poststroke epilepsy

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Poststroke Epilepsy in the Copenhagen Stroke Study:Incidence and Predictors

Lars Peter Kammersgaard, MD, and Tom Skyhj Olsen, DMSci

Poststroke epilepsy (PSE) is a feared complication after stroke and is reported in 3%

to 5% of stroke survivors. In this study we sought to identify incidence and

predictors of PSE in an unselected stroke population with a follow-up period of 7

years. The study was community-based and comprises a cohort of 1197 consecu-

tively and prospectively admitted patients with stroke. Patients were followed up

for 7 years. We defined PSE as recurrent epileptic seizures with onset after stroke

and requiring antiepileptic prophylaxis. PSE was related to clinical factors (age, sex,

onset stroke severity, lesion size on computed tomography scans, stroke subtype,localization, stroke risk factor profile, and early seizures) in univariate analyses.

Independent predictors of PSE were identified through multiple logistic regression

analyses. Overall, 38 patients (3.2%) developed PSE. Univariately, PSE was asso-

ciated with younger age, intracerebral hemorrhage, and larger lesions. PSE was less

frequently associated with atrial fibrillation and ischemic heart disease. In the final

multiple regression model for the dependent variable PSE, independent predictors

were younger age (odds ratio [OR] 1.7/10 years; 95% confidence interval [CI]

1.3-2.1), onset stroke severity (OR 1.3-/10-point decrease; 95% CI 1.0-1.6), lesion

size (OR 1.2-/10-mm enlargement; 95% CI 1.0-1.3), intracerebral hemorrhage (OR

3.3; 95% CI 1.3-8.6), and early seizures (OR 4.5; 95% CI 1.3-16.0). We conclude that

PSE occurs in about 3% of all patients with stroke within 7 years after stroke. Age,

intracerebral hemorrhage, lesion size, increasing stroke severity, and early seizures

are independent predictors of PSE. Key Words: Cerebrovascular diseaselong-

termrisk factorsepilepsystroke severityagecerebral hemorrhagelogis-

tic regression.

2005 by National Stroke Association

Epilepsy is a feared complication to stroke among

patients and their relatives. Hence, identification of fac-

tors that predict epilepsy in patients with stroke is war-

ranted. Age, stroke severity, cortical stroke, and hemor-

rhagic stroke are often found to be predictors in most

studies,1-3 but not in all reports.4 Timing of first seizure

(early v late after stroke)3,5 and stroke recurrence6 are

among other suggested predictive factors for poststroke

epilepsy (PSE).

In this prospective study, which consists of an un-

selected community-based cohort of hospitalized pa-

tients, we followed up 1195 patients with stroke for 7years after onset. The aim of the study was to investigate

the overall risk for PSE in a long-term perspective and to

determine independent predictors for PSE.

Methods

The study included all patients with acute stroke ad-

mitted consecutively during a 25-month period to the

stroke department at Bispebjerg Hospital, Copenhagen,

Denmark. It was a prospective and community-based

From the Stroke Unit, Hvidovre University Hospital, Hvidovre,

Denmark.

Received May 1, 2005; accepted June 28, 2005.

Supported by grants from the Danish Health Foundation, the

Danish Heart Foundation, Ebba Celinders Foundation, the Indepen-

dent Order of Odd Fellows, Scandinavia Lodge 2, and HjerneSagen.

Address correspondence to Lars Peter Kammersgaard, MD, Stroke

Unit, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark.

E-mail: [email protected].

1052-3057/$see front matter

2005 by National Stroke Association

doi:10.1016/j.jstrokecerebrovasdis.2005.07.001

Journal of Stroke and Cerebrovascular Diseases,Vol. 14, No. 5 (September-October), 2005: pp 210-214210


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were tested backwards to fit the full model with all

explanatory variables. Unimportant variables were then

removed one by one, until all those remaining in the

model each contributed with aPless than .2. To select the

final model, backward logistic regression, including only

variables with aP less than .2, was followed by forward

logistic regression including the same variables. The ex-

planatory power of the equation was determined by the

value of correct classification. The required level of sig-

nificance for all tests was set at .05.

