Sarcoid neuropathy: clinico-pathological study of 4 new cases and review of the literature.

There are several reviews devoted to neurosarcoidosis and a few reports restricted to sarcoid neuropathy. Since 1989, we have investigated 4 new cases of sarcoid neuropathy, 1 with chronic sensory motor neuropathy (CSMN), another with painful neuropathy and 2 with atypical chronic inflammatory demyelinating polyneuropathy (CIDP). In each case, biopsy specimens from the superficial peroneal nerve and peroneus brevis muscle were taken by the same cutaneous incision and studied on paraffin sections, semi-thin sections and under electron microscope. We compared neuropathological findings from our 4 cases with those from 34 well-studied nerve biopsies previously reported in the literature, and which concerned 16 cases of CSMN, 13 cases ofmononeuropathy multiplex, 2 cases of painful neuropathy and three cases of CIDP. In all of these 38 cases of sarcoid neuropathy, the characteristic noncaseiting granulomas (NCG) were observed on the nerve in 11 cases, on the muscle alone in 5, on both muscle and nerve in 10, and in the nerve and another parenchyma in 4. In the 8 remaining cases, NCG were observed in another parenchyma, mainly lung or lymph nodes. Moreover, necrotizing vasculitis was present in nerve biopsies from 8 cases and microvasculitis without obvious necrosis in 2 others. Nerve fiber lesions, which are mainly axonal, are probably related to mechanical compression by NCG and/or to an ischemic process due to vasculitis. Cytokines and immune factors may also play a role, especially in certain cases with a clinical presentation of CIDP.

Anti-myelin-associated glycoprotein antibodies and endoneurial cryoglobulin deposits responsible for a severe neuropathy.

A 73-year-old man was investigated for a peripheral neuropathy which occurred in the course of a Waldenstrom's macroglobulinemia. Serum immuno-fixation electrophoresis demonstrated two IgM monoclonal gammopathies of the kappa and lambda chain isotypes, and one had the physical characteristics of cryoglobulin. Immunoblot studies on the patient's serum revealed antibodies which reacted with peripheral nervous system proteins of different molecular weights including the myelin-associated glycoprotein (MAG). An immunofluorescence study of a superficial peroneal nerve biopsy revealed not only a binding of IgM and kappa light chain on several myelin sheaths but also the presence of IgM and kappa light chain deposits in the endoneurium. On electron microscopic examination, numerous fibres presented a widely spaced myelin and the endoneurial deposits had the ultrastructure of cryoglobulin. This is the first case presenting features of widely spaced myelin related to serum anti-MAG activity associated with monoclonal cryoglobulin deposits in the endoneurium.

Histopathological features of X-linked Charcot-Marie-Tooth disease in 8 patients from 6 families with different connexin32 mutations.

There is still confusion as to whether X-linked Charcot-Marie-Tooth disease (CMTX) is primarily an axonal disorder or is primarily demyelinating. Eight symptomatic patients, 7 males and 1 female, from 6 families with identified connexin32 mutations underwent a superficial peroneal nerve biopsy. Quantitative and ultrastructural studies were performed, and histopathological lesions in these 8 patients proved to be quite homogeneous. The myelinated fiber count was within normal values or only moderately decreased. In 7 cases, the distribution of myelinated fibers was unimodal due to a loss of large fibers, coexisting with numerous clusters of small regenerating fibers. At ultrastructural level, these clusters were often surrounded by flattened Schwann cell processes giving an aspect of "pseudo-onion bulb" formation. There was no "naked axon" (ie, demyelinated axon), and real "onion bulb" formations composed of flattened Schwann cell processes surrounding an isolated myelinated fiber were discrete and not numerous. Macrophages laden with myelin debris were scarce or absent in the endoneurium. Several fibers appeared discretely hypomyelinated and the calculated g-ratio was scarcely higher than the mean control value. Lesions of unmyelinated fibers were absent in 7 cases and mild in one. Given that the primary defect concerns connexin32, we think that the histopathological features observed in our patients correspond to primary hypomyelination rather than to ongoing demyelination. The associated axonal degeneration might be secondary to defective axon-Schwann cell interactions.