Case Report

Case of Moyamoya Disease in a Patient With Advanced
Acquired Immunodeficiency Syndrome
Sophia R. Sharfstein, MD,* Shadab Ahmed, MD,† Mohammed Q. Islam, MD,§
Mamoun I. Najjar, MD,† and Vladimir Ratushny, BS,¶

Background: Moyamoya disease is an occlusion of the terminal portion of internal
carotid arteries and proximal portion of middle and anterior cerebral arteries of
unknown origin. Moyamoya syndrome is associated with meningitis, tuberculosis,
syphilis, head trauma, head irradiation, brain tumor, von Recklinghausen’s disease,
tuberous sclerosis, Marfan syndrome, sickle cell anemia, arteriosclerosis, hypertension, and oral contraceptive use. To our knowledge, acquired immunodeficiency
syndrome (AIDS) as a cause of moyamoya syndrome has not been reported in an
adult population. Objective: We report a case of moyamoya syndrome in a patient
with AIDS and without other conditions associated with occlusion of the circle of Willis
and formation of collateral network at the base of the brain and basal ganglia. Methods:
We present a case report. Results: A 29-year-old woman with an 8-year history of
AIDS on multiple antiretroviral medications presented with recurrent tingling of the
left extremities which 1 month later progressed to mild hemiparesis and dysarthria.
During the next few months the patient developed progressive cognitive decline and
on-and-off fluctuations in the degree of hemiparesis. Brain magnetic resonance imaging showed multiple small subcortical infarct’s in both parietal lobes. Magnetic resonance angiography showed occlusion of middle cerebral arteries distal internal carotid
arteries, with prominent collateral network. Cerebral angiography confirmed moyamoya pattern. Lumbar puncture showed: white blood cell count 1, red blood cell count
418, protein 56, glucose 53, negative bacterial and acid-fast bacilli smear and culture,
negative VDRL test, India ink, cryptococcal antigen, cytology and negative polymerase
chain reaction for cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, and
herpes simplex virus type 1 and 2. Electroencephalography showed diffuse background slowing. Conclusions: We hypothesize that human immunodeficiency virus
(HIV) caused central nervous system vasculitis, which eventually led to formation of
moyamoya pattern. No other definite causes of central nervous system vasculitis were
found in our patient. Cerebrovascular disorders should be considered in patients with
HIV/AIDS with focal neurologic deficit. Moyamoya syndrome as a cause of stroke
should be considered in patients with HIV/AIDS, especially as survival improves. Key
Words: Stroke—moyamoya disease—acquired immunodeficiency syndrome.
© 2007 by National Stroke Association

Moyamoya disease is an occlusion of the circle of Willis
of unknown origin associated with the formation of collateral network at the base of the brain and basal gan-

glia.9-11 Occlusion of the terminal portion of internal
carotid arteries (ICAs) and proximal portion of middle
cerebral arteries (MCAs) and anterior cerebral arteries are

From the Department of *Neurology, SUNY Downstate Medical
Center, New York; †Department of Medicine; §Department of Neurology, Nassau University Medical Center, East Meadow; and
¶Third Year MD/PhD candidate, Drexel University College of Medicine, Philadelphia, PA.
Received April 16, 2007; revision received June 25, 2007; accepted
July 3, 2007.

Address correspondence to Sophia R. Sharfstein, MD, Department
of Neurology, SUNY Downstate Medical Center, Box 1213, 450
Clarkson Ave, Brooklyn, NY 11203. E-mail: Sophia.Sharfstein@
Downstate.edu.
1052-3057/$—see front matter
© 2007 by National Stroke Association
doi:10.1016/j.jstrokecerebrovasdis.2007.07.001

268

Journal of Stroke and Cerebrovascular Diseases, Vol. 16, No. 6 (November-December), 2007: pp 268-272

