ORIGINAL CONTRIBUTION

Seizures After Stroke

A Prospective Multicenter Study
Christopher F. Bladin, MD, FRACP; Andrei V. Alexandrov, MD; André Bellavance, MD, PhD;
Natan Bornstein, MD; Brian Chambers, MD; Robert Coté, MD; Louise Lebrun, MD;
Angelo Pirisi, MD; John W. Norris, MD; for the Seizures After Stroke Study Group

Background: Studies of seizures after stroke have largely
been retrospective, with small patient numbers and lim-
ited statistical analysis. Much of the doctrine about sei-
zures after stroke is not evidenced based.
Objective: To determine the incidence, outcome, and
risk factors for seizures after stroke.
Design: International, multicenter, prospective, ana-
lytic inception cohort study conducted for 34 months.
Patients and Setting: There were 2021 consecutive
patients with acute stroke admitted to university teach-
ing hospitals with established stroke units. After exclu-
sion of 124 patients with previous epilepsy or without
computed tomographic diagnosis, 1897 were available
for analysis. Mean follow-up was 9 months.
Main Outcome Measures: Occurrence of 1 or more
seizures after stroke, stroke disability, and death after stroke.
Results: Seizures occurred in 168 (8.9%) of 1897 pa-
tients with stroke (28 [10.6%] of 265 with hemorrhagic
and 140 [8.6%] of 1632 with ischemic stroke). On Kaplan-
Meier survival analysis, patients with hemorrhagic stroke
were at significantly greater risk of seizures (P=.002), with
an almost 2-fold increase in risk of seizure after stroke (haz-
ard ratio [HR], 1.85; 95% confidence interval [CI], 1.26-
2.73; P=.002). On multivariate analysis, risk factors for
seizures after ischemic stroke were cortical location of in-
farction (HR, 2.09; 95% CI, 1.19-3.68; P,.01) and stroke
disability (HR, 2.10; 95% CI, 1.16-3.82; P,.02). The only
risk factor for seizures after hemorrhagic stroke was cor-
tical location (HR, 3.16; 95% CI, 1.35-7.40; P,.008). Re-
current seizures (epilepsy) occurred in 47 (2.5%) of 1897
patients. Late onset of the first seizure was an indepen-
dent risk factor for epilepsy after ischemic stroke (HR,
12.37; 95% CI, 4.74-32.32; P,.001) but not after hemor-
rhagic stroke.
Conclusions: Seizures occur more commonly with hem-
orrhagic stroke than with ischemic stroke. Only a small
minority later develop epilepsy. Patients with a dis-
abling cortical infarct or a cortical hemorrhage are more
likely to have seizures after stroke; those with late-onset
seizures are at greater risk of epilepsy.
Arch Neurol. 2000;57:1617-1622

The affiliations of the authors
and a complete list of the
members of the Seizures After
Stroke Study Group appear at
the end of this article.
S
EIZURES secondary to stroke
havebeenrecognizedformany
years and are considered by
some authorities as a major
cause of epilepsy in the elder-
ly.1 Although the frequency of seizures af-
ter stroke is variously estimated at 4% to
10%,2-9 many of these data were based on ret-
rospective studies with variable follow-up,
often without computed tomographic (CT)
confirmation of the lesion, or on patient
numbers so small that no reliable statisti-
cal analysis was possible. Often included
were patients with arteriovenous malfor-
mations, brainstem strokes, subarachnoid
hemorrhage, or a previous history of sei-
zures or epilepsy. Previous assumptions
such as seizures being more frequent in ce-
rebral hemorrhage4,10 or cardioembolic
stroke2,3,11 are not reliably evidence based.
Results of population-based stud-
ies6-9 using multivariate analysis have in-
dicated that risk factors for poststroke sei-
zures include hemorrhagic stroke, cortical
location of stroke, and severity of stroke.
Other studies have proposed that the risk
of epilepsy is greater in patients with late
onset of the initial seizure after stroke,2,12,13
and early-onset seizures are considered a
risk factor for stroke-related death.4,5,12,14,15
Black et al15 found seizures only in
stroke patients with cerebral hemispheric
lesions and established that because sei-
zures occurred in less than 10% of pa-
tients, statistical evaluation would only be
valid with prospective data in large num-
bers of patients. A multicenter study was
therefore undertaken to investigate the fre-
quency of seizures after stroke, their effect
on stroke mortality, their effect on neuro-
logical and functional outcome, and the re-
lation to underlying cerebral pathological
lesions. Because a preliminary study15 found
that no patients had seizures associated with

(REPRINTED) ARCH NEUROL / VOL 57, NOV 2000 WWW.ARCHNEUROL.COM

1617

©2000 American Medical Association. All rights reserved.

