Progressive multifocal leukoencephalopathy in patients with HIV infection.

Progressive multifocal leukoencephalopathy (PML), a formerly rare disease, is estimated to occur in up to 5% of all patients with AIDS. The high prevalence of PML in AIDS patients currently enables a comprehensive evaluation of this disorder. We evaluated the clinical and radiographic features of PML in a large cohort of AIDS patients identified by retrospective chart review from 1981 to 1994. Two hundred and five patients were diagnosed with PML of which 154 met the inclusion criteria. Seventy-two (47%) were pathologically confirmed and the remaining 82 (53%) met clinical and radiographic criteria. There was a 12-fold increase in the frequency of PML between 1981-1984 and 1991-1994. PML affected 136 men and 18 women with AIDS. Eighty-four percent of cases were 20-50 years old (range 5 to 68 years). The most common AIDS risk factors were homosexuality (57%) among men and heterosexual transmission (28%) and intravenous drug abuse (28%) among women. In 27% of patients, PML heralded AIDS. Common manifestations included weakness, gait abnormalities, speech disturbance, cognitive disorders, headache, and visual impairment. The CD4 lymphocyte counts exceeded 200 cells in 11% at the time of presentation. Involvement of posterior fossa structures was evident in 48% of cranial magnetic resonance imaging (MRI) studies, but in only 11% of computed tomographies (CT) of the brain. Contrast enhancement, typically faint and peripheral, was seen in 10% of CT scans and 15% of MRIs. The median survival was 6 months and survival exceeded 1 year in 9%. PML is no longer a rare disease. It often heralds AIDS and may occur in the absence of significant decline in CD4 lymphocytes. Survival is generally poor, although prolonged survival beyond 1 year is not unusual.

Oxandrolone in AIDS-wasting myopathy.

OBJECTIVE: To evaluate oxandrolone, an oral anabolic steroid with potent anabolic activity and minimal androgenic effects, for the treatment of AIDS-associated myopathy and wasting. METHODS: In a multicenter, double-blind study, 63 HIV-seropositive men with > 10% loss of body weight were randomized to receive either placebo, 5 mg/day oxandrolone, or 15 mg/day oxandrolone for 16 weeks. Body weight, neuromuscular evaluation, and measures of well-being were repeatedly assessed. RESULTS: Patients who received 15 mg/day oxandrolone showed weight gain throughout the 16-week treatment period. Overall, the 5 mg/day oxandrolone group maintained their weight gain over the 16-week period, whereas the placebo group showed continual weight loss. At week 16, significantly more patients in the 15 mg/day dose group reported increases in appetite and activity than those receiving placebo. There were no consistent, dose-related, statistically significant differences from baseline in laboratory values or adverse events. CONCLUSION: Oxandrolone, at a dose of either 5 mg/day or 15 mg/day, in contrast to placebo, had a positive impact on the weight and well-being of HIV-seropositive patients suffering from wasting and weakness. Measurable improvement in muscle strength was not noted at the doses employed in this study. Oxandrolone was well tolerated in all the patients who were enrolled in the study. Based on the results reported here, additional studies using higher doses of oxandrolone seem warranted.

Headache and human immunodeficiency virus infection: a case control study.

The new onset of headache in a person infected with human immunodeficiency virus (HIV) may be an ominous sign of a significant underlying neurological disorder. This case control study compares the prevalence of headache in HIV-seropositive persons without identifiable neurological disease on study entry to that in an HIV-seronegative control population with similar risk factors for HIV infection. Features of headache that were evaluated included frequency, duration, location, severity, and recent change in characteristics. In the HIV-seropositive population, the presence of headache and its specific features were correlated with the degree of immunosuppression as determined by absolute CD4 counts and Centers for Disease Control stages, the presence of other neurological symptoms and neurological signs, cranial magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) values. Headaches were common; approximately 50% of all subjects reported headache at study entry and 2 years later. Headache frequency and characteristics were not different between HIV-seropositive and HIV-seronegative subjects. Headache was neither more frequent nor different in HIV-seropositive individuals with advanced immunosuppression. There was no correlation between headache and abnormal CSF parameters, cranial MRI abnormalities, including the presence of sinusitis, or the use of zidovudine.

