The sural-sparing pattern in clinical variants and electrophysiological subtypes of Guillain-Barré syndrome / Padrão de preservação do sural nas variantes clínicas e subtipos eletrofisiológicos da síndrome de Guillain-Barré

Abstract Background Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis worldwide and can be classified into electrophysiological subtypes and clinical variants. Objective This study aimed to compare the frequency of the sural-sparing pattern (SSP) in subtypes and variants of GBS. Methods This retrospective cohort study analyzed clinical and electrophysiological data of 171 patients with GBS hospitalized in public and private hospitals of Natal, Rio Grande do Norte, Brazil, between 1994 and 2018; all cases were followed up by the same neurologist in a reference neurology center. Patients were classified according to electrophysiological subtypes and clinical variants, and the SSP frequency was compared in both categories. The exact Fisher test and Bonferroni correction were used for statistical analysis. Results The SSP was present in 53% (57 of 107) of the patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 8% (4 of 48) of the patients with axonal subtypes, and 31% (5 of 16) of the equivocal cases. The SSP frequency in the AIDP was significantly higher than in the axonal subtypes (p < 0.0001); the value was kept high after serial electrophysiological examinations. Only the paraparetic subtype did not present SSP. Conclusion The SSP may be present in AIDP and axonal subtypes, including acute motor axonal neuropathy, but it is significantly more present in AIDP. Moreover, the clinical variants reflect a specific pathological process and are correlated to its typical electrophysiological subtype, affecting the SSP frequency.

Resumo Antecedentes A síndrome de Guillain-Barré (GBS) é a causa mais comum de paralisia flácida aguda em todo o mundo e pode ser classificada em subtipos eletrofisiológicos e variantes clínicas. Objetivo Este estudo teve como objetivo comparar a frequência do padrão de preservação do sural (SSP) em subtipos e variantes de GBS. Métodos É um estudo de coorte retrospectivo que analisou dados clínicos e eletrofisiológicos de 171 pacientes com GBS internados em hospitais públicos e privados de Natal, Rio Grande do Norte, Brasil, entre 1994 e 2018. Todos os casos foram acompanhados pelo mesmo neurologista em centro de referência em neurologia. Os pacientes foram classificados de acordo com os subtipos eletrofisiológicos e variantes clínicas e a frequência do SSP foi comparada em ambas as categorias. O teste exato de Fisher e a correção de Bonferroni foram utilizados para análise estatística. Resultados O SSP esteve presente em 53% (57 de 107) dos pacientes com polirradiculoneuropatia desmielinizante inflamatória aguda (PDIA), em 8% (4 de 48) dos pacientes com subtipos axonais e em 31% (5 de 16) dos casos não definidos. A frequência do SSP no AIDP foi significativamente maior do que nos subtipos axonais (p < 0,0001); o valor manteve-se elevado após exames eletrofisiológicos seriados. Apenas o subtipo paraparético não apresentou SSP. Conclusão O SSP pode estar presente na PDIA e nos subtipos axonais, incluindo a neuropatia axonal motora aguda, mas está significativamente mais presente na PDIA. Além disso, as variantes clínicas refletem um processo patológico específico e estão correlacionadas ao seu subtipo eletrofisiológico típico, afetando a frequência do SSP.

Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro / Experiência de vida-real com inotersena no CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro

Abstract Background Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype. Objective To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN). Methods Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures. Results Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted. Conclusion The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.

Resumo Antecedentes Amiloidose hereditária por transtirretina (ATTRv) é uma doença hereditária, progressiva e fatal ainda largamente subdiagnosticada. Mutações no gene transtirretina (TTR) promovem desestabilização, desdobramento, agregação e depósito da proteína TTR em tecidos do corpo, o que faz da ATTRv uma doença de fenótipo clínico heterogêneo. Objetivo Descrever a eficácia e segurança da terapia com inotersena no longo prazo em pacientes com neuropatia periférica ATTRv (ATTRv-PN). Métodos Pacientes que completaram o estudo pivotal NEURO-TTR e o estudo de extensão aberta NEURO-TTR OLE migraram para este estudo e foram acompanhados por no mínimo 18 meses adicionais, em média por 67 meses, e por até 76 meses, desde o dia 1 da terapia com inotersena (D1-primeira dose de inotersena). A progressão da doença foi avaliada por medidas padronizadas. Resultados Dez pacientes com ATTRv-PN com mutação Val30Met foram incluídos. A duração média da doença no D1 era de 3 anos, e a média de idade dos pacientes era de 46,8 anos. Durante o período de acompanhamento adicional de 18 meses, a função neurológica, baseada no Neuropathy Impairment Score e no Polyneuropathy Disability Score, os aspectos de funcionalidade (Karnofsky Performance Status), nutricional e cardíacos estavam mantidos. Não se observou nenhum novo sinal de segurança. Conclusão O tratamento com inotersena foi eficaz e bem tolerado por 67 meses em média, e por até 76 meses. Nossos resultados são consistentes com os de estudos maiores de fase III.

