Journal of the International Neuropsychological Society (2003), 9, 806–810.

Copyright © 2003 INS. Published by Cambridge University Press. Printed in the USA.
DOI: 10.10170S1355617703950132

CASE STUDY

Moyamoya disease in a patient with schizophrenia

DAN I. LUBMAN,1,2,4 CHRISTOS PANTELIS,1,2 PATRICIA DESMOND,3

TINA-MARIE PROFFITT,1,2 and DENNIS VELAKOULIS 1,2,4
1
Cognitive Neuropsychiatry Research and Academic Unit, University of Melbourne and Sunshine Hospital, Victoria, Australia
2
Mental Health Research Institute, Victoria, Australia
3
Department of Radiology, 4 Department of Psychiatry, Royal Melbourne Hospital, Victoria, Australia
(Received June 11, 2002; Revised October 4, 2002; Accepted October 4, 2002)

Abstract
We present the case of a 23-year-old Vietnamese male with a 2-year history of a psychotic illness marked by
prominent negative symptoms, fatuousness and disturbed behavior. Neuroimaging revealed a prominent vascular
flow void affecting the middle and anterior cerebral arteries, with associated increased collateral supply to the
frontal cortex, consistent with Moyamoya disease. Neurological examination was unremarkable; however,
neuropsychological assessment revealed significant executive dysfunction, including stimulus-driven behavior.
Whilst the diagnosis of schizophrenia and Moyamoya disease may be coincidental, an interaction between the 2
diseases may have led to some of the atypical features of this case, including prominent executive dysfunction
and marked sensitivity to psychotropic medication. We discuss the nature of possible interactions between the 2
conditions. This case also highlights the importance of re-evaluating patients with atypical or treatment-resistant
psychoses for cerebral pathology. (JINS, 2003, 9, 806–810.)
Keywords: Moyamoya disease, Schizophrenia, Neuroimaging

INTRODUCTION psychosis in adults with asymptomatic Moyamoya disease.

There is now a substantial body of literature describing
structural brain abnormalities in patients with schizophre-
nia. Current etiological theories propose a neurodevelop-
mental model, where brain lesions occurring early during
brain development increase the risk for subsequent devel-
opment of schizophrenia (McGrath & Murray, 1995).
Moyamoya disease is a rare chronic occlusive arteritis of
unknown etiology, with a peak incidence in childhood and
early adulthood (Farrugia et al., 1997; Nishimoto & Takeu-
chi, 1968; Suzuki & Kodama, 1993; Ueki et al., 1994). It is
characterized by a progressive stenosis of the arteries of the
circle of Willis, typically affecting the anterior and middle
cerebral arteries, thereby resulting in progressive cerebral
ischemia of brain regions within the affected vascular ter-
ritories. McDade (1991) and Klasen et al. (1999) have re-
ported psychotic symptoms in 2 patients with childhood
Moyamoya disease, but there are no published reports of
Reprint requests to: Dan Lubman, Cognitive Neuropsychiatry
Research and Academic Unit, Sunshine Hospital, 176 Furlong Rd., St.
Albans, Victoria 3021, Australia. E-mail: dan.lubman@mh.org.au
806
We report a single case study of a patient with co-existing
schizophrenia and Moyamoya disease.
CASE HISTORY
R.P., a Vietnamese male aged 23, with a DSM–IV diagnosis
of Paranoid Schizophrenia, was referred for rehabilitation
following a two year history requiring seven in-patient acute
admissions. His psychotic episodes were characterized by
auditory hallucinations, persecutory delusions, low mood
and suicidal ideation, often in the context of non-compliance
with anti-psychotic medication and cannabis misuse. He
generally responded quickly to antipsychotic medication,
but tolerated conventional antipsychotics poorly due to
marked extra-pyramidal side-effects. He had previously de-
veloped Neuroleptic Malignant Syndrome (NMS) on typi-
cal antipsychotics, but was successfully re-challenged with
risperidone. A family history of psychosis was suggested
but not confirmed.
On admission, R.P complained of persistent psychotic
symptoms, and was noted to have a fatuous affect, with

https://doi.org/10.1017/S1355617703950132 Published online by Cambridge University Press

