Late onset neuropathy in leprosy patients released from treatment: not all due to reactions?

OBJECTIVES: To evaluate the clinical, neurophysiological and histological features of cases of neuropathy developing after completion of anti-leprosy treatment, where biopsy showed inflammatory changes. PATIENTS AND METHODS: Seven patients were evaluated by a single neurologist. Electro-neuro-myography and peripheral nerve biopsy were performed in all patients. RESULTS: Median age was 50-6 years. Time from release from treatment and onset of symptoms ranged from 1 to 12 years (median of 6.6 years). Sensory symptoms were the most common complaint, including pain (71%) and paresthesiae (71%). Muscle weakness was found in 51% and muscle atrophy in 43% of the subjects. Peripheral nerve thickening was present in all patients. Neurophysiological studies suggested sensory-motor polyneuropathy and multiple mono-neuropathy. Nerve biopsy showed inflammatory processes with fibrosis of endoneurium, perineurium and epineurium and total or partial loss of fibres. No bacilli were detected with Wade staining. Patients treated with corticosteroids had some relief of symptoms. CONCLUSION: After release from treatment, leprosy patients may insidiously develop progressive peripheral nerve symptoms not fulfilling criteria for relapse or leprosy reactions. Sensory symptoms predominate and peripheral nerve thickening is an important finding. We speculate that these late onset symptoms are secondary to chronic immune-mediated processes in response to antigens of M. leprae.

Leprous neuropathy.

Leprous neuropathy, which is due to infection of nerve cells by Mycobacterium leprae, still affects millions of people in many developing countries. The clinical and pathological manifestations are determined by the natural resistance of the host to invasion of M. Leprae. Failure of early detection of leprosy often leads to severe disability in spite of eradication of mycobacterium at a later date. In the lepromatous type, bacilli are easily found in the skin and in nerve cells including Schwann cells, endothelial cells, and macrophages. In the tuberculoid type, a strong cell-mediated immune reaction leads to formation of granulomas and destruction of cells harboring bacilli and neighboring nerve fibers. In many cases, treatment of patients with the multibacillary leprosy is complicated by reversal reaction and further nerve damage. Nerve lesions lead to a symmetrical, pseudo-polyneuritic pattern in most cases of lepromatous leprosy, which is usually associated with typical skin lesions, but pure neuritic forms occur in up to 10% of patients with lepromatous leprosy. In the pure neuropathic cases, only nerve biopsy permits diagnosis. The multifocal pattern is more common in tuberculoid leprosy. Treatment is currently based on multidrug therapy with dapsone, rifampicin, and clofazimine. The use of corticosteroids can reduce or prevent nerve damage in reversal reactions. It is important to remember that sequelae, especially sensory loss, are extremely common, which can lead to secondary trophic changes due to repeated trauma in painless areas.

Infectious neuropathy.

PURPOSE OF REVIEW: Infectious neuropathy affects a large number of people worldwide. There is evidence of direct involvement of nerves by the infective agent, from the immune reaction of the patient or secondary to the toxicity of the drugs used during treatment. This group of neuropathies is often treatable or preventable. RECENT FINDINGS: There is a complex clinical picture of the neuropathy of leprosy, different pathological features and immunological mechanisms. If the skin is unaffected in leprosy it is not always easy to demonstrate that the neuropathy is due to leprosy. Peripheral neuropathy in patients with chronic infection with hepatitis C virus may be due to the virus, the development of vasculitis or direct neurotoxic effects of the treatment. Peripheral neuropathy has become the chief neurological syndrome in individuals infected with HIV-1. The antiretroviral therapies themselves can cause peripheral neuropathies clinically indistinguishable from those caused by the virus. The occurrence of chronic polyneuropathy as a late manifestation in Lyme disease is extremely rare and is not well understood. SUMMARY: Although infectious neuropathies are very frequent, mainly in developing countries, further studies are needed to elucidate their mechanisms of action, focusing on preventive interventions.

Isolated superficial peroneal nerve lesion in pure neural leprosy: case report.

Patients with leprosy may have only nerve involvement without skin changes. These cases are known as pure neural leprosy and can be seen in 10% of leprosy patients. Most patients have mononeuritic or multiple mononeuritic neuropathy patterns. The isolated lesion of the superficial peroneal nerve is uncommonly seen. We report a patient with involvement of this nerve in which there was no thickening of superficial nerves. The performed nerve biopsy showed inflammatory infiltration, loss of fibers and presence of Mycobacterium leprae. We believe that in prevalent leprosy countries we should take in mind the possibility of isolated pure neural leprosy in some patients without skin lesion. In these cases the diagnosis of leprosy is impossible on clinical grounds and nerve biopsy is mandatory.

Small-fiber polyneuropathy in leprosy without skin changes: study of 17 cases.

Leprosy is one of the most common diseases of the peripheral nerves. In some cases there is only neural involvement without skin changes (neuritic form). The neuropathy has often 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. We reported 17 patients with a predominantly small-fiber polyneuropathy due to leprosy. All patients had distal temperature and pain anesthesia with different individual variations. The tendon reflexes were normal in seven patients and in eight there was thickening of the nerves. The nerve conduction was normal in three patients. Sural nerve biopsy consisted of: 1) inflammatory infiltrates, 2) vacuolated "foamy" cells, 3) fibrosis of endoneurium, perineurium, and epineurium, 4) partial or total loss of nerve fibers, 5) large number of bacilli. We concluded that in countries where leprosy is frequent, nerve biopsy is an obligatory procedure in patients with predominantly small-fiber polyneuropathy.