Consideraciones bioéticas en el manejo de la esclerosis lateral amiotrófica: Una aproximación al quehacer fonoaudiológico

Introducción: La esclerosis lateral amiotrófica (ELA) es la forma más común de enfermedad degenerativa de motoneurona en la edad adulta y es considerada una enfermedad terminal. Por lo mismo, el accionar del fonoaudiólogo debe considerar el respeto a los principios bioéticos básicos para garantizar una asistencia adecuada. Objetivo: Conocer aquellas consideraciones bioéticas relacionadas al manejo y estudio de personas con ELA para luego brindar una aproximación hacia el quehacer fonoaudiológico. Método: Se efectuó una búsqueda bibliográfica en las bases de datos PubMed, Scopus y SciELO. Se filtraron artículos publicados desde 2000 hasta junio de 2023 y fueron seleccionados aquellos que abordaban algún componente bioético en población con ELA. Resultados: Aspectos relacionados al uso del consentimiento informado y a la toma de decisiones compartidas destacaron como elementos esenciales para apoyar la autonomía de las personas. Conclusión: Una correcta comunicación y una toma de decisiones compartida son claves para respetar la autonomía de las personas. A su vez, la estandarización de procedimientos mediante la investigación clínica permitirá aportar al cumplimiento de los principios bioéticos de beneficencia y no maleficencia, indispensables para la práctica profesional.

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common form of degenerative motor neuron disease in adulthood and is considered a terminal disease. For this reason, the actions of the speech therapist must consider respect for basic bioethical principles to guarantee adequate assistance. Objective: To know those bioethical considerations related to the management and study of people with ALS to then provide an approach to speech therapy. Methodology: A bibliographic search was carried out in the PubMed, Scopus, and SciELO databases. Articles published from 2000 to June 2023 were filtered and those that addressed a bioethical component in the population with ALS were selected. Results: Aspects related to the use of informed consent and shared decision-making stood out as essential elements to support people's autonomy. Conclusion: Proper communication and shared decision-making are key to respecting people's autonomy. In turn, the standardization of procedures through clinical research will contribute to compliance with the bioethical principles of beneficence and non-maleficence, essential for professional practice.

Noninvasive mechanical ventilation assistance in amyotrophic lateral sclerosis: a systematic review

ABSTRACT BACKGROUND: Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS), and morbidity is related to poor quality of life (QOL). Non-invasive ventilation (NIV) may be associated with prolonged survival and QOL in patients with ALS. OBJECTIVES: To assess whether NIV is effective and safe for patients with ALS in terms of survival and QOL, alerting the health system. DESIGN AND SETTING: Systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards using population, intervention, comparison, and outcome strategies. METHODS: The Cochrane Library, CENTRAL, MEDLINE, LILACS, EMBASE, and CRD databases were searched based on the eligibility criteria for all types of studies on NIV use in patients with ALS published up to January 2022. Data were extracted from the included studies, and the findings were presented using a narrative synthesis. RESULTS: Of the 120 papers identified, only 14 were related to systematic reviews. After thorough reading, only one meta-analysis was considered eligible. In the second stage, 248 studies were included; however, only one systematic review was included. The results demonstrated that NIV provided relief from the symptoms of chronic hypoventilation, increased survival, and improved QOL compared to standard care. These results varied according to clinical phenotype. CONCLUSIONS: NIV in patients with ALS improves the outcome and can delay the indication for tracheostomy, reducing expenditure on hospitalization and occupancy of intensive care unit beds. SYSTEMATIC REVIEW REGISTRATION: PROSPERO database: CRD42021279910 — https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=279910.

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy / Consenso da Academia Brasileira de Neurologia para diagnóstico, aconselhamento genético e uso de terapias modificadoras na atrofia muscular espinhal 5q

Abstract Spinal muscular atrophy linked to chromosome 5 (SMA-5q) is an autosomal recessive genetic disease caused by mutations in the SMN1. SMA-5q is characterized by progressive degeneration of the spinal cord and bulbar motor neurons, causing severe motor and respiratory impairment with reduced survival, especially in its more severe clinical forms. In recent years, highly effective disease-modifying therapies have emerged, either acting by regulating the splicing of exon 7 of the SMN2 gene or adding a copy of the SMN1 gene through gene therapy, providing a drastic change in the natural history of the disease. In this way, developing therapeutic guides and expert consensus becomes essential to direct the use of these therapies in clinical practice. This consensus, prepared by Brazilian experts, aimed to review the main available disease-modifying therapies, critically analyze the results of clinical studies, and provide recommendations for their use in clinical practice for patients with SMA-5q. This consensus also addresses aspects related to diagnosis, genetic counseling, and follow-up of patients under drug treatment. Thus, this consensus provides valuable information regarding the current management of SMA-5q, helping therapeutic decisions in clinical practice and promoting additional gains in outcomes.

