Nerve Damage In Leprosy Research Articles

Predicting Neuropathy and Reactions in Leprosy at Diagnosis and Before Incident Events—Results from the INFIR Cohort Study

BackgroundLeprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.Methodology/Principal FindingsThe study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.Conclusions/SignificanceThese findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability.

High-resolution sonography: a new technique to detect nerve damage in leprosy.

BackgroundLeprosy is the most common treatable peripheral nerve disorder worldwide with periods of acute neuritis leading to functional impairment of limbs, ulcer formation and stigmatizing deformities. Since the hallmarks of leprosy are nerve enlargement and inflammation, we used high-resolution sonography (US) and color Doppler (CD) imaging to demonstrate nerve enlargement and inflammation.Methology/Principal FindingsWe performed bilateral US of the ulnar (UN), median (MN), lateral popliteal (LP) and posterior tibial (PT) nerves in 20 leprosy patients and compared this with the clinical findings in these patients and with the sonographic findings in 30 healthy Indian controls.The nerves were significantly thicker in the leprosy patients as compared to healthy controls (p<0.0001 for each nerve). The two patients without nerve enlargements did not have a type 1 or type 2 reaction or signs of neuritis. The kappa for clinical palpation and nerve enlargement by sonography was 0.30 for all examined nerves (0.32 for UN, 0.41 for PN and 0.13 for LP). Increased neural vascularity by CD imaging was present in 39 of 152 examined nerves (26%). Increased vascularity was observed in multiple nerves in 6 of 12 patients with type 1 reaction and in 3 of 4 patients with type 2 reaction. Significant correlation was observed between clinical parameters of grade of thickening, sensory loss and muscle weakness and US abnormalities of nerve echotexture, endoneural flow and cross-sectional area (p<0.001).Conclusions/SignificanceWe conclude that clinical examination of enlarged nerves in leprosy patients is subjective and inaccurate, whereas sonography provides an objective measure of nerve damage by showing increased vascularity, distorted echotexture and enlargement. This damage is sonographically more extensive and includes more nerves than clinically expected.

Decompressive surgery for treating nerve damage in leprosy. A Cochrane review

Decompressive surgery is used for treating nerve damage in leprosy. We assessed the effectiveness of decompressive surgery for patients with nerve damage due to leprosy. A broad search strategy was performed to find eligible studies, selecting randomised controlled trials (RCTs) comparing decompressive surgery alone or plus corticosteroids with corticosteroids alone, placebo or no treatment. Two authors independently assessed quality and extracted data. Where it was not possible to perform a meta-analysis, the data for each trial was summarised. We included two randomised controlled trials involving 88 people. The trials examined the added benefit of surgery over prednisolone for treatment of nerve damage of less than 6 months duration. After 2 years follow-up there was no significant difference in nerve function improvement between people treated with surgery plus prednisolone or with prednisolone alone. Adverse effects of decompression surgery were not adequately described. Evidence from randomised controlled trials does not show a significant added benefit of surgery over steroid treatment alone. Well-designed randomised controlled trials are needed to establish the effectiveness of the combination of surgery and medical treatment compared to medical treatment alone.

Corticosteroids for treating nerve damage in leprosy. A Cochrane review

Corticosteroids are commonly used for treating nerve damage in leprosy. We assessed the effectiveness of corticosteroids for treating nerve damage due to leprosy. A systematic search was undertaken to identify randomised controlled trials (RCTs) comparing corticosteroids with placebo or with no treatment. Two authors independently assessed quality and extracted data. Where it was not possible to perform a meta-analysis, the data for each trial was summarised. Three RCTs involving 513 people were found. Two trials compared prednisolone with placebo. One trial treated mild sensory impairment of less than 6 months duration and the other trial treated nerve function impairment of 6 to 24 months duration. Both trials examined nerve function improvement 12 months from the start of treatment, but found no significant difference between the two groups. The third trial compared three corticosteroid regimens for severe type 1 reactions. After 12 months, a significantly higher proportion of individuals on a 3 month course required extra corticosteroids compared to the groups with a high-dose and low-dose regimen of 5 months duration. Diabetes and peptic or infected ulcers were not significantly more often reported in the corticosteroid compared to the placebo group. Evidence from RCTs does not show a significant long-term effect for either long-standing nerve function impairment or mild sensory impairment. A 5 month corticosteroid regimen was significantly more beneficial than a 3 month corticosteroid regimen. Further RCTs are needed to establish the effectiveness and optimal regimens of corticosteroids and to examine new therapies.

