Silent peripheral neuropathy determined by high-resolution ultrasound among contacts of patients with Hansen's disease.

Introduction: Hansen's disease (HD) primarily infects peripheral nerves, with patients without HD being free of peripheral nerve damage. Household contacts (HHCs) of patients with HD are at a 5-10 times higher risk of HD than the general population. Neural thickening is one of the three cardinal signs that define a case of HD according to WHO guidelines, exclusively considering palpation examination that is subjective and may not detect the condition in the earliest cases even when performed by well-trained professionals. High-resolution ultrasound (HRUS) can evaluate most peripheral nerves, a validated technique with good reproducibility allowing detailed and accurate examination. Objective: This study aimed to use the peripheral nerve HRUS test according to the HD protocol as a diagnostic method for neuropathy comparing HHCs with healthy volunteers (HVs) and patients with HD. Methods: In municipalities from 14 different areas of Brazil we selected at random 83 HHC of MB-patients to be submitted to peripheral nerve ultrasound and compared to 49 HVs and 176 HD-patients. Results: Household contacts assessed by HRUS showed higher median and mean absolute peripheral nerve cross-sectional area (CSA) values and greater asymmetries (ΔCSA) compared to HVs at the same points. Median and mean absolute peripheral nerve CSA values were higher in patients with HD compared to HCCs at almost all points, while ΔCSA values were equal at all points. Mean ± SD focality (ΔTpT) values for HHCs and patients with HD, respectively, were 2.7 ± 2.2/2.6 ± 2.2 for the median nerve, 2.9 ± 2.7/3.3 ± 2.9 for the common fibular nerve (p > 0.05), and 1.3 ± 1.3/2.2 ± 3.9 for the ulnar nerve (p < 0.0001). Discussion: Considering HRUS findings for HHCs, asymmetric multiple mononeuropathy signs (thickening or asymmetry) in at least 20% of the nerves evaluated could already indicates evidence of HD neuropathy. Thus, if more nerve points are assessed in HHCs (14 instead of 10), the contacts become more like patients with HD according to nerve thickening determined by HRUS, which should be a cutting-edge tool for an early diagnosis of leprosy cases.

Innovative tracking, active search and follow-up strategies for new leprosy cases in the female prison population.

BACKGROUND: Regarding the leprosy transmission through the upper airways, overcrowded locations such as prisons can become a risk to get sick. Like the leprosy hidden endemic demonstrated in male prison population, being interesting to assess the leprosy scene also among confined women. METHODS: A prospective descriptive study conducted at Female Penitentiary, Brazil. Leprosy Suspicion Questionnaire (LSQ) were applied to the participants, and submitted to specialized dermatoneurological exam, peripheral nerve ultrasonography, and anti-PGL-I serology. FINDINGS: 404 female inmates were evaluated, 14 new cases were diagnosed (LG-leprosy group), a new case detection rate (NCDR) of 3.4%, 13 multibacillary, while another 390 constituted the Non-Leprosy group (NLG). Leprosy cases were followed up during multidrug therapy with clinical improvement. The confinement time median was 31 months in LG, similar to NLG, less than the time of leprosy incubation. Regarding LSQ, the neurological symptoms reached the highest x2 values as Q1-numbness (5.6), Q3-anesthetizes areas in the skin (7.5), Q5-Stinging sensation (5.8), and Q7-pain in the nerves (34.7), while Q4-spots on the skin was 4.94. When more than one question were marked in the LSQ means a 12.8-fold higher to have the disease than a subject who marked only one or none. The high 34% rate of anti-PGL-I seropositivity in the penitentiary, higher levels in LG than NLG. Three additional leprosy cases each were diagnosed on the second (n = 66) and third (n = 14) reevaluations 18 and 36 months after the initial one. Semmes-Weinstein monofilaments demonstrated lower limbs (32.2%) more affected than the upper limbs (25%) with improvement during the follow-up. INTERPRETATION: The NCDR in this population showed an hidden endemic of leprosy as well as the efficacy of a search action on the part of a specialized team with the aid of the LSQ and anti-PGL-I serology as an auxiliary tracking tools.

