CENTRAL

HYPERSOMNIA
WHO, WHAT, WHERE?
● A group of sleep disorders
● Excessive Daytime Sleepiness in the absence of uninterrupted
nocturnal sleep or circadian rhythm disorders
● Narcolepsy was first described by Jean Baptiste Gélineau of a 38
y/o wine merchant >200 sleep attacks per day
● Idiopathic Hypersomnia - detailed by Bedrich Roth in a series of
642 patients seen over 30 days.
INTERNATIONAL CLASSIFICATION OF SLEEP
DISORDERS

● Narcolepsy Type 1
● Narcolepsy Type 2
● Idiopathic Hypersomnia
● Kleine Levin Syndrome
● Hypersomnolence due to medical disorder
● Hypersomnolence due to medication/substance use
● Hypersomnolence associated with psychiatric disease
● Insufficient Sleep Syndrome
INSUFFICIENT SLEEP SYNDROME
● Arguably not central
● Behaviourally Induced lack of sleep resulting in sleepiness
● Huge piece of DD for other central hypersomnias
● Diagnostic criteria-
● Daily sleepiness (in prepubertal children-behavioural problems),
● Sleep shorter than expected for age
● Sleep pattern must be present for most days x at least 3 months
● Use measures to shorten sleep
● Sleep longer without these measures
● Symptoms resolve with sleep extension.
HYPERSOMNIA DUE TO A MEDICAL DISORDER

● Daily sleepiness for 3 months

● Not due to other sleep disorder, psychiatric condition, or medication
● If MSLT done, MSL “usually” <8 minwith 0-1 SOREM- distinguishes
narcolepsy due to a medical disorder

MEDICAL NEUROLOGIC
Encephalopathies- Metabolic and Hepatic Parkinsonism

Systemic Inflammation- Rheumatoid Myotonic dystrophy

arthritis, Cancer, Chronic infection

Genetic Syndromes- Niemann Pick type C, Traumatic Brain Injury

Prader-Willi, Fragile X

Endocrine disease- Hypothyroidism Injury/Insult to Hypothalamus, B/L thalamus

and Midbrain- Stroke, Tumor, Sarcoid.
HYPERSOMNIA DUE TO DRUG/SUBSTANCE
● Daily sleepiness , duration not included
● Caused by either initiation of sedating medication or withdrawal of alerting medication
● Medications
● Sedatives and hypnotics
● AEDs, Dopamine agonsits
● Psychiatric - antidepressants, antipsychotics(dopamine antagonists), BZDs, Barbiturates
● Anticholinergics
● Antihistamines
● Muscle relaxants, pain meds
● Anti-arrhythmics
● Beta-blockers
● Discontinuation of wake promoting agents
● Substance abuse-
HYPERSOMNIA COMORBID TO PSYCHIATRIC CONDITION

● Daily sleepiness for 3 months

● Comorbid psychiatric disorder
● Not better explained by other causes of central hypersomnolence
● AGNOSTIC about cause/effect
● Conditions-
● Most common-

Mood disorders- atypical depression, SAD, Bipolar type 2, Anxiety Disorders

Somatoform disorders

● Least common-

Thought disorders, Adjustment Disorders and Personality disorders.

KLEINE LEVIN SYNDROME
At least 2 episodes of excessive sleepiness for 2 days to 5 weeks(median
duration-13 days, median frequency- 3-6 months without cataplexy.
1 in 5 million, Age of onset- 12-20, 2/3rd-boys, ~5% have family history
Triggers- viral infection, alcohol, sleep deprivation, stress, head trauma.
Recurrences at least once every 18 months(usually more than once a year)
In addition to excessive sleepiness, bouts must demonstrate at least one of:
● Cognitive dysfunction
● Altered perception (derealisation, depersonalisation)
● Eating disorder(anorexia or hyperphagia)
● Disinhibited behaviour
Normal alertness, cognition, behaviour and mood between bouts
MSLT mean sleep latency, no of SOREM, 24hr measured sleep time are not
required for diagnosis.
Hypersexuality, megaphagia, depressive or flat mood, anxiety, psychotic
symptoms(hallucinations, delusions), regressive behaviour, puerility
NARCOLEPSY TYPE 1
● Daily periods of irrepressible need to sleep OR daytime lapses into sleep, occurring
for at least 3 months, AND
● One or both of:

1. Cataplexy AND

MSL </= 8 min AND

2 + SOREMs ( or nocturnal 15 min SOREM and 1+ MSLT SOREM)

2. Low CSF Orexin concentration ( </= 110 pg/ml OR <⅓ of control values

1 in 2000

Family members have increased risk of hypersomnolence

25-31 % concordance in monozygotic twins

 Core features Clinical Aspect Presentation of Cataplexy

Tetrad : Duration Seconds to minutes

● EDS-100 % Typical muscle groups Neck, face, limbs

● Cataplexy- most
Laterality Bilateral
● Sleep paralysis- 53 %
● Hypnagogic /hypnopompic Consciousness retained
hallucinations-63 %
Tone Atonic
Other features-
Reflexes Reduced/absent in
● Sleep fragmentation affected muscles
● REM sleep behaviour disorder
Trigger Strong positive emotions

