Cerebral toxoplasmosis and alcohol abuse in AIDS: dementia with multiple etiologies / Neurotoxoplasmose e abuso de álcool em aids: demência com múltiplas etiologias

ABSTRACT Major neurocognitive disorder due to multiple etiologies, or dementia due to multiple etiologies (DME), is a term coined by the Diagnostic and Statistical Manual of Mental Disorders to refer to complex cases when multiple pathologies, such as Alzheimer's disease, Lewy Bodies, human immunodeficiency virus (HIV), vascular-related brain damage or frontotemporal lobar degeneration, are identified as contributing to neurocognitive impairment and/or behavioral alterations, based on patient's neuroimaging tests, laboratorial exams, associated symptomatology and medical history. In this study, we report the case of a 63-year-old male patient who presented with parkinsonism symptoms, aphasia and cognitive impairment on multiple domains after cerebral toxoplasmosis related to acquired immunodeficiency syndrome, vascular damage and a history of alcohol abuse. We discuss the neurocognitive and neurobehavioral variables that characterized this diagnosis, as well as the importance of the differential diagnosis of DME on the field of neuropsychology of aging and, especially, for individuals living with HIV infection.

RESUMO Transtorno neurocognitivo maior devido a múltiplas etiologias, ou demência por múltiplas etiologias (DME), é um termo estabelecido pelo Manual Diagnóstico e Estatístico de Transtornos Mentais para se referir a casos complexos em que múltiplas patologias, como a Doença de Alzheimer, Corpos de Lewy, o vírus da imunodeficiência humana (HIV), danos de origem vascular ou a degeneração lobar frontotemporal, são identificados como contribuintes para o comprometimento neurocognitivo e/ou para alterações comportamentais, com base em testes de neuroimagem do paciente, exames laboratoriais, sintomatologia associada e histórico médico. Neste artigo, relatamos o caso de um paciente do sexo masculino de 63 anos que apresentou sintomas de parkinsonismo, afasia e comprometimento cognitivo em múltiplos domínios após neurotoxoplasmose relacionada à síndrome da imunodeficiência adquirida, dano vascular e histórico de abuso de álcool. Foram discutidas as variáveis neurocognitivas e neurocomportamentais que caracterizaram esse diagnóstico, assim como a importância do diagnóstico diferencial de DME para a neuropsicologia do envelhecimento e, especialmente, para indivíduos portadores do HIV.

Evolución y secuelas cognitivas en un paciente con encefalopatía por VIH/SIDA con tratamiento antirretroviral / Evolution and cognitive consequences in a patient with HIV/AIDS encephalopathy with antiretroviral treatment

El VIH/SIDA es una enfermedad neurotrópica que afecta al sistema nervioso central y dependiendo de la fase clínica de la enfermedad genera deterioro neurológico, psiquiátrico y neuropsicológico en grado variable. Se describe el caso de un paciente que presentó un cuadro de deterioro cognitivo severo (demencia SIDA) con posterior mejoría de signos y síntomas, y establecimiento posterior de secuelas neuropsicológicas después de un año de su diagnóstico. Se comparó una evaluación neuropsicológica en etapa de deterioro cognitivo severo con otra de seguimiento, realizada un año después de iniciar el tratamiento antirretroviral. Se presentan las características clínicas del paciente utilizando el estudio de caso como herramienta metodológica y sobre la base de un procedimiento clínico y psicométrico.

HIV/AIDS is a neurotropic disease that affects the central nervous system and depending on the clinical phase of the disease generates neurological, psychiatric and neuropsychological impairment to varying degrees. The case of a patient who presented severe cognitive impairment (AIDS dementia) is described with subsequent remission of signs and symptoms, and establishment of neuropsychological sequelae after one year of diagnosis. A neuropsychological evaluation in stage of severe cognitive impairment was compared with another follow-up one year after initiating antiretroviral treatment. The clinical characteristics of the patient are presented using the case study as a methodological tool and based on a clinical and psychometric procedure.

Trastornos neurocognitivos en pacientes VIH positivos: datos preliminares de una cohorte prospectiva uruguaya / Neurocognitive disorders in positive HIV patients: preliminary data of a Uruguayan prospective cohort

Introducción: la incidencia de formas leves y moderadas de trastornos neurocognitivos (TNC) en pacientes con VIH (virus de inmunodeficiencia humana) permanece en ascenso a pesar del uso de terapia antirretroviral (TARV). En la región existen escasos trabajos que estudiaron los TNC en VIH. Objetivos: describir características de pacientes con TNC, identificar posibles etiologías y si se realiza su búsqueda. Material y método: estudio transversal de recolección prospectiva. Se reclutaron en forma consecutiva pacientes de 18 a 60 años VIH positivos sin patología estructural del sistema nervioso central. Se aplicaron exámenes de laboratorio, preguntas para tamizaje de TNC, escala instrumental de actividades de la vida diaria (EIAVD) e internacional de demencia por VIH (EIDV), Adenbrooke's Cognitive Examination Revisado (ACE-R). ACE-R fue elegida como prueba de referencia de desempeño neurocognitivo. Se utilizó inventario de Beck para pesquisa de trastorno depresivo. Análisis estadístico con sistema SPSS. Resultados y discusión: se reclutaron 20 pacientes, se diagnosticó TNC en 9/20 (45%). Los médicos tratantes plantearon TNC en 2/9 pacientes. El análisis multivariado encontró asociación entre desempleo (p=0,012) y menor escolarización (p=0,035) en pacientes con TNC. Etiología de TNC en 9/9 fue multifactorial. Refirieron TNC en el tamizaje 8/9 pacientes. EIDV fue adecuada para detección de TNC severo, pero no para leve. EIAVD tampoco logró detectar algunos casos de TNC. Conclusiones: casi la mitad de pacientes presentaron TNC de causa multifactorial con asociación a desempleo y menor escolarización. Los médicos tratantes no plantearon este diagnóstico, lo que marca la importancia de la evaluación neuropsicológica sistemática en pacientes VIH.

