K.Mugundhan (1),T.C.R.Ramakrishnan (2). HOSPITAL TIENTS WITH IN CARE ATERTIARY CLINICAL EVALUATION OF IN PA epilepsy or headache/ 4. Spreading depression a ronal membrane hyperexcitability, could manifest as either converging on acommonpathway final represented by neu and epilepsy, such as Na ability might explain comorbidity the headache between andological therapeutic overlap 3. Neuronal hyperexcit two conditions show awell-recognized clinical, pathophysi of arelationship epilepsy and between migraine 2.since the last century Gowers first advancedthe clinical hypothesis tween headache and epilepsy remains unresolved1. In the problems inneurological practice. seen The relationshipbe INTRODUCTION either as pre ictal, ictal or post ictal headache. ictal patients post or of ictal 14.5% ictal, pre as in either seen is associated epilepsy. of type and subtype headache specific between no is correlation There epilepsy. with patients in interictally seen headache primary common most the is headache of type without in Migraine the headache remaining. in seen and secondary 94% of headache patients primary with : Conclusion headache. ictal post or (14.5%) had ictal 18 ictal, pre and (14.1) classified elsewhere be not could which headache as classified activity seizure accompanying without beictus an 24might headache, which with (19.3%) headache had associated seizure with 42 patients Among patients epilepsy. of 6% (n=5) in seen was headache Secondary epilepsy. with patients 6 in seen was headache stabbing mary pri and and patient one in patients seen was of headache cluster (n=45) 54% Episodic patients, (n=25)in of 30.4% in seen occurred was headache type type migraine headache, primary with patients 77 Among epilepsy. with (33.4%) patients 42 in headache associated seizure and (66.6%) patients 82 in present was headache Interictal tion. of were cases 27 2*GTCS, with simple seizures partial and generalisation with secondary 21patients were ofcomplex partial 48 in nature generaliza with secondary Among seizures. tonic-clonic generalised secondary have (n=48) patients of 38.7% and (n=52) patients of 42% is which seizures clonic tonic generalised were seen seizures of type common most The : Results : analysisStatistical used study. the for selected were criteria exclusion of features any have not did who headaches perictal or interictal either have who epilepsy with Patients study. the from excluded were maneuver valsalva signs or such by as cough,triggered exertion headache rash, fever,with headache papilloedema, cutaneous neck stiffness, Criteria: Exclusion headache ictal peri have who epilepsy with Patients and seizures of onset the Criteria: Inclusion study. the for up taken were 2005) August to 2003 (July period study the during Chennai O.P.Hospital, General Government Population:Study Study Design: Materials Methods and study. the for up taken were both or periictally or ictally : design and Setting . of types different with associated headaches of Aim: NEUROLOGY - ARTICLE ORIGINAL Key Words : The aimThe of the is headaches study in to with patients occurring analyseepilepsystudy andand the classify pattern Epilepsy and headache are common neurological The total number of patients studied were 124 of which males comprised 33% (n=42) and females 66% (n= 82). 82). (n= 66% females and (n=42) 33% comprised males which of 124 were studied patients of number total The Headache,Epilepsy The most common type of seizures seen in patients with headache is primary generalized tonic-clonic tonic-clonic generalized primary is headache with patients in seen seizures of type common most The Cross Sectional Descriptive study. Descriptive Sectional Cross 1. DEPT.OF NEUROLOGY, GOVT.MOHAN KUMARAMANGALAM MEDICAL COLLEGE HOSPITAL, SALEM,TAMILNADU. HOSPITAL, COLLEGE MEDICAL 1. DEPT.OF KUMARAMANGALAM GOVT.MOHAN NEUROLOGY, Patients with epilepsy who have headache either interictally or peri ictally or both who attended attended who both or ictally peri or interictally either headache have who epilepsy with Patients Patients with epilepsy who have inter ictal headache of >3 months duration antecedent to or after or to antecedent of duration months >3headache havewho ictal inter epilepsy with Patients + Patients with epilepsy who developed sudden onset severe headache, headache with systemic systemic with headache headache, severe onset sudden developed who epilepsy with Patients It is a Cross Sectional Descriptive study of Patients with epilepsy who have headache either inter either headache have who epilepsy with Patients of study Descriptive Sectional Cross a is It −K + ATPase pump impairment, SPSS software SPSS 2. CONSULTANT NEUROPHYSICIAN,KG HOSPITAL& PG INSTITUTE,COIMBATORE. PG HOSPITAL& NEUROPHYSICIAN,KG CONSULTANT 2. Abstract - - - - tics inpatientstics with epilepsy. done astudy inour centre to analyse headache characteris characteristics of headache inpatients with epilepsy we have numbers.small As there are only few studies evaluating the data are complicated, and studies the have limited by been demonstratedlepsy has been studies inseveral 5,7. But the mous disorders6. An association migraine between and epi epileptic two autono seizures these may between link the be postulated pathophysiological mechanism of migraine and

