Early detection of neuropathy in leprosy: a comparison of five tests for field settings.

BACKGROUND: Early detection and treatment of neuropathy in leprosy is important to prevent disabilities. A recent study showed that the Nerve Conduction Studies (NCS) and Warm Detection Thresholds (WDT) tests can detect leprosy neuropathy the earliest. These two tests are not practical under field conditions, however, because they require climate-controlled rooms and highly trained staff and are expensive. We assessed the usefulness of alternative test methods and their sensitivity and specificity to detect neuropathy at an early stage. METHODS: Through a literature search we identified five alternative devices that appeared user-friendly, more affordable, portable and/or battery-operated: the Neuropad®, Vibratip™, NC-Stat®DPNCheck™, NeuroQuick and the Thermal Sensibility Tester (TST), assessing respectively sweat function, vibration sensation, nerve conduction, cold sensation and warm sensation. In leprosy patients in Bangladesh, the posterior tibial and sural nerves that tested normal for the monofilament test and voluntary muscle test were assessed with the NCS and WDT as reference standard tests. The alternative devices were then tested on 94 nerves with abnormal WDT and/or NCS results and on 94 unaffected nerves. Sensitivity and specificity were the main outcomes. RESULTS: The NeuroQuick and the TST showed very good sensitivity and specificity. On the sural nerve, the NeuroQuick had both a sensitivity and a specificity of 86%. The TST had a sensitivity of 83% and a specificity of 82%. Both the NC-Stat®DPNCheck™ and Vibratip™ had a high specificity (88% and 100%), but a low sensitivity (16% and 0%). On the posterior tibial nerve, the NeuroQuick and the TST also showed good sensitivity, but the sensitivity was lower than for the sural nerve. The Neuropad® had a sensitivity of 56% and a specificity of 61%. CONCLUSIONS: The NeuroQuick and TST are good candidates for further field-testing for reliability and reproducibility. The feasibility of production on a larger scale should be examined.

Correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy.

BACKGROUND: In leprosy, sensory function of nerves is evaluated with monofilaments test and the motor function with voluntary muscle test, however electroneuromyography is considered as the gold-standard tool. OBJECTIVES: This study aimed: i) to evaluate the correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy; and ii) to identify the prevalence of leprosy neuropathy and the most compromised peripheral nerves in leprosy. METHODS: We analysed the data from a nested case-control study that identified 166 patients diagnosed with leprosy neuropathy confirmed by electromyography. This study was designed for an analysis of correlation between the diagnostic tests. RESULTS: The most prevalent type of the neural damage was the sensory and motor multiple mononeuropathy, observed in 62 (37.3%) cases. The highest prevalence was the ulnar nerve in 67 (40.3%) cases. Agreement specified by nerves was moderate, ranging from k = 0.58 in the deep peroneal nerve to k = 0.41 in the posterior tibial nerve). Overall agreement between the clinical tests and electroneuromyography was very poor. Monofilaments test with k = 0.02 (95% CI 0.00-0.12) and voluntary muscle test with 0.16 (95% CI 0.04 to 0.28, P = 0.01). CONCLUSIONS: There is a low to moderate correlation between clinical tests (monofilaments and voluntary muscle tests) and the electroneuromyography examination. The most prevalent type of neural impairment was the sensory and motor multiple mononeuropathy, and the most affected nerve was the ulnar.

Prevalence of leprous neuropathy determined by neurosensory testing in an endemic zone in Ecuador: Development of an algorithm to identify patients benefiting from early neurolysis.

The success of a microneurosurgical intervention in leprous neuropathy (LN) depends on the diagnosis of chronic compression before irreversible paralysis and digital loss occurs. In order to determine the effectiveness of a different approach for early identification of LN, neurosensory testing with the Pressure-Specified Sensory Device™ (PSSD), a validated and sensitive test, was performed in an endemic zone for leprosy. A cross-sectional study was conducted to analyze a patient sample meeting the World Health Organization (WHO) criteria for Hansen's disease. The prevalence of LN was based on the presence of ≥1 abnormal PSSD pressure threshold for a two-point static touch. A total of 312 upper and lower extremity nerves were evaluated in 39 patients. The PSSD found a 97.4% prevalence of LN. Tinel's sign was identified in 60% of these patients. An algorithm for early identification of patients with LN was proposed using PSSD testing based on the unilateral screening of the ulnar and deep peroneal nerves.