Resumo Atrofia muscular espinhal ligada ao cromossomo 5 (AME-5q) é uma doença genética de herança autossômica recessiva causada por mutações no gene SMN1. A AME-5q cursa com degeneração progressiva dos motoneurônios medulares e bulbares, acarretando grave comprometimento motor e respiratório com redução da sobrevida, especialmente nas suas formas clínicas mais graves. Nos últimos anos, terapias modificadoras da doença altamente eficazes, ou que atuam regulando o splicing do exon 7 do gene SMN2 ou adicionando uma cópia do gene SMN1 via terapia gênica, têm surgido, proporcionando uma mudança drástica na história natural da doença. Dessa forma, o desenvolvimento de guias terapêuticos e de consensos de especialistas torna-se importante no sentido de direcionar o uso dessas terapias na prática clínica. Este consenso, preparado por especialistas brasileiros, teve como objetivos revisar as principais terapias modificadoras de doença disponíveis, analisar criticamente os resultados dos estudos clínicos dessas terapias e prover recomendações para seu uso na prática clínica para pacientes com AME-5q. Aspectos relativos ao diagnóstico, aconselhamento genético e seguimento dos pacientes em uso das terapias também são abordados nesse consenso. Assim, esse consenso promove valiosas informações a respeito do manejo atual da AME-5q auxiliando decisões terapêuticas na prática clínica e promovendo ganhos adicionais nos desfechos finais.

Telehealth for amyotrophic lateral sclerosis in a multidisciplinary service in a Brazilian reference center / Telessaúde para esclerose lateral amiotrófica em um serviço multidisciplinar em um centro de referência brasileiro

Abstract Background Telehealth has been used in the treatment of different diseases, and it has been shown to provide benefits for patients with amyotrophic lateral sclerosis (ALS). Due to the social distancing measures put into effect during the coronavirus disease 2019 (COVID-19) pandemic, there was an urgent need for telehealth to ensure the provision of healthcare. Objective To evaluate the feasibility of telehealth for the provision of multidisciplinary ALS care, and to assess its acceptability among patients and caregivers. Methods We conducted a retrospective cohort study in which multidisciplinary evaluations were performed using the Teleconsulta platform. The patients included had ALS and at least one in-person clinical evaluation. The patients and the caregivers answered satisfaction questionnaires. Results The sample was composed of 46 patients, 32 male and 14 female subjects. The average distance from their residences to the reference services was of 115 km. Respiratory adjustment was the most addressed topic. Conclusion The strategy is viable and well accepted in terms of satisfaction. It was even more positive for patients in advanced stages of the disease or for those living far from the referral center.

Resumo Antecedentes A telessaúde tem sido utilizada no tratamento de diferentes doenças, e demonstrou-se que ela traz benefícios para pacientes com esclerose lateral amiotrófica (ELA). Devido às medidas de distanciamento social postas em prática durante a pandemia de doença do coronavírus 2019 (coronavirus disease 2019, COVID-19, em inglês), houve uma necessidade urgente de se usar a telessaúde para garantir a provisão dos cuidados de saúde. Objetivo Avaliar a viabilidade da telessaúde para a prestação de cuidados multidisciplinares na ELA, e verificar a sua aceitabilidade entre os pacientes e os cuidadores. Métodos Realizou-se um estudo de coorte retrospectivo, com avaliações multidisciplinares realizadas por meio da plataforma Teleconsulta. Os pacientes incluídos apresentavam ELA, e já haviam passado por pelo menos uma avaliação clínica presencial. Os pacientes e os cuidadores responderam a questionários de satisfação. Resultados A amostra continha 46 pacientes, 32 do sexo masculino e 14 do sexo feminino. A distância média de suas residências ao serviço de referência era de 115 km. O ajuste respiratório foi o tema mais abordado. Conclusão A estratégia é viável e bem-aceita em termos de satisfação. Foi ainda mais positiva para os pacientes com doença avançada ou residentes em uma cidade distante do centro de referência.

Clinical profile of genetically confirmed Spinal Muscular Atrophy (SMA) Among Filipino children less than 18 years old

@#Spinal muscular atrophy (SMA) is the most common inherited lethal disease in children. Confirmatory diagnosis is based on molecular genetic testing of survival motor neuron (SMN) genes. We aimed to describe the phenotypic presentation of Filipino infants and children with SMA based on the copy number analysis of SMN genes. Medical records of 17 Filipino children were reviewed from January 2017 to December 2019. De-identified clinical data fulfilled the diagnostic criteria defined by the International SMA Consortium. Among Filipino children, the predominant SMA type by copy number was type I having two copies of SMN2 gene. The clinical severity based on symptom onset and highest functional motor capacity attained correlated with SMN2 copy number congruent with existing data. A significant time lag between symptom onset to confirmation of genetic diagnosis was noted. Nine out of the 17 (52%) children did not have a family history of the disease, raising the possibility of mutation carriers in these families since the incidence of de novo mutations in literature is about 2%. These data offered the first epidemiological pattern of genetically confirmed SMA among Filipino children; provided additional information for genetic counselling; and an avenue to consider pre-symptomatic newborn screening and carrier testing that would change proactive measures and opportunities for therapy. These measures unavoidably will decrease the incidence and prevalence of disease in the future.

