response to 2 (33% and 36% vs 11%; (Month 1/2/3: 675 mg (CM), 225 mg (EM)/225 mg/225 P=0.0014 and P=0.0003, respectively), 3 (23% and 26% mg), or matched monthly PBO for the 12-week DBP. All vs 6%; P=0.0260 and P=0.0147, respectively), or 4 (21% pts completing the DBP entered the OLE and received and 20% vs 5%; P=0.0477 and P=0.0284, respectively) three monthly doses of fremanezumab (225 mg). The migraine preventive medication classes. In pts with PGIC describes the impact of migraine on quality of life EM, proportions achieving ≥50% reduction in migraine and health status since beginning treatment using a 7- days were higher with quarterly and monthly point scale. The proportion of PGIC responders (score, fremanezumab, respectively, vs PBO among pts with 5-7 out of 7) and non-responders (score, 1-4 out of 7) inadequate response to 2 (46% and 45% vs 12%; both was summarized at the end of the DBP and the OLE by P<0.0001), 3 (52% and 30% vs 9%; P=0.0010 and double-blind randomization group. 0.0592, respectively), or 4 (50% and 60% vs 0%; sample size too small for logistic regression model) migraine Results: Of the 838 pts randomized, 807 completed the preventive medication classes. DBP and entered the OLE; 772 pts completed the OLE. At the end of the DBP, the proportion of PGIC responders in the PBO, quarterly fremanezumab, and 174

monthly fremanezumab groups were 29%, 58%, and (BL) in PHQ-9 were measured at the end of the DBP 64%, respectively. At the end of treatment in the OLE, and the OLE. the proportion of PGIC responders was 69% in the PBO double-blind randomization group, 77% in the Results: Of 838 patients randomized, 807 completed quarterly fremanezumab randomization group, and the DBP and entered the OLE; 772 completed the OLE. 75% in the monthly fremanezumab randomization Mean (SD) BL PHQ-9 scores were 3.9 (5.34), 4.3 (5.62), group. and 3.5 (5.11) in the PBO, quarterly fremanezumab, and monthly fremanezumab double-blind Conclusion: Patients treated with fremanezumab were randomization groups, respectively. During the DBP, more likely to find migraine improved as measured by LSM (SE) changes from baseline in PHQ-9 scores in the PGIC compared to PBO, with an increase of responders PBO, quarterly fremanezumab, and monthly after an additional 12 weeks of open-label treatment. fremanezumab groups were –0.7 (0.34), –1.3 (0.35), and –1.8 (0.34), respectively. During the OLE, mean (SD) changes in PHQ-9 scores from BL to end of treatment were −2.0 (4.89), −2.4 (5.26), and −1.6 (5.52) P283 in the PBO, quarterly fremanezumab, and monthly Effect of Fremanezumab on Depression Status in fremanezumab double-blind randomization groups, Patients With Episodic and Chronic Migraine and respectively. Documented Inadequate Response to 2-4 Classes of Migraine Preventive Medications During the Open- Conclusion: Improvement in depression symptomology label Period of the Phase 3b FOCUS Study was maintained during the OLE of the FOCUS study D. C. Buse1, J. M. Cohen2, V. Ramirez–Campos2, R. with fremanezumab treatment in patients with CM or Yang2, X. Ning2, M. Galic3 EM and inadequate response to 2-4 migraine 1Department of Neurology, Albert Einstein College of preventive medication classes. Medicine, New York, NY, United States 2Teva Pharmaceutical Industries, West Chester, PA, United States 3Teva Pharmaceuticals, Amsterdam, Netherlands P284 Impact of Fremanezumab on Disability Severity Objective: Fremanezumab, a fully-humanized According to the AHS Consensus: Pooled Results of 3 monoclonal antibody (IgG2Δa) that selectively targets Randomized, Double-blind, Placebo-controlled Phase calcitonin gene-related peptide (CGRP), has 3 Studies demonstrated efficacy as a preventive treatment in A. J. Nagy1, J. M. Cohen2, X. Ning2, V. Ramirez-Campos2, adults with chronic or episodic migraine (CM or EM) M. Ashina3 and documented inadequate response to 2-4 prior 1Nevada Headache Institute, Las Vegas, NV, United migraine preventive medication classes in the double- States blind period (DBP) of the FOCUS trial. The PHQ-9 was 2Teva Pharmaceutical Industries, West Chester, PA, used to evaluate depression severity during the open- United States label extension (OLE) of FOCUS. 3Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup, Denmark Methods: Patients were initially randomized (1:1:1) to quarterly fremanezumab (Month 1/2/3: Question: This pooled analysis of fremanezumab 675mg/placebo (PBO)/PBO), monthly fremanezumab clinical trial data evaluated disability response using (Month 1/2/3: 675mg(CM), American Headache Society (AHS) consensus 225mg(EM)/225mg/225mg), or matched PBO. Patients statement guidelines, which assert that Migraine completing the 12-week DBP entered the 12-week OLE Disability Assessment (MIDAS) and 6-item Headache and received 3 monthly doses of fremanezumab Impact Test (HIT-6) provide evidence of treatment (225mg). The PHQ-9 consists of 9 items (each scored, benefits on disability outcomes. 0-3) corresponding to diagnostic criteria for major depressive disorder; 0-4 indicates none-minimal and 5- Methods: This analysis included subjects with episodic 9 indicates mild symptomology. Changes from baseline or chronic migraine (EM or CM) from 3 double-blind phase 3 trials (HALO EM, HALO CM, and FOCUS). 175