Introduction: the incidence of mild and moderate neurocognitive disorders (NCDs) in HIV patients continues to increase in spite of antiretroviral therapy (ART). Only a few studies in the region focused on HIV associated NCDs. Objective: to describe the characteristics of NCDs patients, identify posible etiologies and decide whether to start the search. Method: transversal study with a prospective collection of data. HIV positive patients between 18 and 60 years old with no structural defects of the central nervous system (CNS) were consecutively recruited. Laboratory tests were applied as well as screening for CNS, the Instrumental activities of daily living (IADLs) scale, the International HIV Dementia Scale (IHDS), and the Adenbrooke's Cognitive Examination revised exam (ACE-R). The latter was chosen as the reference test for neurocognitive performance. The Beck Depression inventory (BDI) was used to identify drepression. Statistical analysis was conducted with the SPSS system. Results and discussion: 20 patients were recruited, NCD was diagnosed in 9 out of 20 patients (45%). Treating physicians spoke about NCD in 2 of the 9 patients. Multivariate analysis revealed an association between unemployment (p=0.012) and a lower schooling rate (p=0.035) in patients with NCDs. Etiology of NCD was multifactorial in all 9 patients. 8 out of 9 patients were referred as NCDs in the screening. IHDS was appropriate to identify severe NCDs, although it failed in mild cases. Also, IADLs failed to identify a few cases of NCDs. Conclusions: almost half of the patients presented multifactorial NCDs, associated to unemployment and a lower rate of schooling. Treating physicians did not consider this diagnosis, what reflects the importance of a systematic neuropsychological assessment in HIV patients.

Introdução: a incidência de formas leves e moderadas de transtornos neurocognitivos (TNC) em pacientes com VIH (vírus de imunodeficiência humana) continua crescendo apesar do uso da terapia antirretroviral (TARV). Poucos trabalhos estudaram TNC em pacientes VIH positivos na regiao. Objetivos: descrever as características dos pacientes com TNC, identificar possíveis etiologias e se são pesquisados no paciente. Método: estudo transversal com coleta de dados prospectiva. Foram incluídos de forma consecutiva pacientes com idades entre 18 e 60 anos VIH positivos sem patologia estrutural do sistema nervoso central (SNC). Foram realizados exames de laboratório, um questionário para triagem dos TNC, e foram aplicadas as escalas Instrumental de Atividades da Vida Diária (EIAVD), Internacional de Demência por VIH (EIDV) e Adenbrooke's Cognitive Examination Revisado (ACE-R). Esta última foi escolhida como prova de referencia de desempenho neurocognitivo. O inventário de Beck foi utilizado para pesquisa de transtorno depressivo. A análise estatística foi realizada com o pacote SPSS. Resultados e discussão: foram incluídos 20 pacientes sendo que os TNC foram diagnosticados em 9/20 (45%). Os médicos que atenderam esses pacientes diagnosticaram TNC em 2/9 pacientes. A análise multivariada mostrou uma associação entre desemprego (p=0,012) e menor escolarização (p=0,035) em pacientes com TNC. A etiologia dos TNC em 9/9 foi multifatorial. A triagem mostrou TNC em 8/9 pacientes. O teste EIDV foi adequado para a detecção dos TNC severos porém não para leves, e também não pode detectar alguns casos de TNC. Conclusões: quase a metade dos pacientes apresentou TNC de causa multifatorial associados a desemprego e menor escolarização. Os médicos que atenderam os pacientes não diagnosticaram esses transtornos o que mostra a importância da avaliação neuropsicológica sistemática em pacientes VIH.

Estudio de alteraciones neurocognitivas en pacientes infectados por el virus de la inmunodeficiencia humana / Study of neurocognitive alterations in patients infected by the human immunodeficiency virus

El virus de inmunodeficiencia humana, conocido por su impacto en el sistema inmunológico, ocasionamanifestacionesneurológicas progresivas con afectación cognitiva, perturbando funciones de atención, memoria, lenguaje, ejecución y procesamiento de la información, lo cual interfiere de forma negativa en la vida social, laboral y familiar del paciente. Objetivos: Evaluar las alteraciones de diferentes funciones neurocognitivas de los pacientes con infección por el virusde inmunodeficienciahumana, en una institución prestadora de servicios de salud de la cuidad de Ibagué - Colombia. Método: Se utilizó la Evaluación Cognitiva Montreal (MoCA), la cual fue diseñada como un instrumento ágil para determinar alteraciones cognitivas leves. La población objeto de estudio la constituyeron 44 pacientes portadores de virus de inmunodeficiencia humana, seleccionados dentro de un marco de muestreo no-probabilístico con muestra intencional o de conveniencia, entre los 14 y 75 años de edad. Resultados: Mayor deterioro neurocognitivo en los pacientes diagnosticados con virus de inmunodeficiencia humana de mayor edad; datos epidemiológicos indican que la edad más avanzada se asocia a una mayor prevalencia de desorden neurocognitivo asociado al virus de inmunodeficiencia humana. Conclusiones: El estudio de los mecanismos del deterioro neurocognitivo en pacientes con virus de inmunodeficiencia humana se hace cada vez más relevante, porque cada día aumenta su esperanza de vida, pero a su vez genera complicaciones con mayor predominio de la comorbilidad médica, psiquiátrica y neurológica(AU)

