Search

Background: Hepatitis C virus (HCV)-associated neuropathy is usually associated with mixed cryoglobulinemia (MC) and vasculitis. MC may contain viral RNA, and tissues showing vasculitis may contain intracellular HCV. Local HCV replication remains to be evidenced., Objective: To delineate the spectrum of HCV-associated neuropathy and to assess the presence of HCV in nerve and muscle tissues., Methods: Thirty consecutive HCV-infected patients with peripheral neuropathy were included. Genomic and replicative strands of HCV RNA were detected in both nerve and muscle biopsy samples using distinctive reverse transcription nested PCR., Results: Neuropathy was consistent with distal axonal polyneuropathy (DPN) in 25 of 30 patients, mononeuropathy multiplex (MM) in 3 of 30, and demyelinating polyneuropathy in 2 of 30. Pain was present in 18 of 30 patients and MC in 16 of 30. Biopsy showed inflammatory vascular lesions in 26 of 30 patients (87%), including necrotizing arteritis (6/30), small-vessel vasculitis (12/30) of either the lymphocytic (9/12) or the leukocytoclastic (3/12) type, and perivascular inflammatory infiltrates (8/30). All patients with necrotizing arteritis had DPN and positive MC detection. Both pain (p < 0.03) and positive MC detection (p < 0.01) were associated with the presence of vasculitis. Positive-strand genomic HCV RNA was detected in tissues of 10 of 30 patients (muscle 9, nerve 3). In contrast, negative-strand replicative RNA was never detected. Genomic RNA was found in nerve tissue samples showing vasculitis (necrotizing arteritis 2, small-vessel lymphocytic vasculitis 1)., Conclusion: Painful DPN associated with MC and neuromuscular vasculitis is the most frequent type of HCV neuropathy. The usual detection of MC and the lack of local HCV replication indicate that HCV neuropathy results from virus-triggered immune-mediated mechanisms rather than direct nerve infection and in situ replication.

To investigate the role of MMP-9 in Guillain-Barré syndrome, the authors correlated electrophysiologic abnormalities and MMP-9 plasma levels in a series of 21 patients. MMP-9 plasma levels were higher in the demyelinating group than in the nondemyelinating group, and in patients with high CSF protein level. Increase of MMP-9 circulating levels correlated with the increase of F waves latencies, reduction of CMAP amplitude, and decrease of nerve conduction velocities. Circulating MMP-9 may contribute to the peripheral nerve dysfunction of demyelinating Guillain-Barré syndrome.

The adhesion capacities, transmigration capacities, and integrin expression of lymphocytes from patients with Guillain-Barré syndrome incubated with interferon-beta were studied. Interferon-beta induced a dose-dependent inhibition of lymphocyte adhesion to recombinant vascular adhesion molecule-1 (p < 0.0001) and recombinant intercellular adhesion molecule-1 (rICAM-1) (p < 0.01) without modulation of very late activation molecule-4 and lymphocyte function-associated antigen-1 expressions and a dose-dependent decrease of lymphocyte transmigration across fibronectin (p < 0.0001). Inhibition of adhesion to rICAM-1 was similar after long (18 hours) or short (5 minutes) incubation time. These results support the potential therapeutic benefit of interferon-beta in Guillain-Barré syndrome.

Objective: To study the expression and activity of matrix metalloproteinases (MMPs) MMP-2 (72-kd type IV collagenase, gelatinase A), MMP-3 (58-kd stromelysin-1), and MMP-9 (92-kd type IV collagenase, gelatinase B) and tissue inhibitors of MPs (TIMP) in patients with Guillain-Barre syndrome (GBS)., Background: MMPs are able to proteolysis of basement membranes and other matrix components, promoting transmigration of inflammatory cells from circulation to nerve tissue., Methods: Twenty-five patients with GBS were analyzed according to the phase of the disease, i.e., progression, plateau, early recovery, and late recovery. Determinations of MMP-2, MMP-3, MMP-9, and TIMP-1 were performed using ELISA, zymography, and immunocytochemistry in circulation or peripheral nerve., Results: MMP-9 plasma levels were increased in 67% of patients on admission and decreased from progression to late recovery (p < 0.002). During the course of GBS, MMP-9 was progressively balanced by its inhibitor TIMP-1, as assessed by the MMP-9/TIMP-1 ratio. MMP-9 and TIMP-1 plasma levels and the MMP-9/TIMP-1 ratio correlated positively with disability. MMP-2 expression was similar to controls. MMP-3 activity was not detected, and plasma levels were not different from those in controls. Positive MMP-9 immunolabeling was 51 +/- 11% of circulating lymphocytes. It was observed in some endothelial cells and mononuclear cells adherent to the endothelium and close to myelinated fibers., Conclusions: Circulating matrix metalloproteinases (MMP-9) correlates with disease severity in Guillain-Barré syndrome (GBS). MMP-9 likely represents an important molecule in the pathogenesis of GBS and therefore could represent an interesting therapeutic target.

