C: Topic 18 : The symptoms and treatment of neuroleptic malignant syndrome.

Definition of NMS

Life threatening neuro disorder caused by dopamine blocking agents such as antipsychotics.

Causes of NMS

• genetic predisposition

• High-potency first-generation antipsychotics (most common association)

• Second-generation antipsychotics

• Other dopamine antagonists, e.g., metoclopramide, promethazine

Pathophysiology

• Central D₂ receptor blockade in the nigrostriatal pathway and hypothalamus, resulting in movement disorders and impaired thermoregulation

• Increased sympathetic tone disrupts autonomic regulation and increases muscle tone and metabolism.

• Increased release of calcium from the smooth endoplasmic reticulum of striated muscle cells, resulting in increased contractility and muscle breakdown

When do clinical features usually start?

Within 2 weeks of 1st dose

what are the main categories of symptoms?

• mental status changes

• autonomic instability

• hyperthermia

• parkinsonism

What mental status changes will be seen?

• Delirium (e.g., reduced vigilance)

• Confusion

• Stupor

• Catatonia

Symptoms seen with autonomic instability?

• Tachycardia, dysrhythmias, labile blood pressure

• Tachypnea

• Diaphoresis, often with a greasy appearance

• Sialorrhea

• Urinary incontinence

Symptoms seen with Parkinsonism?

• Muscle rigidity (lead-pipe rigidity)

• Akinesia

• Tremor

Which blood lab results will be seen?

• ↑↑ Creatine kinase

• Liver ↑ transaminases, ↑ ALP, ↑ LDH

• leukocytosis

• Metabolic acidosis

What’ll be the electrolyte abnormalities?

• hypocalcemia

• hyperkalemia

• hypo/hypernatremia

What is the treatment approach?

• discontinue drug

• Supportive care eg ICU admission

Whch drugs can help treat?

• Dantrolene: Ryanodine rec antagonist- prevents release of Ca from SR so dec muscle rigidity & hyperthermia

• Benzos for psychomotor agitation

• dopamine agonists eg bromocriptine, amantadine

• CCB for HTN

What complication can occur?

rhabdomyolysis