Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG. OBJECTIVE: This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG. METHODS: This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile. RESULTS: The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment. CONCLUSION: Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups.

ANTECEDENTES: A Miastenia gravis (MG) é uma desordem autoimune geralmente causada por anticorpos antirreceptores de acetilcolina (anti-RACh), tirosina quinase músculo-específica (anti-MuSK) ou proteína 4 relacionada ao receptor de lipoproteína de baixa densidade (anti-LRP4). No entanto, em uma parcela dos pacientes, nenhum destes três anticorpos pôde ser detectado, sendo estes casos denominados "triplo-soronegativos". OBJETIVO: Descrever a frequência, bem como as características clínicas e epidemiológicas dos pacientes com MG triplo-soronegativa. MéTODOS: Consiste em um estudo transversal e restrospectivo, realizado através da análise de prontuários médicos. Foi realizada análise estatística descritiva e analítica entre os subgrupos de pacientes, classificados de acordo com o perfil sorológico. RESULTADOS: A população consistiu de 93 pacientes com MG: 85 pacientes apresentavam positividade para anticorpos, sendo 80 (86%) com anticorpos anti-RACh, cinco (5,4%) com anti-MuSK, e não foram encontrados pacientes com anti-LRP4. Oito (8,6%) eram pacientes triplo-soronegativos, que apresentaram idade média de início da doença de 30 anos (21-45), e com sintomas iniciais mais comuns de ptose, diplopia e fraqueza generalizada. 75% dos pacientes triplo-soronegativos apresentaram resposta adequada ao tratamento. CONCLUSãO: O estudo demonstrou uma baixa frequência da pacientes com MG triplo-soronegativa na população brasileira. A MG triplo-soronegativa foi predominante nas mulheres, que se apresentaram com ptose, diplopia ou fraqueza generalizada, e a maioria dos pacientes apresentou resposta adequada ao tratamento imunossupressor. Não houve diferença significativa entre a MG triplo-soronegativa e os demais subgrupos.

Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil.

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive inherited disorder related to lipid metabolism affecting skeletal muscle. The first cases of CPT II deficiency causing myopathy were reported in 1973. In 1983, Werneck et al published the first two Brazilian patients with myopathy due to CPT II deficiency, where the biochemical analysis confirmed deficient CPT activity in the muscle of both cases. Over the past 40 years since the pioneering publication, clinical phenotypes and genetic loci in the CPT2 gene have been described, and pathogenic mechanisms have been better elucidated. Genetic analysis of one of the original cases disclosed compound heterozygous pathogenic variants (p.Ser113Leu/p.Pro50His) in the CPT2 gene. Our report highlights the historical aspects of the first Brazilian publication of the myopathic form of CPT II deficiency and updates the genetic background of this pioneering publication.

Deficiência de carnitina palmitoiltransferase II (CPT II) é uma desordem de herança autossômica recessiva relacionada com o metabolismo do lipídio afetando músculo esquelético. Os primeiros dois casos de deficiência de CPT II causando miopatia foram relatados em 1973. Em 1983, Werneck et al. publicaram os primeiros pacientes brasileiros com miopatia por deficiência de CPT II, nos quais a análise bioquímica confirmou a atividade deficiente da CPT nos músculos em ambos os casos. Após 40 anos desde a publicação pioneira, fenótipos clínicos e loci genético no gene CPT2 foram descritos, bem com os mecanismos patológicos foram melhor elucidados. A análise genética de um dos casos da publicação original apresentou variantes patogênicas em heterozigose composta (p.Ser113Leu/p.Pro50His) no gene CPT2. O nosso relato destaca os aspectos históricos da primeira publicação brasileira da forma miopática da deficiência de CPT II e atualiza as bases genéticas dessa publicação pioneira.

Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics / Miastenia gravis triplo-soronegativa: características clínicas e epidemiológicas

Abstract Background Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG. Objective This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG. Methods This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile. Results The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment. Conclusion Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups.

