Eaton-Lambert Syndrome

An autoimmune disorder affecting muscular function that is frequently associated with small cell carcinoma of the lung (especially in men) and autoimmune diseases (especially in women and younger patients).

This syndrome occurs about five times more often in men than in women. It is an immune-mediated, myasthenia-like syndrome of muscle weakness, characterized by diminished release of acetylcholine from the motor nerve terminal. Serum from patients with Eaton-Lambert syndrome contains circulating IgG antibodies that block the voltage-dependent calcium channels in the terminals of normal motor nerve fibers.

Symptoms, Signs, and Diagnosis

Muscle fatigue with little or no muscle atrophy primarily affects the leg and trunk muscles. Extraocular and bulbar muscles are often unaffected. Hyporeflexia may occur, but contraction of the muscle for a few seconds temporarily restores normal tendon reflex activity.

About 50% of patients have autonomic abnormalities; the most frequent symptom is dry mouth. Impotence, decreased lacrimation and sweating, orthostatic symptoms, and diminished pupillary response to light also occur. Subacute cerebellar degeneration may occur in patients with Eaton-Lambert syndrome of any cause.

Diagnosis requires identification of electrophysiologic responses to repetitive nerve stimulation. Rapid repetitive nerve stimulation (50 Hz) causes a marked increase in the amplitude of the compound muscle action potential. Slow repetitive nerve stimulation (2 to 5 Hz) causes a marked decrease in the amplitude of the muscle response, similar to that of myasthenia gravis. However, slow repetitive nerve stimulation performed immediately after exercise causes a severalfold increase in the amplitude. This increase also occurs in patients with botulism, hypermagnesemia, or hypocalcemia or in those taking certain antibiotics, typically aminoglycosides.

An elevated level of antibodies to the voltage-gated P/Q-type calcium channel confirms the diagnosis. Such elevation occurs in virtually all cases due to lung carcinoma and in about 90% of cases due to other causes.

Treatment

Elderly patients should be evaluated and monitored for carcinoma for at least 2 to 3 years after diagnosis. In some patients, neuromuscular transmission improves after the carcinoma is removed. Patients should also be monitored for the development of other immune-mediated diseases.

Drugs that increase acetylcholine availability and control immune-mediated disease mechanisms are used. Initial treatment usually consists of prednisone in a moderate dose (1 to 1.5 mg/kg every other day) and azathioprine 1.5 to 2 mg/kg/day po. Immune globulin 2 g/kg IV in divided doses is the treatment of choice for patients refractory to immunosuppressive therapy, who may also benefit from plasmapheresis (5 or 6 exchanges) to remove circulating antibodies. Another effective treatment, 3,4-diaminopyridine, is available investigationally in the USA. Guanidine 10 to 35 mg/kg/day po is effective but causes significant adverse effects.