Effect of Steroid Prophylaxis on Nerve Function Impairment in Multi-bacillary Leprosy Patients on MDT-MB.

The effects of corticosteroids in varying doses and duration for the treatment of reaction and nerve function impairment (NFI) in leprosy have been studied extensively. However, an optimal dose and duration of steroid when used as a prophylactic agent for NFI is yet to be established. This study was aimed to determine whether addition of low dose steroid for the initial 8 months of multi drug therapy (MDT) can prevent further deterioration of nerve function (DON) in multibacillary leprosy patients. Sixty multibacillary leprosy patients were randomized into two groups and B consisting of 30 patients each. Group A received MDT-MB for 12 months with prednisolone 20 mg/day from the beginning of treatment for 6 months followed by tapering by 5 mg/2 weeks in 7th and 8th month. Group B received MDT-MB alone for 12 months. Nerve function assessment (NFA) using various modalities was done at the beginning (0 month), at the end of 8 months and at the completion of MDT (12 months). The proportion of patients showing DON was significantly higher in group B, while proportion of patients showing improvement was more in group A. This study thus shows all MB cases with or without NFI at registration should receive prophylactic steroid at least for 8 months. Since preventing deformities using; prophylactic steroids in leprosy is an important issue larger randomized control trials using longer duration of low dose steroid witha longer follow up period should be conducted.

Facial burning in women with leprosy, physiological or pathological?

INTRODUCTION: Eight peri-menopausal women, five with borderline lepromatous leprosy and three with borderline tuberculoid leprosy, self-referred complaining of 'burning of the face. Four were seen in 1993, three having been treated as 'menopausal'without betterment and four were seen in 1997. METHODS: Eight peri-menopausal women who self-referred because of facial burning', and seven women who self-referred for other problems had a careful review of clinical records and were assessed fully for leprosy including graded sensory skin testing of the face, and standard nerve function tests. RESULTS: On examination three in each group of four complaining of facial burning were found to have major loss of facial sensation and one had generalised neuritis without significant facial involvement. Treatment with antileprotics and steroids resulted in recovery of facial sensation, although one later became blind. Of the seven who self-referred without facial burning, five had no facial sensory loss and two had slight loss of facial sensation.

The prognostic importance of detecting mild sensory impairment in leprosy: a randomized controlled trial (TRIPOD 2).

This study was designed to investigate whether leprosy patients diagnosed with mild sensory impairment have a better prognosis when treated with steroids than similarly impaired patients treated with placebo. A multi-centre, randomized, double-blind, placebo-controlled trial was conducted in Nepal and Bangladesh. Patients were eligible if they had a confirmed leprosy diagnosis, were between 15 and 50 years old, had mild sensory impairment of the ulnar or posterior tibial nerve of less than 6 months duration and did not require steroids for other reasons. 'Mild impairment' was defined as 'impaired on the Semmes-Weinstein monofilament test, but testing normal on the ballpen sensory test'. Subjects were randomized to either prednisolone treatment starting at 40 mg per day, tapering over 4 months, or placebo. Nerve function was monitored monthly. Any patient who deteriorated was taken out of the trial and was put on full-dose steroid treatment. Outcome assessment was done at 4, 6, 9 and 12 months from the start of the treatment. Outcome measures were the proportion of patients needing full-dose prednisolone and the Semmes-Weinstein sum scores. Each patient contributed only one nerve to the analysis. Seventy-five patients had nerves eligible for analysis, of whom 41 (55%) and 34 (45%) were allocated to the prednisolone and placebo arms, respectively. At 4 months, three patients in the prednisolone arm (7%) and six in the placebo arm (18%) had an outcome event requiring full dose steroids. At 12 months, these proportions had almost reversed, 11 (27%) and 6 (18%) in the treatment and placebo arms, respectively. In the latter group, 75% had recovered spontaneously after 12 months. Prednisolone treatment of sensory impairment of the ulnar and posterior tibial nerves detectable with the monofilament test, but not with the ballpen test, did not improve the long-term outcome in terms of recovery of touch sensibility, not did it reduce the risk of leprosy reactions or nerve function impairment beyond the initial 4-month treatment phase. Two unexpected main findings were the strong tendency of mild sensory impairment to recover spontaneously and the fact that patients with mild sensory impairment without any other signs or symptoms of reaction or nerve function impairment are relatively rare.

Treatment with corticosteroids of long-standing nerve function impairment in leprosy: a randomized controlled trial (TRIPOD 3).

