Update on the diagnosis and management of neurocysticercosis.

BACKGROUND: Neurocysticercosis (NCC) is a serious public health problem in several developing countries, including those in Latin America, Asia, and Africa. NCC is considered to be the main cause of late-onset epilepsy in endemic areas. OBJECTIVE: This review summarizes recent advances in diagnosis and therapy of NCC. Methods: Relevant articles and books were reviewed and used as a source of information for this review. RESULTS: The diagnosis of NCC is based upon neuroimaging studies (MRI and computed tomography) and laboratory analysis of the cerebrospinal fluid (CSF). Praziquantel and albendazole are considered parasiticidal drugs against NCC, but there is an intense debate over the value and safety of these drugs. CONCLUSION: Given the relative scarcity of clinical trials, more comparative interventional studies, especially randomized controlled trials in long-term clinical evolution, are required in order to clarify the controversy over the validity of parasitic therapy in patients with NCC.

The Expression of Tax and HBZ Genes in Serum-Derived Extracellular Vesicles From HTLV-1 Carriers Correlates to Proviral Load and Inflammatory Markers.

Human T-lymphotropic virus 1 (HTLV-1) is the etiologic agent of adult cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). One of the major questions in HTLV-1 studies is related to the understanding of causes that lead to different clinical manifestations. However, it is well known that the viral genes tax and HTLV-1 basic leucine zipper factor (HBZ) are related to viral infectivity and the development of neurological and hematological diseases. Currently, there is evidence that HTLV-1 infected cells can release small extracellular vesicles (sEVs) involved in the mechanisms of viral particles spreading. Therefore, we evaluated the expression levels of tax and HBZ viral transcripts in serum-derived sEVs from HTLV-1 carriers, as well as the role of these vesicles in the modulation of the immune response. Three HAM/TSP carriers presented detectable levels of tax and HBZ transcripts in sEVs and were positively correlated to the proviral load (PVL) in peripheral blood mononuclear cells (PBMCs). The viral transcripts were only detectable in individuals with a PVL higher than 6,000/105 PBMCs. Additionally, it was observed that HBZ presented a 2-12-folds increase over tax expression units. Gene expression and secretory protein analysis indicated that PBMCs from blood donors and HTLV-1 carriers exposed to increasing doses of tax+ HBZ+ sEVs showed a dose-dependent increase in interferon (IFN)-γ and interleukin (IL)-8 transcripts and proteins. Interestingly, the increase in IL-8 levels was close to those seen in HTLV-1-infected PBMCs with high PVL. Taken together, these findings indicate that the expression of viral transcripts in serum-derived sEVs of HTLV-1 carriers is related to the PVL presented by the infected individual. Additionally, tax+ HBZ+ sEVs can induce the production of inflammatory cytokines in patients with low PVL, which may be related to the development of symptoms in HTLV-1 infection.

Update on the diagnosis and management of neurocysticercosis / Atualização no diagnóstico e manejo da neurocisticercose

ABSTRACT Background: Neurocysticercosis (NCC) is a serious public health problem in several developing countries, including those in Latin America, Asia, and Africa. NCC is considered to be the main cause of late-onset epilepsy in endemic areas. Objective: This review summarizes recent advances in diagnosis and therapy of NCC. Methods: Relevant articles and books were reviewed and used as a source of information for this review. Results: The diagnosis of NCC is based upon neuroimaging studies (MRI and computed tomography) and laboratory analysis of the cerebrospinal fluid (CSF). Praziquantel and albendazole are considered parasiticidal drugs against NCC, but there is an intense debate over the value and safety of these drugs. Conclusion: Given the relative scarcity of clinical trials, more comparative interventional studies, especially randomized controlled trials in long-term clinical evolution, are required in order to clarify the controversy over the validity of parasitic therapy in patients with NCC.