Assessing nerves in leprosy

Leprosy neuropathy is dependent on the patient's immune response and expresses itself as a focal or multifocal neuropathy with asymmetric involvement. Leprosy neuropathy evolves chronically but recurrently develops periods of exacerbation during type 1 or type 2 reactions, leading to acute neuropathy. Nerve enlargement leading to entrapment syndromes is also a common manifestation. Pain may be either of inflammatory or neuropathic origin. A thorough and detailed evaluation is mandatory for adequate patient follow-up, including nerve palpation, pain assessment, graded sensory mapping, muscle power testing, and autonomic evaluation. Nerve conduction studies are a sensitive tool for nerve dysfunction, including new lesions during reaction periods or development of entrapment syndromes. Nerve ultrasonography is also a very promising method for nerve evaluation in leprosy. The authors propose a composite nerve clinical score for nerve function assessment that can be useful for longitudinal evaluation.

New sonographic measures of peripheral nerves: a tool for the diagnosis of peripheral nerve involvement in leprosy.

To evaluate ultrasonographic (US) cross-sectional areas (CSAs) of peripheral nerves, indexes of the differences between CSAs at the same point (∆CSAs) and between tunnel (T) and pre-tunnel (PT) ulnar CSAs (∆TPTs) in leprosy patients (LPs) and healthy volunteers (HVs). Seventy-seven LPs and 49 HVs underwent bilateral US at PT and T ulnar points, as well as along the median (M) and common fibular (CF) nerves, to calculate the CSAs, ∆CSAs and ∆TPTs. The CSA values in HVs were lower than those in LPs (p < 0.0001) at the PT (5.67/9.78 mm2) and T (6.50/10.94 mm2) points, as well as at the M (5.85/8.48 mm2) and CF (8.17/14.14 mm2) nerves. The optimum CSA- receiver operating characteristic (ROC) points and sensitivities/specificities were, respectively, 6.85 mm2 and 68-85% for the PT point, 7.35 mm2 and 71-78% for the T point, 6.75 mm2 and 62-75% for the M nerve and 9.55 mm2 and 81-72% for the CF nerve. The ∆CSAs of the LPs were greater than those of the HVs at the PT point (4.02/0.85; p = 0.007), T point (3.71/0.98; p = 0.0005) and CF nerve (2.93/1.14; p = 0.015), with no difference found for the M nerve (1.41/0.95; p = 0.17). The optimum ∆CSA-ROC points, sensitivities, specificities and p-values were, respectively, 1.35, 49%, 80% and 0.003 at the PT point, 1.55, 55-85% and 0.0006 at the T point, 0.70, 58-50% and 0.73 for the M nerve and 1.25, 54-67% and 0.022 for the CF nerve. The ∆TPT in the LPs was greater than that in the HVs (4.43/1.44; p <0.0001). The optimum ∆TPT-ROC point was 2.65 (90% sensitivity/41% specificity, p < 0.0001). The ROC analysis of CSAs showed the highest specificity and sensitivity at the PT point and CF nerve, respectively. The PT and T ∆CSAs had high specificities (> 80%) and ∆TPT had the highest specificity (> 90%). New sonographic peripheral nerve measurements (∆CSAs and ∆TPT) provide an important methodological improvement in the detection of leprosy neuropathy.