Vitaminas B neurotrópicas y neuropatía periférica: estado del arte y acuerdo de expertos / Neurotropic B vitamins and peripheral neuropathy: State of the art and agreement of experts

Propósito: La neuropatía periférica tiene un espectro clínico inespecífico y multifactorial, con frecuente subdiagnóstico y terapéutica de eficacia variable. Existe una heterogénea prescripción de vitaminas B, las cuales pueden desempeñar un rol importante en el manejo de diferentes neuropatías; sin embargo, en Colombia no existen guías clínicas al respecto. El propósito de este trabajo es orientar en el reconocimiento temprano de las neuropatías periféricas y generar recomendaciones sobre el uso adecuado de vitaminas B neurotrópicas. Descripción de la metodología: Acuerdo de expertos sobre la neuropatía periférica y el rol terapéutico de las vitaminas B con énfasis en la epidemiología en Colombia, diagnóstico y tratamiento. Contenidos: En Colombia, la prevalencia de neuropatía periférica se estima cercana al 10 %, sin embargo, no hay datos recientes. Dentro de las etiologías más frecuentes se encuentran la neuropatía diabética, infecciosa, inflamatoria, carenciales, toxica y farmacológica. Se recomiendan las siguientes herramientas de tamizaje en población de riesgo: DN4, MNSI, test de monofilamento, test de vibración y valoración de reflejos. Las vitaminas B1, B6 y B12 son seguras, accesibles y pueden ser eficaces en neuropatía periférica, incluso cuando el déficit no ha sido demostrado, pero con requerimientos particulares en su administración conjunta. Conclusiones: Las neuropatías periféricas son un reto diagnóstico y terapéutico que requiere la identificación oportuna para el tratamiento de la etiología subyacente y el control de síntomas. El uso de vitaminas B neurotrópicas es efectivo y seguro en neuropatía periférica carencial, y también parece ser eficaz en el manejo de neuropatías periféricas de diferentes etiologías.

Purpose: Peripheral neuropathy has a nonspecific and multifactorial clinical spectrum, with frequent underdiagnosis and therapeutics of variable efficacy. There is a high but heterogeneous prescription of B vitamins, which can play an important role in the management of different neuropathies; however, in Colombia there are no clinical guidelines in this regard. The purpose of this article is to guide the early recognition of peripheral neuropathy and generate recommendations on the proper use of neurotropic B vitamins. Description of the methodology: Expert agreement on peripheral neuropathy and the therapeutic role of B vitamins with emphasis on epidemiology in Colombia, diagnosis and treatment. Contents: In Colombia, there are no recent data to estimate the prevalence of peripheral neuropathy; the main etiologies are: diabetes mellitus, nutritional deficiencies, herpes zoster and neuropathies due to chemotherapy. Given risk factors in the anamnesis, the use of DN4, MNSI, monofilament test, vibration test and assessment of reflexes is recommended. Vitamins B1, B6, and B12 are safe and can be effective in peripheral neuropathy, even when the deficit has not been demonstrated, but with special requirements in their joint administration. Conclusions: peripheral neuropathies are a diagnostic and therapeutic challenge, and require timely identification, for the treatment of the underlying etiology and symptom control. The use of neurotropic B vitamins is effective and safe in deficient peripheral neuropathy, and also appears to be effective in the management of peripheral neuropathies of different etiologies.

Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition / Consenso brasileiro para o diagnóstico, manejo e tratamento da polineuropatia amiloidótica familiar associada à transtirretina: segunda edição

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.

Profile of neurological disorders in a tertiary center of education in orthopedics / Perfil de diagnósticos neurológicos em um centro terciário de ensino em ortopedia

Abstract Background Neurological conditions can cause secondary orthopedic disorders and can result from orthopedic surgical procedures. In addition, misdiagnosis and overtreatment involve both specialties. Epidemiological studies of neurological patients in tertiary units are often performed in emergency departments of general hospitals or rehabilitation centers. Objective Describe the clinical and epidemiologic profile of neurological disorders in a Brazilian federal tertiary center and education hospital in orthopedics in Rio de Janeiro. Methods We performed a retrospective study of the medical records of patients attended by neurology specialists of the internal medicine's department of the National Institute of Traumatology and Orthopedics from February 2014 to March 2020. Results We reviewed neurological referrals in the medical records of 1,349 patients in the period. The mean age of patients was 49.67 years (standard deviation [SD] ± 18.99). There was a predominance of females, corresponding to 751 (55.7%) patients. Regarding ethnicity, 684 (50.7%) participants were white, 550 (40.8%) non-white, and 115 (8.5%) non-classified. Peripheral neuropathies (34.1%), osteoarticular diseases (10%), epilepsy (8.3%), developmental disorders (7.9%), and neuromuscular diseases (7.3%) were the 5 groups with the largest numbers of cases. Conclusion The sample consisted mostly of females and white individuals, and approximately one third of the cases were of peripheral neuropathies. Epidemiological studies in neurology from tertiary centers of another medical specialty can improve the professional development of both specialties. This interdisciplinary approach can also optimize resources, help avoid misdiagnosis, and reduce disability.

Resumo Antecedentes Condições neurológicas tanto podem causar distúrbios ortopédicos secundários como podem ser consequências de procedimentos cirúrgicos ortopédicos. Além disso, erros de diagnóstico e sobre tratamento também envolvem ambas as especialidades. Estudos epidemiológicos de atendimento neurológico em unidades terciárias de saúde são geralmente realizados em serviços de emergência ou em centros de reabilitação. Objetivo Descrever o perfil clínico e epidemiológico de diagnósticos em neurologia em um centro terciário de saúde no Brasil e hospital de educação em ortopedia no Rio de Janeiro. Métodos Realizamos um estudo retrospectivo com revisão de prontuários dos pacientes atendidos pela neurologia do setor de clínica médica do Instituto Nacional de Traumatologia e Ortopedia no período de fevereiro de 2014 a março de 2020. Resultados Revisamos os prontuários de 1.349 pacientes atendidos pela neurologia no período. A média de idade dos pacientes foi de 49,67 anos (desvio padrão [DP] ± 18,99). Houve predomínio do sexo feminino correspondendo a 751 (55,7%) dos atendimentos. Quanto à etnia, a amostra foi composta de 684 (50,7%) de brancos, 550 (40,8%) de não brancos e 115 (8,5%) de não classificados. Neuropatias periféricas (34,1%), doenças osteoarticulares (10%), epilepsias (8,3%), transtornos do desenvolvimento (7,9%) e doenças neuromusculares (7,3%) corresponderam aos 5 grupos com os maiores números de casos. Conclusão A amostra se constituiu predominante de indivíduos do sexo feminino, brancos, e cerca de um terço dos casos corresponderam às neuropatias periféricas. Estudos de perfil de atendimento neurológico em hospitais terciários de outra especialidade médica podem aperfeiçoar a capacitação de ambos os profissionais. Esta abordagem interdisciplinar também pode otimizar recursos, contribuir para evitar erros diagnósticos e reduzir incapacidades.