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MATERIALS AND METHODS ated headache) on the basis of its relationship with epilepsy. STUDY DESIGN: Cross Sectional Descriptive study. Patients with interictal headache, who have structural le- STUDY POPULATION: Patients with epilepsy who sions or other recognisable causes such as sinusitis, cervi- have headache either interictally or peri ictally or both who cal spine disease were classified as secondary headache as attended Neurology O.P. Government General Hospital, recommended in the International Headache society clas- Chennai during the study period (July 2003 to August 2005) sification and those without a recognisable cause as having were taken up for the study. primary headache. All patients in the study were examined INCLUSION CRITERIA: Patients with epilepsy who clinically for focal neurological deficit. Otorhinolaryngolo- have inter ictal headache of >3 months duration antecedent gist and dentist opinion were sought whenever necessary. to or after the onset of seizures and Patients with epilepsy Patients who had headaches along with the onset of seizures who have peri ictal headache and continued throughout the ictus which resolves with Vol 3 | Issue 4 | October-December | 2016 4 | October-December 3 | Issue Vol EXCLUSION CRITERIA : Patients with epilepsy subsidence of seizure activity were classified as ictal head- who developed sudden onset severe headache, headache aches or hemicrania epileptica. Peri ictal headaches were with systemic signs such as fever, neck stiffness, cutaneous subdivided into postictal headache and pre ictal headache rash, headache with papilloedema, headache triggered by based on their relationship with seizures. Patients who have cough, exertion or valsalva maneuver were excluded from headache just preceding the onset of seizures were classi- the study. Patients with epilepsy who have either interictal fied as preictal headache. Patients who had headaches with or perictal headaches who did not have any features of ex- varying characteristics and severity which develops within clusion criteria were selected for the study. 3 hours of seizure and lasts for less than 72 hours are clas- DEFINITIONS AND CLASSIFICATIONS sified as postictal headaches. Patients who initially had sei- Headache were classified according to interna- zures and in whom seizures got controlled with drugs with tional headache society classification (IHS-2)8 and their new onset headache or persistence of precedent headache duration noted in the study. The International classification which are of short duration lasting for 5-10 minutes, severe of Headache disorders, 2nd edition, groups headache disor- in intensity stabbing or bounding in nature associated with ders into primary and secondary headaches. The four cate- transient unawareness or incontinence were classified as gories of primary headaches include migraine, Tension Type headache not classified elsewhere. Primary headaches were Headache (TTH), (CH) other Trigeminal further analysed based on the frequency and duration of Autonomic Cephalalgias (TAC’s) and other primary head- headache episodes. On the basis of frequency they were sub- aches. There are also eight categories of secondary headache divided into low to moderate frequency headaches. On the and a third group that includes central and primary causes basis of duration they were