Insomnia with physiological hyperarousal is associated with lower weight: a novel finding and its clinical implications

Previous studies on the association of insomnia with body mass index (BMI) have been controversial. Physiological hyperarousal, the key pathological mechanism of insomnia, may be an important reason for different findings. We explored whether insomnia with physiological hyperarousal measured by the multiple sleep latency test (MSLT) is associated with body-weight differences. A total of 185 normal sleepers and 440 insomniacs were included in this study. Insomnia was defined by standard diagnostic criteria with symptoms lasting ≥6 months. All subjects underwent one night of laboratory polysomnography followed by a standard MSLT. We used the median MSLT value (i.e., ≥14 min) to define physiological hyperarousal. BMI was based on measured height (cm) and weight (kg) during the subjects’ sleep laboratory visit. BMI > 25 kg/m2 was defined as overweight, while BMI < 18.5 kg/m2 was defined as underweight. After controlling for confounders, the odds of lower weight rather than overweight were significantly increased among insomnia patients with increased MSLT: insomnia with MSLT 14–17 min and MSLT > 17 min increased the odds of lower weight by approximately 89% (OR = 1.89, 95% CI 1.00–4.85) and 273% (OR = 3.73, 95% CI 1.51–9.22) compared with normal sleepers, respectively. In contrast, insomnia in patients with MSLT 11–14 min and 8–11 min was not different from normal sleepers in terms of body weight. Insomnia associated with physiological hyperarousal, the most severe phenotype of chronic insomnia, is associated with higher odds of lower weight and underweight compared with normal sleepers. This is a novel finding consistent with previous physiologic data and has significant clinical implications.

Approach to Common Sleep Disorders

Sleep disorders are highly relevant in clinical practice given their prevalence as well as their impact on health outcomes and quality of life. The most common concerns are excessive daytime sleepiness, insomnia, disordered breathing, and abnormal movements or behaviors during sleep. A detailed but targeted history is vital, particularly from the sleep partner/witness. In-laboratory sleep testing (polysomnography and multiple sleep latency test) remains vital in the diagnosis of certain sleep disorders (such as sleep-disordered breathing and central hypersomnia) and in specific populations (such as in children and individuals with comorbid medical disorders). Advances in technology have allowed for a variety of methods in assessing a patient's sleep, from compact devices to evaluate for sleep apnea, wrist actigraphy, and mobile device-based applications. As the pathophysiology of various sleep disorders becomes better elucidated, disease-specific medications have been developed for these conditions. Nonetheless, a multidisciplinary approach to management is necessary, including improving sleep hygiene and cognitive behavioral therapy.

Polysomnography and Other Sleep Testing

Multiple methods are available for evaluating sleep concerns: clinical screening instruments, sleep diaries, polysomnography with multiple sleep latency test and maintenance of wakefulness test, and actigraphy. This chapter reviews the tools used to assess patients with sleep concerns. Screening tools such as questionnaires are used to stratify patients on the basis of their clinical characteristics and risk factors for sleep difficulties. Patients at high risk may need urgent polysomnography or further treatment.

P003 The impact of forced wake from overnight polysomnography on multiple sleep latency test results

Introduction The multiple sleep latency test (MSLT) is used to diagnose disorders of hypersomnolence. Although internationally-recognised protocols do not stipulate whether patients should be woken from the preceding overnight polysomnography (PSG), many labs wake their patients for logistic reasons. This study analyses the impact on PSG and MSLT parameters of forced wake (FW) from the overnight PSG compared with unrestricted sleep (US). Methods 400 consecutive patients (FW=200; US=200) undergoing PSG/MSLT were included and the following parameters were compared: Epworth Sleepiness Scale (ESS), Morningness-Eveningness Questionnaire score (MEQ), PSG total sleep time (TST), wake-up time from the PSG, overall MSLT sleep latency (MSL), individual nap latencies (SLNap 1–4), number of MSLT naps with sleep-onset REM periods (#SOREMP), and percentage of MSLTs with overall MSL&lt;8 minutes (%MSLT&lt;8). Results The 2 groups were well-matched for ESS and MEQ. The FW group had more males (49% vs 39%). When compared to FW, patients with US had longer TST (+38 minutes; p=&lt;0.0001), later wake-up time (+52 minutes; p&lt;0.0001), longer MSL (+1.9 minutes; p=0.0049), 50% fewer #SOREMP (p=0.0224), and 16% fewer %MSLT&lt;8 (p=0.0018). SLNap1 increased by 1.5 minutes (p=0.0623), SLNap2 increased by 2.0 minutes (p=0.0067), SLNap3 increased by 0.75minutes (p=0.0533) and SLNap4 increased by 2.5 minutes (p=0.0059). Discussion Allowing patients to have unrestricted sleep on the night prior to the MSLT resulted in significantly longer TST, longer sleep latencies during the MSLT, fewer SOREMP and fewer tests with MSL&lt;8 minutes. International protocols should stipulate unrestricted sleep on the PSG prior to the MSLT to improve diagnostic accuracy.

