Neurophysiological comparative response to clinical and surgical treatment of the ulnar neuropathy in leprosy / Padrões neurofisiológicos da resposta tardia ao tratamento clínico e cirúrgico da neuropatia ulnar na hanseníase

Leprosy neuropathy may develop into subacute and chronic inflammatory scenarios, called reactions, which may cause entrapments in the anatomic tunnels. Objective: This study describes the late nerve conduction findings in patients with ulnar neuropathy at the elbow that were submitted to clinical and surgery treatments. Methods: A total of 27 nerves of 21 patients with borderline leprosy during type 1 (reversal) reaction were selected in a non- competing retrospective cohort for three years. The nerves with treated clinically active neuropathy (Group A1) were randomized for inclusion of surgical treatment (Group A2) after one month of clinical treatment without clear signs of clinical and neurophysiological improvement. Fifteen nerves were randomly chosen for surgery while 12 were clinically treated, after steroids treatment without expected response. Nerve conduction was measured before and after treatment on four occasions. Results: The authors observed significant improvement in the following variables in the surgically treated nerves: compound motor action potential amplitude (CMAP) at elbow and above elbow and conduction velocity (CV) along the forearm. Conclusion: The improvement of CMAP amplitudes and conduction velocity (CV) along the forearm express the late effect of nerve decompression. Persistence of temporal dispersion (TD) along the elbow was related to the new reaction or to incomplete surgical solution. However, moderate reduction in CV along the elbow, without TD, was considered an indication of na expected partial remyelination. Previous gradation of the nerve lesion based on the CMAP amplitude was related to the most severe results

A neuropatia de hanseníase pode desenvolver quadros inflamatórios subagudos e crônicos denominados reações, os quais podem evoluir para compressões nos túneis anatômicos. Objetivo: Descrever os achados de condução nervosa (CN) tardios em pacientes com neuropatia ulnar no cotovelo submetidos aos tratamentos clínico e cirúrgico. Método: Vinte e sete nervos de 21 pacientes foram selecionados em uma coorte retrospectiva não-concorrente por um a três anos, sendo formados dois grupos. Após o tratamento clínico sem sinais inequívocos de melhora os nervos foram randomizados para manter o tratamento clinico (Grupo A1) ou adicionar a descompressão do nervo (Grupo A2). Resultados: Os autores observaram melhora significativa nas seguintes variáveis no Grupo A2, tratado com a adição da descompressão cirúrgica, amplitude do potencial de ação motor composto (PAMC) no cotovelo e acima do cotovelo e velocidade de condução (VC) ao longo do antebraço. Conclusão: O ganho em amplitudes dos PAMCs no cotovelo e acima do cotovelo e da velocidade de condução (VC) ao longo do antebraço são a expressão do efeito tardio da descompressão do nervo ulnar. A persistência de dispersão temporal (DT) através do cotovelo foi relacionada a nova reação ou solução cirúrgica incompleta. Entretanto, a persistência de redução moderada da VC através do cotovelo sem a DT foi discutida e considerada como remielinização parcial esperada. A graduação previa da lesão do nervo baseada na amplitude dos PAMCs apresentou relação direta aos resultados menos favoráveis

Effect of Mycobacterium leprae on neurotrophins expression in human Schwann cells and mouse sciatic nerves.

BACKGROUND: Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. OBJECTIVES: We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. METHODS: We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. FINDINGS AND MAIN CONCLUSIONS: Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.

Effect of Mycobacterium leprae on neurotrophins expression in human Schwann cells and mouse sciatic nerves

BACKGROUND Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. OBJECTIVES We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. METHODS We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. FINDINGS and MAIN CONCLUSIONS Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.

Effect of Mycobacterium leprae on neurotrophins expression in human Schwann cells and mouse sciatic nerves

BACKGROUND: Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. OBJECTIVES: We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. METHODS: We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. FINDINGS and MAIN CONCLUSIONS: Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy(AU).

