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Neuroleptic Malignant Syndrome in the Acquired Immunodeficiency Syndrome

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Neuroleptic Malignant Syndrome in the Acquired Immunodeficiency Syndrome Postgrad Med J 1997; 73: 779-784 (© The Fellowship of Postgraduate Medicine, 1997 HIV medicine Postgrad Med J: first published as 10.1136/pgmj.73.866.779 on 1 December 1997. Downloaded from Neuroleptic malignant syndrome in the acquired immunodeficiency syndrome Jose L Hemaindez, Luis Palacios-Araus, Santiago Echevarria, Andres Herran, Juan F Campo, Jose A Riancho Summary The neuroleptic malignant syndrome (NMS) is a life-threatening process, Patients infected by the human typically, but not exclusively, induced by drugs of the neuroleptic group. Its immunodeficiency virus are pre- main clinical manifestations include fever, rigidity of skeletal muscles, disposed to many infectious and fluctuating consciousness and autonomic disturbances.' Since first described noninfectious complications and by Delay and Deniker in 1968,2 the syndrome has received increasing attention often receive a variety of drugs. and more than 1600 cases have been reported to date, including a few cases in Furthermore, they seem to have a patients with the acquired immunodeficiency syndrome (AIDS).3-8 Never- particular susceptibility to idio- theless, outside psychiatry, the syndrome probably remains underdiagnosed, as syncratic adverse drug reactions. its manifestations may be also caused by other processes such as infections and It is therefore surprising that only neoplasms. Thus, a high index of suspicion is needed to not miss the diagnosis a few cases of the neuroleptic in medical patients. This is particularly important in patients infected by the malignant syndrome have been human immunodeficiency virus (HIV), who commonly suffer infectious described in patients with the complications but also often receive psychoactive drugs. This article reviews acquired immunodeficiency syn- the main features of NMS in AIDS patients. A typical case history is given in drome. A high index of suspicion box 1. is required to diagnose the neuro- leptic malignant syndrome in Epidemiology these patients, as its usual mani- festations, including fever and Agitation and other psychotic symptoms are common in HIV-infected patients altered consciousness, are fre- and they are frequently treated with neuroleptics. In fact, apathy, social quently attributed to an under- withdrawal and personality changes have been reported to occur even before the lying infection. development of the typical manifestations of HIV infection.9 In addition, neuroleptic-related drugs are commonly used to control other symptoms, such Keywords: neuroleptic malignant syn- as nausea and vomiting. drome, acquired immunodeficiency syn- The first case describing the association of NMS with AIDS was reported in drome, antipsychotic agents 1986 by Bernstein and Scherokman, in a patient with disseminated histoplasmosis. Up to date, only eight cases of this association have been http://pmj.bmj.com/ reported (see table). However, the actual incidence of NMS in the setting of AIDS is unknown. It is likely that many cases still go unrecognised because of the limited knowledge of this syndrome by clinicians. In a recent study, the majority of healthcare professionals tested did not know enough about NMS to aid early detection and to prevent its high mortality.'0 NMS can occur in all age groups, but is more often found in young and middle-aged adults." Among AIDS patients, NMS also predominantly affects on September 30, 2021 by guest. Protected copyright. young men (table). The average age was 34.1 years (range 21 to 49). The drugs most frequently implicated in AIDS-related NMS have been haloperidol, trimethobenzamide and prochlorperazine. Pathogenesis and risk factors NMS is considered an idiosyncratic reaction to antipsychotic and related drugs. The prevailing theory relates NMS to a profound decrease of dopaminergic function in the central nervous system. The loss of dopaminergic activity in the nigrostriatal system would cause rigidity and tremor. The sustained muscle activity would result in increased production of heat, which, together with the alteration of hypothalamic and other autonomic centres, may cause fever and Department of Internal Medicine, rhabdomyolysis."1"' Hospital Marques de Valdecilla, University of Cantabria, 39008 The incidence of extrapyramidal side-effects due to neuroleptics and related Santander, Spain drugs, including metoclopramide, is increased in AIDS patients.'3"14 The cause JL Hemrndez of this higher frequency of adverse effects remains speculative, but is probably L Palacios-Araus related to the presence of predisposing structural brain abnormalities, due to S Echevarria opportunistic infections or to HIV infection itself. In this sense, the report of A Herrin