Neuroleptic malignant syndrome: an easily overlooked neurologic emergency

Figures & data

Table 1 A list of some known drugs (of different categories) that can cause neuroleptic malignant syndrome

Drug	Pharmacologic category
Amoxapine	Antidepressant, tetracyclic
Amisulpride	Nonconventional antipsychotic
Aripiprazole	Nonconventional antipsychotic
Chlorpromazine	Conventional antipsychotic, anticholinergic, and antihistaminic
Citalopram	SSRI antidepressant
Clozapine	Potent nonconventional antipsychotic
Desipramine	Antidepressant, tricyclic
Domperidone	Dopamine antagonist, antiemetic
Dosulepine	Antidepressant, tricyclic
Droperidol	Antipsychotic, antiemetic, and neuroleptanalgesic
Fluphenazine	Conventional antipsychotic
Haloperidol	Potent conventional antipsychotic
Lithium salts	Mood stabilizer
Metoclopramide	Antiemetic
Olanzapine	Nonconventional antipsychotic
Paliperidone	Nonconventional antipsychotic
Perphenazine	Potent conventional antipsychotic
Phenelzine	Antidepressant, anxiolytic, and irreversible nonselective MAOI
Prochlorperazine	Antiemetic, conventional antipsychotic
Promethazine	Antihistaminic, conventional antipsychotic
Quetiapine	Nonconventional antipsychotic
Reserpine	Antihypertensive, antipsychotic
Risperidone	Nonconventional antipsychotic
Tetrabenazine	VMA2 inhibitor, used in movement disorders (hyperkinesia)
Thioridazine	Nonconventional antipsychotic
Valproate	Anticonvulsant
Ziprasidone	Nonconventional antipsychotic

Abbreviations: MAOI, mono amine oxidase inhibitor; SSRI, selective serotonin reuptake inhibitors; VMA2, vesicular monoamine transporter 2.

Table 2 Unrelated disorders as elements necessary to be differentially diagnosed from neuroleptic malignant syndrome

Category	Description	Detail
CNS	Infections	Meningitis, encephalitis, tetanus
	Diseases	Autoimmune encephalitis, seizures, CNS vasculitis
	Trauma	Acute hydrocephalus
		Acute spinal cord injuries
Systemic infections	Pneumonia, sepsis
Endocrine diseases	Thyrotoxicosis
	Pheochromocytoma
Drugs	Intoxication	Phencyclidine, ecstasy, cocaine, amphetamine, lithium salts
	Impaired thermoregulation	Neuroleptics can predispose heat stroke
	Withdrawal	Intrathecal baclofen
Neuromuscular	Acute dystonia	Muscle rigidity
Porphyria	CNS and dermatologic types	Accumulation of porphyrin in the body

Abbreviation: CNS, central nervous system.

Table 3 Suggested workup blood tests required when neuroleptic malignant syndrome is suspected

Requested test	Why requested
Complete blood picture	To exclude leukocytosis and all kinds of hemolysis and its consequences
Blood cultures	To exclude possibilities of septic shock (coma)
LFTs	To exclude hepatic failure for one reason or another
BUN and creatinine levels	To exclude renal failure
Calcium, phosphate, potassium, and sodium levels	To exclude electrolyte imbalances and hemolysis
CK level	To exclude or prove rhabdomyolysis or other myocytes type necrosis
Serum iron level	Because of rhabdomyolysis and other hemolytic pathologies
Urine myoglobin level	To exclude myoglobinuria
Arterial blood gas analysis	To exclude respiratory failure and metabolic acidosis
Coagulation studies	To exclude hepatic failure and DIC
Serum and urine toxicologic screening	To exclude ASA, cocaine and amphetamines poisoning

Abbreviations: ASA, acetyl salicylic acid; BUN, blood urea nitrogen; CK, creatine kinase; DIC, disseminated intravascular coagulopathy; LFTs, liver function tests.

Table 4 Laboratory data expected to be seen in a typical case of neuroleptic malignant syndrome

Parameters	Changes
Enzymes and abnormal protein in plasma
LDH	Increased
CK	Increased in (50%–100% of cases)
ALP	Increased
ASAT and ALAT	Increased
Myoglobin	Myoglobinemia
Serum electrolytes and proteolysis remnants
Phosphate	Hyperphosphatemia
Potassium	Hyperkalemia
Calcium	Hypocalcemia
Magnesium	Hypomanesemia
Sodium	Hypo or hypernatremia
Uric acid	Hyperuricemia
Urea	Uremia (increased BUN)
Serum iron	Decreased
Elements of blood
Leukocytes	Leukocytosis (70%–80% of cases)
Blood platelets (thrombocytes)	Thrombocytosis (thrombocytopenia*)
Urine
Protein	Proteinuria (increased protein)
Myoglobin	Myoglobinuria (increased myoglobin)
pH (blood gas analysis)	Decreased (metabolic acidosis)

Note:

* Very rarely, for more information see the study by Ghani et al.⁸¹

Abbreviations: ALP, alkaline phosphatase; ALAT, alanine aminotransferase; ASAT, aspartate aminotransferase; BUN, blood urea nitrogen; CK, creatine kinase; LDH, lactate dehydrogenase.

Figure 1 Chemical structures of dopamine and some of the agents referred to in this work.

GhaniSOAhmedWMarcoLANeuroleptic malignant syndrome and severe thrombocytopenia: case report and literature reviewAnn Clin Psychiatry2000121515410798826

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