Use of a Calcium Channel Blocker
(Nicardipine HCl) in the Treatment
of Childhood Moyamoya Disease
Syed A. Hosain, MD; John T. Hughes, MD; Sandra L. Forem, MD; Jeffrey Wisoff, MD; Irving Fish, MD

ABSTRACT

Moyamoya disease is a cerebrovascular disease characterized radiologically by progressive narrowing and occlusion of
the arteries contributing to the circle of Willis and its branches. There is formation of an exuberant collateral network
of blood vessels at the base of the brain, which is thought to arise in response to chronic ischemia. Clinically, the course
is variable, with patients having repeated transient ischemic attacks, strokes, migraine, and seizures. Effective treatment is not available. The etiology and pathophysiology of moyamoya disease are largely unknown. Two patients with
arteriographically proven moyamoya disease were identified. Both patients were symptomatic before age 5 years.
Despite successful encephaloduroarteriosynangiosis revascularization procedures, they continued to experience an
inexorable downhill course. A calcium channel blocker (nicardipine HCl) was introduced in order to prevent further
symptoms. After the introduction of nicardipine, no further strokes occurred in either patient. There were no further
episodes of transient ischemic attacks, seizures, or headache in one patient and decreased frequency in the other. In
patients with moyamoya disease, nicardipine may have a beneficial effect on cerebral hemodynamics and may prevent
ischemic sequelae by optimizing existing collateral circulation. (J Child Neurol 1994;9:378-380).

Moyamoya disease is a peculiar progressive cerebrovascular disease first described by Shimzu and Takeuchi in
1966.1-5 The Japanese term moyamoya describes the typical angiographic appearance, which consists of bilateral
stenosis of the internal carotid arteries and basal telangiectasias, which are dilated collateral lenticulostriate and
thalamoperforating arteries.2,6-9 Children typically present with repeated transient ischemic attacks, strokes,
seizures, involuntary movements, and migrainelike
headaches. Adults, on the other hand, commonly present
with subarachnoid hemorrhages due to rupture of
aneurysms that form on the enlarged moyamoya vessels.’°-12 Aspirin, steroids, and low molecular weight dextran have not been effective in preventing the progression
of the disease.13-15 Surgical therapy may be helpful on
occasion but is not entirely satisfactory. The most commonly employed treatment in children at present is a surgical revascularization procedure, encephaloduroarteriosynangiosis.16-20 Prognosis in children is directly
related to age of onset of symptoms: the earlier the onset
of symptoms, the worse the outcome. 1°>21

Received May 20, 1993. Received revised Dec 21, 1993. Accepted for publication Dec 22, 1993.
From the Departments of Pediatric Neurology and Pediatric Neurosurgery, New York University Medical Center, New York, NY.
This work was presented in part at the 21st Annual Meeting of the Child
Neurology Society, New Orleans, October 22-24, 1992.

Address correspondence to Dr Irving Fish, New York University Medical
Center, 550 First Avenue, New York, NY 10016.

378

Two patients with symptomatic moyamoya disease
underwent encephaloduroarteriosynangiosis surgery but
continued to have symptoms and signs of progressive
deterioration despite angiographic evidence of revascularization. Both patients were given nicardipine hydrochloride, a calcium channel blocker known to dilate central nervous system vessels, in an attempt to alleviate
their progressive symptomatology.
CASE 1
T.D. is an 81/2-year-old right-handed boy of Korean descent who
was

adopted at the age of 41/z months. Growth and development
developed sudden right-sided

was normal until 3 years, when he

weakness. He was admitted to New York University Medical

Center for evaluation. General physical examination was normal. Neurologic examination revealed a moderate right hemi-

paresis. Extensive blood workup and cardiac workup were normal. A computed tomographic (CT) scan of the brain showed a
deep white-matter infarct in the left parietal region, and a cerebral angiogram showed moyamoya disease.
Thirty-six hours after the angiogram, T.D. developed another sudden episode of right-sided weakness, which improved partially over 5 days. Encephaloduroarteriosynangiosis revascularization was successfully performed on the left side on March 9,
1987, and on the right side on August 13, 1987. At the age of 3
years 10 months, T.D. developed sudden left-sided weakness
and dysarthric speech. CT scan of the brain demonstrated old
bilateral ischemic infarcts and a new infarct in the region sup-

plied by the right middle cerebral artery. The weakness partially
improved, and at the time of discharge, he was able to walk with

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379

assistance. Due to the continued clinical deterioration after
surgery, a calcium channel blocker (nicardipine HCI) was started in November 1987 on a compassionate use basis. He was prescribed nicardipine 10 mg three times a day.