MOYAMOYA DISEASE IN A PATIENT WITH AIDS
12,15

characteristic.
The posterior circulation involvement
is not typical but is reported.29 It is diagnosed primarily
by magnetic resonance (MR) angiography, cerebral angiography, or both. A similar radiographic picture is
found in certain systemic infections, autoimmune, hematologic, metabolic, genetic/chromosomal disorders, and
neoplasms. This condition is called “moyamoya syndrome.” Disorders associated with moyamoya syndrome
are: leptospirosis, tuberculosis, sickle cell anemia, thalassemia, aplastic anemia, lupus anticoagulant, glycogen storage disease (type 1), hyperlipoproteinemia (type 2A),
hyperthyroidism, pseudoxanthoma elasticum, neurofibromatosis, tuberous sclerosis, retinitis pigmentosa,
sellar and parasellar tumors (craniopharyngioma, optic
glioma), Sjögren’s syndrome, fibromuscular dysplasia,
cranial trauma, cranial irradiation, and oral contraceptive
use.13,15,16,18
The age of onset of moyamoya disease peaks at 5 years
(juvenile type) and 30 to 40 years (adult type).15 It presents with cerebral infarct (CI) at an early age because of
hypoperfusion of certain areas of the brain through stenotic cerebral vessels, and intracerebral hemorrhage
(ICH) later in life as a result of a rupture of the collaterals.11,15 It may manifest with a variety of symptoms and
signs: headache; seizures; motor, sensory, and speech
deficits; involuntary movements; disturbance of consciousness; psycho-organic syndrome; and mental retardation.14,15,19
Pathology of moyamoya disease is unclear. It was
found that basic fibroblast growth factor (bFGF) is increased in the vessels of patients with moyamoya disease.
bFGF concentration in cerebrospinal fluid (CSF) is significantly higher in patients with moyamoya disease than in
patients with arteriosclerotic cerebrovascular occlusive
disease and spinal disk disease.15,21 There is increased
activity of bFGF and bFGF receptors in the superficial
temporal artery obtained during bypass surgery in moyamoya disease. It is possible that bFGF induces smoothmuscle proliferation with inflammatory response and
progressive narrowing of the vessels of the circle of
Willis.12 Stenosis of intracranial arteries leads to the development of collaterals at the base of the brain and basal
ganglia.12 When collaterals become insufficient, cerebral
ischemia develops. Hemodynamic stress leads to the
formation of microaneurysm and berry aneurysm formation.12 Cerebral aneurysm is found in 4% to 14% of
patients with moyamoya disease.15 Rupture of the microaneurysm and berry aneurysm causes ICH and subarachnoid hemorrhage.12
There are reports that elastin synthesis is increased
in patients with moyamoya disease compared with
control subjects.24 Yamamoto et al24 suggest that moyamoya disease results from abnormal regulation of extracellular matrix metabolism with increased steady
levels of elastin messenger RNA, elastin accumulation,
and intimal thickening. Elastin accumulation is a

269

marker of vascular smooth-muscle cell change in patients with moyamoya disease.24 Possible genetic predisposition to moyamoya disease may be marked by
major histocompatibility complex HLA antigen 2.
DRB1 1601 is significantly higher in the age group
younger than 10 years, and DRB1 0201 is significantly
higher in the age group older than 10 years.25
Treatment of moyamoya disease consists of antithrombotic medications that prevent ischemic events by influencing progression of vascular stenosis. Surgical treatment consists of revascularization procedures aimed at
augmenting cerebral blood flow.9,11,12,15
We describe a case of moyamoya disease in a patient
with (human immunodeficiency virus) HIV/AIDS. No
other definite causes of moyamoya syndrome had been
identified in our patient. To our knowledge, association
between moyamoya disease and acquired HIV infection
in adult patient has not been reported. Hsiung et al5
described a case of moyamoya syndrome in a 10-year-old
child with congenital HIV infection, manifested by recurrent hemiparesis.
Morgello and Laufer1 reported a case of 22-year-old
Haitian man with a 15-month course of chronic progressive meningitis associated with multiple CIs. He died 5
months after he had been given the diagnosis of moyamoya syndrome by cerebral angiography. The autopsy
showed that the patient had meningovascular syphilis
with necrotizing encephalitis and massive treponemal
invasion of the brain, which is consistent with “quaternary” neurosyphilis. On postmortem examination he was
also found to have HIV DNA in the brain by dot blot
hybridization and retrovirus-like particles by electron
microscopy. Moyamoya disease in this case was ascribed
to an advanced syphilis that is an established cause of
moyamoya syndrome. Diagnosis of postmortem HIV infection in this patient was considered to be a provoking
factor for massive central nervous system (CNS) involvement by syphilis.1

Case Report
A 29-year-old African American woman with HIV
infection of 9 years’ duration and advanced AIDS, with
CD4 count fluctuating between 8 and 31 ␮L for the last 6
months, was admitted to the HIV service of our hospital
with hemolytic anemia and vaginal bleeding. The patient
also had history of syphilis diagnosed 4 years before this
presentation and treated with intravenous ceftriaxone (2
g every 12 hours) for 4 weeks (she was treated as having
neurosyphilis despite negative test results on multiple
CSF VDRL tests). A neurology service consult was requested 3 days after current admission for patient’s
symptom of left arm tingling and tingling of the left half
of her tongue. According to the patient, it had started 3
weeks before admission and was episodic in nature,

S.R. SHARFSTEIN ET AL.

