High frequency of Depressive Disorders and Suicidal Phenomena in Late-Stage Parkinson´s Disease - A Cross-Sectional Study.

BACKGROUND: Depressive disorders (DD) are widely recognized as one of the most frequent neuropsychiatric disorders in Parkinson´s disease. Patients with late-stage Parkinson´s disease (LSPD) continue to be a neglected population, and little is known about DD frequency in LSPD. OBJECTIVES: To determine the frequency of DD in LSPD patients through a clinical diagnostic interview (CDI) and according to diagnostic DSM- 5 criteria. Secondary objectives were to determine the predictive ability of depressive scales to detect DD, to identify potential predictors of DD in LSPD and, to evaluate suicidal phenomena in LSPD. METHODS: A cross-sectional study including LSPD patients (≥7 years from symptom onset and Hoehn and Yahr scale score >3 or a Schwab and England scale score <50% in the ON condition) was conducted. Patients were subjected to psychiatric, neurological, and neuropsychological evaluations. Six depression scales were applied. RESULTS: 92 LSPD patients were included. 59.78% of LSPD patients had a current diagnosis of DD according to CDI, 38.04% patients had a diagnosis of major depressive disorder, and 21.72% non-major depressive disorder. Suicidal ideation was present in 36.96% of patients. All applied scales were able to detect depressive disorders. CONCLUSIONS: More than half of LSPD patients met DD diagnostic criteria and over one-third were diagnosed with major depressive disorder. Overall, the LSPD population seem to have a unique clinical phenotype regarding the frequency and features of DD, whose early identification and treatment could improve the quality of life of patients and caregivers.

A distinct neuromelanin magnetic resonance imaging pattern in parkinsonian multiple system atrophy.

BACKGROUND: Parkinsonian variant of multiple system atrophy is a neurodegenerative disorder frequently misdiagnosed as Parkinson's disease. No early imaging biomarkers currently differentiate these disorders. METHODS: Simple visual imaging analysis of the substantia nigra and locus coeruleus in neuromelanin-sensitive magnetic resonance imaging and nigrosome 1 in susceptibility-weighted sequences was performed in thirty patients with parkinsonian variant of multiple system atrophy fulfilling possible/probable second consensus diagnostic criteria. The neuromelanin visual pattern was compared to patients with Parkinson's disease with the same disease duration (n = 10) and healthy controls (n = 10). Substantia nigra semi-automated neuromelanin area/signal intensity was compared to the visual data. RESULTS: Groups were similar in age, sex, disease duration, and levodopa equivalent dose. Hoehn & Yahr stage was higher in parkinsonian multiple system atrophy patients, 69% of whom had normal neuromelanin size/signal, significantly different from Parkinson's disease patients, and similar to controls. Nigrosome 1 signal was lost in 74% of parkinsonian multiple system atrophy patients. Semi-automated neuromelanin substantia nigra signal, but not area, measurements were able to differentiate groups. CONCLUSIONS: In patients with parkinsonism, simple visual magnetic resonance imaging analysis showing normal neuromelanin substantia nigra and locus coeruleus, combined with nigrosome 1 loss, allowed the distinction of the parkinsonian variant of multiple system atrophy from Parkinson's disease and healthy controls. This easy and widely available method was superior to semi-automated measurements in identifying specific imaging changes in substantia nigra and locus coeruleus.

Kalirin: a novel genetic risk factor for ischemic stroke.

Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases.

Inhaled levodopa for intermittent treatment of OFF episodes in patients with Parkinson's disease.

Introduction: Many patients with advanced Parkinson's disease (PD) have inadequate control of motor symptoms despite optimized treatment. Predictable and unpredictable OFF periods severely interfere with the quality of life. A drug that easily and rapidly reverts the OFF state is still needed. Subcutaneous apomorphine, the only approved drug for this indication, although efficacious, is not widely used probably due to its potential side effects and complicated administration.Levodopa is the most efficacious drug for the treatment of PD motor symptoms. However, issues related to the oral route and intestinal absorption in later disease stages render this route lengthy and inefficacious.Areas covered: Literature on the development of an inhaled formulation of levodopa has been reviewed. Significant advances in the field of pulmonary delivery systems and in dry powders have enabled the development of a new formulation of levodopa that can be inhaled and adequate blood levels rapidly achieved, bypassing intestinal absorption. Several clinical trials have reported efficacy, safety, and tolerability data. Some pulmonary-related adverse events have been reported but are mostly mild.Expert opinion: This new way of administering levodopa is likely to be very welcome and may fill a gap for OFF rescue treatments, at least for some patients.

[Recommendations about Multiple Sclerosis Management during Pregnancy, Partum and Post-Partum: Consensus Position of the Portuguese Multiple Sclerosis Study Group]. / Recomendações sobre a Abordagem da Esclerose Múltipla na Gravidez, Parto e Pós-Parto: Posição de Consenso do Grupo de Estudos de Esclerose Múltipla.

Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare professionals involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and postpartum, existing uncertainties have been complicated by the increase in the number of treatments available in recent years. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period.