New sonographic measures of peripheral nerves: a tool for the diagnosis of peripheral nerve involvement in leprosy

To evaluate ultrasonographic (US) cross-sectional areas (CSAs) of peripheral nerves, indexes of the differences between CSAs at the same point (∆CSAs) and between tunnel (T) and pre-tunnel (PT) ulnar CSAs (∆TPTs) in leprosy patients (LPs) and healthy volunteers (HVs). Seventy-seven LPs and 49 HVs underwent bilateral US at PT and T ulnar points, as well as along the median (M) and common fibular (CF) nerves, to calculate the CSAs, ∆CSAs and ∆TPTs. The CSA values in HVs were lower than those in LPs (p < 0.0001) at the PT (5.67/9.78 mm2) and T (6.50/10.94 mm2) points, as well as at the M (5.85/8.48 mm2) and CF (8.17/14.14 mm2) nerves. The optimum CSA- receiver operating characteristic (ROC) points and sensitivities/specificities were, respectively, 6.85 mm2 and 68-85% for the PT point, 7.35 mm2 and 71-78% for the T point, 6.75 mm2 and 62-75% for the M nerve and 9.55 mm2 and 81-72% for the CF nerve. The ∆CSAs of the LPs were greater than those of the HVs at the PT point (4.02/0.85; p = 0.007), T point (3.71/0.98; p = 0.0005) and CF nerve (2.93/1.14; p = 0.015), with no difference found for the M nerve (1.41/0.95; p = 0.17). The optimum ∆CSA-ROC points, sensitivities, specificities and p-values were, respectively, 1.35, 49%, 80% and 0.003 at the PT point, 1.55, 55-85% and 0.0006 at the T point, 0.70, 58-50% and 0.73 for the M nerve and 1.25, 54-67% and 0.022 for the CF nerve. The ∆TPT in the LPs was greater than that in the HVs (4.43/1.44; p <0.0001). The optimum ∆TPT-ROC point was 2.65 (90% sensitivity/41% specificity, p < 0.0001). The ROC analysis of CSAs showed the highest specificity and sensitivity at the PT point and CF nerve, respectively. The PT and T ∆CSAs had high specificities (> 80%) and ∆TPT had the highest specificity (> 90%). New sonographic peripheral nerve measurements (∆CSAs and ∆TPT) provide an important methodological improvement in the detection of leprosy neuropathy.

Leprosy late-onset neuropathy: an uncommon presentation of leprosy.

Clinical and pathological findings in leprosy are determined by the natural host immune response to Mycobacterium leprae. We previously described cases of painful neuropathy (PN) with no concurrent cause apart from a past history of leprosy successfully treated. Four leprosy previously treated patients who developed a PN years after multidrug therapy (MDT) are reported. The mean patient age was 52.75 years (47-64). The mean time interval of the recent neuropathy from the previous MDT was 19 years (12-26). A painful multiplex neuritis or polyneuropathy were observed respectively in two cases. Electrophysiological studies disclosed a sensory axonal neuropathy in two cases. Microvasculitis with no bacilli was seen in nerve biopsy. Neuropathic symptoms were improved with prednisone. We consider these cases as being a leprosy late-onset neuropathy (LLON) form of presentation. A delayed immune reaction could explain the late appearance of LLON.

Leprosy late-onset neuropathy: an uncommon presentation of leprosy / Neuropatia de início tardio: uma apresentação incomum da hanseníase

Clinical and pathological findings in leprosy are determined by the natural host immune response to Mycobacterium leprae. We previously described cases of painful neuropathy (PN) with no concurrent cause apart from a past history of leprosy successfully treated. Four leprosy previously treated patients who developed a PN years after multidrug therapy (MDT) are reported. The mean patient age was 52.75 years (47-64). The mean time interval of the recent neuropathy from the previous MDT was 19 years (12-26). A painful multiplex neuritis or polyneuropathy were observed respectively in two cases. Electrophysiological studies disclosed a sensory axonal neuropathy in two cases. Microvasculitis with no bacilli was seen in nerve biopsy. Neuropathic symptoms were improved with prednisone. We consider these cases as being a leprosy late-onset neuropathy (LLON) form of presentation. A delayed immune reaction could explain the late appearance of LLON.