Peripheral nerve tumor, a differential diagnosis with primary neural leprosy: five case reports / Tumor de nervo periférico, diagnóstico diferencial com hanseníase neural primária: relato de cinco casos

From December 1999 to May 2015, five patients with nerve tumors were sent to Lauro de Souza Lima Institute. It was suspected that they suffered from primary neural leprosy towards the tuberculoid clinical form, a prevalence of 4.5:10000 among the new patients assessed during the study period. All of the patients had similar clinical conditions characterized by mononeuropathy with nerve tumor associated with pain, absence of skin lesions and positive Mitsuda reaction. The authors report the main clinical characteristics and complementary tests: immunologic investigation of Mitsuda's reaction and the antigen Phenolic GlicoLipid-1 test (PGL-1), bacilloscopic index, neurophysiologic study and image procedures. All patients were submitted to tumor resection and anatomopathological study. Four out of the five patients were diagnosed with peripheral nerve tumor (one of them with malignant schwannoma, two of them with benign schwannomas and the other with neural fibrolipoma), whereas the fifth patient was diagnosed with tuberculoid leprosy.

No período de dezembro de 1999 a maio de 2015, foram encaminhados ao Instituto Lauro de Souza Lima (ILSL) cinco pacientes com tumoração em nervos suspeitos de hanseníase neural primária (HPN) da forma clinica tuberculoide, uma prevalência de 4,5/10000 entre os casos novos atendidos nesse período. Todos os pacientes apresentavam quadro clínico semelhante caracterizado por mononeuropatia com tumoração do nervo associada à dor, ausência de lesões de pele e reação de Mitsuda positiva. Os autores relatam as principais características clinicas e os exames complementares: investigação imunológica da reação de Mitsuda e o teste do antigeno Glicolipídeo-Fenólico-1, índice baciloscópico, avaliação neurofisiológica e estudos de imagem. Todos os pacientes foram submetidos a ressecção cirúrgica do tumor e estudo anatomopatológico. Dentre os cinco pacientes, quatro foram diagnosticados como tumor de nervo periférico (um Schwannoma maligno, dois Schwannomas benignos e um fibrolipoma neural) e um como hanseníase tuberculoide.

The contribution of HLA molecules to Dupuytren's contracture in a Southeast Brazilian population.

PURPOSE: The aim of the present study was to investigate the HLA phenotype in Dupuytren's contracture (DC) patients in order to verify the correlation of these alleles with risk factors for development of DC in the Brazilian population. METHODS: This was a case-controlled study of 25 DC patients and 443 healthy individuals with no history of HLA-associated diseases. HLA class I and class II typing was performed using the polymerase chain reaction sequence-specific primer method. RESULTS: The HLAB*18 phenotype was observed in 32% of the patients and 10.5% of controls. However, P values did not remain significant after correction. DISCUSSION: Although we observed an increased tendency of DC patients to possess the HLA-B*18 allele, the results were not statistically significant after correction. This allele was higher in patients of Italian and/or Spanish ethnicity, localities with frequencies higher than 18.0% and 14.0% respectively. Further investigation with a larger cohort of DC patients is required to confirm the potential role of HLA in this disease.

Contribuicao das moleculas de antigeno de histocompatibilidade leucocitaria (HLA) para a contratura de Dupuytren em uma populacao do Sudeste do Brasil / The contribution of HLA molecules to Dupuytren's contracture in a Southeast Brazilian population

Objetivo: O objetivo deste estudo foi investigar o fenótipo do HLA em pacientes com contratura de Dupuytren (CD) para verificar a correlação desses alelos com os fatores de risco para o desenvolvimento da CD na população brasileira. Métodos: Este foi um estudo de caso-controle de 25 pacientes com CD e 443 indivíduos saudáveis sem histórico de doenças associadas ao HLA. As tipagens classe I e classe II do HLA foram feitas utilizando o método iniciador de sequências específicas da reação em cadeia da polimerase. Resultados: O fenótipo HLA-B*18 foi observado em 32% dos pacientes e 10,5% do grupo controle. Contudo, os valores de p não permaneceram significativos após correção. Discussão: Apesar de termos observado um aumento na tendência de os pacientes com CD terem o alelo HLA-B*18, os resultados não foram estatisticamente significativos após correção. Esse alelo foi maior em pacientes de etnia italiana e/ou espanhola, locais com frequências superiores a 18% e 14%, respectivamente. São necessárias investigações adicionais com uma coorte maior de pacientes com CD para confirmar o possível papel do HLA nessa doença. .