Some leprosy patients with long-standing nerve function impairment (NFI) appear to have responded favourably to treatment with corticosteroids. This study investigated whether patients with untreated NFI between 6 and 24 months duration and who are given standard regimen corticosteroid therapy, will have a better treatment outcome than a placebo group. A multicentre, randomized, double-blind placebo-controlled trial was conducted in Nepal and Bangladesh. Subjects were randomised to either prednisolone treatment starting at 40 mg/day, tapered by 5 mg every 2 weeks, and completed after 16 weeks, or placebo. Outcome assessments were at 4, 6, 9, and 12 months from the start of treatment. 92 MB patients on MDT were recruited, of whom 40 (45%) received prednisolone and 52 (55%) placebo treatment. No demonstrable additional improvement in nerve function, or in preventing further leprosy reaction events was seen in the prednisolone group. Overall, improvement of nerve function at 12 months was seen in about 50% of patients in both groups. Analysis of subgroups according to nerve (ulnar and posterior tibial), duration of NFI, and sensory and motor function, also did not reveal any differences between the treatment and placebo groups. There was however, indication of less deterioration of nerve function in the prednisolone group. Finally, there was no difference in the occurrence of adverse events between both groups. The trial confirms current practice not to treat long-standing NFI with prednisolone. Spontaneous recovery of nerve function appears to be a common phenomenon in leprosy. Leprosy reactions and new NFI occurred in a third of the study group, emphasizing the need to keep patients under regular surveillance during MDT, and, where possible, after completion of MDT.

Restoration of sensibility in irreparable ulnar and median nerve lesions with use of sensory nerve transfer: long-term follow-up of 20 cases.

A prospective study was conducted to evaluate patient outcomes following sensory nerve transfer. Twenty patients with irreparable ulnar or median nerve lesions underwent the procedure. Nerve involvement was bilateral in 5 cases. The mean age of the patients at the time of surgery was 29 years. The mean paralysis time and the average length of follow-up were 59 and 78 months, respectively. Eighteen of 20 patients attended a sensory re-education program after surgery. Outcome was assessed objectively by functional sensory recovery testing and by the British Medical Research Council standards. Subjective outcome was assessed by a questionnaire. Two-point discrimination of less than 10 mm was achieved in 15 of 25 hands. The mean functional sensory recovery score was 83. Eighteen of 20 patients reported that the function of their hands improved after the procedure. Good or excellent results were associated with immediate transfer of the nerve, young age, and patients' attendance to the sensory re-education program after surgery. No differences were found between the recovery of ulnar and median nerves. Based on these results we suggest that sensory nerve transfer is a simple and reliable way of restoring sensibility to the hand with favorably comparable results over conventional nerve grafting in selected cases.

Reliability of Semmes Weinstein monofilament and ballpoint sensory testing, and voluntary muscle testing in Bangladesh.

The reliability of methods of testing nerve function is important, since diagnostic decision making is a direct function of the quality of the test. Three methods of nerve function testing were investigated at the Danish Bangladesh Leprosy Mission (DBLM) in north Bangladesh, and assessed for inter-observer reliability. The three methods were 1) ballpoint pen test (BPT) for sensory function; 2) graded Semmes Weinstein monofilament test (SWM) for sensory function and 3) voluntary muscle testing (VMT) for motor function. The weighted kappa (kappa w) statistic was used to express inter-observer reliability. Using this statistic, 0 represents agreement no better than random, and 1.0 complete agreement. kappa w values of > or = 0.80 are reckoned to be adequate for monitoring and research. Fifty-three patients were tested, a Senior physiotechnician acting as 'gold standard' against whom four other staff physiotechnicians were assessed. All three testing methods were found to have minimal inter-observer variation, with the kappa w for inter-observer agreement using BPT being 0.86, the SWM 0.92, and VMT 0.94. It is concluded that in trained and experienced hands, all three methods are reliable and repeatable to a level allowing confident use of results obtained in monitoring and research.

Clinical and electrophysiological evaluation of nerve function impairment following cessation of multidrug therapy in leprosy.

Seventeen multibacillary (MB) and 15 paucibacillary (PB) cases of leprosy who had had regular and adequate multidrug therapy (MDT) were examined clinically and electrophysiologically at periodic intervals for 1 year following cessation of MDT. All the major nerves were assessed for nerve function impairment (NFI). Overall, two MB (13.3%) and three PB (20%) cases showed signs of deterioration clinically and/or electrophysiologically. The nerve conduction (NC) follow-up studies revealed no significant improvement in the sensory conduction in both the MB and PB groups of nerves, whilst motor conduction showed a significant improvement at the first 6-monthly follow-up among the MB group of nerves. At the study onset, sensory impairment (MB = 62%, PB = 25%) predominated over motor in terms of both severity and frequency. The lower extremity was more frequently and severely affected than the upper in both groups of patients. As an individual test, NC measurement proved to be more sensitive in detecting NFI, but the combination of physical palpatation for nerve thickening and graded nylon test (GNT) was closely comparable to measurement of nerve conduction.

Cytodiagnosis of primary neuritic leprosy.

The diagnosis of primary neuritic leprosy (PNL) and its differentiation from other causes of peripheral neuropathy is difficult since acid-fast bacilli (AFB) smears and skin biopsy are negative from anesthetic areas. A biopsy of the involved nerve is the only conclusive method of diagnosis. Such a biopsy may not necessarily be free of complications when a large nerve is involved. However, fine needle aspiration has in this study proved to be a simple technique to demonstrate inflammation granulomas and AFB from these involved nerves in 18 of the 27 cases suspected to have PNL. The validity of the cytological classification into morphological subtypes may have to be supplemented by a large series of studies.

