British Journal of Psychiatry (1996), 168, 237—240

Acute Frontal Lobe Syndrome and Dyscontrol
Associated with Bilateral Caudate Nucleus Infarctions
RICHARD G. PETTY DEIRDRE BONNER,VASSIUS

MOURATOGLOU

andMARISASILVERMAN
Background.

A 67-year-okl man presented with acute onset of spatial and temporal disorien

tation, memory loss and associated episodic dyscontrol Investigations showed mfarctions of
both caudate nuclei.This patient presenteda unique opportunity to study the relationship
between
Method.

the lesions, his behaviour, and neuropsychological
testing.
Single case report Investigations
included interviews to determine

cognitive

impair

ment,i.e.Wi@JS-R@
MMSE,andneurological
examination.
Results. Extensiveneuropsychologicaltesting revealedsevere impairmenton tasks requiring
plannmg,memoryorabstractthought.Thesefindingsareverysimilarto those seen inHunting
ton'sdisease.
Conclusions. A neurobiologicalhypothesis is proposed to account for his symptoms, and
recent discovenes inthe basic sciences used to informhis management.

Case report

State Examination
(MMSE)
score was 22/30.
Neurological
examination
revealed a prominent

Mr C, a 67-year-old man, with a 13 year history of
type 2 diabetes mellitus complicated by peripheral
vasculopathy, was found late one night wandering
beside the electrified track between two stations on
the London Underground system. When found by
police, he appeared confused and stated that he was
walking through the tunnel to get to Portsmouth en
route to France. A former policeman and well
respected company worker, he was described by

pout reflex, but no other neurological abnormal
ities, and in particular no other frontal lobe signs
or movement disorders. He was normotensive and
apart from an elevated plasma glucose, blood
chemistry and haematology were normal. During
the first interview and subsequently, until treat
ment was started, he had repeated, severe,
catastrophic rage reactions which were usually
precipitated by minor frustrations, and would be
associated with violent and aggressive outbursts
which would cease only very gradually. On some
occasions he absconded from the ward and would
immediately become lost. His subsequent rage
reactions constituted a very real danger to the
public. A full psychometric assessment was clearly
impossible at this stage. A CT brain scan was
performed (Fig. 1) which showed infarctions in
the heads of both caudate nuclei and the

informants

as a hard-working

man

with

a normal

premorbid personality. There was a six year history
of minor cognitive decline. During this time he had
become gradually

less interested

in social activities

and his previously high standards
hygiene,

although

he

had

been

of personal
able

to

live

independently and to care for himself until the
day prior to admission.
On admission he was alert and in clear
consciousness. He was elated, jocular and disin
hibited. His speech was loud, pressured and
difficult to interrupt. There was severe confabula
tion, perseveration, and circumstantiality, but no
evidence of grandiosity, delusional beliefs,
hallucinatory experiences or of a change in
appetite or sleep patterns. He was grossly
disoriented in time, place and person. It was
difficult to engage and maintain his attention. He

had very poor concentration and severely im
paired short-term memory. Initial Mini Mental

thalamus;

large

cerebral

ventricles,

and

periven

tricular lucencies consistent with vascular disease
within the white matter. Treatment was success
fully instituted initially using halopendol to
achieve some behavioural control, which was
gradually phased out as carbamazepine was
introduced. A full psychological assessment was
then carried out.
He had an average premorbid intellectual
capacity, as indicated by his educational and
employment history. The Wechsler Adult

237

238

PETTY

ET AL

pout reflex. In addition it was established that the
onset had been extremely rapid, indicating a
catastrophic event. It is of interest that the results
of the neuropsychological
testing were not only

indicative of a subcortical type of dementia, but
were virtually identical to those observed in
Huntington's
disease (HD), in which degeneration
of the caudate nuclei (CN) is a prominent feature
(Jacobs & Huber, 1992).

The caudate nucleus and behaviour
Increasing

evidence

subcortical

structures

supports

the

are

involved

notion

that

in many

behavioural
and psychological
activities (Cum
mings, 1993). One of the most studied of these

structures is the CN, which has attracted parti
cular attention because of its association with HD.
The involvement of the CN in psychological and
behavioural
activity is not surprising
since it
receives

projections

from

higher

order

cortex, as well as the hippocampus
(Parent, 1990).

association

and amygdala

Acquired lesions of the CN are quite rare: there
Fig. I Computerised tomographic scan showing infarctions in
the central portion of the heads of both caudate nuclei (arrows). A

small area of infarction can also be seen inferiorly in the thalamus.

are fewer than 50 cases in the world literature,

language,
Intelligence

Scale Revised (WAIS-R)

revealed: full

scale IQ = 80, performance IQ 72, and verbal
IQ = 86. Analysis of the various sub-tests of the

WAIS-R showed a very good performance on tests
of information and digit span, while he did
moderately well on tests of vocabulary, arithmetic,
similarities, picture completion, and block design.
However, he did very poorly on tests of
comprehension, picture arrangement and digit
symbol.

