Navegando por Palavras-chave "Amyotrophic lateral sclerosis"
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- ItemAcesso aberto (Open Access)Caracterização clínica, epidemiológica, neurorradiológica e genética de pacientes com síndrome Fosmn(Universidade Federal de São Paulo (UNIFESP), 2018-07-26) Pinto, Wladimir Bocca Vieira de Rezende [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; http://lattes.cnpq.br/3911841387107665; http://lattes.cnpq.br/8416591409563935; Universidade Federal de São Paulo (UNIFESP)Objectives: Perform clinical characterization of motor and nonmotor aspects of FOSMN (facialonset sensory and motor neuronopathy) syndrome in Brazilian patients. Secondary objectives included: (i) evaluation of the genetic basis associated with FOSMN syndrome, especially in patients with familial history of MND (Motor Neuron Disease)/ALS (Amyotrophic Lateral Sclerosis) or other neurodegenerative diseases or a specific genetic spectrum; (ii) discussion of the main pathophysiological mechanisms involved with FOSMN syndrome correlating genetic findings observed in sporadic and familial MND/ALS and the main atypical variants. Methods: A retrospective clinical study was performed and a wide evaluation and review of clinical, laboratorial, neurophysiological and neurogenetic findings from ten nonrelated Brazilian patients with FOSMN syndrome selected from a group of 900 patients followedup from January 2012 and December 2016 in MND/ALS Unit, Division of Neuromuscular Diseases, Federal University of São Paulo (UNIFESP), São Paulo, Brazil. Medical records were verified including clinical characterization of signs and symptoms of motor and nonmotor compromise (including basic cognitive profile), laboratorial evaluation, neuroimaging studies and specific genetic exams. Genetic studies were reviewed and performed in cases with previously established or suggestive familial (or hereditary) context of a specific neurodegenerative phenotype of familial MND/ALS. Results: Mean age at onset of symptoms was at 52.1 years, with equal involvement of men and women. Patients presented with hemifacial paraesthesia (including oral cavity mucosa) or bialteral paraesthesia and weakness in the face, evolving with dysphagia, dysphonia and amyotrophy in the face and tongue, eventually with compromise of other bulbar and pontine cranial nerves, and finally at latestages with dropped head syndrome, weakness in the upper limbs and sensory changes in the upper limbs in a similar pattern to syryngomyelialike. Eight patients presented with multidomain cognitive compromise, half of them with cortical brain atrophy and none of them with spontaneous cognitive or behavioral complaints. All patients had diffuse chronic denervation involving the bulbar, cervical and thoracic myotomes (most of them also with acute denervation) and abnormal testing of the blink reflex. Positive family history of neurodegeneration was identified in six cases, disclosing monogenic pathogenic variants in three families (VCP, TARDBP and CHCHD10 genes). The worst clinical prognosis regarding mortality and severe motor handicap was observed in one single case with early bulbaronset of symptoms and high tendency of early cervical weakness (droppedhead syndrome). Conclusion: This case series has demonstrated new clinical and neurogenetic findings associated with FOSMN syndrome: (i) motor clinical course is not always benign with worse prognosis associated with “droppedhead” syndrome and early bulbar compromise; (ii) although considered a sporadic MND in current literature, FOSMN syndrome may be part of a complex familial neurodegenerative spectrum; (iii) it has been observed the association of FOSMN syndrome in three patients with pathogenic variants in TARDBP, VCP and CHCHD10 genes; (iv) cognitive compromise may be underdiagnosed in cases of FOSMN syndrome possibly due to subclinical involvement.