 Moyamoya disease in a patient with schizophrenia
periods of sexual disinhibition. At times he seemed stimulus-
driven, with his affect appearing to react to the current ward
environment. There was no past medical history of note,
and physical examination was unremarkable. In particular
there were no neurological deficits identified. His psy-
chotic symptoms were successfully treated with 6 mg0day
of risperidone, and a behavioral plan was devised to man-
age his inappropriate behavior. He subsequently developed
a depressive syndrome with suicidal ideation, which re-
sponded to sertraline. The development of profound dyski-
netic symptoms led to cessation of the sertraline, with
subsequent resolution of the dyskinesia. By this time, the
most prominent feature of his presentation was marked neg-
ative symptoms, including anhedonia, avolition, apathy, and
attentional impairment.
As part of a research study, R.P. had a magnetic reso-
nance imaging (MRI) scan, which revealed a prominent
vascular flow void, suggestive of a vascular malformation
(Figure 1). Subsequent magnetic resonance angiography
(MRA) showed that the flow void consisted of several ves-
sels, with vessels of the posterior cerebral artery being sig-
nificantly prominent. Catheter angiography (Figure 2)
revealed marked stenosis of the supraclinoid distal internal
carotid artery bilaterally, with severe stenosis of the proxi-
mal anterior cerebral and middle cerebral arteries. Numer-
ous dilated medial and lateral lenticulostriate perforating
arteries provided a collateral supply to the frontal middle
cerebral artery vascular territory. Collateral supply from
the ophthalmic arteries was also seen. From the posterior
cerebral arteries there were extensive bilateral collateral
vessels supplying the posterior middle cerebral and anterior
cerebral vascular territories. A single photon emission to-
Fig. 1. T1 sagittal MR. Nidus of vessels seen superior to body of
corpus callosum (Arrow A). Note an incidental finding of Rath-
ke’s cleft cyst (Arrow B).
https://doi.org/10.1017/S1355617703950132 Published online by Cambridge University Press
807
Fig. 2. Cerebral angiogram of right internal carotid demonstrates
stenosis of anterior and middle cerebral arteries, with multiple
collateral lenticulostriate vessels.
mography (SPECT) study revealed mild posterior parietal
hypoperfusion.
Neuropsychological assessment revealed significant dif-
ficulties on high-level attention, reasoning and problem-
solving tasks, with most of R.P.’s scores falling within the
Intellectually Deficient–Borderline range (see Table 1). In
particular, the initiation and use of strategies and the mon-
itoring of information within working memory were mark-
edly impaired. R.P. also demonstrated a significantly reduced
intellectual capacity with respect to both verbal and visuo-
spatial intellectual skills. His premorbid verbal IQ was as-
sessed as Average, whereas his estimated current IQ of 63
fell in the Intellectually Deficient–Borderline range. On
memory and new learning tasks immediate recall was rea-
sonably well preserved, however, difficulty organizing in-
formation during the encoding phase of new learning resulted
in a lower than expected overall acquisition score. Psycho-
motor speed varied with task complexity.
A neurology consultation suggested conservative man-
agement, with regular neurological reviews recommended.
There was no evidence of psychotic or affective symptom-
atology prior to discharge, although the patient was still
noted to be fatuous in affect and socially disinhibited. He was
discharged into community care on risperidone 4 mg0day.
DISCUSSION
Moyamoya disease is a rare disease that is mainly seen in
Japan, typically affecting Asians (Farrugia et al., 1997; Nish-
imoto & Takeuchi, 1968; Suzuki & Kodama, 1993; Ueki
et al., 1994). The onset of the disorder tends to follow a
bimodal distribution, with patients typically presenting dur-
ing the first or fourth decades of life. Adults with the dis-
 808 D.I. Lubman et al.

Table 1. Neuropsychological test results: R.P.

