RESUMO
BACKGROUND: We hypothesized that the induction of monocyte activation biomarkers, especially soluble urokinase-type plasminogen activator receptor (suPAR) and interferon γ-inducible protein 10 (IP-10), is lower in HIV-1C than HIV-1B, owing to a defective Tat cysteine dimotif (C30S). METHODS: A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH), free of CNS opportunistic infections, from a Southern Brazil outpatient HIV clinic were evaluated such as HIV-1B subtype (n = 27), HIV-1C (n = 26), other (n = 15), and 19 HIV-negative controls. The levels of suPAR, IP-10, neopterin, and ß2 microglobulin (ß2m) in the CSF and serum were quantified using different immunoassays. RESULTS: Overall, in PWH, increases in CSF suPAR, CSF/serum suPAR, and CSF/serum ß2m correlated with worse working memory deficits (r = 0.303, 0.353, and 0.289, respectively, all P < 0.05). The medians of IP-10, suPAR, neopterin, and ß2m in CSF and serum and the CSF/serum ratio and suPAR index were comparable between the HIV-1B and HIV-1C subtypes. CSF IP-10 and neopterin and serum IP-10 and suPAR levels were higher in PWH than the HIV-negative controls (P = 0.015, P = 0.001, P < 0.0001, and P < 0.001, respectively). The serum ß2m level was higher in HIV-associated dementia than neuropsychologically normal or asymptomatic (P = 0.024). DISCUSSION: We observed that higher levels of CSF suPAR and the suPAR quotient correlated with worse working memory deficit. Elevated levels of monocyte activation were similar in both HIV-1 B and C subtypes, providing no evidence of reduced neuropathogenicity of HIV-1 subtype C Tat compared with subtype B.
Assuntos
Complexo AIDS Demência , Quimiocina CXCL10 , Infecções por HIV , Transtornos da Memória , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Complexo AIDS Demência/líquido cefalorraquidiano , Complexo AIDS Demência/virologia , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Quimiocina CXCL10/líquido cefalorraquidiano , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/virologia , HIV-1 , Humanos , Transtornos da Memória/líquido cefalorraquidiano , Transtornos da Memória/virologia , Neopterina , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
PURPOSE: Changes in cerebral cortical regions occur in HIV-infected patients, even in those with mild neurocognitive disorders. Working memory / attention is one of the most affected cognitive domain in these patients, worsening their quality of life. Our objective was to assess whether cortical thickness differs between HIV-infected patients with and without working memory deficit. METHODS: Forty-one adult HIV-infected patients with and without working memory deficit were imaged on a 1.5 T scanner. Working memory deficit was classified by composite Z scores for performance on the Digits and Letter-Number Sequencing subtests of the Wechsler Adult Intelligence Scale (third edition; WAIS-III). Cortical thickness was determined using FreeSurfer software. Differences in mean cortical thickness between groups, corrected for multiple comparisons using Monte-Carlo simulation, were examined using the query design estimate contrast tool of the FreeSurfer software. RESULTS: Greater cortical thickness in left pars opercularis of the inferior frontal gyrus, and rostral and caudal portions of the left middle frontal gyrus (cluster 1; p = .004), and left superior frontal gyrus (cluster 2; p = .004) was observed in HIV-infected patients with working memory deficit compared with those without such deficit. Negative correlations were found between WAIS-III-based Z scores and cortical thickness in the two clusters (cluster 1: ρ = -0.59; cluster 2: ρ = -0.47). CONCLUSION: HIV-infected patients with working memory deficit have regions of greater thickness in the left frontal cortices compared with those without such deficit, which may reflect increased synaptic contacts and/or an inflammatory response related to the damage caused by HIV infection.
