THE MOYA-MOYA SYNDROME:

A REPORT OF TWO CHILDREN

P. M. M. wn Erven*, F. J. M. Gubree1.P. H. 0. M. Th~sse~~~ and W. 0. Renier*

SUMMARY

Two patients with Maya-Maya syndrome are reported. The first patient has a trisomy 21 and is to our
knowledge the third patient reported with the a\socintion of Down’s syndrome and Moya-Moya. The
second patient also demonstrates the typical Maya-Moga pxture in angiography. Angiographic follow-up
is demonstrated.
The presenting age and symptoms. the symptoms in the course of the disease and the prognosis of 120
non-mongoloid cases of Mova-Maya are reviewed.

INTRODUCTION

TAKEUCHI (1961) was the first to describe an occlusive disease of the carotid artery,
later given the descriptive name Moya-Moya (i.e. puff of vulcan0 smoke). This
condition is characterized by a progressive stenosis or occlusion of the distal seg-
ment of the internal carotid artery and not infrequently of the proximal anterior and
middle cerebral arteries associated with a dense collateral network in the region of
the basal ganglia and upper brain stem. It is now recognized as a radiologic entity
(HANDA and HANDA, 1972).
We would like to report here two case studies of Moya-Moya syndrome. In one
case this syndrome is associated with Down’s syndrome. In both cases a Moya-Moya
network irradiates from branches of the carotid and of the basilar artery.

CASE REPORTS

Case 1
This patient was the first child of a healthy 22-year-old woman. Pre-, peri- and
postnatal periods were uneventful, although the child was small for its gestational
age (38 weeks), weighing only 2139 g. Shortly after birth a clinical diagnosis of
trisomy 21 was made and subsequently confirmed by karyotyping. Psychomotor
development was delayed.

* Institute of Neurology, Department of Child Neurology

** Institute of Radiology, Department of Neuroradiolo~. Radboud University Hospital. Nijmegen, The
Netherlands

Clin. Neural. Neurosurg. 1982. Vol. 84-3. (Accepted 8.682).

1x0

At the age of 3 years and 3 months the child was admitted to hospital after
suddenly developing a right-sided hemiparesis with aphasia, which had been pre-
ceded by an episode of viral enteritis. Electroencephalogram (EEG) and cerebro-
spinal fluid (CSF) indicated no abnormalities, but gradually a spasticity ofthe right
arm and leg appeared.
At the age of 9 the patient was admitted to our department for further inves-
tigation as to the cause of the hemiparesis. Upon examination we saw a friendly
young boy with the stigmata of Down’s syndrome. His height was 109 cm (P < 2.5).
weight 17 kg (P < 2.5) and head circumference (OFC) 49 cm (10 < P < 25). There
was a marked dysphasia: the boy gave only one-word responses. Language per-
ception was better. His skin was dry, the acra were cold and cyanotic. Pediatric
examination indicated no abnormalities. Neurologic examination revealed a right-
sided spastic paresis with hyperactive tendon reflexes and an extensor plantar
response. Sensory testing revealed a right-sided impairment of the gnostic quality.
Vital sensation was intact.

LABORATORY INVESTIGATIONS

The results from standard blood and urinary studies, including haematologic evalu-
ation (RBC, WBC and platelet function), renal and hepatic functions, serum protein
and protein electrophoresis were normal, as were the results from standard tests for
serum glucose, lactate and pyruvate, serum lipids and short-chain fatty acids.
aminoacids in plasma and urine, lysosomal enzymes. T:,. T,, cortisone rhythm, oral
glucose tolerance, serum copper and ceruloplasmin. Lead and mercury in-
toxications were excluded, as were tuberculosis, toxoplasmosis and syphilis.
CSF protein content was slightly elevated: 356 mg/ 1 (normal 140-340): lactate
was elevated: 2020 prnolil (normal 1200-1600)~ pyruvate: 105 pmol/ I (normal
85-132); ratio lactate-pyruvate: 19.3 (normal I 1.O-14.6). The results obtained from
cell counts and protein- and immune-electrophoresis were all normal, as were the
levels of minerals, acetoacetate, D-hydroxybutyrate, homovanillic acid (HVA) and
5hydroxyindolacetic acid (SHIAA).

ELECTRONEURO~HYSIOLOGIC INVESTIGATIONS

The EEG showed a poorly developed background activity with an excess of high
voltage beta activity, the right hemisphere being more markedly disturbed (es-
pecially the temporal region) than the left. Electromyography (EMG) and nerve
conduction velocities were normal. The hematotachogram indicated an insuf-
ficiency of both internal carotid arteries and both vertebral arteries. Compression of
the right temporal artery reduced flow in the right orbital artery to zero.

