| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2001;32:1169.)
© 2001 American Heart Association, Inc.
Original Contributions |
Status Epilepticus After Stroke
lu, MDlu, MDlu, MDFrom Karadeniz Technical University, Medical Faculty, Neurology Department, Trabzon, Turkey.
Correspondence to Sibel K. Veliolu, Neurology Department, Karadeniz Technical University, Medical Faculty, Trabzon, Turkey. E-mail sveli{at}meds.ktu.edu.tr
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Background and Purpose—The main objective of our study was to determine the risk and predictive factors of status epilepticus (SE) after stroke.
Methods—From 1988 to 2000, 1174 patients were admitted to the Department of Neurology at the Karadeniz Technical University Farabi Hospital with first-time strokes. Of these, 180 patients had poststroke first-time seizures (PFSs). We followed these 180 PFS patients for an average of 3.7 years or until death to determine the occurrence rate of SE. By comparing these data with those of PFS patients without SE, we investigated whether there were significant differences.
Results—A total of 17 of the 180 PFS patients (9%) had SE. There was no relationship between the occurrence of SE and stroke risk factors, stroke type (ischemic or hemorrhagic stroke), stroke topography and cause, cortical involvement, size of lesion, seizure type, or electroencephalographic findings. SE occurred more frequently among patients with a higher disability rating (Rankin scale >3; odds ratio, 4.36). Recurrent SE was identified in 5 of 17 patients with SE. In all 5 of these patients, the first episode of SE occurred within the first 7 days after stroke (early-onset SE). Statistical analysis demonstrated that early-onset SE was associated with a higher risk for SE recurrence (P=0.003) and a higher mortality rate (P=0.04).
Conclusions—SE was not associated with a higher mortality rate but with higher functional disability. We also found that early-onset SE (within the first 7 days after stroke) was associated with a higher risk for SE recurrence and a higher mortality rate than late-onset SE (after 7 days after stroke).
Key Words: epilepsy • seizures • stroke outcome • stroke, acute
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Status epilepticus (SE) is defined as a seizure or a series of repetitive seizures without recovery between episodes that lasts >30 minutes. The role of stroke as an etiologic factor for SE is accepted.1 2 Although the occurrence of epileptic seizures complicating acute stroke is well recognized, SE has received little attention.3 4 5 6 Few studies on clinic data or prognosis are available.2 7 8
Using a hospital-based stroke cohort, we studied a series of patients with poststroke first-time seizure (PFS) to find out which factors may be associated with SE.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Included in this study were 1676 stroke patients without an accompanying diagnosis of brain tumor or arteriovenous malformation who were admitted consecutively to the Department of Neurology of Karadeniz Technical University Farabi Hospital (an acute-care, 492-bed hospital in Trabzon, Turkey) between February 1988 and January 2000. A retrospective chart review was performed. We excluded patients with a history of seizure, subarachnoid hemorrhage, head injury, hypertensive encephalopathy, and cerebrovenous thrombosis. We included only patients with first-time ischemic strokes and primary intracerebral hemorrhages. After these restrictions, a study population of 1174 patients with first-time stroke was defined. All patients were admitted to the hospital within the first 3 days of onset of symptoms. There were 161 patients with transient ischemic attack who had no seizures. One hundred eighty patients had a PFS; 17 of these patients had SE.
All patients with PFS had a cerebral computed tomography (CT) scan and electroencephalography (EEG). The patients with lesions that could not be identified from CT as cortical or subcortical also had magnetic resonance imaging (MRI). In all patients, plasma urea, creatinine, electrolyte, and plasma glucose levels were measured on admission. Overall, 72% of patients were studied by MRI. Other investigations included arterial digital subtraction angiography in 24%, duplex ultrasound of the carotid arteries in 42%, and echocardiography in 82%. The degree of functional disability at the end of the acute phase was graded by a modified Rankin scale.9 Seizures were diagnosed and classified according to the definitions of the International League Against Epilepsy.10 11 SE was defined as a seizure or a series of continuing seizures lasting >30 minutes without full recovery between seizures.12 Unprovoked seizures refer to seizures that occurred without identifiable acute precipitants. "Early" referred to seizures and SE occurring within 1 week after stroke that were considered to be provoked by the stroke. Unprovoked seizures and SE developing beyond 1 week after stroke were called "late." The diagnosis was based on direct observation of seizures by the medical staff at the time of hospitalization or on the history of the neurologist in charge of the patient or was determined according to reliable descriptions obtained from ambulance personnel when seizures occurred during transportation or from the patients or close family members when seizures occurred at home. EEG was performed 24 to 48 hours after the seizures in all PFS patients. EEGs were considered abnormal when focal, lateralized, or generalized slowing or epileptiform discharges were present. All hospital and outpatient records since the stroke were reviewed. Survivors were contacted by telephone or in person in 1998 and again in 2000. Follow-up data were evaluated for a mean of 3.7 years.
