Chapter 2

Seizures in Ischemic Stroke

Benny S. Kim and Cathy Sila

Introduction

Stroke is the most common cause of new-onset seizures in older adults. Cerebro-
vascular disease accounts for 11% of adult epilepsy, and, in older adults, stroke is
the underlying cause in over a third of all cases [1]. Seizures secondary to ischemic
stroke are generally categorized into early seizures (occurring up to 24 weeks after
a stroke) and late seizures (occurring after 4 weeks). Risk factors for developing
poststroke seizures generally include cortical involvement, anterior hemisphere lo-
cation, early seizures, and possibly cardioembolic etiology [2]. Early seizures may
be associated with increased mortality, while late or recurrent seizures may hinder
long-term neurologic outcome [3]. There is a paucity of evidence for the prophy-
lactic use of antiepileptic drugs (AEDs) in ischemic stroke without seizures. The
decision to start patients on a long-term AED after their first poststroke seizure is
debatable; consideration of the probability of seizure recurrence and the negative
influence of some AEDs on neurological recovery must be taken into account.

Epidemiology

Cerebrovascular disease is the most commonly identified antecedent for adult epi-
lepsy, accounting for 11% of cases [1]. Stroke becomes an increasingly common
cause of seizures when examining older populations. A population-based study in
Sweden found that in patients over 60 years of age, 45% of seizures were secondary

B.S.Kim()
Department of Interventional Neuroradiology, Lahey Hospital and Medical Center,
41 Mall Road, Burlington, MA 01805, USA
e-mail: [email protected]
C.Sila
Department of Neurology, University Hospitals Case Medical Center,
11100 Euclid Avenue, Cleveland, OH 44106, USA
Springer Science+Business Media New York 2015 17
M. Z. Koubeissi et al. (eds.), Seizures in Cerebrovascular Disorders,
DOI 10.1007/978-1-4939-2559-9_2
18 B. S. Kim and C. Sila

to stroke, followed by tumors (11%), and Alzheimers disease (7%) [4]. Stroke is
associated with a 2335-fold increase in the incidence of seizure, and a 17-fold
higher risk for the development of epilepsy [2, 5]. Stroke may also be a significant
source of seizures in younger adults. A prospective cohort of 697 patients 1850
years old who suffered a cerebrovascular event was found to have a cumulative risk
of poststroke epilepsy with recurrent seizures of 8% after a mean follow-up of 10
years [6].
The timing of early seizures after stroke has been examined in a number of large
studies. The Oxfordshire study found in their 545 ischemic stroke patients, 2% had
suffered a seizure at the onset of stroke [5]. Labovitzet etal. found that when acute
stroke patients suffered early seizures, they occurred at stroke onset in 40.5% of
cases [7]. The Copenhagen stroke study reported that 86% of early seizures oc-
curred within 3 days after a stroke, with 66% occurring within the first 24h. Seizure
subtypes included focal seizures with or without secondary generalization in 68%,
and generalized tonicclonic seizures with no clear antecedent focal seizure mani-
festations in 22% [8]. The frequency of early seizures occurring within a 2-week
window after stroke ranges from 4.8 to 6.5% [3]. This incidence may be higher due
to variability in the definition and detection methods and study setting [9].
The functional impact, underlying mechanism, and epilepsy risk of late seizures
may be different than early seizures. Approximately, 35% of stroke survivors ex-
perience a late seizure within a year of their first episode, with 5466% of these
patients going on to develop epilepsy [3]. At 5-year follow-up, the frequency of
seizure after stroke was 9.7% [10]. The risk of developing epilepsy at 5 years after
a first stroke is 3.8%, and increases to 9.6% when patients suffer recurrent strokes
[2]. Stroke has also been demonstrated to be a risk factor for status epilepticus in
2232% of cases [9]. The overall poststroke incidence of status epilepticus is rela-
tively low in large series; a single-institution study reported status epilepticus in
1.1% of a cohort of 904 acute stroke patients [7].

