Case Report
Nepal Med Coll J 2011; 13(2): 144-146
Neuroleptic malignant syndrome: Case report
DP Limbu, RB Tajhya, A Limbu, PM Singh, P Batajoo, B Gurung, S Lamichhane and B Rai
Department of Psychiatry, Nepal Medical College and Teaching Hospital, Jorpati, Kathmandu, Nepal.
Corresponding author: Dr. Durga Prasad Limbu, Department of Psychiatry, Nepal Medical College and Teaching Hospital, Kathmandu,
Nepal; e-mail: dr.durgalimbu@gmail.com
ABSTRACT
Neuroleptic Malignant Syndrome (NMS), a potentially fatal complication of neuroleptic therapy is described.
It is found to be associated with a variety of medical and psychiatric conditions. Various risk factors and non
specific investigations pathognomic to various medical conditions has been proposed. The mortality and
morbidity associated with NMS can be decreased with early recognition, early discontinuation of the neuroleptics
and aggressive treatment.
Keywords: Neuroleptic Malignant Syndrome, neuroleptics.
Neuroleptic malignant syndrome, rare but life
threatening neurological disorder most often caused by
neuroleptics is characterized by hyperthermia, muscle
rigidity, elevated creatinine phosphokinase and
autonomic instability. A case of 20 yrs old female
diagnosed with mental retardation with behavioral
problem with neuroleptic malignant syndrome is
reported here under.
CASE REPORT
A 20 yrs female, with mental retardation with behavioral
problems, was brought to this hospital from a psychiatric
rehabilitation centre. She was treated with
Carbamazepine 200mg twice a day, Haloperidol 5mg
thrice a day, Chlorpromazine 100mg twice a day. Due
to her uncontrolled exhausting hostile behavior and
disorganized behavior, she was given inj. Haloperidol
5mg i.m and inj.promethazine 25mg twice a day for 17
days. Then she developed symptoms like tremor of
limbs, salivation, slurred speech, incontinence of urine,
rigidity and was not able to stand or walk. All
medications were then stopped and Tab Trihexyphenidyl
2mg 1 tab thrice a day was prescribed. She showed no
any signs of improvement but after 7 days she developed
fever .On examination, Temperature- 102 0F, pulse
rate:140/min, Blood pressure: 110/80 mm of Hg,
Respiratory rate:28/min. Central nervous system
examination showed Clonus, lead pipe like rigidity of
limbs. Babinski sign: negative. On examination of Chest,
Cardiovascular system, Per abdomen examination
showed no abnormality.
Toxicology Screening showed Total Count: 10400/
cumm, Neutrophils: 73%, Erythrocyte sedimentation
rate: 18, Urine examination: Within normal limits,
Blood/urine Culture and Sensitivity: sterile, HbsAg:
negative, HIV: negative, VDRL: non reactive.
Na: 131mEq/L, K: 3.9mEq/L, CPK total: 45, Serum
Creatinine: 0.8mg/dl, serum urea: 33mg/dl, SGPT: 45,
SGOT: 6, ALP: 692 U/L, Total Bilirubin: 0.6mg/dl,
Direct Bilirubin: 0.1mg/dl, Random blood sugar: 90mg/
dl.
Along with consultation from medicine department she
was kept on I.V. fluids, catheterization done and treated
with Inj. Ceftriaxone 1mg twice a day, inj. Phenargan
1amp once a day, Tab Paracetamol 1 tab thrice a day,
Tab Trihexiphenidyl 2mg thrice a day. She had persisting
spike of fever, tachycardia and fluctuating BP with severe
perspiration. Patient was not responding well up to end
of 9 days and started passing sleepless nights, with
minimal feeding, and passing brownish urine. However
the patient looked alert, but was not speaking.
Despite management along with antibiotics and
anticholinergics condition of the patient was not
improving. Then preliminary diagnosis of NMS was
done and conservative management was continued. After
9th day Trihexyphenidyl was stopped and Tab Baclofen
1 tab twice a day, Tab Bromocriptin 1.25 mg twice a
day were added. Inj. lorazepam 2 mg was given stat
.Next day she slept well, tremors were reduced, but
rigidity persisted. She started talking; she was then kept
on oral lorazepam 1 mg twice a day along with
bromocriptin & baclofen. Gradually the signs and
symptoms of patient improved and all medications were
tapered off. After one month of hospital stay patient’s
condition improved remarkably and was discharged.
DISCUSSION
Probable diagnosis of NMS was made on the basis of
risk factor, persisting hyperthermia, muscular rigidity,
and exclusion of other medical illnesses. Investigations
done showed no findings specific for any medical
conditions and patient was not improving.
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DP Limbu et al
Among 373 patients treated with neuroleptics during two
years at psychiatric hospital, 1% developed Neuroleptic
Malignant Syndrome.1 Pooling data from 16 studies of
incidence of NMS in the literature yields 66 cases among
33,720 neuroleptics treated patients i.e. an incidence of
about 0.2%.2,3 NMS has been reported in all age groups,
in cold climates and throughout the seasons in parallel
with the use of neuroleptics.3,4
From the various studies, risk factor was found to be
prior exhaustion, psychomotor activity, dehydration3 in
patient treated with neuroleptics. It has been reported in
association with diverse psychiatric illnesses –mood
disorder,3,5 Catatonia, schizophrenia.6,7
Data on dosage indicate that NMS is not a result of
overdose and usually occurs with dosage within the
therapeutic range.3,4 Moreover, Carroff et al4 and Shalev
and Menitz6 found that high potency agents increased
the risk, whereas in a prospective study Rosebush et al8
found no relationship between potency or dosage and
recurrence of NMS. Shalev and Munitz6 further proposed
that loading rate of neuroleptics is key factor, supported
by Keck et al 9 in which pt with NMS received
significantly higher doses of neuroleptics at greater rates
of increase and more intramuscular inj. than control.