The size of the lesion imaged on the cerebral CT scan was
measured in 17 patients with SE. Lesion size was compared with a group
of 163 stroke patients with cerebral infarction and
intracerebral hemorrhage without SE to
determine whether there was an association between SE occurrence and
lesion size and between SE occurrence and cerebral cortex involvement
(cortical or subcortical). Lesions were classified as 
10 mm and
<5 slices or as >10 mm and 5 slices or complete vascular
territory. The term "cortical" referred to lesions that were
cortical or corticosubcortical (partial or total involvement of the
supratentorial arterial territories),
and "subcortical" referred to lesions that were exclusively
subcortical.
Univariate analysis for each
variable was made with the Student
t test for continuous
variables and the 
2 test (with
Yates’ correction when necessary) for categorical variables.
Statistical significance was set at
P<0.05. Variables were
subjected to multivariate analysis with a
logistic regression procedure and forward stepwise selection if
P<0.10 after
univariate testing. The level of significance to remain in
the model was 0.15. The independent predictive value of each
variable on SE and mortality was analyzed in 2 predictive
models based on demographic (sex and age), clinical (functional
disability and SE on mortality and functional disability on SE), and
neuroimaging (type of stroke, size and localization of lesion)
variables, with a total of 6 in the first model (on SE) and 7 in
second model (on mortality). Odds ratios (ORs) and 95% confidence
intervals were calculated from the ß coefficients and standard
errors. The hypothesis that the logistic model adequately fit the data
was tested by means of the goodness-of-fit
2
test.13
We studied stroke type and cause, stroke risk factors, cerebral cortex involvement, size of lesion, and functional disability in PFS patients, and then we studied type of seizure and SE, time of onset and recurrence of SE, EEG findings, and the number of deaths in follow-up period. We also compared the characteristics of 17 patients with SE (group 1) and 163 patients with PFS without SE (group 2).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Among 1174 hospitalized first-time stroke patients (mean age, 59.7 years; range, 17 to 103 years; 681 men, 493 women), 180 (15%) experienced a PFS. Of the 180 PFS patients (mean age, 62.2 years; range, 41 to 85 years; 88 men, 92 women), 17 (%9) developed SE. Of the 180 PFS patients, 121 (67%) had ischemic stroke and 59 (33%) had an intracranial hemorrhage. Approximately one half of the patients with SE (53%; 9 of 17) had SE manifested by seizures classified as generalized in onset, and the remainder (47%; 8 of 17) had seizures that were partial in onset.
No difference was noted between PFS patients with (group 1,
n=17) and without (group 2, n=163) SE for sex, age, stroke risk
factors, seizure types, and EEG findings
(Table 1
). The presence of SE was not associated
with stroke type, cause, topography, cortical involvement, or size of
lesion
(Table 1). However, SE occurred more frequently among the
most disabled patients (Rankin scale >3,
P=0.002;
Table 1).
|
In 7 of 17 patients with SE, SE occurred within the
first 7 days after stroke (early onset;
Table 2). Of these 7 patients, SE occurred as the
first epileptic symptom in 6 patients (In 2 of these 6 patients, stroke
began with SE); in 1 patient, 
1 seizure occurred before SE. In 10
patients, SE occurred >7 days after stroke (late onset). In 3 of these
10 patients, SE occurred as the first epileptic symptom. Stroke risk
factors, stroke type, and functional disability of SE patients were not
significantly different in patients with early- or late-onset SE
(Table 2) .
|
Recurrent SE occurred in 5 of 17 patients with SE
(Table 3). In 5 of 7 patients with early-onset SE,
recurrent SE occurred. However, none of the 10 patients with late-onset
SE experienced recurrent SE. Stroke type and functional disability did
not have a significant role in the recurrence of SE.
Statistical analyses demonstrated that early-onset SE was
associated with a higher risk for additional SE occurrence
(P=0.003;
Table 3).
|
Nine of the 17 patients with SE and 81 of the 163 patients
without SE died, with an overall 50% mortality in patients with PFS
(Table 4). Two patients in group 1 and 24 in group 2
died within the first month after the stroke
(Table 4). In group 1, death was a direct consequence of SE
in 2 patients (who died during the first month after stroke), was
attributed to cardiovascular disease in 5 patients, and
was due to unrelated causes in 2 patients. In group 2, death was
related to seizures in 10 patients, 38 deaths were caused by
cardiovascular disease, and 33 deaths were from
unrelated causes. There was no significant difference in mortality rate
between those patients with and those without SE
(Table 4). However, the mortality rate of patients with
early-onset SE was higher than in patients with late-onset SE
(Table 4).
|
After multivariate analysis
(Table 5), only poor functional disability (OR=4.36)
appeared to be an independent clinical factor for developing SE
(goodness-of-fit 2=11.502;
df=6;
P=0.0741), and only age
(OR=1.06) appeared to be an independent factor for mortality
(goodness-of-fit 2=20.419;
df=6;
P=0.0047).
