Cataplexy, Idiopathic Hypersomnia, Narcolepsy
Conditions
Keywords
orexin/hypocretin, sleepiness
Brief summary
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.
Interventions
DIAGNOSTIC_TESTQuantitative mass spectrometry assay
ORX-A determination by quantitative mass spectrometry
Sponsors
University Hospital, Montpellier
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 8 years * Complaint of hypersomnolence and suspected central hypersomnolence * Benefiting from a standardised assessment: clinical, biological and neurophysiological * Lumbar puncture necessary for the assessment * Sufficient cerebrospinal fluid taken for biological analysis (at least 1 ml) * Signed informed consent
Exclusion criteria
* Contraindication to lumbar puncture * Secondary hypersomnolence * Refusal to participate in the study or refusal of the lumbar puncture * Adult protected by law, or subject deprived of liberty, by judicial or administrative decision or patient under guardianship or curatorship * Subject not affiliated to the French social security system * Pregnant or breastfeeding woman
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Orexin-A dosage by Multiple Reaction Monitoring Mass Spectrometry | Day 1 (=day of inclusion) | Multiple Reaction Monitoring mass spectrometry for orexin-A dosage in cerebrospinal fluid |
| Orexin-A dosage by radioimmunoassay | Day 1 | Radioimmunoassay for orexin-A dosage in cerebrospinal fluid |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Age of onset of hypersomnia symptoms | Day 1 | — |
| Frequency of cataplexy | Up to 24 hours | — |
| Characteristics of cataplexy | Up to 24 hours | — |
| Average duration of cataplexy | Up to 24 hours | — |
| Epworth sleepiness scale (ESS) | Day 1 | the score will be between 0 and 24, higher scores mean a worse outcome |
| Narcolepsy severity scale (NSS) | Day 1 | the score will be between 0 and 57, higher scores mean a worse outcome |
| Hypersomnolence severity scale (IHSS) | Day 1 | the score will be between 0 and 50, higher scores mean a worse outcome |
| Insomnia severity index | Day 1 | the score will be between 0 and 32, higher scores mean a worse outcome |
| Iterative sleep latency tests (TILE) | Up to 24 hours | — |
| Presence of the HLA allele DQB1*06:02 | Day 1 | — |
Countries
France
Outcome results
None listed