Pediatric Neuroleptic Malignant Syndrome 

  • Author: Mary C Mancini, MD, PhD; Chief Editor: Timothy E Corden, MD   more...
 
Updated: Nov 21, 2011
 

Background

Neuroleptic malignant syndrome (NMS), first described in 1963 by Delay et al in the French psychiatric literature, is a rare but potentially lethal complication of treatment with potent neuroleptics.

Neuroleptic drugs (ie, antipsychotic drugs, antischizophrenic drugs) are primarily used to treat schizophrenia and other psychotic states. Traditional drugs have action through inhibition of dopaminergic receptors, whereas the newer agents work by causing blockade of serotonin receptors.

Neuroleptic malignant syndrome often occurs as treatment begins, when physicians progressively increase doses of neuroleptics. No clear relationship has been established between neuroleptic dosage and risk of developing neuroleptic malignant syndrome. A drug's potential for inducing neuroleptic malignant syndrome seems to parallel its antidopaminergic activity.

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Pathophysiology

Neuroleptic malignant syndrome pathophysiology is largely speculative. Neuroleptic drugs block dopaminergic receptors, creating a functional dopamine-deficiency state. Dopaminergic receptor blockade in the substantia nigra causes muscle rigidity and alters thermoregulation in the hypothalamus. Increased heat production from muscle rigidity causes fever, impaired heat dissipation (by reducing cutaneous vasodilatation or by sweating), and possibly a higher core temperature set point in the hypothalamus.

MM isoenzyme of creatine kinase increases. Muscle biopsy demonstrates morphologic and histoenzymologic abnormalities in muscle fibers.

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Epidemiology

Frequency

International

Incidence varies because of differing diagnostic criteria, patient characteristics, and available information. Reported incidence of neuroleptic malignant syndrome in neuroleptic-treated patients ranges from 0.1-5.5%.

Neuroleptic malignant syndrome onset ranges from 1-44 days following administration of neuroleptic drug; mean onset is 10 days. Lazarus et al reported neuroleptic malignant syndrome occurring in 67% of patients within 1 week and 96% of patients within 30 days following administration of neuroleptics.[1, 2]

Mortality/Morbidity

Once reported to be 20-30%, the mortality rate is now estimated at 5-11.6%. Mortality is caused by one or more complications (eg, respiratory failure, cardiovascular collapse, renal failure, arrhythmias, thromboembolism).[3] Renal failure is associated with a 50% mortality rate.

No consistent long-term physical, neurological, cognitive, or laboratory sequelae have been attributed to neuroleptic malignant syndrome alone, although sequelae may result from such secondary complications as prolonged hypoxia or ischemic encephalopathy. Researchers have noted sporadic cases of prolonged rigidity and long-term neuropsychological deficits.

Sex

The male-to-female ratio is 2:1.

Age

Neuroleptic malignant syndrome occurs in people of all age groups, with a reported mean age of 40 years.[2]

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Contributor Information and Disclosures
Author

Mary C Mancini, MD, PhD  Professor and Chief of Cardiothoracic Surgery, Department of Surgery, Louisiana State University School of Medicine in Shreveport

Mary C Mancini, MD, PhD is a member of the following medical societies: American Association for Thoracic Surgery, American College of Surgeons, American Surgical Association, Phi Beta Kappa, Society of Thoracic Surgeons, and Southern Surgical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Girish G Deshpande, MD, MBBS, FAAP  Associate Professor of Pediatrics, Interim Director and Division Chief of Critical Care Medicine, Department of Pediatrics, University of Illinois College of Medicine at Peoria; Consulting Staff, Division of Critical Care Medicine, Children's Hospital of Illinois at OSF St Francis Medical Center

Girish G Deshpande, MD, MBBS, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

G Patricia Cantwell, MD  FCCM, Professor of Clinical Pediatrics, Chief, Division of Pediatric Critical Care Medicine, University of Miami, Leonard M Miller School of Medicine; Medical Director, Palliative Care Team, Director, Pediatric Critical Care Transport, Holtz Children's Hospital, Jackson Memorial Medical Center; Medical Manager, FEMA, Urban Search and Rescue, South Florida, Task Force 2; Pediatric Medical Director, Tilli Kids – Pediatric Initiative, Division of Hospice Care Southeast Florida, Inc

G Patricia Cantwell, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Heart Association, American Trauma Society, National Association of EMS Physicians, Society of Critical Care Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry J Evans, MD  Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children's Medical Center

Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Mary E Cataletto, MD  Director of Children's Sleep Services, Winthrop Sleep Disorders Center, Mineola, NY; Professor of Clinical Pediatrics, State University of New York at Stony Brook, Stony Brook, NY

Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians

Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Timothy E Corden, MD  Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society

Disclosure: Nothing to disclose.

References

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