subdivided into shorter duration of facial pain and other headaches. The criteria for primary or longer duration headaches. Headaches were classified ac- headaches are clinical and descriptive with a few exceptions cording to the predominant headache type if the patient had not based on etiology. multiple headache types. The classification is hierarchical, allowing diagno- sis with varying degrees of specificity, using up to four digits RESULTS AND ANALYSIS for coding at subordinate levels. The first digit specifies the The total number of patients studied were 124.Out of major diagnostic type e.g. migraine (1). The second digit this, the age of patients ranged from 9 to 54 years. The age indicates a subtype within the category, e.g., migraine with range and sex distribution of patients within each age range aura (1.2) subsequent digits permit more specific diagnosis is shown in Table No.1. Males comprised 33% (n=42) and for some subtypes of headache according to circumstantial females 66% (n= 82)of the total study population. requirements, FHM for example could be coded as 1.2.4. SEIZURE TYPES: The most common type of seizures In clinical practice patients should receive a diagnosis for seen were generalised tonic clonic seizures. 42% of patients each headache type or subtype they currently have. Multiple (n=52) had primary generalised tonic- clonic seizures and diagnostic codes should be listed in their order of impor- 38.7% of patients (n=48) have secondary generalised tonic- tance to the patient. For headaches that meet all but one clonic seizures. Among 48 patients with 2*GTCS, 27 cases of a set of diagnostic criteria without fulfilling those of an- were of simple partial seizures with secondary generalisa- 96 other headache disorder there are “probable” subcategories tion and 21 were of complex partial in nature with second- for e.g.: probable migraine (1.6).Headache was categorised ary generalisation (See Table 2). Simple partial seizures were into inter ictal, ictal or periictal headache (seizure associ- seen in 9 cases and complex partial seizures seen in 14 cases. TABLE 4: SHOWING INTERICTAL HEADACHE SUBTYPES IN EPILEPSY PATIENTS TABLE 2: SHOWING OF SEIZURES TYPE SEEN IN HEADACHE PATIENTS TABLE 1: SHOWING AGE AND SEX DISTRIBUTION OF PATIENTS IN EACH AGE RANGE disease. 11. Headache with ear, sinus or tooth 9. Headache with intracranial infn 5. Headache with neck trauma SECONDARY HEADACHE Primarily tensiontype Primarily migrainetype MULTIPLEHEADACHE TYPES 4.1: PrimarystabbingHeadache 3.1: Episodicclusterheadache Chronic TTH 2.3: 2.2: FrequentEpisodic TTH 2.1: InfrequentEpisodic TTH HEADACHE TENSION TYPE 1.6: Probablemigraine 1.5.1: Chronicmigraine 1.2.6: Basilartypemigraine 1.2: Migrainewithaura 1.1: Migrainewithoutaura MIGRAINE Primary Headache Type >50 yrs 41-50 31-40 21-30 11-20 0-10 Age Absence seizure Complex partialseizure Simple partialseizure CPS with2 SPS with2 Secondary GTCS Primary GTCS Seizure type * * GTCS GTCS 1 4 8 19 10 - Male SEX 1/82 2/25 14/25 9/25 25/82 3/45 12/45 1/45 10/45 19/45 45/82 77 No. ofPatients 3 1 1 5/82 4/11 7/11 11 6/82 1 4 3 8 11 19 15 Male 39 17 1 Female 2 7 16 3 11 24 58 27 1 No ofpatients 2 1 2 1 4 3 1 3 1 2 6 Male 10 6 13 16 29 37 Female 1 1 4 2 10 6 2 9 8 13 Female 2 8 19 46 21 0..8 Percentage % Stanley Medical Journal 6% 36.3% 63.6% 13.4% 7.3% 1.2% 8% 56% 36% 30.4% 6.6% 26% 2.2% 22.2% 42% 54% 94% % 97

