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From the Divisions of Neurology (M.R.U., S.E.B., J.R.P.) and Neurosurgery
(C.L.M., D.W.R.) and the Department of Radiology (R.F.), Sunnybrook Health
Science Centre, Toronto, Canada.
Correspondence to Melanie R. Ursell, MD, Room A-442, Division of Neurology, Sunnybrook Health Science Centre, 2075 Bayview Ave, Toronto, Ontario, Canada M4N 3M5.
Case Description—A 39-year-old woman presented with
postpartum intracranial hemorrhage and, 32 months later, with
subarachnoid hemorrhage, following normal pregnancies.
Cerebral angiography obtained after each stroke demonstrated diffuse
irregularity of branches of the middle cerebral arteries
consistent with a diffuse vasospastic process or classic
vasculitis. Neurological deficits resolved and results of a
transcranial Doppler study normalized after a short
course of high-dose corticosteroids following the
second stroke.
Conclusions—Postpartum cerebral angiopathy should be considered
in the differential diagnosis of recurrent intracranial hemorrhagic
stroke in young women. Recognition of this condition may preclude
treatment with potentially toxic therapies for vasculitis and will have
important implications for counseling women on subsequent pregnancies.
Four months later a repeat cerebral angiogram demonstrated somewhat
decreased but persistent irregularity in the MCA branch. The patient
was doing well with no neurological deficits.
Elective cesarean section was recommended for her next delivery 32
months later because of the intracerebral bleed. Five
days after giving birth, she experienced sudden headache with nausea
and vomiting. CT scan of the brain demonstrated no new changes. She
refused a lumbar puncture. Four days later she returned with sudden
confusion, drowsiness, headache, and vomiting. On admission, she was
not following commands and had a mild fluent aphasia and right
hemiparesis. A brain CT demonstrated a small left frontal
subarachnoid hemorrhage (Figure 2
As before, there had been no medical problems during the pregnancy, and
the patient remained normotensive, without proteinuria or edema. The
personal and family histories were negative for coagulopathy and
collagen-vascular or autoimmune disease. Laboratory examination
revealed a mild postpartum anemia but was otherwise unremarkable,
including normal results for renal function, urinalysis, international
normalized ratio, partial thromboplastin time, thrombin time,
antithrombin III, functional protein C, protein S,
D-dimers, fibrin monomers, and negative protein C
resistance. Tests were negative for antinuclear and anticardiolipin
antibodies, and complement indices were normal.
The patient was treated with methylprednisolone (1 g IV daily for 3
days), followed by prednisone tapering from 60 mg daily over 2 weeks.
On discharge 6 days after admission, the patient's only complaint was
of right arm and perioral numbness. Transcranial
Doppler performed just before discharge showed abnormally high flow
velocities in the left MCA. During follow-up the patient was symptom
free, and her transcranial Doppler study 1 month after
discharge had normalized.
There are 22 reports of women presenting shortly after a normal
pregnancy with the sudden onset of headache, vomiting, seizures, and
focal neurological deficits in the absence of intracranial
hemorrhage.2 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Some of these cases
were associated with the use of vasospastic
drugs,14 15 16 17 with
preeclampsia,18 or with labile
hypertension,19 20 21 22 suggesting an alternative
etiology for the presentation. In the remaining cases, no
etiology for the neurological deficits was found despite extensive
workups for stroke risk factors.2 10 11 12 13 23 24
Cerebral angiography in each case revealed areas of stenosis
and ectasia in multiple intracranial vessels, suggesting vasculitis or
a diffuse vasospastic process.
There are at least 4 additional reports of women presenting shortly
after a normal pregnancy with intracranial hemorrhage secondary
to postpartum cerebral angiopathy.2 12 13 25 One
of these women had an intraparenchymal bleed2 ; 3
suffered subarachnoid hemorrhage revealed by CT and
lumbar puncture.12 13 25 No etiology for the
bleeds could be found, and none of the patients had evidence of
hypertension or toxemia during pregnancy or the postpartum period. In
each case, angiography revealed a classic vasculitic picture involving
several intracranial vessels, often bilaterally, and not confined to
the area of hemorrhage. Two of the patients underwent repeat
cerebral angiography that showed complete normalization of vessels.
Three of the patients had rapid resolution of neurological
deficits,12 13 25 while the fate of the fourth
patient was not reported.2
The pathogenesis of postpartum cerebral angiopathy is unknown, and the
term "angiopathy" has been chosen intentionally to reflect the
uncertain underlying pathophysiology of this
condition.26 The rapid improvement in symptoms
and resolution of angiographic findings within weeks of
presentation suggests transient vasoconstriction rather
than a true inflammatory vasculitis. Cerebrospinal fluid
analyses in cases of postpartum cerebral angiopathy have been
normal or have shown a modest pleocytosis or elevated
protein.2 5 10 23 Postmortem examination in 1
fatal case showed no inflammatory changes in the
vessels involved.10 These
features, along with the early improvement observed in flow velocities
on transcranial Doppler, strongly support a vasospastic
process.
