Neuroleptic Malignant Syndrome Clinical Presentation

Updated: Aug 08, 2022
  • Author: Theodore I Benzer, MD, PhD; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
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The diagnosis of neuroleptic malignant syndrome is based on clinical features. Cardinal features are as follows:

  • Severe muscular rigidity
  • Hyperthermia
  • Autonomic instability
  • Changes in the level of consciousness

The syndrome occurs only after exposure to a neuroleptic drug. Most cases develop shortly after initiation of therapy or increasing the dose. The onset can be within hours, but on average is 4-14 days, after the start of therapy; 90% of cases occur within 10 days. However, neuroleptic malignant syndrome can occur at any time during neuroleptic use, even years into therapy. Once the syndrome starts, it usually evolves over 24-72 hours.

A summary of the clinical features of neuroleptic malignant syndrome includes the following:

  • Rigidity
  • Hyperthermia
  • Diaphoresis
  • Pallor
  • Dysphagia
  • Dyspnea
  • Tremor
  • Incontinence
  • Tachycardia
  • Shuffling gait
  • Psychomotor agitation
  • Delirium progressing to lethargy, stupor, coma

Patients with atypical presentations of neuroleptic malignant syndrome may not exhibit muscle rigidity or hyperthermia initially; those features may develop over time or not at all. [33, 34] Clozapine-induced neuroleptic malignant syndrome may be more likely to manifest without extrapyramidal features, including rigidity and tremor, but cases involving other atypical antipsychotic drugs generally present in a typical manner. [3]


Physical Examination

Neuroleptic malignant syndrome tends to start with muscular rigidity and progress to hyperthermia with autonomic instability and a fluctuating level of consciousness. Compared with adults, children and adolescents with neuroleptic malignant syndrome tend to present with more dystonia and less tremor.

General examination findings indicative of autonomic dysregulation include the following:

  • Hyperthermia (temperature > 38°C)
  • Diaphoresis
  • Sialorrhea
  • Tachycardia
  • Tachypnea, respiratory distress (31% of cases)
  • Increased or labile blood pressure
  • Hypoxemia (low pulse oximeter reading)
  • Incontinence

Patients may exhibit signs of dehydration secondary to hyperpyrexia and inadequate oral intake. Pallor or rash may be present. In rare cases, a reversible cardiomyopathy mimicking cardiac infarction may develop. [35]

Signs and symptoms of decreased dopaminergic activity include the following:

  • Muscular rigidity (typically, “lead pipe” rigidity)
  • Dysphagia
  • Short, shuffling gait
  • Resting tremor
  • Dystonia
  • Dyskinesia

Excessive or purposeless motor activity and tremor can reflect psychomotor agitation. Mental status may be altered, ranging from agitation to drowsiness, confusion, and coma. Delirium is characterized by the following:

  • Loss of awareness of both the internal and external worlds
  • Loss of orientation in time and space
  • Reduced ability to direct and sustain attention
  • Speech that is often mumbled and incoherent
  • Delusions and hallucinations, especially visual
  • Fluctuating level of consciousness, from lethargy to stupor and coma