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© Blackwell Publishing Ltd
Cephalalgia,
2004,
24
, 23–28 23
Blackwell Science, Ltd
Oxford, UKCHA
Cephalalgia
1468-2982Blackwell Publishing, 2003
2412328
Original Article
Postictal headache in patients with partial epilepsyM Ito et al.
†
Deceased
Characteristics of postictal headache in patients with partial epilepsy
M Ito
1
, N Adachi
2
, F Nakamura
3
, T Koyama
3
, T Okamura
4
, M Kato
5
, K Kanemoto
6
, T Nakano
7
, M Matsuura
8
& S Hara
†
1
Tenshi Hospital, Sapporo,
2
Adachi Mental Clinic, Sapporo,
3
Hokkaido University Graduate School of Medicine, Sapporo,
4
Osaka Medical College, Osaka,
5
National Centre of Psychiatry and Neurology, Tokyo,
6
Aichi Medical University, Aichi,
7
Dokkyo University School of Medicine, Tochigi and
8
Nihon University School of Medicine, Tokyo, Japan
Ito M, Adachi N, Nakamura F, Koyama T, Okamura T, Kato M, Kanemoto K,Nakano T, Matsuura M & Hara S. Characteristics of postictal headache in patientswith partial epilepsy. Cephalalgia 2004; 24:23–28. London. ISSN 0333-1024
Migraine-like features sometimes characterize the headache that follows epilepticseizure (postictal headache, PIH). We compared patients with different types ofepilepsy to investigate the association between migraine-like PIH and seizuretype. Subjects comprised 364 patients with partial epilepsy. Epilepsy types weretemporal lobe epilepsy (TLE,
n
=
177), frontal lobe epilepsy (FLE,
n
=
116), andoccipital lobe epilepsy (OLE,
n
=
71). Patients participated in a structured inter-view pertaining to PIH as well as interictal headache and family history ofmigraine. Headaches were classified according to the International HeadacheSociety criteria, which was modified for this study. Forty percent had PIH and26% of these patients had migraine-like PIH. Migraine-like PIH occurred signifi-cantly more often in cases of TLE and OLE than in cases of FLE. In addition, theincidence of interictal migraine headache was significantly higher in patients withmigraine-like PIH. These results suggest that migraine-like PIH is related to par-ticular regions of epileptogenic focus and that susceptibility to migraine headachepredisposes to migraine-like PIH.
�
Postictal headache, migraine, temporal lobeepilepsy, frontal lobe epilepsy, occipital lobe epilepsy
Dr Masumi Ito, Tenshi Hospital, Kita-12, Higashi-3, Higashi-ku, Sapporo 065-8611, Japan. Tel.
+
81 11 711 0101, fax
+
81 11 751 1708, e-mail [email protected] 16 July 2002, accepted 21 May 2003
Introduction
Patients with epilepsy often exhibit headache duringthe postictal period, but the pathophysiology of suchheadaches remains unclear. Post-ictal headache(PIH) can be of the migraine type, tension type orunclassified type of headache (1–3). Severalresearchers (3–6) have pointed out that the PIH hassimilar symptoms to migraine such as poundingpain and accompanying nausea, photophobia andphonophobia in a significant proportion of patients(41–56%). In addition, an effect of antimigraine
drugs on PIH has been found in some cases (7, 8).Previous reports have suggested that migraine typeheadaches often occur during postictal periods insome epilepsy syndromes such as occipital lobe epi-lepsy (8–11). These findings suggest that migraine-like PIH and migraine have underlying mechanismin common, but the mechanisms themselves havenot been clarified. Investigation of PIH with charac-teristics of migraine would contribute to under-standing of the relation between migraine andmigraine-like PIH. However, there have been veryfew studies on migraine-like PIH. We compared epi-lepsy patients with migraine-like PIH to those withother PIH and no PIH to find possible factors asso-ciated with migraine-like PIH.
24
M Ito et al.
