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Original Article

Postictal headache in South Africanadult patients with generalisedepilepsy in a tertiary care setting:A cross-sectional study

Stephanus Schmidt Botha1, Clara-Maria Schutte1,

Steve Olorunju2 and Mandisa Kakaza1

Abstract

Postictal headache (PIH), although it occurs in 3459% of epilepsy patients, has not been adequately studied. This studyaims to describe clinical characteristics and associations of PIH in generalised epilepsy in a South African tertiaryneurology clinic.

Methods: Two-hundred consecutive adults with generalised epilepsy underwent semi-structured interviews, dividing theminto study (with PIH) and control patients (no PIH), and data was statistically analysed.Results: PIH occurred in 104/200, with 63% having headache after every seizure. Pain duration was 424 hours in 43% andpain intensity severe in 55%. The criteria of the International Headache Society (2004), International Classificationof Headache Disorders, second edition (ICHD-II) classified 47% as migraine, 38% tension-type and 15% unclassified(but 13% probable migaine). Self-medication occurred in 81% and interictal headache was significantly associated withPIHpresent in 64% of study patients versus 5% of control patients.Conclusion: PIH occurs commonly in generalised epilepsy, mostly as migraine headache, with interictal headache a specificrisk factor. PIH is underdiagnosed and undertreated, leading to self-medication. Optimal management should be eluci-dated in future studies.

Keywords

Postictal headache, generalized epilepsy, migraineDate received: 26 August 2009; accepted: 14 February 2010

Introduction

Headache in relation to seizures is a well-known phe-

nomenon, occurring prior to, during or after seizures

(pre-ictal, ictal and postictal headache). Of these, the

postictal form has been reported in 3459% of patients

and thus is the most common type of seizure related

headache (1,2).

As an entity postictal headache (PIH) is underdiag-

nosed. Contributing to this problem is the fact that the

International Classification of Headache Disorders

(ICHD-II) (3) does not have a category for PIH and

the fact that doctors treating patients with epilepsy

rarely address PIH by prescribing treatment for it

(46), even though several studies have shown that

PIH has a significant impact on morbidity, independent

of the effect of seizures (6,7).

The undertreatment of PIH may on one hand be

due to issues directly related to seizure occurrence

and control which overshadow those of the headache,

and on the other hand the fact that PIH remains a

poorly understood entity, with scanty data available

about its clinical characteristics and optimal treatment.

The few studies which have investigated PIH have

several shortcomings. Some have not made use of stan-

dardised tools like the ICHD criteria (810). Although

the ICHD criteria do not provide a category for PIH,

trying to classify this form of headache according to

1University of Pretoria, South Africa.2Medical Research Council, South Africa.

Corresponding author:

C-M Schutte, Department of Neurology, Steve Biko Academic Hospital,

University of Pretoria, Private Bag X169, Pretoria 0001, South Africa

Email: [email protected]

Cephalalgia

30(12) 14951501

! International Headache Society 2010

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known types of headache may be useful in elucidating

the pathophysiology of the condition. Another defi-

ciency in the available data on PIH involves the types

of epilepsy in which this condition has been investi-

gated. Research done by Fo rderreuther (4) and Syver-

sten (6), respectively, looked at the characteristics of

PIH in epilepsy in general but did not differentiateclearly between different types of epilepsy. This may

be an essential distinction to make because there may

be a unique association between specific seizure types

and PIH. Other studies have investigated PIH exten-

sively in patients with partial epilepsy (2,5,11,12).

Despite some reports finding up to 96% of PIH in

patients with generalised epilepsy, no study could be

found that specifically evaluated this sub-population

(6). Most of the PIH studies are from developed coun-

tries and as the etiological profile (13) of epilepsy differs

between developing and developed countries; this might

also have an effect on the characteristics of PIH.

The aim of this study is therefore to describe the

clinical characteristics of PIH in patients with general-

ised epilepsy in a tertiary hospital outpatient clinic of a

developing country, also evaluating potential associa-

tions between PIH and demographics, seizure type,

family history and medication usage.

