CD8 + T-lymphocyte Encephalitis: A Systematic Review.

The increase of CD8 + T lymphocytes in the perivascular spaces of patients with HIV encephalopathy has been reported in some studies. CD8 + T lymphocyte encephalitis was first described in 2013 and then a few other similar cases were published. We proposed to analyze the clinical, MR imaging, and histopathology findings of CD8 + T lymphocyte encephalitis. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyzes protocol using the PubMed, Scopus, Lilacs, and IBECS databases up to February 3, 2018. Seven articles were included, two case series and five case reports. A total of 19 individuals were evaluated. MRI showed alterations in the white matter signal in all cases. Histopathology showed a predominance of CD8 + T lymphocytes. The findings described so far may resemble the inflammatory immune reconstitution syndrome. New studies on the subject are needed in an attempt to characterize the differences between these two entities.

Regional differences in astrocyte activation in HIV-associated dementia

Since astrogliosis is a histological marker usually observed in HIV-associated dementia (HIV-D),we decided to investigate the potential relationship between the expression of glial fibrillary acidicprotein (GFAP) and the regional distribution of cells positive (+) for this specific marker of astrocyte activation.Histological sections of brain tissues obtained at necropsy from 5 HIV-D patients and 5 age-matched controlswithout history of neuropsychiatric illness were immunostained with peroxidase. Mean numbers of GFAP(+)astrocytes were significantly increased in entorhinal cortex, hippocampus and subcortical white matter of patients,but values in frontal cortex and basal ganglia were similar to those of controls. In contrast, surface density ofimmunoreactive GFAP was significantly increased in all tested brain areas from all patients, including unusuallyaffected regions such as entorhinal cortex and hippocampus. Therefore, such consistent finding of hypertrophicastrocytes, ranging from highest cell percentajes in subcortical white matter to lowest in basal ganglia indicatesthat quantification of surface density in GFAP (+) cells appears to be a more reliable approach to score gliosisthan the counting of their cell nuclei. Because astrocyte activation involves both protective and detrimental effectson adjacent neuronal subsets, the evidence of regional differences in this reactive potential highlights theimportance of accurately defining their contribution to the neuropathogenesis not only of HIV-D, but of a widerange of neurodegenerative disorders.

Diferencias regionales en la activación astrocitaria en demencia asociada a HIV. Siendo laastrogliosis un signo histológico habitualmente presente en demencia asociada a HIV, se investigóla eventual relación entre expresión de proteína gliofibrilar ácida (GFAP) y localización regional de células positivaspara ese marcador específico de la activación astrocitaria. Por inmunoperoxidasa, se procesaron cortes histológicosde tejidos cerebrales obtenidos por necropsia de 5 pacientes y 5 controles de edades similares pero sin antecedentesneuropsiquiátricos. Según los valores de las medias registrados por conteo de astrocitos GFAP(+) en pacientes,el número fue significativamente mayor en corteza entorrinal, hipocampo y sustancia blanca subcortical, mientrasque en corteza frontal y ganglios basales no se encontraron diferencias con controles. En cambio, la densidad desuperficie del material GFAP inmunorreactivo en pacientes estuvo significativamente aumentada en todas las áreascerebrales analizadas, incluso en regiones inusualmente afectadas, como corteza entorrinal e hipocampo. Entreesos astrocitos hipertróficos, el mayor porcentaje correspondió a sustancia blanca subcortical, y el menor a gangliosbasales. Cabe concluir que el constante hallazgo de agrandamiento astrocitario señala a la medida de la superficieinmuno-reactiva como mejor índice de activación celular que el conteo de núcleos de las células marcadas. Dadoslos reconocidos efectos de la astrogliosis sobre las subpoblaciones neuronales vecinas, la comprobadaregionalización de ese potencial reactivo destaca el interés de precisar su contribución en la neuropatogenia, tantode demencia asociada a HIV como de otras enfermedades neurodegenerativas.

Regional differences in astrocyte activation in HIV-associated dementia

Since astrogliosis is a histological marker usually observed in HIV-associated dementia (HIV-D),we decided to investigate the potential relationship between the expression of glial fibrillary acidicprotein (GFAP) and the regional distribution of cells positive (+) for this specific marker of astrocyte activation.Histological sections of brain tissues obtained at necropsy from 5 HIV-D patients and 5 age-matched controlswithout history of neuropsychiatric illness were immunostained with peroxidase. Mean numbers of GFAP(+)astrocytes were significantly increased in entorhinal cortex, hippocampus and subcortical white matter of patients,but values in frontal cortex and basal ganglia were similar to those of controls. In contrast, surface density ofimmunoreactive GFAP was significantly increased in all tested brain areas from all patients, including unusuallyaffected regions such as entorhinal cortex and hippocampus. Therefore, such consistent finding of hypertrophicastrocytes, ranging from highest cell percentajes in subcortical white matter to lowest in basal ganglia indicatesthat quantification of surface density in GFAP (+) cells appears to be a more reliable approach to score gliosisthan the counting of their cell nuclei. Because astrocyte activation involves both protective and detrimental effectson adjacent neuronal subsets, the evidence of regional differences in this reactive potential highlights theimportance of accurately defining their contribution to the neuropathogenesis not only of HIV-D, but of a widerange of neurodegenerative disorders. (AU)

