Assessment of neuropathic pain, functional activity limitation and quality of life of people affected by leprosy in an endemic area in Northeast Brazil: a cross-sectional study.

BACKGROUND: This study investigated the prevalence of neuropathic pain (NP) among people affected by leprosy and its effects on functional limitation and health-related quality of life (HRQoL) in an endemic area in Northeast Brazil. METHODS: This is a cross-sectional study of 122 leprosy patients. Functional limitation and HRQoL were assessed using the Screening of Activity Limitation and Safety Awareness (SALSA) and WHO Quality-of-Life (WHOQoL-BREF) scales, respectively. Participants were assessed for the presence of pain and completed the Douleur Neuropathique 4 and the Brief Pain Inventory scales. RESULTS: The prevalence of NP was 59%. Participants with NP had higher SALSA scores than those without pain (median; IQR: 42; 32-49.5 vs 27.5; 24-34; p=0.002). Increasing SALSA scores were related to decreasing WHOQoL-BREF scores in the physical (r=-0.54; p<0.001), psychological (r=-0.33; p=0.002) and environmental (r=-0.22; p=0.01) domains, but not in the social domain (r=-0.14; p=0.10). Individuals with NP had the lowest scores in all domains compared with individuals without pain. CONCLUSIONS: Appropriate tools and training of clinicians for diagnosing NP in leprosy patients are necessary for their appropriate management and better HRQoL outcomes.

A-waves are associated with neuropathic pain in leprosy.

INTRODUCTION/AIMS: The A-wave is a late response related either to demyelination or early axonal regeneration. It may be helpful in the evaluation of some peripheral neuropathies. In leprosy, previous studies suggested that A-waves could be a neurophysiological marker of pain in patients during reactions. Herein we have attempted to further assess the profile and clinical correlates of A-waves by exploring a large leprosy cohort. METHODS: Between 2015 and 2018, 63 patients with leprosy (47 men and 16 women) had A-waves in nerve conduction studies and were included in this study. We included patients regardless of whether they were experiencing leprosy reactions or not. We then compared clinical features in nerves with and without A-waves. RESULTS: The mean age of study participants was 46.5 ± 12.3 years and most had borderline leprosy. From this cohort, we assessed separately 83 motor nerves that demonstrated A-waves (group A+ ) and 29 motor nerves that did not demonstrate A-waves (group A- ). Neuropathic pain (NP) was found in 66 of 83 nerves in group A+ , but only 5 of 29 in group A- (79.5 vs 17.2%, P < .001). In contrast, no significant between-group difference emerged regarding presence of reactions, sensory function (based on Semmes-Weinstein evaluations), or muscle strength. A-waves were found in nerves with neuropathic pain experiencing (39 of 66 = 59%) or not experiencing (27 of 66 = 41%) leprosy reactions. DISCUSSION: These results show that A-waves are associated with neuropathic pain in leprosy patients, regardless of the nerves affected and the immune status (in reaction or not).

Clinical and electrophysiological characteristics of neuropathic pain in leprosy patients: A prospective cross-sectional study.

Introduction Neuropathic pain is a common and disabling late complication of leprosy. We investigated the clinical and electrophysiological characteristics of neuropathic pain in leprosy patients by evaluating nerve conduction, sympathetic skin response (SSR) and A-waves. Methods Twenty one leprosy patients with neuropathic pain validated by the Douleur Neuropathique en 4 (DN4)Questionnaire were selected for study. Pain intensity was measured by the visual analog scale. Demographic and clinical data were collected for all patients. Clinical data included appraisal of the median, ulnar, radial, tibial and common peroneal nerves, assessment of the sympathetic skin response and conventional electrophysiological recordings. Results Among all electroneuromyographic presentations, multifocal mononeuropathy was still the most prevalent. Sensory loss was observed more frequently than motor deficits. As most patients presented advanced clinical forms of leprosy and were under treatment, this high mean was found and the ulnar nerve was most frequently affected. The sympathetic skin response was absent in 16 patients. Higher DN4 Questionnaire scores were observed in women and in those receiving corticosteroid therapy. These inferences are possible to be made, but our study's limitations don't allow us to be certain about it. The statistical significance found only permits us to evidence what we related on the textual part of the study. Limitations The small number of patients studied, the lack of sophisticated diagnostic methods for leprosy, as well as the difficulties in assessing nerve conduction were the main limitations of this study. Conclusion The neurophysiological and clinical findings in leprous neuropathy were modest despite the conspicuous neuropathic pain. Although electrophysiological studies are a vital tool to verify nerve damage, variations in the clinical presentation of leprosy neuropathic pain render the diagnosis challenging. Further studies are needed to describe the neurophysiological evolution of this disease.