Dados clínicos e patológicos são determinados pela resposta imune ao Mycobacterium leprae. Já haviamos descrito previamente casos de neuropatia dolorosa (ND) sem causa associada exceto história de hanseníase tratada. Relatamos agora quatro pacientes previamente tratados que desenvolveram ND anos após multidrogaterapia (MDT). A média de idade foi de 52,75 anos (47-64). O intervalo de tempo para o aparecimento da neuropatia recente, em relação à MDT prévia, foi de 19 anos (12-26). Neurite múltipla ou polineuropatia dolorosa foram observadas em dois casos. Estudos eletrofisiológicos revelaram ocorrência de neuropatia sensitiva axonal em dois casos. Em biópsia de nervos, foi observada microvasculite sem a presença de bacilos. Os sintomas neuropáticos melhoraram com o uso de prednisona. Consideramos esses casos como sendo a forma de apresentação de neuropatia da hanseníase de início tardio (NHIT). Reação imune tardia poderia explicar o aparecimento da NHIT.

Early detection of leprosy by examination of household contacts, determination of serum anti-PGL-1 antibodies and consanguinity

A cross-sectional clinical trial in which the serum anti-phenolic glycolipid (anti-PGL-1) antibodies were analysed in household contacts (HHC) of patients with leprosy as an adjunct early leprosy diagnostic marker was conducted. The families of 83 patients underwent clinical examination and serum anti-PGL1 measurement using enzyme-linked immunosorbent assay. Of 320 HHC, 98 were contacts of lepromatous leprosy (LL), 80 were contacts of borderline lepromatous (BL), 28 were contacts of borderline (BB) leprosy, 54 were contacts of borderline tuberculoid (BT), 40 were contacts of tuberculoid (TT) and 20 were contacts of indeterminate (I) leprosy. Consanguinity with the patients was determined for 232 (72.5 percent) HHC. Of those 232 contacts, 183 had linear consanguinity. Forty-nine HHC had collateral consanguinity. Fifty-eight contacts (18.1 percent) tested positive for anti-PGL1 antibodies. The number of seropositive contacts based on the clinical forms of the index case was 17 (29.3 percent) for LL, 15 (25.9 percent) for BL, one (1.7 percent) for BB, 14 (24.1 percent) for BT, three (5.2 percent) for TT and eight (13.7 percent) for I. At the one year follow-up, two (3.4 percent) of these seropositive contacts had developed BT leprosy. The results of the present study indicate that the serum anti-PGL-1 IgM antibody may be useful for evaluating antigen exposure and as a tool for an early leprosy diagnosis in HHC.

Near nerve potential of sural nerve in leprosy

Na hanseníase, as fibras de pequeno calibre são acometidas antes que as fibras mais grossas, ocasião em que o estudo da condução torna-se anormal. Neste estudo, utilizou-se a técnica de registro com eletrodos justa-nervo com a finalidade de aumentar a precocidade e a acurácia diagnóstica, devido à sua capacidade de detectar potenciais oriundos de fibras com cerca de 3-6 mm. Contrário às nossas expectativas, o componente principal do potencial sensitivo do nervo sural foi anormal em todos os pacientes, enquanto a velocidade de condução mínima foi normal ou discretamente alterada em 3 pacientes. Além disso, os resultados são sugestivos de degeneração axonal e não mielinopatia, como seria esperado em uma doença que compromete inicialmente a bainha de mielina. Para um melhor entendimento da fisiologia e fisiopatologia, e para aumentar a precocidade diagnóstica, é fundamental estudar casos bem precoces e correlacionar os dados neurofisiológicos com a respectiva anatomia patológica.

Near-nerve potential in lepromatous leprosy

In leprosy, sensory action potentials (SAPs) may be normal in spite of clinical sensory loss. This may result from the early involvement of small nerve fibers, which have potentials that are not detected in routine studies. To evaluate this possibility, we used a near-nerve recording technique that records potentials from nerve fibers as small as 4-6 microm in diameter. We hypothesized that this technique might increase the sensitivity of nerve conduction studies in detecting leprosy neuropathy. We found the technique to be useful for recording conduction abnormalities in recently diagnosed patients, including those with preserved sensation, suggesting that axonal loss may be the underlying mechanism. Contrary to our hypothesis, however, recording the late SAP components did not improve the sensitivity of nerve conduction studies. We suggest that the late components having normal conduction velocities may be generated by either regenerating or remyelinating abnormal fibers, which have an electrophysiological behavior similar to that of normal 4-6-microm-diameter fibers.