Reyes et al, showing that nigral degeneration is common in AIDS patients is JF Campo JA Riancho interesting,'5 as this would certainly predispose to extrapyramidal effects. Although the prevailing theory relates NMS to a profound decrease of Accepted 4 March 1997 dopaminergic function in the central nervous system, drugs triggering NMS 780 Herncndez, Palacios-Araus, Echevamra, et al interact not only with dopaminergic transmission, but also with several other Case report cell systems. It remains unclear why only some patients develop the syndrome. Postgrad Med J: first published as 10.1136/pgmj.73.866.779 on 1 December 1997. Downloaded from A 32-year-old HIV seropositive white Dehydration and acute psychotic agitation are common features in AIDS man with a previous diagnosis ofAIDS patients. The former is associated with an increase of extracellular sodium, and (stage C3 according to CDC criteria), the second with an decrease of calcium in the cerebrospinal fluid. These presented with pneumonia. He was an mechanisms may lead to a decrease of intraneuronal calcium, which could intravenous drug abuser with eight facilitate an increase of adenylate cyclase activity, and a subsequent disturbance months of abstinence, and there was of thermoregulation, thus predisposing to NMS.'6 no history of dementia or psychiatric disorders. Whatever pathophysiological mechanisms may be involved, clinical studies The patient was febrile and have suggested that some concomitant factors increase the risk of developing inspiratory crackles were heard over NMS.'7 Many of these factors often occur in HIV-infected patients (box 2), the lowest third of right lung. The several of which were present in the reported patients with AIDS and NMS, remainder of the examination was including malnutrition, concomitant brain disease, increasing dose of or normal. Chest X-ray showed an treatment with a new schizo-affective and the antecedent alveolar infiltrate in the right lower neuroleptic, disorder, lobe. Intravenous erythromycin and of a preceding attack of NMS (table, cases 1, 2 and 8). cefotaxime were given. Blood cultures yielded Streptococcus pneumoniae and Clinical features erythromycin was withdraw. By the fifth day he became afebrile. SYMPTOMS AND SIGNS On hospital day 11, the patient The characteristic tetrad of NMS includes hyperthermia, extrapyramidal developed agitation and paranoid ideations. He was started on rigidity of skeletal muscles, fluctuating consciousness, and instability of the haloperidol (6 mg/day per os), and oral autonomic nervous system. 11,12,18 Symptoms and signs of NMS in AIDS biperiden. Three days later, the patient patients are summarised in the table. The clinical features of patients with became febrile (39.50C), with AIDS do not seem to differ from those observed in other patients with NMS. tachycardia, tachypnoea, profuse Hyperthermia was constant in all patients; in about half body temperature was diaphoresis, cogwheel rigidity of all higher than 40'C. Extrapyramidal-type hypertonia, often along with bradyki- extremities, akinesia and fluctuating consciousness with mutism. nesia or akinesia, was also present in the vast majority ofpatients. Rigidity ofthe Leukocytosis with a left shift was thoraco-abdominal muscles may result in hypoventilation and respiratory present, and creatine kinase level was failure (cases 5 and 9). Tremor was present in two patients. 2365 U/1. Exhaustive microbiological The development of the complete NMS may be preceded by insidious studies were negative. Chest X-ray changes in mental status or autonomic functions. All AIDS-patients with NMS showed no infiltrates. A cranial CT displayed alteration of consciousness, psychomotor excitement or aggressive scan was normal, and CSF examination and cultures failed to behaviour before the onset of the full syndrome. In AIDS-patients the most reveal any evidence of infection. common signs of autonomic dysfunction were tachycardia, tachypnoea and Haloperidol was discontinued. Within diaphoresis. Mild dysphagia was present in one case. 48 h his temperature, creatine kinase Most cases developed in the first week after initiating the offending drug, but and neurological status were normal. in two patients NMS was diagnosed later. Symptoms usually developed over a However, psychotic symptoms period of 24 to 72 hours, and the mean recovery time was five to 10 recurred and oral loxapine (100 mg/ days. day) was given. One day later fever LABORATORY FINDINGS (39°C), stupor, and extrapyramidal http://pmj.bmj.com/ signs reappeared. As before, no Leucocytosis with or without a left shift is very common.""2'18 However, the evidence for infection was found. By number of leukocytes was not always reported in the published cases of NMS the second day after loxapine and AIDS. Therefore, it is unclear how frequent leucocytosis is in this withdrawal his body
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