NEUROLOGICAL REVIEW

SECTION EDITOR: DAVID E. PLEASURE, MD

Poststroke Seizures
Isaac E. Silverman, MD; Lucas Restrepo, MD; Gregory C. Mathews, MD, PhD

S
troke is the most common cause of seizures in the elderly, and seizures are among the most
common neurologic sequelae of stroke. About 10% of all stroke patients experience sei-
zures, from stroke onset until several years later. This review discusses current understand-
ing of the epidemiology, pathogenesis, classification, clinical manifestations, diagnostic stud-
ies, differential diagnosis, and management issues of seizures associated with various cerebrovascular
lesions, with a focus on anticonvulsant use in the elderly. Arch Neurol. 2002;59:195-202

EPIDEMIOLOGY Bladin et al2 found the incidence of sei-

In population studies, stroke is the most
commonly identified cause of epilepsy in
adult populations older than 35 years.1 In
the elderly, stroke accounts for more than
half of the newly diagnosed cases of epi-
lepsy in which a cause is determined, ahead
of degenerative disorders, brain tumors, and
head trauma.1 From stroke registry data,
about 5% to 20% of all individuals who have
a stroke will have subsequent seizures,2,3 but
epilepsy (recurrent seizures) will develop
in only a small subset of this group. Given
that, in each year, more than 730000 people
in this country have a stroke, a conserva-
tive incidence of seizures after stroke is about
36500 new cases per year.
The largest and most rigorous meth-
odological attempt to examine poststroke
seizures was the prospective multicenter re-
port from the Seizures After Stroke Study
Group.2 The study enrolled 1897 patients
and found an overall incidence of seizures
of 8.9%. Recurrent seizures consistent with
the development of epilepsy were rare, oc-
curring in 2.5% of the patients, but the mean
follow-up was only 9 months.
Seizures may be a more common ac-
companiment of hemorrhagic rather than
ischemic stroke.
From The Stroke Center at Hartford Hospital, Hartford, Conn (Dr Silverman); the
Cerebrovascular Program (Dr Restrepo) and The Johns Hopkins Epilepsy Center
(Dr Mathews), Department of Neurology, The Johns Hopkins University School of
Medicine, Baltimore, Md; and the Synaptic Physiology Unit, National Institute of
Neurological Disorders and Stroke, Bethesda, Md (Dr Mathews).
zures to be 10.6% among 265 patients with
intracerebral hemorrhage vs 8.6% among
1632 with ischemic stroke. In another
prospective series,4 seizures occurred in
4.4% of 1000 patients, including 15.4% with
lobar or extensive intracerebral hemor-
rhage, 8.5% with subarachnoid hemor-
rhage, 6.5% with cortical infarction, and
3.7% with hemispheric transient ischemic
attacks. A seizure was the presenting fea-
ture of intracranial hemorrhage in 30% of
1402 patients.5 Among 95 patients with an-
eurysmal subarachnoid hemorrhage, the
incidence rate of prehospital seizures was
higher (17.9%) than that occurring in the
hospital (4.1%).6
CLASSIFICATION AND
PATHOGENESIS
Seizures after stroke are classified as early
or late onset, according to their timing af-
ter brain ischemia, in a paradigm compa-
rable to post-traumatic epilepsy.2,7 An
arbitrary cut point of 2 weeks after the pre-
senting stroke has been recognized to dis-
tinguish between early- and late-onset
poststroke seizures.5,8,9 Different charac-
teristics and mechanisms of poststroke sei-
zures, according to their proximity to the
onset of brain ischemia, have been pro-
posed, but no clear pathophysiological
basis exists for the 2-week cut point.
Most early-onset seizures occur dur-
ing the first 1 to 2 days after ischemia. Al-