Introduction: The Human Immunodeficiency Virus, known for its impact on the immune system, causes progressive neurologic manifestations with cognitive impairment, disrupting attention functions, memory, language, execution and processing of information. The latter negatively interferes in social, work and family life of the patient. Objectives: To evaluate alterations in varied neurocognitive functions on patients with Human Immunodeficiency Virusinfection, at a health institution in Ibague, Colombia. Method: The Montreal Cognitive Assessment (MoCA) was used. It was designed as a tool to determine mild cognitive alterations. The study population was made up of 44 carriers of Human Immunodeficiency Virus who were selected within a framework of non-probabilistic sampling and with purposive sample or convenience, between 14 and 75 years old. Results: Greater neurocognitive impairment in patients diagnosed with Human Immunodeficiency Virus in legal age; someepidemiological data indicate that the older age is associated with a higher prevalence of neurocognitive disorder associated with Human Immunodeficiency Virus. Conclusions: The study of the neurocognitive impairment mechanisms in patients with Human Immunodeficiency Virus becomes increasingly more relevant, as their life expectancy increases daily. On the other hand, it causes complications with greater prevalence of medical psychiatric and neurological comorbidity(AU)

Comparison between the Mini-Mental State Examination and Montreal Cognitive Assessment as a Cognitive Screening Tool in Patients with Human Immunodeficiency Virus-Associated Neurocognitive Disorders

Abstract INTRODUCTION: The number of human immunodeficiency virus-associated neurocognitive disorders has increased, reaching more than 50% of the cases. However, there are currently no substantial data on the screening methods for this disease. This study aimed to evaluate and compare the Mini-Mental State Examination to the Montreal Cognitive Assessment in human immunodeficiency virus-infected patients. METHODS: This was an observational study comprising 82 human immunodeficiency virus-positive individuals with and without cognitive complaints. RESULTS: Positive correlation (p<0.001) between the Mini-Mental State Examination and the Montreal Cognitive Assessment test scores was observed, but the mean scores revealed that the Mini-Mental State Examination showed worse performance for trails (p<0.001), cube copying (p<0.001), and clock drawing (p<0.001) than the Montreal Cognitive Assessment. CONCLUSIONS: The Mini-Mental State Examination and the Montreal Cognitive Assessment tests should be used concomitantly for the assessment of human immunodeficiency virus-associated neurocognitive disorders, but visuoexecutive and visuospatial dysfunctions are better evaluated using the Montreal Cognitive Assessment test than the Mini-Mental State Examination.

Detección de trastornos neurocognitivos en pacientes infectados por HIV mediante pruebas rápidas de cribado / Detection of neurocognitive disorders in patients infected by Human Immunodeficiency Virus through fast screening tests

Introducción: Los trastornos neurocognitivos asociados con el HIV (HAND, por sus siglas en inglés) son altamente prevalentes entre las personas que viven con el virus. Existen tres categorías: demencia asociada a HIV, deterioro neurocognitivo leve y trastorno cognitivo asintomático. Diferentes pruebas de cribado son utilizadas para detectarlos: HIV Dementia Scale (HDS), International Dementia Scale (IHDS) y Mini Mental Test (MMSE). Objetivo: Identificar mediante tres pruebas la presencia de trastornos cognitivos en pacientes infectados con HIV y su relación con diferentes factores de riesgo.Métodos: Estudio prospectivo analítico. Criterios de exclusión: neuroinfecciones, patologías psiquiátricas, uso de drogas de abuso, alcoholismo, TCE y antecedentes de neurocirugía. Resultados: Se incluyeron 51 pacientes entre 18 y 67 años. La prevalencia de HAND fue 25,5%. Presentaban deterioro neurocognitivo: el 66% HDS, 14% IHDS y 29% MMSE; y demencia el 73% HDS, 29% IHDS y 7% MMSE. Se encontró asociación entre HAND y diferentes factores de riego, como edad, desnutrición, nivel instructivo bajo, ≥ tiempo desde el diagnóstico de la infección, bajo recuento de LTCD4+, carga viral detectable y tiempo de inicio de TARV. El 100% de los pacientes tenía al menos un antirretroviral con alta penetración de la barrera hematoencefálica.Conclusiones: Los diferentes grados de deterioro neurocognitivo variaron según la prueba utilizada. Todos los pacientes tratados tenían en su esquema al menos un antirretroviral que atraviesa la barrera hematoencefálica. Factores de riesgo como edad, bajo nivel educativo, bajo peso, carga viral detectable, menor recuento de LTCD4 y tiempo de inicio TARV se asociaron a diferentes grados de deterioro neurocognitivo

