Frequency and characteristics of interictal headaches in patients with epilepsy

ELSEVIER

Frequency

and Characteristics of Interictal Patients with Epilepsy

Headaches

in

lT2Masumi Ito and lf2Steven C. Schachter

Using a questionnaire, we studied the incidence and characteristics of interictal headaches (IHs) in 162 patients with epilepsy. IHs occurred in 64% of patients. In this group, the frequency of IHs was weekly or monthly in 69%. IHs had a “pounding” component in 56%, and the severity was moderate to severe (interfering with normal daily activities) in 67%. IHs lasted more than several hours in 67% and were accompanied by nausea, vomiting, and photophobia or phonophobia in 68%, symptoms that are consistent with migraine headaches. There were no differences in the duration of epilepsy, seizure type, or seizure frequency between patients with IHs and patients without IHs. In contrast, the presence of postictal headaches (PIHs) and a family history of migraine were significantly more common in patients with IHs than in patients without IHs. Key Words: Epilepsy-Headache-Interictal headache-Migraine-Postictal headache.

Although patients with epilepsy often have headaches, the relation between seizures and headaches

is multifactorial. Headaches may occur immediately before seizures or during the postictal period. In addition to seizure-associated headaches, patients often experience headaches that are not temporally related to seizures-interictal headaches (IHs). The nature of these headaches is not clear. Some researchers have reported that postictal headaches (PIHs) occurred in 13-51% of patients with epilepsy (14) and that generalized tonic-clonic seizures (GTC) were more often associated with PIHs Received August 4,1995; accepted September 27,1995. From the ‘Beth Israel Comprehensive Epilepsy Program and ‘Departments of Neurology, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A. Address correspondence and reprint requests to Dr. Steven C. Schachter at Department of Neurology, Beth Israel Hospital, 330 Brookline Avenue, Room K-222, Boston, MA, 02215, U.S.A.

than were other seizure types (24). Some PIHs have the characteristics of migraine headaches (2,3), suggesting a relation between PIHs and migraine. In contrast, very few studies of IHs have been made. Rossi et al. (4) showed that 36% of children with epilepsy had recurrent headaches that were independent of seizures. In a study of IHs in patients with nonconvulsive seizures, D’Alessandro et al. (1) reported

an incidence

of 45%.

Savoldi

et al.

(5) reported that 21 of 36 adult patients with epilepsy (58%) had IHs. However, there is no report of the correlations of IHs with the clinical aspects of epilepsy. We wished to define the prevalence and characteristics of IHs and to evaluate associations between IHs and other clinical features of epilepsy to discover possible predictive factors of IHs.

Methods One hundred sixty-two patients with epilepsy (82 men and 80 women aged 19-65 years, mean 36

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M. IT0 AND

S. C. SCHACHTER

years) followed at a seizure clinic by one of the authors (S.C.S.) were studied. Questionnaires on IHs were mailed to the subjects. The subjects were surveyed on the frequency, characteristics, severity, duration, and accompanying symptoms of any IHs, including nausea and/or vomiting, and photophobia or phonophobia. The subjects were asked to classify the frequency as daily, weekly, monthly, or yearly and to grade the severity as mild, not disturbing normal daily activity; moderate, slowing normal daily activity; or severe, preventing normal daily activity. The subjects were also asked about the occurrence of PIHs. Medical records were reviewed for each patient, and the factors duration of epilepsy, type and frequency of seizures, and family history of migraine were abstracted. Seizure types were classified as GTCS, complex partial seizures (Cl’s), mixed GTCS and CPS, and other [simple partial seizures (SPS), absence seizures, or myoclonic seizures]. Seizure frequency was classified as daily, weekly, monthly, or yearly or less.