The study was approved by the Ethics Committee of

Frederiksberg and Copenhagen (approval numbers KF/

V.100.2263/91 and KF 01-287/98).

Results

The crude cohort consisted of 1197 patients, but two

patients were excluded because they had epilepsy before

stroke onset. Basic characteristics for the 1195 patients

included are shown inTable 1.PSE emerged in 16 (1.3%)

patients within 3 years, and in 38 patients within 7 years.

At stroke onset patients with subsequent PSE were

younger, more often had hemorrhagic strokes, and more

often had larger lesions. Fewer patients with subsequent

PSE had ischemic heart disease and atrial fibrillation. No

differences between patients with and without PSE and

PSE were found for sex, initial stroke severity, cortical

involvement, hypertension, diabetes, intermittent claudi-

cation, smoking, daily intake of alcohol, previous stroke,

or pre-existing disability. There was a trend toward a

higher frequency of early seizures among patients with

subsequent PSE.Fig 1gives the frequencies of PSE as a function of initial

stroke severity divided into mild (SSS score 45-58), mod-

erate (SSS score 30-44), severe (SSS score 15-29), and very

severe (SSS score 0-14), with frequencies being 2.3%,

3.6%, 4.5%, and 2.7%, respectively.

In the final multiple logistic regression model shown in

Table 2,independent predictors of PSE were hemorrhagic

stroke, early seizure, larger lesion diameter, increased

initial stroke severity, and younger age. Cortical involve-

ment was not found to be an independent predictor of

PSE.

Discussion

In this community-based study 3.2% of all patients

with stroke developed PSE during the follow-up period

of mean 7 years after stroke onset. A few smaller studies

reported frequencies of PSE in as many as 6% to 9%.14,15

In the Oxfordshire Community Stroke Project, PSE devel-

oped in 3.8% within 5 years after onset of first ever

stroke.2 In the Rochester, Minn, study that included 535

patients with ischemic strokes, 3.4% developed PSE

within a follow-up period of 5.5 years after onset of

stroke.6 In the prospective Seizures After Stroke Study

with a 9-month observation period, PSE emerged in 2.5%

of the 1897 patients included.3 In the current study we

found 1.3% to develop PSE within 3 years after onset.

Younger age appeared to predispose to PSE in our

cohort. After adjustment for other basic clinical charac-

teristics a 10-year decrease of age at stroke onset inde-

pendently increased the risk for PSE by 65%. Previous

studies of PSE have focused on other factors and not age

per se. We found only one previous study that had

analyzed age as a risk factor for developing PSE and in

Figure 1. Frequency of poststroke epilepsy as function of initial stroke

severity. Patients were stratified into 4 groups: mild (Scandinavian Stroke

Scale [SSS] 45-58 points), moderate (SSS 30-44 points), severe (SSS 15-29

points), and very severe (SSS 0-14 points) strokes.

Table 2. Independent predictors of poststroke epilepsy

Variable Covariate P OR 95% CI

PSE Cerebral hemorrhage .02 3.3 1.38.6

Lesion size, per 10-mm enlargement .02 1.2 1.01.3

Severity, per 10-point decrease .03 1.3 1.01.6

Age, per 10-year decrease .0001 1.7 1.32.1

Early seizure .02 4.5 1.316.0

Cortical involvement .67 1.2 0.52.7

CI, Confidence interval; OR, odds ratio; PSE, poststroke epilepsy.

Multiple regression analysis (final model): dependent variable PSE overall 2 0.0001, value of correct classification 95.4%.