RESUMO Antecedentes: A neurocisticercose (NCC) é grave problema de saúde pública nos países em desenvolvimento, especialmente na América Latina, Ásia e África. A NCC é considerada a principal causa de epilepsia de início tardio nas regiões endêmicas. Objetivo: Este artigo pretende discutir os recentes avanços no diagnóstico e tratamento da NCC. Métodos: Artigos científicos e livros relevantes serviram de fonte de informação para esta revisão. Resultados: O diagnóstico da NCC é fundamentado nos exames de neuroimagem (ressonância magnética e tomografia computadorizada) e do líquido cefalorraquiano (LCR). Atualmente, praziquantel e albendazole são considerados eficazes na terapêutica etiológica da NCC, mas há intenso debate quanto à validade e segurança desses medicamentos. Conclusão: Pela relativa carência de ensaios clínicos, são necessários novos estudos particularmente randomizados, controlados e com análise de desfechos clínicos a longo prazo para o esclarecimento da polêmica envolvendo a validade da terapêutica parasiticida na NCC.

Monitoring of HTLV-1-associated diseases by proviral load quantification using multiplex real-time PCR.

Proviral load (PVL) is one of the determining factors for the pathogenesis and clinical progression of the human T-lymphotropic virus type I (HTLV-1) infection. In the present study, we optimized a sensitive multiplex real-time PCR for the simultaneous detection and quantification of HTLV-1 proviral load and beta-globin gene as endogenous control. The values obtained for HTLV-1 PVL were used to monitor the clinical evolution in HTLV-1-infected individuals. A vector containing cloned DNA targets of the real-time PCR for the beta-globin gene and the HTLV-1pol region was constructed. For the reaction validation, we compared the amplification efficiency of the constructed vector and MT-2 cell line containing HTLV-1. The analytical sensitivity of the reaction was evaluated by the application of a standard curve with a high order of magnitude. PVL assay was evaluated on DNA samples of HTLV-1 seropositive individuals. The construct showed adequate amplification for the beta-globin and HTLV-1 pol genes when evaluated as multiplex real-time PCR (slope = 3.23/3.26, Y-intercept = 40.18/40.73, correlation coefficient r2 = 0.99/0.99, and efficiency = 103.98/102.78, respectively). The quantification of PVL using the MT-2 cell line was equivalent to the data obtained using the plasmidial curve (2.5 copies per cell). In HTLV-1-associatedmyelopathy/tropical spastic paraparesis patients, PVL was significantly higher (21315 ± 2154 copies/105 PBMC) compared to asymptomatic individuals (1253 ± 691 copies/105 PBMC). The obtained results indicate that the optimized HTLV-1 PVL assay using plasmidial curve can be applied for monitoring and follow-up of the progression of HTLV-1 disease. The use of a unique reference plasmid for both HTLV-1 and endogenous gene allows a robust and effective quantification of HTLV-1 PVL. In addition, the developed multiplex real-time PCR assay was efficient to be used as a tool to monitor HTLV-1-infected individuals.

Short Communication: Human Bone Marrow Stromal Cells Exhibit Immunosuppressive Effects on Human T Lymphotropic Virus Type 1 T Lymphocyte from Infected Individuals.

Human multipotent mesenchymal stromal cells (MSCs) display immunoregulatory functions that can modulate innate and adaptive cellular immune responses. The suppressive and immunomodulatory activities of MSCs occur through the action of soluble factors that are constitutively produced and released by these cells or, alternatively, after MSC induction by stimuli of inflammatory microenvironments. However, to date the contribution of MSCs in the inflammatory microenvironment resulting from viral infection is unknown. In our study, we evaluated the MSC immunosuppressive effect on human T lymphotropic virus type 1 (HTLV-1) infected T lymphocytes. To evaluate if MSC immunoregulation can influence the proliferation of HTLV-1 infected T lymphocytes, we compared the proliferation of lymphocytes obtained from HTLV-1 infected and healthy individuals cocultured in the presence of MSCs. It was observed that the lymphoproliferative inhibition by MSCs on infected lymphocytes was similar compared to the cells obtained from healthy individuals. In addition, this suppressive effect was related to a significant increase of indoleamine-2,3-dioxygenase and prostaglandin E2 gene expression (p ≤ .05). Furthermore, the HTLV-1 pol gene was less expressed after coculturing with MSCs, suggesting that the MSC immunoregulation can have effective suppression on HTLV-1 infected T cells. In conclusion, this study suggests that MSCs could be involved in the immunomodulation of the HTLV-1 infected T lymphocytes.

