Moyamoya Disease in an Infant

With Autonomic Dysfunction:
Angiographic and MRI Findings
William C. Welch, MD; Margaret McBride, MD; Daniel K. Kido, MD;
Curtis N. Nelson, MD, PhD

Abstract
An infant with persistent Harlequinism went on to develop a hemiparesis secondary to Moyamoya disease at 21h months of
age. The sympathetic nervous system is proposed to be an etiologic factor in the pathophysiology of Moyamoya disease as
well as Harlequinism. This is one of the youngest patients reported in the English literature with Moyamoya disease and the
only report of the coexistence of Moyamoya disease and atypical Harlequinism. Magnetic resonance imaging led to the
diagnosis, which was confirmed by cerebral angiography. (J Child Neurol 1988;3:110-113).

disease (&dquo;puff of cigarette smoke
in the air&dquo;) is an uncommon clinical

Moyamoya
drifting

and pathologic entity characterized by occlusion of
terminal portions of the internal carotid arteries.
Although the exact etiology is uncertain, there is
evidence to support autonomic dysfunction as a contributing factor.’ We have recently used both angiography and magnetic resonance imaging (MRI) to
evaluate one of the youngest patients with Moyamoya disease reported in the English literature. This
patient also had other findings of autonomic imbalance including supraventricular tachycardia and
atypical Harlequinism. Harlequinism is a rare condition consisting of a red, mottled appearance of the
dependent half of the body of a newborn when laying
on his or her side, with a sharp line of demarcation
at the midline separating these changes from the

normal skin coloring of the nondependent side. This
skin coloring change may occur alternately in each
side as the infant changes position. It is thought to be
related to aberrant autonomic regulation of blood

Received May 20, 1987. Received revised Sept 17, 1987.
Accepted for publication Oct 1, 1987.

From the Divisions of Neurologic Surgery (Drs Welch and
Nelson), Pediatric Neurology (Dr McBride), and Neuroradiology
(Dr Kido), University of Rochester School of Medicine and Dentistry, Rochester, NY.
Address correspondence to Dr William C. Welch, Division of
Neurologic Surgery, University of Rochester School of Medicine

and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642.

110

vessels and it is usually a transient phenomenon in
the newborn.22
Case Report
The patient is a white female born after a full-term, un-

complicated pregnancy by spontaneous vaginal delivery.
Birth weight was 3500 g. Meconium staining, an occasional
irregular heart beat, and mild postnatal hyperbilirubinemia
requiring phototherapy were noted, as was red and purple
mottling of the left half of the body. She was otherwise
normal and was discharged from the hospital.
At 1 month of age, follow-up examination revealed
multifocal atrial tachycardia, and she was admitted for evaluation. Fluoroscopy demonstrated normal heart size and
pulmonary blood flow. Digoxin therapy was begun. The
Harlequin-type skin mottling on the left half of her body
was unchanged, and otherwise her examination was normal.
At age 21/2 months, the patient was readmitted with the
new onset of left
hemiparesis, right gaze preference and
poor tracking, which had developed insidiously over four
days of affliction with a flu-like illness. Her head circumference was 40 cm, 50th percentile. The left body mottling
was more cyanotic than red at this time, and the left
extremities were cold. Heart rate and rhythm were normal
and the infant was still taking digoxin.
A noncontrast computed tomographic (CT) scan-of the
head revealed increased density of the entire right hemisphere, with focal areas of low density in the frontal and
deep parieto-occipital white matter. With contrast, the entire
right hemisphere enhanced, suggesting either blood flow
asymmetry (&dquo;luxury perfusion&dquo;) or abnormal vascularity.
The ventricles were moderately enlarged. Electroencephalogram revealed diffusely decreased voltage in the right hemisphere. Echocardiogram was normal.
At age 4 months, the patient was readmitted with the

onset of a seizure disorder. Harlequin discoloration was still
noted in the left trunk and intermittently in the left

extremities. Head CT scan demonstrated atrophy of the
right hemisphere presumed to be secondary to infarction.
Electroencephalogram showed low voltage in the right
hemisphere and sharp forms in the left lateral hemisphere.
At age 12 months, her head circumference was 41.5
cm, two standard deviations below the 3rd percentile. She
had no purposeful movement due to severe spastic quadriparesis (left greater than right) but could follow visually and
smiled responsively. There were no neuroectodermal markings. Tine test was negative.
An MRI scan was therefore obtained which demonstrated bilateral hemispheric atrophy (right greater than
left), enlarged cerebral ventricles, absence of flow in the
carotid arteries bilaterally, and multiple small vessels in the
area of origin of the left middle and anterior cerebral arteries,
as well as within the basal ganglia (Figures 1 and 2). Moyamoya disease was suspected, and neurosurgical consultation
was obtained regarding the possibility of performing an
extracranial-intracranial bypass procedure. In order to better
define the collateral flow, a cerebral angiogram was performed.