51 patients (50%), and >24 h in 18 patients (18%). Seventy patients (68%) had accompanying symptoms, including nausea and/or vomiting in 22 (21%), photophobia in 45 (44%), and phonophobia in 48 (47%). PIHs occurred in 85 patients (52%), including 44 (52%) who had a PIH after every seizure. Among the patients with IHs, 72 (70%) had PIHs. In contrast, among the patients without IHs, 13 (22%) had PIHs (p = 0.0001) (Table 2). The PIHs were similar in type to the IHs in 57 patients (80%), and 35 patients (41%) had PIHs with a pounding component. The duration of epilepsy, types and frequencies of seizures, and family histories of migraine for this sample are shown in Table 2. Eighteen patients with IHs (17%) had a positive family history of migraine as compared with 3 patients without IHS (5%; p = 0.02). There were no significant differences between the patients with IHs and the patients without IHs with respect to duration of epilepsy and type and frequency of seizures.

Results

Discussion

The mean duration of epilepsy in this sample was 21 f 11 (SD) years. The distribution of seizure types was 7% GTCS, 35% CPS, 49% mixed, and 9% other. The distribution of seizure frequencies was 16% daily, 39% weekly, 22% monthly, and 23% yearly or less. IHs occurred in 103 patients (64%). Among the patients with IHs, 48 were male (47%); among the patients without IHs, 34 were male (58%, ns). The features of the IHs in this sample are shown in Table 1. The frequency of IHs was daily in 7 patients (7%), weekly in 39 patients (38%), monthly in 32 patients (31 v/o),and yearly in 10 patients (10%). In 58 patients (56%), headaches had a pounding component. The severity of IHs was mild in 27 patients (26%) and moderate to severe in 69 patients (67%). IHs lasted
n

Clinical features of interictal headaches

%

Type

n

%

Severity

n

%

Duration (h)

n

%

Associated symptoms’

%

7

7

Pounding Steady

25 37

24 36

Mild Moderate

27

26

<1

23

33

22

21

38

51

50

1-12

51

50

32

31

Both

33

32

Severe

23

22

>24

18

45 48

44 47

10 15

10 14

Uncertain

8

8

Uncertain

11

11 Uncertain

16

25

7

7

J EPILEPSY,

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11

Nausea/vomiting Photophobia 17 Phonophobia 11 None Uncertain

n

39

“Each associated symptom may overlap 84

The prevalence of IHs in the present study was 6410, which is similar to that reported in a previous study (58%) (5), although higher than those reported in other studies. Rossi et al. (4) reported a lower incidence of IHs in children with epilepsy (36%), an incidence equivalent to that of agematched controls. D’Alessandro et al. (1) reported that 45% of adult patients with partial, myoclonic, and absence seizures had IHs, a frequency lower than observed in our study, which may be due to differences in samples and methodologic limitations; i.e., the evaluation of headaches is dependent on subjective reports, and we analyzed only subjects who responded to a questionnaire. According to Waters (6), the prevalence of headaches in the general population was 65% in males and 79% in females, prevalence findings which are

HEADACHES

Table 2.

Clinical features

Feature Duration of epilepsy (yr, mean + SD) Seizure type GTCS CPS Mixed Other Seizure frequency Daily Weekly

of epilepsy

IHs(+) n = 103 n (S/F)

IHs(-)

20*11

24 IL 12

6 34 56 7

6 22 24 7

(6) (33) (54) (7)

18 (17) 42 (41)

Monthly Yearly or less Family history of migraine” Yes No Postictal headache&’ Yes No

n = 59

n (%,)

(10) (37) (41) (12)

8 (14) 21 (36)

17 (17)

18 (30)

26 (25)

12 (20)

18 (17) 85 (83)

3 (5) 56 (95)

72 (70) 31 (30)

13 (22) 46 (78)

IHs(+), patients with interictal headaches; IHs(-), patients without IHs; GTCS; generalized tonic-clonic seizures; CPS, complex ap = 0.02. bp = 0.0001.

