Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy.

For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.

Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy / Imunossupressores e imunomoduladores em Neurologia - Parte I: um guia para o manejo de pacientes em imunoterapia

ABSTRACT For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.

RESUMO Pacientes com doenças autoimunes exigem uma constante preocupação com os riscos e benefícios do tratamento imunossupressor ou imunomodulador. O conhecimento das rotinas no uso de cada uma dessas drogas é fundamental para o bom desfecho clínico, evitando a piora da doença ou efeitos colaterais. As drogas imunossupressoras e imunomoduladoras agem em diferentes pontos da resposta imunológica a fim de controlar a doença para qual são indicadas. O conhecimento do mecanismo de ação, principais posologias, efeitos adversos e os riscos de infecções e neoplasias relacionadas ao uso dessas medicações são fundamentais para um tratamento seguro. Cada uma delas apresenta um perfil específico de complicações e o manejo deve ser individualizado em diferentes cenários ao longo do seguimento do paciente. O uso de medicações para profilaxia primária de infecções e a vacinação são pontos essenciais no planejamento do tratamento, prevenindo potenciais complicações infecciosas ao longo do acompanhamento. O uso de imunossupressores e imunomoduladores é uma frequente realidade no dia-a-dia do neurologista, e o conhecimento das características de cada droga é crucial para o sucesso do tratamento. A realização de uma rotina antes, durante e depois do uso dessas medicações evita complicações relacionadas com o tratamento e alcança um melhor controle da doença.

Reliability, validity and description of timed performance of the Jebsen-Taylor Test in patients with muscular dystrophies.

BACKGROUND: The Jebsen-Taylor Test evaluates upper limb function by measuring timed performance on everyday activities. The test is used to assess and monitor the progression of patients with Parkinson disease, cerebral palsy, stroke and brain injury. OBJECTIVES: To analyze the reliability, internal consistency and validity of the Jebsen-Taylor Test in people with Muscular Dystrophy and to describe and classify upper limb timed performance of people with Muscular Dystrophy. METHODS: Fifty patients with Muscular Dystrophy were assessed. Non-dominant and dominant upper limb performances on the Jebsen-Taylor Test were filmed. Two raters evaluated timed performance for inter-rater reliability analysis. Test-retest reliability was investigated by using intraclass correlation coefficients. Internal consistency was assessed using the Cronbach alpha. Construct validity was conducted by comparing the Jebsen-Taylor Test with the Performance of Upper Limb. RESULTS: The internal consistency of Jebsen-Taylor Test was good (Cronbach's α=0.98). A very high inter-rater reliability (0.903-0.999), except for writing with an Intraclass correlation coefficient of 0.772-1.000. Strong correlations between the Jebsen-Taylor Test and the Performance of Upper Limb Module were found (rho=-0.712). CONCLUSION: The Jebsen-Taylor Test is a reliable and valid measure of timed performance for people with Muscular Dystrophy.

A Study of a Cohort of X-Linked Myotubular Myopathy at the Clinical, Histologic, and Genetic Levels.

BACKGROUND: Myotubular myopathy is a rare X-linked congenital myopathy characterized by marked neonatal hypotonia and respiratory insufficiency, facial and ocular involvement, and muscle biopsy with prominent central nuclei in the majority of muscle fibers. It is caused by mutations in MTM1, which codes for the phosphoinositides phosphatase myotubularin. In this work, we established and detailed a new cohort of six patients at the clinical, histologic, and genetic levels. PATIENTS AND METHODS: Patients were recruited after screening 3065 muscle biopsy reports from two large biopsy banks in Sao Paulo, Brazil from the years 2008 to 2013, and from referrals to a neuromuscular outpatient clinic between 2011 and 2013. We reviewed biopsy slides, evaluated patients, and Sanger sequenced MTM1 in the families. RESULTS: All patients but one had classic phenotypes with a stable course after a severe onset. Two patients died suddenly from hypovolemic shock. Muscle biopsies had been performed in five patients, all of whom showed a classic pattern with a predominance of centrally located nuclei and increased oxidative activity in the center of the fibers. Two patients showed necklace fibers, and two families had novel truncating mutations in MTM1. CONCLUSIONS: X-linked myotubular myopathy is rare in the Brazilian population. Necklace fibers might be more prevalent in this condition than previously reported. Direct Sanger sequencing of MTM1 on clinical suspicion avoids the need of a muscle biopsy.