Resumo Antecedentes A Miastenia gravis (MG) é uma desordem autoimune geralmente causada por anticorpos antirreceptores de acetilcolina (anti-RACh), tirosina quinase músculo-específica (anti-MuSK) ou proteína 4 relacionada ao receptor de lipoproteína de baixa densidade (anti-LRP4). No entanto, em uma parcela dos pacientes, nenhum destes três anticorpos pôde ser detectado, sendo estes casos denominados "triplo-soronegativos". Objetivo Descrever a frequência, bem como as características clínicas e epidemiológicas dos pacientes com MG triplo-soronegativa. Métodos Consiste em um estudo transversal e restrospectivo, realizado através da análise de prontuários médicos. Foi realizada análise estatística descritiva e analítica entre os subgrupos de pacientes, classificados de acordo com o perfil sorológico. Resultados A população consistiu de 93 pacientes com MG: 85 pacientes apresentavam positividade para anticorpos, sendo 80 (86%) com anticorpos anti-RACh, cinco (5,4%) com anti-MuSK, e não foram encontrados pacientes com anti-LRP4. Oito (8,6%) eram pacientes triplo-soronegativos, que apresentaram idade média de início da doença de 30 anos (21-45), e com sintomas iniciais mais comuns de ptose, diplopia e fraqueza generalizada. 75% dos pacientes triplo-soronegativos apresentaram resposta adequada ao tratamento. Conclusão O estudo demonstrou uma baixa frequência da pacientes com MG triplo-soronegativa na população brasileira. A MG triplo-soronegativa foi predominante nas mulheres, que se apresentaram com ptose, diplopia ou fraqueza generalizada, e a maioria dos pacientes apresentou resposta adequada ao tratamento imunossupressor. Não houve diferença significativa entre a MG triplo-soronegativa e os demais subgrupos.

Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil / Miopatia por deficiência de carnitina palmitoiltransferase II: atualizando os aspectos genéticos da primeira publicação no Brasil

Abstract Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive inherited disorder related to lipid metabolism affecting skeletal muscle. The first cases of CPT II deficiency causing myopathy were reported in 1973. In 1983, Werneck et al published the first two Brazilian patients with myopathy due to CPT II deficiency, where the biochemical analysis confirmed deficient CPT activity in the muscle of both cases. Over the past 40 years since the pioneering publication, clinical phenotypes and genetic loci in the CPT2 gene have been described, and pathogenic mechanisms have been better elucidated. Genetic analysis of one of the original cases disclosed compound heterozygous pathogenic variants (p.Ser113Leu/p.Pro50His) in the CPT2 gene. Our report highlights the historical aspects of the first Brazilian publication of the myopathic form of CPT II deficiency and updates the genetic background of this pioneering publication.

Resumo Deficiência de carnitina palmitoiltransferase II (CPT II) é uma desordem de herança autossômica recessiva relacionada com o metabolismo do lipídio afetando músculo esquelético. Os primeiros dois casos de deficiência de CPT II causando miopatia foram relatados em 1973. Em 1983, Werneck et al. publicaram os primeiros pacientes brasileiros com miopatia por deficiência de CPT II, nos quais a análise bioquímica confirmou a atividade deficiente da CPT nos músculos em ambos os casos. Após 40 anos desde a publicação pioneira, fenótipos clínicos e loci genético no gene CPT2 foram descritos, bem com os mecanismos patológicos foram melhor elucidados. A análise genética de um dos casos da publicação original apresentou variantes patogênicas em heterozigose composta (p.Ser113Leu/p.Pro50His) no gene CPT2. O nosso relato destaca os aspectos históricos da primeira publicação brasileira da forma miopática da deficiência de CPT II e atualiza as bases genéticas dessa publicação pioneira.

Brain abscesses caused by Listeria monocytogenes in a patient with myasthenia gravis - Case report and systematic review.