Subjects were randomized 1:1:1 to quarterly (qtly) or disability severity category shifts after fremanezumab monthly (mthy) fremanezumab, or matched placebo treatment or placebo (PBO). (PBO) over 12 weeks. MIDAS was used in HALO EM and FOCUS, and HIT-6 in HALO CM and FOCUS. Methods: This analysis included subjects with episodic Measurements of disability and response to treatment or chronic migraine (EM or CM) from 3 double-blind followed AHS guidelines: for MIDAS, ≥5-point (pt) phase 3 trials (HALO EM, HALO CM, and FOCUS). reduction when baseline score is 11-20 or ≥30% when Subjects were randomized 1:1:1 to quarterly or baseline score is >20, and for HIT-6, ≥5-pt reduction. monthly fremanezumab, or matched PBO over 12 weeks. Migraine Disability Assessment (MIDAS) was Results: Based on baseline MIDAS scores for this used in HALO EM and FOCUS, and 6-item Headache population (n=1,702), 74%, 14%, 6%, and 5% of Impact Test (HIT-6) was used in HALO CM and FOCUS. subjects experienced severe, moderate, mild, and little MIDAS severity categories: little or no (score, 0-5), mild or no disability, respectively. Similarly, for baseline HIT- (6-10), moderate (11-20), and severe (≥21) disability. 6 scores (n=1,958), 87%, 8%, 3%, and <1% of subjects HIT-6 severity categories: little or no (score, ≤49), some indicated that there was severe, substantial, some, and (50-55), substantial (56-59), and severe (60-78) impact. little or no impact, respectively, due to headache. For subjects with baseline MIDAS score 11-20, the Results: Baseline MIDAS scores for this pooled proportion achieving 5-pt reduction was significantly population (n=1,702) demonstrated 74%, 14%, 6%, and higher with fremanezumab (qtly, 71%; mtly, 70%) vs 5% of subjects experienced severe, moderate, mild, PBO (49%; both P<0.01). For subjects with baseline and little or no disability, respectively. Similarly, MIDAS score >20, the proportion achieving ≥30% baseline HIT-6 scores (n=1,958) demonstrated 87%, reduction was significantly higher with fremanezumab 8%, 3%, and <1% of subjects indicated severe, (qtly, 69%; mtly, 79%) vs PBO (58%; both P<0.001). The substantial, some, and little or no impact, respectively, proportion achieving 5-pt reduction from baseline in due to headache. The proportion of subjects HIT-6 scores was also significantly higher with experiencing a shift of 1-3 severity categories down on fremanezumab (qtly, 53%; mtly, 55%) vs PBO (39%; MIDAS scores was significantly greater with both P<0.0001). fremanezumab (quarterly, 293 [55%]; monthly, 305 [58%]) vs PBO (209 [40%]; both P<0.0001). The Conclusion: In this pooled analysis, fremanezumab proportion experiencing a shift of 1-3 severity resulted in clinically meaningful improvements in categories down on HIT-6 scores was also significantly headache- and migraine-related disability for the greater with quarterly (288 [47%]) and monthly (307 majority of subjects, most of whom had severe [50%]) fremanezumab vs PBO (199 [33%]; both disability at baseline. P<0.0001).

Conclusion: Significantly higher proportions of subjects experienced a shift in disability severity of 1-3 P285 categories with fremanezumab vs PBO, suggesting Disability Severity Category Shift with Fremanezumab fremanezumab may result in clinically meaningful Treatment: Pooled Results of 3 Randomized, Double- improvements in headache- or migraine-related blind, Placebo-controlled Phase 3 Studies disability severity and may be relevant for subjects A. J. Nagy1, J. M. Cohen2, X. Ning2, V. Ramirez-Campos2, with difficult-to-treat migraine. L. Janka2, P. McAllister3 1Nevada Headache Institute, Las Vegas, NV, United States 2Teva Pharmaceutical Industries, West Chester, PA, United States 3New England Institute for Neurology and Headache, Stamford, CT, United States

Objective: Fremanezumab has proven efficacy for preventive treatment of migraine in adults across 3 phase 3 studies. This pooled analysis evaluated 176

P286 Conclusion: Sustained improvements in work Work Productivity and Activity Impairment Outcome productivity and activity impairment were observed With Fremanezumab in Patients With Episodic and during the DBP and OLE, as measured by the WPAI Chronic Migraine and Documented Inadequate questionnaire, with fremanezumab treatment in Response to 2-4 Classes of Migraine Preventive patients with EM or CM and documented inadequate Medications: Open-label Extension of the Phase 3b response to 2-4 prior classes of migraine preventive FOCUS Study medications. R. B. Lipton1,2, J. M. Cohen3, V. Ramirez-Campos3, X. Ning3, R. Yang3 Figure 1 1Albert Einstein College of Medicine, Bronx, NY, United States 2Montefiore Medical Center, Bronx, NY, United States 3Teva Pharmaceutical Industries, West Chester, PA, United States