Downloaded From: http://archneur.jamanetwork.com/ by a University of North Dakota User on 05/24/2015
 PATIENTS AND METHODS
The Seizures After Stroke Study (SASS) was a prospective, mul-
ticenter study undertaken by the Stroke Research Unit, Uni-
versity of Toronto, Ontario, and involving university teach-
ing hospitals in Canada, Australia, Israel, and Italy. Patients
were recruited during 34 months. All consecutive patients with
acute stroke admitted to these hospitals were enrolled except
those with (1) brainstem and cerebellar stroke; (2) subarach-
noid hemorrhage, arteriovenous vascular malformations, sub-
dural hematoma, or inflammatory vascular disease; (3) tran-
sient ischemic attack, a history of previous seizures or epilepsy,
or “pseudostroke,” eg, strokelike symptoms due to metabolic
dysfunction, brain tumor, migraine, or psychiatric disorders;
and (4) early death precluding CT confirmation of diagnosis.
At each hospital all patients were evaluated by a neu-
rologist, and seizures were classified according to the Inter-
national League Against Epilepsy criteria.16 Epilepsy was de-
fined as a condition characterized by recurrent seizures
separated by more than 24 hours. As in previous studies,17
a cluster of seizures occurring in a single 24-hour period was
considered a single seizure episode. “Early onset” refers to
the first seizure occurring 2 weeks or less after stroke onset
and “late onset” refers to the first seizure occurring more than
2 weeks after stroke onset. Patients underwent a standard-
ized clinical neurological evaluation, with disability graded
according to a modified Canadian Neurological Score (re-
corded as Canadian Neurological Score310)18 on days 1,
3, 7, and 14, and CT imaging on admission to the hospital
and at approximately 7 to 10 days.
To determine the pathogenesis of ischemic stroke, all
patients were investigated in a standardized fashion, includ-
ing duplex ultrasound to assess carotid stenosis; the likeli-
hood of cardioembolic stroke was graded as high or low us-
ing clinical and laboratory data.19 Lacunar infarction was
defined according to clinically recognized lacunar syn-
dromes, with or without CT evidence of a small deep in-
farct.20 For intracerebral hemorrhage, a previously vali-
dated scoring system was used to categorize the amount of
blood in the ventricular and cisternal cerebrospinal fluid
spaces.21 Volumes of CT lesions were measured using a com-
puterized technique (Sigma Scan; Jandel Scientific, Corte
Madera, Calif). An electroencephalogram was not a require-
ment for inclusion in the study but was performed if pos-
sible within the first week of admission.
The study protocol was approved by the research eth-
ics committee (or equivalent) in each participating hospi-
tal. All data and CT scans were recorded in a standardized
format and sent to the coordinating center (Stroke Re-
search Unit, University of Toronto).
brainstem stroke, in the present study only patients with
hemispheric stroke were included. We believed that con-
clusions concerning the role of anticonvulsant drug ther-
apy would be limited because, for ethical and method-
ological reasons, a placebo-controlled study would not be
practical.
RESULTS
Of 2021 patients with stroke enrolled in the study, 68
did not undergo CT and 56 had epilepsy before their
(REPRINTED) ARCH NEUROL / VOL 57, NOV 2000
1618
©2000 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a University of North Dakota User on 05/24/2015
Follow-up of surviving patients was by telephone at ap-
proximatelyyearlyintervals,orsoonerifseizureswerereported.
When necessary, family relatives or the familyphysician, hos-
pital, or nursing home was contacted. Patients identified as
having symptoms suggestive of seizures attended neurology
outpatient clinics for further evaluation. Functional outcome
was assessed by the Modified Rankin Scale.
Univariate comparisons of characteristics between pa-
tients with and without seizures after stroke were per-
formed using the x2 test for categorical variables and the
2-sample t test for continuous variables.
Multivariate analysis was performed using a Cox propor-
tional hazards model. Covariates in the Cox multivariate re-
gressionanalysisofseizuresafterstrokeweredeterminedapriori
based on review of the literature and results of univariate analy-
sis. Variables in the Cox proportional hazards model for risk
of seizures after ischemic stroke were age, presence or absence
of hemorrhagic infarction, high or low risk of cardioembolism,
size of infarct on CT, cortical location, and stroke disability.
For the multivariate analysis for risk of recurrent seizures af-
ter ischemic stroke, the same set of variables were used but with
addition of late-onset seizures. For the multivariate analysis
for risk of death, the same variables were again used but with
addition of early-onset seizures. For the purposes of multivar-
iate analysis, infarct size on CT was entered as a categorical
variable: no measurable lesion (0 cm3), small (,10 cm3),
medium (10 to ,100 cm3), or large ($100 cm3). Stroke dis-
ability was also entered as a categorical variable based on the
Canadian Neurological Score: mild disability (.90-115),
moderate disability (.50-90), or severe disability (30-50).22
Covariates in the Cox multivariate regression analysis
for risk of seizures after hemorrhagic stroke were age, grad-
ing of amount of cisternal and ventricular blood, hemorrhage
location (lobar hemorrhage abutting onto cortex is “cortical”
anddeepsubcorticalhemorrhageis“subcortical”),sizeofhem-
orrhageonCT,andstrokedisability.Forthemultivariateanaly-
sis for risk of recurrent seizures after hemorrhagic stroke, the
same set of variables were used with addition of late-onset sei-
zures. For the multivariate analysis for risk of death, the same
variables were again used but with addition of early-onset sei-
zures. Hemorrhage size was entered as a categorical variable:
small (,20 cm3), medium (20 to ,50 cm3), large ($50 cm3),
and very large (100-320 cm3). Stroke disability was also en-
tered as a categorical variable based on the Canadian Neuro-
logical Score as for seizures after ischemic stroke.
Kaplan-Meier survival analysis was carried out for the
cohorts with ischemic and hemorrhagic stroke analyzing
survival free of first ever seizure during follow-up. Log-
rank analysis was performed to compare the event curves
for patients with seizures after ischemic stroke and sei-
zures after hemorrhagic stroke.
stroke, leaving 1897 patients available for analysis. Dur-
ing the study, seizures occurred in 168 patients (8.9%),
including 140 (8.6%) of 1632 with ischemic stroke and
28 (10.6%) of 265 with hemorrhagic stroke. The Kaplan-
Meier survival analysis indicated a significantly greater
probability of seizures occurring in patients with hem-
orrhagic stroke (P=.002), with a 1-year actuarial risk of
seizures in stroke survivors of 20% in patients with hem-
orrhagic stroke and 14% in patients with ischemic stroke
(Figure 1). Recurrent seizures (epilepsy) developed in
47 (2.5%) of 1897 patients with stroke overall and in 47
WWW.ARCHNEUROL.COM
 1
Table 1. Univariate Analysis of Patients
0.95 With Seizures After Stroke*
Proportion Free of Seizures

