Adverse reactions induced by MDT/WHO (Rifampicin+Clofazimine+Dapsone) and ROM (Rifampicin+Ofloxacin+Minocycline) regimens used in the treatment of leprosy: a cohort study in a National Reference Center in Brazil.

Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.

Identification of types of wound bed tissue as a percentage and total wound area by planimetry in neuropathic and venous ulcers.

BACKGROUND: Neuropathic and venous leg ulcers are chronic wounds associated with devitalized tissue and recurrent infection. Management should be guided by accurate tissue assessment, including the use of planimetry, which provides tissue types as a percentage of the total wound bed surface area. OBJECTIVE: This innovative study aimed to assess and identify the wound bed tissues, as a percentage, of neuropathic and venous ulcers using digital planimetry, providing support to nurses optimize the management of necrotic tissues and, consequently, to avoid wound infection. METHODS: This cross-sectional study enrolled 24 patients with chronic wounds who were assessed from January to March 2021 at the Wound Outpatients Clinic. The wound photographs were analyzed using Image J 1.53e and a smartphone with WoundDoc Plus® 2.8.2 via digital planimetry. Statistical analyses were performed using the binomial test, t-test, and Mann-Whitney. RESULTS: Median wound areas (p=0.3263) did not differ between the group with 2 or 3 risk factors for delayed healing (Md: 31.7) and the group with up to 1 risk factor (Md: 5.3). A low exudate level was associated with the up-to-1-risk-factor-for-delayed-healing group (p=0.0405), while a medium level was associated with the two-or-three-risk-factor group (p=0.0247). A heat map displayed the tissue percentages in the wound bed. In the group with 2 or 3 risk factors for delayed healing, 91.7% (11/12) had less than 70% granulation tissue, which was the primary factor for this group (p<0.0001). Additionally, 66.7% (8/12) of patients with 2 or 3 risk factors for delayed healing exhibited discolored and/or dark red granulation tissue as the primary factor (p=0.0130). CONCLUSION: This novel identification of wound area and tissue types as a percentage, using digital planimetry, can play a crucial role in assisting nurses in decision-making related to the appropriate management of devitalized tissues. Furthermore, this measurements may facilitate the conducting of virtual wound consultations and offer valuable support in the development of protocols aimed at preventing infection and biofilm formation in the wound bed.

High-resolution ultrasonography for early diagnosis of neural impairment in seropositive leprosy household contacts.

Leprosy household contacts (HC) represent a high-risk group for the development of the disease. Anti-PGL-I IgM seropositivity also increases the risk of illness. Despite significant advances in leprosy control, it remains a public health problem; and early diagnosis of this peripheral neuropathy represents one of the main goals of leprosy programs. The present study was performed to identify neural impairment in leprosy HC by analyzing differences in high-resolution ultrasonographic (US) measurements of peripheral nerves between leprosy HC and healthy volunteers (HV). Seventy-nine seropositive household contacts (SPHC) and 30 seronegative household contacts (SNHC) underwent dermato-neurological examination and molecular analysis, followed by high-resolution US evaluation of cross-sectional areas (CSAs) of the median, ulnar, common fibular and tibial nerves. In addition, 53 HV underwent similar US measurements. The US evaluation detected neural thickening in 26.5% (13/49) of the SPHC and only in 3.3% (1/30) among the SNHC (p = 0.0038). The CSA values of the common fibular and tibial nerves were significantly higher in SPHC. This group also had significantly greater asymmetry in the common fibular and tibial nerves (proximal to the tunnel). SPHC presented a 10.5-fold higher chance of neural impairment (p = 0.0311). On the contrary, the presence of at least one scar from the BCG vaccine conferred 5.2-fold greater protection against neural involvement detected by US (p = 0.0184). Our findings demonstrated a higher prevalence of neural thickening in SPHC and support the role of high-resolution US in the early diagnosis of leprosy neuropathy. The combination of positive anti-PGL-I serology and absence of a BCG scar can identify individuals with greater chances of developing leprosy neuropathy, who should be referred for US examination, reinforcing the importance of including serological and imaging methods in the epidemiological surveillance of leprosy HC.

