Associated Sleep Disorders and their treatments Flashcards
1
Q
Delayed Sleep wake phase disorder, characteristics?
A
stable delay in timing of sleep/wake cycle CBTmin and DLMO are delayed longer tau Altered response to light polymorphism in hPer3 typical schedule 4am-12pm
2
Q
Delayed sleep wake phase disorder, Treatment
A
Good sleep hygiene Avoid bright light in evening Bright light in morning (5000 lux) melatonin low dose melatonin 4 - 8 hours before your natural bedtime. If you then get tired earlier, move your schedule an hour earlier and take the melatonin an hour earlier. Let it stabilize. Then move another hour earlier.
Chronotherapy
This technique aims to reset the circadian clock by slowly delaying the bedtime (and hence the sleep period) by about two hours every few days. This strategy is used less commonly than the light therapy method. It invariably disrupts normal schedule of activity during the shift, when day and night are reversed.
3
Q
Leg cramps and restless legs syndrome (RLS) can mimic each other. What statement is true?
A
In leg cramps, patients describe an actual cramp or hardening of the muscle
Sometimes it is difficult to distinguish between RLS and sleep related leg cramps. However, there is an actual cramp and hardening of the muscle in sleep related leg cramps.
4
Q
A 37-year-old patient with BMI of 35 Kg/M2, depression and pain is brought to the clinic by his wife. She is very distressed by his lack of participation in daily chores and family-related activities. She attributes it to his lack of engagement. He used to work as a manager in a retail store but following a car accident 2 years ago associated with loss of consciousness, has not been able to return to his former job. He had incurred serious injuries which required prolonged hospitalization and rehabilitative efforts. Gradually he recovered and was cleared to return to work.
He is currently taking sertraline and naproxen. Wife reports that he is sleeping much longer now, total of about 11-13 hours every night with bedtime of 10:00 PM and arise time of 11:00 AM. He also takes naps during the day. He has had mild snoring for last 10 years but no vivid dreaming or any sudden changes in muscle tone during the day.
What is the most likely cause of his hypersomnia?
A
Traumatic Brain injury
Patient has post traumatic hypersomnolence which falls into the category of hypersomnia due to medical condition. TBI can cause hypersomnolence which can severely affect quality of life. Wake-promoting drugs can help alleviate the condition. Limited studies have shown a decrease in CSF hypocretin in some post-traumatic cases as compared to normal. In this case his sleepiness started after the accident and persisted despite of recovery. Thus, a temporal association makes that etiology most plausible.
5
Q
What is ERRT?
A
Exposure, relaxation and rescription therapy
6
Q
What is ERRT used for?
A
Treatment of nightmares
7
Q
What is the DDSI?
A
Disturbing Dream and severity Index
Developed by Dr. Barry Krakow
8
Q
What is the normal human circadian cycle?
A
24.3 hours is our normal cycle
9
Q
How do we entrain our circadian clock?
A
With zeitbebers (time keepers)
10
Q
What is the most powerful zeitgeber?
A
Light/dark cycle is the most powerful zeitgeber for entraining our clock
11
Q
What are social zeitgebers?
A
Meals
Exercise
Social cues such as work, etc.
12
Q
What is the prevalence of nightmare disorder?
A
2-6% of adults meet criteria for nightmare disorder
13
Q
What is the relationship between nightmares and PTSD?
A
Presence of nightmares before trauma increases likelihood of developing PTSD
14
Q
What is the definition of nightmare disorder, DSM 5?
A
Repeated occurrences extended, extremely dysphoric and well remembered dreams
2nd half of major sleep episode
On awakening, rapidly becomes oriented and alert
Clinically significant distress or impairment
Not attributable to substance
Coexisting mental/medical d/o do not explain complaint
15
Q
What is the clinical threshold for nightmare d/o and consideration for Tx?
A
Consider treatment if >1 nightmare per week
Duration: persistent, >6 months
16
Q
What happens when patient with nightmare d/o avoids sleep (common response)?
A
Causes REM rebound
17
Q
What is a common non medication Tx for nightmare d/o?
A
Imagery rehearsal therapy (IRT)
Recommended for both nightmare disorder and PTSD nightmares
Individual and group
1-3 sessions
Tx very simple
18
Q
What is the recommended pharmacological Tx for Nightmares?
A
Prazosin
19
Q
How does Prazosin work?
A
Alpha-1 adrenergic receptor antagonist
Decreases CNS sympathetic outflow
1st choice for pharmacologic Tx
20
Q
What is chronotherapy?
A
Treatment for delayed sleep phase d/o
This technique aims to reset the circadian clock by slowly delaying the bedtime (and hence the sleep period) by about two hours every few days. This strategy is used less commonly than the light therapy method. It invariably disrupts normal schedule of activity during the shift, when day and night are reversed.
21
Q
What is Advanced sleep phase disorder (ASWPD)?
A
Significant advance in phase of major sleep period (>2 hrs relative to socially acceptable time)
Sxs present for at least 3 months
Ad lib sleep improves sleep quality, quantity, consistency
Early morning awakening
Est. 1% of population likely low (less likely to perceive as problematic vs DSWPD)
Tau <24hrs
22
Q
What is the DSM-5 definition of Chronic insomnia?
