Sleep

Question 1

Sleep

Answer 1

• reversible behavioral state of perceptual disengagement from, and unresponsiveness to the environment
• essential for heath in all mammals (sleep deprivation can be fatal)
• not absence of all brain activity, but series o complex, precisely regulated brain states that are activated & deactivated by multiple sets of diencephalic & brainstem nuclei

Question 2

Sleep Demographics

Answer 2

• normal adults average 7.5 +/- 2 hrs per night
• sleep occupies approximately 1/3 of lifespan
• normal sleep duration dec. with inc. age
• sleep deprivation leads to decreased mental & physical performance & eventually death

Question 3

Biological Clock

Answer 3

• group of cellular/molecular cycles inherent in a variety of body organs that drive a host of circadian rhythms
• contain + & - feedback loops that allow the mechanism to cycle with a regular time constant

Question 4

Suprachiasmatic Nucleus

Answer 4

• anatomical pathway by which ambient light regulates melatonin synthesis and secretion
• rise of melatonin beginning in early evening as daylight wanes & peaking around 2-4 am

Question 5

Polysomnography

Answer 5

-method of measuring sleep

Question 6

Sleep Lab

Answer 6

• sleep room with wall mounts for connecting physiological monitors to the patient
• monitors air flow of nose
• scalp to monitor EEG, face sensors to monitor eyelid movement, monitor respiration, monitor blood ox

Question 7

Sleep frequencies

Answer 7

• 5 stages (changes of EEG)
• Beta > 13 Hz
• Alpha 8-13 Hz
• Theta 4-7 Hz (stage I & II)
• Delta <4 Hz (stage III & IV)

-alpha & beta normal awake humans

Question 8

REM stage

Answer 8

• 5th
• Rapid Eye Movement
• associated eye movements, physiological changes
• EEG characteristics: fast frequency, low voltage, close to awake state
• theta and beta

Question 9

Sleep Stages (Cycle)

Answer 9

Stage I - IV Non Rapid Eye Movement Sleep or NREM sleep & stage V is rapid eye movement REM

• Frequency (hertz, cps) and voltage
• Stage I sleep is lightest sleep and stage IV is deep sleep
• Stage II is characterized by bursts of activity called sleep spindles and K complexes

Question 10

Stage II Sleep

Answer 10

-unique “spindle” and “K-complex” patterns

Question 11

Sleep Cycle

Answer 11

• starts with Stage I and ends with REM sleep (90 min)
• during duration of stages 3 & 4 sleep lasts longer early in the sleep cycle while REM sleep duration & frequency increase toward the morning or waking hours
• tend to be 5-6 cycles of NREM and REM sleep during a 7-8 hr sleep period

Question 12

Physiologic Changes in Sleep Cycle: NREM sleep

Answer 12

• few eye movements, when they occur they are slow, rolling
• decreased muscle tone but movement still occurs
• decreased HR, BP, RR, temp, metabolic rate
• dreams occur but they are less vivid with low emotional content
• sleep walking and night terrors occur during slow wave sleep
• all changes reach a maximum during stage IV sleep

Question 13

Physiologic Changes in Sleep Cycle: REM sleep

Answer 13

• rapid, ballistic eye movements
• muscle paralysis
• HR, BP, RR, temp., metabolic rate approach awake level
• dreams are vivid with strong emotional content, bizarre
• penile and clitoral erection in REM

Question 14

Neural Sleep Circuits

Answer 14

-awake state: activation of the following nuclei promote wakefulness
Brainstem Nuclei:
-cholinergic neurons in pedunculopontine (PPT) and lateral-dorsal tegmental (LDT) areas
-noradrenergic neurons in the locus ceruleus
-dopaminergic neurons in substantia nigra
-serotonergic neurons in raphe nuclei
Hypothalamic Nuclei:
-histaminergic neurons in tuberomammillary nucleus
-orexin/hypocretin neurons in the lateral hypothalamus

Question 15

Cholinergic Neurons

Answer 15

• from pedunculopontine (PPT) & lateral dorsal tegmental (LDT) areas project to the thalamus and other brainstem areas
• activation signals thalamic-cortical signaling with high frequency, low voltage EEG consistent with arousal and alertness

Question 16

Noradrenergic Circuits

Answer 16

-imput from locus ceruleus to the neocortex is highly activated during wakefulness, less so during NREM sleep, and nearly silent during REM sleep

Question 17

Serotonergic Circuits

Answer 17

• from dorsal and medial raphe nuclei are highly active during wakefulness, less during NREM sleep, and nearly silent during REM sleep
• variety of drugs influence sleep (tricyclic antidepressants & selective serotonin reuptake inhibitors (SSRIs)

Question 18

Histaminergic Circuits

Answer 18

• out put from tuberomammillary nucleus is high during wakefulness, lower during NREM sleep, and still lower during REM sleep
• drugs that block histamine H1 reeceptors, such as diphenhydramine inc. NREM and REM sleep

Question 19

Hypothalamic Nuclei

Answer 19

-suprachiasmatic & paraventricular nuclei involved in the light/dark regulation of pineal gland production of Melatonin

