Dataset Information

Early diagnosis of neuropathy in leprosy--comparing diagnostic tests in a large prospective study (the INFIR cohort study).

ABSTRACT:

Background

Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest.

Methods and findings

One hundred and eighty-eight multibacillary (MB) leprosy patients were selected from a cohort of 303 and followed for 2 years after diagnosis. Nerve function was evaluated at each visit using nerve conduction (NC), quantitative thermal sensory testing and vibrometry, dynamometry, monofilament testing (MFT), and voluntary muscle testing (VMT). Study outcomes were sensory and motor impairment detected by MFT or VMT. Seventy-four of 188 patients (39%) had a reaction, neuritis, or new nerve function impairment (NFI) event during a 2-year follow-up. Sub-clinical neuropathy was extensive (20%-50%), even in patients who did not develop an outcome event. Sensory nerve action potential (SNAP) amplitudes, compound motor action potential (CMAP) velocities, and warm detection thresholds (WDT) were most frequently affected, with SNAP impairment frequencies ranging from 30% (median) to 69% (sural). Velocity was impaired in up to 43% of motor nerves. WDTs were more frequently affected than cold detection thresholds (29% versus 13%, ulnar nerve). Impairment of SNC and warm perception often preceded deterioration in MF or VMT scores by 12 weeks or more.

Conclusions

A large proportion of leprosy patients have subclinical neuropathy that was not evident when only MFT and VMT were used. SNC was the most frequently and earliest affected test, closely followed by WDT. They are promising tests for improving early detection of neuropathy, as they often became abnormal 12 weeks or more before an abnormal monofilament test. Changes in MFT and VMT score mirrored changes in neurophysiology, confirming their validity as screening tests.

SUBMITTER: van Brakel WH

PROVIDER: S-EPMC2270341 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Publications

Early diagnosis of neuropathy in leprosy--comparing diagnostic tests in a large prospective study (the INFIR cohort study).

van Brakel Wim H WH Nicholls Peter G PG Wilder-Smith Einar P EP Das Loretta L Barkataki Pramila P Lockwood Diana N J DN

PLoS neglected tropical diseases 20080402 4

<h4>Background</h4>Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest.<h4>Methods and findings</h4>One hundred and eighty-eight multibacillary (MB) leprosy patients were selected from a cohort of 303 and f ...[more]

PMID: 18382604

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Project description:BackgroundPrevious studies have shown that leprosy multi-drug therapy (MDT) does not stop the progression of nerve function impairment. There are no prospective studies investigating the evolution of nerve anatomic abnormalities after treatment. We examined leprosy patients aiming to investigate the evolution of nerve ultrasonography (US) abnormalities and the risk factors for poor outcomes after MDT.Methodology/principal findingsWe performed bilateral US of the ulnar (U), median (M) and common fibular (CF) nerves in 9 paucibacillary (PB) and 64 multibacillary (MB) patients before and after MDT. Forty-two patients had leprosy reactions (type 1, type 2, acute neuritis) during the study. We analyzed nerve maximum cross-sectional areas (CSA), echogenicity and Doppler signal. Poor outcomes included a post-treatment CSA above normal limits with a reduction of less than 30% (U, M) or 40% (CF) from the baseline, echogenicity abnormalities or intraneural Doppler in the post-treatment study. We found that PB and patients without reactions showed significant increases in CSA at CF, whereas MB and patients with reactions had CSA reduction in some nerves after treatment (p<0.05). Despite this reduction, we observed a greater frequency of poor CSA outcomes in the MB compared to the PB (77.8% and 40.6%; p>0.05) and in the patients with reactions compared to those without (66.7% and 38.7%; p<0.05). There was significantly higher odds ratio (7.75; 95%CI: 1.56-38.45) for poor CSA outcomes only for M nerve in patients with reactions. Poor echogenicity outcomes were more frequent in MB (59.4%) compared to PB (22.2%) (p<0.05). There was significant association between poor Doppler outcomes and neuritis. Gender, disease duration, and leprosy classification were not significant risk factors for poor outcomes in CSA, echogenicity or Doppler.Conclusions/significanceUS nerve abnormalities can worsen after treatment despite the leprosy classification or the presence of reactions.

Project description:BackgroundThe ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.Methodology/principal findingsThree hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.Conclusions/significanceLeprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.

Project description:BackgroundEarly 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.MethodsThrough 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.ResultsThe 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%.ConclusionsThe 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.

Dataset Information

Early diagnosis of neuropathy in leprosy--comparing diagnostic tests in a large prospective study (the INFIR cohort study).

Background

Methods and findings

Conclusions

Publications

Early diagnosis of neuropathy in leprosy--comparing diagnostic tests in a large prospective study (the INFIR cohort study).

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