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 2 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).