0.90 Nonseizure
Ischemic Stroke Seizure Group Group
0.85 Variable (n = 168) (n = 1729) P

0.80 Hemorrhagic Stroke

Total patient cohort
Age, mean ± SD, y 71.7 ± 13.6 72.8 ± 11.9 .24
0.75 Male sex, No. (%) 100 (60) 993 (57) .66
Left hemisphere, No. 71 908 .22
0.70 Hypertension, No. 97 955 .59
0 100 200 300 400 500 600 700 800 Cardiac disease, No. 82 805 .63
Time, d Diabetes, No. 32 355 .72
Family history of 6 53 .90
Figure 1. Kaplan-Meier survival curves for patients with ischemic and epilepsy, No.
hemorrhagic stroke showing the probability of remaining free of seizures Smoker, No. 73 682 .35
after stroke. There was a significant difference (log-rank test) between the Cancer, No. 16 146 .74
seizure event curves ( P =.002).
Alcohol use, No. 22 183 .30
Previous stroke, No. 64 639 .84
(28.0%) of 168 patients with seizure. Follow-up (mean, Head trauma, No. 0 3 .62
9 months) was available for 1841 patients (97.0%). Subdural hemorrhage, No. 0 2 .40
Craniopharyngioma, No. 0 1 .14
UNIVARIATE ANALYSIS Ischemic stroke (n = 140) (n = 1492)
Topography, No. (%)
Total Patient Cohort Normal CT scan 12 (9) 400 (27) .001
Subcortical infarction 28 (20) 479 (32) .001
Cortical infarction 88 (63) 613 (41) ,.001
Mean±SD patient age was 72.0 ± 11.5 years, with no dif-
Hemorrhagic infarction 12 (9) 51 (3) .005
ference between seizure and nonseizure groups accord- Size, mean ± SD, cm3
ing to age, sex, hemisphere side, previous stroke, or other All infarcts 76.7 ± 84.9 45.6 ± 76.5 ,.001
risk factors for stroke or seizures (Table 1). Cortical infarcts 95.0 ± 66.3 75.2 ± 90.1 .03
Small infarcts 4.53 ± 2.94 3.37 ± 2.83 ,.001
Ischemic Stroke Medium infarcts 39.65 ± 26.87 38.69 ± 24.14 .40
Large infarcts 199.79 ± 100.32 183.55 ± 68.54 .008
Cortical infarction was present in the majority of pa- Cause, No.
tients with seizures after ischemic stroke (Table 1). Sei- High-risk embolic 57 519 .19
infarct
zures were reported in 8 (2.6%) of 307 patients with deep Carotid stenosis .70% 18 106 .65
lacunar infarction, although confounding factors made Disability, day 1 CNS 67.0 ± 29.6 74.9 ± 29.0 .001
this association tenuous (see the “Comment” section). score, mean ± SD†
Infarct size on CT was significantly larger in patients with Outcome
30-d mortality, No. (%) 35 (25) 100 (7) ,.001
seizures than in those without seizures. Hemorrhagic in-
1-y mortality, No. (%) 53 (38) 239 (16) ,.001
farcts were significantly more common in patients with Follow-up Rankin 3.1 ± 1.6 2.3 ± 1.5 ,.001
seizures. However, there was no significant difference in score, mean ± SD
the numbers of patients with and without seizures with Hemorrhagic stroke (n = 28) (n = 237)
a high risk of cardioembolic stroke (Table 1). Topography
Cortical location 19 (68) 103 (43)
Forty percent of seizures after ischemic stroke oc- Subcortical location 9 (32) 134 (57)
.03
curred in the first 24 hours (Figure 2). Early-onset sei- Size, mean ± SD, cm3
zures (#2 weeks) occurred in 4.8% (78/1632) and late- All hemorrhages 72.3 ± 75.6 75.1 ± 74.6 .84
onset seizures (.2 weeks) occurred in 3.8% (62/1632) Cortical hemorrhages 86.2 ± 79.4 115.3 ± 83.5 .13
of patients with ischemic stroke. Recurrent seizures (epi- Subcortical hemorrhages 42.9 ± 56.8 44.4 ± 48.0 .93
CSF blood score, mean ± SD
lepsy) occurred in 55% (34/62) of patients with late- Ventricular 2.8 ± 5.1 3.0 ± 5.2 .85
onset seizures. Partial seizures (including simple partial Cisternal 0.7 ± 1.6 0.6 ± 2.3 .84
and secondarily generalized seizures) accounted for 53% Disability, day 1 CNS 61.0 ± 32.8 50.0 ± 30.4 .05
(74/140) of seizures after ischemic stroke. score, mean ± SD†
Compared with ischemic stroke patients without sei- Outcome
30-d mortality, No. % 10 (36) 57 (24) .30
zures, those with seizures had a significantly worse neuro- 1-y mortality, No.% 13 (46) 85 (36) .40
logical score during the hospital stay and Rankin score on Follow-up Rankin score, 2.3 ± 1.7 3.0 ± 2.0 .16
long-term follow-up (Table 1). This was primarily due to mean ± SD
cortical infarction because no significant differences in mor-
bidity were detected between patients with and without *CT indicates computed tomographic; CNS, Canadian Neurological Score;
and CSF, cerebrospinal fluid.
seizureswithsubcorticalinfarction(Figure3A).Mortalitywas †A lower CNS value indicates greater neurological disability.
greaterinpatientswithseizureat30daysand1year(Table1).
Hemorrhagic Stroke location. Overall, there was no significant difference in
hemorrhage size between the seizure and nonseizure
In patients with seizures after hemorrhagic stroke, the groups and no significant difference in the amount of cis-
parenchymal hemorrhage was predominantly cortical in ternal or ventricular blood present (Table 1).