A
o Difficulty initiation sleep (kids: w/o intervention) OR o Difficulty maintaining sleep (kids: w/o intervention) OR o Early morning awakening o Impairment in social, occupational, educational, academic, behavioral, or other area of functioning o 3+ nights a week, 3+ months o Adequate opportunity for sleep o Not purely from a substance o Specify With Non-sleep dx mental comorbidity With other medical comorbidity With other sleep disorder Episodic: 1-3 months Persistent: 3+ months Recurrent: 2+ episodes in a year Substance/medication Other specified Unspecified
23
Q
ICSD-3 Chronic insomnia disorder definition
A
o The patient reports or the patient’s parent or caregiver, one or more of the following:
Initiating sleep
Maintaining sleep
Waking earlier than desired
Resistance to going to bed on appropriate schedule
Difficulty sleeping without parent or caregiver
NOTE: dissatisfaction with sleep quality was removed in ICSD-3
o Daytime complaints (fatigue, attention, behavioral probs, motivation, etc.)
o Need adequate time/opportunity
o 3 nights per week for 3 months
o 10% prevalence, adults
o 30M in US with chronic insomnia
o Insomnia high risk for depression
o Insomnia + short sleep, increased HTN, DM, mortality
24
Q
What is the most common cause of insomnia in teens?
A
Delayed Sleep phase syndrome
25
What is definition of Delayed Sleep Phase Syndrome?
o Persistent (>3 months) inability to fall asleep and arise at conventional clock times
o Sleep onset delayed until early morning (3am-6am) with rise-times in early afternoon (11am-2pm)
o Patient complains of sleep onset insomnia
o Often presents in adolescence
o Awakening early because of social/occupational requirements results in daytime sleepiness
o Sleep is normal in pattern and duration
26
What is a treatment for Delayed sleep. Phase syndrome?
Chronotherapy:
o Bedtime is systematically delayed 2-3 hours each day
o Patients sleep only 7-8 hours without naps
o Chronotherapy is maintained until the desired bedtime is reached (11pm or midnight)
o Bedtime subsequently rigidly maintained
o Consider early morning bright light therapy (2500 lux) for 1-2 hours and light restriction after 4pm
27
What is the American College of Physicians (ACP) guidelines for Tx of chronic insomnia?
o All get CBTi for chronic insomnia, 1st line recommendation
o But a supply and demand issues with BSM providers
o 60,000 patients per 1 BSM provider
o CBTI helpful for ~2/3 pt but still a high number suffering with sx
o Cons of digital CBT-I
Adoption, appropriateness, feasibility, costs, coverage, etc
o 2nd recommendation – if pt does not respond or does not prefer BSM
Clinicians use a shared decision making approach to add medication
28
Survey of patients with insomnia
| Sleep 2014
87% use zolpidem of Non-BzRA
| 20% use a med to help them sleep
29
What are the Neurobiological targets for medication?
o Meds either (flip between sleep and wake)
Enhance sleep (gaba receptor)
Or target arousal cycle
30
• What are the Classes of Pharmacologic Treatment for Insomnia?
o Benzodiazepine receptor agonist (BzRA)
o Melatonin agonists
o Orexin antagonists (DORA)
o Sedating antidepressants
o Antipsychotics (e.g., dopaminergic antagonists)
o Anticonvulsants (e.g., gabapentin)
o OTC agents (nonselective antihistamines)
31
GABA-A Receptor
| Alpha subunits
6 alpha subunits
Alpha 1 effects: sedative, amnestic, anticonvulsive
Alpha 2 effects: anxiolytic, muscle relaxant
Alpha 3 effects: muscle relaxant
32
What are typical Benzodiazepine (GABA)-Receptor Agonists (BzRA)?
Clonazepam (Klonopin), .25-1.0mg, half life: 40 hrs
Temazepam (Restoril), 7.5-30 mg, half life 4-18 hrs (FDA approved for insomnia)
Lorazepam (Ativan), 0.5-2 mg, half life10-20 hrs
Oxazepam (Serax), 10-30 mg, half life 5-10 hrs
Eszopiclone (Lunesta), 1-3 mg, half life 5.5-8 hrs
FDA approved for insomnia
Triazolam (halcion), 0.125-0.25mg), half life 2-3 hrs
FDA approved for insomnia
Zolpidem (Ambien), 3.75-12.5mg, half life 2-3 hrs, CR extends duration of action, FDA approved
Zaleplon (Sonata), 5-10mg, half life 1-2 hrs, FDA approved
33
What is the biggest discerning factor when comparing BzRA drugs?
the half-life
Klonopin has fallen out of favor, reasonable to suppress anxiety but not ideal for insomnia
long half life = 40 hrs
risk for falls
34
What is the most common BzRA drug used for insomnia?
Zolpidem
35
What are the “Z” drugs?
