CLINICAL

AND

RESEARCH

REPORTS

Successful
Treatment
Subcortical

Methyiphenidate
of Apathy
After
Infarcts

CASE

REPORT

A 38-year-old

of Illinois

right-handed
Hospital

weakness.
Medical
and childhood
poliomyelitis

Ph.D.

A patient with prominent
apathy secondary
to multiple subcortical
infarcts was treated successfully
with methyiphenidate.
SPECT and reaction time
testing showed selective improvement
of frontal
system function,
consistent
with a recent model of
frontal-subcortical
circuits and behavior.
(The Journal
Neurosciences

Apathy

is

in patients
regions

a major
ing.

of Neuropsychiatry
1995; 7:502-504)

a prominent
with
lesions

projecting
problem

Dopamine
apathy

neurobehavioral
of frontal
cortex

to frontal
cortex,1
in rehabilitation
and
agorusts,

in

including

Clinical

complication

or subcortical
and
it presents

social
bromocriptine

function-

have

been

employed

successfully

patients

with

anterior

communicating

methylphenidate,
treat
artery

and

aneurysm,
Wilson’s
disease,
and HIV-related
mentia.7
We report
a case of successful
methylphenidate treatment
of apathy
secondary
to cocaine-related
subcortical
strokes.
We
behavioral
observations,

documented

and
to
de-

improvement

SPECT.

Results

indicate

reaction
time (RT) testing,
that clinical
improvement

was

associated

with

selective

improvement

residual

University

and

left facial

for cocaine

abuse

paraplegia.

CT

internal
horn

testing
was positive
for psychomotor
slowing,
on memory
testing,
and impaired
planning
and judgment.
EEC
showed
mild slow waves
in the left frontal and temporal
areas. MRI of the brain
was positive
for multiple subcortical
infarcts
involving
the periventricular
white

poor free recall

matter bilaterally;
right internal
capsule,
basal ganglia,
and
cerebellum;
and left thalamus.
The patient
was treated
with bromocriptine
20 mg qd.
Ward staff reported
that he showed
improved
sodal behavior
and increased
interest
in activities.
However,
his behavior
deteriorated
after discharge,
with reemergence
of apathy,
incontinence,
and neglect
of personal
hygiene.
He was readmitted
to the neuropsychiatry
unit 3 months
later. Urine toxicology
screens
for street drugs were negative,
and serum prolactin
levels

with

were negligible,
corroborating
bromocriptine
treatment
and
After a 5-day washout
period,

assessments

were

performed

and

of compliance

his report

abstinence
baseline
the

from
SPECT

cocaine
and

RT

patient
was started
on
After 7 days of methyl-

a trial of methylphenidate
5 mg bid.
phenidate
therapy,
the patient
was reassessed.
Ward staff reported
that the patient
showed
a marked
increase
in interest
and improved
social behavior
following
initiation
of methylphenidate
therapy.
His personal
hygiene
improved
(he
bathed himself with minimal assistance
and ceased urine
spifiage),
and he increased
his participation
in unit activities.
Clinical improvement
has been maintained
at follow-up
9 months

after

discharge.

studies

were

of frontal-

function.

Received
April 27, 1994; revised November
8, 1994; accepted
December
7, 1994. From the Departments
of Pharmacy
Practice,
Psychiatry,
and
Radiology,
University
of Illinois-Chicago,
and the Veterans
Affairs
Medical
Center-West
Side, Chicago.
Address
correspondence
to Dr.
Martin,
Department
of Psychiatry
(M/C 913), University
of illinois, 912
S. Wood St., Chicago,
IL 60612.
Copyright
© 1995 American
Psychiatric
Press, Inc.

502

with

to the

psychological

use.

with
and

subcortical

presented

capsule
infarction
with comof the right lateral ventricle.
The
patient
was discharged
with a diagnosis
of cocaine-related
stroke. Five months
later he was readmitted
to a rehabilitation unit. His family
reported
that he was “different
in thinking,” had stopped
walking
with crutches,
and refused
to
leave the house.
He became
doubly
incontinent
and neglected
his personal
hygiene.
He laughed
inappropriately,
manipulated
his catheter
to spill urine,
and showed
poor
safety judgment.
On transfer
to the neuropsychiatric
unit, he
presented
as uncooperative
and indifferent
but without
delusions, hallucinations,
or depressive
complaints.
Formal
neuroscan revealed
a right
pression
of the frontal

Mark D. Watanabe,
Pharm.D.,
Eileen
M. Martin,
Ph.D.
Ovidio
A. DeLeon,
M.D.
Moises
Gaviria,
M.D.
Dan G. Pavel, M.D.
Donald
W. Trepashko,
M.D.

man

with right-sided
headache
history
was remarkable

METHODS
SPECT
detector

rotating

performed

gamma

on

camera

tems,
Columbia,
MD)
with
Amersham,
Arlington
Heights,

VOLUME

a Sopha
(Sopha

[Tc]HMPAO
IL) as the

7

#{149}
NUMBER

DSX

single-

Medical

Sys-

tracer.