Objective: To determine whether idiopathic sensory neuropathies could be associated with circulating dominant T-cell clones, a T-cell equivalent to monoclonal gammopathy of unknown significance., Background: A number of predominantly sensory neuropathies remain of unknown etiology. Circulating dominant T-cell clones may be observed in the elderly, in autoimmune disorders, and in chronic viral infections., Methods: Twenty patients with chronic sensory or predominantly sensory neuropathies considered idiopathic after intensive investigation were evaluated for the presence of dominant T-cell clones in blood using PCR amplification of the variable region of the T-cell receptor gamma-chain gene. They were classified as chronic idiopathic axonal polyneuropathy (CIAP) or sensory neuronopathy, i.e., chronic idiopathic ataxic neuropathy (CIAN), according to clinical and electrophysiologic criteria., Results: Occurrence of clonal expansions of T cells was strikingly high in patients with idiopathic sensory neuropathies (16/20, 80%), with a similar proportion in CIAP (12/15, 80%) and CIAN (4/5, 80%), as compared with elderly normal controls (2/10, 20%), elderly controls with degenerative neurologic diseases (2/10, 20%), and elderly patients with idiopathic chronic inflammatory demyelinating polyneuropathy (2/10, 20%) (all p < 0.005)., Conclusion: Both CIAN and CIAP are associated with dominant T-cell clones of unknown significance that cannot simply be attributed to the age of patients. Relevance of T-cell clones to the pathogenesis of idiopathic sensory neuropathies remains to be determined.

Objective: To determine whether CD8 lymphoid infiltrates in nerves of patients with HIV-associated diffuse infiltrative lymphocytosis syndrome (DILS) corresponds to a lymphomatous neoplastic process or to a proliferation of T cells reactional to HIV., Background: DILS is characterized by persistent CD8 hyperlymphocytosis and multivisceral CD8 T-cell infiltration, which may affect peripheral nerves., Methods: Presence of monoclonal T cells and HIV-1 proviral load were evaluated by polymerase chain reaction (PCR) techniques in frozen peripheral nerve samples from six patients with DILS neuropathy and 22 patients with other HIV-associated peripheral neuropathies, including mononeuritis multiplex (MM:6), inflammatory demyelinating polyneuropathies (IDP:6), distal sensory polyneuropathy (DSP:5), and toxic distal sensory polyneuropathy (TDSP:5)., Results: Five of six patients with DILS showed no detectable monoclonal T-cell clones in their nerves. Nerve proviral load in DILS (6.8 +/- 0.2 log/10(5) cells) was much higher than in MM (p < 0.008), IDP (p < 0.001), DSP (p < 0.001), and TDSP (p < 0.005)., Conclusions: DILS neuropathy represents a separate entity among HIV-associated neuropathies. It is associated with massive HIV proviral load in nerve and must not be confused with a peripheral nerve T-cell lymphoma.

In 1991, Emslie-Smith and Engel described a distinct form of idiopathic inflammatory myopathy they called "necrotizing myopathy with pipestem capillaries, microvascular deposition of the complement membrane attack complex (MAC) and minimal cellular infiltration." We describe a patient with exercise-dependent painful myopathy related to a necrotizing myopathy with pipestem capillaries in whom mild cutaneous signs of dermatomyositis were detected 7 years after onset and who subsequently developed multiple cerebral infarcts.