Methods

The study had a observational, cross-sectional design.

Two hundred eligible patients with generalised epilepsy

were consecutively recruited from the neurology clinic

at the Steve Biko Academic Hospital, a tertiary carefacility in Pretoria, South Africa. These patients were

divided into the study and control groups based on the

presence or absence of PIH.

Patients of an age of 18 years or older had to meet

the criteria for generalised epilepsy according to the

International League against Epilepsy (ILEA) classifi-

cation. The diagnosis of generalised epilepsy was aided

by the available clinical and electro-encephalopgraphic

(EEG) evidence. PIH was defined as a headache with an

onset within one hour after the termination of a seizure

or the regaining of consciousness. This is in correspon-

dence with the definition used by other studies on PIH.

In order to limit recall bias, patients had to have had at

least one of these headaches in the preceding year.

Patients with a potential secondary cause for head-

ache despite having epilepsy were specifically excluded

from enrolment. These included patients with condi-

tions such as intracranial tumours or progressive neu-

rological illnesses. Also excluded was anyone who had

been diagnosed with epilepsy within the previous six

months, in order to prevent including subjects in the

study who might have an undiagnosed cause for head-

ache. Patients in whom a diagnosis of non-epileptic

seizures was confirmed or suspected were not eligible

for enrolment and the ability of patients to reliably

report seizures and headache characteristics was also

taken into account, thus excluding patients with

mental retardation from the study.

After enrolment patients participated in a semi-struc-

tured interview conducted by the principal investigatorusing a data capturing sheet. Demographic information

was collected regarding the age, race and gender of

patients. Data about seizures included the duration of

epilepsy history as well as seizure frequency. Seizures

were further described as primary or secondary general-

ised based on existing electrophysiological and radiolog-

ical tests. Classification according to tonic, clonic,

absence or myoclonic seizures was also undertaken.

Further information was collected from patients

reporting PIH to characterise this entity more specifi-

cally. Headache frequency was measured in terms of the

percentage of seizures which were followed by PIH, and

categorised as 25%, 50%, 75% or 100%. The onset

of PIH was recorded according to the patients recall

of how soon the headache started after termination of a

seizure or upon regaining consciousness.

The severity of the headache was measured by the

patients score on the Visual Analog Scale (VAS) for

pain and converted into a score out of 10 (10 being

the most severe pain). Further data were collected

regarding localisation, accompanying symptoms and

headache quality (pulsating/throbbing or pressing/

tightening) and then analysed according to ICHD-II

criteria. Headaches not meeting specific criteria for

either migraine or tension-type headache were indicatedas unclassified.

Subjects were further asked whether they experi-

enced interictal headache. This was defined as any

form of headache commencing more than 24 hours

after a seizure. Data regarding the type of interictal

headache were not collected.

Family data collected consisted of first-degree rela-

tives with epilepsy or headache. The final category of

information gathered pertained to medication usage.

Patients indicated if they self-medicated for the pain

of PIH or whether a doctor had prescribed medication.

Additionally, all currently used anti-epileptic drugs

(AEDs) were listed.

All patients enrolled in the study provided signed

informed consent before participating in the semi-struc-

tured interview. Data were collected anonymously and

are not traceable to a particular individual. The study

was approved by the MMed Committee and the

Research Ethics Committee of the Faculty of Health

Sciences, University of Pretoria, as well as the Chief

Executive Officer of the Steve Biko Academic

Hospital. Statistical analysis was conducted by a

biostatistician of the Medical Research Council

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in Pretoria. Based on previous reports (indicating the

prevalence of PIH at 3459%), with p-a set at 0.05 and

a power level of 0.9, it was calculated that 200 patients

should be enrolled. Data were analysed by descriptive

statistics utilising mean, median, standard deviation

and range as appropriate. Categorical data were com-

pared using Pearsons chi-square test, Kruskal-Wallisand Mantel-Haenszel (recommended if multiplicity is

suspected) testing. In addition, logistics regression was

used for the binary variables. STATA version 10 was

employed throughout.

