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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease usually associated with severe weakness and death within 2-5 years. SOD1 mutations cause hereditary ALS in autosomal dominant and rarely in recessive pattern. We describe a new phenotype of slowly progressive fALS due to homozygous SOD1 mutations (c.358G > C, p.Val120Leu) in a Brazilian family. We reviewed the medical chart and interviewed the index patient and other relatives. A 41-year-old man developed weakness in his legs, leading to frequent falls, followed over the next few months with progressive arm fasciculations and muscle atrophy. The SOD1 enzymatic activity in erythrocytes was slightly decreased. A genetic test panel disclosed homozygous SOD1 mutations (c.358G > C, p.Val120Leu). His asymptomatic parents also carried one mutant allele and 2 brothers and a sister had died with ALS. We reported a new family with homozygous SOD1 mutation and slowly progressive ALS course. Further studies are necessary to confirm whether this mutation can also lead to disease in heterozygosis with incomplete penetrance.

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BACKGROUND: Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions. BACKGROUND: • What is already known? BACKGROUND: • The prevalence and spectrum of neuropsychiatric co-morbidities varies among different epidemiologic studies. BACKGROUND: • What is new here? BACKGROUND: • Patients self report a high percentage of neuropsychiatric diseases but tend to better recognize central rather than peripheral nervous system disorders. BACKGROUND: • How can this study help patient care? BACKGROUND: • This study may guide practioners to educate IBD patients about their neuropsychiatric co-morbidities.

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BACKGROUND: Patients with anti-MAG neuropathy present with distal demyelinating polyneuropathy, IgM monoclonal gammopathy, and elevated titers of anti-MAG antibodies. OBJECTIVE: This paper reviews what is known about the clinical presentation, course, pathophysiology, and treatment of anti-MAG neuropathy, with considerations for the design of therapeutic trials. METHODS: A literature review of the medical and scientific literature related to anti-MAG neuropathy, and the design of therapeutic clinical trials in peripheral neuropathy. RESULTS: Anti-MAG neuropathy can remain indolent for many years but then enter a progressive phase. Highly elevated antibody titers are diagnostic, but intermediate titers can also occur in chronic inflammatory demyelinating polyneuropathy (CIDP). The peripheral nerves can become inexcitable, thereby masking the demyelinating abnormalities. There is good evidence that the anti-MAG antibodies cause neuropathy. Reduction of the autoantibody concentration by agents that target B-cells was reported to result in clinical improvement in case series and uncontrolled trials, but not in controlled clinical trials, probably due to inadequate trial design. CONCLUSION: We propose that therapeutic trials for anti-MAG neuropathy include patients with the typical presentation, some degree of weakness, highly elevated anti-MAG antibody titers, and at least one nerve exhibiting demyelinating range abnormalities. Treatment with one or a combination of anti-B-cell agents would aim at reducing the autoantibody concentration by at least 60%. A trial duration of 2 years may be required to show efficacy. The neuropathy impairment score of the lower extremities (NIS-LL) plus the Lower Limb Function (LLF) score would be a suitable primary outcome measure.

ANTECEDENTES: Pacientes com neuropatia anti-MAG apresentam polineuropatia desmielinizante distal, gamopatia monoclonal IgM e títulos elevados de anticorpos anti-MAG. OBJETIVO: Este artigo revisa o que se sabe sobre a apresentação clínica, curso, fisiopatologia e tratamento da neuropatia anti-MAG, com considerações para o desenho de ensaios terapêuticos. MéTODOS: Revisão bibliográfica da literatura médica e científica relacionada à neuropatia anti-MAG e desenho de ensaios clínicos terapêuticos em neuropatia periférica. RESULTADOS: A neuropatia anti-MAG pode permanecer indolente durante muitos anos, mas depois entra numa fase progressiva. Títulos de anticorpos altamente elevados são diagnósticos, mas títulos intermediários também podem ocorrer na polineuropatia desmielinizante inflamatória crônica (CIDP). Os nervos periféricos podem tornar-se inexcitáveis, mascarando, assim, as anomalias desmielinizantes. Há boas evidências de que os anticorpos anti-MAG causam a neuropatia. Foi relatado que a redução da concentração de autoanticorpos por agentes direcionados às células B resultou em melhora clínica em séries de casos e ensaios não controlados, mas não em ensaios clínicos controlados, provavelmente devido ao desenho inadequado dos ensaios. CONCLUSãO: Propomos que os ensaios terapêuticos para neuropatia anti-MAG incluam pacientes com apresentação típica, algum grau de fraqueza, títulos de anticorpos anti-MAG altamente elevados e pelo menos um nervo exibindo anormalidades na faixa desmielinizante. O tratamento com um ou uma combinação de agentes anticélulas B teria como objetivo reduzir a concentração de autoanticorpos em pelo menos 60%. Pode ser necessária uma duração de ensaio de 2 anos para demonstrar eficácia. A pontuação de comprometimento da neuropatia das extremidades inferiores (NIS-LL) mais a pontuação da função dos membros inferiores (LLF) seria uma medida de resultado primário adequada.

