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.

Nutritional neuropathies / 中华神经科杂志

Neuropathies associated with nutritional deficiencies are not uncommon. Most neuropathies associated with nutritional deficiency are length dependent sensory axonal lesions, whereas the exception is cobalamin deficiency neuropathy, which is usually manifested as non-length dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy are characterized by myelopathy, while vitamin E deficiency is associated with spinocerebellar syndrome. Contrary to the neuropathy caused by nutrient deficiency, pyridoxine toxicity leads to non-length dependent sensory neuropathy. Malnutrition, malabsorption, increased nutritional loss (such as dialysis), autoimmune diseases (such as pernicious anemia) and some drugs that inhibit nutrient absorption can all lead to nutritional deficiency. Early detection and therapeutic nutritional supplement can stabilize or improve these neuropathies.

Hereditary neuropathy with liability to pressure palsies / 中华神经科杂志

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant hereditary sensory and motor neuropathy characterized by recurrent numbness and limb weakness. In clinical practice, some patients may present with mild or atypical clinical symptoms, which tends to result in missed diagnosis or misdiagnosis of HNPP. This article summarizes the pathogenesis, epidemiology, clinical manifestations, auxiliary examination, diagnosis and differential diagnosis, management, and prognosis of HNPP.

Risk factors of bortezomib-related peripheral neuropathy and the clinical features and electrophysiological characteristics of patients during treatment of multiple myeloma / 白血病·淋巴瘤

Objective:To explore the risk factors of bortezomib-related peripheral neuropathy (BIPN) and the clinical and electrophysiological characteristics of patients in treatment of multiple myeloma (MM).Methods:The clinical data of 71 newly diagnosed MM patients treated with BD (bortezomib + dexamethasone) regimen in Yancheng First People's Hospital from March 2016 to December 2019 were retrospectively analyzed. The bone marrow morphology, immunology, cytogenetics, molecular biology (MICM), routine electrophysiological examination before and after treatment were performed. All patients were divided into the peripheral neuropathy (PN) group and the non-PN group according to the presence or not of BIPN, and the clinicopathological differences of both groups were also compared; a binary logistic regression model was used to analyze the factors affecting the occurrence of PN. The electrophysiological characteristics were summarized and fluorescence in situ hybridization (FISH) was used to detect karyotype of BIPN patients.Results:Among 71 MM patients, there were 40 cases (56.3%) of PN and 31 cases (43.7%) of non-PN. The proportion of patients at international staging system (ISS) staging Ⅲ, and the levels of IgA, IgG, IgM, serum creatinine, β 2-microglobulin (β 2-MG) in the PN group were higher than those in the non-PN group, and hemoglobin (Hb) level in the PN group was lower than that in the non-PN group, and the differences were statistically significant (both P < 0.05). Binary logistic regression analysis showed that increased IgA ( OR = 1.151, 95% CI 1.012-1.309, P = 0.033), increased IgG ( OR = 1.055, 95% CI 1.000~1.112, P = 0.049), increased IgM ( OR = 1.010, 95% CI 1.001-1.018, P = 0.022), increased serum creatinine ( OR = 1.037, 95% CI 1.011~1.065, P = 0.005), increased β 2-MG ( OR = 1.564, 95% CI 1.039-2.354, P = 0.032) were risk factors for BIPN. Among 40 patients with BIPN, 33 cases (82.5%) of sensory nerve conduction velocity (SCV) were abnormal, 23 cases (57.5%) of motor nerve conduction velocity (MCV) were abnormal; 31 cases (77.5%) showed demyelination damage, 9 cases (22.5%) had axonal damage. Among 40 patients with BIPN, 24 cases underwent FISH detection, including 19 cases (79.2%) with chromosomal mutations, of which 12 cases (50.0%) were mixed subtype abnormal. Conclusions:MM patients with high levels of β 2-MG, IgA, IgG, IgM and serum creatinine are more prone to PN when treated with bortezomib. The electrophysiology of patients with BIPN is mainly characterized by demyelination of sensory nerves.

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.

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.

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.

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.

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.

The genetic distribution in Chinese patients with Charcot-Marie-Tooth diseases: a 14-year cohort study / 中华神经科杂志