Background: Listeriosis is a known cause of community acquired bacterial meningitis/meningoencephalitis. It occurs more frequently in neonates, older people and immunocompromised hosts. Rarely, brain abscesses can complicate the course of infection, which poses a difficulty in the management and elevates morbidity and mortality. Myasthenia gravis is an autoimmune disease that often requires immunosuppressive treatment, which increases the risk for invasive infections. Case description: A 75-year-old myasthenic patient, treated with prednisone and pyridostigmine, was diagnosed with invasive listeriosis. He presented with muscle weakness, dyspnea, hemiparesis and altered mental status. Brain imaging revealed multiple abscesses and blood cultures were positive for Listeria monocytogenes. Despite combination antibiotic therapy, he died 6 weeks after admission. Systematic review: Ninety-six cases of brain abscesses from 1968 to 2023 were reviewed; the majority of the patients were men, 54 years-old on average, and had at least one risk factor for invasive listeriosis. The mortality exceeded 22%. Blood cultures and CSF/abscess cultures were positive in only 79.2% and 54.6%, respectively. The most common therapeutic approach was a combination regimen that included amoxicillin or ampicillin. Only 8 patients underwent surgery, of which one died. Conclusion: This case highlights the importance of L. monocytogenes as a cause of brain abscesses in populations at risk, including myasthenic patients. The challenge of diagnosing and treating this condition is aggravated by the paucity of literature and the high mortality rate.

Single-centre experience with autosomal recessive limb-girdle muscular dystrophy: case series and literature review.

Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations. The aim of the present study was to analyze a series of patients with autosomal recessive LGMD (LGMD-R) to contribute to a better characterization of the disease and to find the relative proportion of the different subtypes in a Southern Brazil cohort. The sample population consisted of 36 patients with LGMD-R. A 9-gene targeted next-generation sequencing panel revealed variants in 23 patients with LGMD (64%), and it identified calpainopathy (LGMD-R1) in 26%, dysferlinopathy (LGMD-R2) in 26%, sarcoglycanopathies (LGMD-R3-R5) in 13%, telethoninopathy (LGMD-R7) in 18%, dystroglicanopathy (LGMD-R9) in 13%, and anoctaminopathy (LGMD-R12) in 4% of the patients. In these 23 patients with LGMD, there were 27 different disease-related variants in the ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG, and TCAP genes. There were different causal variants in different exons of these genes, except for the TCAP gene, for which all patients carried the p.Gln53* variant, and the FKRP gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort.

A distrofia muscular de cinturas (DMC) é um grupo de miopatias que leva à fraqueza muscular progressiva, e envolvendo predominante as cinturas escapular e pélvica. A DMCtem uma etiologia genética heterogênea, com variação na prevalência de subtipos de acordo com as origens étnicas e geográficas das populações. O objetivo deste estudo foi analisar uma série de pacientes com DMC do tipo autossômico recessivo (DMC-R) para contribuir para uma melhor caracterização da doença e encontrar a proporção relativa dos diferentes subtipos em uma coorte do Sul do Brasil. A população amostral foi composta por 36 pacientes com DMC-R. O painel de sequenciamento de nova geração com 9 genes revelou variantes em 23 pacientes com DMC (64%), e identificou calpainopatia (DMC-R1) em 26%, disferlinopatia (DMC-R2) em 26%, sarcoglicanopatias (DMC-R3­R5) em 13%, teletoninopatia (D-MCR7) em 18%, distroglicanopatia (D-MCR9) em 13%, e anoctaminopatia (DMC-R12) em 4% dos pacientes. Nesses 23 pacientes com DMC, havia 27 variantes diferentes nos genes ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG e TCAP. Foram encontradas diferentes variantes em diferentes éxons desses genes, com exceção do gene TCAP, para o qual todos os pacientes eram portadores da variante p.Gln53*, e do gene FKRP, que apresentou recorrência da variante p.Leu276Ile. As características fenotípicas, genotípicas e imuno-histoquímicas musculares desta coorte do Sul do Brasil foram analisadas.

Spectrum of SPTLC1-related disorders: a novel case of 'Ser331 syndrome' that expand the phenotype of hereditary sensory and autonomic neuropathy type 1A and motor neuron diseases.

We report a patient with early-onset hereditary sensory and autonomic neuropathy type 1A (HSAN-1A) who developed a distinct phenotype, with tongue fasciculation and atrophy, due to a mutation at serine 331 in the SPTLC1 gene. HSAN-1A manifestation causing tongue fasciculation and atrophy have been rarely found. Our report adds to the growing evidence of the existence of an overlap between hereditary neuropathy and motor neuron disease caused by pathogenic p.S331Y variant in SPTLC1 gene.