Risk Factors

Traditionally, certain stroke subtypes, such as embolic stroke, have been thought to
be associated with an increased risk of new-onset seizures. However, seizures oc-
cur with most stroke subtypes. An increased risk of seizures after embolic strokes
of cardiac origin has been shown in some studies, but not others [2, 11, 12]. The
Seizure After Stroke Study (SASS), a large, prospective, multicenter study found
that patients with presumed cardioembolic stroke were not at an increased risk for
new-onset or recurrent seizures [13]. Interestingly, seizures have been associated
with lacunar strokes in up to 3.5% of cases [14]. These seizures may develop from
the release of glutamate from axonal terminals arising from injured thalamocorti-
cal neurons [12]. Consistent with this theory are studies demonstrating lateralized
electroencephalography (EEG) abnormalities in 2238% of patients with lacunar
infarctions [15].
2 Seizures in Ischemic Stroke 19

In the differential diagnosis of seizures are seizure-like involuntary movements

that occur with specific stroke subtypes. Convulsive movements have been de-
scribed in patients with brain-stem strokes; it has been postulated that these move-
ments are related to ischemia of the corticospinal tract rather than a true seizure [16].
Various nonseizure transient hypokinetic and hyperkinetic movements have been
infrequently described in patients with acute strokes, the most common of which are
hemichorea and hemiballismus in the setting of lesions involving the basal ganglia
or its pathways and the frontal lobe. Some of these movements may be delayed for
months or years [17]. Kim etal. described nine patients with anterior cerebral artery
strokes presenting with hemi-parkinsonism or asterixis. Symptom onset ranged from
simultaneous with stroke onset to 1 month, and all patients improved [18].
Transient ischemic attacks (TIAs) have been associated with seizures in 1.8
3.7%. However, the true frequency is uncertain due to the diagnostic limitations
of distinguishing some TIAs with focal seizures versus limb-shaking TIA. The lat-
ter are a particular type of seizure-like movement thought to be secondary to fo-
cal cerebral hypoperfusion due to severe stenotic or occlusive contralateral carotid
disease [15]. Fischer in 1962 first described these movements as brief, arrhythmic,
flailing, or jerking movements of an extremity that may be confused for a focal
motor seizure or a movement disorder [19]. Clues which may help distinguishing
limb-shaking TIAs from other diseases are lack of a Jacksonian march, nonepilep-
tiform EEG, ineffectiveness of AEDs, precipitation of symptoms with maneuvers
that cause cerebral hypoperfusion, and cessation of symptoms when improving ce-
rebral perfusion. Maneuvers such as rising from a chair, hyperventilation, and hy-
perextension of the neck may provoke shaking movements, whereas laying supine
may eliminate symptoms [20, 21].
Studies examining cerebral perfusion using positron emission tomography or
transcranial Doppler have demonstrated hemodynamic failure in the contralateral
hemisphere on the symptomatic side [22]. Reduced cerebral blood flow to criti-
cal watershed areas in patients who suffer limb-shaking TIAs are at a high risk
for stroke [23]. In 147 patients with symptomatic internal carotid artery (ICA) oc-
clusions, 28.6% were found to have contralateral limb-shaking symptoms. Multi-
variate analysis found the presence of limb shaking to be a significant independent
predictor of adverse short-term and long-term outcomes when compared to patients
with ICA occlusions without limb-shaking symptoms, in addition to severe Na-
tional Institutes of Health Stroke Scale/Score (NIHSS) and the presence of diabe-
tes. Symptomatic patients had a nonsignificant tendency toward increased recur-
rent strokes and TIAs [24]. Management may entail careful optimization of blood
pressure and possible revascularization procedures to improve cerebral blood flow
[20, 24].
Strokes involving the cortex have been characterized as having a high incidence
of early seizures [25]. Strokes involving the anterior and posterior hemisphere, as
well as the temporoparietal lobe have all been associated with increased risk of
seizures, with early seizures associated with stroke in the anterior hemisphere. Cor-
tically located strokes are twice as likely to cause seizure than subcortical strokes.
Large infarcts involving the supramarginal or superior temporal gyrus have a
20 B. S. Kim and C. Sila