- ItemSomente MetadadadosThe frequency of the C9orf72 expansion in a Brazilian population(Elsevier Science Inc, 2018) Cintra, Vivian Pedigone; Bonadia, Luciana Cardoso; Andrade, Helen Maia T.; Albuquerque, Milena de; Eusebio, Mayara Ferreira; Oliveira, Daniel Sabino de; Claudino, Rinaldo; Goncalves, Marcus Vinicius Magno; Teixeira Junior, Antonio Lucio; Prado, Laura de Godoy Rousseff; Souza, Leonardo Cruz de; Dourado Junior, Mario Emilio Teixeira; Oliveira, Acary Souza Bulle [UNIFESP]; Tumas, Vitor; Franca Junior, Marcondes C.; Marques Junior, WilsonG(4)C(2) hexanucleotide repeat expansions in the C9orf72 gene seem to be the cause of numerous cases of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). In this study, we investigated the presence of the G(4)C(2) repeat expansion in 463 Brazilian probands, of whom 404 had ALS/motor neuron disease and 67 FTD, and in 63 healthy controls in the southeastern region of Brazil. The highest frequencies of the C9orf72 mutation were in the ALS-FTD group (50% of familial and 17.6% of sporadic cases), although it was also present in 5% of pure ALS/motor neuron disease patients (11.8% of familial and 3.6% of sporadic cases) and in 7.1% of pure familial FTD. Among G(4)C(2) repeat mutation carriers, 68.8% of the subjects who developed dementia symptoms were females. This frequency was significantly higher than the percentage reached by men with C9orf72 expansion who had this phenotype (p = 0.047). No abnormal repeat expansion was found in control groups. Inclusion of the C9orf72 genetic test in the molecular panels for Brazilian populations with these neurodegenerative diseases should be strongly considered. (C) 2018 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Histórico da atividade física habitual dos pacientes com esclerose lateral amiotrófica(Universidade Federal de São Paulo (UNIFESP), 2016-03-30) Pereira, Roberto Dias Batista [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; http://lattes.cnpq.br/3911841387107665; http://lattes.cnpq.br/4044980759880943; Universidade Federal de São Paulo (UNIFESP)Objective: To identify the historical profile of habitual physical activity in people with Motor Neurone Disease / Amyotrophic Lateral Sclerosis (MND/ALS) and compared to healthy subjects. Methods: 202 subjects were selected, these 71 diagnosed with ALS, 18 with Paralysis Progressive Bulbar (PBP) and 8 with Family ELA (FAMILY), of the remaining 105 consisted of healthy individuals as a control group. The patients underwent medical evaluation, physiotherapy and all participants responded to the questionnaire on habitual physical activity Baecke, for periods from 10 to 20 years, 21 to 30 years, the last 12 months; and related will MND/ALS the last two years before the first symptom. Results: When comparing the scores of the questionnaire was shown that patients with MND/ALS, regardless of the type of disease evolution, performed more habitual physical activity (HPA) from 10 to 20 years, especially the occupational physical activity (OPA), and OPA from 21 to 30 years compared with the control group. The OPA more strongly related with the development of the disease was the Farmer (30% of patients), regardless of subtype classification, in the period from 10 to 20 years old. Earlier detection of initial symptoms was more related to HPA more intense, between 21 and 30 years, in patients with Family ALS, and OPA more intense in the last two years before the appearance of symptoms. Greater physical activity in leisure and locomotion (LLA) in the period from 10 to 20 years, especially men, was related to the need to use a wheelchair later. The HPA most intense the last 12 months was related to an earlier need to use wheelchair and installation of noninvasive mechanical ventilation and percutaneous endoscopic gastrostomy. Conclusions: The history of habitual physical activity most intense in patients with MND/ALS, especially OPA, has a direct bearing on the development of the disease, in anticipation of need for special care.