Background: HIV-associated neurocognitive disorders (HAND) arehighly prevalent among people living with the virus. There are 3 clinical categories; dementia associated with HIV, mild neurocognitive disorder and asymptomatic neurocognitive disorder. Fast screening tests are used to detect them, such as HIV Dementia Scale (HDS), International HIV Dementia Scale (IHDS) and Mini-mental test (MMSE). The objective of this research was identified through 3 fast screening tests the presence of neurocognitive impairment in patients infected by HIV and his relationship with different risks factors. Methods: Prospective, analytical research.Exclusion criteria: patients with neuroinfections, psychiatric disorders, use of drugs, alcoholism, traumatic brain injury and history of neurosurgery.Results: 51 patients were includedbetween 18 and 67 years old. The prevalence of HAND was 25,5%. 66% HDS, 14% IHDS and 29% MMSE presented neurocognitive impairment; and 73% HDS, 29% IHDS and 7% MMSE exhibited dementia. Significant association was found between HAND and different risk factors like, age, underweight, low educational level, less time since HIV diagnosis, low LTCD4+ count, detectable viral load and time since TARV was initiated. Besides 100% of patients had almost one antiretroviral drug with high penetration through the blood brain barrier.Conclusions: Different levels of neurocognitive disorders varied according to the screening test used. Although all patients treated, had a least one antiretroviral drug which cross the blood brain barrier in their scheme, risk factors such asage, low educational level, underweight, detectable viral load and low LTCD4 level and less time since diagnosis of the infection were associated with different level of neurocognitive disorders.

Dementia and behavioral disorders in progressive multifocal leukoencephalopathy (PML) ­ case report / Demência e alterações comportamentais na leucoencefalopatia multifocal progressive (LEMP) ­ relato de caso

Psychiatric disturbances in Progressive Multifocal Leukoencephalopathy (PML) are rarely adressed and its study can offer insights into the neurobiology of psychosis. The authors report a case of male patient, 42 years old, HIV positive, with PML and psychotic symptoms. The present case shows the need for regular neurological and neuropsychological evaluations of HIV positive patients and the importance of studying diseases that cause lesions in the white matter,such as PML, to elucidate the neurobiology of psychosis.(AU)

Os distúrbios psiquiátricos na Leucoencefalopatia Multifocal Progressiva (LEMP) raramente são abordados e seu estudo pode oferecer insights sobre a neurobiologia da psicose. Os autores relatam caso de paciente do sexo masculino, 42 anos, HIV positivo, com LEMP e sintomas psicóticos. O caso apresentado evidencia a necessidade de realização regular de avaliações neurológicas e neuropsicológicas de pacientes HIV positivos e a importância de se estudar doenças que causam lesões na substância branca, como a LEMP, para elucidar a neurobiologia da psicose.(AU)

Aging, neurocognitive impairment and adherence to antiretroviral therapy in human immunodeficiency virus-infected individuals

ABSTRACT Background/objective: There is an increasing number of older patients with human immunodeficiency virus infection due to the success of antiretroviral therapy, the improved prognosis and life expectancy of patients, and the higher number of new infections among older individuals. The main objective of the present study was to compare the characteristics of older human immunodeficiency virus patients with those of younger patients. Materials and methods: We conducted a cross-sectional study with human immunodeficiency virus-infected patients who were treated at the Specialized Care Service (Serviço de Assistência Especializada) for human immunodeficiency virus/AIDS in the city of Pelotas, South Brazil. Sociodemographic information as well as data on human immunodeficiency virus infection and treatment were collected. All participants underwent psychiatric and neurocognitive assessments, and their adherence to antiretroviral therapy was evaluated. Results: A total of 392 patients participated in the study, with 114 patients aged 50 years and older. The characteristics showing significant differences between older and younger human immunodeficiency virus-infected patients included race/ethnicity, comorbidities, duration and adherence to antiretroviral therapy, currently undetectable viral load, and cognitive impairment. Compared to younger patients, older patients were at higher risk of exhibiting cognitive impairment [OR 2.28 (95% CI: 1.35-3.82, p = 0.002)] and of having increased adherence to antiretroviral therapy [OR 3.11 (95% CI: 1.67-5.79, p < 0.001)]. Conclusions: The prevalence of neurocognitive impairment remained high in human immunodeficiency virus-infected patients despite antiretroviral therapy. In the present study, the prevalence of this type of impairment was significantly higher in patients aged ≥50 years, most likely due to aging, human immunodeficiency virus infection, and a possible synergistic effect between these factors. Despite this higher prevalence, older patients exhibited higher rates of adherence to antiretroviral therapy and of undetectable human immunodeficiency virus viral load.