270

lasting from minutes to hours and recurring weekly. Her
medications included ritonavir, stavudine, lamivudine,
azithromycin, and erythropoietin. Her physical examination was significant for systolic murmur, splenomegaly,
and hepatomegaly. Neurologic examination revealed
normal findings, as did noncontrast computerized tomography of the head. The patient was given the diagnosis of simple partial sensory seizures, and phenytoin
(300 mg/day) was started. Electroencephalography and
contrast-enhanced MR imaging of the brain were suggested but not performed because the patient left the
hospital against medical advice. She was readmitted to
HIV service 3 weeks later with generalized weakness,
diarrhea, and abdominal discomfort. Above symptoms
were self-limited, resolved in 2 days, and no further
work-up was necessary because diarrhea, generalized
weakness, and abdominal discomfort are frequent in
patients with HIV. Neurologic examination at that time
revealed mild left hemiparesis (4/5) and left hemisensory
loss. Spinal tap was performed at that time. CSF analysis
showed 1 white blood cell and 418 red blood cells –
traumatic tap, protein 56, glucose 53, negative bacterial
and acid-fast bacilli smear and culture, negative VDRL
test, India ink, cryptococcal antigen, cytology and negative polymerase chain reaction for cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus type 1 and 2. Electroencephalography showed
diffuse background slowing and no epileptiform activity.
Brain MR imaging (Fig 1) showed multiple small subcortical infarcts in both parietal lobes. MR angiography of
intracranial vessels showed occlusion of proximal MCAs
and distal ICAs, with prominent collateral network. Cerebral angiography (Fig 2) confirmed a moyamoya pattern. The patient was given the diagnosis of moyamoya
disease and aspirin (325 mg/day) was started.

Figure 2. Conventional cerebral angiography, lateral view, shows occlusion of distal ICAs, MCAs, and prominent collateral network.

She was re-evaluated 3 weeks later in the neurology
clinic. Neurologic examination at that time showed flat
affect, diminished attention and concentration, decreased
short-term memory 1/3 at 3 minutes, and difficulty with
abstract thinking and spelling. Our patient did not have
aphasia or dysarthria but was extremely slow in her
answers and was inattentive. In addition to previously
noted mild left hemiparesis and left hemisensory loss, she
had mild left central facial palsy, dysmetria on left fingernose test out of proportion to weakness, and dystonic
posturing of the left hand. The patient was lost for follow-up in our clinic and reappeared on our HIV service 4
months later with worsening of anemia and bronchitis.
At that time she was not taking antiretroviral medications
as a result of noncompliance. Her neurologic examination
showed progressive cognitive decline in addition to left
hemiparesis. The patient’s cognitive impairment and inattention, and left hemiparesis, fluctuated in severity. She
had episodes of worsening of left hemiparesis and stupor.
During this admission she refused blood transfusions
for anemia and was transferred to a nursing home because she could no longer take care of herself.
Two months later she was readmitted to our hospital
for repair of rectovaginal fistula. Her neurologic examination at that time showed further progression of cognitive deficit, increased left hemiparesis, and periods of
stupor lasting hours to days. She died suddenly 4 months
later in the nursing home while watching television.
Autopsy was not performed.

Discussion
Figure 1. T2-weighted MR imaging of brain shows multiple subcortical
infarcts (arrows) in both parietal lobes.

