case study
A case of postpartum cerebral angiopathy
with subarachnoid hemorrhage
Yolanda Chik, Robert E. Hoesch, Christos Lazaridis, Carla J. Weisman and Rafael H. Llinas
Background. a 33-year-old woman experienced a thunderclap headache immediately postpartum. the headache
recurred over the next 10 days, and the patient also developed generalized tonic–clonic seizures. a subarachnoid
hemorrhage was demonstrated on a head ct scan.
Investigations. Physical examination, laboratory tests, brain ct scan, brain MRI scan, brain magnetic resonance
angiogram, brain magnetic resonance venogram, cerebral angiography, transcranial doppler ultrasound, eeG.
Diagnosis. Postpartum cerebral angiopathy.
Management. NsaIds and opioid analgesics administered on postpartum day 3 provided partial headache
relief. the next day, a blood patch was performed and intravenous caffeine, fluid and opioid analgesia were
given to treat a suspected dural puncture headache. Following diagnosis of postpartum cerebral angiopathy
on postpartum day 10, nimodipine was initiated to treat the vasospasm, and the headache was treated with
opioid analgesics and toradol, followed by naproxen. the patient also received a 3-day course of intravenous
magnesium sulfate.
chik, y. et al. Nat. Rev. Neurol. 5, 512–516 (2009); doi:10.1038/nrneurol.2009.114

The case

department of
Neurology (Y. Chik,
R. H. Llinas),
department of
anesthesiology and
critical care Medicine
(R. E. Hoesch,
C. Lazaridis), Johns
Hopkins school of
Medicine, Baltimore,
Md, usa. department
of Obstetrics and
Gynecology, sinai
Hospital, Baltimore,
Md, usa
(C. J. Weisman).
correspondence:
R. H. Llinas,
department of
Neurology, Johns
Hopkins Bayview
Medical center, 4940
eastern avenue B122b,
Baltimore, Md 21224,
usa
rllinas@jhmi.edu

After a normal, 38-week pregnancy, a 33-year-old
Filipino woman gave birth to her second child, a healthy
boy (2,940 g), by cesarean section. For the delivery, she
underwent spinal anesthesia with a 24-gauge needle,
and, shortly after the procedure, experienced the “worst
headache of her life”. The headache started with a painful
sensation ascending from the middle of her back to the
occipital region of the skull. The pain spread to involve
her entire head within seconds. She described the pain
as 10/10 in severity and explosive in nature. An eclampsia work-up revealed no peripheral edema, proteinuria,
abnormal laboratory tests or arterial hypertension. After
delivery and discontinuation of the spinal catheter, and
during the early postpartum period, her headache persisted with fluctuating severity, but her neurological
examination remained normal. The patient had no
other complications associated with her delivery. On
postpartum day 3, she experienced a severe exacerbation of her headache, which was only partially relieved
with NSAIDs and opioid analgesics.
The next day, several hours after she was discharged
home, the patient returned to the emergency room
complaining of a severe, unremitting headache that
was worse in the upright position. On the basis of this
history, she was presumed to have a dural puncture
headache, and a blood patch was performed, which
produced immediate, moderate relief. The patient was
Competing interests
the authors declare no competing interests.

