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      Clinical evolution of neural function in a series of leprosy neuropathy cases after ulnar neurolysis ☆☆

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          Abstract

          Dear Editor, Leprosy is a chronic infectious disease with a disabling potential due to the affinity of the agent, Mycobacterium leprae, for peripheral nerves and skin. Of the 208,619 new cases detected worldwide in 2018, a total of 11,323 cases already had apparent deformities, of which 2,109 (18.6%) were from Brazil, a figure that was second only to India, with 3,666 new cases with deformities. 1 Neuropathy in leprosy can occur insidiously, more commonly as multiple mononeuropathy, with the simultaneous involvement of two or more peripheral nerves in different regions of the body, with the ulnar and posterior tibial nerves being the most frequently affected. Neural damage can also often occur during acute episodes of immunological reactions against bacillary antigens that may occur during the course of the disease or even after polychemotherapeutic treatment, in the form of neuritis with edema, vascular obstruction, ischemia, and strangulation in the passage through the osteofibrous channels of the limbs, leading to pain and deficit of function, the main cause of physical disabilities and stigma of the disease.2, 3 The basis for neuritis treatment is prednisone, used to control the inflammatory process and pain, preventing permanent neural damage. Neurolysis is surgery for nerve decompression through an incision in the epineurium and opening of the osteofibrous canal to release the nerve, at the level of the elbow and/or wrist. 3 It is performed mainly in cases of nerve abscess, neuritis not responsive to clinical treatment for four weeks, recurrent or subentrant episodes of neuritis, chronic neuritis with deficit and pain, and neuritis in patients with comorbidities that contraindicate the use of corticosteroids aiming to decrease the dose and in cases of corticosteroid contraindications. 4 With the purpose of describing the clinical evolution of neural function and neuritis recurrences of leprosy patients with neuritis submitted to neurolysis, we present a series of 22 cases of ulnar nerve surgery performed in the years 2015 and 2016, at Fundação de Dermatologia Tropical e Venereologia Alfredo da Matta, located in the state of Amazonas, in the city of Manaus, Brazil. Immediately before the neurolysis and after it (30, 90 days and according to the follow-up), the Simplified Neurological Assessment was carried out according to the protocol of the Ministry of Health of Brazil. 4 Sensibility evaluation was performed with an esthesiometer or Semmes-Weinstein monofilament, which consists in a set of six nylon threads of different colors and thicknesses that, pressed against the skin, correspond to different weights (from 0.05 g to 300 g). The 0.05 g (green) and 0.2 g (blue) monofilaments were considered as normal sensibility and above that, as decreased sensibility. 5 For the assessment of muscle strength, the abductor muscle of the fifth finger was assessed and the Medical Research Council scale was used, which ranks strength from zero (no muscle movement) to five (complete movement against gravity with maximum resistance). 4 Levels four (full movement against gravity with partial resistance) and five were considered normal. 5 The time between the first episode of neuritis and the performance of neurolysis was, on average, 25.3 months (SD = 63.3; Min. = 1; Max. = 303), with the procedure being performed after up to six months in 11 (50.0%) patients, which is related to the best results by other authors. 