Calabrese et al27 have suggested that postpartum
cerebral angiopathy may represent a continuum of vascular
pathology, with an initial vasospastic lesion ending in a true
arteritis. Such a pathophysiology could explain the persistence of
irregularity in the right MCA branch observed in our patient after the
first intraparenchymal bleed. Experimental data have shown that acute
hypertension can produce areas of vasospasm and
dilatation,22 and some reported cases of
postpartum cerebral angiopathy have been associated with acute and
transient attacks of hypertension in the absence of
toxemia.12 19 20 21 22 In this way, postpartum
cerebral angiopathy may represent a hormonally mediated effect
on the vessel intima precipitated by acute elevations in blood
pressure28 29 ; mild intimal hyperplasia was
observed in a fatal case.10 Because hypertension
was not demonstrated in our patient and in other cases of postpartum
angiopathy, a direct vasospastic effect secondary to insults other than
hypertension must be considered.15 16
There are now several reports of a benign form of isolated central
nervous system angiitis occurring in the absence of pregnancy or the
postpartum.30 31 32 Patients are usually healthy
young women with relatively benign disease characterized by acute
headache, seizures, neurological deficits, and angiographic findings
consistent with vasospasm or
vasculitis.27 This nearly identical clinical
picture suggests that postpartum cerebral angiopathy may be an
important clinical subset of benign angiitis of the central nervous
system.
Postpartum cerebral angiopathy is a significant pathological entity
that should be considered in the differential diagnosis of postpartum
hemorrhage. Our case emphasizes the association of intracranial
hemorrhage with this disorder and its potential for
recurrence in subsequent pregnancies, which introduces
important questions regarding recommendations made to patients
considering future pregnancies.
Our patient and others have had good outcomes with short courses of
high-dose corticosteroids.5 25 33
Recognition of this condition may preclude unnecessarily aggressive and
potentially toxic treatment with long courses of immunosuppressive
therapy for vasculitis. In at least 1 other case, there was full
recovery without steroid treatment19 ; thus, the
role of corticosteroid treatment in this condition
requires further investigation. Elucidation of the
pathophysiology of this condition will be important in the future
counseling and management of these patients.
Received March 5, 1998;
revision received May 27, 1998;
accepted May 27, 1998.
2.
Kittner SJ, Stern BJ, Feeser BR, Hebel JR, Nagey DA,
Buchholz DW, Earley CJ, Johnson CJ, Macko RF, Sloan MA, Wityk RJ,
Wozniak MA. Pregnancy and the risk of stroke. N Engl J
Med. 1996;335:768–774.
3.
Knepper LE, Giuliani MJ. Cerebrovascular disease
in women. Cardiology. 1995;86:339–348.[Medline]
[Order article via Infotrieve]
4.
Amias AG. Cerebral vascular disease in pregnancy, I:
hemorrhage. J Obstet Gynecol Br Comm. 1970;77:100–120.[Medline]
[Order article via Infotrieve]
5.
Tuttleman R, Gleicher N. Central nervous system
hemorrhage complicating pregnancy. Obstet Gynecol. 1981;58:651–656.[Medline]
[Order article via Infotrieve]
6.
Wilterdink JL, Feldmann E. Cerebral
hemorrhage. In: Devinsky O, Feldmann E, Hainline B, eds.
Neurological Complications of Pregnancy. New York, NY: Raven
Press Publishers; 1994:13–22.
7.
Barno A, Freeman D. Maternal deaths due to spontaneous
subarachnoid hemorrhage. Am J Obstet
Gynecol. 1976;125:384–392.[Medline]
[Order article via Infotrieve]
8.
Donaldson J. Cerebrovascular disease. In:
Neurology of Pregnancy. 2nd ed. London, UK: WB Saunders;
1989:137–184.
9.
Carmel P, Swift D. Spontaneous intracranial
hemorrhage occurring during pregnancy. In: Kaufman H, ed.
Intracerebral Hematomas. New York, NY: Raven
Press Publishers; 1992:117–125.
10.
Geraghty JJ, Hock DB, Robert ME, Vinters HV. Fatal
puerperal cerebral vasospasm and stroke in a young women.
Neurology. 1991;41:1145–1147.
11.
Calabrese, L. H., Mallek, J. A. Primary
angiitis of the central nervous system: report of 8 new cases, review
of the literature, and proposal for diagnostic criteria.
Medicine. 1987;67:20–39.
12.
