lecture 6/7- sleep disorders 1 (narcolepsy + insomnia)

narcolepsy, insomnia

what is narcolepsy? prevalence + age of onset (4)

• irresistible =, recurring short episodes of sleep accompanied by cataplexy (elicited by strong emotion)

• most prominent symptom: excessive daytime sleepiness

• ~1/2000 people

• starts at age 15-25

symptoms of narcolepsy (4)

1. daytime sleepiness

2. cataplexy

3. sleep paralysis

4. hypnagogic hallucinations

how can narcolepsy be debilitating? how do patients feel after an attack? (3)

• intrudes into wakefulness at any time → recurs throughout the day

• each attack can last for minutes/hours

• patient feels refreshed after attack and enters refractory period where attack is unlikely

describe cataplexy, what is it, what causes it, effects? (3)

• loss of muscle tone during wake resulting in total collapse, slight bucking of knees, or drooping of jaw

• caused by intense emotion ie. laughter/anger

• causes speech to slur, eyesight impaired

describe the sleep paralysis associated with narcolepsy onset vs offset paralysis (5)

• typically occurs when falling asleep/waking up

• total inability to move/speak

• fully conscious + aware of paralysis

• sleep onset → rare

• sleep offset → more common occurs when waking from REM sleep

hypnagogic hallucinations associated with narcolepsy (3) how are they different from other hallucinations (2)

• vivid perceptions → visual, auditory, tactile, kinetic

  • sensation of threat, suffocation, floating, spinning, falling

• occur at transition from wake to sleep/REM to sleep

• 40-80% experience this

different from other hallucinations:

1. ppl know they are not real

2. only occur around sleep

cataplexy, sleep paralysis, hypnagogic hallucinations are all pathological manifestations of ___ and point to a problem in the ____ since the medulla + ____ actively suppress ___ during REM and ____ can be induced with injections of cholinergic/glutamatergic agonist into the ____, medulla, or ___

1. REM

2. brainstem

3. pons

4. muscle tone

5. cataplexy

6. brainstem

7. pons

REM latency & narcolepsy: what’s the hallmark finding on MSLT, and what does it imply? (3)

• Narcolepsy hallmark: sleep-onset REM on MSLT (REM within ~2–3 min)

• Normal tired people almost never enter REM on MSLT

• Short REM latency can occur with high REM pressure (REM deprivation / stopping REM-suppressing drugs), but narcolepsy is mainly REM timing at sleep onset, not necessarily more or stronger REM

current treatments for narcolepsy (2) what are their shortcomings (2)?

• excessive sleepiness treated with stimulants, naps, xyrem (GHB)

• cataplexy treated with REM suppressing drugs like antidepressants

• problems: tolerance to stimulants

  • treatments focused on symptoms not cause

potential causes for narcolepsy (3)

1. hereditary component → only 30% concordance in monozygotic twins → susceptibility

2. associated with antigens for a major histocompatibility complex on chromosome 6 also seen on MS/rheumatoid arthritis

3. may be an autoimmune disease

narcolepsy is caused from the loss of cells containing ____ in the ____

• hypocretin (orexin)

• hypothalamus

which arousal systems does orexin activate + what is the evidence

• excites/stabilizes wakefulness by activating arousal systems (TMN/LC/raphe)

• evidence: applying hyprocretin increases action potential firing rate in these neurons

what might future treatments for narcolepsy try to do?

• develop drugs that activate HCRT2 receptor to promote arousal

In hypocretin-knockout mice, what did viral hypocretin gene therapy do, and what were the limitations? (2)

• Viral delivery (herpes) of hypocretin gene → normalizes CSF hypocretin, reduces cataplexy, normalizes nighttime REM

• Limitations: KO isn’t the typical human cause; effect fades ~after 1 week

In the ataxin-3 (hypocretin-cell loss) narcolepsy model, what did hypocretin gene therapy improve? (3)

• Virus delivered hypocretin to target regions → improved REM, NREM, and wakefulness

• Normalized wake bout duration

• Maybe small drop in cataplexy (depends on area treated)

insomnia is characterized by ____ where sleep ___ and/or ___ become difficult with ___% of adults saying they have some symptoms while ___% say it is chronic.

