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Overview of Sleep Disorder.pdf
1. Overview of sleep disorders and
approach to common sleep
disorders
SA Abubakar
2. Outline :
• Introduction and definition
• Stages of sleep and sleep cycle
• Brain mechanism of wakefulness and sleep
• Wakefulness, non-REM and REM sleep generating circuits
• Parasomnias
• Hypersomnias
• Insomnia
• Conclusion
3. Definition:
• Sleep literally defines the state of the body and mind that typically
recurs for several hours every night, in which the nervous system is
relatively inactive, the eyes closed, the postural muscles relaxed, and
consciousness practically suspended.
• Sleep is defined on the basis of behavioral and physiological criteria
dividing it into two stages: non rapid eye movement (NREM) sleep
which is subdivided into three stages (N1, N2, N3); and rapid eye
movement (REM) sleep characterized by rapid eye movements,
muscle atonia and desynchronized EEG.
4. • From birth until death the human brain spends one or more periods
of each 24-hour day in wakefulness and the remaining hrs in sleep.
• Different people sleep different amount of hours (typically 7 to 9 hrs
per day) to equip them with optimal alertness, attention,
performance and executive function .
• Below is a summary of recommendation for sleep time duration
across the life span based on extensive lit review
5. sleep amounts across human lifespan:
Age brackets Recommended hours per day Not recommended
Older adults
>65 years
7 to 8 >10
Adults
26-64 years
7 to 9 >10
Young adults
18-25 years
7 to 9 >11
Teenager
14-17 years
8 to 10 >11
School-aged children
6-13 years
9 to 11 >12
Pre-schoolers
3 – 5 years
10 to 13 >14
Toddlers
1-2 years
11 to 14 >16
Infants
4-11 months
12 to 15 >18
New born
0-3 months
14 to 17 >19
6. Introduction:
• Sleep duration is one of the two major components underlying optimal sleep, the other
being sleep intensity.
• Sleep intensity or depth is commonly measured as the difficulty in waking someone up
from sleep in response to given stimulus such as an auditory tone. Such index of sleep
depth is correlated with the prominence of high-voltage slow waves in the EEG.
• Based on the distribution of sleep stages throughout the night, normal sleep is typically
characterized by;
i. Deep non-REM sleep predominately at the beginning of the night
ii. Lighter non-REM sleep and increasing intrusions of the of wakefulness toward the end
of the night
iii. Increasing REM sleep amounts and intensity throughout the night
7. Stages of sleep:
AASM recognizes and recommends the following stages of sleep
➢Stage W: wakefulness
➢Stage N1: non-REM sleep or NREM 1
➢Stage N2: NREM 2
➢Stage N3: NREM 3
➢Stage R: REM sleep
8. Sleep cycle
• In the first portion of a typical night’s sleep, the normal adult passes successively
through stages N1, N2, N3, and R (REM) sleep.
• After about 70 to 100min, a large proportion of which consist of stage N3, the
first REM period occurs, usually heralded by a transient increase in body
movement and a shift from N3 to N2.
• This NREM-REM cycle is repeated at about same interval four to six times during
the night
• The first REM may be brief, the later cycles have less stage N3 or none at all
• In the latter portion of a night’s sleep, the cycle consist essentially of two
alternating stages ie REM sleep and N2 (spindle-K-complex) sleep
9. Brain Mechanism of wakefulness and sleep:
• Several discrete clusters of cells exit in distinct regions of the brain that together
comprise the interconnected circuit generating the state we recognize as wakefulness,
non-REM and REM sleep
• These interconnecting clusters of brain cells use individual neurotransmitter or collection
of neurotransmitter to inhibit or excite their target sites.
• Some commonly used drugs modulates these excitatory or inhibitory connections and
thus exert alerting or sedating properties or influence specific components of sleep
behavior.
• Individuals experience what is classified as normal sleep behavior when the activity of
these cells clusters and circuit, change in a normally coordinated sequence in time and
place within the brain
10. Brain Mechanism of wakefulness and sleep:
• Sleep disorders are common and varied , suboptimal timing or quality of sleep can occur as a
result of two major factors that are not mutually exclusive:
Primary sleep disorder eg
o Insomnia
o Narcolepsy
o Restless leg syndrome
o Sleep wake disorder
Lifestyle influence eg
Phase shift due to occupational or recreational activities such as
• Shift work
• Lack of exposure to direct sunlight or
• Extended nocturnal artificial light.