Objective: Fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), has demonstrated efficacy and tolerability for the preventive treatment of migraine in adults with episodic migraine (EM) or chronic migraine (CM) and P287 documented inadequate response to 2-4 prior Efficacy of Fremanezumab in Patients With Episodic migraine preventive medication classes in the 12-week and Chronic Migraine And Inadequate Response to 2- double-blind period (DBP) of the FOCUS trial. 4 Classes of Migraine Preventive Medication Due to Significant improvements were also observed in the Lack of Efficacy: Results of the International, Work Productivity and Activity Impairment (WPAI) Multicenter Phase 3b FOCUS Study questionnaire at the end of the DBP. The WPAI was A. J. Nagy1, X. Ning2, V. Ramirez-Campos2, J. M. Cohen2, also evaluated during a 12-week open-label extension R. Yang2, K. Carr2, L. Pazdera3 (OLE) of the FOCUS study. 1Nevada Headache Institute, Las Vegas, NV, United States Methods: The FOCUS study consisted of a 12-week, 2Teva Pharmaceutical Industries, West Chester, PA, placebo-controlled DBP, followed by a 12-week, OLE United States period. Patients were initially randomized (1:1:1) to 3Vestra Clinics, Rychnov nad Kněžnou, Czech Republic quarterly fremanezumab (Month 1/2/3: 675 mg/placebo/placebo), monthly fremanezumab (Month Question: Fremanezumab, a fully-humanized 1/2/3: 675 mg (CM), 225 mg (EM)/225 mg/225 mg), or monoclonal antibody (IgG2Δa) that selectively targets matched monthly placebo for the 12-week DBP. All calcitonin gene-related peptide (CGRP), has proven patients completing the DBP entered the OLE and efficacy for migraine prevention in adults. This analysis received three monthly doses of fremanezumab (225 of the FOCUS study, which included patients with mg). Mean changes from baseline in the WPAI episodic or chronic migraine (EM or CM) and questionnaire were measured at the end of the DBP documented inadequate response to 2-4 classes of and at the end of the OLE and summarized using migraine preventive medications, evaluated efficacy in descriptive statistics by double-blind treatment group. patients with inadequate response to ≥1 preventive due to lack of efficacy. Results: Of the 838 patients randomized, 807 completed the DBP and entered the OLE; 772 patients Methods: In the 12-week, double-blind period of completed the OLE. During the OLE, improvement in FOCUS, patients were randomized (1:1:1) to quarterly work productivity and activity impairment was (qtly) fremanezumab (Month 1/2/3: maintained in all 4 domains and across all double-blind 675mg/placebo/placebo), monthly (mtly) randomization groups, and the magnitude of change fremanezumab (Month 1/2/3: 675mg (CM), 225mg was consistent with that observed during the DBP in (EM)/225mg/225mg), or matched placebo. Definitions the fremanezumab groups (Table). 177

of inadequate response included lack of efficacy, monthly migraine frequency, days of headache and intolerability, or medication was contraindicated or not rescue medication used per month were collected. suitable for the patient. This analysis looked at the cohort of patients with inadequate response to ≥1 Results: Responder rates were similar between the preventive medication due to lack of efficacy. two treatment groups at 6-month follow-up (Table I). Interestingly, responder rates for aura frequency and Results: Of 838 patients randomized, 741 duration were higher in the lamotrigine group demonstrated inadequate response to prior preventive compared to the topiramate group (88% vs 79% and migraine medication classes due to lack of efficacy. 73% vs 54%). Moreover, 50% of the lamotrigine Change from baseline in mtly average migraine days treated patients reported a complete disappearance of over 12 weeks was significantly greater with qtly and migraine aura compared to 37% of topiramate treated mtly fremanezumab, respectively, vs placebo in this patients (Table II). Side effects were more frequent in population (least-squares mean difference (LSMD) vs topiramate group compared to lamotrigine group placebo: -3.1 and -3.4; P<0.0001). Change from (p=0.004). baseline in headache days of at least moderate severity was also significantly greater with fremanezumab vs Conclusions: Lamotrigine should be considered in placebo (LSMD: qtly, -3.3; mtly, -3.6; P<0.0001). At 12 clinical practice for the preventive treatment of weeks, proportions of patients with ≥50% reduction in migraine with aura, especially for patients reporting migraine days were significantly greater with qtly prolonged aura and who do not respond, have (34%) and mtly (34%) fremanezumab vs placebo (9%; contraindications, or discontinue topiramate treatment P<0.0001). due to side effects

Conclusion: In patients with EM or CM and lack of Figure 1 efficacy to ≥1 prior preventive medication, fremanezumab demonstrated efficacy as measured by significant reductions in the number of migraine and headache days and improved response rates versus placebo.

P288 May lamotrigine be an alternative to topiramate in the prevention of migraine with aura? Results of a retrospective study 1 1 1 1 C. L. Smeralda , G. L. Gigli , F. Janes , M. Valente 1 Clinical Neurology, University Hospital of Udine, Udine, Italy

Question: Evidence suggests that lamotrigine could be effective in reducing aura frequency and duration. However, studies comparing lamotrigine to other, first line prophylactic agents involving a population of solely migraine with aura patients are still lacking. The aim of this study was to compare the efficacy of lamotrigine and topiramate for the preventive treatment of migraine with aura.

Methods: Fifty-three migraine with aura patients treated with lamotrigine or topiramate for at least 6 months were included. Pre and post-treatment clinical data regarding monthly aura frequency and duration, 178

Figure 2 headache days and proportion of patients achieving ≥50% and ≥75% reduction in monthly migraine headache days across the 3-month double-blind period. Migraine-Specific Quality of Life (MSQ) Role Function-Restrictive (RF-R) and Migraine Disability Assessment (MIDAS) were assessed at Month 3.

Results: Overall, 166 patients (36% of all patients in CONQUER; HFEM=80, CM=86) were included in baseline analyses. Baseline characteristics were not statistically different between treatment groups. Following treatment, there were statistically significant differences between placebo and galcanezumab in the mean change from baseline in monthly migraine P289 headache days, ≥50% response, ≥75% response, MSQ Efficacy of galcanezumab in patients with high- RF-R score and MIDAS score (Table; *p<0.01). frequency episodic or chronic migraine and ≥3 previous preventive treatment failures: a subgroup Conclusion: This analysis shows that treatment with analysis from the CONQUER study galcanezumab significantly improved key efficacy 1 2,3 4 M. Weatherall , M. Matharu , A. Pain , A. Tockhorn- endpoints compared with placebo, in patients with 4 4 4 Heidenreich , M. A. Paget , G. Dell'Agnello , G. HFEM or CM who had previously failed ≥3 preventive 5,6 Lambru treatment categories. 1Buckinghamshire Healthcare NHS Trust, Stoke Mandeville Hospital, Aylesbury, United Kingdom This study was funded by Eli Lilly and Company. 2UCL Queen Square Institute of Neurology, London, United Kingdom Figure 1 3The National Hospital for Neurology and

Neurosurgery, London, United Kingdom 4Eli Lilly and Company, Indianapolis, United States 5Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom 6King's College London, London, United Kingdom

Question: Is galcanezumab efficacious in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM), and a prior history of failure with ≥3 preventive treatments?