Selecting a Test for Leprous Neuropathy Screening.

BACKGROUND: Worldwide, leprosy represents a significant cause of disability due to progressive neurological impairment. Screening for leprous neuropathy is performed with Semmes-Weinstein monofilament (SWM) or ballpoint pen testing (BPT), which results in underreporting of its prevalence. The Pressure-specified sensory device (PSSD; Sensory Management Services, LLC, Baltimore, MD) is a sensitive, noninvasive, portable, neurosensory instrument, which has not been field-tested for leprosy screening. Early identification of leprous neuropathy would permit early antibiotic treatment to prevent contagion and early microsurgical neurolysis. METHODS: A prospective, clinical diagnostic, cross-sectional study screened a consecutive sample of patients for leprous neuropathy in the leprosy-endemic province of Los Ríos, Ecuador. Patients meeting the World Health Organization criteria for leprosy and complaining of neuropathy symptoms were classified as leprous neuropathy patients. Patients without any signs of leprosy were used as normal controls. Bilateral ulnar nerve screening with the PSSD, SWM (0.07, 0.4, 2, 4, 10, and 300 g), and BPT was performed in all patients. Sensitivity and specificity were calculated and compared across tests. A total of 71 patients (142 nerves) were evaluated. RESULTS: Compared with the 10 g SWM and the BPT, the PSSD was found to have significantly higher sensitivity (78.3 vs. 0% with p < 0.001, for both) with comparable specificity (97.8 vs. 100% with p > 0.999, for both). Compared with the 0.07 g SWM (lightest filament in our series), the PSSD showed better sensitivity (78.3 vs. 65.2%, p = 0.514) and significantly higher specificity (97.8 vs. 51.1%, p < 0.001). CONCLUSIONS: The PSSD provides superior diagnostic accuracy for detecting leprous neuropathy as compared with SWM and BPT.

Comparison between Different Methods of Monofilament Test in Multibacillary Leprosy.

BACKGROUND: Leprosy or Hansen's disease predominantly affects skin and peripheral nerves; therefore, can cause visible deformities from sensory and motor impairment. Early detection of sensory deficit has been of great benefit in a vigorous preventive role. OBJECTIVE: To compare the result of sensory evaluation in multibacillary leprosy (AB) patients using Semmes-Weinstein monofilament (SWM) and conventional monofilament technique used in Thailand and to observe the course of neuritis detected during the study period MATERIAL AND METHOD: MB patients from Hansen's clinic at the Department of Dermatology, Siriraj Hospital, and Leprosy clinic at Raj Pracha Samasai Institute were evaluated for sensory impairment using monofilament test by both SWM and conventional technique for two consecutive follow-up visits. The patients'demographic data, clinical and laboratory findings, and course of disease were recorded RESULTS: Seventy MB patients were enrolled Two-third of the patients were male (71.4%) and a mean (SD) age was 43 (15.75) years with a range of 19 to 85-years-old. The results from SWM and conventional Thai technique were not statistically different for ulnar median, and posterior tibial nerve distribution excluding heel area (p = 1.00). Twenty-eight (40%) patients who mentioned of numbness at either palms or soles had impaired sensation detected by SWMtechnique (p = 0.014). CONCLUSION: Using SWMwith less tested points can minimize the time spent on sensory evaluation in MB patients; hence, we encourage the application of the present SWM technique to shorten the time in each follow-up visit and to improve the follow-up practice for better services of leprosy patients in Thailand.

Degree of skin denervation and its correlation to objective thermal sensory test in leprosy patients.