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ABSTRACT Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions.

RESUMO A doença inflamatória intestinal (DII) pode ser acompanhada por vários distúrbios neurológicos. Desde 2004, iniciamos uma coorte brasileira para avaliar complicações neuropsiquiátricas em pacientes com DII. Mudanças na estratégia terapêutica e diferenças na prevalência e relevância dos transtornos neuropsiquiátricos têm sido relatadas na literatura. Realizamos uma breve pesquisa relatada pelos pacientes sobre o manejo médico da DII (com foco especial no manejo neuropsiquiátrico) e suas complicações. Durante o período de 01/09/2021 a 31/08/2022, 279 pacientes com DII responderam à pesquisa (128 pacientes com retocolite ulcerativa e 151 com doença de Crohn). Esta é a primeira pesquisa de gestão médica que visa verificar o nível de percepção dos pacientes com DII acerca de suas condições neuropsiquiátricas. Encontramos uma alta prevalência de comorbidades neurológicas (59%), psiquiátricas (32%) e neuropsiquiátricas (69%). Há uma discrepância marcante entre os achados de distúrbios neurológicos relatados em nossos estudos durante os primeiros 10 anos da coorte em comparação com a percepção/conhecimento atual entre os pacientes da presente pesquisa de manejo. Os pacientes tendem a ter uma melhor compreensão das condições que afetam o sistema nervoso central do que as que afetam o sistema nervoso periférico.

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Abstract Background Patients with anti-MAG neuropathy present with distal demyelinating polyneuropathy, IgM monoclonal gammopathy, and elevated titers of anti-MAG antibodies. Objective This paper reviews what is known about the clinical presentation, course, pathophysiology, and treatment of anti-MAG neuropathy, with considerations for the design of therapeutic trials. Methods A literature review of the medical and scientific literature related to anti-MAG neuropathy, and the design of therapeutic clinical trials in peripheral neuropathy. Results Anti-MAG neuropathy can remain indolent for many years but then enter a progressive phase. Highly elevated antibody titers are diagnostic, but intermediate titers can also occur in chronic inflammatory demyelinating polyneuropathy (CIDP). The peripheral nerves can become inexcitable, thereby masking the demyelinating abnormalities. There is good evidence that the anti-MAG antibodies cause neuropathy. Reduction of the autoantibody concentration by agents that target B-cells was reported to result in clinical improvement in case series and uncontrolled trials, but not in controlled clinical trials, probably due to inadequate trial design. Conclusion We propose that therapeutic trials for anti-MAG neuropathy include patients with the typical presentation, some degree of weakness, highly elevated anti-MAG antibody titers, and at least one nerve exhibiting demyelinating range abnormalities. Treatment with one or a combination of anti-B-cell agents would aim at reducing the autoantibody concentration by at least 60%. A trial duration of 2 years may be required to show efficacy. The neuropathy impairment score of the lower extremities (NIS-LL) plus the Lower Limb Function (LLF) score would be a suitable primary outcome measure.