Neuromuscular Alterations Associated with COVID-19. A Scientific Literature Review

Introduction: The COVID-19 pandemic has brought short, medium, and long-term consequences on the quality of life of those affected. Among the complications are those related to the involvement of the nervous system and the structures involved in body movement, with sequelae that may be transitory and/or definitive, and require rehabilitation. Objective: Identify the neuromuscular alterations that affect body movement, associated with COVID-19. Material and methods: A search was made for observational works published in the SCOPUS, PubMed, EBSCO, and Nature databases between January 2020 and June 2022 under the PRISMA methodology, to answer the PICO question: what are the neuromuscular alterations that can potentially affect movement, associated with COVID-19? The established filters were type of study, language, age, availability, publication dates. The MeSH terms were SARS-Cov-2, COVID-19, Long Covid, Motor Activity Neuromuscular Diseases, Neurological Disorders, Guillain-Barré Syndrome, Myelitis Transverse, Stroke, Patient, Peripheral Nervous System Diseases. The methodological quality was evaluated according to STROBE and the level of evidence was established according to CEBM. Results: In the first search, 645 articles were identified. 637 were discarded by filters, titles, duplicate abstracts, methodological quality, and level of evidence. There were 8 articles selected for the present review in which neuromuscular alterations of central and peripheral origin were identified, such as myalgias, fatigue, polyneuroradiculopathies, CNS inflammation, among others, with clinical manifestations that affect movement. Conclusion: COVID-19 is a multisystemic disease that can affect the nervous system with symptoms of neuromuscular alterations that compromise body movement.

Introducción: La pandemia por la COVID-19 ha traído consecuencias a corto, mediano y largo plazo sobre la calidad de vida de los afectados. Entre las complicaciones se encuentran aquellas relacionadas con la afectación del sistema nervioso y las estructuras involucradas en el movimiento corporal, con secuelas que pueden ser transitorias y/o definitivas, y requieren rehabilitación Objetivo: Identificar las alteraciones neuromusculares que afectan el movimiento corporal, asociadas a la COVID-19. Material y métodos: Se hizo una búsqueda de trabajos observacionales publicados en las bases de datos SCOPUS, PubMed, EBSCO y Nature entre enero de 2020 y junio de 2022 bajo metodología PRISMA, para dar respuesta a la pregunta PICO: ¿cuáles son las alteraciones neuromusculares que potencialmente pueden afectar el movimiento, asociadas a la COVID-19? Los filtros establecidos fueron tipo de estudio, idioma, edad, disponibilidad y fechas de publicación. Los términos MesH fueron SARS-Cov-2, COVID-19, Long Covid, Motor Activity Neuromuscular Diseases, Neurological Disorders, Guillain-Barré Syndrome, Myelitis Transverse, Stroke, Patient, Peripheral Nervous System Diseases. La calidad metodológica se evaluó según STROBE y el nivel de evidencia se estableció según CEBM. Resultados: En la primera búsqueda se identificaron 645 artículos. Posteriormente se descartaron 637 por filtros, títulos, resúmenes duplicados, calidad metodológica y nivel de evidencia. Así, quedaron seleccionados 8 para la presente revisión, en los cuales se identificaron alteraciones neuromusculares de origen central y periférico, como mialgias, fatiga, polineuroradiculopatías, inflamación del SNC, entre otras, con manifestaciones clínicas que afectan el movimiento. Conclusión: La COVID-19 es una enfermedad multisistémica que puede afectar el sistema nervioso con síntomas de alteraciones neuromusculares que comprometen el movimiento corporal.

Charcot-Marie-Tooth disease: from historical landmarks in Brazil to current care perspectives / Doença de Charcot-Marie-Tooth: dos marcos históricos no Brasil até as perspectivas atuais de cuidado

Abstract Hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease (CMT), traditionally refers to a group of genetic disorders in which neuropathy is the main or sole feature. Its prevalence varies according to different populations studied, with an estimate between 1:2,500 to 1:10,000. Since the identification of PMP22 gene duplication on chromosome 17 by Vance et al., in 1989, more than 100 genes have been related to this group of disorders, and we have seen advances in the care of patients, with identification of associated conditions and better supportive treatments, including clinical and surgical interventions. Also, with discoveries in the field of genetics, including RNA interference and gene editing techniques, new treatment perspectives begin to emerge. In the present work, we report the most import landmarks regarding CMT research in Brazil and provide a comprehensive review on topics such as frequency of different genes associated with CMT in our population, prevalence of pain, impact on pregnancy, respiratory features, and development of new therapies.