© Blackwell Publishing Ltd
Cephalalgia,
2004,
24
, 23–28
Methods
Subjects comprised 364 patients(163 males and 201females) with temporal lobe epilepsy (TLE), frontallobe epilepsy (FLE) or occipital lobe epilepsy (OLE).All subjects were being treated at one of seven adultepilepsy clinics in Japan. Epilepsy type was deter-mined according to the International League AgainstEpilepsy criteria (12) on the basis of clinical symp-toms, electroencephalography, and neuroimagingfinding such as computed tomography or magneticresonance imaging (MRI). Although neuroimagingstudy findings were available in all cases, we did notanalyse precise structural abnormalities because ofdifferences in the specificities of the devices andscanning conditions at each institution. Patientswere classified as symptomatic or cryptogenic,whereas idiopathic type was not included. Nopatient with progressive brain disease or recentbrain injury was included. We defined epigastricascending sensations and elementary visual signs asnecessary for the diagnosis of TLE and OLE, respec-tively, as the initial seizure symptom. Motor symp-toms or gestural automatisms without prolongedpostictal confusions were required for the diagnosisof FLE. Patients who matched the above criteria forTLE, FLE or OLE were consecutively asked to par-ticipate in the study. Informed consent was obtainedfrom each subject.
The epilepsy types were as follows: 177 patientswith TLE, 116 patients with FLE, and 71 patientswith OLE. Patients ranged in age from 12 to 81 years(mean 37.2 years). Duration of epilepsy and age atonset of epilepsy was 0–56 years (mean 21.9 years)and 0–56 years (mean 15.3 years), respectively.
The data obtained for each patient included sei-zure type, seizure frequency, and number of antiepi-leptic drugs (AEDs) taken. Seizure types consistedof 109 patients with simple partial seizures (SPS)and/or complex partial seizures (CPS), and 255patients with SPS and/or CPS combined with sec-ondarily generalized tonic-clonic seizures (SGTC).The distribution of seizure frequency was 21 patientswith daily seizures, 59 patients with weekly seizures,123 patients with monthly seizures and 161 patientswith yearly seizures or less frequent. Number ofAEDs ranged 0–5 (mean 1.9).
PIH was defined as any headache occurringwithin 30 min after seizure. PIH was further classi-fied according to the diagnostic criteria of the Inter-national Headache Society (IHS) (13). In this study,we used the modified criteria that excluded the limitof the duration of headache because the headachesin some patients matched the criteria for migraine
without aura except that their durations wereshorter. These headaches were often described aslasting for less than four hours. However, since mostpatients had been treated for both epilepsy andmigraine symptoms, it was difficult to determine thespecific duration of PIH. Therefore, we consideredthese PIHs as migraines without aura. Other typesof PIH that did not meet the IHS migraine criteriawere classified as other PIH.
Principal investigators of each institution con-ducted a structured interview with each subjectusing a standardized questionnaire that had beenadministered in our previous studies (5, 14, 15). Thequestionnaire addressed characteristics of the head-ache pain, the duration and severity of PIH, andaccompanying symptoms such as nausea/vomiting,photophobia or photophobia. Subjects were askedif they had any headaches independent of seizure(interictal headache) about the frequency of thoseheadaches, characteristics of the pain, the severityand duration of those headaches, and accompanyingsymptoms. Then we classified interictal headache asmigraine or other headache in accordance with theIHS criteria. A family history of migraine in first-degree relatives was also inquired about.
For data analyses, patients with migraine-likeheadache were categorized as migraine-like PIHgroup and patients with other headaches as otherPIH group. We regarded patients without PIH ascontrols for the statistical analyses. One-way analy-sis of variance (
ANOVA
) was used for lineal data.
