Novel drug of choice in Eaton-Lambert syndrome.

Sir: Muscle weakness in the myasthenic syndrome of Eaton-Lambert' is caused by diminished transmitter release from motor nerve endings2 secondary to morphological destruction of the active release zones in the nerve terminals3 which is thought to have an autoimmune aetiology."5 Immunosuppressive therapy has recently been recommended5 but its full effect is delayed by several months and severe side effects may be expected during prolonged treatment. Symptomatic treatment with an immediately acting drug would be of value to the cancer patient with Eaton-Lambert syndrome, and if such a drug is proved safe it could also be used in the cryptogenetic form of the disease. 4-aminopyridine has been tested,6'8 but its usefulness is limited by central nervous system stimulant effects sometimes causing seizures. We have tried another aminopyridine, 3,4-diaminopyridine (3,4-DAP), in three patients with Eaton-Lambert syndrome. This drug is known from animal experiments to be more potent in improving neuromuscular transmission9 and less convulsant'° than 4-aminopyridine. Our first patient was a 70-year-old woman with cryptogenic Eaton-Lambert syndrome with marked difficulties in walking, pronounced dysarthria, ptosis, difficulty in swallowing, and constipation and inability to urinate. She further deteriorated and required mechanical respiratory assistance because of respiratory muscle weakness. The intravenous injection through a central venous cannula of 8 mg 3,4-DAP within 5 minutes caused marked improvement. The patient was able to breathe without respiratory assistance, ptosis disappeared, facial expression reappeared and muscle strength in arms and legs improved a lot. Examination of neuromuscular transmission by repetitive nerve stimulation showed marked decrease of the neuromuscular block. The i.v. injection caused much salivation and secretion from the respiratory tract, which was blocked by atropine intravenously. Treatment with repeated intravenous infusions of 3,4-DAP gave satisfactory clinical and electrophysiological improvement (fig). She received daily intravenous infusions of 6-9 mg 3,4-DAP 4 times a day with 0-5 mg atropine for 5 months without side effects. During this treatment she could breathe 12