4

(Ceretec”,
Standard

#{149}
FALL

1995

CLINICAL

cal lesions.8’9

The

task

consisted

of 192 voice-activated

trials.10

On

each

trial,

a colored

word

patient
Stimuli

named
were

and
error
rates
decreased
slightly,
5% to 3%. Improvement
was most evident
in the
incongruent
condition,
which
is considered
most sensitive to frontal
system
dysfunction8’9
(Figure
2).

stimulus
gruent

We

color),

for

speed.

For

each

pressed

a key

of color.

pressed
was

task,

changes

ignored
color

the word.
name
and

in

motor

single

colored

squares

In the 32-trial

simple

condition,

as soon

as he detected

In the 64-trial

one

and

key

the

(animal
names in color), or inconname and stimulus
color).
simple
and choice RT tasks11 as

nonspecific

monitor.

less

neutral

(different
color
also administered

controls

the

the stimulus
color and
either
congruent
(same

RT

appeared,

if the

choice

the

or

on

the patient
regard-

studies
nuclear

were

blind

were

observed

date
more

study
severe

FIGURE

1.

JOURNAL

(Figure

reviewed
(D.G.P.,
All rCBF

after
conditions

all Stroop

methyiphenidate
improved

treatfollowing

from

DISCUSSION

report
presents
a patient
with apathy
secondary
to
multiple
subcortical
infarcts
who had symptomatic
resolution with methyiphenidate
therapy.
His improvement
This

frontal

1) were

medicine
physicians
to details
of the case.

for

methylphenidate,

was

if it

RESULTS
SPECT

in

for each RT condition.
There
RTs (270 vs. 282 ms) and

RTs (441 vs. 410 ms)

another

and

improvement

in simple

RTs

red

was

computed

change

ment.

the patient

square

were

minimal

choice

condition,

green.

by two

Medians

marked

bilaterally.

mental

appeared
square,

perfusion

showed

REPORTS

stration,
frontal
was

SPECT

RESEARCH

sagittal,
and transaxial
images
were obtained
with
the subject
at rest, with eyes closed
and ears unocciuded.
The patient
was administered
three
computerized
RT
tasks.
We selected
the Stroop
task because
of its association with activation
of frontal
and cingulate
cortex
on PET
scanning
and susceptibility
to disruption
by frontal
corticoronal,

the

AND

accompanied

an

increase

in blood

flow

to

the

and selective
improvement
on a reaction
time version
of the Stroop
task. The Stroop
interference
effect
is cognitively
complex
and is associated
with activation
of multiple
cerebral
regions;
however,
the increased
activity
is most
prominent
in
frontal
and
cingulate
cortex.8
Thus,
SPECT
and
RT results
suggest

independently

that

the

D.W.T.)
who
abnormalities

with

improvement

in frontal
regions.
The pre-methylphenishowed
bilateral
frontal
hypoperfusion,
on the left. After methylphenidate
admini-

by

cortex

patient’s

These
posed

results
by

of apathy
involving

clinical

improvement

in frontal-subcortical
are consistent
with

Cummings4
that
with
lesions
of
anterior
cingulate,

was

associated

function.

a recent

model

pro-

associates
the development
a frontal-subcortical
circuit
basal
ganglia,
thalamus,

images
obtained
before and after treatment
with methylphenidate.
The pretreatment
study (upper series) shows
decreased
perfusion
of the lateral aspect of both frontal lobes, extending
on the right to the superior
aspect and on the left to
the orbitofrontal
area. The posttreatment
study
(lower
series)
shows improved
relative
perfusion
of both frontal
lobes.
SPECT

OF

NEUROPSYCHIATRY

503

CLINICAL

FIGURE

AND

2.