also given intravenous caffeine (one intravenous 500 mg
dose) and fluids, as well as opioid analgesia, which are
the standard medical therapies to treat dural puncture
headache in our institutions. Approximately 90 minutes
later, she experienced two generalized tonic–clonic seizures (GTCSs), each lasting approximately 1 minute and
preceded by blurry vision. She did not experience diplopia, dysarthria, dysphagia, vertigo, nausea, vomiting,
visual field obscuration, fortification spectra, scotomata,
or focal weakness in association with her headaches.
Because of the seizures, she underwent head CT, brain
MRI, magnetic resonance (MR) angiography, MR venography and EEG, all of which were normal. She was discharged on postpartum day 7 with a persistent headache,
which she rated 4/10 in severity. No antiepileptic drugs
were prescribed.
On postpartum day 10, the patient again developed
a severe, progressive headache without obvious positional exacerbation, and she was readmitted to the
hospital. Head CT on admission revealed a subtle hyperdense signal over the right cortical convexity within the
right Sylvian fissure, and over the tentorium cerebelli.
Approximately 12 hours after the initial CT scan, the
patient experienced another GTCS, again preceded by a
vague visual prodrome. She did not experience any associated diplopia, dysarthria, dysphagia, vertigo, nausea,
vomiting, visual field obscuration, or focal weakness. A
repeat CT scan revealed a substantial accumulation of
subarachnoid blood over the right cortical convexity,
the right Sylvian fissure, the interhemispheric fissure, and

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case study
the basal cisterns, with thick clot in the right ambient
cistern (Figure 1). Owing to suspicion of aneurysmal
rupture, she was then transferred to our Neuroscience
Critical Care unit (NCCu). On admission, she complained of a nonpositional headache, which she rated
3/10 in severity. Neurological and general medical
examinations were both normal.
The patient’s past medical history was notable for
migraines and recurrent positional vertigo. She had no
history of hypertension, stroke or seizures. She was taking
no medications, other than over-the-counter analgesics,
and received no sympathomimetics at any time, including around delivery. She did not use ethanol, tobacco,
or illicit drugs such as cocaine, and she had no family
history of subarachnoid hemorrhage (SAH). 8 years
before her current presentation, she had an entirely
uncomplicated pregnancy and delivery of a healthy child,
the only notable occurrence being a 1-day headache
following epidural anesthesia for that delivery.
During the time that the patient spent on the NCCu,
the following serologies and laboratory values were
all normal: antinuclear antibody, antidouble stranded
DNA antibody, rapid plasma reagin, antineutrophil
cytoplasmic antibody, Sjögren antibodies (SS–Ro and
SS–la), lupus anticoagulant and antiphospholipid antibody panel, renal and hepatic function panels, complete blood count, basic metabolic panel, urine analysis,
blood cultures, and serum and urine toxicologies. Her
C-reactive protein was elevated at 27 mg/l (normal
upper limit 5 mg/l), raising suspicion of vasculitis or an
inflammatory disease.
A transfemoral cerebral angiogram was performed
and revealed no aneurysm, cerebral sinus thrombosis,
vascular malformation, or dissection to account for the
SAH. The angiogram was remarkable, however, for a
diffuse pattern of sausage-like dilatation with proximal
and distal stenoses (the pearl and string sign; Figure 2a).
MRI of the brain revealed high fluid-attenuated inversion
recovery signal consistent with SAH with no restricted
diffusion, and hemosiderin deposition on the cortical
convexity and right ambient cistern on gradient echo
sequences (Figure 3). Transcranial Doppler ultrasound
(TCD) demonstrated high blood-flow velocities consistent with vasospasm, most notably within the right
M1 segment of the middle cerebral artery (MCA; velocity 206 cm/s; normal range 50–60 cm/s) and the C1
segment of the right internal carotid artery (ICA; velocity
165 cm/s; normal range 30–40 cm/s). The left vertebral
artery also showed elevated velocity (80 cm/s; normal
value 30–40 cm/s).
The patient was closely monitored in the NCCu for
2 days and was subsequently sent to the neurology floor.
Nimodipine (30 mg by mouth every 2 hours) was initiated at this time to treat the vasospasm, and the patient’s
headache was treated with opioid analgesics and toradol
(30 mg administered intravenously every 6 hours for
5 days) followed by naproxen (500 mg by mouth every
12 hours). No lumbar puncture was performed. The

Figure 1 | Brain ct scan. arrows indicate areas of increased density consistent with
subarachnoid hemorrhage. Hemorrhage is visible in the convexity on the right sylvian
fissure and along the tentorium—a typical pattern seen in subarachnoid hemorrhage.

