Serum -Glycan Profiling of Patients with Narcolepsy Type 1 Using LC-MS/MS.

The neurological condition known as narcolepsy type 1 (NT1) is an uncommon condition marked by extreme daytime sleepiness, cataplexy, sleep paralysis, hallucinations, disrupted nocturnal sleep, and low or undetectable levels of orexin in the CSF fluid. NT1 has been hypothesized to be an immunological disorder; its treatment is currently only symptomatic, and misdiagnosis is not uncommon. This study compares the -glycome of NT1 patients with healthy controls in search of potential glycan biomarkers using LC-MS/MS.

LC-MS/MS Quantitation of HILIC-Enriched -glycopeptides Derived from Low-Abundance Serum Glycoproteins in Patients with Narcolepsy Type 1.

Glycoproteomic analysis is always challenging because of low abundance and complex site-specific heterogeneity. Glycoproteins are involved in various biological processes such as cell signaling, adhesion, and cell-cell communication and may serve as potential biomarkers when analyzing different diseases. Here, we investigate glycoproteins in narcolepsy type 1 (NT1) disease, a form of narcolepsy characterized by cataplexy-the sudden onset of muscle paralysis that is typically triggered by intense emotions.

Repeated measures of hypocretin-1 in Danish and Italian patients with narcolepsy and in controls.

Study Objectives: The assay currently used worldwide to measure cerebrospinal fluid hypocretin-1 (CSF-hcrt-1) for diagnosing narcolepsy uses a competitive radioimmunoassay with polyclonal anti-hcrt-1 antibodies. This assay detects multiple hypocretin-1 immunoreactive species in the CSF that are all derived from full-length hcrt-1. We aimed to revalidate CSF-hcrt-1 cut-offs for narcolepsy type 1 (NT1) diagnosis and to evaluate temporal changes in CSF-hcrt-1 levels in patients suspected of having central hypersomnia.

Multidisciplinary care of patients with narcolepsy during coronavirus disease 2019 pandemic in Italy via televisit: the TElemedicine for NARcolepsy feasibility study.

Study Objectives: Narcolepsy is a rare chronic central disorder of hypersomnolence with frequent endocrine-metabolic comorbidities. To address the complex care needs of patients during the COVID-19 emergency, we carried out a feasibility study of the TElemedicine for NARcolepsy (TENAR) protocol with the aim of assessing the feasibility of a multidisciplinary care approach via televisit for patients with narcolepsy.

Methods: A feasibility single open-arm study on the multidisciplinary care of children (>7 y.

The role of mtDNA haplogroups on metabolic features in narcolepsy type 1.

Narcolepsy type 1 (NT1) is due to selective loss of hypocretin (hcrt)-producing-neurons. Hcrt is a neuropeptide regulating the sleep/wake cycle, as well as feeding behavior. A subset of NT1 patients become overweight/obese, with a dysmetabolic phenotype.

Searching for Novel Candidate Biomarkers of RLS in Blood by Proteomic Analysis.

Purpose: We performed comparative proteomic analyses of blood of patients with RLS and healthy individuals aiming to identify potential biomarker and therapeutic target candidate for RLS.

Patients And Methods: Blood serum samples from 12 patients with a clinical diagnosis of RLS (8 females and 4 males, with a mean age of 68.52 years) and 10 healthy controls (5 females and 5 males, with a mean age of 67.

Onset of narcolepsy type 1 in a paraneoplastic encephalitis associated with a thymic seminoma.

Unlabelled: Narcolepsy type 1 results from probable autoimmune disruption of hypothalamic hypocretinergic neurons. Secondary narcolepsy can occur as a result of other conditions affecting the central nervous system, including limbic paraneoplastic encephalitis. We report the case of a 19-year-old patient presenting with acute-onset diurnal hypersomnolence, hyperphagia, sexual dysfunction, and psychiatric disturbances.

The importance of social zeitgeber in paediatric type 1 narcolepsy: What we can learn from the COVID-19 restrictions adopted in Italy?

The lockdown due to the new coronavirus pandemic (COVID-19) has led to unparalleled changes in several aspects of human behaviour. During the lockdown, the general population delayed sleep timing and spent more time in bed; however, little is known on the effects of COVID-19 restriction on children and adolescents suffering type 1 narcolepsy. In the last months of 2019, we performed follow-up actigraphy in 18 type 1 narcolepsy children and adolescents under stable pharmacological treatment with sodium oxybate.

Pre-treatment of blood samples reveal normal blood hypocretin/orexin signal in narcolepsy type 1.

The hypocretin/orexin system regulates arousal through central nervous system mechanisms and plays an important role in sleep, wakefulness and energy homeostasis. It is unclear whether hypocretin peptides are also present in blood due to difficulties in measuring reliable and reproducible levels of the peptides in blood samples. Lack of hypocretin signalling causes the sleep disorder narcolepsy type 1, and low concentration of cerebrospinal fluid hypocretin-1/orexin-A peptide is a hallmark of the disease.

Impact of COVID-19 pandemic lockdown on narcolepsy type 1 management.

