HYPERSOMNIAS OF CENTRAL ORIGIN
Not due to a circadian rhythm sleep disorder, sleep related breathing disorder, or other cause of disturbed nocturnal sleep

Hypersomnias of central origin are recognized within the international classification of sleep disorders and includes:

• Narcolepsy with cataplexy
• Narcolepsy without cataplexy
• Narcolepsy due to medical condition
• Narcolepsy, unspecified
• Recurrent hypersomnia
• Idiopathic hypersomnia with long sleep time
• Idiopathic hypersomnia without long sleep time
• Behaviorally induced insufficient sleep syndrome
• Hypersomnia due to medical condition
• Hypersomnia due to drug or substance
• Hypersomnia not due to substance or known physiologic condition
• Physiological hypersomnia (Unspecified)
  
  

Narcolepsy with/without cataplexy:
This is a medical condition associated with excessive daytime sleepiness, hypnagogic hallucinations, sleep paralysis, cataplexy and poor night time sleep.
The incidence of narcolepsy is 0.2-1/1000 individuals. The first signs of narcolepsy (excessive daytime sleepiness) usually manifest in adolescence but are frequently unrecognized. Most patients are diagnosed as adults when cataplexy (sudden loss of voluntary muscle tone) occurs,
The classic tetrad of symptoms include

       Excessive daytime sleepiness: Typically the patient complains of increased daytime sleepiness. In children this is typically ignored or considered secondary to poor sleep habits.  This is usually the most debilitating of the features as the patient repeated naps or sleep phases during the day. In some cases the patient can have an automatic or semiautomatic behavior in which they appear to be continuing a task while in actual fact, they are asleep. The task usually does not get done appropriately.

 Hypnagogic hallucinations:
This is a condition in which the patient relates a history of having episodes wherein the patient goes to sleep, and promptly goes into a dream state, wakes up abruptly and has difficulty differentiating between wakefulness and dream events.

Sleep paralysis:
In this condition, the patient has episodes in which they awake from sleep and are unable to move. The sensation typically only lasts a few seconds. Sleep paralysis is as a result of REM related atonia continuing into wakefulness, with an associated inability to move skeletal muscles.

Cataplexy: This is a condition in which the patient has a sudden loss of muscle tone. It is typically associated with a strong emotional event (laughter, anger, happiness, extreme sadness). It may affect facial muscles and affect speech. There is no loss of consciousness.

A  fifth manifestation is poor night time sleep:
Patients with narcolepsy tend to report fragmented and poor night time sleep which runs counter to the fact that they have excessive daytime sleepiness
Several teenage patients with narcolepsy have mood disorders, mostly depression at the time of diagnosis. Occasionally patients are diagnosed following negative evaluations by cardiology and neurology for suspected seizures and near syncopal events.

Differential diagnosis:
Idiopathic hypersomnia
Depression
Bipolar disorder
Unexplained falls
Partial complex seizures
Near syncopal attacks

Associated psychopathology
The patient is more likely to have:
poor or falling school grades (>50%)
Recurrent depression
Obsessive thoughts
Recurring suicidal thoughts
Reduced job performance, earnings, promotions.
Required psychotherapy

Diagnosis:
Cataplexy is diagnostic for narcolepsy in the presence of excessive daytime somnolence.
Multiple sleep latency test with 2 sleep onset REM episodes in a 4-5 nap series is also diagnostic.
HLA typing alone does not confirm diagnosis in the absence of either cataplexy or a multiple sleep latency test.
CSF hypocretin levels are helpful but not required for diagnosis.

Evaluation:
Patients require an evaluation by a sleep specialist and this should include a full history and physical examination, completion of a subjective sleepiness scale (Epworth sleepiness scale), maintenance of sleep logs, and performance of an overnight sleep study and a multiple sleep latency test.

Multiple sleep latency test:
A multiple sleep latency test is used for the diagnosis of narcolepsy and for differentiation from idiopathic hypersomnia.
The test is done following a diagnostic sleep polysomnogram and involves 4-5 naps 2 hours apart.
The patient is allowed 20 minutes to fall asleep and 15 minutes to sleep if sleep is achieved.  
 
Parameters recorded include:
Time of lights out
Sleep latency
REM presence and latency 

Results:
A sleep latency of < 8 mins is abnormal and < 5 minutes is pathologic. Between 8-10 minutes requires a correlation with patient functioning. > 10minutes is normal.
<2 sleep onset REM in 5 naps is normal.
2 or more sleep onset REM diagnostic for narcolepsy 

Maintenance of wakefulness test:
A maintenance of wakefulness test is used to assess the efficacy of treatment of excessive daytime somnolence.
The test involves 4-5 sessions 2 hours apart.
The patient is placed in a chair in a dark and quiet room for 40 minutes and asked to stay awake

Treatment:
Excessive daytime sleepiness: Behavioral and Medical management
Behavioral: Improved sleep hygiene, addition of a daytime nap, education of all parties involved with the patient including, parents, teachers, supervisors.

