SLEEP-WAKE

DISORDERS
PART-II
Dr. Subhechhya Basnet
2nd-year Resident
Department of Psychiatry
 Narcolepsy
This disruption can
Narcolepsy is a
cause excessive
disorder that
sleepiness (the
disrupts sleep-wake
primary symptom
processes.
of narcolepsy)
In narcolepsy,
• Changes in the brain disrupt how sleep works.

• As a result, REM sleep is irregular and often begins within minutes after
falling asleep, which is much earlier than normal.

• The inability to properly regulate the sleep cycle can lead to serious
daily problems.
 Neurobiology
• During typical wakefulness, the hypocretin (orexin) increases the
activity of RAS.

• RAS activates different nuclei found in the CNS, which generate

wakefulness-promoting neurotransmitters (dopamine, NE, Ach,
serotonin, histamine)

Prevent REM sleep, and help maintain muscle tone and wakefulness
throughout the day.
• RAS inhibits the VLPO area (sleep-promoting brain region)

Suppresses GABA

Increases muscle tone and activity of motor neurons

• In Narcolepsy Loss of Hypocretin (Orexin) neurons

Mechanism separating sleep and awake states becomes unstable

RAS no longer stimulates the release of wake-promoting

neurotransmitters and inconsistently suppresses the VLPO area.

Leading to EDS
Narcolepsy was characterized by a tetrad of symptoms:
Excessive sleepiness
Cataplexy
Sleep paralysis
Hypnagogic hallucinations
The sleep attacks of narcolepsy represent episodes of irresistible
sleepiness, leading to perhaps 10 to 20 minutes of sleep, after which
the patient feels refreshed, at least briefly.

REM sleep includes hypnagogic and hypnopompic hallucinations,

cataplexy, and sleep paralysis.
Cataplexy
• Involves the sudden loss of muscle tone, usually
with continuing full or partial consciousness.
• Commonly precipitated by laughter.
• Severity ranges widely from transient weakness
in the knees to total paralysis while the patient
is fully conscious.
• Episodes may last from several seconds to
minutes.
• Usually, the patient is unable to speak and may
fall to the floor.
 Neurons located in
the lateral
Why cataplexy occurs?
hypothalamus
produce orexin-A

It potentiates the
production of Leading to the
dopamine, suppression of REM
histamine, sleep.
norepinephrine,
and serotonin.
 With loss of orexins,
During REM sleep, These paralysis
levels of these two
most muscles are circuits are normally
neurotransmitters
paralyzed by circuits blocked by
may be lower,
in the lower norepinephrine and
permitting paralysis
brainstem and serotonin during
to occur even
spinal cord. wakefulness.
during wakefulness.
• Orexin neurons are active in the response to strong emotions.

• Loss of orexin-positive neurons in patients who have narcolepsy or

narcolepsy with cataplexy.

• Destabilizes the motor control system within the brainstem such that
positive emotions trigger severe muscle weakness or total motor
paralysis.
Sleep paralysis and hypnagogic hallucinations are nonspecific
symptoms and may occur in isolation.

Sleep paralysis is similar to the muscle atonia occurring during REM

sleep and hypnagogic hallucinations resembling dreaming.
 According to
the International
Types of Narcolepsy
Classification of Sleep
Disorders (ICSD-3)

Narcolepsy type 1 (NT1) Narcolepsy type 2 (NT2)

 Narcolepsy Type 2
1

• NT1
Peopleis with
associated
NT2 have
withmany
the
symptoms
similar symptoms
of cataplexy.
as people
• with
NT1 NT1,
can but
alsothey
bedodiagnosed
not have
cataplexy or low
when a person levels
has low of
levels
hypocretin-1.
of hypocretin-1.
NT1 affects 0.02%–0.05% of the adult general population worldwide.
Epidemiology & Course
It occurs roughly equally in men and women and can affect both
children and adults.
It can occur at any age, but onset has been found to peak at around
age 15 and again around age 35.
Onset can be abrupt or progressive, with cataplexy developing over the
years.
Once the disorder has manifested, the course is persistent and lifelong.
Diagnostic Criteria (DSM-5 TR)
Irresistible sleep episodes, lapses into sleep, or napping at least 3
days per week for at least 3 months.
This hyper somnolence profile must occur in conjunction with one or
more of the following:
1. Cataplexy occurring at least a few times per month.
2. CSF hypocretin-1 deficiency ( less than or equal to 110 pg/ml )
3. An overnight polysomnography revealing a REM sleep latency
of 15 minutes (or less)
or a multiple sleep latency test (MSLT) in which
mean sleep latency is 8 minutes (or less)
and REM sleep occurs on two (or more) nap opportunities.
Hypersomnolence disorder
Differential
Sleep apnea syndromes Diagnosis
Insomnia disorder