Post hoc
pairwise multiple comparisons and rangetests were carried out with the Dunnett’s test (16)because the Levene test indicated unequal variancesacross groups. Kruskal–Wallis test was used forcomparison of seizure frequency. The
c
2
test (contin-gency table analysis) was used for categorical data.To identify special conditions responsible for signif-icant
c
2
values in the n
¥
m contingency table analy-sis, the expected number (EN) of patients andadjusted standardized residual (ASR) were com-puted for each cell (17). In accordance with a nor-mal standard deviation, the absolute value of theASR (z score) was used to identify cells that variedmarkedly from independence (i.e. z
>
1.96 for
P
<
0.05).
P
-values
<
0.05 were taken to be significant.All statistical analyses were performed with SPSSver.9.0.
Results
One hundred and forty-seven patients of the 364(40.4%) subjects experienced PIH. Of these 147patients, 38 (25.9% PIH patients, 10.4% total patients)
Postictal headache in patients with partial epilepsy
25
© Blackwell Publishing Ltd
Cephalalgia,
2004,
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, 23–28
fulfilled the modified IHS criteria for migraine with-out aura.
Demographic and clinical features of the threestudy groups are shown on Table 1. There were nosignificant differences in sex, age at onset, numberof AEDs, family history of migraine, duration ofepilepsy and seizure frequency between the threegroups. Patients with both migraine-like and otherPIH were significantly younger than patients with-out PIH were (
P
=
0.008). However, there was nosignificant difference between patients withmigraine-like PIH and those with other PIH. Withregard to seizure type, SGTC was significantly asso-ciated with other PIH, but not with migraine-likePIH (
P
=
0.000). Other PIH occurred at a significantlyhigher frequency in patients with SGTC (
n
=
90,EN
=
76.4, ASR
=
3.4,
P
=
0.001), whereas patientswithout SGTC showed PIH less frequently (
n
=
82,EN
=
65.0, ASR
=
4.0,
P
=
0.000). Epilepsy type wassignificantly associated with PIH (
P
=
0.000, Table 2).Patients with TLE showed no PIH more frequently(
n
=
120, EN
=
105.5, ASR
=
3.1,
P
=
0.002) and otherPIH less frequently (
n
=
39, EN
=
53, ASR
=
-
3.2,
P
=
0.001). Patients with FLE showed migraine-like PIHless frequently (
n
=
6, EN
=
12.1, ASR
=
-
2.2,
P
=
0.028). Patients with OLE showed other PIH (
n
=
29,EN
=
21.3, ASR
=
2.2,
P
=
0.028) and migraine-likePIH more frequently (
n
=
14, EN
=
7.4, ASR
=
2.8,
P
=
0.005).Interictal headaches were observed in 182 patients
(50.0%). Of these, 29 patients (15.9% of patients withinterictal headache, 8.0% of the total patients) hadmigraine with or without aura in accordance withthe IHS criteria. There was a significant correlationbetween PIH and interictal headache (
c
2
=
15.0,
P
=
0.005, Table 3). Subsequent residual analysis showedthat patients with migraine-like PIH had interictalmigraine more frequently (
n
=
9, EN
=
3.0, ASR
=
3.8,
P
=
0.000) and that patients without PIH had interic-tal migraine less frequently (
n
=
12, EN
=
17.3,ASR
=
-
2.1,
P
= 0.036).