(REPRINTED) ARCH NEUROL / VOL 57, NOV 2000 WWW.ARCHNEUROL.COM

1619

©2000 American Medical Association. All rights reserved.

Downloaded From: http://archneur.jamanetwork.com/ by a University of North Dakota User on 05/24/2015
 80
significantly less early disability than patients without sei-
Ischemic Stroke
Hemorrhagic Stroke zure and also possibly a trend to less disability on follow-
70
up Rankin score (Table 1). This was particularly evident in
60
patientswithcorticalcerebralhemorrhage(Figure3B).There
First Seizures, %

50 were no significant differences in disability between patients

40 with and without seizure with deep cerebral hemorrhage.
30 There was no difference in mortality between patients with
20 and without seizure at 30 days or 1 year (Table 1).
10
MULTIVARIATE ANALYSIS
0
<24 h 24 h to 1 mo >1-6 mo >6-12 mo >12-18 mo >18-24 mo
Time Interval After Stroke Total Patient Cohort
Figure 2. Occurrence of the first seizure after stroke during set intervals.
Most seizures occurred in the first 24 hours after stroke onset. Compared with ischemic stroke, there was an almost
2-fold increased risk of seizures in patients with hemor-
rhagic stroke (hazard ratio, 1.85; 95% confidence inter-
With Seizure
Without Seizure
val, 1.26-2.73; P=.002). For the total patient cohort, those
P = .02 P = .02 with late-onset seizures were at greater risk of develop-
A P = .06
P = .03 ing epilepsy (hazard ratio, 23.77; 95% confidence inter-
95 val, 12.89-43.81; P,.001).
85
Ischemic Stroke
Canadian Neurological Score

75

65 On Cox proportional hazards analysis, risk factors for sei-

55
zures after ischemic stroke were cortical location of in-
farction and stroke disability (Table 2). Neither hem-
45
orrhagic infarction nor high embolic risk of stroke were
35 significant. The only risk factor for epilepsy (recurrent
25 seizures) was late onset (.2 weeks) of the initial sei-
zure after ischemic stroke (Table 2).
15

