Depression and diagnosis of neurocognitive impairment in HIV-positive patients

Neurocognitive impairment (NCI) is frequently observed in patients infected with human immunodeficiency virus (HIV) and results from the compromise of subcortical brain structures by the virus. The manifestations of NCI range from asymptomatic impairment to dementia. In addition to cognitive impairment resulting from HIV infection, other factors such as depression are associated with the loss of cognitive functions. The aim of this study was to estimate the prevalence of NCI in HIV-positive patients in a city in southern Brazil and to establish possible associations for the prevalence of NCI with HIV-related and other risk factors. This cross-sectional study of HIV-positive outpatients was conducted in a specialized care service in the city of Pelotas in Southern Brazil. Sociodemographic data and HIV-related information were collected, and all patients underwent psychiatric and neurocognitive evaluations. The prevalence of NCI among the 392 patients was 54.1% when tracked using the IHDS (International HIV Dementia Scale) and 36.2% when the IHDS was associated with a battery of complementary tests. A bivariate analysis suggested an association of NCI with gender, age, educational level, depression, current CD4 count and lowest CD4 count. The association of NCI with depression remained in the Poisson regression (PR=1.96, 95%CI=1.12-3.42). The prevalence of cognitive impairment in HIV-positive patients estimated in this study is in accordance with international and Brazilian data. Of the factors analyzed, depression showed the greatest evidence of association with neurocognitive loss. Based on our findings, the inclusion of instruments to evaluate depression in our services for patients with HIV and acquired immunodeficiency syndrome (AIDS) is recommended.

Prevalence of neurocognitive disorders and depression in a Brazilian HIV population

Combined antiretroviral therapy has enabled human immunodeficiency virus (HIV) carriers to live longer. This increased life expectancy is associated with the occurrence of degenerative diseases, including HIV-associated neurocognitive disorders (HAND), which are diagnosed via a complex neuropsychological assessment. The International HIV Dementia Scale (IHDS) is a screening instrument validated in Brazil for use in the absence of neuropsychological evaluation. HIV patients are frequently diagnosed with depression. We aimed to determine the prevalence of neurocognitive impairment using the IHDS and depressive disorders using the Hamilton Rating Scale for Depression (HAM-D17), compare the IHDS performance with the performances on the Timed Gait Test (TGT), the Digit Symbol Coding Test (DS) and the Brazilian version of the Scale of Instrumental Activities of Daily Living (IADL), and evaluate the association between the IHDS performance and clinical-demographic variables.

Preliminary report of HIV and Toxoplasma gondii occurrence in pregnant women from Mozambique / Descrição preliminar da ocorrência de infecção pelo HIV e toxoplasmose em mulheres grávidas em Moçambique

Toxoplasmosis, a protozoan disease, causes severe disease in fetuses during pregnancy and deadly encephalitis in HIV patients. There are several studies on its seroprevalence around the world, but studies focusing on African countries are limited in number and mostly anecdotal. We studied two groups of samples from Mozambique by ELISA, using serum samples from 150 pregnant women and six Cerebrospinal fluid (CSF) samples from AIDS patients with encephalitis. HIV status was confirmed, and CD4 blood counts were obtained from HIV-positive pregnant women. IgG seroprevalence of the group as a whole was 18.7 percent (28/150), with a higher prevalence in HIV-positive individuals compared to those who were HIV-negative (31.3 percent, [18/58] vs. 10.9 percent, [10/92]) patients. These data may be biased due to cumulative effects of exposition affecting disease prevalence. If corrected, this data may indicate an interaction of HIV and T. gondii. Prevalence of both diseases increases with age, but this is more clearly seen for toxoplasmosis (p < 0.005) than HIV infection, possibly explained by higher transmission of HIV after childhood. In HIV patients suffering from encephalitis, CSF serology showed that 33 percent of specific IgG CSF had a high avidity, which was in accordance with the data from the group of pregnant women. Lower prevalence rates of both infections in older groups could be explained by more deaths in the infected groups, resulting in an artificially lower prevalence. Using CD4 counts as a marker of time of HIV infection, and correcting for age, patients with contact with T. gondii had fewer CD4 cells, suggesting prolonged HIV disease or other causes. Toxoplasma IgG prevalence is higher in HIV+ groups, which could be ascribed to HIV- and T. gondii-associated risk factors, such as exposure to higher and more diverse social contacts. The low incidence of Toxoplasma IgG in younger age groups shows that transmission could be related to better access to cyst-containing meat in adulthood, as environmental transmission due to oocysts is usually blamed for higher incidence in children. Taken together, these data support the urgent need of research in toxoplasmosis in Africa, especially in the presence of HIV epidemics.