partial

seizures,

similar to ours. Because headaches may be caused by many conditions, the characteristics of IHs in our sample should be compared with those detected in the general population. Approximately half of the patients with IHs in our sample reported a pounding quality to their headaches, and almost 70% of IHs were often accompanied by nausea and/or vomiting, photophobia, or phonophobia. IHs were moderate to severe in almost 70%, and the duration was several hours in half of the patients and >1 day in some. The frequency of IHs was weekly or monthly in -7O%, suggesting an episodic occurrence of IHs. Waters (6) reported that headaches in a community-based population were severe in 48% of those with headaches and that 29% of the headaches were accompanied by nausea. Therefore, the patients in our sample appear to have more severe headaches than does the general population. Although the characteristics of the IHs in our study were similar to those of migraine headaches (7), the diagnosis of migraine cannot be firmly made on the basis of questionnaires. Yet these results suggest that a significant proportion of the IHs in our sample are migraine headaches. The relation between epilepsy and migraine has long been investigated, but is still not fully understood. Previous researchers (2,8-10) reported that the preva-

IN EPILEPSY

lence of migraine in patients with epilepsy is 9-24%. Ottman and Lipton (8) reported an increased incidence of migraine in patients with epilepsy as compared with nonepileptic controls. In addition, a high prevalence of migraine has been reported among the relatives of patients with epilepsy (8,9,11). In the present study, we also noted a high frequency of a positive family history for migraine headaches among patients with IHs, consistent with a comorbid relation between migraine and epilepsy. Furthermore, because anticonvulsant drugs such as valproate have been reported to be effective in the treatment of migraine (12,131 and chronic headaches (14,151, there may be a common underlying pathogenic mechanism for migraine and epilepsy. On the other hand, not all studies (4,5,16) have shown an association between migraine and epilepsy. The duration of epilepsy and the type and frequency of seizures were not different between patients with and without IHs. A family history of migraine and the presence of PIHs were significantly more common in patients with IHs than in those without IHs, however. Rossi et al. (4) reported that the frequency of IHs was higher in patients with rolandic epilepsy but that there were no differences among patients with other types of seizures. Ottman and Lipton (8) reported that the risk of migraine in epilepsy was independent of the seizure type, in agreement with our findings. In contrast, PIHs were highly prevalent after GTC (24), although D’Alessandro et al. (1) showed that PIHs occurred after CPS as well. Different mechanisms may trigger pain in PIHs and IHs. The precise relation between PIHs and IHs is uncertain, although a common etiology is suspected in patients with symptomatically similar PIHs and IHs (2,3). In our study, PIHs were similar to IHs in 80% of patients with both IHs and PIHs. This similarity of the pain in such a high percentage of patients and the high frequency of PIHs among patients with IHs in this study are consistent with that supposition. The etiology of IHs is probably multifactorial. Schon and Blau (2) suggested that postictal intracranial vascular changes, which are similar to those that occur in migraine headaches (17), may be related to PIHs. D’Alessandro et al. (1) hypothesized that seizure discharges may activate serotonergic brainstem pathways, which in turn trigger the vascular changes associated with migraine (18). These vascular changes may be partly related to IHs in our sample because of the migrainous features of IHs noted. Furthermore, neurochemical changes J EPILEPSY,

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M. IT0 AND

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such as increased glutamate release and reduced y-aminobutyric acid (GABA) activity have been proposed to be associated with both migraine and epilepsy (19). The observation that valproate, a GABA agonist, is effective against migraine headaches is consistent with this speculation. Whether these neurochemical changes are responsible for IHs is unknown. Finally, IHs may be the only symptom of an otherwise subclinical seizure. Laplante et al. (20) reported two patients with headaches that were clinical manifestations of ictal activity. They noted that ictal headache was of brief duration (~1 min) and of a nonspecific nature. Most IHs in our sample are not likely to be ictal events, given the long duration and migrainous features reported by patients. EEG monitoring would be useful to define the correlation between IHs and subclinical seizures, especially in patients who also have PIHs. IHs occurred in 64% of all patients with epilepsy sampled and had migrainous features in many patients. Although every subgroup of patients was affected, a family history of migraine and the existence of PIHs were associated with IHs.

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as an epi-