Nine patients with inflammatory demyelinating polyneuropathies (IDP) were found to have human T-cell lymphotropic virus type III (HTLV-III) infection. The 8 men, 6 of whom were homosexual, and 1 woman, a former intravenous drug user, presented with progressive weakness. Two had lymphadenopathy but all were otherwise asymptomatic. Six had chronic IDP and 3 had Guillain-Barre syndrome. In addition to an elevated cerebrospinal fluid (CSF) protein level (mean, 193 mg/dl), most patients had cerebrospinal fluid pleocytosis (mean, 23 cells/mm3), a distinctive feature. All had reduced T4:T8 T-cell ratios. Results of nerve conduction studies were characteristic of demyelination. Nerve biopsies revealed intense inflammatory cell infiltrates and macrophage-mediated demyelination. The patients recovered either spontaneously or following treatment with corticosteroids or plasmapheresis. During a mean interval of 20 months after presentation, only 1 patient had developed acquired immune deficiency syndrome. Patients with HTLV-III infection have disordered immune function, and the mechanism of the development of the IDP is likely to be immunopathogenic. As a result of our experience, we suggest that all patients with IDP be tested for evidence of HTLV-III infection. We also found, although in uncontrolled trials, that treatment with either prednisone or plasmapheresis was followed by clinical improvement; since plasmapheresis is not likely to further depress cell-mediated immunity, we suggest that it be the initial therapy.

Inflammatory demyelinating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection.

Neuromuscular disorders reported in association with human immunodeficiency virus (HIV) infection include several forms of peripheral neuropathy and polymyositis. We report 11 patients with HIV-associated myopathy. Five patients with acquired immunodeficiency syndrome (AIDS), 2 with AIDS-related complex, and 4 otherwise asymptomatic HIV-infected patients developed progressive proximal muscle weakness. Serum creatine phosphokinase levels were elevated and electromyography revealed abnormal spontaneous activity and myopathy in most patients. All 8 muscle biopsy specimens showed fiber necrosis. Four had inflammatory infiltrates, and nemaline rod bodies were prominent in 3. Immunosuppressant therapy in 5 patients resulted in improvement. Attempts at viral localization in 4 muscle biopsy specimens were unsuccessful. These findings suggest a distinct association between HIV infection and myopathy with features atypical for polymyositis.

Human immunodeficiency virus—associated myopathy: Analysis of 11 patients

The ability to productively infect fresh normal human peripheral blood mononuclear leukocytes with HTLV-III was improved by supplementing cell culture medium with either the gonadal steroid, chorionic gonadotropin, or insulin, and more substantially with the adrenocortical steroid, hydrocortisone. Several other sex hormones and another corticosteroid, dexamethasone, had no significant effect. In addition, the isolation of HTLV-III from lymphocytes established in culture from patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), and healthy, at-risk donors was greatly facilitated by the inclusion of hydrocortisone in cell culture media. In 13/20 primary cell cultures tested from AIDS and ARC patients from whom virus was isolated, the amount of virus produced was elevated from low to easily detectable levels in those containing hydrocortisone. In 3/20 specimens tested, virus was detected and isolated from cell cultures supplemented with hydrocortisone but was undetectable in those lacking the hormone. These experiments demonstrate that hydrocortisone, a readily available, inexpensive supplement to cell culture media, can facilitate the detection and isolation of HTLV-III. These studies, furthermore, suggest a role for corticosteroids and possibly gonadal steroids in the modulation of virus expression and/or release and suggest that the viral inductive capacity of these and other compounds should be considered as they are evaluated for clinical use.

Hydrocortisone and some other hormones enhance the expression of HTLV-III.

Myopathy may occur as a complication of human immunodeficiency virus type 1 (HIV) infection or from its treatment, zidovudine (ZDV). We reviewed our experience with HIV-infected subjects referred for neuromuscular evaluation and compared features of myopathy in ZDV-treated (+ZDV) and untreated (-ZDV) patients. Fifty patients had myopathy, 25 diagnosed by pathologic criteria and 25 by clinical and other laboratory support. Twenty patients with myopathy had weight loss sufficient for the diagnosis of HIV wasting syndrome. Thirty-one subjects were +ZDV and 19 were -ZDV. Patients in each group presented with proximal weakness, although myalgia was more common in +ZDV patients. Both groups had elevated serum CK to a similar degree (medians: +ZDV, 485; -ZDV, 471). Muscle biopsies revealed myofiber degeneration, variable inflammatory infiltrates, inclusion bodies, and mitochondrial abnormalities in both groups. We followed response to ZDV withdrawal in 15 patients. Four had increased strength, three noted less myalgia, and eight had no clinical improvement. Twelve of 13 patients improved with prednisone. Although it is difficult to distinguish the myopathies of HIV and ZDV by clinical or pathologic criteria, in the majority of our patients, myopathy is due to HIV rather than ZDV.

Myopathies associated with human immunodeficiency virus and zidovudine: Can their effects be distinguished?

• We studied 14 patients with neuromuscular disorders and concomitant infection with human immunodeficiency virus to define clinical syndromes and prognosis. Eight patients had painful sensorimotor peripheral neuropathy; two, chronic inflammatory demyelinating polyneuropathy; two, mononeuropathy or mononeuropathy multiplex; one, recurrent myoglobinuria; and one, chronic proximal weakness and elevated creatine kinase levels. All eight patients with painful neuropathy had overt symptoms of acquired immunodeficiency syndrome. Chronic inflammatory demyelinating polyneuropathy was the first manifestation of acquired immunodeficiency syndrome in both patients with this syndrome. Both died from overwhelming sepsis within six months of the neuropathy's onset. Patients with mononeuropathy multiplex had a variable course. Immunosuppressant medication had no effect in two patients.

IraR. Hoffman

Papers

Possible risk of steroid administration in patients at risk for AIDS.