fivefold increased risk of developing late seizures [2, 3, 12]. Denier et al. found
that a watershed mechanism of stroke was associated with a fourfold increase in
early seizures compared to other cortical infarcts in 328 consecutive patients with
magnetic resonance imaging (MRI)-confirmed cerebral infarctions [26]. The rela-
tionship between stroke severity and seizures has been variable. The Copenhagen
stroke study found that only initial stroke severity predicted the occurrence of early
seizures when using multivariate analysis [8]. Stroke disability and cortical loca-
tion were found to be risk factors for developing poststroke seizures in SASS and
in prospective studies specifically examining affected younger adults [6, 7, 13]. So
etal. found that early seizures and recurrent strokes were the only factors predictive
of developing late seizures or epilepsy. Patients who suffered an early seizure were
eight times more likely to develop a late seizure and 16 more times likely to develop
epilepsy. Stroke recurrence tripled the risk of suffering a late seizure or developing
epilepsy [2]. Other studies found that late-onset seizures were independent risk fac-
tors for developing epilepsy after stroke [6, 13]. Hemorrhagic transformation of an
ischemic stroke seems to increase the risk of seizures. An Italian study of 714 stroke
patients found the incidence of seizure to be 4.2% in patients with bland infarcts,
12.5% in patients with hemorrhagic transformation, and 16.2% in patients with
primary intracerebral hemorrhage (ICH) [27].
Of special note is ICH occurring secondary to cerebral hyperperfusion after sur-
gical or endovascular treatment of a critical carotid artery stenosis. Cerebral hyper-
perfusion syndrome is characterized by a headache ipsilateral to the treated artery,
with or without nausea, vomiting, neurological deficit, post-procedural hyperten-
sion, and seizures. Chronic low blood flow from a significant carotid stenosis may
cause blood vessels distally to lose their ability to autoregulate vascular resistance.
Excessive blood flow directed to an impaired vascular bed may disrupt vessels and
cause hemorrhage, which may be associated with seizures. Cerebral hyperperfusion
syndrome peaks between 3 and 5 days postoperatively, carrying a high morbidity
when ICH develops. Transcranial Doppler may be able to predict patients who are at
a higher risk for this syndrome by demonstrating increased mean flow velocity and
diminished pulsatility index. In a study of 450 consecutive cases of carotid artery
stenting, 0.67% had cerebral hyperperfusion syndrome with ICH. Vigilant periop-
erative control of systemic blood pressure may prevent this syndrome [28, 29].

Pathophysiology

The mechanism of early poststroke seizure may differ from that of late seizures.
Early seizures may be secondary to biochemical dysfunction, whereas late seizures
may be due to epileptogenic gliotic scarring [25]. Acute ischemia is marked by
glutamate-induced excitotoxicity causing an overload of intracellular calcium and
sodium, which activate variety of cellular enzymes and depolarization of the trans-
membrane potential, ultimately leading to neuronal loss. Glutamate has also been
found to induce epileptiform type of discharges in surviving neurons [30]. Seizure
activity in the acute setting of cerebral ischemia may have a deleterious effect of
increasing metabolic demand in tenuous hypoxic tissue. Potentially salvageable
2 Seizures in Ischemic Stroke 21

