Avaliação Cintilográfica e Ecocardiográfica em Portadores de Variantes Patogênicas ou Provavelmente Patogênicas do Gene TTR sem Envolvimento Cardíaco Manifesto / Scintigraphic and Echocardiographic Study of Patients with Pathogenic or Probably Pathogenic Variants of the TTR Gene without Overt Cardiac Involvement

Resumo Fundamento: A amiloidose por transtirretina (ATTR) é uma doença infiltrativa causada pela deposição anormal de proteína principalmente no coração e no sistema nervoso periférico. Quando acomete o coração, a doença manifesta-se como uma cardiomiopatia restritiva e, quando afeta o sistema nervoso periférico e autônomo, apresenta-se como uma polineuropatia, podendo ser chamada de Polineuropatia Amiloidótica Familiar (PAF). Existem dois subtipos de ATTR, a ATTR selvagem, em que não há variantes genéticas, e a ATTR hereditária, caracterizada por uma variante no gene que codifica a proteína transtirretina (T/TR). Em ambos os subtipos, o envolvimento cardíaco é o principal marcador prognóstico. Objetivos: Avaliar a prevalência do envolvimento cardíaco subclínico em uma amostra de pacientes com variantes genéticas no gene TTR usando a cintilografia com pirofosfato e o ecocardiograma com strain; comparar os achados cintilográficos e as medidas de strain; avaliar a associação entre PAF e o envolvimento subclínico; e analisar se existe uma associação entre uma variante genética específica e o envolvimento cardíaco. Métodos: Estudo transversal com carreadores de variantes no gene TTR sem sintomas cardiovasculares e sem alterações nos parâmetros da eletrocardiografia ou do ecocardiograma convencional. Todos os pacientes foram submetidos à cintilografia com pirofosfato e à ecocardiografia com análise de strain. O envolvimento cardíaco subclínico, definido como um escore de Perugini ≥ 2, razão Coração (C)/ Hemitórax Contralateral (CL) ≥ 1,5 em uma hora, C/CL ≥ 1,3 na terceira hora, ou um strain longitudinal global (SGL) ≤ −17%. Realizadas análises descritiva e analítica, e aplicados o teste exato de Fisher e o teste de Mann-Whitney. Um valor de p<0,05 foi considerado significativo. Resultados: Os 23 pacientes avaliados apresentavam uma idade mediana de 51 (37-57) anos, 15 (65,2%) eram do sexo feminino, 12 (52,2%) eram pardos, nove (39,1%) apresentavam hipertensão arterial sistêmica, e nove (39,1%) tinham um diagnóstico prévio de PAF. Dos nove pacientes com PAF, oito (34,8%) usavam tafamidis. As variantes genéticas identificadas foram Val142IIe, Val50Met e IIe127Val. O valor mediano do SGL foi −19% (-16% - −20%). Dos 23 pacientes, nove (39,1%; 95% CI = 29-49%) preencheram os critérios de envolvimento cardíaco, seis (26%) somente pelo critério do SGL. Não houve associação entre PAF e um carreador assintomático avaliado por ecocardiograma com análise de strain e pela cintilografia com pirofostato (p=0,19). A prevalência de hipertensão arterial sistêmica, diabetes mellitus, dislipidemia, tabagismo e SGL reduzido não foi diferente entre os grupos. A velocidade da onda e' septal foi a única variável que apresentou diferença significativa entre os indivíduos com e sem SGL reduzido, com uma área sob a curva ROC de 0,80 (IC95% = 0,61-0,98, p = 0,027). A melhor acurácia diagnóstica foi alcançada com uma velocidade e' septal ≤ 8,5 cm/s. Não houve associação entre o tipo de variante genética e o envolvimento cardíaco pré-clínico, nem entre o uso de tafamidis e este mesmo envolvimento (37,5% versus 40,0%, p = 0,90). Conclusão: O envolvimento cardíaco subclínico foi frequente em uma amostra de carreadores da variante genética do gene TTR. Um valor do SGL reduzido foi o achado mais comum. Não houve associação entre a presença de polineuropatia amiloidótica e o envolvimento subclínico. O tipo de variante genética não foi associado com envolvimento cardíaco precoce. Nesta amostra, o uso de tafamidis (20mg/dia) não foi associado com uma menor prevalência de envolvimento cardíaco subclínico.