Question 20

Somnogens

Answer 20

• endogenous sleep-promoting chemicals that may accumulate during wakefulness and promote sleep onset
• Adenosine: accumulates in CNS during wakefulness & declines during sleep
• Cytoines: IL-1B and TNF promotes sleep
• Melatonin: Synthesis turned on by dec. light

Question 21

Sleep Symptoms

Answer 21

• Sleepiness
• Insomnia
• Snoring
• Abnormal Behaviors
• Nightmares
• Abnormal Movements

Question 22

Multiple Sleep Latency Test

Answer 22

-EEG defined sleep latency, the time required to fall asleep measured during 4-5 daytime naps

Question 23

Epworth Sleepiness Scale

Answer 23

-self-reported tendency to fall asleep in 8 different situations differing in their soporific nature

Question 24

Obstructive Sleep Apnea (OSA)

Answer 24

-repetitive blockage of the respiratory pathway during sleep causing apneic periods lasting longer than 10 sec and causing oxyhemoglobin desaturations of more than 4%

Question 25

OSA epidemiology

Answer 25

- 3-5% of population (4% men, 2% women age 30-60) - more common in men - incidence inc. with obesity but occurs also in the non-obese - strong association b/w OSA, heart disease, HTN

Question 26

OSA Pathogenesis

Answer 26

-complex interaction b/w pharyngeal muscles, tongue, and soft tissues leading to airway obstruction

Question 27

OSA Physical Findings

Answer 27

- Nasal obstruction - Tonsillar/adenoid hypertrophy - macroglossia - reflux laryngitis - shirt collar size > 17 in - hypothyroidism with goiter - truncal obesity - HTN - congestive heart failure - pitting edema of lower extremities - enlargement of hands & feet (acromegaly)

Question 28

OSA Symptoms

Answer 28

- excessive daytime fatigue - snoring - heartburn - memory loss - irritability - depression - morning headache - shortness of breath - nocturia - impotence

Question 29

Narcolepsy

Answer 29

- excessive daytime sleepiness associated with one or more of the following tetrad - sleep attacks/intrusions, irresistible, daytime sleep onset - cataplexy (abrupt loss of muscle tone during waking hours - sleep paralysis - persistent REM sleep atonia after awakening - hypnagogic hallucinations - dream persistent after awakening

Question 30

Narcolepsy Epidemiology

Answer 30

- 0.05-0.2% (200,000 in US) - symptom onset 90% develop symptoms by 2nd-3rd decade - symptoms persist throughout life - male = female - familial tendency: 1st deg. relatives have 1-2% inc. risk

Question 31

Secondary Narcolepsy

Answer 31

-associated with multiple sclerosis, pituitary tumors, vascular malformations, stroke

Question 32

Narcolepsy Pathogenesis

Answer 32

- loss of hypocretin/orexin secreting neurons in the posterior lateral hypothalamus related to: - HLA genes DQ1, DQB1*0602 that may predispose to an autoimmune attack on orexin secreting neurons - secondary to tumor, stroke, to orexin secreting neurons

Question 33

Naracolepsy Lab

Answer 33

- clinical presentation with components of tetrad - low CSF hypocretin-1 level (10% normal) - Polysomnography (mean sleep latency test - MSLT of < 8 min) - sleep onset REM period >2 episodes of SOREMPs

Question 34

Naracolepsy Treatment

Answer 34

- Daytime sleepiness - methylphenidate, Modafinil, Gama-hydroxybutyrate - Cataplexy - tricyclic antidepressants, SSRIs

Question 35

Insomnia

Answer 35

-difficulty falling asleep or remaining asleep

Question 36

Epidemiology of Insomnia

Answer 36

- Transient insomnia - days to weeks; affects 50% of adults during lifetime - Chronic insomnia - >6 weeks, affects 25% of adults - Female: Male 1.3:1 - Strong association b/w insomnia & depression

Question 37

Insomnia Causes

Answer 37

- delayed sleep onset - primary: idiopathic, psychophysiologic - secondary: anxiety, physical activity, jet lag, shift work, sedative withdrawal, stimulant drug use - Failure to maintain sleep: obstructive sleep apnea, aging, sedative wear-off, depression, REM disorder, medication effects, CNS degenerations

Question 38

REM sleep Behavior Disorder

Answer 38

-loss of atonia/paralysis during REM sleep leading to physical acting out of dream states including verbalization, punching, kicking, jumping from bed; this activity can cause physical injury to the bed partner or patient

Question 39

REM sleep Behavior Disorder: Epidemiology

Answer 39

- RBD present in 0.5% of population | - most common in adult makes over 50

Question 40

REM sleep Behavior Disorder: Pathogenesis

Answer 40

- primary RBD may be idiopathic or associated with alpha-synucleinopathies (parkinsons, multisystems atrophy, lewy body dementia, progressive supranuclear palsy) - secondary RBD can be caused by EtOH withdrawal, TCA, and SSRI use

Question 41

REM sleep Behavior Disorder: Treatment

Answer 41

-RBD responds well to Clonazepam