CLINICAL

in both our patients
deserves
comment.
These
mood
changes
presented
as abrupt
changes
from a cheerful
and
cooperative
mood
to an irritable
and depressed
mood
with features
of anxiety.
This lasted
for about
2 and 4
hours,
respectively,
after which
both mood
and affect
returned

to base

underlying

line.

cholinergic

Alzheimer’s

patients,

with

their

abnormalities,

may

be more

vul-

has

im-

nerable

to this

side

plicated

in the

pathophysiology

and

depression

effect.

can

predominance

be

Acetylcholine
of affective

Likewise,
in patients

disorders,

a manifestation

or stimulation

disorders.7
occurring

of

in patients

Mohs8
reported
with
AD who

been

with

affective
depression
the cholin-

ergic agonist
oxotremorine.
Depressed
mood
was
the side effects
of choline
and
lecithin
treatments
ployed
to improve
the memory
deficit
of AD. Our
vations
Mood

are consistent
with
and affect changes

sostigmine

should

described

in detail

transformation

be comprehensively
in future

studies.

of a demanding

and

to withdrawal
and
may be interpreted
when,

in fact,

lethargy
upon
as improvement

it may

other
investigators
tive changes,
but
fluctuations
hancement

these
reports.
in AD patients

reflect

in AD
therapy.

phyand

Conceivably,

induced

patients

of
emobser-

receiving

the

AD

physostigmmne
by family

to thoroughly
also subjective

one

investigated
agitated

patient

therapy
members

depression.

We

assess
not
complaints

undergoing

urge

only
and

cognimood

cholinergic

en-

This study was supported
in part by Public Health Service
Grant NIA 05433 andagrantfrom
the Jean and Louis Dreyfus
Foundation.
We thank Darren R. Gitelman,
M.D., Marvin
H.
Lipkowitz,
M.D., Georges Casimir, M.D., and Cyrisse Russell,
R.N., for their help in conducting
and evaluating
this study.

References
1. Davis

K, Hollister

nition

and

J, et al: Physostigmine

L, Overall

affect

in normal

subjects.

effects

on cog-

Psychopharmacology

1976;

51:23-27
2. Janowski

DS,

Risch

fects

of physostigmine

3. Davis

K, Mohs

ALzheimer’s
mine.

RC:

of memory

multiple-dose

1982;

rCBF

J: HTN

stigmine

with

with

Alzheimer’s

DS, Risch
CS,
and neostigmine

51
7. Janowski,

DS,

tive

disorders:

JOURNAL

OF

Risch

SC:

a review

1985;
processes

intravenous

ef-

7(1 ):140-145
in
physostig-

139:1421-1424
N, et al: Intravenous
physodisease
evaluated
by psycho-

measurement,
1987; 93:31-35

associated
with

cardiovascular

Hypertension

L, Edvinsson
L, Dahlgren
treatment
of Alzheimer’s

in a patient
143:910-912
6. Janowski

LY, et al: Central

Enhancement

J Psychiatry

metric
testing,
Psychopharmacology
5. Cain

Huey

in humans.

disease

Am

4. Gustafson
stigmine

CS,

oral

and

EEC.

administration

disease.

Am

of physostigmine

J Psychiatry

in New
AJ, Altschuler

8. Mohs
ment

RC,

Advances

NEUROPSYCHIATRY

therapeutic

REPORTS

of Depression.

Guilford,

Johns

CA,

et al: Oral

with

Alzheimer’s

disease.

Edited

1984

physostigmine

treat-

I Psychiatry

Am

1985;

142:28-33

Cerebral

Infarction

in

Malignant

Syndrome
Patrick
Alfred
Conrad

Pullicino,
M.D., Ph.D.
Caruana
Galizia,
M.R.C.P.
Azzopardi,
M.D.

Two young women with no risk factors for cerebrovascular disease developed
hyperpyrexia,
rigidity,
and autonomic
features while taking neuroleptic
agents. The first presented
with increasing
rigidity, profuse diaphoresis
and dehydration,
and a
right hemiparesis,
and computed
tomography
(CT)
showed a left striato-capsular
infarction.
The second became unresponsive
following
severe hypoxia
and was found to have left-sided
pyramidal
signs
three days later. Hemoconcent
ration and hypoxemia predispose
to cerebral ischemic injury in the
neuroleptic
malignant
syndrome
and should be
avoided as much as possible.
(The Journal
Neurosciences

of Neuropsychiatry
1991; 3:75-77)

and

Clinical

Neuroleptic
malignant
syndrome
(NMS)
is an uncommon, potentially
fatal side effect of the major tranquilizers. The
main
features
of NMS are marked
muscular
rigidity,
hyperpyrexia,
and altered
consciousness
in patients taking
therapeutic
doses of either phenothiazines,
the thioxanthenes,
or haloperidol.’
A variety
of clinical
features
have
been
observed
in NMS,
and most
are
thought
to reflect
dysfunction
of different
central
dopammnergic
pathways.2
Systemic
complications,
vascular,
respiratory,
and
NMS3
and are responsible
These
include
respiratory

including
those
of the cardiorenal
systems,
are frequent
in
for a mortality
rate of 20%.
failure,
myoglobinuric
renal

1986;
Received

September

25,1989.