Median
(Pre-Tx)

RESEARCH

REPORTS

reaction times on the Sfroop
and after (Post-Tx)
treatment.

task before

or postsynaptic
also compatible

synaptic

ings

are

associated

1600

with

thus,

that

disordered

However,
we cannot
rule
activity
as an additional
improvement.

1400

Our
patient’s
dopamine
agonist

1200
-

1

ioo:

behavior
improved
bromocriptine,

ployed
to
development

treat
apathy
of tolerance

fluenced

his

by

proposals

with
been
mutism.54’13

the
emHis

(possibly

in-

initially
which
has

and akinetic
to bromocriptine

history
of cocaine
abuse,
in
central
dopaminergic

which
causes
pathways14)

dysregulation
prompted
the substitution
of methyiphenidate.
The literature
on attention-deficit/hyperactivity
disorder
suggests
that tolerance
to chronic
methyiphenidate
can be
minimized
with appropriate
dosage
adjustments.15
The
patient
has been abstinent
from cocaine
since his stroke
and
continues
to maintain
a therapeutic
benefit
of

600

400

methylphenidate

200
0

Congruent

Neutral

Incongruent

cortex.
Methyiphenidate
neurotransmission,

enhances
central
either
through
pre-

at 15mg/day,

suggesting

that

tolerance

development
may not pose a problem
in medication
management.
The results
of this promising
single
case await
replication in a group design with employment
of standardized
measures

and frontal
dopaminergic

our findapathy
is
dopaminergic
activity.1’4
out enhanced
noradrenergic
influence
on our patient’s

mechanisms;12

with

of apathy,

such

as the

Apathy

Evaluation

Scale

developed
by Mann.1
In addition,
our results suggest
that
SPECT scanning
and reaction
time tasks have much potential
as outcome
measures
in clinical
trials
of psychostimulants

for neurologically

based

apathy.

References
1. Mann RS: Apathy: a neuropsychiatric
syndrome.
J Neuropsychiaby Clin Neurosci
1991; 3:243-254
2. Mann RS, Fininciogullari
S, Biedrzycki
RC: Group differences
in
the relationship
between
apathy
and depression.
J Nerv Ment Dis
1994; 182:235-239
3. Starkstein
SE, Fedoroff JP, Price TR, et al: Apathy following
cerebrovascular
lesions. Stroke 1993; 24:1625-1631
4. Cummings
JL: Frontal-subcortical
circuits and human
behavior.
Arch Neurol 1993; 50:873-880
5. Parks RW, Crockett
DJ, Manji HK, et al: Assessment
of bromocriptine
intervention
for the treatment
of frontal lobe syndrome: a case study (letter). J Neuropsychiatry
Clin Neurosci
1992; 4:109-111
6. Barrett K: Treating
organic
abulia with bromocniptine
and
lisuride:
four studies.
J Neurol Neurosurg
Psychiatry
1991; 54:718721
7. Holmes
VF, Fernandez
F, Levy JK: Psychostimulant
response
in
AIDS-related
complex
patients. J Clin Psychiatry
1989; 50:5.-S
8. Pardo JV, Pardo
PJ, Janer KW, et al: The anterior cingulate
cortex
mediates
processing
selection
in the Stroop attentional
conflict

504

paradigm.
Proc Nail Acad So USA 1990; 87:256-259
9. Perret E: The left frontal lobe of man and the suppression
of habitual responses
in verbal categorical
behavior.
Neuropsychologia
1974; 12:323-330
10. Martin EM, Robertson
LC, Edelstein
HE, et al: Performance
of
patients with early HIV-1 infection
on the Stroop task. J Clin Exp
Neuropsychol
1992; 14:857-868
11. Martin EM, Sorensen
DJ, Edelstein
HE, et al: Decision-making
speed in HIV infection.
AIDS 1992; 6:109-113
12. Costall B, Naylor
RJ: The involvement
of dopammergic
systems
with

the

phenidate.

stereotyped

J Pharm

behaviour
Pharmacol

patterns

13. Ross ED, Stewart
RM: Akinetic
age: successful
treatment
with a dopamine
1981; 31:1435-1439
14. Post RM, Kopanda
RT: Cocaine,
kindling,
Psychiatiy
15.

1976;

induced

by methyl-

1974; 26:30-33
mutism
from hypothalamic
agonist.

dam-

Neurology

and psychosis.

Am J

133:627-634
RI’: Absence

Safter DJ, Allen
of tolerance
to the behavioral
effects
of methylphenidate
in hyperactive
and inattentive
children.
J Pediatn 1989; 115:1003-1008

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