Case Report: Insulinoma Presenting as Excessive Daytime Somnolence

Currently, undiagnosed insulinomas remain a difficult clinical dilemma because its symptoms in most cases can easily be misdiagnosed as other diseases. In this article, we present the case of a 14-year-old girl who presented to our hospital with recurrent episodes of excessive daytime sleepiness and abnormal behavior during sleep that had been going on for 3 months. Insulinoma is a rare neuroendocrine tumor that causes excessive release of insulin, resulting in episodes of hypoglycemia. It usually manifests as autonomic sympathetic symptoms. These symptoms resolved rapidly with the administration of glucose. After successful removal of the tumor, daytime sleepiness and abnormal nighttime behavior of the patient did not reappear.

A Non-Invasive Determination of Ketosis-Induced Elimination of Chronic Daytime Somnolence in a Patient with Late-Stage Dementia (Assessed with Type 3 Diabetes): A Potential Role of Neurogenesis

Background: The study involved a female patient diagnosed with late-stage dementia, with chronic daytime somnolence (CDS) as a prominent symptom. Objective: To explore whether her dementia resulted from Type 3 diabetes, and whether it could be reversed through ketosis therapy. Methods: A ketogenic diet (KD) generating low-dose 100 μM Blood Ketone Levels (BKL) enhanced by a brief Ketone Mono Ester (KME) regimen with high-dose 2–4 mM BKLs was used. Results: Three sets of data describe relief (assessed by % days awake) from CDS: 1) incremental, slow, time-dependent KD plus KME-induced sigmoid curve responses which resulted in partial wakefulness (0–40% in 255 days) and complete wakefulness (40–85% in 50 days); 2) both levels of wakefulness were shown to be permanent; 3) initial permanent relief from CDS with low-dose ketosis from 6.7% to 40% took 87 days. Subsequent low-dose recovery from illness-induced CDS (6.9% to 40%) took 10 days. We deduce that the first restoration involved permanent repair, and the second energized the repaired circuits. Conclusion: The results suggest a role for ketosis in the elimination of CDS with the permanent functional restoration of the awake neural circuits of the Sleep-Wake cycle. We discuss whether available evidence supports ketosis-induced bioenergetics alone or whether other mechanisms of functional renewal were the basis for the elimination of CDS. Given evidence for permanent repair, two direct links between ketosis and neurogenesis in the adult mammalian brain are discussed: Ketosis-induced 1) brain-derived neurotrophic factor, resulting in neural progenitor/stem cell proliferation, and 2) mitochondrial bioenergetics-induced stem cell biogenesis.

Sleep Disorders and Future Diagnosis of Parkinsonism: A Prospective Study Using the Canadian Longitudinal Study on Aging

Background: Earlier detection of parkinsonism, specifically during its prodromal stage, may be key to preventing its progression. Previous studies have produced contradictory results on the association between sleep symptoms and prodromal parkinsonism. Objective: We conducted a prospective study within the Canadian Longitudinal Study on Aging (CLSA) to determine whether self-reported symptoms of insomnia, somnolence, apnea, and restless legs syndrome predate the diagnosis of parkinsonism after three years of follow-up. Methods: At baseline, amongst other information, participants completed a questionnaire for difficulty initiating or maintaining sleep, daytime somnolence, snoring or stopping breathing during sleep, and symptoms of restless legs syndrome. After 3 years of follow-up, baseline responses from participants who self-reported a new diagnosis of parkinsonism (cases) were compared to those who did not (controls). For each case, 10 controls were individually matched by age, sex, education, BMI, caffeine, smoking, and alcohol. Binary unconditional logistic regression models were used to estimate the association between sleep symptoms and new-onset parkinsonism, adjusting for age, sex, education, BMI, smoking, alcohol, and caffeine. Results: We identified 58 incident-parkinsonism cases and 580 matched controls (65.5%male, mean age = 69.60, SD = 8.0). Baseline symptoms of sleep-onset insomnia (12.1%vs. 13.0%, Adjusted OR[95%CI] = 0.87[0.32,2.33]), sleep-maintenance insomnia (24.1%vs. 20.2%, AOR = 1.01[0.46,2.20]), daytime somnolence (8.6%vs. 7.4%, AOR = 1.11[0.37,3.39]), obstructive sleep apnea (27.3%vs. 26.2%, AOR = 0.84[0.40,1.79]), and restless leg syndrome (20.6%vs. 9.9%, AOR = 1.34[0.42,4.25]) were similar among those who developed parkinsonism and those who did not. Conclusion: Symptoms of insomnia, somnolence, apnea, and restless legs did not predate a new diagnosis of parkinsonism over 3 years.