Methods: CONQUER (NCT03559257) was a Phase 3, P290 multicentre, randomised-controlled trial assessing the No additive effect of combining sumatriptan and efficacy and safety/tolerability of galcanezumab in olcegepant in the GTN mouse model of migraine patients with treatment-resistant migraine. Patients C. Ernstsen1, S. L. Tangsgaard Christensen1, J. Olesen1, aged 18-75 years with 2-4 migraine prevention D. Møbjerg Kristensen1,2 medication category failures in the past 10 years were 1Danish Headache Center, Glostrup, Denmark randomised 1:1 to placebo and galcanezumab 120 2University of Rennes, Inserm, EHESP, Irset, Rennes, mg/month (240 mg loading dose). In this post-hoc France analysis, we evaluated a subgroup of patients with HFEM (<15 headache days/30-day period, 8-14 are Introduction: Despite recent advances in the field of migraine headache) or CM (≥15 headache days/30-day migraine treatment, there is a need for improved period, ≥8 are migraine headache), and ≥3 prior therapies with high clinical efficacy. Triptans (5- preventive medication category failures. Evaluated HT1B/1D agonists) are essential in the present endpoints included change in monthly migraine treatment regime and gepants (CGRP-receptor

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antagonists) are likewise recognized as effective in Introduction: in chronic migraine (CM), central acute migraine treatment. Triptans and gepants have sensitization, reduced descending pain inhibitory different mechanisms of action and here we tested the control and cortical hyperexcitability are involved. hypothesis that combinations of these drugs Botulinum toxin type A (BoNT-A) acts attenuating (sumatriptan and olcegepant) would result in an peripheral sensitization, leading an indirect reduction additive effect. of central sensitization. We used Transcranial Magnetic Stimulation (TMS) to evaluate excitability and cerebral Methods: Using the validated glyceryl trinitrate (GTN) plasticity in chronic migraineurs treated with mouse model of migraine, we initially tested dose- Botulinum. response relationships of sumatriptan (0.1, 0.3, and 0.6 mg/kg IP) and olcegepant (0.25, 0.50, and 1.0 mg/kg IP) Methods: we enrolled 11 patients with CM treated to find optimal and suboptimal doses. Subsequently, with BoNT-A (treatment group) and 11 patients with we performed a combination study of the two drugs episodic migraine (EM). We used single and double combining sub-optimal and optimal doses. TMS protocol at the beginning and at the end of treatment period and at baseline in the control group. Results: Overall, sumatriptan significantly reduced GTN-induced allodynia (F(4,54) = 13.51, p < 0.0001) Results: at baseline, we observed a significant with both 0.1, 0.3 and 0.60 mg/kg having significant difference in the level of excitability threshold between effect. Similarly, olcegepant had an overall significant the two groups in both cerebral hemispheres: chronic effect on GTN-induced allodynia (F(4,53) = 16.11, p < migraineurs have a lower threshold (right hemisphere: 0.0001) but only 0.50 and 1.0 mg/kg olcegepant being 46±7,8 vs 52±4,28, p=0,03; left hemisphere: 52±4,28 vs effective. However, combining 0.50 mg/kg olcegepant 53,54±6,58, p=0,02). In EM double TMS shows a with 0.1 or 0.6 mg/kg sumatriptan did not have any physiological response. In CM, at baseline, there is a improved effect in the mouse model compared to lack of physiological response: with a facilitating either drug alone (p > 0.50 on all days). Visualization of response for interstimulus intervals between 1-3 msec. the effects via AUC normalized to vehicle showed an This facilitation is maintained for the 6, 10 and 15 msec overall significant effect compared to GTN control intervals, in the left hemisphere and for the 10 and 15 group (F(5,53) = 9.02, p < 0.0001) with an effect size msec intervals also in the right hemisphere. After between 73-81%. However, no differences were seen treatment, cortical excitability did not change, between the two single-treatment groups and the two facilitation is maintained, although the MIDAS score combination groups. decreased from 20.7 to 9.8 (p=0.008).

Conclusion: Our results show that combining Discussion: The values of motor threshold are olcegepant and sumatriptan did not have an additive significantly lower in the treatment group, this could effect compared to single-drug treatment. Triptan- represent a sign of greater cortical reactivity. The lack gepant combinations will most likely not improve of physiological intracortical inhibition could be migraine treatment. Nevertheless, combinations interpreted as a sign of the maintenance of a should also be examined in patients with migraine. sensitization of the trigeminovascular system. After treatment, the clinical improvement, was not followed by a consensual change of neurophysiological data. Our study confirms the hypothesis of an alteration of P291 cortical plasticity due to chronic pain. Treatment with type-A BOTULINUM TOXIN in chronic migraine is effective on pain, but does not change cortical excitability and plasticity M. Valente1, V. Russo2, G. Macorig3, C. Gentile3, G. L. Gigli1 1Neurological Clinic University of Udine, Udine, Italy 2Hospital of Udine, Physical Medicine and Rehabilitation, Udine, Italy 3Hospital of Gorizia, Neurology, Gorizia, Italy

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P292 Taking into account both the peripheral and the central Effects of erenumab on sleep and migraine, a clinical release of CGRP by neurons of the trigeminal ganglion, and polysomnographic (ERESON) study. a possible interpretation is that antibodies against the M. Valente1, G. Pellitteri1, A. Surcinelli1, S. Pez1, G. L. CGRP system could have a modulating action on CGRP Gigli1 also in CNS structures involved in sleep, such as the 1Neurological Clinic University of Udine, Udine, Italy brainstem and the hypothalamus.