There

was poverty

on tests

of verbal

fluency and marked concreteness when asked to
explain proverbs. On the short Wisconsin Card
Sorting Test (WCST) he made 48 errors, and no
correct

categories.

praxis
abilities

and
and

gnosis.

Impaired

disinhibition

have

problem
also

been

described (Richfield et a!, 1987). Two series have
attempted a more systematic delineation of the

neurobehavioural

associations of caudate lesions.

Mendez et al (1989) described 12 patients with
lesions in the CN, in only one of whom was the

damage bilateral. Two also had other neurological
lesions,

and

the patient

with

bilateral

lesions

was

described as having dementia (MMSE score of 18/
30).

These

patients

displayed

acute

behavioural

changes characterised by apathy, disinhibition or
disturbances

of mood. Interestingly

hallucinations

also occurred in two patients: auditory in one and
visual in another. Seven of these patients (exclud

findings

any neurological

dicated impairment

of tasks requiring planning

and sequencing.
In a second series, Caplan et a! (1990) described

The initial clinical picture was suggestive of an acute
dementia of the frontal lobe type. However, while
chronic frontal lobe lesions are notorious for not

having

solving

ing the individual
with bilateral
CN lesions)
underwent neuropsychological
testing,
which in

Discussion
Clinical

and

ours is only the second bilateral case. Sporadic
case reports (e.g. Pozzilli et al, 1987) have
indicated that lesions of the CN may be associated
with apathy and with disturbances of memory,

localising signs, this

neurological
‘¿silence'is more unusual in acute
frontal lobe lesions, and here there was only a

18 patients with unilateral lesions of the CN. This
study is more difficult to interpret since lesions
extended into the internal capsule in nine of the
patients, and into the putamen in five. There were
variable abnormalities,
including disturbances
of
language and speech, apathy, agitation and

239

BILATERALCAUDATE NUCLEUS INFARCfIONS
hyperactivity. Clearly in none of these subjects was
the behavioural disturbance as profound as in the

of the lesions in this case, provides a clear

patient described here.
Dysfunction
within

logical findings.
While it is quite clear that the observed
behavioural changes were superimposed upon a
picture of a very gradual cognitive decline over the
preceding years, it is also apparent that there was
a sudden catastrophic change in this man. He
changed, in a matter of hours, from being a self
caring individual to one who was seriously
incapacitated, and a danger both to himself and
to others. Over the subsequent two months his
behaviour gradually normalised as treatment was
instituted, although there was presumably also
improvement as the acute effects of the cere
brovascular accident receded. Unfortunately his
severe cognitive impairment remained entirely tin
changed.

the caudate

nucleus

has

been implicated in depressive illness (Krishnan et
a!, 1992) and perhaps in schizophrenia (Buchs
baum, 1990). Our patient showed no evidence of
either of these disorders. While one could
speculate that this was attributable to the
‘¿protective'
effect of a normal premorbid person

ality, it must be recognised that the CN is a large
volume of tissue, and it is highly likely that it
contains

many

functional

domains.

Specific psy

chiatric symptoms may be a consequence of
lesions within specific—and as yet poorly-de
fined-regions in the CN.
Evidence from patients and from animal work
indicates a series of five frontal-subcortical
circuits,

explanation

for the behavioural

and neuropsycho

all of which run from specific regions in the frontal
lobes to the thalamus via the CN (Cummings,
1993). Lesions

in the CN

have

the effect

of

disconnecting frontal cortex from subcortical and
perhaps limbic structures. The first is a motor
circuit originating in the supplementary motor
area, which runs through the ventral caudate to
the

globus

pallidus

and

finally

the

thalamus.

Lesions in this circuit appear not to have
behavioural consequences. The second is an
oculomotor circuit which originates in the frontal
eye fields and passes through the central body of
the CN. The third circuit passes from the
dorsolateral prefrontal cortex through the dorso
lateral head of the CN. Deficits in this circuit lead
to difficulties in ‘¿executive
function' and motor
programming. Particular deficits occur on the
Wisconsin Card Sorting Test, and on tests of
verbal and design fluency. These problems were
clearly present in this patient, indicating that this

Management
Initially he presented a serious problem because of
his highly aggressive behaviour and rage reactions.
Benzodiazepines
may
be associated
with
paradoxical effects, particulary in brain damaged
individuals. Haloperidol was selected partly for its
sedative effects, but mainly because of its high
affinity for dopamine receptors, which appear to

have a ‘¿permissive'
effect for aggressive behaviour.
in mice aggression can be ameliorated by blockade
of dopamine—D2receptors (Nikulina & Kapravola,
1992). His catastrophic reactions began to
respond to this treatment in three days, allowing
titration of the dosage against his response. The
speed of this response suggests, but does not
prove, that it was due to dopaminergic blockade,
which has normally been attained in this period,