BACKGROUND: Leprosy is an infectious disease affecting skin and peripheral nerves resulting in increased morbidity and physical deformities. Early diagnosis provides opportune treatment and reduces its complications, relying fundamentally on the demonstration of impaired sensation in suggestive cutaneous lesions. The loss of tactile sensitivity in the lesions is preceded by the loss of thermal sensitivity, stressing the importance of the thermal test in the suspicious lesions approach. The gold-standard method for the assessment of thermal sensitivity is the quantitative sensory test (QST). Morphological study may be an alternative approach to access the thin nerve fibers responsible for thermal sensitivity transduction. The few studies reported in leprosy patients pointed out a rarefaction of thin dermo-epidermal fibers in lesions, but used semi-quantitative evaluation methods. METHODOLOGY/PRINCIPAL FINDINGS: This work aimed to study the correlation between the degree of thermal sensitivity impairment measured by QST and the degree of denervation in leprosy skin lesions, evaluated by immunohistochemistry anti-PGP 9.5 and morphometry. Twenty-two patients were included. There were significant differences in skin thermal thresholds among lesions and contralateral skin (cold, warm, cold induced pain and heat induced pain). The mean reduction in the density of intraepidermal and subepidermal fibers in lesions was 79.5% (SD = 19.6) and 80.8% (SD = 24.9), respectively. CONCLUSIONS/SIGNIFICANCE: We observed a good correlation between intraepidermal and subepidermal fibers deficit, but no correlation between these variables and those accounting for the degree of impairment in thermal thresholds, since the thin fibers rarefaction was homogeneously intense in all patients, regardless of the degree of sensory deficit. We believe that the homogeneously intense denervation in leprosy lesions should be objective of further investigations focused on its diagnostic applicability, particularly in selected cases with only discrete sensory impairment, patients unable to perform the sensory test and especially those with nonspecific histopathological finds.

[Silent neuropathy in patients with leprosy in the city of Fortaleza, Ceará State, Brazil]. / Neuropatia silenciosa em portadores de hanseníase na cidade de Fortaleza, Ceará, Brasil.

One of the clinical forms of Hansen's disease is silent neuropathy, which consists of progressive nerve damage in the absence of pain and hypersensitivity to palpation. This study estimated the proportion of silent neuropathy and associated factors. A cross-sectional study was performed in Fortaleza, Ceará State, Brazil. Patients were asked about the presence of decreased sensation involving touch, heat, pain, and numbness. Nerves were palpated to identify thickness, abscess, and pain. Lymph samples were drawn for parasitological tests. Strength of voluntary muscles in the feet and hands was evaluated. The sensitivity of specific points on the feet and hands was measured using Semmes-Weinstein monofilament. The sample included 233 patients. The proportion of silent neuropathy was 5.6% (95%CI: 3.0-9.4), and factors significantly associated with silent neuropathy were: age (p = 0.011) and disability (p < 0.000). These results will help identify cases of silent neuropathy, targeting patients at higher risk.

Neuropatia silenciosa em portadores de hanseníase na cidade de Fortaleza, Ceará, Brasil / Silent neuropathy in patients with leprosy in the city of Fortaleza, Ceará State, Brazil

Uma das formas da hanseníase é a neuropatia silenciosa que consiste em perda progressiva da função motora ou sensorial na ausência de dor e hipersensibilidade dos nervos. Realizou-se um estudo transversal em Fortaleza, Ceará, Brasil, o qual estimou a proporção de neuropatia silenciosa e fatores associados. O paciente foi interrogado sobre a presença de dor, dormência, alteração da sensibilidade, e foi realizada palpação de nervos para identificar espessamento, abscesso e dor. Amostras de linfa foram obtidas para exames parasitológicos. Foi medida a força de músculos voluntários dos membros e a sensibilidade de pontos das mãos e dos pés por meio de monofilamentos de Semmes-Weinstein. De uma amostra de 233 portadores de hanseníase, a proporção de pacientes com neuropatia silenciosa foi 5,6 por cento (IC95 por cento: 3,0-9,4), e a ocorrência de neuropatia silenciosa esteve significativamente associada à idade (p = 0,011) e à incapacidade (p < 0,000). Esses resultados poderão ajudar a identificar casos de neuropatia silenciosa, focalizando pacientes com maior probabilidade de desenvolver a doença.