Objectives: Our data on efficacy and safety of erenumab in migraine prophylaxis are consistent with those in the 1. To assess sleep quality in episodic (EM) and literature. chronic migraine (CM) before and after 12 weeks treatment with erenumab. Figure 1 2. To collect post-marketing data on treatment efficacy and safety.

Methods: ERESON is an ongoing pilote study on patients with EM and CM without sleep disorders, except for poor sleep quality due to migraine attacks, not taking drugs with effects on sleep.

Patients were tested before and after 12 weeks treatment with erenumab 70 mg using polysomnography (PSG), headache diaries and interview-based questionnaires on sleep, migraine, life quality and depression.

Results: A total of 29 patients were enrolled. To date, 26 of them completed 12 weeks headache diaries, questionnaires and PSG follow-up. At this time, we analyzed clinical data for 26 patients and PSG data for 17 of them (see table 1).

PSG showed a significant increase in sleep efficiency (SE) and a reduction in awakenings/hour index (see table 2).

We observed a significant reduction in monthly migraine days (MMD), headache intensity and a significant improvement in all questionnaires (MIDAS, HIT-6, PSQI, BDI) (see table 1).

Discussion: This is the first polysomnographic study on Figure 2 sleep quality after treatment with erenumab, demonstrating an amelioration of both sleep profile and migraine severity. Sleep and migraine share common subcortical structures and signaling molecules. However, little is known about the role of some neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase- activating peptide (PACAP), in circadian rhythm.

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P293 P294 Intranasal zucapsaicin for acute treatment of migraine Real world efficacy of candesartan in the treatment of S. Shokhimardonov1 migraine: a retrospective cohort study: 1Tashkent Medical Academy, Neurology, Tashkent, D. García-Azorín1, C. Sánchez-Rodriguez1, î Sierra- Uzbekistan Mencía1, M. Gutierrez-Sánchez1, D. Gil Contreras1, î Guerrero Peral1 Objectives: To study effectiveness degree of the drug 1Hospital Clínico Universitario de Valladolid, Headache Zucapsaicin for treactemnt of acute migraine with and Unit, Valladolid, Spain without aura, as well as to evaluate its safety for intranasal use. Question: To date, two randomized, double-blind, placebo-controlled studies support candesartan use on Materials and methods: We conducted a double-blind, migraine, however its efficacy and tolerability in real randomized trial among 120 patients diagnosed with world setting has been scarcely described. acute migraine. Patients were divided into two groups. 1 - group received a 20 μg dosage of the drug, 2 - group Methods: Retrospective cohort study on patients with received 80 μg of the drug intranasally. The episodic and chronic migraine (CM) diagnosis, effectiveness of treatment was evaluated according to according to the International Classification of the FLACC scale, the safety of the treatment was by the Headache Disorders. We systematically reviewed every manifestation of an adverse reaction 2 and 4 hours patient treated in our headache unit in the period after use. between 2008 and 2015, that received Candesartan as migraine prophylaxis. We analyzed demographic and Results: 55.6% of patients receiving a dose of 20 mcg clinical data. We defined response as 50% headache and 72% of patients with a dose of 80 mcg showed a reduction in the frequency of headache days per decrease in the severity of pain after 2 hourse ( FLACC month between weeks 8 to 12 of treatment, compared scale 5,4 to 2,2, p= 0,05). 4 hours after the dose was with baseline. We analyzed which factors were administered 72.7% of patients with a dose of 20 μg associated with response. and 84% with a dose of 80 μg showed a decrease in the severity of pain ( from 3,7 to 0,9 on FLACC scale). Results: During the study period we included 4070 Adverse events were the same for both doses: 22% of patients, and 128 of them used candesartan. We patients experienced a burning sensation in the nose excluded 48 patients that received it before migraine and 14.1% of patients experienced lacrimation. No diagnosis due to arterial hypertension. Candesartan systemic side effects were observed. was prescribed for migraine prophylaxis in 80 patients (1.9% of the sample). Mean age of patients was 45.7 Conclusions: Based on the results of this study, years (11.4), 65 of them female (81.3%), and 57 of intranasal zucapsaicin is effective in the acute them CM (71.3%). Mean time since migraine onset was treatment of migraine. 24.8 years (13.8), with 79 months [39.2-109.5] since CM onset in median. Mean number of prior prophylactics was 3.46 (2.1) (figure 1).

At the moment of candesartan use patients had 20.0 headache days per month (8.3), being 11.0 (7.3) of those migraine days. Eight patients discontinued the treatment within the first month due to tolerability (10%). After three months 26 patients had a 50% response (32.5%). Response was associated with a lesser number of prior prophylactics (OR: 0.70, 95% CI: 0.52-0.94) but not with CM duration or frequency of headache at baseline.

Conclusion: In our cohort, a third of patients using candesartan had a 50% response, similar to the pivotal

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trials. Discontinuations due to adverse events were Results: The mean(±SD) age of participants was 48±12 infrequent. years and 83% were female. Compared to placebo BP comparison, the low-dose triple BP combination group Figure 1 had 0.8 fewer monthly migraine days, with 95% CI from 2.4 fewer to 0.9 more; and the propranolol group had 0.6 fewer days (95% CI -2.2 to 1.0). Compared to placebo for the cholesterol comparisons, the low-dose cholesterol combination group and the simvastatin group differed by +0.5 days, 95% CI -1.4 to 2.4 and +0.6 days, 95% CI -1.3 to 2.5, respectively. There were no serious adverse events in the active or placebo groups.A systematic search from previous trials of BP lowering drugs in migraine patients from 1972 – 2019 identified 61 trials with 4709 participants, and the current results will be presented in the context of the results of this systematic review.