Purpose: The aim of the present study was to investigate the HLA phenotype in Dupuytren's contracture (DC) patients in order to verify the correlation of these alleles with risk factors for development of DC in the Brazilian population. Methods: This was a case-controlled study of 25 DC patients and 443 healthy individuals with no history of HLA-associated diseases. HLA class I and class II typing was performed using the polymerase chain reaction sequence-specific primer method. Results: The HLAB*18 phenotype was observed in 32% of the patients and 10.5% of controls. However, P values did not remain significant after correction. Discussion: Although we observed an increased tendency of DC patients to possess the HLA-B*18 allele, the results were not statistically significant after correction. This allele was higher in patients of Italian and/or Spanish ethnicity, localities with frequencies higher than 18.0% and 14.0% respectively. Further investigation with a larger cohort of DC patients is required to confirm the potential role of HLA in this disease. .

Case for diagnosis.

Lipomas are common benign mesenchymal tumors composed of mature fat cells that may or may not be surrounded by a thin, fibrous capsule. The link with trauma has already been described. Lipomas involving the fingers are extremely rare but must be considered in the differential diagnosis of benign soft tissue masses in this particular location.

Borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis.

We describe a case of borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis in a patient who presented at our hospital with skin lesions and joint complaints.

Case for diagnosis / Caso para diagnóstico

Lipomas are common benign mesenchymal tumors composed of mature fat cells that may or may not be surrounded by a thin, fibrous capsule. The link with trauma has already been described. Lipomas involving the fingers are extremely rare but must be considered in the differential diagnosis of benign soft tissue masses in this particular location.

Lipomas são neoplasias mesenquimais benignas comuns constituídas de células gordurosas maduras que podem ou não estar envoltas por cápsula conjuntiva. A relação com o trauma já foi descrita. Aqueles envolvendo os dedos são extremamente raros, mas devem ser considerados no diagnóstico diferencial das massas benignas de tecidos moles em tal localização.

Borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis / Hanseníase dimorfa tuberculoide associada à histoplasmose cutânea primária

We describe a case of borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis in a patient who presented at our hospital with skin lesions and joint complaints.

Descrevemos um caso de hanseníase dimorfa tuberculoide associada à histoplasmose cutânea primária em um paciente que procurou nosso hospital com lesões dermatológicas e queixas articulares.

Accidental Jorge Lobo's disease in a worker dealing with Lacazia loboi infected mice: a case report

INTRODUCTION: Jorge Lobo's disease (Lacaziosis) is a subcutaneous infection of humans living in the Amazon region of Latin America, and in dolphins inhabiting the east coastal areas of the United States. The disease mainly affects people from rural areas living or working in close contact with vegetation and aquatic environments. Most patients refer having developed lesions after accidental trauma with plant thorns or insect bites. Inter-human transmission has never been confirmed suggesting that Lacazia loboi is acquired from environmental propagules. CASE PRESENTATION We report the case of a 41-year-old woman from São Paulo, Brazil, a non-endemic area of Jorge Lobo's disease, with L. loboi skin infection most likely accidentally acquired while manipulating experimentally infected mice in the laboratory. CONCLUSION: Because many patients with Jorge Lobo's disease do not recall accidental skin trauma before their infections, the possibility of accidentally acquired Jorge Lobo's disease through unnoticed broken skin should be considered during the clinical investigation of nodular skin diseases in people who have contact with the fungus or who live in endemic areas. This is the second report of animal to human transmission of this disease.

Hanseníase tuberculóide apresentando-se como lesão em raquete de tênis: relato de um caso típico / Tuberculoid leprosy presenting as a racket lesion: report of a typical case

A hanseníase tuberculóide é caracterizada, em geral, por lesões únicas ou em pequeno número, sendo o comprometimento neural intenso e localizado. A lesão "em raquete de tênis" caracteriza de forma particular esse comprometimento, e se apresenta sob a forma de um ramo nervoso sensitivo cutâneo emergindo de uma placa tuberculóide. Relata-se o caso de paciente masculino, 61 anos, com diagnóstico de hanseníase tuberculóide, cuja lesão permaneceu ativa mesmo após o término de poliquimioterapia paucibacilar (PQT-PB). Ao exame dermatológico, foi observado espessamento do ramo superficial do nervo ulnar, emergindo da placa tuberculóide típica em dorso da mão direita, caracterizando a "lesão em raquete de tênis". A sorologia para anti-PGL-1 foi negativa, o exame histopatológico da lesão demonstrou hanseníase de padrão tuberculóide com baciloscopia negativa, e a reação de Mitsuda foi fortemente positiva, confirmando o diagnóstico de hanseníase tuberculóide ativa. Foi reiniciado o tratamento com PQT-PB, além de emprego de neurolépticos, com discreta regressão da lesão. Neste relato, ao ser apresentado um caso típico de lesão "em raquete de tênis", evidencia-se a evolução clássica dos casos de hanseníase em pacientes Mitsuda positivos, onde a PQT geralmente não modifica a história natural da doença.