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TABLE 5: TABLE SHOWING NO.OF PATIENT WITH SEIZURE ASSOCIATED HEADACHE

Headache type No. of Patients Male Female % SEIZURE ASSOCIATED HEADACHE 18 14.5% Preictal Headache 4/18 2 2 22.2% 7.6.1: Hemicrania epileptica 1/18 1 5.5% 7.6.2: Postictal headache 13/18 8 5 72.2% 14.1: Headache not elsewhere classified 24/124 16 8 19.3%

TABLE 6: SHOWING SEIZURE TYPE IN PATIENTS WITH SEIZURE ASSOCIATED HEADACHE Seizure Type Headache Headache not Elsewhere Clas-

Vol 3 | Issue 4 | October-December | 2016 4 | October-December 3 | Issue Vol sified Preictal Epileptic Post ictal Aura hemicrania headache Primary GTCS – – 9 4

Secondary GTCS

SPS with 20GTS 3 9

CPS with 20 GTS 11

Simple partial seizure 1 1 – –

Complex Partial Seizure 3 1

Absence seizure was seen in one patient and tonic seizure in sociated with neck trauma (5) was seen in one patient and 1 patient. intracranial infection (9) in one patient with epilepsy (CT HEADACHE TYPE: scan Brain showed tuberculoma). The remaining three pa- Interictal headache was present in 82 patients tients had sinus disease (11) along with seizures. 11 patients (66.6%) and seizure associated headache in 42 patients with epilepsy had multiple headache types. Among them 7 (33.4%) with epilepsy. Seizure associated headache include patients had primarily migraine type of headache along with preictal, ictal and post ictal headaches. Among 77 patients infrequent episodic tension type headache. One patient had with primary headache (see table 4) migraine type headache migraine without aura with dental caries. One patient with was seen in 54% (n=45) of patients. Among these 45 patients, migraine had frontal sinus disease.Four patients had fre- 19 of them satisfied the criteria for migraine without aura. quent episodic tension type headache along with dental car- (1.1) 10 of them had features of migraine with aura (1.2). ies. Basilar type migraine (1.2.6) was seen in one and chronic Seizure associated headache (Pre ictal, ictal & post ictal migraine 1.5.1 was seen in 12 patients with epilepsy. Among headache) them 10 of them were transformed from migraine without Among 42 patients with seizure associated head- aura and two from migraine with aura. Probable migraine ache, 24 (19.3%) had headache which might be an ictus (1.6) is seen in 3 patients with epilepsy. Tension type head- without accompanying seizure activity classified as head- ache occurred interictally in 30.4% (n=25) of patients with ache which could not be elsewhere classified (14.1) and 18 epilepsy. Among these 25 patients nine had infrequent epi- had (14.5%) pre ictal, ictal or post ictal headache( table 5). sodic tension type headache (2.1), 14 have frequent episodic Pre ictal Headache was seen in (4/18) of cases with epilep- tension type headache (2.2) and 2 had chronic tension type sy of whom 3 is seen in complex partial seizures and 1 in headache (2.3).Episodic cluster headache (3.1.1) was seen in simple partial seizures. Pre ictal headache occurs equally in 98 one patient and primary stabbing headache (4.1) was seen both sexes and the seizures were >10 years in duration. EEG in 6 patients with epilepsy.Secondary headache was seen in was abnormal in one and CT scan brain showed old infarct 6% (n=5) of patients with epilepsy. Of them headache as- in right parietal region in one patient. Post ictal headache aches could which not classified be and are probably ictus in treatment however patients the continued to suffer head event along with seizures, seizures has got subsided with in 25%and abnormal in75%of patients. two patients and old infarct inone of EEGwas them. normal 3 out of 24patients and show they calcification old healed in patientsthese occasionally. brain CTscan was abnormal in (100%)ofness inall patients. Incontinence is present in5of or pulsating innature, associated with transient unaware day to once infew days, character of headache was stabbing severe inintensity, from varied frequency per 1-2episodes tion of patients the headache was 5-10mininall (24/24)and patients andin4patients GTCS was primary seen The dura generalisation seizures with secondary in9 waspartial seen generalisationwith in11patients. secondary