Bell J E, Brettle R P, Chiswick A, Simmonds P
Department of Pathology, University of Edinburgh, UK.
Brain. 1998 Nov;121 ( Pt 11):2043-52. doi: 10.1093/brain/121.11.2043.
In this consecutive autopsy study, the pathological evidence of HIV encephalitis, which included the presence of giant cells and/or HIV p24 immunopositivity, was found more frequently in drug users (25 of 45; 56%) than in homosexual men (6 of 35; 17%) with AIDS (P < 0.01). Productive infection, as shown by HIV p24 positivity, was found in frontal lobe white matter in 29 of the 31 HIV encephalitis cases, but was also present in grey matter in 50% of the HIV encephalitis cases. Immunopositivity was confined to microglia, monocytes and most but not all giant cells. HIV-1 proviral load was determined by quantitative PCR in 65 of the 80 cases (separately in grey and white matter in 49 of these), and correlated well with the presence of HIV encephalitis (P < 0.001). Twenty-five patients with AIDS (13 male homosexuals, 12 drug users) showed no HIV encephalitis, opportunistic infection or cerebral lymphoma, while 18 (2 male homosexuals, 16 drug users) showed pure HIV encephalitis. Cognitive function had been assessed prospectively in this cohort and graded as normal or mildly, moderately or severely impaired. Because opportunistic infections and lymphomas of the brain may also lead to dementia, patients found to have these conditions at autopsy were excluded from the final analysis of the cases with dementia, so that the precise correlation between cognitive impairment and pure HIV encephalitis could be determined in this cohort without possible confounding variables. Fourteen of 18 patients with pure HIV encephalitis had shown cognitive impairment. Severe dementia correlated better with pure HIV encephalitis in cases in which grey matter involvement was present (7 out of 9) than in those in which only white matter was involved (2 out of 9) (P < 0.05), although milder degrees of cognitive impairment had been present in a further 5 HIV encephalitis cases. No correlation was found between zidovudine therapy and the degree of cognitive impairment. Systemic and cerebral opportunistic infections and lymphoma showed a negative association with HIV encephalitis, being more common in homosexuals than in drug users, despite comparable CD4 counts in the two groups. These findings suggest that neocortical productive HIV infection is a significant factor in AIDS-related dementia, although this may reflect merely a higher overall viral burden in the brain.
在这项连续性尸检研究中，发现艾滋病患者中，吸毒者（45例中有25例；56%）出现HIV脑炎病理证据（包括存在巨细胞和/或HIV p24免疫阳性）的频率高于同性恋男性（35例中有6例；17%）（P<0.01）。在31例HIV脑炎病例中，29例在额叶白质中发现有HIV p24阳性所显示的有效感染，但50%的HIV脑炎病例的灰质中也存在有效感染。免疫阳性仅限于小胶质细胞、单核细胞以及大部分但并非全部的巨细胞。80例中的65例（其中49例分别对灰质和白质进行检测）通过定量PCR测定HIV-1前病毒载量，其与HIV脑炎的存在密切相关（P<0.001）。25例艾滋病患者（13例男性同性恋者，12例吸毒者）未出现HIV脑炎、机会性感染或脑淋巴瘤，而18例（2例男性同性恋者，16例吸毒者）表现为单纯性HIV脑炎。该队列中对认知功能进行了前瞻性评估，并分为正常或轻度、中度或重度受损。由于脑部机会性感染和淋巴瘤也可能导致痴呆，在尸检中发现患有这些病症的患者被排除在痴呆病例的最终分析之外，以便在该队列中确定认知障碍与单纯性HIV脑炎之间的精确关联，而不存在可能的混杂变量。18例单纯性HIV脑炎患者中有14例出现认知障碍。在存在灰质受累的病例（9例中有7例）中，重度痴呆与单纯性HIV脑炎的相关性优于仅白质受累的病例（9例中有2例）（P<0.05），尽管另有5例HIV脑炎病例存在较轻程度的认知障碍。未发现齐多夫定治疗与认知障碍程度之间存在相关性。全身性和脑部机会性感染及淋巴瘤与HIV脑炎呈负相关，在同性恋者中比在吸毒者中更常见，尽管两组的CD4计数相当。这些发现表明，新皮质的HIV有效感染是艾滋病相关痴呆的一个重要因素，尽管这可能仅仅反映了大脑中更高的总体病毒载量。
