Agrawal, Amit MCh*; Joharapurkar, Sudhakar R. MS†; Pandit, Lekha DM‡; Bhake, Arvind MD§
Leprosy is one of the most common and potentially treatable causes of peripheral neuropathy. Patterns of peripheral neuropathy in leprosy can be varied and may include mononeuropathy, mononeuritis multiplex, and symmetric polyneuropathy. Cranial nerves, especially facial and trigeminal nerves, are also commonly involved in leprosy.1,2 In this article, we review the available literature relevant in the surgical management of nerve injury in leprosy and surgery.
Leprosy is primarily a disease of nerves,3 and pathologically, more than 30% of the nerve should be involved for functional impairment to be appreciated clinically.4 Highly effective antimicrobial chemotherapy is available against leprosy with excellent results and helped to control and eliminate the disease,5-7 yet leprosy continues to be a major public health problem.7 Despite the effective antibiotics to cure the infection, the immune-mediated peripheral nerve damage can continue long after effective antimicrobial treatment has started, and patients continue to be stigmatized.6 In pure neuritic form of leprosy without skin changes, there can be a distal stocking and glove distribution with thermal and pinprick anesthesia and preservation of proprioception. There is no weakness, the tendon reflexes may be preserved, and sometimes the nerves are thickened.8 There can be rare cases in which the polyneuropathy is of large fibers, with touch and proprioceptive loss,9 sensory-motor polyneuropathy,10 and with prominent autonomic disfunction.11 The differential diagnosis of pure neuritic form of leprosy (small-fiber polyneuropathy) include diabetes mellitus, amyloidosis,12 and familial amyloid polyneuropathy.8 However, in diabetes and amyloidosis, there is also an autonomic neuropathy involving bowel, bladder, and circulatory reflexes.12
DETECTION OF NERVE DAMAGE
Early detection and prompt intervention are the key in limiting nerve damage and preventing the disability.6,13 Clinically detectable sensibility changes in leprosy neuropathy suggest that the disease is no longer at the "early" stage.14 Many methods are used to detect early nerve damage in leprosy including the voluntary muscle test,15 monoflilamanet,15,16 ballpoint pen,15,17 neonatal sphygmomanometer cuff (for the early detection of motor function loss),18 and electronic device (eg, the vibrameter and electronic pressure device). An ideal test for neuropathy should be sensitive (so as to detect all cases of neuropathy), specific (so as not to detect those without neuropathy), accurate (it should reflect severity closely), reproducible, and repeatable.19 Nerve conduction studies and warm detection thresholds (WDT) measurements seem to be the most promising tests for early detection of leprous neuropathy.15 The nylon Semmes-Weinstein monofilaments accurately detect sensory loss in silent neuropathy.13,20 However, all traditional systems for evaluating peripheral nerve function including monofilaments, electrodiagnostic testing, or by observing motor palsy or digital ulcers identify only late sequelae of peripheral nerve dysfunction.21 Electronic devices are not viable options in the field, and20 more sensitive tests are necessary to detect real "early" sensory impairment in the field.14 Recently, the role of portable neurosensory system (Pressure-Specified Sensory Device) has been investigated for the detection of early as well as late nerve damage with good correlation in both upper and lower extremities.21
ROLE OF SEROLOGY
Serological tests for leprosy diagnosis have shown a certain potential for detection and identification of the host immune response against the mycobacteria.22 The availability of monoclonal antibodies against the protein and carbohydrate components of Mycobacterium leprae and the use of these antibodies in immunohistological staining techniques have permitted the detection of specific M. leprae antigens at the sites of active immunopathology.23,24 Several investigators have used polymerase chain reaction (PCR) to amplify various genomic sequences of M. leprae to improve detection when low numbers of bacteria are present. DNA probes offer a route to the more sensitive detection and identification of bacterial DNA in clinical samples.25-29 Different target sequences for PCR include the 36-kDa antigen,30 the 18-kDa antigen,31 or the 65-kDa antigen25 and the repetitive sequences.32 It would be useful to detect M. leprae DNA by PCR on regularly bacteriologically negative samples and simple and specific PCR systems for detection of small numbers of bacteria in clinical samples.33 Lockwood et al34 have demonstrated the presence of individual protein and carbohydrate M. leprae antigens (65, 35, and 28 kD and lipoarabinomannan) in type I reaction skin and nerve lesions and emphasized the importance of detection of the expression of local, rather than circulating, antigen that provokes the delayed-type hypersensitivity response in leprosy lesion. Current available serological tests show a relatively low sensitivity, which, in combination with the low prevalence of leprosy, limits their application to early case finding and detection of infection.35 The role and importance of these antigens need to be further defined by performing a longitudinal study.34
The initial management of leprous neuritis is always medical, using high doses of corticosteroids and anti-inflammatory drugs.36 Anti-inflammatory drugs and chemotherapy combined with operative decompression improve results and help to protect patients from the static and dynamic sequelae of neuritis.37 Surgery has its place only for certain indications, and the usual techniques used in peripheral nerve surgery must be applied. The affected nerves in leprosy sometimes can be very hard and stiff. The blood supply and its intraneural anastomoses must be carefully respected while performing surgery on the affected nerves.36
If medical treatment fails, nerve decompression by external neurolysis or by transposition of the ulnar nerve may be attempted but have proven to be of limited value. Surgical release of external physical compression improves circulation and helps steroids to reach the affected nerves effectively, thus minimizing the ischemic and compression damage to nerve fibers.38
ROLE OF SURGERY