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 most half (43%) of all patients in the Stroke After Sei-
zures Study experienced a seizure within the first 24 hours
after stroke.2 In a series restricted to early-onset sei-
zures, 90% of the 30 patients had ictal activity within the
first 24 hours.10 Most seizures associated with hemor-
rhagic stroke also occur at onset or within the first 24
hours.11
During acute ischemic injury, accumulation of in-
tracellular calcium and sodium may result in depolar-
ization of the transmembrane potential and other calcium-
mediated effects. These local ionic shifts may lower the
seizure threshold.2,12 Glutamate excitotoxicity is a well-
established mechanism of cell death in the experimen-
tal stroke model. Antiglutamatergic drugs may also have
a neuroprotective role in ischemic settings, aside from
the role of treating seizures.
The size of regional metabolic dysfunction may also
be relevant in causing early-onset seizures. In the setting
of large regions of ischemic hypoxia, high levels of exci-
totoxic neurotransmitters may be released extracellu-
larly. In studies of the postischemic brain in experimen-
tal animal models, neuronal populations in the neocortex13
and hippocampus14 have altered membrane properties and
increased excitability, which presumably lower the thresh-
old for seizure initiation. The ischemic penumbra, a re-
gion of viable tissue adjacent to the infarcted core in is-
chemic stroke, contains electrically irritable tissue that may
be a focus for seizure activity.
In addition to focal ischemia, global hypoperfusion
can cause seizure activity. Hypoxic-ischemic encepha-
lopathy is one of the most common causes of status epi-
lepticus and carries a poor prognosis. Particularly vul-
nerable to ischemic insult is the hippocampus, which is
an especially epileptogenic area.
In late-onset seizures, by contrast, persistent changes
in neuronal excitability occur. Replacement of healthy
cell parenchyma by neuroglia and immune cells may play
a role in maintaining these changes. A gliotic scarring has
been implicated as the nidus for late-onset seizures, just
as the meningocerebral cicatrix may be responsible for
late-onset post-traumatic epilepsy.2
An underlying permanent lesion appears to ex-
plain the higher frequency of epilepsy in patients with
late- than early-onset seizures. As in post-traumatic epi-
lepsy,15 late occurrence of a first seizure appears to carry
a higher risk for epilepsy. In patients with ischemic stroke,
epilepsy developed in 35% of patients with early-onset
seizures and in 90% of patients with late-onset sei-
zures.16 The risk for epilepsy was comparable in pa-
tients with hemorrhagic stroke; epilepsy developed in 29%
of patients with early-onset seizures vs 93% with late-
onset seizures.5
The concept that cardiogenic emboli to the brain are
more likely to cause seizures acutely is controversial, with
few supporting data. Among 1640 patients with cere-
bral ischemia,17 events attributed to a cardiac source were
most commonly associated with early-onset seizures
(16.6%), even compared with supratentorial hemato-
mas (16.2%). However, the definition of cardiogenic
mechanism in this series was often based on nonspe-
cific criteria. Several authors have questioned the asso-
ciation of seizures with cardioembolic events.3,4 Sei-
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zures at onset were not a criterion in a data bank study
of the cardiac causes of stroke.18 Intuitively, there is no
reason to suspect that cardioembolic lesions would be
more likely than emboli from large-vessel sources to cause
seizures, as cardiac and large-vessel emboli frequently in-
volve lesions to distal cortical branches. The mecha-
nism by which cortical emboli precipitate seizures is un-
certain,12 but possibilities include depolarization within
an ischemic penumbra, rapid reperfusion after the frag-
mentation and distal migration of the embolus,19 or a com-
bination of both.
Cortical location is among the most reliable risk fac-
tors for poststroke seizures.2 Poststroke seizures were more
likely to develop in patients with larger lesions involv-
ing multiple lobes of the brain than in those with single
lobar involvement.20 However, any stroke, including those
with only subcortical involvement, may occasionally be
associated with seizures.20 Earlier studies, relying on less
sensitive neuroimaging techniques, may not have de-
tected concomitant small cortical lesions that could cause
ictal activity. The mechanism by which deep hemi-
spheric subcortical lesions, most commonly due to small-
vessel disease, cause seizures is not understood.2
Analogous to cortical involvement in ischemic stroke,
a lobar site is considered to be the most epileptogenic lo-
cation in patients with intracerebral hemorrhage. In a se-
ries of 123 patients,21 seizure incidence was highest with
bleeding into lobar cortical structures (54%), low with
basal ganglionic hemorrhage (19%), and absent with tha-
lamic hemorrhage. Caudate involvement of the basal gan-
glia and temporal or parietal involvement within the cor-
tex predicted seizures.21 Hemorrhage due to cerebral
venous thrombosis also commonly presents with sei-
zures. Parenchymal, often cortical, hemorrhage result-
ing from local venous congestion is the likely cause of
seizure activity.
The mechanism of seizure initiation by hemorrhage
is not established. Products of blood metabolism, such as
hemosiderin, may cause a focal cerebral irritation leading
to seizures, analogous to the animal model of focal epi-
lepsy produced by iron deposition on the cerebral cor-
tex.22 In subarachnoid hemorrhage, there is often exten-
sive hemorrhage into the basal cisterns, which directly
contacts the frontal and temporal lobes. Patients with sub-
arachnoid hemorrhage also may have an intraparenchy-
mal component to the hemorrhage (Figure 1).
The only clinical predictor for seizures after ische-
mic stroke is the severity of the initial neurologic deficit.
Greater initial stroke severity9 or stroke disability2 pre-
dicted seizures. By contrast, in the Oxfordshire Commu-
nity Stroke Project, only 3% of 225 patients who were in-
dependent 1 month after a stroke experienced a seizure
between 1 month and 5 years.23 Patients presenting with
greater neurologic impairment tend to have larger strokes
that involve wider cortical areas.
In retrospective studies, risk factors for seizures af-
ter subarachnoid hemorrhage included middle cerebral
artery aneurysms,24 intraparenchymal hematoma,25 ce-
rebral infarction,26 a history of hypertension,27 and thick-
ness of the cisternal clot.6 By contrast, clinical predic-
tors for seizures after intraparenchymal hemorrhage have
been lacking.2
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 A B

