International Swiss Primary Hypersomnolence and Narcolepsy Cohort Study

Inclusion Criteria: Study participants:

• Subjective complaints of Excessive daytime sleepiness (EDS) and/or Hypersomnia (H) asdefined above
• EDS and/or H present daily or almost daily for at least 1 month prior to theconsultation
• Ability and consent to undergo electrophysiological routine assessment
• Ability to give informed consent Healthy controls:
• Age and gender matched healthy subjects
• Including blood related relatives of study participants
• Ability and consent to undergo electrophysiological routine assessment
• Ability to give informed consent Controls with Sleep disordered breathing (SDB):
• Subjective complaints of EDS with Epworth Sleepiness Scale (ESS) > 10 (adults) and/orH due to SDB: Presence of clinically significant and untreated obstructive sleep apnea (OSA) as determined by the investigator with an apnea-hypopnea-index >30/h
• Multiple sleep-latency test (MSLT) mean sleep latency ≤ 8min
• Subjective and objective improvement of EDS and/or H within 3 months after treatmentwith
• Positive airway pressure (PAP) therapy with documented
• Reduction of apnea-hypopnea index below <10/h
• Reduction of ESS by ≥ 25%
• MSLT mean Sleep Latency > 12min
• Ability and consent to undergo electrophysiological routine assessment
• Ability to give informed consent

Exclusion Criteria: Study participants and controls:

• SDB for study participants and healthy controls: Presence of clinically significantand untreated obstructive sleep apnea (OSA) or central sleep apnea (CSA) as determinedby the investigator or documented previously; or documentation of one of thefollowing:
• Apnea index (AI) > 10 if on OSA treatment or untreated; or
• Clinically significant hypoventilation; or
• Noncompliance with primary OSA therapy
• except if NT1 has been diagnosed including decreased or missing cerebrospinalfluid (CSF) hypocretin
• SDB for control population with SDB:
• Central Sleep Apnea (CSA)
• Noncompliance with primary OSA therapy and/or
• No reported improvement of EDS and/or H within 3 months of positive airwaypressure (PAP) treatment
• The following disorders/conditions that on clinical grounds are considered to be thecause of EDS / H
• Other sleep disorders (e.g. Restless legs syndrome (RLS) with periodic legmovement syndrome (PLMS), sleepwalking, clear-cut circadian disorder)
• Other neurological disorders (e.g. stroke, multiple sclerosis, parkinsonism,severe traumatic brain injury)
• (Auto-)immune and systemic disorders (such as Hashimoto Thyroiditis, Chron'sDisease, ulcerous colitis, Diabetes mellitus type I, Systemic lupuserythematosus)
• Malignancy (except: Status in Remission for at least > 10 years)
• Instable psychiatric disorder (e.g. acute psychotic, acute suicidal, episode ofmajor depression requiring in-hospital treatment, active substance abuse)
• Active infectious disease at screening
• Permanent medications / drugs
• Chronic infectious diseases (such as Hepatitis B/C, HIV)
• Chronic use of antibiotics
• Recent use (< 8 weeks) of immune-modulating drugs Healthy controls additional:
• Subjective complaints of EDS and / or H
• ESS > 10
• Polysomnography (PSG) with AI > 10/h and / or PLMS Index > 30/h
• MSLT mean Sleep Latency < 12 min