Light and electron microscopic study of peripheral nerve damage in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL).

Cutaneous branches of radial nerves in patients with lepromatous leprosy (LL) and borderline lepromatous (BL) were studied by light and electron microscopy. Foamy macrophages were found more or less in the nerve fibers of all leprosy patients and distributed in the epineurial, perineurial and endoneurial areas. In the endoneurium, the foamy macrophages were mainly located in the subperineurial and perivascular spaces. Vacuolated Schwann cells were also found in the nerve fasciculus. In electron microscopy, these foamy macrophages and vacuolated Schwann cells contained numerous small dense materials, irregular in size and shape, considered to be degenerated and fragmented mycobacterium leprae. These dense materials were found also in the cytoplasm of vascular endothelial cells. These findings suggest that mycobacteria enter into the endoneurium via the blood vessels. In our present study, on the other hand, it was very difficult to find the intact mycobacteria in the cytoplasm of the foamy macrophages, Schwann cells or endothelial cells, as well as in the Ziehl-Neelsen staining of paraffin sections. The disappearance of intact bacilli in our present study might have been caused by multi drug therapy. The myelinated nerve fibers were degenerated and disappeared in variable degrees. Degenerative changes of the myelin sheath developed from the outer layer to the inner layer with disarrangement of the lamellar structure. These findings were different from myelin destruction of peripheral nerves in Wallerian degeneration. The degenerative changes of the myelin sheath are caused by degeneration and destruction of Schwann cells in leprosy patients. Fibrosis surrounding myelinated and unmyelinated nerve fibers, i.e., periaxonal fibrosis, was found to a greater or lesser extent in the endoneurium. In the present study, it is still unclear whether the periaxonal fibrosis was due to necrosis of the Schwann cells by infection of mycobacteria or to an autoimmune mechanism such as antiperipheral nerve antibody. However, lamellated concentric fibrosis surrounding regenerative myelinated and unmyelinated nerve fibers with the disappearance of mycobacteria suggests that degenerations and regenerations of nerve axons were repeated during clinical cause. These findings indicated that autoimmune mechanisms play an important role in the pathogenesis of periaxonal fibrosis.

Myelin changes in leprous neuropathy.

Myelin changes were observed in fibres of nerves from cases of leprosy. The myelin had a 'loosened' appearance caused by increased and irregular separation of the intraperiod line. 'Loosening' might affect all, or only some, of the lamellae forming a myelin sheath. There was a patchy distribution of fibres with abnormal myelin, and they were seen only in nerves showing other marked pathological changes including the presence of oedema. The appearances are suggestive of intramyelinic oedema which may be related to the presence of endoneurial oedema.

Study of evolution of nerve damage in leprosy. Part II--Observations on the index branch of the radial cutaneous nerve in contacts of leprosy.

A total of 35 contacts from 20 families of lepromatous index cases were screened clinically. All of them were subjected for nerve conduction velocity (NCV) studies of both left and right index branch of the radial cutaneous (IRC) nerve. Fifteen of these nerves were biopsied. Out of 15 IRC nerves biopsied 10 had slightly reduced average NCV values and 5 were normal. Four nerves out of 10 where average NCV was reduced and 1 nerve out of 5 where NCV was normal showed significant ultrastructural changes and higher percentage of segmental demyelination (10%--13%). There was a striking similarity between the changes seen in the IRC nerves of early cases of leprosy and of contacts.

Study of the evolution of nerve damage in leprosy. Part I--Lesions of the index branch of the radial cutaneous nerve in early leprosy.

A total of six index finger branch of the radial cutaneous (IRC) nerves from three BL, two BB and one BT cases of leprosy, with less than 6 months history of disease were subjected for nerve conduction velocity (NCV) studies followed by biopsy. The biopsy was divided into three parts and subjected for light microscopy quantitative histology, electron-microscopy and fibre tease studies. The nerves revealed a slight reduction in NCV and a varying degree of segmental demyelination ranging from 10% to 35%. The earliest changes observed were the thickening and proliferation of Schwann cell processes of the unmyelinated fibres and degeneration of their axons regardless of the type of leprosy.

Study of the evolution of nerve damage in leprosy. Part I--Lesions of the index branch of the radial cutaneous nerve in early leprosy / Study of evolution of nerve damage in leprosy. Part II--Observations on the index branch of the radial cutaneous nerve in contacts of leprosy

A total of six index finger branch of the radial cutaneous (IRC) nerves from three BL, two BB and one BT cases of leprosy, with less than 6 months history of disease were subjected for nerve conduction velocity (NCV) studies followed by biopsy. The biopsy was divided into three parts and subjected for light microscopy quantitative histology, electron-microscopy and fibre tease studies. The nerves revealed a slight reduction in NCV and a varying degree of segmental demyelination ranging from 10% to 35%. The earliest changes observed were the thickening and proliferation of Schwann cell processes of the unmyelinated fibres and degeneration of their axons regardless of the type of leprosy. A total of 35 contacts from 20 families of lepromatous index cases were screened clinically. All of them were subjected for nerve conduction velocity (NCV) studies of both left and right index branch of the radial cutaneous (IRC) nerve. Fifteen of these nerves were biopsied. Out of 15 IRC nerves biopsied 10 had slightly reduced average NCV values and 5 were normal. Four nerves out of 10 where average NCV was reduced and 1 nerve out of 5 where NCV was normal showed significant ultrastructural changes and higher percentage of segmental demyelination (10%--13%). There was a striking similarity between the changes seen in the IRC nerves of early cases of leprosy and of contacts.

Clinical, electrophysiological, quantitative, histologic and ultrastructural studies of the index branch of the radial cutaneous nerve in leprosy. I. Preliminary report.

The index branch of the radial cutaneous nerve has been demonstrated as a constant nerve which can readily biopsied under local anesthesia and yields a nerve which is of suitable size for quantitative and qualitative studies both by light and electron microscopy. It supplies a limited but constant area where the sensory loss does not disturb the patient. Definite ultrastructural changes have been demonstrated in the clinically normal nerves of leprosy patients. These nerves have also revealed a loss in the small myelinated and unmyelinated fibers, which correlated with the common clinical findings of the absence of sweating and dissociated sensory loss in this disease. Gross damage has been encountered in nerves which showed only early signs of clinical damage even with refined methods of sensory testing. These nerves would have passed as normal on routine testing by No. 5 nylon. Regeneration of small fibers was noted following loss of large size fibers. Nerve conduction velocity may be a useful tool in early diagnosis.