Rousseaux P, Scherpereel B, Bernard MH, Guyot JF.
Angiopathie cerebrale aigue benigne: six observations. Presse
Med. 1983;12:2163–2168.
13.
Rascol A, Guiraud B, Manelfe C. Accidents vasculaires
cerebraux de la grossesse et du post partum. In: 2e Conference de la
Salpetriere sur les maladies vasculaires cerebrales. 1980:84–127.
14.
Barinagarrementeria F, Cantu C, Balderrama J.
Postpartum cerebral angiopathy with cerebral infarction due to
ergonovine use. Stroke. 1992;23:1364–1366.
15.
Raroque HG, Tesfa G, Purdy P. Postpartum cerebral
angiopathy: Is there a role for sympathomimetic drugs?
Stroke. 1993:24:2108–2110.
16.
Janssens E, Hommel M, Mounier-Vehier F, Leclerc X,
Guerin du Masgenet B, Leys D. Postpartum cerebral angiopathy possibly
due to bromocriptine therapy. Stroke. 1995;26:128–130.
17.
Kulig K, Moore LL, Kirk M, Smith D, Stallworth J,
Rumack B. Bromocriptine-associated headache: possible life-threatening
sympathomimetic interaction. Obstet Gynecol. 1991;78:941–943.[Medline]
[Order article via Infotrieve]
18.
Raps EC, Galetta SL, Broderick M, Scott W. Delayed
peripartum vasculopathy: cerebral eclampsia revisited. Ann
Neurol. 1993;33:222–225.[Medline]
[Order article via Infotrieve]
19.
Bogousslavsky J, Despland PA, Regli F, Dubuis PY.
Postpartum cerebral angiopathy: reversible vasoconstriction assessed by
transcranial Doppler ultrasound Eur Neurol.. 1989;29:102–105.[Medline]
[Order article via Infotrieve]
20.
Farine D, Andreyko J, Lysikiewicz A, Simha S, Addison
A. Isolated angiitis of brain in pregnancy and puerperium. Obstet
Gynecol. 1984;63:586–588.[Medline]
[Order article via Infotrieve]
21.
Masuzawa T, Shinoda S, Furuse M, Nakahara N, Abe F,
Sato F. Cerebral angiographic changes on serial examination of a
patient with migraine.
Neuroradiology. 1983;24:277–287.[Medline]
[Order article via Infotrieve]
22.
Garner BF, Burns P, Bunning RD, Laureno R. Acute blood
pressure elevation can mimic arteriographic appearance of cerebral
vasculitis: a postpartum case with relative hypertension. J
Rheum. 1990;17:93–97.[Medline]
[Order article via Infotrieve]
23.
Sharshar T, Lamy C, Mas JL, for the Stroke in
Pregnancy Study Group. Incidence and causes of strokes associated with
pregnancy and puerperium: a study in Public Hospitals of Ile de France.
Stroke. 1995;26:930–936.
24.
Dupuy G, Lechevalier B, Chevalier D, et al.
Complication vasculaires a rechute liees a las prise de methergin en
milieu obstetrical. Rev Otoneuroophtalmol. 1979;51:293–299.[Medline]
[Order article via Infotrieve]
25.
Langlois PF, Sharon E, Gawryl MS. Plasma concentrations
of complement- activation complexes correlate with disease activity in
patients diagnosed with isolated central nervous system vasculitis.
J Allergy Clin Immunol. 1989;83:11–16.[Medline]
[Order article via Infotrieve]
26.
Calabrese LH, Gragg LA, Furlan AJ. Benign angiopathy: a
distinct subset of angiographically defined primary angiitis of the
central nervous system. J Rheumatol. 1993;20:2046–2050.[Medline]
[Order article via Infotrieve]
27.
Calabrese LH, Furlan AJ, Gragg LA, Ropos TJ. Primary
angiitis of the central nervous system: diagnostic criteria
and clinical approach. Cleve Clin J Med. 1992;59:293–306.[Medline]
[Order article via Infotrieve]
28.
Caseby NG. Postpartum stroke successfully treated with
high-dose pentobarbitone therapy: a case report. Can Anaesth Soc
J. 1983;30:77–83.[Medline]
[Order article via Infotrieve]
29.
Digre KB, Varner MW, Osborn AG, Crawford S. Cranial
magnetic resonance imaging in severe preeclampsia vs. eclampsia.
Arch Neurol. 1993;50:399–406.
30.
Bettoni,L, BortJuvarra G, Lechi A. Isolated benign
cerebral vasculitis. Acta Neurol Belg. 1984;84:161–173.[Medline]
[Order article via Infotrieve]
31.
Snyder BD, McClelland, RR. Isolated benign cerebral
vasculitis. Arch Neurol. 1978;35: 612–614.
