Resumen en Portugués:

Objetivo : Descrever o perfil funcional, clínico e de qualidade de vida (QV) de pacientes com distonia cervical (DC) com efeito residual ou sem efeito da toxina botulínica (BTX), bem como verificar a existência de correlação entre o nível de comprometimento motor, dor e QV. Método : Setenta pacientes foram avaliados através do Craniocervical dystonia questionnaire-24 (CDQ 24) e Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Resultados : Quanto maior a incapacidade, dor e gravidade da distonia pior a QV (p<0,0001). A maior gravidade está relacionada à maior incapacidade (p<0,0001). A dor esteve presente em 84% da amostra sendo fonte de incapacidade em 41%. Dificuldade em manter-se com as demandas profissionais e pessoais (74,3%), sentir-se desconfortável em público (72,9%), prejudicado pela dor (68,6%), deprimido, irritado ou amargurado (47,1%), solitário ou isolado (32,9%) foram as queixas mais frequentes. Conclusão : Os domínios físico, social e emocional são os mais prejudicados na QV desses pacientes.

Resumen en Inglés:

Objective : Describe the functional, clinical and quality of life (QoL) profiles in patients with cervical dystonia (CD) with residual effect or without effect of botulinum toxin (BTX), as well as verify the existence of correlation between the level of motor impairment, pain and QoL. Method : Seventy patients were assessed through the Craniocervical dystonia questionnaire-24 (CDQ-24) and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Results : The greater the disability, pain and severity of dystonia, the worse the QoL (p<0.0001). Greater severity relates to greater disability (p<0.0001). Pain was present in 84% of the sample, being source of disability in 41%. The most frequent complaints were: difficulty in keeping up with professional and personal demands (74.3%), feeling uneasy in public (72.9%), hindered by pain (68.6%), depressed, annoyed or bitter (47.1%), lonely or isolated (32.9%). Conclusion : The physical, social and emotional aspects are the most affected in the QoL of these patients.

Resumen en Portugués:

Os efeitos da galantamina (GAL) sobre qualidade de vida (QdV) e velocidade de processamento cognitivo, bem como da combinação com nimodipina (NIM) no tratamento da doença de Alzheimer (DA) com doença cerebrovascular (demência mista) ainda não foram investigados. Método : Estudo multicêntrico brasileiro, duplo-cego, controlado com placebo, avaliando os efeitos de GAL/NIM x GAL/placebo (PLA) na demência mista leve a moderada. Pacientes receberam tratamento com GAL/NIM ou GAL/PLA por 24 semanas. Medidas de eficácia primária foram as variações no desempenho em bateria de testes neuropsicológicos computadorizados e na escala QdV-DA ao final do estudo. Resultados : Vinte um pacientes receberam pelo menos uma dose da droga (9 GAL/NIM e 12 GAL/PLA). Os grupos foram emparelhados por idade, sexo, escolaridade, escores cognitivos e de QdV na linha de base. Não foram observadas diferenças significativas entre os dois grupos nas medidas de eficácia primária e secundária. Na avaliação de todos os pacientes que receberam GAL, houve melhora significativa (p<0,05) em QdV-DA e desempenho cognitivo. Os eventos adversos foram predominantemente leves a moderados. Conclusão : O tratamento com GAL proporcionou melhora da QdV na demência mista, além dos benefícios cognitivos previamente conhecidos. A combinação GAL/NIM não foi vantajosa. O reduzido tamanho amostral impede conclusões definitivas.

Resumen en Inglés:

The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. Method : Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimer's Disease (QoL-AD) from baseline to week 24. Results : Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate. Conclusion : GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658

Resumen en Portugués:

Objetivo : Descrever um novo sinal clínico associado à síndrome de negligência unilateral (SNU) em pacientes com acidente vascular cerebral isquêmico (AVCi). Método : Em 150 pacientes com acidente vascular cerebral isquêmico, foram realizadas tomografias de crânio e aplicada a National Institute of Health Stroke Scale. Aqueles pacientes com lesões vasculares à direita, hemiplegia esquerda e perna direita persistentemente cruzada sobre a esquerda, foram submetidos a testes específicos para SNU. Trinta pacientes também com lesões vasculares à direita, hemiplegia esquerda, porém sem evidências de permanecerem com as pernas cruzadas, foram submetidos aos mesmos testes clínicos. Resultados : Entre 150 pacientes com AVCi, 9 apresentaram lesão vascular cerebral à direita, hemiplegia esquerda e tendência em permanecer com a perna direita cruzada sobre a esquerda. Em 8 deles, testes específicos realizados nos primeiros dias de internação, confirmaram SNU à esquerda. Um paciente morreu antes que os testes pudessem ser aplicados. Dos 30 pacientes que não cruzaram as pernas, os testes foram normais em 20. Dez pacientes apresentaram alterações mínimas, insuficientes para o diagnóstico de SNU. Conclusão : A perna direita cruzada sobre a esquerda pode representar um novo sinal semiológico associado à hemiplegia esquerda e SNU à esquerda.

