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.

Analysis of genetic diversity and amino acid sequence of HIV-1 Vpr from a patient with AIDS dementia complex / 中华实验和临床病毒学杂志

Objective@#To study the sequence characteristics and variation of HIV-1 Vpr gene in different parts of an AIDS dementia complex (ADC) patient and provide basis for the study of the neurologic pathogenesis of HIV-1-assciatd dementia.@*Methods@#Genomic DNA was extracted from peripheral samples (lymph nodes, spleen, liver) and central nervous system (meninges, frontal lobe, temporal lobe gray matter, frontal white matter, basal ganglia cortex) of an ADC patient, The Vpr gene was amplified with nested polymerase chain reaction (PCR). PCR products were cloned into the pMD19-T vector. After transformation into DH5α competent E. coli, five positive clones were sequenced. The phylogenetic tree was built and genetic distance was calculated through MEGA6, and the values of ds/dn was calculated through SNAP, then the changes of the amino acid sites were analyzed.@*Results@#HIV-1 Vpr genes isolated from different tissues of the ADC patient had variations. Vpr HIV-1 gene sequences from central nervous system and peripheral tissues were intercrossed together in the phylogenetic tree. Central nervous system and peripheral HXB2 Vpr had no significant differences in genetic distance. The ds/dn of all the HIV-1 Vpr gene sequences were 3.3749.@*Conclusions@#The HIV-1 Vpr sequences were different in the ADC patient, and there were different variations in different parts of the peripheral and central regions. Whether these variations are related to the pathogenesis of ADC remains to be further studied.

Research progress of HIV-related cognitive impairment / 中国医师杂志

The prevalence rate of human immunodeficiency virus (HIV)-related neurological cognitive impairment is very high, which not only affects the quality of life and daily function, but also is an important death factor.Since the pathophysiology of HIV-related neurological impairment has not been fully i dentified, prevention of HIV-associated neurocognitive impairment becomes particularly important.However, the complexity and specificity of HIV-related neurological cognitive impairment make preventive research progress slowly.This review article will mainly describe the clinical features, risk factors, and pathogenesis of HIV-related neurological impairment, and discuss its latest advances in treatment.

MRI manifestations of AIDS dementia complex / 实用放射学杂志

Objective To analyse MRI findings of AIDS dementia complex to improve the understanding of this disease.Methods Clinical and MRI data of 35 cases of AIDS dementia complex were analyzed retrospectively.Results The total of brain tissue of 31 cases was reduced and cerebral cortex and basal ganglia showed diffuse atrophy;the sulci broadened and ventricle expanded.Lateral ventricle white matter of 25 cases showed signal abnormalities.3 cases of simple brain atrophy.Conclusion AIDS dementia complex has characteristic MRI findings,most patients had signs of brain atrophy,the sulci broadened and ventricle expanded;lateral ventricle white matter and centrum semiovale showed signal abnormalitiesCombined with the clinical history,MRI examination had important significance for the early diagnosis of this disease.

TCM Syndrom Type Distribution Characteristics for 186 Cases of AIDS Dementia Complex / 中国中医药信息杂志

Objective To study the relationship between different syndromes of AIDS dementia complex (ADC) and different disease severity, age, CD4+ T cell count and infection. Methods Totally 186 patients with ADC were classified into different syndrome types, and the distribution in different degree of disease, different age, different CD4+T cell count and different routes of infection was analyzed. Results There were 48, 51, 15, 37 and 35 cases of deficiency of kidney and marrow, yin deficiency of liver and kidney, deficiency of heart and spleen, syndrome of phlegm obstruction, syndrome of qi deficiency and blood stasis, respectively. Moderate and severe degrees with yin deficiency of liver and kidney were more common. There was statistical significance in the distribution of different syndromes in different degree of disease (χ2=82.495, P=0.000). Deficiency of kidney and marrow, yin deficiency of liver and kidney were more common in different age groups. The distribution of the syndrome types in different age groups was statistically significant (χ2=72.710, P=0.000), the patients were mainly in two age groups of>50–60 years old and>60 years old. The distribution of the syndrom types in diffenrent CD4+T cell count stratum was statistically significant (χ2=66.778, P=0.000). Blood pathway infection mainly included deficiency of kidney and marrow and syndrome of qi deficiency and blood stasis, sexual pathogens mainly yin deficiency of liver and kidney. Conclusion CD4+T cells layers, age group, progression of disease and transmission way are the influencing factors of syndrom type.

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.