Assessment of the upper motor neuron degeneration by detailed motor homunculus cortex thickness in amyotrophic lateral sclerosis / 西安交通大学学报(医学版)

【Objective】 The involvement of upper motor neuron (UMN) degeneration is crucial to the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to determine objective and sensitive UMN degeneration markers for an accurate and early diagnosis. 【Methods】 A total of 108 ALS patients and 90 age- and gender-matched control subjects were recruited from ALS Clinic of The First Affiliated Hospital of Xi’an Jiaotong University. The motor homunculus cortex thickness data in MRI were collected from all the participants. The clinical characteristics and UMN clinical examination of bulbar, cervical, thoracic and lumbosacral regions were collected from the ALS patients. 【Results】 Cortical thickness was significantly thinner in the ALS group than in the control group in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the global UMN positive group was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the UMN positive group in the corresponding region was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). 【Conclusion】 The thinning of the motor homunculus cortex can be used as an objective marker of UMN involvement in ALS patients in clinical practice.

Neuroimaging advances in patients with amyotrophic lateral sclerosis / 西安交通大学学报(医学版)

Amyotrophic lateral sclerosis (ALS) is a multi-system neurodegenerative disease characterized with degeneration of both motor and non-motor areas. Complicated clinical manifestations and lack of objective biomarkers for upper motor neuron deficits challenged the early diagnosis of ALS. Meanwhile, heterogeneous non-motor symptoms and conflicted treatment effects exacerbated the management and therapy of the disease. The multiparametric functional MRI has the potential to address all the needs for diagnosis, management, and disease modified therapy in ALS. The present paper summarizes the research progress in both motor and non-motor impairment in ALS, as well as their potential value in visualizing disease stages and drug effect evaluation. Focusing on the heterogeneity of the disease and combining with brain and spinal cord imaging may provide direct evidence for disease diagnosis and treatment and be the priority in the future for ALS.

ZHANG Yunling's Experience in the Treatment of Amyotrophic Lateral Sclerosis from Emphasis on both Spleen and Kidney / 中医杂志

This paper summarized Professor ZHANG Yunling's experience in the treatment of amyotrophic lateral sclerosis （ALS） from emphasis on both spleen and kidney. It is considered that the characteristic of ALS manifested as overlap of atrophy-flaccidity disease and convulsive disease， and the core pathogenesis are the deficiency of spleen and kidney and the inner pathogenic qi. ZHANG advocated that ALS should be treated from tonifying both the spleen and kidney， as strong spleen and kidney led the latent pathogen at peace. Usually applied Huangqi （Astragalus mongholicus）， Baizhu （Atractylodes macrocephala） combined with Taizishen （Pseudostellaria heterophylla）， fried Yiyiren （Coix lacryma-jobi）， Doukou （Myristica fragrans） and Sharen （Wurfbainia villosa） to tonify the middle and replenish qi， ascend lucidity and descend turbidity to invigorate the spleen； Roucongrong （Cistanche deserticola）， Tusizi （Cuscuta chinensis） combined with Shanyao （Dioscorea oppositifolia）， Shanzhuyu （Cornus officinalis） and prepared Dihuang （Rehmannia glutinosa） are used to support the fire and nourish the water， so as to replenish the spleen. The empirical formula regarded invigorateing the spleen and replenishing the kidney as the core therapeutic principle throughout the treatment of the whole process， which aimed at extinguishing inner wind and pacifying latent pathogen when treating the root.

Misdiagnoses in a Brazilian population with amyotrophic lateral sclerosis / Erros de diagnóstico em uma população brasileira com esclerose lateral amiotrófica

Abstract Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the upper and lower motor neurons. The correct diagnosis at the onset of the disease is sometimes very difficult, due to the symptoms being very similar to those of other neurological syndromes. Objective This study aimed to analyze the initial manifestations, the specialty of the first physician visited due the initial complaint, the misdiagnoses, as well as the unnecessary surgical interventions in a new ALS Brazilian population. Methods The medical records of 173 patients with typical ALS were reviewed. Results The present study demonstrated that other symptoms, besides weakness, were very frequent as initial presentation of ALS, and orthopedics was the medical specialty most sought by patients at the onset of symptoms. Our frequency of misdiagnoses was 69.7%, and in 7.1% of them, an unnecessary surgical intervention was performed. Conclusions Amyotrophic lateral sclerosis presents a very large pool of signs and symptoms; therefore, there is an urgent need of increasing the disease awareness to other specialties due to the high frequency of misdiagnoses observed in clinical practice.

Resumo Antecedentes A esclerose lateral amiotrófica (ELA) é uma doença neurodegenerativa que afeta os neurônios motores superior e inferior. O diagnóstico correto no início da doença é, às vezes, muito difícil, pois os sintomas de início são muito semelhantes aos de outras síndromes neurológicas. Objetivo Este estudo teve como objetivo analisar as manifestações iniciais, a especialidade do primeiro médico visitado devido à queixa inicial, os diagnósticos errôneos, bem como as intervenções cirúrgicas desnecessárias em uma nova população brasileira acometida por ELA. Métodos Os prontuários médicos de 173 pacientes com ELA típica foram revisados. Resultados O presente estudo demonstrou que outros sintomas, além da fraqueza, foram muito frequentes como apresentação inicial da ELA, sendo a ortopedia a especialidade médica mais procurada pelos pacientes no início dos sintomas. Nossa frequência de diagnósticos errôneos foi de 69,7%, e em 7,1% deles foi realizada intervenção cirúrgica desnecessária. Conclusões A ELA apresenta um conjunto amplo de sinais e sintomas; portanto, há necessidade urgente de uma melhor educação de outras especialidades devido à alta frequência de diagnósticos equivocados observada na prática clínica.