Major depressive disorder

Atonic seizures

Syncope
There is no cure for narcolepsy type 1 or type 2.
Treatment
The goals of treatment for narcolepsy are improving symptoms,
reducing risks, and enhancing quality of life.
For many people, narcolepsy remains generally stable over time.

In some cases, certain symptoms may improve over time, and rarely,
remission of symptoms may happen spontaneously.
Planning short naps
Behavioral Approaches to
Having healthy sleep hygiene Treatment

Avoiding alcohol and other sedatives

Driving with caution

Exercising and eating a balanced diet

 Pharmacological Treatment
• Modafinil and armodafinil: promote wakefulness and are typically the first
therapy for EDS.

• Methylphenidate: this is a type of amphetamine that can reduce EDS.

• Solriamfetol: this drug was approved by the FDA in 2019 and has
shown comparable effects on EDS as modafinil.

• Sodium oxybate: This medication can reduce cataplexy, EDS, and nighttime
sleep disturbances.

• Pitolisant: approved by the FDA in 2019, shown a positive effect on cataplexy.

ParasomniasParasomnias (Disorders
are disorders characterized by abnormal behavioral, of
experiential, or physiological events associated with sleep, specific
Partial
sleep stages, or sleep-wake transitions.
Arousal)

The most common parasomnias are

• NREM Sleep Arousal Disorders

• REM Sleep Disorders
 Sleepwalking (Somnambulism)
Non-rapid Eye Movement
• A condition in which an individual arises from bed
Sleep
and ambulates without Arousal
fully awakening. Disorders
• Individuals can engage in a variety of complex
behaviors while unconscious.
• Occurs during NREM slow-wave sleep.
• Sleep deprivation and interruption of slow-wave
sleep appear to exacerbate, or even provoke,
sleepwalking in susceptible individuals.
Sleepwalking episodes may range from sitting up and attempting to walk to
conducting an involved sequence of semi-purposeful actions.

An individual who is sleepwalking is difficult to awaken.

Sleepwalking in adults is rare, has a familial pattern, and may occur as a primary
parasomnia or secondary to another sleep disorder (e.g., Sleep apnea).

Sleepwalking is very common in children with peak prevalence between ages 4

and 8 years. After adolescence, it usually disappears spontaneously.

Nightly to weekly sleepwalking episodes associated with physical injury to

patients and others are considered severe.
Sleep-related eating:
• This occurs when an individual experiences episodes of ingesting food
during sleep with varying degrees of amnesia.
• Individuals may find evidence of these episodes the next morning
with little to no memory of their eating.

Sexsomnia:
• Sleep-related sexual behavior, or sexsomnia, is when a person
engages in sexual activities during sleep without conscious awareness.
Sleep Terrors(Pavor nocturnus, incubus, or
night terror)
• A sleep terror is characterized by a sudden
arousal with intense fearfulness.
• An individual experiencing a sleep terror usually
sits up in bed, is unresponsive to stimuli, and if
awakened is confused or disoriented.
• Vocalizations may occur but they usually are
incoherent.
• Amnesia for the episodes usually occurs.
 Episodes Fever and CNS
usually arise depressant withdrawal
from slow- potentiates sleep
wave sleep. terror episodes.