A-waves associated are with neuropathic pain in leprosy

Introduction/Aims:The A-wave is a late response related either to demyelination or early axonal regeneration. It may be helpful in the evaluation of some peripheral neuropathies. In leprosy, previous studies suggested that A-waves could be a neurophysiological marker of pain in patients during reactions. Herein we have attempted to further assess the profile and clinical correlates of A-waves by exploring a large leprosy cohort. Methods: Between 2015 and 2018, 63 patients with leprosy (47 men and 16 women) had A-waves in nerve conduction studies and were included in this study. We included patients regardless of whether they were experiencing leprosy reactions ornot. We then compared clinical features in nerves with and without A-waves. Results:The mean age of study participants was 46.5 ± 12.3 years and most had borderline leprosy. From this cohort, we assessed separately 83 motor nerves that demonstrated A-waves (group A+) and 29 motor nerves that did not demonstrate A-waves (group A-). Neuropathic pain (NP) was found in 66 of 83 nerves in group A+,but only 5 of 29 in group A-(79.5 vs 17.2%,P< .001). In contrast, no significant between-group difference emerged regarding presence of reactions, sensory function (based on Semmes-Weinstein evaluations), or muscle strength. A-waves were found in nerves with neuropathic pain experiencing (39 of 66=59%) or not experiencing (27 of 66=41%) leprosy reactions. Discussion: These results show that A-waves are associated with neuropathic pain in leprosy patients, regardless of the nerves affected and the immune status (in reaction or not).

Functional Outcome of Early, Selective Surgical Nerve Decompression in Leprous Neuropathy.

Background: Leprous neuropathy is a significant, yet preventable, cause of disability worldwide. Decompressive surgery and oral steroids have been used along with Multi Drug Therapy (MDT) for treating leprous neuropathy with varied success as reported in literature. Methods: We prospectively studied 16 peripheral nerves in 10 patients with leprous neuropathy of less than a year duration and not responding to steroid therapy in 3 weeks. The patients were divided into 2 groups: Group-A (decompressive nerve surgery was done within 12 weeks of onset of neurological deficit), and Group-B (nerve decompression was performed after 12 weeks from onset of neurological deficit). Post-operatively patients were assessed for regression of deformity, sensory, motor, vasomotor recovery and neuropathic pain. Results: Median age of patients was 32 years (range; 18 years to 46 years). Mean motor score and mean grip strength was significantly better for group A patients at 2 years follow-up (p < 0.05). Mean sensory score improved significantly in both the groups (p < 0.05). Similarly, mean VAS score for neuropathic pain improved significantly in both the groups (p < 0.05). Recovery of autonomic function was observed in 3 nerves in group A and 1 in group B. Conclusions: The cases who underwent nerve decompression surgery within 12 weeks had better functional outcomes, especially in terms of motor recovery, than those who were operated after that. Studies involving larger number of patients are required to draw firm conclusions.

Diagnosis and impact of neuropathic pain in leprosy patients in Nepal after completion of multidrug therapy.

OBJECTIVES: Neuropathic pain (NP) can occur as a chronic complication of leprosy neuropathy. NP epidemiology and its impact on patients have not been well documented. This study investigates NP prevalence and impact in the years after patients are declared "released from treatment" (RFT) following multidrug therapy (MDT) completion. METHODS: In this cross-sectional study, 85 RFT patients were recruited within leprosy referral services in Nepal. The Douleur Neuropathique 4 Questionnaire (DN4) was used to screen for NP. Pain severity, impacts on patients' daily activities and mental health were measured by using the Brief Pain Inventory (BPI), Screening of Activity Limitation and Safety Awareness (SALSA), and General Health Questionnaire-12 (GHQ-12) respectively. RESULTS: 96% surveyed had been treated for multibacillary leprosy. 44 (52%) complained of pain of which 30 (68%) were diagnosed with NP. NP was not associated with age, gender, or presence of skin lesions or nerve symptoms at leprosy diagnosis. 70% of patients with NP had either history of or ongoing reactions and 47% had grade 2 disability. Nerve tenderness (p = 0.023) and current reactions (p = 0.018) were significant risk factors for NP. Patients with NP suffered significantly higher intensity pain (p = 0.023) and daily life interference (p = 0.003) and were more likely to have moderate to extreme daily activity limitations (p = 0.005). 13 (43%) exhibited psychological distress, and medications only reduced moderate degree (50-60%) of pain. CONCLUSIONS: In our study, 35% of RFT patients had ongoing NP. Risk factors include nerve tenderness and reaction. They suffer from more daily life interference and psychological distress. Leprosy patient care should include recognition and management of NP.