Positive phenomena Phasic muscle twitching

of the face may be seen
More dyskinetic
movements can be seen
in children
PATHOPHYSIOLOGY
Due to loss of hypocretin/orexin producing
neurons in the hypothalamus

The autoimmune hypothesis- HLA-DQB1*0602 ,

seen to be positive in 85% patients with
Narcolepsy Type 1. They have more hypocretin
reactive CD4+ and CD8+ T-cells

Clue to pathogenesis than as a diagnostic test

Also seen in patients

vaccinated with Pandemrix
for H1N1
H1N1 itself
NARCOLEPSY TYPE II
● Daily periods of irrepressible need to sleep OR daytime lapses into sleep,
occurring for at least 3 months, AND
● MSL < 8 min AND 2 + SOREMs ( or nocturnal 15 min SOREM and 1+ MSLT SOREM)
AND
● NO Cataplexy, AND
● Hypocretin is >110 ( or > ⅓ controls) or unmeasured, AND
● Not better explained by any other causes
● Prevalence-
1. Medical claims database of 8.4 million people of which 0.065% are type 2
narcoleptic
2. According to the Wisconsin sleep cohort 0.20 % are type 2 narcoleptic.

Family members have increased risk of hypersomnolence

IDIOPATHIC HYPERSOMNIA
● Excessive daytime sleepiness lasting at least 3 months
● No cataplexy
● No more than 1 SOREM between PSG and MSLT
● Not better explained by any other causes

● 3 different options for objective diagnosis( need to meet at least

one):
1. MSLT - MSL </= 8 mins
2. 24 hr PSG >/= 660 mins of sleep duration
3. 7 day actigraphy- total estimated sleep time- >/= 660 minutes
● severe/prolonged sleep
inertia PATHOPHYSIOLOGY
● Unrefreshing naps > 1 hour
● PSG sleep efficiency >/= 90% ● Abnormal activation of GABA-A
● Prevalence- rare receptors.
● Onset- late
adolescence/early adulthood ● Autonomic dysfunction- heart
● Probable Female rate variability during sleep
predominance
● Circadian dysfunction-
peripheral clocks and gene
expressions (fibroblasts).
TREATMENT
Non-pharmacologic strategies
NARCOLEPSY TYPE-1 IDIOPATHIC HYPERSOMNIA
● Regular nocturnal sleep times AND ● Naps are not typically helpful
short scheduled naps(in those with
severe residual EDS)

● School/work accommodations- late

start time
● School/work accommodations

● Counselling/support ● Counselling/support
1. Safety 1. Safety
2. Medication side effects 2. Medication side effects
3. Support groups 3. Support groups
 Narcolepsy Idiopathic Kleine-Levin Hypersomnia Post Genetic
Hypersomnia syndrome 2o to traumatic disorders
𝛼-synucleinopathies hypersomnia

Modafinil +++ +++ conditional conditional condition

al

Pitolisant +++ conditional

Solriamfetol +++

Sodium +++ conditional conditional

oxybate

Armodafinil conditional conditional conditional

Methyl- conditional conditional

phenidate

Dextro- conditional
amphetamine

Lithium conditional
SIDE EFFECTS
Modafinil/armodafinil-
● nervousness/irritability
● palpitations/tachycardia
● Headache
● Nausea
● rhinitis/pharyngitis
● SJS
● mania/psychosis/hallucinations/suicidal ideation
● Angioedema

MUST USE BIRTH CONTROL OTHER THAN/IN ADDITION TO OCPs

AMPHETAMINES/METHYLPHENIDATE

● irritability/anxiety
● Palpitations, elevated HR/BP
● Drug dependence (methylphenidate) and high abuse
potential(dextroamphetamine) - black box warnings

SODIUM OXYBATE

● Sodium salt of GHB, thus restricted distribution and drug

diversion/misuse
● Dosed at bedtime and 2.5-4 hrs later, short t ½
● Bed wetting, nausea, sleepwalking, mood changes/thought changes
● Black box warning - high abuse potential, CNS depression ->
respiratory depression, seizures, coma and death
Solriamfetol

● Dopamine and norepinephrine reuptake inhibitor

● Used for sleepiness associated with Narcolepsy(type 1 or type 2), OSA
● Available since 2019
● Schedule IV
S/E- headache, nausea, decreased appetite, nasopharyngitis, dry mouth, anxiety,
small increase in HR and BP

PITOLISANT

● H3 antagonist/inverse agonist
● Used for EDS with Narcolepsy (type 1 or 2)
● Decreased cataplexy by 75 %

S/E- headache, insomnia, GI distress and discomfort,

MUST USE OTHER CONTRACEPTIVE ALTERNATIVES OTHER THAN OCPs.

References
1. [Link]
2. [Link]
3. [Link]
on/sleep-and-health-education-program/sleep-health-education-
2
4. [Link]
on/sleep-and-health-education-program/sleep-health-education-
4
5. [Link]
6581000119
6. [Link]
7.