Conclusion: This study was successful in developing a multicentre collaboration of expert migraine trialists; P295 piloting trial procedures and materials. The pilot Pilot assessment of the effectiveness and tolerability demonstrated potential effect of BP lowering despite of low-dose combination blood pressure and small sample size, good tolerability and high cholesterol lowering therapy in migraine patients. compliance to medication. Randomised double-blind placebo-controlled 3x3 factorial trial (HAPPy pilot). F. Haghdoost1, C. Delcourt1, C. Carcel1, L. Davies1, D. Cordato1, A. Zagami1, A. Rodgers1 1The George Institute for Global Health, University of New South Wales (UNSW), Sydney, Australia., Sydney, Australia

Objective: To pilot a double-blind randomised factorial trial whether treatment with low-dose combination blood pressure (BP) and cholesterol lowering therapy reduces migraine frequency compared to standard therapy and placebo. The secondary aim was to assess if this approach was safe, tolerable and improved Health Related Quality of Life (HRQoL) when compared to placebo.

Method: Thirty migraine patients (based on ICHD3) were enrolled in a 12-week double-blind, randomized controlled trial. Participants were randomly assigned to one of 3 BP arms - low-dose telmisartan (20mg), amlodipine (2.5mg) and indapamide (1.25mg) [9 patients] vs standard dose propranolol (160mg/day) [10 patients] vs placebo [11 patients] and to a one of 3 cholesterol-lowering arms - rosuvastatin (10mg) and ezetimibe (10mg) [10 patients] vs simvastatin (20mg/day) [9 patients] vs placebo [11 patients]. All analyses of study outcomes were conducted according to the principle of intention-to-treat.

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P296 10 (IQR 4.5-20) to 2 IQR 0-5; P<0.001), and median Efficacy and safety of erenumab: real-life data from monthly days of triptan use from 5 (IQR 0-15.5) to 1 the Abruzzo region, central Italy (IQR 0-4; P<0.001). We recorded 24 adverse events in R. Ornello1, A. Casalena2, I. Frattale1, A. Gabriele3, G. 20 (22.5%) patients, the most common being Affaitati4, M. A. Giamberardino4, M. Assetta2, M. constipation (14.2%). Two adverse events led to Maddestra5, S. Viola6, F. Marzoli6, D. Cerone7, C. treatment discontinuation, namely allergic reaction in Marini8, F. Pistoia1, S. Sacco1 one patient and vertigo in one further patient. 1University of L'Aquila, Department of Applied Clinical Sciences and Biotechnology, L'Aquila, Italy Conclusions: Our data confirm the efficacy of 2Department of Neurology, 'G. Mazzini' Hospital, erenumab for the prevention of migraine, especially in Teramo, Italy patients with chronic migraine and medication 3Department of Neurology, 'SS. Annunziata' Hospital, overuse, in a real-life setting. The treatment was well Sulmona, Italy tolerated over a 6 month period. Further data are 4"G. D’Annunzio" University, Department of Medicine needed to assess the contribution of dose escalation and Science of Aging, Chieti, Italy and of oral add-on treatments. 5Department of Neurology, 'F. Renzetti' Hospital, Lanciano, Italy 6Department of Neurology, 'S. Pio da Pietrelcina' Hospital, Vasto, Italy P297 7Department of Neurology, 'S. Salvatore' Hospital, Erenumab treatment after a stroke like episode in a L'Aquila, Italy paient suffering MELAS and migraine - a case report 8University of L'Aquila, Department of Internal S. Naegel1, P. Burow1, S. Zierz1, T. Kraya1,2 Medicine, Public Health, Life and Environmental 1University Hospital Halle, Neurology, Halle (Saale), Sciences, L'Aquila, Italy Germany 2St. Georg Hospital, Neurology, Leipzig, Germany Question: We aimed to assess the efficacy and safety of erenumab, a fully human monoclonal antibody History: We present the case of a 25-year-old woman inhibiting the calcitonin gene related peptide receptor suffering MELAS (mitochondrial encephalomyopathy, (CGRPr), for the prevention of migraine in a real-life lactic acidosis, and stroke-like episodes)-Syndrom and setting. chronic migraine. Headache was present for many years as a nearly daily headache with mostly severe Methods: We included in our observational study all intensity (NRS 9/10), unilateral manifestation, a patients treated with erenumab during the year 2019 marked tendency to withdraw, regular nausea and in the Abruzzo region, central Italy. All included vomiting, moderate photo- and phonophobia, but only patients had a 6 month follow up. little increase in pain during physical activity. For acute therapy, the patient used oral triptans without success. Results: Among the 89 included patients, 76 (85.4%) For prophylactic treatment, topiramate (without received 6 doses of erenumab, 11 (12.4%) success) and flunarizine (with side effects) were used. autonomously withdrew the drug due to perceived Valproate, amitriptiline and beta-blockers were inefficacy, and 2 (2.2%) due to adverse events. Among considered to be contraindicated. the 76 patients completing treatment, 66 (86.8%) were female, with a mean age of 46.6+/-10.7 years; 71 Course and treatment: After two (7/2018) botox (93.4%) had chronic migraine, and 55 (72.4%) injections this was considered ineffective. Although medication overuse. All patients had ≥2 prior there was an increase in headache intensity, nasal preventive treatment failures. Fifty three patients zolmitriptan was effective and overused (MOH). (69.7%) had a 50% decrease in monthly migraine days Admission for a drug holiday was arranged, But the (MMDs) within the first three doses (Figure 1); 46 patient presented with a severe attack (NRS 10/10) (83.6%) of 55 patients withdrew medication overuse. lasting for 4 days. The patient described a persistent In the 76 patients who completed a 6 dose treatment, left-sided ciliated scotoma, hemianopia, and MRI erenumab decreased median MMDs from 19 revealed a right occipital stroke-like lesion. (interquartile range [IQR] 12-27.5) to 4 (IQR 2-9.5; Subsequently, treatment with L-arginine and P<0.001), median monthly days of analgesic use from erenumab was started.In the next month patient had 184