Single-centre experience with autosomal recessive limb-girdle muscular dystrophy: case series and literature review / Experiência de um único centro em distrofia muscular de cinturas do tipo autossômica recessiva: série de casos e revisão de literatura

Abstract Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations. The aim of the present study was to analyze a series of patients with autosomal recessive LGMD (LGMD-R) to contribute to a better characterization of the disease and to find the relative proportion of the different subtypes in a Southern Brazil cohort. The sample population consisted of 36 patients with LGMD-R. A 9-gene targeted next-generation sequencing panel revealed variants in 23 patients with LGMD (64%), and it identified calpainopathy (LGMD-R1) in 26%, dysferlinopathy (LGMD-R2) in 26%, sarcoglycanopathies (LGMD-R3-R5) in 13%, telethoninopathy (LGMD-R7) in 18%, dystroglicanopathy (LGMD-R9) in 13%, and anoctaminopathy (LGMD-R12) in 4% of the patients. In these 23 patients with LGMD, there were 27 different disease-related variants in the ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG, and TCAP genes. There were different causal variants in different exons of these genes, except for the TCAP gene, for which all patients carried the p.Gln53* variant, and the FKRP gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort.

Resumo A distrofia muscular de cinturas (DMC) é um grupo de miopatias que leva à fraqueza muscular progressiva, e envolvendo predominante as cinturas escapular e pélvica. A DMCtem uma etiologia genética heterogênea, com variação na prevalência de subtipos de acordo com as origens étnicas e geográficas das populações. O objetivo deste estudo foi analisar uma série de pacientes com DMC do tipo autossômico recessivo (DMC-R) para contribuir para uma melhor caracterização da doença e encontrar a proporção relativa dos diferentes subtipos em uma coorte do Sul do Brasil. A população amostral foi composta por 36 pacientes com DMC-R. O painel de sequenciamento de nova geração com 9 genes revelou variantes em 23 pacientes com DMC (64%), e identificou calpainopatia (DMC-R1) em 26%, disferlinopatia (DMC-R2) em 26%, sarcoglicanopatias (DMC-R3-R5) em 13%, teletoninopatia (D-MCR7) em 18%, distroglicanopatia (D-MCR9) em 13%, e anoctaminopatia (DMC-R12) em 4% dos pacientes. Nesses 23 pacientes com DMC, havia 27 variantes diferentes nos genes ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG e TCAP. Foram encontradas diferentes variantes em diferentes éxons desses genes, com exceção do gene TCAP, para o qual todos os pacientes eram portadores da variante p.Gln53*, e do gene FKRP, que apresentou recorrência da variante p.Leu276Ile. As características fenotípicas, genotípicas e imuno-histoquímicas musculares desta coorte do Sul do Brasil foram analisadas.

Stroke-related mortality analysis in Paraná, Brazil, over 10 years.

BACKGROUND: Stroke is the second leading cause of death and disability around the world. OBJECTIVE: The purpose of this study is to evaluate the age- and sex-specific mortality rates related to stroke in the state of Paraná, Brazil, between 2007 and 2016. METHODS: In this cross-sectional study, residents in the state of Paraná were selected by death certificates (from 2007-2016); the basic cause of death was stroke. A descriptive analysis was performed, and mortality rates were calculated with a 95% confidence interval (95% CI) for each year. RESULTS: From 2007 to 2016, there were 62,607 deaths in the state of Paraná due to stroke. Most individuals had medical assistance before death (85.7% in 2007 versus 83.9% in 2016), and most of these deaths occurred in hospitals (73.6% in 2007 versus 74.8% in 2016). Death rates due to stroke increased from 138 (95% CI 135-142) to 163 (95% CI 159-166) per 100,000 inhabitants. This raise occurred mainly in those over 79 years old. For the ages groups of 34 to 44 and 44 to 54 years, mortality rate decreased. CONCLUSIONS: In the past 15 years, despite the advances in the diagnosis and treatment of stroke, there has been an increase in mortality due to stroke in the state of Paraná. This fact is possibly associated with the aging of the population because there was a more pronounced increase in the group over 79 years old. Thus, new health strategies are necessary to improve the survival and quality of life of poststroke individuals.