B
Hemorrhagic Stroke
P < .001 P = .003 P < .001
115
The only risk factor for seizures after hemorrhagic stroke
105 P = .004
was cortical location (Table 3). Neither size of intrace-
95
Canadian Neurological Score

rebral hemorrhage nor cerebrospinal fluid blood was in-

85
75
65
55
45
35
25
15
1 3
Days After Cortical Cerebral Hemorrhage
Figure 3. Disability of patients with and without seizures. The higher the
Canadian Neurological Score, the less the neurological disability. A, Cortical
cerebral infarction. Disability is greater in patients with seizure. B, Cortical
cerebral hemorrhage. Disability is less in patients with seizure. Error bars
represent SD.
Fifty-seven percent of seizures after hemorrhagic
stroke occurred in the first 24 hours (Figure 2). Early-
onset seizures (#2 weeks) occurred in 7.9% (21/265) and
late-onset seizures (.2 weeks) occurred in 2.6% (7/
265) of patients with hemorrhagic stroke. Recurrent sei-
zures (epilepsy) occurred in 100% (7/7) of patients with
late-onset seizures after hemorrhagic stroke. Partial sei-
zures (including simple partial and secondarily general-
ized seizures) accounted for 50% (14/28) of seizures.
Compared with patients with seizures after ischemic
stroke, patients with seizures after hemorrhagic stroke had
dependently associated with seizures. No independent risk
factors were identified for the development of epilepsy (re-
current seizures) after hemorrhagic stroke (Table 3).
COMMENT
Results of the SASS indicate that although 8.9% of pa-
tients with stroke experienced seizures during the study,
7 14
epilepsy was a sequela in only 2.5%. On Kaplan-Meier
analysis, patients with hemorrhagic stroke were at sig-
nificantly greater risk of seizures (20% per year) com-
pared with patients with ischemic stroke (14% per year),
particularly in the first few days after stroke onset; pro-
portional hazards analysis identified hemorrhagic stroke
as an independent risk factor for seizures. This was a pro-
spective, hospital-based study enrolling all consecutive
patients with stroke. Patients without a CT scan were ex-
cluded from the study but constituted only a small pro-
portion of the final study number.
The frequency of epilepsy as a late sequela of stroke
has been estimated previously at 3% to 10%,2 with a higher
risk after late-onset than early-onset seizures.2,12,13 In SASS,
epilepsy occurred in 2.5% of patients overall but was pres-
ent in approximately half of those with late-onset sei-
zures after ischemic stroke and in all patients with late-
onset seizures after hemorrhagic stroke. After controlling

(REPRINTED) ARCH NEUROL / VOL 57, NOV 2000 WWW.ARCHNEUROL.COM

1620

©2000 American Medical Association. All rights reserved.