Detection of HTLV-1 proviral DNA in BM mononuclear cells and cultured mesenchymal stromal cells isolated from patients with HTLV-1 infection.

The bone marrow (BM) biology during HTLV-1 infection is obscure. In this study, we investigated BM mononuclear cells and mesenchymal stromal cells (MSC) from HTLV-1 asymptomatic and symptomatic individuals. An infiltration of CD4+ T-cell lymphocytes in the BM of HTLV-1-infected individuals was observed when compared to healthy controls. The provirus detection in the BM CD4+ T cells confirmed the presence of integrated HTLV DNA. In regard to MSC, we observed that the number of fibroblast progenitor cells was lower in HTLV-1 infected individuals than in healthy controls. Isolated HTLV-1 infected BM-MSC demonstrated surface expression markers and in vitro differentiation potential similar to uninfected individuals. The presence of HTLV-1 proviral DNA in the BM-MSC of HTLV-1-infected patients was demonstrated but no p19 antigen was detected in supernatant from cultured MSC. We suppose that HTLV-1 infects human MSC probably by cell-to-cell contact from the infected CD4+ T-lymphocytes infiltrated into the bone marrow.

Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

ABSTRACT Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800 mg.

Analysis of unbound plasma concentration of oxcarbazepine and the 10-hydroxycarbazepine enantiomers by liquid chromatography with tandem mass spectrometry in healthy volunteers.

This study describes the development and validation of a method for the analysis of unbound plasma concentrations of oxcarbazepine (OXC) and of the enantiomers of its active metabolite 10-hydroxycarbazepine (MHD) [S-(+)- and R-(-)-MHD] using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Additionally, the free fraction of the drug is described in healthy volunteers (n=12) after the oral administration of 300mg OXC/12h for 5days. Plasma aliquots of 200µL were submitted to ultrafiltration procedure and 50µL of the ultrafiltrate were extracted with a mixture of tert-butyl methyl ether:dichloromethane (2:1, v/v). OXC and the MHD enantiomers were separated on a OD-H chiral phase column. The method was linear in the range of 4.0-2.0µg/mL for OXC and of 20.0-6.0µg/mL plasma for the MHD enantiomers. The limit of quantification was 4ng for OXC and 20ng for each MHD enantiomer/mL plasma. The intra- and inter-day precision and inaccuracy were less than 15%. The free fraction at the time of peak plasma concentration of OXC was 0.27 for OXC, 0.37 for S-(+)-MHD and 0.42 for R-(-)-MHD. Enantioselectivity in the free fraction of MHD was observed, with a higher proportion of R-(-)-MHD compared to S-(+)-MHD.

Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections.

Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800mg.

Downregulation of histone methyltransferase EHMT2 in CD4+ T-cells may protect HTLV-1-infected individuals against HAM/TSP development.

Approximately 5% of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals will develop one of the HTLV-1-related diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia. However, the mechanisms responsible for the appearance of symptoms have not been fully clarified. It is believed that viral factors, host genetic and epigenetic mechanisms are implicated in this process. Studies have shown the involvement of histone methyltransferases in retrovirus infection, but no study observed their expression in HTLV-1-infected patients. Among them, euchromatic histone-lysine N-methyltransferase (EHMT)-1 and EHMT-2 were related to retroviral latency in HIV-1 infection. We investigated whether histone methyltransferases EHMT1 and EHMT2 exert any influence on HAM/TSP development by assessing their expression levels in CD4+ T-cells from HTLV-1-infected patients. CD4+ T-cells were immunomagnetically isolated from peripheral blood mononuclear cells of HTLV-1-infected or non-infected individuals and the expression levels of EHMT1 and EHMT2 were determined by RT-qPCR. We observed that EHMT2 was negatively regulated in HTLV-1 asymptomatic carriers compared to non-infected individuals. No difference was observed for EHMT1. These results suggest that EHMT2 downregulation in CD4+ T-cells may be linked to a protection mechanism against the development of HAM/TSP.