Resumen en Inglés:

Objective : To describe a new clinical sign associated with left unilateral neglect syndrome (UNS) in patients with ischemic stroke. Method : Head computed tomography (CT) and National Institute of Health Stroke Scale were obtained in 150 patients with ischemic stroke. Those with right cerebral vascular lesions, left hemiplegia and right leg persistently crossed over the left were submitted to specific tests for UNS. The tests were also applied to 30 patients with right cerebral vascular lesions, left hemiplegia but without crossed legs. Results : From 9 patients with persistent tendency to cross the right leg over the left, UNS was detected in 8. One patient died before the clinical tests were applied. Of the 30 patients without the crossed legs, 20 had normal clinical tests for UNS and 10 had minimal alterations, not sufficient for the diagnosis of UNS. Conclusion : The right leg crossed over the left may represent a new neurological semiotic sign associated with left hemiplegia and left UNS.

Resumen en Portugués:

O objetivo deste estudo foi pesquisar a prevalência de sintomas de disfunção temporomandibular (DTM) em pacientes com esclerose múltipla (EM) na forma remitente-recorrente e sua relação com o grau de acometimento da doença e a presença de sintomas de DTM entre os grupos avaliados. Foram avaliados 60 indivíduos, sendo 30 com diagnóstico de EM e 30 controles pareados em gênero e faixa etária. Para avaliação de sintomas de DTM, foi aplicado o questionário recomendado aos clínicos pela Academia Europeia das Desordens Craniomandibulares . Para avaliação do nível de acometimento da EM foi utilizada a escala EDSS (Expanded Disability Status Scale). Os resultados da pesquisa mostraram que a prevalência de sintomas de DTM em pacientes com EM foi de 56,7% e 16,7% para o controle, havendo diferença estatística significativa entre os grupos. Não houve correlação entre o nível de acometimento pela EM e a prevalência de sintomas de DTM.

Resumen en Inglés:

The aim of the present study was to assess the prevalence of symptoms of temporomandibular disorders (TMD) in patients with the relapsing-remitting form of multiple sclerosis (MS), the relationship between TMD and the severity of MS, and the presence of TMD symptoms in the evaluated groups. Sixty individuals were evaluated: 30 patients diagnosed with relapsing-remitting MS and 30 control individuals matched for gender and age range with no neurologic pathology. In order to investigate the TMD symptoms, the questionnaires of the EACD (European Academy of Craniomandibular Disorders) and the RDC/TMD (Research Diagnostic Criteria for Temporomandibular Disorders), both validated for TMD research, were administered. To assess the extent of disability produced by MS, the Expanded Disability Status Scale (EDSS) was used. The prevalence of TMD symptoms in patients with MS was 56.7% versus 16.7% for the control group, with a statistically significant difference between the groups (p=0.0016). No correlation was found between the severity of MS and the prevalence of TMD symptoms (Fisher's test, p=1.0).

Resumen en Portugués:

Objetivo : Testar a hipótese que a gravidade do prejuízo cognitivo modifica a associação entre depressão e doença de Parkinson (DP). Método : Estudo populacional através da análise secundária de 1.451 pessoas com idade maior ou igual a 65 anos com prejuízo cognitivo que residiam em áreas de abrangência definidas. A depressão foi estimada de acordo com a CID-10, auto-relato de DP, incapacidade conforme a WHODAS-II e nível cognitvo de acordo com a CSI-D. Resultado : A média de idade foi 79,3 anos, predominaram as mulheres (69%). Do total de indivíduos, 16,1% tinham depressão, significantemente maior entre os participantes com DP. Houve aumento gradativo na OR relativa à associação entre depressão e DP com a diminuição do escore no teste cognitivo (OR ajustado variou de 0,98 a 8,04). Conclusão : A associação entre depressão e DP parece aumentar com a gravidade do prejuízo cognitivo.

