NMS

• Neuroleptic malignant syndrome is a life-threatening neurological disorder characterised by confusion, fever, and rigidity.
• Overview:

  • Neuroleptic malignant syndrome is a life-threatening neurological disorder characterised by confusion, fever, muscle rigidity and dysautonomia
  • Associated with high mortality (10-20%)
  • Treatment is largely supportive and most episodes will resolve within 2 weeks of removing the offending drug
• Epidemiology:

  • Affects up to 3% of patients taking antipsychotics
  • Can occur at any age but predominantly occurs in young adults
  • More common in males
• Pathophysiology:

  • Most commonly associated with potent typical antipsychotics
  • Suspected that central blockade of dopamine in the hypothalamus leads to hyperthermia and dysautonomia
  • Blockage of other central pathways can give rise to movement disorders
  • There may be direct toxic effects of these drugs on peripheral muscle or disruption of the sympathetic nervous system
  • Typically occurs within the first 2 weeks of starting an antipsychotic or increasing the dose
• Neuroleptic malignant-like syndrome:

  • Also called parkinsonism hyperpyrexia syndrome
  • Precipitated by a sudden dose reduction or withdrawal of antiparkinson agents e.g. L-DOPA
• Risk factors:

  • Higher dose
  • higher potency antipsychotics e.g. haloperidol, fluphenazine
  • Concomitant drug use e.g. lithium
  • Depot formulations - long acting
  • Acute medical illness
  • Acute catatonia
  • Previous NMS
• Clinical features:

  • Altered mental status - often presents with agitation and delirium. Catatonia can be present. may progress to severe encephalopathy and coma
  • Rigidity
  • Fever - less pronounced with atypical antipsychotics
  • Dysautonomia - autonomic instability - tachycardia, labile blood pressure, diaphoresis and arrhythmias
• Diagnosis:

  • Diagnosis usually made in patients who present with characteristic clinical features who are taking antipsychotics
  • Diagnosis can be supported with elevated creatinine kinase due to muscle rigidity - may be normal if early in presentation
  • If severe, muscle necrosis and rhabdomyolysis may develop
• Hyperreflexia and clonus are characteristic of serotonin syndrome but not present in NMS
• Investigations:

  • U&Es - electrolyte derangements and AKI may be seen particularly with the development of rhabdomyolysis
  • Imaging - CT/MRI head important to rule out other causes of confusion
  • Lumbar puncture may be needed to exclude cerebral infection or autoimmune encephalitis
• Management:

  • Stop antipsychotic
  • IV fluids to maintain euvolemic state
  • Antipyretics and cooling blankets for hyperthermia
  • Antihypertensives (e.g. clonidine) for profound hypertension
  • Benzodiazepines for agitation
  • In severe cases patients may require organ support e.g. hemofiltration
• Medical therapy for moderate-severe cases:

  • Dantrolene - ryanodine receptor agonist
  • Causes skeletal muscle relaxation
  • Helps treat hyperthermia and rigidity
  • Bromocriptine - dopamine agonist
  • Restores dopaminergic tone - helps rigidity
• Complications:

  • Cardiac arrest
  • Cardiac arrhythmias
  • AKI
  • Rhabdomyolysis
  • DIC
  • Seizures
  • Respiratory failure
  • VTE