Facility = Yale–New Haven Hospital Clinic = EEG Laboratory

C
Fp1 F7
F7 T7(T3)
T7 P7(T5)
P7 O1
Fp1 F3
F3 C3
C3 P3
P3 O1
FZ CZ
CZ PZ
PZ OZ (Ref)
Fp2 F4
F4 C4
C4 P4
P4 O2
Fp2 F8
F8 T8(T4)
T8 P8(T6)
P8 O2

Figure 1. Seizures after intracerebral and subarachnoid hemorrhage. An 82-year-old woman presented with sudden-onset headache, dysphasia, and right
hemiparesis while receiving anticoagulation therapy for chronic atrial fibrillation. Computed tomographic (CT) scan at admission (A) demonstrates an acute left
temporal lobe intraparenchymal hematoma, with adjacent subdural and subarachnoid hemorrhage. The responsible lesion, an aneurysm of the middle cerebral
artery, was treated surgically. During the postoperative period, she had episodes of right-sided facial twitching associated with transient worsening of her aphasia.
A postoperative CT scan 3 months later (B) showed a hypodense lesion of the midtemporal lobe in the middle cranial fossa. Electroencephalographic (EEG)
findings (C) demonstrated focal spike waves, consistent with seizure activity, followed by focal slowing and periodic lateralizing epileptiform discharge in the left
hemisphere. Ref indicates reference.

Vascular lesions may cause seizures by other mecha-
nisms. Seizures due to arteriovenous malformations and
aneurysms typically occur when these lesions rupture,
but these vascular lesions may cause seizures by di-
rectly irritating adjacent brain parenchyma (Figure 2).
Finally, seizures associated with vascular lesions oc-
cur in the setting of significant reperfusion after revascu-
larization procedures, most commonly carotid endarter-
ectomy for chronic severe extracranial carotid stenosis. The
reperfusion syndrome, first described by Sundt and col-
leagues,28 includes transient focal seizure activity, atypical
migrainous phenomena, and intracerebral hemorrhage, al-
though the clinical triad is often incomplete. Onset of this
rare syndrome ranges from several days to 3 weeks after
revascularization29 and often is signaled by a new ipsilat-
eral headache.30 Surgical correction of an arteriovenous mal-
formation may also cause intraoperative or postoperative
hyperemia, with subsequent seizures or hemorrhage.19,31