Fig. 2.1 A patient with late poststroke seizures; EEG (a) shows seizure pattern in left fronto-
central region, onset at C3F3>f7Fp1. Onset consisted of rhythmic alpha activity at F3C3,
then involved Fp1F7, to evolve into rhythmic theta, then sharply contoured delta; seizure lasted
3060s. This patient suffered 18 seizures over 9h. MRI (b) shows a focal encephalomalacia in the
left posterior temporal and parietal lobes compatible with remote ischemic infarction

brain may be further recruited into the infarct core, leading to increased infarct size
[31]. Experimental models have demonstrated transient peri-infarct depolarization
in the penumbra of middle cerebral artery occlusions, and correlated the duration of
depolarization with infarct volume [15]. The early phase of stroke is also accompa-
nied by noncerebral factors such as systemic electrolyte imbalances, acid-base dis-
turbances, and potential infections such as pneumonia which can reduce the seizure
threshold [12]. Late seizures may be secondary to gliosis and development of me-
ningocerebral scarring. Changes in membrane properties, deafferentation, selective
neuronal loss, and collateral sprouting may result in hyperexcitability and neuronal
synchrony sufficient to elicit seizures (Fig.2.1ab) [15].

Imaging

Five to thirty percent of cases identified as brain attacks may be due to stroke-
mimicking conditions [23]. Winkler etal. found that of 250 consecutive patients
treated with intravenous thrombolysis, 2.8% were stroke mimics; none of whom
were harmed by thrombolysis. Seizure was the most frequent diagnosis in these pa-
tients (85.7%), with global aphasia without hemiparesis presenting ten times more
frequently in the mimic than in the stroke group [33]. The clinical significance of
advanced neuroimaging studies and EEG to distinguish stroke mimics from strokes
before intravenous thrombolysis is unclear [33]. Furthermore, seizures may pro-
duce radiological changes that may make it difficult for a clinician to distinguish
a seizure at the onset of an ischemic stroke from a seizure with postictal paresis,
known as Todds paresis. Seizure activity may lead to metabolic exhaustion of neu-
rons within the epileptogenic focus, producing clinical paralysis. Increased regional
permeability in the bloodbrain barrier and edema at this site may subsequently
be visualized by neuroimaging. An MRI of the brain may demonstrate focal corti-
cal swelling, signal change in fluid-attenuated inversion recovery sequences, and
22 B. S. Kim and C. Sila

Fig. 2.2 ab Periodic lateralizing epileptiform discharges (PLEDs) in a patient with acute ischemic
stroke. EEG (a) shows intermittent PLEDs in the left parietal-central region, maximum P3 > C3,
approximately 20 % of the record, lasting 310 s in a patient with acute ischemic stroke of the
left hemisphere. MRI (b) shows a diffusion restriction in the left hemisphere in the distribution of
the middle cerebral artery with mass effect and midline shift in an 83-year-old man who suffered
acute-onset aphasia and right hemiplegia

cortical blush when contrast is administered [34]. Seizure duration may correlate
with the intensity and size of these changes. Angiography after seizure may dem-
onstrate a focal area of enhanced blood flow secondary to disruption of the blood
brain barrier [35]. Cerebral perfusion imaging may also demonstrate large areas
of ictal hyperperfusion or postictal hypoperfusion. When this is observed without
corresponding arterial pathology, it may be more indicative of a seizure than acute
stroke (Fig.2.2) [36, 37]. Computed tomography (CT) perfusion brain imaging has
recently gained popularity as a method for evaluating penumbral tissue. Masterson
et al. reported the CT perfusion changes in four patients presenting with stroke
symptoms who were subsequently diagnosed with status epilepticus. Focal cortical
hyperperfusion was demonstrated in all patients, with approximately 50% increase
in cerebral blood flow, 3040% increase in cerebral blood volume, and 40% de-
crease in mean transit time. These findings were attributed to the peri-ictal phases
of status epilepticus and are the opposite of perfusion changes found in acute stroke.
The authors cautioned that migraines or strokes with reperfusion can produce simi-
lar results [32]. Table2.1 demonstrates the common CT perfusion changes in isch-
emic infarction, penumbral tissue, and seizures.