11. Brain Mechanism of wakefulness and sleep:
• A. Sleep is best optimized when the sleep period is appropriately aligned
with an individuals circadian body clock ie when the sleep type is aligned
with chronotype .
Misalignment or mismanagement of this optimal relation can result in
experience of poor sleep quality, inappropriate sleepiness, and sleep
initiation or maintenance insomnia. Such misalignment occur in
oShift work sleep disorder
oadvanced or delayed sleep –wake phase disorders
oIrregular sleep-wake disorder
12. • B. Sleep Parasomnia are best explained by basic premise that sleep
and wakefulness are not mutually exclusive state and can dissociate.
Such dissociation can result in component of behaviors that are
normally associated wakefulness temporally overlapping with sleep
• Such overlap causes a class of sleep disorder that classified as
parasomnia .
• Parasomnia are defined as behavior or experiences intruding into
sleep
14. Wakefulness-generating circuit:
• Several neuronal groups contribute to the brain activation of wakefulness,
which is characterized by low-voltage and fast-wave EEG activity and
resting postural tone in EMG.
• Lesion or degeneration of the ascending progression of the arousal circuit
can produce excessive sleepiness.
• Drug-induced modulation of these circuit facilitate sedation and sleep
• Monoamines that are concerned with neuromodulation include;
• Norepinephrine, histamine, serotonin and Dopamine. Other cells also
contribute to activated brain state of wakefulness. E.g orexin(hypocretin),
acetylcholine, and glutamate containing cell groups.
15. • Norepinephrine-containing neurons of the locus coeruleus in the dorsal
pons have widespread projections throughout the brain including ;
forebrain and cerebral cortex in addition to the brain stem arousal and
autonomic system
• Their activation contributes to attention, cortical arousal as well as
autonomic activation.
• Activation of locus coeruleus neurons is maximum in wakefulness and
decline in non-REM sleep and minimal in REM sleep
• Stimulants medication e.g methylphenidate, amphetamine facilitate
noradrenergic projections to promote alertness in patients with
hypersomnia disorder.
16. • Histamine-containing neuron in the tuberomammillary nucleus of the
caudal hypothalamus contribute to brain arousal via excitatory projections
to forebrain, cerebral cortex and brain stem.
• Tuberomammillary nucleus is the one major source of brain histamine and
has widespread projections throughout the CNS.
• The activity of histaminergic neurons are maximum in wakefulness, decline
in non-REM and minimal in REM sleep.
• Through this organization and activity profile, antihistamine that penetrate
the BBB promote drowsiness and sleep.
17. Two major collection of serotonin-containing neuron ;
❖Rostral group in pons project to cerebral cortex
❖Caudal group in medulla projects to brainstem and spinal cord.
Activity of serotoninergic neuron is maximum in wakeful, decline in
non-REM and minimal in REM sleep.
18. • Dopamine-containing neurons of the ventral tegmental area and periaqueductal
gray project to the striatum and frontal cortex. Activation of these dopamine
containing neuron is relevant in arousal and movement.
• Orexin-containing neurons located in the lateral hypothalamus also have
widespread projections to the brain stem, thalamus, hypothalamus and cerebral
cortex.
• The strongest projection are to the locus coeruleus.
• The activity of orexinergic neuron is maximum in the period of wakefulness
associated with overt movement and motor activation and decline to minimal
levels in NREM sleep and REM sleep without muscle twitches (Atonic REM)
19. • Loss of Orexin (hypocretin) neuron is involved in clinical signs and
symptoms of Narcolepsy and cataplexy.
The two collection of acetylcholine containing
20. Non-REM sleep generating circuit:
• NREM sleep is facilitated and maintained by a group of neurons that inhibit the
brain-arousal system of wakefulness.
• The major NREM sleep generating cell groups are located in ;
✓Ventrolateral preoptic area
✓Anterior region of hypothalamus
✓Basal forebrain
• These regions have activity level that are maximum in NREM sleep and lowest in
wakefulness with maintained (or moderately reduced) activity in REM sleep
•
21. • These sleep-active cell groups synthesize and secrete the inhibitory
amino acid Y-aminobutyric acid (GABA) and neuropeptide galanin
• Inhibitory non-REM sleep generating system initiates and sustain
sleep and inhibit arousal once these cell groups are released from
inhibition and became active at sleep onset.
• The arrangement of reciprocal inhibition between arousal and non-
REM sleep –generating neuronal system has been termed the sleep-
wake switch.