Population pharmacokinetics of oxcarbazepine and its metabolite 10-hydroxycarbazepine in healthy subjects.

Oxcarbazepine is indicated for the treatment of partial or generalised tonic-clonic seizures. Most of the absorbed oxcarbazepine is converted into its active metabolite, 10-hydroxycarbazepine (MHD), which can exist as R-(-)- and S-(+)-MHD enantiomers. Here we describe the influence of the P-glycoprotein (P-gp) inhibitor verapamil, on the disposition of oxcarbazepine and MHD enantiomers, both of which are P-gp substrates. Healthy subjects (n=12) were randomised to oxcarbazepine or oxcarbazepine combined with verapamil at doses of 300mg b.i.d. and 80mg t.i.d., respectively. Blood samples (n=185) were collected over a period of 12h post oxcarbazepine dose. An integrated PK model was developed using nonlinear mixed effects modelling using a meta-analytical approach. The pharmacokinetics of oxcarbazepine was described by a two-compartment model with absorption transit compartments and first-order elimination. The concentration-time profiles of both MHD enantiomers were characterised by a one-compartment distribution model. Clearance estimates (95% CI) were 84.9L/h (69.5-100.3) for oxcarbazepine and 2.0L/h (1.9-2.1) for both MHD enantiomers. The volume of distribution was much larger for oxcarbazepine (131L (97-165)) as compared to R-(-)- and S-(+)-MHD (23.6L (14.4-32.8) vs. 31.7L (22.5-40.9), respectively). Co-administration of verapamil resulted in a modest increase of the apparent bioavailability of oxcarbazepine by 12% (10-28), but did not affect parent or metabolite clearances. Despite the evidence of comparable systemic levels of OXC and MHD following administration of verapamil, differences in brain exposure to both moieties cannot be excluded after P-glycoprotein inhibition.

Linguagem oral e escrita de crianças soropositivas para o HIV: um acompanhamento longitudinal / Oral and written language of children seropositive for HIV: a longitudinal follow up

RESUMO Introdução A incidência de distúrbios do Sistema Nervoso Central (SNC) em portadores de HIV pode variar de 30% a 90% em pacientes pediátricos, sendo a idade, a intensidade e o comprometimento imunológico, fatores importantes. Objetivo Avaliar a leitura e a escrita de crianças com HIV e comparar com o desenvolvimento fonológico e com marcadores clínicos e imunovirológicos da AIDS. Métodos Estudo longitudinal com 26 crianças, 12 meninos e 14 meninas, que haviam contraído a infecção pelo HIV por transmissão vertical. Foram avaliadas quanto aos aspectos fonológicos da linguagem oral e reavaliadas cinco anos depois, quanto aos aspectos fonológicos e de leitura e escrita. Os dados obtidos foram avaliados de acordo com o estadiamento clínico da AIDS, carga viral e contagem de moléculas CD4, nos dois momentos. Resultados Observou-se relação entre o desenvolvimento fonológico e o desempenho acadêmico, na leitura e escrita de crianças com HIV. Não foi detectada relação entre os aspectos fonológicos, quanto às habilidades de leitura e escrita com estadiamento clínico e aos marcadores imunovirológicos da AIDS. Conclusão Crianças infectadas com HIV representam um grupo de risco para alterações da linguagem oral e escrita, que não dependem da gravidade e quadro clínico, ou do perfil imunovirológico da AIDS. Além disso, a relação observada entre as mudanças no desenvolvimento fonológico e o desenvolvimento da leitura e da escrita confirma a hipótese do deficit fonológico como uma das causas das dificuldades no processo de alfabetização.