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Figure 2. Mass lesion causing focal seizures. A 43-year-old woman
presented to the emergency department after focal-onset right-sided clonic
movements, followed by loss of consciousness. Computed tomographic
scan with contrast demonstrated a giant aneurysm of the middle cerebral
artery with adjacent cerebral edema, contrast uptake into the aneurysm, and
an adjacent region in which a thrombus has formed. The patient underwent
successful craniotomy, with thrombectomy and aneurysm clipping.
By contrast, arteriovenous malformations located in border-
zone regions subject to relatively low flow rates have a lower
risk for hemorrhage.32
The reperfusion syndrome has been attributed to im-
paired cerebral autoregulation.19 In the setting of chronic
hypoperfusion due to high-grade carotid stenosis, the ar-
terioles responsible for normal autoregulation in the
downstream cerebral hemisphere become chronically di-
lated. Subsequently, when perfusion is improved by a re-
vascularization procedure, the vessels are incapable of
vasoconstriction, and the brain parenchyma is sub-
jected to a massive augmentation of blood flow. The re-
lease of vasoactive neuropeptides from perivascular sen-
sory nerves may contribute to the development of the
reperfusion syndrome,19 to oxidants that develop before
revascularization,33 and to an inflammatory response to
the reestablishment of circulation.34
CLINICAL MANIFESTATIONS
Given that most poststroke seizures are caused by a fo-
cal lesion, poststroke seizures are typically focal at on-
set. In a study of early-onset seizures in 90 patients,17
simple partial seizures were the most common type (61%),
followed by secondarily generalized seizures (28%). In
other series,3,10 early-onset seizures were more likely to
be partial, whereas late-onset seizures were more likely
to generalize secondarily. Most recurrent seizures are of
the same type as the presenting episode, and they tend
to recur within 1 year on average.
In a large series of patients with poststroke sei-
zures, 9% had status epilepticus.35 The only associated
finding was higher functional disability; status epilepti-
cus was not associated with a higher mortality rate, stroke
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type (ischemic or hemorrhagic), topography (cortical in-
volvement), lesion size, or electroencephalographic (EEG)
patterns.
The phenomenological features of the reperfusion
syndrome are similar in that focal onset with occasional
secondary generalization is the rule. Seizure activity
always occurs in the ipsilateral vascular territory of the
surgically treated internal carotid artery.28 Occasion-
ally, status epilepticus ensues (Figure 3).
DIAGNOSTIC STUDIES
Holmes36 found that patients with periodic lateralizing
epileptiform discharges and bilateral independent peri-
odic lateralizing epileptiform discharges on EEG after
stroke were especially prone to the development of sei-
zures. Those patients with focal spikes also had a high
risk of 78%. Focal slowing, diffuse slowing, and normal
findings on EEG, by contrast, were associated with rela-
tively low risks of 20%, 10%, and 5%, respectively. Other
work found that cortical involvement on results of
neuroanatomical imaging studies was more predictive
of epilepsy than any single EEG finding.10
Focal slowing on EEG may simply reflect a wide re-
gion of ischemic or infarcted tissue involving the cere-
bral cortex or subcortical territory. In addition to neu-
roimaging, EEG may be helpful in the early evaluation
of poorly defined poststroke focal neurologic symp-
toms. In selected patients, focal slowing may confirm the
clinical impression of hemispheric ischemia and argue
against ongoing seizures as an explanation for an acute
neurologic syndrome. The absence of EEG abnormali-
ties does not definitively exclude cerebral ischemia, par-
ticularly in subcortical or subtentorial structures, or
intermittent seizure activity.
Uncommonly, seizures may mimic ischemia and in-
farction on neuroimaging findings. Lansberg et al37 recently
described several acute magnetic resonance imaging find-
ings in 3 patients with partial status epilepticus. These stud-
ies showed cortical hyperintensity on diffusion-weighted
imaging and T2-weighted sequences and a corresponding
area of low apparent diffusion coefficient. However, these
findings were readily differentiated from typical ischemic
stroke in their nonvascular distributions, increased signal
of the ipsilateral middle cerebral artery on magnetic reso-
nance angiography, and leptomeningeal enhancement on
postcontrast magnetic resonance imaging. Another study
showed a hyperintensity on diffusion-weighted images in
the dorsolateral portion of the ipsilateral thalamus in 2
patients (Figure 3).38
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of ischemia-induced seizures in-
cludes secondary seizures due to other causes. Medica-
tions, drug therapy withdrawal (eg, benzodiazepines), and
metabolic disturbances (eg, glucose abnormalities) typi-
cally cause generalized seizures, unless an underlying le-
sion is already present. Migraine-related focal phenom-
ena and transient ischemic attacks may produce focal
slowing on EEG findings. Among these entities, glucose
abnormalities should not be overlooked.
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 A Facility = Yale–New Haven Hospital Clinic = EEG Laboratory

Fp1 F7
F7 T7(T3)
T7 P7(T5)
T5 O1
Fp1 F3
F3 C3
C3 P3
P3 O1
FZ CZ
CZ PZ
PZ OZ (Ref)
Fp2 F4
F4 C4
C4 P4
P4 O2
Fp2 F8
F8 T8(T4)
T8 P8(T6)
P8 O2
Eyes (x2)

B C

Figure 3. Status epilepticus due to the reperfusion syndrome. A 66-year-old woman underwent an otherwise uncomplicated right carotid endarterectomy for
asymptomatic extracranial carotid artery disease 3 days earlier. She awoke with a headache, followed by left-arm clonic movements. These progressed to
generalized, tonic-clonic seizures, which were not aborted by administration of lorazepam and phenytoin sodium therapy. The continuous electroencephalographic
(EEG) monitor showed periodic lateralized epileptiform discharges occurring every 2 to 5 minutes, lasting a few seconds (A). Subsequent T2- and
diffusion-weighted magnetic resonance imaging studies of the brain showed right-sided thalamic (B) and cortical lesions (C). Phenobarbital sodium was then
administered, which arrested seizure activity. Ref indicates reference.

