J Neurol (2003) 250 : 839843

DOI 10.1007/s00415-003-1091-3 ORIGINAL COMMUNICATION

Chun-Ming Cheung Epileptic seizure after stroke

Tak-Hong Tsoi
Man Au-Yeung in Chinese patients
Amy Suk-Yan Tang

Received: 27 May 2002
Received in revised form:
17 December 2002
Accepted: 13 February 2003
Dr. C.-M. Cheung () T.-H. Tsoi
M. Au-Yeung
Department of Medicine
Pamela Youde Nethersole Eastern Hospital
3 Lok Man Road
Chai Wan, Hong Kong
Tel.: +852/25 956 111
Fax: +852/25 153 182
E-Mail: chun-ming@graduate.hku.hk
A. S.-Y. Tang
Centre for clinical trials
and epidemiological research
The Chinese University of Hong Kong
Hong Kong Special Administrative Region
Abstract This was a hospital-
based cohort study aiming at deter-
mining the occurrence rate of post-
stroke seizures and the associated
risk factors. From 27 July 1996 to 16
June 1998, the first 1000 consecu-
tive patients in the acute stroke
registry were retrospectively re-
viewed for one year after acute
stroke to identify seizure occur-
rence. The demographic data,
seizure onset time, seizure type,
drug treatment, response to med-
ication, electroencephalogram
findings and cranial computed to-
mogram findings were collected.
Thirty-four patients (3.4 %) devel-
oped seizure within one year after
acute stroke. Univariate analysis re-
vealed that male, age greater than
65 years, total anterior circulation
infarction, partial anterior circula-
tion infarction, cortical location
and large lesion were significantly
associated with post-stroke seizure
while multivariate analysis showed
that only male (adjusted OR 3.21,
p < 0.01) and cortical location (ad-
justed OR 3.83, p < 0.05) were sig-
nificant independent risk factors.
Fifty-six percent of early seizures
were partial type whereas 72 % of
late seizures were generalized
tonic-clonic type of undetermined
onset. Seizures occurred in 3.4 % of
patients within one year after the
onset of stroke. This percentage of
seizure occurrence and associated
risk factors were similar to other
studies. However, intracerebral and
subarachnoid haemorrhage were
not shown to be risk factors in our
study.
Key words stroke risk factors
seizures

11], subarachnoid haemorrhage [2, 5,9, 12], cortical in-

Introduction
Stroke is one of the most frequent causes of seizures in
adulthood. The occurrence rate of post-stroke seizure
varies considerably in published series: 2.5 % Lo et al.
[1], 4.4 % Kilpatrick et al. [2], 5.4 % Giroud et al. [3], 10 %
Lancman et al. [4], 16.5 % Kotila et al. [5], 4.1 % Labovitz
et al. [9], 4.96 % Berges et al. [10], 8.9 % Bladin et al. [11]
and 7.8 % Butzkueven et al. [12]. The differences were
largely due to the different recruitment criteria of the
studied patients including the stroke types and the on-
volvement [14, 611], large lesion (involving more than
one lobe) [2, 4], male [3], infarct due to cardiogenic em-
bolus [3], stroke disability [11]. The use of prophylactic
anticonvulsant in acute stroke patients remains contro-
versial. We retrospectively studied a cohort of the first
1000 consecutive patients in the Stroke Registry of our
hospital to determine the occurrence of post-stroke
seizures, their clinical features, treatment and response,
and possible risk factors.
JON 1091