Asymptomatic and neurologically symptomatic HIV-seropositive subjects: results of long-term MR imaging and clinical follow-up.

Cranial magnetic resonance (MR) images were prospectively obtained in 74 human immunodeficiency virus (HIV)-seropositive subjects, all of whom had undergone MR imaging 24-42 months earlier. The images were interpreted by neuroradiologists blinded to the subject's clinical status and were compared with the initial MR images and clinical findings. Ten subjects had mild neurologic symptoms, with mildly abnormal unchanged images in five (50%). Sixty-four subjects were neurologically asymptomatic, with mildly abnormal images in 13 (20%), most of which remained unchanged. chi 2 analysis revealed a significant difference (P = .042) between the asymptomatic and symptomatic groups with regard to the number of subjects with abnormal follow-up images. The number of abnormal images in the asymptomatic subjects was significantly less than that in the symptomatic subjects. During follow-up of 2-3 1/2 years, most asymptomatic subjects had persistently normal MR images. When abnormal, the imaging abnormalities were usually static and minor.

Effect of anabolic steroids on HIV-related wasting myopathy.

Human immunodeficiency virus type 1 (HIV-1) is frequently associated with weakness and muscle wasting, referred to as HIV-1 wasting myopathy. This illness, often observed in the advanced stages of acquired immunodeficiency syndrome (AIDS), responds poorly to therapeutic intervention. We describe the cases of three AIDS patients with HIV-1 wasting myopathy who had a favorable response to anabolic steroids as evidenced by an improvement in strength, muscle bulk, body weight, and sense of well-being.

Syphilitic cerebral gumma with HIV infection.

We describe two human immunodeficiency virus (HIV)-infected patients with syphilitic cerebral gummas. Both patients presented with a seizure disorder associated with an isolated, peripherally located, contrast-enhancing lesion of the brain on CT. Cranial MRI performed on one patient revealed dural thickening in the region of the lesion. A brain biopsy in that patient revealed a lymphoplasmacytic infiltrate with extensive perivascular inflammation. Clinical manifestations, radiographic resolution of the lesions, and a decline in nontreponemal serologic tests for syphilis followed high-dose aqueous penicillin therapy in both patients. These patients illustrate that (1) cerebral mass lesions occurring with HIV infection may result from syphilis; (2) seizures may be the presenting manifestation of this form of neurosyphilis; and (3) high-dose, intravenous, aqueous penicillin is effective in treating these lesions.

Danazol therapy for autoimmune hemolytic anemia.

We evaluated the use of danazol in 15 patients with autoimmune hemolytic anemia of the warm antibody type. Danazol, 600 to 800 mg/d, was added to previous regimens or given initially in conjunction with high-dose prednisone treatment. Twelve patients with autoimmune hemolytic anemia associated with nonmalignant disorders or idiopathic autoimmune hemolytic anemia and 1 of 3 patients with underlying neoplasms showed a rise in hematocrit within 1 to 3 weeks. Thereafter, glucocorticoid doses were tapered to a minimum requirement or stopped. Once remission was sustained, the dose of danazol was reduced to 200 to 400 mg/d. Although levels of erythrocyte-bound IgG antibody and C3 decreased with therapy, only the decrease in C3 was statistically significant (p less than 0.05) in this limited study. Danazol was effective regardless of the severity of the disorder and success or failure of previous treatments. Danazol is valuable in the treatment of autoimmune hemolytic anemia and may be better suited than glucocorticoids for long-term management.

Slow infusion of vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura.

