Spectrometry (MRM) Versus I 125 Radioimmunoassay (RIA) for Quantification of Orexin-A of Patients With Hypersomnolence

In humans, selective loss of orexin neurons is responsible for type 1 narcolepsy (NT1), or narcolepsy with cataplexy, or orexin deficiency syndrome.The International Classification of Sleep Disorders 3rd edition (ICSD-3) distinguishes between hypersomnolence of central origin: NT1, narcolepsy type 2 (NT2), or narcolepsy without cataplexy, and idiopathic hypersomnia (HI). These rare conditions are all characterised by hypersomnolence (excessive daytime sleepiness, or excessive need for sleep), which is the primary and often most disabling symptom. A level of ORX-A in cerebrospinal fluid (CSF) (<110 pg/mL) is a very sensitive and specific biomarker of NT1, currently sufficient for the diagnosis of this condition. In contrast, ORX neurons are thought to be intact in IH and NT2, and the pathophysiological mechanisms underlying these diseases remain unknown. Thus, their diagnosis is based solely on clinical and electrophysiological criteria.The objective of this project is to determine the validity of a mass spectrometric technique for the determination of ORX-A in the cerebral spinal fluid of patients suffering from hypersomnolence in comparison with the radioimmunoassay which is the reference technique.

Inclusion Criteria:Age ≥ 8 yearsComplaint of hypersomnolence and suspected central hypersomnolenceBenefiting from a standardised assessment: clinical, biological and neurophysiologicalLumbar puncture necessary for the assessmentSufficient cerebrospinal fluid taken for biological analysis (at least 1 ml)Signed informed consentExclusion Criteria:Contraindication to lumbar punctureSecondary hypersomnolenceRefusal to participate in the study or refusal of the lumbar punctureAdult protected by law, or subject deprived of liberty, by judicial or administrative decision or patient under guardianship or curatorshipSubject not affiliated to the French social security systemPregnant or breastfeeding woman