Abstract Background: Transthyretin amyloidosis (ATTR) is an infiltrative disease caused by abnormal protein deposition mainly in the heart and peripheral nervous system. When it affects the heart, the disease presents as restrictive cardiomyopathy; when it affects the peripheral and autonomic nervous system, it manifests as polyneuropathy, and is called familial amyloid polyneuropathy (FAP). There are two ATTR subtypes: wild-type ATTR, where there is no mutation, and mutant ATTR (ATTRm), which is characterized by a mutation in the gene encoding the transthyretin protein (TTR). In both subtypes, cardiac involvement is the major marker of poor prognosis. Objectives: To assess the prevalence of subclinical cardiac involvement in a sample of patients with TTR gene mutation by using pyrophosphate scintigraphy and strain echocardiography; to compare scintigraphy and strain findings; to evaluate the association between neurological manifestations (FAP) and subclinical cardiac involvement; and to analyze whether there is an association between any specific mutation and cardiac involvement. Methods: This is a cross-sectional study with carriers of the TTR gene mutation, without cardiovascular symptoms or changes in electrocardiographic or conventional echocardiographic parameters. All patients underwent pyrophosphate scintigraphy and strain echocardiography. Subclinical cardiac involvement was defined as a Perugini score ≥ 2, heart-to-contralateral lung (H/CL) ratio ≥ 1.5 at 1 h, H/CL ≥1.3 at 3 h, or global longitudinal strain (GLS) ≤ −17%. Descriptive and analytical analyses were performed and Fisher's exact test and Mann-Whitney test were applied. A value of p < 0.05 was considered significant. Results: The 23 patients evaluated had a median age of 51 years (IQR 37-57 years), 15 (65.2%) were female, 12 (52.2%) were Pardo, nine (39.1%) had systemic arterial hypertension, and nine (39.1%) had a previous diagnosis of FAP. Of the nine patients with FAP, 8 (34.8%) were on tafamidis. The associated mutations were Val142IIe, Val50Met, and IIe127Val. The median GLS in the sample was −19% (−16% to −20%). Of the 23 patients, nine (39.1%; 95% CI = 29-49%) met criteria for cardiac involvement, six (26%) by the GLS-based criteria only. There was no association between having FAP and being an asymptomatic carrier, as assessed by strain echocardiography and pyrophosphate scintigraphy (p = 0.19). The prevalence of systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and reduced GLS did not differ between groups. Septal e' wave velocity was the only variable that significantly differed between individuals with and without reduced GLS, with an area under the ROC curve of 0.80 (95% CI = 0.61-0.98, p = 0.027). The best diagnostic accuracy was achieved with a septal e' velocity ≤ 8.5 cm/s. There was no association between mutation type and preclinical cardiac involvement, nor between tafamidis use and lower degree of cardiac involvement (37.5% versus 40.0%, p = 0.90). Conclusion: Subclinical cardiac involvement was common in a sample of TTR mutation carriers without cardiac involvement. Reduced left ventricular GLS was the most frequent finding. There was no association between the presence of amyloid polyneuropathy and subclinical cardiac involvement. Type of mutation was not associated with early cardiac involvement. In this sample, the use of tafamidis 20 mg/day was not associated with a lower prevalence of subclinical cardiac involvement.

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.

Do you mind the role of spinal sensory block duration in a crucial endocrine disorder of diabetes mellitus? A prospective observational study

SUMMARY OBJECTIVE: Diabetes mellitus, per se, is a global health concern, which is often accompanied by complications such as diabetic neuropathy. This prospective observational study purposed to assess the durations of spinal sensory block and motor blocks in individuals with and without diabetes mellitus who had undergone spinal anesthesia. METHODS: This study incorporated 80 cases, which were evenly divided into spinal sensory block without diabetes mellitus and spinal sensory block with diabetes mellitus. Various parameters were recorded at different time points, including heart rate, mean arterial blood pressure, SpO2, and spinal block characteristics. Notable measures included maximum spinal sensory block onset time, time to reach the 10th thoracic vertebra (T10), maximal spinal sensory block, time for Bromage scores, and block regression while controlling for age-related variations. RESULTS: Patients in the diabetic group exhibited extended block durations, with significant differences in heart rate noted at specific time points. Regarding the spinal block characteristics, the "maximum onset of SSB" and the "time to reach the T10" were more prolonged in the SSBwDM without significance. Maximum sensory spinal sensory block did not differ. However, some cases in the SSBwDM displayed blocks extending up to the T6. The times to achieve Bromage motor block scores 1-3 were shorter in SSBwDM and lost significance regarding age. Notably, the regression time was longer in SSBwDM, which held significance for both parameters. CONCLUSION: Diabetic cases commonly encounter prolonged block durations post-subarachnoid intervention, potentially linked to nerve sensitivity, age-related changes, and glycemic control. As such, attenuated local doses for diabetic neuropathic cases may enhance early mobilization, attenuate thromboembolic events, and expedite gastrointestinal recovery.

¿Qué hay de nuevo en el diagnóstico de amiloidosis? / What is new in diagnosis of amyloidosis?

La amiloidosis siempre ha representado un desafío diagnóstico. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA), confeccionó la Guía de Práctica Clínica para el Diagnóstico de Amiloidosis. Nuevas líneas de investigación se han desarrollado posteriormente. Esta revisión narrativa tiene como intención explorar el estado del arte en el diagnóstico de la amiloidosis. En pacientes con amiloidosis se recomienda la tipificación de la proteína mediante espectrometría de masa, técnica de difícil ejecución por requerir de microdisectores láser para la preparación de la muestra. Algunas publicaciones recientes proponen otros métodos para obtener la muestra de amiloide que se va a analizar, permitiendo prescindir de la microdisección. Por otra parte, en pacientes con Amiloidosis ATTR confirmada, la recomendación de secuenciar el gen amiloidogénico se encontraba destinada a los casos sospechosos de ATTR hereditaria (ATTRv,), pero actualmente esta se ha extendido a todos los pacientes sin importar la edad. En lo que respecta a los estudios complementarios orientados al diagnóstico de compromiso cardíaco, se ha propuesto el uso de la inteligencia artificial para su interpretación, permitiendo la detección temprana de la enfermedad y el correcto diagnóstico diferencial. Para el diagnóstico de neuropatía, las últimas publicaciones proponen el uso de la cadena ligera de neurofilamento sérica, que también podría resultar un indicador útil para seguimiento. Finalmente, con referencia a la amiloidosis AL, la comunidad científica se encuentra interesada en definir qué características determinan el carácter amiloidogénico de las cadenas livianas. La N-glicosilación de dichas proteínas impresiona ser uno de los determinantes en cuestión. (AU)

