Central Nervous System Opportunistic Infections Research Articles

The neuropathology of pediatric acquired immunodeficiency syndrome.

Central nervous system disease has emerged as an important manifestation of acquired immunodeficiency syndrome in both the adult and pediatric populations, with neurologic abnormalities occurring in up to 90% of pediatric patients in some series. Neuropathologic studies, based primarily on the autopsy, have provided valuable insights into the spectrum and pathogenesis of acquired immunodeficiency syndrome-associated neurologic disorders, including primary human immunodeficiency virus encephalopathy and as the spectrum of infectious, neoplastic, and cerebrovascular diseases that may complicate the course of acquired immunodeficiency syndrome. Progressive encephalopathy represents the single most common neurologic disorder in pediatric acquired immunodeficiency syndrome and appears to be caused in most cases by direct infection in brain parenchyma by human immunodeficiency virus. Central nervous system lymphoma and cerebrovascular disease continue to account for most focal central nervous system lesions in the pediatric population. In contrast to adults with acquired immunodeficiency syndrome, opportunistic central nervous system infections remain relatively uncommon in the pediatric population. Our understanding of acquired immunodeficiency syndrome-associated neurologic disease remains far from complete. A plea is made for regular postmortem examination of the central nervous system in all patients dying with human immunodeficiency virus infection.

Cytokine expression in the brain during the acquired immunodeficiency syndrome.

The pathogenesis of central nervous system (CNS) disease in acquired immunodeficiency syndrome (AIDS) is poorly understood but may be related to specific effects of the immune system. Cytokines such as tumor necrosis factor and interleukin-1 may have toxic effects on CNS cells and have been postulated to contribute to the pathogenesis of the neurological complications of human immunodeficiency virus (HIV) infection. To characterize viral and immunological activity in the CNS, frozen specimens taken at autopsy from the cerebral cortex and white matter of HIV-seropositive and -seronegative individuals were stained immunocytochemically for mononuclear cells, major histocompatibility complex (MHC) antigens, HIV, astrocytes, and the cytokines interleukin-1 and -6, tumor necrosis factor-alpha and -beta, and interferon gamma. Levels of soluble CD4, CD8, and interleukin-2 receptor, as well as interferon gamma, tumor necrosis factor-alpha, beta 2-microglobulin, neopterin, and interleukin-6 and -1 beta were assayed in the cerebrospinal fluid and plasma of many of these individuals during life. The HIV-seropositive group included individuals without neurological disease, those with CNS opportunistic infections, and those with HIV encephalopathy. Perivascular cells, consisting primarily of macrophages with some CD4+ and CD8+ T cells and rare B cells, were consistently MHC class II positive. MHC class II antigen was also present on microglial cells, which were frequently positive for tumor necrosis factor-alpha. HIV p24 antigen, when present, was found on macrophages and microglia. Endothelial cells were frequently positive for interleukin-1 and interferon gamma and less frequently for tumor necrosis factor and interleukin-6. There were gliosis and significant increases in MHC class II antigen, interleukin-1, and tumor necrosis factor-alpha in HIV-positive patients compared to HIV-negative brains. Cerebrospinal fluid from most of the patients tested had increased levels of tumor necrosis factor, beta 2-microglobulin, and neopterin. There was no correlation in HIV-positive individuals between levels of cytokines and the presence or absence of CNS disease. These data indicate that there is a relative state of "immune activation" in the brains of HIV-positive compared to HIV-negative individuals, and suggest a potential role for the immune system in the pathogenesis of HIV encephalopathy.

Cerebral Blood Flow SPECT with Tc-99m Exametazlne Correlates in AIDS Dementia Complex Stages A Preliminary Report

Human immunodeficiency virus (HIV) infection is frequently complicated by a variety of disease processes affecting the central nervous system (CNS). One of them is AIDS dementia complex (ADC), which, in the absence of opportunistic infection, is believed to be caused by HIV itself. ADC is characterized by a constellation of cognitive, motor, and behavioral symptoms that progressively get worse. This study was coined to recruit AIDS patients without any opportunistic CNS infection but with signs of CNS abnormality as evidenced by behavioral and subtle motor changes, then to categorize them into five stages, and finally to perform the cerebral blood flow scan using Ceretec. The aim of this study was to correlate the abnormalities of the brain scan with the different stages of ADC. Five patients were analyzed, with dementias ranging from mild to severe according to Price's classification. After confirming the absence of CNS opportunistic infections and AIDS associated malignancies by CT of the brain, the patients underwent psychiatric evaluation and brain scans. The SPECT scans were very sensitive in showing uptake defects in the brain, even in the early stages of ADC. The blood flow defects were more pronounced in the later stages, while the CT scans remained negative except in patients with the most severe dementia.

Calprotectin in Cerebrospinal Fluid of the HIV Infected: A Diagnostic Marker of Opportunistic Central Nervous System Infection?

The calprotectin level in the cerebrospinal fluid (CSF) of 15 HIV positive patients with symptoms from the central nervous system (CNS) was measured. All 5 patients with opportunistic infections had levels above the reference range and all 10 patients with HIV associated encephalopathy had levels within the reference range. Thus, the calprotectin level in CSF can be of diagnostic value in differentiating between HIV associated encephalopathy and opportunistic infection in the HIV positive patient with symptoms from the CNS.