Table 2.1 Cerebral CT perfusion changes in acute ischemic stroke and seizure
Perfusion changes Penumbral tissue Core infarct Seizure
Cerebral blood flow (CBF)

Cerebral blood volume (CBV) Normal or a

Mean transit time (MTT)

Time to peak (TTP)
a
In the presence of penumbral tissue, perfusion map may show no changes in the cerebral blood
volume; an important distinguishing feature for patients requiring immediate stroke intervention.
indicate decrease; indicate increase
2 Seizures in Ischemic Stroke 23

Electroclinical Manifestations of Acute Stroke

Acute ischemic stroke may have a number of EEG patterns, of which periodic lat-
eralized epileptiform discharges (PLEDs) are of particular significance. PLEDs are
electrographic phenomena characterized by widely distributed, polymorphic, and
repetitive complexes of approximately 0.53Hz, having one or more sharp com-
ponents, present over one or more hemispheres (Fig. 2.3a) [38]. PLEDs may be
an expression of dynamic brain damage in the very acute stage. While PLEDs are
commonly associated with large cortical destructive processes, they may be seen
in patients with subcortical, chronic lesions, or metabolic disturbances [32, 39].
Mecarelli etal. analyzed the EEGs performed within 24h of a cohort of 232 pa-
tients admitted with acute ischemic or intraparenchymal hemorrhagic stroke. Focal

Fig. 2.3 CT perfusion analysis showing the cerebral blood volume (CBV), cerebral blood flow
(CBF), and mean transit time (MTT) of a patient with ischemic penumbra in the right hemisphere
due to a hyperacute occlusion of the right middle cerebral artery (a CBV, b CBF, and c MTT), and
a second patient with a seizure emanating from the left hemisphere (d CBV, e CBF, and f MTT)
followed by a complete resolution of the hyperperfusion (g CBV, h CBF, and i MTT)
24 B. S. Kim and C. Sila

or diffuse slowing of background was found in 84% of patients, epileptiform focal

abnormalities in 10%, and PLEDs in 6%. Three out of the 23 patients with epilep-
tiform abnormalities developed isolated partial motor seizures without secondary
generalization, while none of the patients with slowing had seizures. Of the 14 pa-
tients with PLEDs, 10 had focal status epilepticus (9 convulsive, 1 nonconvulsive),
and 2 had focal motor seizures. Multivariate analysis demonstrated that only early
epileptic manifestations were independently associated with PLEDs [39].Various
theories regarding the neurophysiology of PLEDs have been suggested. Some au-
thors have proposed that cortical PLEDs are produced from a large external zone of
hyperexcitability, which generates synchronous discharges that communicate with
subcortical structures, where they are modulated and returned via corticopetal con-
nections. In addition, subcortical lesions disrupt the basal gangliathalamuscortex
network, causing oscillations to be propagated through the thalamocortical projec-
tions and eventually widespread areas of cortex [38]. An EEG maybe normal in
5% of cases, and therefore, a normal EEG does not exclude epileptogenic lesions
[40]. Acute ischemia may produce EEG changes within minutes of onset, provid-
ing real-time and dynamic information of the neurophysiologic state. Progressive
reductions in cerebral blood flow and degree of neuronal injury lead to changes in
EEG characteristics, from loss of fast beta frequencies in reversible mild ischemia,
to suppression of all frequencies, or isoelectric EEG activity in neuronal death [41].

