From periphery to center, untold story of pure neuritic leprosy: an electrophysiological study.

BACKGROUND: Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. METHODS: We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. RESULTS: Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35 years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. DISCUSSION: This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

Anti-natural octyl disaccharide-leprosy IDRI diagnostic (NDO-LID) antibodies as indicators of leprosy reactions and neuritis.

Background: Leprosy is a complex infectious and neurological disease caused by Mycobacterium leprae. Nerve damage is related to immunological hypersensitivity responses known as leprosy reactions (LRs). Diagnostic tools to predict LRs are not available. We hypothesized that natural octyl disaccharide-leprosy IDRI diagnostic (NDO-LID) would be helpful as an indicator of LRs and neuritis. Methods: To assess the utility of NDO-LID in indicating reactions, ELISA were used to detect specific antibodies in serum samples from 80 Colombian leprosy patients (40 with and 40 without history of LRs). Responses were detected using a range of detection reagents detecting IgG, IgM or both isotypes. Results: Patients with a history of LRs had an increased seropositivity rate for anti-NDO-LID antibodies compared to patients without (anti-NDO-LID protein A [p=0.02], IgG anti-NDO-LID [p=0.01] and IgM anti-NDO-LID [p=0.01]). Further analyses of patients with a history of LRs indicated that both seropositivity rate and magnitude of responses were elevated among patients with neuritis versus those without neuritis (anti-NDO-LID protein A [p=0.03], IgG anti-NDO-LID [p=0.001] and IgM anti-NDO-LID [p=0.06]). Conclusions: Our data indicate that testing for serum anti-NDO-LID antibodies can be a useful screen to identify patients at risk of developing LRs and neuritis.

Minocycline in leprosy patients with recent onset clinical nerve function impairment.

Nerve function impairment (NFI) in leprosy may occur and progress despite multidrug therapy alone or in combination with corticosteroids. We observed improvement in neuritis when minocycline was administered in patients with type 2 lepra reaction. This prompted us to investigate the role of minocycline in recent onset NFI, especially in corticosteroid unresponsive leprosy patients. Leprosy patients with recent onset clinical NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3 months to these patients. The primary outcome was the proportion of patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI. Secondary outcomes included any improvement in nerve tenderness and pain. In this pilot study, 11 patients were recruited. The progression of NFI was halted in all; with 9 out of 11 patients (81.82%) showing ?restored? or ?improved? sensory or motor nerve functions, on assessment with MFT and VMT. No serious adverse effects due to minocycline were observed. Our pilot study demonstrates the efficacy and safety of minocycline in recent onset NFI in leprosy patients. However, larger and long term comparative trials are needed to validate the efficacy of minocycline in leprosy neuropathy.

Mechanisms of nerve injury in leprosy.

All patients with leprosy have some degree of nerve involvement. Perineural inflammation is the histopathologic hallmark of leprosy, and this localization may reflect a vascular route of entry of Mycobacterium leprae into nerves. Once inside nerves, M. leprae are ingested by Schwann cells, with a wide array of consequences. Axonal atrophy may occur early in this process; ultimately, affected nerves undergo segmental demyelination. Knowledge of the mechanisms of nerve injury in leprosy has been greatly limited by the minimal opportunities to study affected nerves in man. The nine-banded armadillo provides the only animal model of the pathogenesis of M. leprae infection. New tools available for this model enable the study and correlation of events occurring in epidermal nerve fibers, dermal nerves, and nerve trunks, including neurophysiologic parameters, bacterial load, and changes in gene transcription in both neural and inflammatory cells. The armadillo model is likely to enhance understanding of the mechanisms of nerve injury in leprosy and offers a means of testing proposed interventions.

Disability among new leprosy patients, an issue of concern: an institution based study in an endemic district for leprosy in the state of West Bengal, India.

BACKGROUND: Both magnitude and severity of disability in new leprosy patients measure indirectly the disease transmission in the community and rapidity of case detection. Various factors might be associated with the presence of impairment at registration. AIMS: To find out the prevalence of both grade 1 and grade 2 disability among new leprosy patients along with association of some clinical and sociodemographic factors. METHODS: A cross-sectional study was carried out in the Skin out patient department (OPD) of a Tertiary care hospital in West Bengal, which is situated in a highly endemic district of leprosy (prevalence was 6.5/10,000, year 2007). About 244 new leprosy patients were interviewed and clinically examined during Aug'06-Jun'07. Data was analysed in percentages, χ2 test, Anova. RESULTS: Proportion of disability was quite high among the studied new leprosy patients, 11.5% had grade-1 and 8.6% had grade-2. Disability was more among the patients with pure neuritic type of leprosy (<0.001), multibacillary leprosy (P=0.000), patients with delayed registration (P=0.000) and who were engaged as manual laborers (P=0.001). Feet were commonly involved site and nerve function impairment, both sensory and motor were the commonest nature of disability found in this study. CONCLUSION: To reduce new leprosy cases with grade-2 disability, early diagnosis of the leprosy patients and searching for grade-1 disability should be routine procedure in our health system, for which thorough neurological examination along with appropriate preventive measures is the need of the hour.

