2108

Postpartum Cerebral Angiopathy
Is There a Role for Sympathomimetic Drugs?
Henry G. Raroque, Jr, MD; Ganana Tesfa, MD; Phillip Purdy, MD
Background: Postpartum cerebral angiopathy is associated with the use of ergot alkaloids. The exact
mechanism is unclear but may be related to their sympathomimetic properties, as evidenced in patients
already on other ergot derivatives who deteriorated only after taking additional sympathomimetic drugs.
We postulate that sympathomimetic agents, independent of ergot alkaloids, may produce the same
complication.
Case Description: A postpartum patient, initially presenting with headaches, subsequently manifested
rapid neurological deterioration after ingesting isometheptene, a sympathomimetic drug. She was not on
any ergot derivative but presented similar clinical and radiological manifestations. She experienced
increased headache severity, visual disturbance, and seizures associated with multiple segmental cerebral
vasoconstriction on angiography and increased T2-weighted signal in the occipital areas on magnetic
resonance imaging.
Conclusions: This case is additional evidence that sympathomimetic actions of some drugs, such as ergot
derivatives and isometheptene, may lead to postpartum cerebral angiopathy. Documentation of medication used by postpartum women suffering similar complications is needed to verify these findings. (Stroke.
1993;24:2108-2110.)

KEY WoRDs * sympathomimetics * vasoconstriction * women

E rgot alkaloids, such as ergonovine, have been
implicated as possible causes of postpartum
cerebral angiopathy.1 Physicians have not
clearly defined nor consistently recognized this condition, which is generally characterized by headache,
seizures, and focal neurological deficits associated with
cerebral vasoconstriction on angiography.2 Similar clinical neurological presentation has been reported in
postpartum women who do not carry clear diagnoses
but who deteriorate after the ingestion of another ergot
derivative, bromocriptine.,3 Of the many properties of
ergot derivatives, it is unclear what produces this complication, but one report suggests that mechanisms
relating to the sympathomimetic properties may play a
role in the pathogenesis.4 In the report, two postpartum
women who were already taking bromocriptine had
neurological symptoms after ingesting other sympathomimetic drugs, one containing isometheptene and the
other containing phenylpropanolamine. We encountered a postpartum patient who was not on bromocriptine but who exhibited similar clinical manifestations
associated with cerebral vasoconstriction after ingesting
isometheptene, adding further support to the possible
role of agents with sympathomimetic properties in the
pathogenesis.
Received May 17, 1993; final revision received August 11, 1993;
accepted August 11, 1993.
From the Departments of Neurology (H.G.R., G.T.), Radiology
(P.P.), and Neurosurgery (P.P.), The University of Texas Southwestern Medical Center at Dallas.
Reprint requests to Henry G. Raroque, Jr, MD, cdo The
Editorial Office, Department of Neurology, The University of
Texas Southwestern Medical Center, 5323 Harry Hines Blvd,
Dallas, TX 75235-9115.

Case Report
A 32-year-old woman, gravida 3, para 3, was admitted
to the hospital after complaining of increasingly severe
headaches 5 days after an uncomplicated pregnancy and
delivery. She had a 4-year history of poorly defined
headaches characterized as diffuse and throbbing, without aura, and occasionally associated with nausea. The
headaches had occurred approximately every 3 months,
were of variable duration, and were relieved by acetaminophen or aspirin. Aside from the persistence and
increasing severity, her present headaches exhibited the
same characteristics as those occurring during the previous 4-year period.
On initial presentation, her blood pressure, physical
and neurological examinations, and routine laboratory
tests, including urinalysis, were normal. Contrast computed tomography scan and cerebrospinal fluid analysis
also were normal. She was treated with chlorpromazine
50 mg IV, and the headaches subsided. She was discharged and instructed to take a commercial preparation containing isometheptene mucate 65 mg per tablet,
dichloralphenazone 100 mg per tablet, and acetaminophen 325 mg per tablet (Midrin, Carnrick Laboratories, Inc, Cedar Knolls, NJ). She was advised to take this
medication as needed for headaches but not to exceed
ingesting six tablets in 24 hours and 10 tablets in 1 week.
She was also prescribed amitriptyline 25 mg every night,
but she denied taking them.
After discharge, she experienced the headaches
again, for which she took eight tablets of isometheptene
within 24 hours. Subsequently, she complained of flashing lights and photophobia, followed immediately by
generalized tonic-clonic seizures. She was readmitted.
Her physical examination, including blood pressure, was

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Raroque et al Postpartum Effect of Sympathomimetic Drugs

i.