set time of seizures. Risk factors for post-stroke seizure

were reported to be intracerebral haemorrhage [24, 9,
840
Methods
Pamela Youde Nethersole Eastern Hospital (PYNEH) is a district
acute hospital in Eastern Hong Kong serving half a million popula-
tion. Any patients who presented with acute stroke within the catch-
ment area would be sent to PYNEH for further management irre-
spective of the severity of the stroke. All stroke patients would be
initially admitted to medical wards and they would only be trans-
ferred to the neurosurgical team if neurosurgical operation was con-
sidered necessary.
Since 27 July 1996, all acute stroke patients admitted to PYNEH
have been enrolled into the Stroke Registry. All stroke patients were
assessed by the neurology team and all had cranial computed tomog-
raphy performed within 24 hours after admission. Cranial computed
tomography would be repeated if there was subsequent clinical dete-
rioration or in case of uncertain diagnosis.
The demographic data, risk factors, types and severity of stroke as
well as size and site of the lesion were collected in the Stroke Registry.
Types of stroke were classified as infarction, intracerebral haemor-
rhage and subarachnoid haemorrhage. Infarction was further sub-
classified into total anterior circulation infarction, partial anterior
circulation infarction, posterior circulation infarction and lacunar in-
farction, according to the Oxfordshire Community Stroke Project
classification [13]. The first 1000 consecutive patients admitted from
27 July 1996 to 16 June 1998 in the Registry formed the cohort of this
study. Patients who were known to be epileptics before stroke and
those whose post-stroke seizures were possibly caused by brain
surgery, central nervous system infection or toxic-metabolic distur-
bances were excluded from the study.
To determine the occurrence rate of post-stroke seizure, the pa-
tients data in the Stroke Registry, in-patient hospital records, out-pa-
tient follow up case notes and subsequent hospital admission records
were retrospectively reviewed for one year after the stroke. Telephone
contacts with patients or their caretakers were done for those who
were not actively followed up in our clinic.An out-patient visit for his-
tory taking and physical examination was arranged if post-stroke
seizure was diagnosed or suspected. The type, onset time, recurrence,
response to medication and treatment of the seizure were then as-
sessed. Electroencephalography (EEG) was arranged if it had not
been done. At the end of the study period, EEG was performed in the
35 % of patients who were found to have post-stroke seizures.
Univariate analysis was used to assess the association between the
demographic risk factors with the occurrence of post-stroke seizures
after follow-up for one year. These crude associations were assessed
by chi-square or Fishers exact test with the unadjusted odds ratio
(OR). Multiple logistic regression [14] was then used to identify the
significant risk factors after adjusting for the confounding effects. In
both univariate and multivariate analyses, ORs with 95 % confidence
intervals were used to estimate the effect of each factor on the occur-
rence of post-stroke seizure. All statistical analyses were performed
with SPSS 9.0 with statistical significance of 0.05 (2-sided).
Table 1 Distribution of stroke subtypes and occur-
rence rate of seizures in each subtype Stroke subtypes
Total anterior circulation infarction (TACI)
Partial anterior circulation infarction (PACI)
Posterior circulation infarction (POCI)
Lacunar infarction (LACI)
Intracerebral haemorrhage
Subarachnoid haemorrhage
Total
Results
Out of the 1000 patients, six could not be contacted. All
these 994 patients (532 male and 462 female) had data
available for analysis. At one year after onset of acute
stroke or before their death, 34 (24 male and 10 female)
patients had developed seizures. Therefore, the post-
stroke seizure occurrence was 3.4 %. The corresponding
mean ages for the total, seizure and non-seizure group
were respectively 70.7 years (range 2798; SD 10.3), 74.4
years (range 5996; SD 8.6) and 70.5 years (range 2798;
SD 10.4). The distribution of the stroke subtypes and the
seizure occurrence in each stroke subtype are shown in
Table 1.
Six risk factors were investigated and the results are
shown in Table 2. Male, age greater than 65 years, total
anterior circulation infarction, partial anterior circula-
tion infarction, cortical location and large lesions
(greater than 3x3x3 cm3) were found to be significantly
associated with the occurrence of post-stroke seizure by
chi-square or Fishers exact test, whichever test was ap-
propriate. When multiple logistic regression was used
for multivariate analysis, only male and cortical location
remained as significant risk factors with adjusted OR of
3.21 (95 % CI 1.45 to 7.08, p < 0.01) and 3.83 (95 % CI 1.05
to 14.01, p < 0.05) respectively. Those patients with cor-
tical location of their lesions were mostly anterior (19
out of 21).
Cortical and subcortical locations of lesions in each
type of stroke are shown in Table 3. Cortical location was
a significant risk factor for seizure occurrence in intra-
cerebral haemorrhage patients (p = 0.011), ischaemic
stroke patients (p = 0.001) and the whole group of pa-
tients (p < 0.01).
The type of seizure, onset time and recurrence of
seizure are shown in Table 5. Early onset seizure was de-
fined as a seizure that occurred within 30 days from on-
set of stroke and late onset seizure was defined as a
seizure that occurred after 30 days to one year from on-
set of stroke.
Number of patients Number (%) of seizures
in each stroke type
57 5 (8.8%)
186 13 (7%)
57 0
452 7 (1.5%)
222 9 (4.1%)
20 0
994 34 (3.4%)
 841