Toxoplasmose, uma protozoonose, causa doença grave em fetos de mulheres grávidas com infecção aguda e encefalite letal em portadores de HIV. Apesar de muitos estudos sobre sua prevalência no Mundo, existem apenas alguns relatos da toxoplasmose na África Austral, geralmente anedóticos. Estudamos por ELISA dois grupos de amostras de Moçambique, usando 150 amostras de soros de mulheres grávidas e seis amostras de Liquido Cefalorraquidiano (LCR) de pacientes com AIDS e encefalite. O estado da infecção pelo HIV foi confirmado e a contagem de células CD4+ no sangue foi obtida das pacientes grávidas infectadas pelo HIV. No grupo das gestantes, IgG anti T.gondii foi encontrada em 18.7 por cento (28/150), mais freqüente em pacientes HIV positivas (31.3 por cento, 18/58) do que em HIV negativas (10.9 por cento, 10/92). A ocorrência de ambas as doenças aumenta com a idade, mais claramente vista na toxoplasmose (p < 0.005) do que na infecção pelo HIV, devido maior transmissão do HIV após a infância. Na encefalite em pacientes HIV+, a sorologia do LCR mostrou uma ocorrência de 33 por cento de IgG especifica de alta avidez, que está de acordo com a ocorrência neste grupo etário, baseado nos dados de nossas gestantes. A menor ocorrência de ambas as infecções em grupos etários mais idosos pode ser explicada pela mortalidade cumulativa por qualquer causa nos grupos mais idosos, resultando em menor ocorrência relativa. Usando as contagens de células CD4+ como marcadores da progressão da infecção pelo HIV e corrigindo para grupos etários, as gestantes HIV+ com contato com T. gondii tem menores níveis de células CD4+ do que as gestantes HIV+ sem contato com T.gondii. A ocorrência maior da toxoplasmose em gestantes HIV+ pode ser atribuída a fatores de risco semelhantes, como exposição a maior contato social. A baixa ocorrência da toxoplasmose em grupos mais jovens pode se relacionar com menor acesso a carne contendo cistos, já que a transmissão ambiental por oocistos está associada à maior incidência em crianças. Todos estes dados reforçam a necessidade de pesquisa da toxoplasmose na África Austral, especialmente na presença da epidemia pelo HIV.

Alterações cognitivas na infecção pelo HIV e Aids / Cognitive alterations associated with HIV-1 infection and Aids

Dentre as complicações neurológicas primária da Aids temos déficits cognitivos como a demência associada ao HIV e formas mais leves, como o transtorno cognitivo/motor menor, sendo que ambas podem alterar as atividades da vida diária e reduzir a qualidade de vida dos pacientes. Infecção pelo HIV-1 é a mais comum, previsível e tratável causa de déficits cognitivos em indivíduos com menos de 50 anos. A despeito do avanço no conhecimento das características clínicas, patogênese, aspectos neurobiológicos e ao amplo uso de terapia antirretroviral altamente ativa (HAART), complicações neurológicas e déficits cognitivos ainda persistem levando a graves consequências pessoais e socioeconômicas tornando-se um grande desafio terapêutico. Na era pré- HAART, a demência era uma complicação comum da infecção, entretanto na era HAART a incidência da demência diminuiu, mas a prevalência tem aumentado principalmente das formas mais leves devido ao aumento do número de pessoas infectadas e ao aumento da expectativa de vida. Alterações cognitivas associadas ao HIV são tipicamente subcorticais e podem estar associadas a comprometimentos comportamentais e motores. Estas síndromes são de diagnóstico clínico, sendo que testes neuropsicológicos, neuroimagem e líquido cerebrorraquidiano corroboram no diagnóstico. Esta revisão faz uma atualização do estado atual da epidemiologia, características clínicas e diagnóstico das complicações cognitivas no curso da infecção pelo HIV.

Primary neurological complications of AIDS include cognitive deficits such as HIV-associated dementia and milder forms such as cognitive/motor disorders, which cause changes in daily activities and reduce the quality of life of patients. Infection with HIV-1 is the most common, predictable and treatable cause of cognitive deficits in individuals with less than 50 years of age. . Despite advances in the understanding of clinical characteristics, pathogenesis and neurobiological aspects and widespread use of highly active antiretroviral therapy (HAART), neurological complications and cognitive deficits still persist with serious personal and socioeconomic consequences, thus representing a great therapeutic challenge. In the pre-HAART era dementia was a common complication of infection whose incidence declined during the HAART era. However, prevalence of dementia has increased, especially that of milder forms due to the increased number of infected individuals and increased life expectancy. Cognitive alterations associated with HIV are typically sub cortical and can be associated with behavioral and motor disorders. These syndromes are clinically diagnosed by neuropsychological tests, while neuroimaging and analysis of cerebrospinal fluid contribute to diagnosis. This review is an update on current epidemiological status, clinical characteristics and diagnosis of cognitive complications observed during the course of HIV infection.