Resumen en Inglés:

Objective : To test the hypothesis that severity of cognitive impairment modifies the association between depression and Parkinson’s disease (PD). Method : One-phase population-based door-to-door surveys. This is a secondary analysis of 1,451 people aged 65 years and older with cognitive impairment living in defined catchment areas. Depression was estimated according to ICD-10, self-reported PD, disability according to WHODAS-II and cognitive status according to the CSI-D. Results : The mean age of the sample was 79.3 years old and most (69%) were women. Of the total sample, 16.1% had depression and it was significantly higher among participants with PD. There was an increase on the ORs of the association between depression and PD with decreased scores in the cognitive test (Adjusted OR from 0.98 to 8.04). Conclusion : The association between depression and PD increases with the severity of the cognitive impairment.

Resumen en Portugués:

A cintilografia miocárdica com meta-iodo-benzil-guanidina (123I cMIBG) foi estudada na doença de Parkinson (DP), especialmente nos países asiáticos, mas não na América Latina. A quase totalidade desses estudos inclui indivíduos com DP com disautonomia definida. Nosso objetivo é relatar a neurotransmissão simpática cardíaca em doentes brasileiros com DP de novo esporádica, sem disautonomia clinicamente definida. Foi avaliada retrospectivamente uma série de 21 casos consecutivos com DP sem sintomas ou sinais de disautonomia observáveis pelos testes de beira-de-leito. Com a aplicação dos critérios de exclusão, este número foi reduzido para 14. A captação do 123I MIBG pelo SPECT foi baixa ou ausente em todos os pacientese; a relação coração / mediastino foi baixa em 12 dos 14. Concluímos que a 123c MIBG é capaz de identificar alteração da neurotransmissão simpática cardíaca em doentes com DP de novo sem disautonomia clinicamente definida.

Resumen en Inglés:

Myocardial scintigraphy with meta-iodo-benzyl-guanidine (123I cMIBG) has been studied in Parkinson's disease (PD), especially in Asian countries, but not in Latin America. Most of these studies include individuals with PD associated to a defined dysautonomia. Our goal is to report the cardiac sympathetic neurotransmission in de novo Brazilian patients with sporadic PD, without clinically defined dysautonomia. We evaluated retrospectively a series of 21 consecutive cases with PD without symptoms or signs of dysautonomia assessed by the standard bedside tests. This number was reduced to 14 with the application of exclusion criteria. 123I cMIBG SPECT up-take was low or absent in all of them and the heart/mediastinum ratio was low in 12 of 14. We concluded that 123I cMIBG has been able to identify cardiac sympathetic neurotransmission disorder in Brazilian de novo PD patients without clinically defined dysautonomia.

Resumen en Portugués:

A hidrocefalia de pressão normal (HPN) é caracterizada por distúrbios da marcha, demência e/ou incontinência urinária associada com dilatação do sistema ventricular e pressão de abertura do líquido cefalorraquidiano normal. Evidências científicas confirmam associação entre HPN e sintomas psiquiátricos. Foram selecionados 35 pacientes com hidrocefalia de pressão normal idiopática, de janeiro de 2010 a janeiro de 2012 em um hospital terciário brasileiro e realizada uma avaliação psiquiátrica formal para identificar transtornos psiquiátricos. Transtornos psiquiátricos foram detectados em 71% dos pacientes, principalmente depressão, ansiedade e síndromes psicóticas. Pacientes com HPN podem desenvolver sintomas com predomínio frontal, tais como mudanças de personalidade, ansiedade, depressão, síndromes psicóticas, transtorno obsessivo compulsivo, síndrome de Otelo, furtos e mania. Sintomas incomuns de HPN podem dificultar o diagnóstico precoce e o tratamento adequado.

Resumen en Inglés:

Normal pressure hydrocephalus (NPH) is characterized by gait disturbance, dementia and/or urinary incontinence associated with dilation of ventricular system with normal opening cerebrospinal fluid pressure. Wide scientifical evidence confirms association between NPH and psychiatric symptoms. We selected 35 patients with idiopathic normal pressure hydrocephalus from January 2010 to January 2012 in a Brazilian tertiary hospital and performed a formal psychiatric evaluation to identify psychiatric disorders. Psychiatric disorders were present in 71% of these patients, especially anxiety, depression and psychotic syndromes. NPH patients may develop symptoms with frontal dominance, such as personality changes, anxiety, depression, psychotic syndromes, obsessive compulsive disorder, Othello syndrome; shoplifting and mania. Unusual appearances of NPH symptoms may hinder early diagnosis and consequently proper treatment.