Soluble interleukin-2 receptor and soluble CD8 in serum and cerebrospinal fluid during human immunodeficiency virus-associated neurologic disease

We have measured levels of soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) in serum and cerebrospinal fluid (CSF) of 127 human immunodeficiency virus (HIV)-seropositive and 51 HIV-seronegative individuals. Serum levels of sIL-2R and sCD8 were higher in HIV + than in HIV − individuals. HIV + individuals were grouped by neurological status: asymptomatic, abnormal on neuropsychological screening, HIV-related meningitis, inflammatory demyelinating polyneuropathy, opportunistic central nervous system (CNS) infections and HIV-related dementia, myelopathy or sensory neuropathy. Serum levels of sIL-2R and sCD8 were higher in all HIV + categories compared to HIV − individuals. Patients with HIV-related meningitis had higher levels of sIL-2R and sCD8 than asymptomatic HIV + individuals, and inflammatory polyneuropathy patients had higher levels of sCD8. CSF levels of sCD8 were higher in all categories of HIV + than in HIV − individuals. Patients with HIV-related meningitis, inflammatory neuropathy and opportunistic infections had higher levels than asymptomatic individuals. Examination of the time course showed that serum and CSF levels of sIL-2R and sCD8 increased to very high levels during acute HIV infections. Serum levels then declined over several months to relatively stable elevated levels. By 1–2 years after HIV infection sIL-2R was relatively low in CSF, while sCD8 ramained elevated with a gradual decrease over the subsequent years of follow-up.

Nature, incidence and prognosis of neurological involvement in the acquired immunodeficiency syndrome in central London.

Clinical neurological involvement at various times throughout the illness was recorded in 52% of 122 patients seen in central London who died from acquired immunodeficiency syndrome (AIDS). Various metabolic encephalopathies, dementias, focal encephalopathies, retinopathies and peripheral nerve pathology were the most frequent manifestations. Seven of 9 patients with a neurological presentation had no other major systemic illness. The median time from diagnosis of AIDS to death was 9 months and from onset of neurological symptoms to death 4 months. Human immunodeficiency virus dementia, central nervous system opportunistic infections, presence of Kaposi sarcoma, neurological presentations and minor symptoms were not associated with major change in survival time.

Human Immunodeficiency Virus (HIV) Infection in Brains with AIDS-Related Leukoencephalopathy

In addition to central nervous system (CNS) opportunistic infections and neoplasms, patients with acquired immunodeficiency syndrome (AIDS) develop unexplained dementia and encephalopathy and degeneration of the white matter. We studied autopsied brains from 20 adult patients who expired from AIDS to determine the relationship of human immunodeficiency virus (HIV) infection to white matter lesions and to clinical findings. In four patients with dementia/encephalopathy and abnormalities of the white matter, there was evidence of HIV infection as shown by in situ hybridization. In contrast, the remaining 16 patients who had no evidence of white matter degeneration revealed no hybridization to the HIV probe. The cells infected with HIV included endothelial cells, perivascular macrophages/monocytes, and multinucleated giant cells and were found in or adjacent to white matter degeneration. These results demonstrate a correlation between HIV-infected cells and AIDS leukoencephalopathy and provide further evidence for HIV-related dementia/encephalopathy.

Prevention of central nervous system infections in patients at risk

Infections of the central nervous system in patients at risk are relatively uncommon when compared with pneumonia, bacteremia, and soft tissue infection. However, they carry serious morbidity and are frequently fatal. Each of the diverse conditions that can place a patient at risk for central nervous system infection is associated with a fairly predictable spectrum of etiologic organisms. Various forms of trauma (including blunt and penetrating injuries and neurosurgery, especially when a cerebrospinal fluid shunt is implanted) predispose to infection with common pathogenic bacteria. Defects of cellular immunity including congenital immune deficiencies, immunosuppressive drug therapy, leukemia, lymphoma, and the acquired immune deficiency syndrome are more likely to give rise to infection with a distinctive spectrum of opportunistic viruses, fungi, and protozoa. Other underlying conditions include sinus, ear, and mastoid infections, congenital heart disease, intrathoracic suppuration, endocarditis, and bacteremia, hypogammaglobulinemia, and complement deficiencies. Some preventive measures including vaccines, antibiotics, and surgical procedures are available. However, for many of these central nervous system infections, preventive measures are lacking or less effective than those for infections in other organs. In the future, opportunistic central nervous system infections will increase in frequency as the number of patients at risk continues to grow.

Neurological complications of Kaposi's sarcomat. An analysis of 5 cases and a review of the literature.

We analyzed the neurological complications in 25 patients with Kaposi's sarcoma, 5 encountered at Memorial Sloan-Kettering Cancer Center and 20 culled from the literature. Patients with all clinical forms of Kaposi's sarcoma [14 classical cases, 2 African cases, 5 cases associated with immunosuppressive therapy and 4 cases associated with acquired immunodeficiency syndrome (AIDS)] suffered neurological dysfunction which included neoplastic involvement of the nervous system (Kaposi's sarcoma or another primary), autoimmune disorders and opportunistic infections. Neoplastic involvement was recorded most frequently in patients with classical and African Kaposi's sarcoma and was favored in a setting of extensive tumor dissemination. Opportunistic infections (cryptococcal meningitis and cerebral toxoplasmosis) were observed in all forms of Kaposi's sarcoma but were most frequent in AIDS cases and correlated with the degree of immune dysfunction. Our data suggest that more diverse opportunistic central nervous system infections, neurological disorders of an autoimmune nature, and neoplastic involvement of the nervous system are to be anticipated in AIDS.