Intraneural injection of corticosteroids to treat nerve damage in leprosy: a case report and review of literature

IntroductionNerve damage in leprosy patients leads to deformities and disabilities. Oral corticosteroids are given early to prevent permanent injury. We present a new approach to treat well-established nerve damage with local injection of corticosteroids.Case presentationA 60-year-old leprosy patient presented with right claw hand deformity secondary to right ulnar and median neuropathy. Monthly intraneural injection of corticosteroids resulted in improvement in sensory and motor function of his right hand over a 6-month period. Nerve conduction velocity testing documented the success of our therapy.ConclusionWe report the first case of successful nerve regeneration in neglected neuropathy secondary to leprosy after local injection of corticosteroids. Intraneural extra-fascicular injection of corticosteroids improved the sensory and motor nerve function in our patient with borderline leprosy regardless of the duration of nerve function loss.

Nerve damage in leprosy and its management

Leprosy is the most common treatable peripheral nerve disorder worldwide. Deformity and disability result from nerve-function impairment; however, early treatment is associated with good outcome. Leprosy is often diagnosed late as many physicians have little experience with the clinical picture. Recent research using nerve conduction and thermal threshold tests has identified that nerve impairment is detectable long before it turns clinical. This discovery could have important implications for treatment because steroid therapy for nerve-function impairment that is detected clinically is unsatisfactory. Evidence that clinical neuropathy represents only the 'tip of the iceberg' of nerve damage, together with an understanding that the underlying inflammatory immunological processes require longer, more-aggressive treatment, could help usher in new and more-successful approaches to the treatment of nerve-function impairment in leprosy. This Review focuses on the neurological manifestations of leprosy and the pathophysiology of nerve damage. Early detection and treatment of nerve-function impairment are crucial for outcome, so special emphasis is given to developments in detecting and treating nerve impairment in leprosy early.

Leprosy, Nerves, and Surgery

Leprosy is one of the most common and potentially treatable causes of peripheral neuropathy. Despite the effective antibiotics to cure the infection, the immune-mediated peripheral nerve damage can continue long after effective antimicrobial treatment has started, and patients continue to be stigmatized. The initial management of leprous neuritis is always medical, using bactericidal drugs and high doses of corticosteroids given systemically. If medical treatment fails, nerve decompression by external neurolysis or by transposition of the nerves is attempted with variable success. Indications for decompressive surgery for neuritis include pain, motor, and/or sensory deficits. Preventing nerve damage in leprosy remains a challenge, and it is better to overtreat leprosy than to undertreat it. We still need to define the role of surgery on nerves in leprosy. Recently, the role of portable devices in early detection of nerve damage has been recognized; however, who are the candidates for surgery, when to perform surgery, extent of surgery, and what kind of procedure will give the best results are yet to be defined.

Entry of M. leprae into Schwann cells: old studies revisited

All leprosy is neural and the role of Schwann cells as preferential host cells for M. leprae is undoubted. It is within these that M. leprae grow and exhibit their dual roles of nerve damage and immune subversion. These roles have been dissected by the innovative use of experimental mouse models and murine Schwann cell culture extensively used at FMR in the last two decades. It is debatable whether the entry of M. leprae into Schwann cells (Sc) is specific. The evidence suggests that early entry into Sc is mediated only by viable M. leprae though no evidence of a single specific bacterial structure mediating bacterial entry was obtained. The role of weakly phagocytic cells (like Sc) in M. leprae pathogenesis was expanded in intervention studies in mice wherein actively phagocytic cells were killed by ingestion of injected silica. Since M. leprae growth in both foot pad and nerve damage was not affected, it implied that the weakly phagocytic cells were responsible for these features. Additionally murine tissue culture studies demonstrated that active entry of M. leprae into Sc resulted in deposition of bacterial antigens within the Sc membrane blocking cellular communication and nerve regeneration. Evidence for breakdown of cellular communication was obtained from the down regulation of NgCAM and NGF receptor which matched the pattern of limited/progressive nerve damage in murine experimental models involving C57Bl/6 and Swiss White mice. The antigen deposits paradoxically served as a focal point for either (i) functional tissue damaging lymphocytic stimulation or (ii) their death via apoptosis – a representation of immune evasion. Cumulatively mechanisms amplified in experimental models and nerve tissue culture could provide insights into precipitation of immune-mediated lepra reactions and for the silent phases of nerve damage in leprosy, which are non immune in nature. Unfortunately the insights provided have not been mainstreamed into the understanding of leprous neuropathy. The observations will be therefore amalgamated with those of recent studies towards identifying fresh approaches to intriguing questions in leprous neuropathy.