Resumo A neuropatia sensitivo-motora hereditária, também conhecida como doença de Charcot-Marie-Tooth (CMT), tradicionalmente se refere a um grupo de doenças genéticas em que a neuropatia é a principal ou única manifestação. Sua prevalência varia de acordo com as diferentes populações estudadas, com estimativa entre 1:2.500 a 1:10.000. Desde a identificação da duplicação do gene PMP22 no cromossomo 17, por Vance et al., em 1989, mais de 100 genes foram relacionados a esse grupo de doenças e temos visto avanços no atendimento aos pacientes, com identificação de condições associadas e melhores tratamentos de suporte, incluindo intervenções clínicas e cirúrgicas. Além disso, com as descobertas no campo da genética, incluindo técnicas de interferência de RNA e de edição genética, novas perspectivas de tratamento começaram a surgir. No presente trabalho, relatamos os marcos mais importantes sobre a pesquisa de CMT no Brasil e fornecemos uma revisão abrangente sobre tópicos como frequência de diferentes genes associados à CMT em nossa população, prevalência de dor, impacto na gravidez, alterações respiratórias e desenvolvimento de novas terapias.

Early and Midterm Outcomes of "No-Touch" Saphenous Vein Grafts in Japanese Institutions.

INTRODUCTION: There have been several attempts to overcome the poor graft patency of saphenous vein grafts. "No-touch" saphenous vein graft (NT-SVG) could be a solution to improve graft patency. We aimed to investigate the early and midterm outcomes of coronary artery bypass grafting (CABG) using NT-SVGs in our hospitals. METHODS: This is a retrospective study of 105 patients who underwent CABG using 130 NT-SVGs between August 2013 and December 2021. NT-SVGs were harvested with about a 5-mm margin of surrounding tissue on both sides of the vein with minimal manipulation. Then, the NT-SVG was dilated by natural arterial pressure without manual distension. After surgery, most of NT-SVGs were assessed by cardiac catheterization or multidetector computed tomography (MDCT) to determine early graft patency. Late graft assessments by MDCT were performed about every five years after surgery. RESULTS: The early graft patency of NT-SVGs was 100% (125/125); however, two cases of graft twisting were found. Both cases spontaneously resolved. Leg wound infections of NT-SVG harvesting site were seen in 6.2% of patients. Peripheral neuropathy of the legs such as skin numbness and tingling were frequently observed, which lasted up to one year, but no more than two years after surgery. The midterm graft patency of NT-SVGs was excellent (five-year patency of NT-SVGs was 95.8%). CONCLUSION: The early and midterm graft patency of NT-SVGs was satisfactory. Although leg wound complications can be seen on the harvesting NT-SVG site, the "no-touch" harvesting technique of SVG could improve graft patency and clinical outcomes of CABG.

Epidural morphine for chronic pain in a patient with peripheral neuropathy and DRESS syndrome. Case report / Morfina peridural para tratamento de dor crônica em paciente com polineuropatia periférica e síndrome DRESS. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Peripheral neuropathy is a rare condition with many etiologies. Common symptoms are numbness, paresthesia, weakness and neuropathic pain. Treatment consists in frst-line agents such as anticonvulsants and some antidepressants. Te aim of this study was to report a case of chronic pain refractory to several therapies in a patient with absolute contraindication to the use of all anticonvulsants and antidepressants drugs. CASE REPORT: Female patient, a 40-year-old treated for trigeminal neuralgia with decompression that developed chronic occipital pain refractory to radiofrequency and onset of transient and bilateral T4 sensory and motor polyneuropathy after viral meningitis. In addition, she showed a severe pharmacodermy (Drug Rash with Eosinophilia and Systemic Symptoms- DRESS Syndrome) after using carbamazepine and other anticonvulsants, as well as allergy to all analgesics and opioids except morphine. Epidural puncture with insertion of a catheter was performed aiming at a 5-day test through intermittent epidural morphine bolus to assess the possibility of morphine pump implantation. CONCLUSION: The test was successful and the patient referred to the neurosurgery team. At the 6-month follow-up after the insertion of the morphine intrathecal pump, the strategy has proven to be efective in controlling pain secondary to polyneuropathy.

RESUMO JUSTIFICATIVA E OBJETIVOS: Neuropatia periférica é uma condição rara, de etiologia multifatorial. Dormência, parestesia, redução de força muscular e dor neuropática são sintomas comuns. O tratamento consiste em uso de anticonvulsivantes e antidepressivos. O objetivo deste estudo foi relatar o caso de dor crônica refratária a diversas terapias de uma paciente com contraindicação absoluta para uso de todos os fármacos anticonvulsivantes e antidepressivos. RELATO DO CASO: Paciente do sexo feminino, 40 anos, com história de neuralgia do trigêmeo abordada previamente com cirurgia, com cefaleia occipital crônica refratária à radiofrequência e polineuropatia bilateral T4 sensorial e motora após meningite viral. No curso do tratamento, apresentou grave farmacodermia (Drug Rash with Eosinophilia and Systemic Symptoms - Síndrome DRESS) após o uso de carbamazepina e outros anticonvulsivantes, além de reação alérgica a todos analgésicos e opioides, exceto morfina. Optou-se por analgesia teste por via peridural, durante 5 dias, com bolus intermitentes e diários de morfina para avaliação de possibilidade de implante de bomba de morfina. CONCLUSÃO: O teste foi considerado bem-sucedido e a paciente encaminhada para neurocirurgia. No seguimento de 6 meses após implante de bomba por via subaracnoidea, esta estratégia se mostrou eficaz no controle da dor secundária à polineuropatia.