22. Coordinating influences of the circadian
timing system:
• In an average adult, a decline in body temperature at night (usually
10.00-11pm) precipitate optimal and typical sleep onset.
• Body temperature cycle has influence on sleep wake switch. The
circadian-mediated decline in body temperature at night activates
sleep active GABA neuron thus promoting sleep.
23. Effect of drugs on sleep-wake switch
Commonly used drugs can also flip the sleep-wake switch toward alertness
or sedation
➢GABA-ergic drugs such as Benzodiazepine, imidazopyridine , barbiturate
,and IV and inhalational anaesthetia propofol
➢These drugs can induce sedation/sleep through stimulation of GABA.
➢Development of antagonism for the orexin (hypocretin) peptide also offer
promising avenue for drug development for insomnia as well providing for
brain sedation with reduced risk of respiratory depression due to lack of
direct effects of the orexinergic antagonist on GABA-ergic system.
24. Caffeine:
• Widely used as stimulants and act as adenosine receptor antagonist.
• Adenosine inhibit wake active neurons and blockade of this inhibition
with caffeine promotes brain arousal and effectively tip sleep-wake
switch toward arousal .
25. REM-sleep generating circuit:
• REM sleep is a state accompanied by ;
o dreaming
oHeightened brain neuronal activity
oParalysis of skeletal muscles (except the diaphragm)
oHeightened cardiovascular and respiratory variability
oDepressed respiratory response to hypoxia and hypercapnia
• Disorder in discrete component of REM sleep circuitry can lead
distinct clinical motor disorders and parasomnia
26. • Two major circuit are involved in REM sleep generation and their essential
elements include interaction
• GABA-nergic and Glutaminergic
• Monoaminoergic and cholinergic neurons
• The critical REM-sleep generating regions is located in dorsal pons and activation
of these region produces the defining signs of REM sleep low-voltage and fast
wave EEG activity and muscle atonia due to active suppression of postural muscle
tone
• In GABA and glutaminergic mech of REM sleep generation, activation of pontine
glutaminergic neurons of the sub coeruleus nucleus leads to REM sleep
• Those glutaminergic cells became active to generate REM sleep when they are
released from inhibition by pontine GABA-ergic neurons located in ventrolateral
periaquedutal gray and lateral pontine tegmentum
27. • In monoaminergic and cholinergic explanation of REM sleep,
decreased activity of monoaminergic cell groups withdraws inhibition
of pontine cholinergic neurons and thus results in increased
acetylcholine release into pontine reticular formation and promotes
entry into REM sleep.
29. REM Sleep Behavior Disorder:
➢Repeated episodes of sleep-related vocalization and/or complex motor
behavior
➢These behaviors are documented by polysomnography to occur in REM
sleep or base on clinical history of dream enactment, are presumed to
occur in REM sleep.
➢Polysomnographic recording demonstrates REM sleep without atonia
➢The disturbance is not better explained by another sleep disorder, mental
disorder, medication or substance use.
ICSD-3 diagnostic criteria for RBD: AASM-2014
30. Nightmares:
➢Repeated occurrences of extended, extremely dysphoric and well-remembered dreams that
usually involve threats to survival, security or physical integrity
➢On waking from the dysphoric dreams, the person rapidly becomes oriented and alert
➢The dream experience, or the sleep disturbance produced by awakening from it, causes clinically
significant distress or impairment in social, occupational or other important areas of functioning
as indicated by the report of at least one of the following:
1. Mood disturbance e.g persistence of nightmare effect, anxiety, dysphoria
2. Sleep resistance
3. Cognitive impairment
4. Negative impact on caregivers
5. Behavioral problems e.g bedtime avoidance, fear of the dark
6. Daytime sleepiness
7. Fatigue or low energy
8. Impaired occupational or educational function
9. Impaired interpersonal/social function ICSD-3
31. Recurrent isolated sleep paralysis:
• In RBD the persisting muscle tone during the REM sleep permits the
occurrence of RBD behaviors, whereas in recurrent isolated paralysis
the REM sleep atonia persists and extend into wakefulness
• The characteristic clinical feature of sleep paralysis is the complete
inability to move (not only heaviness) in the presence of full
wakefulness
• Ancillary respiratory muscle are affected from REM sleep atonia but
not the diaphragm
• Frequent triggers include sleep deprivation, jet lag, comorbid OSA
32. Disorder of sleep wake cycle
Hypersomnias
• Narcolepsy types 1 and 2
• Idiopathic hypersomnia
• Kleine levin syndrome
• Other central hypersomnias
33. Disorders of sleep:
Narcolepsy
• is debilitating sleep disorder that can impair a person ability to work,
socialize and drive safely
• Is caused by loss of hypothalamic orexin cells and is characterized by;
oExcessive sleepiness
oDisturbed REM sleep
oSleep paralysis(atonia)
oHypnagogic and hypnopompic hallucinations
oCataplexy which is involuntary onset of skeletal muscle paralysis or
weakness during otherwise normal wakeful
34. Disorders of sleep:
Narcolepsy
• During periods of sleepiness automatic activities e.g
❖saying something inappropriate or out of context in a conversation
❖Writing something inappropriate or illegible
❖Doing an act such as driving to an inappropriate place/location with
no memory of event
35. Disorders of sleep:
Narcolepsy
• Cataplexy:Is pathognomonic symptom of narcolepsy type1 defined
by loss of muscle tone in full consciousness triggered by emotions
particularly positive ones such as laughter or surprise.