CASE 2

Several months later, T.M. had another stroke, and she continued to have transient ischemic attacks, most frequently con-

sisting of numbness or weakness of a limb.
In August 1989, in order to prevent further symptoms, a calcium channel blocker (nicardipine HCI) was introduced. She has
been maintained on a dose of 10 mg three times a day without
any adverse effects.

T.M. is an 81/2-year-old right-handed white girl. She was well

until 41/z years of age, when she developed several episodes of
sudden numbness in the left upper extremity, which resolved
over minutes to hours. She also developed migrainelike
headaches and was treated with aspirin and acetaminophen as
needed, with some relief. Five months later, she had sudden
onset of left-sided weakness and incoherent speech. This

episode lasted for about 5 to 10 minutes and subsided without
any residual deficits. Cardiac, blood, and urine workups were
normal. A magnetic resonance imaging (MRI) scan of the brain
at the time showed an abnormal vascular pattern at the base of

the brain, and a cerebral angiogram revealed a vascular pattern

consistent with the diagnosis of moyamoya disease (Figures 1
and 2). Because of this, bilateral revascularization procedures-

encephaloduroarteriosynangioses-were performed.
One month after the second surgical procedure, the patient
developed right arm and leg numbness, which rapidly resolved.
She had a right focal motor seizure for which she was workedup and placed on carbamazepine. An MRI of the brain performed at that time showed a new ischemic infarct in the white
matter of the left parietal lobe (Figure 3).

RESULTS

In the 41/2 years after the initiation of nicardipine HCI therapy in patient 1, no further signs or symptoms have
occurred. MRI of the brain has not shown any new
infarcts. Magnetic resonance angiography showed adequate revascularization and no further progression of
moyamoya disease. In the 31/2 -year follow-up of patient 2,
no strokes or transient ischemic attacks have occurred,
but she continues to have migrainelike headaches and has
had seizures despite therapeutic levels of carbamazepine.
DISCUSSION

Moyamoya disease, especially when symptoms arise
before age 5 years, is very often a progressive disease
that ends either in death or severe permanent neurologic
deficits. The ultimate course of the disease depends on
the rapidity of the occlusive process and the patient’s
ability to develop adequate collaterals.22,23 Since the original description of moyamoya disease by Shimzu and
Takeuchi, studies on moyamoya disease have failed to
satisfactorily elucidate the pathogenesis. Effective treatment is still not available. Surgical revascularization procedures are occasionally of benefit, but many of these
patients continue to deteriorate neurologically. Pharmacotherapeutic agents, such as aspirin, steroids, and
vasodilators have been tried in the past without success.

Figure 1. Right carotid angiogram of patient 2 (anteroposterior
projection) showing narrowing of the internal carotid artery and
prominent moyamoya vessels.

Figure 2. Right carotid angiogram of patient 2 (lateral projection)
showing stenosis of the terminal internal carotid artery and its
major branches with lush basal anastomosis.

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Acknowledgments
We wish to acknowledge Vivian Catenaccio for her secretarial assistance. We
wish to thank Syntex Corporation for providing the nicardipine hydrochloride.

References
1.

Suzuki J, Kodoma N: Moyamoya disease—a review. Stroke

2.

Suzuki J, Takaku A: Cerebrovascular "moyamoya" disease.
Arch Neurol 1969;20:288-299.
Suzuki J: Moyamoya Disease. Berlin, Springer Verlag, 1986.
Gordon N, Isler W: Childhood moyamoya disease. Dev Med

1983;14:104-109.

3.
4.

Child Neurol
1989;31:103-106.
5.

Maki Y, Enomoto T: Moyamoya disease. Childs Nerv Syst 1988;
4:204-212.

6.

Suzuki J, Takaku A, Asahi M: The disease showing the abnormal network at the base of the brain, particularly found in
Japan. II. A follow-up study, in Japanese. Brain Nerve 1966;18:
897-908.

7.

Figure 3. MRI showing an fresh ischemic infarct in white matter of
left parietal lobe and an old infarct in the right posterior temporoparietal lobe. This MRI was obtained after the revascularization
procedure.