Clinical and Neurophysiological Features of Leprosy Patients with Neuropathic Pain.

Neural pain is a frequent symptom in leprosy disease. There is a paucity of data regarding neural pain diagnostics resulting in common prescriptive errors when neuritis is confused with neuropathic or mixed nociceptive-neuropathic pain. The present study identified important demographic, clinical, and neurophysiological features of 42 leprosy neuropathy patients presenting neuropathic pain (NP). During routine evaluations, patients were selected asking if they had ever experienced neural pain. Data analyses of their pain characteristics, clinical examination results, and both the Douleur Neuropathique 4 Questionnaire and Hamilton Depression Scale scores were used to classify these patients. The most common word they used to describe the sensation of pain for 25 (60%) of these patients was "burning." In the early stages of the disease and before leprosy diagnosis, 19 (45%) had already complained about NP and leprosy treatment was unable to prevent its occurrence in 15 (36%). Leprosy reactions, considered NP risk factors, occurred in 32 (76%) cases. Knowledge of typical NP characteristics could be used to develop more effective therapeutic approaches for a notoriously difficult-to-treat pain condition.

Peripheral Nerve Stimulation for Painful Mononeuropathy Secondary to Leprosy: A 12-Month Follow-Up Study.

OBJECTIVE: Leprosy affects approximately 10-15 million patients worldwide and remains a relevant public health issue. Chronic pain secondary to leprosy is a primary cause of morbidity, and its treatment remains a challenge. We evaluated the feasibility and safety of peripheral nerve stimulation (PNS) for painful mononeuropathy secondary to leprosy that is refractory to pharmacological therapy and surgical intervention (decompression). METHODS: Between 2011 and 2013 twenty-three patients with painful mononeuropathy secondary to leprosy were recruited to this prospective case series. All patients were considered to be refractory to optimized conservative treatment and neurosurgical decompression. Pain was evaluated over the course of the study using the neuropathic pain scale and the visual analog scale for pain. In the first stage, patients were implanted with a temporary electrode that was connected to an external stimulator, and were treated with PNS for seven days. Patients with 50% or greater pain relief received a definitive implantation in the second stage. Follow-ups in the second stage were conducted at 1, 3, 6, and 12 months. RESULTS: After seven days of trial in the first stage, 10 patients showed a pain reduction of 50% or greater. At 12-month follow-up in the second stage, 6 of the 10 patients who underwent permanent device implantation showed a pain reduction of 50% or greater (75% reduction on average), and two patients showed a 30% reduction in pain. Two patients presented with electrode migration that required repositioning during the 12-month follow-up period. CONCLUSIONS: Our data suggest that PNS might have significant long-term utility for the treatment of painful mononeuropathy secondary to leprosy. Future studies should be performed in order to corroborate our findings in a larger population and encourage the clinical implementation of this technique.

Neuropathic pain in leprosy: symptom profile characterization and comparison with neuropathic pain of other etiologies

Introduction: Previous studies reported a high prevalence of neuropathic pain in leprosy, being especially present in "pharmacologically cured" patients. The presence of neuropathic pain in leprosy poses a supplementary burden in patient's quality of life, daily activities, and mood.Objectives: The aim of this study was to assess whether neuropathic pain in leprosy has similar symptom profile as neuropathic pain of other etiologies and to retrospectively assess the efficacy of neuropathic pain medications regularly prescribed to leprosy. Methods: Leprosy and nonleprosy patients had their neuropathic pain characterized by the neuropathic pain symptom inventory (NPSI, ranges from 0 to 100, with 100 being the maximal neuropathic pain intensity) in a first visit. In a second visit, leprosy patients who had significant pain and received pharmacological treatment in the first evaluation were reassessed (NPSI) and had their pain profile and treatment response further characterized, including information on drugs prescribed for neuropathic pain and their respective pain relief. Results: The pain characteristics based on NPSI did not significantly differ between leprosy and nonleprosy neuropathic pain patients in visit 1 after correction for multiple analyses, and cluster analyses confirmed these findings (ie, no discrimination between leprosy and nonleprosy groups; Pearson x2 5 0.072, P 5 0.788). The assessment of pain relief response and the drugs taken by each patient, linear regression analysis showed that amitriptyline, when effective, had the highest percentage of analgesic relief. Conclusions: Neuropathic pain in leprosy is as heterogeneous as neuropathic pain of other etiologies, further supporting the concept that neuropathic pain is a transetiological entity. Neuropathic pain in leprosy may respond to drugs usually used to control pain of neuropathic profile in general, and amitriptiline may constitute a potential candidate drug for future formal clinical trials aimed at controlling neuropathic pain in leprosy.