One of the clinical forms of Hansen's disease is silent neuropathy, which consists of progressive nerve damage in the absence of pain and hypersensitivity to palpation. This study estimated the proportion of silent neuropathy and associated factors. A cross-sectional study was performed in Fortaleza, Ceará State, Brazil. Patients were asked about the presence of decreased sensation involving touch, heat, pain, and numbness. Nerves were palpated to identify thickness, abscess, and pain. Lymph samples were drawn for parasitological tests. Strength of voluntary muscles in the feet and hands was evaluated. The sensitivity of specific points on the feet and hands was measured using Semmes-Weinstein monofilament. The sample included 233 patients. The proportion of silent neuropathy was 5.6 percent (95 percentCI: 3.0-9.4), and factors significantly associated with silent neuropathy were: age (p = 0.011) and disability (p < 0.000). These results will help identify cases of silent neuropathy, targeting patients at higher risk.

The effect of corticosteroids usage on bacterial killing, clearance and nerve damage in leprosy; part 3--Study of two comparable groups of 100 multibacillary (MB) patients each, treated with MDT + steroids vs. MDT alone, assessed at 6 months post-release from 12 months MDT.

OBJECTIVE: To investigate effects of therapeutic usage of corticosteroids on M. leprae killing and clearance, on clearance of granuloma and on nerve damage in multibacillary (MB) leprosy patients. DESIGN: From a cohort of 400 untreated MB patients, a comparable group of 100 each receiving MDT + steroids (group A) vs MDT alone (group B) were assessed at 18 months as compared to month zero with respect to clinical and granuloma regression, M. leprae killing and clearance, and nerve functions. Analysis was performed using SPSS version 10.0. The significance of association was tested using Chi square and Fisher's exact tests. RESULTS: Regression of lesions assessed clinically and by histopathology was seen in 52% and 53% patients in group A and 46% and 63% in B respectively (P not significant). Clearance of bacteria assessed by bacteriological index (BI) in slit skin smears (SSS) and extent and intensity of antigen using anti-BCG staining were also comparable in the two groups. Multiplication of M. leprae in the mouse foot pad (MFP) indicating the presence of viable bacilli was seen in 14% and 16% of SSS positive BL-LLs patients in groups A and B respectively (P not significant). The occurrence of viable M. leprae was higher among patients with repeat reaction (19%) than single (11%). Using clinical tests (nerve palpation, monofilament and voluntary muscle testing), the proportion of sensory and motor nerves showing improvement or deterioration were similar in the two groups. However using nerve conduction studies, the overall proportion of nerves showing deterioration (22%) was significantly higher than improvement (9%) (P < 0.001). CONCLUSIONS: Treatment with MDT + corticosteroids does not adversely affect the clearance of granuloma, M. leprae and/or its antigens and M. leprae killing. However the continued presence of viable bacteria in > 14% of BL-LLs patients indicate that 12 months of MDT may be insufficient for complete bacterial killing. In both groups nerve conduction studies indicated that deterioration of nerves was high suggesting, MDT + corticosteroids was not very efficacious in the prevention or reversal of nerve damage. A better immuno-modulatory drug or a modified corticosteroid regime is needed.

Sensitivity and specificity of nerve palpation, monofilament testing and voluntary muscle testing in detecting peripheral nerve abnormality, using nerve conduction studies as gold standard; a study in 357 patients.

OBJECTIVE: To determine sensitivity and specificity of clinical tools viz. nerve palpation (NP), monofilament (MF), and voluntary muscle testing (VMT), for assessing peripheral nerve function impairment (NFI) in leprosy, using nerve conduction studies (NCS) as gold standard. STUDY POPULATION AND METHODS: 357 untreated multibacillary (MB) leprosy patients were assessed using above tests. The nerves assessed were left and right ulnar, median, radial cutaneous, sural, common peroneal and posterior tibial. The concordance between the clinical and NCS tests was done for each nerve. The sensitivity and specificity of clinical tests for detecting nerve impairment was determined, using NCS as gold standard. Analysis was performed using SPSS version 10.0. RESULTS: The sensitivity of NP ranged between 71% to 88% for all nerves, except the median (43%) and sural (59%) nerves. Specificity was > 60% for all, but low for ulnar (34%) and common peroneal (40%) nerves. The specificity of MF testing was > 80% and of VMT assessment was >90% for all nerves. The sensitivity of MF testing ranged between 35-44%, while of VMT assessment was very low i.e. 4-5%, the maximum was for the ulnar nerve (25%). Detection sensitivity of MF testing and VMT assessment improved two fold when combined with NP and was closely comparable to NCS test findings. CONCLUSIONS: Both MF testing and VMT assessment showed good specificity, but moderate to low sensitivity. NP was less specific but more sensitive than MF testing and VMT assessment. Combining NP with MF testing and VMT assessment gives a two fold improvement in the sensitivity for assessing nerve damage and could therefore serve as the most useful clinical tools for diagnosis of leprosy and detecting nerve damage at field level.