A esclerose múltipla afecta tipicamente mulheres jovens em idade reprodutiva. Desta forma, todo os profissionais de saúde envolvidos no seguimento destes doentes deverão estar preparados para abordar as questões relacionadas com a gravidez e amamentação e fornecer o melhor aconselhamento possível. No entanto, existem ainda muitas dúvidas e abordagens clínicas heterogéneas em parte devido à ausência de consensos e normas orientadoras. No que concerne ao manuseamento das terapêuticas modificadoras de doença durante os períodos de gravidez e pós-parto, as incertezas têm sido agravadas devido ao aumento do número de fármacos disponíveis nos últimos anos. Este artigo visa apresentar a informação mais atual e fornecer orientações baseadas no melhor nível de evidência disponível e na opinião de peritos relativamente ao seguimento das doentes com esclerose múltipla em diferentes etapas: planificação da gravidez, gravidez, parto e período pós-parto.

Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients.

BACKGROUND: The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk. METHODS: We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk. RESULTS: Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect. CONCLUSION: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.

[Recommendations About Multiple Sclerosis Management During Pregnancy, Partum and Post-Partum: Consensus Position of The Portuguese Multiple Sclerosis Study Group and The Portuguese Society of Obstetrics and Maternal-Fetal Medicine]. / Recomendações Sobre a Abordagem da Esclerose Múltipla na Gravidez, Parto e Pós-Parto: Posição de Consenso do Grupo de Estudos de Esclerose Múltipla e da Sociedade Portuguesa de Obstetrícia e Medicina Materno-Fetal.

Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare providers involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues, and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and the postpartum period, uncertainties have been complicated by the increase in recent years of the number of available treatments. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period.

A esclerose múltipla afeta tipicamente mulheres jovens em idade reprodutiva. Desta forma, todo os profissionais de saúde envolvidos no seguimento destes doentes deverão estar preparados para abordar as questões relacionadas com a gravidez e amamentação e fornecer o melhor aconselhamento possível. No entanto, existem ainda muitas dúvidas e abordagens clínicas heterogéneas em parte devido à ausência de consensos e normas orientadoras. No que concerne ao manuseamento das terapêuticas modificadoras de doença durante os períodos de gravidez e pós-parto, as incertezas têm sido agravadas devido ao aumento do número de fármacos disponíveis nos últimos anos. Este artigo visa apresentar a informação mais atual e fornecer orientações baseadas no melhor nível de evidência disponível e na opinião de peritos relativamente ao seguimento das doentes com esclerose múltipla em diferentes etapas: planificação da gravidez, gravidez, parto e período pós-parto.

Consensus Recommendations of the Multiple Sclerosis Study Group and Portuguese Neuroradiological Society for the Use of the Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 1.

INTRODUCTION: Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. MATERIAL AND METHODS: The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper. RESULTS: We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis. CONCLUSION: We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.

Introdução: A esclerose múltipla caracteriza-se pela presença de lesões inflamatórias a nível do encéfalo e medula espinhal. A ressonância magnética é atualmente um exame indispensável no diagnóstico, na avaliação da atividade da doença e na resposta ao tratamento. Embora na nossa prática as vantagens da ressonância magnética estejam bem estabelecidas, continuam a existir dificuldades técnicas (uso de sequências e protocolos não padronizados) e clínicas (frequência de exames não adequada) que podem dificultar o diagnóstico e o seguimento dos doentes. Neste contexto, o Grupo de Estudos de Esclerose Múltipla e a Sociedade Portuguesa de Neurorradiologia, após discussão conjunta, designaram um comité de peritos para a criação de recomendações adaptadas à realidade nacional sobre a utilização da ressonância magnética na esclerose múltipla. O objetivo deste documento é publicar as primeiras recomendações de consenso portuguesas sobre a utilização da ressonância magnética na esclerose múltiplana prática clínica.Material e Métodos: O Grupo de Estudos de Esclerose Múltipla e a Sociedade Portuguesa de Neurorradiologia, após discussão do tema em reuniões de âmbito nacional e de uma reunião do grupo de trabalho que teve lugar na Figueira da Foz em maio de 2017, designaram um comité de peritos que elaboraram por método de consenso vários protocolos padronizados sobre o uso da ressonância magnética no diagnóstico e seguimento da esclerose múltipla. O documento teve como base a melhor evidência científica e a opinião dos peritos. Posteriormente, o documento foi enviado para escrutínio à maioria dos responsáveis de consulta de esclerose múltipla e dos departamentos de neurorradiologia; os comentários e sugestões foram considerados. Os protocolos técnicos referentes à aquisição de imagem e a informação que deverá constar no relatório destes exames serão publicados numa publicação separada.Resultados: Neste artigo são propostas várias orientações práticas para promover estratégias padronizadas para serem aplicadas na prática clínica dos profissionais de saúde portugueses no que se refere ao uso da ressonância magnética na esclerose múltipla.Conclusão: Os autores esperam que estas primeiras orientações portuguesas, sobre a utilização da ressonância magnética na esclerose múltipla na prática clínica, baseadas nas melhores evidências e práticas clínicas disponíveis, sirvam para otimizar a gestão da esclerose múltipla e melhorar o tratamento destes doentes em Portugal.