Vinca alkaloids are useful in the treatment of idiopathic thrombocytopenic purpura, a disorder in which macrophages remove platelets sensitized with antibody. Because vinca alkaloids avidly bind to platelets, drugs can be delivered selectively to macrophages. However, drugs given by bolus injection are cleared too rapidly to bind optimally to autologous platelets, and the use of allogeneic platelets loaded with drug in vitro is cumbersome, expensive, and dangerous. Therefore, slow infusions were devised to prolong the duration of enhanced plasma drug concentrations, thereby providing better conditions for in-vivo drug loading into autologous platelets. Twenty-four patients with refractory idiopathic thrombocytopenic purpura were given slow infusions; 17 had good to excellent responses. Eleven of eighteen patients who had been treated with bolus injections had better results when treated with slow infusions. Patients with improved responses had slower plasma clearance rates than did patients with poor responses. Slow infusion therapy had fewer side effects than bolus injection therapy. Slow infusions are the best method for long-term management.

Treatment of idiopathic thrombocytopenic purpura.

ITP is a common disease that is sorely in need of better management. Treatment strategy requires consideration of both long-term benefits and long-term hazards of each available therapeutic option. This discussion reviews conventional therapy as well as newer approaches to refractory ITP, including immunosuppressants, vinca alkaloids, colchicine, androgens, tamoxifen, and plasmapheresis.

Danazol for the treatment of idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura is an autoimmune disorder, most common in young women. We treated 22 patients with this disorder (12 of whom were women) with danazol, an androgen with reduced virilizing capability, for two months or longer. Fifteen had undergone splenectomy, all were receiving glucocorticoids, and 18 had also been given other treatments. Fifteen of the patients were benefited, 11 with sustained normalization of their platelet counts. Six of eight patients tested had initial increases in circulating platelet-reactive IgG; in all six there was a marked decrease concomitant with danazol therapy. Danazol was effective in both men and women, irrespective of previous treatments. The duration of remissions ranged from 2 to 13 months. The drug was well tolerated and appears to be better suited than glucocorticoids for long-term management of idiopathic thrombocytopenic purpura, but the exact indications for the use of danazol in this disorder remain to be determined.

Treatment of autoimmune hemolytic anemia with Vinca-loaded platelets.

We worked with a new strategy for the treatment of autoimmune hemolytic anemia (AIHA) of the warm antibody type. Platelets were loaded with Vinca alkaloids and reacted with antiplatelet antibodies to facilitate their phagocytosis by macrophages, resulting in a measure of selective delivery of the drugs to the cells of the mononuclear phagocyte system, which destroy RBCs in AIHA. Four patients were studied. Three with AIHA refractory to splenectomy and the use of moderate doses of glucocorticoids achieved hematologic and clinical remissions. Administration of steroids was either discontinued or reduced to minimal doses after treatment. Remissions lasted three years in two patients and one year in the other. Responses were characterized by prompt prolongation of RBC survival, correction of anemia, and gradual decrease in cell-bound antibody. In one nonsplenectomized patient, the disorder did not respond. Platelet-Vinca alkaloid complex is useful in the treatment of AIHA refractory to splenectomy and use of steroids.

The treatment of idiopathic thrombocytopenia with vinblastine-loaded platelets.

We devised a method to enhance delivery of vinblastine to macrophages, the cells believed to be responsible for platelet destruction in idiopathic thrombocytopenic purpura. Our strategy was based on the ability of platelets to bind vinca alkaloids such as vinblastine. Platelets were incubated with an excess of vinblastine, concentrated and then, after excess alkaloid had been removed, given to 11 patients with idiopathic thrombocytopenia refractory to other treatment (including intravenous injections of vinca alkaloids). Platelet antibodies in the patients' plasma led to ingestion of the vinca-laden platelets by macrophages. There were six complete remissions, three partial remissions and two failures. Side effects in a few patients, reversible but annoying, were minimized as technics were refined. We conclude that in patients with idiopathic thrombocytopenia refractory to all other measures, including the use of vinca alkaloids, platelet-vinca complex may be effective.