Resumen en Portugués:

Introdução : A Medida de Independência da Medula Espinhal III (SCIM III) avalia especificamente a funcionalidade de indivíduos com lesões da medula espinhal. Objetivo : Traduzir e validar a versão brasileira da SCIM III. Método : A SCIM III foi traduzida, contra-traduzida e adaptada para o idioma português brasileiro. Dois entrevistadores avaliaram 83 indivíduos com lesões da medular espinhal em sete centros de reabilitação colaboradores. A Medida de Independência Funcional (FIM™) e índices motor e sensitivo da ASIA também foram usados. Após seis meses, os sujeitos foram reavaliados com os mesmo instrumentos. Resultados : Os avaliadores entenderam claramente a versão brasileira da SCIM III. O coeficiente de correlação intraclasse (ICC) inter-examinadores foi 0,918, e de teste-reteste foi 0,991. Após seis meses, a variação de ganhos na FIM™ correlacionou-se positivamente com os ganhos da SCIM III. Conclusão : A versão brasileira da SCIM III é de fácil entendimento, apresenta boas propriedades psicométricas e é válida.

Resumen en Inglés:

Introduction : The Spinal Cord Independence Measure (SCIM III) specifically assesses individuals with spinal cord injuries. Objective : To translate and validate the Brazilian version of SCIM III. Method : SCIM III was translated, back-translated and adapted to the Portuguese language. Two interviewers assessed 83 subjects with spinal cord injuries in each one of seven collaborating rehabilitation centers. Functional Independence Measure (FIM™) and ASIA motor and sensory indices were also used. After six months, subjects were re-evaluated with the same instruments. Results : Examiners clearly understood the Brazilian version of SCIM III. Inter-rater intraclass correlation coefficient (ICC) was 0.918, and test-retest ICC was 0.991. After six months, the variation of gains in the FIM™ positively correlated with gains in SCIM III. Conclusion : The Brazilian version of the SCIM III is easy to understand, has good psychometric properties, and is valid.

Resumen en Portugués:

O espectro da neuromielite óptica (NMOSD) é caracterizado por ataques graves de neurite óptica e mielite. Anticorpos séricos contra a aquaporina-4 (AQP4) são usualmente presentes nestes pacientes. Entretanto, alguns pacientes com NMOSD são seronegativos mesmo com testes repetidos em amostras obtidas durante ataques usando métodos altamente sensíveis baseados em células. O diagnóstico diferencial não é restrito à esclerose múltipla e inclui muitas doenças que podem produzir mielite longitudinalmente extensa e/ou neurite óptica. São abordadas as características clínicas, de imagem e de laboratório que podem ser úteis no diagnóstico, as diferenças entre os pacientes positivos para o anticorpo anti-AQP4 e os negativos, incluindo as características dos pacientes com NMOSD que possuem anticorpos contra a glicoproteína associada ao oligodendrócito.

Resumen en Inglés:

Neuromyelitis optica spectrum disorders (NMOSD) are characterized by severe optic neuritis and/or longitudinally extensive transverse myelitis, and some brain lesions are also unique to NMOSD. Serum autoantibodies against aquaporin-4 (AQP4) are detected in most cases of NMOSD. However, some patients with NMOSD remain seronegative despite repetitive testing during attacks with highly sensitive cell-based assays. The differential diagnosis of NMOSD is not restricted to multiple sclerosis and it includes many diseases that can produce longitudinally extensive myelitis and/or optic neuritis. We review the clinical features, imaging, and laboratory findings that can be helpful on the diagnostic work-up, discuss the differences between AQP4 antibody positive and negative patients with NMOSD, including features of NMOSD with antibodies against myelin oligodendrocyte glycoprotein.