Early diagnosis of neural impairment in seropositive leprosy household contacts: The experience of a reference center in Brazil.

Introduction: Leprosy is an infectious disease that remains with a high number of new cases in developing countries. Household contacts have a higher risk for the development of the disease, but the neural impairment in this group is not well elucidated yet. Here, we measured the chance of occurrence of peripheral neural impairment in asymptomatic leprosy household. Methods: Contacts who present anti-PGL-I IgM seropositivity, through electroneuromyography (ENMG) evaluation. We recruited 361 seropositive contacts (SPC) from 2017 to 2021, who were subjected to an extensive protocol that included clinical, molecular, and electroneuromyographic evaluations. Results: Our data revealed a positivity of slit skin smear and skin biopsy qPCR of 35.5% (128/361) and 25.8% (93/361) respectively. The electroneuromyographic evaluation of the SPC showed neural impairment in 23.5% (85/361), with the predominance of a mononeuropathy pattern in 62.3% (53/85). Clinical neural thickening was observed in 17.5% (63/361) of seropositive contacts, but among the individuals with abnormal ENMG, only 25.9% (22/85) presented neural thickening in the clinical exam. Discussion: Ours results corroborates the need to make the approach to asymptomatic contacts in endemic countries more timely. Since leprosy in its early stages can present an indolent and subclinical evolution, serological, molecular, and neurophysiological tools are essential to break the disease transmission chain.

Description of electroneuromiographic and laboratorial findings in leprosy neuropathy, according to its clinical forms: the confirmation of a spectral disease.

Introduction: Leprosy is one of the most common infectious cause of peripheral neuropathy in the world and can lead to sequelae and physical disabilities. Electroneuromyography (ENMG) is the gold-standard test for evaluating neural impairment, detecting from subclinical abnormalities to advanced lesions. This study aims to describe the electroneuromyographic findings in patients with leprosy, according to their clinical forms. Methods: The study is a retrospective observational analysis of the medical records of patients with leprosy, of a National Reference Center of Sanitary Dermatology and Leprosy in Brazil between 2014 and 2022. 513 patients underwent ENMG at leprosy diagnosis and also underwent a clinical, serological and molecular evaluation of the disease. Results: The electroneuromyographic findings showed 2,671 altered nerves, with an average of 6.9 (±5.1) altered nerves per patient. The most affected sensory nerves were the superficial peroneal (25.0%; 413/1649), sural (15.1%; 397/2627) and ulnar (13.8%; 363/2627), with average of 4.3 (±3.2) affected sensory nerves per patient. The most affected motor nerves were the ulnar (33.1%; 338/1022) and common peroneal (12.1%; 319/2627), with average of 2.6 (±2.5) motor nerves affected per patient. 126 patients presented normal ENMG and, among the 387 with abnormalities in the exam, 13.2% (51/387) had mononeuropathy and 86.8% (336/387) had multiple mononeuropathy. Axonal involvement was more frequent in primary neural leprosy, borderline-tuberculoid, borderline-lepromatous and lepromatous forms. Discussion: Our findings support that leprosy is a spectral disease, characterized by a balance between host immunity and bacillary load. Therefore, the impairment and electroneuromyographic characteristics are distinct and may vary according to the clinical form.

Clinical, epidemiological, and laboratory prognostic factors in patients with leprosy reactions: A 10-year retrospective cohort study.