Swallowing disorders after ischemic stroke.

OBJECTIVE: To investigate occurrences of swallowing disorders after ischemic stroke. METHOD: This was a retrospective study on 596 medical files. The inclusion criterion was that the patients needed to have been hospitalized with a diagnosis of ischemic stroke; the exclusion criteria were the presence of associated cardiac problems and hospital stay already more than 14 days. RESULTS: 50.5% were men and 49.5% women; mean age 65.3 years (SD= ± 11.7) (p ≤ 0.001). Among the risk factors, 79.4% had hypertension, 36.7% had diabetes (p ≤ 0.001) and 42.7% were smokers. 13.3% of the patients died. Swallowing disorders occurred in 19.6%, among whom 91.5% had mild difficulty and 8.5% had severe difficulty. 87.1% had spontaneous recovery after a mean of 2.4 months. A lesion in the brainstem region occurred in 6.8% (p ≤ 0.001). CONCLUSION: Swallowing disorders occurred in almost 20% of the population and most of the difficulty in swallowing found was mild. The predictors for swallowing disorders were older age, diabetes mellitus and lesions in the brainstem region.

Swallowing disorders after ischemic stroke / Alteração da deglutição após acidente cerebrovascular isquêmico

OBJECTIVE: To investigate occurrences of swallowing disorders after ischemic stroke. METHOD: This was a retrospective study on 596 medical files. The inclusion criterion was that the patients needed to have been hospitalized with a diagnosis of ischemic stroke; the exclusion criteria were the presence of associated cardiac problems and hospital stay already more than 14 days. RESULTS: 50.5 percent were men and 49.5 percent women; mean age 65.3 years (SD=±11.7) (p<0.001). Among the risk factors, 79.4 percent had hypertension, 36.7 percent had diabetes (p<0.001) and 42.7 percent were smokers. 13.3 percent of the patients died. Swallowing disorders occurred in 19.6 percent, among whom 91.5 percent had mild difficulty and 8.5 percent had severe difficulty. 87.1 percent had spontaneous recovery after a mean of 2.4 months. A lesion in the brainstem region occurred in 6.8 percent (p<0.001). CONCLUSION: Swallowing disorders occurred in almost 20 percent of the population and most of the difficulty in swallowing found was mild. The predictors for swallowing disorders were older age, diabetes mellitus and lesions in the brainstem region.

OBJETIVO: Verificar alteração da deglutição após acidente cerebrovascular isquêmico (AVCI). MÉTODO: Estudo retrospectivo de 596 prontuários. Critérios de inclusão: pacientes hospitalizados com diagnóstico de AVCI. Critérios de exclusão: pacientes com problemas cardíacos associados e com mais de 14 dias de internação. RESULTADOS: 50,5 por cento homens e 49,5 por cento mulheres, idade média 65,3 anos (DP=±11,7) (p<0,001). Entre os fatores de risco, 79,4 por cento hipertensão arterial, 36,7 por cento diabetes (p<0,001), 42,7 por cento tabagismo. Óbito ocorreu em 13,3 por cento dos pacientes. Alteração de deglutição ocorreu em 19,6 por cento, sendo 91,5 por cento com dificuldade leve e 8,5 por cento com dificuldade grave; 87,1 por cento tiveram recuperação espontânea com tempo médio de 2,4 meses. A lesão em região de tronco encefálico ocorreu em 6,8 por cento (p<0,001). CONCLUSÃO: A alteração da deglutição ocorreu em quase 20 por cento da população e a dificuldade de deglutição mais encontrada foi a leve. Os fatores preditores para alteração de deglutição foram aumento da idade, diabetes mellitus e lesão em região de tronco encefálico.

