Moyamoya Syndrome
With Spherocytosis:
Effect of Splenectomy
on Strokes
Yoichi Tokunaga, MD*,
Shouichi Ohga, MD*, Sachiyo Suita, MD†,
Toshio Matsushima, MD‡, and
Toshiro Hara, MD*
A 3-year-old male patient with hereditary spherocytosis who developed moyamoya syndrome, presenting
hemiplegia, and slurred speech is reported. Transient
ischemic attacks occurred repeatedly with hemolytic
crises. Magnetic resonance imaging and angiography
revealed bilateral occlusion of the internal carotid and
middle cerebral arteries with the formation of moyamoya vessels and multiple infarctions in the basal
ganglia. Although splenectomy can increase the risk of
stroke, no stroke occurred after splenectomy. On aspirin and dipyridamole therapy the patient has been free
of neurologic deficits and progression of the vasculopathy for 5 years. This rare observation suggests that
anemic hypoxia more greatly contributes to the progression of moyamoya syndrome than postsplenectomy
thrombocytosis or reduced deformability of spherocytes. © 2001 by Elsevier Science Inc. All rights
reserved.
Tokunaga Y, Ohga S, Suita S, Matsushima T, Hara T.
Moyamoya syndrome with spherocytosis: Effect of splenectomy on strokes. Pediatr Neurol 2001;25:75-77.

Introduction
Moyamoya disease is an idiopathic cerebral vasculopathy characterized by bilateral occlusion of the intracranial
carotid arteries and proximal portions of anterior and/or
middle cerebral arteries associated with a collateral net-

From the Departments of *Pediatrics, †Pediatric Surgery, and
‡
Neurosurgery; Graduate School of Medical Sciences; Kyushu
University; Fukuoka, Japan.

© 2001 by Elsevier Science Inc. All rights reserved.
PII S0887-8994(01)00283-1 ● 0887-8994/01/$—see front matter

work of telangiectatic vessels (“moyamoya” vessels) in an
adjacent area [1]. Ischemic attacks of hemiplegia or
seizures constitute the major presentation in childhood,
whereas subarachnoid hemorrhage occurs more frequently
in adults. Because of its progressive nature, the disease’s
neurologic outcome is unfavorable without surgical intervention to reconstitute the cerebral circulation [2,3]. To
diagnose moyamoya disease, other underlying diseases,
including vasculitis, atherosclerosis, and malformations
must be excluded. Such a vasculopathy with any underlying diseases is called moyamoya syndrome. Hereditary
spherocytosis is a common inherited hemolytic anemia
caused by the abnormal molecules in red cell membranes,
such as spectrin and ankyrin [4]. Cerebrovascular accidents are major complications of sickle cell disease,
accompanied by narrowing and occlusion of the internal
carotid arteries [5]. On the other hand, only one patient
with hereditary spherocytosis and moyamoya disease or
moyamoya syndrome has been reported so far [6].
A 3 year-old male with hereditary spherocytosis who
developed stage 2 moyamoya syndrome is presented.
After successful splenectomy, the transient ischemic attacks disappeared with no progression of the vasculopathy.
The potential role of spherocytic anemia in the pathophysiology of moyamoya syndrome is also discussed.
Case Report
A 37-month-old Asian male was hospitalized with transient hemiplegia. This patient had no family history of consanguinity or cerebrovascular accidents. His father had undergone splenectomy for hereditary
spherocytosis. He was born to a healthy mother via a full-term delivery.
Phototherapy was initiated for neonatal jaundice. On day 5 after birth, the
patient was diagnosed with hereditary spherocytosis from the findings of
microspherocytic anemia (Hb 9.8 g/dL), reticulocytosis (6.7%), and
increased osmotic fragility of red cells. The hemoglobin concentration
was around 6.5 g/dL until he was 2 years old. Hemolytic crises repeatedly
occurred with infections. At 35 months of age, left hemiparesis, lasting
15 minutes, occurred. Recurrent episodes of hemiplegia and slurred
speech made hospitalization necessary.
On admission, physical examination revealed a pale icteric male of 92
cm in height (30th percentile) and 14 kg in weight (46th percentile). His
pulse rate was 120 beats/minute, and his blood pressure was 108/64 mm
Hg. Auscultation revealed normal respiratory sounds and a functional
heart murmur. The liver was palpated 4 cm, and the spleen was palpable
8 cm below the costal margin. No neurologic abnormality was observed
on the examination. The peripheral blood counts revealed leukocytes
6.41 ⫻ 109/L, erythrocytes 1,400 ⫻ 109/L, hemoglobin 3.5 g/dL,
hematocrit 11.1%, reticulocytes 7.2%, and a platelet count of 159 ⫻
109/L. Blood chemistry indicated hemolysis; lactate dehydrogenase 810
IU/L, and indirect bilirubin 4.0 mg/dL. The protein C (47%) and protein

Communications should be addressed to:
Dr. Ohga; Department of Pediatrics; Faculty of Medicine; Kyushu
University; 3-1-1 Maidashi; Higashi-ku; Fukuoka 812-8582; Japan.
Received December 14, 2000; accepted March 19, 2001.

Tokunaga et al: Splenectomy for HS and Moyamoya Syndrome 75

Figure 1. (A) MRI of the brain illustrates multiple small infarctions in the bilateral frontal lobes and left parietal white matter (T2-weighted image TR ⫽
2500 ms, TE ⫽ 110 ms). (B) Cranial magnetic resonance angiography demonstrates bilateral narrowing of the supraclinoid portions of the internal
carotid arteries and the proximal portions of the anterior and middle cerebral arteries (arrows).

