Differentials

Sepsis

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SIGNS / SYMPTOMS

Central nervous system or systemic signs/symptoms of infection.

Sepsis may be the primary diagnosis but may also be present (later in course) as a complication of NMS. Sometimes concurrent infections (e.g., respiratory or urinary tract infection) may further complicate diagnostic assessment.[6][15]​​[53]

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Blood, urine, sputum, cerebrospinal fluid (from lumbar puncture), and other cultures may be positive for infective organisms.

Status epilepticus

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Non-convulsive status epilepticus is difficult to distinguish clinically from NMS.

INVESTIGATIONS

EEG may differentiate between status epilepticus and NMS.[54]

Drug misuse/overdose

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

History of drug misuse, overdose symptoms.

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Diagnosis is usually based on history, physical examination, and toxicology screen. Stopping all possible causative medications, when appropriate, is important.

Catatonia

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SIGNS / SYMPTOMS

Withdrawal, predominance of motor abnormalities, absence of hyperthermia, gradual evolution of presentation, potential history of prior episodes.

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Diagnosis is usually based on history and physical examination.

Serotonin syndrome

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SIGNS / SYMPTOMS

Rapid onset after administration of a serotonergic drug, hyperreflexia, clonus, diarrhoea.

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Diagnosis is usually based on history and physical examination.[55]

Mania

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SIGNS / SYMPTOMS

Patients usually present with marked agitation, psychosis, and confusion.

INVESTIGATIONS

Diagnosis is usually based on history and physical examination.

Malignant hyperthermia

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Occurs in genetically susceptible people following exposure to anaesthetics or depolarising muscle relaxants; rapid onset, trismus.

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Diagnosis is usually based on history and physical examination.

Heat stroke

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SIGNS / SYMPTOMS

Rapid onset, occurs during episodes of prolonged elevations in ambient temperatures; diaphoresis and muscle rigidity usually not present.

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Diagnosis is usually based on history and physical examination, and confirmed by muscle contracture test.

Metabolic conditions

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SIGNS / SYMPTOMS

Various metabolic effects (e.g., dehydration, hyponatraemia, hypokalaemia) can cause delirium presentation.

INVESTIGATIONS

Basic and extended metabolic panels (e.g., serum electrolytes, osmolality, serum transaminases, and blood glucose) may be abnormal depending on the specific metabolic condition present.

Brain infarcts

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SIGNS / SYMPTOMS

May mimic NMS.

INVESTIGATIONS

CT/MRI head may show signs of stroke.

Normal pressure hydrocephalus

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Slowing of gait, urinary urgency, possibly with cognitive impairment. Onset of symptoms is generally insidious (over months to years).

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CT/MRI head may show mild to moderate ventricular enlargement, periventricular leukomalacia, cerebral infarction, relative preservation of cortical gyri and sulci, aqueduct flow void, reduced diameter of the corpus callosum, and widened callosal angle.

Brain tumours

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

May mimic NMS.

INVESTIGATIONS

CT/MRI head may show evidence of tumour.

Autoimmune encephalitis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Anti-NMDA receptor encephalitis can mimic psychiatric disorders and prompt treatment with antipsychotic medications.

Patients may have signs and symptoms suspicious for NMS.

INVESTIGATIONS

Anti-NMDA-receptor antibodies.

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