#14 Sleep and Sleep Disorders

Question 1

What are the five types of clinicians involved in treating sleep disorders?

Answer 1

Family physician, respirologist, pulmonologist, psychiatrist, neurologist

Question 2

How are EEGs used in relation to sleep?

Answer 2

It is a non-invasive measure to determine brain waves during certain stages of sleep.
EEG rhythms are named according to the frequency of the activity (number of waves in 1s of recording)
DELTA: slow waves, 0-3.99 Hz
THETA: 4-7.88 Hz
ALPHA: 8-13 Hz
BETA: greater than 13 Hz

Question 3

What are the three basic states of sleep?

Answer 3

1. Awake: presence of the alpha rhythm
2. Non-REM sleep: you get three phases here (N1 which is alpha dropout, N2 which is sleep spindles and K-complexes, and N3 which is slow wave sleep)
3. REM sleep: no muscle tone, and rapid eye movements
   nREM and REM sleep alternate during sleep, with each cycle lasting about 90-100 mins
   4-6 cycles per normal sleep period

Question 4

What happens in terms of neuronal activity in non-REM sleep? What other condition does the same pathway effect?

Answer 4

There is an increase in the reticular neuron activity which hyperpolarizes relay neurons via GABA receptors.
This hyperpolarization activated T-type calcium channels which allows for low threshold depolarization and BURST mode thalamo-cortical activation by relay neurons. This generates sleep spindles
This circuit is active in absence seizures (same process that causes sleep spindles) and generates 3 per second spike-wave seizures
Ethosuximide acts as a T-type calcium channel antagonist and decreases absence seizures

Question 5

How are benzos associated with sleep?

Answer 5

They increase N2 sleep (sleep spindles and k-complexes, not slow wave), increase spindle activity
This is possibly due to increased GABAergic signaling

Question 6

What happens during REM sleep?

Answer 6

Rapid eye movements, lack of EMG muscle activity (paralysis), yet you have an awake looking EEG due to the absence of morphologies for slow waves, and it is considered a lighter phase of sleep

Question 7

TRUE OR FALSE: The amount of time spent in REM sleep decreases throughout the cycles

Answer 7

FALSE
This is why REM sleep disorders present themselves closer to morning, because your longest REM cycles are there and SWS disorders present themselves early in the cycles

Question 8

What are the wakefulness parts of the brain? What NT is involved?

Answer 8

Glutamate is secreted by the parabrachial/pre coeruleus nuclei (in pons), and the supramammillary nucleus (midbrain)

Question 9

How does the parts of the brain transmit to wakefulness?

Answer 9

Wakefulness is supported by excitatory transmission from the brain stem nuclei:
1. Caudally to motor neurons in the spinal cord
2. Rostrally to neurons throughout the cortex
This is excitation of the cortex (awake) and excitation of muscle (posture and tone).
The thalamo-cortical transmission is supported through the dorsal pathway (PPT and the LDT) using acetylcholine to maintain consciousness

Question 10

How does the brain act in nREM sleep?

Answer 10

During nREM sleep we have inhibitory synaptic transmission from the VLPO to all of the brainstem nuclei important for wakefulness
This means there is inhibition of the normal wakefulness pathway

Question 11

How does the brain act in REM sleep?

Answer 11

REM-on neurons in the PPT and the LDT have:
1. Excitatory connection to the thalamus, resulting in an awake looking EEG
2. Excitatory connections to glycinergic neurons in the medial medulla which inhibits motor neurons in the spinal cord so that the muscles of the body do not move in response to all the excitation (muscle atonia)

Question 12

What are the three other NT involved in sleep?

Answer 12

Hypocretin (orexin), adenosine, melatonin

Question 13

How is hypocretin (orexin)?

Answer 13

It is produced by cells in the hypothalamus, and is thought to provide inputs to various nuclei important in sleep to support these and stabilize sleep states
Functions:
1. Promote wakefulness
2. Helps stabilize sleep/wake periods
2. Involved in maintenance of skeletal tone during wakefulness

Question 14

How is adenosine involved in sleep?