Introduction: Leprosy reactions, the main cause of neural damage, can occur up to 7 years after starting multidrug therapy. We aimed to approach the prognostic factors that may influence the leprosy reactions over the follow-up time. Methods: Retrospective cohort study, encompassing 10 years of data collection, composed of 390 patients, divided into 201 affected by reactions and 189 reaction-free individuals. Epidemiological, clinical, and laboratory variables were approached as prognostic factors associated with leprosy reactions. The association among variables was analyzed by a binomial test and survival curves were compared by the Kaplan-Meier and Cox proportional-hazards regression. Results: 51.5% (201/390) of patients were affected by leprosy reactions. These immunological events were associated with lepromatous leprosy (16.2%; 63/390; p < 0.0001) and multibacillary group (43%; 169/390; p < 0.0001). This study showed that survival curves for the prognostic factor anti-PGL-I, comparing positive and negative cases at diagnosis, differed in relation to the follow-up time (Log Rank: p = 0.0760; Breslow: p = 0.0090; Tarone-Ware: p = 0.0110). The median survival times (time at which 50% of patients were affected by leprosy reactions) were 5 and 9 months for those reactional cases with negative (26/51) and positive serology (75/150), respectively. The time-dependent covariates in the cox proportional-hazards regression showed anti-PGL-I as the main prognostic factor to predict leprosy reactions (hazard ratio=1.91; p = 0.0110) throughout the follow-up time. Conclusions: Finally, these findings demonstrated that anti-PGL-I serology at diagnosis is the most important prognostic factor for leprosy reactions after starting multidrug therapy, thus enabling prediction of this immunological event.

Fever of Unknown Origin, Wasting Syndrome and Bone Marrow Involvement: A Leprosy Case Report.

Mycobacterium leprae, the etiologic agent of leprosy, is an acid-fast-staining and slow-growing bacilli that infect macrophages and Schwann cells individually or through forming globi. The clinical presentation of leprosy is broad and depends on the host immune response. We report a case of a 42-year-old Brazilian man presenting with fever of unknown origin (FUO), anemia, wasting syndrome, and neuropathy. The diagnosis of lepromatous leprosy was made after an extensive investigation revealed the presence of M. leprae in the bone marrow. Bone marrow involvement in leprosy is rare and some authors believe the presence of M. leprae in the bone marrow can act as a reservoir of the disease facilitating future relapses. It is important to investigate bone marrow involvement in leprosy, especially when the patient presents with cytopenias and positive epidemiologic history.

Leprosy Relapse: A Retrospective Study on Epidemiologic, Clinical, and Therapeutic Aspects at a Brazilian Referral Center.

OBJECTIVES: We aimed to characterize the profile of patients diagnosed with leprosy relapse and understand the influence of different multidrug therapy (MDT) treatments and initial disease presentation. METHODS: This retrospective study included patients diagnosed with leprosy relapse at a referral center in Brazil from 2013 to 2018. We analyzed their clinico-epidemiologic characteristics, laboratory data, and bacilloscopic tests. Survival analysis was used to determine the time elapsed until relapse according to the previous treatment and clinical forms of the disease. RESULTS: A total of 126 cases of relapse were analyzed, which comprised 11.89% (126/1059) of the cases. The median time elapsed until a relapse was 10 years, and most patients had previously undergone 12 doses of MDT (40.48%; 51/126). Undergoing 24 doses of MDT was associated with a better prognosis regarding relapse over time compared with 6 or 12 doses of MDT therapy. Most cases of relapse were classified as multibacillary (96.03%; 121/126). CONCLUSION: The incidence of relapse was greater than observed in other studies. The high percentage of multibacillary patients who had negative bacillary indices demonstrated that the bacillary index cannot be considered to be an essential criterion for relapse, especially concerning making an early diagnosis.

Late follow-up of peripheral neural decompression in leprosy: functional and clinical outcomes.

BACKGROUND: Peripheral neural surgical decompression (PNSD) is used as a complementary therapy to the clinical treatment of neuritis to preserve neural function. OBJECTIVE: To evaluate the long-term (≥ 1 year) clinical and functional results for PNSD in leprosy neuritis. METHODS: This cross-sectional study included leprosy patients who were in late postoperative period (LPO) of surgical decompression of ulnar, median, tibial, and fibular nerves. Socioeconomic, epidemiological, and clinical data were collected. The following instruments were used in this evaluation: visual analogue pain scale (VAS), Douleur Neuropathique en 4 Questions (DN4), SALSA scale, and simplified neurological assessment protocol. The preoperative (PrO) and 180-day postoperative (PO180) results were compared. RESULTS: We evaluated 246 nerves from 90 patients: 56.6% were on multidrug therapy (MDT) and 43.3% discharged from MDT. Motor scores and pain intensity showed statistically significant improvement (p<0.01). There was an increase in sensory scores only for bilateral ulnar nerves (p<0.05). Of the operated cases, 26.0% of patients were referred for surgery of ulnar neuritis and 23.6% of tibial neuritis. Neuropathic pain was reported in 41% of cases. Daily dose of prednisone reduced from 39.6 mg (±3.0) in PrO, 16.3 mg (±5.2) in PO180, to 1.7 mg (±0.8) in LPO. The SALSA scale results showed mild activity limitation in 51% and moderate in 34% of patients. Eighty percent of individuals reported that the results reached their expectations. CONCLUSIONS: PNSD in leprosy was effective in the long term to decrease the prevalence and intensity of pain, improve motor function, and reduce the dose of corticosteroids, which is reflected in the patients' satisfaction.

