Cytodiagnosis of primary neuritic leprosy.

The diagnosis of primary neuritic leprosy (PNL) and its differentiation from other causes of peripheral neuropathy is difficult since acid-fast bacilli (AFB) smears and skin biopsy are negative from anesthetic areas. A biopsy of the involved nerve is the only conclusive method of diagnosis. Such a biopsy may not necessarily be free of complications when a large nerve is involved. However, fine needle aspiration has in this study proved to be a simple technique to demonstrate inflammation granulomas and AFB from these involved nerves in 18 of the 27 cases suspected to have PNL. The validity of the cytological classification into morphological subtypes may have to be supplemented by a large series of studies.

Isolation and characterization of infiltrates in the nerves of patients with neuritic leprosy.

A study was done on the characteristics of infiltrating cells in the nerves of 9 patients with pure neuritic leprosy, by preparing a single cell suspension. The patients had no skin lesion. Histopathological examination revealed that 2 of the 9 nerves showed granulomas characteristics of tuberculoid leprosy, while the remaining 7 had features of lepromatous granulomas. In the nerves showing tuberculoid granulomas, a high proportion of lymphocytes were T cells as they formed rosettes with sheep erythrocytes and only a few percent were EAC rosette forming cells. On the other hand, the nerves showing lepromatous granulomas contained only occasional lymphocytes which formed E and EAC rosettes. Macrophages from the granulomas of all the nerves were esterase positive, peroxidase negative, contained M. leprae and did not exhibit C3 surface receptors.

Isolation and characterization of cells in granulomas of nerves of leprosy patients.

Single cell suspension from the granulomas in nerves of leprosy patients were prepared for an in vitro study of the properties of infiltrating cells. Nerve biopsies from 17 patients with tuberculoid (n = 9) and lepromatous (n = 8) leprosy cases were analysed. The granulomas were found to contain lymphocytes and macrophages. Lymphocytes were the predominant infiltrating cells in the tuberculoid nerves. In contrast, lepromatous nerves contained very few of these cells. The majority of lymphocytes in tuberculoid granulomas were activated T cells as they formed rosettes with sheep erythrocytes, exhibited esterase dots in the cytoplasm and expressed HLA-DR antigens. A small proportion of the lymphocytes also formed rosettes with EAC. Most macrophages from both the granulomas were mature macrophages as they were esterase positive, did not exhibit peroxidase activity and expressed HLA-DR antigens. The macrophages did not possess C3 surface receptors.

Sural nerve biopsy findings in leprosy: a qualitative and quantitative light and electron microscope study in 4 treated cases of the lepromatous spectrum.

Reports on biopsy findings in multifascicular nerves in lepromatous leprosy (LL) are rare and detailed morphometrical data are not available. In a case of early LL with normal electrodiagnostic findings in sural nerve, the present study revealed marked segmental de- and remyelination concomitant with the sequelae of considerable Wallerian degeneration of preferentially small myelinated fibers (MF) in spite of a normal number/nerve and density/mm2. Segmental de- and remyelination of several consecutive internodes in teased fibers suggests continuous bacterial spread via Schwann cells. In 2 more advanced LL-cases, nervous parenchyme was severely reduced, in a borderline lepromatous (BL) case obviously in part caused by cell infiltrates and granulomata. Distinct fascicle differences in MF-involvement were demonstrated by coefficients of variation of MF/mm2 and teased fiber preparations in LL, consistent with the hypothesis of initial focal spread of bacteria. Numbers and densities of endoneurial vessels were increased only in the later stages of LL. Enlargement of endoneurial area, due to different factors, was encountered except for the most severe LL-case with extensive endoneurial collagenization. Morphometric results were compared with those of other neuropathies. Intact and degenerating bacteria mostly in phagosomes of Schwann cells associated with unmyelinated axons and in macrophages were seen only in the early LL- and the BL-case. Sparse mononuclear cell infiltrates and small focal necrosis, present even in LL-cases, underline the complex pathogenesis of nerve fiber involvement.

Sural nerve biopsy in leprosy patients after varying periods of treatment: histopathological and bacteriological findings on light microscopy.

As part of a larger study of nerve biopsies from leprosy patients in Ethiopia for the presence of muramidase (lysozyme), sections were also examined by light microscopy after staining with hematoxylin and eosin for cellular infiltrate and a modification of the Ziehl-Neelsen stain for leprosy bacilli. The muramidase findings will be reported separately. This paper describes the infiltrative and bacterial findings in a group of 18 patients, including four with nonlepromatous forms of leprosy who were suffering from delayed hypersensitivity reaction at the time of biopsy. The findings were unexpectedly interesting and revealing. Lepromatous and borderline-lepromatous patients all showed endoneurial and perineurial infiltration of considerable extent and, in several instances, bacilli were wide-spread from one end of the biopsy to the other; in two patients, solid-staining bacilli and globi were found, indicating relapse. In all except two of the nonlepromatous patients (mainly borderline-tuberculoid) there was an extensive and severe granulomatous infiltration, and in one case there was marked caseation in the endoneurial zone. Within the limits of the present study, the findings indicate that biopsy of a peripheral nerve, even when it is not obviously associated with a skin lesion, may reveal pathological changes which are greater in degree than those suggested by skin biopsy or clinical examination. These observations in a somewhat heterogeneous group of patients treated for varying periods of time, and in a study which was not prospectively planned, suggest that similar observations in a larger group of untreated and treated patients, including those who have relapsed, may be of value.

Vascular changes in leprosy and its role in the pathogenesis of leprous neuritis.

The arteriographic pattern of left hand vessels was studied in 20 patients in leprosy by percutaneous brachial arteriography. Arteriographic abnormalities noted consisted of occlusion, narrowing, tortuosity, dilatation, irregularity and incomplete filling of the lumen by contrast medium. Such abnormal findings were seen in all the arteriograms studied and more than one vessel involvement was noted in over 50 percent cases. This study clearly demonstrated that arterial involvement in leprosy was frequent. No correlation was found between motor weakness and vascular abnormalities. There was no difference in arterial lesions between the patients with and without trophic changes. There was also no correlation between the severity of vascular changes and decline in motor nerve conduction. Degree of histopathological abnormalities in the sural nerve biopsy from these patients showed no features of micro angiopathic neuropathy. It is concluded that the observed vascular abnormalities do not contribute significantly in the genesis of neurological deficit in leprosy.

Vascular changes in leprosy and its role in the pathogenesis of leprous neuritis

The arteriographic pattern of left hand vessels was studied in 20 patients in leprosy by percutaneous brachial arteriography. Arteriographic abnormalities noted consisted of occlusion, narrowing, tortuosity, dilatation, irregularity and incomplete filling of the lumen by contrast medium. Such abnormal findings were seen in all the arteriograms studied and more than one vessel involvement was noted in over 50 percent cases. This study clearly demonstrated that arterial involvement in leprosy was frequent. No correlation was found between motor weakness and vascular abnormalities. There was no difference in arterial lesions between the patients with and without trophic changes. There was also no correlation between the severity of vascular changes and decline in motor nerve conduction. Degree of histopathological abnormalities in the sural nerve biopsy from these patients showed no features of micro angiopathic neuropathy. It is concluded that the observed vascular abnormalities do not contribute significantly in the genesis of neurological deficit in leprosy.