Evaluation of simplified tests for the diagnosis of nerve function impairment in leprosy: the Sensory Motor Screening (SMS) study.

OBJECTIVE: Rapid and simple tests for diagnosing nerve function impairment (NFI) in leprosy are required in integrated settings. We examined whether simplified tests performed by newly trained general health workers (GHWs) have comparable diagnostic accuracy to the reference test conducted by experienced physiotherapists. DESIGN: This multi-centre study from India and Bangladesh evaluated three simplified tests named: ILEP Learning Guide Two (M2), Indian dance (M3), and a questionnaire (M4) in 408 people affected by leprosy. Sensitivity (Se) and specificity (Sp) of the three tests were calculated using the full assessment (M1) as reference. Se and Sp were calculated at both whole body and individual nerve levels: whether any NFI and if single NFI (voluntary muscle testing of lid gap, eye closure, little finger out, thumb up and foot up, sensory testing of hands and of feet) was present. RESULTS: M2 had 83% Se and 69% Sp, M3 had 76% Se and 84% Sp and M4 had 85% Se and 46% Sp in diagnosing any NFI. At the level of single NFI, M2 was most or similarly accurate in diagnosing single NFIs with highest prevalence (ST feet, ST hands, little finger out, thumb up), compared to M3 and M4. CONCLUSIONS: ILEP Learning Guide Two (M2) and Indian dance (M3) were found to be the most accurate simplified tests for diagnosing the presence of NFI compared to the reference. M2 was the most useful test, because of greatest accuracy for most of the common types of NFI and inclusion of sensory testing of the hands. M2 is considered to be a useful tool in the hands of GHWs with time constraints in integrated settings.

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.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Comparative study of the cutaneous sensation of leprosy-suspected lesions using Semmes-Weinstein monofilaments and quantitative thermal testing.

The objective of the present study was to compare the warm cold perception thresholds (WPT), cold perception thresholds (CPT) and the warm and cold perception interval (WCPI) determined in our previous study with the touch-pressure thresholds, in leprosy-suspected skin lesions ('patch'). Thermal testing was conducted using a thermal sensory analyser TSA-2001 (Medoc Ltd., Israel) and the method of levels. The touch-pressure thresholds were measured using Semmes-Weinstein monofilament (SWM) of 0-05 g, 0.2 g, 2 g, 4 g, 10 g and 300 g. A cross-sectional study of 112 patients presenting with leprosy-suspected skin lesions, with no clinical evidence of peripheral nerve damage, was conducted. Leprosy diagnoses were based on clinical dermato-neurological examinations. One-hundred-and-eight subjects (45 males, 63 females; average age 37.7 years) completed the tests: 82 were positively diagnosed with leprosy and 26 with diseases of different aetiologies. The SWM test showed a sensitivity of 81.7% and a specificity of 96.1%, while the warm and cold perception thresholds presented sensitivity of 90.2% and 92-2%, respectively (both with 100% specificity). In leprosy patients, lesions that exhibited pressure thresholds of 0.05 g typically showed significantly different WPT, CPT and WCPI values when compared with skin lesions of different aetiologies. Within the leprosy group, the mean values of WPT, CPT and WCPI increased according to the increase in touch-pressure thresholds. Some of the patients exhibiting leprosy lesions with touch-pressure thresholds of 0-05 and 0-2 g presented normal WPT or CPT values. However, all patients with SWM equal or above 2.0 g presented altered WPT and CPT. All patients with leprosy, including those that exhibited pressure thresholds of 0.05 g, presented altered WCPI in the skin lesions. Despite a higher sensitivity to thermal tests, the SWM has adequate validity as a screening tool in the diagnosis of cutaneous forms of leprosy and in the selection of patients who should be submitted to a more detailed examination.

