Clinical Neurology and Neurosurgery 110 (2008) 529–531

Case report

Cryptogenic stroke in the setting of intravaginal prostaglandin
therapy for elective abortion
Nirali Patel, Ron Shatzmiller, Nerses Sanossian, Soma Sahai-Srivastava ∗
Department of Neurology, University of Southern California, Los Angeles, CA, United States
Received 16 October 2007; received in revised form 16 February 2008; accepted 19 February 2008

Abstract
Vaginal prostaglandin pessaries are considered safe and effective method of abortion within the first two trimesters of pregnancy. We present
a case of a young woman, with no known risk factors for cerebrovascular events, who developed a cryptogenic stroke following administration
of intravaginal Misoprostol.
Case report and review of the relevant literature.
A 30-year-old woman presented with right hemiparesis and aphasia after having received three 600 ␮g tablets of intravaginal Misoprostol
for an elective abortion earlier in the day. A brain MRI revealed an acute ischemic infarction in the left middle cerebral artery territory. An
extensive workup for possible etiologies was negative.
Intravaginal Misoprostol may be associated with stroke in young women. Further study is required to determine if this case represents an
isolated incident, or a true association.
© 2008 Elsevier B.V. All rights reserved.
Keywords: Misoprostol; Prostaglandin E1; Stroke; Cerebrovascular; Cryptogenic stroke; Induced abortion

1. Introduction
Vaginal prostaglandin pessaries are considered safe and
effective methods of abortion if they are administered during
first two trimesters of pregnancy. Although adverse events
are associated with their use, to our knowledge there are no
reported cerebrovascular side effects [1,2]. The most commonly used vaginal pessary contains a synthetic analog of
prostaglandin E1 (Misoprostol), with a reported side effect
profile consisting of uterine hyperstimulation, uterine rupture, genital bleeding and amniotic fluid embolism. Other
less common side effects from systemic use of Misoprostol
include hypotension, arrhythmia, dizziness, thrombocytopenia and purpura [1,2]. We present the case of a young woman,
with no know cerebrovascular risk factors, who developed
a stroke within 13 h of the administration of intravaginal
∗ Corresponding author at: Department of Neurology, LAC+USC Medical
Center, 1200N State St. Room 5640, Los Angeles, CA 90033, United States.
Tel.: +1 323 226 7381; fax: +1 323 226 5869.
E-mail address: sahai@usc.edu (S. Sahai-Srivastava).

0303-8467/$ – see front matter © 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.clineuro.2008.02.018

Misoprostol. A search of the Medline database from 1966
to 2007 revealed only one similar case, reported by Lauren
and Berentelg in a German journal [3].

2. Case report
A 30-year-old right-handed Chinese-Vietnamese woman
presented to the emergency department (ED) of an outside
hospital with right-sided paresis and aphasia of 7 h duration.
The patient (gravida 3, para 2) had received three 600-␮g
tablets of intravaginal Misoprostol for an elective abortion at
8 a.m. that morning. Gestation was 12 weeks. At approximately 9 p.m. on the same day she developed difficulty
with production of speech and right-sided weakness. Her past
medical history was significant for a previous elective abortion several months prior to this event. She had no family
history of stroke, hypercoagulability, vasculitis, illicit drug
abuse or smoking. A non-contrast head CT performed in
the ER showed hypodensity in the distribution of the superior division of the left middle cerebral artery (MCA), with

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N. Patel et al. / Clinical Neurology and Neurosurgery 110 (2008) 529–531

Fig. 1. MRI and MRA of the brain preformed the day after symptom onset demonstrating restricted diffusion in the left frontal lobe on diffusion weighted
imaging (A), corresponding area of hyper intensity on FLAIR (B), petechial hemorrhage on gradient echo (C), and normal intracranial MR angiography (D).