Results

Characteristics of postictal headache

From the total of 200 recruited patients, 104 were

found to have PIH, yielding a prevalence of 52% in

this population of adult patients with generalised

epilepsy.

Among the subjects with PIH (N 104), a majority

of 63% (N 65) reported experiencing headache after

every seizure, in contrast to 37% (N 39) having PIH

less frequently (Figure 1).

The onset of PIH was immediate upon termination

of the seizure or upon regaining consciousness in 94.2%

(N 98) of subjects. PIH lasted less than four hours in

35.6% of patients, from 4 to 24 hours in 43.3% and

longer than a day in 21.1% (Figure 2). One patient

reported that her headache lasted up to seven days.

It was slightly more common for PIH to localise

unilaterally; this was the case in 55.8% (N 58) ofpatients as opposed to 44.2% (N 46) who experienced

pain bilaterally. Topographically, frontal PIH was the

most frequent (75%), followed by temporal (48.1%),

parietal (21.2%) and occipital (11.5%). Some patients

indicated more than one location.

The mean pain intensity of PIH as measured by

the VAS was 7.06 cm (standard deviation [SD] 1.68).

If the results are classified into mild (3 cm), moderate

(>3< 7 cm) and severe (!7 cm), the majority of patients

(54.8%) fall in the severe category, although the mean is

on the border between moderate and severe (Figure 3).

Three patients indicated a score of 10/10 on the VAS for

the severity of their PIH pain.

The quality of the pain was reported in 51% (N 53)

as pressing or tightening in nature, while 49% (N 51)judged it to be throbbing or pulsating. Aggravation by

physical activity (54.8%; N 57), photophobia (54.8%;

N 57) and nausea (40.4%; N 42) were the most

common symptoms which accompanied PIH (Figure 4).

Using the ICHD-II criteria to classify the type of PIH

experienced by patients, of 104 subjects, 49 had a

migraine-like headache, 39 tension-type and 16 could

not be classified (Figure 5). It is, however, noteworthy

that of the latter 16 cases, 14 met all the criteria for migra-

ine, except for the duration of the headache, which was

stated as less than four hours. These 14 cases would

therefore meet the criteria for probable migraine.

Additional analysis did not show any significant

associations with the type of seizures, age or race and

the PIH type. Interestingly, 63% of migraine PIH was

experienced by males, as opposed to 37% by females

(Table 1). Of the eight patients with absence seizures

who experienced postictal headache, three were classi-

fied as migraine, two as tension-type and three

remained unclassified.

Figure 1. Frequency of PIH, as measured by the percentage of

seizures which are followed by a headache (e.g. the 75% category

indicates that 20% of patients experience PIH in relation to 75%

of their seizures).

Patient(n)

50

60

40

30

20

10

0Mild Moderate Severe

VAS

Figure 3. Pain intensity of PIH as measured on the Visual

Analog Scale (VAS) for pain (N104). Mild 3 cm; moderate

>3< 7 cm; severe !7cm.

50

40

30

20Patients(n)

10

0

24

Figure 2. Duration of postictal headache (N104).

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There were 84 (81%) patients with PIH who

acknowledged that they self-medicated their headaches,

mostly with paracetamol and non-steroidal anti-inflam-

matory drugs (NSAIDS). In contrast, only 20 (19%)

patients had been given a prescription from a doctor

to treat PIH, usually also paracetamol or NSAIDS,

except for three subjects who had received amitripty-lene. No patients had used specific migraine medication

such as a triptan.

Comparison of study and control groups

Basic demographical data are summarised in Table 2.

The study (subjects with PIH) and control

(subjects without PIH) groups were comparable to

each other regarding gender, age, employment and

race. The mean duration of epilepsy, although slightly

higher in patients with PIH (14.4 years) as opposed to

those without (12.8 years), was not meaningfully

discrepant.