Diferencias regionales en la activación astrocitaria en demencia asociada a HIV. Siendo laastrogliosis un signo histológico habitualmente presente en demencia asociada a HIV, se investigóla eventual relación entre expresión de proteína gliofibrilar ácida (GFAP) y localización regional de células positivaspara ese marcador específico de la activación astrocitaria. Por inmunoperoxidasa, se procesaron cortes histológicosde tejidos cerebrales obtenidos por necropsia de 5 pacientes y 5 controles de edades similares pero sin antecedentesneuropsiquiátricos. Según los valores de las medias registrados por conteo de astrocitos GFAP(+) en pacientes,el número fue significativamente mayor en corteza entorrinal, hipocampo y sustancia blanca subcortical, mientrasque en corteza frontal y ganglios basales no se encontraron diferencias con controles. En cambio, la densidad desuperficie del material GFAP inmunorreactivo en pacientes estuvo significativamente aumentada en todas las áreascerebrales analizadas, incluso en regiones inusualmente afectadas, como corteza entorrinal e hipocampo. Entreesos astrocitos hipertróficos, el mayor porcentaje correspondió a sustancia blanca subcortical, y el menor a gangliosbasales. Cabe concluir que el constante hallazgo de agrandamiento astrocitario señala a la medida de la superficieinmuno-reactiva como mejor índice de activación celular que el conteo de núcleos de las células marcadas. Dadoslos reconocidos efectos de la astrogliosis sobre las subpoblaciones neuronales vecinas, la comprobadaregionalización de ese potencial reactivo destaca el interés de precisar su contribución en la neuropatogenia, tantode demencia asociada a HIV como de otras enfermedades neurodegenerativas. (AU)

Regional differences in astrocyte activation in HIV-associated dementia

Since astrogliosis is a histological marker usually observed in HIV-associated dementia (HIV-D),we decided to investigate the potential relationship between the expression of glial fibrillary acidicprotein (GFAP) and the regional distribution of cells positive (+) for this specific marker of astrocyte activation.Histological sections of brain tissues obtained at necropsy from 5 HIV-D patients and 5 age-matched controlswithout history of neuropsychiatric illness were immunostained with peroxidase. Mean numbers of GFAP(+)astrocytes were significantly increased in entorhinal cortex, hippocampus and subcortical white matter of patients,but values in frontal cortex and basal ganglia were similar to those of controls. In contrast, surface density ofimmunoreactive GFAP was significantly increased in all tested brain areas from all patients, including unusuallyaffected regions such as entorhinal cortex and hippocampus. Therefore, such consistent finding of hypertrophicastrocytes, ranging from highest cell percentajes in subcortical white matter to lowest in basal ganglia indicatesthat quantification of surface density in GFAP (+) cells appears to be a more reliable approach to score gliosisthan the counting of their cell nuclei. Because astrocyte activation involves both protective and detrimental effectson adjacent neuronal subsets, the evidence of regional differences in this reactive potential highlights theimportance of accurately defining their contribution to the neuropathogenesis not only of HIV-D, but of a widerange of neurodegenerative disorders. (AU)

Diferencias regionales en la activación astrocitaria en demencia asociada a HIV. Siendo laastrogliosis un signo histológico habitualmente presente en demencia asociada a HIV, se investigóla eventual relación entre expresión de proteína gliofibrilar ácida (GFAP) y localización regional de células positivaspara ese marcador específico de la activación astrocitaria. Por inmunoperoxidasa, se procesaron cortes histológicosde tejidos cerebrales obtenidos por necropsia de 5 pacientes y 5 controles de edades similares pero sin antecedentesneuropsiquiátricos. Según los valores de las medias registrados por conteo de astrocitos GFAP(+) en pacientes,el número fue significativamente mayor en corteza entorrinal, hipocampo y sustancia blanca subcortical, mientrasque en corteza frontal y ganglios basales no se encontraron diferencias con controles. En cambio, la densidad desuperficie del material GFAP inmunorreactivo en pacientes estuvo significativamente aumentada en todas las áreascerebrales analizadas, incluso en regiones inusualmente afectadas, como corteza entorrinal e hipocampo. Entreesos astrocitos hipertróficos, el mayor porcentaje correspondió a sustancia blanca subcortical, y el menor a gangliosbasales. Cabe concluir que el constante hallazgo de agrandamiento astrocitario señala a la medida de la superficieinmuno-reactiva como mejor índice de activación celular que el conteo de núcleos de las células marcadas. Dadoslos reconocidos efectos de la astrogliosis sobre las subpoblaciones neuronales vecinas, la comprobadaregionalización de ese potencial reactivo destaca el interés de precisar su contribución en la neuropatogenia, tantode demencia asociada a HIV como de otras enfermedades neurodegenerativas. (AU)