Gene therapy in neuromuscular disorders / Terapia gênica nas doenças neuromusculares

Abstract Monogenic neuromuscular disorders are potentially treatable through gene therapy. Using viral vectors, a therapeutic transgene aims to restore normal levels of a protein not produced by the defective gene, or to silence a gene whose expression leads to toxic effects. Spinal Muscular Atrophy (SMA) is a good example of a monogenic disease that currently has an AAV9-based vector gene therapy as a therapeutic option. In this review, we intend to discuss the viral vectors and their mechanisms of action, in addition to reviewing the clinical trials that supported the approval of gene therapy (AVXS-101) for SMA as well as neuromuscular diseases that are potentially treatable with gene replacement therapy.

Resumo Doenças neuromusculares monogênicas são potencialmente tratáveis através de terapia gênica. Utilizando-se de vetores virais, um transgene terapêutico objetiva repor os níveis normais de uma proteina não produzida pelo gene defeituoso ou silenciar um gene cuja expressão leva a efeitos tóxicos. A Atrofia Muscular Espinhal (AME) é um bom exemplo de doença monogenica que atualmente tem uma terapia gênica com vetor viral AAV9 como opção terapêutica. Nesta revisão, pretendemos discutir os vetores virais e macanismos de ação utilizados, além de revisar os ensaios clínicos que embasaram a aprovação da terapia gênica (AVXS-101) para AME, assim como doenças neuromusculares potencialmente tratáveis com terapia de reposição gênica.

Recent research on the treatment of spinal muscular atrophy / 中国当代儿科杂志

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscular weakness and atrophy. SMA, as an inherited disease, is the leading cause of death in infants and young children. Rapid progress has been made in the research field of SMA in recent years, and some related treatment drugs have been successfully approved for marketing. This article reviews the recent research advances in the treatment of SMA.

Effects of survival motor neuron gene knockdown on acute kidney injury induced by cisplatin in mice / 中华肾脏病杂志

Objective:To investigate the role of survival motor neuron ( SMN) gene knockout in mice with cisplatin-induced acute kidney injury (AKI). Methods:A mouse model (C57BL/6) of cisplatin-induced AKI was constructed. Twenty male wild type (WT) and SMN+/- mice weighing 22-24 g were randomly divided into four groups: WT mice with saline injection group (WT vehicle, n=5), SMN+/- mice with saline injection group ( SMN+/- vehicle, n=5), WT mice with cisplatin injection group (WT cisplatin, n=5) and SMN+/- mice with cisplatin injection group ( SMN+/- cisplatin, n=5). Mice were injected intraperitoneally with 20 mg/kg cisplatin or 0.9% saline. 72 hours later, the mice were sacrificed, and serum and kidney tissues were collected. The real time PCR and Western blotting were used to measure the expression levels of SMN mRNA and protein. The sarcosine oxidation and urease method were used to measure serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Renal pathologic changes were observed by PAS staining. TUNEL immunofluorescence assay was used to detect the level of apoptosis. Western blotting and immunohistochemistry were used to detect the protein expression levels of apoptosis index poly (ADP-ribose) polymerase (PARP) and endoplasmic reticulum stress index CHOP. Results:Compared with WT mice, SMN mRNA and protein expression levels were lower in SMN+/- mice, and the expression level of SMN mRNA and protein was further decreased after intraperitoneal cisplatin injection (all P<0.05). Compared with WT mice with saline injection group, WT mice with cisplatin injection group had higher levels of Scr, BUN, tubular damage scores, TUNEL positive cell numbers, PARP and CHOP, while the expression levels of above indexes in the SMN+/- mice with cisplatin injection group were higher than those in the WT mice with cisplatin injection group (all P<0.05). Conclusions:SMN gene knockout can aggravate renal pathological damage and apoptosis of renal tubular epithelial cell in cisplatin-induced AKI mice. SMN may be a potential therapeutic target of AKI.