Assuntos
Córtex Cerebral/patologia , Córtex Cerebral/virologia , Infecções por HIV/patologia , Transtornos da Memória/virologia , Memória de Curto Prazo/fisiologia , Adulto , Idoso , Brasil/epidemiologia , Feminino , HIV/isolamento & purificação , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Masculino , Transtornos da Memória/epidemiologia , Transtornos da Memória/patologia , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Human t-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM) is a progressive neurological disease whose diagnosis is defined by clinical manifestations and seropositivity for HTLV-1 infection. Cognitive impairment (CI) is considered to occur after spinal impairment. A 51-year-old HTLV-1-infected man classified as an asymptomatic carrier presented difficulties in listening comprehension and executive memory. He was assessed for central auditory processing (CAP), cognition (event-related auditory evoked potential [P300]), and otoneurological functions (galvanic vestibular-evoked myogenic potential [gVEMP]). Altered responses were found in CAP, P300, and gVEMP, but the neurological examination and cognitive screening were normal. After a 2-year follow-up, we disclosed a positive Babinski sign, a mild CI, worsened P300, and gVEMP latencies, and the patient reported progressive lumbar pain and difficulty running. He was, then, reclassified as HAM. The first examination, in 2016, had already shown abnormal results in P300 and gVEMP despite the HTLV-1-asymptomatic carrier status. Therefore, tests that provide subclinical measures of neurological disease progression can be useful tools for an early diagnosis and intervention in HTLV-1 patients. Electrophysiological results had worsened as well as the clinical status and the cognitive function and the progression from asymptomatic status to an HTLV-1-associated neurological disease occurred within 2 years. Thus, HTLV-1-infected individuals with complaints of CI, hearing, or otoneurological manifestations should be submitted to neuropsychological and electrophysiological tests, allowing them to be properly cared in case of HAM progression.
Assuntos
Disfunção Cognitiva/virologia , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical/patologia , Paraparesia Espástica Tropical/virologia , Transtornos da Percepção Auditiva/virologia , Humanos , Masculino , Transtornos da Memória/virologia , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/diagnóstico , Reflexo de BabinskiRESUMO
BACKGROUND: Although classical human T-cell lymphocyte virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis syndrome is the most frequent HTLV-1-associated neurological disorder, some "minor" neurological disorders can be seen in "asymptomatic" carriers. These disorders, including cognitive alterations already described in clinical cases and studies, may constitute an intermediate syndrome (IMS) between the asymptomatic state and myelopathy. The aim of this study was to investigate the presence of cognitive deficits in patients with HTLV-1 virus, who usually are diagnosed as asymptomatic. METHODS: A total of 54 HTLV-1-infected patients were evaluated, 35 asymptomatic and 19 with minor neurological alterations (evaluated by a neurologist); 25 HTLV-1-seronegative individuals served as controls. The instruments used were: Beck's Depression Inventory, Lawton's Daily Life Activity Scale, and a complete neuropsychological battery. The application of these evaluation instruments was performed blindly, with the evaluator neuropsychologist not knowing the clinical condition of the patient. RESULTS: Most of the participants in this cohort, including seronegative controls, were female (n = 57, 72.21%), their mean age was 52.34 years (SD = 14.29) and their average schooling was 9.70 years (SD = 4.11). DISCUSSION: Participants classified with IMS had lower gross scores when compared with both the patients classified as asymptomatic and with the control group, and when tested for auditory episodic memory of immediate (p < 0.01), and late (p = 0.01), recall. CONCLUSION: Patients with IMS presented with memory impairment when compared with asymptomatic patients and seronegative individuals; this is one of the symptoms that aids in the classification of the syndrome.
Assuntos
Disfunção Cognitiva/virologia , Infecções por HTLV-I/psicologia , Transtornos da Memória/virologia , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Disfunção Cognitiva/fisiopatologia , Estudos Transversais , Escolaridade , Feminino , Infecções por HTLV-I/fisiopatologia , Humanos , Masculino , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valores de Referência , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
Background Although classical human T-cell lymphocyte virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis syndrome is the most frequent HTLV-1-associated neurological disorder, some "minor" neurological disorders can be seen in "asymptomatic" carriers. These disorders, including cognitive alterations already described in clinical cases and studies, may constitute an intermediate syndrome (IMS) between the asymptomatic state and myelopathy. The aim of this study was to investigate the presence of cognitive deficits in patients with HTLV-1 virus, who usually are diagnosed as asymptomatic. Methods A total of 54 HTLV-1-infected patients were evaluated, 35 asymptomatic and 19 with minor neurological alterations (evaluated by a neurologist); 25 HTLV-1-seronegative individuals served as controls. The instruments used were: Beck's Depression Inventory, Lawton's Daily Life Activity Scale, and a complete neuropsychological battery. The application of these evaluation instruments was performed blindly, with the evaluator neuropsychologist not knowing the clinical condition of the patient. Results Most of the participants in this cohort, including seronegative controls, were female (n = 57, 72.21%), their mean age was 52.34 years (SD = 14.29) and their average schooling was 9.70 years (SD = 4.11). Discussion Participants classified with IMS had lower gross scores when compared with both the patients classified as asymptomatic and with the control group, and when tested for auditory episodic memory of immediate (p < 0.01), and late (p = 0.01), recall. Conclusion Patients with IMS presented with memory impairment when compared with asymptomatic patients and seronegative individuals; this is one of the symptoms that aids in the classification of the syndrome.