Effect of corticosteroid usage combined with multidrug therapy on nerve damage assessed using nerve conduction studies: a prospective cohort study of 365 untreated multibacillary leprosy patients.

The purpose of this study is to determine the extent of nerve involvement and to study the effect of corticosteroids combined with multidrug therapy on nerve damage in leprosy patients using sensory and motor nerve conduction studies. A cohort of 365 untreated multibacillary leprosy patients were prospectively studied using sensory and motor nerve conduction studies on upper and lower limb nerves. They were subgrouped as those to be treated with 12-week regimen of corticosteroids for reaction and/or neuritis or silent neuropathy of <6 months duration along with 12-month multidrug therapy (group A), and those with no reaction were treated with multidrug therapy only (group B). Analysis was performed using SPSS version 10.0. Significance of association was tested using chi(2) test. At registration, abnormality by nerve conduction studies was seen in 92% of patients and majority (65%) showing involvement of more than five sensory and motor nerves. Sensory nerve abnormalities were higher (52%) than motor (37%) (P < 0.001). Affection of sensory and motor nerves was higher in group A (P < 0.001). Notably, 40% nerves in group B also showed impairment at 0 month. This implies that almost all patients showed abnormal nerve conduction studies at onset regardless of reaction, proving nerve damage is more widespread than envisaged. At 18 months, overall percentile deterioration (23%) of nerves was higher than improvement (9%) (P < 0.001) indicating that corticosteroids combined with multidrug therapy failed to significantly improve the nerve status. Sensory nerve (57%) affection was significantly higher than motor (46%) (P < 0.001). Moreover, percentile deterioration of sensory nerves was higher in group A (P < 0.001) implying corticosteroids is not very efficacious in the prevention or reversal of nerve damage. Electrophysiological tests provide valuable information for detecting nerve function impairment and evaluating appropriate therapeutic regimens.

A study of leprosy reactions in a tertiary hospital in Delhi.

A retrospective study of 531 leprosy patients was undertaken to study the profile of reactions in the post Multi-Drug-Therapy period in a tertiary hospital in Delhi. BT was the most common group. The prevalence of reactions was found to be 8.09% for the Type 1 and 4.70% for the Type 2 reactions for a male:female ratio of 2.2. The Type 1 reaction was most frequently observed in the BB group followed by BL, BT and LL groups respectively. More than half of the patients had reactions at the time of presentation. In only 39.8% of the patients did reaction follow Multi-Drug-Therapy. In 4.5% of the patients with Type 1 reactions (T1R), concomitant infections were noted. The most common presentation of T1R was cutaneous lesions (74.41%) followed by cutaneous lesions and neuritis (53.6%), neuritis alone (12.1%), and only edema of hands and feet (7.31%) respectively. The Type 2 reactions (T2R) presented chiefly as papulo-nodular (92%) lesions followed by pustulonecrotic (8%) lesions. Associated neuritis was found in 40% and periosteitis and iritis in 8% and 4%, respectively. In 8.6% of the patients with T2R, precipitating factors could be observed. The prevalence of deformities in patients with reaction was 25%, and was more common in females. Deformities were observed in 23.25% of the T1R patients and 28% of the T2R patients.

Clinical, electrophysiological, and immunopathological study of peripheral nerves in Hansen's disease.

Hansen's disease is a disease of peripheral nerves. Some patients develop peripheral neuropathy before the diagnosis of the disease, and others develop these complications after starting therapy. Electrophysiological (EP) studies were carried out in Hansen's disease patients. This work studied the neural deficits, electromyography (EMG) and motor nerve conduction (MNC) variables in different types of leprosy and the immunopathology of sural nerve tissue in patients with severe neural deficits. Forty leprosy patients had neurological examinations and EP study. Histopathological and immunopathological study of sural nerve biopsy specimens was performed for 10 patients with severe neural deficits. The results of the neurological study showed that there was involvement of cranial nerves, muscular system, motor reflexes and sensory system and trophic and vasomotor changes. EP study showed significant changes in EMG of abductor digiti minimi in patients as compared to controls. MNC variables of common peroneal nerve were abnormal in 80% of all patients, MNC of median nerve was abnormal in 72.5%, while MNC of ulnar nerve was abnormal in 70% and SNC of ulnar nerve was abnormal in 77.5% of the total. In conclusion, electrophysiological investigations have an important role in the detection of muscle denervation and neuropathic changes in leprosy patients. These investigations are safe, rapid and non-invasive techniques. On the other hand immunopathological study revealed that the degree of immune positivity correlated with the degree of nerve fibrosis.

