Identification of autoantibodies associated with rippling muscles and myasthenia gravis that recognize skeletal muscle proteins: possible relationship of antigens and stretch-activated ion channels.

The role of mechanosensitive calcium channels in skeletal muscle physiology is not understood. This study takes advantage of an autoimmune neuromuscular disorder (myasthenia gravis associated with rippling muscles) to identify components in the skeletal muscle myocyte that may play a role in mechanosensitive calcium channel activity. Rippling muscles are characterized by stretch or percussion activated wave-like muscle contractions that do not require motor unit action potentials for propagation. Autoantibodies from the sera of patients with autoimmune rippling muscles (associated with myasthenia gravis) are directed against high molecular weight muscle proteins. Some of these proteins are uniquely recognized by antisera from patients with autoimmune rippling muscles. This suggests these autoantigens are distinct from those normally associated with myasthenia gravis, and may play a role in the mechanosensitive activation of muscle contraction.

Immunosuppressive treatment of rippling muscles in patients with myasthenia gravis.

Rippling muscle disease is a rare autosomal dominant disorder that may occur sporadically. In this report two patients presenting with rippling muscles followed by myasthenia gravis are described. Our first patient developed rippling muscles about 1 month after infection with Yersinia enterocolitica. Two years later myasthenia gravis appeared. Our second patient had a 2-year history of asthma prior to the onset of rippling muscles which preceded the myasthenic symptoms by 4-8 weeks. Acetylcholine receptor and anti-skeletal muscle antibody titers were positive in both patients. In both patients the rippling phenomena worsened with pyridostigmine treatment but markedly improved after immunosuppression with azathioprine.

Rippling muscles and myasthenia gravis with rippling muscles.

OBJECTIVE: To describe a patient with rippling muscles and myasthenia gravis. DESIGN: Clinical, laboratory, electrophysiologic, and muscle biopsy data are reported. SETTING: Medical office and hospital. PATIENT: We describe a patient with rippling muscles (as seen in rippling muscle disease) and myasthenia gravis (MG) with thymoma. There was no family history of rippling muscle disease in our patient. Diplopia and other symptoms of MG were initially overshadowed by the striking rippling phenomenon. The rippling resolved when the MG became florrid. INTERVENTIONS: The patient was treated with pyridostigmine, prednisone, and plasmaphereses before removal of a thymoma. MAIN OUTCOME AND RESULTS: His MG improved with treatment and the rippling has not recurred 4 months after thymectomy. CONCLUSIONS: Rippling muscle disease is rare and usually inherited. Our patient with rippling muscles (but no family history of rippling muscle disease) and MG suggests that rippling muscles may also be triggered by an autoimmune phenomenon.

Variable waveforms in downbeat nystagmus imply short-term gain changes.

A patient with downbeat nystagmus subsequent to ankylosing spondylitis was studied. His nystagmus was found to exhibit both increasing- and decreasing-velocity exponential slow phases as well as the linear form more often reported. Alternation between waveforms sometimes occurred on a beat-to-beat or even intrabeat basis. Possible explanations for all three waveforms are presented in terms of short-term gain changes in cerebellar compensation for leaky brainstem neural integrators. A computer model was developed and its results are discussed.

Reye syndrome: serum-induced alterations in brain mitochondrial function are blocked by fatty-acid-free albumin.

Oxygen utilization and pH changes were monitored simultaneously in mitochondria isolated from rat brain. Addition of serum from four patients with Reye syndrome stimulated the resting respiratory rate, decreased respiratory control, stimulated ATPase activity, and decreased the rate of phosphorylation as measured by changes in pH. Serum from normal individuals did not have these effects. Convalescent serum from the three surviving patients showed a return of values toward normal. These changes were most marked with serum from the more deeply comatose patients. Contrary to a previous study of rat liver mitochondria, the changes were blocked by preincubation of the patients' sera with fatty-acid-free albumin. The serum factor responsible for the impairment in mitochondrial function may be a short- or medium-chain fatty acid.