ABSTRACT Introduction The incidence of disorders the Central Nervous System (CNS) in HIV-infected may range from 30 to 90% in pediatric patients, with age, intensity and immunological impairment being important factors. Purpose Evaluate reading and writing of children with HIV and compare with the phonological development and with clinical markers and immunovirological of AIDS. Methods This is a longitudinal study in which 26 children, 12 boys and 14 girls, who had acquired HIV infection by vertical transmission, were assessed regarding the phonological aspects of oral language and reassessed five years later regarding the phonological aspects, and reading and writing skills. The data obtained were assessed according clinical staging of AIDS, viral load and CD4 count, at the two time points. Results There is a relationship between the phonological development and the academic performance in reading and writing of children with HIV and we did not detect relation between the phonological aspects and assessed regarding reading and writing skills with clinical staging and to the immunovirological markers of AIDS. Conclusion HIV-infected children represent a risk group for alterations of oral and written language that do not depend of the severity and clinical picture or the immunovirological profile of AIDS. Moreover, observed relationship between changes in phonological development and further development of reading and writing corroborates the hypothesis of phonological deficit as one of the causes of difficulties in the literacy process.

Clinical Symptoms, Imaging Features and Cyst Distribution in the Cerebrospinal Fluid Compartments in Patients with Extraparenchymal Neurocysticercosis.

Extraparenchymal neurocysticercosis has an aggressive course because cysts in the cerebrospinal fluid compartments induce acute inflammatory reactions. The relationships between symptoms, imaging findings, lesion type and location remain poorly understood. In this retrospective clinical records-based study, we describe the clinical symptoms, magnetic resonance imaging features, and cyst distribution in the CSF compartments of 36 patients with extraparenchymal neurocysticercosis. Patients were recruited between 1995 and 2010 and median follow up was 38 months. During all the follow up time we found that 75% (27/36) of the patients had symptoms related to raised intracranial pressure sometime, 72.2% (26/36) cysticercotic meningitis, 61.1% (22/36) seizures, and 50.0% (18/36) headaches unrelated to intracranial pressure. Regarding lesion types, 77.8% (28/36) of patients presented with grape-like cysts, 22.2% (8/36) giant cysts, and 61.1% (22/36) contrast-enhancing lesions. Hydrocephalus occurred in 72.2% (26/36) of patients during the follow-up period. All patients had cysts in the subarachnoid space and 41.7% (15/36) had at least one cyst in some ventricle. Cysts were predominantly located in the posterior fossa (31 patients) and supratentorial basal cisterns (19 patients). The fourth ventricle was the main compromised ventricle (10 patients). Spinal cysts were more frequent than previously reported (11.1%, 4/36). Our findings are useful for both diagnosis and treatment selection in patients with neurocysticercosis.

Evaluation of postural balance in mild cognitive impairment through a three-dimensional electromagnetic system / Avaliação do equilíbrio corporal no comprometimento cognitivo leve através de sistema eletromagnético tridimensional

ABSTRACT INTRODUCTION: Elderly people with cognitive impairment are at greater risk for falls; thus, an understanding of the earliest stages of cognitive decline is necessary. OBJECTIVE: To compare postural balance between elderly people with and without mild cognitive impairment using a three-dimensional system. METHODS: Thirty elderly people with mild cognitive impairment and thirty healthy elderly subjects were selected. Static posturography was performed using three-dimensional electromagnetic equipment and the following parameters were evaluated: maximum displacement, mean speed and total trajectory. Open- and closed-eye stabilometric variable comparisons between groups and within each group were carried out, and a relationship between the Mini Mental State Examination and the total trajectory of all elderly subjects was determined. RESULTS: The analysis among open- and closed-eye conditions showed a significant difference in maximum anteroposterior displacement in the control group and a significant difference in all stabilometric variables in the mild cognitive impairment group. A significant difference between the groups in all variables in the closed-eye condition was observed. There was a strong correlation between cognitive performance and total trajectory. CONCLUSION: Evaluations showed decrease in balance in elderly people with mild cognitive impairment. Presence of anteroposterior displacement can be an early sign of postural control impairment, and the evaluation with visual restriction can be useful in detecting small postural instabilities.

