Overview of sleep disorders and

approach to common sleep

disorders
By
Prof. F.A Imarhiagbe FMCP
 Disclosure
• None
 Learning objectives
• 1. To understand the neuronal and chemical
substrates of sleep and wakefulness
• 2. to understand disruptions of normal cycle
of sleep and how to approach common
disorders arising from this
 Outline
• Intro/preamble
• Neuronal and chemical substrates for sleep
and wakefulness
• Common sleep disorders
• Approach to sleep disorders
• Conclusion
• Q and A
 Intro
• Sleep is a multi phased physiologic state of
decreased level of wakefulness and increased
threshold of arousal that has been described
in all animals from mammals to birds to
reptiles, fishes, helminthes, insects and ants
and even lower forms
• It has complex behavioural, homeostatic and
electrophysiologic correlates
 Intro’
• It is an essential component of existence and
needed by the brain and body to maintain
homeostasis.
• It is known that prolonged sleep deprivation is
a recipe for multi organ dysfunction and
cardiovascular disease, immune dysfunction,
cognitive, endocrine and psychiatric disorders.
 Intro’
• It is an opportunity for the brain to detoxify
from toxins acquired during wakefulness, form
newer neuronal connections and build
memories
• It is regulated by 2 physiologic mechanisms –
the circadian rhythm and the sleep/wake
homeostatic mechanism
 Neural and chemical substrate for
sleep/wakefulness
• Arousal or wakefulness is maintained by the
following:
• Monoaminergic neurons of the brain stem
locus cereulus, raphe nucleus, dopaiminergic
neurons from the VTA in the midbrain and
pontine cholinergic fibres input the ARAS of
the brain stem to maintain wakefuness
 Neural and chemical substrate….
• Together with cholinergic inputs from the basal
forebrain(BF) to the hypothalamic preoptic area,
tuberomammilary histaminergic neurons, lateral
and posterior hypothalamic hypocretin/orexin all
input rostral midbrain and posterior
hypothalamus then through thalamus to the
cerebral cortices, to maintain wakefulness.
• Activation of GABAergic inputs from the pons and
basal forebrain with adenosine also from the BF
to the hypothalamic preoptic area initiates sleep .
 Neural and chemical substrate….
• During NREM sleep, the excitatory inputs to the
ARAS shuts down and there is inhibition by
GABAergic inputs from the brainstem and basal
forebrain.
• During REM, though the monoamainergic inputs
to the brainstem ARAS shuts down, pontine
cholinergic REM generators are activated with
inputs from hypothalamic hypocretin/orexin cells
to cause partial excitation of the cerebral cortex
with with muscle atony.
 Neural and chemical substrate….
• This is what differentiates a normal REM sleep
from REM sleep behaviour disorder.
• Absence or decreased inputs from the
hypocretin/orexin cells of the hypothalamus
both in the maintenance of wakefulness and
during REM is the major underlying disorder
in naracolepsy.
 Summary of chemicals and neuronal
substrates of sleep and wakefulness
• 1. Cholinergic and monoaminergic inputs to the
brain stem ARAS maintain wakefulness
• 2. Cholinergic inputs from the basal forebrain to
the ARAS
• 3. Inputs from hypothalamic hypocretin/orexin to
brainstem ARAS and cholinergic REM generators
in the pons
• 4. Inputs from the hypothalamic
tuberomammilary histaminergic cells to the
brainstem ARAS
 Summary of chemicals and neuronal
substrates of sleep and wakefulness
• 5.Brainstem and Basal forebrain GABAergic
inhibition of ARAS occurs in NREM sleep with
release of adenosine.
• 6. Partial Cholinergic excitation of the ARAS from
special REM generators in the pons aided by
hypocretin/orexin pathway in the hypothalamus
occurs during REM
• 7. Inputs from the biologic clock in the
suprachiasmatic nucleus(SCN) to the pineal
melatonin releasing cells in darkness enhances
sleep.
 Summary of chemicals and neuronal
substrates of sleep and wakefulness
• It is pertinent to mention that the
understanding of the entire chemicals
involved and neurocircuitry of sleep is far from
complete.
 Summary of chemicals and neuronal
substrates of sleep and wakefulness
• The 24 hours circadian day and night
regulation of sleep and wakefulness is
controlled in part from the SCN which is the
super biologic clock in the anterior
hypothalamus
• The circadian rhythm is aided by homeostatic
mechanisms to strike a delicate balance in
normal sleep time and duration
 Sleep stages
• Normal sleep cycles from Non-Rapid Eye
Movement (NREM) to REM many times during
with distinct behavioural and electrophysiologic
characteristics.