HIV and dementia: prevalence and risk factors / HIV e demência: prevalência e fatores de risco / VIH y demencia: prevalencia y factores de riesgo

Objective: To determine the prevalence of patients at risk of developing HIV-associated neurocognitive disorder (HAND) and identify factors possibly associated with its occurence. Methods: Quantitative cross-sectional study conducted at the Specialized Care Service (Serviço de Atendimento Especializado - SAE) for HIV/Aids of the Integrated Medical Care Center (Núcleo de Atendimento Médico Integrado - NAMI) of the University of Fortaleza (Universidade de Fortaleza - UNIFOR), Fortaleza, Ceará, Brazil. We reviewed medical records of all 249 patients that started medical follow-up at SAE/NAMI since its foundation (August/2010) until January/2014, including in the analysis those who completed the international HIV dementia scale - IHDS during routine medical visits. Epidemiological, clinical and laboratory variables were collected in addition to IHDS score and the sample was classified in two groups: patients with IHDS≥10 (Group 1) and IHDS<10 (Group 2). Chisquared test was used for categorical variables and student t test, mann whitney test and linear regression were used for numerical variables. Results: The study population consisted of 178 patients with mean IHDS score of 9.5 (+/- 1.6). HAND prevalence was 41.6% (74/178) (IHDS<10). These patients presented older mean age (37.4 years) and longer mean time from HIV diagnosis to medical follow-up than the others (10.1 months) when compared to Group 2 (31 years old and 4.6 months, respectively), suggesting that these two variables were possibly associated with HAND occurrence. Conclusion: The IHDS application showed a high prevalence of HAND in the study population. More advanced age and longer time from HIV diagnosis to medical follow-up are possibly associated with its occurence.

Objetivo: Determinar a prevalência de pacientes sob risco de desenvolver desordem cognitiva relacionada ao HIV (HAND ­ HIV associated neurocognitive disorder) e identificar fatores que possivelmente estariam associados à sua ocorrência. Métodos: Estudo quantitativo, transversal, conduzido no Serviço de Atendimento Especializado (SAE) em HIV/AIDS do Núcleo de Atenção Médica Integrada (NAMI), Universidade de Fortaleza (UNIFOR), Fortaleza/Ceará/Brazil. Foram revisados todos os 249 prontuários de pacientes que iniciaram acompanhamento no SAE/NAMI desde a sua criação (agosto/2010) até janeiro/2014, incluindo-se na análise aqueles que apresentavam o registro da aplicação da escala de demência do HIV (IHDS ­ international HIV dementia scale) nas consultas de rotina. Coletaram-se variáveis epidemiológicas, clínicas e laboratoriais, além do valor do IHDS, classificando-se a amostra em dois grupos: pacientes com IHDS≥10 (Grupo 1) e IHDS<10 (Grupo 2). Utilizaram-se testes Qui-quadrado para variáveis categóricas, e T de Student, Mann Whitney e regressão linear para variáveis numéricas. Resultados: A população do estudo consistiu em 178 pacientes, com escore médio da IHDS de 9.5 (+/-1.6). A prevalência de HAND foi de 41,6% (74/178) (IHDS<10). Nesses pacientes, a idade média era mais elevada (37,4 anos) e o intervalo médio de tempo entre o diagnóstico do HIVe o início do acompanhamento era maior que os demais (10,1 meses), quando comparados com o Grupo 2 (31 anos e 4,6 meses respectivamente), sugerindo que essas duas variáveis possivelmente estavam associadas com a ocorrência da HAND. Conclusão: A utilização do IHDS demonstrou uma elevada prevalência de HAND na população estudada. A idade mais elevada e o intervalo de tempo maior entre o diagnóstico do HIV e o início do acompanhamento estão possivelmente relacionados com essa ocorrência.

Objetivo: Determinar la prevalencia de pacientes con riesgo para el desarrollo del desorden cognitivo relacionado al VIH (HAND ­ HIV associated neurocognitive disorder) y identificar los factores que posiblemente estarían asociados a su ocurencia. Métodos: Estudio cuantitativo, transversal realizado en el Servicio de Atención Especializada (SAE) en VIH/SIDA del Núcleo de Atención Médica Integrada (NAMI), Universidad de Fortaleza (UNIFOR), Fortaleza/Ceará/Brasil. Se revisó todos los 249 historiales clínicos de pacientes que iniciaron seguimiento em el SAE/NAMI desde su creación (agosto/2010) hasta enero/2014, incluyéndose en el analisis aquellos que presentabam el registro de la aplicación de la escala de demencia del VIH (IHDS ­ international HIV dementia scale) en las consultas de rutina. Se recogieron variables epidemiológicas, clinicas y de laboratório además del valor del IHDS clasificando la muestra en dos grupos: pacientes con IHDS≥10 (Grupo 1) y IHDS<10 (Grupo 2). Se utilizó las pruebas Chi-cuadrado para las variables categóricas y la prueba T de Student, Mann Whitney y regresión linear para las variables numericas. Resultados: La población del estudio fue de 178 pacientes con puntuación media para la IHDS de 9.5 (+/- 1.6). La prevalencia de HAND fue del 41,6% (74/178) (IHDS<10). En eses pacientes la edad media fue más elevada (37,4 años) y el intervalo de tiempo medio entre el diagnostico del VIH y el inicio del seguimiento fue mayor que los demás (10,1 meses) al comparar con el Grupo 2 (31 años y 4,6 meses respectivamente) lo que sugiere que esas dos variables posiblemente estaban asociadas a la ocurrencia de la HAND. Conclusión: La utilización del IHDS demonstró una elevada prevalencia de HAND en la población estudiada. La edad más elevada y el intervalo de tiempo mayor entre el diagnostico del VIH y el inicio del seguimiento están posiblemente relacionados con esta ocurrencia.