Assessment of neuropathic pain in leprosy patients with relapse or treatment failure by infrared thermography: A cross-sectional study.

BACKGROUND: Neuropathic pain (NP) is one of the main complications of leprosy, and its management is challenging. Infrared thermography (IRT) has been shown to be effective in the evaluation of peripheral autonomic function resulting from microcirculation flow changes in painful syndromes. This study used IRT to map the skin temperature on the hands and feet of leprosy patients with NP. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study included 20 controls and 55 leprosy patients, distributed into 29 with NP (PWP) and 26 without NP (PNP). Thermal images of the hands and feet were captured with infrared camera and clinical evaluations were performed. Electroneuromyography (ENMG) was used as a complementary neurological exam. Instruments used for the NP diagnosis were visual analog pain scale (VAS), Douleur Neuropathic en 4 questions (DN4), and simplified neurological assessment protocol. The prevalence of NP was 52.7%. Pain intensity showed that 93.1% of patients with NP had moderate/severe pain. The most frequent DN4 items in individuals with NP were numbness (86.2%), tingling (86.2%) and electric shocks (82.7%). Reactional episodes type 1 were statistically significant in the PWP group. Approximately 81.3% of patients showed a predominance of multiple mononeuropathy in ENMG, 79.6% had sensory loss, and 81.4% showed some degree of disability. The average temperature in the patients' hands and feet was slightly lower than in the controls, but without a significant difference. Compared to controls, all patients showed significant temperature asymmetry in almost all points assessed on the hands, except for two palmar points and one dorsal point. In the feet, there was significant asymmetry in all points, indicating a greater involvement of the lower limbs. CONCLUSION: IRT confirmed the asymmetric pattern of leprosy neuropathy, indicating a change in the function of the autonomic nervous system, and proving to be a useful method in the approach of pain.

Late follow-up of peripheral neural decompression in leprosy: functional and clinical outcomes / Seguimento tardio da descompressão neural periférica na hanseníase: resultados funcionais e clínicos

ABSTRACT Background: Peripheral neural surgical decompression (PNSD) is used as a complementary therapy to the clinical treatment of neuritis to preserve neural function. Objective: To evaluate the long-term (≥ 1 year) clinical and functional results for PNSD in leprosy neuritis. Methods: This cross-sectional study included leprosy patients who were in late postoperative period (LPO) of surgical decompression of ulnar, median, tibial, and fibular nerves. Socioeconomic, epidemiological, and clinical data were collected. The following instruments were used in this evaluation: visual analogue pain scale (VAS), Douleur Neuropathique en 4 Questions (DN4), SALSA scale, and simplified neurological assessment protocol. The preoperative (PrO) and 180-day postoperative (PO180) results were compared. Results: We evaluated 246 nerves from 90 patients: 56.6% were on multidrug therapy (MDT) and 43.3% discharged from MDT. Motor scores and pain intensity showed statistically significant improvement (p<0.01). There was an increase in sensory scores only for bilateral ulnar nerves (p<0.05). Of the operated cases, 26.0% of patients were referred for surgery of ulnar neuritis and 23.6% of tibial neuritis. Neuropathic pain was reported in 41% of cases. Daily dose of prednisone reduced from 39.6 mg (±3.0) in PrO, 16.3 mg (±5.2) in PO180, to 1.7 mg (±0.8) in LPO. The SALSA scale results showed mild activity limitation in 51% and moderate in 34% of patients. Eighty percent of individuals reported that the results reached their expectations. Conclusions: PNSD in leprosy was effective in the long term to decrease the prevalence and intensity of pain, improve motor function, and reduce the dose of corticosteroids, which is reflected in the patients' satisfaction.