Resumo Antecedentes Pacientes com neuropatia anti-MAG apresentam polineuropatia desmielinizante distal, gamopatia monoclonal IgM e títulos elevados de anticorpos anti-MAG. Objetivo Este artigo revisa o que se sabe sobre a apresentação clínica, curso, fisiopatologia e tratamento da neuropatia anti-MAG, com considerações para o desenho de ensaios terapêuticos. Métodos Revisão bibliográfica da literatura médica e científica relacionada à neuropatia anti-MAG e desenho de ensaios clínicos terapêuticos em neuropatia periférica. Resultados A neuropatia anti-MAG pode permanecer indolente durante muitos anos, mas depois entra numa fase progressiva. Títulos de anticorpos altamente elevados são diagnósticos, mas títulos intermediários também podem ocorrer na polineuropatia desmielinizante inflamatória crônica (CIDP). Os nervos periféricos podem tornar-se inexcitáveis, mascarando, assim, as anomalias desmielinizantes. Há boas evidências de que os anticorpos anti-MAG causam a neuropatia. Foi relatado que a redução da concentração de autoanticorpos por agentes direcionados às células B resultou em melhora clínica em séries de casos e ensaios não controlados, mas não em ensaios clínicos controlados, provavelmente devido ao desenho inadequado dos ensaios. Conclusão Propomos que os ensaios terapêuticos para neuropatia anti-MAG incluam pacientes com apresentação típica, algum grau de fraqueza, títulos de anticorpos anti-MAG altamente elevados e pelo menos um nervo exibindo anormalidades na faixa desmielinizante. O tratamento com um ou uma combinação de agentes anticélulas B teria como objetivo reduzir a concentração de autoanticorpos em pelo menos 60%. Pode ser necessária uma duração de ensaio de 2 anos para demonstrar eficácia. A pontuação de comprometimento da neuropatia das extremidades inferiores (NIS-LL) mais a pontuação da função dos membros inferiores (LLF) seria uma medida de resultado primário adequada.

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BACKGROUND: Detailed information about the electromyography practice in Brazil is largely unavailable. OBJECTIVE: To evaluate where and how electromyography is performed in Brazil, as well as regional disparities and the professional and academic credentials of electromyographers. METHODS: We conducted an internet-based survey of active Brazilian electromyographers. The websites of health insurance companies, professional academies, medical cooperatives, online search engines, and social networks in each Brazilian state were screened and we evaluated the credentials of each electromyographer listed in the Brazilian Federal Medical Board (BFMB) registration website and their online curricula vitae in the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, in Portuguese). We also evaluated the same parameters in a control group of non-electromyographer neurologists randomly matched by geographical distribution and gender. RESULTS: We found 469 electromyographers (384 neurologists and 85 non-neurologists), with a male predominance. In total, 81.9% were BFMB-certified neurologists, 49.9%, BFMB-certified clinical neurophysiologists, and 10.4%, BFMB-certified physiatrists. Among the non-neurologists, 48.2% were physiatrists. Most electromyographers practiced in states on the Southern and Southeastern regions of Brazil. When adjusted by population, the Federal District and the states of Mato Grosso do Sul and Goiás presented the highest of eletromyographers density. Electromyographers were not more likely to have current/past academic affiliations. CONCLUSION: In Brazil, electromyography is performed predominantly by neurologists, and half of them are BFMB-certified clinical neurophysiologists. The present study highlights regional disparities and may guide government-based initiatives, for instance, to improve the diagnosis of leprosy and the management of neuromuscular disorders within the Brazilian territory.