1. hyperarousal

2. initiation and/or maintenance

3. 30-40%

4. 10-15%

criteria for the diagnosis of insomnia (name a few)

causes for acute (3) vs chronic insomnia (2)

• acute insomnia (<30 days)

  • situational stressors

  • environmental stressors

  • death/illness of a loved one

• chronic insomnia (>30 days)

  • medical/psychiatric/sleep disorder

  • circadian disruption

Physiological (hyperarousal) model of insomnia: core idea, evidence, and main weakness? (3)

• Core idea: elevated physiological arousal during the normal sleep period is incompatible with sleep continuity (arousal vs sleep are mutually exclusive)

• Evidence: poor sleepers show higher arousal measures (HR, respiration, temperature, muscle tone), especially at sleep onset (sometimes ↑ 24h metabolic rate)

• Weakness: doesn’t explain how insomnia develops or why it persists/promotes sleeplessness

Cognitive model of insomnia: what are the 3 P’s and what does each mean? (3)

• Predispose: worry-prone / stress-reactive → easier to become hyperaroused

• Precipitate: stress triggers worry/problem-solving → arousal → insomnia starts

• Perpetuate: insomnia becomes focus of worry/rumination → keeps insomnia going

Cognitive model: two “other features” that maintain insomnia?

• Selective attention to sleep-related threats (keeps arousal high)

• Distorted perception of deficits: focus on daytime problems, over-detect deficits, blame sleep loss (even if not the cause)

Behavioural models of insomnia: what’s the key idea of sleep hygiene, and what’s the stimulus control model? (2)

• Sleep hygiene: good advice, but poor hygiene isn’t necessary or sufficient → hygiene alone usually won’t cure insomnia

• Stimulus control: insomnia is maintained by conditioning (bedroom paired with wake activities) → weaken bed=sleep link

Stimulus control: 2 key rules + what does CBT evidence suggest about insomnia?

• Rules: use bed/bedroom for sleep (and intimacy) only; if you can’t sleep, get up and leave the bedroom

• CBT improves symptoms (~50% acutely) and patients may keep improving → suggests insomnia isn’t purely behavioural (cognitive/arousal factors matter too)

Neurocognitive model: what causes acute vs chronic insomnia, and what’s the key “worry” point? (3)

• Acute insomnia: cognitive + behavioural factors

• Chronic insomnia: behavioural factors + classical conditioning of arousal

• Worry/rumination extends wake but isn’t the root cause: “worry because awake,” not “awake because worry.”

Neurocognitive model: 3 arousal dimensions + key EEG marker; plus 2 other modulators of insomnia.

• Arousal dimensions: somatic, cognitive, cortical

• Cortical arousal marker: high-frequency EEG (14–45 Hz) during sleep onset/NREM

• Other modulators:

  • Homeostasis impaired (less delta power / lower % SWS after deprivation)

  • Circadian phase shifts (sleep-onset insomnia = delayed clock; early awakening = advanced clock)

non-pharmacological treatments for insomnia include (6)

1. CBT

2. exercise

3. relaxation therapy

4. sleep restriction (paradoxical intention therapy)

5. stimulus control therapy

6. temporal control measures

pharmacotherapy for insomnia (6)

1. hypnotics may be the best choice for immediate relief → treat serious symptoms but don’t address root cause

2. benzos

3. sedating anti-depressants

4. non-benzos benzodiazepines receptor agonist

5. antihistamines

6. antipsychotics

general advice for insomnia (7)

1. follow bedtime routine

2. keep bedroom quiet, dark, at comfortable temp

3. exercise regularly

4. drink less caffeine

5. avoid alcohol/smoking

6. eat regular meals

7. bedroom only for sleep/intimacy

insomnia is usually comorbid with other disorders like (6)

• pain

• substance use/abuse

• breathing disorders

• cardiovascular disorder

• endocrine

• mental health