Risk factors for neurocognitive impairment in HIV-infected patients and comparison of different screening tools / Fatores de risco para alterações neurocognitvas em pacientes infectados pelo HIV e comparação de diferentes ferramentas de triagem

HIV-associated neurocognitive disorder (HAND) is relatively frequent among HIV-infected patients and is often underdiagnosed. Assessment of HAND in daily clinical practice is challenging and different tools have been proposed. Objective : To evaluate risk factors and compare different screening tools for neurocognitive impairment in HIV-infected patients. Methods : HIV-infected patients were evaluated using the International HIV-Dementia Scale (IHDS), Mini-Mental State Examination (MMSE) and a neurocognitive self-perception questionnaire recommended by the European AIDS Clinical Society. Sociodemographic, clinical and laboratory data were obtained through chart review and patient interview. Results : Among the 63 patients included, low performance on the IHDS was observed in 54.0% and IHDS score was inversely associated with age (OR 0.13; 95%CI [0.02-0.67]). Regarding cognitive self-perception, 63.5% of patients reported no impairment on the three domains covered by the questionnaire. Among those patients self-reporting no problems, 42.1% had low performance on the IHDS. None of the patients scored below the education-adjusted cut-off on the MMSE. Conclusion : IHDS scores suggestive of HAND were observed in more than half of the patients and lower scores were found among older patients. There was low agreement between the different tools, suggesting that the MMSE may be inadequate for assessing HAND. The self-assessment questionnaire had low sensitivity and might not be useful as a screening tool.

As alterações neurocognitivas associadas ao HIV (HAND) são relativamente frequentes entre pacientes infectados pelo HIV, porém são subdiagnosticadas. Avaliação de HAND na prática clínica diária é desafiador e diferentes ferramentas têm sido propostas. Objetivo : Avaliar fatores de risco e comparar diferentes ferramentas de rastreamento de alterações neurocognitivas em pacientes infectados pelo HIV. Métodos : Pacientes infectados pelo HIV foram avaliados usando a Escala Internacional de Demência pelo HIV (IHDS), Mini Exame do Estado Mental (MEEM) e um questionário de autopercepção neurocognitiva recomendado pela Sociedade Clínica Europeia de AIDS. Dados sociodemográficos, clínicos e laboratoriais foram obtidos por revisão de prontuário e entrevista com o paciente. Resultados : Entre os 63 pacientes incluídos no estudo, um baixo desempenho no IHDS foi observado em 54,0% e o escore no IHDS esteve inversamente associado à idade (OR 0,13; IC95% [0,02-0,67]). Em relação à autopercepção cognitiva, 63,5% dos pacientes não relataram nenhum prejuízo nos três domínios avaliados pelo instrumento. Nenhum paciente apresentou escore no MEEM abaixo do ponto de corte ajustado para escolaridade. Conclusão : Escores no IHDS sugestivos de HAND foram observados em mais da metade dos pacientes e valores mais baixos foram encontrados entre pacientes mais velhos. Houve pouca concordância entre os diferentes métodos de avaliação, sugerindo que o MEEM é inadequado para avaliação de HAND e o questionário de auto-avaliação tem uma baixa sensibilidade, não parecendo ser útil como ferramenta de triagem.

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.

Cognitive impairment among Indonesia HIV naïve patients

Background: Antiretroviral treatment (ART) can decreased the incidence of HIV dementia, but milder cognitive impairment may not resolve when patients receive ART. In Indonesia, cognitive screening of HIV patients is not routinely performed before starting ART. Here we assess cognitive impairment in ART- naïve HIV patients beginning treatment in Jakarta. Methods: This is a cross sectional study with inclusion criteria: HIV positive, ART naïve, CD4 T-cells below 200 cells/uL, Karnofsky Performance Score (KPS) above 70. HIV-associated neurocognitive disorder (HAND) was defined by performance at least 1 Standard Deviation (SD) below the mean of demographically adjusted normative scores in at least two cognitive areas. Results: We studied 82 subjects with median (range) age 31 (19-48) years. Fifty six subjects (68%) were males. HAND was found in 42 subjects (51%). Eight subjects (19%) had impairment in 4 domains, 15 subjects (36%) in 3 and 19 (45%) in 2. The most common domain affected was memory (63%). Conclusion: Our results show the prevalence of HAND is high among HIV naïve patients in Jakarta. This establishes the need for screening of cognitive function before initiating ART.

Demencia en pacientes adultos con síndrome de inmunodeficiencia adquirida, atendidos en el Hospital Mario Catarino Rivas / Dementia in adult patients with acquired immunodeficiency syndrome treated at Hospital Mario Catarino Rivas

Introducción: La demencia asociada al virus de inmunodeficiencia humana (D-VIH) es un tipo de demencia subcortical debido a infecciones crónicas por VIH; y combina alteraciones cognitivas, motoras y conductuales, afectando del 20 al 30% de los pacientes adultos que sufren esta enfermedad. La Escala de Demencia por VIH (EDV) es una herramienta sensible que se utiliza para tamizaje de pacientes infectados por VIH y con riesgo de desarrollar demencia. Objetivos. Aplicar la EDV en pacientes con infección avanzada por VIH que asistían al Centro de Atención Integral (CAI) del Hospital Mario Catarino Rivas (HMCR) y analizar su relación con el conteo de células TCD4 <200. Metodología. Se trata de un estudio cuantitativo, descriptivo, de corte transversal con un muestreo intencionado. En el estudio se incluyó pacientes mayores de 18 años con VIH confirmado, quienes asisten al CAI, alfabetos, con conteo reciente de linfocitos CD4 menor de 200 células y que consintieron participar en el estudio. Se les aplicó la EDV como tamizaje para evaluar su función mental. Resultados. El 81% de los pacientes entrevistados presentaron riesgo de D-VIH con un rango de edad de mayor prevalencia entre 38 y 57 años, siendo el género femenino el de mayor riesgo. Conclusión de acuerdo a los resultados obtenidos, la EDV es una herramienta costo-efectiva para determinar la función cognitiva en los pacientes...(AU)