ANTECEDENTES: Informações detalhadas sobre a prática de eletromiografia no Brasil são em grande parte indisponíveis. OBJETIVO: Avaliar onde e como a eletromiografia é realizada no Brasil, as disparidades regionais, e as credenciais profissionais e acadêmicas dos eletromiografistas. MéTODOS: Realizamos uma enquete via internet de eletromiografistas brasileiros ativos. Foram rastreados sites de operadoras de planos de saúde, academias profissionais médicas, cooperativas médicas, ferramentas de busca online e redes sociais em cada estado brasileiro. Em seguida, avaliamos as credenciais de cada eletromiografista listado no site de registro do Conselho Federal de Medicina (CFM) e seus curricula vitae online no Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Também avaliamos os mesmos parâmetros em um grupo controle de neurologistas não eletromiografistas pareados aleatoriamente por distribuição geográfica e gênero. RESULTADOS: Encontramos 469 eletromiografistas (384 neurologistas e 85 não neurologistas), com predominância do sexo masculino. Ao todo, 81,9% eram neurologistas com certificação confirmada pelo site do CFM, 49,9%, neurofisiologistas clínicos com certificação confirmada pelo site do CFM, e 10,4%, fisiatras com certificação confirmada pelo mesmo site. Entre os não neurologistas, 48,2% eram fisiatras. A maioria dos eletromiografistas atuava nos estados do Sul e do Sudeste. Quando ajustados pela população, o Distrito Federal e os estados de Mato Grosso do Sul e Goiás apresentaram a maior densidade de eletromiografistas. Os eletromiografistas não eram mais propensos a ter vínculos acadêmicos atuais/passados. CONCLUSãO: No Brasil, a eletromiografia é realizada predominantemente por neurologistas, e metade deles são neurofisiologistas clínicos com certificação confirmada pelo site do CFM. Este estudo destacou as disparidades regionais, e pode orientar ações governamentais para, por exemplo, melhorar o diagnóstico da hanseníase e o manejo das doenças neuromusculares no território brasileiro.

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Abstract Background Detailed information about the electromyography practice in Brazil is largely unavailable. Objective To evaluate where and how electromyography is performed in Brazil, as well as regional disparities and the professional and academic credentials of electromyographers. Methods We conducted an internet-based survey of active Brazilian electromyographers. The websites of health insurance companies, professional academies, medical cooperatives, online search engines, and social networks in each Brazilian state were screened and we evaluated the credentials of each electromyographer listed in the Brazilian Federal Medical Board (BFMB) registration website and their online curricula vitae in the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, in Portuguese). We also evaluated the same parameters in a control group of non-electromyographer neurologists randomly matched by geographical distribution and gender. Results We found 469 electromyographers (384 neurologists and 85 non-neurologists), with a male predominance. In total, 81.9% were BFMB-certified neurologists, 49.9%, BFMB-certified clinical neurophysiologists, and 10.4%, BFMB-certified physiatrists. Among the non-neurologists, 48.2% were physiatrists. Most electromyographers practiced in states on the Southern and Southeastern regions of Brazil. When adjusted by population, the Federal District and the states of Mato Grosso do Sul and Goiás presented the highest of eletromyographers density. Electromyographers were not more likely to have current/past academic affiliations. Conclusion In Brazil, electromyography is performed predominantly by neurologists, and half of them are BFMB-certified clinical neurophysiologists. The present study highlights regional disparities and may guide government-based initiatives, for instance, to improve the diagnosis of leprosy and the management of neuromuscular disorders within the Brazilian territory.

Resumo Antecedentes Informações detalhadas sobre a prática de eletromiografia no Brasil são em grande parte indisponíveis. Objetivo Avaliar onde e como a eletromiografia é realizada no Brasil, as disparidades regionais, e as credenciais profissionais e acadêmicas dos eletromiografistas. Métodos Realizamos uma enquete via internet de eletromiografistas brasileiros ativos. Foram rastreados sites de operadoras de planos de saúde, academias profissionais médicas, cooperativas médicas, ferramentas de busca online e redes sociais em cada estado brasileiro. Em seguida, avaliamos as credenciais de cada eletromiografista listado no site de registro do Conselho Federal de Medicina (CFM) e seus curricula vitae online no Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Também avaliamos os mesmos parâmetros em um grupo controle de neurologistas não eletromiografistas pareados aleatoriamente por distribuição geográfica e gênero. Resultados Encontramos 469 eletromiografistas (384 neurologistas e 85 não neurologistas), com predominância do sexo masculino. Ao todo, 81,9% eram neurologistas com certificação confirmada pelo site do CFM, 49,9%, neurofisiologistas clínicos com certificação confirmada pelo site do CFM, e 10,4%, fisiatras com certificação confirmada pelo mesmo site. Entre os não neurologistas, 48,2% eram fisiatras. A maioria dos eletromiografistas atuava nos estados do Sul e do Sudeste. Quando ajustados pela população, o Distrito Federal e os estados de Mato Grosso do Sul e Goiás apresentaram a maior densidade de eletromiografistas. Os eletromiografistas não eram mais propensos a ter vínculos acadêmicos atuais/passados. Conclusão No Brasil, a eletromiografia é realizada predominantemente por neurologistas, e metade deles são neurofisiologistas clínicos com certificação confirmada pelo site do CFM. Este estudo destacou as disparidades regionais, e pode orientar ações governamentais para, por exemplo, melhorar o diagnóstico da hanseníase e o manejo das doenças neuromusculares no território brasileiro.

