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Cognitive Function
Conscious Level
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Idiopathic Intrancranial Hypertension
Myasthenia Gravis
Serotonin Syndrome
Neuroleptic Malignant Syndrome
Guillain-Barré Syndrome
Acute Vertigo
Transient Global Amnesia
Brain Tumours
Lumbar Puncture
Transient Loss of Consciousness
Other Funny Turns
Haematemesis – ACP
Head and Neck Injury
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Status Epilepsy in Adults
The First Seizure
Multiple Sclerosis
Coma
Neuroleptic Malignant Syndrome
Last updated 3rd December 2020
Page Created on 4th February 2020. Due for Review 4th February 2021.
Introduction
- A serious, potentially life-threatening complication of treatment with antipsychotic drugs or abrupt withdrawal of dopamine agonists.
- Characterised by a tetrad of altered mental status, muscle rigidity, autonomic instability, and hyperthermia.
- A diagnosis of exclusion. Common differential diagnoses are sepsis and drug reactions.
- NMS is a medical emergency. Treatment consists of immediate withdrawal of antipsychotic medication, supportive measures eg rehydration and cooling and pharmacological therapy with benzodiazepines if supportive measures fail.
- Documenting this reaction in the medical records is important.
Aetiology
- All antipsychotic medications have been associated with NMS, presumably through their antagonism of dopamine D2 receptors.
- A syndrome indistinguishable from NMS occurs in Parkinson’s disease in the context of abrupt dopamine agonist withdrawal. Generally, any rapid reduction in dopamine/dopamine agonist availability at post-synaptic receptors increases the risk of NMS, but even long-term dopamine antagonism increases NMS risk.
- Predisposing structural brain abnormalities and CNS disorders of dopamine eg Parkinson’s disease raise the risk of NMS on exposure to antipsychotic medications.
- NMS is also associated with exposure to dopamine antagonists other than antipsychotics, including metoclopramide, lithium, and certain antidepressants.
Diagnosis is a Quintad
- Altered mental status: characterised by confusion, delirium, or stupor
- Muscle rigidity: patients can develop muscle rigidity de novo, or worsening of preexisting muscle rigidity. It can be difficult to distinguish these 2 entities.
- Hyperthermia: may occur simultaneously with diaphoresis or flushing, indicating a disruption of normal thermoregulatory coordination.
- Autonomic disturbances: may include labile hypertension, tachycardia, tachypnoea, urinary incontinence, and diaphoresis.
- Serum CK levels: patients with NMS may have significant increases in serum CK indicating muscle injury, with the risk of myoglobinuric acute kidney injury.
Differential Diagnosis
-
None of these signs are exclusive to NMS and other important diagnoses should be excluded eg
- Sepsis
- Catatonia
- Serotonin syndrome
- Mania
Management
- Withdrawal of antipsychotic medication
- Supportive therapy
- Pharmacological therapy
Withdrawal of Antipsychotic Medication
- If NMS is suspected, antipsychotics and dopamine antagonists must be stopped, and dopamine agonists must be restored or continued. Other drugs that may be contributory eg lithium may need to be stopped.
- If the patient’s psychiatric symptoms compel resumption of antipsychotic medication, a delay of at least 2 weeks following complete resolution of the NMS episode is advisable.
Supportive Therapy
- Most patients are dehydrated in the acute phase of the illness; therefore, administration of fluids and monitoring and correction of electrolyte abnormalities are essential. When rhabdomyolysis occurs, vigorous hydration with intravenous fluids is recommended to prevent acute kidney injury.
- Hyperthermia can be treated with physical cooling measures; antipyretics such as paracetamol or ibuprofen do not appear to be effective in NMS.
- Patients with dysphagia might require a nasogastric tube for the administration of fluids, nutrition, and pharmacological therapy.
Pharmacological Therapy
- Lorazepam: 1-4 mg orally/intravenously as a single dose
- Dantrolene (muscle relaxant), bromocriptine and amantadine (dopamine agonists) are often used in the treatment of NMS despite limited evidence of their effectiveness.
Outcome
- Some cases of NMS are milder than those in published reports, which may reflect a greater awareness of the risk for this syndrome and more prompt intervention, but it is possible that NMS manifests itself in a spectrum of clinical severity.
- Mortality is between 5 and 10%
- Recurrence of NMS has been estimated to be as high as 30%, but there are no reliable data regarding recurrence.
- It is usually recommended that rechallenge be postponed until at least 2 weeks after complete resolution of the syndrome.
- Rechallenge should proceed slowly and under close monitoring.