- ItemAcesso aberto (Open Access)Índice do número de unidades motoras (MUNIX) : aspectos técnicos e correlações clínicas em pacientes com esclerose lateral amiotrófica(Universidade Federal de São Paulo (UNIFESP), 2017-08-18) Bezerra, Marcio Luiz Escorcio [UNIFESP]; Manzano, Gilberto Mastrocola [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; http://lattes.cnpq.br/3911841387107665; http://lattes.cnpq.br/1662881809387292; http://lattes.cnpq.br/4788464407515502; Universidade Federal de São Paulo (UNIFESP)Introdução: MUNIX é uma técnica neurofisiológica utilizada fundamentalmente para quantificar a perda de unidades motoras. Para tal fim, tem se mostrado eficaz e de utilização relativamente rápida. Devido à necessidade de marcadores de perda de neurônios motores inferiores (NMI) na Esclerose Lateral Amiotrófica (ELA), há crescente interesse pela técnica nos últimos anos. Objetivos: Estudar a reprodutibilidade intra-examinador do MUNIX em controles saudáveis e em pacientes com ELA e avaliar abordagens que possam levar a uma melhoria do método. Utilizar o MUNIX de maneira transversal e longitudinal em pacientes com ELA, com o intuito de detectar a perda de unidades motoras. Mais especificamente, estudar a capacidade do método para detecção da perda de unidades motoras em regiões corporais ainda clinicamente não afetadas. Métodos: Em um primeiro estudo foi avaliada a reprodutibilidade intra-examinador do método em indivíduos saudáveis e pacientes com ELA com duas aferições realizadas no mesmo dia. Adicionalmente, com os valores de referência extraídos dos controles, foram estabelecidos pontos de corte para o MUNIX em cada músculo e então avaliado se a técnica é capaz de separar pacientes com ELA dos controles saudáveis de maneira transversal. Em um segundo estudo, foi testada a reprodutibilidade de testes realizados com intervalo de três meses, primeiramente com uma medida isolada de MUNIX (S-MUNIX) e então com a média de três valores nas duas avaliações (M-MUNIX). Foram comparadas então as reprodutibilidades dessas duas abordagens. Em um terceiro estudo, foram recrutados pacientes com ELA, com o objetivo de incluir indivíduos com extremidades clinicamente não afetadas e avaliar como o M-MUNIX e o índice neurofisiológico (IN) se comportam nessas regiões corporais e se há queda dos índices com o seguimento longitudinal. Resultados: O primeiro estudo mostrou que a reprodutibilidade intra-examinador do MUNIX foi boa em 51 controles saudáveis e 30 pacientes com ELA, como demonstrado pelos valores dos coeficientes de correlação intraclasse (CCI) e pelos coeficientes de variação individual (CVi). Os valores do CVi, no entanto, foram mais elevados nos pacientes com ELA, principalmente o abdutor curto do polegar (ACP) que mostrou 24% de variabilidade individual. A análise da curva ROC, para distinguir indivíduos com a doença dos saudáveis, mostrou boa área sob a curva: 0,9504. No segundo estudo foram avaliados 21 controles saudáveis de acordo com o protocolo descrito. O M-MUNIX se mostrou mais reprodutível que o S-MUNIX nesses indivíduos. Houve uma melhora mais acentuada no CVi do que no CCI, de forma que a variabilidade individual passou a ficar abaixo de 10% em todos os músculos testados. No terceiro estudo foi demonstrado que o M-MUNIX, quando utilizado de maneira longitudinal, é capaz de detectar perda de unidades motoras precocemente em extremidades clinicamente não afetadas de pacientes com ELA. Essa queda se deu de maneira significativa nos parâmetros neurofisiológicos (M-MUNIX e IN), em contraste com os parâmetros clínicos, que tiveram queda apenas discreta durante os intervalo pré- sintomático. O M-MUNIX do músculo ACP foi o parâmetro afetado de forma mais precoce. Conclusão: A técnica teve boa performance diagnóstica e capacidade para diferenciar indivíduos saudáveis daqueles com ELA, de forma que possui o potencial para ser usado como instrumento de triagem para a detecção de músculos desnervados. O M-MUNIX se mostrou mais reprodutível e preciso do que a utilização de uma medida isolada do MUNIX, sendo portanto, uma abordagem recomendável em estudos longitudinais. O M-MUNIX e o IN foram capazes de detectar a perda de neurônios motores no seguimento de extremidades/membros clinicamente ainda não afetados de pacientes com ELA e foram mais sensíveis que os parâmetros clínicos para tal intuito. Dessa forma, a utilização dessas técnicas podem ser vantajosa em estudos clínicos que tenham como objetivo testar a eficácia de uma determinada droga, uma vez que uma ferramenta mais sensível pode ser especialmente relevante nos estágios iniciais da ELA.
