Case Report
Cerebrovasc Dis 2002;14:54–57

Received: August 14, 2001
Accepted: December 12, 2001

Seizure at Stroke Onset: Should
It Be an Absolute Contraindication to
Thrombolysis?
Magdy Selim Sandeep Kumar John Fink Gottfried Schlaug
Louis R. Caplan Italo Linfante
Department of Neurology, Division of Cerebrovascular Diseases, Beth Israel Deaconess Medical Center,
Boston, Mass., USA

Abstract
Background: Current guidelines for the treatment of
acute ischemic stroke exclude patients with seizure at
stroke onset from consideration for thrombolytic therapy. It may be difficult to differentiate an ischemic stroke
from postictal Todd’s paralysis by clinical examination
and noncontrast CT scan. Magnetic resonance imaging
(MRI) with diffusion- (DWI) and perfusion-weighted
images (PWI) and angiography (MRA) can be used to
confirm the diagnosis of an acute ischemic process in the
presence of concurrent seizures. Methods: A case report
of a patient who presented with seizures, in whom the
combination of DWI/PWI MRI and MRA confirmed the
diagnosis of an embolic ischemic stroke. The patient was
treated with intravenous recombinant tissue plasminogen activator with clinical and radiological improvement.

The authors have no conflicts of interest to declare.

ABC

© 2002 S. Karger AG, Basel
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Conclusions: Treatment decisions with regard to thrombolysis in acute stroke patients should be based on
parameters of cerebral perfusion, assessment of collateral blood flow and presence of potentially salvageable
tissue. Modern neuroimaging techniques that can rapidly assess these variables, such as DWI/PWI MRI and
MRA, can improve the current selection of patients who
are likely to benefit from thrombolysis and extend its
benefit to patients who would otherwise be excluded,
such as those with seizures at stroke onset.
Copyright © 2002 S. Karger AG, Basel

Introduction

Current treatment guidelines for acute ischemic stroke
list ‘seizure at onset’ as an exclusion criterion for the use
of recombinant tissue plasminogen activator (rt-PA) [1,
2]. Occasional patients, with acute ischemic stroke,
present with seizures at stroke onset [3]. It may be difficult to differentiate an ischemic stroke from postictal
Todd’s paralysis by clinical examination and noncontrast
CT scan. Magnetic resonance imaging (MRI) with sequences that include diffusion- (DWI) and perfusionweighted images (PWI) and angiography (MRA) allows

Magdy H. Selim, MD, PhD
University of Massachusetts Medical School, Department of Neurology
UMass Memorial Medical Center, 119 Belmont Street
Worcester, MA 01605 (USA)
Tel. +1 508 334 6641, Fax +1 508 334 6695, E-Mail selimm@ummhc.org

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Key Words
Stroke W Magnetic resonance imaging W
Diffusion-weighted images W Perfusion-weighted
images W Tissue plasminogen activator W Seizures

Fig. 1. MRI findings at 120 min from symptom onset (A–C) and at 24 h after treatment
with intravenous rt-PA (D–F). A Axial DWI
showing restricted diffusion (increased signal) in the right temporoparietal region. B
PWI, relative mean transit time map, showing a large area of hypoperfusion in the right
cerebral hemisphere. C MRA showing cutoff of the M1 segment of the right middle
cerebral artery, consistent with occlusion.
D DWI showing evolution of the right temporoparietal diffusion abnormality, 24 h after thrombolysis, without significant increase in size. E Susceptibility-weighted
image showing hemorrhagic transformation
within the area of infarction. F MRA showing recanalization of the right middle cerebral artery.

Case Report
An 86-year-old woman with a history of hypertension, hyperlipidemia, coronary artery disease and atrial flutter developed seizures
characterized by ‘jerking of her right arm and leg and immediate
unresponsiveness’, witnessed by her internist during a routine followup office visit. She was immediately rushed to our emergency department, where she was thought to have a focal motor seizure with secondary generalization. She received intravenous lorazepam and phenytoin that aborted her clonic activity. Her medications included
moexipril, nitroglycerine, digoxin and furosemide. She had no history of prior strokes or seizures. She lived alone, independently. She
did not smoke and rarely consumed alcohol.
On examination, her temperature was 37.2 C °, blood pressure
180/60 mm Hg and pulse 100 beats/min and regular. Her cardiac and
general examinations were normal. On neurological examination,
she was unarousable. She grimaced and withdrew the right side in
response to nail bed pressure. Her eyes were deviated to the right.
Oculocephalic reflexes were intact. Her pupils were regular with a
sluggish response to light. She had weakness of the left lower face.