Resumo Introdução: Idosos com alteração cognitiva apresentam maior risco de quedas; assim, é importante compreender as primeiras fases do declínio cognitivo. Objetivo: Comparar o equilíbrio corporal entre idosos com e sem comprometimento cognitivo leve através de um sistema tridimensional. Método: Trinta idosos com comprometimento cognitivo leve e 30 idosos saudáveis foram selecionados. A posturografia estática foi realizada utilizando equipamento eletromagnético tridimensional, e foram avaliados os parâmetros deslocamento máximo, velocidade média e trajetória total. Foi realizada comparação das variáveis estabilométricas com olho aberto e olho fechado intragrupo e intergrupos, e foi estabelecida a relação entre o Mini Exame do Estado Mental e a trajetória total de todos os idosos. Resultados: A análise entre olho aberto e olho fechado no grupo de controle evidenciou uma diferença significativa no deslocamento anteroposterior máximo; no grupo com comprometimento cognitivo leve, houve diferença significativa em todas as variáveis estabilométricas. Foi observada diferença significativa entre os grupos em todas as variáveis na condição de olho fechado. Houve forte correlação entre desempenho cognitivo e trajetória total. Conclusão: As avaliações evidenciaram diminuição do equilíbrio nos idosos com comprometimento cognitivo leve. O deslocamento anteroposterior pode ser um sinal precoce de comprometimento do controle postural, e a avaliação com restrição visual pode ser útil na detecção de pequenas instabilidades posturais.

HLA-G 3'-untranslated region polymorphisms are associated with HTLV-1 infection, proviral load and HTLV-associated myelopathy/tropical spastic paraparesis development.

Most human T-lymphotropic virus type 1 (HTLV-1)-infected patients remain asymptomatic throughout life. The factors associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development have not been fully elucidated; immunological and genetic factors may be involved. The association of 14 bp INS/DEL HLA-G polymorphism with HTLV-1 infection susceptibility has been reported previously. Here, other polymorphic sites at the HLA-G 3'-UTR (14-bp D/I, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G and +3196C/G) were evaluated in 37 HTLV-1-infected individuals exhibiting HAM/TSP, 45 HTLV-1 asymptomatic carriers (HAC) and 153 uninfected individuals, followed up at University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. It was observed that: (i) 14bpDI genotype is a risk factor for HTLV-1 infection, while the 14bpDD and +3142CC genotypes were associated with protection against infection; (ii) the +3142C allele and the +3003CT and +3142CC genotypes were associated with susceptibility, while 14bpII and +3003TT genotypes were associated with protection against HAM/TSP development; and (iii) the 14bpII, +3010CC, +3142GG and +3187AA genotypes were associated with lower HTLV-1 proviral load compared to respective counterpart genotypes. Findings that HLA-G has a well-recognized immunomodulatory role and that the genetic variability at HLA-G 3'-UTR may post-transcriptionally modify HLA-G production indicate a differential genetic susceptibility to: (i) the development of HTLV-1 infection, (ii) the magnitude of HTLV-1 proviral load and (iii) HAM/TSP development.

Predictors of quality of life after moderate to severe traumatic brain injury.

Objective To verify correlations between age, injury severity, length of stay (LOS), cognition, functional capacity and quality of life (QOL) six months after hospital discharge (HD) of victims of traumatic brain injury (TBI). Method 50 patients consecutively treated in a Brazilian emergency hospital were assessed at admission, HD and six months after HD. The assessment protocol consisted in Abbreviated Injury Scale, Injury Severity Score, Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), Mini Mental Test, Barthel Index and World Health Organization QOL - Brief. Results Strong negative correlation was observed between LOS and GCS and LOS and RTS. An almost maximal correlation was found between RTS and GCS and functional capacity and GCS at HD. Age and LOS were considered independent predictors of QOL. Conclusion Age and LOS are independent predictors of QOL after moderate to severe TBI.