Score 95% C.I. Percentile Description

Psychometric intelligence
Schonell Graded Word Reading Test
Estimated premorbid IQ 92 — 44th A
Wechsler Adult Intelligence Scale–Revised
Age Scaled Scores
Verbal scale
Arithmetic 5 — 5th BO
Similarities 5 — 5th BO
Performance scale
Picture Completion 3 — 1st ID
Block Design 5 — 5th BO
Digit Symbol 4 — 2nd BO
Full-Scale IQ 1 63 52–75 ,0.1–5th ID–BO
Learning and memory
Wechsler Memory Scale–Revised
Information and Orientation 14 — — —
Digit Span Forward 6 — 12th LA
Digit Span Backward 6 — 42nd A
Visual Reproduction (I) 32 — 37th A
Verbal Paired Associates (I) 14 — ,0.1 ID
CANTAB Spatial Span
Span 5 — 5th BO
Rey Auditory Verbal Learning Test
Number Recalled
Trial A1 5 — 6th BO
Trial A2 6 — 2nd BO
Trial A3 9 — 9th BO
Total A1–A3 20 — — —
20’ recall 8 — — —
Psychomotor, complex attention and executive function
Adult Memory and Information Processing Battery Part B
Motor Speed 65 — 93rd S
Cognitive Speed 36 — 7th BO
Adjusted Total 38 — 7th BO
Trail Making Test
Part A Time (s) 27 — 48th A
Part B Time (s) 101 — 9th BO
Stroop Test T-scores
Word Naming 15 — ,0.1 ID
Color Naming 23 — 0.4 ID
Color–Word Naming 37 — 9th BO
Interference Score 62 — 87th HA
CANTAB Spatial Working Memory Test
Between-search errors 68 — ,0.1 ID
Strategy use 26 — 0.1 ID
CANTAB Tower of London Test
Percent Perfect Solutions 58 — 6th BO

Percentiles refer to R.P.’s ranking compared to his peer age level; e.g., a score at the 60th percentile reflects a performance that is
better than that of 60% of age peers. The terms Intellectually Deficient (ID), Borderline (BO), Low Average (LA), Average (A), High
Average (HA), and Superior (S) are used to describe levels of performance on the tests administered. The 95% C.I. represents the
range of scores within which R.P.’s estimated true score falls with a chance of 95 out of 100. IQ scores have a mean of 100 and
standard deviation of 15. T-scores have a mean of 50 and a standard deviation of 10.
1
Kaufman four-subtest short form.

order usually present with intracranial hemorrhage or ing, coughing, straining or hyperventilation classically in-
occasionally, cerebral infarction, whereas pediatric cases duce these ischemic attacks, and seizures may occur. Thus,
present with recurrent episodes of cerebral ischemia. Cry- younger patients may initially present with motor, sensory,

https://doi.org/10.1017/S1355617703950132 Published online by Cambridge University Press