only 10 headache days and hemianopsia decreased superior-inner angle of orbit associated to pressure rapidly.In the following 6 months patient suffered only tenderness over the same area, photo/phonophobia 4-5 migraine days. Acute medication was no longer and unilateral cranial autonomic symptoms. The third necessary and headache intensity was reduced. No case was a 16-year old female affected since seven side effects were reported. The effect of the therapy years by recurrent unilateral headache attacks with the was persistent and erenumab was discontinued in following features: pulsating quality, trochlear 1/2020. localization, association with nausea, vomit, photophobia and phonohobia. Conclusion: We here present the case of a patient with chronic migraine and MELAS with a stroke-like episode. Conclusions: although the term "Trochlear Migraine" Treatment with erenumab was started early after. refers to the association of two concurrent painful Early and until the end of the therapy with erenumab, disorders that have causal relationship each other, few the efficacy was convincing and there were no side cases and no one pediatric has been reported with this effects. Certainly, more case reports are needed to particular correlation. In our opinion it would be more assess the safety of erenumab in MELAS syndrome. useful if the term was referred to the relationship between topographical localization and other clinical features, just like in the above described cases.

P298 The true trochlear migraine: three case reports E. Correnti1, A. D'Amico1, M. L. Manzo1, L. M. Messina1, P299 F. Vanadia2, V. Raieli2 Monoclonal Antibody treatment of Migraine in Lisboa 1University of Palermo, AOUP "P.Giaccone", Child – Real life data Neuropsychiatry, Palermo, Italy R. Gil-Gouveia1,2, I. B. Marques1,2, A. R. Pinheiro3, E. 2 ISMEP – , “G.Di Cristina” Hospital- ARNAS Civico, Child Parreira1,3, I. Pavão-Martins4 Neuropsychiatry Unit, Palermo, Italy 1Hospital da Luz, Headache Center & Neurology, Lisboa, Portugal Question: Trochlear Migraine is the association of two 2Hospital da Luz, Neurology Department, Lisboa, concurrent painful disorders represented by unilateral Portugal trochlear pain and ipsilateral migraine attacks, where 3Hospital Fernando Fonseca, Neurology Department, the appearence of the first worsen the second pain as Amadora, Portugal well as the migraine improves after succesful 4Centro Hospitalar de Lisboa Norte, Headache treatment of trochleodynia. Outpatient Clinic, Lisboa, Portugal

Methods: we collected clinical data of three children Introduction: Prophylaxis of migraine with monoclonal admitted to our Pediatric Headache Centre of antibodies (MAb) against CGRP or r-CGRP has been "ISMEP"Palermo, Italy in the last three years. proven effective and safe in clinical trials, but there is scarce real-life data available to support this evidence. Results: we reported three pediatric patients which Two of such drugs have been made available in showed a clinical migrainous syndrome with strict Portugal, erenumab since dec.2018 and fremanezumab trochlear localization of pain. The first case was a 12- since oct.2019. year old male with severe left infraorbital pain, nausea and vomit at the admission. He reported an history of Objective: To explore real-life data on the efficacy and episodic headache caracterized by gradual onset, safety of erenumab and fremanesumab in migraine pulsating quality, severe intensity, localization strictly treatment in Lisboa, Portugal. limited to the unilateral superior-inner angle of orbit, alternating side and association with nausea, Methods: All patients treated with MAbs in three photo/phonophobia and vomit. The second case was headache clinics in Lisboa since dec.2018 were an 11-year old male presented several migrainous followed prospectively and data on headache attacks from an early age. He reported episodic attacks frequency and impact measures were collected. of migraine with pulsating quality and severe intensity, many of which strictly localized in the unilateral Results: We collected preliminary data of 95 patients 185

(96% females, age average 44.2 years), 29% with Material and Method: This study included 33 patients chronic migraine and 47% with medication overuse; 75 (18 females, avarage age was 34±6.6 years old). All were on erenumab and 20 on fremanezumab, after an patients suffered from intensive chronic persistent or average of 4.4 failed prophylactic treatments for recurrent one- or two-sided pain in temporal and/or migraine. At the moment, we have follow-up data on occipital areas; sometimes radiation to neck, arm. The 79 patients at 3 months, 61 at 6 months, 26 at 9 approach by R. Bubnov [doi: 10.1186/1878-5085-3-13] months and 4 at 1 year. Discontinuations due to was applied that included US identification of MTrPs inefficacy were 2 (at 3 months) and 1 for insufficient with following DN under US guidance using steel 28G improvement (at 9 months). Discontinuations due to needles to elicit the LTR. Visual analogue scale data high efficacy occurred in 7 patients between the 3rd (VAS 0-10) were measured before, immediately after and 6th treatments. At months 3 and 6 there was a and 24 hours, 1 month after the intervention. median decrease of 6 and 6.8 headache days/ month. Results: Main active MTrPs were diagnosed in rectus Adverse events occurred in at least 18 patients, most and obliquus capitis inferior muscles, the additional were mild and included constipation, fatigue and local (latent) MTrPs were defined and effectively needled in cutaneous reactions. Seven (.3%) patients had ddverse muscles of the ipsilateral shoulder rotator cuff. In one events leading to discontinuation that included severe session 1-3 needles were inserted, 1-2 sessions applied constipation (3 patients), transient hemiparesis (1), de to each patient. Shoulder dysfunction (impingement) novo hemiplegic aura (1), erythema nodosum (1) and with active trigger points in shoulder rotator muscles asymptomatic brain aneurysm (1). was detected and successfully treated in 27 patients. 25 patients showed decrease in pain as measured by a Discussion: Preliminary data on monoclonal antibody VAS of 90%, the difference was significant (p<0.01) and treatment for migraine in real-life setting in Lisboa sustainable pain relief outcome after one month suggests high efficacy with a higher than expected observation (did not need another session). discontinuation rate due to adverse events. Preliminary data shows decreasing levels of migraine type attacks in 7 patients.