Distrofia muscular de Duchenne: análise eletrocardiográfica de 131 pacientes / Duchenne muscular dystrophy: electrocardiographic analysis of 131 patients

FUNDAMENTO: É conhecido o envolvimento cardíaco em pacientes com distrofia muscular de Duchenne (DMD). O eletrocardiograma (ECG) apresenta algumas alterações típicas na DMD, fato que o torna um exame útil no diagnóstico da lesão cardíaca nessa patologia. OBJETIVO: Avaliar as alterações eletrocardiográficas em pacientes portadores de DMD, correlacionando-as com a idade da população estudada. MÉTODOS: Foram analisados os ECG de 131 pacientes com diagnóstico de DMD. Avaliaram-se diversas variáveis eletrocardiográficas, sendo os pacientes separados em dois grupos: aqueles com e sem alterações, por variável estudada. Fez-se a correlação desses dois grupos com a idade dos pacientes. Foram utilizados os critérios de Garson para estabelecer os parâmetros eletrocardiográficos de normalidade. RESULTADOS: O ECG estava anormal em 78,6 por cento dos pacientes. Todos apresentavam ritmo sinusal. Foram os seguintes os percentuais encontrados para as principais variáveis estudadas: PR curto = 18,3 por cento, ondas R anormais em V1 = 29,7 por cento, ondas Q anormais em V6 = 21,3 por cento, alterações da repolarização ventricular = 54,9 por cento, ondas QS anormais em paredes inferior e/ou lateral alta = 37,4 por cento, distúrbios de condução pelo ramo direito = 55,7 por cento, intervalo QT C prolongado = 35,8 por cento e alargamento do QRS = 23,6 por cento. O teste t não pareado foi utilizado para se estabelecer a correlação da idade com as variáveis eletrocardiográficas estudadas nos dois grupos e, apenas a variável alteração da repolarização mostrou diferença estatisticamente significante. CONCLUSÃO: As alterações eletrocardiográficas na DMD são frequentes, revelando comprometimento cardíaco precoce. Apenas a variável alteração da repolarização ventricular foi mais frequente, porém em faixa etária menor (p < 0,05).

BACKGROUND: Cardiac involvement is known to occur in patients with Duchenne muscular dystrophy (DMD). The electrocardiogram (ECG) shows some typical changes in DMD, which makes it a useful test for the diagnosis of cardiac lesion in this disease. OBJECTIVE: To evaluate the electrocardiographic changes in patients with DMD and to correlate these changes with the age of the population studied. METHODS: ECG of 131 patients diagnosed with DMD were examined. Several electrocardiographic variables were analyzed, and the patients were divided into two groups - one with and one without changes, for each variable studied. The correlation between the two groups and the age of the patients was analyzed. Garson's criteria were used to establish the electrocardiographic parameters of normality. RESULTS: ECG was abnormal in 78.6 percent of the patients. All showed normal sinus rhythm. The following percentages were found for the main variables studied: short PR interval = 18.3 percent; abnormal R waves in V1 = 29.7 percent; abnormal Q waves in V6 = 21.3 percent; abnormal ventricular repolarization = 54.9 percent; abnormal QS waves in inferior and/or upper lateral wall = 37.4 percent; conduction disturbances in right bundle branch = 55.7 percent; prolonged QT C interval = 35.8 percent, and wide QRS = 23.6 percent. Unpaired t test was used to establish the correlation between age and the electrocardiographic variables studied in the two groups. Statistically significant differences were found only for the abnormal repolarization variable. CONCLUSION: Electrocardiographic abnormalities are common in DMD, revealing early cardiac involvement. Only the abnormal ventricular repolarization variable was more frequent, however at a lower age range (p < 0.05).

[Duchenne muscular dystrophy: electrocardiographic analysis of 131 patients]. / Distrofia muscular de Duchenne: análise eletrocardiográfica de 131 pacientes.