Deng et al9 compared treatment data on 12 NMS Patient
and 102 control, NMS per treated with i.m fluphenazine
Deconate, had 3 times rate of NMS rising to 10 times if
administered without antiparkinsonian. Concomitant use
adjunctive psychotropic drugs like Lithium carbonate,
Tricyclic, Monoamine Oxidase, anti parkinsonian, BZD,
have been proposed another potential risk factor.
Although NMS may progress within hour, it is usually
preceded by insidious neurologic and autonomic signs
that defy diagnosis and prove refractory to conventional
treatment.
Hyperthermia associated with profuse sweating occurs
in 98% of reported NMS Cases, exceeding 38 c in
87%and 40 C in 40%.4,10 Generalized rigidity described
as lead pipe rigidity in its most severe form is reported
in 97% of NMS cases and was associated with
myonecrosis.
The classic NMS patient appears to be alert but dazed
and mute. Autonomic activation and instability,
manifested by sinus tachycardia in 88% of fluctuation
of BP (61%) have been reported in 95% of cases.
Moderate to severe respiratory distress may result from
metabolic acidosis, hyperthermia, chest wall restriction
aspiration pneumonia or pulmonary emboli was
observed in 31% of cases.7
Nevertheless none laboratory findings are specific or
pathognomic, elevated serum creatinine phosphokinase
has been reported in 95%of NMS cases and
myoglobinuria in 67% of cases. 10 Non specific
leucocytosis in 98%, metabolic acidosis in 75% of
cases4,10 non focal generalized slowing on EEG in 54%
of cases.5,11 CT scans of head have been negative in
95%of cases.4,10
Caroff and Mann4 reported 16% of patients developed
NMS within 24hr of initiating neuroleptics, 66% by 1
week, 96% within 30 days and is found to be less likely
after 30 days.
Broad range of disorders presenting with fever, rigidity,
mental status changes, autonomic dysfunction need to
be assessed. Viral encephalitis or post infectious
encephalomyelitis confers great difficulty to distinguish
from NMS. Several cases have been reported in patient
infected with HIV. Clinical examination and brain
imaging need to be done to reveal anatomic lesions
particularly damage to anterior cingulated gyri,
mamillary bodies, periventricular nuclei in the
hypothalamus or brain stem may produce akinetic
mutism resembling NMS, probably due to dopamine
tract passing through these regions.3,12
Though seizure is not common with NMS, fever with
elevation of creatinine phosphokinase has been reported
in status epilepticus. Uncontrolled hyperactivity in major
psychosis (lethal catatonia) can cause exhaustion, stupor,
hyperthermia and death.13,14
Intercurrent infections or metabolic disorder that also
has Parkinsonism or catatonia needs to be ruled out.
Endocrinopathies
like
thyrotoxicosis;
pheochromocytoma may present with extreme
hyperthermia and raised plasma or urine catacholamines.
Also SLE or mixed connective tissue disease may
present with fever, altered mental status and movement
disorder. Most cases of heat stroke associated with
neuroleptics resemble classic heat stroke characterized
by anhidrosis and respiratory alkalosis but not associated
with muscle rigidity. NMS may occur in patients at rest
independent of ambient temperature 2.occupational
exposure to phenolic compounds can cause hyperthermia
, and with muscle rigidity has also followed carbon
monoxide and L asparaginase toxicity.3,10 Malignant
hyperthermia associated with the use of anesthetic gases
and succinylcholine is another drug induced
hypermetabolic disorder indistinguishable from NMS
that results from the effects of triggering drugs on skeletal
muscle.3 Antidopaminergic drugs like metoclopramide
, amoxapine , tetrabenazine and resrpine have been
associated with NMS.10 Lithium in combination with
neuroleptics may increase the risk of NMS. 3,10
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Nepal Medical College Journal
Withdrawal from alcohol or sedative –hypnotics may
present with mental status changes, autonomic
dysfunction and elevated temperature. Withdrawal also
may increase the risk of NMS. In view of this, as well
as their tendency to lower the seizure threshold,
neuroleptics should be used cautiously in these patients.
Based on recent prospective studies. 2,15-17 Basis of
treatment is reduction of risk factors, early recognition,
cessation of neuroleptics, and institution of intensive
medical care focusing on fluid replacement, reduction
of temperature and support of cardiac, respiratory and
renal functions. Based on retrospective data, Rosenberg
and Green 18 found both Datrolene sodium and
Bromocriptine effective in ameliorating the signs and
symptoms.
Dopamine has been implicated by several evidences in
pathogenesis of NMS. Drug dosage or potency2,16 rate
and route of drug administration19 and recurrences4,20 has
supported the correlation of NMS and neuroleptics.
Besides metoclopramide and amoxapine which are
dopamine antagonists have been also known to cause
NMS. Moreover, dopamine agonists for idiopathic
Parkinson’s disease have developed NMS like states
when drugs were withdrawn or lost effectiveness.
Ultimately, dopamine agonists appear to be effective in
treating NMS and contribute to recrudescence of
symptoms if withdrawn prematurely.21,22
It has been reported that hyperthermia of NMS is due to
peripheral heat production associated with severe
muscular rigidity secondary to withdrawal of striatal
dopamine drive, rather than being initially mediated by
the hypothalamus, which is not involved in striatonigral
degeneration.23
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