Cardiovascular Events, Sleep Apnoea, and Pulmonary Hypertension in Primary Sjögren's Syndrome: Data from the French Health Insurance Database.

Primary Sjögren's syndrome (pSS) is an autoimmune disease, associated with a high risk of lymphoma. Mounting evidence suggests that cardiovascular morbidity and mortality are higher in patients with pSS, although data are heterogeneous. The aim of this study was to assess whether pSS patients are at higher risk of hospitalisation for cardiovascular events (CVEs), venous thromboembolic events (VTEs), pulmonary hypertension (PH), and sleep apnoea syndrome (SAS). Through a nationwide population-based retrospective study using the French health insurance database, we selected new-onset pSS in-patients hospitalised between 2011 and 2018. We compared the incidence of CVEs (ischemic heart diseases (IHDs), strokes, and heart failure), SAS, VTEs, and PH with an age- and sex-matched (1:10) hospitalised control group. The calculations of adjusted hazard ratios (aHR) included available confounding factors. We studied 25,661 patients hospitalised for pSS compared with 252,543 matched patients. The incidence of hospitalisation for IHD, SAS, and PH was significantly higher in pSS patients (aHR: 1.20 (1.06-1.34); p = 0.003, aHR: 1.97 (1.70-2.28); p < 0.001, and aHR: 3.32 (2.10-5.25); p < 0.001, respectively), whereas the incidence of stroke, heart failure, and VTE was the same between groups. Further prospective studies are needed to confirm these results and to explore the pathophysiological mechanisms involved.

Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study.

STUDY OBJECTIVES: Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population. METHODS: We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview. RESULTS: An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls. CONCLUSIONS: We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other hypersomniacs, without any change in alcohol dependence or abuse frequency. Although disruption of hypocretin signaling in rodents reduces drug-seeking behaviors, our results do not support that hypocretin deficiency constitutes a protective factor against the development of drug addiction in humans.

Preliminary results on CSF biomarkers for hypothalamic dysfunction in Kleine-Levin syndrome.

OBJECTIVE: To measure CSF biomarkers of hypothalamic dysfunction in patients with typical Kleine-Levin syndrome (KLS) during symptomatic and asymptomatic periods. PATIENTS/METHODS: Two patients with typical KLS were admitted during symptomatic and asymptomatic periods to a research Sleep Disorders Center. Cerebrospinalfluid (CSF) hypocretin-1, histamine (HA), and its major metabolite tele-methylhistamine (t-MHA) levels were measured in two KLS patients in and out of episode. RESULTS: CSF biomarkers of hypothalamic dysfunction measured in two KLS patients in and out of episode revealed low hypocretin levels (within the narcolepsy-cataplexy range) during a hypersomnia episode in the more severe patient, and a 42% decrease (although within normal range) in the second patient. CSF HA and t-MHA measurements in and out of episode revealed a two-fold in-episode decrease in HA in the more severe patient, with no significant change for the second patient, nor for t-MHA levels. CONCLUSION: We reported reversible changes in CSF hypothalamic biomarkers in a typical patient with KLS that reinforces the hypothesis that in some patients KLS episodes may be caused by recurrent functional alterations of the hypothalamus.