Ramin Khatami

Study Objectives: E-cigarettes can help smokers quit, but how e-cigarettes used for tobacco smoking cessation impact sleep is still unclear. The primary objective was to evaluate the effect of e-cigarettes for smoking abstinence on sleep quality. Secondary objectives included subscales of sleep quality. Methods: We conducted a secondary analysis of the Efficacy, Safety, and Toxicology of electronic nicotine delivery systems for smoking cessation (ESTxENDS) randomized controlled trial, which included adult smokers in Switzerland (five sites, 7.2018-6.2021). The intervention group received free e-cigarettes and e-liquids over 6 months plus standard-of-care smoking-cessation counseling (SOC); the control group received SOC alone. The primary outcome was overall self-reported sleep quality at 6 months, measured by the Pittsburgh Sleep Quality Index (PSQI). We considered a minimal clinically important difference (MCID) of 2.5–5. Secondary outcomes included PSQI subscales. We used adjusted linear regressions with inverse probability of attrition weights (IPAW). Results: ESTxENDS included 1246 participants. Of these, 831 participants completed the PSQI at follow-up. For the primary outcome, there was no significant difference in PSQI score between groups (b = −0.20, p = .256, adjusted analyses with IPAW). For PSQI subscales, only sleep efficiency was significantly better in the intervention group (b = 1.87, p = .018), below MCID. Conclusion: E-cigarettes added to SOC for tobacco smoking abstinence did not significantly alter participant’s self-reported sleep quality compared to SOC alone. Clinicians can inform patients willing to quit smoking with e-cigarettes that their use is not likely to disrupt their perceived sleep quality on average.

Objective: The international Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (iSPHYNCS) is a multicenter study aimed at identifying novel biomarkers for central disorders of hypersomnolence (CDH). We analyzed questionnaires and metadata to uncover distinct clusters of participants and explore phenotypic variability within CDH. Methods: Data were collected from 227 patients with CDH and 33 healthy controls. Participants completed validated clinical questionnaires and study-specific questions addressing CDH-related symptoms such as excessive daytime sleepiness, fatigue, cataplexy, disrupted sleep, and sleep paralysis. Demographic metadata (age, gender, BMI) were included. After excluding participants with missing over 30% of data (n = 40), missing values were imputed using a multiple random forest algorithm. A robust clustering pipeline was employed: (1) random sampling of 60% of the dataset, (2) dimensionality reduction via UMAP, (3) K-means clustering, and (4) consensus clustering across 500 iterations. Post hoc analysis was performed to identify biomarkers in data not used for clustering. Results: We identified four distinct clusters. One predominantly comprised healthy controls, while another primarily contained individuals with narcolepsy type 1 (NT1). Two clusters represented predominantly the narcolepsy borderland group (NBL), with one distinctly characterized by higher symptom severity and psychiatric comorbidities. Conclusions: The clustering pipeline produced reproducible results, with the NT1 and healthy control clusters serving as internal validation. The differentiation between the two NBL clusters aligns with prior studies, suggesting a possible NBL subtype marked by increased fatigue and psychiatric comorbidities. These findings emphasize the phenotypic heterogeneity of CDH and the potential for cluster-based approaches in management. Statement of Significance: Central disorders of hypersomnolence (CDH) are complex and heterogeneous, challenging conventional diagnostic frameworks. This study employed an innovative clustering pipeline to identify four distinct phenotypic clusters within a large, multicenter cohort. The identification of a subtype in the narcolepsy borderland group with a high psychiatric burden adds critical insights into the variability of CDH and underscores the need for personalized diagnostic and therapeutic strategies. The internal validation of clusters through healthy controls and NT1 phenotypes enhances confidence in the pipeline’s robustness. Furthermore, the study highlights the potential for integrating clinical data to define disease severity and developing therapeutic strategies. These findings pave the way for novel approaches to understanding and managing CDH.

Background: Stimulants are potent treatments for central hypersomnolence disorders or attention-deficit/hyperactivity disorders/attention deficit disorders but concerns have been raised about their potential negative consequences and their increasing prescription rates. Objective: We aimed to describe stimulant prescription trends in Switzerland from 2014 to 2021. Second, we aimed to analyze the characteristics of individuals who received stimulant prescriptions in 2021 and investigate the link between stimulant prescriptions and hospitalization rates in 2021, using hospitalization as a potential indicator of adverse health outcomes. Methods: Longitudinal and cross-sectional data from a large Swiss health care insurance were analyzed from all insureds older than 6 years. The results were extrapolated to the Swiss general population. We identified prescriptions for methylphenidate, lisdexamfetamine, modafinil, and sodium oxybate and calculated prevalences of each drug prescription over the period from 2014 to 2021. For 2021 we provide detailed information on the prescribers and evaluate the association of stimulant prescription and the number and duration of hospitalization using logistic regression models. Results: We observed increasing prescription rates of all stimulants in all age groups from 2014 to 2021 (0.55% to 0.81%, 43,848 to 66,113 insureds with a prescription). In 2021, 37.1% (28,057 prescriptions) of the medications were prescribed by psychiatrists, followed by 36.1% (n=27,323) prescribed by general practitioners and 1% (n=748) by neurologists. Only sodium oxybate, which is highly specific for narcolepsy treatment, was most frequently prescribed by neurologists (27.8%, 37 prescriptions). Comorbid psychiatric disorders were common in patients receiving stimulants. Patients hospitalized in a psychiatric institution were 5.3 times (odds ratio 5.3, 95% CI 4.63‐6.08, P <.001) more likely to have a stimulant prescription than those without hospitalization. There were no significant associations between stimulant prescription and the total length of inpatient stay (odds ratio 1, 95% CI 1‐1, P =.13). Conclusions: The prescription of stimulant medication in Switzerland increased slightly but continuously over years, but at lower rates compared to the estimated prevalence of central hypersomnolence disorders and attention-deficit/hyperactivity disorders/attention deficit disorders. Most stimulants are prescribed by psychiatrists, closely followed by general practitioners. The increased odds for hospitalization to psychiatric institutions for stimulant receivers reflects the severity of disease and the higher psychiatric comorbidities in these patients.