Trastorno neurocognitivo asociado al virus de inmunodeficiencia humana / Human immunodeficiency virus-associated neurocognitive disorders (HAND)

El trastorno neurocognitivo asociado a VIH (TNAV) es una complicación poco conocida pero de elevada prevalencia e impacto en los pacientes con VIH. El término TNAV agrupa un espectro de complicaciones progresivas del sistema nervioso central (SNC), desde un compromiso neurocognitivo asintomático y un trastorno neurocognitivo leve hasta una demencia asociada a VIH (DAV). Mientras que la incidencia de DAV ha disminuido significativamente con el tratamiento antirretroviral de gran actividad (TARGA), las formas más leves de TNAV se han incrementado. En esta revisión, describimos la nomenclatura actualizada y definiciones de caso para orientar el diagnóstico del TNAV. También, resumimos las manifestaciones clínicas, diagnóstico y recomendaciones para el tratamiento. Finalmente, mientras que el deterioro cognitivo es típicamente diagnosticado con una evaluación neuropsicológica completa, la interpretación de los resultados se basa en la comparación entre el rendimiento del paciente con valores normalizados en poblaciones ajustados culturalmente y según edad; así, los resultados de estas pruebas son válidos solo si existen datos representativos normalizados adecuadamente para un paciente. Por lo tanto, proponemos un grupo de pruebas neuropsicológicas breves validadas en nuestra población peruana, que pueden ser utilizadas para la detección temprana del TNAV no solo por los neurólogos sino también por el médico tratante del paciente con VIH o en centros de escasos recursos...

HIV-associated neurocognitive disorder (HAND) is not a well recognized entity but has high prevalence and impact in individuals infected with HIV. The term HAND encompasses a spectrum of progressive central nervous system (CNS) involvement, ranging from asymptomatic neurocognitive impairment and minor neurocognitive disorder through to the most severe form of HIV-associated dementia (HAD). While the incidence of HAD has declined significantly with highly active antiretroviral treatment (HAART), the milder forms of HAND have increased. In this review, updated nomenclature and research case definitions to guide HAND diagnosis are described. Clinical manifestations, diagnosis and treatment recommendations are also outlined. Finally, while neurocognitive impairment is typically diagnosed with full neuropsychological evaluation, the interpretation of test results is based on comparing the patientÆs performance to age and culturally adjusted population based normal values; thus, test results are valid only if adequate representative normative data exist for a given patient. Therefore, we propose a group of brief neuropsychological tests validated in Peruvian population that could be used to detect HAND opportunely not only by neurologists but also by a primary HIV-care provider or in resource-poor settings...

Effects of HIV-1 tat on secretion of TNF-α and IL-1β by U87 cells in AIDS patients with or without AIDS dementia complex / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the role of HIV-1 tat gene variations in AIDS dementia complex (ADC) pathogenesis.</p><p><b>METHODS</b>HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations in the supernatant of U87 cells were determined with ELISA.</p><p><b>RESULTS</b>HIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area (38-47aa). All Tat proteins could induce U87 cells to produce TNF-α and IL-1β, but the level of IL-1β production was different among Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen. The level of Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen were obviously higher than that from the non-ADC patient's basal ganglia.</p><p><b>CONCLUSION</b>Tat protein core functional area (38-47aa) may serve as the key area of enhancing the secretion of IL-1β. This may be related with the neurotoxicity of HIV-1 Tat.</p>

Validity of the International HIV Dementia Scale in Brazil / Validade da Escala Internacional de Demência pelo HIV no Brasil

HIV-associated neurocognitive disorders (HAND) remain prevalent in highly active antiretroviral therapy (HAART) era. Tests to detect HAND are needed for early diagnosis and treatment. Validity of International HIV Dementia Scale (IHDS) has been determined in different countries. The aims of this study were validate IHDS in a Brazilian cohort of HIV-patients and verify if IHDS can be reliably administered by a non-clinician health professional. One hundred and eighty-seven (187) patients were submitted to a full neuropsychological assessment. IHDS was administered twice to each patient (by a non-clinician and by a neurologist). HAND was diagnosed in 98 individuals (68 on HAART). IHDS had sensitivity of 55% and specificity of 80%. IHDS had fair agreement with neuropsychological tests (k 0.355) and moderate-to-strong agreement between different evaluators (interclass correlation coefficient (ICC) 0.684). HAND is prevalent nowadays. IHDS is quick and easy to administer, but has marginal sensitivity for the detection of HIV cognitive impairment other than dementia.