a

b

Figure 2 | cerebral angiography. a | Initial angiogram performed on postpartum day 6.
arrows indicate areas of vasoconstriction. b | Follow-up angiogram performed
2 weeks later, showing resolution of angiographic abnormalities.

patient was also treated with a 3-day course of intravenous
magnesium sulfate (2 g every 6 hours) with her serum
magnesium level peaking at 2.9 mg/dl (1.19 mmol/l).
The patient’s neurological examination remained normal
and her headache improved. Follow-up TCD studies
during her stay on the neurology floor showed resolving vasoconstriction, with blood-flow velocity falling
to ~180 cm/s in the M1 segment of the right MCA. A
second cerebral angiogram was performed on postpartum day 20 and the vasospasm was unchanged. A
CT angiogram on postpartum day 14 also confirmed
proximal and distal cerebral vasospasm. 10 days after
discharge, the patient was evaluated in the outpatient
clinic, and her headache had continued to improve. Her
neck stiffness and pain had completely resolved and
her neurological examination continued to be normal.

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case study

Figure 3 | MRI FLaIR sequences of the patient’s brain.
the FLaIR abnormalities are typical of those seen in
subarachnoid hemorrhage, namely, bright signal in the
sulci of the cortical convexities consistent with the bright
signal of the ct scan, and edema of the cerebral cortex
where the blood collects. Of note, no hypertension-related
abnormalities are evident in the occipital lobes. arrows
indicate areas of increased FLaIR signal consistent with
acute or subacute subarachnoid hemorrhage.
abbreviation: FLaIR, fluid-attenuated inversion recovery.

TCD performed during this clinic visit demonstrated
decreased velocities in the M1 segment of the right
MCA (140 cm/s) and the C1 segment of the right ICA
(140 cm/s), consistent with significantly improved vasospasm. A follow-up brain MRI scan demonstrated no
ongoing injury.

Discussion of diagnosis

Postpartum cerebral angiopathy (PCA) is characterized
by a reversible, multifocal, diffuse segmental narrowing
of the cerebral arteries that presents with neurological
deficits. Sequelae of PCA commonly include both ischemic strokes and intracerebral hemorrhages. SAH, as
described in this case, is a less common sequela of PCA,
which is itself a rare disorder.
The differential diagnoses in this case initially included
pre-eclampsia–eclampsia, aneurysmal SAH, venous sinus
occlusion, persistent low pressure postdural puncture
headache, and migraine.1 Eclampsia can, in rare cases,
produce a reversible vasoconstriction syndrome with a
similar appearance on conventional angiogram to the
vasoconstriction seen in our patient.2,3 Indeed, PCA and
eclampsia could be considered together on the same spectrum of peripartum cerebrovascular illness. In this case,
however, a negative eclampsia panel ruled out eclampsia
according to the traditional definition: during hospitalization, the patient’s systolic blood pressure stayed in the low
100s, which was near her baseline; urinalysis was negative
for proteinuria; her liver enzymes were normal; and she