P034 Inter-scorer concordance impacts MSLT results

Introduction A retrospective study on the effect of inter-scorer concordance and impact of analysing polysomnography (PSG) data prior to the Multiple Sleep Latency Test (MSLT) on clinical interpretation of Narcolepsy (N) and Idiopathic Hypersomnolence (IH). Methods Data of four individuals was randomly selected from a cohort of patients that participated in MSLT studies. De-identified MSLT fragments from four nap periods (n=16) were scored in two groups: analysis of PSG conducted prior to the respective MSLT fragments, and analysis without access to prior PSG. Individual scorers were compared to a master score set, by consensus from two experienced sleep scientists. Spearman correlation and percentage agreement statistics were applied to calculate the inter-scorer concordance in sleep latency and REM latency. Mann-Whitney test was utilised to assess differences between the two groups. A positive result was assigned as: mean (n=4) sleep latency of &lt;10min (IH), and mean (n=4) sleep latency of &lt;8min including (n=2) SOREMs (N). Results From 16 sets of data, four false positive results were identified when PSG was not analysed prior to scoring the MSLT fragments. Additionally, statistically significant differences were present when PSG analysis was conducted prior to scoring MSLT sleep latency and REM latency data. Discussion These results support a recommendation that PSG analysis (sleep and REM latency) should be encouraged prior to MSLT studies and performed by the same sleep scientist. Furthermore, including MSLT data in intra-lab concordance activities is important, particularly in relation to medical interpretation and practice.

P166 Measures of overnight sleep stability in patients with hypersomnolence

Introduction Hypersomnolence causes significant impairment of daytime functioning. The multiple sleep latency test (MSLT) measures objective hypersomnolence (OH). Patients with hypersomnolence with a normal MSLT are said to have subjective hypersomnolence (SH). The mechanisms of hypersomnolence in such patients is uncertain. This study describes differences in measures of sleep stability derived from the overnight polysomnography (PSG) in patients with OH and SH. Methods A retrospective analysis of 100 patients undergoing PSG/MSLT for investigation of hypersomnolence was performed. Patients were classified as OH (MSLT≤8 min) or SH (MSLT&gt;8min). Sleep stage distribution and PSG-derived markers of sleep stability including cardiopulmonary coupling (CPC), cyclic alternating pattern (CAP) and sleep stage shifts were compared between the two groups. Results When compared to OH patients (N=50), SH patients (N=50) had significantly more sleep stage shifts, more shifts to stage N1 and longer PSG sleep latency. Small but significantly lower sleep efficiency, higher stage N1 and N3 proportions were also observed in SH patients. OH patients had a small but significantly higher CAP rate and CAP index compared to SH patients. There were no significant differences in CPC metrics between the two groups. Conclusion Several PSG-derived markers of sleep stability indicated that patients with SH experienced more unstable sleep than OH patients. This may provide insight into the underlying pathophysiological mechanisms which differentiate these patient groups and may serve as a future therapeutic target.

P106 Evaluating the correlation between objective daytime sleepiness, daytime functioning and subjective sleepiness

