Neuroleptic malignant syndrome

Introduction

Characterised by neuromuscular rigidity, altered mental status and autonomic instability
Central deficiency of dopamine at nigrostriatal, mesolimbic and hypothalamic-pituitary pathways is pivotal +- peripheral skeletal muscle mitochondrial dysfunction
Develops in 0.02-2.5% of patients on neuroleptics and hasn’t altered since atypical antipsychotics introduced
More likely in those with severe illness, dehydrated, catatonia or previous NMS
10-20% mortality rate

Clinical features

CNS – Confusion, delirium, stupor, coma
Autonomic instability – Hyperthermia, tachycardia, hypertension, abnormal respiratory function and cardiac dysrhythmias
Neuromuscular – Lead pipe rigidity, generalised bradykinesia/akinesia, mutism/staring, dysarthria, dystonia and abnormal posturing, abnormal involuntary movements and incontinence
Onset takes 24-72 hours and recovery may take days to months
Leukocytosis >40 is common
LFT, renal, metabolic acidosis, hypocalcaemia, hypomagnesaemia and decreased serum iron are all seen
Cranial CT and MRI are normal
LP may show elevated CSF protein in 37% of cases
Metabolic encephalopathy (generalised slow wave activity) on EEG

Diagnostic criteria

High risk factors

High doses of neuroleptic agent
Increased dosing of neuroleptic agent in last 5 days
Large magnitude dose increase
Parenteral administration
Simultaneous use of two or more neuroleptic agents
Use of haloperidol or IM fluphenazine
Young age
Male sex
Psychiatric comorbidity
Genetic factors
Pre-existing organ brain disorders e.g. infectious encephalitis, AIDS, tumors)
Dehydration
High CK levels during psychosis
Pre-existing medical disorders e.g. trauma, infection, malnutrition, premenstrual phase, thyrotoxicosis

Differential

Acute lethal (malignant) catatonia
- Does not need history of recent neuroleptic use
- Typically has abnormal posturing and waxy flexibility
Malignant hyperthermia
Serotonin syndrome
Anticholinergic syndrome
Sympathomimetic syndrome
Encephalitis
Metabolic encephalopathy

Complications

Management

ABC
Avoid any dopamine antagonists
Benzodiazepines are useful in mild-moderate cases for muscle relaxation and control of behaviour HOWEVER may play a role in aetiology of NMS and as such more specific agents such as bromocriptine are preferred in severe cases
Hypertension and tachycardia can be managed with GTN or sodium nitroprusside infusions BUT
Bromocriptine indicated if significant autonomic instability

Bromocriptine

Dopamine agonist indicated in moderate to severe cases
Bromocriptine 2.5mg PO/NG every 8 hours, increasing to 5mg every 4 hours
Adverse effects
- Postural hypotension, headache, nausea, vomiting, dyskinesia, erythromelalgia,
Autonomic instability and fever usually improve within hours
Neuromuscular changes (1-2 days) and delirium (several days) may take days to resolve
Should be continued for 1-2 weeks before tapering

Dantrolene

For severe muscle rigidity and fever
IV 2-3mg/kg/day up to total dose 10mg/kg/day
Can convert to oral and give 100-400mg/day in divided doses for 10 days or convert to bromocriptine

ECT

Has been useful in treating fever, sweating and conscious level through central dopaminergic upregulation
Controversial but indicated if:
- Severe NMS refractory to all else
- Severe NMS that is difficult to differentiate from malignant catatonia
- Treatment of residual catatonic effects of NMS
- To treat underlying psychotic depression or catatonia that lead to neuroleptic use in the first place

Last Updated on October 14, 2020 by Andrew Crofton

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