benzofurans and Neuromuscular-Diseases

Lambert-Eaton syndrome, an autoimmune disorder frequently associated with small-cell carcinoma of the lung, is characterized by impaired evoked release of acetylcholine from the motor nerve terminal. Immunoglobulin G (IgG) antibodies from patients with the syndrome, applied to bovine adrenal chromaffin cells, reduced the voltage-dependent calcium channel currents by about 40 percent. When calcium was administered directly into the cytoplasm, however, the IgG-treated cells exhibited normal exocytotic secretion, as assayed by membrane capacitance measurement. Measurement with the fluorescent calcium indicator fura-2 indicated that the IgG treatment reduced potassium-stimulated increase in free intracellular calcium concentration. The pathogenic IgG modified neither kinetics of calcium channel activation nor elementary channel activity, suggesting that a reduction in the number of functional calcium channels underlies the IgG-induced effect. Therefore, Lambert-Eaton syndrome IgG reacts with voltage-dependent calcium channels and blocks their function, a phenomenon that can account for the presynaptic impairment characteristic of this disorder.

Topics: Adrenal Glands; Autoantibodies; Autoimmune Diseases; Benzofurans; Calcium; Carcinoma, Small Cell; Cell Membrane; Chromaffin System; Electric Conductivity; Exocytosis; Fluorescent Dyes; Fura-2; Humans; Immunoglobulin G; Ion Channels; Lung Neoplasms; Neuromuscular Diseases; Sodium; Synapses; Syndrome; Tetrodotoxin

Five patients developed neurological symptoms during treatment with amiodarone for intervals ranging between five and 40 months. In each case the daily maintenance dose did not exceed 600 mg. The neurological manifestations included gait ataxia, tremor, polyneuropathy, and myopathy. In all five patients, the neurological symptoms were severe and disabling. In one patient with a myopathy, there was no improvement after amiodarone was withdrawn. The neurological side effects of amiodarone may be disabling and are not always reversible with drug withdrawal. Neurological complications may arise during treatment with usual maintenance doses.

Topics: Aged; Amiodarone; Benzofurans; Biopsy; Electromyography; Female; Gait; Humans; Male; Muscle Hypotonia; Muscles; Neurologic Examination; Neuromuscular Diseases; Tremor

A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.

Topics: Adult; Amiodarone; Atrial Fibrillation; Atrial Flutter; Benzofurans; Combined Modality Therapy; Exercise Test; Humans; Male; Motor Neurons; Neural Conduction; Neuromuscular Diseases; Pacemaker, Artificial; Pericardial Effusion; Pleural Effusion; Pneumonia, Aspiration; Pneumonia, Lipid; Tachycardia

Clinical, electrophysiological, and the nerve and muscle biopsy findings from a case treated with amiodarone are reported. Marked distal motor and sensory impairment and distal muscular atrophy were observed clinically. The electrophysiological examination revealed normal motor and sensory conduction velocities in the median nerve; the sensory action potentials were polyphasic and reduced in amplitude. Electromyography revealed denervation potentials and severe loss of motor units in the M. extensor digitorum brevis and in the M. tibialis anterior. The light and electronmicroscopical study of a N. suralis biopsy displayed total loss of large myelinated fibers and an almost total reduction of small myelinated fibers. The number of unmyelinated axons was markedly reduced. Fibrocytes and degenerative axons polymorphous inclusion bodies were present in Schwann cells. The muscle biopsy revealed both neurogenic and myopathic changes. Lipid storage was also present in the muscle fibers. Physical and chemical analysis of the nerve and muscle biopsy revealed the content of iodine to be more than 40 times increased. The findings indicate damage of axons, schwann cells and muscle fibers. It is suggested that the lipid storage in nerve and muscle tissue might be related to the accumulation of the drug or its metabolites.

Topics: Aged; Amiodarone; Benzofurans; Humans; Iodine; Male; Microscopy, Electron; Muscles; Neuromuscular Diseases; Peripheral Nerves; Peripheral Nervous System Diseases

Topics: Aged; Angina Pectoris; Anticoagulants; Benzofurans; Electromyography; Humans; Male; Neuromuscular Diseases