From

and

affecim-

Copyright

the

8,1989;

Adrenergic-cholinergic

balance

York,

BM,

Dr. Pullicino,
Department
Medical
Center,
462 Grider

and

Treatment

New

Davis

St. Luke’s

evidence

RESEARCH

of patients

Kennedy
B, et al: Acute
effects
of physoin man.
Military
Medicine
1986; 151:48-

of clinical

and

KC.

Neuroleptic

cholmnergic

severe
received

plications,
by Rush

AND

revised

University

Hospital,

© 1991

Gwardamangia,

American

October

of Malta

and
Malta.

24,1989;
the

accepted

Department

Address

reprint

of Neurology/SUNY
Street,
Buffalo,

NY

Buffalo,
14215.

Psychiatric

Press,

Inc.

October
of Medicine,
requests
Erie

to

County

75

CLINICAL

failure,
lism

AND

RESEARCH

REPORTS

and

cardiovascular
collapse.”3
occurs,’
but
cerebrovascular
not been reported
previously.

Thromboembocomplications

also

have

Her speech was slurred.
She had conjugate
ocular deviation
to the right. There was a right
flaccid
hemiparesis
with
a
right
extensor
plantar
response.
Increased
tone and cogwheeling

were

present

on

Investigations
55.1;

CASE

REPORTS

glucose,

Case 1. A 47-year-old
woman
with a 20-year
history of
schizophrenia
was started on monthly doses of intramuscular
flupenthixol
decanoate
(20 mg) and procyclidine
hydrochloride (10 mg) five months prior to admission.
She had no risk
factors for cerebrovascular
disease, was a nonsmoker,
and
was premenopausal.

Four

complained
of generalized
mg doses of benzhexol
mission
the stiffness
She started
leaning
She

fell several

white

months

prior

stiffness

that

three times

increased,
to the right,

to admission
she
did
not respond
to 2

a day. A week

and her gait became
and her speech
was

prior

to ad-

slower.
slurred.

with

On

second

mute and catatonic.
and semirhythmic

limb. Her temperature
(EEG)

started

on

FIGURE

FIGURE

76

infarction
in the neuroleptic
(Case 1)

malignant

1,400 U/l

levodopa

venous

was

attenuation

lesion

tient gradually
2.

and

and
with

Serum

range,

carbidopa

110

mg

three

a

times

5 mg three times a day.
but she did develop
a left femoroconfirmed

a repeat
some

infarction

(Case

by

CT scan

reduction

was mobilized,

Cerebral
syndrome

became

levels of cre10 to 70 U/l). She

slowing.

(normal

thrombosis,

instituted,

patient

was 38.3.#{176}C.
An electroencepha-

left-sided

day, and bromocriptine
The patient
improved,
arm

Cerebral
syndrome

showed

was

the

She had left-sided
and truncal
rigidity
small amplitude
movements
of the left

logram

were

and

1).

of hospitalization,

upper

kinase

394x109/l;

fluid was normal. A
showed
a left striato-capsu-

(CT) scan
effect (Figure

day

atine

182 g/l; hematocrit,
platelets,

The cerebrospinal

tomography
mass

the

On admission,
examination
revealed
a profuse
diaphoresis,
despite
a temperature
of 36#{176}C.
The pulse was 80 per minute,
sinus rhythm,
and the blood pressure
was 140/95
mmHg.
1.

hemoglobin,
11.7x109/l,

5.2 mmol/l.

computed
lar infarct

left.

count,

blood

popliteal

times.

the

showed

venography.

again
of mass

Hep-

showed
a low
effect. The pa-

and she was discharged
in the neuroleptic

malignant

3 #{149}
NUMBER

1 #{149}
WINTER

with

2)

VOLUME

1991

CLINICAL

persistent
hospital

right
day.

brachio-facial

weakness

hemiparesis.
injury gave

on the seventy-third

akinetic

Case 2.

A 37-year-old

nonsmoking
woman
with no risk factors for cerebrovascular
disease
presented
with a psychotic
illness. She was started
on trifluoperazine
5 mg a day, procyclidine
hydrochloride
5 mg a day, chiorpromazine
25 mg
three times a day, and triazolam
0.5 mg at night, as an outpatient.
A week later, she was admitted
to the hospital
with a
fever of 39.8#{176}C
and diffuse rigidity
with cogwheeling,
trismus, and episodes
of opisthotonus.
On examination,
she was agitated
and tachypneic
and had
shallow
respirations.
There was increased
tone in the limbs
with a fine fast tremor.
The blood pressure
was 210/120
mmHg,
and the pulse was 102 per minute,
sinus rhythm.
Power in the limbs was normal.
On the third day of hospitalization
the patient’s
right lung collapsed
and she developed
severe hypoxemia.
She was initially
unresponsive
to ventilation, but by the sixth hospital
day she was breathing
spontaneously
but remained
akinetic
and mute. She responded
to
pain only on the right side and only by withdrawing
her
hand. Her left arm and leg were flaccid, but elsewhere
tone
was increased.
The left plantar
was extensor.
She had episodes of sudden
hypertension
associated
with diaphoresis
and salivation.
Investigations
showed
serum creatine
kinase,
240 U/l; hemoglobin,
101 g/l; white blood count, 21x109/l;
and plasma
glucose,
12.5 mmol/l.
An EEC showed
right posterior
slowing. CT scan showed
questionable
areas of low attenuation
in
the corona
radiata
regions
(Figure 2).
Once the patient
was started
on bromocriptine,
her level of
consciousness
gradually
improved,
and she began to move
her left side. On discharge,
three months
after admission,
she
had increased
tone in the upper
limbs and slight left lower
limb weakness,
with a left extensor
plantar
response.