P058 Neural aperiodic activity as a novel objective measure of daytime somnolence

Background Current assessment of excessive daytime somnolence (EDS) requires subjective measurements like the Epworth Sleepiness Scale (ESS), and/or resource heavy sleep laboratory investigations. Electroencephalographic (EEG) measures index intrinsic properties of the central nervous system. One such component is aperiodic neural activity which is thought to reflect excitation/inhibition ratios of neural populations and is altered in various states of consciousness. From this perspective, resting-state aperiodic activity may be a potential biomarker for hypersomnolence. We aim to analyse retrospective EEG data from patients who underwent a Multiple Sleep Latency Test (MSLT) and determine if aperiodic activity is predictive of subjective and objective measures of EDS. Methods Participants having undergone laboratory polysomnogram (PSG) and next day MSLT will be grouped into those with and without sleepiness (mean sleep latency (MSL) of < 8min and > 10min respectively). Forty patients in each group (n=80) will be assessed. The primary objective is to compare the aperiodic slope between these groups, and secondary objectives comparing aperiodic activity with ESS and time of day. Data will be analysed using linear mixed-effect models. Simple linear regressions will be performed between the aperiodic slope and MSL and ESS, with R2 values used to estimate of effect size. Progress: Formal ethics approval has been submitted and is pending. Intended Outcome and Impact In this exploratory study we hypothesise that EDS is associated with a lower aperiodic exponent/flatter slope, and hope to provoke further investigation of this metric as a novel biomarker for sleepiness.

Anxiety, Insomnia, and Napping Predict Poorer Sleep Quality in an Autistic Adult Population

Autistic adults have a high prevalence of sleep problems and psychiatric conditions. In the general population sleep problems have been associated with a range of demographic and lifestyle factors. Whether the same factors contribute to different types of disturbed sleep experienced by autistic adults is unknown and served as the main aim of this study. An online survey was conducted with 493 autistic adults. Demographic information (e.g., age, gender), about lifestyle (e.g., napping), and information about comorbid conditions was collected. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and the Epworth Sleepiness Scale (ESS) was used to assess daytime somnolence. Stepwise multiple regression analyses were used to examine predictors of each subscale score on the PSQI, as well as PSQI and ESS total scores. Results indicated that individuals who reported having a diagnosis of anxiety and insomnia were more likely to have poorer sleep quality outcomes overall. Furthermore, individuals who reported habitually napping had higher daytime dysfunction, increased sleep disturbances, and increased daytime sleepiness. These results provide novel insights into the demographic and lifestyle factors that influence sleep quality and daytime somnolence in autistic adults and can be used for targeted sleep interventions.