Amyloidosis has always represented a diagnostic challenge. In 2020, the Amyloidosis Study Group (ASG) developed the "Clinical Practice Guideline for the Diagnosis of Amyloidosis". New lines of research have subsequently emerged. This narrative review aims to explore the state of the art in the diagnosis of amyloidosis diagnosis. In patients with amyloidosis, protein typing by mass spectrometry is recommended, a technique hard to perform because it requires laser microdissection for sample preparation. Recent publications propose other methods to obtain the amyloid sample to be analyzed, making it possible to dispense with microdissection. On the other hand, in patients with confirmed TTR amyloidosis (aTTR), the recommendation to sequence the amyloidogenic gene was intended for suspected cases of hereditary aTTR but has now been extended to all patients regardless of age. (AU)

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.

F-waves persistence in peripheral sensory syndromes / Persistência das ondas-F nas síndromes sensitivas periféricas

Abstract Background The distinction between sensory neuronopathies (SN), which is by definition purely sensory, and sensory polyneuropathies (SP) and sensory multineuropathies (SM) is important for etiologic investigation and prognosis estimation. However, this task is often challenging in clinical practice. We hypothesize that F-wave assessment might be helpful, since it is able to detect subtle signs of motor involvement, which are found in SP and SM, but not in SN. Objective The aim of the present study was to determine whether F-waves are useful to distinguish SN from SP and SM. Methods We selected 21 patients with SP (12 diabetes mellitus, 4 transthyretin familial amyloid polyneuropathy, 4 others), 22 with SM (22 leprosy), and 26 with SN (13 immune-mediated, 10 idiopathic, 3 others) according to clinical-electrophysiological-etiological criteria. For every subject, we collected data on height and performed 20 supramaximal distal stimuli in median, ulnar, peroneal, and tibial nerves, bilaterally, to record F-waves. Latencies (minimum and mean) and persistences were compared across groups using the Kruskal-Wallis and Bonferroni tests. P-values < 0.05 were considered significant. Results All groups were age, gender, and height-matched. Overall, there were no significant between-group differences regarding F-wave latencies. In contrast, F-wave persistence was able to stratify the groups. Peroneal F-wave persistence was higher, bilaterally, in the SN group compared to SM and SP (p < 0.05). In addition, F-waves persistence of the ulnar and tibial nerves was also helpful to separate SN from SP (p < 0.05). Conclusion F-wave persistence of the peroneal nerves might be an additional and useful diagnostic tool to differentiate peripheral sensory syndromes.

Resumo Antecedentes A distinção entre neuronopatias sensitivas (SN) e polineuropatias sensitivas (SP) e multineuropatias sensitivas (SM) é importante para a investigação etiológica e para o prognóstico. Contudo, esta tarefa é desafiadora na prática clínica. Hipotetizou-se que a avaliação das ondas-F pode ser útil, por ser capaz de detectar envolvimento motor nas SP e SM, mas não nas SN. Objetivo Determinar se as ondas-F podem ajudar a distinguir entre SN, SP e SM. Métodos Selecionou-se 21 pacientes com SP (12 diabetes mellitus, 4 ATTR-FAP e 4 com outras neuropatias), 22 com SM (22 hanseníases) e 26 com SN (13 imunomediadas, 10 idiopáticas e 3 com outras neuronopatias), de acordo com critérios clínicos, etiológicos e eletrofisiológicos. Para cada indivíduo, foi aferida a altura e foram aplicados 20 estímulos distais supramáximos nos nervos mediano, ulnar, fibular e tibial, bilateralmente, para registrar as ondas-F. Uma comparação foi feita, por grupo, das latências (mínimas e médias) e persistências pelos testes Kruskal-Wallis e Bonferroni. Valores de p < 0.05 foram considerados estatisticamente significativos. Resultados Todos os grupos foram pareados por idade, sexo e altura. Não houve diferença estatística significativa entre os grupos quanto às latências das ondas-F. A persistência da onda-F foi capaz de estratificar os grupos, sendo as dos nervos fibulares bilateralmente maiores no grupo SN que nos grupos SM e SP (p < 0.05). Adicionalmente, a persistência das ondas-F dos nervos ulnares e tibiais também foi útil para distinguir SN de SP (p < 0.05). Conclusão A persistência das ondas-F dos nervos fibulares pode ser uma ferramenta adicional e útil para diferenciar síndromes sensitivas periféricas.

Neuropatía Diabética: Una revisión narrativa de fisiopatología, diagnóstico y tratamiento

La neuropatía diabética se presenta hasta en el 60 % de los pacientes diabéticos. La neuropatía diabética periférica es la causa más común de neuropatía en el mundo. La fisiopatología de la neuropatía diabética involucra daño periférico nervioso por acumulación de productos tóxicos derivados de la hiperglicemia. El sistema nervioso central se ve posteriormente involucrado a través de sensibilización, disminución de la función del sistema inhibitorio y aumento en la excitabilidad del sistema de facilitación. La clínica más común se manifiesta de manera simétrica afectando fibras sensitivas pequeñas y grandes, aunque se han encontrado formas atípicas de presentación. Las pruebas diagnósticas confirmatorias se reservan para la duda diagnóstica, casos de síntomas atípicos o investigación. El consenso en cuanto a tratamiento es el uso de gabapentinoides, antidepresivos tricíclicos e inhibidores de recaptura de serotonina y noradrenalina. Estas tres familias se consideran como primera línea de tratamiento.