- ItemAcesso aberto (Open Access)Marcadores clínicos fonoaudiológicos como modelo prognóstico nas funções orofaringolaringeais em pacientes com doença do neurônio motor(Universidade Federal de São Paulo (UNIFESP), 2016-12-16) Oda, Adriana Leico [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; http://lattes.cnpq.br/3911841387107665; http://lattes.cnpq.br/8976619669743557; Universidade Federal de São Paulo (UNIFESP)Purpose: To identify clinical markers of bulbar alterations during progressive dysfunction of the oropharyngolaryngeal musculature in patients with Amyotrophic Lateral Sclerosis (ALS) and to compare the patients with Progressive Bulbar Paralysis (PBP). Methods: 89 (74.17%) patients with ALS, with a mean age of 58.19 years (51.68% male and 48.32% female), and patients with PBP, mean age 62.71 years (32.26% male and 67.74% female). The evaluation instruments were: speech-language clinical evaluation, peak cough flow, speech intelligibility scale, FOIS food consistency scale, ALSFRS-R and EGELA functional scales, and quality of life scale. Results: Patients with PBP differed from patients with ALS in the bulbar domains of the functional scales (p <0.01) and quality of life (p <0.01). The fatigue index is a clinical marker that showed a significant correlation (p <0.01) with the bulbar domains (r = 0.843) and the sum of the functional (r = 0.423) and quality of life scales (r = 0.493) (R = 0.741), speech intelligibility (r = 0.866) and peak cough flow (r = 0.581). 38.2% of patients with appendicular onset had a need for changes in food consistency or in the alimentary route, in contrast to 71% of patients with bulbar onset. Patients with ALS had median values of: 7.0 in the Speech Intelligibility Scale, 190 liters / minute in the Peak Cough Flow and Fatigue Index of 9.0 movements, for almost all muscle groups evaluated. Patients with bulbar onset had a median of: 4.0 on the Speech Intelligibility scale, 170 liters / minute on the Peak Cough Flow and Fatigue Index of 4.0 movements for most of the muscle groups evaluated. Orofacial muscles severity, Fatigue Index, besides diagnosis and age, are factors related to survival. Conclusion: Changes in the orofacial musculature and dysphagia were predictors of the outcomes analyzed, increasing the risk of death in patients with Motor Neuron Disease. Fatigability proved to be a consistent marker of clinical severity and prognosis.
- ItemAcesso aberto (Open Access)Modulação autonômica cardíaca e sua relação com a capacidade pulmonar em indivíduos com paralisia bulbar progressiva e esclerose lateral amiotrófica(Universidade Federal de São Paulo (UNIFESP), 2018-08-29) Pimentel, Renata Martins [UNIFESP]; Ferreira, Celso [UNIFESP]; Abreu, Luiz Carlos de [UNIFESP]; http://lattes.cnpq.br/6796970691432850; Cardiac autonomic modulation and pulmonary capacity in individuals with amyotrophic lateral sclerosis and progressive bulbar palsy; http://lattes.cnpq.br/6851397444757156; http://lattes.cnpq.br/1417020520652193; Universidade Federal de São Paulo (UNIFESP)Introduction: Motor neuron diseases (MND), characterized by amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy (PBP), is defined by progressive, irreversible and incapacitating motor paralysis with survival from two to five years after the beginning of the symptomatology. Death is traditionally related to ventilatory impairment and / or systemic complications, although unexplained sudden death is not infrequent. Considering that DNM may compromise other systems, including the autonomic nervous system, proposed to evaluate the cardiac autonomic modulation and relation with pulmonary capacity in patients with ALS and PBP. Method: A total of 91 patients were analyzed: 58 with diagnosis of Amyotrophic Lateral Sclerosis and 33 with Progressive Bulbar Palsy. Clinical diagnoses were obtained from medical observations; the data collection and data were obtained from the Research Section of Neuromuscular Diseases of UNIFESPEPM. In these patients, heart rate variability and spirometry were performed. Thus, they were classified according to Forced Vital Capacity (FVC) with values greater than and less than 50%. In addition, subsequently the statistical analysis. Results: Patients with ALS and PBP presented significant differences in linear indices SDNN, pNN50, RMSSD when compared to normal values; there was no significant difference between the PBP and ALS groups in the linear indices. However, in the nonlinear indices, it was observed that the α1 index was higher in the ALS group when compared to PBP. However, when compared to FVC, there was a lower value in the pNN50 index, only in the PBP group, especially in those patients requiring noninvasive ventilation. Conclusion: There was a decrease in global variability and parasympathetic hypoactivity in relation to normality; strong shortterm fractal correlation in the ELA group in relation to PBP group; lower parasympathetic activity in patients with noninvasive mechanical ventilation.