Study Objectives: Narcolepsy type 1 (NT1) is a chronic rare hypersomnia of central origin requiring a combination of behavioral and pharmacological treatments. During the coronavirus disease 2019 (COVID-19) pandemic, in Italy the population was forced into a lockdown. With this study, we aimed to describe the lockdown impact on NT1 symptom management, according to different patients' working schedule.

REM Sleep Behavior Disorder in Children With Type 1 Narcolepsy Treated With Sodium Oxybate.

Objective: To study the effect of stable treatment with sodium oxybate (SO) on nocturnal REM sleep behavior disorder (RBD) and REM sleep without atonia (RSWA) that severely affected children with type 1 narcolepsy (NT1).

Methods: Nineteen children and adolescents with NT1 (9 female, mean age 12.5 ± 2.

Protocols of a diagnostic study and a randomized controlled non-inferiority trial comparing televisits vs standard in-person outpatient visits for narcolepsy diagnosis and care: TElemedicine for NARcolepsy (TENAR).

Background: Narcolepsy is a rare chronic sleep disorder that typically begins in youth. Excessive daytime sleepiness is the main disabling symptom, but the disease is often associated with severe endocrine-metabolic and psychosocial issues, worsened by a long diagnostic delay, requiring a multidisciplinary approach. The scarcity of reference Sleep Centres forces the patient and family to travel for seeking medical consultations, increasing the economic and psychosocial burden of the disease.

Flow cytometry T cell profiling in a recent-onset narcoleptic type 1 child: a case report.

Background: Recent studies have disclosed the involvement of T cells in narcolepsy type 1 pathogenesis. We characterized the T cell subsets distribution in a recent-onset child at two different time points, two months from disease onset (T0) and 10 months later (follow-up), respectively.

Methods: Peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) lymphocytes were characterized by flow cytometry at both evaluations.

Development and validation of volumetric absorptive microsampling coupled with UHPLC-MS/MS for the analysis of gamma-hydroxybutyric acid in human blood.

A volumetric microsampling (VAMS) device (20 μl) was evaluated and validated for the analysis of γ-hydroxybutyric acid (GHB) in venous blood using a simple ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. GHB was extracted from VAMS device by acetonitrile, after a re-hydration step in a temperature-controlled ultrasonic bath at 60°C for 10 min. Chromatographic analysis was carried out on a Kinetex C column using 0.

Cerebrospinal fluid biomarkers of neurodegeneration in narcolepsy type 1.

Study Objectives: To measure the levels of five neurodegenerative biomarkers in the cerebrospinal fluid (CSF) of patients with narcolepsy type 1 (NT1) with variable disease duration.

Methods: Following a standardized protocol of CSF collection and storage, we measured CSF total- and phosphorylated-tau, amyloid-beta 1-40 and 1-42, and neurofilament light chain (NfL) proteins in 30 nonneurological controls and 36 subjects with NT1, including 14 patients with recent disease onset (i.e.

Biomarkers for REM sleep behavior disorder in idiopathic and narcoleptic patients.

To search for discriminating biomarkers, 30 patients with idiopathic rapid-eye-movements sleep behavior disorder (iRBD) were compared with 17 patients with RBD within narcolepsy type 1. Both groups underwent extensive examinations, including skin biopsy searching for phosphorylated α-synuclein deposits and whole-night video-polysomnography. Skin biopsy was positive for phosphorylated α-synuclein deposits in 86.

Cardiovascular autonomic dysfunction, altered sleep architecture, and muscle overactivity during nocturnal sleep in pediatric patients with narcolepsy type 1.

Study Objectives: Arterial blood pressure (ABP) decreases during sleep compared with wakefulness and this change is blunted in mouse models of and adult patients with narcolepsy type 1 (NT1). We tested whether: (1) pediatric patients with NT1 have similar cardiovascular autonomic abnormalities during nocturnal sleep; and (2) these abnormalities can be linked to hypocretin-1 cerebrospinal fluid concentration (CSF HCRT-1), sleep architecture, or muscle activity.

Methods: Laboratory polysomnographic studies were performed in 27 consecutive drug-naïve NT1 children or adolescents and in 19 matched controls.

Excessive daytime sleepiness in narcolepsy and central nervous system hypersomnias.

Purpose: Excessive daytime sleepiness (EDS) is the core complaint of central nervous system (CNS) hypersomnias. In this mini-review, we summarized EDS features in CNS hypersomnias to provide a guide for differential diagnosis purposes.

Methods: A review of recent literature was performed to provide an update in CNS hypersomnias.

Novel biomarker signatures for idiopathic REM sleep behavior disorder: A proteomic and system biology approach.

Objective: To perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes.

Methods: Serum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography-mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos Data were analyzed with a systems biology approach to identify altered pathways in RBD.

Results: We identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls.

Segmental Hair Testing of Triazolam to Unmask a Suspected Case of Idiopathic Recurrent Stupor.

Stupor is a diagnostic challenge at emergency department. Differential diagnosis includes idiopathic recurrent stupor, formerly attributed to "endozepine-4" accumulation. This condition has been recently questioned because many suspected cases resulted in exogenous benzodiazepine intake that eludes the conventional toxicological assay.