Medical:
Somnolytic agents: Modafinil (Provigil) 200-400mg/day, Armodafinil (Nuvigil) 150-250mg/day
Psychostimulants: Amphetmine-Dextroamphetamine salts (Adderall, Adderall XR) 5-50mg/day, Methylphenidate (Ritalin). 5-50mg/day
Cataplexy management:
Sodium Oxybate (Xyrem) 4.5-9gm/night
SSRI’s: Sertraline (Zoloft), Fluoxetine (Prozac) 10-80mg/day
SNRI’s: Venlafaxine (Effexor) 75-375mg/day
TCA’s: Clomipramine (Anafranil) 10-200mg/day, Protriptyline (Vivactil)

Idiopathic Hypersomnia with long sleep time:
Essential Features
Constant and severe sleepiness with prolonged naps
Unrefreshing naps of up to 3 or 4 hours
Prolonged major sleep episode (typically 12 to 14 hours)
Difficulty awakening from nap or in morning
Few or no nocturnal awakenings
Post – awakening confusion (sleep drunkenness) often reported

Associated Features:
Sleep drunkenness
Use special procedures to wake up
Symptoms of autonomic nervous system dysfunction
Headaches
Orthostatic hypotension with syncope
Peripheral vascular complaints (Raynaud’s type phenomena)
Unpredictable response to stimulants
Lack of drug efficacy, tolerance and side effects common
Timing of drug to relieve sleep drunkenness problematic

Demographics
Unknown
Ratio 1:10 (Narcolepsy)?

Predisposing and Precipitating Factors
Familial predisposition
No HLA association
Possible autosomal-dominant mode of inheritance
No consistent precipitating factors

Familial Patterns
Autosomal-dominant mode of inheritance suggest

Onset, Course and Complications
Onset usually before age 25
Stable in severity and long lasting
Few with spontaneous improvement
Social and professional complications

Pathology and Pathophysiology
Normal hypocretin-1 levels in CSF
Histamine transmission may be decreased

Polysomnography and Other Objective Findings
Normal sleep of prolonged duration
Increase in slow wave sleep may occur
MSLT  6.2 + 3.0 < 2 SOREMPs
Consider 24 – hour continuous PSG

Diagnostic Criteria
Complaint of EDS almost daily for at least 3 months
Prolonged nocturnal sleep (more than 10 hours) documented
Nocturnal PSG excluded other causes of EDS
PSG demonstrates short sleep latency and sleep period greater than 10 hours
If MSLT performed ,  mean latency < 8 minutes, < 2 SOREMPs
Hypersomnia not better explained by another condition

Differential Diagnosis
Idiopathic Hypersomnia without long sleep time
Sleep disordered breathing
Narcolepsy without cataplexy
Hypersomnia not due to substance or known physiological condition (personality or psychiatric condition)
Hypersomnia due to drug or substance
Hypersomnia due to medical condition
Posttraumatic hypersomnia
Chronic fatigue syndrome
Behaviorally induced insufficient sleep syndrome

Idiopathic hypersomnia without long sleep time
Essential Features

Constant and severe excessive daytime sleepiness
Unintended naps – nonrefreshing
Major sleep period normal or slightly prolonged (< 10 hrs.)
Difficulty awakening from naps or in morning
Few or no nocturnal awakenings
Post- awakening confusion (sleep drunkenness)

Associated Features
Sleep drunkenness
Use special procedures to wake up
Symptoms of autonomic nervous system dysfunction
Headaches
Orthostatic hypotension with syncope
Peripheral vascular complaints (Raynaud’s –type phenomenon)
Unpredictable response to stimulants
Lack of drug efficacy, tolerance and side effects common

Demographics
Unknown

Predisposing and Precipitating Factors
Unknown

Familial Patterns
Autosomal-dominant mode of inheritance suggested

Onset, Course and Complications
Onset usually before age 5
Stable in severity and long lasting
Few with spontaneous improvement
Social and professional complications

Pathology and Pathophysiology
Unknown

Polysomography and other objective findings
Normal sleep or sleep of slightly prolonged duration (< 10 hrs)
Nocturnal sleep must be more than 6 hours
NREM and REM are in normal proportion
MSLT 6.2 + 3.0 < 2 SOREMPs

Diagnostic Criteria
Complaint of EDS almost daily for at least 3 months
Normal nocturnal sleep (greater than 6 hours,
but less than 10 hours) documented
Nocturnal PSG excluded other causes of EDS
PSG demonstrates a major sleep of normal duration
MSLT following PSG,  mean latency < 8 minutes,  < 2 SOREMPs
Hypersomnia not better explained by another condition

Differential Diagnosis
Idiopathic hypersomnia with long sleep time
Sleep disorder breathing
Narcolepsy without cataplexy
Hypersomnia not due to substance or known physiological conditions (personality or psychiatric conditions)
Hypersomnia due to drug or substance
Hypersomnia due to medical condition
Posttraumatic hypersomnia
Chronic fatigue syndrome
Behaviorally induced insufficient sleep syndrome

Full history and physical examination:
Also completion of sleep logs, and an Epworth sleepiness scale. Finally, an overnight sleep study and multiple sleep latency test to rule out cataplexy.