had no peripheral edema on examination. Eclampsia
without hypertension but with cerebral edema was also
considered, but was deemed unlikely because of an
absence of any other defining features of eclampsia and a
lack of relevant findings on MRI.
Two conventional angiograms separated by approximately 13 days showed no aneurysm, and also showed
resolution of vasoconstriction (Figure 2b), which argues
strongly against aneurysmal rupture. Occlusion of the
venous sinuses and cerebral veins was also considered,
but was ruled out on the basis of normal MR venography
and patent venous sinuses on cerebral angiography.
Arteriovenous malformation and arterial dissection
related to childbirth were also ruled out by cerebral
angiography and MR angiography. Pituitary apoplexy or
infarction (Sheehan syndrome) was considered, but was
excluded by brain MRI. In light of the cerebral angiogram, which revealed a diffuse pattern of focal arterial
stenosis, clinical suspicion was narrowed to PCA and
CNS vasculitis. On the basis of angiography alone, PCA
can be difficult to distinguish from CNS vasculitis. The
possibility of the SAH occurring secondary to spinal
anesthesia or blood patch was also raised. Spinal MRI
imaging was normal, however, and asymmetric layering
of blood over the brain convexity would be an unusual
occurrence in the latter etiology. The rapid clinical and
angiographic improvement, as well as the close temporal
relationship with her pregnancy, led to the final diagnosis
of PCA in this patient.4,5
Reversible cerebral vasoconstriction syndrome (RCvS),
of which PCA is a subset, is rare, and its pathogenesis
is poorly understood.6 RCvS is defined by a reversible,
segmental, multifocal vasoconstriction of the cerebral
arteries, and severe headaches (usually characterized
as ‘thunderclap’ with an acute and excruciating onset),
with or without focal neurological deficits or seizures.7
The typical findings on imaging consist of diffuse segments of narrowing involving large and medium-sized
arteries in the anterior and posterior circulations, with
occasional dilated segments. This pathology gives rise
to the radiological pearl and string sign.6 In the present
case, the diffuse findings on angiography did not match
up perfectly with the TCD findings. It is possible, however, that the vasoconstriction was patchy, causing focal
areas of elevated velocities to be missed on TCD.
PCA is typically self-limited and occurs within the
first postpartum week in women after an uneventful
pregnancy and delivery.8 In some instances, it can be
associated with either ischemic strokes or intracerebral
hemorrhage.5 Of note, in one case series, a cortical hematoma occurred in eight out of nine patients, which suggests that either cortical or leptomeningeal vessels are
primarily involved in the process.4 The occurrence of
SAH is rare in the context of PCA, with a review of the
literature revealing only six such cases (Table 1).4,9–11
The pathophysiology of PCA remains uncertain,
although several mechanisms have been proposed.
Pathological or toxic processes that affect cerebrovascular

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case study
Table 1 | Published cases of saH associated with postpartum cerebral angiopathy
Study

Patient characteristics and
history

neurological
features

Imaging results

Treatment

outcome

Present case

33-year-old woman; 0 days
postpartum; blood pressure
136/82 on presentation

Persistent headache
following cesarean
section, generalized
tonic–clonic seizures

diffuse saH on ct and MRI
scans; diffuse segmental
narrowing on transfemoral
cerebral angiogram;
increased velocities in Mca
and posterior cerebral artery
on tcd

Nimodipine, opioid
analgesics, toradol,
naproxen, intravenous
magnesium sulfate

Headache
resolved, normal
examination and
imaging

edlow et al.
(2007)9

37-year-old woman; 8 days
postpartum; uncomplicated
pregnancy; history of childhood
meningitis; blood pressure
174/90 on presentation

Generalized
tonic–clonic seizures

Frontal saH on ct and MRI
scans; diffuse segmental
narrowing on angiogram

Intravenous magnesium
sulfate; diltiazem,
amlodipine

Normal
examination,
persistent focal
narrowing at
3 weeks

edlow et al.
(2007)9

25-year-old woman; 0 days
postpartum; uncomplicated
pregnancy; history of migraines;
blood pressure 170/100 on
presentation

None

Frontal saH on ct and MRI
scans; mild narrowing of
supraclinoid Ica, Mca and
basilar artery on angiogram

calcium channel blocker

Persistent
headache and
chronic saH on
MRI scan

singhal et al.
(2004)10

21-year-old woman; 7 days
postpartum; history of common
migraine; blood pressure
180/108 on presentation

Headache,
generalized
tonic–clonic seizures

RPLs and cortical saH on
MRI scan; narrowing of
left posterior cerebral artery
and vertebral and basilar
arteries on angiogram