Treatment

Treatment and recurrence of seizures of varying etiology other than stroke have
been studied in depth. Berg and Shinnar used a meta-analysis to study the issue of
recurrence after a first unprovoked seizure. Among 16 reports, the average risk of
a first unprovoked seizure was 51%. At 2 years following the first seizure, the risk
of recurrence was 36% in prospective studies and 47% in retrospective studies.
Recurrence risk varied depending on a number of factors, such as seizure etiology,
seizure type, and electrographic findings. The recurrence risk was as low as 24%
and as high as 65% [42].
The development of poststroke epilepsy occurs in 5466% of those who experi-
ence late seizures, and less than 43% in early-seizure patients. The risk of develop-
ing a second seizure is similar to the nonstroke patient who experiences a first un-
provoked seizure. In these non-stroke patients, initiating AED treatment only after
a recurrent seizure does not appear to be harmful [43]. Furthermore, indiscriminate
treatment of a first unprovoked seizure without regard to patients EEG character-
istics, the presence of structural lesion, or riskbenefit profile is not recommended
[27, 44]. Similarly, the use of prophylactic AEDs in acute traumatic brain injury
without an initial seizure is not recommended because it has been found to be in-
effective in reducing mortality, functional outcome, and eventual development of
epilepsy, even if it potentially reduces the likelihood of early seizures [3].
2 Seizures in Ischemic Stroke 25

However, strokes produce a structural lesion and some authors have favored
initiating AEDs after an early poststroke seizure, while others have recommended
treatment only after a late seizure [1]. Labovitz and Hauser etal. suggested that the
risk of epilepsy in some patients with a single-poststroke seizure is high enough
to justify the initiation of AEDs before the second seizure [40, 45]. Others have
suggested treating an early seizure for 1 month, then stopping the AED if seizures
have not recurred during this period [40]. One approach is to initiate one AED at
standard dosage if a patient has developed immediate poststroke seizure. Therapy
would be continued for 13 months during the time of highest risk for recurrence
and discontinued if no further seizures had occurred. A more conservative approach
is to attempt discontinuation of AEDs only after 1 year of seizure freedom; an ap-
proach facilitated in part by the emergence of newer-generation AEDs that have
more tolerable adverse effect profiles and little to no drugdrug interactions. Re-
current seizures while on AED therapy may be milder in severity and type (focal
instead of secondarily generalized). Because late seizures carry higher risk of recur-
rence, AED therapy is recommended.
No single AED has been shown in studies to be clearly and consistently superior
to another in the treatment of early seizures or epilepsy after stroke [36]. Therefore,
when choosing among the different AEDs, the clinician must take into account the
potential side effects of the drug, its pharmacokinetic profile, interaction with other
medications, and the potential influence on the neurologic recovery process. Phenyt-
oin, phenobarbital, and carbamazepine are hepatic enzyme inducers, while valproic
acid is an enzyme inhibitor. Phenytoin and valproic acid are highly protein bound, and
the former also interferes with vitamin K metabolism. These properties of older-gen-
eration AEDs may lead to difficulties in maintaining a therapeutic drug range when a
patient is concurrently on warfarin. Salicylates may displace valproate from its plas-
ma protein binding sites, leading to reduction in total plasma level. Newer-generation
AEDs do not demonstrate significant interactions with warfarin or antiplatelet agents
[3]. For example, levetiracetam and lamotrigine lack hepatic metabolism and have
a favorable pharmacokinetic profile in terms of drug interaction, compared to older
AED [35, 46]. Animal models and clinical studies suggested that older AEDs may
impair the recovery after stroke. Phenytoin, phenobarbital, and benzodiazepines have
been shown to impair the motor and behavioral recovery process in brain-injured rats
and functional recovery in patients [15]. In contrast, vigabatrin and carbamazepine
have not demonstrated negative effects on poststroke outcome [47].
Tolerability of the drug remains an important issue to consider when initiating
AEDs. Studies comparing various AEDs have suggested better tolerability and re-
tention rates for lamotrigine, gabapentin, or levetiracetam when compared with
carbamazepine, a medication known to be effective in poststroke seizure [3, 46].
The long-term tolerability and efficacy of gabapentin was studied in patients who
had their first seizure at least 2 weeks after stroke: 81.7% of the cohort remained
seizure-free at a mean follow-up of 30 months. Side effects were reported in 38%,
but were mild to moderate with only 2.8% withdrawing from the study as a re-
sult. The authors concluded that gabapentin was safe and useful for poststroke sei-
zures [48]. Other authors randomized 106 patients with late poststroke seizures to
26 B. S. Kim and C. Sila