Non-benzo-benzos
Eszopiclone
Zolpidem
Zaleplon
36
What are characteristics of “Z drugs”?
o Work fundamentally in the same way and bind to same receptor of benzo, but differ in terms of half-life
o Don’t have anxiety reducing effects – so other benzos might be good for pts w/ anxiety that are not interested in behavioral treatment
37
Are PSG’s required for FDA approval of medications?
Yes
38
Are sleeping pills addictive?
Tolerance
Physiological dependence
Psych dependence
Non-medical diversion
39
Do Benzos increase risk of dementia
| Do Benzos increase mortality risk
There are no RCT studies that prove benzos increase risk of dementia
No RCT studies that show benzos increase mortality risk
40
What is the SHARE approach to Shared Decision Making?
Seek your patient’s participation
Help your patient explore and compare treatment options
Assess your patient’s values and preferences
Reach a decision with your patient
Evaluate your patient’s decision
41
What is Ramelteon?
It’s a melatonin agonist that stimulates melatonin receptor
42
What are orexin antagonist?
| DORA: dual orexin receptor antagonists
Suvorexant (Better for staying asleep/not as great for SL) Belsomra
Lemborexant: FDA approval 2019: better for sleep onset insomnia (Dayvigo)
Daridorexant : FDA approval 2022 (Quviviq)
Blocks the effects of neurotransmitter orexin
Orexin promotes wakefulness
DORAs bind to orexin receptor 1 and orexin receptor 2, blocking the effects of orexin, reducing wakefulness and helping people sleep
Newest classification for insomnia
Stabilize the wake-promoting neurons
Lower abuse potential
43
What are DORA risks (Dual Orexin Receptor Antagonists) ?
```
Somnolence
Dose-dependent increase in suicidality
Complex behaviors
Sleep paralysis
Abnormal thinking
Behavioral changes
(history of SUD or can’t take BZRAs)
```
44
What sedating antidepressants are used for insomnia?
```
Doxepin
Mirtazapine
Trazodone
Amitriptyline
Nortriptyline
```
Potential advantages: No abuse, effective for WASO
Potential disadvantages: Anticholinergic at high doses, cardiac effects, falls
45
What are selective H1 antagonist used for insomnia?
Doxepin (only approved med in this class for sleep maintenance insomnia, 3-6mg) Silenor
Mirtazapine (2-4 mg selective effects)
46
What sedating antidepressants used for insomnia are working on mixed receptors?
```
Trazodone
Amitriptyline
Doxepin (at higher doses)
Mirtazapine (higher dose)
```
Little abuse potential, non-scheduled
Primary problem staying asleep
47
What is the efficacy data on doxepin?
Dose-dependent effects on sleep efficiency – especially on LAST 3rd of the night
Blocks histamine
48
What are antidepressant side effects?
Anticholinergic side effects (amitriptyline, Trazodone)
• cardiac conduction issues, urinary retention, dementia risk over time, orthostatic hypotension (BP drops when they stand up)
somnolence (non H1 selective)
complex behaviors
abnormal thinking
behavioral changes
49
How does Trazodone work for insomnia?
Low dose Trazodone use exerts a sedative effect for sleep through antagonism of 5-HT-2A receptor, H1 receptor and alpha-1 adrenergic receptors
Reduces levels of neurotransmitters associated with arousal effects, such as serotonin, NE, dopamine, ACH and histamine (Mixed receptors)
50
What are advantages and disadvantages of BzRA drugs (Benzodiazepine receptor agonists)?
Advantages: Efficacious, variety of half-lives
Disadvantages: Cognitive effects, falls, dependence
Examples: zolpidem, zalpelon, Eszopiclone, temazepam
51
What are advantages and disadvantages of Antihistamines for insomnia
Advantages: widely available
Disadvantages: cognitive effects, limited efficacy data
Examples: diphenhydramine, doxylamine
52
What are advantages and disadvantages melatonin, receptor agonist
Melatonin, ramelteon
Advantages: “natural” mechanism
Blocks wake signal
Ramelteon reasonable to use in elderly and patients at risk for abuse
Disadvantages: limited efficacy on WASO
53
What are advantages and disadvantages Orexin antagonist?
Example: suvorexant (belsomra)
Advantage: novel mechanism, blocks wake signal
Disadvantage: limited efficacy, effectiveness data
54
What are advantages and disadvantages of sedating antipsychotics?