BACKGROUND: Cardiac involvement is known to occur in patients with Duchenne muscular dystrophy (DMD). The electrocardiogram (ECG) shows some typical changes in DMD, which makes it a useful test for the diagnosis of cardiac lesion in this disease. OBJECTIVE: To evaluate the electrocardiographic changes in patients with DMD and to correlate these changes with the age of the population studied. METHODS: ECG of 131 patients diagnosed with DMD were examined. Several electrocardiographic variables were analyzed, and the patients were divided into two groups - one with and one without changes, for each variable studied. The correlation between the two groups and the age of the patients was analyzed. Garson's criteria were used to establish the electrocardiographic parameters of normality. RESULTS: ECG was abnormal in 78.6% of the patients. All showed normal sinus rhythm. The following percentages were found for the main variables studied: short PR interval = 18.3%; abnormal R waves in V1 = 29.7%; abnormal Q waves in V6 = 21.3%; abnormal ventricular repolarization = 54.9%; abnormal QS waves in inferior and/or upper lateral wall = 37.4%; conduction disturbances in right bundle branch = 55.7%; prolonged QT C interval = 35.8%, and wide QRS = 23.6%. Unpaired t test was used to establish the correlation between age and the electrocardiographic variables studied in the two groups. Statistically significant differences were found only for the abnormal repolarization variable. CONCLUSION: Electrocardiographic abnormalities are common in DMD, revealing early cardiac involvement. Only the abnormal ventricular repolarization variable was more frequent, however at a lower age range (p < 0.05).

Esporte como fator de integraçäo do deficiente físico na sociedade / Sport as integration factor of the physically handicapped in our society

O objetivo deste estudo consiste em avaliar o esporte como método de reabilitaçäo e analisar os aspectos físicos, psicológicos e sociais dos portadores de limitaçäo física, especialmente com enfermidades crônicas e que já näo se encontram em programa de reabilitaçäo. Foram avaliados 30 deficientes físicos, de causas diversas, sendo 15 iniciados ao basquetebol e outros 15 à nataçäo, de acordo com a preferência específica de cada atleta. Foram utilizadas a escala social (Rivermead), a classificaçäo funcional do esporte, a aplicaçäo das escalas funcionais (Barthel e Rivermead) e o teste do perfil psicológico (POMS). Essas escalas e o perfil psicológico foram aplicados antes da prática do esporte e dois anos depois. O sexo masculino predominou nos dois grupos e a idade variou entre 17 e 59 anos. Näo notamos alteraçöes nas avaliaçöes fisioterápias, nas escalas de Barthel e Rivermead. No teste psicológico os dois grupos apresentaram um alto vigor e baixa depressäo. Nos aspectos sociais houve importante mudança principalmente nos seus relacionamentos com uma ou mais pessoas e nas atividades da vida diária (social, lazer e doméstica). Este estudo mostra que o esporte pode trazer para o portador de limitaçäo física uma melhor integraçäo social e adaptaçäo a sua condiçäo física

Estudo histoquímico dos músculos "vastus medials" e "vastus lateralis" do músculo "quadriceps femoris" na síndrome do mau alinhamento da patela / Histochemical studies of the \"vastus medials\" and \"vastus lateralis\" muscles the \"quadriceps femoris\" muscle in the malalignment of the patella

Vinte e cinco pacientes portadores de síndrome do mau alinhamento da patela (SMAP) foram submetidos a biópsia muscular, com estudo histoquímico dos músculos vastus medialis e vastus lateralis do músculo quadriceps femoris. As patologias estudadas foram: luxaçäo recidivante da patela (56%), síndrome de hipertensäo lateral da patela (24%) e luxaçäo habitual da patela (20%). Procurou-se averiguar se havia diferenças histopatológicas entre essas patologias. Das 41 biópsias musculares realizadas, apenas três apresentaram-se normais. As demais mostraram-se com alteraçöes inflamatórias (a mais freqüente), por desuso e neurológicas. As características do infiltrado inflamatório säo fortemente sugestivas de que este tenha origem traumática (microtraumatismos), além de facilite com proliferaçäo de tecido conjuntivofibroso. Näo se encontrou uma patologia neuromuscular de base entre estes pacientes e as alteraçöes histológicas tiveram as mesmas características entre as patologias estudadas