Diabetic neuropathy occurs in up to 60% of diabetic patients. Diabetic peripheral neuropathy is the most common cause of neuropathy in the world. The pathophysiology of diabetic neuropathy involves peripheral nerve damage due to the accumulation of toxic products derived from hyperglycemia. The central nervous system is subsequently involved through sensitization, decreased function of the inhibitory system, and increased excitability of the facilitative system. The most common symptoms manifest symmetrically, affecting small and large sensory fibers, although atypical forms of presentation have been found. Confirmatory diagnostic tests are reserved for diagnostic doubt, atypical symptoms, or research. The consensus regarding treatment is the prescription of gabapentinoids, tricyclic antidepressants, and serotonin and norepinephrine reuptake inhibitors. These three families are considered the first line.

Perfil clínico-metabólico de pacientes pé diabéticos frequentadores de uma Unidade Básica de Saúde de Altamira, Pará, Brasil / Clinical-metabolic profile of diabetic foot patients attendinga Basic Health Unit in Altamira, Pará, Brazil

Introdução: o pé diabético é de origem neuropática e representa uma das complicações do diabetes mellitus, abrange várias condições patológicas, que incluem neuropatia, doença arterial periférica, neuroartropatia de Charcot, ulceração do pé e, em alguns casos, amputação. Objetivo: descrever o perfil clínico-metabólico de pacientes pé diabéticos frequentadores de uma Unidade Básica de Saúde (UBS). Material e Método: trata-se de um estudo descritivo exploratório com abordagem quantitativa. Foram avaliados 15 pacientes portadores de úlceras do pé diabético atendidos em uma Unidade Básica de Saúde de Altamira, estado do Pará, Brasil. Os dados foram submetidos à análise de acordo com os indicadores dos perfis investigados. Resultados: todos os pacientes possuem diabetes tipo II, baixos níveis de renda familiar e escolaridade. O Índice de Massa Corpórea (IMC) foi de 92%, circunferência abdominal 93%, proteína C reativa ultrassensível, interleucina-6 e hemoglobina glicada estavam superiores ao normal em mais da metade dos doentes, assim como a vitamina D estava deficiente em mais da metade dos pacientes. Conclusões: há barreiras ao manejo adequado dos portadores de pé diabético na atenção básica da cidade de Altamira que podem contribuir para o desenvolvimento de complicações macro e microvasculares. Recomendações técnicas direcionadas aos gestores locais contribuem para a atenção básica na região.

Introduction: the diabetic foot is of neuropathic origin and represents one of the complications of diabetes mellitus, encompasses several pathological conditions, including neuropathy, peripheral arterial disease, Charcot neuroarthropathy, foot ulceration, osteomyelitis and, in some cases, amputation. Objective: to describe the clinical-metabolic profile of diabetic foot patients attending a Basic Health Unit (BHU). Material and Method: this is a descriptive exploratory study with a quantitative approach. Fifteen patients with diabetic foot ulcers treated at the Basic Health Unit in Altamira, state of Pará, Brazil, were evaluated. The data were submitted to analysis according to the indicators of the investigated profiles. Results: all patients have Type 2 Diabetes, low level of family income and education. The Body Mass Index (BMI) was 92%, abdominal circumference (93%), Ultrasensitive C-Reactive Protein, Interleukin-6 and glycated hemoglobin were higher than normal in more than half of the patients, as well as vitamin D was deficient in more of half of the patients. Conclusions: there are barriers to the proper management of patients with diabetic foot in primary care in the city of Altamira that can contribute to the development of macro and microvascular complications. Technical recommendations directed at local managers contribute to primary care in the region.

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.

Oscilações no equilíbrio estático relacionadas a diabetes mellitus tipo 2 ­ uma revisão sistemática / Oscillations in static balance related to type 2 diabetes mellitus ­ a systematic review

INTRODUÇÃO: A diabetes mellitus tipo 2 (DM2) é uma doença crônica sistêmica ligada às mudanças no estilo de vida, fatores genéticos e ambientais, ocasionando complicações como a neuropatia diabética periférica (NDP). Além disso, pessoas com DM2 apresentam um retardo na condução nervosa das vias motoras e sensoriais, podendo levar a alterações no equilíbrio. OBJETIVO: Descrever as alterações de equilíbrio estático em pacientes com DM2. MATERIAIS E MÉTODOS: A revisão sistemática iniciou em outubro de 2021 ocorrendo a última busca em março de 2023, os artigos foram selecionados por dois autores de forma independente nas bases de dados Pubmed, Scopus e Web of Science. Seguindo o protocolo registrado no PROSPERO e descrito com base nas recomendações do PRISMA, foram selecionados estudos observacionais sem restrição a ano de publicação e idioma, envolvendo equilíbrio de DM em qualquer idade. RESULTADOS: Foram eleitos 20 artigos com indivíduos DM e NPD em um total de 1564 voluntários, demonstrando: DM causa mudança na velocidade e deslocamento do COP alterando o equilíbrio estático, a presença da NPD piora a estabilidade corporal devido as alterações sensitivo motoras. CONCLUSÃO: Indivíduos com DM e NPD demonstram alterações na estabilidade postural como velocidade e deslocamento do centro de pressão (COP) para as direções AP e ML, com ou sem informação visual e na presença da NPD.