AND

RESEARCH

REPORTS

It is likely that cerebral
hypoxic-ischemic
rise to the pyramidal
signs and possibly

mutism,

although

akinetic

mutism

the

is known

to

be a complication
of NMS.
Thromboembolic
complications
are frequent
in NMS”5
and include
deep-vein
thrombosis,6
pulmonary
embolism,3’6 and myocardial
infarction.7’8
The causes
of these
complications
are not known,
but they may be related
to
the diaphoresis,
dehydration,
and hemoconcentration
seen in NMS.2
Abnormal
coagulation
also has been
described
in a case of NMS,3 and abnormal
platelet
aggregation

has

been

suggested

as a cause

of thrombosis.8

The

patient
presented
with diaphoresis
and hemoconcentration.
She had a hemiparesis
and a corresponding
striatocapsular
infarct on CT, and she developed
a thrombosis in a deep leg vein. Striatocapsular
infarction
may
first

arise

from

either

thrombosis

that

the

cerebral

infarct

thrombotic
In

or embolism,9

in this

complication

order

patient

and

it is likely

was

due

to a

in NMS,

the

of NMS.

to prevent

hypoxic

complications

pO should
be carefully
monitored,
particularly
if tachypneic hypoventilation
develops.
Adequate
intravenous
fluid replacement
must be given to patients
with NMS,
particularly
if diaphoresis
or hemoconcentration
are
present.
An assessment
of the value
of subcutaneous
heparin
in preventing
thromboembolic
complications
of
NMS

is needed.

Presented
at the 41st Annual Meeting
of the American
emy of Neurology,
Chicago, Illinois, April 1989.

Acad-

References
1.

Guze

BH,

Baxter

LR: Neuroleptic

malignant

syndrome.

J

N Engl

Med 1985; 313:163-166

DISCUSSION

Our

patients
fulfilled
the criteria
diagnosis
of NMS
and had features
volvement

of

different

rigidity,
Previously

including

mutism,

akinetic

coupled

from
with

farction.”3
unresponsive
tachypnea

the

respiratory

and

She subsequently
to have left-sided

OF

was found
pyramidal

NEUROPSYCHIATRY

malignant

syndrome:

a

1985;

142:1137-1145

Both

4.

Pope

HG,

5.

neuroleptic
malignant
syndrome
in a large
psychiatric
hospital.
Am I Psychiatry
1986; 143:1227-1233
Smego
RA, Durack
DT: The neuroleptic
malignant
syndrome.

hyperpyrexia,
described

and autosigns
of NMS,
trismus,

wall
or

signs
of NMS prior
severe
hypoxemia.
was

Neuroleptic

pathways.

chest

hypoventilation

failure

GF:

3.

pneumonia

Patient
2 had
following

ing

JOURNAL

decreased

Wooten

the
in-

opisthotonus,

aspiration

VW,

of Pope
et al.4 for
compatible
with

phoresis,
and blood
pressure
lability,
were
also
Respiratory
failure,
the most
common
serious
cation
of NMS,
appears
to be caused
by tachypneic
ventilation

Henderson

pathogenetic
role for dopamine
receptor
blockade?
Neurology
1981; 31:132-137
Levensen
IL: Neuroleptic
malignant
syndrome.
Am I Psychiatry

dopaminergic

had extreme
muscular
nomic
dysfunction.

2.

strongly

dia-

seen.”2
complihypo-

compliance

suggest

that
NMS.

to be mute and catatonic
signs,
with a persisting

and
left

Med

1982;

7.

Malignant

Psychosomatics

1979;

Becker

D, Birger

M, Samuel

usual
Ment

complication
Dis 1988;

Bladin
the

hyperthermies

dues

and

presentation

of

neuroleptic

aux

neuroleptiques.
syndrome:

Encephale
an atypical

case.

20:840-846
F, et al: Myocardial

of neuroleptic
176:377-378

PF, Berkovic

lenticulostriate

SL: Frequency

142:1183-1185

1973; 62:126-159
Bernstein
RA:

9.

C: Les

McElroy

Aubert

in-

to becoming
The preced-

Intern

PE,

6.

8.

pulmonary

of the

a complication

Arch

Keck

SF: Striatocapsular
arterial

territory.

malignant

infarction:
syndrome.

infarction:
Neurology

large
1984;

an un-

J Nerv
infarcts

in

34:1423-1430

77