Case Reports

Ischemic Stroke and
Excellent Recovery
After Administration
of Intravenous Tissue
Plasminogen Activator
Sejal V. Jain, MD and
Lawrence D. Morton, MD

Intravenous tissue plasminogen activator has become a
mainstream treatment for ischemic hyperacute stroke
in the adult population. Its safety and efficacy remain
undetermined in the pediatric population. We present
a teenager who was hospitalized with left-sided paralysis, and with decreased sensations on the left side.
Head computed tomography indicated hyperdensity in
the middle cerebral artery region, which confirmed the
diagnosis of acute ischemic stroke. Her score on the
National Institutes of Health stroke scale was 11. She
received intravenous tissue plasminogen activator without any complications. At a follow-up visit 5 months after
the stroke, the patient manifested mild apraxia in her left
hand and mild expressive amusia. This case underscores
the need for emergency head imaging in the pediatric
population to establish a diagnosis. The excellent recovery in our patient indicates the need to establish thrombolytic treatment as an option for acute stroke in pediatric populations. It also suggests that tissue plasminogen
activator can be used safely and effectively, even in
pediatric populations. However, further studies are
needed to establish the adequate dosage and adverseeffect profile in pediatric populations.
© 2008 by
Elsevier Inc. All rights reserved.

From the Department of Neurology, Virginia Commonwealth
University Medical Center, Richmond, Virginia.

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PEDIATRIC NEUROLOGY

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Jain SV, Morton LD. Ischemic stroke and excellent recovery
after administration of intravenous tissue plasminogen
activator. Pediatr Neurol 2008;38:126-129.

Introduction
Acute ischemic stroke is an emergently diagnosed and
treated condition in the adult population. The Food and
Drug Administration of the United States has approved
tissue plasminogen activator as a treatment for acute
ischemic stroke in patients aged ⱖ18 years presenting
within 3 hours of the onset of signs of stroke. There are no
data available regarding tissue plasminogen activator for
pediatric stroke. We present a teenage girl who presented
with an acute stroke and was given intravenous tissue
plasminogen activator, based on criteria used for the adult
population [1].
Case Report
A 15-year-old, right-handed, white female presented to the emergency
room at Virginia Commonwealth University Health System with a
sudden onset of left-sided paralysis, left-sided facial weakness, and
decreased sensations in her left arms and leg. Before the onset of
symptoms, the patient had been running track for 45 minutes, experienced dizziness, and fell to the ground. She was then observed to have
left-sided weakness. The patient was brought to the emergency room via
ambulance within 1 hour of the onset of her signs. Her medical history
was negative for migraine, seizures, or trauma. Her family history was
positive for factor V Leiden mutation in a grandfather, but there was no
history of young-onset stroke. Her social history was negative for
smoking, and the use of drugs or oral contraceptive pills. She was not
taking any medications.
The patient’s vital signs included a temperature of 36.7 C axillary, a
blood pressure of 128/72, pulse at 124/min, and a respiratory rate of
22/min. On general examination, the patient was anxious, but a mentalstate examination produced otherwise normal results. No murmurs or
bruits were recognized. She had weakness of the lower face on her left
side, including weakness of the orbicularis oculi. Her left arm and leg
were completely flaccid. She had trace movements in her left foot.
Babinski was positive on the left side. Sensory loss was noticed in left
arm and leg. Her score on the National Institutes of Health stroke scale
was 11. A computed tomography scan of her head revealed a hyperdense
right middle cerebral artery in the distal branch (Fig 1). No hemorrhage
or hypodensity was seen on computed tomography. Her prothrombin
time, activated partial thromboplastin time, and international normalized
ratio were normal. A decision was made to administer intravenous tissue
plasminogen activator. Her parents were informed of the risks and

Communications should be addressed to:
Dr. Morton; Division of Child Neurology, Children’s Pavilion;
1001 East Marshall St. Box 980211; Richmond, VA 23298.
E-mail: lmorton@mcvh-vcu.edu
Received June 15, 2007; accepted October 15, 2007.

© 2008 by Elsevier Inc. All rights reserved.
doi:10.1016/j.pediatrneurol.2007.10.006 ● 0887-8994/08/$—see front matter

have been a potential cause of her seizures after the administration of
tissue plasminogen activator. A magnetic resonance angiogram revealed
a reestablished flow through the middle cerebral artery (Fig 3). A
repeated head computed tomography scan 24 hours after the administration of tissue plasminogen activator did not indicate a hemorrhage. A
cerebral angiogram performed 5 days later confirmed good flow through
the right middle cerebral artery.
During a follow-up visit about 5 months after the event, the only
apparent abnormality was mild apraxia in her left hand and mild
expressive amusia. Her score on the modified Rankin scale was 1.