ANTECEDENTES: O acidente vascular cerebral (AVC) é a segunda principal causa de morte e invalidez em todo o mundo. OBJETIVO: O objetivo desse estudo é avaliar as taxas de mortalidade específicas por idade e sexo relacionadas ao AVC no estado do Paraná, Brasil, entre 2007 e 2016. MéTODOS: Neste estudo transversal, foram selecionados residentes no estado do Paraná por certidões de óbito (de 2007­2016); a causa básica da morte foi AVC. Uma análise descritiva foi realizada e as taxas de mortalidade calculadas com intervalo de confiança de 95% (IC 95%) para cada ano. RESULTADOS: De 2007 a 2016, ocorreram 62.607 óbitos no estado do Paraná por AVC. A maioria dos indivíduos teve assistência médica antes do óbito (85,7% em 2007 contra 83,9% em 2016), e a maioria desses óbitos ocorreu em hospitais (73,6% em 2007 contra 74,8% em 2016). As taxas de mortalidade por AVC aumentaram de 138 (IC 95% 135­142) para 163 (IC 95% 159­166) por 100.000 habitantes. Esse aumento ocorreu principalmente em maiores de 79 anos. Para as faixas etárias de 34 a 44 e 44 a 54 anos, a taxa de mortalidade diminuiu. CONCLUSõES: Nos últimos 15 anos, apesar dos avanços no diagnóstico e tratamento do AVC, houve aumento da mortalidade no estado do Paraná. Este fato está possivelmente associado ao envelhecimento da população, pois houve um aumento mais acentuado no grupo acima de 79 anos. Assim, novas estratégias de saúde são necessárias para melhorar a sobrevida e a qualidade de vida dos indivíduos pós-AVC.

Stroke-related mortality analysis in Paraná, Brazil, over 10 years / Análise da mortalidade relacionada ao acidente vascular cerebral no estado do Paraná, Brasil, ao longo de 10 anos

Abstract Background Stroke is the second leading cause of death and disability around the world. Objective The purpose of this study is to evaluate the age- and sex-specific mortality rates related to stroke in the state of Paraná, Brazil, between 2007 and 2016. Methods In this cross-sectional study, residents in the state of Paraná were selected by death certificates (from 2007-2016); the basic cause of death was stroke. A descriptive analysis was performed, and mortality rates were calculated with a 95% confidence interval (95% CI) for each year. Results From 2007 to 2016, there were 62,607 deaths in the state of Paraná due to stroke. Most individuals had medical assistance before death (85.7% in 2007 versus 83.9% in 2016), and most of these deaths occurred in hospitals (73.6% in 2007 versus 74.8% in 2016). Death rates due to stroke increased from 138 (95% CI 135-142) to 163 (95% CI 159-166) per 100,000 inhabitants. This raise occurred mainly in those over 79 years old. For the ages groups of 34 to 44 and 44 to 54 years, mortality rate decreased. Conclusions In the past 15 years, despite the advances in the diagnosis and treatment of stroke, there has been an increase in mortality due to stroke in the state of Paraná. This fact is possibly associated with the aging of the population because there was a more pronounced increase in the group over 79 years old. Thus, new health strategies are necessary to improve the survival and quality of life of poststroke individuals.

Resumo Antecedentes O acidente vascular cerebral (AVC) é a segunda principal causa de morte e invalidez em todo o mundo. Objetivo O objetivo desse estudo é avaliar as taxas de mortalidade específicas por idade e sexo relacionadas ao AVC no estado do Paraná, Brasil, entre 2007 e 2016. Métodos Neste estudo transversal, foram selecionados residentes no estado do Paraná por certidões de óbito (de 2007-2016); a causa básica da morte foi AVC. Uma análise descritiva foi realizada e as taxas de mortalidade calculadas com intervalo de confiança de 95% (IC 95%) para cada ano. Resultados De 2007 a 2016, ocorreram 62.607 óbitos no estado do Paraná por AVC. A maioria dos indivíduos teve assistência médica antes do óbito (85,7% em 2007 contra 83,9% em 2016), e a maioria desses óbitos ocorreu em hospitais (73,6% em 2007 contra 74,8% em 2016). As taxas de mortalidade por AVC aumentaram de 138 (IC 95% 135-142) para 163 (IC 95% 159-166) por 100.000 habitantes. Esse aumento ocorreu principalmente em maiores de 79 anos. Para as faixas etárias de 34 a 44 e 44 a 54 anos, a taxa de mortalidade diminuiu. Conclusões Nos últimos 15 anos, apesar dos avanços no diagnóstico e tratamento do AVC, houve aumento da mortalidade no estado do Paraná. Este fato está possivelmente associado ao envelhecimento da população, pois houve um aumento mais acentuado no grupo acima de 79 anos. Assim, novas estratégias de saúde são necessárias para melhorar a sobrevida e a qualidade de vida dos indivíduos pós-AVC.