5 For comparison purposes, the last neurological evaluation was considered in the present study, which ranged from three to 168 months, with 12 (54.5%) patients having more than one year of follow-up. Of 12 cases that already had altered sensibility before surgery, seven (58.3%) showed improvement and, of the six that had altered muscle strength, five (83.3%) maintained the same level, and only one (16.7% ) showed worsening. Fifteen (68.2%) patients did not have any neuritis in the operated nerve; however, three of these patients still had to use prednisone, because they had a leprosy reaction and/or neuritis in other nerves. Two patients had only a single episode of neuritis, which occurred three and four months after surgery. Another five patients (18.2%) had subentrant episodes of neuritis in the operated nerve, for an average of 52.6 months (SD = 63; Min. = 17; Max. = 172) after surgery, without necessarily developing loss of function (Table 1). Table 1 Characteristics of leprosy cases submitted to ulnar neurolysis. Table 1 Numerical order Sex Age at diagnosis (years) Clinical form Time in months between Sensibilitya Muscle strengthb Time with recurrences (months) Neuritis and neurolysis Neurolysis and evaluation Initial Final Initial Final 1 M 31 BL 01 03 0.05 g 0.05 g 4 5 – 2 M 22 BL 02 20 0 10 g 4 5 21 3 M 34 LL 02 05 0.05 g 0.2 g 5 5 – 4 M 8 TT 02 44 300 g 10 g 0 0 – 5 M 20 BT 02 08 300 g 0 0 0 – 6 M 26 BL 02 18 0.05 g 300 g 5 4 03c 7 M 13 BT 03 34 300 g 300 g 4 5 – 8 M 35 LL 04 14 0.2 g 0.2 g 5 5 – 9 M 39 LL 04 30 0 4g 3 3 – 10 M 49 LL 05 24 0.2 g 0.2 g 5 5 – 11 M 51 BL 6 03 300 g 0 2 2 – 12 M 24 LL 09 26 300 g 0.2 g 5 5 – 13 M 24 LL 10 02 0.2 g 0.2 g 5 5 – 14 M 11 BL 12 21 0.05 g 0.05 g 5 5 21 15 M 36 BL 16 17 300 g 10 g 3 3 17 16 M 15 LL 17 04 0.05 g 0.05 g 5 5 – 17 F 57 BT 20 08 300 g 0.2 g 4 4 – 18 M 18 BL 20 168 300 g 0 3 1 172 19 M 17 LL 31 10 0.05 g 0.2 g 5 5 32 20 F 12 BT 36 04 300 g 4g 4 5 04c 21 M 19 BL 49 135 0.05 g 0.05 g 5 5 – 22d M 26 LL 303 03 10 g 10 g 2 2 – a Monofilament: 0.05 g (green) and 0.2 g (blue) = normal sensibility; 2.0 g (violet) = decrease in protective sensibility, with decreased discrimination of shape and temperature; 4.0 g (dark red) = decreased protective sensibility; 10.0 g (orange) = can feel deep pressure and pain; 300.0 g (magenta red) = loss of deep pressure feeling, can feel pain; and 0 = does not feel any monofilament or absence of sensibility to pressure or pain. b Medical Research Council scale. c Month of occurrence of the single episode of neuritis. d This patient had a recurrence. This series of cases emphasizes the clinical importance of the results in a routine situation, where the greatest contribution of neurolysis associated with the clinical treatment of leprosy neuritis was the non-recurrence or non-chronicity of the condition. Neurolysis also prevents prolonged corticosteroid therapy and its consequences, in addition to the possible evolution into physical disabilities. There was sensory function gain in most of the assessed cases. However, it is necessary to carry out studies with appropriate methodology to evaluate the effectiveness of neurolysis or its benefits in comparison to clinical treatment alone, even considering the studies that have been published for decades. 5 Financial support 10.13039/501100004916 Fundação de Amparo à Pesquisa do Estado do Amazonas - undergraduate scholarship. Authors’ contributions Juliana Barroso-Freitas: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature. Pedro Arthur da Rocha Ribas: Critical review of the literature; collection, analysis, and interpretation of data. Paula Frassinetti Bessa Rebello: Design and planning of the study; critical review of the literature; analysis of data; critical review of the manuscript. Silmara Navarro-Pennini: Design and planning of the study; drafting and editing of the manuscript; critical review of the literature; analysis of data. Conflicts of interest None declared.

