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Neurol Med Chir (Tokyo) 47, 419¿423, 2007

Akinetic Mutism Responsive to Bromocriptine Following
Subdural Hematoma Evacuation in a Patient
With Hydrocephalus
—Case Report—
Myoung Soo KIM, Jong Joo RHEE, Seung Jun LEE, Seon-Joo KWON*,
and Chae Heuck LEE
Departments of Neurosurgery and *Neurology, Seoul Paik Hospital,
Inje University College of Medicine, Seoul, R.O.K.

Abstract
An 11-year-old girl with obstructive hydrocephalus developed akinetic mutism after treatment for
hydrocephalus due to aqueductal stenosis by ventriculoperitoneal (VP) shunting. Bilateral chronic subdural hematomas developed about 2 months after insertion of the VP shunt and were evacuated.
Postoperatively, the patient developed akinetic mutism, but her condition improved after administration of bromocriptine. Absence of abnormalities on dopamine transporter single photon emission computed tomography, lack of clinical response to levodopa treatment, and normal homovanillic acid concentration in the cerebrospinal fluid all indicated normal dopamine production. Pressure on the
periventricular monoamine projections in the thalamus and hypothalamus without major dopamine
deprivation in the striatum may have been the most important factors in the development of akinetic
mutism in this patient.
Key words:

akinetic mutism,

hydrocephalus,

bromocriptine

Introduction

ry of gait disturbance, memory disturbance, and
learning difficulty. She was lethargic and had developed slurred speech and urinary incontinence. Computed tomography (CT) demonstrated obstructive
hydrocephalus (Fig. 1). A ventriculoperitoneal (VP)
shunt with a pressure-adjustable valve (Codman
Medos programmable valve, Medos SA, Le Locle,
Switzerland; opening pressure 100 mmH2O) was
inserted. Subsequently, the patient complained of
intermittent headache. On day 51 after insertion of
the VP shunt, she was lethargic and complained of
severe headache. CT in the emergency department
demonstrated a right subdural hematoma (SDH)
(Fig. 2). Burr hole trephination was performed on
the right. CT obtained 2 days postoperatively
showed a left SDH (Fig. 3), and further burr hole
trephination was performed on the left. CT performed after the burr hole trephinations showed that
the SDHs had almost completely disappeared. After
surgery, the patient remained awake, motionless,
and mute, and she would move all extremities only

Akinetic mutism is a state in which a seemingly
awake patient remains motionless and silent, and is
associated with lesions involving the ascending
dopaminergic activating system. Akinetic mutism is
typically a transient disorder following posterior
fossa tumor resection, and may also occur after
recurrent shunt failures in patients with hydrocephalus, who show no improvement either spontaneously or with shunt revisions but respond to
bromocriptine.2,4,13,19,24) However, little is known
about the state of dopamine production in the brain
of patients with akinetic mutism.20)
We treated a patient with akinetic mutism caused
by ventricular wall expansion and discuss the involvement of dopamine production.

Case Report
An 11-year-old girl presented with a 16-month histo-

Received January 9, 2007;
Accepted June 23, 2007
Author's present address: J. J. Rhee, M.D., Department of Neurosurgery, Cheongju Saint Mary's Hospital, Cheongju, R.O.K.

419

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420

Fig. 1

Fig. 2

M. S. Kim et al.

Computed tomography scan obtained on
first admission at another hospital demonstrating marked hydrocephalus.

Computed tomography scan obtained at
follow-up examination 51 days after ventriculoperitoneal shunting showing right
subdural hematoma.

in response to deep pain. The patient showed no
improvement despite conservative treatment and
adjustment of the shunt valve opening pressure from
100 to 140 mmH2O on several occasions (i.e., from
100 to 120 mmH2O, 120 to 140 mmH2O, 140 to 130
mmH2O, and 130 to 110 mmH2O). She was referred
to our department for evaluation and treatment 30
days after the left burr hole trephination.
Examination on admission revealed features consistent with akinetic mutism. She appeared to be
awake but was almost completely unresponsive to
her surroundings. She seldom responded to painful
somatosensory, loud auditory, or threatening visual
stimuli. Occasionally, she seemed to make spontaneous but weak attempts to move her extremities. She
required complete tube feeding and total nursing

Fig. 3

Computed tomography scan obtained at
follow-up examination 2 days after right
burrhole trephination demonstrating left
subdural hematoma.