Protocol paper: kainic acid excitotoxicity-induced spinal cord injury paraplegia in Sprague-Dawley rats

BACKGROUND: Excitotoxicity-induced in vivo injury models are vital to reflect the pathophysiological features of acute spinal cord injury (SCI) in humans. The duration and concentration of chemical treatment controls the extent of neuronal cell damage. The extent of injury is explained in relation to locomotor and behavioural activity. Several SCI in vivo methods have been reported and studied extensively, particularly contusion, compression, and transection models. These models depict similar pathophysiology to that in humans but are extremely expensive (contusion) and require expertise (compression). Chemical excitotoxicity-induced SCI models are simple and easy while producing similar clinical manifestations. The kainic acid (KA) excitotoxicity model is a convenient, low-cost, and highly reproducible animal model of SCI in the laboratory. The basic impactor approximately cost between 10,000 and 20,000 USD, while the kainic acid only cost between 300 and 500 USD, which is quite cheap as compared to traditional SCI method. METHODS: In this study, 0.05 mM KA was administered at dose of 10 µL/100 g body weight, at a rate of 10 µL/min, to induce spinal injury by intra-spinal injection between the T12 and T13 thoracic vertebrae. In this protocol, detailed description of a dorsal laminectomy was explained to expose the spinal cord, following intra-spinal kainic acid administration at desired location. The dose, rate and technique to administer kainic acid were explained extensively to reflect a successful paraplegia and spinal cord injury in rats. The postoperative care and complication post injury of paraplegic laboratory animals were also explained, and necessary requirements to overcome these complications were also described to help researcher. RESULTS: This injury model produced impaired hind limb locomotor function with mild seizure. Hence this protocol will help researchers to induce spinal cord injury in laboratories at extremely low cost and also will help to determine the necessary supplies, methods for producing SCI in rats and treatments designed to mitigate post-injury impairment. CONCLUSIONS: Kainic acid intra-spinal injection at the concentration of 0.05 mM, and rate 10 µL/min, is an effective method create spinal injury in rats, however more potent concentrations of kainic acid need to be studied in order to create severe spinal injuries.

Impacto do tratamento medicamentoso na voz, fala e deglutição de pacientes com esclerose lateral amiotrófica: revisão sistemática / Impact of drug treatment on voice, speech, and swallowing in patients with amyotrophic lateral sclerosis: a systematic review

RESUMO Objetivos Revisar sistematicamente a literatura sobre o impacto do tratamento medicamentoso nas funções de voz, fala e deglutição de indivíduos adultos com esclerose lateral amiotrófica esporádica, mensuradas por meio de escalas e seus respectivos escores, em relação ao grupo placebo. Estratégia de pesquisa A busca foi realizada com base na estratégia PICO (problema/população/paciente; intervenção; comparação/controle; desfecho/outcome). As palavras-chave foram selecionadas a partir de consulta aos Descritores em Ciências da Saúde (DeCS) e ao Medical Subject Headings (MeSH). Dois pesquisadores independentes fizeram busca na American Speech-Language-Hearing Association (ASHA), Cochrane, LILACS, PubMed, Scopus e Web of Science, em inglês, espanhol e português. Critérios de seleção Foram incluídos ensaios clínicos randomizados, realizados em adultos, e excluídos artigos cujos desfechos estavam relacionados à autoavaliação e à qualidade de vida, teses, dissertações, apenas resumos disponíveis, estudos de caso, estudos experimentais, capítulos de livro, enciclopédias e comunicações breves. Os estudos foram avaliados por meio das ferramentas Robins II (Risk Of Bias In Non-randomized Studies II) e GRADE (Grading of Recommendations Assessment, Development and Evaluation). Resultados dos 9824 artigos encontrados, 5 realizaram a intervenção medicamentosa e foram selecionados para análise. Observou-se ausência de estudos voltados para reabilitação das funções bulbares. A qualidade de evidência gerada variou de alto a baixo risco e o nível de evidência, de baixo a muito baixo. Conclusão a maioria dos estudos demonstra que o tratamento medicamentoso atrasa a degeneração das funções bulbares, com relação ao placebo, embora tal achado não tenha sido observado nos escores de escalas que mensuram tais funções. Os estudos apresentam risco de viés de seleção e muito baixa/baixa qualidade metodológica, limitando a confiança nos achados.

ABSTRACT Purpose To carry out a systematic review of the literature on the impact of drug treatment on the voice, speech, and swallowing functions of adult individuals with sporadic ALS, measured through scales and their respective scores, concerning the placebo group. Research strategy The search strategy was created based on the PICO strategy. The keywords were selected from a consultation with the health sciences descriptors - DECS and the medical subject headings - MeSH. Two independent researchers searched ASHA, Cochrane, Lilacs, Pubmed, Scopus and Web of Science, in English, Spanish and Portuguese. Selection criteria Randomized clinical trials, carried out on adults, were included, and articles with outcomes related to selfassessment and quality of life, theses, dissertations, abstracts only , case studies, experimental studies, book chapters, encyclopedia and brief communication were excluded. The studies were evaluated using the Robins II and Grade tool. Results Of the 9824 articles found, 5 were selected for analysis and underwent drug intervention. It is noticed the absence of studies aimed at the rehabilitation of bulb functions. The quality of evidence generated varied from high to low risk and the level of evidence low and very low. Conclusion Most studies show a delay in the degeneration of bulbar functions in relation to placebo, although this finding has not been observed in the scores of scales that measure such functions. Studies are at risk of selection bias and very low/low methodological quality makes the findings questionable.