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The spectrum of neuropsychiatric phenomena observed in amyotrophic lateral sclerosis (ALS) is wide and not fully understood. Disorders of laughter and crying stand among the most common manifestations. The aim of this study is to report the results of an educational consensus organized by the Brazilian Academy of Neurology to evaluate the definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in ALS patients. Twelve members of the Brazilian Academy of Neurology - considered to be experts in the field - were recruited to answer 12 questions about the subject. After exchanging revisions, a first draft was prepared. A face-to-face meeting was held in Fortaleza, Brazil on 9.23.22 to discuss it. The revised version was subsequently emailed to all members of the ALS Scientific Department from the Brazilian Academy of Neurology and the final revised version submitted for publication. The prevalence of pseudobulbar affect/pathological laughter and crying (PBA/PLC) in ALS patients from 15 combined studies and 3906 patients was 27.4% (N = 1070), ranging from 11.4% to 71%. Bulbar onset is a risk factor but there are limited studies evaluating the differences in prevalence among the different motor neuron diseases subtypes, including patients with and without frontotemporal dementia. Antidepressants and a combination of dextromethorphan and quinidine (not available in Brazil) are possible therapeutic options. This group of panelists acknowledge the multiple gaps in the current literature and reinforces the need for further studies.

O espectro de fenômenos neuropsiquiátricos observados na ELA é amplo e não completamente entendido. Desordens do riso e do choro estão entre as manifestações mais comuns. O objetivo deste estudo é relatar os resultados de um Consenso organizado pela Academia Brasileira de Neurologia para avaliar definições, fenomenologia, diagnóstico, e manejo dos distúrbios do riso e do choro em pacientes com ELA. Doze membros da Academia Brasileira de Neurologia ­ considerados experts na área ­ foram recrutados para responder 12 questões na temática. Depois da verificação das revisões, um primeiro manuscrito foi preparado. Após, foi realizado um encontro presencial em Fortaleza, Brasil, em 23/09/2022, para discussão do conteúdo. A versão revisada foi posteriormente enviada por e-mail para todos os membros do Departamento Científico de DNM/ELA da Academia Brasileira de Neurologia e a versão final revisada foi submetida para publicação. A prevalência da síndrome pseudobulbar em pacientes com ELA em 15 estudos combinados com 3906 pacientes foi de 27,4% (n = 1070), variando entre 11,4% e 71%. Início bulbar é um fator de risco, mas há limitados estudos avaliando as diferenças em prevalência entre os diferentes subtipos de Doença do Neurônio Motor, incluindo pacientes com e sem Demência Frontotemporal. Antidepressivos e uma combinação de dextrometorfana e quinidina (indisponíveis no Brasil) são opções terapêuticas possíveis. Esse grupo de panelistas reconhece as múltiplas demandas não atendidas na literatura atual e reforça a necessidade de futuros estudos.