At present, surgery can correct paralytic deformities, debride trophic u1cers, and drain abscesses.38-40 External, extraneural, and funicular neurolysis, transposition, and treatment of nerve abscess proved to be the methods of choice.41,42 Indications for decompressive surgery for neuritis include pain, motor, and/or sensory deficits.37 The only contraindication is painless long-standing paralysis; in this condition, the degree of neural fibrosis prevents any hope of improvement.37
NERVE DAMAGE DETECTION
Detecting and treating nerve damage early are the key to preventing deformity. Nerve damage may occur before diagnosis, during treatment, or after it.6 Thirty percent of patients with multibacillary leprosy will either have a reaction or develop new nerve damage, often within the first few months of starting antileprosy drugs.6 Nerve damage can be detected by palpating nerves for tenderness, testing muscle function in hands and feet, and assessing sensory loss with monofilaments every month.43
APPEARANCE OF AFFECTED NERVES
Affected nerves in leprosy may be normal looking or thickened (fusiform swelling), and these thickened nerves can show skip or scattered lesions.44,45
The electroneuromyographic pattern of leprosy neuropathy includes the impairment of conduction of nerve impulse46 and decreased amplitude of sensory-motor potentials.47 It has been shown that nerve damage can extend far proximally from the thickened segments in otherwise inconspicuous sections.48,49 Intraoperative electroneurodiagnostics is an effective tool for detecting the most proximal site of lesion and ensuring effective surgery.48,49 Intraoperative spinal root stimulation has been used successfully to decide the proximal extent of neurolysis, and the site at which amplitudes reached a maximum is considered as the most proximal site of lesion.48,49
TIMING OF SURGERY
It has been shown that nerve regeneration persists for years in leprosy.50,51 Surgery could therefore promote regeneration, even if performed late also.44 There is now a trend toward early operation on the painful leprous nerve with a corresponding reduction of other therapy proposed by some authors.37,52-54 The decision to perform decompressive surgery can be facilitated by noninvasive neurosensory examination, especially when the test becomes abnormal to suggest that this is the point where axons are being lost.21
Surgical approaches are aimed at extensive and wide extraneural neurolysis from the origin of the nerve lesions to the point of termination while preserving its blood supply.37 Nerve release improves muscle function in leprous facial neuropathy, provided surgery is performed on all affected segments. Intraoperative electroneurodiagnostics is an effective tool for detecting the most proximal site of lesion and ensuring effective surgery.44,55
Excision of the Granulomatous Lesions
Excision of the granulomatous lesions and bridging with nerve autografts have been unsuccessful.56 The reasons for this are, first, that major nerve trunks are involved, needing long-cable graft repairs with multiple cutaneous nerves. Limited donor material means that large lesions cannot be repaired. Second, the loss even of one sensory nerve is detrimental to a patient already having some anesthesia. Finally, the donor nerve may itself be diseased.39
Free Muscle Transfer
Facial reanimation was achieved with a free gracilis-muscle transfer, coapting its motor nerve to the ipsilateral facial nerve trunk proximal to the site of the leprosy pathology, with a moderate clinical result.57
Muscle as a Substitute
Keynes et al58 showed that mouse peripheral nerve can be regenerated into degenerating skeletal muscle, and regenerating axons could pass through degenerating muscle to enter and populate the distal nerve, and a pilot study on repair of human digital nerves was also successful.59 In experimental models, muscle grafting has been shown to restore or improve sensory function.39,60 It has been shown that in experimental animals, a treated graft with correctly orientated empty myotubes can facilitate and guide the regeneration of peripheral nerve after injury and therefore lead to decolonization of the distal stump with functional recovery.58,61 The availability of appropriately orientated empty basement membrane tubes both facilitate and guide the growth of regenerating nerve with subsequent recovery of function.61 Fawcett and Keynes62 have also shown the efficacy of muscle basal lamina grafts as an effective nerve autografts for repairing severed rat or rabbit peripheral nerves. Specific clinical uses for such grafts include situations where direct repair of a peripheral nerve is impossible and where the damaged nerve is too large to be repaired usefully with a conventional nerve graft,58,61-63 a condition that is common in leprosy patients with nerve function impairments.
EXTENT OF SURGERY
Surgical approach must provide sufficient and extensive decompression without excessive damage from the origin of the lesion to the most distal extent of the lesion.36 Interfascicular, microsurgical neurolysis is beneficial, provided that it is performed on all affected nerve segments.55 The extent of surgery and external decompression should minimize the aggressive procedures performed on nerve trunks, decrease the morbidity of surgical action on the nerve vascular structures, and consequently preserves all possible sensory and motor functions of a nerve.64
Multiple factors influence the results, and recovery in nerve function depended on many factors, including the duration of the neuritis, the extent of the compression, the immunopathological status of the patient, and the efficacy of medical treatment.37 Patients with shorter duration of acute symptoms and history of smaller number of attacks of acute painful neuritis showed a higher incidence and better grade of recovery.64-69
Preventing nerve damage in leprosy remains a challenge,70 and it is better to overtreat leprosy than to undertreat it.71 We still need to define the role of surgery on nerves in leprosy. Recently, the role of portable devices in early detection of nerve damage has been recognized; however, who are the candidates for surgery, when to perform surgery, extent of surgery, and what kind of procedure will give the best results are yet to be defined.
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