Proteomic fingerprinting of human immunodeficiency virus type 1-associated dementia from patient monocyte-derived macrophages: A case study.

The emergence of a subset of circulating monocytes during human immunodeficiency virus type 1 (HIV-1) disease has been shown to correlate with cognitive impairment. Thus, it is hypothesized that diagnostic protein profiles may be obtained from these cells from patients with or at risk for HIV-1-associated dementia (HAD). To address this possibility, we used ProteinChip assays to define a unique monocyte-derived macrophage (MDM) protein fingerprint during HAD and whether it is affected by highly active antiretroviral therapy (HAART). The study included five Hispanic women, one with HAD, two HIV-1-infected without cognitive impairment, and two seronegative controls. All patients were matched by age and immune status. Monocytes were recovered from the peripheral blood leukocytes by Percoll gradient centrifugation and allowed to differentiate in vitro for 7 days. Cell lysates and supernatants were collected from the MDM and analyzed by surface enhanced laser desorption/ionization-time of flight ProteinChip assays. Seven unique protein peaks between 3.0 and 20.0 kDa were found in the HAD MDM sample. Each of these proteins were abrogated after HAART. Additional studies extending this one time point determination would serve to confirm the general utility of MDM protein profiling for the diagnosis and monitoring of HAD.

Degenerative and inflammatory lesions in sympathetic ganglia: further morphological evidence for an autonomic neuropathy in AIDS.

There is accumulating evidence that autonomic dysfunction occurs in HIV infection. While many studies have demonstrated autonomic abnormalities on clinical basis, only one has studied the morphology of sympathetic ganglia. The superior sympathetic ganglia of 12 randomly selected AIDS patients and those of 6 controls were examined morphologically in order to determine the frequency and severity of their involvement. Although they had not been investigated for autonomic dysfunction, 5 had suffered from non-infectious diarrhoea, one showed bilateral ptosis and another had non-specified visual problems. All cases showed clusters, and perivascular mononuclear inflammatory cells, occasionally infiltrating vessel walls, some evidence of nerve cell degeneration, and proliferation of capsule cells. Immunostainings showed T lymphocytes and an increased number of macrophages. HIV antigens were detected in macrophages, in 6 cases (50%). This study provides further morphological support for the autonomic dysfunction in association with HIV infection. As for the mechanism of this dysfunction, it has been postulated a direct infection, the virus entering the ganglia through macrophages and acting as a reservoir for HIV, and an autoimmune pathogenesis. Since HIV antigens were not detected in 50% of the cases in this and in a previous study, despite the existence of morphological lesions, it is possible that, as in HIV-related sensory-motor peripheral neuropathies, an autoimmune mechanism may also play a role in the development of the autonomic lesions.

[Dynamics of intrathecal immunoglobulin synthesis]. / Dinámica de la síntesis intratecal de inmunoglobulinas.

INTRODUCTION: Dynamics of the immune response in Central Nervous System (CSN) is different from the well-known switch of IgM synthesis to IgG synthesis in blood. OBJECTIVE: Broadcast the behavior and the factors involved in the dynamics of the intrathecal immune response in infectious neurological disorders. DEVELOPMENT: The lack of a switch from IgM class response to IgG response could be more related to regulation-modulation mechanisms of the CNS immune response than differs from blood in a different cytokines composition, and the possibility of chemokines synthesis during the neuroinflammatory process, and the neuroimmune-endocrine mechanisms. The immune pattern can be stable like neuroborreliosis, and can be modify like in herpes simplex meningoencephalitis. It could have a typical pattern like in Neisseria meningitidis meningoencephalitis and neurotuberculosis. Also the pattern could be still detectable for many years after sufficient treatment and complete recovery of the symptom-free patients like in neurosyphilis or an advanced precocious response during the childhood. In HIV encephalopathy the pattern remains the same during the evolution but in other virus infections, like Echo 6 or Coxsackie B5, depends on the biological agent. CONCLUSIONS: In order to know the acuity of the disease, we have to know the physiopathologic characteristics of the biological agents, time courses, locations of the pathological processes, and the host age. The main signs in cerebrospinal fluid of an acute, active disease of CNS are the increased of cerebrospinal fluid cell count and the increased of albumin ratio.