Store-and-forward teleneurology results in a large Brazilian city.

BACKGROUND: Neurology is a high-demand specialty with long waiting lines. Some pathologies require rapid decision-making. Through technology, telemedicine can allow neurological patients to have faster access to specialized assessment. In store-and-forward telemedicine, the specialist physician evaluates data collected by a general practitioner and optimizes screening. OBJECTIVE: The aim of the present study is to evaluate the effectiveness of asynchronous telemedicine, used to refer patients from primary care to neurology, in the city of Curitiba, in southern Brazil. METHODS: A retrospective analysis of all patients referred from primary care to neurology between September 2019 and February 2020. After a request is made by a general medical doctor for a specialist's opinion, 5 neurologists with complete access to patients' records are tasked with the decision-making. The main variables analyzed were clinical reasons for telemedicine request, neurologist decision, final diagnosis, indication for diagnostic procedures, and subsequent follow-up. RESULTS: Between September 2019 and February 2020, 1,035 asynchronous telemedicine consultations were performed. Headache (30.43%), epilepsy (19.03%), and dementia (15.85%) accounted for almost two-thirds of the primary care requests; one-third of the cases (33.62%) required a complementary diagnostic procedure. More than 70% of the cases did not require face-to-face assessment by a neurologist. CONCLUSIONS: In this study, store-and-forward teleneurology successfully reduced the need for in-visit consultation in 70% of cases. Further studies should identify the best opportunities for teleneurology in the city of Curitiba to facilitate better integrated care between primary care providers and neurologists.

ANTECEDENTES: Neurologia é uma especialidade de alta demanda com grandes filas de espera. Algumas doenças necessitam de rapidez na tomada de decisões. A telemedicina permite que pacientes neurológicos tenham acesso mais rápido à avaliação especializada. Na telerregulação, um ramo da telemedicina, o especialista avalia os dados coletados pelo generalista e otimiza a triagem. OBJETIVO: Avaliar a eficácia da telerregulação assíncrona, usada para referenciar pacientes da atenção primária à neurologia, na cidade de Curitiba, no sul do Brasil. MéTODOS: Análise retrospectiva de todos os pacientes referenciados da atenção primária para a especialidade de neurologia, no período entre setembro de 2019 e fevereiro de 2020, em Curitiba, Brasil. Para cada pedido de avaliação do médico generalista, 5 neurologistas experientes tiveram acesso completo ao prontuário para a tomada de decisão. As variáveis analisadas foram: razões para o referenciamento, decisão do especialista, diagnóstico final, indicação de exame complementar e necessidade de acompanhamento com a especialidade. RESULTADOS: Durante o período de estudo, 1.035 telerregulações foram realizadas. Cefaleia (30.43%), epilepsia (19.03%) e demência (15.85%) compreenderam aproximadamente dois terços de todos os pedidos de consulta; para um terço dos casos, o especialista indicou exame complementar. Mais de 70% dos pacientes não necessitaram de consulta presencial com neurologista. CONCLUSõES: A telerregulação assíncrona diminuiu de forma importante a necessidade de avaliação presencial pelo neurologista em 70% dos casos. Através da tecnologia, é possível conseguir melhor integração entre atenção primária e serviços especializados. Ainda são necessários mais estudos para explorar as janelas de oportunidade para a teleneurologia no Brasil.

