Effects of zidovudine in 30 patients with mild to end-stage AIDS dementia complex.

OBJECTIVE: Zidovudine (ZDV) is an inhibitor of HIV replication that may have a beneficial effect on patients with AIDS dementia complex (ADC). However, little is known about the association between long-term ZDV treatment and severity of ADC, ZDV dose or clinical and laboratory response to therapy. DESIGN: An open study on ZDV administration in 30 consecutive patients with ADC. SETTING: An infectious diseases hospital. PATIENTS: Thirty consecutive patients followed-up for 12 months. INTERVENTIONS: Three oral ZDV doses were used: 1000 mg (nine patients), 750 mg (eight patients) and 500 mg (13 patients) per day, depending on haematological status. MAIN OUTCOME MEASURES: Clinical and neurological examinations, neuropsychological evaluations, high-field brain magnetic resonance imaging (MRI) and 99mTc-HM-PAO single photon emission computerized tomography (SPECT). RESULTS: A favourable clinical response, defined as reversal to a less severe ADC stage (Price and Brew's criteria), was observed after 1, 3, 6, 9 and 12 months in 15, 22, 25, 19 and 14 patients, respectively. Neither severity of ADC at entry nor ZDV dose correlated with response to treatment. Seven patients died during the 12-month follow-up. The only factor associated with longer survival was ADC severity at entry (12-month survival, 0.94 and 0.53, in patients in stages 1 or 2 and in stages 3 or 4, respectively; P < 0.01). After 6-12 months of ZDV treatment six patients who initially responded to therapy showed a relapse in initial ADC stage, and two patients a less severe neurological deterioration. Neuropsychological evaluations showed significant improvement in the Wisconsin Card-Sorting test (P = 0.006 for categories, P = 0.029 for perseverative errors), which is particularly sensitive to cognitive and frontal-lobe type functions. Brain MRI revealed a reduction of the extent of white matter lesions in six out of 13 patients, who also showed clinical improvement. SPECT scanning revealed a reduction in the extent of uptake defects concomitant with clinical response in nine out of 14 patients. CONCLUSIONS: ZDV is effective in most patients with mild to end-stage ADC, although the benefit is sometimes only transient; several relapses and deaths occurred after the sixth month of treatment.

Methods for detecting early signs of AIDS dementia complex in asymptomatic HIV-1-infected subjects.

OBJECTIVES: To determine the optimal diagnostic procedures for identifying early signs of AIDS dementia complex (ADC) in asymptomatic HIV-1-infected individuals, in order to prevent further cognitive function impairment by early treatment. DESIGN: Study patients had been referred electively and consecutively to hospital; all had been referred for the first time and gave informed consent. Inclusion criteria were (1) lack of history and/or symptoms of psychosis and neurological disorders; (2) lack of active viral, protozoan or fungal pathology; (3) abstinence from heroin and/or cocaine for at least 6 months before baseline evaluation. SETTINGS: Subjects were seen at the L. Spallanzani Hospital for Infectious Diseases, Rome, Italy between March 1989 and March 1991. PARTICIPANTS: Eighty-two asymptomatic HIV-1-infected subjects: 41 drug users, 27 homosexuals and 14 heterosexuals. MAIN OUTCOME MEASURES: All subjects were evaluated using Wechsler-Bellevue I, Benton C form and Bender tests. Thirty-nine subjects underwent single-photon emission computed tomography (SPECT) and 12 magnetic resonance imaging (MRI). The immunological status of each subject was determined. RESULTS: On psychometric testing, 23 out of the 82 (28%) asymptomatic subjects had a mental decay percentage (MD%) > or = 20%. Cerebral perfusion abnormalities were detected in 31 out of 39 (79.48%) subjects who underwent SPECT; MRI abnormalities were observed in seven out of 12 (58%) subjects. Twelve out of 23 subjects with MD% > or = 20, 15 out of 29 subjects with SPECT abnormalities and four out of seven patients with MRI abnormalities had total CD4+ lymphocyte counts > or = 500 x 10(6)/l. CONCLUSIONS: The high incidence of abnormal SPECT and of MD% > or = 20 in asymptomatic HIV-1-infected patients, and the lack of correlation between immunological status and degree of mental decay, SPECT and MRI abnormalities raise many questions about subclinical HIV-1 neurological disease.

Positive and sustained effects of highly active antiretroviral therapy on HIV-1-associated neurocognitive impairment.

