Neurology International 2014; volume 6:5369

Moyamoya in Hispanics: increased familial incidence suggests a genet-

ic cause. Accumulating evidence suggests that Correspondence: Hasan J. Salameh, Department
not only in Japanese the RNF213 gene on chromosome 17q25.3 is of Internal Medicine, Paul L. Foster School of
an important susceptibility factor for MMD in Medicine, Texas Tech University Health Sciences
Sarmad Said, Chad J. Cooper, East Asian populations.5,6 In a report from Center, 4800 Alberta Avenue, El Paso, 79905 TX,
Haider Alkhateeb, Juan M. Galvis, Japan, the c.14576 G>A variant of RNF213 was USA.
German T. Hernandez, Hasan J. Salameh found in 95% of 41 patients with familial MMD, Tel.: +1.915.443.5505 - Fax: +1.915.545.6634.
E-mail: [email protected]
Department of Internal Medicine, Paul L. 79% of 163 patients with sporadic MMD, and
Foster School of Medicine, Texas Tech 2% of 283 normal control subjects.6 Other stud-
Key words: moyamoya disease, moyamoya syn-
University Health Sciences Center, El ies have linked familial Moyamoya disease to drome, stroke, Hispanic population.
Paso, TX, USA chromosomes 3p24.2-p26, 6q25, 8q23, and
12p12.7,8 Familial cases of MMD in the US are Contributions: SS took care of the patient and
approximately 2%, but in Japan a family histo- arranged all required medical steps, wrote the
ry of Moyamoya disease is present in 12.1% of draft of the manuscript; CC collected literature
patients. Environmental factors can be consid- and reviewed the final version of the manuscript;
Abstract ered as contributing factors to this observa- HA took care of the patient and contributed in
tion.3,9 updating the team, he reviewed the final version,
Especially in North American patients the edited and approved it; JMG, GTH, analyzed the
Moyamoya disease was first described in
manuscript and performed independent proof-
1957 as hypoplasia of the bilateral internal clinical presentation can be atypical with a
reading; HJS, controlled all the above-mentioned
carotid arteries, the characteristic appearance later onset and may cause a delay of the diag-
steps and made the final medical decisions.
of the associated network of abnormally dilat- nosis. These patients are less likely to have
ed collateral vessels on angiography was later hemorrhagic stroke.10,11 Kuroda et al. pub- Conflict of interests: the authors declare no
likened to something hazy, like a puff of ciga- lished in 2005 an article about the clinical fea- potential conflict of interests.
rette smoke, which, in Japanese, is moyamoya. tures of MMD in adults indicating that the dis-
This paper describes two cases of moyamoya ease has a high rate of progression, even in Received for publication: 24 February 2014
presentations, including moyamoya disease asymptomatic patients, and medical alone can- Revision received: 25 March 2014.
and moyamoya syndrome. Moyamoya may not stop the disease progression.12 Over a peri- Accepted for publication: 28 March 2014.
rarely occur in North American Hispanic od of 5 years about 70% of the MMD-patients
This work is licensed under a Creative Commons
patients. The presentation can vary signifi- experience a symptomatic progression; with- Attribution NonCommercial 3.0 License (CC BY-
cantly and ranges bwtween fulminant outcome out a treatment the disease outcome is poor.13 NC 3.0).
and prolonged survival. Awareness about moy- In contrast surgical intervention may be more
amoya and its different presentations may be beneficial. A meta-analysis of 2005 on pedi- ©Copyright S. Said et al., 2014
beneficial for the patients and can improve the atric patients involving 1156 subjects showed Licensee PAGEPress, Italy
outcome. that symptomatic disease progression Neurology International 2014; 6:5369
doi:10.4081/ni.2014.5369
occurred only in 2.6% of the patients after sur-
gery.14
We describe a case series of advanced tests for systemic autoimmune, inflammatory,
Introduction Moyamoya disease in a Hispanic male and pro- and infectious diseases, and neoplasm were all
tracted Moyamoya syndrome in a Hispanic negative.
Moyamoya disease (MMD), translated in female with an acute, fulminant and protract- Initial unenhanced head computed tomogra-
Japanese as hazy or puffy, is a chronic progres- ed progression, respectively. phy (CT) showed hypodense lesions in the
sive occlusive arteriopathy of the anterior body and genu of the corpus callosum and right
cerebral circulation. The vascular pathology of basal ganglia. A subsequent brain magnet-res-
MMD causes large intracranial artery occlu- onance-imaging revealed multiple supratento-
sion and collateral circulation leading to acute Case Report #1 rial lesions involving the rostrum of the corpus
infarcts, which have a higher tendency to callosum, genu of the right internal capsule
develop recurrent strokes causing a significant A 42-year-old Hispanic male without signifi- and basal ganglia and subcortical cingulate
cognitive impairment and neurologic cant past medical history presented with a 4- white matter, with variable degrees of
decline.1,2 Overall incidence of Moyamoya is week history of slow mentation, difficulty con- enhancement associated with mass effect
0.086 cases per 100,000 people. MMD has the centrating, and change in personality. He com- (Figure 1). Initial differential diagnoses
highest prevalence among Japanese children plained of bilateral lower extremity weakness, included an acute demyelinating process ver-
(6.03 per 100,000). An increase in the preva- as well as a presyncopal episode and sudden sus primary CNS lymphoma, glioma, or
lence of Moyamoya has been demonstrated onset of numbness involving his right body acute/subacute ischemic infarct.
among non-Asian populations. The reported side 3 days before admission. Other symptoms Cerebrospinal fluid analysis (CSF) showed
occurrence in the Caucasian population in the included intermittent nausea and vomiting. mild increase of total protein and elevated CSF
US is the highest compared to other popula- Physical examination included slow menta- levels of myelin basic protein, without oligo-
tions, but Caucasians represent 72.4% of the tion, impaired concentration, facial weakness clonal bands. High doses of intravenous
US population. In general, Moyamoya disease of the right lower half, dysarthria, and mild methylprednisolone (1 gm/day) were adminis-
is observed among the various races based on weakness in the lower extremities without tered; 72 hours after admission, the patient
their proportions of the total US population.3 sensory level or sphincter dysfunction. Full developed altered level of consciousness, apha-
The occurrence of the disease shows a strength in his upper extremities, diminished sia, left gaze deviation, and right hemiplegia.
bimodal age distribution at 5-9 years and 35-50 reflexes throughout, and intact sensation were Cerebral angiography (Figure 2) demon-
years with female predominance.4 The exact noted. No cerebellar dysfunction, nystagmus, strated bilateral intracranial arteriopathy with
etiology of MMD is unknown, however the or Babinski signs were present. Laboratory occlusion of the supraclinoid segment of the