• Cataplexy can either be generalized and lead to fall or partial
• Muscle tone and reflexes are abolished during cataplexy since the
pathophysiology of cataplexy seems mediated by intrusion of
physiologic REM sleep into wakefulness.
36. Disorders of sleep:
Narcolepsy
• Other symptoms associated with Narcolepsy but non-specific which is a
transient paralysis lasting a few seconds or minutes while falling asleep
• Hypnagogic and hypnopompic hallucinations can occur at the same time as
the paralysis and can be frightening
• Night time sleep is altered and fragmented with multiple nocturnal arousal
and sometime with sleep maintenance insomnia.
• Diagnosis : include a medical history, sleep logs and polysomnography,
HLA- genotype and CSF examination for Hypocretin
Narcolepsy is caused by selective loss of a small population of neurons in
the lateral hypothalamus that synthesize hypocretin.
37. Diagnosis of Narcolepsy
• ICSD-3:
Narc 1
• Presence of excessive day time sleepiness >3 months associated with
presence of cataplexy and hypocretin-1 level of 110pg/ml or less in
the CSF
Narc 2
• Presence of excessive daytime sleepiness without cataplexy for
longer than 3months, hypocretin-1 level of greater than 110pg/ml
39. Idiopathic hypersomnias
• Is a rare dx but epidemiological more common in women
• There are two phenotyes, one with excessive daytimne sleepiness with
prolonged nocturnal sleep duration > 10 or 11 hours and the other without long
nighttime sleep.
• There is associated difficulty in waking up in the morning
• Diagnosis: requires the presence of all the fll (ICSD-3)
➢Excessive daytime sleepiness, irrepressible need to sleep or daytime lapses into
sleep for the past 3 months
➢Mean sleep latency on multiple sleep test of 8 or few minutes and or total sleep
time on 24-hour polysomnography
➢No more than one sleep-onset REM period on polysomnography recording and
the multiple sleep latency test
41. Kleine Levin syndrome
• Is a recurrent hypersomnia with a prevalence of 1-2 per million and largely affect young
adults.
• Clinical features
Relapsing-remitting episodes of severe hyper somnolence associated with
❖behavioral and psychiatric disturbance
❖Cognitive abnormalities
❖Hyperphagia or hypersexualty
Mean duration of an episode is 10 days recurring every 1-12months .
Triggering factors such infection or alcohol intake are often reported
Treatment : No randomized trial
42. Insomnia disorder:
• Is common in Neurology practice but is largely most often
underdiagnosed.
Definition: insomnia disorders refer to persistent difficulties
oFalling asleep
oMaintaining sleep or waking up earlier than habitual rise time
oAssociated with impairment of daytime functioning despite the
opportunity for sufficient sleep duration
oDiagnosis : ICD-10 DSM-5
43. Epidemiology:
• More common in women and older adults
• In general population about 1/3 of adults report intermittent
symptoms of insomnia, while about 10% meet the criteria for chronic
insomnia disorder associated with daytime sequel.