Estudo das neuropatias periféricas no Estado de Säo Paulo de 1939 a 1985 / Study on peripheral neuropathies in the State of Säo Paulo from 1939 to 1985

Constam do presente trabalho estudos sobre neuropatias perifericas de pesquisadores redicados no Estado de Sao Paulo, publicados a partir das decadas de trinta e quarenta. Maior impulsodas investigacoes na area ocorreu com o surgimento do periodo Arquivos de Neuro-Psiquiatria. Oswaldo Freitas juliao pode ser considerado o autor que iniciou os referidos estudos e suas contribuicoes mais importantes se fizeram em relacao a hanseniase e a doenca de Andrade, embora tenha tambem publicado trabalhos sobre outros tipos de neuropatias perifericas. Horacio Martin Canelas contribuiu sobremaneira para o estudo de difenrentes neuropatias, em particular das por deficientci de vitamina B12. Uma serie de trabalhos sobre o tema, publucada por neurologistas radicados no Estado, e sumariada. Apresentamos ainda, um catalogo dos principais centros universitarios em que ha grupos de neurologistas que se dedicam preferencialmente ao estudo das doencas neuromusculares em Sao Paulo e uma bibliografia selecionada sobre neuropatias, de investigadores do referido Estado.

Estudo das neuropatias periféricas no Estado de Säo Paulo de 1939 a 1985 / Study on peripheral neuropathies in the State of Säo Paulo from 1939 to 1985

Constam do presente trabalho estudos sobre neuropatias periféricas de pesquisadores radicados no Estado de Säo Paulo, publicados a partir das décadas de trinta e quarenta. Maior impulso das investigaçöes na área ocorreu com o surgimento do periódico Arquivos de Neuro-Psiquiatria. Oswaldo Freitas Juliäo pode ser considerado o autor que iniciou os referidos estudos e suas contribuiçöes mais importantes se fizeram em relaçäo à hanseníase e à doença de Andrade, embora tenha também publicado trabalhos sobre outros tipos de neuropatias periféricas. Horacio Martin Canelas contribuiu sobremaneira para o estudo de difenrentes neuropatias, em particular das por deficiência de vitamina B12. Uma série de trabalhos sobre o tema, publicada por neurologistas radicados no Estado, é sumariada. Apresenta, ainda, um catálogo dos principais centros universitários em que há grupos de neurologistas que se dedicam preferencialmente ao estudo das doenças neuromusculares em Säo Paulo e uma bibliografia selecionada sobre neuropatias, de investigadores do referido Estado. (AU)

O potencial de ação sensitivo do nervo mediano com eletrodos de agulha justapostos ao nervo na hanseniase virchowiana e dimorfo-virchowiana / ?