INTRODUCTION: Type 2 diabetes mellitus (DM2) is a chronic systemic disease linked to changes in lifestyle, genetic and environmental factors, causing complications such as peripheral diabetic neuropathy (PDN). In addition, people with DM2 have a delay in nerve conduction in motor and sensory pathways, which can lead to changes in balance. OBJECTIVE: To describe static balance changes in patients with DM2. MATERIALS AND METHODS: The systematic review started in October 2021 with the last search occurring in March 2023, the articles were selected by two authors independently from the Pubmed, Scopus and Web of Science databases. Following the protocol registered in PROSPERO and described based on the PRISMA recommendations, observational studies were selected without restriction on year of publication and language, involving DM balance at any age. RESULTS: 20 articles were chosen with DM and NPD individuals in a total of 1564 volunteers, demonstrating that DM causes changes in the speed and displacement of the COP, altering the static balance and the presence of NPD worsens body stability due to sensory-motor changes. CONCLUSION: Individuals with DM and NPD demonstrate changes in postural stability such as velocity and displacement of the center of pressure (COP) for the AP and ML directions, with or without visual information and in the presence of DPN.

Endoscopic Cubital Tunnel Release in Leprosy Neuritis of the Ulnar Nerve / Liberação endoscópica do túnel cubital na neurite hansênica do nervo ulnar

Abstract Objectives To better characterize the role of endoscopic cubital tunnel release in leprosy neuritis and determine whether there is an improvement in pain, sensitivity, and strength with the use of this minimally invasive technique. Methods A total of 44 endoscopic procedures for ulnar nerve decompression at the elbow were performed in patients who were previously diagnosed with leprosy neuritis. The inclusion criteria were surgical indication for ulnar nerve release and clinical treatment failure for 4 weeks in patients with cubital tunnel syndrome who had their ulnar nerve function, whether motor or sensitive, deteriorated progressively despite the treatment with prednisone 1 mg/kg/day and physiotherapy. For endoscopic release, the CTS Relief Kit (Linvatec. Largo, FL, USA) and a standard 4mm 30° arthroscope were used. Results The study included 39 patients, 29 (74.4%) males and 10 (25.6%) females. The age of the patients ranged from 12 to 64 years (33 ± 14.97). Five patients underwent bilateral release. The release demonstrated a statistically significant improvement in pain (p 0.002), in sensitivity (p< 0.001), and in strength (p< 0.001). The best results were obtained when ulnar release was performed less than 6 months after surgery indication. None of the procedures were converted from endoscopic to open. No major complications (infection, vascular injury, and nervous injury) were reported. One patient had ulnar nerve subluxation. Conclusion The endoscopic release of the ulnar nerve at the elbow in leprosy neuritis entails true and safe benefits for the patient, such as improvement in pain, sensitivity and strength.

Resumo Objetivos Os objetivos deste estudo foram caracterizar melhor o papel da liberação endoscópica do túnel cubital na neurite hansênica e determinar se há melhora da dor, sensibilidade e força com esta técnica minimamente invasiva. Métodos Um total de 44 procedimentos endoscópicos para descompressão do nervo ulnar no cotovelo foram realizados em pacientes previamente diagnosticados com neurite por hanseníase. Os critérios de inclusão foram indicação cirúrgica para liberação do nervo ulnar e insucesso do tratamento clínico por 4 semanas em pacientes com síndrome do túnel cubital que sofreram deterioração progressiva da função motora ou sensitiva do nervo ulnar apesar do tratamento de 1 mg/kg/dia de prednisona e fisioterapia. A liberação endoscópica foi realizada com CTS Relief Kit (Linvatec. Largo, FL, EUA) e um artroscópio padrão de 4 mm e 30°. Resultados O estudo incluiu 39 pacientes, sendo 29 (74,4%) homens e 10 (25,6%) mulheres. A idade dos pacientes variou de 12 a 64 anos (33 ± 14,97). Cinco pacientes foram submetidos à liberação bilateral. A liberação provocou melhora estatisticamente significativa de dor (p= 0,002), sensibilidade (p <0,001) e força (p <0,001). Os melhores resultados foram obtidos quando a liberação ulnar foi realizada em menos de 6 meses após a indicação da cirurgia. Nenhum procedimento foi convertido de endoscópico para aberto. Não foram relatadas complicações maiores (infecção, lesão vascular e lesão nervosa). Um paciente apresentou subluxação do nervo ulnar. Conclusão A liberação endoscópica do nervo ulnar no cotovelo na neurite hansênica traz benefícios verdadeiros e seguros para o paciente, como melhora da dor, sensibilidade e força.