Corneal confocal microscopy in patients with distal symmetric polyneuropathy compared to controls / Microscopia confocal de córnea em pacientes com polineuropatia simétrica distal comparados a controles

Abstract Background Diabetic neuropathy (DN) is a very common clinical condition throughout the world. The diagnostic tests currently recommended have low sensitivity, such as electromyography, or are invasive, such as skin biopsy. New techniques have been developed to identify the early involvement of the peripheral nerve. With the advent of corneal confocal microscopy (CCM), a reduction in corneal innervation in patients with DN has been observed. Objective To compare, through CCM, diabetic patients with symptomatic distal symmetric polyneuropathy (DSP) and controls. Methods In the present study, through CCM, we compared the morphological changes in the sub-basal epithelial corneal plexus of 35 diabetic patients with symptomatic DSP with 55 controls. Moreover, we sought to determine a pattern of change regarding the severity stages of DSP, comparing the clinical, laboratory, and nerve-conduction (NC) variables. Results Differences between the control and diabetic groups were observed for the following variables, respectively: age (44.9 ± 13.24 years versus 57.02 ± 10.4 years; p< 0.001); fiber density (29.7 ± 10.2 versus 16.6 ± 10.2; p< 0.001); number of fibers (4.76 ± 1.30 versus 3.14 ± 1.63; p< 0.001); number of Langerhans cells (4.64 ± 8.05 versus 7.49 ± 10.3; p= 0.035); tortuosity (p< 0.05); and thickness (p< 0.05). Furthermore, inverse relationships were found regarding fiber density and age (p< 0.01) and fiber density and the severity of the disease (p< 0.05). A positive relationship between the conduction velocity of the fibular nerve and fiber density (p< 0.05) was also observed. Conclusion Corneal confocal microscopy proved to be a fast, noninvasive and reproducible method for the diagnosis, staging, and monitoring of diabetic DSP.

Resumo Antecedentes A neuropatia diabética (ND) é condição clínica muito frequente no mundo inteiro. Os testes diagnósticos atualmente preconizados são pouco sensíveis, como a eletroneuromiografia, ou invasivos, como a biópsia de pele. Novas técnicas de investigação complementares têm sido desenvolvidas a fim de identificar o acometimento precoce do nervo periférico. Com o advento da microscopia confocal de córnea (MCC), observou-se redução da inervação da córnea em pacientes com ND. Objetivo Comparar, por meio da MCC, pacientes diabéticos com polineuropatia simétrica distal (PSD) sintomática e controles. Métodos Neste estudo, por meio da MCC, comparamos as alterações morfológicas do plexo sub-basal epitelial da córnea de 35 pacientes diabéticos com PSD sintomática com 55 indivíduos controles. Além disso, buscamos determinar um padrão de alteração entre os estágios de gravidade da PSD, comparando variáveis clínicas, laboratoriais e de neurocondução. Resultados Diferenças entre os grupos controle e diabéticos foram verificadas com relação às seguintes variáveis, respectivamente: idade (44,9 ± 13,24 anos versus 57,02 ± 10,4 anos; p< 0,001); densidade das fibras (29,7 ± 10,2 versus 16,6 ± 10,2; p< 0,001); número de fibras (4,76 ± 1,30 versus 3,14 ± 1,63; p< 0,001); número de células de Langerhans (4,64 ± 8,05 versus 7,49 ± 10,3; p= 0,035); tortuosidade (p< 0,05), e espessura (p < 0,05). Além disso, relações inversamente proporcionais foram verificadas entre a densidade das fibras e a idade (p< 0,01), e entre a densidade das fibras e a gravidade da doença (p< 0,05). Observou-se ainda uma relação positiva entre a velocidade de condução do nervo fibular e a densidade das fibras (p< 0,05). Conclusão A MCC constitui um método rápido, não invasivo e reprodutível para o diagnóstico, o estadiamento, e o acompanhamento da PSD diabética.

Peripheral neuropathy in leprosy: Clinical manifestations and disability in a Colombian national referral center.

To aim of the paper was to describe the neurological features of the physical examination in patients with Hansen's disease who were treated in Bogotá, Colombia. We carried out a descriptive study of all patients with a Hansen's disease diagnosis treated at a referral center between 2003-2018. There were 327 eligible electronic health records (EHRs) with a final sample of 282 subjects. Leprosy was most common in males (57.45%), median age at the diagnosis was 54 years, and lesions of the lower limbs were more common (75.1%). The median time from disease onset to consult was 12 months. Most of them were classified as having lepromatous leprosy (39.7%). Pain over the median nerve trunk was the most common manifestation of disease (28%), followed by pain over the radial trunk (22%). Sensitive alterations were more common than motor ones. Specifically, the posterior tibial nerve was affected in nearly half of subjects. Dual impairment was more common in the ulnar nerve (13.8%). Some disability was apparent in 23.8% of subjects; predominantly grade 1 disability. Findings regarding age, leprosy type, and the frequency of individual nerve compromise were consistent with reports from other countries. Nerve trunk thickening was infrequent, which might be a consequence of subjectiveness in the examination and sample differences in sex distribution, degree of disability and time since disease onset. The frequency of morbidity and disability found in this sample, though low when compared with other series, fails to meet public health goals, including those limiting disability in younger subjects.