Cellular & molecular basis of HIV-associated neuropathogenesis.

Although a plethora of molecules have been implicated in the development of HIV associated dementia (HAD), the identity of the indispensable ones is still elusive. The action of various molecules appears to follow a cascade path with one molecule activating another thereby regulating the expression and modulation of the regulatory machineries. Two pathways have been proposed leading to HIV-induced central nervous system (CNS) injury. First involving neurotoxic effect of viral proteins and second, with immunomodulatory substances secreted by the infected cells playing vital role. The viral transfer from infected cells (for example, cells representing macrophage-microglial lineage) to uninfected cells (such as same cell type or nerve cells) occurring perhaps via virological synapse is also not well documented. While the mechanism underlying transfer of HIV-1 through blood-brain barrier is not clearly understood, macrophage-microglial cell lineages are undisputedly predominant cell types that HIV uses for transmission in CNS. The present review describes existing knowledge of the modus operandi of HIV-induced neuropathogenesis gathered through research evidences. of HIV-induced neuropathogenesis gathered through research Mechanisms by which regulatory molecules exploit such cell types in promoting neuropathogenesis would provide key insights in intersecting pathway(s) for designing intervention strategies.

Demencia asociada a infección por virus de inmunodeficiencia humana tipo 1 / Human immunodeficiency virus type 1 infection associated dementia

La demencia asociada a infección por virus de inmunodeficiencia humana (DVIH) es una entidad caracterizada por la tríada de compromiso cognitivo, síntomas conductuales y motores, que generan serias dificultades en la capacidad funcional del paciente. Las múltiples denominaciones generan confusión y alta probabilidad de subreconocimiento. No obstante, la incidencia de DVIH es controversial; se tiene claro que más de 90 por ciento de pacientes con sida tiene anormalidades neuropatólogicas compatibles con DVIH. Los mecanismos patogénicos involucran una compleja interacción entre el VIH y las células del cerebro, que generan claramente dos vías incluyentes, la inflamatoria y la no inflamatoria, las cuales generan factores neurotóxicos y quimiotácticos, inductores de apoptosis, que conducen a una disrupción neuronal-glial, probablemente responsable de la injuria y/o muerte neuronal, que conduciría a un fenómeno de neurodegeneración acelerada. Los síntomas son de una demencia subcortical, siendo los síntomas de presentación más comunes el compromiso de la memoria, enlentecimiento mental, dificultad para la marcha y depresión. El diagnóstico es esencialmente clínico y se realiza por exclusión. Son de utilidad práctica la HIV Dementia Scale (HDS) y la internacional HIV Dementia Scale (IHDS), como pruebas iniciales de descarte. El tratamiento debe incluir la combinación de antiretrovirales y neuroprotectores. Como conclusión, la DVIH es una complicación devastadora de la infección por VIH que debe ser reconocida tempranamente.

Dementia associated to human immunodeficiency virus infection (DHIV) is an entity distinguished by three main signs -cognitive, behavioral and motor symptoms- which generate serious difficulties in the functional capacity of the patient. The multiple denominations generate confusion and diagnostic difficulties. In spite of controversy in DHIV incidence, it is clear that more than 90 per cent of patients with AIDS has compatible neuropathological anormalities with DHIV. The pathogenic mechanisms involve complex interactions between the HIV and the brain cells generating two inclusive paths, inflammatory and non inflammatory, that produce neurotoxic and chemotactic factors, inductors of apoptosis that lead to neuro-glial disruption probably responsible of injury and/or neuron cell death, that finally would lead to accelerated neurodegeneration phenomenon. Symptoms are subcortical dementia, mental sluggishness, walking difficulties and depression. Diagnosis is essentially clinical and by exclusion. The HIV Dementia Scale (HDS) and the International HIVD Scale (IHDS) are of practical usefulness as initial screening tests. Treatment should include the combination of antiretrovirals and neuroprotectors. We conclude that DHIV is a devastating complication of HIV infection that should have early recognition.