Introduction Increased narcolepsy type 1 (NT1) incidence rates have been reported globally in 2010, and were linked to the type A H1N1 2009-2010 influenza pandemic and Pandemrix vaccination. A European child-specific NT1 incidence peak was additionally observed in 2013 post the H1N1 pandemic. Thus, the relationship between NT1 and influenza infection remains unclear. Whether other influenza viruses may also trigger NT1 or other central disorders of hypersomnolence (CDH), is unknown. This study investigated annual European incidence patterns of all CDH in complete samples from multiple European centers, in relation to the severity of individual flu strains in preceding influenza seasons. Methods Incidence rates of NT1 (N=981) and the combined group of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) (N=545) from eight European countries were temporally analysed to identify possible incidence peaks from 1995 to 2019. Linear mixed models and spearman correlations were conducted between hypersomnolence disorder incidence rates and the number of influenza infections of preceding influenza season, split for types A H1N1 and H3N2, and in the Netherlands also types B Victoria and Yamagata influenza. Results 2010 and 2013 incidence peaks were present in NT1, and a 2010 children peak was unexpectedly found in the combined group of NT2 and IH. Both hypersomnolence groups exhibited a significantly positive relationship with preceding H1N1 influenza season severity and a negative relationship with H3N2 influenza. NT1 was additionally significantly positively correlated with influenza type B Victoria in the Netherlands and showed highest correlation in children. Conclusions Besides H1N1 influenza, the temporal association and severity correlation suggest that influenza type B Victoria may be a novel potential trigger for NT1 that requires further investigation. We additionally provide insights into possible immune-related pathophysiologies of NT2 and IH associated with the 2009-2010 H1N1 influenza pandemic. Further immunological investigations are warranted to unravel the complexities of these relationships and their implications for CDH.

Introduction and aims: Narcolepsy type 1 (NT1) is a central disorder of hypersomnolence (CDH) characterized by excessive daytime sleepiness and cataplexy. The Swiss Narcolepsy Scale (SNS), which includes the updated and short (sSNS) versions, has recently been introduced as a reliable diagnostic tool for identifying NT1. This study aims to assess the validity of the SNS scales in a new cohort of patients with CDH, while also introducing the French and Italian versions of the SNS and providing a summary of the existing literature on SNS. Materials and methods: The current study is based on the international Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (iSPHYNCS) which aims to identify new biomarkers for CDH. Diagnostic accuracy of the SNS was assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value. Results: In our population, 108 participants with suspected CDH (including 28 NT1 patients) and 14 healthy controls completed the scale. Original SNS, updated SNS and sSNS scores showed a high sensitivity (86%, 89% and 79%, respectively) and high specificity (96%, 90% and 95%, respectively) for diagnosing NT1 compared to other CDH. The French version was completed by 5 participants, and the Italian version by 8 participants. Regarding previous studies, the SNS has now been assessed in six different populations, involving a total of 1247 subjects (including 326 with narcolepsy with cataplexy/NT1), suggesting high sensitivity (85–100%) and specificity (86–100%) of the SNS for the diagnosis of NT1. Conclusion: The SNS is a simple screening tool validated in seven languages (German, English, French, Italian, Dutch, Turkish and Japanese), demonstrating high sensitivity and specificity for the diagnosis of NT1.

Sleep-related eating disorder (SRED) is a relatively rare but probably underestimated disorder, where affected patients exhibit nocturnal eating episodes with impaired consciousness and subsequent amnesia. SRED has originally been classified as NREM (non-rapid eye movement) parasomnia, with an obviously high number of concomitant sleep disorders. We suggest that SRED may represent a heterogenous disease, based on accumulating data in recent studies. Some SRED patients may be better classified as sleep-related movement disorders with an underlying dopaminergic dysfunction. Hypnotic drugs may play a crucial role in triggering amnestic SRED in both parasomnic and sleep-related movement-disordered SRED.

We present a new study design aiming to enhance the understanding of the mechanism by which continuous theta burst stimulation (cTBS) or intermittent theta burst stimulation (iTBS) paradigms elicit cortical modulation. Using near-infrared spectroscopy (NIRS), we compared the cortical hemodynamics of the previously inhibited (after cTBS) or excited (after iTBS) left primary motor cortex (M1) as elicited by single-pulse TMS (spTMS) in a cross-over design. Mean relative changes in hemodynamics within 6 s of the stimulus were compared using a two-sample t-test (p < 0.05) and linear mixed model between real and sham stimuli and between stimuli after cTBS and iTBS. Only spTMS after cTBS resulted in a significant increase (p = 0.04) in blood volume (BV) compared to baseline. There were no significant changes in other hemodynamic parameters (oxygenated/deoxygenated hemoglobin). spTMS after cTBS induced a larger increase in BV than spTMS after iTBS (p = 0.021) and sham stimulus after cTBS (p = 0.009). BV showed no significant difference between real and sham stimuli after iTBS (p = 0.37). The greater hemodynamic changes suggest increased vasomotor reactivity after cTBS compared to iTBS. In addition, cTBS could decrease lateral inhibition, allowing activation of surrounding areas after cTBS.