RESUMO Antecedentes: A descompressão cirúrgica neural periférica (DCNP) é usada como uma terapia complementar ao tratamento clínico da neurite hansênica para preservar a função neural. Objetivo: Avaliar a longo prazo (≥ 1 ano) os resultados clínicos e funcionais da DCNP na neurite hansênica. Métodos: Este estudo transversal incluiu pacientes que estavam no pós-operatório tardio (POT) de cirurgia de descompressão dos nervos ulnares, medianos, tibiais e fibulares. Foram coletados dados socioeconômicos, epidemiológicos e clínicos. Os instrumentos utilizados foram: escala visual analógica de dor (EVA), questionário de dor neuropática 4 (DN4), escala SALSA e protocolo de avaliação neurológica simplificada. Os resultados obtidos foram comparados com os do pré-operatório (PrO) e pós-operatório de 180 dias (PO180). Resultados: Foram avaliados 246 nervos de 90 pacientes: 56,6% estavam em poliquimioterapia (PQT) e 43,3% em alta da PQT. Escores motores e intensidade da dor apresentaram melhora significante (p<0,01). Houve aumento nos escores sensitivos nos nervos ulnares bilaterais (p<0,05). Neurite ulnar foi indicação cirúrgica em 26,0% dos casos operados, seguida pela neurite tibial (23,6%). Dor neuropática foi relatada em 41% dos casos. Dose diária de prednisona reduziu de 39,6 mg (±3,0) na PrO, 16,3 mg (±5,2) na PO180, para 1,7 mg (±0,8) na POT. Escala SALSA mostrou limitação leve da atividade em 51% e moderada em 34% dos pacientes. 80% dos indivíduos relataram que os resultados atingiram suas expectativas. Conclusão: DCNP na hanseníase foi eficaz a longo prazo na redução da prevalência e intensidade da dor, na melhora da função motora e redução da dose de corticosteroides, refletindo na satisfação do paciente.

Peripheral nerve biopsy: a tool still needed in the early diagnosis of neural leprosy?

BACKGROUND: The early recognition of neural impairment in leprosy, especially in primary neural forms, represents a challenge in clinical practice and a peripheral nerve biopsy may be required for diagnostic confirmation. This study aims to characterize the epidemiological, clinical, electroneuromyographic, laboratory and histopathological aspects of patients undergoing peripheral nerve biopsy during investigation of primary neural cases in leprosy. METHODS: A total of 104 patients with peripheral neuropathy who were referred to a national reference centre for leprosy were biopsied from 2014 to 2018. All cases underwent clinical, laboratory, histopathological and electroneuromyographic evaluations. RESULTS: Of 104 biopsied patients, leprosy was confirmed in 89.4% (93/104). The biopsied nerves were the ulnar (67.8% [63/93]), superficial fibular (21.5% [20/93]), sural (8.6% [8/93]), radial (1.1% [1/93]) and deep fibular (1.1% [1/93]). Twenty-nine percent (27/93) presented histopathological abnormalities and 4.4% (4/93) presented acid-fast bacilli. Nerve and superjacent skin quantitative polymerase chain reaction were positive in 49.5% (46/93) and 24.8% (23/93) of cases, respectively. Patients with multiple mononeuropathy had a higher frequency of histopathological abnormalities (p=0.0077). CONCLUSIONS: This study reinforces peripheral nerve biopsy's role as an important tool in the investigation of primary neural cases, contributing to the early diagnosis and also reducing diagnostic errors and the need for empirical treatment.

BCG vaccine and leprosy household contacts: Protective effect and probability to becoming sick during follow-up.

