Neuroleptic Malignant Syndrome

Chapter 82 Neuroleptic Malignant Syndrome



Jennifer M. Hall, DO , James L. Jacobson, MD




1 What is neuroleptic malignant syndrome (NMS)?


NMS is a rare, potentially fatal, idiosyncratic complication of antipsychotic medications. The usual presentation consists of four primary features:



image Hyperthermia


image Extreme generalized muscular rigidity


image Autonomic instability


image Altered mental status


These features generally appear 24 to 72 hours after the administration of an antipsychotic; however, NMS can also occur with chronic use. Altered mental status is the first presenting symptom in 80% of NMS cases. Mean recovery time after antipsychotic discontinuation is 7 to 10 days but may be prolonged when long-acting depot antipsychotics are implicated. For other common features of NMS, see Box 82-1.



Box 82-1 Signs and Symptoms of Neuroleptic Malignant Syndrome



Primary Features




Hyperthermia


Altered mental status


Autonomic instability


Extreme generalized rigidity (often called lead pipe rigidity)



Other Common Features




Laboratory evidence of muscle injury (elevated creatine kinase muscle fraction)


Tremor


Mutism


Leukocytosis


Labile hypertension (less often hypotension)


Tachycardia


Tachypnea


Dysphagia


Diaphoresis


Sialorrhea


Incontinence



2 How common is NMS?


Recent data suggest that the incidence of NMS in patients treated with antipsychotics ranges between 0.01% and 0.02%. Previous estimates were as high as 3%; however, because of increased awareness, judicious antipsychotic use, and rapid recognition and treatment the incidence of NMS has declined.



3 What is the mortality rate for NMS?


Despite the declining incidence of NMS, it remains a significant source of morbidity and mortality among patients receiving antipsychotics. The original description of NMS in 1968 estimated a mortality rate as high as 75%, which subsequently declined to 20% to 30% in the 1980s. More recently, the U.S. Agency for Healthcare Research and Quality reports that, of an estimated 2000 cases diagnosed annually in hospitals, mortality rates approximate 10%. Cause of death in NMS is usually a result of cardiac or respiratory arrest (cardiac failure, infarction, arrhythmia, aspiration pneumonia, or pulmonary emboli), myoglobinuric renal failure, or disseminated intravascular coagulation.



4 What is the pathogenesis of NMS?


Although the pathophysiology of NMS is poorly understood, dopamine receptor antagonism in the basal ganglia, hypothalamus, and postganglionic sympathetic neurons is hypothesized to be the primary culprit. Given the complexity of NMS, it is also hypothesized that other neurotransmitter systems involving γ-aminobutyric acid (GABA), serotonin, and glutamate have a contributing role in initiation and progression of NMS.



5 What are the diagnostic criteria for NMS?


The diagnosis of NMS is a clinical diagnosis of exclusion in which the administration of an antipsychotic medication has occurred (usually 24-72 hours) before the onset of the syndrome.


Research criteria in the American Psychiatric Association’s Diagnostic and Statistical Manual, fourth edition (DSM-IV-TR), include the following:



A. The development of severe muscle rigidity and elevated temperature associated with the use of neuroleptic medication.


B. Two or more of the following: diaphoresis, dysphagia, tremor, incontinence, changes in level of consciousness ranging from confusion to coma, mutism, tachycardia, elevated or labile blood pressure, leukocytosis, and laboratory evidence of muscle injury.


C. The symptoms in criteria A and B are not due to another substance or a neurologic or other general medical condition.


D. The symptoms in criteria A and B are not better accounted for by a mental disorder.



6 What is the differential diagnosis of NMS?


NMS is a clinical diagnosis of exclusion; therefore central, systemic, and toxic causes of hyperthermia, rigidity, rhabdomyolysis, and altered mental status must be excluded. See Box 82-2.



Box 82-2 Differential Diagnosis of Neuroleptic Malignant Syndrome



Infectious




Meningitis or encephalitis


Postinfectious encephalomyelitis syndrome


Brain abscess


Sepsis



Psychiatric or Neurologic




Idiopathic malignant catatonia


Agitated delirium


Benign extrapyramidal side effects


Nonconvulsive status epilepticus


Structural lesions, particularly involving the midbrain



Toxic or Pharmacologic




Anticholinergic delirium


Salicyl poisoning


MH (inhalational anesthetics, succinylcholine)


Serotonin syndrome (monoamine oxidase inhibitors, triptans, linezolid)


Substances of abuse (amphetamines, hallucinogens)


Withdrawal from dopamine agonists, baclofen, sedative-hypnotics, and alcohol



Endocrine




Thyrotoxicosis


Pheochromocytoma



Environmental




Heat stroke



7 Are there specific laboratory findings for NMS?


No laboratory findings are pathognomonic for NMS, but findings may support or confirm the diagnosis of NMS while excluding other systemic illnesses. Common laboratory abnormalities include the following:



image Elevated serum creatine kinase level of 1000 to 100,000 International Units/L


image Leukocytosis (10,000-40,000/mm3)


image Elevated lactate dehydrogenase, alkaline phosphatase, and liver transaminase levels


image Electrolyte disturbances: hypernatremia, hyponatremia, hyperkalemia, hypocalcemia, hypomagnesemia, and hypophosphatemia


image Metabolic acidosis


image Myoglobinuric acute renal failure: proteinuria, elevated blood urea nitrogen and creatinine levels


image Low serum iron concentration

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Jul 6, 2016 | Posted by in CRITICAL CARE | Comments Off on Neuroleptic Malignant Syndrome

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