Introduction Daytime sleepiness is typically assessed in clinical settings with the Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test (MWT). However, these tests do not necessarily assess daytime functioning. This study aimed to assess the correlation between a 10-min Psychomotor Vigilance Test (PVT), as a measure of daytime functioning, and excessive daytime sleepiness as measured with the MSLT or MWT. Methods Patients attending the sleep clinic for assessments of daytime sleepiness underwent overnight polysomnography (PSG) and completed the Epworth Sleepiness Scale (ESS). The following day, patients completed four test sessions every 2h starting 1.5h after waking. Testing sessions included the Stanford Sleepiness Scale (SSS), PVT, MWT or MSLT. PVT lapses (reaction time &gt;500ms), SSS score and sleep latencies (MSLT and MWT) were averaged within participants across sessions and regression analyses performed to assess the relationship between PVT lapses and sleepiness measures. Results A total of 41 patients (BMI: 33.7±8.7kg/m²; aged 44.8±17.8 years) completed the study. Of these, 22 (19 F) underwent the MSLT and 19 (2 F) underwent the MWT. PVT lapses correlated with MWT mean sleep latency (r²=0.62; p&lt;0.001), ESS (r²= 0.19; p&lt;0.01) and SSS (r²= 0.12; p&lt;0.05) but not MSLT mean sleep latency (r²= 0.02; p = 0.50). Discussion In clinical practice, MWT and ESS are often used in conjunction to assess daytime functioning. Results suggest that the PVT could be used alongside MWT to aid clinical judgments around an individuals’ daytime functioning.

O050 Hypersomnolence in children: the diagnostic dilemma

Background Excessive daytime sleepiness (EDS) is reported to affect up to 20% of pre-pubertal children and 50% of adolescents. EDS can be due narcolepsy and idiopathic hypersomnolence (IH). Currently diagnosis is by a multiple sleep latency test (MSLT) with protocols adapted from adults. The aim of this study was to describe the results of MSLTs in a paediatric population and assess whether a 5th nap altered diagnosis. Methods Retrospective analysis of 253 MSLTs at a single tertiary paediatric centre from May 2004 – Jan 2021 with consent obtained in 214 patients. Narcolepsy defined as a mean sleep latency (MSL) &lt;8min with ≥2 sleep onset REM (SOREM). IH defined as a MSL &lt; 8 minutes with &lt;2 SOREMs. Results outside these parameters were grouped as hypersomnolence not otherwise specified (HNOS), with ambiguous HNOS defined as MSL 8–12 minutes or ≥2 SOREM. Progress to date There were 108 (50%) females, 132 (62%) &gt;12 years old (range 3.3–19.4 years) and 17 patients had repeat studies. Narcolepsy was diagnosed in 48 (22%) and IH in 22 (10%). Criteria for ambiguous HNOS were met by 43 (20%) patients including 11 (5%) with MSL &gt;12 minutes with ≥2 SOREMs. A 5th nap was performed in 58 (27%) MSLTs which did not change the diagnosis. Obstructive sleep apnoea was diagnosed in 48 (22%) patients and 27 (13%) had elevated periodic limb movement index. Intended outcome and impact Applying current MLST criteria in children may significantly under-estimate diagnostic categories for paediatric EDS as evidenced by the ambiguous HNOS.

P130 An audit of urinary drug screening use in multiple sleep latency and maintenance of wakefulness testing in an Australian tertiary centre

Multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT) are objective measures of excessive daytime sleepiness, used in diagnosing and monitoring patients with sleep disorders. MSLT and MWT can be affected by substances such as psychotropics, stimulants, opioids and sedatives. Recent studies demonstrate high prevalence of positive urine drug screening (UDS) results in patients undergoing MSLT and MWT. We retrospectively audited patients who underwent UDS with MSLT/MWT at a tertiary centre from 1st January 2019 to 1st January 2020. The following data was collected: MSLT/MWT/UDS results, sleep disorder diagnosis/es, return to driving/work after testing and pre-existing and subsequent prescription of stimulants/wakefulness-promoting agents/psychotropics/sodium oxybate. Our cohort featured 32 patients (23 female). 29 MSLTs and 3 MWTs were performed. Median age was 31 years old. 13 patients were on wakefulness-promoting agents/psychotropics when tested, where 8 were on serotonin–norepinephrine reuptake inhibitors/selective serotonin reuptake inhibitors. 13 patients (~45%) had a reduced mean sleep latency (MSL), where 10 minutes was used as the cut-off. All 3 MWTs were within normal limits. 5 patients (~16%) had a positive UDS. 1 patient had a low MSL and tested positive for cannabinoids and opioids. The other 4 patients with normal MSL tested positive for benzodiazepines (2), cannabinoids (1) and opioids (1). All patients were cleared for work and 85% of patients who had a low MSL returned to work during follow-up. The rate of positive UDS in patients undergoing MSLT/MWT was comparable to existing publications and re-emphasizes the relevance of mandating UDS prior to MSLT/MWT.