Lucie Barateau

Absence of GABA‐A receptor potentiation in central hypersomnolence disorders

The pathophysiology of idiopathic hypersomnia (IH) remains unclear. Recently, cerebrospinal fluid (CSF)‐induced enhancement of γ‐aminobutyric acid (GABA)‐A receptor activity was found in patients with IH compared to controls.

Absence of γ-aminobutyric acid-a receptor potentiation in central hypersomnolence disorders.

The pathophysiology of idiopathic hypersomnia (IH) remains unclear. Recently, cerebrospinal fluid (CSF)‐induced enhancement of γ‐aminobutyric acid (GABA)‐A receptor activity was found in patients with IH compared to controls.

Temporal changes in the Cerebrospinal Fluid Level of Hypocretin-1 and Histamine in Narcolepsy.

Abstract Study Objectives: To follow the temporal changes of cerebrospinal fluid (CSF) biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. Methods: From 2007 to 2015, 170 human leukocyte antigen (HLA) DQB1*06:02-positive patients with primary narcolepsy and definite (n = 155, 95 males, 60 females, 36 children) or atypical cataplexy (n = 15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95.5% and 20% of patients with definitive and atypical cataplexy, respectively. CSF hypocretin-1 (n = 6) and histamine/tele-methylhistamine (n = 5) levels were assessed twice (median interval: 14.4 months) in four patients with definite and in two with atypical cataplexy and hypocretin level greater than 100 pg/mL at baseline. Results: CSF hypocretin levels decreased from normal/intermediate to undetectable levels in three of the four patients with definite cataplexy and remained stable in the other (>250 pg/mL). Hypocretin level decreased from 106 to 27 pg/mL in one patient with atypical cataplexy, and remained stable in the other (101 and 106 pg/mL). CSF histamine and tele-methylhistamine levels remained stable, but for one patient showing increased frequency of cataplexy and a strong decrease (−72.5%) of tele-methylhistamine levels several years after disease onset. No significant association was found between relative or absolute change in hypocretin level and demographic/clinical features. Conclusions: These findings show that in few patients with narcolepsy with cataplexy, symptoms and CSF marker levels can change over time. In these rare patients with cataplexy without baseline hypocretin deficiency, CSF markers should be monitored over time with potential for immune therapies in early stages to try limiting hypocretin neuron loss.

Vitamin D deficiency in type 1 narcolepsy: a reappraisal

OBJECTIVESnNarcolepsy type 1 (NT1) is considered to be an immune-mediated disease in which environmental factors, such as vitamin D, might play a major role. The association between NT1 and vitamin D deficiency has previously been reported. The aim of this case-control study was to reassess vitamin D levels in a large clinic-based adult and paediatric population of patients with NT1 by considering several potential confounding factors.nnnMETHODSnThe serum level of 25-hydroxyvitamin D (25OHD) was measured in 174 Caucasian patients with NT1 and 174 controls. Demographic and clinical features, body mass index (BMI), Pandemrix® vaccination, age, and season at the time of blood sampling were recorded. Between-group comparisons were made using univariate and multivariate logistic regression analyses. When appropriate, interaction terms were tested using the Wald Chi-squared test.nnnRESULTSnAge, BMI, and season of blood sampling were different between groups. Conversely, the 25OHD level and fraction of subjects with vitamin D deficiency (serum level <75u2009nmol/L: 46.6% of patients vs 48.3% of controls; <50u2009nmol/L: 20.7% vs 17.2%) did not differ between patients with NT1 and controls. Overall, vitamin D deficiency was more frequent in men, obese subjects, and in samples collected in winter, without any association with NT1. In the patients group, no significant association was found between vitamin D deficiency, NT1 duration and severity, treatment, and Pandemrix® vaccination.nnnCONCLUSIONSnVitamin D levels were not associated with NT1 in a large case-control population when potential demographic and clinical confounding factors were taken into account.

Diagnostic criteria for disorders of arousal: A video-polysomnographic assessment: Disorders of Arousal

To assess video‐polysomnographic (vPSG) criteria and their cutoff values for the diagnosis of disorders of arousal (DOAs; sleepwalking, sleep terror).

Depression and Hypersomnia: A Complex Association

Hypersomnolence is a clinically defined syndrome characterized by the association of prolonged nocturnal sleep, impaired arousal quality, and sleep inertia. Hypersomnolence is the major feature of central hypersomnias and is frequently reported in various mood disorders, such as major depressive disorder, bipolar disorder, or seasonal affective disorder. Assessment of hypersomnolence is challenging in depressed patients, with objective tests often in the normal range despite a high level of sleepiness complaint. On the other hand, many patients with central hypersomnias reported depressive symptoms. The self-assessment of mood symptoms in patients with central hypersomnias may overdiagnose depression with an overlap between both conditions.

Cardiac Sympathetic Activity differentiates Idiopathic and Symptomatic Rapid Eye Movement Sleep Behaviour Disorder

The pathophysiology of rapid eye movement sleep behavior disorder (RBD) associated with narcolepsy type 1 (NT1) is still poorly understood, potentially distinct from idiopathic RBD (iRBD), but may share affected common pathways. We investigated whether MIBG cardiac uptake differs between iRBD and NT1 comorbid with RBD. Thirty-four patients with NT1-RBD and 15 patients with iRBD underwent MIBG cardiac scintigraphy. MIBG uptake was measured by calculating the early and delayed heart to mediastinum (H/M) ratios. A delayed H/M ratio lower than 1.46 was considered abnormal based on a population of 78 subjects without neurological or cardiac diseases. Patients with iRBD were older, had an older RBD onset age and higher REM sleep phasic and tonic muscular activities than NT1-RBD. Lower delayed and early H/M ratios were associated with iRBD, but not with NT1-RBD, in crude and adjusted associations. The delayed H/M ratio differed between iRBD and controls, after adjustment, but not between patients with NT1-RBD and controls. In conclusion, the MIBG cardiac uptake difference between NT1-RBD and iRBD supports the hypothesis of different processes involved in RBD pathogenesis, providing for the first time a cardiac biomarker to differentiate those disorders.

Alternative diagnostic criteria for idiopathic hypersomnia: A 32-hour protocol: Idiopathic Hypersomnia

To assess the diagnostic value of extended sleep duration on a controlled 32‐hour bed rest protocol in idiopathic hypersomnia (IH).