BACKGROUND: Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) vaccine is still the most effective intervention in the prevention of leprosy among household contacts (HHCs) of leprosy patients. METHODS: A retrospective cohort study using data of 5.061 HHCs for a period of 16 years (follow-up of 7 years per leprosy HHCs), evaluating the occurrence of disease as the main outcome and the presence or absence of BCG scars verified at the first evaluation. Statistical analyzes were performed using the relative risk, hazard ratio and survival curves by Kaplan-Meier test. RESULTS: A total of 92 contacts sickened, of which 41.3% (38/92) in the first year and 58.7% (54/92) in the course of the other years of follow-up. Of those who became sick, 62% (57/92) developed borderline tuberculoid (BT). The additional protective effect occurred for those who had 2 BCG scars at the first follow-up assessment (Relative Risk: 0.41; p = 0.007) when compared to those not previously exposed to the vaccine. The number of BCG scars examined at the first assessment (t0 = time zero) affected the occurrence of the outcome evidenced by the difference in survival curves throughout the follow-up (Log Rank, p = 0.041; Breslow, p = 0.012; Tarone-Ware, p = 0.020). Leprosy HHCs with 0 BCG scar at time zero (t0) have a shorter survival time (average time of 22 months between t0 and outcome) when compared to those with 2 BCG scars (average time of 36 months between t0 and outcome). CONCLUSIONS: Vaccination of healthy individuals without signs and symptoms of leprosy is extremely important because BCG vaccine has an additional protective effect in those cases with 2 BCG scars throughout follow-up. Reducing the risk of leprosy HHCs becoming sick depends on preventive actions such as immunoprophylaxis and index cases treatment.

Evaluation of the cutaneous sensation of the face in patients with different clinical forms of leprosy.

BACKGROUND: Leprosy can be considered to be the most common peripheral neuropathy of infectious etiology and constitutes a public health problem. The standard routine examination for assessing sensory impairment in leprosy neuropathy basically evaluates hands, feet and eyes. However, evaluation of facial cutaneous sensation is not routinely performed. OBJECTIVES: The aim of this study was to evaluate facial cutaneous sensation in patients with different clinical forms of leprosy and compare the findings with those from healthy individuals. METHODOLOGY: 19 healthy controls and 71 leprosy patients who were being treated at a national reference center for leprosy in Brazil underwent facial sensation assessment using the Semmes-Weinstein monofilament test. This test was applied over the facial areas corresponding to the ophthalmic, maxillary and mandibular distal branches of the trigeminal nerve. RESULTS: The predominant clinical form in terms of changes to facial cutaneous sensation was lepromatous leprosy (LL), followed by the borderline-borderline (BB), and borderline-lepromatous (BL) forms, in comparison with healthy individuals. The distal branches most affected were the zygomatic (28.2%; 20/71), buccal (23.9%; 17/71) and nasal (22.5%; 16/71). There was asymmetrical sensory impairment of the face in 62.5% (20/32) of the cases. CONCLUSION: The face is just as impaired in leprosy as are the feet, hands and eyes, but facial impairment is underdiagnosed. Our evaluation on the different sensory branches and evidence of asymmetrical impairment of the face confirm the classically described pattern of leprosy neuropathy, i.e. consisting of asymmetrical and predominantly sensory peripheral neuropathy.

Molecular, immunological and neurophysiological evaluations for early diagnosis of neural impairment in seropositive leprosy household contacts.

BACKGROUND: Household contacts constitute the highest risk group for leprosy development, and despite significant progress in the disease control, early diagnosis remains the primary goals for leprosy management programs. METHODS: We have recruited 175 seropositive and 35 seronegative household contacts from 2014 to 2016, who were subjected to an extensive protocol that included clinical, molecular (peripheral blood qPCR, slit-skin smear qPCR, skin biopsy qPCR) and electroneuromyographic evaluations. RESULTS/PRINCIPAL FINDINGS: The positivity of peripheral blood qPCR of seropositive contacts was 40.6% (71/175) whereas only 8.6% (3/35) were qPCR positive in seronegative contacts (p = 0.0003). For the slit-skin smear, only 4% (7/175) of seropositive contacts presented positive bacilloscopy, whereas the qPCR detected 47.4% (83/175) positivity in this group compared with only 17.1% (6/35) in seronegative contacts (p = 0.0009). In the ENMG evaluation of contacts, 31.4% (55/175) of seropositives presented some neural impairment, and 13.3% (4/35) in seronegatives (p = 0.0163). The presence of neural thickening conferred a 2.94-fold higher chance of ENMG abnormality (p = 0.0031). Seropositive contacts presented a 4.04-fold higher chance of neural impairment (p = 0.0206). The peripheral blood qPCR positivity presented odds 2.08-fold higher towards neural impairment (OR, 2.08; p = 0.028). Contrarily, the presence of at least one BCG vaccine scar demonstrated 2.44-fold greater protection against neural impairment (OR = 0.41; p = 0.044). CONCLUSIONS/SIGNIFICANCE: ELISA anti-PGL-I is the most important test in determining the increased chance of neural impairment in asymptomatic leprosy household contacts. The combination of the two assays (ELISA anti-PGL-I and peripheral blood qPCR) and the presence of BCG scar may identify individuals with higher chances of developing leprosy neuropathy, corroborating with the early diagnosis and treatment.