Treatment:
Use of Somnolytics; Modafinil (Provigil), Armodafinil (Nuvigil)
Use of psychostimulants; Methylphenidate (Ritalin), Amphetamine-Dextroamphetamine salts (Adderall)

Recurrent Hypersomnia
Essential Features
Recurrent episodes of hypersomnia
Last a few days to several weeks
Occur once to 10 times a year
Prodrome of fatigue or headache may precede episodes
Sleep may last 16 to 18 hrs. per day
Weight gain often occurs
Cognitive Abnormalities: feelings of unreality,  confusion, hallucinations
Behavioral Abnormalities: binge eating, hypersexuality, irritability, aggressiveness
Episode Termination associated with amnesia, transient dysphoria or elation, insomnia
Sleep and general behavior must be normal between episodes

Associated Features
Occasional reddish face with severe perspiration
Social and occupational impairment during attacks

Demographics
Rare - ~ 200 cases reported
Male to female ratio 4:1

Predisposing Factors
Increase frequency of HLA DQB1* 02

Precipitating Factors
Flu-like or upper airway infection
Alcohol
Head trauma
Exposure to anesthesia

Familial Patterns
Rare

Onset, Course and Complications
Early adolescence age of onset
Recurrent episodes of severe sleepiness
Episodes last up to several weeks
Normal functioning between episodes
Duration, severity and frequency lessen over several years
Complications mainly social and occupational

Pathology and Pathophysiology
Inconsistent findings
lymphocytic infiltrations in the hypothalamus, amygdala and temporal grey matter (one case reported)
Symptoms may be of hypothalamic origin
In a few cases, moderately and transitory decreased CSF hypocretin-1 levels during episodes of hypersomnia

Diagnostic Criteria
Recurrent episodes of excessive sleepiness
of 2 days to four weeks duration
Episodes recur at least once a year
Normal alertness, cognitive functioning,
and behavior between attacks
Hypersomnia not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder

Clinical and Pathophysiologal subtypes
Kleine-Levin Syndrome:
This is a condition associated with excessive somnolence which may last for a few days to several weeks and can occur between one to ten times in a year.  Individuals may sleep up to 16 hours a day and typically wake up just to void and eat. The patients tend to have neurocognitive manifestations such as hypersexuality, irritability and aggressiveness. Physical manifestations may include a reddish face with associated severe sweating.
Extremely rare disorder with male predominance, 4:1.
Flu like illnesses have been reported prior to the onset of the first episode in some cases.
Symptoms usually begin to occur in early adolescence and the median range for symptoms is 4 years in this self limiting condition.  Differential diagnosis of waxing and waning sleepiness include, tumors in the 3rd ventricle, bipolar disorder, seasonal affective disorder and other disorders of excessive sleepiness including extrinsic disorders like sleep apnea, periodic limb movement in sleep and seizure disorders.

Features:
Recurrent episodes of hypersomnia clearly associated with behavioral abnormalities
Binge eating
Hypersexuality
Irritability, aggression and odd behavior
Cognitive abnormalities (feelings of unreality, confusion, and hallucinations)

Common Symptoms 
Hypersomnia 100%
Cognitive changes 96%
Eating disorders 80%
Hypersexuality 43%
Compulsions 29%
Depressed mood 48%

Precipitating  Factors
Infection 38%
Head Trauma 9%
Alcohol Consumption 5.4%
Somnolence ↓ with stimulants in 40% of cases
Neuroleptics and antidepressants poor benefit
Lithium, not carbamazepine or other antidepressants, stopped relapses 41%
Lasted longer in women
Secondary cases (stroke, hematoma, MS, developmental disease, encephalitis) had more frequent and longer episodes

Menstrual Related Hypersomnia:
Recurrent episodes of hypersomnia in association with menstrual cycle
Occurs within 1st months after menarche
Last generally 1 week with rapid resolution at menses.
Oral contraceptives usually lead to prolong remission

Differential Diagnosis
Tumors within 3rd ventricle
Psychiatric disorders
OSAS
Narcolepsy
Idiopathic hypersomnia
PLMD
Insufficient sleep
Environmental sleep disorder