Objective:To investigate the genetic distribution of pathogenic genes of Charcot-Marie-Tooth diseases (CMT) in Chinese Han population, and compare the similarity and difference with the data in Peking University Third Hospital in 2013.Methods:Five hundred and twenty families with CMT and related diseases in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to March 2021 were collected. After peripheral myelin protein 22 (PMP22) gene duplication and deletion mutations were initially detected by multiple ligation probe amplification, the probands of these families were sequenced by next-generation sequencing (NGS) gene panel or whole exome sequencing, and validated by Sanger sequencing.Results:Among the 520 families, 336 CMT families were genetically confirmed, and the mutation detection rate increased from 48.6% (51/105) in 2013 to 64.6% (336/520) in 2021 (χ 2=9.54, P=0.003). Among them, 139 families had PMP22 gene duplication mutation (139/520, 26.7%), 46 families had gap junction beta-1 (GJB1) gene mutation (46/520, 8.8%), 26 families had mitofusin-2 (MFN2) gene mutation (26/520, 5.0%), 12 families had myelin protein zero (MPZ) gene mutation (12/520, 2.3%), 11 families had PMP22 gene point mutation (11/520, 2.1%), and 10 families had heat shock protein B1 gene mutation (10/520, 1.9%). There were 10 families with ganglioside induced differentiation associated protein 1 (GDAP1) gene mutation (10/520, 1.9%), 8 families with SH3 domain and tetratricopeptide repeats 2 (SH3TC2) gene mutation (8/520, 1.5%), 7 families with immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene mutation (7/520, 1.3%), 6 families with MORC family CW-type zinc finger 2 (MORC2) gene mutation (6/520, 1.2%), 5 families with sorbitol dehydrogenase (SORD) gene mutation (5/520, 1.0%), 16 families with very rare gene mutation (16/520, 3.1%) and 184 families without genetic diagnosis (184/520, 35.4%). Conclusions:Compared with the results in 2013, the 3 most common genes affecting CMT were still PMP22, GJB1 and MFN2 genes, but the proportion difference of patients with MPZ gene mutation gradually decreased with other genes such as SH3TC2 and GDAP1 genes. The proportion of newly discovered CMT genes, such as MORC2 and SORD genes, was similar with IGHMBP2 gene, which should be paid more attention. NGS greatly improved the detection rate of CMT, especially for patients with autosomal recessive-CMT.

The voxel-based morphometry of cerebral gray matter volume in patients with diabetic peripheral neuropathy / 中国医师杂志

Objective:To explore the structural alterations in functional brain areas of patients with diabetic peripheral neuropathy (DPN) using voxel-based morphometry (VBM), and to investigate the abnormal region of grey matter and its distribution in DPN.Methods:A total of 124 patients with DPN and 88 patients with type 2 diabetes without DPN (NDPN) diagnosed in Haikou Hospital and the First Affiliated Hospital of Guangdong Pharmaceutical University from June 2019 to December 2020 were selected as the study subjects, and 40 healthy volunteers matched with gender and age were included as the control group.All subjects underwent whole-brain MRI examination, and 3D-T1WI data were collected for post-processing and analysis based on voxel morphological analysis.Results:Compared with NDPN patients, decreased gray matter volume in DPN patients was observed in the bilateral anterior central gyrus and thalamus, with statistical signifcant difference ( P<0.05), and there was no significant difference between the two sides ( P>0.05). Compared with healthy control group, decreased gray matter volume in DPN was observed in the the bilateral anterior central gyrus, central posterior gyrus, superior frontal gyrus and thalamus, with statistical signifcant difference ( P<0.05) and there was no significant difference between the two sides ( P>0.05). Conclusions:DPN patients also have decreased volumes of the brain greymatter, suggesting that the occorrence of DPN patients may be caused by the of injury of central structure.

Serum levels of complement B and D in patients with diabetic peripheral neuropathy and their correlation / 中国医师杂志

Objective:To investigate the serum level and significance of complement factor B (CFB) and complement factor D (CFD) in patients with type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN).Methods:From October 2019 to October 2020, 110 patients with T2DM in the endocrinology department of Affiliated Hospital of Jining Medical College were divided into DPN group ( n=60) and simple T2DM group ( n=50) according to whether or not DPN was combined. In addition, 52 cases of physical examination population in the physical examination center in the same period were selected as the normal control group ( n=52). The serum levels of CFB, CFD and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA). The correlation between CFB, CFD and clinical indexes was analyzed, and the influencing factors of DPN were analyzed by logistic regression. Results:The serum levels of CFB and CFD in DPN group were higher than those in T2DM group and normal control group [CFB: (845.43±101.10)μg/ml vs (792.19±116.59)μg/ml, (739.20±123.43)μg/ml, P<0.05], [CFD: (491.71±41.03)mg/L vs (467.58±45.16)mg/L, (445.16±50.47)mg/L, P<0. 05]. Pearson correlation analysis showed that the serum level of CFB was positively correlated with glycosylated hemoglobin (HbA 1c), fasting plasma glucose (FPG) and TNF-α (all P<0.05) and negatively correlated with triiodothyronine (FT3) and total bilirubin (TBIL) (all P<0.05). Serum CFD level was positively correlated with systolic blood pressure, HbA 1c, FPG and TNF-α (all P<0.05), but negatively correlated with FT3 and TBIL (all P<0.05). Logistic regression analysis showed that CFB and CFD were still influential factors for the occurrence and development of DPN after excluding confounding factors such as systolic blood pressure, HbA 1c, FPG, FT3, DBIL, TBIL and TNF-α. Conclusions:(1) Serum CFB and CFD levels were significantly increased in DPN patients, suggesting that CFB and CFD may be involved in the occurrence and development of DPN. (2) Serum TNF-α level was significantly increased in DPN patients, confirming the role of TNF-α in the pathogenesis of DPN.

