Early Diagnosis of Neuropathy in Leprosy—Comparing Diagnostic Tests in a Large Prospective Study (the INFIR Cohort Study)

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. Author Summary: Leprosy is the most frequent treatable disease of the peripheral nerves. Yet, every year, thousands of patients develop nerve damage as a result of leprosy. If this is detected and treated early, the prognosis is good. We conducted the largest prospective study on this topic to date to determine which test would detect nerve damage earliest. One hundred and eighty-eight leprosy patients were selected from centres in North India and followed for 2 years after diagnosis. Nerve function was tested at each visit using a battery of nerve function tests. A large proportion of the patients had or developed subclinical nerve damage that was not detected with the standard clinical tests (monofilaments and voluntary muscle testing). Sensory nerve conduction was the most frequently and earliest affected test, closely followed by the warm temperature perception test. They are promising tests for improving early detection of nerve damage, as they often became abnormal 12 weeks or more before the monofilament test became abnormal. Changes measured with the monofilament and voluntary muscle tests mirrored changes in more advanced electronic measures, confirming their validity as screening tests. These findings open the door to future improvement of the prognosis of nerve damage in leprosy.