OBJECTIVES: To determine whether highly active antiretroviral therapy (HAART) is effective in HIV-associated neurocognitive impairment. DESIGN: An open label, prospective, observational study. METHODS: Since April 1996, 116 patients with advanced HIV infection, reverse transcriptase inhibitor (nRTI) experienced but protease inhibitor (PI) naive, were screened for the presence of neurocognitive impairment. Ninety patients with confounding neurological illness, opportunistic infections or drug abuse were excluded. The remaining 26 patients underwent comprehensive neuropsychological testing, and laboratory measures before, after 6 and after 15 months of treatment with one PI plus two nRTI. RESULTS: The prevalence of neurocognitive impairment decreased from 80.8% (baseline) to 50.0% (P<0.05) (sixth month) and to 21.7% (P<0.001) (15th month). Among the functions explored, the impairment of concentration and speed of mental processing decreased from 65.4 to 21.7% (P<0.01) and of memory impairment from 50 to 8.7% (P<0.01). Comparing baseline with the sixth and 15th month raw scores, a statistically significant improvement was seen in measures exploring concentration and speed of mental processing (P<0.05), mental flexibility (P<0.05), memory (P<0.05), fine motor functions (P<0.05) and visuospatial and constructional abilities (P<0.01). After 6 months of HAART patients with a normal neuropsychological examination had lower mean plasma viraemia (2.95 versus 3.97 log copies/ml, P<0.05) and greater mean log plasma HIV RNA changes from baseline (-1.84 versus -0.83 log copies/ml, P<0.05) than neuropsychologically impaired subjects. CONCLUSION: HAART produces a positive and sustained effect on neurocognitive impairment in HIV-infected patients. A reduction of plasma viral load was associated with the regression of neuropsychological test abnormalities.

Cerebral blood flow in AIDS-related neurotoxoplasmosis: a preliminary 99mTc-HMPAO SPECT study.

Cerebral blood flow (CBF) was evaluated by gamma camera 99mTc-HMPAO SPECT in 11 patients with AIDS-related neurotoxoplasmosis and correlated with neurological findings and the results of CT and MRI. Evident CBF abnormalities were observed in all patients with involvement of at least two cerebral lobes. In 10 patients the abnormalities were bilateral and in 8 patients basal ganglia were involved; no specific hypoperfusion pattern was however evident. Focal lesions were found in 7 patients by CT (sensitivity: 63.6%) and in 10 patients by MRI (sensitivity: 90.9%). It may be concluded that neurotoxoplasmosis in AIDS patients is associated with a high prevalence of focal cortical and subcortical hypoperfusion but that the scintigraphic findings are not specific; that HMPAO SPECT may show focal hypoperfusion in patients with normal CT studies and/or non-focal MRI abnormalities; that the hypoperfusion may be more extensive than the corresponding MRI lesion(s) and that it may be present even in areas with normal MRI signals; and that more experience and longitudinal studies are needed to assess the possible impact of HMPAO SPECT on follow-up and therapy monitoring.

Cortical cerebral blood flow in HIV-1-related dementia complex.

Dementia complex is a syndrome that affects a high percentage of AIDS patients. Neuroradiological findings may be non-specific and the diagnosis can be difficult in its earlier stages. Preliminary radionuclide studies have recently reported derangements of regional cerebral blood flow (CBF) which may be present before overt anatomical injury. This study reports on cortical and cerebellar CBF changes in 26 patients studied with 99Tcm-HM-PAO and single photon emission computed tomography (SPECT). Extensive cortical CBF derangements were observed in all patients and an evident cerebellar hypoperfusion was also present in three. The prevalence of hypoperfusion was highest in the frontal and parietal lobes. The extension of the hypoperfusion showed a highly significant correlation with the severity of the dementia complex (P less than 0.01 by chi 2 test). The SPECT also showed hypoperfused areas in three patients with normal CT scans and in two patients with normal MRI scans. These results confirm previous preliminary reports on the high prevalence of cortical hypoperfusion in dementia complex and suggest the use of this radionuclide technique to assist in the early diagnosis and follow-up of AIDS patients, especially when CT and MRI are still normal.

MACOP-B and involved field radiation therapy is an effective therapy for primary mediastinal large B-cell lymphoma with sclerosis.

PURPOSE: To evaluate the clinical features of presentation and the response to two different third-generation regimens (F-MACHOP and MACOP-B) of primary mediastinal large B-cell lymphoma (MLBCL), a recently defined distinct clinicopathological entity of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-seven consecutive patients with MLBCL, eight male and 29 female (F/M ratio 1:3.5) with a median age of 35 years, were enrolled in the present study. Thirty-five (94.5%) patients presented disease confined to thorax, with chest symptoms of a rapidly enlarging mass in the mediastinum in 70% and superior vena cava syndrome (SCVS) in 43% of these patients. The first 10 patients received F-MACHOP and the succeeding 27 patients MACOP-B chemotherapy, associated in 24 (88.8%) with involved field radiation therapy (IFRT). 67Gallium scan was routinely performed pre- and post-IFRT in 18 patients. RESULTS: All 37 patients were assessable for response: 10 of 10 (100%) in the F-MACHOP and 26 of 27 (96.3%) in the MACOP-B group achieved overall responses (CR + PR). Three of 24 (12.5%) patients in PR after chemotherapy obtained CR after IFRT. Persistent Gallium avidity was observed in 16 patients after chemotherapy and in only four patients after IFRT. Thus far, four of the 10 F-MACHOP and two of the 26 MACOP-B responders have presented disease progression. The probability of progression-free survival (PFS) was 91% and 60% (P < 0.02) while overall survival (OS) was 93% and 70% (P = n.s.) at a mean follow-up of 27 and 52 months in the MACOP-B + IFRT and F-MACHOP groups, respectively. CONCLUSION: MACOP-B + IFRT has proved to be a highly effective and less toxic therapeutic approach for primary MLBCL and appears to be superior to other third-generation chemotherapy regimens.