Tuberculoid leprosy is characterized, usually, by single or few lesions which show intense and localized neural impairement. The "racket lesion", which is described as pathognomonic of tuberculoid leprosy, presents with a cutaneous nerve branch emerging from a tuberculoid plaque. It is reported a case of a 61 years old male, with diagnosis of tuberculoid leprosy, whose lesion remained active even after the end of PB multidrugtherapy (PB-MDT). At dermatologic examination, enlargement of the sensitive cutaneous branch of the ulnar nerve was observed, which emerged from a tuberculoid plaque on the dorsum of the right hand, characterizing a "racket lesion". Serology for anti-PGL-1 was negative, and the Mitsuda reaction was highly positive, confirming the diagnosis of tuberculoid leprosy. MDT-PB was reinitiated, with little improvement. In this report, we describe the typical evolution of leprosy in individuals with positive Mitsuda reaction, where the MDT does not change the natural history of the disease.

Hanseníase multibacilar com baciloscopia dos esfregaços negativa: a importância de se avaliar todos os critérios antes de se definir a forma clínica / Multibacillary leprosy with the smear negative smears: the importance of evaluating all the criteria before to define the clinical form

Homem de 36 anos de idade, procedente de Bauru-SP, refere que há 4 meses apresenta bolhas periungueais em mão esquerda associadas à perda de sensibilidade local;evolui com reabsorção parcial e progressiva de todas as falanges distais desta mão. Procurou serviço médico por várias vezes, sendo prescritos apenas antibióticos para as infecções nas falanges. Ao exame físico, reabsorção de falanges distais em mão esquerda, ausência alterações motoras de origem neural, presença de múltiplasmáculas e placas hipocrômicas em nádegas e membros superiores e inferiores, além de discreta perda de sensibilidade em ambos os pés. As duas primeiras biópsias em duas máculas mostraram quadro compatível com hanseníase indeterminada, com baciloscopia da biópsia negativa, e uma terceira revelou hanseníase na faixa tuberculóide com baciloscopia 1+. As baciloscopias de pontos índices e das lesões foram todas negativas.A reação de Mitsuda foi de 3,5mm, e o Teste Ml-Flowmostrou positividade 3+. O quadro neurológico era deu ma neuropatia sensitiva do membro superior esquerdo,e o estudo neurofisiológico evidenciou uma mononeuropatia múltipla sensitiva e motora do membro superior esquerdo com comprometimento dos nervos ulnar e mediano. O ramo dorsal do nervo ulnar foi submetido à biópsia que demonstrou quadro histológico inflamatório não granulomatoso, mas com baciloscopia 4+ com muitos bacilos típicos. Discute-se a importância de se avaliar todos os critérios antes de se definir a forma clínica de uma doença sistêmica como a hanseníase

Efeito da osteotomia de Salter no crescimento do osso ilíaco do coelho / The effect of the Salter osteotomy in the growth of the iliac bone of the rabbit

Foi avaliada a influência da osteotomia de Salter no crescimento do osso ilíaco. Para isso, nove coelhos de quatro semanas de idade foram submetidos à osteotomia de Salter no ilíaco direito e cinco coelhos foram submetidos a operaçao simulada. A pelve de cada animal foi radiografada imediatamente após a cirurgia e depois de seis meses, quando ocorreu o sacrifício. Nas radiografias foram realizadas medidas segmentares do comprimento da pelve, com o objetivo de avaliar o crescimento ósseo longitudinal dos ilíacos direito e esquerdo. Além disso, a pelve foi dissecada e, livre das partes moles, foi avaliada e medida diretamente. Foi constatado que o ilíaco operado (D) cresceu significativamente menos em todos os animais submetidos à osteotomia, em comparaçao como o ilíaco contralateral. Em 50 por cento dos animais operados, houve alteraçao significativa do contorno interno do anel pélvico, assim como assimetria da asa do ilíaco em que ocorreu a intervençao. Nos animais submetidos à operaçao simulada, nao houve diferença entre os lados.