Agreement Between the Douleur Neuropathique in 4 Questions and Leeds Assessment of Neuropathic Symptoms and Signs Questionnaires to Classify Neuropathic Pain Among Patients with Leprosy.

Neuropathic pain (NP) often occurs during the course of leprosy, and screening tools to differentiate NP from non-NP are often used. However, their performance varies in different settings. The most frequently used scales are the Douleur Neuropathique in 4 questions (DN4) and the Leeds assessment of neuropathic symptoms and signs (LANSS) questionnaires. Thus, we conducted a study to evaluate the agreement between DN4 and LANSS questionnaires to classify NP in 195 leprosy patients attending two reference centers in Sergipe, Brazil. The DN4 and LANSS classified 166 and 110 patients, respectively, as having NP. One hundred and seven (54.8%) were classified as NP by both questionnaires; 59 (30.2%) solely by the DN4 questionnaire and three (1.5%) solely by the LANSS. The agreement of the questionnaires was 66.2% (weak agreement, Kappa = 0.30). Although both questionnaires identified a high proportion of NP, the development of more robust instruments is necessary to ensure the accuracy of diagnosis of leprosy patients classified as having NP.

Neuropathic pain in leprosy.

Nerve impairment is a key clinical aspect of leprosy and may present the distribution of mononeuropathy or multiple nerve trunks, small cutaneous nerve fibers, and free nerve endings. The clinical range of leprosy is determined by individual cell-mediated immune response to infection that also may play a role in different types of pain syndromes in leprosy. Previous studies reported a high prevalence of neuropathic pain in leprosy. In an Ethiopian study with 48 patients, pure nociceptive pain was experienced by 43% of patients and pure neuropathic pain (NeP) by 11% of patients. In an Indian study, 21.8% of leprosy patients had pain with neuropathic characteristics. These rates underlie the need to develop tools for the early diagnosis and detection of infection and its complications, such as nerve damage and pain. In a larger sample with leprosy-associated NeP (n = 90), we have applied the Douleur Neuropathique en 4 questions (DN4) and found sensitivity = 97.1% and specificity = 57.9%. The high sensitivity of this tool in leprosy patients suggests that it could be a valuable tool to screen for neuropathic pain in this population and could be used as part of health care programs aimed at detecting, treating, and rehabilitating leprosy in endemic areas.

Neuropathic pain in leprosy

Nerve impairment is a key clinical aspect of leprosy and may present the distribution of mononeuropathy or multiple nerve trunks, small cutaneous nerve fibers, and free nerve endings. The clinical range of leprosy is determined by individual cell-mediated immune response to infection that also may play a role in different types of pain syndromes in leprosy. Previous studies reported a high prevalence of neuropathic pain in leprosy. In an Ethiopian study with 48 patients, pure nociceptive pain was experienced by 43% of patients and pure neuropathic pain (NeP) by 11% of patients. In an Indian study, 21.8% of leprosy patients had pain with neuropathic characteristics. These rates underlie the need to develop tools for the early diagnosis and detection of infection and its complications, such as nerve damage and pain. In a larger sample with leprosy-associated NeP (n = 90), we have applied the Douleur Neuropathique en 4 questions (DN4) and found sensitivity = 97.1% and specificity = 57.9%. The high sensitivity of this tool in leprosy patients suggests that it could be a valuable tool to screen for neuropathic pain in this population and could be used as part of health care programs aimed at detecting, treating, and rehabilitating leprosy in endemic areas.

Psychological distress and quality of life in leprosy patients with neuropathic pain.

Leprosy is widely known because of progressive damage to the peripheral nerves. In spite of multidrug therapy, some patients develop chronic neuropathic pain after bacteriological cure. Chronic pain is associated with psychological distress and is also an important predictor of poor quality of life. The aim of this study is to assess psychological distress in leprosy patients with chronic neuropathic pain, and its repercussions on their quality of life. The sample of this cross-sectional study comprised patients with chronic neuropathic pain after multidrug therapy. Neuropathic pain was confirmed by clinical examination and by the Douleur neuropathique en 4 questions questionnaire. Pain intensity was assessed using a visual analogic scale (VAS) ruler. The psychological health of the participants was measured using the 12-item General Health Questionnaire, and the WHOQOL-bref was used to assess quality of life. The mean pain intensity reported by participants on the VAS was 7.1 cm (SD = 2.9). No differences in pain intensity with respect to gender were observed. Psychological distress was present in 76.2% of participants, being higher in those with Grade 2 of disability. Patients with psychological distress had the lowest mean scores in all domains of the WHOQOL-bref. The lowest mean scores according to domain were physical (9.9; SD = 3.3), followed by environment (11.9; SD = 3.0), psychological (13.5; SD = 2.6) and social relations (14.0; SD = 3.7). In conclusion, our study identified the presence of psychological distress in most of the participants. Patients with chronic neuropathic pain who were also found to have high psychological distress levels had higher pain intensity and a poorer quality of life.

