Lecture 10 - Disorders of the Sleep Control System

Question 1

What does narcelepsy stand for?

Answer 1

Seized by sleep.

Question 2

What is the mandatory symptom of narcelepsy?

Answer 2

Excessive Daytime Sleepiness (EDS).

Question 3

What are the other symptoms that can present with EDS in Narcelepsy?

Answer 3

Type I Narcelepsy - experience cataplexy (lose of muscle tone in response strong emotions, such as humour or joy).

Type II - hypnagogic hallucinations - extreme hallucinations as you are falling asleep or as you are waking up, such as floating above the bed.

Type III - sleep paralysis - experience paralysis when conscious, such as consciously waking up but not being able to move the body.

Question 4

What type of narclepsy would experience cataplexy?

Answer 4

Type I.

Question 5

What type of narclepsy would experience hypnagogic hallucinations?

Answer 5

Type II

Question 6

What type of narcelpsy is defined by the experience of sleep paralysis?

Answer 6

Type III.

Question 7

Most of the experiences of narcelepsy are intrusions of REM sleep in states on wakefulness.

T/F?

Answer 7

True.

Question 8

What are the known causes of narcelepsy?

Answer 8

Abnormal orexin production or signalling.

Those with narcelepsy either low or absent orexin or have an abnormality in the orexin receptors.

Question 9

What is a well known sleep disorder caused by low levels or abnormal signalling of orexin and its receptors?

Answer 9

Narcelepsy.

Question 10

Can narcelepsy be present from birth?

Answer 10

Yes.

Question 11

If narcelepsy has been present from birth, what is it most likely due to?

Answer 11

A genetic abnormality in the orexin receptor.

Question 12

How was orexin identified as playing a key role in narcelepsy?

Answer 12

in dogs at Stanford University that had narcelepsy.

Question 13

Are there strong links between the emotional control centres, such as the amygdala, and the REM control centres, such as the subcoeruleus?

Answer 13

Yes.
This can be seen when we have such strong emotions in dreams.

Question 14

Briefly explain why people with narcelepsy experience cataplexy?

Answer 14

People with narcelepsy, who also experience cataplexy, do not have enough orexin or have an abnormality in their orexin receptors. As orexin is the master modulator of wakefulness, not enough orexin means that sleep is more likely to be induced, but also orexin inhibits the brain areas that induce REM sleep. This means that these regions are more active, or rather, more easily activated. There are also links between the amygdala and the areas associated with REM, such as the subcoeruleus, so when people experience intense emotions the REM areas receive activating signals from the amygdala, and because orexin is not there to inhibit this area whilst awake, the individual gets intrusions of REM sleep, such as loss of muscle tone, which is cataplexy.

Question 15

Are the subcoeruleus and the sublaterodorsal tegmental area the same thing?

Answer 15

Yes. This area is known to induce REM.

Question 16

Do people with narcelepsy have more REM sleep?

Answer 16

Yes.

Question 17

People with narcelepsy often experience intrusions of sleep into wakefulness.
Do they also wake up often during sleep?

Answer 17

Yes (fragmentation).

Issues with sleep on/off switch and REM on/off switches, which are controlled by OREXIN.

Question 18

When is narcelepsy most often diagnosed?

Answer 18

In teens and early twenties, often after illness or vaccination.

This suggests an autoimmune component.

Question 19

Do those with narcelepsy go into REM sleeo much sooner than those without this condition?

Answer 19

Yes.

Question 20

What are some treatments for the excessive daytime sleepiness experienced in narcelepsy?

Answer 20

CNS stimulants, such as modafinil.
Planned naps.
Sodium oxybate.

Question 21

What are some treatments for the cataplexy some experience in narcelepsy?

Answer 21

SSRI’s, as they reduced REM sleep, and therefor reduce intrusion of cataplexy.

Sodium oxybate - induces deep NREM sleep, which reduces sleepiness and likelihood of triggering REM during wakefulness.

Question 22

What is REM Behaviour Disorder?

Answer 22

The loss of atonia during REM sleep.
Atonia lack of muscle tone experienced during REM sleep.

Those with REM Behaviour Disorder experience a loss of this atonia during REM sleep, which results in them acting out their dreams. This can be very dangerous.

Question 23

Is REM Behaviour Disorder becomjng a key marker of neurodegenerative disorders, such as Parkinson’s?

Answer 23

Yes.

Question 24

What is considered to cause/drive REM Behaviour Disorder?

Answer 24

Damage to the SLD or subcoeruleus.

Question 25

What is FATAL FAMILIAL INSOMNIA?

Answer 25

Fatal Familial Insomnia is caused by a prion, which is a misfolded protein, which in turn s causes the misfolding of normal variants of the protein and causes degeneration and then death.

In Fatal Familial Insomnia the first areas affected are the VLPO areas, which is why individuals start to experience insomnia.

It is genetic and inheritable.

Question 26

Where are the VLPO areas located in the brain?

Answer 26

In the anterior of the hypothalamus.