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Changes in cerebral blood flow, hypoxia, involvement of the cerebral cortex by hemorrhage or infarct, and development of epileptogenic changes in cortical neurons, their connections, or their environment have been proposed as potential mechanisms underlying seizures in patients with stroke.14 15 16 In this retrospective series of 1174 patients with stroke, PFS occurred in 15%. Of the patients with PFS, 9% had SE. Many authors have examined seizure disorders after stroke, but few have noted the interaction between SE and stroke.2 7 The incidence of SE after stroke either is low or is not cited at all in some reports.1 2 3 4 5 17 18 19 20 Three studies reported the rate of SE as 19%, 17%, and 14%.7 21 22 We found that SE occurred in 9% of all patients admitted for a PFS to our Neurology Department.
In this study, there was no relationship between the occurrence of SE and sex, age, stroke risk factors, stroke type (ischemic or hemorrhagic), stroke topography and cause, cortical involvement, or size of lesion in patients with PFS. Comparisons across studies are difficult because many authors have examined the possible etiologies of SE in large series, but only a few have noted the interaction between etiologic factors and SE in poststroke SE patients.7 Rumbach et al,7 in a study of 159 patients with PFS, also found no relationship between SE occurrence and risk factors and stroke type. In our series, neither seizure types, such as generalized or partial onset, nor EEG findings of SE patients were significantly different from those of patients without SE.
Consistent with a prior report, we found that SE was associated with poor functional disability score.7 Patients with SE have poorer functional disability than those without SE.
We found that in 59% of patients with SE (10 of 17), SE occurred 7 days after stroke onset; 5 of the 17 SE patients had recurrent SE. In all patients with recurrent SE, the first episode of SE occurred within the first 7 days after stroke (early-onset SE). In the univariate analysis, we showed that recurrent SE is significantly more likely in patients with early-onset SE.
Our study revealed no significant difference in mortality rate and cause of death among PFS patients with and without SE; a similar finding was reported by Rumbach et al.7 In this study, death was directly related to SE in 2 of 17 patients with SE (12%; the remaining 7 deaths were related to other causes), which was similar to findings by Rumbach et al (16%).7 A mortality rate of 23.3% among patients with SE secondary to all causes was reported in 1 study; this rate was even higher among patients with cerebrovascular disease.23 Our findings also have shown that early onset of SE after stroke (within 7 days after stroke) is associated with a higher mortality rate than late-onset SE in univariate analysis. Arboix et al24 25 showed that seizures at the onset of a first-ever stroke were an independent prognostic factor for in-hospital mortality and that cortical involvement and agitated acute confusional state at the onset of stroke were independent predictive factors of early seizures in first-ever stroke patients. This study reviews the incidence of SE in the stroke population and focuses on patients without a history of epilepsy or seizures who present with SE or seizures for the first time after an acute stroke. The retrospective design of this study is an important limitation.
Data from this group of patients permit the following statements. First, the incidence of SE in patients with PFS was 9%. Second, on the basis of results of the multivariate analysis, there was no relationship between the SE occurrence and stroke risk factors, stroke type (infarction or hemorrhage), stroke topography and cause, cortical involvement, size of lesion, seizure type, or EEG findings, and the mortality rate for PFS patients with SE was not significantly different from that of patients without SE. Third, on the basis of results of the multivariate analysis, the only identified predictor of SE was poor functional disability, and we also concluded that age at a first-ever stroke is an independent prognostic factor for mortality. Finally, early-onset SE was associated with a higher risk for SE recurrence and with a higher mortality rate than late-onset SE in the univariate analysis.
|
Acknowledgments |
|---|
We thank Gamze Çan, MD, Department of Public Health, Karadeniz Technical University, Medical Faculty, Trabzon, Turkey, for her assistance with the analysis of the data.
Received October 30, 2000; revision received January 29, 2001; accepted February 2, 2001.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
- Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology. 1993;43:483–488.
-
Barry E, Hauser WA.
Status epilepticus: the interaction of epilepsy and acute brain
disease. Neurology. 1993;43:1473–1478.
[Abstract/Free Full Text] - Kilpatrick CJ, Davis SM, Tress BM, Rossiter SC, Hopper JL, Vandendriesen ML. Epileptic seizures in acute stroke. Arch Neurol. 1990;47:157–160.[Abstract]
-
Faught E, Peters D,
Bartolucci A, Moore L, Miller PC. Seizures after primary
intracerebral hemorrhage.
Neurology. 1989;39:1089–1093.