McLean et a124 reported a case of moyamoya disease in
which intravenous verapamil, a calcium channel blocker,
was thought to be effective during acute deterioration.
There have been no reports of the long-term use of
an oral calcium blocker in childhood moyamoya disease.
Nicardipine HCI proved successful in our two cases, both
of whom had undergone encephaloduroarteriosynangiosis surgery and had shown adequate revascularization but
continued to have symptoms. Calcium channel blockers
perhaps optimize the dilation of the preexisting collateral
vessels. Because of the vasodilating effect on cerebral
arteries and the lack of adverse side effects, it is justifiable to use such a drug in moyamoya disease. We used 10
mg of nicardipine orally three times a day, and no side
effects, such as dizziness, lowering of blood pressure,
nausea, or palpitations, were reported.
CONCLUSION

Two patients with documented moyamoya disease whose
symptoms continued after successful encephaloduroarteriosynangiosis revascularization surgery were given
nicardipine 10 mg three times a day orally on a chronic
basis. After the introduction of nicardipine, their symptoms abated.
Further studies, both physiologic and controlled clinical trials, will have to be done to determine the place for
calcium channel blockers in the treatment of this condition.

Suzuki J, Kowada M, Asahi M, Takaku A: A study on disease
showing singular cerebral angiographic findings which seem to
be new collateral circulation. Proceedings of the 22nd Annual
Meeting of the Japan Neurological Society, 1963.
8. Fukuyama Y, Umerzu R: Clinical and cerebral angiographic
evolutions of idiopathic progressive angioocclusive disease of
circle of Willis ("moyamoya" disease) in children. Brain Dev
1985;7:21-37.
9. Taveras JM: Multiple progressive intracranial arterial occlusion: A syndrome of children and young adults. AJR Am J
Roentgenol 1969;106:235-268.
10. Matsushima Y, Aoyagi M, Niimi Y, et al: Symptoms and their
pattern of progression in childhood moyamoya disease. Brain
Dev 1990;6:784-789.
11. Adam HP, Kassell NF, Wisoff HS, Drake CG: Intracranial saccular aneurysm and moyamoya disease. Stroke 1979;10:174-179.
12. Kowada M, Momma F, Kikuchi K: Intracranial aneurysm associated with cerebrovascular moyamoya disease: Report of a case
and review of 13 cases. 1979;52:236-237.
Br J Radiol
13. Fukuyama Y, Kuriya Y, Imezu R: An experience of neurocorticosteroid hormone in childhood occlusion of circle of Willis, in
Japanese, in Annual Report of Special Working Group of Welfare Ministry of Moyamoya Disease in Fiscal Year 1981,
1980.
pp 45-51.

14.

Suzuki J, Takaku A, Kodama N, Sato S: An attempt to treat
cerebrovascular "moyamoya disease" in children. Childs Brain

1975;1:193-206.
Spitther JF, Smektala K: Pharmacotherapy in moyamoya disease. Hokkaido J Med Sci 1990;2:235-240.
16. Matsushima T, Fiyiwara S, Nagata S: Surgical treatment for
pediatric patients with moyamoya disease by indirect revascularization procedures (EDAS, EMS, EMAS). Acta Neurochem
1989;3-4:135-140.
17. Ou MV, Griebel RN, Hoffman HJ: The surgical treatment of
childhood moyamoya disease. J Neurosurg 1987;66:675-680.
18. Matsushima Y, Iwaba Y: Moyamoya disease in children and its
surgical treatment. Introduction of a new surgical procedure
and its follow-up angiograms. Childs Brain 1984; 11:155-170.
19. Miyamoto S, Kikuchi H, Karasawa J, et al: Pitfalls in the surgical
treatment of moyamoya disease. J Neurosurg 1988;68:537-543.
20. Cahan LD: Failure of encephaloduro-arterio-synangiosis procedure in moyamoya disease. Pediatr Neurosci 1985-1988;12:58-62.
21. Kurokawa T, Tomita S, Ueda K, et al: Prognosis of occlusive
disease of circle of Willis (moyamoya disease). Pediatr Neurol
1985;5:274-277.
22. Yoshihara M, Yutaka I: The specificity of the collaterals to the
brain through the study of surgical treatment of moyamoya disease. Stroke 1986;17:117-122.
23. Eller W, Pasternak JF: Revascularization of moyamoya disease.
Five year follow-up. Surg Neurol
1987;28:463-467.
24. McLean MJ, Gebarski SS, Van der Spek AF, Goldstein GW:
15.

Treatment of acute deficits of moyamoya disease with verapamil. Ann Acad Med Singapore 1985;1:65-70.

Downloaded from jcn.sagepub.com at UNIV OF PENNSYLVANIA on June 19, 2015