3,4-Diaminopyridine in the Treatment of Lambert–Eaton Myasthenic Syndrome

Lambert–Eaton myasthenic syndrome is characterized by muscle weakness, hyporeflexia, and autonomic dysfunction, which result from impaired release of acetylcholine from cholinergic nerve terminals. It is frequently associated with cancer, it is autoimmune-mediated, and treatment has been unsatisfactory. 3,4-Diaminopyridine enhances the release of acetylcholine. In this prospective, double-blind, placebo-controlled crossover study of 12 patients with Lambert–Eaton myasthenic syndrome (7 of whom had cancer), 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome. Muscle strength increased from an average of 70 percent of normal to 81 percent of normal in the upper extremities, and from 45 to 65 percent of normal in the lower extremities. The amplitudes of compound-muscleaction potentials nearly doubled, increasing from an average of 2.9 mV to 5.0 mV in the arm and from 1.6 mV to 3.1 mV in the leg. Autonomic symptoms were relieved. One patient had a seizure after 10 months of treatment, but other side effects from the drug were minimal and doserelated. We conclude that 3,4-diaminopyridine, either alone or in conjunction with other therapies, may be useful in the treatment of Lambert–Eaton myasthenic syndrome. LAMBERT–EATON myasthenic syndrome is a disorder of peripheral cholinergic neurotransmission that results in muscle weakness, hyporeflexia, and autonomic dysfunction. The electrophysiologic defect of the myasthenic syndrome was characterized in 1956 by Lambert, Eaton, and Rooke, who found an association with carcinoma of the lung.¹ About half of all cases are not associated with cancer, however, and subsequent work has demonstrated an autoimmune pathogenesis in all cases.^{2 3 4 5 6 7} The defect in neurotransmission is due to impaired release of acetylcholine from nerve terminals.⁸ This release is strongly calcium-dependent,⁹ and antibody-mediated impairment of calcium influx is probably the primary pathophysiologic event in Lambert–Eaton myasthenic…