Progress of diagnosis and treatment of monoclonal gammopathy of neural significance / 白血病·淋巴瘤

Monoclonal gammopathy of neural significance (MGNS) belongs to the category of monoclonal gammopathy of clinically significance. It is an early-stage disease that mainly occurs in peripheral nerves and is not sufficient for the diagnosis of multiple myeloma or lymphoma. MGNS needs to be differentiated from neuropathies due to POEMS syndrome and light-chain amyloidosis; if necessary, nerve biopsy can be performed to clarify the relationship between peripheral nerve symptoms and lymphoplasmacytic disease. Treatment of MGNS is recommended to give intravenous gammaglobulin, plasma exchange and targeted anti-lymphoplasmacytic tumour therapy such as CD20 monoclonal antibody. Early recognition and intervention of MGNS, with multidisciplinary cooperation, will help to reduce the risk of malignancy and the incidence of disability.

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.

Review of systematic reviews of acupuncture for diabetic peripheral neuropathy / 针灸推拿医学（英文版）

Objective: To review the systematic reviews of acupuncture for diabetic peripheral neuropathy (DPN) and to provide evidence for clinical decisions. Methods: Published systematic reviews targeting acupuncture treatment of DPN were searched using computer through both Chinese and English databases till July 1, 2019. Two researchers screened the papers based on inclusion and exclusion criteria and conducted report quality evaluation, methodological quality assessment and evidence quality grading using the preferred reporting items for systematic reviews and meta-analyses (PRISMA), assessment of multiple systematic review 2 (AMSTAR 2) and grading of recommendations assessment, development and evaluation (GRADE). Results: Ten systematic reviews were included, involving 11 outcome measures. According to PRISMA, 6 items were sufficiently reported while 1 item was not; AMSTAR 2 appraised that all the included systematic reviews were of low quality in the methodological evaluation; according to GRADE, of the 30 clinical evidences, only 5 were graded moderate while the remained were graded low or extremely low. Descriptive analysis showed that acupuncture can significantly improve DPN symptoms, accelerate the conduction velocities of sensory and motor nerves, and up-regulate the content of plasma nitric oxide (NO), while the adverse reaction rate was low. Conclusion: Acupuncture can produce satisfactory clinical efficacy in treating DPN, but the existing problems, such as low-quality evidence, unitary outcome measures, poor methodological quality of systematic reviews and nonstandard reporting, need to be treated cautiously; meanwhile, more high-quality clinical trials are required to elevate the level of evidence.

The level and significance of CD4 + CD25 + Foxp3 + Treg in peripheral blood of patients with type 2 diabetic peripheral neuropathy / 中国医师杂志

Objective:To investigate the level and significance of CD4 + CD25 + Foxp3 + Treg in peripheral blood of patients with type 2 diabetes mellitus (T2DM) peripheral neuropathy. Methods:160 patients with T2DM (T2DM group) treated in Yancheng First People's Hospital from January 2018 to March 2019 were selected, including 54 patients with peripheral neuropathy and 106 patients without peripheral neuropathy. At the same time, 160 healthy people were selected as the control group to detect the levels of CD4 + CD25 + Foxp3 + Treg and 25-(OH)D 3 in peripheral blood. Pearson correlation analysis was used to analyze the correlation between CD4 + CD25 + Foxp3 + Treg in peripheral blood and other indexes. The receiver operating characteristic (ROC) value curve was used to analyze the predictive value of CD4 + CD25 + Foxp3 + Treg in peripheral blood of type 2 diabetic peripheral neuropathy. Results:The ratio of CD4 + CD25 + Foxp3 + Treg in T2DM group was (7.82±1.03)%, which was significantly lower than that in control group [(15.53±3.82)%, P<0.05]; The duration of T2DM patients with peripheral neuropathy was (7.71±1.18)years, which was significantly longer than that without peripheral neuropathy ( P<0.05), while the proportions of 25-(OH)D 3 and CD4 + CD25 + Foxp3 + Treg were (49.88±12.27)mmol/L and (5.88±1.20)% respectively, which were significantly lower than that without peripheral neuropathy ( P<0.05); Patients with peripheral neuropathy in group T2DM had significantly higher Michigan Diabetic Neuropathy Scores (MDNS) than that in patients without peripheral neuropathy [(14.82±2.01) vs (4.41±0.43), P<0.05]. The CD4 + CD25 + Foxp3 + Treg was positively correlated with 25-(OH)D 3 ( r=0.367, P<0.05), and negatively correlated with MDNS ( r=-0.398, P<0.05); the CD4 + CD25 + Foxp3 + Treg predicted that the area under the ROC curve of T2DM patients with peripheral neuropathy was 0.822, the cut-off value was 6.50%, and the sensitivity and specificity were 80.00% and 72.00% respectively. Conclusions:The level of CD4 + CD25 + Foxp3 + Treg in peripheral blood of T2DM patients decreased, which may play a role in the occurrence and development of peripheral neuropathy.

Recent research focus in peripheral neuropathy / 中华神经科杂志

Peripheral neuropathy consists of a group of diseases due to different pathogenesis. This article discussed the recent research focus in four categories of peripheral neuropathies, including immune mediated neuropathy, diabetic neuropathy, hereditary neuropathy and chemotherapy-induced neuropathy.