 Moyamoya disease in a patient with schizophrenia
visual, or speech disturbances or mental retardation (Suzu-
ki & Kodama, 1993). Nishimoto (1979) described mortal-
ity rates of 10% in adults, and 4.3% in children, although
Ueki et al. (1994) noted that in a study of those receiving
treatment, a good prognosis was reported in 58%, with the
remainder having some degree of disability. Kurokawa et al.
(1985) observed patients with transient ischemic attacks
(TIAs) who received no treatment and noted that, although
the TIAs gradually resolved, a majority of patients demon-
strated cognitive decline over 5 to 15 years.
Little is known about the natural history of the disorder
in neurologically asymptomatic adult patients, and the re-
lationship between psychiatric or behavioral symptoms and
Moyamoya disease is unclear. Only two other papers have
reported psychotic symptoms in patients with Moyamoya
disease (Klasen et al., 1999; McDade, 1991). Klasen et al.
(1999) described a 12-year old boy who presented with an
acute transient psychosis and was subsequently diagnosed
with Moyamoya disease. His symptoms were precipitated
by heavy physical exertion at school. Physical and neuro-
logical examinations were unremarkable, and neuropsychol-
ogy scores were noted to be in the average range. McDade
(1991) described a 19-year old Asian man who presented
with a schizophrenia-like psychosis twelve years after di-
agnosis of childhood Moyamoya disease. Mild right upper
motor neurone signs and a clumsy gait were observed on
physical examination, and neuropsychological testing re-
vealed learning difficulties (a global IQ of 65). CT scan-
ning demonstrated a chronic loss of cortex in the left
temporal0parietal and occipital lobes. Both patients’ psy-
chotic symptoms rapidly settled on neuroleptics. McDade
(1991) and Klasen et al. (1999) postulated a causal relation-
ship between Moyamoya disease and the psychotic symp-
toms seen in their patients. The authors noted left sided
vascular abnormalities, and McDade (1991) suggested a
symptomatic schizophrenia due to left temporal dysfunction.
In the current case, Moyamoya disease was identified as
an incidental finding in a young Asian man who presented
with severe psychotic symptoms that responded poorly to
treatment. This was in the context of behavioral disturbance,
hypoperfusion on SPECT scanning and neuropsychologi-
cal dysfunction. Whilst the clinical and neuropsychological
deficits were similar to those observed in schizophrenia
(Pantelis et al., 1997), the severity of these, particularly the
behavioral disinhibition, emotional lability, and marked ex-
ecutive deficits with associated stimulus-driven behavior,
suggest an organic component. Incidental neuroimaging find-
ings have been described in up to 50% of patients with
treatment-resistant schizophrenia (Larson et al., 1981; Lub-
man et al., 2002; Woods, 1976), though only a small per-
centage have such significant clinical implications as were
found in the current case. Whilst the diagnosis of schizo-
phrenia and Moyamoya disease may be coincidental, an
interaction between the two diseases may have led to some
of the atypical features of this case, including prominent
executive dysfunction and marked sensitivity to psycho-
tropic medication.
https://doi.org/10.1017/S1355617703950132 Published online by Cambridge University Press
809
Mental retardation has been associated with Moyamoya
disease and is thought to be secondary to the resultant chronic
ischemia (Farrugia et al., 1997). Not all patients with
Moyamoya disease, however, have mental retardation, sug-
gesting that there is a spectrum of ischemia severity and
cerebrovascular compensation. Cerebral perfusion studies
with SPECT in patients with Moyamoya disease suggest
hemispheric mean cerebral blood flow (mCBF) is normal,
but regional cerebral blood flow (rCBF) is abnormal (Kuro-
da et al., 1995). Surgical revascularization of the anterior
circulation has been shown to dramatically improve cere-
bral hemodynamics, especially in the frontal lobe, and is
advocated in children to prevent further cerebral ischemia.
Surgical procedures are associated with a reduction in is-
chemic symptoms, although preoperative cognitive deficits
are usually residual (Kuroda et al., 1995; Ueki et al., 1994).
These studies suggest that frontal hypoperfusion deficits,
which may lead to impaired frontal functioning, are partic-
ularly prominent in Moyamoya disease. It is possible that
chronic ischemia in the distribution of the anterior and mid-
dle cerebral arteries in a patient with schizophrenia may
increase or exacerbate the frontal0executive deficits asso-
ciated with schizophrenia. Whilst the SPECT scan revealed
hypoperfusion of the parietal cortex, hypoperfusion fron-
tally during neurodevelopment (i.e., before collateral revas-
cularisation has occurred) may be causally related to the
development of psychosis in this man, consistent with cur-
rent neurodevelopmental hypotheses of schizophrenia
(McGrath & Murray, 1995). Indeed, the neuropsychologi-
cal profile in R.P. was consistent with frontal pathology.
These deficits, particularly of attention and executive func-
tion were observed together with marked negative symp-
toms, both of which have been related to hypofrontality in
schizophrenia (Liddle, 1996; Pantelis & Brewer, 1996). Thus,
the chronic ischemia of Moyamoya disease may accentuate
the picture of disinhibition and related neuropsychological
deficits that are well documented in schizophrenia (Pan-
telis et al., 2001). Further, abnormal basal ganglia function,
that has been described in Moyamoya disease (Kuroda et al.,
1995), may also help explain the psychotic symptoms and
perhaps the observed medication sensitivity, and has also
been linked to stimulus-driven behavior (Rudd et al., 1998).
We are not aware of any other reports of patients with
schizophrenia who have had Moyamoya disease diag-
nosed incidentally. This case highlights the importance of
thoroughly excluding organic pathology in patients with
atypical or treatment-resistant psychoses. Although the
Moyamoya pathology may not be the primary cause of
the psychotic illness, the atypicality of the psychosis may
reflect an interaction between the two conditions. It re-
mains critical that this group of patients have regular re-
views of their history and presentation, as physical symptoms
and signs may be easily overlooked or attributed to their
psychotic illness. This masking of underlying physical ill-
ness may in part contribute to the high incidence of inci-
dental MRI findings in patients with treatment-resistant
schizophrenia.
 810
ACKNOWLEDGMENTS
This patient was investigated as part of a larger study of schizo-
phrenia, supported by the National Health and Medical Research
Council (Australia), Grants 970598 and 981112. Dan Lubman is
supported by the Nauma Licht Fellowship.
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