sulcal effacement and loss of the gray–white junction. An
electrocardiogram and cardiac catheterization were normal.
A trans-esophageal echocardiogram showed mild left ventricular hypertrophy, but no evidence of thrombus, valve
abnormality or foramen between the chambers of heart. She
was transferred to a tertiary-care center for further workup
and treatment.
Upon transfer her physical examination was notable for
an expressive aphasia and complete right-sided hemiplegia with intact comprehension. A brain magnetic resonance
image (MRI) showed acute ischemic infarction in the
middle cerebral artery territory (Fig. 1A–C). Intracranial
magnetic resonance angiography (MRA) (Fig. 1D), and
MRA of the neck and carotid duplex scan were unremarkable. Multiple additional studies were performed to
identify stroke and thromboembolic risk factors, including

cardiac monitoring, trans-esophageal echocardiogram, and
serum tests of hypercoaguability, and vasculitis (including
D-dimers, fibrinogen, protein C, protein S, antithrombin
III, activated protein C resistance, antineutrophilic antibody,
antineutrophilic cytoplasmic antibodies (ANCA), factor V
deficiency, lupus anticoagulant, anticardiolipin antibodies,
homocysteine, alpha-galactosidase mutation and rheumatoid
factor). All were negative.
The patient was in the intensive care unit for 48 h. During
this time, continuous cardiac monitoring was conducted. No
arrhythmias were noted. She was treated with a standard dose
of aspirin during her hospitalization. Over a period of 5 days,
there was gradual improvement in her expressive aphasia and
arm strength until her discharge to acute rehabilitation. Upon
a follow-up visit 2 months later, she demonstrated significant
improvement of strength and language.

N. Patel et al. / Clinical Neurology and Neurosurgery 110 (2008) 529–531

3. Discussion
Prostaglandins are 20-carbon derivatives of unsaturated
fatty acids that are found in almost all organs and tissues and
function as hormones in a wide variety of physiological contexts. The prostaglandin family of molecules are designated
A-K, with numerical or Greek subscripts further defining key
structural features of individual PG family members. Misoprostol is a synthetic analog of PGE1, and is available as
oral and intravaginal preparations [1]. Intravaginal preparations are considered safe and effective methods of abortion
if administered within the first two trimesters of pregnancy,
often prescribed in a regimen of 400 ␮g every 3 h to a maximum of five doses [2]. The duration of the biological actions
of Misoprostol is 2–6 h.
Prostaglandins are potent vasodilators; increasing peak
cardiac output and cerebral blood flow. They also inhibit
platelet aggregation [4,5]. These properties are considered
potentially beneficial in the setting of ischemic stroke [5].
However, some studies in animals have revealed a biphasic,
dose dependent action of PGs, especially PGE1, in which
low doses cause vasoconstriction and high doses induce
vaso-relaxation [6,7]. This has also been demonstrated upon
intracarotid injection and topical application of PGE1 in
humans [8].
Prostaglandins also have direct effects in the brain. PGE
binds to a family of G protein-coupled receptors, the EP
receptors, which are expressed in brain tissue. Stimulation
of the EP3 receptor subtype results in enhanced release of
intracellular calcium reserves, which activates enzymes such
as phospholipase C, phospholipase A2 and neuronal nitric
oxide synthase [9]. Activation of these enzymes may lead to
cerebral ischemia [9].
It should be noted that the dose of Misoprostol administered in this case was 1800 ␮g as a one-time dose. Misoprostol
is often given in doses up to 2000 ␮g, in 400 ␮g increments.
The reason this patient received a higher initial dose was not
clear, but we suggest that it may have triggered or contributed
to her stroke. This possibility is supported by the lack of evidence for any known risk factor, such as reversible cerebral
vasoconstrictive syndrome (RCVS), eclampsia, vasculitis
or thromboembolic phenomena. Reversible cerebral vasoconstrictive syndrome typically presents with thunderclap
headache, seizures, focal neurological deficits and segmental narrowing of cerebral arteries [10]. The absence of these
symptoms and the normal MRA argues against RCVS. In
addition, the patient showed no evidence of high blood pressure, proteinuria or seizures in her history or during her
hospitalization, ruling out pre-eclampsia. Serum markers and
clinical signs of vasculitis were also negative.
The only published report of a stroke following PG treatment indicated that prostaglandins can cause ischemic stroke
due to their dose dependant vasoconstrictive effects [3].

531

It is also important to note that myocardial infarctions have
been reported to occur upon PGs administration [11–15].
Although a formal diagnosis of cryptogenic stroke was
made in the current case, we hypothesize that intravaginal
Misoprostol may have provided a trigger for the event. In
order to determine whether this case represents an isolated
incident, or reflects an increased risk for stroke associated with Misoprostol treatment, requires more extensive
studies.

Acknowledgement
We thank Dr. Wendy Gilmore for critical reading of the
manuscript.

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