Analysis of seizure type did not show differencesbetween the two groups (Table 3). Seizure frequency

in patients without PIH tended to be lower (49% 1

seizures/month) than in patients with PIH (39% 1

seizures/month), but the difference did not reach statis-

tical significance (p 0.157).

A history of interictal headache was found to be

significantly associated with PIH. A total of 67 of 104

subjects (64.4%) in the study group indicated that they

experienced headaches which were unrelated to

Table 3. Comparison of seizure characteristics between study

and control groups

Seizure characteristics PIH (N104) PIH (N 95)

Seizure type1

Generalised

Primary 38 (36.5%) 39 (40.6%)

Secondary 66 (63.5%) 58 (60.4%)

Tonic 96 (92.3%) 84 (87.5%)

Clonic 83 (79.8%) 64 (66.7%)

Absences 8 (7.7%) 8 (8.3%)

Myoclonic 1 (1.0%) 2 (2.1%)

Seizures/month2

1 or less 41 (39.4%) 47 (49%)

210 58 (55.8%) 41 (42.7%)

>10 5 (5%) 8 (8.3%)

PIH postictal headache. 1p .728. 2p .453.

Patient(n)

50

60

40

30

20

10

0

Nausea

Vomitin

g

Phon

opho

bia

Phon

opho

bia

Conjun

ctiva

linje

ctio

n

Tearin

g

Aggrav

atio

n

Focals

igns

57 (54.8%) 57 (54.8%)

42 (40.4%)

25 (24%)

18 (17.3%)

13 (12.5%)

Symptoms

11 (10.6%) 10 (9.6%)

Figure 4. Symptoms accompanying postictal headache.

Table 2. Demographical data for study and control groups

Patient characteristics

PIH

(N 104)

No PIH

(N 96)

Gender (M/F)1 54/50 50/46

Age (mean 5D)2 35.5 years

(12.6)

38.2 years

(12.8)

Employed 42 (40%) 33 (34%)

Race3

Black 41 (39.4%) 29 (30.2%)

White 55 (52.9%) 52 (54.0%)

Indian 2 (1.9%) 5 (5.2%)

Multiracial 6 (5.8%) 10 (10.4%)

Epilepsy duration(mean SD)4

14.4 years(11.2)

12.8 years(10.9)

PIH postictal headache. SD standard deviation. 1p .982. 2p .133.3p .249. 4p .211.

Migraine

Tension-type

Unclassified

Figure 5. Classification of PIH according to ICHD-II criteria.

Table 1. Breakdown of postictal headache type according to

gender

PIH type Female Male Total

Migraine 18 (36.7%) 31 (63.3%) 49

Tension-type 24 (61.5%) 15 (38.5%) 39

Unclassified 8 (50%) 8 (50%) 16

PIH postictal headache.


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seizures, versus only 5 out 96 subjects (5.2%) in the

control group (p .9991). Further subgroup analysis

was conducted for the 67 patients who had both post-

ictal and interictal headache (Figure 6), showing that 40

(59.7%) had migraine-like, 14 (20.9%) tension-type and

13 (19.4%) an unclassified type of PIH. A clear rela-

tionship between interictal and migraine-like postictalheadache thus emerged (p .0001).

A family history of first-degree relatives with either

headache or epilepsy did not have a noteworthy associ-

ation with the PIH group when compared to the controls.

The mean number of AEDs prescribed for subjects

with PIH (2.10 0.75) was remarkably similar to the

number being used by subjects without PIH

(2.11 0.86). The most commonly used AEDs in both

groups were valproate, clonazepam and carbamazepine

(Figure 7).

Among patients with migraine-like PIH (N 49),

31 (63.4%) were using valproate, which did not differ

appreciably from the 67 (70%) patients without PIH

(N 96) who were using the same drug. Similarly, no

notable disparity was found in the usage of topiramate

among the aforementioned two subgroups (migraine-

like PIH: 16.3%; no PIH: 12.5%).