O'Sullivan-McLeod Syndrome: A Case Report / 罕见病研究

O'Sullivan-Mcleod syndrome is a very rare variant of MND with a good prognosis. Its clinical feature is distal lower motor neuron syndrome of both upper limbs, and there is no effective treatment at present. We reported a case of O'Sullivan-Mcleod syndrome in this paper.The patient exhibited with middle-aged progressive distal muscle weakness and atrophy of both upper limbs, without sensory, cognitive or behavioral impairment and without pyramidal tract sign. Laboratory examination, imaging and genetic tests showed no obvious abnormalities. EMG revealed neurogenic damage to the small muscles of both hands. Now we retrospectively analyzed the clinical features of a patient with O'Sullivan-McLeod syndrome, and data from 18 cases for comparative analysis, in order to improve its understanding by clinicians.

Associations of motor neuron disease research productivity and socioeconomic factors in Southeast Asia: a bibliometric analysis / Associações entre produtividade em pesquisa sobre doenças do neurônio motor e fatores socioeconômicos no sudeste asiático: uma análise bibliométrica

ABSTRACT Background: Scientific productivity on motor neuron disease (MND) research has been hypothesized to be low in Southeast Asia (SEA). Objective: To investigate the scientific productivity of SEA countries on MND and the associations between research metric indices and various country-specific socioeconomic parameters. Methods: We searched electronic databases for relevant articles from SEA on MND from the earliest indexed record to June 30, 2020. We obtained the following research productivity indices: bibliometric (number of publications in journals with impact factor (IF) and Scopus citations) and altmetric indices (PlumX metrics). We also collected data from published literature and reliable sources on the following socioeconomic variables: population, gross domestic product (GDP), GDP per capita, %GDP allocated for research and development (R&D) and the number of neurologists per country. Results: We included 196 articles that satisfied our inclusion criteria. Amyotrophic lateral sclerosis studies comprised the majority of the articles (n = 112; 57.1%). The top three countries in terms of the numbers of publications in journals with IF and in PlumX metrics were Singapore (n = 129), Malaysia (n = 26), and Thailand (n = 18). GDP per capita, %GDP for R&D and number of neurologists per one million population had strong positive correlations with the bibliometric and altmetric indices. Conclusions: This study highlights that although the scientific productivity of MND research in SEA has been low, it is continuously growing. This also emphasizes the imperative to improve economic indices and the number of neurologists in SEA to enhance scientific output on MND.

Resumo Antecedentes: A produtividade científica em pesquisa sobre doenças do neurônio motor (DNM) tem sido considerada baixa no sudeste asiático. Objetivo: Investigar a produtividade científica sobre DNM em países do sudeste asiático e as associações entre os índices métricos de pesquisa e vários parâmetros socioeconômicos específicos de cada país. Métodos: Foram consultadas bases de dados eletrônicas em busca de artigos relevantes sobre DNM provenientes do sudeste asiático, partindo do registro indexado mais antigo até 30 de junho de 2020. Obtivemos os seguintes índices de produtividade em pesquisa: bibliométrico (número de publicações em periódicos com fator de impacto (FI) e citações na base Scopus) e índices altmétricos (métrica PlumX). Também coletamos dados da literatura publicada e fontes confiáveis ​​sobre as seguintes variáveis ​​socioeconômicas: população, produto interno bruto (PIB), PIB per capita, % do PIB alocada para pesquisa e desenvolvimento (P & D) e o número de neurologistas por país. Resultados: Selecionamos 196 artigos que atenderam aos nossos critérios de inclusão. Estudos sobre esclerose lateral amiotrófica representaram a maioria dos artigos (n = 112; 57,1%). Os três principais países em termos de número de publicações em periódicos com FI e em métricas PlumX foram Cingapura (n = 129), Malásia (n = 26) e Tailândia (n = 18). O PIB per capita, a % do PIB para P & D e o número de neurologistas por um milhão de habitantes tiveram fortes correlações positivas com os índices bibliométricos e altmétricos. Conclusões: Embora a produtividade científica em pesquisa sobre DNM no sudeste asiático ainda seja baixa, este estudo mostra que ela vem crescendo continuamente. Isto também enfatiza a necessidade de melhorar os índices econômicos e o número de neurologistas na região para aumentar a produção científica sobre o assunto.

Adult-onset non-5q proximal spinal muscular atrophy: a comprehensive review / Atrofia muscular espinhal não-5q proximal de início no adulto: uma revisão abrangente

Abstract Background: Adult-onset spinal muscular atrophy (SMA) represents an expanding group of inherited neurodegenerative disorders in clinical practice. Objective: This review aims to synthesize the main clinical, genetic, radiological, biochemical, and neurophysiological aspects related to the classical and recently described forms of proximal SMA. Methods: The authors performed a non-systematic critical review summarizing adult-onset proximal SMA presentations. Results: Previously limited to cases of SMN1-related SMA type 4 (adult form), this group has now more than 15 different clinical conditions that have in common the symmetrical and progressive compromise of lower motor neurons starting in adulthood or elderly stage. New clinical and genetic subtypes of adult-onset proximal SMA have been recognized and are currently target of wide neuroradiological, pathological, and genetic studies. Conclusions: This new complex group of rare disorders typically present with lower motor neuron disease in association with other neurological or systemic signs of impairment, which are relatively specific and typical for each genetic subtype.