Association between AIDS and cerebrovascular disorders (CVD) is uncertain.2-6,8,22,23 Forty percent of patients

MOYAMOYA DISEASE IN A PATIENT WITH AIDS

with AIDS, have neurologic complications, and only 1.3%
of them have cerebrovascular disorders.2 True incidence
of cerebrovascular complications in AIDS is difficult to
establish because of a high rate of association of HIV
infection with opportunistic bacterial, viral, and spirochetal infections of the CNS that also produce cerebral
vessel involvement.7,17,26 –28 The CNS in AIDS is affected
by direct infection of CNS cells with HIV, and by opportunistic infections or neoplasms. There is also clinical and
histopathologic evidence suggesting that HIV infection
may cause inflammatory vascular disorders.20,26 HIV infection can cause CNS vasculitis with subsequent
strokes.1,5-8,26,27 Different mechanisms are implicated in
pathogenesis of CNS vasculitis in HIV/AIDS, including
infection of endothelial cells by HIV or other infectious
agents, immune complex deposition, and dysregulation
of cytokines and adhesion molecules. It is not clear
whether vasculitis is caused by HIV itself, some associated viral structure, or unusual endothelial reaction to the
virus.27 Besides vascular inflammation, protein S deficiency and vasospasm may be other pathogenetic mechanisms of cerebrovascular complications in AIDS.8 Expression of CVD in AIDS consists of CI, transient
ischemic attacks, and ICH.2,3,8 CI seems to be more frequent than ICH.2 ICHs are usually associated with
thrombocytopenia, primary CNS lymphoma, and metastatic Kaposi’s sarcoma. CIs are associated with nonbacterial thrombotic endocarditis and opportunistic CNS
infections. The role of antiphospholipid antibodies,
including anticardiolipin antibodies, in pathogenesis
of stroke in HIV/AIDS is uncertain.2 To our knowledge, moyamoya syndrome as a complication of AIDS
has not been reported in an adult patient population.
We hypothesize that in our case HIV infection induced
CNS vasculitis that eventually led to moyamoya pattern
formation. HIV infection has been described previously
as a cause of CNS vasculopathy.2,4,8,26,27 No other definite
causes of CNS vasculitis were found in our patient.
Polymerase chain reaction for DNA of cytomegalovirus,
Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus type 1 and 2 in CSF revealed negative findings.
Acid-fast bacilli smear and culture results had been negative in CSF as well. Even though our patient was given
the diagnosis of syphilis 4 years before diagnosis of
moyamoya syndrome, VDRL test in CSF had produced
negative results on multiple occasions in the past and
during recent admissions. In addition, despite negative
CSF VDRL test results, the patient was treated with
intravenous ceftriaxone for 4 weeks in the past because of
AIDS and the possibility of developing CNS syphilis.
Serum rapid plasma reagin (RPR) was always reactive at
a very low titer (1:1), including time of initial diagnosis
and after treatment, and never increased to higher numbers. It is common practice to consider a patient treated if
RPR titers do not increase, because treatment of syphilis
is difficult in AIDS populations, and, in the experience of

271

our HIV service, RPR titers usually do not reverse to zero
even after treatment. Anticardiolipin antibodies were in a
normal range and lupus anticoagulant was negative in
the patient’s serum. Our patient had hemolytic anemia
presumably as a result of AIDS and antiretroviral medications. To our knowledge, hemolytic anemia is not listed
as a cause of moyamoya syndrome. Besides, our patient’s
anemia was not long standing and it is long-standing
anemia that is necessary for moyamoya pattern formation.
It is possible that, in our patient, HIV infection had
caused CNS vasculopathy, which eventually led to the
formation of moyamoya pattern. Despite 9 years of HIV
diagnosis and aggressive treatment with the addition of
new available antiretrovirals to the regimen, it is possible
that our patient did not receive optimal treatment because she did not adhere to the regimen. Besides, antiretroviral medications were periodically stopped because of
worsening of hemolytic anemia (it was thought that
worsening of patient’s anemia was at least partially related to antiretroviral medications). CVD should be considered in patients with HIV/AIDS with focal neurologic
deficit. Moyamoya syndrome as a cause of stroke should
be considered in patients with HIV/AIDS, especially as
survival improves. More research is necessary on vascular presentation of HIV infection, cerebral vasculitis, its
causes, and natural course in patients with HIV/AIDS.
At this point, our impression is that HIV infection
caused cerebral vasculopathy, which led to moyamoya
syndrome. It is quite possible that in future, as knowledge about AIDS accumulates, we will find that cerebral
vasculopathy leading to moyamoya syndrome is caused
by another agent, similar to the story of Kaposi’s sarcoma, which was thought to be caused by HIV, but now
we know that it is caused by human herpesvirus 8. It is
also possible that we will see more cases of moyamoya
syndrome in patients with AIDS as survival increases,
and diagnosis of moyamoya disease improves.

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