Treatment of Peripheral Neuropathy in Leprosy: The Case for Nerve Decompression.

Leprosy (Hansen’s disease) is an ancient disease that continues to impose a significant societal burden and is still relevant to peripheral nerve and plastic surgery.1,2 At least 213,899 new cases globally were last reported,3 and currently, more than 4 million people worldwide experience disabilities due to Hansen’s disease.4 In the United States, leprosy continues to exist, with 175 new cases in 2014 and a prevalence of 293 as of today.3 Physical disabilities resulting from Hansen’s disease include paresthesias, muscle paralysis (eg, lagophthalmos, foot drop, and claw hands), ulcers, and amputations. Before the late 1940s, the cause of paralysis among patients with Hansen’s disease was unclear. A major advancement occurred when the late leprologist and hand surgeon Paul Brand (1914–2003) observed that the Hansen’s bacilli, Mycobacterium leprae, preferentially targeted peripheral nerves; he saw that abnormal “nerve swellings” occurred at specific locations “where the nerve lay close to the skin surface:” “[the tibial nerve] behind the ankle, [the peroneal nerve] just above the knee, […the median and ulnar nerves] at the wrist, […the facial nerve] at the chin and cheekbone, and […the ulnar nerve] just above the elbow.”5 Brand witnessed the cause of leprous neuropathy. Since Brand’s observations in the late 1940s and the introduction of multidrug therapy in 1981, more attention has gradually been placed on understanding, preventing, and treating nerve damage as the source of the disabilities and deformities, and therefore as the root of the stigma associated with Hansen’s disease.6,7 In 1975, Antia et al.8 demonstrated that even clinically uninvolved nerves, such as the superficial branch of the radial nerve, could present with definite nerve damage. At the turn of the century, Ng et al.9 demonstrated that phenolic glycolipid-1 of M. leprae binds specifically to laminin-2 (see Supplementary Digital Content 1, which displays structure of the C-terminal laminin G-like domains 4 and 5 of the laminin alpha-2 chain; http://links.lww.com/PRSGO/A179) within the basal lamina of Schwann cell-axon units, promoting bacterial invasion and, even after bacterial cell death, damage to Schwann cells and nerves. Around the same time, Scollard et al.10 observed that M. leprae extensively colonized epi- and endoneural blood and lymphatic vasculature as well. In 2010, Teles et al.11 found that M. leprae can also bind mannose receptors on Schwann cells via lipoarabinomannan, which, as Bahia El Idrissi et al.12 recently demonstrated, can also activate complement and promote inflammation. Molecular studies in 2007 revealed that M. leprae has a defective heat stress response that restricts the bacterium to superficial and cooler regions of the body, such as the peripheral nerves.13 Taken together, the evidence seems to support that after bacterial colonization of superficial peripheral nerves via phenolic glycolipid-1 and/or lipoarabinomannan, and/or after immunologic reactions, the nerve is more likely to suffer ischemia from “inflammation, trauma, or mechanical stress [such nerve compression at tunnels and near the joints],”10 contributing to the development of neuropathy.14,15 Despite arising from different mechanisms, nerve compression among diabetics may help us understand the treatment of leprous neuropathy. In diabetics, nerve compression results from narrow anatomic sites, such as tunnels, placing increased external pressure on peripheral nerves predisposed by the diabetes to increased water retention and therefore swelling.16–18 The resulting compression causes ischemia of the nerve and paresthesias, 2 aspects that diabetic and leprous neuropathies have in common. Surgical decompression has been shown to be effective in treating diabetic neuropathy, when chronic nerve compression is present and using techniques designed to decompress each peripheral nerve at multiple sites along its pathway at known locations for anatomic narrowing.19,20 Here, we present evidence to support the use of similar nerve decompressions in the upper and lower extremities in the treatment of leprous neuropathy.