Grand Ground

Question 1

Excessive daytime sleepiness

Answer 1

• OSA
• Insufficient seep syndrome
• Drugs
• Psychiatric problem
• Medical problem —> hypothyroid, liver/renal disease
• Neurological disease —> Trauma, CNS lesion, genetic (prader-Willi syndrome, myotonic dystrophy), Parkinsonism, Kleenex Levin Syndrome
• Insomnia
• Hypersomnia —> Nacrolepsy, idiopathic hypersomnia

Question 2

Around the clock assessment

Answer 2

• LIfestyle
• Abnormal behaviour -> cataplexy(head drop and weaker limb), restless leg syndrome, sleep paralysis, hallucinations, REM sleep behaviour
• drug use
• neurological syndrome e.g. tremor

Question 3

Multiple sleep latency test

Answer 3

• mostly 4 naps, can be 5 naps
• objective measures for excessive daytime sleepiness
• rule our OSA, PLM beforehand
• do a urine drug screen
• 4-5naps, 2 hours apart, each last for 20 mins, standard EEG, EOG, EMG, ECG

80% sensitivity, 90%specificity

Question 4

narcolepsy

Answer 4

• NT1, NT2
• hypocretin as the stabilising modulator of the sleep-wake hormone
• hypocretin/Orexin deficiency may lead to nacrolepsy —> maybe autoimmune
• Mx: Pitolisant (H3R inverse agonist)
  Solriamfetol
  Orexin receptor agonist
• need to first rule out secondary cause —> obesity, depression
• delayed diagnosis: lack of awareness, atypical or mild symptoms, paediatric-onset may not be able to explain the symptoms, mislabelling to other disease, ADHD drug may mask the symptoms

Question 5

Nacrolepsy type 1

Answer 5

• Excessive dat time sleepiness
• Cataplexy
• low hypocretin
• other sleep related behaviour
• young age-onset
• highest prevance in Japan
• increase CVS Risk, e.g. stroke, AF, HF
• blood test: HLA DQ1B 0602

Question 6

Cataplexy

Answer 6

Sudden loss of muscle tone after emotional trigger, but excluded oculomotor and respiratory muscle, patients still have consciousness and memory

Question 7

HLA DQ1B 0602

Answer 7

• NT1: 80-90%
• NT2: 70%
• may related to severity

Question 8

Maintenance of wakefulness test

Answer 8

• measure the ability to remain awake in quiet situation
  4naps, 2 hours apart, last for 40 mins
• assess efficacy of treatment and fitness for driving for commercial driver

Question 9

Mx of Nacrolepsy

Answer 9

Old Mx: stimulant

• New Mx:
  1. Modafinil (lower dependency risk, but caution for depression and suicaidal risk)
• (MWT from 5-8mins)

2. Sodium oxybate
   - expensive
   - short half life, three times per day (MWT from 5 to 11 mins)
3. Solriamfetol
   - MWT to 5-10mins
4. Pitolisant
   - target histamine pathway
   - interferes with OCP
   - C/I for liver impairment
5. Orexin 2 receptor selective agonist danavorexton
   - IV infusion
   - dose-dependent effect
6. TAK-994
   - S/E urinary frequency, hepatotoxicity
   - study terminated
7. TAK-861
   -phase 3 trial in 2024