levetiracetam or sustained-release carbamazepine [35]. No statistically significant

difference in the number of seizure-free patients was found between the two groups.
At the 52-week follow-up, 94% of levetiracetam and 85% of carbamazepine were
seizure free. Attention deficit, frontal executive function, and functional scales were
significantly worse in the carbamazepine group. Premature discontinuation due to
serious adverse effects was not statistically significant between the groups [35]. In a
smaller study, 64 patients presenting with the first (early or late) poststroke seizure
received lamotrigine or carbamazepine in a randomized 1:1 ratio. After 12-month
follow-up, significant differences between the two groups were found in terms of
efficacy, side effects, and tolerability in favor of the lamotrigine. The number of
patients remaining seizure free was found to be 72% in the lamotrigine group and
44% in the carbamazepine group. Three percent of patients in the lamotrigine group
dropped out because of adverse events, compared to 31% in the carbamazepine
group [46].

Prognosis

Animal stroke models suggest that early seizures may be associated with increased
infarct volume; however, it is unclear if early seizures have deleterious effects on
the eventual functional outcome after stroke. A significant number of studies found
worse outcomes in patients with late or recurrent seizures after stroke, but others
failed to demonstrate this effect. The differences in these outcomes may be due to
the lack of accounting for confounding factors such as stroke severity, stroke loca-
tion, or AED treatment at the time of assessment, which has been shown to indepen-
dently contribute to worse functional outcome with certain drugs [3, 15]. Previous
studies have demonstrated increased hospital mortality rates among patients with
early seizures after stroke. These studies did not account for stroke severity or rule
out seizures as an independent predictor of poor outcome. It has been proposed that
seizures maybe a sign of severe brain injury rather than a predictor of poor recov-
ery [11, 49]. It is unclear if seizures independently alter functional outcome after
stroke. SASS demonstrated a worse neurological score during initial hospitalization
and worse Rankin scale at 9 months of follow-up in patient who had seizures after
stroke; however, SASS failed to correct for stroke severity and did not analyze the
role of early versus late seizures [3, 50]. Seizures do not influence the rehabilita-
tion outcome in poststroke patients [10, 50]. Prospective studies which did account
for stroke severity found no association between early seizures and outcome or
mortality [7].
Status epilepticus rarely occurs in patients with acute stroke, and constitutes less
than 10% of cases of poststroke seizures [9]. The clinical relevance of poststroke
status epilepticus has also been inconsistent. Patients with generalized convulsive
status epilepticus after a stroke have a threefold increase in mortality rate compared
to stroke patients without status epilepticus [51]. This increase in mortality is seen
only if the status epilepticus occurred within the first week after the stroke [9]. A
2 Seizures in Ischemic Stroke 27

multivariate analysis found no relationship between the occurrence of status epi-

lepticus and stroke subtype (infarction vs. hemorrhage), stroke risk factors, stroke
topography, cortical involvement, lesion size, or EEG findings [9]. In addition, no
difference in mortality rate was found between poststroke patients who had status
and those who had seizures. The only predictor of status epilepticus was poor func-
tional status (modified Rankin scale>3), and the only predictor of mortality was
age [52]. Status epilepticus at presentation of stroke has not been shown to predict
subsequent development of epilepsy [40].

Summary

Stroke is an important cause of seizures especially in older adults. The incidence of

poststroke seizure varies based on the setting and detection method. When patients
suffer these seizures, they often occur at stroke onset or very soon after; however,
they continue to be at risk for seizures many years later. The mechanism of early
seizures may differ from late seizures. In treating these seizures, clinicians should
consider the potential negative effects of some AEDs on functional outcome and the
interaction with other medications especially the antithrombotic and anticoagulants.

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