MANAGEMENT absence of absolute predictors of poststroke epilepsy, most

Choice of an anticonvulsant medication should be guided
by the individual characteristics of each patient, includ-
ing concurrent medications and medical comorbidities.
To our knowledge, no controlled trials evaluating only
poststroke seizures have been conducted to assess spe-
cific agents. Perhaps a more important issue is whether
to initiate treatment at all, because only a few post-
stroke seizures have been demonstrated to recur. In the
physicians empirically treat patients for their seizures
when they occur in the setting of a recent stroke. Thus,
Bladin et al2 argue that a controlled trial including pa-
tients with poststroke epilepsy would pose extensive lo-
gistical challenges and would likely be unethical. De-
spite the relatively low incidence of poststroke seizures,
the absolute numbers are still high, arguing that an im-
portant problem exists. Arboix et al39 concluded that the
efficacy of anticonvulsant prophylaxis should be as-

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 sessed in prospective, randomized trials conducted with
high-risk patients.
Poststroke seizures are usually well controlled with
a single anticonvulsant. In 1 retrospective study, seizures
in 88% of the 90 patients could be managed with mono-
therapy.10 Given the typical focal onset of poststroke sei-
zures, first-line therapy options include carbamazepine and
phenytoin sodium. The latter has the advantage of paren-
teral administration, which may be necessary given that
swallowing or mental status likely will be impaired. Fos-
phenytoin sodium is also a noteworthy option in stroke
patients because of lesser cardiotoxicity than phenytoin.
Benzodiazepines, particularly lorazepam, should be ini-
tially administered to the patient with ongoing seizures.
No data support the use of different agents to treat early-
vs late-onset seizures.
The newer antiepileptic drugs are being touted as first-
line agents for elderly patients because of their effective-
ness and favorable side-effect profiles. Approximately 10%
of nursing home residents in the United States receive an-
tiepileptic drugs, most often for the treatment of seizure
disorders.40 In a trial of newly diagnosed epilepsy in the el-
derly, lamotrigine was recently demonstrated to be better
tolerated and to maintain patients free of seizures for longer
intervals than carbamazepine.41 Although many of the newer
anticonvulsants, eg, topiramate42 and levetiracetam,43 have
been studied as adjunctive agents for refractory partial sei-
zures, in practice they are often used as monotherapy. Gaba-
pentin has been shown to be efficacious as monotherapy
for partial epilepsy.44 For all antiepileptic drugs, the chief
relevant dose-limiting adverse effect is sedation, particu-
larly in the elderly stroke patient.
Drug interactions are an important consideration, since
most stroke patients take multiple medications.40 The first-
generation antiepileptic agents undergo significant he-
patic metabolism, and phenytoin and valproic acid are highly
protein bound. For example, the well-recognized interac-
tion of warfarin with phenytoin makes it difficult to main-
tain consistent therapeutic ranges of both agents.
In its guidelines, the Stroke Council of the Ameri-
can Heart Association45,46 recommended uniform sei-
zure prophylaxis in the acute period after intracerebral
and subarachnoid hemorrhage. For intracerebral hem-
orrhage, seizure activity may result in further neuronal
injury and contribute to coma, although no clinical data
support this recommendation.45 Patients with solely cer-
ebellar or deep subcortical (eg, thalamic) lesions are at
very low risk for seizures and need not be treated. The
guideline suggests a dose of phenytoin sodium titrated
by serologic levels (14-23 µg/mL), with discontinuation
of therapy after 1 month if no seizure activity occurs dur-
ing treatment.47 Patients with seizure activity more than
2 weeks after presentation are at a higher risk for recur-
rence and may require long-term seizure prophylaxis.48
Small retrospective studies suggest no benefit of pro-
phylactic anticonvulsants after aneurysmal subarach-
noid hemorrhage.49 However, because of the relatively
low risk associated with antiepileptic therapy and the great
concern about aneurysmal rebleeding, a clinical trial ad-
dressing this issue may never occur. Long-term use of
antiepileptic agents is not recommended for patients with
