AUTONOMIC DYSFUNCTION IN THE LAMBERT-EATON-MYASTHENIC-SYNDROME - SEROLOGIC AND CLINICAL CORRELATES

Autonomic dysfunction is a recognized feature of the Lambert-Eaton mya sthenic syndrome (LES). However, the characteristic pattern of dysauto nomia has not been clearly documented and its pathophysiologic basis i s not known. We therefore abstracted autonomic symptomatology and resu lts of quantitative tests for salivation, and vasomotor, cardiovagal, and sudomotor reflexes from records of 30 LES patients, Dry mouth (77% ) and impotence (45% of men) were the most common symptoms. Composite Autonomic Scoring Scale results were abnormal in 93% of patients, and autonomic failure was severe in 20%. The frequency of specific test ab normalities were the following: sudomotor function, 83%; cardiovagal r eflexes, 75%; salivation, 44%; and adrenergic function, 37%. Although voltage-gated N-type calcium (Ca2+) channels are implicated in autonom ic transmission, the low frequency of serum antibodies to N-type Ca2channels found in the patients of this study (31% positive) argues aga inst a pathogenic role in mediating LES-related dysautonomia. In contr ast, 93% of the patients were seropositive for P/Q-type Ca2+ channel a ntibodies. A subset of these antibodies is thought to impair neuromusc ular transmission, Autoantibodies of thyrogastric or glutamic acid dec arboxylase specificity (markers of predisposition to type 1 diabetes m ellitus) were found in 45% of patients, and type 1 antineuronal nuclea r antibody (or anti-Hu, a marker of autoimmune neuropathy associated w ith small-cell lung carcinoma) was found in 3%, No autoantibody correl ated with autonomic dysfunction severity, Sensorimotor neuropathy was documented in five patients, and was not significantly associated with autonomic neuropathy. Autonomic failure was most severe in older subj ects with cancer (p = 0.02, age by cancer interaction).