Neurologic complications of drugs. Tardive dyskinesias, neuroleptic malignant syndrome, and cocaine-related syndromes.

Drugs, either self-administered or prescribed by physicians, can result in substantial neurologic disability in psychiatric patients. It is clear that the use of neuroleptic agents to treat psychiatric illness may result in a variety of tardive movement disorders. Most commonly, these take the form of orobuccal dyskinesias, but choreic movements of the trunk and extremities, dystonic postures, myoclonus, tics, parkinsonism, and akathisic syndromes also may occur. The choreic tardive syndromes are thought to occur more commonly in the elderly female population, but tardive variants may affect a different population. The neuroleptic malignant syndrome carries a significant mortality and remains a diagnostic and therapeutic challenge. Early detection and vigorous treatment reduces the morbidity and mortality from this condition. Stroke, seizures, and various movement disorders may complicate the illicit use of cocaine and complicate the rehabilitation of those patients dependent on its use. The unsatisfactory treatment of tardive syndromes, neuroleptic malignant syndrome, and cocaine-induced neurologic disease underscores our incomplete understanding of the neurochemistry of dopamine, the function of newly discovered dopamine receptors, and the role they play in maintaining normal emotional and motoric function. For now, awareness of the varied neurologic syndromes related to neurotransmitter-modulating agents should provide the impetus for careful use of these agents and for the continued development of improved drugs for the treatment of psychiatric disease.

Neuroleptic malignant syndrome in Parkinson's disease after withdrawal or alteration of dopaminergic therapy.

Neuroleptic malignant syndrome is characterized by altered consciousness, fever, extrapyramidal signs, autonomic instability, elevated creatine kinase level, and leukocytosis. Although originally described in patients receiving neuroleptic drugs, this syndrome may also occur in patients with Parkinson's disease during withdrawal or reduction of levodopa therapy or other dopaminergic drug therapy. We have encountered three cases of neuroleptic malignant syndrome related to withdrawal of levodopa therapy. These cases illustrate the variety of circumstances in which alteration of therapy with dopaminergic drugs can cause this syndrome and the relative unfamiliarity of the neuroleptic malignant syndrome-levodopa relationship among physicians who do not treat large numbers of patients with Parkinson's disease. An understanding of the role of brain dopamine in the pathogenesis of neuroleptic malignant syndrome and an appreciation of the great variety of drugs whose manipulation can result in this potentially fatal syndrome will aid its proper and timely recognition, especially when the offending pharmacologic manipulation does not involve neuroleptic drugs.

Neurologic complications of late prosthetic valve endocarditis.

We reviewed the records of 20 patients with late prosthetic valve endocarditis who were hospitalized at the University of Iowa between 1985 and 1988. There were 14 men and six women, aged 20-80 (mean 57.9) years. The infected valves were mechanical in 11 patients (six aortic and five mitral) and bioprosthetic in the other nine. Echocardiography in 12 patients demonstrated vegetations in one. Among the 20 patients, neurologic complications occurred in eight (40%), six of whom had mechanical valves (five mitral and one aortic). Infection with Staphylococcus aureus occurred in four of the eight patients (50%) with neurologic complications. Of the eight patients with neurologic complications, ischemic stroke was diagnosed in four, transient ischemic attacks in one, and intracranial hemorrhage in three. Prothrombin times at the time of the intracranial hemorrhage were 2.2, 1.5, and 1.3 times control in these three patients. Cerebral angiography done in four of the eight patients with neurologic complications failed to show mycotic aneurysms. Nine of the 20 patients (seven men and two women, mean age 66.8 years) died less than or equal to 90 days after the diagnosis of late prosthetic valve endocarditis. Half of the eight patients with neurologic complications died (three men and one woman, mean age 62.3 years), and all three patients with intracranial hemorrhage died. Our data suggest that the neurologic complications of late prosthetic valve endocarditis are more common with mechanical valves, particularly in the mitral position, and are associated with a high mortality.