Abstract
Purpose: Excessive daytime sleepiness is highly prevalent in the general population, is the hallmark of narcolepsy, and is linked to significant morbidity. Clinical assessment of sleepiness remains challenging and the common objective multiple sleep latency test (MSLT) and subjective Epworth sleepiness scale (ESS) methods correlate poorly. We examined the relative utility of pupillary unrest index (PUI) as an objective measure of sleepiness in a group of unmedicated narcoleptics and healthy controls in a prospective, observational pilot study. Methods: Narcolepsy (n = 20; untreated for >2 weeks) and control (n = 56) participants were tested under the same experimental conditions; overnight polysomnography was performed on all participants, followed by a daytime testing protocol including: MSLT, PUI, sleepiness visual analog scale (VAS), ESS, and the psychomotor vigilance test (PVT). Results: The narcolepsy and control groups differed significantly on psychomotor performance and each measure of objective and subjective sleepiness, including PUI. Across the entire sample, PUI correlated significantly with objective (mean sleep latency, SL) and subjective (ESS and VAS) sleepiness, but none of the sleepiness measures correlated with performance (PVT). Among narcoleptics, VAS correlated with PVT measures. Within the control group, mean PUI was the only objective sleepiness measure that correlated with subjective sleepiness. Finally, in an ANCOVA model, SL and ESS were significantly predictive of PUI as measure of sleepiness. Conclusion: The role of PUI in quantifying and distinguishing sleepiness of narcolepsy from sleep-satiated healthy controls merits further investigation as it is a portable, brief, and objective test.
Highlights
Comprehensive clinical evaluation of excessive daytime sleepiness (EDS) includes diagnostic testing to distinguish narcolepsy, 20% of the sleep clinic population, from other primary sleep disorders (Partinen and Hublin, 2000)
ANOVA analyses revealed that all performance and sleepiness measures, including pupillary unrest index (PUI), in participants with narcolepsy were different from controls
Examination and comparison of circadian effects on these instruments will better define the role of pupillometry in narcolepsy. These results show that PUI distinguishes pathologic sleepiness of narcolepsy and is an accurate indicator of sleep propensity in controls
Summary
Comprehensive clinical evaluation of excessive daytime sleepiness (EDS) includes diagnostic testing to distinguish narcolepsy, 20% of the sleep clinic population, from other primary sleep disorders (Partinen and Hublin, 2000). Multiple sleep latency test (MSLT), the de facto gold standard for objective measurement of sleepiness and differential diagnosis of narcolepsy has several limitations (Chervin et al, 1995; Johns, 2000; Littner et al, 2005), making it unreliable as the sole indicator of manifest sleepiness in narcolepsy (Kotterba et al, 2004; Wise, 2006). Pupillometry is a brief, non-invasive, physiologically based technique shown to concur with behavioral indicators of sleepiness in several populations (Lichstein et al, 1994; Wilhelm et al, 1998a, 2001, 2009; Wilhelm, 2008), including in narcolepsy, where its use dates back several decades (Yoss et al, 1969, 1970). The potential role of PUI in differentiating pathological sleepiness, in narcolepsy, relative to sleepiness associated with societal factors in a normal control population has not been systematically evaluated
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