Interventions for skin changes caused by nerve damage in leprosy

More than three million persons are disabled by leprosy worldwide. The main complication of sensory nerve damage is neuropathic ulceration, particularly of the feet. In this review we explored interventions that can prevent and treat secondary damage to skin and limbs. To assess the effects of self-care, dressings and footwear in preventing and healing secondary damage to the skin in persons affected by leprosy. We searched the Cochrane Skin Group Specialised Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2008), MEDLINE (from 2003 to April 2008), EMBASE (from 2005 to April 2008), CINAHL (1982-2006) and LILACS (1982- April 2008 ) as well as online registers of ongoing trials (April 2008). Randomised controlled trials involving anyone with leprosy and damage to peripheral nerves treated with any measures designed to prevent damage with the aim of healing existing ulcers and preventing development of new ulcers. Two authors assessed trial quality and extracted data. Eight trials with a total of 557 participants were included. The quality of the trials was generally poor. The interventions and outcome measures were diverse. Although three studies that compared zinc tape to more traditional dressings found some benefit, none of these showed a statistically significant effect. One trial indicated that topical ketanserin had a better effect on wound healing than clioquinol cream or zinc paste, RR was 6.00 (95% CI 1.45 to 24.75). We did not combine the results of the two studies that compared topical phenytoin to saline dressing, but both studies found statistically significant effects in favour of phenytoin for healing of ulcer (SMD -2.34; 95% CI -3.30 to -1.39; and SMD -0.79; 95% CI -1.20 to 0.39). Canvas shoes were not much better than PVC-boots, and double rocker shoes did not promote healing much more than below-knee plasters. One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Nerve and skin damage in leprosy is associated with increased intralesional heat shock protein.

Leprosy is frequently complicated by the development of reversal reactions in which peripheral nerve and skin lesions become inflamed and irreversible nerve damage may ensue. Increased expression of proteins belonging to the 70-kD heat shock family (hsp 70) occurs in cells of the central nervous system exposed to hyperthermia, physical damage or drug-induced trauma. In the present study we have used immunocytochemical staining to monitor hsp70 levels in peripheral nerves infected by Mycobacterium leprae. Hsp70 was detected in skin and nerve lesions from all leprosy patients, but was particularly prominent in lesions from patients undergoing reversal reactions. Hsp70 immunocytochemistry can thus be used as a marker of neural injury in the peripheral as well as in the central nervous system. The cellular dynamics of nerve damage in leprosy are currently poorly understood, and we postulate that the immunopathology of leprosy may be partly due to an autoimmune response to heat shock proteins.

The effect of corticosteroid usage on the bacterial killing, clearance and nerve damage in leprosy: A prospective cohort study: Part 1 – Study design and baseline findings of 400 untreated multibacillary patients