Resumen en Portugués:

Lesão medular (LM) e esclerose lateral amiotrófica (ELA) são condições devastadoras que acometem pessoas em todo o mundo, reduzindo a qualidade de vida tanto de pacientes como de entes queridos. Objetivo : A atual revisão tem como alvo as múltiplas abordagens restauradoras para a regeneração medular, o uso de diferentes tipos celulares e o atual conhecimento a cerca da terapia com células tronco. Método : Revisão de literatura dos últimos 10 anos usando transplantes de células tronco como estratégia principal, com ou sem terapia adjuvante, em humanos. Conclusão : A presente revisão oferece uma visão geral acerca da restauração medular e serve de ponto de partida para estudos futuros.

Resumen en Inglés:

Spinal cord injury (SCI) and amyotrophic laterals sclerosis (ALS) are devastating neurological conditions that affect individuals worldwide, significantly reducing quality of life, both for patients and their relatives. Objective : The present review aims to summarize the multiple restorative approaches being developed for spinal cord repair, the use of different stem cell types and the current knowledge regarding stem cell therapy. Method : Review of the literature from the past 10 years of human studies using stem cell transplantation as the main therapy, with or without adjuvant therapies. Conclusion : The current review offers an overview of the state of the art regarding spinal cord restoration, and serves as a starting point for future studies.

Resumen en Portugués:

Restauração do sistema nervoso central (SNC) é um importante desafio clínico e o transplante de células-tronco tem sido considerado uma opção terapêutica promissora para muitas doenças neurológicas. Objetivo : O presente trabalho tem como objetivo descrever brevemente a biologia das células-tronco, assim como sua aplicação clínica no tratamento de doenças do SNC. Método : Revisão da literatura de experimentação animal e ensaios clínicos com humanos, usando as seguintes palavras chave: “células-tronco”, “neurogênese”, “Parkinson”, “Huntington”, “esclerose lateral amiotrófica”, “lesão cerebral traumática”, “lesão da medula espinal”, “acidente vascular cerebral isquêmico” e “doenças desmielinizantes”. Conclusão : Grandes avanços em pesquisas com células-tronco nos conduziram a novas perspectivas para uma aplicação clínica efetiva, visando desenvolver formas eficazes de regeneração do SNC.

Resumen en Inglés:

Central nervous system (CNS) restoration is an important clinical challenge and stem cell transplantation has been considered a promising therapeutic option for many neurological diseases. Objective : The present review aims to briefly describe stem cell biology, as well as to outline the clinical application of stem cells in the treatment of diseases of the CNS. Method : Literature review of animal and human clinical experimental trials, using the following key words: “stem cell”, “neurogenesis”, “Parkinson”, “Huntington”, “amyotrophic lateral sclerosis”, “traumatic brain injury”, “spinal cord injury”, “ischemic stroke”, and “demyelinating diseases”. Conclusion : Major recent advances in stem cell research have brought us several steps closer to their effective clinical application, which aims to develop efficient ways of regenerating the damaged CNS.

Resumen en Portugués:

Edgar Allan Poe foi um dos mais celebrados escritores do mundo. Ele publicou várias obras primas, algumas delas com referências a diversas doenças neurológicas. O autor apresentou quadro depressivo recorrente, sugestivo de distúrbio bipolar, com abuso de álcool e de drogas, e morreu devido a complicações do alcoolismo, com diferentes hipóteses, incluindo a encefalopatia de Wernicke.

Resumen en Inglés:

Edgar Allan Poe was one of the most celebrated writers of all time. He published several masterpieces, some of which include references to neurological diseases. Poe suffered from recurrent depression, suggesting a bipolar disorder, as well as alcohol and drug abuse, which in fact led to his death from complications related to alcoholism. Various hypotheses were put forward, including Wernicke's encephalopathy.

Resumen en Portugués:

Marcel Proust foi um dos maiores escritores franceses de todos os tempos. Desde jovem, Proust era interessado em artes e especialmente literatura. Ele também demonstrava um grande conhecimento sobre medicina, especialmente neurologia. Seu pai era um médico, e contribuiu para a neurologia através de estudos sobre a afasia, acidente vascular cerebral, histeria, neurastenia. Durante sua infância, Proust teve o primeiro ataque de asma, inicialmente considerado uma manifestação da neurastenia. Devido à sua doença, Proust estava frequentemente em contato com vários neurologistas renomados, tais como Brissaud, Babinski e Sollier, entre outros discípulos de Charcot. Proust passou a maior parte do tempo nos últimos três anos da sua vida confinado em seu quarto, após deterioração da sua saúde. Em um determinado momento, Babinski foi chamado, examinou Proust e depois de sair de seu quarto, anunciou a seu irmão que Proust estava praticamente morto. Poucas horas depois, Proust desenvolveu vômica e faleceu.

