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Eleven patients with motor neuron disease associated with a monoclonal gammopathy were studied. One patient had a previously known multiple myeloma. In the other patients neurological symptoms preceded diagnosis of the gammopathy by one month to 8 years. They were 5 multiple myeloma, 1 macroglobulinemia, 1 chronic lymphatic leukemia, 1 lymphoma and 3 benign monoclonal gammopathies. EMG and motor conduction velocities results were consistent with anterior horn cell disease but sensory conduction studies were abnormal in seven cases out of eight. Superficial peroneal nerve biopsy performed in all patients confirmed peripheral nerve involvement. The relations between gammopathy, clinical symptoms and electrophysiological data are discussed. The interest of sensory conduction studies in every patient with motor neuron disease is emphasized.

Five cases of peripheral neuropathies occurring with monoclonal gammapathies are studied by means of nerve biopsies. Immunofluorescence and HRP-immunolabelling with the electron microscope are performed. The direct pathogenic role of a subperineurial immunoglobulin deposit is pointed out. The relationship of the heavy chain monoclonal immunoglobulin with amyloid fibrils is discussed.

Analysis of 105 peripheral and central nervous system complications in 1062 monoclonal gammapathies draws attention to two types of phenomena. The possibility of pure neurological manifestations of IgM monoclonal gammapathies with macroglobulinorachia leads to discussion of their nosological position in relation to Waldenström's disease, Burkitt's lymphoma and Marek's disease. It is suggested that these cases should be reclassified under the heading "secreting neurolymphomatosis". Immunofluorescence and electron microscopy of 10 biopsies of the peripheral nerve showed deposits of monoclonal immunoglobulin whose function in determining peripheral neuropathies is discussed. The simultaneous presence of lymphoid infiltration, amyloid deposits and the monoclonal immunoglobulin (M component) suggests that this immunoglobulin could be the link between the cellular infiltrate secreting it and amyloid infiltration which would be the visible manifestation of it.

Particular clinical pictures of ALS may occur during the course of some "benign gammapathies". We observed 12 patients (age range 57 to 74 years; 9 men-3 women) with initially benign gammapathy (9 IgG, 1 IgA, 2 IgM) associated to a clinical picture of progressive anterior horn and pyramidal tract involvement. These cases led us to recognize some particularities of gammapathy-associated ALS: Relative frequency of asymmetrical clinical manifestations, rarity of bulbar signs; Decrease of sensory nerve conduction velocities without evidence of sensory clinical symptoms (8 out 9); Increase CSF protein content including the monoclonal component, axonal degeneration and immunostaining evidence of the paraprotein fixation observed on nerve biopsies (5 out 7 cases). Association of ALS and gammapathy is not fortuitous as shown by epidemiology, experiments, pathology and effects of different immunological treatments as related in this study. Demonstration of infra-clinical neuropathy face to a clinical syndrome of ALS should prompt too careful screening for a gammapathy.