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

Nerve damage in leprosy and its management

10.1038/ncpneuro0941Nature Clinical Practice Neurology412656-66

Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy.

Sensory peripheral neuropathy caused by paclitaxel is a common and dose limiting toxicity, for which there are currently no validated predictive biomarkers. We investigated the relationship between the Charcot-Marie-Tooth protein NDRG1 and paclitaxel-induced neuropathy.Archived mammary tissue specimen blocks of breast cancer patients who received weekly paclitaxel in a single centre were retrieved and NDRG1 immunohistochemistry was performed on normal nerve tissue found within the sample. The mean nerve NDRG1 score was defined by an algorithm based on intensity of staining and percentage of stained nerve bundles. NDRG1 scores were correlated with paclitaxel induced neuropathy.111 patients were studied. 17 of 111 (15%) developed severe paclitaxel-induced neuropathy. The mean nerve NDRG1 expression score was 5.4 in patients with severe neuropathy versus 7.7 in those without severe neuropathy (p = 0.0019). A Receiver operating characteristic (ROC) curve analysis of the mean nerve NDRG1 score revealed an area under the curve of 0.74 (p = 0.0013) for the identification of severe neuropathy, with a score of 7 being most discriminative. 13/54 (24%) subjects with an NDRG1 score 7 (p = 0.017).Low NDRG1 expression in nerve tissue present within samples of surgical resection may identify subjects at risk for severe paclitaxel-induced neuropathy. Since nerve biopsies are not routinely feasible for patients undergoing chemotherapy for early breast cancer, this promising biomarker strategy is compatible with current clinical workflow

Feature selection via sensitivity analysis of SVM probabilistic outputs

10.1007/s10994-007-5025-7Machine Learning7011-2

Diagnosing carpal tunnel syndrome - Clinical criteria and ancillary tests

10.1038/ncpneuro0216Nature Clinical Practice Neurology27366-37

NDRG1 Analyses.

<p>2A. Correlation of NDRG1 scores between investigator 1 and investigator. 2B. Mean NDRG1 expression scores in nerve tissue in subjects who did or did not develop paclitaxel-induced severe neuropathy. 2C. ROC analysis of predictive validity of NDRG1 for paclitaxel-induced severe neuropathy.</p

NDRG1 expression in normal nerve tissue.

<p>Photo micrographs (x 40 objective) depicting NDRG1 IHC, scale bar is 50μm. A: Score 0: Nerve highlighted by circles, with no expression of NDRG1. B: Score 1: Minimal expression of NDRG1 in less than 50% of the nerve bundle. C: Score 2: Strong expression of NDRG1 in less than 50% of the nerve bundle. D: Score 3: Strong expression of NDRG1 in more than 50% of the nerve bundle</p