Store-and-forward teleneurology results in a large Brazilian city / Telerregulação em neurologia e seus resultados em uma grande cidade brasileira

Abstract Background Neurology is a high-demand specialty with long waiting lines. Some pathologies require rapid decision-making. Through technology, telemedicine can allow neurological patients to have faster access to specialized assessment. In store-and-forward telemedicine, the specialist physician evaluates data collected by a general practitioner and optimizes screening. Objective The aim of the present study is to evaluate the effectiveness of asynchronous telemedicine, used to refer patients from primary care to neurology, in the city of Curitiba, in southern Brazil. Methods A retrospective analysis of all patients referred from primary care to neurology between September 2019 and February 2020. After a request is made by a general medical doctor for a specialist's opinion, 5 neurologists with complete access to patients' records are tasked with the decision-making. The main variables analyzed were clinical reasons for telemedicine request, neurologist decision, final diagnosis, indication for diagnostic procedures, and subsequent follow-up. Results Between September 2019 and February 2020, 1,035 asynchronous telemedicine consultations were performed. Headache (30.43%), epilepsy (19.03%), and dementia (15.85%) accounted for almost two-thirds of the primary care requests; one-third of the cases (33.62%) required a complementary diagnostic procedure. More than 70% of the cases did not require face-to-face assessment by a neurologist. Conclusions In this study, store-and-forward teleneurology successfully reduced the need for in-visit consultation in 70% of cases. Further studies should identify the best opportunities for teleneurology in the city of Curitiba to facilitate better integrated care between primary care providers and neurologists.

Resumo Antecedentes Neurologia é uma especialidade de alta demanda com grandes filas de espera. Algumas doenças necessitam de rapidez na tomada de decisões. A telemedicina permite que pacientes neurológicos tenham acesso mais rápido à avaliação especializada. Na telerregulação, um ramo da telemedicina, o especialista avalia os dados coletados pelo generalista e otimiza a triagem. Objetivo Avaliar a eficácia da telerregulação assíncrona, usada para referenciar pacientes da atenção primária à neurologia, na cidade de Curitiba, no sul do Brasil. Métodos Análise retrospectiva de todos os pacientes referenciados da atenção primária para a especialidade de neurologia, no período entre setembro de 2019 e fevereiro de 2020, em Curitiba, Brasil. Para cada pedido de avaliação do médico generalista, 5 neurologistas experientes tiveram acesso completo ao prontuário para a tomada de decisão. As variáveis analisadas foram: razões para o referenciamento, decisão do especialista, diagnóstico final, indicação de exame complementar e necessidade de acompanhamento com a especialidade. Resultados Durante o período de estudo, 1.035 telerregulações foram realizadas. Cefaleia (30.43%), epilepsia (19.03%) e demência (15.85%) compreenderam aproximadamente dois terços de todos os pedidos de consulta; para um terço dos casos, o especialista indicou exame complementar. Mais de 70% dos pacientes não necessitaram de consulta presencial com neurologista. Conclusões A telerregulação assíncrona diminuiu de forma importante a necessidade de avaliação presencial pelo neurologista em 70% dos casos. Através da tecnologia, é possível conseguir melhor integração entre atenção primária e serviços especializados. Ainda são necessários mais estudos para explorar as janelas de oportunidade para a teleneurologia no Brasil.

Seventy years since the invention of the averaging technique in Neurophysiology: Tribute to George Duncan Dawson / 70 anos da invenção da técnica de promediação na Neurofisiologia: Tributo a George Duncan Dawson

ABSTRACT In 1951, the physiologist George Duncan Dawson presented his work with the averaging of the signal in the evoked potentials (EPs), opening a new stage in the development of clinical neurophysiology. The authors present aspects of Professor Dawson's biography and a review of his work on the EPs and, mainly, the article reveals the new technique in detail that would allow the growth of the clinical application of the visual, auditory, and somatosensory EPs.

RESUMO Em 1951 o fisiologista George Duncan Dawson apresentou seu trabalho com a promediação de sinal nos potenciais evocados, abrindo uma nova etapa no desenvolvimento da neurofisiologia clínica. Os autores apresentam aspectos da biografia do professor Dawson e uma revisão de seus trabalhos sobre os potenciais evocados, principalmente do artigo que mostrava a nova técnica, que viria a permitir o crescimento da aplicação clínica dos potenciais evocados visual, auditivo e somatossensitivo.