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Abstract The spectrum of neuropsychiatric phenomena observed in amyotrophic lateral sclerosis (ALS) is wide and not fully understood. Disorders of laughter and crying stand among the most common manifestations. The aim of this study is to report the results of an educational consensus organized by the Brazilian Academy of Neurology to evaluate the definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in ALS patients. Twelve members of the Brazilian Academy of Neurology - considered to be experts in the field - were recruited to answer 12 questions about the subject. After exchanging revisions, a first draft was prepared. A face-to-face meeting was held in Fortaleza, Brazil on 9.23.22 to discuss it. The revised version was subsequently emailed to all members of the ALS Scientific Department from the Brazilian Academy of Neurology and the final revised version submitted for publication. The prevalence of pseudobulbar affect/pathological laughter and crying (PBA/PLC) in ALS patients from 15 combined studies and 3906 patients was 27.4% (N = 1070), ranging from 11.4% to 71%. Bulbar onset is a risk factor but there are limited studies evaluating the differences in prevalence among the different motor neuron diseases subtypes, including patients with and without frontotemporal dementia. Antidepressants and a combination of dextromethorphan and quinidine (not available in Brazil) are possible therapeutic options. This group of panelists acknowledge the multiple gaps in the current literature and reinforces the need for further studies.

Resumo O espectro de fenômenos neuropsiquiátricos observados na ELA é amplo e não completamente entendido. Desordens do riso e do choro estão entre as manifestações mais comuns. O objetivo deste estudo é relatar os resultados de um Consenso organizado pela Academia Brasileira de Neurologia para avaliar definições, fenomenologia, diagnóstico, e manejo dos distúrbios do riso e do choro em pacientes com ELA. Doze membros da Academia Brasileira de Neurologia - considerados experts na área - foram recrutados para responder 12 questões na temática. Depois da verificação das revisões, um primeiro manuscrito foi preparado. Após, foi realizado um encontro presencial em Fortaleza, Brasil, em 23/09/2022, para discussão do conteúdo. A versão revisada foi posteriormente enviada por e-mail para todos os membros do Departamento Científico de DNM/ELA da Academia Brasileira de Neurologia e a versão final revisada foi submetida para publicação. A prevalência da síndrome pseudobulbar em pacientes com ELA em 15 estudos combinados com 3906 pacientes foi de 27,4% (n = 1070), variando entre 11,4% e 71%. Início bulbar é um fator de risco, mas há limitados estudos avaliando as diferenças em prevalência entre os diferentes subtipos de Doença do Neurônio Motor, incluindo pacientes com e sem Demência Frontotemporal. Antidepressivos e uma combinação de dextrometorfana e quinidina (indisponíveis no Brasil) são opções terapêuticas possíveis. Esse grupo de panelistas reconhece as múltiplas demandas não atendidas na literatura atual e reforça a necessidade de futuros estudos.

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Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ∼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ∼ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

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Abstract Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ~ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Resumo Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ~ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

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ABSTRACT Transthyretin familial amyloidosis is the most common form of inherited systemic amyloidosis worldwide. The condition develops secondary to more than 100 different point mutations in the transthyretin gene (18q12.1). The mutations lead to abnormal amyloid deposits, mainly in the heart and peripheral nerves. Leptomeningeal and mainly ocular involvement is common. Although there are several different types of treatment available, ocular involvement, which occurs also in liver transplant recipients, remains a major challenge, progressing even in liver transplant recipients. Patients with ocular involvement require efficient ophthalmological follow-up to prevent vision loss. In this review, different forms of ocular involvement characterizing the subtypes of transthyretin mutations were described, and the effects of different treatments were summarized. Further research is necessary to fully elucidate these issues.

RESUMO A amiloidose familiar por transtirretina é a forma mais comum de amiloidose sistêmica hereditária mundialmente. A condição é secundária a mais de 100 mutações ponto diferentes no gene da transtirretina (18q12.1). Mutações levam a depósitos anormais de amilóide principalmente no coração e nos nervos periféricos. O envolvimento leptomeníngeo, e principalmente ocular também é comum. Apesar do advento de várias formas diferentes de tratamento, o envolvimento ocular ainda é um grande problema, progredindo mesmo em pacientes submetidos à transplante hepático. Nesta revisão, avaliamos as diferentes formas de envolvimento ocular presentes entre os subtipos de mutações da transtirretina e os efeitos dos diferentes tratamentos disponíveis. O envolvimento ocular é desafiador na amiloidose familiar por transtirretina, exigindo acompanhamento oftalmológico eficiente para mitigar a perda de visão. Mais pesquisas são necessárias para auxiliar na resolução dessas questões.