RADIOLOGIC INVESTIGATIONS

Radiograms of chest, skull and vertebral column,and intravenous peylogram ([VP)

 181

Fig. I.
Left carotid arterqraphv in case I. There is an occlu\wn of the di\tal part of the internal carotid artery
and the proximal part of ;he anterior and middle cerebral artery. A collateral network supplying the did
anterior ( 0 ) and middle ( 4 ) cerebral arteries is \isihle. There are transdural anastomoses in the
frontal ( 4 ) and parietal ( +- ) region.

were normal. The pneumoencephalogram revealed central atrophy of both hem-

ispheres, more pronounced on the left side. In addition there was insular cortical
atrophy on both sides. Computed tomography (CT) scanning was not performed.

ANGlOGRAPHIC EXAMINATION

Right Carotid Artrriograph_y: There was a total occlusion of the internal carotid
artery (ICA) distal to the ophthalmic artery and collateral filling of the A, portion of
the anterior cerebral artery (ACA) and some branches of the middle cerebral artery
(MCA). The cortex of the frontal, parietal and occipital area was supplied through
external carotid transdural anastomotic vessels.
Left Carotid Arteriogruphy: Occlusion of the distal portion of the ICA and of the
proximal portion of the ACA and MCA was present. There was an extensive
collateral network of mainly lenticulostriate arteries, supplying distal ACA and
MCA branches. Transdural anastomoses were observed here from the external
carotic branches in the frontal and parietal region (Fig. 1).
Vertebral Arteriogruphy: There was an occlusion at the end of the basilar artery,
tilling of the posterior cerebral arteries through collaterals. The arteries supplying
182

Fig. 2.
Vertebral arteriography in case I. There is an occlusion of the top of the basilar artery ( 9 ). A
collaleral network supplies the distal posterior cerebral arteries ( 4 )~An extensive collateral network
supplies the basal ganglia ( + ). There are also lransdural anastomoses from dural branches of the
vertebral arterie supplying the occipital lobes ( 4 1.

the basal ganglia were increased in number and size, probably following occlusion
of the posterior choroidal arteries. Flow rate was retarded above the tentorium. The
dural branches of the vertebral arteries contributed to the vascularization of the
occipital lobes through transdural anastomoses (Fig. 2).

CASE 2
At the time of the conception the patient’s mother was using phenobarbitone (150
mg daily). This medication was stopped after the first six weeks of pregnancy. Pre-.
peri- and postnatal periods were uneventful.
At the age of 3 months the child was operated for an incarcerated inguinal hernia.
Motor development was slow, but at the limit of the normal range. Mental retar-
dation, however. was soon noticed.
At the age of 2 years and 10 months the child was admitted to our department
with a left hemiparesis, sudden onset of which lasted 24 hours. Four days later, after
having had walking difficulties during one day, the patient fell to the ground and
was unable to rise. This time the left hemiparesis remained.
On examination we saw an alert, dysphoric boy with non-cooperative behaviour.
 183

His height was 98.5 cm (50 < P < 75) weight 17 kg (P < 90) and OFC 47 cm (2.5 <
P < 10). Pediatric examination showed no abnormalities. The child was dysphasic:
he could only speak a few words and communicated on a preverbal level. There was
a left facial paresis of central origin, a left-sided spastic hemiparesis with hyperac-
tive tendon reflexes and an extensor plantar response, and a left-sided gnostic and
vital hemihypaesthesia.
After discharge we conducted control check-ups at regular intervals. Despite
extensive physical therapy, there was a considerable residual left hemiparesis. The
mental retardation and the dysphasia became more apparent.
At the age of 4 years and 7 months the child was re-admitted to our department to
evaluate the feasibility of a superficial temporal artery - middle cerebral artery
anastomosis (STA - MCA anastomosis) (KARASAWA et al., 1978). Because of the
small calibre of the intra- and extracranial arteries (Fig. 4) such an anastomosis could
not be performed.

