Tradução para o português e validação da Escala Cooperativa Internacional para Avaliação das Ataxias (ICARS)

Introduction: The clinical assessment of patients with ataxias requires reliable scales. We aimed to translate, adapt and validate the International Cooperative Ataxia Rating Scale (ICARS) into Brazilian Portuguese. Methods: The steps of this study were forward translation, translation synthesis, backward translation, expert committee meeting, preliminary pilot testing and final assessment. Thirty patients were enrolled in the preliminary pilot testing and 61 patients were evaluated for construct validity, internal consistency, intra- and inter-rater reliability and external consistency. Results: This study showed good validity of the construct and high internal consistency for the full scale, except for the oculomotor domain (Cronbach’s alpha = 0.316, intraclass correlation coefficients intra- = 82.4% and inter- = 79.2%). A high correlation with the Scale for the Assessment and Rating of Ataxia was observed. We found good intra-rater agreement and relative inter-rater disagreement, except in the posture and gait domain. Conclusion: The present ICARS version is adapted for the Brazilian culture and can be used to assess our ataxic patients.Introdução: A avaliação clínica de pacientes atáxicos requer instrumentos confiáveis. Nosso objetivo foi traduzir, adaptar culturalmente e validar a International Cooperative Ataxia Rating Scale (ICARS) para a língua portuguesa do Brasil. Métodos: As etapas foram tradução, síntese das traduções, retrotradução, comitê de especialistas, pré-teste e avaliação final. O pré-teste foi realizado com 30 pacientes. Outros 61 pacientes foram avaliados para validade do constructo, consistência interna, confiabilidade intra e interexaminadores e consistência externa. Resultados: Este estudo mostrou boa validade do constructo e alta consistência interna para o total da escala, exceto para o domínio Oculomotor (alfa de Cronbach = 0.316, CCIintra = 82.4% e CCIinter = 79.2%). Alta correlação com a Scale for the Assessment and Rating of Ataxia foi observada. Nós encontramos boa concordância intraexaminador e relativa discordância interexaminadores, com exceção dos domínios postura e marcha. Conclusão: Esta versão da ICARS está adaptada para a cultura brasileira e pode ser usada em pacientes com ataxia

Biallelic Loss‐of‐Function NDUFA12 Variants Cause a Wide Phenotypic Spectrum from Leigh/Leigh‐Like Syndrome to Isolated Optic Atrophy

Abstract: Background: Biallelic loss‐of‐function NDUFA12 variants have hitherto been linked to mitochondrial complex I deficiency presenting with heterogeneous clinical and radiological features in nine cases only. Objectives: To fully characterize, both phenotypically and genotypically, NDUFA12‐related mitochondrial disease. Methods: We collected data from cases identified by screening genetic databases of several laboratories worldwide and systematically reviewed the literature. Results: Nine unreported NDUFA12 cases from six pedigrees were identified, with presentation ranging from movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. MRI showed basal ganglia abnormalities (n = 6), optic atrophy (n = 2), or was unremarkable (n = 1). All carried homozygous truncating NDUFA12 variants, three of which are novel. Conclusions: Our case series expands phenotype–genotype correlations in NDUFA12‐associated mitochondrial disease, providing evidence of intra‐ and inter‐familial clinical heterogeneity for the same variant. It confirms NDUFA12 variants should be included in the diagnostic workup of Leigh/Leigh‐like syndromes – particularly with dystonia – as well as isolated optic atrophy

Far beyond the motor neuron: the role of glial cells in amyotrophic lateral sclerosis

ABSTRACT Motor neuron disease is one of the major groups of neurodegenerative diseases, mainly represented by amyotrophic lateral sclerosis. Despite wide genetic and biochemical data regarding its pathophysiological mechanisms, motor neuron disease develops under a complex network of mechanisms not restricted to the unique functions of the alpha motor neurons but which actually involve diverse functions of glial cell interaction. This review aims to expose some of the leading roles of glial cells in the physiological mechanisms of neuron-glial cell interactions and the mechanisms related to motor neuron survival linked to glial cell functions

Clinical, neuroimaging and genetic findings in Brazilian patients with neurodegeneration with brain iron accumulation

Neurodegeneration with brain iron accumulation (NBIA) encompasses a clinically and genetically heterogeneous group of rare disorders. Here, we report clinical, neuroimaging and genetic studies in twenty three Brazilian NBIA patients. In thirteen subjects, deleterious variants were detected in known NBIA-causing genes (PANK2, PLA2G6, C9ORF12, WDR45 and FA2H), including previously unreported variants in PANK2 and PLA2G6. Two patients carried rare, likely pathogenic variants in genes not previously associated with NBIA: KMT2A c.11785A &gt; C (p.Ile3929Leu), and TIMM8A c.127T &gt; C (p.Cys43Arg), suggesting an expansion of their associated phenotypes to include NBIA. In eight patients the etiology remains unsolved, suggesting variants undetectable by the adopted methods, or the existence of additional NBIA-causing genes.</p