Resumen en Inglés:

Marcel Proust was one of the greatest French writers of all times. Since early in his life, Proust was interested in arts and particularly literature. He also demonstrated a great knowledge of medicine, particularly neurology. His father was a doctor, and contributed to neurology through studies on aphasia, stroke, hysteria, and neurasthenia. During his childhood, Proust had the first asthma attack, initially considered a manifestation of neurasthenia. Regarding his illness, Proust was in touch with several renowned neurologists, such as Brissaud, Babinski and Sollier, and other disciples of Charcot. Proust spent the last three years of his life mostly confined to his bedroom since his health had badly deteriorated. In one moment, Babinski was called, examined Proust and after leaving his bedroom, announced to his brother that Proust was practically dead. Few hours later, Proust developed vomica and died.

Resumen en Inglés:

Purpose: To investigate in patients with Parkinson's disease (PD), which are the coping strategies used and the relation between type of coping, voice symptoms and communicative aspects. Method: 73 subjects, 33 in the experimental group, with diagnosis of PD, and 40 subjects in the control group, healthy and without vocal complaints. They underwent the following procedures: application of the Voice Symptons Scale – VoiSS – Brazilian Version, Voice Disability Coping Questionnaire – VDCQ – Brazilian Version, and the questionnaire Living with Dysarthria – LwD. Results: The experimental group showed deviations in all protocols: VDCQ (p<0.001), VoiSS (p<0.001), LwD (p<0.001). The most frequently used coping strategy was self-control (p<0.001). The correlation between vocal symptoms and communicative aspects showed that the greater the impairment in communication, the greater the VoiSS emotional scores and the greater will be the amount of voice symptoms and signs. However, the vocal signs and symptoms and communicative aspects showed no correlation with coping. Conclusion: Patients with PD have a high amount of vocal signs and symptoms and the higher the occurrence, the more the patient reports being difficult to live with dysarthria, particularly when there are deviations in the emotional domain.

Resumen en Inglés:

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetic muscular dystrophies, involving 16 autosomal recessive subtypes and eight autosomal dominant subtypes. Autosomal recessive dystrophy is far more common than autosomal dominant dystrophy, particularly in children. The clinical course in this group is characterized by progressive proximal weakness, initially in pelvic and after in shoulder-girdle musculature, varying from very mild to severe degree. Significant overlap of clinical phenotypes, with genetic and clinical heterogeneity, constitutes the rule for this group of diseases. Muscle biopsies are useful for histopathologic and immunolabeling studies, and DNA analysis is the gold standard to establish the specific form of muscular dystrophy. Objectives: The aim of this study was to characterize the clinical, histological and molecular aspects in children with LGMD who attend a big public neuromuscular centre in our country to determine the frequency of different forms. Method: Thirty seven patients were classified as LGMD and included in this analysis. The study period extended from 2009-2012. The female to male ratio was 3:1. The age of onset ranged from two to 13 years, mean 7,5 years. Onset in the first decade was seen in 90%. Results: The initial clinical signs included: frequent falls (22 cases), difficulty in climbing stairs (13 cases), walk on tip toes (2 cases), difficulty in rising from the floor (2 cases) and difficulty on walking (1 case). The serum CK levels were high in all cases. Among the 37 patients, 15 (40,5%) were classified as sarcoglycanopathies (LGMD2C-F), five (13,5%) as dysferlinopathy (LGMD2B), five (13,5%) as calpainopathy (LGMD2A). Mutations in LMNA gene (LGMD1B), FKRP gene (LGMDI) and caveolin gene (LGMD 1C) were identified in two (5,5%), two (5,5%) and one patient (2,5%), respectively. In seven of 37 cases (19%) it was impossible to determine specific diagnosis. Calf hypertrophy, scapular winging and scoliosis were the most characteristic signs in sarcoglycanopathies. In LGMD2I calf hypertrophy is also observed. Atrophy of posterior compartment of thighs is frequent in children with LGMD2B and could suggest the diagnosis. In LGMD2A winging of scapulae and contractures in Achilles tendons were important findings. Muscle biopsy showed a dystrophic pattern in all cases, more intense in sarcoglycanopathies and LGMD2I. Differently from adult’s patients, inflammation changes in dysferlinopaties were uncommon. Lobuled fibers were characteristic changes in calpainopathies in children. Conclusions: A definitive diagnosis among various subtypes of LGMD in children is challenging. Our series was a large study on LGMD in Brazilian children and showed high frequency of sarcoglycanopathies followed by LGMD2A, LGMD2B, LGMD2I, LGMD1B and LGMD1C.