Discussion

Comparison with other studies

The main strength of our study lies in the fact that we

evaluated PIH in 200 patients with exclusively general-

ised epilepsy. Previous studies on PIH have included

patients with both partial and generalised seizures,

and as a result these sub-groups of patients with gen-

eralised epilepsy were quite small. To our knowledge

this study is the largest of its kind to evaluate PIH

specifically in patients with generalised epilepsy.

Not many studies on aspects of PIH are available in

the literature; however, PIH does seem to occur more

commonly after generalised seizures than after partial

ones (11,12). While Schachter et al. (9) reported that

96% of patients with generalised epilepsy experienced

PIH, they did not make use of a standardised epilepsy

classification system. The lowest reported prevalence of

peri-ictal headache, including PIH, was 4.8% in a study

by Kwan et al. In contrast to other studies, which

mostly had a cross-sectional design, this study was per-

formed prospectively, therefore raising concern that

recall bias may be an important confounder in other

studies. However, this study only collected data over

three months, during which half of the patients did

not experience a seizure and this may thus account at

least in part for the low prevalence observed. The 52%prevalence of PIH in our study in which patients with

primary and secondary generalised seizures were

Phenobarbital

Gabapentin

Topiramate

Lamotrigine

Phenytoin

AED

Carbamazepine

Clonazepam

Valproate

PIH

No PIH

0 20 40

Percentage of patients

60 80

Figure 7. Use of anti-epileptic drugs (AEDs) among patients with (N 104) and without (N96) PIH. No significant differences are

present.

Migraine

Tension-type

Unclassified

Figure 6. Type of postictal headache experienced by patients

with a history of interictal headache.

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assessed is still lower than that found by others, such as

Karaali-Savrum (10) (67%) and Syversten (6) (68%),

where sub-groups of patients with primary generalised

seizures were assessed.

One has to consider the possibility that our study

population may have contained patients with partial epi-

lepsy, which would also have influenced the prevalence.Studies of PIH in patients with partial epilepsy

reported a slightly lower prevalence in this sub-popula-

tion, ranging from 16% to 44% (2,4,5). A significant

association between PIH and occipital lobe epilepsy in

particular has been demonstrated (2,11,14). It is postu-

lated that the occipital area may play a key role in the

pathophysiology of PIH, at least in patients with partial

epilepsy.

In our study, 63% of subjects had PIH after every

seizure, which compares well with the results of Leniger

(1) (60%) and Fo rderreuther (4) (66%). As these stud-

ies included patients with all types of epilepsy, one may

tentatively deduce that in so far as the frequency of PIH

is concerned there are no differences in patients with

generalised or partial seizures.

The mean duration of PIH in our study was 17.9

hours; variations from 5.9 to 12.8 and 20 hours, with

large standard deviations (1,6,10), are seen in other

studies. Thus, if the results are categorised, the majority

of patients in various studies have postictal headaches

which last from 4 to 24 hours (4,5,8).

In patients with partial seizures, up to 90% experi-

ence PIH ipsilateral to the epileptic focus (5). In our

study, about half of the patients had PIH even though

generalised seizures had occurred. The possibility thatpatients with secondary generalised epilepsy had PIH

lateralising to the original insult has to be considered

but was not further investigated.

In this study we calculated a mean value of 7 cm for

the pain intensity of PIH on the VAS, with the majority

of patients falling in the severe (!7 cm) category. Other

studies, performed in populations of patients with

mixed types of seizures, generally reported lower

values: Kwan (7) found a mean of 5.4 and Leniger (1)

found a mean 6.4 on the VAS. The majority of patients

in Fo rderreuthers study (4) experienced PIH of mod-

erate (37 cm) severity. The PIH in patients with gen-

eralised epilepsy, therefore, seems to be more severe.

A recent trend in PIH research has been to attempt

classification of the PIH according to the ICHD-II cri-

teria. Applying this the present study demonstrated

that 47% of subjects with PIH had a migraine type of

headache. This matches up to others, which have found

postictal migraine rates of 3455% (1,4,6). If the 14

patients from the unclassified group in our study

(who had probable migraine) are also included with

the main migraine group, the figure for patients with

a migraine PIH would actually be 60%.