Aspectos moleculares de la demencia asociada con el SIDA / Molecular aspects of dementia associated with AIDS

Se ha observado una variedad de trastornos neuropsiquiátricos entre 20 y 30 por ciento de los pacientes que padecen del síndrome de inmunodeficiencia adquirida (SIDA). Debido a que las neuronas no se infectan directamente con el virus de la inmunodeficiencia adquirida (HIV), las manifestaciones fisiopatológicas de la demencia asociada con el SIDA (ADC) podrían estar relacionadas con mecanismos indirectos. La glucoproteína 120 de la envoltura viral (gp 120) derivada del VIH parece desempeñar un papel importante en el desarrollo de la ADC. Una cantidad cada vez mayor de experimentos han indicado que las concentraciones nanomolares de la gp120 derivada del VIH produce muerte neuronal in vivo, en tanto que las concentraciones picomolares matan a las neuronas in vitro. Los datos recientes sugieren que para inducir el daño neuronal, los receptores a citocinas y el CD4+ desempeñan un papel muy importante en la activación de eventos intracelulares que conducen a un incremento del Ca++ intracelular con la participación de los canales NMDA, lo que dispara los eventos intracelulares y la apoptosis. Entender el mecanismo del daño neuronal desde un punto de vista molecular y conductual, probablemente nos proporcionará el conocimiento para encontrar el tratamiento y la manera de prevenir esta complicación clínica. En esta revisión se incluye también el desarrollo de modelos animales para el estudio del mecanismo fisiopatológico de la demencia asociada con el SIDA

Encephalopathy and progression of human immunodeficiency virus disease in a cohort of children with perinatally acquired human immunodeficiency virus infection. Women and Infants Transmission Study Group.

OBJECTIVE: To describe the incidence, predictors, and survival of children with human immunodeficiency virus (HIV) encephalopathy followed in the Women and Infants Transmission Study cohort. STUDY DESIGN: Retrospective review of clinical and immunologic staging of perinatally HIV-infected infants, based on the 1994 Centers for Disease Control and Prevention Classification System. RESULTS: Data were available for 128 HIV-infected children, with a median follow-up of 24 months. HIV encephalopathy was diagnosed in 27 (21%) of children. Median survival after diagnosis was 14 months. Of children with encephalopathy, 74% had at least moderate immunosuppression by the time of diagnosis. Encephalopathy represented the first acquired immunodeficiency syndrome-defining condition in 67%, and the only one in 26% of children. Hepatosplenomegaly or lymphadenopathy during the first 3 months of life was diagnosed in 63%, in contrast to 29% of those without encephalopathy (p value = 0.001). Cardiomyopathy was present in 30% of the children with encephalopathy versus 2% of those without encephalopathy. High viral load in infancy was associated with increased risk of encephalopathy but was not predictive of age at onset. CONCLUSIONS: Encephalopathy in children with HIV is common and is associated with high viral load, immunodeficiency, and shortened survival. Encephalopathy was more likely to develop in infants with early signs and symptoms of HIV, although age at onset could not be predicted.

Encephalopathy in children with perinatally acquired human immunodeficiency virus infection. Pediatric Spectrum of Disease Clinical Consortium.

OBJECTIVE: To define the incidence, characteristics, and survival of children with perinatally acquired human immunodeficiency virus (HIV) infection and encephalopathy. DESIGN: Cross-sectional and longitudinal data collected from 1811 HIV-infected children in a multicenter active surveillance study. SETTING: Health departments and medical centers in six areas of the United States. RESULTS: HIV encephalopathy was diagnosed in 178 (23%) of 766 children with perinatally acquired immunodeficiency syndrome (AIDS). The median age at diagnosis of encephalopathy was 19 months. Among infected children, the estimated risk of having HIV encephalopathy by age 12 months was 4.0% (95% confidence interval, 2.6% to 6.0%). Children with HIV encephalopathy had more hospitalizations (median, 4) than children with other AIDS-defining conditions (median, 2; p = 0.002) and lower CD4+ T-lymphocyte counts in the first year of life (median, 444 cells/mm3). Estimated median survival after diagnosis was 22 months, similar to the 20 months for children with Pneumocystis carinii pneumonia. CONCLUSION: HIV encephalopathy in children with perinatally acquired AIDS is a common condition and is associated with severe morbidity evidenced by frequent hospitalizations, severe immunodeficiency, and short survival.