2109

I,
'44

Left, T2-weighted magnetic resonance scan, axial view,
shows bilateral occipital areas of increased signal intensity. Right, Right vertebral arteriogram, anteroposterior
view, shows multiple areas of segmental vasospasm.

normal. A neurological examination only revealed lethargy. A repeat work-up, including an echocardiogram,
electroencephalogram, erythrocyte sedimentation rate,
and antinuclear antibody, was normal. A toxicological
screen was not performed, but there was no history of
illicit drug use. Magnetic resonance imaging (MRI)
within 24 hours of admission showed bilateral occipital
increased signal on T2-weighted images (Figure, left
panel). There was no evidence of hemorrhage.
Transcranial Doppler study (TCD) performed 2 days
later demonstrated mild to moderate elevated velocities
diffusely, interpreted as diffuse arterial narrowing or
hyperemia. In addition, the anterior cerebral artery
(ACA) velocities were abnormally greater than the
middle cerebral artery (MCA) velocities, and there was
a sudden increase in basilar artery velocity at a depth of
approximately 85 mm, suggesting a focal stenosis of the
basilar artery. Four-vessel cerebral angiography, 3 days
after admission, revealed widespread segmental vasoconstriction (Figure, right panel). After being treated
with phenytoin, her seizures did not recur. In addition,
her headache subsided with acetaminophen. A repeat
cerebral angiography was not performed, but a repeat
TCD was performed 6 days after the first study. The

TCD showed persistent global elevation in velocity but
normalization of the ratio of ACA to MCA velocity as
well as near disappearance of the focal velocity elevation previously seen in the basilar artery. A repeat MRI
10 days later was normal.
Discussion
Our patient had a presentation similar to that of
patients with toxemia and postpartum cerebral angiopathy. However, she did not have hypertension, proteinuria, or edema to satisfy the minimal clinical and
laboratory criteria for toxemia5,6 and more likely had
postpartum cerebral angiopathy. Her rapid deterioration occurred after the ingestion of more than the
recommended amount of medication. The medication
may have been excessive for anyone. Alternatively, the
medication may have been contributory to a predisposed state or a progressing pathological process peculiar to the postpartum period.
Isometheptene, the major component of Midrin, is a
sympathomimetic agent with direct vasoconstrictive activity on cranial and cerebral arterioles and is widely
used in the treatment of migraine and other vascular
headaches.3'7 To our knowledge, the syndrome pre-

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2110

Stroke Vol 24, No 12 December 1993

sented by our patient has not been reported as a specific
side effect of this drug. The only other documented case
involving isometheptene was with a postpartum patient
who was also on bromocriptine for lactation suppression.4 The patient experienced progressively severe
headache and cardiovascular distress 6 days postpartum
after ingesting three tablets of a commercial preparation containing isometheptene. Unfortunately, no angiographic studies were performed. The authors used
the case to suggest a sympathomimetic interaction with
bromocriptine as the mechanism for the complication,
especially since the patient also had been on bromocriptine in a previous pregnancy but did not experience any
complications. They supported this hypothesis by reporting another postpartum patient who was also on
bromocriptine and who deteriorated only with the ingestion of another sympathomimetic drug, phenylpropanolamine. In this case, the patient showed a presentation similar to that of our patient, experiencing
headache, blindness, and two generalized tonic-clonic
seizures associated with cerebral vasoconstriction on
angiography.
No specific mechanism has yet been proven for
postpartum cerebral angiopathy, but mechanisms relating to severe hypertension, as in toxemia, have been
proposed.2 In toxemia, it is postulated that the neurological deterioration is a result of severe hypertension
with resultant cerebral vasospasm and subsequent loss
of autoregulatory control leading to ischemia, edema,
infarction, or hemorrhage.6 In patients on bromocriptine, transient acute increases in blood pressure were
recorded.4 In our patient, hypertension was not recorded at any time. Still, transient hypertension could
have been present but merely missed. However, other
mechanisms, such as reversible vasospasm secondary to
increased vasomotor responsiveness or an arteriopathy
relating to direct vasoconstrictive activity independent
of hypertension, also could have been present. The
latter mechanism already has been implicated in cerebrovascular complications arising from more potent
sympathomimetic drugs, such as cocaine and amphetamine in pregnant and nonpregnant patients.8'9 The
more commonly used sympathomimetic drugs also may
produce vasoconstriction with or without hypertension.
For example, in large doses isometheptene can produce
generalized vasoconstriction and increased blood pressure. However, in low doses it only causes selective

vasoconstriction in certain vascular beds before any
effects on blood pressure can be seen.10 Phenylpropanolamine, a commonly used nasal decongestant, acts
through local vasoconstriction in the nasal mucosa.
However, it also has pressor effects secondary to both
vasoconstriction and increased cardiac output."
Overall, our case lends support to the hypothesis that
postpartum cerebral angiopathy may arise from drugs
with sympathomimetic properties. It also raises the
question of whether postpartum patients are truly more
vulnerable to the less potent sympathomimetic drugs.
Documentation of medications, particularly those with
sympathomimetic properties, in women suffering similar
clinical and radiological manifestations during pregnancy and immediately after delivery is needed to verify
these findings.

Acknowledgments
We thank Cole Giller, MD, PhD, for his suggestions and
detailed interpretation of the transcranial Doppler studies,
and Jane M. Snipes for her editorial work.

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Postpartum cerebral angiopathy. Is there a role for sympathomimetic drugs?
H G Raroque, Jr, G Tesfa and P Purdy
Stroke. 1993;24:2108-2110
doi: 10.1161/01.STR.24.12.2108
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1993 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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