Pathology and pathogenesis of leprous neuritis; a preventable and treatable complication.

In conclusion, it may be said that many advances have been made in the diagnosis, treatment and prevention of nerve damage. It is now a well accepted fact that the affinity of M. leprae for Schwann cells and the property of M. leprae to grow in cooler sites of the body have made certain segments of nerve trunks vulnerable. Trauma that supervenes the inflammation and swelling severely aggravates the nerve damage. The reactive phase in all forms of leprosy, the etiology of which is not clearly understood, produces intraneural caseous necrosis in tuberculoid disease and microabscesses in lepromatous disease, causing much irreversible damage to nerves. The steroid treatment that is administered during the reactive phase has helped greatly to stop further damage, although the damage already done to nerves is not always reversible. Preventive measures like detecting the disease before nerve trunks are infected and offering prompt and adequate antileprosy therapy as early as possible have helped to reduce the prevalence of deformities. It is hoped that administering steroids along with antileprosy therapy to prevent active inflammation and or fibrosis of the nerve will reduce the prevalence of nerve damage significantly. Measures which provide rest for the infected nerve to prevent trauma should be explored.

Field evaluation of WHO-MDT of fixed duration, at ALERT, Ethiopia: the AMFES project--II. Reaction and neuritis during and after MDT in PB and MB leprosy patients.

For a cohort of 286 leprosy patients the incidence rates and clinical manifestations of leprosy reactions during treatment and surveillance are described. Currently, individual patients had been observed for up to 4 years. It is intended that surveillance within this project should continue for up to 5 years after treatment. Of 128 PB patients, observed for 267 person-years (mean 2.1) 27 had 35 episodes of reaction, corresponding to an overall incidence rate of 131 events per 1000 person-years-at-risk (pyar). Of 158 MB patients observed for 402 person years (mean 2.5), 64 had 114 reactions, with an overall incidence of 284 events per 1000 pyar. For both PB and MB patients, incidence rates during treatment and post-MDT surveillance were similar. For PB patients, pre-existing physical impairment at the start of MDT was a significant risk factor for the occurrence of subsequent events, but this was not found in MB patients.

Type 1 reaction, neuritis and disability in leprosy. What is the current epidemiological situation?

Type 1 reaction is one of the major causes of nerve damage in leprosy patients leading to disabilities of varying severity. Though this complication of leprosy has been extensively described, we still know very little of its natural history and of the factors which may predispose to it. This paper examines the descriptive and analytic epidemiology of these reactions in leprosy. We find that they vary greatly in clinical expression, time of onset, duration and severity, which has important implications for the way they are handled in the context of leprosy-control programmes. We review the various risk factors that have been suggested over the last 30 years and the evidence of their utility in identifying 'high-risk' patients is assessed. We then review the specific aspects of neuritis and disability in leprosy and examine the contribution of Type 1 reaction to leprosy-associated disabilities. The prospects for early detection and prevention of Type 1 reaction are examined in the light of current knowledge, both at research and at the leprosy control level.

Manifestaciones neurológicas de la lepra / Neurologic manifestation of the leprosy

La lepra es siempre una enfermedad cutánea y nerviosa periférica. Existen formas clínicas bien definidas localizadas en los troncos nerviosos: cara, cuello, miembros, dando la clásica mononeuritis múltiple. El primer lugar le corresponde al cubital, seguido por el ciático poplíteo externo. Según cifras estadísticas y nuestra propia experiencia hay predominancia para el cubital en la gotera oleacraneana respecto de la palma y en la cabeza del peroné para el ciático poplíteo externo respecto del hueco poplíteo. El engrosamiento nervioso es facilmente palpable y aún visible. Se hace la descripción anatómica y funcional siguiendo a Guy Lazorthes y la interpretación de la biomecánica en base a los estudios y aportes de Manzi, R.O y colaboradores, con las consecuencias ulcerotróficas del disbalance muscular. El panadizo analgésico y el mal perforante plantar son dos cuadros habituales en la lepra. No así el absceso del nervio y el síndrome hombro-mano-dedos. Se citan referencias en nuestro país. Nuestro material es recopilado del Hospital Perrando y servicio de Dermatología de Resistencia. Se observó predominancia de formas múltiples además de formas lepromatosas. En la fisiopatogenia se hace referencia al estado de hibernación en que vive el bacilo en la vaina de Schwann, ya que éste vive años a cambio del histiocito que no vive más de una semana. Como resultado de un conflicto local donde intervienen fenómenos tisulares, inmunológicos y circulatorios, se producen, de acuerdo a la capacidad del huésped, las distintas formas de lepra: tuberculoide, lepromatosa, dimorfa e incaracterística. Se describe otra forma que es la neuritis autoinmune secundaria de Languillon y Carayon como expresión de pérdida de alergia tisular. La isquemia del nervio es la condicionante de la lesión neural que lleva a la esclerosis. La liberación del tronco del canal por sección de fibras de inserción muscular y la neurolisis con epineurotomía son propuestas como los medios más útiles para la cirugía, cuando se han agotado los recursos médicos conservadores