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Transthyretin familial amyloidosis is the most common form of inherited systemic amyloidosis worldwide. The condition develops secondary to more than 100 different point mutations in the transthyretin gene (18q12.1). The mutations lead to abnormal amyloid deposits, mainly in the heart and peripheral nerves. Leptomeningeal and mainly ocular involvement is common. Although there are several different types of treatment available, ocular involvement, which occurs also in liver transplant recipients, remains a major challenge, progressing even in liver transplant recipients. Patients with ocular involvement require efficient ophthalmological follow-up to prevent vision loss. In this review, different forms of ocular involvement characterizing the subtypes of transthyretin mutations were described, and the effects of different treatments were summarized. Further research is necessary to fully elucidate these issues.

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TANK-binding kinase 1 (TBK1) gene mutations cause ALS and frontotemporal dementia (FTD). We report a novel TBK1 mutation in a Brazilian patient with ALS. Symptoms started at age 44 (lower-limb onset). Despite treatment with riluzole, his condition progressed over 5 years to aphemia, dysphagia, gastrostomy and tracheostomy. A diagnostic test panel for neurodegenerative disorders disclosed a novel likely pathogenic heterozygous intronic mutation in the TBK1 gene: c.1189 + 1G > T (Splice donor), intron 9. This mutation is expected to disrupt RNA splicing and lead to loss of protein function. Disruption of this splice site has been observed in patients with TBK1-related disorders. Separate and additional C9ORFF72 testing was negative. To our knowledge, this is the second patient with a TBK1 mutation (novel splice donor intronic mutation) reported in Brazil, and the first to include a full description of the clinical course. Further studies are necessary to establish the frequency of TBK1 mutations in Brazilian ALS patients (and worldwide) and to evaluate the possible different clinical phenotypes and the disease course.

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CONTEXT: Spinal-generated movement disorders are a complex group of medical conditions, frequently misdiagnosed, originating in the spinal cord or from combined peripheral and central nervous system involvement. In this case report, we describe a novel form of position-dependent dyskinesia due to severe craniocervical malformation. FINDINGS: An 83-year-old woman with basilar invagination at the C2 vertebra above the line of Chamberlain, occipitocervical lordosis, platybasia with a short clivus, ankylosis of the C1-C2 complex and fusion of the C1 arch developed an unusual pattern of position-dependent left arm dyskinesia triggered by bending her neck forward with simultaneous contact of the flexed elbow with a flat surface. Symptoms did not improve with anticonvulsants and she progressed and died suddenly. CONCLUSION/CLINICAL RELEVANCE: A newly described form of position-dependent arm dyskinesia can be associated with severe craniocervical malformation.

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BACKGROUND: Bleeding in hemophiliacs can cause complications in the central and peripheral nervous system (CNS and PNS). The incidence of intracranial hemorrhage has reduced after the introduction of prophylactic treatment with factor VIII or IX, but the benefits of this therapy have not yet been evaluated on PNS complications. OBJECTIVE: The aim of this study was to determine the prevalence of neurological complications in hemophiliacs and verify the effect of prophylactic therapy in these patients, including PNS disorders. METHODS: We retrospectively evaluated the prevalence of CNS and PNS disorders caused by bleeding in hemophiliacs seen at the Hemocentro Regional Norte, Ceará, Brazil, from 1992 to 2018, and we compared the incidence in different periods (before and after the introduction of prophylactic treatment in 2011). RESULTS: Of 75 hemophilia A patients evaluated (4.61/100.000 population), 13.3% (n=10) had either CNS (n=5) or PNS (n=5) disorders secondary to bleeding. Patients submitted to factor VIII replacement prophylactic therapy were less likely to have CNS events: from 1992 to 2011, 5 of 63 patients had CNS disease, while from 2011 to 2018, there were no new cases (p=0.0181). From 2011 to 2018, 5 PNS events occurred in patients without prophylactic therapy, whereas none occurred in those covered by prophylactic therapy (5/20 versus 0/29, p=0.0081). CONCLUSIONS: The prevalence of neurological complications in hemophiliacs in our cohort is similar to other studies. Similar to CNS, prophylactic therapy also reduces the risk of PNS complications. This is the first report in the literature showing this benefit.

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