Revisiting primary neural leprosy: Clinical, serological, molecular, and neurophysiological aspects.

BACKGROUND: Leprosy neuropathy is considered the most common peripheral neuropathy of infectious etiology worldwide, representing a public health problem. Clinical diagnosis of primary neural leprosy (PNL) is challenging, since no skin lesions are found and the slit skin smear bacilloscopy is negative. However, there are still controversial concepts regarding the primary-neural versus pure-neural leprosy definition, which will be explored by using multiple clinical-laboratory analyses in this study. METHODOLOGY/PRINCIPAL FINDINGS: Seventy patients diagnosed with primary neural leprosy from 2014 to 2016 underwent clinical, laboratorial and neurophysiological evaluation. All patients presented an asymmetric neural impairment, with nerve thickening in 58.6%. Electroneuromyography showed a pattern of mononeuropathy in 51.4%. Positivity for ELISA anti-PGL1 was 52.9%, while the qPCR of slit skin smear was 78.6%. The qPCR of nerve biopsies was positive in 60.8%. Patients with multiple mononeuropathy patterns showed lower levels of anti-PGL-1 (p = 0.0006), and higher frequency of neural thickening (p = 0.0008) and sensory symptoms (p = 0.01) than those with mononeuropathy. CONCLUSIONS/SIGNIFICANCE: PNL is not a synonym of pure neural leprosy, as this condition may include a generalized immune response and also a skin involvement, documented by molecular findings. Immunological, molecular, and neurophysiological tools must be implemented for diagnosing primary neural leprosy to achieve effective treatment and reduction of its resultant disabilities that still represent a public health problem in several developing nations. Finally, we propose a algorithm and recommendations for the diagnosis of primary neural leprosy based on the combination of the three clinical-laboratorial tools.

NREM-related parasomnias in Machado-Joseph disease: clinical and polysomnographic evaluation.

Spinocerebellar ataxias (SCA) are autosomal dominant neurodegenerative disorders that affect the cerebellum and its connections, and have a marked clinical and genetic variability. Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3)--MJD/SCA3--is the most common SCA worldwide. MJD/SCA3 is characterized classically by progressive ataxia and variable other motor and non-motor symptoms. Sleep disorders are common, and include rapid eye movement (REM) sleep behaviour disorder (RBD), restless legs syndrome (RLS), insomnia, excessive daytime sleepiness, excessive fragmentary myoclonus and sleep apnea. This study aims to focus upon determining the presence or not of non-REM (NREM)-related parasomnias in MJD/SCA 3, using data from polysomnography (PSG) and clinical evaluation. Forty-seven patients with clinical and genetic diagnosis of MJD/SCA3 and 47 control subjects were evaluated clinically and by polysomnography. MJD/SCA3 patients had a higher frequency of arousals from slow wave sleep (P < 0.001), parasomnia complaints (confusional arousal/sleep terrors, P = 0.001; RBD, P < 0.001; and nightmares, P < 0.001), REM sleep without atonia (P < 0.001), periodic limb movements of sleep index (PLMSi) (P < 0.001), percentage of N3 sleep (P < 0.001) and percentage of N1 sleep (P < 0.001). These data show that NREM-related parasomnias must be included in the spectrum of sleep disorders in MJD/SCA3 patients.