LABORATORY INVESTIGATIONS

The results from standard blood and urinary studies, including haematologic evalu-
ation (RBC, WBC and platelet function), renal and hepatic functions, serum protein
and protein electrophoresis, were normal. Other normal studies included serum
glucose, lactate and pyruvate. serum lipids and lipoproteins, aminoacids in plasma
and urine, lysosomal enzymes, T,, cortisone rhythm, levels of vitamin A, D and B,,.
and ANF. Tuberculosis, toxoplasmosis and syphilis were excluded.
CSF at the age of 2 years and 10 months, showed a slightly elevated protein
content: 330 mg/l (normal 100-300). The results of protein- and immune-
electrophoresis were normal. Lactate: 1750 pmol/l (normal 1200-1600); pyruvate:
115 kmol/l (normal 85-132); ratio lactate-pyruvate: 15.2 (normal 11.0-14.6). Glu-
cose, acetoacetate, B-hydroxybutyrate and mineral levels were all normal. Cell
count was also normal.
CSF at the age of4 years and 7 months showed a further rise in protein content to
375 mg/ 1. The results of protein- and immunoelectrophoresis were normal. There
was a further increase in lactate level (1980 kmol/ 1), pyruvate level (128 pmol/ 1)
and ratio lactate-pyruvate (15.5). Glucose, acetoacetate, B-hydroxybutyrate,
minerals. HVA and SHIAA levels and cell count remained normal.

ELECTRONEUROPHYSIOLOGIC INVESTIGATIONS

The EEG showed an asymmetrical pattern with a greater variation of activity over
the right hemisphere. The dominant rhythm was 5-7/set. Electromyography and
nerve conduction velocities were normal.

RADIOLOGIC INVESTIGATIONS

Radiograms of chest, skull and vertebral column, and 1VP were normal.
Pneumoencephalography and CT scanning showed a normal size and configuration
of the ventricular system and a generalized cortical atrophy.

AN~IO~RAPHI~ EXAMINATION AT THE AGE OF 2 YEARS AND to MONTHS

Right Carotid Arreriqraphyv: Partial occlusion of the distal part of the ICA and of
the proximal parts of the ACA and MCA was visible, as was a small collateral
network.
Lxfi Carotid ~r~erjo~ruF~z~:There was a severe stenosis of the supraclinoid part of
the ICA. The ACA and MCA were filled through a collateral network. Ethmoid
branches of the ophthalmic artery formed a collateral transdural network by which
the frontal lobe was supplied (Fig. 3).
VertebralArterio~r~~iz,v: There was an occlusion of the prec~~mmunal part of the left
posterior cerebral artery (PCA), whiie the postcommunal part was supplied through
a small collateral network. An increase in the calibre and the number of the aa.
thalamoperforantes. functioning as a collateral blood supply to the basal ganglia,
was seen. Leptomenin~eal anastomoses between branches of the PCA and MCA
were present.
 185

t. lg. 4.
Left carotid arteriography in case 2. 2’? years after Fig. 3. There IS a progressive stenosis of’ the supra-
clinoidal collateral network. The number ofcollaterals to the distal anterior and middle cerebral arteries i\
diminished. There IS an occlusion of the ethmoidal collateral network. which is no longer visible.

ANGlOGRAPHIC EXAMINATION AT THE AGE OF 4 YEARS AND 7 MONTHS

Carotid Arteriogruph~~: There was a progression of the stenosis of the distal portions
of both internal carotid arteries, but no extension of the collateral circulation. The
ethmoidal network was no longer visible. The small calibre of the intra- and
extracranial arteries was very conspicuous (Fig. 4).

DISC‘USSION

The principal lesion in Moya-Moya syndrome is the stenosis of the distal part of the
internal carotid artery. Pathoanatomical investigations have revealed no specific
abnormality: most authors describe intima proliferation and abnormalities of the
internal elastic membrane and of the media of the internal carotid artery and its
main branches. Quite often there is hypoplasia of the rostra1 part of the circle of
Willis (VUIA et ul., 1970). As the condition progresses, a development, extension and
disappearance of certain collateral networks can be observed by angiographic
follow-up. The progressive course of the disease, which caused SUZUKI and TAKAKU
(1969) to classify it into six stages, is demonstrated by the angiographic follow-up of
patient 2 (stage 3/4 to stage 5). Branches of the basilar artery quite often become
 number
24

22
20
n Male 18 0 Male
m Female 16 m Female
14
12
10
a
6
4
2
0
0 10 20 30 40 50 60 years 0 2 4 6 8 10 12 14 15years
Fig. 5.
a. Age distribution of 120 non-mongoloid cases of MopMoca.
b. Age distribution of68 non-mongoloid cases of Maya-MO); helow the age of 15.

