Das descrições de Charcot à compreensão atual dos sintomas neuropsiquiátricos na esclerose múltipla

Os distúrbios neuropsiquiátricos na esclerose múltipla são conhecidos desde a descrição clínico-patológica original de Charcot no final do século XIX. Charcot nas últimas décadas de sua vida se envolveu no campo da neuropsiquiatria. Isso produziu uma batalha de escolas rivais na época que ainda ecoa até hoje. A intuição de Charcot, incluindo a linha de pensamento de Babinski, um de seus discípulos mais famosos, foi a teoria correta da conexão entre os transtornos do humor e muitas das doenças do sistema nervoso. A preocupação da Medicina em estabelecer uma relação entre transtornos do humor e doenças vem das idades antiga e média, com referências encontradas na doutrina hipocrática. No entanto, foi apenas na segunda metade do século XIX e início do século XX que, com as descobertas de Charcot essa discussão foi realizada de maneira estruturada, estabelecendo os fundamentos da neuropsiquiatria.Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot’s intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine’s concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot’s discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry

Elevated Glutamate and Glutamine Levels in the Cerebrospinal Fluid of Patients With Probable Alzheimer's Disease and Depression

Recent evidence suggests that Alzheimer's disease (AD) and depression share common mechanisms of pathogenesis. In particular, deregulation of glutamate-mediated excitatory signaling may play a role in brain dysfunction in both AD and depression. We have investigated levels of glutamate and its precursor glutamine in the cerebrospinal fluid (CSF) of patients with a diagnosis of probable AD or major depression compared to healthy controls and patients with hydrocephalus. Patients with probable AD or major depression showed significantly increased CSF levels of glutamate and glutamine compared to healthy controls or hydrocephalus patients. Furthermore, CSF glutamate and glutamine levels were inversely correlated to the amyloid tau index, a biomarker for AD. Results suggest that glutamate and glutamine should be further explored as potential CSF biomarkers for AD and depression

Aquaporin-4 Antibodies Are Not Related to HTLV-1\ud Associated Myelopathy

Introduction: The seroprevalence of human T-cell leukemia virus type 1 (HTLV-1) is very high among Brazilians (,1:200).\ud HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the most common neurological complication of\ud HTLV-1 infection. HAM/TSP can present with an acute/subacute form of longitudinally extensive myelitis, which can be\ud confused with lesions seen in aquaporin-4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorders (NMOSD)\ud on MRI. Moreover, clinical attacks in patients with NMOSD have been shown to be preceded by viral infections in around\ud 30% of cases.\ud Objective: To evaluate the frequency of AQP4-Ab in patients with HAM/TSP. To evaluate the frequency of HTLV-1 infection\ud in patients with NMOSD.\ud Patients and Methods: 23 Brazilian patients with HAM/TSP, 20 asymptomatic HTLV-1+ serostatus patients, and 34 with\ud NMOSD were tested for AQP4-Ab using a standardized recombinant cell based assay. In addition, all patients were tested for\ud HTLV-1 by ELISA and Western blotting.\ud Results: 20/34 NMOSD patients were positive for AQP4-Ab but none of the HAM/TSP patients and none of the\ud asymptomatic HTLV-1 infected individuals. Conversely, all AQP4-Ab-positive NMOSD patients were negative for HTLV-1\ud antibodies. One patient with HAM/TSP developed optic neuritis in addition to subacute LETM; this patient was AQP4-Ab\ud negative as well. Patients were found to be predominantly female and of African descent both in the NMOSD and in the\ud HAM/TSP group; Osame scale and expanded disability status scale scores did not differ significantly between the two\ud groups.\ud Conclusions: Our results argue both against a role of antibodies to AQP4 in the pathogenesis of HAM/TSP and against an\ud association between HTLV-1 infection and the development of AQP4-Ab. Moreover, the absence of HTLV-1 in all patients\ud with NMOSD suggests that HTLV-1 is not a common trigger of acute attacks in patients with AQP4-Ab positive NMOSD in\ud populations with high HTLV-1 seroprevalence.This study received financial support from the Brazilian government agencies FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo - www. fapesp.br/en) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - www.capes.gov.br). The work of S.J. and B.W. was supported by research grants from Bayer Schering Healthcare and from Merck Serono. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse

The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process

Ideação suicida, ansiedade e depressão em pacientes com esclerose múltipla

Transtornos psiquiátricos frequentemente ocorrem em pacientes com esclerose múltipla (EM). No entanto, os artigos sobre estas comorbidades são limitados. Pretendemos investigar as relações entre EM, ansiedade, depressão e ideação suicida. Métodos: Cento e trinta e dois pacientes com EM remitente-recorrente foram avaliados usando a Escala de Estado de Incapacidade Expandida, Inventário de Depressão de Beck-II (IDB-II), Escala de Beck para Ideação de Suicídio (BSI) e Escala de Ansiedade e Depressão. Resultados: Uma análise de regressão hierárquica foi realizada para avaliar as variáveis. A equação de regressão previu significativamente o escore BSI (R2 = 0,306; R2 ajustado = 0,273; F (9,125) = 9,18; p < 0,0005) e o escore no IDB-II foi a única variável que contribuiu significativamente para este modelo (p < 0,0005). Conclusões: Uma alta prevalência de depressão e ansiedade e uma maior taxa de ideação suicida foram identificadas em pacientes com EM em comparação com a população em geral. A presença de sintomas depressivos pareceu ter uma influência direta no risco de suicídio.Psychiatric disorders frequently occur in patients with multiple sclerosis (MS); however, limited reports are available on these comorbidities. We aimed to investigate the relationships among MS, anxiety, depression, and suicidal ideation. Methods: One hundred and thirty two patients with relapsing-remitting MS were evaluated using the Expanded Disability Status Scale, Beck Depression Inventory-II (BDI-II), Beck Scale for Suicide Ideation (BSI), and Hospital Anxiety and Depression Scale. Results: A hierarchical regression analysis was performed to evaluate the variables. The regression equation significantly predicted the BSI score (R2 = 0.306; adjusted R2 = 0.273; F (9, 125) = 9.18; p < 0.0005), and the BDI-II score was the only variable that contributed significantly to this model (p < 0.0005). Conclusions: A high prevalence of depression and anxiety, and a higher rate of suicidal ideation were identified in MS patients compared to the general population. The presence of depressive symptoms appeared to have a direct influence on the risk of suicide

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

<p>Abstract</p> <p>Background</p> <p>Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.</p> <p>Methods</p> <p>This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.</p> <p>Discussion</p> <p>The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.</p> <p>Trial Registration</p> <p>Clinical Trials <a href="http://www.clinicaltrials.gov/ct2/show/NCT00970931">NCT00970931</a>.</p

Factors associated to the positive cerebrospinal fuid culture in the tuberculous meningitis Fatores associados à positividade da cultura do líquido cefalorraquidiano na meningite tuberculosa

Central nervous system involvement is the most common neurological complication in the course of tuberculosis. The lack of rapid and sensitive tests delays the early diagnosis. Here, we retrospectively reviewed the cerebrospinal fluid (CSF) examination of 30 patients with tuberculous meningitis confirmed by bacteriological tests (culture and/or polymerase chain reaction). The purpose of the present study was to determine the CSF parameters associated to the positive CSF culture for Mycobacterium tuberculosis in tuberculous meningitis. We found higher frequency of positive CSF culture in patients infected with HIV as well in patients with high number of neutrophils and high protein content (characteristic in the early or acute-stage patients), which suggests that the positive culture found in these patients may be associated with the presence of high bacillary load in CSF occurring in these stages.A meningite tuberculosa é a complicação neurológica mais freqüente no curso da tuberculose. Entretanto, a carência de testes rápidos e sensíveis dificulta o diagnóstico precoce, contribuindo para o elevado índice de letalidade desta condição. Na presente análise, é feita revisão dos achados do líquido cefalorraquidiano (LCR) de 30 pacientes com o diagnóstico de meningite tuberculosa confirmado pelo exame bacteriológico. O objetivo do estudo consiste em caracterizar os parâmetros associados à positividade da cultura para Mycobacterium tuberculosis no LCR. Observamos maior freqüência de cultura positiva entre os pacientes infectados pelo HIV e naqueles que apresentam aumento de neutrófilos e da concentração de proteína no LCR. Nossos achados se justificam pelo fato de que na co-infecção com o HIV ocorre maior carga bacilífera em comparação aos pacientes não co-infectados. A presença de neutrofilorraquia e hiperproteinorraquia são marcadores de inflamação aguda, onde se supõe existir também maior concentração de bactérias no LCR