Examples: Quetiapine, olanzapine
Advantages: Not BzRA, efficacy for psychosis, depression
Disadvantages: metabolic, neurological,
CV effects
55
What are advantages and disadvantages of
| Gabapentin, Lyrica
Advantages: Not BzRA, efficacy for pain
Disadvantages: Limited sleep efficacy data
56
How to choose medications for insomnia
| What is the evidence FOR:
o Weak evidence FOR
Ramelteon (Rozerem) - sleep onset
Doxepin (Silenor) – sleep maintenance
Suvorexant (Belsomra) - sleep maintenance
Eszopiclone (Lunesta) - sleep onset, sleep maintenance
Zaleplon (Sonata) - sleep onset
Zolpidem (Ambien) - sleep onset, sleep maintenance
Triazolam (Halcion) - sleep onset
Temazepam (Restoril) - sleep onset, sleep maintenance
57
How to choose medications for insomnia
| Weak evidence AGAINST
```
Trazodone (Desyrel)
Tiagabine (Gabitril)
Diphenhydramine (Benadryl)
Melatonin
Tryptophan
Valerian
```
58
What should be patient expectations with sleep and sleep aids?
o Sleep is an involuntary biological process influenced by behavior and medication
o Reasonable expectations regarding sleep and medications, it’s not general anesthesia; modest effects, you’re not going to sleep for 8 hrs
20 minutes more of sleep typically with sleep meds
o Detailed instructions – who, what, when, how
o Appropriate timing
59
What is appropriate follow up for patients on sleep aid?
o Ongoing assessments of effectiveness and side effects
o Use lowest dose for shortest period of time
o Discuss challenges
o Answer questions
o Challenge patients to withdraw hypnotics
o Reassess comorbid conditions
o Education regarding long-term use
60
What are hypersomnias
| Central disorder of Hypersomnolence
Narcolepsy Type 1
Narcolepsy Type 2
Idiopathic hypersomnia
Klein-Levin Syndrome
Hypersomnia due to another medical disorder
Hypersomnia due to a medication or substance
Hypersomnia associated with a psychiatric disorder
Insufficient sleep syndrome
61
What is the definition of Hypersomnolence?
| ICSD-3
symptom of excessive sleepiness
o Inability to stay awake and alert during major waking episodes
o Unintended lapses into sleep/irrepressible need for sleep
o Children: may present as inattentiveness, emotional lability, or hyperactive behavior
o Can be due to disturbed nocturnal sleep, misaligned circadian rhythms, or of central origin
62
What is the definition of Hypersomnia?
condition or specific disorder with hypersomnolence as the primary symptom
63
What is chronic Hypersomnia?
| Hypersomnias of central origin
Narcolepsy
| Idiopathic hypersomnia
64
What are the characteristics of Narcolepsy Type I and Type 2 ?
What is cataplexy?
daily periods of hypersomnolence >= 3 months
Gradual or “sleep attacks” (without prodromal symptoms)
EDS
Sleep hallucinations
Sleep paralysis
Disruption of nocturnal sleep (50%)
1 in 2000 incidence, early childhood to 50’s, peaks in 20’s
Daytime naps are refreshing (as opposed to IH where naps are not refreshing)
Cataplexy present in Narcolepsy Type 1, not present in Type II
Cataplexy: brief (<2 min), sudden loss of muscle tone in response to strong emotions (laughter)
Is abrupt, reversible, bilateral
DTR’s absent
Remains conscious
Type 1: cataplexy, orexin <110, EDS
Type 2: no cataplexy, normal orexin, EDS
65
Narcolepsy Type II, definition
EDS and MSLT findings same as Type I, but without cataplexy
CSF Hypocretin-1 levels are unknown or are above threshold for Narcolepsy Type I
Not better explained by insufficient sleep, OSA, Delayed sleep phase, med or substances
66
What are associated features of Narcolepsy
Sleep paralysis (temporarily inability to move at sleep-wake transitions)
Hallucinations (visual, auditory, tactile)
Hypnogogic: transition from wake to sleep, vivid dreams at sleep onset
Hypnapompic: transition from sleep to wake
Symptoms can be variable, wax and wane, occur in different frequencies across individuals
Extremely sleepy, fall asleep in places
Disturbed nocturnal sleep-increase arousals
67
What is the prevalence of Narcolepsy in the population
What is the typical onset?
25-5- per 100,000 people
.025%-.05% of general population
Onset: after age 5, most often between 15-25
Sleepiness, cataplexy and other REM related Sx
68
What is the etiology and pathophysiology of Narcolepsy?
Hypocretin deficiency syndrome
Decrease hypocretin/orexin in in hypothalamus
?Autoimmune destruction
Genetic predisposition: HLA-DR and HLA-DQ alleles
Environmental triggers: infection, seasonal patterns
69
How is the diagnosis of Narcolepsy made?
```
Clinical Evaluation
Lab tests
Nocturnal PSG
Next day MSLT
MWT
```
70
What is the clinical evaluation for Narcolepsy?
Clinical symptoms (hypersomnolence, cataplexy)
Rule out other causes of hypersomnolence (sleep deprivation)
1 week of actigraphy with diary (ideal)
71
What are the Lab tests done for evaluation of Narcolepsy?
Nocturnal PSG
Sleep-onset REM (SOREM) <15 min
Next day MSLT (most common in narcolepsy)
Mean SOL < 8 min. And =>2 SOREMS (one can be from previous night PSG)
CSF of hypocretin-1 (involves spinal tap)
72
How is the MSLT done?
Purpose: Standard measure for objective sleepiness, differential diagnosis
Indications: unexplained EDS, narcolepsy, IH
Includes EEG, chin tone, oxygen, EKG
Protocol:
PSG night prior; let them sleep in when at lab, then get enough sleep, 6 hr TST adult, 7.5 peds
4-5 nap opportunities scheduled at 2hr intervals starting 1.5-3 hrs from end of PSG
Instructions: “try to fall asleep”
Nap session is terminated after 20 min.