subarachnoid hemorrhage who do not have seizures, but
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should be considered when at least 1 of several risk fac-
tors is present.46
In the case of reperfusion syndrome, the critical pre-
ventive measure is likely the aggressive control of systemic
blood pressure.19 The role of antiepileptic therapy in this
population of patients is unclear. Seizures during the reper-
fusion syndrome sometimes respond to antiepileptic drugs,
according to anecdotal evidence,50 but may be difficult to
treat in the absence of heavy sedation. Some surgeons em-
pirically administer prophylaxis owing to the concern about
seizures for 1 to 2 weeks after endarterectomy in patients
with high-grade carotid stenosis. Management of venous
infarction often dictates administration of systemic antico-
agulation, and, recently, intrathrombus thrombolysis via
endovascular delivery has demonstrated success in selected
patients.51 Authorities recommend instituting antiepilep-
tic therapy only if seizures occur.52
PROGNOSIS
The impact of poststroke seizures on stroke outcomes is un-
clear, with conflicting data from different case series. In 2
prospective studies, early-onset seizures were not associated
with higher mortality rates9 or worse neurologic deficits.4
Seizures were associated with better outcomes on the Scan-
dinavian Stroke Scale in another series9; the authors postu-
lated that seizures were a manifestation of a larger ischemic
penumbra that contributed to better recovery. Conversely,
in other work, patients who had early-onset seizures within
48 hours of the presenting stroke or transient ischemic at-
tack were significantly more likely to die in the hospital
(37.9%)vsthosewhodidnotpresentwithseizures(14.4%).39
For subarachnoid hemorrhage, seizures at onset pre-
dicted late-onset seizures and poor outcomes, mea-
sured by disability 6 weeks later using the Glasgow Out-
come Scale.53 In an Icelandic population, epilepsy was
more frequent in patients with severe neurologic re-
sidua (48%) compared with those without (20%).8
Seizures in the reperfusion syndrome are usually self-
limited. Long-term prognosis depends on the develop-
ment of intracerebral hemorrhage. In a series of 1500 ca-
rotid endarterectomies, hemorrhage developed in 11
patients, and 4 of these patients died.54
CONCLUSIONS
Poststroke seizures are a common and treatable phenom-
enon, whereas the development of epilepsy is relatively rare.
Cerebrovascular lesions associated with the development
of seizures include the following: intracerebral (paren-
chymal) and subarachnoid hemorrhage and cerebral ve-
nous thrombosis, with or without venous infarction; le-
sions involving the cerbral cortex; larger neurologic deficits
or disability at presentation; and revascularization proce-
dures involving the extracranial internal carotid artery. The
treatment of poststroke seizures is no different than the ap-
proach to treatment of partial-onset seizures due to other
cerebral lesions, and poststroke seizures usually respond
well to a single antiepileptic drug. Given their tolerability,
the newer generations of anticonvulsant agents hold prom-
ise in treating older patients. Given the low incidence of
poststroke epilepsy, there is no indication for seizure pro-
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 phylaxis in patients with acute ischemic stroke who have
not had a well-documented first event. The need for chronic
anticonvulsant use should be evaluated periodically, per-
haps every 6 months. Despite the absence of clinical data
documenting effectiveness, most patients presenting with
intracerebral or subarachnoid hemorrhage should receive
short-term antiepileptic prophylaxis.45,46
Future areas of research regarding poststroke sei-
zures include assessing their impact on initial lesion size
and on delayed patient outcomes, determining the appro-
priateness of chronic antiepileptic therapy after a single sei-
zure, and establishing risk factors for the reperfusion syn-
drome. Poststroke epilepsy may also become an important
basic model in research that aims to prevent the transfor-
mation of injured cerebral tissue into an epileptic focus.
Accepted for publication September 25, 2001.
Author contributions: Study concept and design (Drs
Silverman, Restrepo, and Mathews); acquisition of data (Dr
Silverman); analysis and interpretation of data (Dr Silver-
man); drafting of the manuscript (Drs Silverman and Re-