RESUMO Antecedentes: Atrofia muscular espinhal (AME) de início no adulto representa um grupo de doenças neurodegenerativas hereditárias em expansão na prática clínica. Objetivo: Este artigo de revisão sintetiza os principais aspectos clínicos, genéticos, radiológicos, bioquímicos e neurofisiológicos relacionados às formas clássicas e recentemente descritas de AME proximal do adulto. Métodos: Os autores realizaram uma revisão crítica não sistemática descrevendo as principais apresentações de AME proximal de início no adulto. Resultados: Previamente restrito às apresentações de AME tipo 4 associada ao gene SMN1, este grupo atualmente envolve mais de 15 diferentes condições clínicas que compartilham entre si a presença de comprometimento progressivo e simétrico do neurônio motor inferior se iniciando no adulto ou no idoso. Novos subtipos clínicos e genéticos de AME proximal de início no adulto foram reconhecidas e são alvos atuais de estudos direcionados a aspectos neurorradiológicos, patológicos e genéticos. Conclusões: Este novo grupo complexo de doenças raras tipicamente se apresenta com doença do neurônio motor inferior em associação com outros sinais de comprometimento neurológico ou sistêmico, os quais apresentam padrões relativamente específicos para cada subtipo genético.

Prescription patterns of riluzole in a population of patients with motor neuron disease / Patrón de prescripción de riluzol en una población de pacientes con enfermedad de neurona motora

SUMMARY OBJECTIVE: To determine the prescription pattern of riluzol and the variables associated to its use in a population of patients with motor neuron disease affiliated to the Colombian General Social Security Health System (SGSSS) in 2017. METHOD: Descriptive cross-sectional study. Through a systemized data base of approximately 3,5 million members to the Colombian SGSSS; patients who had been given riluzol uninterruptedly between April 1 and June 30 of 2017, were selected. Sociodemographic, pharmacological variables and comorbidities were analyzed. Defined daily dose (DDD) was estimated for 1.000 inhabitants/day and its costs. RESULTS: There were found 81 patients with motor neuron disease receiving riluzol, with an average age of 60,8+12,6 years. 48.1% were male. The prevalence of motor neuron disease was 29/100.000 individuals. Patients received riluzol in 50 mg tablets and the doses was estimated in 0,016 DDD for 1.000 inhabitants/day 63% were receiving medicines that reflect comorbidity or could interact with riluzol. The total cost of riluzol dispensed in 2017 was USD 85.348 and per prescribed daily dose on average was USD 2,3. CONCLUSIONS: The use of riluzol in patients with motor neuron disease in Colombia was carried by the recommended doses by the WHO and with a direct cost lower than reported in other countries. Studies are recommended in order to determine the effectiveness of riluzol in real-life conditions.

RESUMEN OBJETIVOS: Determinar el patrón de prescripción de riluzol y las variables asociadas a su utilización en una población de pacientes con enfermedad de neurona motora afiliados al Sistema General de Seguridad Social en Salud de Colombia (SGSSS) en 2017. METODOLOGÍA: Estudio descriptivo de corte transversal. Mediante una base de datos sistematizada de aproximadamente 3,5 millones de afiliados al SGSSS de Colombia; se seleccionaron pacientes a quienes se les haya dispensado riluzol de manera ininterrumpida entre 1 abril y 30 junio de 2017. Se analizaron variables socio-demográficas, farmacológicas y las comorbilidades. Se estimaron la dosis diaria definida (DDD) por 1.000 habitantes/día y los costos. RESULTADOS: Se encontraron 81 pacientes con enfermedad de neurona motora recibiendo riluzol, con edad promedio de 60,8+12,6 años. El 48,1% eran hombres. La prevalencia de enfermedad de neurona motora fue 2,29/100.000 personas. Los pacientes recibieron riluzol en tabletas de 50 mg y se estimó la dosis en 0,016 DDD por 1.000 habitantes/día. El 63% recibían medicamentos que reflejan comorbilidad o pudieran tener interacción con riluzol. El costo total del riluzol dispensado en 2017 fue USD 85.348 y por dosis diaria prescrita en promedio fue USD 2,3. CONCLUSIONES: El uso de riluzol en pacientes con enfermedad de neurona motora en Colombia se realizó a las dosis recomendadas por la OMS y con un costo directo menor al reportado en otros países. Se recomienda realizar estudios que permitan determinar la efectividad del riluzol en condiciones de la vida real.

La enfermedad neurológica de Leonardo da Vinci / The neurological disease of Leonardo da Vinci

