g(m1)-ganglioside and Muscular-Atrophy--Spinal

Multifocal motor neuropathy (MMN) and progressive muscular atrophy (PMA) are associated with IgM monoclonal gammopathy or the presence IgM anti-GM1-antibodies. To further investigate the pathophysiology of MMN and PMA we determined concentrations of 16 mainly B-cell associated inflammatory markers in serum from 25 patients with MMN, 55 patients with PMA, 25 patients with amyotrophic lateral sclerosis (ALS) and 50 healthy controls. Median serum concentrations of the 16 tested cytokines and chemokines were not significantly increased in patients with MMN or patients with PMA, irrespective of the presence of IgM monoclonal gammopathy or high IgM anti-GM1 antibodies. These results argue against a systemic B-cell mediated immune response underlying the pathogenesis of MMN and PMA.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Autoantibodies; B-Cell Activating Factor; Chi-Square Distribution; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Immunoglobulin M; Male; Middle Aged; Muscular Atrophy, Spinal; Polyneuropathies; Statistics, Nonparametric

We report a 63-year-old man who died of respiratory failure. He was well until 1992 (57 years of his age), when he had an onset of progressive weakness of the bilateral upper limbs. He showed no improvement with TRH administration in other hospital. On January 12, 1994, he admitted to our department because of the progressive muscle weakness. Neurologic examination revealed a muscular atrophy associated with severe weakness and hyporeflexia in both upper limbs, and fasciculation were seen in his tongue. Electrophysiological studies revealed mild conduction block in the left medial nerve, and F-waves were not evoked in the left ulnar nerve and bilateral median nerves. After an administration of 25 g/day of human gamma-immunoglobulin for 5 days, conduction block as well as F-wave abnormalities in the left median and left ulnar nerve were improved, yet no improvement of muscle weakness was seen. The anti-GM1 IgG titer was transiently elevated in the patient's serum after gamma-immunoglobulin therapy. On September 8, 1994, subtotal gastrectomy was performed because of the early stage gastric cancer. Histological examination showed poorly differentiated adenocarcinoma (signet-ring cell carcinoma). His muscle weakness had been gradually extended to the lower limbs and he couldn't walk himself on January, 1998. On March, 1998, he developed tetraplegia, mild dysphagia, dysuria and the respiratory disturbance. On April 12, 1998, he admitted to our department for the second time. Neurologic examination revealed a muscular atrophy and fasciculation associated with severe weakness in all of his limbs, tongue and musclus masseter. Neither deep tendon reflex nor pathologic reflex was evoked in his upper and lower extremities. His ocular movements and sensations were well preserved. He died of respiratory failure on May 1, 1998. The patient was presented in a neurological CPC. Neurological and laboratory findings suggested a spinal progressive muscular atrophy (SPMA). However, there were several unusual points as a typical SPMA in this case, that is, an improvement of the electrophysiological abnormalities by gamma-globulin treatment, as well as transient elevation of anti-GM1 antibody. The clinical neurologists have arrived at the conclusion that the patient had lower motor neuron syndrome associated with anti-ganglioside antibody and cause of death was ascribed to the respiratory failure. We discussed whether this case was SPMA or multifocal motor neuropathy. Postmort

Topics: Autoantibodies; Carcinoma, Signet Ring Cell; Diagnosis, Differential; Diverticulum, Colon; G(M1) Ganglioside; gamma-Globulins; Humans; Male; Middle Aged; Motor Neuron Disease; Muscular Atrophy, Spinal; Stomach Neoplasms; Thyroiditis

Increased titers of anti-GM1 antibodies have been associated with motor neuron disease and motor neuropathy with or without conduction block. To investigate the pathogenetic role of anti-GM1 antibodies we injected into rat tibial nerves sera from patients with multifocal motor neuropathy and conduction block (MMN) or progressive spinal muscular atrophy (PMA), both presenting anti-GM1 antibodies. Sera of patients with MMN produced reduction of amplitude and dispersion of compound muscle action potential from proximal stimulation. Morphometry revealed demyelination in 6.2% of fibers. Sera of patients with PMA did not produce clear-cut electrophysiological or morphological changes. Differential effects of sera from patients presenting high-titer anti-GM1 antibodies, but with distinct clinical syndromes, might depend on differences in anti-GM1 antibody affinity, valency, or ability to fix complement. Alternatively, circulating factors other than, or in addition to, anti-GM1 antibodies present in sera of patients with MMN, but not of PMA patients, might be responsible for conduction abnormalities and reproduce them after passive transfer.

Topics: Animals; Antibodies; Demyelinating Diseases; G(M1) Ganglioside; Humans; Male; Motor Neuron Disease; Muscular Atrophy, Spinal; Neural Conduction; Rats; Rats, Sprague-Dawley; Tibial Nerve