care. We found no signs of rigidity. The VP shunt
functioned well, and the opening pressure of the
shunt valve was 110 mmH2O. Electroencephalography disclosed no epileptic discharge. Magnetic
resonance (MR) imaging, including perfusionweighted and diffusion-weighted MR imaging,
showed no abnormal finding except for a small
residual SDH and improved hydrocephalus (Fig. 4).
123I-beta-fluoropropyl-2beta-carbomethoxy-3beta-(4photon
iodophenyl)tropane
(123I-FP-CIT)-single
emission computed tomography (SPECT) demonstrated normal presynaptic dopamine reuptake in
the bilateral putamens and caudate nuclei (Fig. 5).
The concentration of homovanillic acid (HVA) in the
cerebrospinal fluid was 67.86 ng/ml (normal range
1–73 ng/ml).
Treatment with Madopar , Rapid 125 Tablet (La
Roche Ltd., Basel, Switzerland) (benserazide 25 mg,
levodopa 100 mg) was begun on postoperative day
31 after the second burr hole operation, initially
31.25 mg/day and increasing gradually to 187.5
mg/day in three equal doses. Despite 12 days of
Madopar treatment, her symptoms did not improve.
We stopped the Madopar administration and began
treatment with bromocriptine, initially 1.25 mg/day
and increasing gradually to 50 mg/day in three equal
doses. Two days after the initiation of bromocriptine
administration, she began speaking words and
responding to verbal stimuli. Twenty days after the
initiation, she was speaking in full sentences and
demonstrated no gait disturbance, although she had
memory disturbance and learning difficulty. Treatment with trihexyphenidyl was begun on day 66
after the second burr hole operation, initially 2
mg/day and increasing gradually to 6 mg/day in

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Akinetic Mutism

Fig. 4

Fig. 5

421

Axial T1-weighted (A), T2-weighted (B), and diffusion-weighted (C) magnetic resonance
images obtained at follow-up examination 26 days after burrhole trephination for the left subdural hematoma demonstrating improved hydrocephalus and residual subdural hematoma.

123I-beta-fluoropropyl-2beta-carbomethoxy-

3beta-(4-iodophenyl)tropane-single photon
emission computed tomography images
demonstrating normal presynaptic dopamine reuptake in the bilateral putamens and
caudate nuclei.

three equal doses. We did not change the shunt valve
opening pressure during adjustment of the drug
dose. Seven months after the second burr hole operation, she had only slight residual dystonia of the
body and mild memory disturbance. An attempt to
decrease the dosage of bromocriptine 5 months after
initiation because of dyskinesia failed, with rapid
clinical deterioration including decreased spontaneous speech and motor activity. Return to the previous dosage of bromocriptine reversed the decline in
symptoms.

Discussion
The clinical features of patients with akinetic
mutism associated with hydrocephalus are listed in
Table 1. Akinetic mutism can appear in different

Neurol Med Chir (Tokyo) 47, September, 2007

forms, depending on its cerebellar or hydrocephalic
origin. Injury of the mesiofrontal lobes is the most
frequently reported cause of akinetic mutism. One
patient had akinetic mutism caused by hemorrhagic
infarction of both cingulate gyri,3) and three patients
had akinetic mutism caused by anterior cingulate
lesions due to bilateral anterior cerebral artery infarctions.9) Similar symptoms have been associated
with anterior cingulate lesions.6,10,25)
Animal studies and case reports have identified
two primary lesion sites that may be associated
with akinetic mutism: the mesencephalic-diencephalic reticular activating system, including the
midbrain reticular formation, thalamus, and
hypothalamus1,7,12); and the anterior cingulate gyrus
and adjacent mesial frontal lobes. Lesions at these
sites occur along pathways that originate in the
mesencephalon and project widely to dopamine
receptors in the spinal cord, brainstem, diencephalon, corpus striatum, and mesiofrontal lobe.8,18,24)
The diffuse nonspecific reticular activating system,
which normally interacts with these specific projections as a coordinated unit, remains intact. The
resultant behavioral abnormality causes the patient
to remain awake but unable to initiate motor activity
in response to sensory stimuli, that is a state of sensory inattention.
Pressure transmitted to the diencephalon from
hydrocephalus or third ventricular tumors can cause
akinetic mutism.2,4,17,24) The underlying mechanism
is believed to be damage to the periventricular
monoamine projections in the thalamus and
hypothalamus caused by expansion of the third
ventricular wall.19,22) The degree and duration of
ventricular wall expansion required to injure the
monoamine projection fibers remains unknown, but

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M. S. Kim et al.