Downloaded From: http://archneur.jamanetwork.com/ by a University of North Dakota User on 05/24/2015
 for other clinical variables, late-onset seizures were iden-
tified as an independent risk factor (with a 12-fold in- Table 2. Cox Proportional Hazards Analysis of Clinical
crease) only for epilepsy after ischemic stroke. Many fac- Risk Factors for Seizures After Ischemic Stroke*
tors, including patient age, disability, and risk of adverse
All First Seizures Recurrent Seizures
effects, need to be considered before administration of an-
tiepileptic medications. Variable HR (95% CI) P HR (95% CI) P
The occurrence of early and late poststroke seizures Age (per year of age) 0.99 (0.97-1.00) .14 0.99 (0.97-1.02) .64
parallels that of posttraumatic epilepsy.23 In this paradigm, Hemorrhagic 1.14 (0.62-2.12) .68 0.35 (0.08-1.54) .17
seizures in the early phase are thought to be the result of infarction
cellular biochemical dysfunction, and late-onset seizures High-risk embolic 1.00 (0.67-1.50) .99 0.68 (0.31-1.48) .33
stroke
are thought to be due to gliosis and the development of a Infarct size
meningocerebral cicatrix.23 The sequestration of hemosid- Small 0.57 (0.22-1.50) .25 0.31 (0.07-1.35) .12
erin in cortical neurons might also play a role in neurotrau- Medium 0.55 (0.19-1.60) .27 0.42 (0.11-1.58) .20
matic seizures.24 A probable cause of early seizures after Large 0.84 (0.27-2.57) .76 0.94 (0.25-3.57) .93
ischemic stroke is the extent of regional metabolic dysfunc- Cortical location 2.09 (1.19-3.68) .01 2.13 (0.60-7.53) .24
tion and excitotoxic neurotransmitter release secondary to Moderate disability 1.63 (0.97-2.75) .07 3.62 (0.82-15.86) .19
Severe disability 2.10 (1.16-3.82) .02 2.63 (0.52-13.30) .24
ischemic hypoxia. Ischemic brain tissue (the “ischemic
Late-onset seizures ... . . . 12.37 (4.74-32.32) .001
penumbra”) might contain electrically irritable tissue that
provides a focus for seizure activity in patients with ische- *HR indicates hazard ratio; CI, confidence interval.
mic stroke.25 Late-onset seizures have a similar frequency
in ischemic and hemorrhagic lesions, possibly suggesting
a nonspecific epileptogenic effect of gliotic scarring. Table 3. Cox Proportional Hazards Analysis of Clinical
Patients with seizures after ischemic stroke had larger Risk Factors for Seizures After Hemorrhagic Stroke*
cortical infarcts than those without seizures, although on
multivariate analysis only cortical location and stroke dis- All First Seizures Recurrent Seizures
ability (not infarct size or hemorrhagic transformation)
Variable HR (95% CI) P HR (95% CI) P
were independent risk factors for seizures. Although re-
sults of previous studies2,3,7,11 have suggested that sei- Age (per year of age) 1.00 (0.98-1.04) .62 1.00 (0.95-1.10) .89
zures are more common with cardioembolic cerebral in- Cisternal blood 1.15 (0.85-1.55) .38 1.00 (0.78-1.36) .83
Ventricular blood 1.00 (0.91-1.12) .86 0.94 (0.78-1.13) .49
farction, recent studies4,14,26 have questioned this. In a Cortical location 3.16 (1.35-7.40) .008 1.60 (0.35-7.17) .55
National Institute of Neurological and Communicative Dis- Hemorrhage size
orders and Stroke study27 of 1290 patients with cerebral Small 1.15 (0.40-3.25) .80 2.00 (0.32-12.74) .46
infarction, cardioembolic stroke was differentiated by a his- Medium 1.04 (0.35-3.13) .94 1.60 (0.23-10.93) .63
tory of systemic embolism, sudden clinical onset, and loss Large 0.78 (0.23-2.65) .69 0.74 (0.05-9.88) .82
of consciousness but not epileptic seizures. Moderate disability 1.25 (0.44-3.46) .68 ... ...
Severe disability 0.51 (0.17-1.53) .23 ... ...
The relation of seizures to small subcortical in-
Late-onset seizures ... ... 3.38 (0.58-19.54) .17
farcts is uncertain, with a reported seizure frequency of
0% to 23%.5,9,13,14,28,29 Seizures are considered by some as *HR indicates hazard ratio; CI, confidence interval. Neurological disability
an exclusion for lacunar stroke.20 In SASS, 8 (2.6%) of could not be used in the proportional hazards analysis of recurrent seizures
307 patients diagnosed as having lacunar stroke had sei- because of limited patient numbers in this subset.
zures. Of these, 5 had normal results on early CT but were
noted to have an electroencephalographic or single pho- conscious patients. Previous studies also reveal that large
ton emission CT result suggestive of cortical dysfunc- cerebral hemorrhages do not cause seizures, although the
tion and 2 had very late onset of their first seizures dur- associated neurological deficit is more severe,32 and sei-
ing follow-up (possibly not related to stroke). Only 1 zures are not associated with clinical deterioration in pa-
(0.7%) of 140 patients was clearly identified as having tients with cerebral hemorrhage.33
lacunae on CT imaging and poststroke seizures, but a de- What causes a cerebral hemorrhage to produce sei-
lirium precluded further investigation. zures is unclear. Seizures occurring in subarachnoid hem-
Cerebral hemorrhages giving rise to seizures were pre- orrhage relate to the amount of blood in the basal cis-
dominantly cortical in location, although one third of sei- terns,21 but our data and those of others30 reveal that neither
zures arose from deep cerebral hemorrhages, similar to pre- the amount of blood present in brain parenchyma (ie, le-
vious studies.13,30,31 There was no significant difference in sion size) nor in the cisternal and ventricular spaces seemed
overall lesion size between patients with and without sei- to affect the occurrence of seizures. A combination of the
zures. On multivariate analysis, only cortical location (not sudden development of a space-occupying lesion with mass
hemorrhage size, disability, or cerebrospinal fluid blood) effect, focal ischemia, and blood products might possibly
was identified as a risk factor for seizures. account for seizures in the early phase of hemorrhagic
In contrast to patients with seizures after ischemic stroke. Other studies31 have shown no association be-
stroke, patients with seizures after cortical hemorrhagic tween seizures and the presence of hydrocephalus, hem-
stroke had less disability than those without seizures. The orrhage size, intracranial shift, Glasgow Coma Scale score,
reasons for this are unclear but might reflect the greater level of consciousness, or degree of neurological deficit.
overall initial disability of intracerebral hemorrhage and Finally, we did not attempt to address issues of treat-
the inability to detect seizures in severely disabled or un- ment of seizures. To conduct a natural history study (ie,

(REPRINTED) ARCH NEUROL / VOL 57, NOV 2000 WWW.ARCHNEUROL.COM

1621

©2000 American Medical Association. All rights reserved.