L.P. KAMMERSGAARD AND T.S. OLSEN212


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that study age was not found to be an independent

predictor of PSE.1 However, in that study the follow-up

period was considerably shorter and the cohort investi-

gated smaller than the current one. We found no differ-

ences in the univariate analyses when stroke severity at

onset between patients with versus without PSE was

compared. As demonstrated inFig 1, the frequencies of

PSE increased with increasing stroke severity. Althoughthere was a decline in frequency for very severe strokes,

we think this was caused by a higher long-term mortality

among patients with the most severe strokes. In line with

this, the frequency of PSE was directly related to lesion

diameter. After adjustment for differences in basic char-

acteristics we found increasing stroke severity to inde-

pendently raise the relative risk for developing PSE by

27% per 10-point decrease of the SSS score. In the Sei-

zures After Stroke Study, patients who had a seizure after

stroke had more severe strokes as measured by the Ca-

nadian Neurological Score, but no relation between PSE

and stroke severity was detected.3 In the Oxfordshire

Community Stroke population, severe stroke was associ-

ated with both single and recurrent seizures, but stroke

severity was not measured by a stroke scale.2 A Norwe-

gian study found an initial stroke severity below 30

points on the SSS score to significantly increase the risk

for PSE within 12 months after stroke onset.1

Lesion size appeared to be a significant independent

predictor for developing PSE. An increase of the lesion

diameter by 10 mm on CT scans corresponded to a 16%

higher relative risk for PSE within 7 years after stroke

onset. In the Seizures After Stroke Study, large lesion

volumes were not found to be independent predictors for

PSE.3

However, in the Oxfordshire Community StrokeProject, only 1% of patients with lacunar strokes devel-

oped PSE, whereas 11% of patients with total anterior

circulation infarcts developed PSE.2 In addition, two

other studies have suggested that, in patients with very

small stroke lesions, development of seizures at all is

extremely rare.16,17

In the current study 21% of those who developed PSE

had cerebral hemorrhages, whereas that was only the

case in 7% of those without PSE. Furthermore, cerebral

hemorrhage was found to be an independent predictor

for PSE and increased the risk more than 3 times relative

to the risk for patients with ischemic strokes. The moresevere strokes that often accompany cerebral hemor-

rhages is not the only explanation for this finding because

we were able to adjust for differences in stroke severity.

Previous studies have reported seizures to be more fre-

quent among patients with cerebral hematomas3,17-19 and

the risk of seizures after cerebral hematomas has been

reported to be as high as 10 relative to ischemic strokes.2

A study that included a large number of patients with

only intracerebral hematomas found that PSE developed

in 2.5%. However, the prognostic significance of cerebral

hemorrhage per se for the development of PSE has not

been investigated previously using multiple regression

techniques.

It has been discussed that the risk for PSE differs

between patients with early- (occurring within 14 days

after stroke onset) versus late-onset seizures. Some au-

thors have suggested that early seizures predict PSE,6,20

others have found this relation for late seizures,21 and no

relation was reported in one study.

22

In our study, pa-tients who subsequently developed PSE had early sei-

zures twice as often as those without PSE. Although this

difference was only of borderline statistical significance,

early seizure was found to increase the relative risk for

PSE more than 4 times after adjustment for other clinical

characteristics.

In this study we found no correlation between cortical

localization of the stroke lesion and subsequent develop-

ment of PSE. Although stroke with cortical involvement

is well known to be associated with an increased risk for

early seizures,23,24 very few data are available for the

relation to the development of PSE. In a study of patients

with ischemic strokes, hemispheric stroke was found to

be associated with increased risk for recurrent seizures.25

In two studies, cortical stroke was not found to be an

independent predictor of PSE,3,18 and one study even

suggested that only patients with lacunar infarctions are

at greater risk for PSE.21

In conclusion, the current study shows that in an

unselected stroke population PSE develops in very few

(3.2%) patients during a period of 7 years after stroke.

The risk for PSE appears to be highest for younger

patients, patients with severe strokes on admission, those

with large lesions on CT scans, those with hemorrhagic

strokes, and when the patient has a seizure within 14days after onset of stroke.

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