• NREM sleep is in 4 stages
• NREM 1- The transition from wake state to sleep
with reduction in the frequency of alpha waves
may be identified on EEG with positive occipital
sleep transients or lambda waves and may be
characterised by sleep starts or jerks.
 Sleep Stages
• NREM 2- This is the longest NREM sleep stage
and it is characterised on EEG by spindles and
K-complexes and background waves are in the
theta frequency.
• NREM 3 and 4 are called slow wave sleep
stages and characterised by delta waves and
sleep is deeper with higher arousal threshold
with slower heart and respiratory rates
compared to earlier stages
 Sleep stages
• REM sleep-This is also called paradoxical sleep. It
is characterised by movement of the eye ball
behind the closed eyelid. It begins on the average
about 90minutes from onset of sleep in health. It
is brief and duration becomes longer as the
number of sleep hours increase.
• It is characterised by EEG waves similar to the
awake state with increase in hearat ans
respiratory rate. It is however associated with
muscle atony.
 Overview of Sleep disorders
• They are conditions that impair sleep in one way
or the other, either in duration or quality.
• It can have untoward effects on work, school,
relationships, safety and wellbeing.
• Up to 80 different sleep disorders have been
described.
• The 5 most common ones are insomnia, sleep
apnoea, narcolepsy, Periodic limb movement of
sleep/Restless leg syndrome, REM and NREM
Parasomnias.
 Overview..
• Sleep disorders can be caused by various
factors, the ultimate effect is that the natural
pattern or cycle of sleep and daytime
wakefulness is disrupted. Factors involved
could be:
• Physical conditions e,g Peptic ulcer disease,
Asthma or heart failure
• Psychiatric conditions like depression and
anxiety, Burn-out syndrome
 Overview
• Use of recreational substances e.g. alcohol,
caffeine
• Night shift which disrupts the biologic clock
• Genetic e.g. narcolepsy
• Medicines, some interfere with sleep
• Ageing, about half of those above 65 years
have disturbed night sleep
• Poor sleep hygiene
 Common causes
• Insomnia( primary or secondary)
• Breathing related sleep disorder(Sleep apnoea)
• Narcolepsy(hypocretin/orexin disorder)
• REM sleep behaviour disorder
• NREM sleep arousal disorder
• Restless leg syndrome/Periodic limb movement
of sleep
• Nightmare disorder(night terrors)
• Circadian mediated dyssomnias(jet lag syndrome)
 Approach to common sleep disorders
• 1. History and physical exam
• 2. Sleep study or polysomnograpy (PSG)which
is an electronic record of specific physical
activity during sleep. The recording is analysed
by a asleep expert to aid in making a diagnosis
• 3. Multiple Sleep Latency Test(MSLT)
• 4. Sleep logs or diaries
 Approach…
• Relevant questions include:
• How many hours do you sleep at night?
• Do you toss and turn in your sleep?
• How long does it take for you to fall asleep?
• Do you wake up in the middle of the night?
• Do you work at night?
• How sleepy or fatigued do you feel during the
day or have problems with mood, concentration,
accidents at work or while driving?
• How often do you have an unrefreshing sleep?
 Approach…
• General measures to treat sleep disorders
• Practice sleep hygiene such as keeping a regular sleep
schedule
• Regular exercise
• Minimize light at bedtime
• Maintain comfortable room temperature
• Medications or supplements may help and should be
used for a few days
• Counseling/Cognitive behavioural therapy which may
help to recognise and change stress provoking
thoughts
 Approach
• Specific measures depends on the identified cause(s)
• Insomnia-Improve sleep hygiene/Short acting
benzodiazepine like drugs e.g. zopiclone
• Sleep apnoea- CPAP if no treatable cause is found
• Narcolepsy-medications like modafanil and oxbutyrate
for cataplexy
• REM sleep behaviour disorder-in chronic forms
responds to clonzepam
• Restless leg/periodic limb movement of sleep may
respond to levodopa or dopamine precursors or
gabapentin
 Conclusion
• Sleep is a complex multiphased physiologic
condition that is needed for homeostasis of the
brain and body with underlying complex
neurochemical substrates.
• It is regulated by the 24 hour circadian and
homeostatic mechanisms.
• Disturbance can occur primarily or secondarily
from external or environmental influences.
• To manage a sleep disorder requires history,
physical exam and specialised sleep studies like
PSG and MSLT and sleep logs or diary
Q and A