seen Simple (n=20/24). Most common was CPS of seen type seizure type group inthis seen of patients comprise which 83%of them GTCS was most the commonSecondary of type seizure in9patientsyrs seen and <6years in4patients. mostly 6-10years in 11 of as patients seen followed by 11-20 25% of population the (n=6).The duration seizurethe of was tion (n=18)of patients with headache whereas make males 20 years age group. Females comprise 75%of popula the Threepatients arethe in agegroup 41-50 years and 2in11- followed by patients seven age inthe group of 31-40years. years. Twelve patients were age inthe group 21-30years The agegroup patients these of rangedfrom 16 years to 46 in19%(n=24)of patients(14.1) occurred with epilepsy. Headache ictus: as inpatients iteach time occurred with epilepsy. characteristics headache remained of ictal post same, the type of headachefied did not have interictal headache. The headache of probable ictal with post migraine and unclassi have also type tension headache inter type ictally. Patients time. Thetwo patients headache postwithof ictal tension 20%of the headache occurring seizure ictal had post partial only with athird of such seizures. Only patient with complex in 3)(table 6).However headache the ictally recurred post tion to GTCS (n=12/13) (10 GTCS in 9& SPS with 20GTCS patients and could not classifiedpatients. 8in be graine in3out of 13(23%) and were of tension in2 type patients and >12hrs intwo patients. headache lasted for <6hrs in8/13of patients, 6-12hrs in3 in 72.2% (13/18) ofwas seen patients with epilepsy. The Among 24patients, these had headache as ictal Headache could which not elsewhere classified be Majority of Post inrela headache occurred ictal Headache fitted intothe criteria for probable mi ------42 patients among headache contributed ictal whom peri to (5/82) of patients. associated Seizure in headache was seen headachein 94%of in6% (n=77/82)and cases secondary of inpatients interictal headache seen with epilepsy noted headache contributedry to maximum the number of cases by 11-20years of age present in21%of (n=27).Prima cases 21-30 years of age present in48%of (n=47)followed cases whom were patients. male exceptseizure types for absence and tonic seizures of both in48patients.seizures seen Females out number inall males 52 patients followed generalized tonic by secondary clonic were generalized tonic-clonicseen primary in seizures seen DISCUSSION headache in2of them. ing present in4of and them frequent tension episodic type seizures in6of patients these (25%), Episodic migraine be nature. more than The males5. next common form head of primary done by inwhom etal2 Leniger proposition of females were 32 patients than is which males inagreement with study the noted more to be commonly affectedwith in migraineseen andtype migraine study. in this subtype seen Females were population. seizures in our study forms which 42%of total the study may due of be frequency to high generalized tonic-clonic ious of types headache, migrainous or not. The discrepancy noted that of frequency the epilepsy was uniform across var study done by Guidetti and V et al9 by Savoldi who F et al1 in other This is seizurenot types. inaccordancewiththe common generalized tonic-clonic inprimary seizures than explain comorbidily the of migraine and epilepsy. out aura as common.Neuronal the hyper excitability might study done by Velio Flu showed which etal9 migraine with The findings the in present study also correlated the with than migraine with aura was which present in10patients. graine without aura was more common in19of them seen in our study in54%of was (n=45).Mi migraine cases seen totalthe population. (14.1) and probably ictus comprised which 19%(n=24)of hadwho headache could which not elsewhere classified be headache there was asub-group of patients with epilepsy 42.8% (18/42)of patients. In patients with seizure associated The seizuresThe were morefrequently between seen In study, this most the common of type seizures Headache was present antecedent to onset the of There was no correlationspecific seizure between In study this headache the were sub all types more The most common seen headache type of primary Stanley Medical Journal ------99