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          Most cited references6

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          The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in north India.

          The aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as 'gold standard' for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety of immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, these impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed to indicate more severe neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk of those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment.
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            Diretrizes para vigilância, atenção e eliminação da hanseníase como problema de saúde pública: manual técnico-operacional

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              The pattern of leprosy-related neuropathy in the AMFES patients in Ethiopia: definitions, incidence, risk factors and outcome.

              The ALERT MDT Field Evaluation Study (AMFES) began in 1988 and followed patients prospectively for up to 10 years after release from treatment (RFT). This paper presents the findings from this cohort with regard to neuropathy and nerve damage. Five hundred and ninety-four new cases of leprosy are included in the study, 300 multibacillary (MB) and 294 paucibacillary (PB) cases. Fifty-five percent of patients had some degree of impairment at diagnosis and a further 73 (12%) developed new nerve function impairment (NFI) after starting multiple drug therapy (MDT). The overall incidence rate for neuropathy was 39 episodes per 100 PYAR in the first year after diagnosis, gradually declining to 12 episodes per 100 PYAR in the sixth year. In those patients without impairment at diagnosis, the incidence rate of neuropathy was 25 episodes per 100 PYAR for MB cases and 11 per 100 PYAR for PB cases in the first year; in 33% of MB cases whose first episode of neuropathy occurred after diagnosis, that first episode took place after the first year, or after the normal period of treatment with MDT. Seventy-three patients with neuropathy developing after diagnosis are reported more fully: 34 (47%) had only one nerve involved and of these 25 (73%) had a single, acute episode of neuropathy. Nine (27%) had further episodes. Thirty-nine (53%) had more than one nerve involved and of these 16 (41%) had a single, acute episode, while 23 (59%) had further episodes. The terms 'chronic' and 'recurrent' neuropathy are defined and used to describe the pattern of neuropathy in those with repeated attacks. In patients with no impairment at the start of the study, treatment with steroids resulted in full recovery in 88% of nerves with acute neuropathy but only 51% of those with chronic or recurrent neuropathy. The median time to full recovery from acute neuropathy was approximately 6 months, but in a few cases recovery occurred gradually over 2-3 years. Severe neuropathy was less likely to be followed by a complete recovery than mild or moderate neuropathy. Forty-two percent of nerves with acute neuropathy that were not treated with steroids also fully recovered. In the group of patients who were thought to have old, permanent impairments at diagnosis, full recovery of nerve function occurred in 87/374 (23%) of the nerves involved. The overall outcome is illustrated by examining the average EHF score for groups of patients. Patients with no new neuropathy after diagnosis show a gradual improvement in their EHF score, while those with any episodes of neuropathy after diagnosis show a gradual deterioration after completion of MDT. Possible explanations for these findings are discussed. Risk factors for neuropathy, for chronic and recurrent neuropathy, and for a poor outcome 5 years after release from treatment, are examined. Impairment at diagnosis was the main risk factor for a poor outcome, accompanied by the occurrence of chronic/recurrent neuropathy or a reversal reaction.
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                Author and article information

                Contributors
                Journal
                An Bras Dermatol
                An Bras Dermatol
                Anais Brasileiros de Dermatologia
                Sociedade Brasileira de Dermatologia
                0365-0596
                1806-4841
                05 June 2021
                Jul-Aug 2021
                05 June 2021
                : 96
                : 4
                : 500-502
                Affiliations
                [a ]Hospital Universitário Getúlio Vargas, Manaus, AM, Brazil
                [b ]Universidade Nilton Lins, Fundação de Dermatologia Tropical e Venereologia Alfredo da Matta, Fundação de Amparo à Pesquisa do Estado do Amazonas, Manaus, AM, Brazil
                [c ]Fundação de Dermatologia Tropical e Venereologia Alfredo da Matta, Manaus, AM, Brazil
                Author notes
                [* ]Corresponding author. freitassjuliana@ 123456hotmail.com
                Article
                S0365-0596(21)00120-3
                10.1016/j.abd.2020.07.015
                8245705
                34103187
                3597c5ab-7003-4258-9e37-0d68f97b3305

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 May 2020
                : 17 July 2020
                Categories
                Research Letter

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