Exame do pé diabético: fatores de risco de ulceração em pacientes com diabetes mellitus / Examen del pie diabético: factores de riesgo de ulceración en pacientes con diabetes mellitus / Diabetic foot exam: risk factors of ulceration in patients with diabetes mellitus

Objetivo: descrever a evolução dos fatores de risco para o desenvolvimento de úlceras nos pés de pacientes com DM, em três exames subsequentes num período de 3 anos, num centro de especialidades médicas. Método: estudo descritivo, retrospectivo e longitudinal, com 102 pacientes, entre os anos de 2016 e 2019, que realizaram três exames dos pés sequenciais, fundamentado no padrão estabelecido pelo consenso internacional do pé diabético, sendo eles avaliação neuropática, vascular, dermatológica e uso dos calçados, coletado do Sistema do Pé Diabético. Resultados: 86,27% dos pacientes declararam sintomas neuropáticos, principalmente queimação, dormência e formigamento. A maioria hipertensos (74,71%) e idosos (67,65%), desses 13,73% com infarto prévio e 72,55% eram do sexo feminino. Do primeiro ao terceiro exame, o "risco muito baixo" aumentou 7,84% e "risco baixo" 8,83%, já o "risco elevado" reduziu 17,65%. Conclusão: a realização sistemática do exame clínico dos pés, associado a estratégias educativas efetivas, resultam num controle mais eficaz do risco de ulceração.

Objetivo: Describir la evolución de los factores de riesgo para el desarrollo de úlceras en los pies de pacientes con DM, en tres exámenes subsecuentes en un período de 3 años, en un centro de especialidades médicas. Método: estudio descriptivo, retrospectivo y longitudinal, con 102 pacientes, entre los años 2016 y 2019, que realizaron tres exámenes de los pies secuenciales, fundamentado en el patrón establecido por el consenso internacional del pie diabético, siendo ellos evaluación neuropática, vascular, dermatológica y uso de calzado, recogido del Sistema del Pie Diabético. Resultados: 86,27% de los pacientes declararon síntomas neuropáticos, principalmente ardor, entumecimiento y hormigueo. La mayoría hipertensos (74,71%) y ancianos (67,65%), de esos 13,73% con infarto previo y 72,55% eran mujeres. Del primero al tercer examen, el "riesgo muy bajo" aumentó un 7,84% y "riesgo bajo" un 8,83%, mientras que el "riesgo alto" redujo un 17,65%. Conclusión: la realización sistemática del examen clínico de los pies, asociado a estrategias educativas efectivas, resultan en un control más eficaz del riesgo de ulceración.

Objective: to describe the evolution of risk factors for the development of foot ulcers in patients with DM, in three subsequent exams over a period of 3 years, in a medical specialty center. Method: a descriptive, retrospective and longitudinal study, with 102 patients, between the years 2016 and 2019, who performed three sequential foot exams, based on the standard established by the international consensus of the diabetic foot, being use of footwear, collected from the Diabetic Foot System. Results: 86.27% of patients reported neuropathic symptoms, mainly burning, numbness and tingling. Most were hypertensive (74.71%) and elderly (67.65%), of these, 13.73% had previous infarction and 72.55% were female. From the first to the third examination, the "very low risk" increased 7.84% and the "low risk" 8.83%, while the "high risk" reduced 17.65%. Conclusion: the systematic clinical feet exam, associated with effective educational strategies, results in a more effective control of the risk of ulceration.

Autophagy and anti-inflammation ameliorate diabetic neuropathy with Rilmenidine

Purpose: To evaluate the neuroprotective effects of Rilmenidine on diabetic peripheral neuropathy (DPN) in a rat model of diabetes induced by streptozotocin (STZ). Methods: STZ (60 mg/kg) was administered to adult Sprague-Dawley rats to induce diabetes. On the 30th day after STZ administration, electromyography (EMG) and motor function tests confirmed the presence of DPN. Group 1: Control (n = 10), Group 2: DM + 0.1 mg/kg Rilmenidine (n = 10), and Group 3: DM + 0.2 mg/kg Rilmenidine (n = 10) were administered via oral lavage for four weeks. EMG, motor function test, biochemical analysis, and histological and immunohistochemical analysis of sciatic nerves were then performed. Results: The administration of Rilmenidine to diabetic rats substantially reduced sciatic nerve inflammation and fibrosis and prevented electrophysiological alterations. Immunohistochemistry of sciatic nerves from saline-treated rats revealed increased perineural thickness, HMGB-1, tumor necrosis factor-α, and a decrease in nerve growth factor (NGF), LC-3. In contrast, Rilmendine significantly inhibited inflammation markers and prevented the reduction in NGF expression. In addition, Rilmenidine significantly decreased malondialdehyde and increased diabetic rats' total antioxidative capacity. Conclusions: The findings of this study suggest that Rilmenidine may have therapeutic effects on DNP by modulating antioxidant and autophagic pathways.

Diabetic peripheral neuropathy / 中华神经科杂志

Diabetes peripheral neuropathy (DPN) is one of the most common complications of diabetes. It not only causes physical disability and unbearable pain, but also may lead to emotional and psychological problems, reduce the quality of life of patients, and increase mortality. Although early diagnosis of diabetes may improve the clinical prognosis, the occurrence of DPN is sometimes unavoidable and the treatment is limited. This article summarizes the clinical features, diagnosis, investigations and treatment of DPN by reviewing the latest literature.

