AN EVALUATION OF AUTONOMIC NERVOUS-SYSTEM FUNCTION IN PATIENTS WITH PRADER-WILLI-SYNDROME

Objective. Prader-Willi syndrome (PWS) is a complex multisystem geneti c disorder in which many cardinal features may have a neurologically b ased pathophysiology involving both the central and peripheral compone nts of the autonomic nervous system. Autonomic nervous system function was studied noninvasively in a group of subjects with PWS and control subjects to determine whether autonomic nervous system dysfunction ex ists as part of the PWS. Design/setting. This cross-sectional study wa s performed in the neurophysiology laboratory at a tertiary care facil ity. Methods. Evaluation included anthropometric measurements and calc ulation of a body mass index (BMI). Simultaneous electrocardiography a nd serial recordings of pulse rate and systolic/diastolic mean arteria l blood pressures during orthostatic maneuvers were taken. Pupillary r esponse to the instillation of dilute pilocarpine and measurements of plasma norepinephrine at rest and after standing were also obtained. R esults were analyzed using two-tailed t tests, Fisher exact test, anal ysis of variance, and analysis of covariance adjusting for age, gender , and BMI. Patients. There were 14 subjects with PWS (8 female, 6 male ; aged 4 to 40 years, mean age 16 years) and 8 control subjects (4 fem ale, 4 male; aged 5 to 37 years, mean age 19 years). Results. Abnormal findings were obtained only in subjects with PWS. Analysis of covaria nce adjusting for age, gender, and BMI revealed a trend for subjects w ith PWS to have lower resting diastolic blood pressure (P < .09) and s ignificantly less change in diastolic blood pressure after standing (P <.02). Subjects with PWS had significantly greater BMI than did contr ol subjects (P <.001), which correlated significantly with all pulse r ate measurements where the greater the BMI the higher the pulse rate a t rest (r =.25, P <.04) and the lower the pulse rate after arising fro m lying to standing at both 15 and 30 seconds (r =.17, P <.1; r =.55, P <.08 respectively). Pupillary constriction of 2 mm or more was seen in 7 of 14 subjects with PWS and in no control subjects (P <.004). The 30:15 R-R interval ratio was abnormal in 6 of 14 subjects with PWS an d in no control subjects (P <.03). Conclusions. These results suggest that patients with PWS have a detectable underlying autonomic dysfunct ion characterized principally by diminished parasympathetic nervous sy stem activity.