Other considerations:
Preceded by nocturnal PSG (>6 hrs TST adults, 7.5 hrs peds)
Ideally, no medications for 2 weeks prior (i.e. no stimulants, stimulant-like meds, REM suppressing meds such as SSRI/SNRI)
Ideally scheduled at patient’s typical sleep/wake schedule
Sleep logs or actigraphy 1 week prior, make sure not sleep deprived
73
What is the Maintenance of Wakefulness test (MWT) ?
Purpose: measures the ability to stay awake; often used to evaluate response to treatment
Protocol:
4 trials at 2 hr intervals
Instructions: “remain awake for as long as possible”
Trials end after 40 min. If no sleep
Considerations:
PSG prior to MWT?
Unclear if MWT generalizes to occupational safety
74
Hypersomnolence Diagnostic criteria
| ICSD3
Severe sleepiness for >3 months
No cataplexy
<2 SOREMPs (sleep-onset REM periods that occur within 15 min of sleep onset) on MSLT (or no SOREMPs if REM latency on preceding PSG is <15 min.
At least 1 of the following:
MSLT shows mean SL <= 8 min.
Total 24 hr sleep time is >= 660 min (11 hr) on
Either 24 hr PSG or by >= 7 day wrist actigraphy
Insufficient sleep syndrome is ruled out
Can use actigraphy or diary to document increased sleep opportunity
Consider idiopathic unless identified medical, psych, substance underlying
75
What are the treatments for Narcolepsy?
```
Medications
Stress management
CBT techniques
Pomodoro Technique
Mindfulness and acceptance
CBT-H program (Jason Ong)
```
76
What medications are used for treatment of Narcolepsy?
Sodium Oxybate, dose 4.5-9 mg, class: GHB. Indication: EDS and cataplexy
Modafinil, dose 200-400 mg, class: Non-amphetamine Stimulant, indication: EDS (nuvigil, shorter half life)
Armodafinil, dose 150-250mg, longer half life, class: Non-amphetamine stimulant, indication : EDS (provigil)
Dextroamphetamine, dose 5-60 mg, class: stimulant, indication :EDS
Methylphenidate, dose: 10-60mg, class: stimulant, indication: EDS
Imipramine, dose: 50-250 mg, class: TCA, indication: cataplexy
Nortriptyline, dose 50-150 mg, TCA, Cataplexy
Fluoxetine, 20-80 mg, SSRI, cataplexy
Venlafaxine, 75-375mg, SNRI, cataplexy
Selegiline, 5-10 mg, MAO-B inhibitor, EDS & cataplexy, (works by increasing dopamine in the brain). Dopamine controls movement; also used in Parkinson’s
77
What are some special issues with Narcolepsy for patients?
Treatments can reduce sleepiness, but unmet need for improving QOL, improving psychosocial functioning
Patients w/narcolepsy and IH have sig. reduction in health-related QOL
At least 50% w/narcolepsy report symptoms of depression, 15% moderate depression
78
What are stress management techniques for Narcolepsy and IH?
Chronic sleepiness is a form of stress
CBT for chronic pain: similar unrelating pattern, no cure, sig. impact on QOL
Coping strategies (emotion-focused, problem-focused, avoidance)
79
What is the Pomodoro Technique used in Narcolepsy and IH?
Key concept: split up large intervals of time into smaller, more manageable components (set time for work, separate short breaks)
Re-conceptualize wakefulness
Split wakefulness and naps up
The Pomodoro technique is a time management method developed by Francesco Cirillo in the 1980’s. uses a timer to break work into intervals, typically 25 min. In length, separated by short breaks. Each interval is known as a Pomodoro.
Pomodoro means tomato in Italian. Cirillo used a tomato shaped kitchen timer as a university student.
80
How do we apply mindfulness and acceptance to Narcolepsy and IH?
Mindfulness and acceptance:
Being mindful of physical and mental state
Is it possible to accept without giving up? Acceptance is an active (not passive) process
Avoid the “second dart or arrow” (1st dart comes from enemy, part of living)
2nd dart or arrow we throw on ourselves
Comes from Buddhism-suffering from attaching from outcomes
81
What are the details of CBT-H program?
o Cognitive: emotion reg, cope with symptoms, value living
o Behavioral: behave changes to improve structure and efficiency, min impact of symptoms of functioning, reg nighttime sleep
o Interpersonal: how to deal with it
82
What is Kleine-Levin Syndrome?
Rare disorder w/recurrent episodes of excessive sleep along with cognitive and behavioral changes.
May sleep up to 20 hrs per day during episode
A few days to a few weeks
May start abruptly or sometimes preceded by an upper respiratory infection
Additional sx: hyperphagia (excessive food intake), irritability, childishness, disorientation, hallucinations, abnormally uninhibited sex drive
Affects primarily adolescent males
Unknown origin
Stimulants (modafinil, methylphenidate, amphetamine) and mood stabilizers (lithium) may be prescribed
83
Insufficient Sleep syndrome
Working too much!