Discussion
Forty percent of our study population with partialepilepsy exhibited PIH. Migraine-like PIH occurredin 10% of the total study population and in 26% ofpatients with PIH. Leniger et al. (3) reported that outof 341 patients with epilepsy 115 patients (34%) hadseizure-associated headache and that 64 patients
Table 1 Comparison of demographic and clinical factors between postictal headache with and without migraine-like features
Post-ictal headache
Statisticalvalue P-values
Migraine-like(n = 38)
Other(n = 109)
None(n = 217)
Sex (% female) 55.3 56.0 54.8 c2 = 0.4 0.982Age (years) (mean ± SD) 33.6 (11.7) 35.2 (11.1) 38.9 (13.6) F = 4.9 0.008Age at onset (years) (mean ± SD) 13.5 (9.2) 14.3 (9.2) 16.2 (11.6) F = 1.7 0.181Number of AED taken (mean ± SD) 2.0 (0.8) 2.0 (0.9) 1.9 (1.0) F = 0.9 0.405Family history of migraine (% positive) 28.9 18.3 21.7 c2 = 1.9 0.387Seizure type (% with SGTC) 78.9 82.6 62.2 c2 = 15.9 0.000
Epilepsy type (% ) c2 = 24.4 0.000TLE 10.2 22.0 67.7FLE 5.2 35.3 59.5OLE 19.7 40.8 39.4
Duration of epilepsy (mean ± SD) 20.2 (10.4) 20.9 (11.3) 22.8 (12.5) F = 1.4 0.256
Seizure frequency (%) c2 = 1.6 0.450D 7.9 4.6 6.0W 15.8 13.8 17.5M 36.8 33.0 33.6Y 39.5 48.6 42.9
Interictal headache (%) c2 = 15.0 0.005Migraine 23.7 7.3 5.5Other 36.8 44.0 41.9None 39.5 48.6 52.5
AED, antiepileptic drug; TLE, temporal lobe epilepsy; FLE, frontal lobe epilepsy; OLE, occipital lobe epilepsy; SGTC, second-arily generalized tonic clonic seizure; D, daily; W, weekly; M, monthly; Y, yearly or less.
26 M Ito et al.
© Blackwell Publishing Ltd Cephalalgia, 2004, 24, 23–28
(56% of patients with seizure-associated headache,19% of total patients) complained about migraine-like seizure-associated headache. In other reports(4–6), 41–53% of patients with PIH exhibitedmigraine-like headache. The lower frequency ofmigraine-like PIH in our study patients than that inother studies is likely due to the following: Our sam-ple was restricted to patients with TLE, FLE andOLE, whereas other studies included various typesof epilepsy in addition to these three types. Thusthere seemed to be differences in the distribution ofepilepsy type between the samples studied. More-over, some of our patients were taking higher doseof sodium valproate and zonisamide that couldreduce migraine as well as seizures, since sodiumvalproate has proven prophylactic effects onmigraine (18–20). Zonisamide has also been sug-gested to be useful (20).
Demographic features showed that patients withboth migraine-like and other PIH were younger thanthose without PIH. The relation between PIH andage has not been investigated in other studies.Although it would be difficult to draw conclusionsfrom the present data, possible explanation could bea decrease of PIH with age. More extensive epidemi-ological and longitudinal studies would be neededto determine the relation between PIH and age.
With regard to other demographic factors, therewas no difference between the two PIH groups andthe control group. Likewise, Leniger et al. (3)showed no differences in sex and family history ofmigraine between patients with migraine-like andother PIH. In general, women are more susceptiblethan men to migraine: Caucasians, 15.3–25% inwomen and 5.9–8.6% in men (21–24), while Asians,9.2–12.9% in women and 3.6–4.8% in men (24, 25). Incontrast, there seems to be no sex difference in theprevalence of migraine-like PIH. This suggests thatthe occurrence of migraine-like PIH depends on spe-cial conditions in addition to the pathophysiology ofmigraine.
The incidence of PIH was significantly higher inpatients with SGTC than in those without as a num-ber of studies have shown (2–5, 15, 26). However,SGTC was more frequently followed by other PIHthan migraine-like PIH. This finding was compatiblewith other reported findings (2, 3). The reason forthis remains unclear, but one possible explanation isthat generalization of seizure discharge may inducesome other pathophysiological changes within thewhole brain structure. Duration of epilepsy and sei-zure frequency was not related to PIH. This suggeststhat neither prolonged course nor severity of epi-lepsy is likely to have an impact on PIH.