Table 2 Risk factors for developing post stroke seizures

Post stroke No post-stroke Univariate analysis Multivariate analysis

seizure (%) n = 34 seizure (%) n = 960
Unadjusted p value Adjusted p value
odds ratio (95% CI) odds ratio (95% CI)

Male 24 (70.6) 508 (52.9) 2.13 (1.014.51) 0.04* 3.21 (1.457.08) < 0.01**
Age greater than 65 30 (88.2) 696 (72.5) 2.85 (0.998.15) 0.048a * 2.66 (0.907.85) 0.08
TACI 5 (14.7) 52 (5.4) 3.01 (1.128.10) 0.04* 12.04 (0.39369) 0.15
PACI 13 (38.2) 173 (18.0) 2.82 (1.385.73) < 0.01** 12.8 (0.46361) 0.13
POCI 0 57 (5.6) Not available Not available Not available Not available
LACI 7 (20.6) 445 (46.4) 0.299 (0.130.69) < 0.01 6.3 (0.23173) 0.27
Cortical location 22 (64.7) 187 (19.5) 7.58 (3.6815.59) < 0.01** 3.83 (1.0514.01) 0.04*
Large lesion 22 (64.7) 203 (21.1) 6.84 (3.3314.05) < 0.01** 1.94 (0.537.20) 0.32
(greater than 3x3x3 cm3)
Intracranial Haemorrhage 9 (26.5) 233 (24.3) 1.12 (0.522.44) 0.77 7.09 (0.26190) 0.24
(including SAH)

* p < 0.05; ** p < 0.01; a by Fishers exact test

Table 3 Seizure occurrence in different location of

stroke subtypes Location Intracranial haemorrhage Ischaemic Infarct All types of strokes
(including SAH)
With Without With Without With Without
seizure seizure seizure seizure seizure seizure

Cortical 6 57 16 140 22 187

Subcortical 3 176 4 225 7 401
p valuea 0.011 0.001 < 0.01
Undetermined 0 0 5 372 5 372
Total 9 233 25 727 34 960
a by Fishers exact test

Table 4 Estimate of number and percentage of pre-

ventable seizures Stroke subtypes Number of Estimate of Number of % of
seizures number of patients in each preventable
observed potentially stroke type seizure
in each preventable
stroke type seizuresa

Total anterior circulation infarction 5 1 57 1.75

Partial anterior circulation infarction 13 1 186 0.53
posterior circulation infarction 0 0 57 0.46
Lacunar infarct 7 2 452 0.44
Intracerebral haemorrhage 9 2 222 0.90
a
Potentially preventable seizures were arbitrary defined as those seizures occurred after hospital admission of
acute stroke patients and within 30 days from onset of stroke