Predictors of quality of life after moderate to severe traumatic brain injury / Preditores de qualidade de vida após trauma crânio-encefálico moderado a grave

ABSTRACT Objective To verify correlations between age, injury severity, length of stay (LOS), cognition, functional capacity and quality of life (QOL) six months after hospital discharge (HD) of victims of traumatic brain injury (TBI). Method 50 patients consecutively treated in a Brazilian emergency hospital were assessed at admission, HD and six months after HD. The assessment protocol consisted in Abbreviated Injury Scale, Injury Severity Score, Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), Mini Mental Test, Barthel Index and World Health Organization QOL - Brief. Results Strong negative correlation was observed between LOS and GCS and LOS and RTS. An almost maximal correlation was found between RTS and GCS and functional capacity and GCS at HD. Age and LOS were considered independent predictors of QOL. Conclusion Age and LOS are independent predictors of QOL after moderate to severe TBI.

RESUMO Objetivo Verificar correlações entre idade, gravidade do trauma, tempo de hospitalização (TH), cognição, capacidade funcional e qualidade de vida (QV) seis meses após alta hospitalar (AH) de vítimas de trauma crânio-encefálico (TCE). Método 50 pacientes tratados em um hospital de emergência brasileiro foram avaliados na admissão, AH e seis meses após AH. O protocolo de avaliação consistia em Escala Abreviada de Lesões, Índice de Gravidade de Lesão, Escala de Coma de Glasgow (ECG), Escore de Trauma Revisado (RTS), teste Mini-Mental, Índice de Barthel e Questionário Breve de QV da Organização Mundial de Saúde. Resultados Forte correlação negativa foi observada entre TH e ECG e TH e RTS. Correlação quase máxima foi observada entre RTS e ECG e capacidade funcional e ECG na AH. Idade e TH foram considerados preditores independentes de QV. Conclusão Idade e TH são preditores independentes de QV após TCE moderado e grave.

Evaluation of postural balance in mild cognitive impairment through a three-dimensional electromagnetic system.

INTRODUCTION: Elderly people with cognitive impairment are at greater risk for falls; thus, an understanding of the earliest stages of cognitive decline is necessary. OBJECTIVE: To compare postural balance between elderly people with and without mild cognitive impairment using a three-dimensional system. METHODS: Thirty elderly people with mild cognitive impairment and thirty healthy elderly subjects were selected. Static posturography was performed using three-dimensional electromagnetic equipment and the following parameters were evaluated: maximum displacement, mean speed and total trajectory. Open- and closed-eye stabilometric variable comparisons between groups and within each group were carried out, and a relationship between the Mini Mental State Examination and the total trajectory of all elderly subjects was determined. RESULTS: The analysis among open- and closed-eye conditions showed a significant difference in maximum anteroposterior displacement in the control group and a significant difference in all stabilometric variables in the mild cognitive impairment group. A significant difference between the groups in all variables in the closed-eye condition was observed. There was a strong correlation between cognitive performance and total trajectory. CONCLUSION: Evaluations showed decrease in balance in elderly people with mild cognitive impairment. Presence of anteroposterior displacement can be an early sign of postural control impairment, and the evaluation with visual restriction can be useful in detecting small postural instabilities.

Influence of verapamil on the pharmacokinetics of oxcarbazepine and of the enantiomers of its 10-hydroxy metabolite in healthy volunteers.

