Investigating REM-sleep Microarchitecture for Diagnostic Metrics of Idiopathic Hypersomnia Open Access

Dong, Caroline (Spring 2021)

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Background: Hypersomnia and hypersomnolence are debilitating. Diagnosis, cause, and treatment options of what has been termed “idiopathic hypersomnia” (IH) remain ill-defined because its symptoms are not unique. Major depressive disorders (MDD), for example, shares excessively long sleep as a diagnostic criteria with IH—an extremely rare disorder in comparison (1:3,000 – 1:10,000). Unique sleep features of MDD include alterations in rapid-eye-movement sleep (REM-sleep) patterns and one particularly well-established biomarker—namely, increased density of rapid eye movements in REM-sleep. Similar findings in narcolepsy, due to hypocretin deficiency, and IH have been reported. These findings suggest that nosologies of psychiatry and sleep medicine may belie shared biomarkers and biology. Current methodological differences in deriving metrics for phasic movement of REM-sleep such as densities and non-comprehensive assessment of patient symptoms such as depression and hypersomnolence confound interpretations. Thus, we performed a more rigorous analysis of phasic physiological events in REM-sleep of deeply phenotyped, unmedicated healthy controls lacking sleep complaints, and patients with non-hypocretin deficient hypersomnolence refractory to conventional wake promoting medications.

Objective: To determine if elevations in phasic REM-sleep movements exist in non-hypocretin deficient disorders of hypersomnolence.

Methods: Polysomnography of 17 healthy controls and 14 well-characterized, non-depressed, hypersomnolent patients refractory to wake promoting medications was performed. Rapid eye movements and phasic electromyographic movements in chin and both legs were assessed in REM-sleep. These four event types were visually quantified and a density representing the percentage of two-second ‘micro-epochs’ of REM-stage sleep exhibiting at least one event calculated for: a) each individual; and b) individual REM-sleep periods across the night. Robustness in intra- and inter-rater reliability of event scoring was also performed.

Results: Hypersomnolent subject’s sleep macroarchitecture, and eye and phasic muscle movement densities in REM-sleep did not differ from controls. Microarchitecture was also similar between subject groups with the last vs. first REM-sleep period being longer and exhibiting a greater density of eye movements.

Discussion: Our quantification methodology was consistent and accurate. We did not observe increased rapid eye movement densities in idiopathic hypersomnia as reported by others.

Table of Contents

Introduction, 1

Methods, 4

... Subjects, 4

... Polysomnography Recording and Analysis, 6

... Multiple Sleep Latency Test (MSLT), 9

... Statistical Analysis, 10

Results, 12

Discussion, 14

Tables and Figures, 18

... Table 1: Clinical Characteristics of All Subjects, 18

... Table 2: Polysomnographic Variables of Sleep Macroarchitecture, 19

... Table 3: REM Sleep Microarchitecture, 20

... Table 4: REM Sleep Phasic Event Densities, 21

... Table 5: Normalized REM Sleep Phasic Event Densities, 22

... Table 6: Comparison to Literature Densities, 23

... Table 7: Inter-rater ANOVA Results, 24

... Table 8: Intra-rater ANOVA Results, 25

... Figure 1: Example of a Scored REM Epoch, 26

... Figure 2: REM Sleep Duration Between Groups and REM Periods, 27

... Figure 3: Eye Movement Density Between Groups and REM Periods, 28

... Figure 4: Eye Movement Density Across Successive REM Periods, 29

References, 30

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