422
Table 1
Case
No.

Summary of clinical features in patients with akinetic mutism following hydrocephalus (HD) treatment

Author (Year)

Age
(yrs)/
Sex

HD

Operation

Time of onset

Treatment
shunt revision,
cogentin,
DOPA/benserazide
(prolopa)
levodopa,
bromocriptine,
trihexyphenidyl
bromocriptine,
ephedrine

1

Berger et al.
(1985)4)

21/F

obstructive HD
due to AS

multiple shunt
operation due to
shunt malfunction

after 3rd shunt
operation

2

Watahiki et al.
(1987)24)

39/M

obstructive HD
due to AS

after 3rd shunt
operation

3

Anderson
(1992)2)

20/M

obstructive HD
due to AS

4

Lee et al.
(2002)13)

34/M

unilateral
ventricle HD

5

Psarros et al.
(2003)19)

26/F

obstructive HD
due to
cystic mass

multiple shunt
operation due to
shunt malfunction
multiple shunt
operation due to
shunt malfunction
multiple shunt
operation due to
shunt malfunction
endoscopic exploration,
cyst resection,
septostomy

after 4th shunt
operation
after 3rd shunt
operation

bromocriptine

immediately
after
operation

bromocriptine

AS: aqueductal stenosis.

lesioning of these structures in animals induces
akinetic mutism, which can be reversed with dopamine agonists.23) This observation forms the basis of
dopamine agonist use in humans with akinetic
mutism.20) A patient with akinetic mutism caused by
hydrocephalus was treated successfully with levodopa, bromocriptine, and trihexyphenidyl.24) Another
patient with akinetic mutism resulting from obstructive hydrocephalus was treated with bromocriptine
and ephedrine.2)
The causative damage may be maximal in regions
adjacent to the third ventricle.5) This region contains
monoaminergic projection fibers from the brain
stem.21,23) Akinetic mutism does not result from
simple elevation of intracranial pressure,5) which is
consistent with clinical observations of patients
with pseudotumor cerebri, who can experience
pronounced elevation of intracranial pressure
without becoming mute. Akinetic mutism also does
not result from simple dilation of the cerebroventricular system. A review of previous cases revealed
that the syndrome usually develops after multiple
shunt revisions for shunt failure.4,16,24) This observation suggests that the brain undergoes a series of
stretching and contraction cycles, so the repeated
cycles of ventricular dilation and relaxation may
somehow alter the physical characteristics and
result in more rapid dilation in response to increased intracerebral pressure, which exceeds the
speed of compensatory mechanisms and results
in damage.2) Such stretching might occur in the
midbrain structures or the nigrostriatal system, and
might lead to dysregulation of this system without
major dopamine deprivation through the midbrain

lesion, which affects the substantia nigra.2)
HVA concentration was normal in the cerebrospinal fluid of a patient with akinetic mutism caused by
hypothalamic damage.20) However, the dopamine
metabolism is unclear in patients with akinetic
mutism resulting from hydrocephalus. Some patients with chronic hydrocephalus may experience
decreased autoregulatory capacity for cerebral
blood volume. In our patient, this mechanism was
excluded by perfusion-weighted MR imaging, which
revealed no perfusion changes.11) Our patient did not
respond to Madopar, a presynaptic dopaminemimetic drug, so we thought that the medial forebrain bundles were probably destroyed. Therefore,
we decided to try treatment with direct dopamine
agonists based on the results of animal experiments
and a previous case report.14,15)
In our patient, the clinical and pharmacologic
evidence indicated that the lesion predominantly
involved the periventricular monoamine projections
in the thalamus and hypothalamus, more specifically the presynaptic dopamine axons coursing in the
anterior portions of the medial forebrain bundles.
The unresponsiveness of this patient to Madopar
coupled with the initial response to low-dose
dopamine agonists suggest that the presynaptic
catecholaminergic mechanisms were inoperative.
On the other hand, if our patient's lesion had
involved the anterior cingulate gyri, she probably
would not have responded to direct dopamine
agonists because the dopamine receptor targets
would have been destroyed.20) The absence of abnormalities on 123I-FP-CIT-SPECT (dopamine transporter SPECT), lack of clinical response to levodopa

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Akinetic Mutism
treatment, and normal HVA concentration in the
cerebrospinal fluid all indicated normal dopamine
production.
Although we could not determine the exact
pathophysiological mechanisms, pressure on the
periventricular monoamine projections in the thalamus and hypothalamus without major dopamine
deprivation in the striatum may have been the most
important factors in the development of akinetic
mutism in this patient.

14)

15)

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Address reprint requests to: Myoung Soo Kim, M.D.,
Department of Neurosurgery, Seoul Paik Hospital,
Inje University College of Medicine, 85 Jeo–dong
2–ga, Jung–gu, Seoul 100-032, R.O.K.
e-mail: hanibalkms＠hanmail.net