Congenital myasthenic syndrome in a cohort of patients with 'double' seronegative myasthenia gravis / Síndrome miastênica congênita em uma série de pacientes com miastenia gravis duplo soronegativa

ABSTRACT Background: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG). Objective: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort. Methods: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool. Results: We performed genetic analysis in 22 patients with a previous diagnosis of 'double' SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe). Conclusions: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in 'double' SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with 'double' SNMG in whom differential diagnosis is recommended.

RESUMO Antecedentes: As síndromes miastênicas congênitas (SMC) podem ter sobreposição fenotípica com a miastenia gravis soronegativa (MG-SN). Objetivo: Estabelecer a prevalência mínima de SMC diagnosticada inicialmente como MG duplo soronegativa em uma série de casos brasileiros. Métodos: A análise genética das mutações mais comuns nos genes CHRNE, RAPSN e DOK7 foi usada como o principal exame de triagem. Resultados: Vinte e dois pacientes com diagnóstico prévio de MG-SN foram geneticamente analisados, sendo que uma paciente foi confirmada com SMC devido a presença de variante em heterozigose composta no gene CHRNE (c.130insG/p.Cys210Phe). Conclusões: O presente estudo confirma que SMC devido mutação no gene CHNRE pode ser inicialmente diagnosticada como MG-SN. O estudo estimou como 4,5% a prevalência de diagnóstico de SMC entre nossos pacientes préviamente diagnosticados como MG-SN. Com base nesse estudo, a análise genética pode ser recomendada para investigação do diagnóstico diferencial em pacientes com MG-SN.

Seventy years since the invention of the averaging technique in Neurophysiology: Tribute to George Duncan Dawson.

OBJECTIVE: In 1951, the physiologist George Duncan Dawson presented his work with the averaging of the signal in the evoked potentials (EPs), opening a new stage in the development of clinical neurophysiology. The authors present aspects of Professor Dawson's biography and a review of his work on the EPs and, mainly, the article reveals the new technique in detail that would allow the growth of the clinical application of the visual, auditory, and somatosensory EPs.

Congenital myasthenic syndrome in a cohort of patients with 'double' seronegative myasthenia gravis.

BACKGROUND: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG). OBJECTIVE: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort. METHODS: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool. RESULTS: We performed genetic analysis in 22 patients with a previous diagnosis of 'double' SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe). CONCLUSIONS: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in 'double' SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with 'double' SNMG in whom differential diagnosis is recommended.

Peripheral polyneuropathy from electrodiagnostic tests: a 10-year etiology and neurophysiology overview.

BACKGROUND: Polyneuropathies are characterized by a symmetrical impairment of the peripheral nervous system, resulting in sensory, motor and/or autonomic deficits. Due to the heterogeneity of causes, an etiological diagnosis for polyneuropathy is challenging. OBJECTIVE: The aim of this study was to determine the main causes of polyneuropathy confirmed by electrodiagnostic (EDX) tests in a tertiary service and its neurophysiological aspects. METHODS: This observational cross-sectional study from a neuromuscular disorders center included individuals whose electrodiagnostic tests performed between 2008 and 2017 confirmed a diagnosis of polyneuropathy. Through analysis of medical records, polyneuropathies were classified according to etiology and neurophysiological aspect. RESULTS: Of the 380 included patients, 59.5% were male, with a median age of 43 years. The main etiologies were: inflammatory (23.7%), hereditary (18.9%), idiopathic (13.7%), multifactorial (11.1%), and diabetes (10.8%). The main electrophysiological patterns were axonal sensorimotor polyneuropathy (36.1%) and "demyelinating and axonal" sensorimotor polyneuropathy (27.9%). Axonal patterns showed greater etiological heterogeneity, with a predominance of idiopathic and multifactorial polyneuropathy, while demyelinating and "demyelinating and axonal" polyneuropathies had a significantly fewer etiologies, with a predominance of hereditary and inflammatory polyneuropathies. CONCLUSION: The main causes of polyneuropathy confirmed by EDX test in this study were those that presented a severe, atypical and/or rapidly progressing pattern. Other causes were hereditary and those that defy clinical reasoning, such as multiple risk factors; some polyneuropathies did not have a specific etiology. EDX tests are useful for etiological diagnosis of rare polyneuropathies, because neurophysiological patterns are correlated with specific etiologies.