[Abstract/Free Full Text] - Kilpatrick CJ, Davis SM, Hopper JL, Rossiter SC. Early seizures after acute stroke. Arch Neurol. 1992;49:509–511.[Abstract]
- Pohlman-Eden B, Hoch DB, Cochius JI, Hennerici MG. Stroke and epilepsy: critical review of the literature, I: epidemiology and risk factors. Cerebrovasc Dis. 1996;6:332–338.
-
Rumbach L, Sablot
D, Berger E, Tatu L, Vuillier F, Moulin T. Status epilepticus in
stroke: report on a hospital-based stroke cohort.
Neurology. 2000;54:350–354.
[Abstract/Free Full Text] -
Krumholz A, Sung
GY, Fisher RS Barry E, Bergey GK, Grattan LM. Complex partial status
epilepticus accompanied by serious morbidity and mortality.
Neurology. 1995;45:1499–1504.
[Abstract/Free Full Text] - Moulin T, Tatu L, Crepin-Leblond T, Chavot D, Berges S, Rumbach L. The Besancon Stroke Registry: an acute stroke registry of 2,500 consecutive patients. Eur Neurol. 1997;38:10–20.[Medline] [Order article via Infotrieve]
- Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia. 1981;2:489–501.
- Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30:389–399.[Medline] [Order article via Infotrieve]
- Celesia GG. Modern concepts of status epilepticus. JAMA. 1976;235:1571–1574.[Abstract]
- Hosmer DW, Lemeshow S. Applied Logistic Regression. New York, NY: John Wiley & Sons; 1989:25–37.
- Armon C, Radtke RA, Massey EW. Therapy of seizures associated with stroke. Clin Neuropharmacol. 1991;14:17–27.[Medline] [Order article via Infotrieve]
-
Gupta SR, Naheedy
MH, Elias D, Rubino FA. Postinfarction seizures: a clinical study.
Stroke. 1988;19:1477–1481.
[Abstract/Free Full Text] - DeCarolis P, D’Alessandro R, Ferrara R, Andreoli A, Sacquegna T, Lugaresi E. Late seizures in patients with internal carotid and middle cerebral artery occlusive disease following ischemic events. J Neurol Neurosurg Psychiatry. 1984;47:1345–1347.[Abstract]
-
Weisberg LA,
Shamsnia M, Elliott D. Seizures caused by nontraumatic parenchymal
brain hemorrhages.
Neurology. 1991;41:1197–1199.
[Abstract/Free Full Text] -
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.
[Abstract/Free Full Text] - Bogousslavsky J, Martin R, Regli F, Despland P-A, Bolyn S. Persistent worsening of stroke sequelae after delayed seizures. Arch Neurol. 1992;49:385–388.[Abstract]
-
Reith J,
Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Seizures in acute
stroke: predictors and prognostic significance: the Copenhagen Stroke
Study. Stroke. 1997;28:1585–1589.
[Abstract/Free Full Text] - Sung CY, Chu NS. Epileptic seizures in intracerebral haemorrhage. J Neurol Neurosurg Psychiatry. 1989;52:1273–1276.[Abstract]
- Milandre L, Broca P, Sambuc R, Khalil R. Les crises epileptiques au cours et au decours des accidents cerebrovasculaires: aanalyse clinique de 78 cas [in French]. Rev Neurol. 1992;148:767–772.[Medline] [Order article via Infotrieve]
- Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in status epilepticus. Epilepsia. 1994;35:27–34.[Medline] [Order article via Infotrieve]
-
Arboix A, Comes
E, Massons J, Garcia L, Oliveres M. Relevance of early seizures for
in-hospital mortality in acute cerebrovascular disease.
Neurology. 1996;47:1429–1435.
[Abstract/Free Full Text] -
Arboix A,
Garcia-Eroles L, Juan B, Massons JB, Oliveres M, Comes E. Predictive
factors of early seizures after acute cerebrovascular disease.
Stroke. 1997;28:1590–1594.
[Abstract/Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  P. Ryvlin, A. Montavont, and N. Nighoghossian Optimizing therapy of seizures in stroke patients Neurology, December 26, 2006; 67(12_suppl_4): S3 - S9. [Abstract] [Full Text]
|
|
|
|
 |
|
 R Nandhagopal Generalised convulsive status epilepticus: an overview Postgrad. Med. J., November 1, 2006; 82(973): 723 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P K Myint, E F A Staufenberg, and K Sabanathan Post-stroke seizure and post-stroke epilepsy. Postgrad. Med. J., September 1, 2006; 82(971): 568 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Camilo and L. B. Goldstein Seizures and Epilepsy After Ischemic Stroke Stroke, July 1, 2004; 35(7): 1769 - 1775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. E. Silverman, L. Restrepo, and G. C. Mathews Poststroke Seizures Arch Neurol, February 1, 2002; 59(2): 195 - 201. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||