Sleep
Severity ranges from less
deprivation can
than once per month to
provoke or
almost nightly
exacerbate
occurrence.
sleep terrors.
Lifetime prevalence
Occur most commonly in of
childhood andEpidemiology
sleepwalking overall inranges
diminish and Course
from approximately
frequency 6.9%
with increasing [Link]
29.2% around the world,
Sleepwalking and sleep terrors are
frequently outgrown following
The prevalence
infancy of sleep
and childhood terror
and become
disorder
less in thebygeneral
frequent population
adolescence, with
is unknown.
remission rates between 50% and
65% respectively.
Nightmare Disorder
REM sleep disorder
• Nightmares are frightening or terrifying dreams.
• Sometimes called “dream anxiety attacks.”
• Occur in REM sleep and usually evolve from a long, complicated dream that
becomes increasingly frightening.
• Having aroused to wakefulness, the dream content is typically remembered.
• Nightmares usually terminate with awakening and a rapid return to full
alertness.
• However, the dysphoric emotions may persist into wakefulness and contribute
to difficulty returning to sleep and lasting daytime distress.
Individuals at risk for nightmares include those with schizotypal, borderline,
and schizoid personality disorders, as well as those with schizophrenia.
Traumatic events are known to induce nightmares, sometimes immediately,
but at other times delayed.

L-dopa and β-adrenergic blockers, withdrawal from REM suppressant

medications, and drug or alcohol abuse are associated with nightmares.
Associated Features
• Mild autonomic arousal, including sweating, tachycardia, and
tachypnea, may characterize nightmares.
• Body movements and vocalizations are not characteristic because
of REM sleep–related loss of skeletal muscle tone.
Diagnostic Criteria
Prevalence of nightmares during childhood is approximately 1%–5%.
From 1.3% to 3.9% of parentsPrevalence
report that their preschool children have
nightmares “often” or “always.”
Prevalence increases to 5.2% in children ages 5–15 years.

Among adults in several countries, prevalence of weekly nightmares is

2%–6%, whereas prevalence of frequent nightmares is 1%– 5%.
Differential Diagnosis
Sleep terror disorder
REM sleep behavior disorder
Narcolepsy
Sleep-related seizures
Breathing-related sleep disorders
Panic disorder
These behaviors often reflect motor responses to the content of action-
Rapid
filled or violent Eye
dreams of Movement
being attacked Sleep
or trying to escape from a
threatening situation, which may be termed dream-enacting
behaviors. Behavior Disorder
The vocalizations are often loud and emotion-filled.

These behaviors may result in significant injury.

The eyes typically remain closed during these events.

The presence of REM sleep without atonia during a polysomnogram is

typically required for the diagnosis of REM sleep behavior disorder.
Diagnostic criteria
 Prevalence

• One prevalence study found an equal prevalence between men and

women in individuals younger than 50 years.
• While another study reported a prevalence of just over 1% with no
difference between men and women in a population with a mean age
of 59 years.
• Prevalence in individuals with psychiatric disorders may be greater,
possibly related to medications prescribed for the psychiatric disorder.
The onset of REM sleep behavior disorder may be gradual or rapid.
Development and Course
In individuals with idiopathic REM sleep behavior disorder, the risk of
developing a defined neurodegenerative disease is approximately 75%
within 10–15 years following diagnosis.
Symptoms in young individuals, particularly young women, should raise the
possibility of narcolepsy; substance/medication-induced sleep disorder,
parasomnia type; a brainstem lesion; or an autoimmune encephalopathy.
 Differential Diagnosis
Other parasomnias
Nocturnal seizures
Obstructive sleep apnea
Reassurance and education is very important as most kids grow out of
Treatment
these behaviors of parasomnias
without any intervention

Find out potential triggers

Maintaining a good sleep hygiene

It is a sensorimotor, neurological sleep disorder
Restless
characterized legs
by a desire to move syndrome
the legs usually (RLS)
associated with uncomfortable sensations..

Frequent movements of the legs occur to relieve

the uncomfortable sensations.
 The diagnosis
of RLS is The
based symptoms of RLS is
primarily on RLS can delay associated
individual sleep onset with daytime
Symptoms are self-report and awaken sleepiness
often most and history. the individual and is
severe at from sleep frequently
night when It is important and are accompanied
the individual to associated by significant
is at rest. differentiate with clinical
RLS from significant distress or
other sleep functional
conditions fragmentation impairment.
that cause leg .
discomfort.
RLS is about twice as common in women as men and increases in
prevalence with age.