circuit was interrupted, which is confirmed by the

rather

position of the lesions on CT scan.
The fourth circuit begins in

the

orbitofrontal

through

frequently used to treat victims of head injuries
who exhibit catastrophic reactions, and it appears
to help episodic dyscontrol (Lewin & Sumners,
1992).
The dosage was adjusted according to plasma
levels, which were maintained within the
anticonvulsant range. Because of the risks of
antipsychotic agents in the elderly, and the

cortex

and

passes

lateral
the

ventromedial cortex. Lesions in this circuit lead
to marked changes in personality, with disinhibi
tion, inappropriate behaviour, irritability, imita
tion and utilisation —¿
an enslavement to
environmental cues. Clearly all were present in
this patient, and the site of the lesion is shown on
the CT scan. A final circuit runs from the anterior
cingulate gyrus through the ventral portions of the
CN. Lesions here can result in akinetic mutism.
This portion of the CN appears to have been
spared, judging by the clinical picture and the
imaging studies. Consideration
of what is now

known of the connections of the CN, and the site

than

consideration

just

sedation.

Carbamazepine

is

that haloperidol might, by lowering

the seizure threshold, antagonise the effects of
carbamazepine, its dosage was rapidly reduced,
and he was ultimately maintained on 1.5mg/
day, until further medical complications

super

vened. In view of his severe vasculopathy and
accompanying
complications,
his long-term
prognosis is unfortunately very poor, and despite

240

PETTY

the behavioural
control
incapacitated,
requiring
care.

he remains
severely
long-term
residential

ET AL

References
BtJCHSSAUM,M. S. (1990) The frontal lobes, basal ganglia and

temporal

lobes as sites for schizophrenia.

Schizophrenia

Bulletin, 16, 377—387.
CAPLAN,

L. R.,

SCHMAHMANN,

J. D.,

KASE, C. S., et a! (1990)

Caudate infarcts. Archivesof Neurology, 47, 133—143.

•¿
The caudate nucleus has important roles in human
behaviour.

CUMMINGS,J. L. (1993) Frontal-subcortical circuits and human
behavior. Archives of Neurology, 50, 873—880.
JAcoBs, D. H. & HUBER, S. J. (1992) The role of the caudate in
nonmotor behaviors in Huntington's disease. Behavioural
Neurology, 5, 205—214.

•¿
Lesionsat this site should be considered in pa

KRISHNAN,

Implications

tients with acute onset of confusion, disonenta
tion. catastrophic reactions or frontal lobe signs.
•¿
Unless contraindicated, conventional antipsy

choticagents and carbamazepinemaybe ofvalue
incases markedby catastrophicreactionsor dys
control.

K.

R.

R.,

MCDONALD,

LEWIN, J. & SUMNERS, D. (1992)

dyscontrol with carbamazepine.
M.

F.,

ADAMS, N.

University

of Pennsylvania,

P.

Successful

received

27 March

1995. final revision

11 September

et

at

treatment

of episodic

British Journal of Psychiatry,

associated

K.

S. (1989)

with caudate

lesions.

N. S. (1992)

Role

of dopamine

369.
PARENT,

A.

(1990)

Extrinsic

connections

of the

basal

ganglia.

Trends in Neuroscience, 13, 254—258.
Pozziw,

C.,

PASSAFWME,

D.,

BASTIANELLO,

S.,

et

at

(1987)

Remote effects of caudate hemorrhage: a clinical and functional

study. Cortex, 23, 341—349.
RICHFIELD, E. K., TWYMAN, R. & BERENT, 5. (1987)

Neurological

syndrome following bilateral damage to the head of the caudate
nuclei. Annals of Neurology, 22, 768—771.

Department

of Psychiatry,

CPsychol, Marisa Silverman,

Brain

Behavior

Laboratory,

Floor, Gates Building, 3500 Spruce Street, Philadelphia, Pennsylvania 19104-4283, USA. Fax: 215 662 7903
(First

R.,

receptors in the regulation of aggression in mice: relationship to
genotype. Neuroscience and Behavioural Physiology, 22, 364.-

Richard 6 Petty, MRCPsych, Deirdre Bonner, MRCPsych, Vassilis Mouratoglou,
FRCPsych, The Maudsley Hospital, Denmark Hill, London SE5 8AZ
R. G. Petty,

ESCALONA,

L. & LEwAND0w5EI,

NIKULrNA, E. M. & KAP@voi.@,

•¿
A single case report.
•¿
The dramatic findings were superimposed on a
previous, gradual cognitive decline.
•¿
The lesions probably involved several of the dis
crete pathways of the caudate nudeus, preventing
a more detailedcognitive and behaviouraldissec
tion.

M.,

161,261—162.
MENDEZ,

Neurobehavioral
changes
Neurology, 39, 349—354.

Limitations

Correspondence:

W.

(1992) Magnetic resonance imaging of the caudate nuclei in
depression. Archives of General Psychiatry, 49, 553-557.

1995, accepted

18 October

1995)

10th