Intravenous magnesium
sulfate, labetalol,
phenytoin

Normal

ursell et al.
(1998)5

39-year-old woman; 5 days
postpartum (fourth child); history
of IcH following delivery of third
child; blood pressure normal
on presentation

aphasia,
right hemiparesis

Frontal saH on ct scan;
diffuse segmental narrowing
on angiogram

Methylprednisolone

Normal
examination

sengoku et al.
(2005)11

32-year-old woman; 0 days
postpartum; uncomplicated
pregnancy; blood pressure
normal on presentation

altered mental status,
left hemiparesis

saH and right putaminal IcH
on ct scan; diffuse
narrowing on angiogram

None

clinically
improved,
imaging resolved

abbreviations: Ica, internal carotid artery; IcH, intracranial hemorrhage; Mca, middle cerebral artery; RPLs, reversible posterior leukoencephalopathy syndrome; saH, subarachnoid
hemorrhage; tcd, transcranial doppler ultrasound.

tone must be considered. For example, the postpartum
state itself could explain the rapid clinical and radiographical improvements observed in PCA: changes in
vascular tone during pregnancy, which can predispose
to stroke, normalize as the woman transitions from
pregnancy to postpartum. Pregnancy-related hormonal
factors could also have a role;4 for example, hormonal
changes seem to induce remodeling of arterial walls
during pregnancy. Transformations in the connective
tissue of the arterial wall that occur during pregnancy
consist of a reduction in collagen and elastin content,
leading to a transient loss of distensibility that begins to
normalize near term.12 Increased contractility, decreased
stiffness, and an increased relaxant response in the MCA
have all been observed in animal models.13 Such changes,
in light of the altered hemodynamics of pregnancy and
the puerperium (for example, increased blood volume,
heart rate, cardiac output and stroke volume), could
lead to raised endovascular pressure against a weakened
arterial wall, leading to an increased risk of vessel wall
rupture and hemorrhage. 1 In some cases of PCA, the
angiopathy occurred in the setting of vasospastic drug
use (for example, bromocriptine, dihydroergotamine,
heroin, isometheptene or ergonovine).4,8

Treatment and management

Table 1 summarizes the treatment and management of
previously published cases of SAH in association with
PCA. According to the literature, PCA is a self-resolving
disorder, and we chose to treat the symptoms and the
vasoconstriction with pharmacological interventions in
the present case. The headache was initially treated with
NSAIDs and opioid analgesics. Subsequently, nimodipine was used to treat vasoconstriction secondary to
SAH. we also addressed the possibility of subclinical
pre-eclampsia–eclampsia by treating the patient with
intravenous magnesium sulfate, which has also been
shown to reduce vasoconstriction in SAH. we withheld methylprednisolone treatment, as no evidence
of inflammation or vasculitis was present and antivasoconstriction therapies were working, making a fixed
vasculopathy unlikely.

Conclusions

SAH in the context of PCA is rare, and only five other
cases have been reported previously (Table 1). The
rapidly reversible diffuse segmental vasoconstriction
and resolution of symptoms are crucial in differentiating
PCA from other, more-common vasculopathies.

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1.
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3.

4.

5.

6.

Feske, s. K. stroke in pregnancy. Semin. Neurol.
27, 442–452 (2007).
trommer, B. L., Homer, d. & Mikhael, M. a.
cerebral vasospasm and eclampsia. Stroke 19,
326–329 (1988).
Qureshi, a., Frankel, M. R., Ottenlips, J. R. &
stern, B. J. cerebral hemodynamics in preeclampsia and eclampsia. Arch. Neurol. 53,
1226–1231 (1996).
Geocadin, R. G., Razumovsky, a. y., Wityk, R. J.,
Bhardwaj, a. & ulatowski, J. a. Intracerebral
hemorrhage and postpartum cerebral
vasculopathy. J. Neurol. Sci. 205, 29–34 (2002).
ursell, M. R. et al. Recurrent intracranial
hemorrhage due to postpartum cerebral
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vascular disorders. In Wolff’s Headache
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chandrashekaran, s., Parikh, s., Kapoor, P. &
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