Neurological disease in HIV-infected patients in the era of highly active antiretroviral treatment: a Brazilian experience

Com o objetivo de estudar as doencas neurológicas em pacientes HIV/AIDS e sua relacão com a terapia anti-retroviral altamente ativa, foi realizado estudo transversal em hospital público de doencas infecciosas de Belo Horizonte, Brasil, no período de fevereiro de 1999 a marco de 2000. Doenca neurológica foi observada em 194 (46,5%) dos 417 indivíduos incluídos e um novo episódio de doenca neurológica definidora de AIDS ocorreu em 23,7% pacientes. Toxoplasmose (42,3%), criptococose (12,9%) e tuberculose (10,8%) foram as principais causas de complicacões neurológicas. A maioria dos pacientes estava em uso de terapia anti-retroviral altamente ativa (79,3%) e esses indivíduos apresentaram maiores contagens de linfócitos CD4 (p = 0,014) e maior freqüência de doenca neurológica clinicamente estável, embora não tenha havido diferenca no perfil etiológico das complicacões neurológicas. As doencas neurológicas continuam sendo causas freqüentes de complicacões da infeccão pelo HIV/AIdS no Brasil, e a despeito da terapia anti-retroviral altamente ativa, as infeccões são ainda a principal etiologia das doencas do sistema nervoso.

Trastornos neurológicos y psiquiátricos asociados al síndrome de inmunodeficiencia adquirida en pacientes hospitalizados en el Hospital Escuela de Tegucigalpa, Honduras / Neuropsychiatric manifestation of adquired immunodeficient syndrome in patients hospitalized in Hospital Escuela, Tegucigalpa, Honduras

Identificar las principales manifestaciones neuropsiquiátricas en los pacientes, que adolecen del Síndrome de Inmuno Deficiencia Adquirida (SIDA), y que acuden a los servicios de control, consulta externa y hospitalización de adultos en el Hospital Escuela de Tegucigalpa, Honduras. MATERIAL Y METODOS. Estudio descriptivo, transversal y prospectivo. Población: Hombres y mujeres, entre los 14 y 60 años, con diagnóstico de VIH/SIDA que acuden a los servicios de Consulta Externa y Hospitalización del Hospital Escuela en el período de junio de 1998 a febrero de 1999, obteniéndose la información a través de una entrevista dirigida, previamente estructurada, así como de familiares y de datos contenidos en el expediente clínico. RESULTADOS. Sítomas neurológicos y psiquiátricos en personas con VIH/SIDA fueron encontrados en el 52 por ciento de los evaluados, lo que difiere notablemente de los datos reportados hasta ahora en las estadísticas epidemiológicas generales de Honduras, donde sólo se han encontrado en 8.7 por ciento de los casos. La depresión y la demencia fueron los trastornos neuropsiquiátricos más frecuentemente encontrados (47 por ciento y 36 por ciento, respectivamente). CONCLUSION. Los trastornos neurológicos y psiquiátricos son más frecuentes que lo esperado en los pacientes con VIH/SIDA, habiéndose encontrado en el 52 por ciento de los pacientes evaluados en el presente estudio

Achados neuropatológicos na síndrome da imunodeficiência adquirida (SIDA): revisäo de 138 casos / Neuropathological findings in the acquired immunodeficiency syndrome (AIDS): review of 138 cases

Com o objetivo de determinar a incidência das diferentes afecçöes que podem atingir o Sistema Nervoso Central (SNC) na Síndrome da Imunodeficiência Adquirida (SIDA) realizou-se um estudo reetrospectivo através de necrópsias realizadas no hospital de Clínicas de Porto alegre. Para tanto, foram examinadas 138 necrópsias de pacientes portadores de SIDA que haviam morrido entre janeiro de 1985 e dezembro de 1990. Todos os cérebros foram analisados macroscópica e microscópicamente através da hematoxilina-eosina e, quando necessário, coloraçöes, especiais como Grocott, PAS, Giemsa e Ziehl-Nielsen, foram empregadas. As principais lesöes encontradas foram: toxoplasmose cerebral em 29 casos (21 por cento); criptococose em 17 (12 por cento); tuberculose em dois (1 por cento e um (0,7 por cento) de candidíase. Além destas lesöes inflamatórias foram observados 15 casos (10 por cento) com lesöes vasculares; oito (6 por cento) com gliose e sete (5 por cento) com achados sugestivos de encefalopatia pelo HIV. Podemos concluir que o SNC é um dos principais órgäos-alvo da SIDA e que a toxoplasmose cerebral é a principal forma de acometimento do SNC nestes pacientes