part of the Moya-Moya network (HINSHAW et al.. 1975) as was observed in our two
patients.
The existence of familial cases (KITAHARA rr al., 1979: YAMADA et ni., 1980) and
the association of this syndrome with other cerebral vascular malformations
(KOWADA et al., 1979) and other malformative pathologic conditions. suggest a
congenital disease. Idiopathic cases have been described, but its appearance in
association with numerous other disease entities. including Down’s syndrome
(~~HRAGER et al., 1977; SCHULZ ef ai., 1980), renal artery stenosis (ELLISON er ~21..
1981). Fanconi’s anemia (COHEN et ul., 1980), cranial irradiation RAJAKULASINGAM
ei al., 1979), cranial trauma (FERNANDEZ-ALVAREZ et a/., 1979), hemoglobinopathies
(SEELER ef ai.. 1978), neurocutaneous syndromes (IM~IZ~MI et al., 1978: LAMAS er crl.,
1979) meningitis, arteritis (Lru et crl., 1980), tuberculosis. hyperlipoproteinemia.
glycogen storage disease (SUNDER, 198 l), and myopathy (COAKHAM et uf.. 1979). and
the progressive course suggest a symptomatic non-specific acquired syndrome, i.e. a
reaction to a slowly developing stenosis of the distal part of the internal carotid
artery.
We carried out a literature study of 120 non-mongoloid cases of Moya-Moya, in
accordance with the diagnostic criteria developed by LEVESQUE et ul. (1974). Age at
the time of diagnosis is shown in Fig. 5. The delay between the appearance of the
initial symptoms and the diagnosis was on the average 2.5 years, but in 59% of the
cases diagnosis was made immediately after the first symptoms appeared; below the
age of 15 this percentage was44%, above this age 73%. The infantile and adult forms
 187

MOTOR
DISTURBANCES

SPEECH
DISTURBANCES

SEIZURES

SENSORY
DISTURBANCES t

VISUAL
DISTURBANCES 1//I///

DISTURBANCES OF
CONSCIOUSNESS t///L

INTRACRANIAL
HEMORRHAGE 1

below 15 years
B initial symptoms
///I/ Symptoms in the course of the disease

Fig. 6.
S!mptom\ of’Mo>a-Mo>a in 120 non-mongoloid cases.

of Moya-Moya syndrome have different initial symptoms. Fig. 6 shows the relative
occurrence of the initial symptoms and of the symptoms in the course of the disease.
Ninety percent of the motor disturbances are hemiplegias, but mono- and tetraplegia
and tetraparesis also occur. The disturbance of consciousness ranges from
somnolence to coma (3%). The visual disturbances mostly consist of hemianopia.
but cortical blindness, central scotoma and deterioration of vision can also occur.
The possibility of improvement increases with increasing age. Of the group below 16

t.\nLt I. Lactate and pvruvate levels in CSF of patients and controls

Patient 2
Patient I
34 month5 56 man ths

Lactate 12OO- I600 2020 I750 I980

fpmol/ I)

Pyruvate 85-132 10s 115 128

(pmol/l)

Ratlo
Lactate-Pyruvate I I-14.6 19.3 15.2 15.5
188

years of age, death occurs in 19W, the clinical picture worsens in 417 and a recovery
or a stabilization of the disease occurs in 40%. In the group older than IS years of
age, these percentages stand at 19%. 2 1% and 60%, respectively.
The rise of CSF lactate and the ratio lactate-pyruvate in our two patients (Table I)
is indicative of slight cerebral hypoxemia. A rise of CSF lactate accompanies the
progression of the vascular malformations in patient 2. We believe that CSF lactate
and the ratio lactate-pyruvate can be considered an indirect measurement of the
function of the collateral circulation of the Moya-Moya network. This may prove to
be a helpful parameter in the indication of a STA ~ MCA anastomosis and for the
evaluation of the function of such an anastomosis.

ACKNOWLEDGEMENTS

We are indebted to Prof. Dr. S. L. H. Notermans for electroencephalographs. to Dr.

E. J. Colon for hematotachographs, to Dr. H. M. Vingerhoets for electromyographs
and nerve conduction velocities, and to J. C. N. Kok and K. J. B. Lamers for
laboratory investigations.