Manifestaciones neurológicas de la lepra / Neurologic manifestation of the leprosy

La lepra es siempre una enfermedad cutánea y nerviosa periférica. Existen formas clínicas bien definidas localizadas en los troncos nerviosos: cara, cuello, miembros, dando la clásica mononeuritis múltiple. El primer lugar le corresponde al cubital, seguido por el ciático poplíteo externo. Según cifras estadísticas y nuestra propia experiencia hay predominancia para el cubital en la gotera oleacraneana respecto de la palma y en la cabeza del peroné para el ciático poplíteo externo respecto del hueco poplíteo. El engrosamiento nervioso es facilmente palpable y aún visible. Se hace la descripción anatómica y funcional siguiendo a Guy Lazorthes y la interpretación de la biomecánica en base a los estudios y aportes de Manzi, R.O y colaboradores, con las consecuencias ulcerotróficas del disbalance muscular. El panadizo analgésico y el mal perforante plantar son dos cuadros habituales en la lepra. No así el absceso del nervio y el síndrome hombro-mano-dedos. Se citan referencias en nuestro país. Nuestro material es recopilado del Hospital Perrando y servicio de Dermatología de Resistencia. Se observó predominancia de formas múltiples además de formas lepromatosas. En la fisiopatogenia se hace referencia al estado de hibernación en que vive el bacilo en la vaina de Schwann, ya que éste vive años a cambio del histiocito que no vive más de una semana. Como resultado de un conflicto local donde intervienen fenómenos tisulares, inmunológicos y circulatorios, se producen, de acuerdo a la capacidad del huésped, las distintas formas de lepra: tuberculoide, lepromatosa, dimorfa e incaracterística. Se describe otra forma que es la neuritis autoinmune secundaria de Languillon y Carayon como expresión de pérdida de alergia tisular. La isquemia del nervio es la condicionante de la lesión neural que lleva a la esclerosis. La liberación del tronco del canal por sección de fibras de inserción muscular y la neurolisis con epineurotomía son propuestas como los medios más útiles para la cirugía, cuando se han agotado los recursos médicos conservadores

Fisiopatologia da neurite hanseniana / Physiopathology of the neuropathy in leprosy

A hanseniase é uma enfermedade com potencial de incapacidades físicas das mais notáveis. O comprometimento do sistema nervoso é constante e aproximadamente 30% dos doentes sofrem lesöes neurológicas graves. As manifestaçöes dermatológicas e os estudos bacteriológicos encontram-se bem estabelecidos. No entanto, o conhecimento das lesöes nervosas näo atingiu o mesmo desenvolvimento, fazendo com que a terapêutica do comprometimento, neurológico esteja longe de ser satisfatória e as medidas preventivas dificilmente colocadas em prática. Este trabalho tem por finalidade contribuir para o esclarecimento de alguns aspectos de comprometimento dos nervos periféricos nesta doença

[Lepromatous leprosy: clinical and electrophysiological arguments in favor of axonal multi-neuritis]. / Lèpre lépromateuse: arguments cliniques et électrophysiologiques en faveur d'une multinévrite axonale.

UNLABELLED: This work was undertaken because there were only few reports on neurological aspects on lepromatous leprosy. We studied 30 patients suffering from lepromatous leprosy who, at their first visit to the Institute had never been treated. The clinical examination included a quantitative evaluation of the neurological status following the method developed by Pearson. Motor and sensory nerve conduction velocities were measured: values of conduction velocity and distal amplitude were analysed and compared to those of a group of 22 healthy subjects. IN CONCLUSION: (a) There is a high frequency of clinical and especially electrophysiological neurological impairment. This impairment can be extremely precocious and may happen shortly after the first cutaneous signs. (b) Nervous impairment is diffuse, bilateral but not homogeneous. These are characteristics of mononeuritis multiplex. Impairement is predominantly sensitive and tactile sensibility is more involved than thermo-algic sensation. (c) The radial superficial nerve is the most frequently involved clinically and electrophysiologically. (d) The electrophysiological results, showing a normal or slightly reduced conduction velocity and a low amplitude of evoked potentiel are in favour of a predominantly axonal damage.