Evaluation of neurological disorders that develop concurrently with COVID-19 pneumonia: a retrospective analysis / Avaliação de transtornos neurológicos concomitantes à pneumonia por COVID-19: análise retrospectiva

ABSTRACT Background: During the pandemic, many neurological symptoms have been evaluated as complications of COVID-19 pneumonia. Objective: To investigate the frequency and characteristics of neurological findings, and their effects on the prognosis of patients with COVID-19 pneumonia who consulted with the Neurology department. Methods: Data on 2329 patients who were hospitalized with the diagnosis of COVID-19 pneumonia in our hospital were scanned. The clinical, laboratory and radiological findings relating to treatment of 154 patients who required neurological consultation were retrospectively evaluated by reviewing the clinical notes. Results: The number of COVID-19 pneumonia patients who required neurological consultations while hospitalized in the ICU was 94 (61.0%). The most common symptom among these patients was hyperactive delirium. Mean age, ferritin levels and CRP values ​​of those with delirium were higher, while the mean lymphocyte percentage were lower, than those of the patients without delirium. Epileptic seizures were observed in eight patients without an epilepsy diagnosis. Two patients were diagnosed with GBS and one patient with ICU neuropathy. The D-dimer levels of patients with acute hemorrhagic CVD and the thrombocyte levels of patients with acute ischemic CVD were found to be higher than in patients without acute ischemic CVD. Conclusion: The proportion of patients who required neurological consultations was higher in the ICUs. We observed neurological symptoms more frequently in the advanced age group. There were no significant increases in the incidence of other neurological conditions except delirium, in COVID-19 patients. We think that further studies are needed to support our data.

RESUMO Antecedentes: Durante a pandemia, muitos sintomas neurológicos foram avaliados como complicações da pneumonia por COVID-19. Objetivo: Investigar a frequência e as características dos achados neurológicos e seus efeitos no prognóstico de pacientes com pneumonia por COVID-19 que consultaram o departamento de Neurologia. Métodos: Foram analisados os dados de 2.329 pacientes internados com diagnóstico de pneumonia por COVID-19 em nosso hospital. Os achados clínicos, laboratoriais e radiológicos relativos ao tratamento de 154 pacientes que necessitaram de consulta neurológica foram avaliados retrospectivamente por meio da revisão das anotações clínicas. Resultados: O número de pacientes com pneumonia por COVID-19 que necessitaram de consultas neurológicas enquanto internados na UTI foi de 94 (61,0%). O sintoma mais comum entre esses pacientes foi o delírio hiperativo. A média de idade, os níveis de ferritina e os valores de PCR daqueles apresentando delírios foram maiores, enquanto a porcentagem média de linfócitos foi menor do que em pacientes sem delírios. Crises epilépticas foram observadas em oito pacientes sem diagnóstico de epilepsia. Dois pacientes foram diagnosticados com SGB e um paciente com neuropatia na UTI. Os níveis de dímero D de pacientes com DCV hemorrágica aguda e os níveis de trombócitos de pacientes com DCV isquêmica aguda foram maiores do que em pacientes sem DCV isquêmica aguda. Conclusão: A proporção de pacientes que necessitaram consultas neurológicas foi maior nas UTIs. Observamos sintomas neurológicos com mais frequência em pacientes de faixa etária avançada. Não houve aumentos significativos na incidência de outras condições neurológicas, exceto delírio, em pacientes com COVID-19. Acreditamos que mais estudos são necessários para apoiar nossos dados.

Evaluation of peripheral neuropathy in lower limbs of patients with rheumatoid arthritis and its relation to fall risk.

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic disabling systemic disease characterized by joint inflammation, and extra-articular manifestations, including peripheral neuropathy, a condition that can be associated with changes in muscle strength, proprioception and postural balance contributing for the risk of falls. The objective of this study is to analyze the incidence of peripheral neuropathy in patients with RA and its association with the occurrence of falls. METHODS: Patients were assessed by an electroneuromyography (ENMG) exam and by a questionnaire on accidental falls occurrence in the previous 12 months. They were also assessed on balance by the Short Physical Performance Battery (SPPB), functionality by the Health Assessment Questionnaire (HAQ), disease activity by the Disease Activity Score (DAS-28), neuropathic pain by the Questionnaire for the Diagnosis of Neuropathic Pain (DN4), and cutaneous sensitivity of the feet by the monofilament testing of Semmes-Weinstein. Monthly calls on falls were made in the subsequent six months. Data analysis was performed using the Shapiro-Wilk test for normality and Spearman, Chi-square, and T-student correlation tests, with a significant P level ≤ 0.05. RESULTS: A sample of 33 patients were evaluated. The incidence of peripheral neuropathy was 48.5%, of which 68.7% were axonal and 31.3% myelinic. The sensorimotor type was present in 64.7%, motor in 17.6%, and sensorial in 11.7% of the cases. Neuropathy was associated to balance (P = 0.026), neuropathic pain (P = 0.016), deep tendon reflexes absence (P = 0,049), altered skin sensitivity of the feet (P = 0.029) and fear of falling (P = 0.001). No association was found between peripheral neuropathy and age, gender, disease activity, or functionality. No significant association was found between peripheral neuropathy and occurrence of falls, in a 12-month retrospective and 6-month prospective evaluation. CONCLUSION: Peripheral neuropathy has a high incidence in patients with RA, and is related to neuropathic pain, altered postural balance, but not to the occurrence of falls.

"Million dollar nerve" magnetic resonance neurography: first normal and pathological findings.

