Rare chronic CNS d/o with clinical overlap with narcolepsy
~10x less common than narcolepsy
Poorly defined, may be a heterogeneous group of d/o
Onset at any age, most often adolescence or early adulthood

Clinical features
Marked EDS is the core feature
Long sleep duration, typically ≥10 hrs for main sleep period
Long unrefreshing naps, usually ≥1 hr
Sleep inertia (sleep drunkenness): marked difficulty waking with confusion, incoordination, repeated return to sleep
Cognitive dysfunction (brain fog) even when awake
Autonomic sx common: headache, palpitations, orthostatic intolerance, cold extremities

Dx criteria (ICSD-3)

1. Daily irrepressible need to sleep or daytime lapses into sleep for ≥3 months
2. Cataplexy absent
3. MSLT <2 SOREMPs, or none if REM latency on preceding PSG ≤15 min
4. ≥1 of:
   a. MSL ≤8 min
   b. TST ≥660 min/24 hrs on 24-hr PSG or actigraphy + sleep diary (avg ≥7 days)
5. Chronic sleep restriction ruled out, actigraphy ≥1 wk if needed
6. Not better explained by another sleep, medical or psych d/o, or drugs/meds

Pathophysiology
Unknown
Family hx of IH or EDS in ~1/3 of pts, suggests genetic role
Some studies show circadian abnormality with delayed sleep phase

Differential dx
IH is a dx of exclusion, may need to treat alternatives first

1. NT2: significant overlap, ~25% of IH pts have sleep paralysis and hypnagogic hallucinations
2. OSA and UARS: RERA-predominant picture can confuse, trial CPAP if in doubt
3. PLMS: treat significant PLMS before dx IH
4. DSWPD: difficulty waking but also late sleep onset, significant overlap with IH
5. Post-TBI: long sleep time and EDS
6. Myotonic dystrophy: hypersomnia in ~1/3 of pts
7. Medical: post-viral illness, hypothyroidism, iron deficiency, profound vitamin D deficiency (anecdotal)
8. Chronic fatigue syndrome: fatigue not relieved by rest, usually no objective sleepiness, poor sleep efficiency

Treatment
Non-pharm: Behavioral tx generally not very successful, Sleep extension does not give long-term benefit, Focus on safety advice, esp driving

Pharm
Low-sodium oxybate (Xywav) is the only FDA approved tx for IH (2021)
AASM 2021: modafinil strong rec, clarithromycin, methylphenidate, pitolisant, sodium oxybate conditional
Stimulants are mainstay: modafinil, methylphenidate, dextroamphetamine at narcolepsy doses
Caffeine and nicotine, transdermal nicotine anecdotally helps sleep inertia
Nighttime modafinil may ease sleep inertia without worsening night sleep

1. Oxford Handbook of Sleep Medicine 2022