[Neurology International 2014; 6:5369] [page 19]

Case Report

left intracranial internal carotid artery distal to involving the third and forth ventricles result- the internal carotid artery and at the proximal
the takeoff of the left anterior choroidal artery, ing in a left-to-right 4 mm midline shift with portion of the anterior and middle cerebral
occlusion of the right anterior cerebral artery, moderate hydrocephalus. On the following day arteries on MRA or conventional cerebral
and severe disease in the proximal right mid- her GCS declined to 3 and her cardiac rhythm angiography; abnormal vascular networks in
dle cerebral artery. The distal branches of the changed to bradycardia and later asystole. the basal ganglia on MRA; angiographic find-
right middle and anterior cerebral arteries Cardiopulmonary resuscitation was unsuc- ings are present bilaterally.16
were mainly fed by collateral anastomoses cessful and the patient died on the following Magnet-resonance imaging is the preferred
from the anterior and posterior choroidal day of hospitalization. radiological modality. Contrast-enhanced T1-
arteries, producing arterial blush (puff of weighted images and FLAIR (fluid-attenuated
smoke) consistent with an angiographic inversion recovery) images can show a linear
Moyamoya pattern. pattern of increased signal in the lep-
Within few days the patient developed a Discussion tomeninges and perivascular spaces, known as
massive infarction involving almost the entire the ivy sign. Transcranial Doppler ultrasonog-
left hemisphere and the bilateral anterior cere- Moyamoya disease is an idiopathic progres- raphy (TCD) can be used to evaluate large
bral arterial territories, associated cerebral sive intracranial occlusive arteriopathy, which artery stenosis and intracranial hemodynam-
edema, midline shift complicated by brain her- can be complicated with ischemic and hemor- ics by measuring blood flow velocity of the
niation, and eventually death 11 days after rhagic cerebrovascular events. The angio- large intracranial vessels at the circle of Willis.
admission. graphic feature of collateralization is pathog- SPECT can also be used to demonstrate the
nomonic for Moyamoya pattern. The decrease blood and oxygen supply to areas of
Moyamoya syndrome can be associated with the brain.17,18
severe intracranial atherosclerotic disease, Overall, the acute treatment goals are to
Case Report #2 sickle cell disease, neurofibromatosis type I, reduce intracranial pressure, improve cerebral
cranial radiation therapy, and trisomy 21.15 blood flow and control any seizures.
A 29-year old Hispanic female with a signif- Typically moyamoya disease and moyamoya Ventricular drainage and/or hematoma
icant past medical history for repaired patent syndrome present during childhood, however removal may be required. Thrombolytic thera-
foramen ovale, pulmonary valve stenosis and the incidence of both forms in North America py in the event of ischemic stroke is not recom-
right ventricular outflow obstruction, which occurs in the mid-40s.3 mended, since adults usually present with a
were both surgically treated 2 years ago pre- Diagnostic criteria for idiopathic moyamoya hemorrhagic stroke as the collaterals have a
sented with 3-days history of severe bifrontal include the following major requirements: tendency to rupture.19
headache and altered mental status. Physical stenosis or occlusion at the terminal portion of Surgical revascularization is advised in both
examination and laboratory workup were
unremarkable. Head-CT demonstrated sub-
arachnoid hemorrhage seen throughout basi-
lar cisterns including suprasellar, interpedun-
cular, perimesencephalic, and prepontine cis-
terns. Head-CT-angiography (CTA) showed
bilateral intracranial internal carotid artery
(ICA) occlusion with concentric luminal nar-
rowing of the cervical ICAs, diffuse intracra-
nial proliferative arteriopathy in the bilateral
territories of the anterior and middle cerebral
arteries and ruptured saccular aneurysm aris-
ing from the right posterior cerebral artery.
Cerebral angiogram confirmed these findings
and a coiling embolization of a ruptured 3.5
mm high flow aneurysm arising from the dis-
tal aspect of the basilar artery was performed.
The angiogram also demonstrated bilateral
severe stenosis of the internal carotid arteries
with multiple transdural collaterals consistent
with moyamoya angiographic pattern (Figure
3). The neurosurgery service was consulted,
however the patient refused further surgical
evaluation and was discharged on the 7th day
of hospitalization. Unfortunately the patient
did not follow up with neuroradiology and neu-
rosurgery and presented 15 months later with
acute onset of altered level of consciousness.
She was intubated in the emergency depart- Figure 1. Case #1. A) and B) diffusion weighted sequence and apparent diffusion coeffi-
cient map, respectively, demonstrate a focal area of restriction of diffusion involving the
ment, placed on mechanical ventilation and right rostrum, genu and body of the Corpus Callosum with mild enhancement on post-
admitted with a Glasgow Coma Scale (GCS) of gadolinium T1W sequence (C) and moderate edema and local mass effect on T2W
6 to the medical intensive care unit. The sequence (D). A second lesion involving the right basal ganglia and genu of the right
repeat-head-CT showed extensive hemorrhage internal capsule demonstrates incomplete peripheral enhancement with central necrosis,
confined to the choroid plexus bilaterally without mass effect or restriction of diffusion.