By using univariate analysis, the risk factors for post

Discussion
Our study found that the incidence of seizure within one
year from onset of acute stroke was not high (3.4 %). The
incidence was comparable to other studies of similar
scale: 2.5 % in Taiwan by Lo et al. [1], 4.4 % in Australia
by Kilpatrick et al. [2], 4.96 % in France by Berges et al.
[10] and 5.4 % in France by Giroud et al. [3].
stroke seizure identified in our study were also compa-
rable to other studies [18] namely male, large lesion
size and cortical location. No published studies classi-
fied patients with infarction according to the Oxford-
shire Community Stroke Project classification, so we
cannot compare the subtypes of infarction. In contrast
to our findings, Kilpatrick et al. [2], Giroud et al. [3] and
Lancman et al. [4] showed that intracerebral haemor-
842
Table 5 Types of seizure, onset time and recurrence of seizure
Types of seizure Early onset Late onset
Generalized tonic-clonic seizure 7 (43.8%) 13 (72.2%)
of undetermined onset
Simple partial seizure 6 (37.5%) 0 6 (17.6%)
Simple partial seizure with 2 (12.5%) 4 (22.2%)
secondary generalization
Complex partial seizure 1 (6.2%) 1 (5.6%)
Status epilepticus 0 0
Total 16 18
Patients with recurrence 0 7
of seizure
rhage was a risk factor whereas Kilpatrick et al. [2] and
Kotila et al. [5] showed that subarachnoid haemorrhage
was a risk factor. However, in these studies, the location
of the haemorrhage was not specified. In contrast, we
could not demonstrate any association between seizure
and intracerebral or subarachnoid haemorrhage. More-
over, by using logistic regression analysis, only male and
cortical location were the risk factors. This suggested
that there might be a substantial inter-correlation
among these risk factors. The site of the lesion, no mat-
ter whether infarct or haemorrhage, might be the most
determining factor for causing seizures. The study by
Labovitz et al. [9] only included any seizure occurring
within 7 days of stroke onset. Compared with deep in-
farct, deep intracerebral haemorrhage had 7.9 times a
higher risk for seizures, while lobar intracerebral had
25.3 times a higher risk for seizures. This also shows that
cortical location is a very important risk factor. Our co-
hort consisted of all types of stroke and with a large
number of patients, this study may be better than others
for the analysis of the correlationship between the risk
factors. However, we do not have a good explanation for
males being a high risk group.
In our study, generalized tonic-clonic type seizure
was the commonest presentation of post stroke seizure
(58.9 %). However, partial seizure was recognized to be
the most predominant type by Lo et al. (66 %) [1], Kil-
patrick et al. (59 %) [2] and Giroud et al. (89 %) [3],
Labovitz et al. (59.5 %) [9]. In a retrospective study of 90
patients with post-infarction seizures, Gupta et al. [15]
found that 57 % of seizures that occurred within two
weeks were partial whereas 65 % of seizures that oc-
curred after two weeks were generalized tonic clonic
type. Our findings were similar to those of Gupta et al.
[15] in which 56 % of early seizures were partial type
whereas 72 % of late seizures were generalized tonic
clonic type. In our health care setting, patients with
acute stroke were usually cared for in the acute or reha-
bilitation hospital during the early period. It is easier at
Total (%) this time for the health care taker to recognize the par-
20 (58.9%) tial seizure. In the late period, in which patients usually
returned home, those patients with simple partial
seizure might not be recognized at all by the patients or
6 (17.6%) their caretakers. Therefore, in the late period it is more
likely that patients with generalized tonic clonic seizure
2 (5.9%) and complex partial seizure will be recognised. The on-
0 set of generalized tonic-clonic seizure could not be ac-
34 curately determined.
7 Our cohort was collected over a period of 23 months,
30 out of 34 patients with post stroke seizure were over
65 years old. Our hospital has served a population of
500,000 and about 10 % of the population [50,000] is
more than 65 years old [16]. The post-stroke seizure
occurrence in the elderly (age > 65) was then estimated
to be 16 per 50,000 or 32 per 100,000 elderly population
per year. If the incidence of seizure in our population is
consistent with other countries (around 50/100,000 in
the elderly population) [17], it is possible to estimate
that stroke accounts for 64 % of seizures in the elderly
group. Hence, it is confidently concluded that stroke is
the single most important cause of epilepsy in the el-
derly.
All patients with seizures will be treated with anti-
epileptic drugs and they will be maintained on that drug
for at least two years. So we do not know whether early
seizures predicted the recurrence of late seizures. No pa-
tients in the early seizure group had recurrence of
seizures after adequate dosage of phenytoin.
In our study, the percentages of estimated potentially
preventable seizures in all categories were low (0.44 % to
1.75 %) as shown in Table 4. The benefit of prophylactic
anticonvulsant therapy would further be limited be-
cause of the relatively easy control of seizures if they did
occur and the adverse effects of the anticonvulsant ther-
apy.A short course of prophylactic anticonvulsant at on-
set of stroke would certainly not be beneficial in those
patients who developed seizure late, which constituted
half of the post-stroke seizures. For those developing
seizures early, most had onset before arrival at hospital
and anticonvulsant would immediately be started on ad-
mission for therapeutic purpose. Furthermore, in our
patients, seizures that occurred after stroke were usually
easy to control and no serious complications resulted
from the seizure. On balancing the limited benefit and
the potential serious adverse effects of antiepileptic
drugs, prophylactic anticonvulsant should not be used
in all types of acute stroke.
Acknowledgement The authors thank Dr. Lawrence KS Wong for
his useful comments.

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