Answer 14

It is a mediator of sleepiness after prolonged wakefulness, and is though to promote the transition to SWS by inhibiting basal forebrain neurons (important in the maintenance of wakefulness).
Caffeine is an adenosine receptor antagonist

Question 15

How is melatonin involved in sleep?

Answer 15

Light stimulates SCN in hypothalamus which causes inhibitionof the release release of melatonin from the pineal gland
Darkness releases the pineal gland from inhibition, resulting in melatonin release
Links our circadian rhythms to the day and night cycles

Question 16

What are some symptoms of abnormal sleep?

Answer 16

Excessive daytime sleepiness, insomnia, abnormal movements during sleep, awakenings, abnormal breathing during sleep, sleep paralysis, hallucinations while falling asleep (hypnogogic), or upon awakening (hypnopompic)

Question 17

How do you take a sleep history?

Answer 17

Symptoms, talk to bed partner, medication and habits (caffeine, alcohol and tobacco), other medical illnesses, family history

Question 18

What is insufficient sleep syndrome?

Answer 18

Most common cause of sleepiness, daily sleep requirements range from person to person over the lifetime, sometimes excessive sleepiness (moderate or severe), but majority associated with insufficient sleep.

Question 19

What can sleep deprivation do to your body?

Answer 19

Chronic sleep deprivation can lead to weight gain, high blood pressure, and diabetes
Shift work can induce this
Obese children get less sleep than normal weight children.
Potential trigger for breakthrough seizures in epileptic patients, and one night of sleep deprivation impairs hippocampal function and deficits in ability to commit new memories.

Question 20

What is obstructive sleep apnea syndrome?

Answer 20

Second most common cause of sleepiness, temporary pause in breathing during sleep, occurs as muscle tone diminishes during sleep and airway collapses
Person tries to make breathing efforts against closed airways and eventually awakens with effort
Associated with obesity and snoring
Associated with increased risk of heart attack and stroke, best treated with a CPAP machine

Question 21

What are some practical approaches to improving sleep?

Answer 21

Increasing exercise and resulting weight loss, no caffeine after noon, smoking cessation and sleep hygiene

Question 22

What is narcolepsy?

Answer 22

Excessive daytime sleepiness with sleep attacks, may also involve cataplexy (sudden temporary loss of muscle tone with no loss of awareness), sleep paralysis, hallucinations (hypnogogic and hypnopompic)
REM-on neurons turn on inappropriately and cause the paralysis of REM sleep during wakefulness (cataplexy)

Question 23

What is some common associations with narcolepsy?

Answer 23

Associated with low levels of orexin (hypocretin), which is important for stabilizing sleep wake transitions
Inappropriate transitions between sleep and wake occurs, and intrusion of REM phenomena into wakefulness

Question 24

What is restless leg syndrome?

Answer 24

Happens in the earliest period when attempting to fall asleep, uncomfortable sensations in the legs with an urge to move legs
There is a family history in many patients, can be associated iron-deficiency anemia and pregnancy
Treatable depending on severity of symptoms (iron supplementation, GABApentin, dopamine agonists)

Question 25

What is parasomnia?

Answer 25

Defined as abnormal sleep movements or behaviours intruding into sleep. Classified based on what stage of sleep they originate from.
Disorders of arousal from non-REM sleep: confusional arousals, sleep terrors, sleep walking
REM disorders: REM Sleep behaviour

Question 26

What are sleep terrors?

Answer 26

Arise out of slow-wave sleep, more common in kids, can be brought on by stress, sleep deprivation, alcohol, and fever
Associated with sleep walking, confusional arousals, strong family history, different from nightmares (REM sleep)

Question 27

What is REM sleep behaviour disorder?

Answer 27

Loss of REM atonia, act out dreams, kick/yell in sleep, more common in elderly, associated with Parkinsons disease and dementia with lewy bodies (synucleinopathies)
Degeneration of glycinergic neurons in the medulla resulting in loss of REM atonia and dream enactment behaviour