Distúrbios neurocognitivos associados ao HIV (HAND) ainda são comuns em pacientes usando terapia antirretroviral de alta eficácia (HAART). Testes diagnósticos para detecção de HAND são necessários para diagnóstico e terapia precoces. Nossos objetivos foram validar em uma população brasileira a escala internacional de demência pelo HIV (IHDS), já utilizada em outros países, e avaliar se pode ser confiavelmente aplicada por um profissional não médico. Avaliamos 187 pacientes com uma extensa bateria neuropsicológica. IHDS foi ministrada duas vezes (por médico e não médico). HAND foi diagnosticada em 98 indivíduos (68 em uso de HAART). A IHDS teve sensibilidade de 55% e especificidade de 80%, com pouca concordância com os testes neuropsicológicos (k 0,355) e moderada a forte concordância entre observadores (coeficiente de correlação interclasse (ICC) 0,684). HAND ainda é prevalente nos dias atuais. IHDS é um instrumento rápido e fácil de ser aplicado, mas com baixa sensibilidade para detecção de déficit cognitivo outro que não demência.

Analysis of genetic diversity of HIV-1 nef genes from a patient with AIDS dementia complex / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the genetic diversity of HIV-1 nef genes from a patient with AIDS dementia complex(ADC) , so as to research the amino acid variability and the pathogenesis of ADC.</p><p><b>METHODS</b>The nef gene was amplified with PCR from genomic DNA which was extracted from spleen and different brain tissues(basal ganglia, frontal gray matter, meninges, temporal lobe)of a patient who died of ADC. PCR products were cloned into the pMD19-T vector, after transformation and selection by ampicillin and blue/white spotting. Five of positive clones were sequenced and confirmed with BLAST. HIV-1 nef sequences were processed with BioEdit and MEGA4 to do Neighbor-Joining tree, p-Distances, and values of ds/dn.</p><p><b>RESULTS</b>The samples were all identified as HIV-1 B and genetic variation exists in HIV-1 nef gene isolated from different tissues compared with HXB2. In addition,part of the changes were different between periphery and brain.</p><p><b>CONCLUSION</b>Variations exist in the HIV-1 nef gene extracted from the ADC patient and the variations from peripheral and central nerve tissues were different,these variations may change the function of Nef,and it needs more research.</p>

HIV-Associated Neurocognitive Disorders--An issue of Growing Importance

<p><b>INTRODUCTION</b>HIV-associated neurocognitive disorders (HAND) comprise a wide spectrum of cognitive, motor, and mood abnormalities prevalent in people living with HIV and AIDS (PLWHAs). This field of HIV medicine has gained renewed prominence in recent years with evidence contending that anti-retroviral agents with increased central nervous system (CNS) penetration may improve neurocognitive outcomes in those affected. This review aims at evaluating the available evidence and postulating further study direction in Singapore.</p><p><b>MATERIALS AND METHODS</b>A PubMed search was carried out for original articles and systematic reviews on the subject of HIV-associated neurocognitive disorders, and the results reviewed by the authors.</p><p><b>RESULTS</b>There is a growing body of evidence that HAND is not uncommon, and the advent of highly active anti-retroviral therapy has increased its prevalence by improving the prognosis of HIV infection, and hence increasing the likelihood of diagnosing of this neurocognitive condition. Screening and diagnosing HAND is important, and requires clinical suspicion as well as validated test batteries for optimal accuracy. The authors recommend strategies for detection in the local context involving stepwise targeted screening. Anti-retroviral agents with good CNS penetration and activity, as well as adjunctive neuro-rehabilitative interventions, may improve the impairments experienced by affected individuals.</p><p><b>CONCLUSION</b>Increased awareness of HAND, with earlier diagnosis and targeted, multi-disciplinary management of this challenging condition, may lead to better all-round outcomes for people living with HIV and AIDS in Singapore.</p>

Neuropatogenia de HIV en la era HAART / Neuropathogenesis of HIV in the HAART era

La infección de tejidos cerebrales por HIV se asocia a desórdenes neurocognitivos identificados bajo la denominación HAND y categorizados en demencia, formas moderadas y formas asintomáticas. La introducción de terapia de alta efectividad ha implicado un notorio descenso de la demencia, pero no ha influido sobre las formas moderadas y asintomáticas que afectan alrededor del 50% de los pacientes bajo tratamiento. Esa disfunción cognitiva resulta de la pérdida de neuronas que, sin embargo, no han sido infectadas por el virus. De ahí la importancia de mecanismos indirectos en la neuropatogenia de HIV, ya que las citocinas/quimiocinas pro-inflamatorias liberadas por macrófagos/microglia infectados, la excitoxidad y el stress oxidativo se evidencian como principales causas de injuria neuronal, además de la directamente provocada por proteínas virales. Un mejor conocimiento de la interacción de HIV con su huésped humano está posibilitando el desarrollo de abordajes diganósticos más confiables y de estrategias terapéuticas más efectivas a nivel de SNC

HIV-1 associated neurocognitive disorders (HAND) result from brain infection. They are categorized as dementia, mild cases and asymptomatic cases. The introduction of HAART has markedly decreased dementia but no influence has been observed in mild and asymptomatic cases, since they are still identified in around 50 % of treated patients. Such cognitive dysfunction is the outcome of the loss of neurons which, however, have not been infected by the virus. hence, the importance of indirect mechanisms in HIV neuropathogenesis in which cytokines/chemokines released by infected macrophages/microglia, excitotoxic neuronal injury and oxidative stress are relevant causes of neurodegeneration besides that exerted by viral proteins. A better understanding of the HIV interaction with th human host is enabling the development of more reliable diagnostic biomarkers and more effective therapeutic strategies at CNS level