strepo); critical revision of the manuscript for important in-
tellectual content (Drs Silverman, Restrepo, and Mathews);
administrative, technical, and material support (Drs Silver-
man and Restrepo); study supervision (Dr Silverman).
We thank Richard H. Mattson, MD, for his critical re-
view of the manuscript.
Corresponding author and reprints: Isaac E. Silverman,
MD, The Stroke Center at Hartford Hospital, 85 Seymour St,
Suite 800, Hartford, CT 06106 (e-mail: isilver@harthosp.org).
REFERENCES
1. Hauser W, Annegers J, Kurland L. Incidence of epilepsy and unprovoked sei-
zures in Rochester, Minnesota: 1935-1984. Epilepsia. 1993;34:453-468.
2. Bladin C, Alexandrov A, Bellavance A, et al. Seizures after stroke: a prospective
multicenter study. Arch Neurol. 2000;57:1617-1622.
3. Davalos A, de Cendra E, Molins A, et al. Epileptic seizures at the onset of stroke.
Cerebrovasc Dis. 1992;2:327-331.
4. Kilpatrick C, Davis S, Tress B, Rossiter S, Hopper J, Vandendriessen M. Epilep-
tic seizures after stroke. Arch Neurol. 1990;47:157-169.
5. Sung C, Chu N. Epileptic seizures in intracerebral hemorrhage. J Neurol Neuro-
surg Psychiatry. 1989;52:1273-1276.
6. Rhoney D, Tipps L, Murray K, Basham M, Michael D, Coplin W. Anticonvulsant
prophylaxis and timing of seizures after aneurysmal subarachnoid hemorrhage.
Neurology. 2000;55:258-265.
7. Jennett B. Early traumatic epilepsy. Arch Neurol. 1974;30:394-398.
8. Olafsson E, Gudnumdsson G, Hauser W. Risk of epilepsy in long-term survivors
of surgery for aneurysmal subarachnoid hemorrhage: a population-based study
in Iceland. Epilepsia. 2000;41:1201-1205.
9. Reith J, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS, for the Copenha-
gen Stroke Study. Seizures in acute stroke. Stroke. 1997;28:1585-1589.
10. Gupta S, Naheedy M, Elias D, Rubino F. Postinfarction seizures: a clinical study.
Stroke. 1988;19:1477-1481.
11. Berger A, Lipton R, Lesser M, Lantos G, Portenoy R. Early seizures following in-
tracerebral hemorrhage: implications for therapy. Neurology. 1988;38:1363-1365.
12. Lambrakis CC, Lancman ME. The phenomenology of seizures and epilepsy after
stroke. J Epilepsy. 1998;11:233-240.
13. Buchkremer-Ratzmann I, August M, Hagemann G, Witte O. Epileptiform dis-
charges to extracellular stimuli in rat neocortical slices after photothrombotic
infarction. J Neurol Sci. 1998;156:133-137.
14. Congar P, Gaiarsa J, Popovici T, Ben-Ari Y, Crepel V. Permanent reduction of
seizure threshold in post-ischemic CA3 pyramidal neurons. J Neurophysiol. 2000;
83:2040-2046.
15. Willmore L. Post-traumatic epilepsy. Epilepsia. 1990;31(suppl 3):S67-S73.
16. Sung C, Chu N. Epileptic seizures in thrombotic stroke. J Neurol. 1990;237:166-170.
17. Giroud M, Gras P, Fayolle H, Andre N, Soichot P, Dumas R. Early seizures after
acute stroke: a study of 1640 cases. Epilepsia. 1994;35:959-964.
18. Kittner SJ, Sharkness CM, Price TR, et al. Infarcts with a cardiac source of em-
bolism in the NINCDS Stroke Data Bank. Neurology. 1990;40:281-284.
19. Macfarlane R, Moskowitz M, Sakas D, Tasdemiroglu E, Wei E, Kontos H. The
role of neuroeffector mechanisms in cerebral hyperperfusion syndromes. J Neu-
rosurg. 1991;75:845-855.
(REPRINTED) ARCH NEUROL / VOL 59, FEB 2002
201
©2002 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ on 01/27/2013
20. Lancman M, Golinstok A, Horcini J, Granillo R. Risk factors for developing sei-
zures after a stroke. Epilepsia. 1993;34:141-143.
21. Faught E, Peters D, Bartolucci A, Moore L, Miller P. Seizures after primary in-
tracerebral hemorrhage. Neurology. 1989;39:1089-1093.
22. Kucukkaya B, Aker R, Yuksel M, Onat F, Yalcin A. Low dose MK-801 protects
against iron-induced oxidative changes in a rat model of focal epilepsy. Brain
Res. 1998;788:133-136.
23. Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Epileptic sei-
zures after a first stroke. BMJ. 1997;315:1582-1587.
24. Ukkola V, Heikkinen E. Epilepsy after operative treatment of ruptured cerebral
aneurysms. Acta Neurochir (Wien). 1990;106:115-118.
25. Kvam D, Loftus C, Copeland B, Quest D. Seizures during the immediate postop-
erative period. Neurosurgery. 1983;12:14-17.
26. Kotila M, Waltimo O. Epilepsy after stroke. Epilepsia. 1992;33:495-498.
27. Ohman J. Hypertension as a risk factor for epilepsy after aneurysmal subarach-
noid hemorrhage and surgery. Neurosurgery. 1990;27:578-581.
28. Sundt T Jr, Sharbrough F, Piepgras D, Kearns T, Messick J Jr, O’Fallon W. Cor-
relation of cerebral blood flow and electroencephalographic changes during