Foram analisados os componentes principal (fibra com 7um ou mais de diametro) e tardio (fibras de 4um de diametro) de 8 nervos medianos de pacientes com hanseniase formas V e DV, recem diagnosticadas e ainda não submetidos a tratamento ou com menos de 2 semanas de tratamento, atraves de eletrodos de grandeza ideal justapostos ao nervo, 500 a 2000 promediações, um sistema de baixo ruido interno e grande amplificação dos potenciais. Os resultados dos pacientes foram comparados aos resultados de 14 individuos normais. O exame clinico dirigido das funçoes sensitiva e motora dos nervos medianos mostrou que um dos pacientes apresentava comprometimento do tronco do nervo, 2 apresentavam alteração sensitiva correspondendo a lesão de ramos cutaneos e 5 tinham exame normal. Foram detectadas alterações neurofisiologicas nos 3 pacientes com exame clinico alterado e em 4 dos pacienes com exame clinico normal. O componente principal do PAS foi anormal em 7 nervos e o componente tardio em 4. A alteração mais frequente do componete principal foi redução da amplitude. Em 2 pacientes havia, concomitantemente, redução da velocidade de condução deste componente e em uma havia alteração isolada da velocidade de condução. Não se observou alteração isolada do componente tardio em nenhuma situação. As alterações do componente principal sugerem haver lesão predominantemente axonal das fibras com mais de 7um. A origem dos componentes tardios anormais é indeterminada. O estudo concomitante do componente principal e do componete tardio do PAS do nervo mediano não parece ser um metodo mais sensivel que o estudo isolado do componente principal. A avaliação com eletrodos justapostos ao nervo permitiu, não só a detecção de anormalidade em pacientes com lesão do tronco do nervo, mas tambem daqueles com lesão clinicamente restrita aos ramos cutaneos e, de maneira precoce, em pacientes sem manifestação clinica de lesão do nervo. A proporcionalidade de acometimento dos componentes principal e tardio necessita de melhor expliocação. A luz dos conhecimentos atuais esperar-se-ia, na neuropatia da hanseniase, um acometimento maior das fibras finas.

Diagnóstico das neuropatias periféricas: diagnósticos sindrômicos, topográficos e etiológicos / Diagnosis of peripheral neuropathies: syndromic, topographic and etiological diagnoses

Por avaliaçäo retrospectiva, discriminam-se no presente estudo os diagnósticos sindrômicos topográficos e etiológicos aos quais se conseguiu chegar em 209 casos de neuropatias periféricas. A anamnese e o exame clínico-neurológico foram fundamentais para a realizaçäo dos diagnósticos sindrômicos e topográficos. A eletromiografia teve papel relevante, particularmente no que se refere aos diagnósticos topográficos. Os diagnósticos etiológicos dependeram adicionalmente, de outros exames complementares, dentre os quais se destacam: glicemia e curva glicêmica; avaliaçäo nutricional; avaliaçäo familiar; biópsias de nervo, pele, faringe e seio maxilar; teste qualitativo para a presença de porfirinas na urina; ácido delta-aminolevulínico e porfobilinogênio urinários; exames radiológicos. As polineuropatias mais frequentemente encontradas foram as: etílico-carenciais, diabéticas, inflamatórias desmielinizantes agudas e hereditárias. As sídromes do túnel do carpo, as lesöes traumáticas do VII nervo craniano e as neuralgias do trigêmeo foram os diagnósticos mais frequentes entre os de mononeuropatias. A hanseníase, as lesöes traumáticas do plexo braquial e a síndrome do desfiladeiro torácico predominaram entre as multineuropatias

Diagnóstico das neuropatias periféricas: idade, sexo e ocupaçäo em relaçäo às etiologias / Diagnosis of peripheral neuropathies: age, sex and occupation in report to etiology

As etiologias de 209 casos de neuropatias periféricas foram estudadas levando-se em conta as respectivas faixas etárias mais acometidas, o sexo e a ocupaçäo dos pacientes. As faixas etárias das polineuropatias etílico-carenciais, diabéticas,da síndrome de Guillain-Barré e das neuropatias sensitivo-motoras hereditárias em nosso grupo de pacientes foram as seguintes: 20 aos 50, 10 aos 70 e 0 aos 30 anos. A faixa etária dos pacientes com hanseníase e traumatismos de nervos foi: 20 aos 50 anos e, mais frequentemente, até 30 anos de idade. Houve franco predomínio do acometimento de pessoas do sexo masculino nas polineuropatias etílico-carenciais e nas diabéticas. Predominio do sexo feminino ocorreu nas lesöes do nervo mediano e nas multirradiculopatias. Cerca de 1/3 das polineuropatias etílico-carenciais acometeram lavradores. A condiçäo de inativo foi referida por 1/3 das pacientes com polineuropatias diabéticas, 25% das carenciais e 24% da indefinidas