S (51%) activities were subnormal. Echocardiography revealed a mild
left ventricular hypertrophy. Electroencephalogram (EEG) revealed highvoltage slow waves in the left hemisphere. Cranial computed tomography
(CT) revealed multiple low-density across the right caudate and lenticular
nuclei. Magnetic resonance imaging (MRI) disclosed small infarctions in
the bilateral frontal and left parietal white matter (Fig 1A). Magnetic
resonance angiography depicted bilateral narrowing of the supraclinoid
portions of the internal carotid arteries and proximal portions of the
anterior and middle cerebral arteries along with the formation of
collateral vessels (Fig 1B). After the diagnosis of moyamoya syndrome,
ischemic strokes occurred with hemolytic crises (hemoglobin less than 6
g/dL). He underwent splenectomy because transient ischemic attacks
were not prevented without frequent transfusions. The hemoglobin level
exceeded 13 g/dL, and the platelet count peaked at 1,707 ⫻ 109/L.
Cerebral angiography 2 months after the splenectomy illustrated findings
compatible with stage 2 moyamoya disease (Fig 2). Single-photon
emission computed tomography (SPECT) revealed reduced blood flow in

the right striate body and left posterior temporal lobe. With the administration of oral aspirin and dipyridamole therapy, the patient has been
free from neurologic deficits and progression of the vascular lesions for
5 years, as judged on repeated follow-up magnetic resonance angiography.

Discussion
Moyamoya syndrome occurs in patients with brain
tumors, vascular malformations, neurofibromatosis, primary or secondary vasculitis after irradiation, infections,
and head trauma. Holz et al. [6] reported the first association of hereditary spherocytosis and moyamoya syndrome; for example, a 6-year-old male revealed bilateral
occlusion of the supraclinoid internal carotid arteries and

Figure 2. Cerebral angiography illustrates bilateral stenoses at the end of the left internal carotid artery, the proximal portions of the middle cerebral
arteries, and the anterior cerebral arteries (arrows), along with the formation of collateral vessels. These findings are consistent with stage 2 moyamoya
syndrome.

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Vol. 25 No. 1

moyamoya vessels without any other underlying disease.
Our patient manifested typical features of moyamoya
disease with no conceivable predisposition except for
slight decreases in protein C and protein S activities and
abnormal red cells. Patients homozygous for abnormal
hemoglobins are prone to develop cerebral infarction [5],
internal carotid artery narrowing, and occlusion with the
moyamoya pattern being the most common arteriographic
findings [7,8]. The progressive vasculopathy seems to be a
consequence of the flow in the vasa vasorum being
obstructed by sickle cells, which leads to ischemia of the
internal carotid artery wall, intimal proliferation, and
occlusion but not exclusively of direct obstruction of small
cerebral vessels by the cells [7,8]. In 1989 van Hilten et al.
[9] described two hereditary spherocytosis brothers with
cerebral infarction who manifested elevated aggregation
and reduced deformability of red cells along with hyperviscosity. They suggested that similar occlusion of the
vasa vasorum in sickle cell disease induced cerebral
ischemia in hereditary spherocytosis patients. Holz et al.
[6] postulated that increased blood flow, caused by anemia, together with less-deformable spherocytes, produces
progressive endothelial proliferation, which results in
vascular occlusion. Red cells in beta-thalassemia are
resistant to osmotic pressure, and some thalassemic patients have been reported to develop moyamoya syndrome
[10,11]. In this context, less-deformable red cells may
contribute to the development of moyamoya vasculopathy.
Cohen et al. [12] reported a 10-year-old male with
Fanconi’s anemia and moyamoya syndrome, suggesting a
Fanconi’s anemia-associated congenital vascular anomaly.
However, the present patient had no vascular anomalies.
The entire course in our patient may raise the possibility
that both the abnormal rheology of spherocytes and
chronic anemia led to the formation and progression of the
cerebral vasculopathy.
Another concern is the clinical indication for splenectomy. Splenectomized patients are liable to have polycythemia, thrombocytosis, and hyperlipidemia, which substantially raise the risks of strokes and embolism [13,14].
Bruguier et al. [15] emphasized the risk of postsplenectomy thrombocytosis for accidental cerebral infarction in a
3-year-old female with hereditary spherocytosis. Thrombocytosis also contributes to cerebral infarction in patients
with iron-deficiency anemia [16]. Anemic hypoxia by
itself exacerbates cerebral ischemia, especially in infants
and older individuals. Exchange transfusions cannot halt
the progression of the cerebral vasculopathy in patients
with sickle cell anemia [7]. On the other hand, the
preventive effect of transfusions on the strokes in our
patient may reflect the critical role of anemic hypoxia in
the progression of the cerebral vasculopathy. In this
context, severe anemia, as well as thrombocytosis after
splenectomy, might be predisposing factors for ischemic

cerebrovascular accidents [17]. The postoperative condition of our patient was monitored carefully in the intensive
care unit to avoid dehydration, hypotension, and thrombotic accidents. Successful splenectomy on antiplatelet
aggregation therapy could imply the greater contribution
of anemic hypoxia to the progression of moyamoya
disease than that of thrombocytosis or reduced deformability of spherocytes.

The authors thank Drs. Taketsugu Minami, Kenjiro Gondo, Ryutaro Kira,
Hiroyuki Torisu, and Yuka Sasaki of the Department of Pediatrics,
Graduate School of Medical Sciences, Kyushu University, for helpful
discussions.

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