carotid endarterectomy. Mayo Clin Proc. 1981;56:533-543.
29. Ho D, Wang Y, Chui M, Ho S, Cheung R. Epileptic seizures attributed to cerebral
hyperperfusion after percutaneous transluminal angioplasty and stenting of the
internal carotid artery. Cerebrovasc Dis. 2000;10:374-379.
30. Breen J, Caplan L, DeWitt L, Belkin M, Mackey W, O’Donnell T. Brain edema af-
ter carotid surgery. Neurology. 1996;46:175-181.
31. Young W, Kader A, Ornstein E, et al. Cerebral hyperemia after arteriovenous mal-
formation resection is related to “breakthrough” complications but not to feed-
ing artery pressure. Neurosurgery. 1996;38:1085-1093.
32. Stapf C, Mohr J, Sciacca R, et al. Incident hemorrhage risk of brain arteriovenous
malformations located in the arterial borderzones. Stroke. 2000;31:2365-2368.
33. Bacon P, Love S, Gupta A, Kirkpatrick P, Menon D. Plasma antioxidant consump-
tion associated with ischemia/reperfusion during carotid endarterectomy. Stroke.
1996;27:1808-1811.
34. Jean W, Spellman S, Nussbaum E, Low W. Reperfusion injury after focal cere-
bral ischemia horizon. Neurosurgery. 1998;43:1382-1397.
35. Velioglu S, Ozmenoglu M, Boz C, Alioglu Z. Status epilepticus after stroke. Stroke.
2001;32:1169-1172.
36. Holmes G. The electroencephalogram as a predictor of seizure following cere-
bral infarction. Clin Electroencephalogr. 1980;11:83-86.
37. Lansberg M, O’Brien M, Norbash A, Moseley M, Morrell M, Albers G. MRI abnor-
malities associated with partial status epilepticus. Neurology. 1999;52:1021-1027.
38. Fazekas F, Kappeller P, Schmidt R, et al. Magnetic resonance imaging and spec-
troscopy findings after focal status epilepticus. Epilepsia. 1995;36:946-949.
39. 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.
40. Cloyd J, Lackner T, Leppik I. Antiepileptics in the elderly: pharmacoepidemiol-
ogy and pharmacokinetics. Arch Fam Med. 1994;3:589-598.
41. Brodie M, Overstall P, Giorgi L, for the UK Lamotrigine Elderly Study Group. Mul-
ticentre, double-blind, randomised comparison between lamotrigine and carba-
mazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Res. 1999;
37:81-87.
42. Privitera M, Fincham R, Penry J, et al, for the Topiramate YE Study Group. Topi-
ramate placebo-controlled dose-ranging trial in refractory partial epilepsy using
600-, 800-, and 1000-mg daily dosages. Neurology. 1996;46:1678-1683.
43. Cereghino JJ, Biton V, Abou-Khalil B, Dreifuss F, Gauer LJ, Leppik I. Leveti-
racetam for partial seizures: results of a double-blind, randomized clinical trial.
Neurology. 2000;55:236-242.
44. Chadwick D, Anhut H, Greiner M, et al, for the International Gabapentin Mono-
therapy Study Group 945-77. A double-blind trial of gabapentin monotherapy
for newly diagnosed partial seizures. Neurology. 1998;51:1282-1288.
45. Broderick J, Adams H Jr, Barsan W, et al. Guidelines for the management of spon-
taneous intracerebral hemorrhage: a statement for the healthcare professionals
from a special writing group of the Stroke Council, American Heart Association.
Stroke. 1999;30:905-915.
46. Mayberg M, Batjer H, Dacey R, et al. Guidelines for the management of aneu-
rysmal subarachnoid hemorrhage: a statement for healthcare professionals from
a special writing group of the Stroke Council, American Heart Association. Cir-
culation. 1994;90:2592-2605.
47. Qureshi A, Tuhrim S, Broderick J, Batjer H, Hondo H, Hanley D. Spontaneous
intracerebral hemorrhage. N Engl J Med. 2001;344:1450-1460.
48. Cervoni L, Artico M, Salvati M, Bristot R, Franco C, Raaschoo H. Epileptic sei-
zures in intracerebral hemorrhage: a clinical and prognostic study of 55 cases.
Neurosurg Rev. 1994;17:185-188.
49. O’Laoire S. Epilepsy following neurosurgical intervention. Acta Neurochir Suppl.
1990;50:52-54.
50. Kieburtz K, Ricotta J, Moxley R. Seizures following carotid endarterectomy. Arch
Neurol. 1990;47:568-570.
51. Chow K, Gobin Y, Saver J, et al. Endovascular treatment of dural sinus throm-
bosis with rheolytic thrombectomy and intra-arterial thrombolysis. Stroke. 2000;
31:1420-1425.
52. Ameri A, Bousser M-G. Cerebral venous thrombosis. Neurol Clin. 1992;10:87-111.
53. Butzkueven H, Evans A, Pitman A, et al. Onset seizures independently predict
poor outcome after subarachnoid hemorrhage. Neurology. 2000;55:1315-
1320.
54. Pomposelli F, Lamparello P, Riles T, et al. Intracranial hemorrhage after carotid
endarterectomy. J Vasc Surg. 1988;7:248-255.
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