Downloaded From: http://archneur.jamanetwork.com/ by a University of North Dakota User on 05/24/2015
 no treatment) or even a placebo-controlled trial is diffi-
cult logistically, if not unethical, because many physi-
cians will treat patients with antiepileptic drugs if sei-
zures occur.
Accepted for publication May 9, 2000.
From the Stroke Research Unit, University of Toronto,
Ontario (Drs Bladin, Alexandrov, and Norris); the Depart-
ment of Neurology, Sherbrooke University, Montreal, Que-
bec (Dr Bellavance); the Department of Neurology, Uni-
versity of Tel Aviv, Tel Aviv, Israel (Dr Bornstein); the
Department of Neurology, University of Melbourne, Mel-
bourne, Australia (Dr Chambers); the Department of Neu-
rology, McGill University, Montreal (Dr Cote); the Depart-
ment of Neurology, University of Montreal, Montreal (Dr
Lebrun); and the Department of Neurology, University of
Sassari, Sassari, Italy (Dr Pirisi). Dr Bladin is now with
the Department of Neurosciences, Box Hill Hospital, Mel-
bourne, and Dr Alexandrov is now with the Department of
Neurology, University of Texas–Houston Medical School.
We thank the following personnel who assisted in the
collection and processing of data for the SASS Group: Sun-
nybrook Health Science Centre, Toronto, Ontario: Phil-
ippa Johnston, MSc; Beverly Bowyer, RN; Lilliana Smu-
rawska, MD; Natasha Alexandrova, MD; Alastair Dempster;
and Marietta Medel, MD; Hôpital Charles LeMoyne, Mon-
treal, Quebec: Louise Bergeron, RN (research assistant); Mon-
treal General Hospital, Montreal: Lisa Wadup and Susan
Joseph, RN; Hôpital St Luc, Montreal: Marie-Paule Des-
rochers, RN, BSc; Ichilov Hospital, Tel Aviv, Israel: Vadim
Karepov, MD; Austin and Repatriation Medical Centre, Mel-
bourne, Australia: Kim Sukhong, RN; Peter Brimage, FRACP;
and Lichun Quang; and Istituto di Clinica Neurologica,
Sassari, Italy: Marco Zuddas, MD; Maria A. Spanu, MD;
Caterina Fiori, MD; Giacomo Murino, MD; Franco Bandiera,
MD; Luisa Pes, MD; and Francesco Flumene MD.
The SASS Group investigators at each participating hos-
pital are as follows: Sunnybrook Health Science Centre: Chris-
topher F. Bladin, MD, FRACP; Andrei V. Alexandrov, MD;
John W. Norris, MD; and Sandra Black, MD (Stroke Re-
search Unit, University of Toronto [coordinating center]); Hô-
pital Charles LeMoyne: André Bellavance, MD, PhD (Sher-
brooke University, Montreal); Ichilov Hospital: Natan
Bornstein, MD (University of Tel Aviv); Austin and Repa-
triation Medical Centre: Brian Chambers, MD (University
of Melbourne); Montreal General Hospital: Robert Coté, MD,
and Arienne McKay, MD (McGill University, Montreal); Hô-
pital St Luc: Louise Lebrun, MD (University of Montreal);
Istituto di Clinica Neurologica: Angelo Pirisi, MD (Univer-
sity of Sassari); Statistics: Marco Katic and John Szalai, PhD
(University of Toronto); and LiChun Quang (Austin and Re-
patriation Medical Centre, University of Melbourne).
Reprints: Christopher F. Bladin, MD, FRACP, Depart-
ment of Neuroscience, Box Hill Hospital, Nelson Road, Box
Hill 3128, Melbourne, Australia.
(REPRINTED) ARCH NEUROL / VOL 57, NOV 2000
1622
©2000 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a University of North Dakota User on 05/24/2015
REFERENCES
1. Hauser WA. Seizure disorders. Epilepsia. 1992;33(suppl 4):S6-S14.
2. Lesser RP, Luders H, Dinner DS, Morris HH. Epileptic seizures due to throm-
botic and embolic cerebrovascular disease in older patients. Epilepsia. 1985;26:
622-630.
3. So EL, Annegers JF, Hauser WA, O’Brien PC, Whisnant JP. Population-based study
of seizure disorders after cerebral infarction. Neurology. 1996;46:350-355.
4. Kilpatrick CJ, Davis SM, Tress BM, Rossiter SC, Hopper JL, Vandendriesen ML.
Epileptic seizures in acute stroke. Arch Neurol. 1990;47:157-160.
5. Shinton RA, Gill JS, Melnick AK. The frequency, characteristics, and prognosis
of epileptic seizures at the onset of stroke. J Neurol Neurosurg Psychiatry. 1988;
51:273-276.
6. Arboix A, Garcia-Eroles L, Massons JB, Oliveres M, Comes E. Predictive factors