695 Cannabinoids and Sleep Health in Patients with Chronic Neuropathic Pain: A Systematic Review and Meta-Analysis

Introduction Neuropathic pain (NP) syndromes are debilitating conditions which can impact sleep health and overall quality of life significantly. Pharmacological treatment with cannabinoids has not been evaluated for its impact on sleep health. The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain control, and patient impression of treatment efficacy. Methods We reviewed randomized controlled trials comparing synthetic and natural cannabinoids (CB) to placebo in patients with central and peripheral neuropathic pain syndromes. A systematic search of the standard literature databases was conducted, including randomized controlled trials evaluating the pharmacological treatment of NP syndromes using cannabinoids. Data on NRS pain scales, sleep quality, daytime somnolence, nausea, dizziness, and patient global impression of change (PGIC) scores were recorded. Meta-analysis using the random effects model was conducted where appropriate. Results Of the 3536 studies screened, a total of 8 randomized controlled trials including 1051 patients (placebo: 478 patients; CB: 573 patients) with neuropathic pain were included. Cannabinoids included in the studies were Sativex (GW-1000–02), Nabilone, and medical cannabis preparations with THC dose ranging from 1mg to 130mg per day. Pain scores were significantly reduced in the CB group (standardized difference in means (SDM) = -0.236, 95% CI=-0.375 to -0.100, p-value = 0.001) compared to placebo (Figure 1). Significant improvement in sleep quality (Figure 2) was also observed in the CB group (SMD 0.389, 95% CI, 0.233 to 0.546, p<0.013). Additionally, patients in the CB group were more likely to report improvement in PGIC scores (OR=2.3, 95% CI 1.37 to 3.9, p=0.002) compared to patients treated with placebo (Figure 3). Notably, CB-treated patients were more likely to experience daytime somnolence (OR=2.2, 95% CI 1.3 to 3.9, p=0.004), nausea (OR=1.7, 95% CI 1.1 to 2.5, p=0.02), and dizziness (OR=3.8, 95% CI 2.6 to 5.7, p<0.001). Conclusion Cannabinoids are useful agents for NP as evidenced by significant improvement in pain, sleep quality, and PGIC. With the advent of new agents and more refined cannabis derivatives, further research is needed to comprehensively explore treatment effectiveness. Future work should incorporate clinically validated measures of sleep health to better evaluate this outcome. Support (if any):

The prevalence of risk for Obstructive Sleep Apnea among type 2 diabetes mellitus patients

Obstructive sleep apnea (OSA) is a common medical disorder and Type 2 Diabetes mellitus (T2DM) is an endocrine disorder where both of them commonly coexist. T2DM will disturb sleep patterns and disturbed sleep may predispose to insulin resistance resulting in T2DM. The study aim is to evaluate the prevalence of risk for Obstructive sleep apnea among T2DM patients based on patient demographic variables (age, gender and Body Mass Index (BMI)) and Berlin Questionnaire (BQ). In this cross-sectional study a total of 111 patients were included and the prevalence of risk was determined based on the BQ categories and the percentage was calculated accordingly. In BQ, Category 1 includes five questions based on snoring, category 2 includes three questions based on daytime somnolence and category 3 includes two questions based on BMI. These categories were marked as positive if the responses for snoring or daytime somnolence indicate persistent symptoms (> 3-4 times/week). Third category includes the patient’s BMI greater than 30 kg/m2 (obese) indicates positive score. In this study, the patients above 61 years (100%) and obese (94%) were at a higher risk for OSA. Based on the BQ, more positive (89.19%) responses were observed in category 1 (snoring) when compared to category 2 (40.54%) and 3 (74.77%) which concluded that T2DM patients are at a high risk (HR) for developing Obstructive Sleep Apnea.

Sleep Alterations in Female College Students with Migraines

Background: Many factors are thought to potentially trigger migraines, among which sleep disturbances are one of the most frequently reported. Both sleep disorders and migraines affect more women than men. This study aims to analyze sleep alterations in young adult women with migraines and how they are related to the presence, frequency, intensity, and disability of migraines in this population. Methods: Fifty-one female university students with physician-diagnosed migraines and 55 healthy female university students completed surveys assessing demographic information and frequency, intensity, and disability of migraines and sleep quality variables. Results: No differences in sleep quality were found between migraine subjects and healthy women (p = 0.815), but women with migraines presented higher daytime somnolence (p = 0.010), greater sleep disruptions (p = 0.002), and decreased sleep adequacy (p = 0.019). The presence of a migraine was significantly related to daytime somnolence (p = 0.003) and sleep disruptions (p = 0.021). Migraine-related disability was associated with sleep disruptions (p = 0.002), snoring (p = 0.016), and a decreased quantity of sleep (p = 0.040). Migraine frequency was related to sleep disturbance (p = 0.003) and snoring (p < 0.001). The intensity of migraines was associated with sleep disruptions (p = 0.004). Conclusions: Our results suggest a relationship between migraines and sleep alterations.