Entrapment of motor nerves in motor neuron disease: does double crush occur?

OBJECTIVE: To investigate whether "diseased nerves" are more prone to entrapment neuropathy than normal nerves. Nerve conduction studies of human neuropathies have shown that electrophysiological abnormalities are often most prominent at potential sites of nerve entrapment, and entrapments are more common in patients with radiculopathies--a concept designated as "double crush". As entrapment neuropathies commonly occur in otherwise healthy subjects, it is unclear whether this relation is coincidental or whether peripheral nerves affected by disease are rendered more susceptible to effects of repeated minor trauma, traction, or mechanical compression. METHODS: Sequential ulnar nerve conduction studies were prospectively performed at baseline and at four, eight, and 12 month intervals in 16 patients with amyotrophic lateral sclerosis. Ulnar nerve entrapment was defined as a focal reduction (> 10 m/s) in conduction velocity in the across-elbow segment. RESULTS: Ulnar sensory and motor nerve fibres showed similar findings of ulnar nerve entrapment at baseline and at follow up over the period of the study. Nerves with ulnar nerve entrapment showed a significantly greater reduction in distal motor amplitudes than nerves without entrapment, even though distal ulnar sensory amplitudes remained unchanged. CONCLUSIONS: Motor nerves in motor neuron disease do not seem to be more susceptible to entrapment at the elbow than do healthy sensory nerves, thus casting doubt on the double crush hypothesis. Nerves with double pathology (amyotrophic lateral sclerosis and ulnar nerve entrapment), however, seem to undergo more rapid axonal loss than do nerves with single pathology (amyotrophic lateral sclerosis or ulnar nerve entrapment alone).

Differential effects of prednisone and cyclophosphamide on autoantibodies in human neuromuscular disorders.

We compared the effects of treatment of patients with prednisone or cyclophosphamide on a series of different types of autoantibodies. Levels of antiacetylcholine receptor (anti-AChR) antibodies and of antibodies to GM1 and GD1a gangliosides were measured in patients with a variety of neuromuscular disorders before and after treatment. Most patients had several autoantibodies present. We showed that prednisone treatment resulted in a reduction in titers of anti-AChR but not antiganglioside antibodies. Cyclophosphamide treatment produced a reduction of antiganglioside antibody titers. An intravenous and oral regimen was more effective than a single intravenous course of cyclophosphamide. We conclude that an immunosuppressive medication such as prednisone may reduce levels of some autoantibodies while producing no change in others, even in an individual patient. In addition, cyclophosphamide can suppress autoantibodies that prednisone does not. These differences in immunopharmacologic responses suggest that there are several distinct mechanisms of autoantibody production in humans. The utility of immunosuppressive medications in specific disease processes may be related in part to the mechanism of production of pathogenic antibodies.