Neurological pupillary noise in narcolepsy

Abstract

SUMMARY Pupillometry has a long but inconclusive history as a means of measuring human alertness. Spontaneous pupillary oscillations in narcoleptics and the sleep deprived are a recognized but quantitatively elusive indication of alertness. Stimulation of the pupillary light reflex (PLR) has provided contradictory or confusing indications of alertness levels. Results from 10 diagnosed narcoleptics and 10 control subjects in which the PLR system was stimulated and a reliable (90%) discriminator derived for classifying narcoleptics and controls was reported. Random pupillary oscillations, which is called pupillary noise to distinguish these oscillations from spontaneous ones, were estimated from continuous pupil diameter recordings using a recursive least squares method applied to a subject-specific PLR system model. Pupillary noise sum of squares indicate that narcoleptics have significantly (P<O.OOS) less PLR noise than controls. This difference was attributed to supranuclear inhibition of randomly active Edinger-Westphal neurons long hypothesized to be the source of random pupillary oscillations. This inhibition also has been suggested as a cause of PLR sensitivity to nocturnal sleep quality so it may be that these findings apply to the sleep deprived and not just specifically to narcoleptics.

Involvement of the orexin system in sympathetic nerve regulation

“…Erectile dysfunction [15], reduced pupillary oscillations [16], and cardiovascular reactivity dysfunctions [17], which suggest abnormal central modulation of autonomic control, have been reported in human patients. Donald et al reported that catalepsy was associated with co-activation of sympathetic and parasympathetic autonomic systems in narcolepsyecataplexy patients [18].…”

Pupillometric Assessment of Sleepiness in Narcolepsy

“…The interpretation of pupillometry-derived measures of sleepiness is limited by a lack of normative data and a robust “single-best” measure. Several pupillometry-derived measures of sleepiness, e.g., pupillary diameter and stability, pupillary light reflex have been examined in narcolepsy with discrepant results (Kollarits et al, 1982; Pressman et al, 1984; Norman and Dyer, 1987; O’Neill et al, 1996). …”

Detection of Juvenile Sleep Deprivation by Stochastic Optimization of Pupillographic Records

“…The determination of λ is a key stochastic optimization step. The method we use to determine λ is the same as the one we employed in our narcoleptic study [4] and is summarized in the Appendix. In brief, the discount factor λ is chosen to maximize the estimated Kullback-Leibler divergence function between sleepy and rested subjects [15].…”

“…Multiple sleep latency testing of juveniles to assess sleepiness is notoriously problematic so there is an obvious need to develop a rapid and objective measure of sleepiness in children. Previous studies of sleepiness, attention state, and cognition using pupillographic methods have been successful in detecting narcolepsy in adults [4], memory deficits in adults [5], and cognitive memory constraints in adults [6]. A recent pupillographic study under fixed illumination [7] found that prolonged sleep deprivation (> 24 hours) tended to increase a pupillary unrest index which apparently is a measure of the nonstationary pupil size variance.…”