OBJECTIVES: To evaluate prospectively the feasibility of magnetic resonance neurography (MRN) in identifying the anatomical characteristics of thenar muscular branch (TMB) of the median nerve, also known as the "million dollar nerve," in patients and controls. METHODS: Thirteen patients affected by carpal tunnel syndrome (CTS) and four healthy controls had their hands scanned on a 3-T MR imaging scanner for TMB visualization. Median nerve anatomical variations were classified into four groups according to Poisel's classification system modified by Lanz. TMB signal intensity and diameter were assessed for the diagnosis of neuropathy. RESULTS: TMB was successfully identified in all patients and subjects by using MRN. The most suitable pulse sequences to identify and measure nerve diameter were 3D DW-PSIF and T2-FS-TSE. The axial oblique and sagittal oblique planes are complementary in demonstrating its entire course. TMB had mostly an extraligamentous course with radial side origin (93.8%, each). All patients experienced increased T2 signal intensity (p < 0.001) and thickened nerves. Mean TMB diameters were 1.27 ± 0.21 mm (range, 1.02-1.74 mm) and 0.87 ± 0.16 mm (0.73-1.08 mm) (p = 0.008) in the patient and control groups, respectively. CONCLUSION: MRN is a reliable imaging technique for identification and anatomical characterization of TMB in patients affected by CTS. This innovative imaging workup may therefore be included in the preoperative evaluation of patients scheduled for carpal tunnel release, especially in CTS with TMB involvement or even in isolated TMB neuropathy. KEY POINTS: • Magnetic resonance neurography allows precise visualization of the thenar muscular branch of the median nerve. • Thenar muscular branch anatomical variations can be correctly identified. • Preoperative scanning can contribute to reducing the risk of iatrogenic injuries during carpal tunnel release, especially in carpal tunnel syndrome with thenar muscular branch involvement or even in isolated thenar muscular branch neuropathy.

Early and Midterm Outcomes of "No-Touch" Saphenous Vein Grafts in Japanese Institutions

ABSTRACT Introduction: There have been several attempts to overcome the poor graft patency of saphenous vein grafts. "No-touch" saphenous vein graft (NT-SVG) could be a solution to improve graft patency. We aimed to investigate the early and midterm outcomes of coronary artery bypass grafting (CABG) using NT-SVGs in our hospitals. Methods: This is a retrospective study of 105 patients who underwent CABG using 130 NT-SVGs between August 2013 and December 2021. NT-SVGs were harvested with about a 5-mm margin of surrounding tissue on both sides of the vein with minimal manipulation. Then, the NT-SVG was dilated by natural arterial pressure without manual distension. After surgery, most of NT-SVGs were assessed by cardiac catheterization or multidetector computed tomography (MDCT) to determine early graft patency. Late graft assessments by MDCT were performed about every five years after surgery. Results: The early graft patency of NT-SVGs was 100% (125/125); however, two cases of graft twisting were found. Both cases spontaneously resolved. Leg wound infections of NT-SVG harvesting site were seen in 6.2% of patients. Peripheral neuropathy of the legs such as skin numbness and tingling were frequently observed, which lasted up to one year, but no more than two years after surgery. The midterm graft patency of NT-SVGs was excellent (five-year patency of NT-SVGs was 95.8%). Conclusion: The early and midterm graft patency of NT-SVGs was satisfactory. Although leg wound complications can be seen on the harvesting NT-SVG site, the "no-touch" harvesting technique of SVG could improve graft patency and clinical outcomes of CABG.

Factor VIII prophylactic therapy reduces neurological complications in patients with Hemophilia A / Terapia profilática com Fator VIII reduz complicações neurológicas em paciente com Hemofilia A

ABSTRACT 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.

RESUMO Antecedentes: O sangramento em hemofílicos causa complicações no sistema nervoso central e periférico (SNC e SNP). A incidência de hemorragia intracraniana diminuiu após a introdução da profilaxia com fator VIII ou IX, entretanto esse benefício ainda não foi avaliado no SNP. Objetivo: O objetivo deste estudo foi determinar a prevalência de complicações neurológicas em hemofílicos, verificando o efeito da terapia profilática também no SNP. Métodos: Avaliamos retrospectivamente a prevalência de complicações neurológicas causadas ​​por sangramentos em hemofílicos atendidos no Hemocentro Regional Norte, Ceará, Brasil, de 1992 a 2018, comparando a incidência em diferentes períodos (antes e depois da introdução do tratamento profilático em 2011). Resultados: Foram avaliados 75 pacientes com hemofilia A (4,61/100 mil habitantes). Deles, 13,3% (n=10) tinham distúrbios do SNC (n=5) ou do SNP (n=5) secundários a hemorragias. Os pacientes submetidos à terapia profilática com fator VIII apresentaram menor probabilidade de eventos do SNC: de 1992 a 2011, cinco de 63 pacientes apresentaram hemorragia no SNC, enquanto de 2011 a 2018 não ocorreram novos casos (p=0,0181). De 2011 a 2018, cinco eventos no SNP ocorreram entre pacientes sem terapia profilática, e nenhum ocorreu entre aqueles cobertos pela profilaxia (5/20 × 0/29, p=0,0081). Conclusões: A prevalência de complicações neurológicas em hemofílicos em nossa coorte é similar à de outros estudos. Assim como no SNC, a terapia profilática também reduz o risco de complicações no SNP. Este é o primeiro relato na literatura a mostrar esse benefício.

Revisiting the Role of Biologically Active Natural and Synthetic Compounds as an Intervention to Treat Injured Nerves.

Traumatic lesions in nerves present high incidence and may culminate in sensorimotor and/or autonomic dysfunctions or a total loss of function, affecting the patient's quality of life. Although the microenvironment favors peripheral nerve regeneration, the regenerative process is not always successful. Some herbs, natural products, and synthetic drugs have been studied as potential pro-regenerative interventions. We reviewed and discussed the most recent articles published over the last ten years in high impact factor journals. Even though most of the articles contemplated in this review were in vitro and animal model studies, those with herbs showed promising results. Most of them presented antioxidant and anti-inflammatory effects. Drugs of several pharmacological classes also showed optimistic outcomes in nerve functional recovery, including clinical trials. The results are hopeful; however, mechanisms of action need to be elucidated, and there is a need for more high-quality clinical studies. The study presents careful compilation of findings of dozens of compounds with consistent pro-regenerative evidence published in respected scientific journals. It may be valuable for health professionals and researchers in the field.