Association between neuropathic pain and A-waves in leprosy patients with type 1 and 2 reactions.

Neuropathic pain (NP) is a well-recognized feature of leprosy neuropathy. However, the diagnosis of NP is difficult using only clinical criteria. In the study reported here, by means of conventional nerve conduction studies, the authors sought for an association between long-latency responses and NP complaints in leprosy patients with type 1 and 2 reactions. Of the 27 ulnar nerves of leprosy patients, 18 with type 1 reaction (T1R) and 9 with type 2 reaction (T2R) were followed-up for 6 months before and after steroid treatment. Clinical characteristics of pain complaints and clinical function were assessed, as well as the presence of F- and A-waves of the ulnar nerve using nerve conduction studies. The clinical and the neurophysiologic findings were compared to note positive concordances (presence of NP and A-waves together) and negative concordances (absence of NP and A-waves together) before and after treatment. Both reactions presented a high frequency of A-waves (61.1% in T1R and 66.7% in T2R, P < 0.05) and prolonged F-waves (69.4% in T1R and 65.8% in T2R, P = 0.4). No concordances were seen between pain complaints and F-waves. However, significant concordances between NP and A-waves were observed, although restricted to the T2R group (χ(2) = 5.65, P = 0.04). After treatment, there was a significant reduction in pain complaints, as well as the presence of F- and A-waves in both groups (P < 0.05 for all comparisons). In conclusion, the presence of A-waves correlates well with pain complaints of neuropathic characteristics in leprosy patients, especially in those with type 2 reaction. Probably, such response shares similar mechanisms with the small-fiber dysfunction seen in these patients with NP, such as demyelination, intraneural edema, and axonal sprouting. Further studies using specific tools for small-fiber assessment are warranted to confirm our findings.

[The rehabilitation cares at the lepers]. / Prise en charge de la lèpre en Médecine physique et réadaptation.

Leprosy elimination (<1/100 000) is almost reached all around the world, although, but disabled people are still a lot, and they need rehabilitation as soon as possible. The different lesions (neurological, dermatologic and joint) must be treated in order to protect from handicap. Physical rehabilitation medicine can help with a global and polyvalent coverage. Therapeutic education and reinsertion are an important part.

Association between neuropathic pain and A-Waves in leprosy patients with type 1 and 2 reactions

Neuropathic pain (NP) is a well-recognized feature of leprosy neuropathy. However, the diagnosis of NP is difficult using only clinical criteria. In the study reported here, by means of conventional nerve conduction studies, the authors sought for an association between long-latency responses and NP complaints in leprosy patients with type 1 and 2 reactions. Of the 27 ulnar nerves of leprosy patients, 18 with type 1 reaction (T1R) and 9 with type 2 reaction (T2R) were followed-up for 6 months before and after steroid treatment. Clinical characteristics of pain complaints and clinical function were assessed, as well as the presence of F- and A-waves of the ulnar nerve using nerve conduction studies. The clinical and the neurophysiologic findings were compared to note positive concordances (presence of NP and A-waves together) and negative concordances (absence of NP and A-waves together) before and after treatment. Both reactions presented a high frequency of A-waves (61.1% in T1R and 66.7% in T2R, P < 0.05) and prolonged F-waves (69.4% in T1R and 65.8% in T2R, P = 0.4). No concordances were seen between pain complaints and F-waves. However, significant concordances between NP and A-waves were observed, although restricted to the T2R group (χ(2) = 5.65, P = 0.04). After treatment, there was a significant reduction in pain complaints, as well as the presence of F- and A-waves in both groups (P < 0.05 for all comparisons). In conclusion, the presence of A-waves correlates well with pain complaints of neuropathic characteristics in leprosy patients, especially in those with type 2 reaction. Probably, such response shares similar mechanisms with the small-fiber dysfunction seen in these patients with NP, such as demyelination, intraneural edema, and axonal sprouting. Further studies using specific tools for small-fiber assessment are warranted to confirm our findings.