Two studies in cohorts of patients with exclusively

partial epilepsy reported figures of 26% (12) and

16% (15) for migraine-like PIH, respectively.

Considering that the aforementioned rates of 3455%

were from studies involving all types of epilepsy, it

seems as if migraine PIH potentially has a stronger

association with generalised seizures. This observationrequires further verification.

Accounts of usage of over-the-counter analgesics

by patients with PIH vary from 3080% (4,5,7).

Our finding of 81% lies towards the top of the range,

which may be explained by the higher pain intensity

among patients in our study, which would prompt

them to self-medicate more readily.

The significant association between postictal and

interictal headache in our study has also been noted

by other researchers in groups of patients with mixed

or partial epilepsy (4,5,9). Similar to our finding,

Leniger et al. (1) have also reported that this relation-

ship is strongest for patients with a migraine-like PIH.

Other associations with PIH reported by previous

authors include a younger age of onset of epilepsy, as

pointed out by Ito and colleagues (11). Schachter et al.

(9) found that patients with four or fewer seizures per

year were more than twice as likely to have PIH. These

relationships with PIH were not duplicated in our study

nor in others.

Treatment of postictal headache

No studies have been found which have evaluated any

treatments for PIH. Two case reports, however, indi-cated that sumatriptan was able to terminate acute

migraine PIHs (14,16). The triptans are well known

for their efficacy in treating acute migraine attacks,

and the AEDs valproate and topiramate are used for

migraine prophylaxis (17,18). These agents are there-

fore attractive candidates for future research, specifi-

cally in patients who experience migraine-like PIH. In

this study, no difference was found in the use of valpro-

ate or topiramate among the migraine-like PIH group

and the control group. However, it is possible that

patients in the latter group might already have had a

prophylactic effect from the AED. The efficacy of these

drugs needs to be tested in prospective studies, while

controlling for the fact that some AEDs may actually

cause headache as a side effect.

Study limitations

This study had several limitations. First, it was per-

formed at a tertiary referral centre and may of the sub-

jects may have had more refractory epilepsy compared

to epilepsy patients in general. This was also reflected in

the mean number of AEDs being used by study patients


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(2.1) and the fact that 78.5% of subjects were using

polytherapy. As such one should be careful to extrap-

olate the results to general populations of patients with

epilepsy who are well controlled.

Moreover, as a cross-sectional study, recall bias was

a factor. We attempted to limit this by only including

patients who had at least one postictal headache in thepast year in the study group. However, 85.6% of

patients with PIH were experiencing one or more sei-

zures per month and the majority of patients had head-

ache after every seizure. While the frequency of PIH

therefore is unlikely to affect recall, postictal confusion

may very well be a factor influencing a patients ability

to remember headache characteristics. Unfortunately,

by the very nature of the study, this problem is difficult

to work around.

During the semi-structured interview patients were

asked only whether they had interictal headaches. In

retrospect it would have been useful to have charac-

terised these interictal headaches in more detail and

to have classified them according to ICHD-II criteria

as well. In this way the relationship between postictal

migraine and interictal migraine could have been inves-

tigated more thoroughly.

Conclusion

The study confirms that PIH in patients with general-

ised epilepsy is a common occurrence. The results add

to the present literature by indicating in particular an

association between generalised seizures and migraine

postictal headache, as the majority of patients head-aches (60%) could be classified as either migraine or

probable migraine.

The gravity of the condition is reflected by the fact

that the majority of patients experience PIH after every

seizure, with severe headache lasting up to 24 hours and

for which self-medication is mostly used; doctors do not

seem to prescribe specific headache drugs to treat PIH.

A history of interictal headache has emerged as a risk

factor for PIH. Future research should focus on clari-

fying the pathophysiology of the condition and on eval-

uating the efficacy of medications for both acute and

prophylactic treatment.

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