84
Hypersomnia in older adults
```
o Not necessarily more in older adults
o Daytime sleepiness vs naps
o ESS difficult measure because not all older adults do all tasks on ESS
o Treatment
Bright light therapy
Naps
Exercise
```
85
What are the pediatric hypersomnias?
Excessive daytime sleepiness
Hypersomnolence
Narcolepsy
Fatigue
86
What is the definition of EDS in pediatrics population?
```
Increased in sleep duration
Resumption of naps
Falling asleep inappropriately
Inability to awaken in the morning
Daytime inattention
Misbehavior
Mood lability
Hyperactivity
```
87
What is REM Behavior Disorder (RBD) ?
Violent/frightening dreams "acted" out by patient
PSG shows REM sleep without atonia
Typically male >60 years old
88
What diseases is RBD associated with?
Parkinson's disease
Lewy Body disease
Multisystem atrophy
89
RBD is associated with withdrawal from what substances?
ETOH
barbiturates
Meprobamate (miltown)
90
What medications is RBD associated with?
```
SSRI's
TCA's
Fluoxetine
venlafaxine
MAOI
```
SSRI's may also be associated with increased muscle activity in REM sleep even in absence of symptomatic RBD
91
How is the Diagnosis of RBD established?
Dx of RBD is based on clinical symptoms of disturbing behaviors during sleep with dreaming and violent behavior.
Findings of REM without atonia only on PSG doesn't establish dx of RBD
92
What is the Dx criteria for Hypersomnolence in pediatric pop (ICSD3)
Severe sleepiness x 3 mos
No cataplexy
<2 SOREMPs on MSLT (or no SOREMPs if REM latency on preceding PSG is <=15 min
At least 1 of the following: MSLT shows MSL <=8 min, 24 hr TST >=11 hrs on 24 hr PSG or by 7 day actigraphy
Insufficient sleep is ruled out (actigraphy or sleep diary)
o Consider idiopathic unless identified medical, psych, substance underlying
93
What is the diagnostic criteria for Narcolepsy diagnosis in Pediatric population?
o At least 3 months of severe sleepiness
o Children may sometimes present with excessively long nighttime sleep or as resumption of previously discontinued daytime naps
o MSL <= 8 min and 2+ SOREMPs on MSLT
o Hypersomnolence and/or MSLT findings are not better explained by other causes such as insufficient sleep, obstructive sleep apnea, delayed sleep-wake phase disorder, or the effect of medication/substance or withdrawal
o Type 1
Cataplexy
CSF hypocretin-1 concentration is either <= 110
pg/mL or <1/3 of mean values
o Type 2
No Cataplexy
Either CSF hypocretin-1 concentration has not been measured or CSF hypocretin-1 is either >110 pg/mL or > 1/3 of mean values
94
What is the definition of Fatigue in pediatric population?
o Physical sensation of extreme tiredness
o Related to mental or physical exertion
o Relieved by rest
o May be “unrelenting exhaustion”- chronic fatigue (not relieved by rest)
o Chronic fatigue may be improved by exercise
95
What are the features of EDS in pediatrics pop?
```
o Differentiated from fatigue
o Propensity to fall asleep
o Difficulty remaining awake from activities
o Increased in napping
o Longer sleep duration
o Difficult waking the morning
o May vary from mild to severe
```
96
MSLT in pediatric population
4-5 nap opportunities
2 hr intervals
Quiet, dark room (no TV, electronic devices)
EEG, EOG, EMG, EKG
If sleep onset occurs, permitted to sleep for 15 min
No sleep occurs in 20 min, nap opportunity ends
Record # of naps, mean sleep onset minutes, SOREMPs
EDS in preteen <= 15 min
EDS in teens <=10 min
97
What are Associated features w/ hypersomnia and narcolepsy ?
```
o Increased risk of accidents
o Cognitive difficulties
Uneven cog profile
Poor decision making
o Poorer academic performance
Failures
o Behavioral dysregulation
Inattention
Impulsivity
o Depression
o Anxiety
o Low self-esteem
o Reduced QOL
```
98
What are the treatments for narcolepsy in pediatrics?
stimulants
| antidepressants for cataplexy, etc.
99
What is the role of BSM in narcolepsy?
```
Education
Improve sleep habits
structured/planned naps
relaxation as indicated
CBT/ACT
Patients have expressed interest in BSM services
```
100
How should structured naps be carried out in narcolepsy and pediatric population?
15 min duration
Schedule between 12:30pm-5pm
depending on severity, may need 2
School consultation for 504 planning
101
What is the spectrum of SDB?
```
No snoring
Primary snoring/ "mild SDB"
OSA, mild
OSA, mod
OSA, severe
OSA + hypoventilation
```
102
What moves a person down the SDB spectrum?
weight gain
alcohol
hypnotics
sleeping pills
103
What are the Central Disorders of Hypersomnolence?