Clinical, genetic characteristics and follow-up in 14 patients with transthyretin familial amyloid polyneuropathy / 中华神经科杂志

Objective:To summarize the clinical and genetic characteristics in patients with transthyretin familial amyloid polyneuropathy (TTR-FAP).Methods:Fourteen unrelated TTR-FAP patients diagnosed at Xuanwu Hospital, Capital Medical University from September 2014 to February 2022 were retrospectively reviewed. The clinical manifestation, electrophysiology, cardiac function, biopsy and gene mutation were analyzed.Results:In the 14 patients (13 males, 1 female) diagnosed as TTR-FAP, the mean age at onset was 53.9 years (range: 33.0-71.0 years), with a mean course from symptom-onset to diagnosis of 4.1 years. The late-onset type occurred in 9 cases. Seven patients had a family history of TTR-FAP. Distal paresthesia of lower limbs was the commonest initial symptom (8 cases), with sensorimotor neuropathy and autonomic dysfunction seen initially in 4 and 2 cases, respectively. Cardiac involvement occurred in 6/8 of the patients. Nerve conduction studies indicated extremely axonal impairment with demyelinating features. Sural nerve biopsies showed moderate to severe axonal loss of myelinated fibers and the positive rate of Congo red staining was 8/14. Of 8 different TTR mutations detected, V50M was the most common (appearing in 5 cases). No obvious neuropathy progression was seen in the 5 patients who received tafamidis and 2 patients died of dyscrasia. Conclusions:TTR-FAP is more common in males, with sensorimotor axonal polyneuropathy, autonomic dysfunction and cardiac subclinical damage as the predominant symptoms. V50M is the commonest mutation. Tafamidis can delay the progression of disability.

Study on the value of Michigan nerve screening scale, pain and tactile temperature detection and vibration perception threshold in diagnosing diabetic peripheral neuropathy / 中国医师进修杂志

Objective:To analyze the diagnostic value of Michigan nerve screening Scale (MNSI), pain, touch and temperature detection combined with vibratory perception threshold (VPT) in diabetic peripheral neuropathy (DPN).Methods:A total of 500 patients with type 2 diabetes mellitus (T2DM) who received inpatient treatment in Xinhua Hospital Chongming Branch Affiliated of Shanghai Jiao Tong University School of Medicine from January to December 2018 were selected. Sixty four patients with DPN were enrolled in the DPN group, and the remaining 436 patients were enrolled in the no-DPN group. The clinical data and the results of MNSI scale, pain, touch and temperature detection thresholds and VPT of the two groups were compared. Receiver operating characteristic (ROC) curve was drawn to analyze the clinical value of single and combined examination indicators in the diagnosis of DPN.Results:MNSI symptom questionnaire score and MNSI physical examination score in DPN group were higher than those in no-DPN group: (3.00 ± 1.35) scores vs. (1.69 ± 0.52) scores, (1.57 ± 0.50) scores vs. (1.01 ± 0.24) scores; the proportion of touch regression, pain regression and temperature regression was significantly higher than that in no-DPN group; and the levels of VPT in the DPN group was higher than that in the no-DPN group: (26.34 ± 5.03) V vs. (17.97 ± 6.82) V, there were statistical differences ( P<0.01). When the single index was diagnosed, the area under the curve (AUC) value of VPT was the highest (0.825), and significantly higher than the pain, touch and temperature detection ( P<0.01). The AUC value of VPT + MNSI in combined diagnosis was the highest (0.738), and the sensitivity and specificity of DPN diagnosis were 51.56% and 96.10%, respectively. Conclusions:Compared with MNSI scale score, sensory detection such as pain, touch and temperature, VPT has the best diagnostic efficiency for DPN, while combined with MNSI, the specificity can be further improved, but the sensitivity decreases, which is worthy of clinical attention.

Evaluation of alprostadil combined with different doses of mouse nerve growth factor in diabetic peripheral neuropathy / 中国医师进修杂志

Objective:To investigate the application of alprostadil combined with different doses of mouse nerve growth factor in diabetic peripheral neuropathy (DPN) and its effect on motor and sensory nerve conduction and inflammatory factors.Methods:One hundred and fiftypatients with DPN treated in Beihai People′s Hospital from June 2018 to March 2020 were randomly divided into low-dose group and high-dose group, with 75 cases in each group. On the basis of routine treatment, the low-dose group was given alprostadil + mouse nerve growth factor 18 μg/time, once a day. The high-dose group was given alprostadil+mouse nerve growth factor 30 μg/time, once a day, both two groups were treated for 3 weeks. The curative effect, motor and sensory nerve conduction velocity and inflammatory index tumor necrosis factor-α(TNF-α)interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC) and cost-effectiveness analysis, adverse reactions between the two groups were compared.Results:There was no significant difference in the total effective rate between the low dose group and the high dose group ( P>0.05). After 1 and 3 weeks of treatment, the levels ofmotor and sensory nerve conduction velocity and TNF-α, IL-6, hs-CRP and WBC in the two groups has no significant differences ( P>0.05). The cost of each unit effect in the low-dose group was 43.11 Yuan, and the cost of each unit effect in the high-dose group was 57.58 Yuan. The high-dose group was higher than that in the low-dose group, and the high-dose group paid 572.56 Yuan more than the low-dose group for each additional unit effect. There was no significant difference in the total incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Alprostadil combined with 18 μg mouse nerve growth factor in the treatment of DPN has a similar improvement effect on clinical symptoms, motor and sensory nerve conduction and inflammatory factors, and has advantages in cost-effectiveness.