• Brief insomnia episodes have identifiable precipitants such as
situational crises, new medication and stress
44. Chronic insomnia:
Diagnostic criteria
A. The patient/family members/caregivers reports or observes one or more of the fll
1. Difficulty with sleep initiation
2. Difficulty with sleep maintenance
3. Waking up earlier than desired with difficulties reinitiating sleep
4. Opposition to going to bed during habitual bedtime schedule
5. Difficulties sleeping without the intervention of the parent or caregiver.
B. The patient/family members/caregivers reports or observes one or more of the fll difficulties in relationship to the nighttime sleep difficulty
1. Malise/fatigue
2. Impairment in concentration, attention or memory
3. Impairment in domains of social function , fulfillment of family duties or difficulties with occupational or academic performance
4. Disturbance in mood and or iritability
5. Excessive daytime somnolence etc
45. Chronic insomnia:
Diagnostic criteria
C. The reported sleep/wake difficulties cannot be otherwise explained by
inadequate opportunity for sleep
D. Frequency criteria: the sleep difficulties and associated daytime
symptoms must occur at a frequency of at 3 times per week
E. Duration criteria: the sleep disturbance and the associated daytime
symptom must be present at least 3 months
F. The sleep/wake disturbance is not attributed to or explained by another
underlying primary sleep disorder (OSA)
46. Subtypes of insomnia:
Psychophysiologic insomnia:
• The underlying mechanism of psychophysiologic insomnia is behavior
based phenotype reflecting a conditioned heightened arousal
associated with the bed, the environment within the bedroom(e.g
clock) and maladaptive bedtime routine
Adjustment insomnia:
• Occur in temporal association with an identifiable stressor usually
spanning a duration of fewer than 3 months.
• Sleep should improve with resolution of the stressor
• In some cases adj insomnia may evolves into a chronic form.
47. Paradoxical insomnia:
• Refers to sleep state misperception and reflect a complaint of severe
sleep disturbance in absence of corroborative and objective verifiable
indicators of the degree of sleep disturbance claimed.
• Idiopathic insomnia :
• subtype of insomnia not related to any identifiable precipitant that
begins insidiously in childhood and continues chronically in an
unremitting pattern into adulthood.
48. Inadequate sleep hygiene insomnia
Patients with this insomnia subtype engage in maladaptive behavior
that interfere with normal sleep promotion and continuity.
These detrimental behavior may include;
➢Aberrant sleep-wake schedule problems
➢Consumption or use of substance that disrupt sleep (e.g caffeine,
tobacco or alcohol) and engaging in evening routine that are not
conducive to sleep
➢Prolonged daytime napping that is too close to bedtime
➢Regularly using the bedroom for activities other than sleep.
49. Other subtypes of insomnia include;
• Behavior insomnia of childhood
• Insomnia due to mental disorder
• Insomnia due to medical conditions
• Insomnia due to a drug or substance
50. Evaluation and assessment of insomnia:
• A good general rule is to consider potential etiologies and likely predisposing factors
• There is a clinical guidelines for evaluating insomnia published by AASM-2008
• Sleep questionnaire and sleep logs are very important in supplementing the formal
evaluation of a patient with insomnia
• A sleep diary spanning a period of several weeks can be quite helpful
• General physical examination and Neurologic examination
• Sleep medicine examination and mental status examination are essential
• polysomnography
51. Education and health sleep habits
• Sleep hygiene
• Ensure sleep-wake timing is regular
• Avoid excessive time awake in bed
• Refrain from inappropriate and excessive napping behavior
• Encourage environmental condition conducive to sleep
• Minimize noise
• set a cooler room temperature
52. Psychological and behavioral strategies:
• CBT
• Sleep restriction
• Stimulus control therapy
• Relaxation therapy
53. Pharmacologic approaches
Medical mgt of insomnia consist of four main treatment categories
❖Medication approved by FDA for the treatment of insomnia
❖Sedating prescription medication not specifically approved by FDA
for insomnia
❖Over-the-counter sleep aids that are regulated but does not require
prescription
❖Extensive list of unregulated dietary supplements
54. Insomnia medication (approved)
Ƴ-aminobutyric acid and (GABA-A) receptor modulations;
• Benzodiazepine : flurazepam, Temazepam, Triazepam and Estazolam
• Non-Benzodiazepine: Zolpidem, Zaleplon, Eszopidone (immediate
release)
• Non benzodiazepone e.g Zolpidem (ER)
• Melatonin receptor agonist e.g Ramelteon, Tasimelron
• H1 Receptor antagonist: ultra low dose Doxepin for maintenance
• Hypocretin(orexin) receptor antagonist e.g Suvorexant for sleep onset
and maintainence
56. Conclusion:
• Chronic insomnia in neurology practice represent a unique
opportunity for clinicians to help improve the QoL across patients
with comorbid neurologic conditions.
• All patients should be screened to help uncover poor sleep behaviors,
since insomnia may exacerbate health problems, undermine the
quality of sleep, limit the ability to remain awake and worsen daytime
function.