Secondary/associated:
Insufficient sleep syndrome
Hypersomnolence due to a medical disorder
Hypersomnolence due to medication/substance
Hypersomnolence associated with psychiatric disease
Recurrent:
Kleine-Levin syndrome
Primary and persistent:
Narcolepsy Type 1
Narcolepsy Type 2
Idiopathic hypersomnia
104
What is insufficient Sleep syndrome?
| ICSD-3 criteria
Behaviorally induced, not really a central disorder of hypersomnolence
Daily sleepiness (in preteens, can be behavioral problems due to sleepiness)
Sleep shorter than expected for age
Sleep pattern present most days x 3 months at least
Uses measures to shorten sleep (alarm, person); sleeps longer w/o these measures
Sx resolve with sleep extension, but takes some time to see results!
Not better explained
Is behavioral issue fundamentally!
Large piece of differential dx in workup for hypersomnolence
105
Hypersomnia due to a medical disorder (ICSD-3)
Daily sleepiness x 3 months
Not due to other sleep d/o, psych cond, or medication
If MSLT done, MSL “usually” <8 min. With 0-1 SOREM
Implies the medical condition is causal to sleepiness
106
What are the medical conditions commonly implicated in hypersomnia?
```
Medical:
Metabolic encephalopathies (hepatic)
Systemic inflammation (rheum, cancer, chronic infection)
Genetic syndromes (Niemann Pick type c, prader-willi, fragile X)
Endocrine disease (hypothyroidism)
```
```
Neurological:
Parkinsonism
Myotonic dystrophy
TBI
Insult to hypothalamus, bilat. Thalamus, midbrain (stroke, tumor, sarcoidosis)
```
107
What is the criteria for Residual Sleepiness after OSA treatment as dx of hypersomnia due to a medical condition?
Requires FULLY ADEQUATE treatment of OSA
3 mos or more
PAP download showing 7+ hrs of use/night
PSG showing control of AHI at prescribed settings (Don’t rely on AHI from CPAP machine if possible)
108
Hypersomnia due to drug/substance
Dx requires daily sleepiness, no duration criteria
Caused by addition of sedating medication or withdrawal of alerting medication
Not better explained by
109
Which medications are involved with Hypersomnia due to drug/substance?
Sedative-hypnotics (Rx or Non)
Neurological: anti-epileptics, dopamine agonists
Psychiatric: antidepressants, antipsychotics (dopamine antagonists), Benzos/barbiturates
Anticholinergics
Antihistamines
Muscle relaxants/pain medications
Anti-arrhythmias
beta-blockers
Also includes substance abuse of sedating meds and d/c of wake-promoting meds
110
Hypersomnia Comorbid to psychiatric d/o (ICSD3)
| What disorders?
```
Most commonly:
Mood disorders
Atypical depression
Bipolar2
SAD
Anxiety d/o
```
Somatoform d/o
Less commonly:
Thought d/o
Adjustment d/o
Personality d/o
111
What is the ICSD-3 criteria for Kleine-Levin Syndrome?
At least 2 episodes of Excessive sleepiness (2 days-5 weeks, median duration is 13 days)
Recurrences once every 18 mos (usually more than once per year)
Median frequency every 3-6 months
Median duration 15 years
Triggers: infection, ETOH, sleep deprivation, stress, head trauma
In addition to excessive sleepiness, bouts must demonstrate at least one of:
cognitive dysfunction
altered perception (de realization, depersonalization)
disordered eating (anorexia or hyperphagia)
disinhibited behavior
Normal alertness, cognition, behavior and mood between bouts
No MSLT criteria, no requirement to measure sleep duration
112
Kleine-Levin syndrome, typical episode symptoms
```
Neurological sx always present:
hypersomnia (15-22 hr/d)
Altered cognition (mental slowness, confusion, post-episode amnesia)
Neurological sx occasionally present:
Meningitis like
headache
photophobia
painful hyperacousia
Neuropsychiatric
derealization/altered perception (always)
Apathy (always)
disinhibition (megaphagia, hypersexuality), occasionally present
Regressive behavior, puerility (occasionally)
Psychiatric
irritability (always)
depressive or flat mood
anxiety
Psychotic symptoms
reference ideas
hallucinations
delusion
Derealization >90%
Apathy 100%
Hyperphagia/increased intake 66%
Hypersexuality:
boys 58%
girls 35%
```
113
What is the epidemiology of Klein-Levin Syndrome?
```
Rarest of central d/o of hypersomnolence
1-5/million
Onset typically age 12-20
2/3 of patients are boys
~5% have FH of KLS
```
114
ICSD-3 criteria for Narcolepsy Type 1
Daily periods of irrepressible need to sleep OR daytime lapses into sleep, occurring for at least 3 mos, AND
One or both of:
1. Cataplexy AND
MSL <=8 min. AND
2+ SOREMPs (or nocturnal 15 min SOREM and 1+ MSLT SOREM)
2. Low CSF hypocretin-1 (orexin) concentration
<=110pg/ml OR
<1/3 of control values
115
What is the definition of SOREMPs ?