Clinical study of Qigui Tangtongning Granules combined with conventional western medicine in treating diabetic peripheral neuropathy syndrome of Qi deficiency and blood stasis / 国际中医中药杂志

Objective:To observe the clinical efficacy of Qigui Tangtongning Granules in the treatment of diabetic peripheral neuropathy (DPN) with qi deficiency and blood stasis.Methods:Prospective cohort study. A total of 80 DPN patients with Qi deficiency and blood stasis in Endocrinology Department of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2021 to May 2022 who met the inclusion criteria were divided into 2 groups by random number table method, with 40 cases in each group. The control group was treated with epalrestat on the basis of routine hypoglycemia, and the treatment group was treated with Qigui Tangtongning Granules on the basis of control group. Both groups were treated for 8 weeks. TCM syndromes were scored before and after treatment. Disease severity was assessed using the Toronto Clinical Scoring System (TCSS). The motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of median nerve and common peroneal nerve were detected by electromyography/induced potentiometer. Serum CRP, TNF-α and IL-6 were detected by ELISA, fasting blood glucose (FPG) and two hours post-meal blood glucose (2 hPG) were detected by automatic biochemical analyzer, and glycosylated hemoglobin (HbA1c) was detected by automatic HBA1C analyzer. Adverse reactions were recorded and clinical efficacy was evaluated.Results:The total effective rate was 95.0% (38/40) in the treatment group and 77.5% (31/40) in the control group, the difference between the two groups was statistically significant ( χ2=5.17, P=0.023). After treatment, the TCM syndrome score and TCSS score of the treatment group were significantly lower than those in the control group ( t=-3.19 and -7.63, P<0.01); Median nerve SNCV [(47.90±4.51) m/s vs. (44.76±3.72) m/s, t=3.40], MNCV [(53.79±3.65) m/s vs. (51.32±4.25) m/s, t=2.79] and common peroneal nerve SNCV [(44.21±2.08) m/s vs. (40.51±2.49) m/s, t=7.23], MNCV [(44.63±4.72) m/s vs. (41.36±4.87) m/s, t=3.05] were significantly higher than those in the control group ( P<0.01); FPG [(5.05±0.63) mmol/L vs. (7.05±1.23) mmol/L, t=-9.17], 2 hPG [(9.10±1.64) mmol/L vs. (12.19±2.61) mmol/L, t=-6.35], HbA1c [(6.79±0.90) % vs. (7.22±1.02) %, t=-2.02] were significantly lower than those in the control group ( P<0.01 or P<0.05); TNF-α [(15.75±5.44) ng/L vs. (32.01±5.33) ng/L, t=-13.51], hs-CRP [(2.58±0.80) mg/L vs. (3.79±1.04) mg/L, t=-5.83], IL-6 [(18.20±4.92) ng/L vs. (29.97±5.18) ng/L, t=-10.41] were significantly lower than those in the control group ( P<0.01). No obvious adverse reactions were observed in 2 groups during treatment. Conclusion:Qigui Tangtongning Granules combined with conventional Western medicine can improve nerve conduction velocity, reduce inflammation and improve clinical efficacy in DPN patients with Qi-deficiency and blood-stasis syndrome.

An acute case of herpes zoster ophthalmicus with post-herpetic neuralgia and cranial nerve neuropathies

Herpes zoster is a common diagnosis in the emergency department which is caused by reactivation of varicella zoster virus (VZV). Reactivation in ophthalmic division of trigeminal nerve causes Herpes zoster ophthalmicus. It is associated with a rash in the distribution of the trigeminal nerve dermatomes especially in ophthalmic and maxillary divisions. The most often complications of HZO are episcleritis, keratitis, glaucoma, and cataracts. HZO with cranial neuropathy is a very rare condition. So herewith wereport a case 51years old female with swelling, redness in right eye and drooping of eyelids on the right side. She had tearing and double vision. She was diagnosed with herpes zoster ophthalmicus with neuropathy of 3rd,4thand 6th cranial nerves. The patient was treated and discharged in a healthy condition. Timely diagnosis and treatment can decrease morbidity and prevent the complication.

Variations in Innervation Pattern to Dorsum of Foot by Medial Dorsal Cutaneous Nerve, Intermediate Dorsal Cutaneous Nerve, Lateral Dorsal Cutaneous Nerve with Surgical and Clinical Correlations: A Cadaveric Dissection Based Study

The complete reconstruction of any soft tissue defect includes even the sensory recovery which is very significant aspect pertaining to prognosis. Superficial nerves in the vicinity of the vascular axis can be considered as vascular relays and neuroskin grafts can be constructed on them. Variations in innervation to various part of the dorsum of the foot by this nerve should be kept in mind while making these grafts. Authors dissected 50 formalinized cadaveric feet and studied normal anatomy and variations in origin, course, branching pattern, communications, and any other variations in medial, intermediate and lateral dorsal cutaneous nerve. The intermediate dorsal cutaneous nerve was innervating larger area of the skin around 3rd and 4th web spaces in 60% of cadaveric feet. The 2nd web space was innervated by medial dorsal cutaneous nerve in 92% of cadaveric feet. In 52% of cadaveric feet communicating branches were found between intermediate dorsal cutaneous nerve and lateral dorsal cutaneous nerve. In 63% cadaveric feet communicating branches were found between medial dorsal cutaneous nerve and branch of deep peroneal nerve to 2nd web space. The mean distance between lateral malleolus and intermediate dorsal cutaneous nerve was 4.05cm. These all observations can provide anatomical basis at the time of preparing medial dorsal cutaneous nerve flaps and intermediate dorsal cutaneous nerve flaps and also can minimize morbidity at donor site.