Pathomorphological variations of the AIDS-associated progressive multifocal leukoencephalopathy.

Pathological analysis of 20 cases of the progressive multifocal leukoencephalopathy (PML) appearing in the course of acquired immune deficiency syndrome (AIDS) is presented. PML occurred in 10% of all AIDS cases, collected in the period from 1987 to 1999. PML appeared either as the only brain pathology or accompanied HIV-related brain alterations isolated or concomitant with one or several opportunistic infections and/or neoplastic growth (malignant lymphoma). Basing on the pathomorphological picture and clinical symptomatology early, atypical and severe forms of the disease were distinguished. All of them were characterized by typical PML demyelination with oligodendroglial and astrocytic pathology. The group with early changes revealed widespread, multifocal myelin alterations of a moderate intensity with predominant oligodendroglial abnormalities and less advanced astrocytic changes. Atypical form of the disease was represented by cases with unifocal changes, although containing all key elements of PML pathology. The leading pathological feature of the severe form of the disease consisted in a particular intensity of the demyelination, resulting in tissue destruction often with its cavitation, with typical glial reaction and intense macrophage and lymphocytic infiltration. The other distinguishing feature consisted in strong topographic prevalence of the pathological process either to brain hemispheres or cerebellum. Differences of PML pathology in the course of AIDS as compared with non-AIDS cases are discussed. Due to the relatively high frequency of cases of isolated or strongly predominant involvement of cerebellum, separation of the cerebellar form of the disease has been suggested.

Opportunistic infections of the central nervous system in the course of acquired immune deficiency syndrome (AIDS). Morphological analysis of 172 cases.

A neuropathological analysis of 172 cases of AIDS in adults was carried out, to determine the occurrence and nature of the opportunistic infections of the central nervous system (CNS). The material comprised 155 cases of men, and 17 women. Mean age of patients was 38 years. Collection under study originated from the period between 1987 and 1997. Opportunistic infections were present in 57.5 percent of cases being in 38.4 percent the only pathological process, whereas in 19.1 percent they coexisted with HIV-dependent pathology or with neoplastic growth. Cytomegalovirus infection (22.7%), toxoplasmosis (16.3%), cryptococcosis (8.1%) and progressive multifocal leukoencephalopathy (9.3%) were the most common opportunistic infections of CNS. The remaining viral (herpetic encephalitis, tick-borne encephalitis and herpes zoster multifocal encephalitis), bacterial (lues, metastatic encephalitis connected with heart valvular changes) and fungal (candidiasis) infections were present only in single cases. It is worth mentioning 3 cases of brain aspergillosis and 5 cases of leptomeningeal tuberculosis. Great morphological variability in the most common opportunistic infections found in our material (cytomegaly, toxoplasmosis, cryptococcosis and PML) was the most striking phenomenon. Neuropathological abnormalities in cases of toxoplasmosis and cryptococcosis revealed remarkable dependence on clinical medication used. Cases of PML were characterized by strong variances of the type and intensity of demyelination, ranging from disseminated foci of various size to diffuse complete myelin loss in the white matter involving uni- or bilaterally cerebral or cerebellar hemispheres. The coexistence of opportunistic infections with HIV-dependent cerebral pathology or other types of opportunistic processes was a very characteristic feature. Concomitance of HIV-dependent pathology with viral opportunistic processes was common. The frequency of this concomitance and more severe HIV-dependent pathology in cases with other viral cerebral infections may suggest pathogenetic interaction of viral infections. Cerebral tuberculosis was less frequent as compared with other neuropathological collections, especially those from the United States. However, it seems worth mentioning that 3 of 5 cases occurred in the last year of observation.

Cerebral lymphomas in AIDS. Neuropathological study.