RLS associated with pregnancy peaks during the third trimester and
improves or resolves in most cases soon after delivery.

Prevalence rates of RLS vary widely. When the frequency of symptoms

is at least three times per week with moderate or severe distress, the
prevalence rate has been estimated as 1.6%.
 RLS that is severe enough to significantly impair functioning or is
associated with mental disorders, including depression and anxiety,
occurs in approximately 2%–3% of the population.
RLS typically occurs in the second or third decade.

Approximately 40% of individuals diagnosed with RLS during adulthood

report having experienced symptoms before age 20 years, and 20%
report having experienced symptoms before age 10 years.
The RLS includes two groups in general:
• Primary RLS
• Considered to be idiopathic when the cause is truly unknown.
• Among the idiopathic RLS, 40.9–92% of them had a family history
of RLS, indicating the important role of genetic factors in
developing RLS.
• Secondary RLS
• Cases have an onset after 40 years old.
• Associated with a variety of neurological disorders, iron deficiency,
pregnancy, or chronic renal failure.
According to the onset of the symptoms,
• Early-onset RLS
• Refers to those who first have the symptoms before 45 years old.
• Various clinical courses with periodic remissions are common in early-
onset RLS.
• A higher familial history rate was found in early-onset RLS compared
to late-onset RLS.
• Late-onset RLS
• Patients have the symptoms from or after 45 years old.
• A chronic progressive clinical course with more severe symptoms is
seen in late-onset RLS.
RLS has aspects of a genetically moderated neurodevelopmental
Neurobiology
disorder involving mainly the cortico-striatal-thalamic-cortical circuits.

Brain iron deficiency remains the key pathobiological factor.

• Leads to a hyperdopaminergic and hyper-glutamatergic states that

determine the dysfunction of CSTC circuits in genetically vulnerable
individuals.
• Leads to hypoadenosinergic state which contributes to the
sensorimotor signs of RLS and the enhanced arousal state.
 Periodic Limb Movement Disorder

• Previously known as nocturnal myoclonus and is a very common

phenomenon in RLS patients.

• Is defined as involuntary movements of the patient’s limb or torso

during awake or sleep which the patient is not aware of.

• A previous study indicated that PLMS was found in around 80% of RLS
patients

• A movement in PLMS starting in sleep can continue when waking up

and vice versa.
Diagnostic Criteria
Differential
Leg Diagnosis
Positional
cramps discomfort

Arthritis Myalgia
Three aspects should be considered:
Treatment
• Lifestyle change,
• Medication effect and
• Iron deficiency (defined as ferritin < 75 ng/ml or iron/TIBC ratio <
20%)
Pharmacological Treatment
• Dopaminergic agents are considered the first-line treatment for
RLS, including Pramipexole and Ropinirole.

• α2δ agonists like Gabapentin and Pregabalin are advised as first-

line agents in patients with severe sleep disturbance, comorbid
anxiety, RLS-related pain, or previous history of ICDs.
Selective serotonin reuptake inhibitors (SSRIs) and tricyclic
antidepressants (TCAs) can worsen the symptoms of RLS.

Since bupropion, doesn’t show any evidence of exacerbation of RLS

symptoms, it is used as an effective antidepressant in these patients.
 References
Kaplan & Sadock’s Comprehensive Textbook Of Psychiatry, 10th Edition
Kaplan & Sadock’s Synopsis Of Psychiatry, 11th Edition
Diagnostic And Statistical Manual Of Mental Disorders 5th Edition –TR
American Academy Of Sleep Medicine. (2014). International
Classification Of Sleep Disorders — Third Edition (ICSD-3)
[Link]
New Insights into the Neurobiology of Restless Legs Syndrome, 2018
Guo S, Huang J, Jiang H, Han C, Li J, Xu X, Zhang G, Lin Z, Xiong N, Wang
T. Restless Legs Syndrome: From Pathophysiology To Clinical Diagnosis
And Management. Front Aging Neurosci. 2017 Jun