TPA for Stroke with Seizure at Onset

Her left arm and leg were flaccid and plegic. She had a Babinski’s sign
on the left. Her Glasgow Coma Score was 6; the National Institute of
Health Stroke Scale score was 21.
Routine blood counts and chemistries were normal. Noncontrast
CT of the head, within 90 min after symptom onset, excluded hemorrhage and did not show early signs of ischemia. An EEG showed diffuse slowing and frequent right temporal spikes, without evidence of
ongoing seizure activity.
The possibility of stroke with seizure at onset was entertained given the discrepancy between her presentation and focal examination,
i.e. right-sided seizures and left-sided long tract signs and hemiplegia.
DWI, 120 min after symptom onset, revealed increased signal intensity in the right posterior frontal, temporoinsular and occipital cortex
(fig. 1A); PWI showed delayed arrival of the contrast to the right
hemisphere, and an area of hypoperfusion larger than the diffusion
lesion (fig. 1B). Intracranial MRA showed decreased flow in the right
internal carotid artery and cutoff of the M1 segment of the right middle cerebral artery (fig. 1C). The right posterior cerebral artery originated from the internal carotid artery. She was treated with intravenous rt-PA (total dose = 57.2 mg; 5.7 mg as a bolus over 1 min and
51.5 mg as an infusion over 60 min) within 150 min from symptom
onset. Follow-up MRI, 24 h later, showed a small region of hemorrhagic transformation within the infarct (fig. 1D, E) and recanalization of the right middle cerebral artery (fig. 1F).
Her neurological status gradually improved. She was discharged a
week later. At discharge, she had a left homonymous hemianopia and
slightly impaired short-term memory. Her National Institute of
Health Stroke Scale score was 5, with a modified Rankin scale score
of 1.

Cerebrovasc Dis 2002;14:54–57

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identification of ischemic tissue and the corresponding
arterial occlusion within the 3-hour window for thrombolysis [4]. We now report a patient with an ischemic stroke
who presented with seizures, in whom DWI/PWI and
MRA showed the presence of an arterial occlusion and
acute ischemic tissue. The patient was successfully treated
with intravenous rt-PA.

To date, intravenous rt-PA remains the only medication approved by the Food and Drug Administration for
treatment of acute ischemic stroke [5, 6]. The narrow 3hour ‘therapeutic window’ and a list of exclusion criteria,
however, limit its use to only a minority of acute stroke
patients. Published guidelines for thrombolytic therapy
for acute stroke recommend that a CT scan should be performed prior to the administration of rt-PA and exclude
patients who exhibit seizures at stroke onset from consideration for thrombolysis, since the diagnosis of stroke in
this setting may be difficult to distinguish from Todd’s
paralysis [1, 2]. The frequency of seizures during the first
24 h of an ischemic stroke is estimated to be !3% [7].
Nonenhanced CT is of limited value in this setting, since
early signs of ischemia are often subtle [8].
Although stroke is primarily a clinical diagnosis, cerebral imaging studies during the acute phase can play a crucial role in selecting patients who may be candidates for
rt-PA. Several recent advanced cerebral imaging strategies can provide information to ascertain the presence of
an ischemic process, assess its hemodynamics and estimate the tissue at risk [9–13]. The combination of DWI/
PWI MRI coupled with MRA can identify the extent of
infarcted tissue soon after the onset of stroke and permits
simultaneous characterization of hypoperfused tissue at
risk for infarction, major vessel occlusion and regional
cerebral blood flow during the hyperacute phase of stroke
[4, 14, 15]. Emerging evidence suggests that DWI/PWI
MRI can have a substantial impact on patient selection
for thrombolysis and can possibly be used to extend the
current 3-hour time window for tPA on a patient-bypatient basis [16, 17].
This patient illustrates the usefulness of combined
DWI/PWI and MRA in confirming the diagnosis of acute
ischemia in the setting of concurrent seizures. One might
argue that signal changes on DWI can be seen during epileptic seizures [18]. However, they do not correspond to a
vascular territory as in the present case. Furthermore, the
presence of concomitant PWI signal changes in the territory of a documented arterial occlusion is highly suggestive of ischemia. In contrast, studies using single-photon
emission CT show an increase in regional perfusion during epileptic seizures [19]. The Copenhagen Stroke Study
suggested that seizure at stroke onset might signify a large
area of hypoperfused, but potentially salvageable tissue
[20]. The findings in our patient support this hypothesis.
Such patients would likely benefit from early reperfusion.

56

Cerebrovasc Dis 2002;14:54–57

It is important to recognize that involuntary movements of the limbs can occasionally be seen in patients
with acute stroke [21]. These movements may include
intermittent shaking and jerky movements, and may be
reported by witnesses as ‘seizures’. The simultaneous
impairment of consciousness in our patient suggests that
the observed movements were epileptic in nature.
This single-case report highlights the potential value of
multimodal MRI sequences, in improving diagnosis,
management and prognosis of acute stroke patients. It
may also provide a rationale to revise current exclusion
criteria for thrombolysis (i.e. seizure at onset, hypoglycemia and hyperglycemia) since, when in doubt, the diagnosis of ischemic tissue may be supported by the imaging
study. Modern neuroimaging techniques, which can rapidly assess the status of cerebral vasculature, collateral
blood flow and presence of ischemic tissue, such as this
multiple MRI sequence, can improve the selection of
patients who are likely to benefit from thrombolysis.

Acknowledgments
G.S. is presently supported by grants from the Fireman and
Rubenstein Foundations and the Doris Duke Clinical Scientist Development Award. J.F. is supported by the New Zealand Neurological Foundation V.J. Chapman Fellowship Grant.

Selim/Kumar/Fink/Schlaug/Caplan/
Linfante
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Discussion

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