FIGURE 2
MRI scan (TR 2000/TE 30) demonstrating basal ganglionic
collaterals (arrows).
’

A right common carotid injection demonstrated preferential filling of the right external carotid artery with retrograde filling of the supraclinoid segment of the right internal
carotid artery. A prominent anterior cerebral (azygous)
artery supplied both anterior cerebral artery territories. In
turn, vessels from the right anterior cerebral artery filled the
right middle cerebral territory, since both horizontal segments, as well as the posterior cerebral artery, were occluded. The left ophthalmic artery filled from the right
external carotid artery and subsequently supplied the lenticulostriate artery and at least the proximal middle cerebral
artery. The right superficial temporal and occipital arteries
may have also helped to supply some of the cortical vessels

(Figure 3).
The diagnosis of Stage V-VI (Suzuki classification)
Moyamoya was confirmed. In light of the extensive extracranial-intracranial blood flow, we felt that the patient

FIGURE 1
MRI scan (TR 2000/TE 30) demonstrating enlarged right
temporal horn and Moyamoya vessels in middle and anterior cerebral territories bilaterally (age 12 months).

would not benefit from surgery.
At last follow-up, she was 32 months of age. Her heart
rate had been normal for two years and digoxin had been
discontinued four months previously. Bowel and bladder
function were normal for an infant. Head circumference was
42 cm, 4 standard deviations below the 3rd percentile. She
continued to have severe spastic quadriparesis, but could

111

’

FIGURE 4
Left truncal mottling with midline demarcation

(Harle-

quinism).

reach with her right hand and propel herself in a walker.
Her left body mottling persisted (Figure 4), especially truncally, where a sharp line of demarcation remained in the midline anteriorly. Her feet and often her hands were red or
purplish but blanched easily. She had never been noted to
sweat, but she teared readily with crying.

Discussion

Moyamoya is a rare disease of uncertain etiology.
Other processes such as radiation vasculopathy, neurofibromatosis and tuberculous arteritis can result
in a Moyamoya angiographic pattern if the supraclinoid portion of the internal carotid artery is involved,
and these should be included in the formal differential diagnosis.4 Moyamoya is more commonly seen in
those of Japanese descent. Our patient presented with
a right cerebrovascular accident presumably secondary to ischemia or occlusion of her right middle
cerebral artery at age 21/2 months. This is one of the
youngest documented cases of Moyamoya disease in
the English literature and the only one, to our knowledge, that has other signs consistent with autonomic

dysfunction. Magnetic resonance imaging proved to
be a noninvasive screening test for the disease process, as it provided an alternate means of imaging

blood flow. This has been recently described by Fujisawa et a1.5 The diagnosis in this case was confirmed

FIGURE 3

Anterior-posterior (A) and lateral (B) cerebral angiograms
demonstrating multiple extracranial-intracranial anastomoses in the middle cerebral artery territory with occlusion
of the right internal carotid artery.
112

by angiography.
Various etiologies of Moyamoya have been proposed, many of which infer an immunologic vasculitis
as evidenced by a history of recurrent infections
(usually head and neck) and deposition of immune
complexes into the vascular walls. The immune
complexes are thought to be responsible for the
histopathologic findings of &dquo;eccentric and laminated
hypertrophy of the intima, abnormal tortuosity and
duplication of the internal elastic laminae, and thinning of the media&dquo;6 in the distal internal carotid ar-

teries. This, in turn, causes stenosis of these vessels
and results in the formation of collaterals.
Suzuki has performed a series of experiments
autonomic nervous system as a pathoimplicating the
1
He found Moyamoya-type vascular
factor.
genic
in
changes dogs sensitized with heterologous serum
and was able to demonstrate that immunologic complexes had been deposited in the vascular walls.
Suzuki proposed that neck infections may stimulate
the superior cervical ganglion in a retrograde fashion
(Reilly phenomenon’), thereby increasing intimal
permeability. This would allow circulating immune
complexes to be deposited in the vascular walls and
cause the pathologic changes of Moyamoya disease.

Yamada reported the development of Moyamoya
disease in 4-year-old monovular twins.8 Both he and
Isler9 suggested that the development of the collateral
Moyamoya vessels may begin in the prenatal period.
The fact that our patient had persistent and atypical Harlequinism and supraventricular tachycardia
suggest that she may have autonomic dysfunction on
a developmental basis. Such autonomic dysfunction
may explain the early appearance of her Moyamoya
disease.

’

Acknowledgments
Special thanks for the expert secretarial assistance of Donna Sue
Wood and Betty Pender.

References
1. Suzuki J: Moyamoya Disease. New York, Springer-Verlag Inc,
1983, pp 131-143.
2. Burgoon CF Jr: The skin, in Vaugham VC, McKay RJ (eds):
Nelson Textbook of Pediatrics, ed 10. Philadelphia, WB Saunders
Co, 1975, p 1518.
3. Suzuki J, Kodama N: Moyamoya disease—A review. Stroke

1983;14:104-109.
4. Osbern AG: Introduction to Cerebral Angiography. Philadelphia,
Harper & Row, 1980, p 127.
5. Fujisawa I, Asato R, Nishimura H, et al: Moyamoya disease: MR

imaging Radiology 1987;164:103-105.
6. Suzuki J: Moyamoya Disease, New York, Springer-Verlag Inc,
1983, p 130.
7. Reilly J, Rivelier E, Compagnon A, et al: Le role du systeme

neurovegetatif dans le reactions d’hypersensibile. Ann Med
1936;2:165-188.
8. Yamada H, Nakamura S, Kageyama N: Moyamoya disease in
monovular twins Neurosurgery 1980;53:109-112.
9. Isler W: Cerebrovascular diseases in the first three years of life.
Brain Dev 1980;2:95-105.

113