Resumen en Inglés:

Introduction: The multiple sclerosis (MS) is a chronic disease of the central nervous system that affects mainly young adults. This disease is characterized by the spread of demyelinating lesions in time and space. This condition may be influenced by genetic factors as heterogeneity, incomplete penetrance, polygenic inheritance and epigenetic factors, which makes this complex disease a challenge for geneticists. Objectives: The aim of this study was to investigate the association between HLA alleles from DQA1, DQB1 and DRB1 loci (6p21.3), genetic polymorphisms -168A/G (rs3087456) and +1614 G/C (rs4774) in the CIITA gene (16p13) and susceptibility to MS in a miscegenated sample from Rio de Janeiro state, RJ, Brazil. Method: DNA samples from 52 patients with relapsing remitting multiple sclerosis (MSRR) [21 males (40.38%) and 31 females (59.62%)] and 116 healthy controls [46 males (39.65%) and 70 females (60.35%)] matched by race, sex and age were analyzed by techniques of PCR, SSP-PCR, electrophoresis and DNA sequencing. Results: A significant association between MS and HLA-DRB1*15:01 allele was observed [p value=.002; Odds Ratio (OR)=3.2], especially in women (p=.001; OR=4.9), which remained statistically significant after Bonferroni correction. Furthermore, it was observed that the polymorphism +1614 G/C, “C/C” profile, in association with the allele DRB1*15:01 influences the increased susceptibility to MS in women (p=.029; OR=5.6). In addition, it was observed that the "G/G" profile in CIITA polymorphism +1614G/C may be associated with the resistance to MS (p=.02; OR=0.23), as well as HLA-DRB1*11:02 (p=.02, OR=0.5). The HLA-DQB1*06:02 allele also has been implicated as a possible susceptibility factor for MS (p=.02; OR=1.8, data not confirmed after Bonferronís correction). Conclusion: Together, these results reinforce the polygenic nature of MS, and proposed that the CIITA gene, which is the regulator of the expression of HLA-D, is an additive factor to DRB1*15:01 allele, previously described as a genetic susceptibility factor to MS in Brazilians.

Resumen en Inglés:

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system (CNS) that affects mainly young adults. MS seems to be a polygenic and multifactorial disease, and genetic susceptibility has been associated mainly with the major histocompatibility complex (MHC), which in humans is the human leukocyte antigen (HLA). Among non-HLA genes is the alpha chain of interleukin 7 receptor gene (IL7Rα) at the 5p12-14 locus, also known as CD127. The aim of this study was to evaluate the correlations between polymorphism in the IL7Rα (rs6897932C) gene, HLA-class II DRB1* haplotypes and susceptibility to multiple sclerosis in patients with Recurrent Remitting form (RRMS). METHOD: In this study, peripheral blood samples were taken from 50 patients diagnosed using the diagnostic criteria for MS according to Polman (MacDonald) et al (2011). The patients were monitored at the Clinic of Neurology, Hospital Universitário Clementino Fraga Filho, along with 100 healthy control subjects matched for ancestry, sex and age. After DNA extraction by organic method, polymorphism +244 *C (rs6897932) was assessed by PCR followed by capillary electrophoresis on the ABI PRISM® 3500 Genetic Analyzer (Applied Biosystems, USA) platform. RESULTS: The results indicated a significant association between the CC haplotype and RRMS (p=0.02 , OR=2.14), as well as an association between the *C allele (CC and CT) and RRMS (p=0.042, OR=2.15). The same C allele was more frequent in the sample, both in patients (0.82), and in the control group (0.71). The sample, control group and patients included, was in Hardy- Weinberg equilibrium. The correlation between the presence of the CC genotype and HLA-DRB1* 15:01 was significant (OR=3.6, p=0.034). CONCLUSION: These results reinforce the polygenic/multifactorial characteristic or genetic heterogeneity of MS, indicating a relationship between putative polymorphism +244*C (CC genotype) in the IL7Rα gene and susceptibility to MS in the sample.