of early seizures after acute cerebrovascular disease. Stroke. 1997;28:1590-1594.
7. Reith J, Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. Seizures in acute
stroke: the Copenhagen Stroke Study. Stroke. 1997;28:1585-1589.
8. Giroud M, Gras P, Fayolle H, André N, Soichot P, Dumas R. Early seizures after
stroke: a study of 1,640 cases. Epilepsia. 1994;35:959-964.
9. Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Epileptic sei-
zures after a first stroke: the Oxfordshire Community Project. BMJ. 1997;315:
1582-1587.
10. Sung CY, Chu NS. Epileptic seizures in intracerebral haemorrhage. J Neurol Neu-
rosurg Psychiatry. 1989;52:1273-1276.
11. Meyer JS, Charney JZ, Rivera VM, Mathew NT. Cerebral embolization: prospec-
tive clinical analysis of 42 cases. Stroke. 1971;2:541-553.
12. Hornig CR, Buttner T, Hufnagel A, Schrider-Rosenstock K, Dorndorf W. Epilep-
tic seizures following ischemic cerebral infarction: clinical picture, CT findings,
and prognosis. Eur Arch Psychiatry Neurol Sci. 1990;239:379-383.
13. Sung CY, Chu N. Epileptic seizures in thrombotic stroke. J Neurol. 1990;237:
166-170.
14. Davalos A, de Cendra E, Molins A, Ferrandiz M, Lopez-Pouza S, Genis D. Epi-
leptic seizures at the onset of stroke. Cerebrovasc Dis. 1992;2:327-331.
15. Black SE, Norris JW, Hachinski VC. Post-stroke seizures [abstract]. Stroke. 1983;
14:134.
16. Commission on Classification and Terminology of the International League Against
Epilepsy. Proposal for revised clinical and electroencephalographic classifica-
tion of epileptic seizures. Epilepsia. 1981;22:489-501.
17. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked sei-
zures in Rochester, Minnesota: 1935-1984. Epilepsia. 1993;34:453-468.
18. Cote R, Battista RN, Wolfson C, Boucher J, Adam J, Hachinski VC. The Canadian
Neurological Scale. Neurology. 1989;39:638-643.
19. Norris JW, Zhu CZ. Transcranial Doppler: a new test for cerebral embolism? In:
Yao JST, Pearce WH, eds. Technologies in Vascular Surgery. Philadelphia, Pa:
WB Saunders Co; 1992:166-170.
20. Fisher CM. Lacunar strokes and infarcts: a review. Neurology. 1982;32:871-876.
21. Brouwers PJAM, Dippel DWJ, Vermeulen M, Lindsay KW, Hasan D, van Gijn J.
Amount of blood on computed tomography as an independent predictor after
aneurysm rupture. Stroke. 1993;24:809-814.
22. Alexandrov AV, Ehrlich LE, Bladin CF, Norris JW. Cerebral Perfusion Index: a new
marker for clinical outcome in acute stroke. J Neuroimaging. 1993;3:209-215.
23. Jennett B. Posttraumatic epilepsy. Adv Neurol. 1979;22:137-147.
24. Willmore LJ. Post-traumatic seizures. Neurol Clin. 1993;11:823-834.
25. Heiss WD, Huber M, Fink GR, et al. Progressive derangement of periinfarct vi-
able tissue in ischemic stroke. J Cereb Blood Flow Metab. 1992;12:193-203.
26. Ramirez-Lassepas M, Cipolle RJ, Bjork RJ, et al. Can embolic stroke be diag-
nosed on the basis of clinical criteria? Arch Neurol. 1987;44:87-89.
27. Kittner SJ, Sharkness CM, Price TR, et al. Infarcts with a cardiac source of em-
bolism in the NINCDS Stroke Data Bank: historical features. Neurology. 1990;
40:281-284.
28. Shorvon SD, Gilliatt RW, Cox TCS, Yu YL. Evidence of vascular disease from CT
scanning in late onset epilepsy. J Neurol Neurosurg Psychiatry. 1984;47:225-230.
29. Roberts RC, Shorvon SD, Cox TCS, Gilliatt RW. Clinically unsuspected cerebral
infarction revealed by computed tomography scanning in late onset epilepsy. Epi-
lepsia. 1988;29:190-194.
30. Weisberg LA, Morteza S, Elliott D. Seizures caused by nontraumatic parenchy-
mal brain hemorrhages. Neurology. 1991;41:1197-1199.
31. Berger AR, Lipton RB, Lesser ML, Lantos G, Portenoy RK. Early seizures following
intracerebral hemorrhage: implications for therapy. Neurology. 1988;38:1363-1365.
32. Faught E, Peters D, Bartolucci A, Moore L, Miller PC. Seizures after primary in-
tracerebral hemorrhage. Neurology. 1989;39:1089-1093.
33. Mayer SA, Sacco RL, Shi T, Mohr JP. Neurologic deterioration in noncomatose
patients with supratentorial intracerebral hemorrhage. Neurology. 1994;44:1379-
1384.
WWW.ARCHNEUROL.COM