To investigate possible adverse effects of therapeutic usage of corticosteroids on the killing and clearance of M. leprae and the clearance of granuloma, in patients with multibacillary (MB) leprosy. A cohort of 400 untreated MB patients were sub-grouped into those to be treated with corticosteroids (prednisolone 40 mg daily tapered to 5 mg over 12 weeks) along with MB-MDT for reaction and/or neuritis or silent neuropathy (SN) of <6 months duration (group A), and those with no reaction and to be treated with MDT only (group B). Clinical, bacteriological, histopathological and neurological test findings at fixed time points were compared. Analysis was performed using SPSS version 10.0. The significance of association was tested using Chi-square test. In the current report, we describe the study design and baseline findings of 400 untreated MB patients, with special emphasis on differences between patients in groups A and B. At baseline, applying Ridley-Jopling classification, 39% patients were BT, 20% BB, 24% BL, 12% sub-polar LL and 5% pure neural (PN). Overall, 60% patients were slit skin smear (SSS) negative and 33% presented with disability either grades 1 or 2. Overall 140/400 (35%) patients presented with reaction and/or neuritis and 11/400 (3%) presented with SN of <6 months duration. Comparing groups A and B, the percentage of patients presenting with DG2 was significantly higher in group A (43%). By clinical tests, monofilaments (MF) and voluntary muscle testing (VMT), the percentage of patients and nerves showing functional impairment was also significantly higher in group A. However, in the more sensitive nerve conduction velocity (NCV) test, the percentage of patients that showed nerve abnormalities was closely comparable; 94% and 91% in groups A and B respectively while number of affected nerves was higher in group A. At baseline, as recorded by NCV, peripheral nerve function abnormality was observed in almost all the MB patients regardless of reaction; but among those presenting with reaction or neuritis, the nerve damage was more severe and extensive.

Ninjurin 1 asp110ala single nucleotide polymorphism is associated with protection in leprosy nerve damage

Leprosy is the major cause of non-traumatic neuropathy. Herein, we investigated the role of ninjurin 1, an adhesion molecule involved in nerve regeneration in leprosy. Our results demonstrated that M. leprae stimulates in vitro up-regulation of ninjurin mRNA in cultured Schwann and blood cells as well as in vivo mRNA and protein expression in leprosy nerve biopsies. A polymorphism (asp110ala) was investigated in a case–control study (1123 individuals) and no association was found with leprosy per se or with disseminated forms. Nevertheless, ala110 was associated with functional nerve impairment (OR = 2.42; p = 0.02 for ala/ala) and with lower mRNA levels. Our data suggests that asp110ala could be a valuable genetic marker of nerve damage in leprosy.

Expression of metalloproteinases (MMP‐2, MMP‐9, and TACE) and TNF‐α in the nerves of leprosy patients

Matrix metalloproteinases (MMPs) and tumor necrosis factor alpha (TNF-alpha) play important and related roles in the pathogenesis of nerve injury. MMP-dependent and TNF-alpha-dependent processes of neurodegeneration, such as blood-nerve breakdown and immune cell recruitment, are characteristic of leprosy nerve damage. Our work has contributed to the understanding of the role of cytokines in the process, but the role of MMPs in the pathogenesis of neuritic leprosy has not been investigated. This study analyzed the changes in mRNA expression and immunodistribution of MMP-2, MMP-9, TNF-alpha-converting enzyme (TACE), TNF-alpha in nerves of 27 pure neuritic leprosy (PNL) patients, both acid-fast bacilli positive (AFB(+)) and acid-fast bacilli negative (AFB(-)), and 8 non-leprosy patients with control peripheral neuropathic conditions. MMP-2, MMP-9, and TNF-alpha mRNA expression was significantly induced in the AFB(-) relative to the AFB(+) neuritic leprosy group and nonlepritic controls; TACE levels were also elevated in the AFB(-) group, but this change was not statistically significant. Immunoreactive profiles for TNF-alpha and MMPs demonstrated strong reactivity of myelinated axons, infiltrating macrophages, Schwann cells, endothelial cells, and perineurial cells in neuritic leprosy biopsies. This study provides the evidence of the involvement of MMPs in the pathogenesis of PNL neuropathy.

Early nerve damage in leprosy: An electrophysiological study of ulnar and median nerves in patients with and without clinical neural deficits

Peripheral nerve trunk involvement in leprosy is very common. However, by the time it becomes clinically manifest, the damage is quite advanced. If the preclinical nerve damage can be detected early, the deformities and disabilities can be prevented to a large extent. To assess the electrophysiological functions of the ulnar and median nerve trunks in cases of clinically manifest leprosy with and without manifest nerve damage at different durations of nerve damage. Electrophysiological functions of ulnar and median nerves were studied in leprosy patients, both normal and at different stages of disease and damage. PB cases, having disease for six months or less, without neurological symptoms and clinically normal appearing nerve. Mean was taken of different values. The changes in values of different parameters were expressed as percentage change with reference to the control values (increase or decrease). Reduced nerve conduction velocities and changes in latency and amplitude were observed. Changes in sensory nerve conduction were more pronounced. Sensory latencies and amplitude changes were more severe than motor latencies and amplitudes in cases with manifest muscle palsies. Changes in MB cases were less marked. Further studies are needed to identify parameters likely to be helpful in the diagnosis of early nerve damage.

ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli

Demyelination is a common pathologic feature in many neurodegenerative diseases including infection with leprosy-causing Mycobacterium leprae. Because of the long incubation time and highly complex disease pathogenesis, the management of nerve damage in leprosy, as in other demyelinating diseases, is extremely difficult. Therefore, an important challenge in therapeutic interventions is to identify the molecular events that occur in the early phase before the progression of the disease. Here we provide evidence that M. leprae-induced demyelination is a result of direct bacterial ligation to and activation of ErbB2 receptor tyrosine kinase (RTK) signaling without ErbB2-ErbB3 heterodimerization, a previously unknown mechanism that bypasses the neuregulin-ErbB3-mediated ErbB2 phosphorylation. MEK-dependent Erk1 and Erk2 (hereafter referred to as Erk1/2) signaling is identified as a downstream target of M. leprae-induced ErbB2 activation that mediates demyelination. Herceptin (trastuzumab), a therapeutic humanized ErbB2-specific antibody, inhibits M. leprae binding to and activation of ErbB2 and Erk1/2 in human primary Schwann cells, and the blockade of ErbB2 activity by the small molecule dual ErbB1-ErbB2 kinase inhibitor PKI-166 (ref. 11) effectively abrogates M. leprae-induced myelin damage in in vitro and in vivo models. These results may have implications for the design of ErbB2 RTK-based therapies for both leprosy nerve damage and other demyelinating neurodegenerative diseases.

High prevalence of vasomotor reflex impairment in newly diagnosed leprosy patients

Initial nerve damage in leprosy occurs in small myelinated and unmyelinated nerve fibers. Early detection of leprosy in the peripheral nervous system is challenging as extensive nerve damage may take place before clinical signs of leprosy become apparent. In order to determine the prevalence of, and factors associated with, peripheral autonomic nerve dysfunction in newly diagnosed leprosy patients, 76 Brazilian patients were evaluated prior to treatment. Skin vasomotor reflex was tested by means of laser Doppler velocimetry. Blood perfusion and reflex vasoconstriction following an inspiratory gasp were registered on the second and fifth fingers. Vasomotor reflex was impaired in at least one finger in 33/76 (43%) patients. The fifth fingers were more frequently impaired and suffered more frequent bilateral alterations than the second fingers. Multivariate regression analysis showed that leprosy reaction (adjusted odds ratio = 8.11, 95% confidence interval: 1.4-48.2) was associated with overall impaired vasomotor reflex (average of the four fingers). In addition, palmar erythrocyanosis and an abnormal upper limb sensory score were associated with vasomotor reflex impairment in the second fingers, whereas anti-phenolic glycolipid-I antibodies, ulnar somatic neuropathy and a low finger skin temperature were associated with impairment in the fifth fingers. A high prevalence of peripheral autonomic dysfunction as measured by laser Doppler velocimetry was observed in newly diagnosed leprosy patients, which is clinically evident late in the disease. Autonomic nerve lesion was more frequent than somatic lesions and was strongly related to the immune-inflammatory reaction against M. leprae.

Mapping the laminin-binding and adhesive domain of the cell surface-associated Hlp/LBP protein from Mycobacterium leprae