A field trial of detection and treatment of nerve function impairment in leprosy--report from national POD pilot project.

As part of a collaborative project between the Ministry of Health of China (MOH) and The Leprosy Mission International (TLMI) on leprosy rehabilitation and prevention of disability (POD), a total of 1407 patients was monitored for possible nerve function impairment (NFI) through standardized clinical nerve function assessment between May 1995 and February 1998. Of these, 191 patients were found to have NFI and were put on a fixed regimen of prednisolone. In this study, 36.7% of NFI occurred before diagnosis of leprosy, 35.6% developed during MDT and 25.7% after their release from MDT. Overall, 7.5% (105 out of 1407) of all patients, or 55.9% of patients with NFI, suffered from silent neuropathy. Of the affected nerves, 62.6% had silent neuropathy. Sensory impairment responded to prednisolone satisfactorily, giving a recovery rate of 73.8%, 76.5% and 81.0% in ulnar, median and posterior tibial nerve, respectively. Sensibility in patients even with a NFI duration longer than 6 months made significant improvement (p < 0.05). Motor function improvement was less satisfactory, especially in ulnar and c. popliteal nerve. The possible reasons are analysed. Our findings with regard to sensibility changes confirm that once it becomes clinically detectable, NFI is no longer at the 'early' stage. More sensitive tests are necessary to detect real 'early' sensory impairment in the field. Our study also indicates that with well-trained field staff and proper equipment for nerve function assessment, early detection and treatment of NFI can be practical and effective.

A study of pure neuritic leprosy: clinical experience.

Pure neuritic leprosy is a well-recognized clinical entity. Manifestations of leprosy in pure neuritic form accounted for 179 patients out of the total 3853 leprosy patients (4.6%) attending our Poona Urban Leprosy Investigation Centre clinics. Patients with pure neuritic leprosy are prone to develop nerve damage. Eight-seven (48.6%) of our pure neuritic patients presented with deformities. Involvement of upper extremity and right ulnar nerve in particular was the most common clinical feature. Patients presenting with involvement of two nerves of the same extremity was also quite common. None of our patients developed skin lesions while on anti-leprosy treatment. It is important to recognize neuritic symptoms early and suspect leprosy even in the absence of skin lesions.

Sympathetic vasomotor dysfunction in leprosy patients: comparison with electrophysiological measurement and qualitative sensation testing.

Testing of skin vasomotor reflexes (VRs) by laser Doppler flowmetry (LDF) is now a recognised method of measuring peripheral dysautonomia. To assess its specificity as an indicator of impairment to unmyelinated autonomic fibres, VR testing at the fingerpulp was compared with standard qualitative sensation (QST) and with sensory electrophysiological (SNVC) measurements in 39 Iranian leprosy patients. There was a significant relationship between VR and SNCV values (but not QST): these were jointly measurable in 38.5% of fingers, and jointly absent in 35.3% of fingers which also showed significantly reduced LDF perfusion and skin temperatures. However, in 10.3% of fingers, predominantly index and otherwise apparently healthy, VRs were absent but SNCV present, suggesting early sub-clinical autonomic impairment. In a further 16% of fingers, predominantly ulnar and with poor microcirculation, intact (though impaired) VRs could be recorded despite the absence of SNCV responses, suggesting sparing or regeneration of these fibres. This evidence suggests that where there is heterogeneity of nerve damage a combination of VR and electrophysiological testing can indicate the functional status of distinct fibre types.

Ocular manifestations of Hansen's disease.

A detailed ophthalmic evaluation including slitlamp biomicroscopy, measurement of corneal sensitivity using Cochet and Bonnet aesthesiometer, Schirmer's test and Goldmann applanation tonometry was carried out in 89 patients of Hansen's disease attending the leprosy clinic with or without ocular symptoms and willing to undergo eye evaluation. Thirty-one patients had lepromatous leprosy (8 with erythema nodosum leprosum), 56 patients had borderline disease (13 with reversal reactions) and 2 had tuberculoid disease. In addition to the well documented changes of lagophthalmos (6.7%), uveitis (7.3%) and cataracts (19%), we noted prominent corneal nerves in 133 eyes (74.7%), beaded corneal nerves in 19 eyes (10.7%), corneal scarring in 10 eyes (5.6%), corneal hypoaesthesia in 51 eyes (28%) and dry eye in 18 eyes (13%). Beaded corneal nerves and/or stomal infiltrates occurred mainly in the lepromatous group (75%). Ocular hypotony (IOP less than 12 mm Hg) was not seen more frequently in Hansen's as compared to age and sex matched controls with refractive errors or cataracts (33.7%, vs. 37.8%, p = 0.33). Our study highlights the primary corneal involvement with corneal neuropathy as the predominant feature of Hansen's disease.