Table 2 Association between postictal headache and epilepsy type
Post-ictal headache
Migraine-like Other None
n expected n ASR* n expected n ASR* n expected n ASR*
Epilepsy typeTLE 18 18.5 - 0.2 39 53.0 - 3.2 120 105.5 3.1FLE 6 12.1 - 2.2 41 34.7 1.5 69 69.2 - 0.0OLE 14 7.4 2.8 29 21.3 2.2 28 42.3 - 3.9
*adjusted standard residual.
Table 3 Association between postictal and interictal headache
Post-ictal headache
Migraine-like Other None
n expected n ASR* n expected n ASR* n expected n ASR*
Interictal headacheMigraine 9 3.0 3.8 8 8.7 - 0.3 12 17.3 - 2.1Other 14 16.0 - 0.7 48 45.8 0.5 91 91.2 0None 15 19.0 - 1.4 53 54.5 - 0.3 114 108.5 1.2
*adjusted standard residual.
Postictal headache in patients with partial epilepsy 27
© Blackwell Publishing Ltd Cephalalgia, 2004, 24, 23–28
Our most important finding was that the occur-rence of migraine-like PIH was significantly relatedto the region of epileptogenic focus. OLE wasstrongly correlated with migraine-like PIH. Theoccipital lobe is deemed to be the brain structuremost responsible for the development of migraine(27, 28). Although PIH occurred at a lower frequencyin patients with TLE, migraine-like PIH occurredcomparatively higher than other PIH did. The pos-terior temporal cortices locate close to the occipitalcortices and the anatomic connections between themesial temporal structures and occipital lobe areabundant (29, 30). When both the temporal lobes andoccipital lobes are firing, the structures related tomigraine symptoms could become quickly involved.According to the cortical spreading depression(CSD) theory (27), neural activity occurring in theoccipital area spreads forward across the cortical sur-face and discontinues at the Sylvian fissure. Subse-quent reduction in cortical blood flow is likelyassociated with migraine (31). Recent studies withnew methods such as positron-emission tomogra-phy or functional MRI have confirmed the changesin blood flow during migraine attack (32, 33). It isvery likely that CSD plays an important role in theinduction of migraine-like headache in certainpatients with epilepsy. Bowyer et al. (34) conductedmagnetoencephalographical study during migraineaura and observed neuroelectrical activity in notonly the occipital area but also in the temporal area.This finding may support our hypothesis that thereis a link between migraine-like PIH and CSD inpatients with OLE and TLE. In contrast, we foundthat only a few patients with FLE exhibitedmigraine-like PIH. The frontal cortices are both ana-tomically and functionally distant from the occipitalcortices. Therefore CSD may be less associated withthe occurrence of PIH in patients with FLE than inthose with OLE or TLE. Measurements of neuralactivity and cerebral blood flow following epilepticseizure would contribute to clarifying the patho-physiology of PIH.
Patients with migraine-like PIH showed a higherfrequency of interictal migraine in comparison topatients with other PIH or no PIH. Moreover,patients with other PIH did not show a significantrelation to any type of interictal headache. Lenigeret al. (3) found a relation between migraine-like sei-zure-associated headache and a history of migraine,which is compatible with our findings. Susceptibilityto migraine headache may be a factor predisposingto migraine-like PIH.
The present study has several methodological lim-itations. Though our study involved a comparatively
large number of patients recruited from multipleinstitutions, the characteristics of patients are notrepresentative of those of the general populationwith partial epilepsy. Patients visiting the special epi-lepsy clinic tend to suffer from epilepsy complicatingcerebral function. Also, the number of patients withOLE was insufficient for subsequent multiple analy-sis. In addition, structural abnormalities were notfactored into our analysis because of differences inthe specificities of neuroimaging methods betweeninstitutions. Various neuropathological conditionswere likely represented in our subject group.
In conclusion, we did find a relation between par-ticular epileptogenic regions and migraine-like PIHthat can be considered as clinical evidence of CSD.The pathophysiology of PIH may be similar to thatof migraine except in some aspects. Further studieswith a larger sample are needed to confirm ourfindings.
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