- ItemSomente MetadadadosMotor neuron disease in inherited neurometabolic disorders(Masson Editeur, 2018) Souza, Paulo Victor Sgobbi de [UNIFESP]; Bortholin, T. [UNIFESP]; Naylor, F. George Monteiro [UNIFESP]; Chieia, Marco Antonio Troccoli [UNIFESP]; Pinto, Wladimir Bocca Vieira de Rezende [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]Inherited neurometabolic disorders represent a growing group of inborn errors of metabolism that present with major neurological symptoms or a complex spectrum of symptoms dominated by central or peripheral nervous system dysfunction. Many neurological presentations may arise from the same metabolic defect, especially in autosomal-recessive inherited disorders. Motor neuron disease (MND), mainly represented by amyotrophic lateral sclerosis, may also result from various inborn errors of metabolism, some of which may represent potentially treatable conditions, thereby emphasizing the importance of recognizing such diseases. The present review discusses the most important neurometabolic disorders presenting with motor neuron (lower and/or upper) dysfunction as the key clinical and neuropathological feature. (C) 2017 Elsevier Masson SAS. All rights reserved.
- ItemSomente MetadadadosOne family, one gene and three phenotypes: A novel VCP (valosin-containing protein) mutation associated with myopathy with rimmed vacuoles, amyotrophic lateral sclerosis and frontotemporal dementia(Elsevier Science Bv, 2016) Abrahao, Agessandro [UNIFESP]; Neto, Osorio Abath; Kok, Fernando; Zanoteli, Edmar; Santos, Bibiana; Vieira de Rezende Pinto, Wladimir Bocca [UNIFESP]; Povoas Barsottini, Orlando Graziani [UNIFESP]; Bulle Oliveira, Acary Souza [UNIFESP]; Pedroso, Jose Luiz [UNIFESP]Background: VCP (valosin-containing protein gene) variants have been associated with peripheral and central neurodegenerative processes, including inclusion body myopathy (IBM), Paget disease of bone (PDB), frontotemporal dementia (FTD), and familial amyotrophic lateral sclerosis (ALS) type 14. The combination of IBM, PDB (IBMPFD1) can presented in one individual. However, the association of IBMPFD1 and ALS in the same family is rare. Methods: We reported three individuals from a Brazilian kindred with intrafamilial phenotype variability. Whole exome sequencing (WES) of the proband was performed and revealed a novel VCP variant. VCP Sanger sequencing was performed in the proband and his family members to confirm WES finding and segregation. We performed a systematic review of the literature regarding the genotypic-phenotypic VCP correlations. Results: Each individual presented with either myopathy with rimmed vacuoles, ALS, or FTD. There was no PDB. WES of the proband identified the heterozygous variant c.271A> T (p.Asn91Tyr) in the exon 3 of VCP. Sanger sequencing confirmed the segregation of this variant in an autosomal-dominant pattern. Conclusion: This study expands the genotypic spectrum of the missense mutations of the VCP gene with a novel p.Asn9lTyr variant found in a Brazilian family presenting with the unusual intrafamiliar association of myopathy with rimmed vacuoles, ALS and FTD. (C) 2016 Elsevier B.V. All rights reserved.