Clinical, neuroimaging and genetic findings in Brazilian patients with neurodegeneration with brain iron accumulation

Neurodegeneration with brain iron accumulation (NBIA) encompasses a clinically and genetically heterogeneous group of rare disorders. Here, we report clinical, neuroimaging and genetic studies in twenty three Brazilian NBIA patients. In thirteen subjects, deleterious variants were detected in known NBIA-causing genes (PANK2, PLA2G6, C9ORF12, WDR45 and FA2H), including previously unreported variants in PANK2 and PLA2G6. Two patients carried rare, likely pathogenic variants in genes not previously associated with NBIA: KMT2A c.11785A &gt; C (p.Ile3929Leu), and TIMM8A c.127T &gt; C (p.Cys43Arg), suggesting an expansion of their associated phenotypes to include NBIA. In eight patients the etiology remains unsolved, suggesting variants undetectable by the adopted methods, or the existence of additional NBIA-causing genes.</p

Tradução para o português e validação da Escala Cooperativa Internacional para Avaliação das Ataxias (ICARS)

Introduction: The clinical assessment of patients with ataxias requires reliable scales. We aimed to translate, adapt and validate the International Cooperative Ataxia Rating Scale (ICARS) into Brazilian Portuguese. Methods: The steps of this study were forward translation, translation synthesis, backward translation, expert committee meeting, preliminary pilot testing and final assessment. Thirty patients were enrolled in the preliminary pilot testing and 61 patients were evaluated for construct validity, internal consistency, intra- and inter-rater reliability and external consistency. Results: This study showed good validity of the construct and high internal consistency for the full scale, except for the oculomotor domain (Cronbach’s alpha = 0.316, intraclass correlation coefficients intra- = 82.4% and inter- = 79.2%). A high correlation with the Scale for the Assessment and Rating of Ataxia was observed. We found good intra-rater agreement and relative inter-rater disagreement, except in the posture and gait domain. Conclusion: The present ICARS version is adapted for the Brazilian culture and can be used to assess our ataxic patients.Introdução: A avaliação clínica de pacientes atáxicos requer instrumentos confiáveis. Nosso objetivo foi traduzir, adaptar culturalmente e validar a International Cooperative Ataxia Rating Scale (ICARS) para a língua portuguesa do Brasil. Métodos: As etapas foram tradução, síntese das traduções, retrotradução, comitê de especialistas, pré-teste e avaliação final. O pré-teste foi realizado com 30 pacientes. Outros 61 pacientes foram avaliados para validade do constructo, consistência interna, confiabilidade intra e interexaminadores e consistência externa. Resultados: Este estudo mostrou boa validade do constructo e alta consistência interna para o total da escala, exceto para o domínio Oculomotor (alfa de Cronbach = 0.316, CCIintra = 82.4% e CCIinter = 79.2%). Alta correlação com a Scale for the Assessment and Rating of Ataxia foi observada. Nós encontramos boa concordância intraexaminador e relativa discordância interexaminadores, com exceção dos domínios postura e marcha. Conclusão: Esta versão da ICARS está adaptada para a cultura brasileira e pode ser usada em pacientes com ataxia

Cross-cultural adaptation and validation of the International Cooperative Ataxia Rating Scale (ICARS) to Brazilian Portuguese

ABSTRACT Introduction: The clinical assessment of patients with ataxias requires reliable scales. We aimed to translate, adapt and validate the International Cooperative Ataxia Rating Scale (ICARS) into Brazilian Portuguese. Methods: The steps of this study were forward translation, translation synthesis, backward translation, expert committee meeting, preliminary pilot testing and final assessment. Thirty patients were enrolled in the preliminary pilot testing and 61 patients were evaluated for construct validity, internal consistency, intra- and inter-rater reliability and external consistency. Results: This study showed good validity of the construct and high internal consistency for the full scale, except for the oculomotor domain (Cronbach's alpha = 0.316, intraclass correlation coefficients intra- = 82.4% and inter- = 79.2%). A high correlation with the Scale for the Assessment and Rating of Ataxia was observed. We found good intra-rater agreement and relative inter-rater disagreement, except in the posture and gait domain. Conclusion: The present ICARS version is adapted for the Brazilian culture and can be used to assess our ataxic patients