Brain & Development, 15 (1993) 125 127
0387-7604/93/$06.00 ~<') 1993 Elsevier Science Publishers B.V. All rights reserved
BRADEV 00028

Chronic subdural hematoma, as an initial manifestation
of glutaric aciduria type-1
H i t o s h i O s a k a a, M D , Seiji K i m u r a a, M D , A t s u o N e z u a, M D , S h i n Y a m a z a k i a, M D ,
K a z u y o S a i t o h a, M D a n d Seiji Y a m a g u c h i b, M D

aDepartment of Pediatrics, Yokohama City University School of Medicine, Yokohama, Japan and
hDepartment of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Received 11 September 1992; accepted 4 December 1992
A 10-month-old male with glutaric aciduria type-l (GA-1) is reported. This patient showed frequent partial motor seizures, irritability, and
involuntary movements, including oral dyskinesia at the age of 3 months. On admission, magnetic resonance (MR) scanning revealed a chronic
subdural hematoma and widening of the bilateral insular cisterns. Urine organic acid analysis showed marked excretion of glutaric acid, 3-hydroxy
glutaric acid and glutaconic acid, suggesting GA-1. Removal of the subdural hematoma was effective for the irritability but not for the
extrapyramidal signs. This is the first report of a subdural hematoma as an initial symptom in a patient with GA-I. However, the complication of
subdural fluid collection in GA-1 is not rare. To our knowledge, of 29 patients with GA-I who underwent computed tomographic or MR scans, 5
had subdural fluid collection. Disproportional hypoplasia of the temporal lobes may be a suggestive etiology of subdural fluid collection/chronic
subdural hematoma.
Key words: Glutaric aciduria type-l; Chronic subdural hematoma; Subdural fluid collection

INTRODUCTION
Glutaric aciduria type-l (GA-1) is an autosomal recessive metabolic disorder caused by a defect of the
enzyme, glutaryl coenzyme A dehydrogenase. About
40 cases were reported previously, and the clinical manifestations are mainly extrapyramidal; dystonia, oral
dyskinesia and choreoathetosis. In addition to the extrapyramidal signs, subdural fluid collection in GA-1 is
not rare. Computed tomography (CT) scanning or
magnetic resonance (MR) imaging has been reported
in 29 GA-1 patients, of whom 5 had subdural fluid
collection [1-3].
We present herein an infant with GA-I who showed a
chronic subdural hematoma as an initial manifestation.
CASE R E P O R T

This 10-month-old boy was born uneventfully at full
term to unrelated Japanese parents. His birth weight
was 3,550 g. A 2-year-old male sibling was healthy. He
Correspondence address." H. Osaka, MD, Urafune Hospital, Department of Pediatrics, Yokohama City University School of Medicine, 346 Urafune-cho, Minami-ku, Yokohama 232, Japan.
Brain & Development, Vol 15, No 2, 1993

smiled at 1 month and gained head control at 3.5
months. He developed normally until 5 months when
he was admitted to a hospital with an upper respiratory tract infection followed by focal motor seizures.
Although the seizures were controlled by the administration of phenobarbital, he gradually developed irritability and involuntary movements. He was transferred
to our hospital for further evaluation at 6-months old.
His body weight was 7,405 g ( - 0 . 8 S.D.), length 68.2
cm (+0.1 S.D.), and head circumference 43.5 cm (+0.1
S.D.). He was lethargic and irritable. He was hypotonic
and could not support his head. The muscle stretch
reflex was normal and the plantar responses were flexor. He exhibited oral dyskinesia and a dystonic posture,
which were exacerbated by crying. Serum creatine kinase was elevated, being 1,460 mU/ml (46-188 mU/
ml). The serum free and acyl carnitine values were 19.0
mmol/l (30 50 mmol/l) and 8.0 mmol/1 ( < 10 mmol/l),
respectively. CT scanning on admission showed marked
widening of the bilateral insular cisterns (Fig 1). MR
scanning revealed abnormal subdural spaces, which appeared as high intensity areas in both T~ (TE/TR - 440/
15.0) and T2 ( T E / T R - 2,500/100) weighted images
(Fig 2). A chronic subdural hematoma was suspected.
Bilateral craniotomy was performed and xanthochro125

