L12 - Disorders of the sleep control system

Question 1

What are the Classic features of Narcolepsy?

Answer 1

MANDATORY - excessive daytime sleepiness

Typically present

• cataplexy - loss of muscle tone in response to a stimulus, usually elicited by positive emotions
• hypnagogic hallucinations - hallucinations at either onset or offset of sleep.
• sleep paralysis at onset or offset of sleep. can be distressing.
• REM also appears right at the start of sleep.
• More awakenings during the night due to more floppy/less stable flip-flop switch.

day time sleepiness may be exacerbated by lack of night sleep quality.

Question 2

what is cataplexy and what can it be caused by?

Answer 2

Loss of muscle tone in response to a stimulus, usually elicited by positive emotions

It is caused by lack of orexin input, rendering the amygdala input to be stronger and activate inhibitory pathways of the SLD to create muscle atonia

Question 3

What is the relationship between narcolepsy and orexin?

Answer 3

Orexin - master controller of wakefulness and facillitates REM off neurons.

Orexin signalling is altered in Narcolepsy. It is absent or very low levels, and maybe receptor abnormality in some patients.

Excessive sleepiness may also be due to missing projections to the cortex, and lack of synchronous firing of all the wake-active neurons.. not working in a concerted fashion

Question 4

What is involved in the diagnosis of narcolepsy?

Answer 4

• usually followed by illness or vaccination
• abnormal immune func - HLA subtyping from blood sample
• sleep study is needed, must see Short sleep on set, and short rem latency, increased awakenings
• multiple sleep latency test - sleep 1 night, and next day asked to sleep every 2 hours. measure how long it takes them to fall asleep every time. as well as REM onset.

Question 5

What is the treatment of Narcolepsy?

Answer 5

• EDS - planned nats gives some rejuvination, CNS stimulants (modafinil), sodium oxybate
• CATAPLEXY - antidepressants reduce REM, sodium oxybate (date rape drug) to have good sleep and reduces sleepiness and cataplexy after a few weeks

Question 6

What is REM behaviour disorder?

Answer 6

RBD is loss of atonia in REM. Acts out dreams.

Often precedes degenerative disease by years.

Question 7

What is the mechanism behind REM muscle atonia?

Answer 7

• Lesion of sublateral Dorsal region resulted in REM sleep w/o atonia in rats –> lack of inhibition to spinal cord.
• found that the SLD projects to pons, medulla to the spinal ventral horn WHICH CONTAINS ALPHA MOTOR NEURONS

Question 8

How does REM still happen with lesion of SLD?

Answer 8

B/c there are two parts to the SLD.
one part is important for atonia
the other part is important for the flip flop switch of sleep

hard to really know though bc by the time we see the prains they’ve had parkinsons/dementia

Question 9

What is Fatal Familial insomnia?

Answer 9

• autosomal dominant prion disease
• can also be transmissable through blood
• genetic abnormality where the body synthesises a protein which acts like a virus
• fatal in 18 months - quick acting and slow forms of disease

early:
- sleep but have insomnia/unrefreshing sleep
- mild autonomic dysfunc eg. perspiration, fever, impotence.
- vigilance, mild cog/memory problems

middle:

• drowsy but can’t sleep. reduced NREM and/or REM
• sudden onset REM periods with or without atonia (dreams)
• motor disturbances
• IQ unchanged

late:

• bedridden and speechelss
• cerebral atrophy.

Question 10

what are some structural changes in some people with FFI?

Answer 10

• bilateral thalamic hypometabolism
• severe thalamic neuronal loss and gliosis
• gliosis of hypothalamus, periaqueductal area, and serotonergic neurons are selectively lost in raphe nuclei

Question 11

What is sleep like in people with FFI?

Answer 11

• loss of sleep spindles, K complexes and SWS.. and eventually REM.

basically stay in stage 1 and have many awakenings.

REM stages without atonia