Introducción: el año 2019 se conmemoraron los 500 años de la muerte de Leonardo da Vinci en el Chateux du Cloux, Francia. Según registros históricos, Leonardo vivió los últimos años de su vida con una parálisis en su mano derecha, atribuida a un probable accidente cerebrovascular (ACV), lo cual afectó a su capacidad para emprender nuevos proyectos pictóricos. Este trabajo describe como fueron los últimos años de vida de Leonardo, revisa los antecedentes sobre salud y su probable enfermedad neurológica, sus eventuales etio-logías y sus consecuencias. Desarrollo: Leonardo llegó a Francia en 1516 por invitación del rey Francisco I para llevar el Renacimiento y completar su formación personal. En 1517 es visitado por el cardenal Luis de Aragón, y su secretario registra en su diario que Leonardo se encuentra afectado de una parálisis de la mano derecha. Algunos autores sugieren un ACV como causa probable, sobretodo porque según el historiador Vasari, Leonardo vivió sus últimos años en condición de discapacidad. Se llega a plantear que su condición de vege-tariano habría podido influir como factor de riesgo de ACV. Sin embargo, un dibujo no fechado de Figino muestra a Leonardo con una parálisis de tipo periférica de la mano derecha, abriendo el diagnóstico diferencial. Conclusiones: no hay información suficiente para valorar el tipo y la causa de enfermedad neurológica de Leonardo da Vinci, no obstante, está influyó significativamente en su interacción con su discípulo Francisco Melzi y su mecenas Francisco I, hecho que contribuyó a que su legado perdure hasta hoy.

Introduction: the year2019 marked the 500th anniversary of the death of Leonardo da Vinci at the Chateau du Cloux, France. According to historical records, Leonardo lived the last years of his life with palsy on his right hand, attributed to a probable stroke, which affected his ability to undertake new pictorial projects. This study describes how were the last years of Leonardo's life, reviews his medical history and his probable neurological disease, with its possible etiologies and its consequences. Discussion: Leonardo arrived in France in 1516 invited by King Francis I to lead the Renaissance and complete his education. In 1517, cardinal Luis de Aragón visited Leonardo, and his secretary recorded in his diary that he was affected by a palsy on his right hand. Some authors suggest that stroke could have been a probable cause, especially because according to the historian Vasari, Leonardo lived his last years in a condition of disability. His vegetarian food habit could have been a risk factor for his suspected stroke. However, an undated drawing by Figino shows Leonardo with a peripheral nerve palsy on his right hand, opening up the differential diagnosis. Conclusions:there is not enough information to assess the type and cause of Leonardo da Vinci's neurological disease. However, this condition significantly affected his interaction with his discipleFrancisco Melzi and his patron Francisco I, a fact that contributed to his legacy enduring until today.

Perfil epidemiológico dos pacientes com esclerose lateral amiotrófica acompanhados na Associação de Assistência à Criança Deficiente / Epidemiological profile of patients with amiotrophic lateral sclerosis accompanied in the Associação de Assistência à Criança Deficiente

A Esclerose Lateral Amiotrófica (ELA) é uma doença neurodegenerativa caracterizada por perda irreversível dos neurônios motores da medula espinal, tronco encefálico e córtex cerebral, levando à atrofia muscular, espasticidade e consequentemente à morte. Objetivo: Verificar a prevalência da ELA na Associação de Assistência à Criança Deficiente (AACD) ­ Unidade Ibirapuera e caracterizar os indivíduos acometidos quanto à evolução da doença durante o processo de reabilitação, a fim de traçar um perfil epidemiológico desta população. Método: Trata-se de um estudo retrospectivo, baseado em informações contidas em prontuário, referentes a pacientes que realizaram reabilitação durante o período de janeiro de 2008 a janeiro de 2018, sendo a busca pelos dados guiada a partir de formulário desenvolvido exclusivamente para este estudo. Resultados: A prevalência dos pacientes com ELA em tratamento na clínica de doenças neuromusculares é de 11,6%. O perfil desses pacientes é ligeiramente maior do sexo feminino de cor branca, com uma média de idade de 59 anos, sendo a hipertensão arterial sistêmica a comorbidade mais encontrada. A forma de ELA mais frequente foi a esporádica, e o medicamento mais utilizado foi o Riluzole. Houve grande variabilidade de objetivos fisioterapêuticos e aumento do uso da ventilação mecânica não invasiva. Não houve associação entre a presença de marcha na última avaliação e o tempo do paciente em fisioterapia. Conclusão: Os objetivos estão de acordo com a literatura, bem como demonstram a importância de conhecermos melhor a população para termos uma abordagem multidisciplinar mais adequada para estes pacientes.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by irreversible loss of motor neurons in the spinal cord, brainstem and cerebral cortex, leading to muscle atrophy, spasticity and consequently death. Objective: To verify theprevalence of ALS in the Associação de Assistência à Criança Deficiente (AACD) ­ Ibirapuera's unit and to characterize the individuals affected by the disease during the rehabilitation process, in order to draw an epidemiological profile of this population. Method: This is a retrospective study, based on information contained in medical records, referring to a study conducted during the period from January 2008 to January 2018, being a data search guided by a resource developed for this study. Results: The prevalence of patients with ALS in the treatment of neuromuscular diseases is 11.6%. The profile of these patients is slightly higher in white females, with a mean age of 59 years, with systemic arterial hypertension being the most common comorbidity. The most common ALS was sporadic, and Riluzole was the most commonly used drug. There was great variability of physiotherapeutic objectives and an increase in the use of non-invasive mechanical ventilation. There was no association between the presence of gait in the last evaluation and the time of the patient in physical therapy. Conclusion: The objectives are in agreement with the literature, as well as it cites the importance of knowing the population better to have a multidisciplinaryapproach more suitable for these patients.