Discussion

Figure 1. Computed tomography of the head demonstrates hyperdensity
in the right middle cerebral artery region (arrow).

benefits based on adult studies, and they consented to the treatment.
The patient was given intravenous tissue plasminogen activator at 0.9
mg/kg (5.56 mg as bolus, and 51.14 mg over the course of 1 hour)
within 3 hours of the onset of signs. After administration of the tissue
plasminogen activator, she experienced seizures. She had clonic
activity of the left shoulder and torso with the first seizure, and clonic
activity of the shoulder, arm, and face on the left side with the second
seizure. These were thought to be caused by reperfusion and changes
in metabolism after administration of the tissue plasminogen activator. A loading dose of fosphenytoin was given. The patient was
admitted to our Neuroscience Intensive Care Unit, and was monitored
as suggested by adult stroke guidelines.
Laboratory studies, including cholesterol, erythrocyte sedimentation
rate, homocysteine, lipoprotein a, lupus anticoagulant, anti-cardiolipin
antibodies, factor V Leiden, prothrombin mutations, proteins C and S,
antithrombin activity, a factor VIII assay, and vitamin B12 produced
normal results. Antinuclear antibody was positive, with a ratio of
1:320 in an atypical speckled pattern. Anti-SSA antibody, anti-Smith
antibody, and anti-double-stranded DNA antibody were also at
normal levels. Transthoracic echocardiogram with bubble study,
showed a patent foramen ovale and an atrial septal aneurysm.
Coumadin was initiated, and surgical repair was performed about 2
months after the stroke.
Her hypoesthesia and leg weakness improved rapidly after administration of tissue plasminogen activator. Her facial and left-hand weakness
gradually but significantly improved. On formal speech testing, she was
found to have amusia. Neuropsychologic testing, administered 3 months
after the event, suggested excellent cognitive skills.
Magnetic resonance imaging was performed about 3 hours after the
administration of tissue plasminogen activator, and it confirmed ischemia
involving the right posterior frontal and temporal region, consistent with
obstruction of the right distal middle cerebral artery (Fig 2). The
magnetic resonance imaging also ruled out hemorrhage, which could

In pediatric patients, the incidence of stroke involves
about 2-13 per 100,000, when neonatal strokes are excluded [2,3]. Common etiologies of childhood stroke
include sickle-cell disease, cardiac diseases, Moya Moya
disease, prothrombotic disorders, post-varicella vasculopathy, anti-phospholipid antibodies, extracranial arterial
dissections, and metabolic and mitochondrial disorders
[4-6]. Cardiac diseases account for about 25-27% of cases
of stroke. These include congenital anomalies such as
patent foramen ovale, and cardiac procedures and conditions leading to a right-to-left shunt [2,3,5,6]. Our patient
was thought to have an embolic stroke because of cardiac
defects. Data regarding patent foramen ovale and paradoxical embolization as a cause of cryptogenic ischemic stroke
in young patients remain controversial. One study suggested
that atrial septal abnormalities, including patent foramen
ovale, increase atrial vulnerability, which increases the
chances of arrhythmia [7]. Recurrent paradoxical events in
a patient with a patent foramen ovale are an indication
for closure of the patent foramen ovale. Studies related
to the closure of a patent foramen ovale suggested a
good success rate in the prevention of further occurrences of embolization [8].

Figure 2. Apparent diffusion coefficient image confirms ischemia in the
territory of the right distal middle cerebral artery.

Jain and Morton: Tissue Plasminogen Activator for Stroke 127

Figure 3. Magnetic resonance angiogram demonstrates flow through
right middle cerebral artery after administration of tissue plasminogen
activator.

Conditions such as seizure, migraine, altered mental
state, and vision changes may mimic a stroke [9,10]. These
conditions are more common in childhood compared with
stroke, and a differential diagnosis is not immediately
possible clinically. For the treatment of acute stroke, there
is a very narrow time window. Thus it is important to
diagnose it as soon as possible. A nonenhanced computed
tomography scan helps to exclude a hemorrhage, but may
not diagnose a hyperacute stroke. The patient presented
here received her treatment based on hyperdense signs on
a computed tomography scan, which may not be present in
all patients with stroke. Magnetic resonance imaging with
diffusion-weighted images, and computed tomography
perfusion and computed tomography angiography, were
found to be sensitive in diagnosing a hyperacute stroke
[11]. Such a study should be performed in pediatric
patients with signs suggestive of a stroke or its mimics. It
is also important for these services to be available immediately, to diagnose and treat stroke within a 3-hour
window from the onset of signs.
There is significant morbidity associated with childhood
stroke. A review by Jordan [2] suggested that in children
with acute ischemic stroke, 47% had moderate to severe
motor deficits, 25% had recurrent seizures, and 19-44%
had behavioral issues. The mean intelligence quotient was
also lower in children with stroke [2], and 25-30% had
recurrent stroke [2,12]. The mortality rate was reported to
be 7-28% [5]. All these data suggest the need for the
treatment and secondary prophylaxis of childhood stroke.