Impaired warm and cold perception thresholds in leprosy skin lesions.

The aim of the present study was to determine the frequency of alteration in warm perception thresholds (WPT), cold perception thresholds (CPT) and the warm and cold perception interval (WCPI) in leprosy-suspected skin lesions, and to determine if these tests could assist in the diagnosis of leprosy. Tests were conducted using a thermal sensory analyser TSA-2001 (Medoc Ltd, Israel) and the method of levels. A cross-sectional study of 112 patients presenting leprosy-suspected skin lesions ('patch'), with no clinical evidence of peripheral nerve damage, was conducted. Leprosy diagnosis was based on clinical dermato-neurological examinations and complementary tests. One hundred and eight subjects (45 males, 63 females; average age 37.7 years) completed the tests: 82 were positively diagnosed with leprosy and 26 with diseases of different etiologies. The mean values of WPT (45-63 +/- 5.59), CPT (9.64 +/- 11.34) and WCPI 36.01 +/- 15.58) registered in leprosy-skin lesions were significantly different (P < 0.001) from lesions of diverse aetiologies and skin area without lesions. The cut-off point for WPT as determined from the ROC curve (receiver operating characteristic) was 35-10 degrees C, with a sensitivity of 90.2% and a specificity of 100%, and the corresponding cut-off point for CPT was 28.95 degrees C, with a sensitivity of 92.7% and a specificity of 100%. Nevertheless, all patients with leprosy presented a WCPI greater than 6.10 degrees C (ROC curve) in skin lesions. Increase in the thermal thresholds indicated warm hypoaesthesia, cold hypoaesthesia or both. The WCPI, which embraces both warm and cold perception thresholds, was the best indicator of thermal sensation, a term used in literature as a non-specific expression that does not describe warm and cold stimuli explicitly in terms of units of temperature.

Ensuring inter-tester reliability of voluntary muscle and monofilament sensory testing in the INFIR Cohort Study.

OBJECTIVE: To assess the reliability of monofilament (MF) and voluntary muscle strength (VMT) testing carried out by nine physiotherapy staff recruited for the ILEP Nerve Function Impairment & Reaction (INFIR) Cohort Study in India. DESIGN: A multiple pair inter-tester reliability study was carried out in Uttar Pradesh, India. Newly trained testers were paired up with an experienced physiotherapist, whose assessment served as the gold standard. Each pair completed a series of assessments. All testers had undertaken a week of specific VMT and MF training, followed by a month of practice in the hospital setting. Reliability was assessed by calculating weighted Kappa (Kw) statistics, which may be interpreted as the chance-corrected proportion of agreement between testers. RESULTS: Eight newly-trained physiotherapists and one physiotechnician took part in the study. In the early stages of the study some areas of weak agreement were identified and correct assessment technique was reviewed, particularly for the eye. Good to very good reliability (Kw 0.62 to 0.99) was found for all sensory tests and most muscle strength tests. The only lower Kw scores (0-48 to 0-59, suggesting only moderate reliability) were for the VMT of muscles supplied by the median nerve in one of the study's two field centres. Even in this case, testers never varied by more than one grade, but calculation of Kw was negatively influenced by a lack of variation among the subjects. In addition, testers never varied by more than one grade from the gold standard. CONCLUSION: Even though all testers were professionally trained and received additional specific training and practice in MF and VMT testing, discrepancies in technique required an early review and correction. This fact highlights the need for careful training and formal reliability testing. This should extend to referral centres where staff are involved in assessing the symptoms of reaction and monitoring response to treatment. Reliability testing provides the opportunity to address important discrepancies in technique that may persist even in the presence of protocols and qualified and trained staff. It is therefore a valuable tool as part of a training procedure for situations, where patients may be assessed by different testers. Overall, our results were deemed good enough to proceed with the INFIR study, using VMT and MF testing as a baseline against which to compare more sophisticated methods of nerve function testing.

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

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