Research on TCM Syndrome and Treatment Regular for AIDS Dementia Complex Based on ;Experts Questionnaires / 中国中医药信息杂志

Objective To explore TCM syndrome and treatment regular for AIDS dementia complex (ADC). Methods Through literature retrieval, the review of medical records and clinical investigation, expert questionnaires survey was carried out. Results The recovery rate of complete questionnaires in the 1st survey was 88.89%. The agreement rate, the arithmetical mean, the weight coefficient, the mean level and the rank sum of the concept, clinical features, diagnostic criteria, syndrome differentiation and treatment of insufficiency of kidney essence, nursing, period of treatment and curative effect standard were more than others, CV<0.076. The agreement rate, the arithmetical mean, the weight coefficient, the mean level and the rank sum of the etiology and pathogenesis, syndrome differentiation and treatment of deficiency of heart and liver yin were smaller, and CV was within 0.168–0.234. The recovery rate of complete questionnaires in the 2nd survey was 96.00%. The agreement rate, the arithmetical mean, the weight coefficient, the mean level and the rank sum of the etiology and pathogenesis, syndrome differentiation and treatment of deficiency of kidney and liver were more than the 1st survey, and CV was within 0.065–0.106, which was smaller than the 1st survey. The agreement rate, the arithmetical mean, the weight coefficient, the mean level and the rank sum of syndrome differentiation and treatment of deficiency of kidney and liver were smaller, and CV was 0.156. The weight coefficient of the 1st and 2nd survey were within 0.072–0.087, 0.071–0.089. The questionnaire reliability of the 1st and 2nd survey were 0.916 and 0.886 respectively. The half reliability of the 1st and 2nd survey were 0.81 and 0.79 respectively. Conclusion TCM syndrome and treatment regular for ADC is preliminarily formed.

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>

Analysis of genetic diversity and amino acid sequence of HIV-1 tat from a patient with AIDS dementia complex / 中华微生物学和免疫学杂志

Objective To study the variation and characteristics of HIV-1 tat exon 1 gene from a patient with AIDS dementia complex( ADC), so as to research the pathogenesis of ADC. Methods The tat gene was amplified with nested PCR from genomic DNA which was extracted from lymph node, spleen and different brain tissues( meninges, grey matter from frontal cortex, white matter from frontal cortex, temporal cortex and basal ganglia) of a patient who died of ADC. PCR products were cloned into the pGEM-T vector,after transformation and selection by ampicillin and blue/white spotting. Five of positive clones were sequenced. HIV-1 tat sequences were processed with BioEdit and MEGA4. With the softwares, Neighbor-Joining tree, p-Distances, values of ds/dn, and analysis of amino acid motifs were all done. Results The samples were all identified as HIV-1 B and genetic variation exists in HIV-1 tat isolated from different tissue;Compared with HXB2, sixteen sites of the amino acid seque nce coded by the HIV-1 tat gene which was isolated from the patient changed. In addition, part of the changes were different between periphery and brain,especially, the five Q54R changes from basal ganglia and one Q54R change from temporal cortex are deserve to follow with interest. Conclusion Variations exist in the HIV-1 tat genes extracted from the ADC patient and the variations from peripheral and central nerve tissues were different, whether the variations concerned with the pathogenesis of ADC need more research.

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.

A Case of HIV Infection Presented with Cerebellar Ataxia

HIV encephalopathy usually presents with progressive dementia. However the spectrum of neurological manifestations of HIV infection is wide. A 46-year-old man presented with gait disturbance and dysarthria. He was given a neurological examination, which indicated dysarthria, cerebellar ataxia, and pyramidal tract signs. The patient's cognitive functions were intact. On serological study, HIV test was positive. Brain MRI and CSF analyses showed no evidence of tumor or other CNS infection. The patient was treated with highly active anti-retroviral therapy. Three months after treatment, cerebellar ataxia was much improved.

AIDS Dementia Complex: Report of an Autopsy Case

We report a 33-year-old man with AIDS dementia complex, which is one of the most common neurologic complica-tion of HIV-1 infection. The man presented with mild psychomotor slowing and episodic loss of consciousness about 5 years after the detection of the HIV-1 infection. His symptoms included forgetfulness, concentration difficulties, apathy, and psychomotor retardation which progressed rapidly evolving into the characteristic features of terminal HIV-1-asso-ciated dementia complex, such as severe dementia, mutism, incontinence, and paraparesis before death. Brain MRIrevealed diffuse confluent high signal intensity lesions in the subcortical white matter on the T2 weighted image. HIV encephalitis (AIDS dementia complex) was confirmed by a brain autopsy.

Effect of HIV-1 Gp41 Peptide on Expression and Metabolism of Amyloid Precursor Protein in Human Astroglioma Cell

Significant neurodegeneration leading to neurocognitive disorder and dementia has been observed in the central nervous system (CNS) of patients with HIV infection. Part of the neurodegenerative cascade in AIDS dementia may involve glial cells, perhaps through inhibiting the release of glial factors that protect neurons from variety of insults. Here, in an effort to find the mediators of HIV-induced brain damage, we examined the possible effect of a HIV-1 transmenbrane protein gp41 peptide (583-599) on expression and metabolism of amyloid precursor protein (APP) using human astroglial cell line. RT-PCR analysis demonstrated that gp 41 peptide did not significantly change expression patterns of APP mRNAs in lipopolysaccharide (LPS) activated astroglial cells for 6h. In contrast, gp41 peptide remarkably downregulated the level of secreted from of APP (sAPPa), which has been recently demonstrated as a potent neuroprotective factor. The reverse peptide, used as control had no such effect. The mechanism of gp41 peptide-induced down regulation of sAPPa production appears to be TGF-beta independent. These results implicate that gp41 peptide could be one of the mediator involved in the modulation of APP secretion within CNS, possibly contributing to the neuronal degeneration in HIV-1 associated neurological disease.