[page 20] [Neurology International 2014; 6:5369]

 Case Report

children and adults presenting with progres-

sive symptoms and/or cognitive decline. There
are multiple surgical options, but the treat-
ment of choice is thought to be a direct super-
ficial temporal artery to middle cerebral artery
bypass (external carotid-internal carotid
bypass surgery).20 Other surgical modalities
including EDAS (encephaloduroarteriosynan-
giosis), EMS (encephalomyosynangiosis), and
the multiple burr holes procedure are avail-
able, however the outcome remains controver-
sial.

Conclusions
We describe an uncommon variety of moy-
amoya presentation in the setting of moy-
amoya disease with a fulminant progression
(case 1) and moyamoya syndrome with
delayed presentation but also with fatal out-
come (case 2).
Despite the limited prognosis and the evi-
dences known about the disease progression a
fulminant course with multiple bilateral large
lobar infarcts precipitating herniation and
death within days is uncommon (case 1). In
contrast subarachnoid hemorrhage as a result
of saccular aneurysmatic formation in the set-
ting of moyamoya syndrome is more common.
However neurointerventional procedures may
Figure 2. Case #1. Biplanar cerebral angiography of the left internal carotid artery (A and not hold the disease progression but can pro-
B, lateral and AP respectively) demonstrated complete occlusion of the left supraclinoid long survival (case 2). The outcome in both
internal carotid artery with a patent left anterior choroidal artery supplying lenticulos- settings remains unfortunately the same.
triatal vessels giving the angiographic appearance of a I, suggestive of Moyamoya angio-
graphic pattern. Collateral flow from the right posterior choroidal artery supplying the While definitive treatment in the acute ful-
pericollosal, frontopolar and callosmarginal arteries demonstrated on lateral view on minant phase may be futile and not indicated,
selective angiogram of the left vertebral artery (C). Intracranial view of the right inter- ascertaining the correct diagnosis may help
nal carotid artery in the AP projection (D) demonstrates an irregular M1 segment and provide a more accurate prognosis.
complete occlusion of the mid A1 segment of anterior cerebral artery. Cortical branches
also appeared irregularity consistent with a proliferative intracranial vasculopathy.

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