32.
Calenbergh FV, VanDen Berg V, Wilms G. Benign isolated
arteritis of the central nervous system. Clin Neurol
Neurosurg. 1986;88:267–273.[Medline]
[Order article via Infotrieve]
33.
Calabrese LH. Vasculitis of the central nervous system.
Rheum Dis Clin North Am.. 1995;21:1059–1076.[Medline]
[Order article via Infotrieve]
© 1998 American Heart Association, Inc.
Case Report
Recurrent Intracranial Hemorrhage Due to Postpartum Cerebral Angiopathy
Implications for Management
Abstract
Top
Abstract
Introduction
Case Report
Discussion
References
Background—Postpartum cerebral
angiopathy as a cause of hemorrhagic stroke in young women is not well
recognized. It is unknown whether this disorder represents a
true inflammatory vasculitis or transient vasoconstriction related to
the hormonal events of pregnancy and the postpartum period.
Key Words: cerebral hemorrhage • vasoconstriction • pregnancy • vasculitis
Introduction
Top
Abstract
Introduction
Case Report
Discussion
References
Pregnancy is an
important risk factor for stroke in young patients; the incidence of
stroke is 13 times that found in nonpregnant women of similar
age.1 The relationship between pregnancy and
stroke remains controversial; a recent large, population-based study
found the postpartum state rather than pregnancy itself to be
associated with an increased risk of cerebral infarction and
hemorrhage.2 Intracranial
hemorrhage during the peripartum period is responsible for 10%
of all maternal deaths3 ; most are associated with
pregnancy-induced hypertension, sinus thrombosis, or
subarachnoid hemorrhage due to rupture of saccular
aneurysms or arteriovenous
malformations,4 5 6 but in some patients the cause
is unknown.7 8 9 We describe a patient who
presented on 2 separate occasions with postpartum intracranial
hemorrhage and neuroimaging consistent with postpartum
cerebral angiopathy.
Case Report
Top
Abstract
Introduction
Case Report
Discussion
References
A 39-year-old woman presented with a right frontal
intraparenchymal hemorrhage 9 days after spontaneous vaginal
delivery of her third child (Figure 1A
).
She had a mild left hemiparesis and decreased level of consciousness on
admission, both of which resolved in the hospital after 2 weeks. She
was well throughout her pregnancy and in particular was normotensive,
without edema, proteinuria, seizures, or headaches. A 4-vessel cerebral
angiogram demonstrated irregularity of a temporal branch of the right
middle cerebral artery (MCA) (Figure 1B); this was attributed to
vasospasm, although the possibility of vasculitis was considered. The
angiogram was otherwise normal, with no evidence of vascular
malformation or aneurysm. While in the hospital she was treated
with dexamethasone (4 mg IV every 6 hours for 10 days) for
control of intracranial pressure.
View larger version (68K):
[in a new window]
Figure 1. A, Brain CT scan without contrast showing right
frontal intraparenchymal hemorrhage. B, Right internal carotid
artery injection angiogram showing irregular temporal branch of right
MCA 1 week after hemorrhage shown in panel A. ). Cerebral angiography demonstrated
that the inferior temporal branch of the right MCA was
unchanged from 1994, but many branches of the left MCA showed marked
beading, and other distal right MCA branches remote from the area of
subarachnoid hemorrhage were now irregular (Figure 3). A brain MRI 1 week after the event
demonstrated new areas of high signal intensity bilaterally within the
centrum semiovale that had not been present on the MRI
performed 1 week after the first hemorrhage and were thought to
represent areas of ischemic damage (Figure 4).
View larger version (105K):
[in a new window]
Figure 2. CT scan without contrast showing small area of
left frontal subarachnoid hemorrhage.
View larger version (155K):
[in a new window]
Figure 3. Left common carotid artery injection angiogram
showing irregular vessels in multiple territories, in keeping with
vasculitis or diffuse vasospasm.
View larger version (122K):
[in a new window]
Figure 4. Proton density–weighted MRI showing right frontal
hemosiderin/glial scar from first intracranial bleed
(Figure 1 
), with new areas of high signal intensity in centrum
semiovale bilaterally (arrowheads) after subarachnoid
hemorrhage.
Discussion
Top
Abstract
Introduction
Case Report
Discussion
References
Postpartum cerebral angiopathy (PCA) as a cause of
ischemic and hemorrhagic stroke in young women is not well
recognized. Although usually a benign and nonrelapsing disease,
fatalities have been reported,10 and our patient
has demonstrated that it may recur.
References
Top
Abstract
Introduction
Case Report
Discussion
References
1.
Wieber DO. Ischemic cerebrovascular
complications of pregnancy. Arch Neurol. 1985;42:1106–1113.
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