REFERENCES

( OAKHAM. H. B..I..w. DUCHEN and E. t. SC AKAVILLI(~~~~) Maya-moya disease: clinical and pathological
report ofa cast with associated myopathy. J. Neurol. Neuwurg Psychiat. 42:289.
('OHEN. h.. M. BERANT and J. SIMON (1980) Moyamoqa and Fanconi’s anemia. Pediatrics h4:8()4.
ELLISON. p. H.. J. A. LARGENT and A. J. POPP ( 198 I) Maya-Mog’a disease associated v.‘ith renal ilrterv \tcno\i\.
Arch. Neurol. 38:467.
FLRNANDF%-AI.VARE~, F.. M. PINEDA. c. ROYO and R. M.AN%~NARL> (1979) Movamo\a di\caw cauwd h\
cranial trauma. Brain Dev. I: 133.
HANDA. J. and H. HANDA (1972) Progressive cerebral arterial occIu\i\e disease: anal\<l\ of 27 caws.
Neuroradiology 3: I 19.
HINSHAW, u. B.. J. R. THOMPSON and A. N. HASSO (1976) Adult arteriosclerotic Mobamoya Radiology
Il8:633.
IMAILUMI. M., I. NAKUDA. s. YON~UA. I. IAKANO. K. HASEG~WA and 11.ABF (1978) Tuhcrous \clerosi\ with
moya-mova disease. Case report. Med. J. Osaka Univ. 28:345.
KARASAW~.J.. H. KIKUC'HI,S. FURUSE.J. KAWAMURA and T. SAKAKI (1978) Treatment of movamo\;i dl\ea\e
with STA-MCA anastomosis. J. Neurosurg. 49:679.
K1TAHARA.T.. N. 4RIGA. 4. YAMAIIRA. H. MAKINO and Y. MAKI (1979) k:lmilial occurrence Ofm0\a-mo\a
disease: report of three Japanese families. J. Neurol. Neurwurg. Prvchiat. 42:2(J8.
KOWADA. M.. r. MOMMA and K. KIKCIC‘HI (1979) Intracranial aneurvm associated with cerehro\awular
moyamoya disease. Report of a case and review of I3 cawh. B;. J. Radiol. 52:236.
LAMAS. t.. R. DIEL LOBATO. A. CABELLO and J. M. ABAD (1979) Multiple intracranial arterial occlusions
(Moyamoya disease) in patients with neurofibromato\is. One case report with autop\v_ Acta
Neurochir. (Wien) 45: 133.
LFVESQIJE. M.. I. ILEFt+BVRF. J. BORIES and 1. LEGR~ (1974) Les formes Infantiles du \\ndromr de &no\e
progressive des branches du polygone de Willi\. J. Neuroradiologie I :55.
Lit!. x., x. RUAN, %. ('AI, B. YU. s. HE and Y. GONG (1%0)(1%()) M oyamova diwase caused b\ lepto\piral
ccrehral arteritis. Chin. Med.J. (En&l.) 93:599.
RAJAKL~LASINGAM. K.. L. c~t~1~1.1o and A. RAIMoNI~I (1979) Childhood moba-mo\a \vndrome: Po\t-
radiation pathogenesis. Child? Brain 5:467.
SCHRAGER. ci. 0.. s. J. ( OHFNand M. P. VIGMAN (1977) Acute hcmiplegia and cortical blindnc+ due to
moya-moya disease: Report of a case in a child with Down’\ syndrome. Pediatrics ho:33
 189

4~ HULLI.. F.JAHARA.F. POMPEU.F.FIGUEIRA and M.DE OLIVEIRA(~%~) Doen’ca OclUSlVa prOgI'eSSiVa das
art’ertas cerebrais associada a s’indrome de Down. Registro de urn case. Arq. Neuropsiquiatr. 38:
171.
SEELER. R.. J. ROYAL.. L. POWE and H. GOLDBERG (1978) Moyamoya in children with sickle cell anemia and
cerebrovascular occlusion. J. Pediat. 93:808.
st~hit)tn, r. R. (1981) Moyamoya disease in a patient with type I glycogenosis. Arch. Neurol. 38:251.
\~:zc’KI. J. and A. TAKAKU (1969) Cerebrovascular ‘Moyamoya’ disease. Disease showing abnormal net-like
vessels in base of brain. Arch. Neurol. 20:288.
MKEI’C HI. K. (1961) Occlusive disease ofthe carotid artery. Revent Adv. Res. Nerv. Syst. 5:5l I.
L'UIA. o.. M. .AL.EXIANU and s. GABOR (1970) Hypoplasia and obstruction of the circle of Willis in a case 01
atyptcal cerebral hermorrhage and its relationship to Nishimoto’s disease. Neurology 20:361.
YAMAIX H.. s. NAKAMURA and N. KAGEYAMA (1980) Moyamoya disease in monovular twins. Case report.
J. Neurosurg. 53: 109.