Variable clinical response to treatment in four patients with polyneuropathy and IgM gammopathy | STUDIO CLINICO E VARIABILITA DI RISPOSTA TERAPEUTICA IN QUATTRO PAZIENTI CON NEUROPATIA ASSOCIATA A GAMMOPATIA MONOCLONALE IGM
Diagnostic Techniques, Neurological
Polyneuropathy is present in 8-50% of the patients with IgM monoclonal gammopathy, including monoclonal gammopathy of undetermined significance (MGUS) and malignant lymphoproliferative disorders (Waldenstrom macroglobulinemia, multiple myeloma, primary amyloidosis, lymphoma or leukemias). In more than 50% of the cases the M protein reacts wvith carbohydrate epitopes shared by myelin-associated glycoprotein (MAG) and other glycoproteins and glycolipids of the myelin sheat. There is evidence that in the neuropathy with antibodies to MAG the M protein could be pathogenetic. Immunohistochemical studies show deposit of IgM of the same light chain as the M-protein on myelin sheats, as well as some complement components. Moreover intraneural injection of serum containing anti-MAG antibodies passively transfer the disease to animals. Since the disease is immuno-mediated and the M-protein may be responsible for the polyneuropathy, then it should improve with therapy direct at autoantibodies lowering by reducing the circulating antibodies or suppressing their production. However, previous therapeutic approaches led to conflicting results and defined treatment guidelines are still lacking. We describe the response to treatment of 4 patients suffering from polyneuropathy associated with IgM gammopathy, three of which showed anti-MAG reactivity. They were all male, whose age ranged from 45 to 66 years (mean age 55), presenting with a history of progressive sensory-motor polyneuropathy. The onset of symptoms was 1 to 4 years before diagnosis. All patients underwent clinical, immunological and electrophysiological evaluation. All but one underwent nerve biopsy. Our 4 patients with polyneuropathy and antibodies to MAG had a sensory-motor polyneuropathy presenting with paraesthesias, distal weakness, tremor and ataxia. Electrophysiological studies showed demyelinating features with slowing of conduction and prolonged distal latencies. The pathological changes in the affected nerves consisted of demyelinating polyneuropathy with axonal loss, and Widening of Myelin Lamellae (WML) on ultrastructural examination. The entity of the clinical impairment was quantified by a motor and a functional score, that assessed the autonomy of the patients in the daily living. Serum immunoelectrophoresis gave evidence of IgM monoclonal gammopathy in 3 patients and a polyclonal increase of IgM in the third one. The screening for paraproteinemias (bone marrow biopsy enclosed) showed findings consistent with Waldenstrom in one case and MGUS in the other 2 cases of monoclonal gammopathy. The patients were treated for 6 to 11 months with immunosuppressant drugs and/or chemotherapy (corticosteroids, chlorambucil, cyclophosphamide, plasma exchange, human immune globulins, azathioprine, alpha interferon). Therapy was chosen individually according to clinical criteria for each patient and modified during the treatment according to patients' response and tolerance. Of the 3 patients with anti-MAG reactivity, 2 showed clinical improvement, while one remained unchanged. The patient with IgM monoclonal gammopathy without anti-MAG reactivity worsened slowly in spite of therapy. The following factors could be involved in the different therapeutic responses: 1) age of patients 2) early treatment 3) individual susceptibility 4) persistence of B cells secreting antibodies.