Conclusion: DN of MTrPs in suboccipital muscles under P300 ultrasound guidance is effective to treat tension-type Dry needling under ultrasound guidance of trigger headache and can decrease levels of migraine attacks. points in neck and shoulder muscles is effective for Shoulder rotator muscles are important in postural treatment tension-type headaches and of migraine imbalance leading to headaches, evoked by myofascial attacks disorders. R. Bubnov1,2, L. Kalika3 1Clinical hospital `Pheophania`, Ultrasound, Kyiv, Ukraine 2Zabolotny institute of microbiology and virology, NAS P301 of Ukraine, Interferon, Kyiv, Ukraine Real-life data of efficacy and safety of erenumab and 3New York Dynamic Neuromuscular Rehabilitation & galcanezumab in a Headache Unit. Physical Therapy https://nydnrehab.com/, New York, C. Nieves Castellanos1, M. Olivier2, L. Monrós United States Giménez1, R. Baviera Muñoz1, M. Losada López1, S. Díaz Insa1 Introduction: Myofascial pain is widespread, can be 1Hospital Universitari i Politécnic la Fe de Valencia, reliable cause of large number of headaches. Precise Neurology, Valencia, Spain muscle dry needling (DN) of myofascial trigger points 2Hospital Fleni, Neurology, Buenos Aires, Argentina (MTrPs) under ultrasound (US) guidance proved efficacy for treatment numeral pain localizations and Question: We aimed to evaluate the efficacy and widespread pain. safety of erenumab and galcanezumab in prevention of migraine in the first patients treated in our Headache The aim was to evaluate efficacy of deep DN of MTrPs Unit. in suboccipital muscles (rectus and obliquus capitis inferior muscles) treat chronic headaches. 186

Methods: An observational prospective study with P302 erenumab (ER) and galcanezumab (GA) since January No central action of CGRP antagonising drugs 2020. We evaluated demographic data, type and S. L. Christensen1, C. Ernstsen1, J. Olesen1, D. M. intensity of migraine, symptomatic and previous Kristensen1 preventive treatment failed. MIDAS, HIT-6, ASC-12, 1Danish Headache Center, Glostrup, Denmark Pain Catastrophizing Scale and Migraine-Specific Quality of Life Questionnaire (MSQ) were filled. Review Question: CGRP antagonising drugs are recognized as after 3 months of treatment. effective in migraine treatment, but their site of action is debated. Only a small fraction of these compounds Results: We included 36 patients, 28 females (77,8%) passes the blood-brain barrier and access the CNS. and 8 males (22,2%), mean age 48,25 years. 97,2% of Regardless, it has been argued that the CNS is the site patients had chronic migraine. 18 patients were of action. Here, we test this hypothesis bypassing the treated with ER 140mg and 18 patients with GA. The blood-brain barrier through intracerebroventricular patients had failed an average of 6,03 preventive injection of CGRP antagonising drugs. treatment (1,7 DS). They had an average of 24,25 days of migraine per month. Methods: We used the GTN mouse model which is well validated by its response to specific migraine drugs. Monthly migraine headache days reduced an average The CGRP receptor antagonist olcegepant and the of 6,69 days (p < .001). 11 patients (30,6 %) decreased CGRP monoclonal antibody ALD405 were administered more than 50% in monthly migraine days. There was either intraperitoneally or intracerebroventricularly. an average decrease of 7,42 (p < .001) of symptomatic The outcome measure was cutaneous mechanical treatment per month. The abuse of triptans/opioids allodynia. decreased from 80,6% to 36,1% (p<0.001). Results: On day 1, mice given olcegepant Before de treatment, all patients had a MIDAS >20 intraperitoneally + GTN had mean 50 % withdrawal points. After, 44,4% had a MIDAS lower than 20 thresholds of 1.2 g in contrast to mice receiving (average decrease of MIDAS of 58,83 (p<0.001)). 50% placebo + GTN who had a threshold of 0.3 g (p<0.001). of patients reduced HIT-6 in more than 6 points. The Similarly, in the ALD405 + GTN group, mice had pain catastrophizing scale decreased 10 points in 50% thresholds of 1.2 g vs 0.2g in the placebo + GTN group of patients. There was an improvement in MSQ of (p<0.001). However, both drugs were ineffective when 22,12 points (p<0,001), and 52,8% of patients delivered intracerebroventricularly, as control and improved more than 20 points. active groups had identical mechanical sensitivity thresholds, 0.2 g vs 0.1 g and 0.1 g vs 0.1 g for We recorded 13 adverse events in 36% patients, being olcegepant and ALD405, respectively (p>0.99 in both the most common constipation. No adverse events led cases). to discontinuation of the treatment. Conclusion: The site of action of olcegepant and of the We did not find a significant statistical difference monoclonal antibody ALD405 is outside the blood- between both treatments. brain barrier in this mouse model of migraine. It is likely that these results can be generalised to all Conclusions: Our real-life study shows efficacy and gepants and all antibodies and that the results are safety of ER and GA in a very affected population. relevant for human migraine. Although it was not the purpose of this study, we do not find any difference between both treatments.

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Figure 1

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