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Tissue plasminogen activator has become the standard
of care for adult patients with stroke. This treatment was
found to reduce morbidity by 30% [13]. However, there is
little information about adequate doses and safety for its
use in pediatric populations. Data from Janjua et al.
suggest that children who received thrombolytic therapy
had higher rates of in-hospital mortality and longer hospital stays [14]. Another review suggested that major
bleeding occurred in 11% and intracranial hemorrhage in
1-2% of children who received thrombolytic therapy [4].
A review by Carpenter et al. identified a total of 44
cases where intravenous or intra-arterial tissue plasminogen activator was used, but detailed only three patients
who had received intravenous tissue plasminogen activator and who experienced an improvement of signs
[15]. Our patient had not only excellent motor recovery,
but also an excellent cognitive profile after her stroke.
Thus this case is strongly suggestive of the benefits of
tissue plasminogen activator in children with a hyperacute stroke. Another interesting aspect of this case was
an association with seizure. The patient was initially
thought to have undergone a seizure when she fell, and
her weakness was thought to be due to Todd’s paresis.
A computed tomography scan of her head was suggestive of an occluded right middle cerebral artery, which
led to the timely administration of tissue plasminogen
activator. This once again strongly suggests the need for
timely imaging studies, and particularly magnetic resonance imaging with diffusion-weighted imaging. There
are no controlled studies for the use of tissue plasminogen activator in children. Studies are needed to establish dosage, safety, and efficacy for tissue plasminogen
activator in pediatric populations.

References
[1] Quality Standards Subcommittee of the American Academy
of Neurology. Practice advisory: Thrombolytic therapy for acute ischemic stroke—Summary statement. Report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology
1996;47:835-9.
[2] Jordan LC. Stroke in childhood. Neurologist 2006;12:94-102.
[3] Matta AP, Galvao KR, Oliveira BS. Cerebrovascular disorders
in childhood: Etiology, clinical presentation, and neuroimaging findings
in a case series study. Arq Neuropsiquiatr 2006;64:181-5.
[4] Kirton AG, DeVeber G. Therapeutic approaches and advances in
pediatric stroke. Neuro Rx 2006;3:133-42.
[5] Lynch JK, Hirtz DG, DeVeber G, Nelson KB. Report of the
National Institute of Neurological Disorders and Stroke Workshop on
Perinatal and Childhood Stroke. Pediatrics 2002;109:116-23.
[6] Lynch JK, Pavlakis S, DeVeber G. Treatment and prevention of
cerebrovascular disorders in children. Curr Treat Options Neurol 2005;
7:469-80.
[7] Berthet K, Lavergne T, Cohen A, et al. Significant association of
atrial vulnerability with atrial septal abnormalities in young patients with
ischemic stroke of unknown cause. Stroke 2000;31:398-403.
[8] Horton SC, Bunch TJ. Patent foramen ovale and stroke. Mayo
Clin Proc 2004;79:79-88.
[9] Calder K, Kokorowski P, Tran T, Henderson S. Emergency
department presentation of pediatric stroke. Pediatr Emerg Care 2003;
19:320-8.

[10] Shellhaas RA, Smith SE, O’Tool E, Licht DJ, Ichord RN.
Mimics of childhood stroke: Characteristics of a prospective cohort.
Pediatrics 2006;118:704-9.
[11] Hunter JV. New radiographic techniques to evaluate cerebrovascular disorders in children. Semin Pediatr Neurol 2000;7:261-77.
[12] DeVeber G. In pursuit of evidence-based treatments for
paediatric stroke: The UK and Chest guidelines. Lancet Neurol
2005;4:432-6.

[13] National Institute of Neurological Disorders and Stroke
rt-PA Stroke Study Group. Tissue plasminogen activator for acute
ischemic stroke. N Engl J Med 1995;333:1581-7.
[14] Janjua N, Nasar A, Lynch JK, Qureshi AI. Thrombolysis for
ischemic stroke in children. Data from the nationwide inpatient sample.
Stroke 2007;6:1850-4.
[15] Carpenter J, Tsuchida T, Lynch JK. Treatment of arterial
ischemic stroke in children. Expert Rev Neurother 2007;7:383-92.

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