involving S-30 milk (Snow Brand Milk Product Co.).
Excretion of glutaric acid, 3-hydroxy-glutaric acid and
glutaconic acid in the urine decreased, but the extrapyramidal signs and muscle hypotonia did not improve.
Bacrofen (GABA neuron activator) at a dose of 2 nag/
kg was effective for the athetosis and oral dyskmesia.
However, it wets discontinued because of two apneic
episodes. Now he is receiving a protein restriction diet
and L-carnitine (50 mg:kg/day). He can fully tbllow
objects and smiles spontaneously, but cannot support
his head at 10 months old.

DISCUSSION

Fig I. CT scan at the age of 6 months. Widening of the frontal subdural spaces and the insular cisterns can be seen.

mic fluid was removed. The drowsiness and irritability
disappeared after the operation, but the extrapyramidal
signs persisted. In a MR scan, the subdural space was
observed to be slightly decreased.
Urine organic acid analysis revealed marked increases
in glutaric acid, 3-hydroxy-glutaric acid and glutaconic
acid. Glutaryl-CoA dehydrogenase activity was not detected in cultured fibroblasts obtained from biopsied
skin. Thus, the diagnosis of GA-I was made.
He was placed on a low lysine, low tryptophan diet

To our knowledge, around 40 patients with GA-I
have been presented since the first report of G o o d m a n
et al. in 1975 [4]. The neuroradiological features on CT
scanning or M R imaging have been reported in 29 GA1 patients. They are characterized by the following
three points: (i) widening of the insular cisterns (17/29)
[1,3,5,6], (it) enlargement of the frontal horns with loss
of caudate nuclei (13/29) [1,3,5,7,8], and (iii) diffuse
attenuation of the cerebral white matter (8/29) [1,3,8
10]. The first character is the most prominent feature in
this disease. It was also seen in our patient and thus was
a clue lk)r the diagnosis.
There have been no othcr reports of a patient with
both GA-1 and a chronic subdural hematoma, but we
found 5 cases of subdural fluid collection in the literature. The latter cases and ours had no episodes of trauma. The high incidence of GA-I accompanied by sub-

Fig 2. MR imaging at the age of 6 months shows a diffuse bilateral subdural hematoma accompanied by frontotemporal lobe hypoplasia. The
hematoma shows high intensity in both T : and l'~-weighted images.

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BraiH & l)cve/opmeiit, Vol 15. N¢) 2. 1993

dural effusion (5/39) does not seem to be coincidental.
One theory for subdural fluid collection is that rupturing of the arachnoid membrane causes cerebrospinal
fluid to enter the subdural space [11]. There is a possibility that disproportional temporal lobe hypoplasia or
atrophy of GA-1 is prone to tearing the arachnoidal
membrane. We could not find any relationship between subdural collection or a h e m a t o m a and other
metabolic diseases in the literature.
It has been proven in many cases that subdural effusion subsequently develop into a subdural h e m a t o m a
through hemorrhaging from the outer membrane of
the fluid collection [11], and it is sometimes difficult to
distinguish a h e m a t o m a from effusion. We propose
that both subdural effusion and a h e m a t o m a are probable complications of GA-1.
Little attention has been paid to these two diseases
accompanying G A - I . However, we have shown that
they are not rare complications of GA-1. To prevent
secondary neuronal damage, we must be aware of subdural effusion and hematomas in GA-1 patients.

ACKNOWLEDGEMENTS

We are grateful to Dr. S. Yamamoto for the organic acid screening.

Brain & Development, Vol 15, No 2, 1993

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