Advances in imaging technologies for the assessment of peripheral neuropathies in rheumatoid arthritis.

Peripheral neuropathy in patients with rheumatoid arthritis is associated with a maladaptive autoimmune response that may cause chronic pain and disability. Nerve conduction studies are the routine method performed when rheumatologists presume its presence. However, this approach is invasive, may not reveal subtle malfunctions in the early stages of the disease, and does not expose abnormalities in structures surrounding the nerves and muscles, limiting the possibility of a timely diagnosis. This work aims to present a narrative review of new technologies for the clinical assessment of peripheral neuropathy in Rheumatoid Arthritis. Through a bibliographic search carried out in five repositories, from 1990 to 2020, we identified three technologies that could detect peripheral nerve lesions and perform quantitative evaluations: (1) magnetic resonance neurography, (2) functional magnetic resonance imaging, and (3) high-resolution ultrasonography of peripheral nerves. We found these tools can overcome the main constraints imposed by the previous electrophysiologic methods, enabling early diagnosis.

Transcranial Direct Current Stimulation and Mirror Therapy for Neuropathic Pain After Brachial Plexus Avulsion: A Randomized, Double-Blind, Controlled Pilot Study.

Introduction: Although transcranial direct current stimulation (tDCS) and mirror therapy (MT) have benefits in combating chronic pain, there is still no evidence of the effects of the simultaneous application of these techniques in patients with neuropathic pain. This study aims to assess the efficacy of tDCS paired with MT in neuropathic pain after brachial plexus injury. Methods: In a sham controlled, double-blind, parallel-group design, 16 patients were randomized to receive active or sham tDCS administered during mirror therapy. Each patient received 12 treatment sessions, 30 min each, during a period of 4 weeks over M1 contralateral to the side of the injury. Outcome variables were evaluated at baseline and post-treatment using the McGill questionnaire, Brief Pain Inventory, and Medical Outcomes Study 36-Item Short-Form Health Survey. Long-term effects of treatment were evaluated at a 3-month follow-up. Results: An improvement in pain relief and quality of life were observed in both groups (p ≤ 0.05). However, active tDCS and mirror therapy resulted in greater improvements after the endpoint (p ≤ 0.02). No statistically significant differences in the outcome measures were identified among the groups at follow-up (p ≥ 0.12). A significant relationship was found between baseline pain intensity and outcome measures (p ≤ 0.04). Moreover, the results showed that state anxiety is closely linked to post-treatment pain relief (p ≤ 0.05). Conclusion: Active tDCS combined with mirror therapy has a short-term effect of pain relief, however, levels of pain and anxiety at the baseline should be considered. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04385030.

Déficit motor distal como una variante del Síndrome de Guillain-Barré: un reporte de caso / Distal motor deficit as a variant of Guillain-Barré Syndrome: case report

RESUMEN Existen variantes del síndrome de Guillain-Barre (SGB) de muy poca presentación como la debilidad distal de extremidades del SGB (DL-GBS), que muestra una debilidad limitada a las regiones distales de las extremidades (muñecas, manos, tobillos y dedos de los pies) con la fuerza muscular conservada en las regiones proximales durante el curso de la enfermedad. Se reporta el caso de una mujer de 26 años que dos semanas antes del ingreso, presenta leve déficit motor distal de las extremidades superiores y posteriormente las extremidades inferiores, asociado a diarrea. Al examen: leve cuadriparesia distal, sin hipo/arreflexia y Lasegue positivo. Los estudios de laboratorio mostraron: anemia ferropénica, las pruebas inmunológicas para virus comúnmente asociados, marcadores tumorales, pruebas toxicológicas y dosaje de Vitamina B12 fueron normales. Así mismo, el examen de líquido cefalorraquídeo no mostró alteraciones. Los estudios de RMN cerebral y columna cervical fueron normales. Los estudios de electromiografía y velocidad de conducción nerviosa (EMG-VCN) al décimo día de la enfermedad mostro una neuropatía axonal motora aguda sin denervación. Por las características benignas de su presentación y evolución hace suponer que se trata de una variante leve del SGB (DL-SGB), que difiere de las variantes normales de AMAN-SGB que generalmente son graves y de pobre pronóstico.

ABSTRACT There are some variants of Guillain-Barré syndrome (GBS) that are so unusual, such as distal limb weakness (DL-GBS), which features weakness restricted to the distal area of limbs (wrists, hands, ankles, and toes) with preserved muscle strength in the proximal areas during the course of the disease. We report the case of a 26 year-old woman, who at two weeks before admission showed mild distal motor deficit affecting the arms and afterwards her legs, and this was associated to diarrheal disease. Physical examination showed mild distal quadriparesis, with no hyporeflexia/ areflexia, and a positive Lasègue sign. Laboratory studies showed ferropenic anemia, immunological tests for commonly associated viruses, tumor markers and vitamin B12 levels were all normal. Also, CSF examination showed no alterations. Cerebral and cervical spine MRI studies were normal. Electromyography and nerve conduction velocity studies at the 10th day of the disease showed acute motor axonal neuropathy with no denervation. The benign form of presentation and progression led us to think this case is a mild GBS variant (DL-GBS), different from the usual AMAN-GBS variants, which are usually severe and have a poor prognosis.