RESUMO Apesar da síndrome de HAM / TSP clássica ser a perturbação neurológica mais atribuída, alguns distúrbios neurológicos denominados "menores" são vistos em portadores "assintomáticos" de HTLV-1. Esses distúrbios, incluindo alterações cognitivas já observadas em descrições de casos clínicos e estudos, podendo constituir uma verdadeira síndrome clínica intermediária (SI) entre o estado assintomático e mielopatia. O objetivo deste estudo foi investigar a presença de déficits cognitivos em pacientes portadores do vírus HTLV-1 diagnosticados classicamente como assintomáticos. Métodos Foram avaliadas 54 pessoas, sendo 35 assintomáticos, 19 com alterações neurológicas menores (avaliados por um neurologista) e 25 HTLV-1 negativo. Os instrumentos utilizados foram: Inventário Beck de Depressão, Escala de Atividades de Vida Diária de Lawton e uma completa bateria neuropsicológica. A aplicação destes instrumentos de avaliação foi realizada de forma cega, ou seja, a avaliadora não sabia a condição clinica do paciente. Resultados A maioria dos participantes era do sexo feminino (n = 57, 72,21%), com idade média de 52.34 anos (DP = 14,29) e escolaridade média de 9.70 anos (DP = 4,11). Discussão Avaliando o desempenho cognitivo nos três grupos, foi possível observar que os participantes classificados com SI, apresentaram menores escores brutos, quando comparados, com os pacientes com classificação assintomática e grupo controle e, em relação à memória episódica auditiva de evocação imediata (p < 0,01) (p = 0,01) e tardia. Conclusão Diante dos resultados foi possível concluir que os pacientes com SI apresentam comprometimento de memória quando comparado com os outros grupos, sendo possível, ser este um dos sintomas para auxiliar na classificação da síndrome.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Infecções por HTLV-I/psicologia , Disfunção Cognitiva/virologia , Transtornos da Memória/virologia , Valores de Referência , Infecções por HTLV-I/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Inquéritos e Questionários , Análise de Variância , Estatísticas não Paramétricas , Escolaridade , Disfunção Cognitiva/fisiopatologia , Transtornos da Memória/fisiopatologia , Testes NeuropsicológicosRESUMO
OBJECTIVES: We aimed to characterize neurological outcomes and determine the prevalence of HIV encephalopathy in a cohort of HIV-infected children in Jamaica. METHODS: Data for 287 HIV-infected children presenting between 2002 and 2008 were reviewed and neurological outcomes characterized. A nested case-control study was conducted between July and September 2009 used 15 randomly selected encephalopathic HIV-infected children aged 7-10 years and 15 matched controls (non-encephalopathic HIV-infected). Their neurocognitive functions were evaluated using clinical assessment and standardized tests for intelligence, short term memory (visuo-spatial and auditory), selective attention, and fine motor and coordination functions. Outcomes were compared using Fisher's exact test and the Mann-Whitney U-test. RESULTS: Sixty-seven (23.3%) children were encephalopathic. The median age at diagnosis of HIV encephalopathy was 1.6 years (interquartile range (IQR) 1.1-3.4 years). Predominant abnormalities were delayed milestones (59, 88.1%), hyperreflexia (59, 86.5%), spasticity (50, 74.6%), microcephaly (42, 61.7%), and quadriparesis (21, 31.3%). The median age of tested children was 8.7 years (IQR 7.6-10.8 years) in the encephalopathic group and 9 years (IQR 7.4-10.7 years) in the non-encephalopathic group. Encephalopathic children performed worse in all domains of neurocognitive function (p<0.05). CONCLUSIONS: A high prevalence of HIV encephalopathy was noted, and significant neurocognitive dysfunction identified in encephalopathic children. Optimized management through the early identification of neurological impairment and implementation of appropriate interventions is recommended to improve quality of life.