A morphological analysis was done of 15 cases of malignant cerebral lymphomas selected from the material of 160 brains of patients, who died in the course of full-blown acquired immune deficiency syndrome (AIDS) during the period of 1987-1997. Cases with cerebral lymphomas comprised 9.4% of the whole collection. There were 13 males and 2 females in the studied group. The patients age ranged from 25 to 61 years. In 10 cases lymphomas were localized solely in the central nervous system, and in further 4 they were accompanying systemic neoplastic process. In one case lack of clinical and autopsy data did not permit classification of neoplasm to the primary or to the secondary group. In 13 cases immunophenotype of the lymphomas was characterized by immunohistochemical methods. In 11 cases neoplastic cells originated from B cells line and in 2--from T cells line. In 10 cases lymphomas were found in macroscopic examination, in the remaining 5 cases they were disclosed at the brain histopathology. The dynamics and extensiveness of the neoplastic process were different in particular cases. In most of them the process was multifocal and manifested in the form of diffuse proliferation, formed tumors with changing nature of their delineation and as multilayer perivascular cuffs. The characteristic feature of diffuse neoplasmatic growth was the appearance of large coagulative necroses in the central parts of tumors. Neoplastic foci were localized most often in the cerebral hemispheres (white matter, basal ganglia, periventricular regions), less frequently in the brain stem and cerebellum. In one case diffuse lymphoid growth involved selectively leptomeninges. In most of the cases leptomeningeal infiltrations accompanied large parenchymal neoplastic foci. The most striking feature of our collection consisted in concomitance of cerebral lymphomas with HIV-specific brain pathology and/or opportunistic infections mostly of viral etiology. Their frequency was much higher than in cases of AIDS without cerebral lymphomas. Another finding which seems to be worth mentioning was the appearance of morphological exponents of various pathological processes such as for instance multinuclear giant cells, CMV inclusions within neoplastic tissue. The relatively frequent presence of numerous HIV-specific giant cells on the periphery of lymphomatous tumors suggests pathogenetic participation of immune deficiency virus in the blastomatous transformation of lymphoid cells within the central nervous system.

Neuropathological syndromes in the course of full blown acquired immune deficiency syndrome (AIDS) in adults in Poland (1987-1995).

Morphological analysis of the brains from 100 cases of full blown AIDS patients observed in the course of 1987-1995 years was performed. The material comprised 96 males, 3 females and 1 infant, 11 months old. Early material consisted almost exclusively of homo- and bisexuals, while in the last years heterosexual drug addicts prevailed. Gross brain examination revealed focal changes in 25% of cases, most of them being connected either with opportunistic infections or primary proliferating malignancies. Brain atrophy with an evident regional differences was observed macroscopically in 35 cases. Microscopic examination allowed detection of pathological changes in the brains of 87 cases, although in the remaining 13 cases there occurred some slight abnormalities taking the form of non-specific neuronal degeneration and loss, considered as resulting from perimortal cardio-pulmonary insufficiency or bleeding. Specific HIV-related changes in the form of HIV-encephalitis, HIV-encephalopathy or coexistence of both and HIV-leptomeningitis as well as HIV-vasculitis were present in 35 cases. They were accompanied by HIV-associated changes (vacuolar myelopathy, vacuolar leukoencephalopathy and selective poliodystrophy). Very seldom they appeared as independent pathological features and were characterized by very low frequency. Opportunistic infections composed the largest group of 59 cases. Proliferative malignancies occurred altogether in eleven cases, 10 of which were primary and secondary brain lymphomas. One case of Kaposi sarcoma completed the neoplastic series. Sixteen cases revealed various types of brain pathology such as hepatogenic encephalopathy, traumatic cortical scars, central pontine myelinolysis etc. The 59 cases of opportunistic infections consisted of a wide spectrum of viral and bacterial as well as fungal and protozoan infections. Among viral infections cytomegalovirus encephalitis was the most common, way ahead the progressive multifocal leukoencephalopathy. The second in frequency among opportunistic infections was brain toxoplasmosis and some fungal infections such as cryptococcosis and aspergillosis. Bacterial infections were in fact limited to tuberculosis, taking the form of granulomatous leptomeningitis with severe vascular pathology and/or tuberculoma formation. Many pathological processes appearing in a single case was characteristic feature of our collection. There was coexistence of HIV-specific CNS pathology and opportunistic infections, malignant neoplastic growth and other types of pathology. Various opportunistic infections coexisted without HIV-specific changes as well as malignant proliferation with opportunistic infections. Similarities and differences of our series were compared with data characterizing other, earlier collections of NeuroAIDS.