The Neuroleptic Malignant Syndrome: Often an Unrecognized Geriatric Problem

To the Editor: The neuroleptic malignant syndrome (NMS) has been widely described but may be unrecognized in older people. We report four recent cases that underscore the particular vulnerability of geriatric patients for development of NMS and its potential lethality.1 An 87-year-old woman with a history of mild dementia, treated with occasional haloperidol for agitation, developed rhinorrhea, cough, and fever 5 days before admission. Tremors began, then weakness, decreased activity, inability to ambulate, and fever of 102.5°F. Evaluation revealed a serum creatine phosphokinase (CPK) greater than 3000 U/L. The patient was referred for admission. She was combative, unable to follow commands, exhibited lip smacking, and had generalized rigidity. Her blood pressure was 110/70, heart rate 84/minute, respiratory rate 28/minute, and temperature 99.4°F. A urinary tract infection was found. Haloperidol was discontinued; vigorous hydration and antibiotics were administered. After 4 days her symptoms resolved, and CPK decreased. A 62-year-old woman was admitted with fever, rigidity, lethargy, and inability to eat 3 weeks after a stroke. Her history included tuberculosis, venous thrombosis, diabetes, hypertension, and dementia. Medications were aspirin, haloperidol, isoniazid, rifampin, ethambutol, and pyridoxine. A respiratory rate of 20/minute and temperature of 101°F was noted. The CPK was 745 U/L. A CT scan of the head revealed atrophy and periventricular white matter changes; a lumbar puncture demonstrated normal findings except for 25 red blood cells. Haloperidol was discontinued; she was treated with nasogastric feeding, hydration, and bromocriptine. The fever, rigidity, tremors, and CPK elevation persisted for weeks. An exhaustive evaluation was undertaken, but she died. A 92-year-old male nursing home resident was admitted with cellulitis. His medications were quinapril, cobalamin, furosemide, sertraline, and amantadine. Two days later he developed confusion, rigidity, tremor, and fever of 102°F. Amantadine was discontinued. The temperature rose to 106°F. The leukocyte count was 24.3 k/uL and CPK was 523 U/L. Other testing, including lumbar puncture, was unremarkable. Amantadine, bromocriptine, and hydration were begun. It was then discovered that the patient had received levodopa for Parkinson's disease before admission. The CPK rose to 911 U/L. Pneumonia developed. The patient became anuric. The rigidity, CPK elevation, and renal failure slowly resolved, but the patient remained confused and unable to eat. His family declined placement of a feeding tube. He developed a pressure ulcer and recurrent aspiration pneumonia, and died 65 days after admission. A 75-year-old woman with a history of hypertension, syphilis, and dementia and treated with haloperidol for agitation was admitted with a change in mental status, rigidity, and fever after 3 weeks of lethargy, anorexia, and inability to walk. She was cachectic, lethargic, had generalized rigidity and had a temperature of 101°F. The hematocrit was 30%, and CPK 360 U/L. A chest radiograph revealed a right middle lobe infiltrate and possible mass. She was treated with antibiotics and hydration but remained febrile and confused. Bromocriptine was begun; however, she expired 17 days later. The pathophysiology of the neuroleptic malignant syndrome is uncertain, but it involves dopaminergic blockade. NMS has been associated with the use of all neuroleptic drugs, lithium, tricyclic antidepressants, carbamazepine, and with withdrawal of levodopa, either alone or with amantadine, in patients with Parkinson's disease.2,3 NMS is reported to occur more often in men,2,1 with a mean age of 40.4 The neuroleptic malignant syndrome may be unrecognized in older people. Diagnostic criteria include altered mental status, lead-pipe muscular rigidity, fever (without other cause), autonomic dysfunction (tachycardia, diaphoresis, alterations in blood pressure, tachypnea, incontinence), and elevation of CPK. Leukocytosis may be present. Treatment with dopaminergic agents (preferably bromocriptine) and muscle relaxants such as dantrolene has reduced mortality.5 Cases associated with haloperidol have a better prognosis.5 Despite aggressive treatment, however, three of our patients expired as a result of NMS or complications. Our experience highlights several issues regarding the neuroleptic malignant syndrome. Older people are at particular risk, not only because of the frequency of use of neuroleptics in this population, but also because of the possibility that an underlying impairment in central nervous system function may predispose to the development of this syndrome.6 Delays in recognition, confusion with other extrapyramidal syndromes, dementias and Parkinson's disease, and insufficient treatment may be more common in older patients and may increase their mortality rate from NMS. Our experience underscores the need to consider this diagnosis in any older individual presenting with confusion, fever, and rigidity.