PURPOSE: Oxcarbazepine (OXC), a second-generation antiepileptic, and its chiral metabolite 10-hydroxycarbazepine (MHD) are substrates of P-glycoprotein, which can be inhibited by verapamil. This study evaluated the influence of verapamil on the pharmacokinetics of OXC and MHD enantiomers in healthy volunteers. METHODS: Healthy volunteers (n = 12) on occasion O (OXC monotherapy) received 300 mg OXC/12 h for 5 days, and on the O + V occasion (treatment with OXC + verapamil), they received 300 mg OXC/12 h and 80 mg verapamil/8 h for 5 days. Blood samples were collected over a period of 12 h. Total and free plasma concentrations of OXC and the MHD enantiomers were evaluated by LC-MS/MS. Noncompartmental pharmacokinetic analysis was performed using the WinNonlin program. RESULTS: The kinetic disposition of MHD was enantioselective with plasma accumulation (AUC(0-12) S-(+)/R-(-) ratio of 4.38) and lower fraction unbound (0.37 vs 0.42) of the S-(+)-MHD enantiomer. Treatment with verapamil reduced the OXC mean residence time (4.91 vs 4.20 h) and apparent volume of distribution (4.72 vs 3.15 L/kg). Verapamil also increased for both MHD enantiomers C max total [R-(-)-MHD: 2.65 vs 2.98 µg/mL and S-(+)-MHD: 10.15 vs 11.60 µg/mL], C average [R-(-)-MHD: 1.98 vs 2.18 µg/mL and S-(+)-MHD: 8.10 vs 8.83 µg/mL], and AUC(0-12) [R-(-)-MHD: 23.79 vs 26.19 µg h/mL and S-(+)-MHD: 97.87 vs 108.35 µg h/mL]. CONCLUSION: Verapamil increased the AUC values of both MDH enantiomers, which is probably related to the inhibition of intestinal P-glycoprotein. Considering that the exposure of both MHD enantiomers was increased in only 10 %, no OXC dose adjustment could be recommended in the situation of verapamil coadministration.

Percepção dos cuidadores sobre as alterações de deglutição causadas pela demência / Perception of caregivers about swallowing disorders caused by dementia

Objetivo: Identificar o grau de conhecimento dos cuidadores e/ou familiares de pacientes com demência sobre a doença e as alterações de deglutição envolvidas por meio de questionário específico. Material e Métodos: Foram entrevistados 150 acompanhantes de pacientes com demência atendidos em um hospital público terciário. Foram realizadas questões acerca do conhecimento do cuidador sobre o diagnóstico de demência dos pacientes e da atuação fonoaudiológica nestes casos. Coletadas as informações,realizou-se a análise descritiva dos dados. Resultados: A demência de Alzheimer foi diagnosticada em 58,7% dos pacientes envolvidos na pesquisa. Os cuidadores eram, em98% dos casos, familiares dos pacientes, 82,7% do gênero feminino, e 48,7% filhos; 52,7% dos cuidadores descreveram perda de memória como manifestação do quadro clínico do paciente que cuidavam; 56% dos entrevistados relataram conhecer a existência do profissional fonoaudiólogo, e 79,3%não sabiam em que o fonoaudiólogo poderia auxiliar na assistência do paciente com demência. Na percepção das alterações fonoaudiológicas 36,6% observavam comprometimento da deglutição. Conclusão: Os conhecimentos dos cuidadores, acerca da demência e das alterações de deglutição, foram precários. É essencial que os cuidadores recebam orientações específicas para identificar os sinais de alterações de deglutição e favorecer uma alimentação segura para o paciente e evitar complicações futuras como pneumonias aspirativas.

Objective: To identify the degree of knowledge of caregivers and/or family members of patients with dementia about the disease and swallowing alterations. Materials and Methods:We interviewed 150 caregivers of patients with dementia treated in a tertiary health care public hospital. A specific questionnaire was used to collect information about the caregiver’s knowledge on diagnosis of dementia and on the role of speech language therapy in these cases. The data were analyzed descriptively. Results: Alzheimer’s dementiawas diagnosed in 58.7% of patients included in the research. Caregivers were family members in 98% of the cases; 82.7% were female; and 48.7% sons/daughters. A total of 52.7% of caregivers reported that memory loss was the clinical manifestation of the patient who they took care for; 56% reported knowing the existence of a professional speech language therapist, and 79.3% did not know how the speech language therapist could help in the care of the patient with dementia. With regard to the perception of speech language, 36.6% observed impaired swallowing. Conclusion: The knowledge of caregivers about dementia and swallowing disorders was found to be poor. It is essential that caregivers receive specific guidelines to identify signs of swallowing disorders and assist in the patient’s safe eating in order to prevent future complications such as aspiration pneumonia.