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ache seen in this study was Tension type headache which (20/24). CPS with 2 GTCS occurred in 11 patients followed was present in 30.4% (n=25) of cases among which frequent by SPS with 20 GTCS which occurred in 9 patients. Primary episodic tension type headache was the most common type generalized tonic-clonic seizure were seen in 16.6% (n=4) seen in 14 out of 25 patients infrequent episodic tension of patients. The headache seen in these patients was of short type headache is seen in 36% of cases (9/25) and chronic duration lasting for 5-10 minutes severe in intensity, stab- tension type headache in 2 patients. This is in agreement bing or pulsating in nature, associated with impaired aware- with the study made by Yamane et al10 one case (1.2%) had ness in all the patients and urinary incontinence was seen in episodic cluster type headache which was seen in a patient 20% of these patients. CT scan brain was normal in 87.5% of with complex partial seizures. Primary stabbing headache patients. EEG was abnormal in 75% of these patients, show- occurred in 7.3% (n=6) of our patients. Pre ictal headache ing diffuse epileptiform activity. 30% of these patients also occurred in 4 patients in this series. Of these 4 patients 3 had headache along with seizures initially with persistence

Vol 3 | Issue 4 | October-December | 2016 4 | October-December 3 | Issue Vol (75%) had complex partial motor seizures and one (25%) of headache alone after control of seizures. was of simple partial motor type. One patient with simple partial seizure had headache throughout the seizures which recedes with subsidence of seizures and was classified as epi- REFERENCES leptic hemicrania. His CT scan brain showed old infarct in 1. Savoldi F, Tartara A, Manni R, Maurelli M, Cepha- left parietooccipital region. The same degree of involvement lalgia 1984, Mar 39-44. Headache and Epilepsy: Two auton- has been noted in other study done by Karaali et al11 ,Le- omous entities? niger et al al5 and Founderreuther S et al12.The headache 2. Gowers WR (1907) The Border-land of Epilepsy: also has lateralizing value as seen by its location which oc- Faints, Vagal Attacks, Vertigo, Migraine, Sleep Symptoms curred ipsilateral to seizure onset in our patients with both and their Treatment. P. Blakiston’s son and Co, London secondary generalized seizures and complex partial seizures 3. Bianchin MM, Londero RG, Lima JE, Bigal ME of temporal lobe origin which corroborates with the study (2010) Migraine and epilepsy: a focus on overlapping clini- done by Bernasconi A et al13 who showed that peri ictal cal, pathophysiological, molecular, and therapeutic aspects. headache occurred ipsilateral to seizure Curr Pain Headache Rep 14:276–283 Post ictal headache occurred in 72.2% (n=13) of 4. Vanmolkot KR, Kors EE, Hottenga JJ, Terwindt patients with seizure associated headache . Among our pa- GM, Haan J, Hoefnagels WA, Black DF, Sandkuijl LA, Frants tients with post ictal headache, duration of headache is <6 RR, Ferrari MD, van den Maagdenberg AM: Novel muta- hours in 61% (n=8) of patients, 6-12 hours in 23% of pa- tions in the Na+, K + −ATPase pump gene ATP1A2 associ- tients (n=3) and >12 hours in 15% of patients (n=2). The ated with familial and benign famil- diagnosis of headache was probable migraine in 23% (n=3), ial infantile . Ann Neurol 2003, 54: 360–366. tension type headache in 15% (n=2) and could not be clas- 10.1002/ana.10674 sified in 61.5% of cases (n=8). Majority of post ictal head- 5. Leniger T, Van den Driesch S, Isbruch K, Diener ache occurred in relation to GTCS, seen in 12/13 patients. HC, Hufnagel N, Headache 2003, June 43, 672-7: Clinical Primary GTCS occurred in 9 patients and SPS with 2 GTCS characteristics of patients with co morbidity of migraine is seen in 3 patients with post ictal headache. Postictal head- and epilepsy ache followed GTCS one third of the time i.e. 33.3%. 6. Eikermann-Haerter K, Negro A, Ayata C: Spread- The type of headache remained the same with each ing depression and the clinical correlates of migraine. Rev episode of post ictal headache. Patients who had tension Neurosci 2013, 24: 353–363. type of headache postictally also had tension type of head- 7. Ottman R, Lipton RB, Ettinger AB, Cramer JA, ache interictally whereas patients with post ictal headache Reed ML, Morrison A, Wan GJ: Comorbidities of epilepsy: of probable migraine or unclassified type did not have inter results from the Epilepsy Comorbidities and Health (EPIC) ictal headache. survey. Epilepsy 2011, 52: 308–315. Headache which could not be elsewhere classi- 8. International Headache society classification: fied occurred in 19% of patients (24). Most of these patients Cephalalgia- 2004. were in the age group of 21-30 yrs (45.8%) followed by 31- 9. Guidetti V, Fornara R, Marchini R, Moschetta A, 100 40 yrs (29.16%), duration of seizures is between 6-10yrs in Pagliarini M, Ottaviana S, Series of functional neurology 45.8% of patients and 11-20 year in 37.5% of patients. Most 1987. July-Sep. 323-41. of the cases were of secondary generalized tonic-clonic type 10. Yamane LE, Montenegro MA, Guerreiro MM. Co- 2001: Jan. 130-132. A study of 100patients epilepsy. with partial Neurology utens Dubeau F. DC, Lateralizing value headache: of parietal 13. characteristics. associated with epileptic seizures: Epidemiology and clinical A. Neurologische and Klinik Poliknik, Germany. Headache 12. Jan 67-9. zure related headache inpatients with epilepsy. 2002. Seizure 11. diatrics 2004.April 99-102. morbidity of headache and Neurope epilepsy inchildhood, Bernasconi A,Andermann F,Bernasconi N,Re Bernasconi Founder reuther S,Henkel A,Noachtar S,Straube Karaali -Savrun F. Yeni SN, S,Uzun Ertan N,Sei - - - Stanley Medical Journal 101

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