Binding of Mycobacterium leprae to and invasion of Schwann cells (SC) represent a crucial step that initiates nerve damage in leprosy. We and others have described that M. leprae colonization of the peripheral nerve system may be mediated in part by a surface-exposed histone-like protein (Hlp), characterized as a laminin-binding protein (LBP). Hlp/LBP has also been shown to play a role in the binding of mycobacteria to alveolar epithelial cells and macrophages. In the present study we report that M. leprae expresses Hlp/LBP protein during the course of human infection. Additionally, we analyzed the interaction of Hlp/LBP with the extracellular matrix and host cell surface. We show that Hlp/LBP, besides laminin, also binds heparin and heparan sulfate. Testing truncated recombinant Hlp molecules corresponding to the N-terminal (rHlp-N) and the C-terminal (rHlp-C) domains of the protein, we established that interaction of Hlp/LBP with laminin-2 and heparin is mainly mediated by the C-terminal domain of the protein. Moreover, the same domain was found to be involved in Hlp/LBP-mediating bacterial binding to human SC. Finally, evidence is shown suggesting that M. leprae produces a post-translationally modified Hlp/LBP containing methyllysine residues. Methylation of the lysine residues, however, seems not to affect the adhesive properties of Hlp/LBP. Taken together, our observations reinforce the involvement of Hlp/LBP as an adhesin in mycobacterial infections and define its highly positive C-terminal region as the major adhesive domain of this protein.

Challenges presented by nerve damage in leprosy

The basis of nerve damage in leprosy is the unique tendency of Mycobacterium leprae to invade Schwann cells. alphaBeta-Dystroglycan on the basement membrane of Schwann cells binds to laminin alpha2, in turn binding to receptors on the M. leprae surface, comprising a histone-like protein and phenoglycolipid-1. When nerve damage during reversal reactions was found to be associated with an abrupt increase in delayed type hypersensitivity against M. leprae antigenic determinants released from Schwann cells, it suggested that the nerve is damaged as an innocent bystander during the immune response. This strongly influenced the introduction of therapy based on immunosuppression combined with continued anti-mycobacterial medication. Lysis of Schwann cells presenting M. leprae antigenic determinants by activated CD4+ T cells and interaction of M. leprae with Toll-like receptors on Schwann cells are additional mechanisms implicated in nerve damage. Persistence of M. leprae antigen in local lesions after regular multiple drug therapy (MDT) is an important risk factor for late reactions. In spite of significant advances in the provision of MDT globally, early diagnosis, together with effective treatment of the disease and associated nerve damage at initial presentation remains a major challenge for the health services. Reduced prevalence as a result of MDT should not be taken to indicate that the challenges of leprosy control are diminished as long as nerve damage is not controlled and new case detection rates are not declining.

Steroids do not prevent long term nerve damage in leprosy

Steroids do not prevent long term nerve damage in leprosy

Comparative proteomics of the Mycobacterium leprae binding protein myelin P0: its implication in leprosy and other neurodegenerative diseases

Mycobacterium leprae, the causative agent of leprosy invades Schwann cells of the peripheral nerves leading to nerve damage and disfigurement, which is the hallmark of the disease. Wet experiments have shown that M. leprae binds to a major peripheral nerve protein, the myelin P zero (P0). This protein is specific to peripheral nerve and may be important in the initial step of M. leprae binding and invasion of Schwann cells which is the feature of leprosy. Though the receptors on Schawann cells, cytokines, chemokines and antibodies to M. leprae have been identified the molecular mechanism of nerve damage and neurodegeneration is not clearly defined. Recently pathogen and host protein/nucleotide sequence similarities (molecular mimicry) have been implicated in neurodegenerative diseases. The approach of the present study is to utilise bioinformatic tools to understand leprosy nerve damage by carrying out sequence and structural similarity searches of myelin P0 with leproma and other genomic database. Since myelin P0 is unique to peripheral nerve, its sequence and structural similarities in other neuropathogens have also been noted. Comparison of myelin P0 with the M. leprae proteins revealed two characterised proteins, Ferrodoxin NADP reductase and a conserved membrane protein, which showed similarity to the query sequence. Comparison with the entire genomic database (www.ncbi.nlm.nih.gov) by basic local alignment search tool for proteins (BLASTP) and fold classification of structure–structure alignment of proteins (FSSP) searches revealed that myelin P0 had sequence/structural similarities to the poliovirus receptor, coxsackie-adenovirus receptor, anthrax protective antigen, diphtheria toxin, herpes simplex virus, HIV gag-1 peptide, and gp120 among others. These proteins are known to be associated directly or indirectly with neruodegeneration. Sequence and structural similarities to the immunoglobin regions of myelin P0 could have implications in host–pathogen interactions, as it has homophilic adhesive properties. Although these observed similarities are not highly significant in their percentage identity, they could be functionally important in molecular mimicry, receptor binding and cell signaling events involved in neurodegeneration.