Sleep onset REM periods
| REM sleep periods that occur within 15 mins of sleep onset
116
What is cataplexy?
A clinical diagnosis that you make face to face with patient
Describe muscle weakness brought on by emotion.
Sudden loss of muscle tone while a person is awake that leads to weakness and a loss of voluntary muscle control.
Often triggered by sudden, strong emotions such as laughter, fear, anger, stress or excitement.
Sx of cataplexy may appear weeks or even years after the onset of EDS in narcolepsy
117
ICSD-3 Criteria: Narcolepsy 2
Daily periods of irrepressible need to sleep or daytime lapses into sleep, for at least 3 mos, AND
MSLT: MSL < 8 min and 2+ SOREM (or 15 min night SOREM and 1+ SOREM), AND
No cataplexy, AND
Hypocretin is >110 (or >1/3 controls) or unmeasured, AND
Not better explained by other causes (insufficient sleep, OSA, DSPS, medication/substances/withdrawal)
118
What is the prevalence of Narcolepsy?
Prevalence of Type 1: 1/2000
Prevalence of Type 2: 4 times more common that Type 1
Family members of people with either type of narcolepsy have an increased risk of any hypersomnolence
119
What are the core features of Narcolepsy Type1?
```
Classic tetrad:
EDS-100%
Cataplexy- most
sleep paralysis- 53%
hypnogogic/hypnopomic hallucinations - 63%
```
Other common features:
sleep fragmentation
REM behavior disorder
120
What are the signs and symptoms of sleep paralysis?
Inability to move the body when falling asleep or on waking, lasting seconds or several mins.
Being consciously awake
Being unable to speak during the episode
Having hallucinations and sensations that cause fear
Having difficulty breathing
Feeling as if death is approaching
Sweating
Having headaches, muscle pains and paranoia
121
What are hypnagogic hallucinations?
Vivid visual, auditory, tactile or even kinetic perceptions that , like sleep paralysis, occur during the transitions between wakefulness and REM sleep
Occurs at sleep onset
122
What are hypnopompic hallucinations?
Hallucinations that occur as you are waking up in the morning and in a state that falls somewhere between dreaming and fully awake.
Occurs at sleep offset, upon awakening (as opposed to sleep onset)
123
Narcolepsy Type 1: cataplexy
| What is the typical presentation?
Duration: seconds to 2 min
Typical muscle groups involved: neck, face, limbs
Lateraling: bilateral
Effects on consciousness: consciousness retained
Tone: atonic
Reflexes: reduced or absent in affected muscle
Trigger: typically strong positive emotions such as laughter (hearing or telling a joke), can also be with anger
Positive phenomena: phasic muscle twitching of the face may be present, more dyskinetic movements can be seen in children
124
Idiopathic Hypersomnia: ICSD-3 criteria
EDS lasting at least 3 mos
NO cataplexy
No more than 1 SOREM between PSG and MSLT
Not better explained by: including insufficient sleep syndrome
3 different options for objective diagnosis (need to meet at least one)
MSLT showing MSL <= 8 min
24 hr PSG showing TST >= 660 min ( 11 hrs)
7 day actigraphy showing avg TST >= 660 min (11 hrs)
125
What are supportive features for Dx of IH?
Supportive features include:
Severe/prolonged sleep inertia, “sleep drunkenness”
unrefreshing naps > 1 hr
PSG SE >= 90%
24 hr sleep duration for dx may need to be adapted for children/teens and possibly cross/culturally
126
Epidemiology of IH
Rare
Onset often late teen/early adulthood
Probably female predominance
127
Which clinical features are discriminative when compared Narcolepsy Type 1, Narcolepsy Type 2 and IH?
Narcolepsy Tetrad (EDS, cataplexy, paralysis, hallucinations)
Type 1: 42-44%
Type 2: absent
IH: absent
Sleep paralysis:
Type 1: 53-69%
Type 2: 35%
IH: 20%
Sleep hallucinations:
Type 1: 63-77%
Type 2: 42%
IH: 25%
Fragmented nocturnal sleep:
Type 1: common (problem of state control)
Type 2: “may be common”
IH: atypical
RBD:
Type 1: 45-61%
Type 2: ?
IH: ?
Long nocturnal sleep times:
Type 1/2: 18%
IH: common
Effect and duration of naps:
Type 1: refreshing, short
Type 2: ?
IH: Unrefreshing, long, “I don’t take a nap, I take a coma”
Sleep drunkenness:
Type 1: 8%
Type 2: 47%
IH: 48%
128
What is the underlying pathophysiology of Narcolepsy Type 1:
It is due to loss of hypocretin producing neurons in the hypothalamus
129
Narcolepsy Type 1: The autoimmune hypothesis
HLA DQB1*0602, positive in 85% + of patients with narcolepsy and cataplexy
Positive in 26% of controls
More helpful as a clue to pathogenesis than as a diagnostic test
Maybe Narcolepsy Type 1 is an autoimmune problem?
People with narcolepsy have more hypocretin-reactive T cells
Increased incidence of narcolepsy dx after H1N1 pandemic
130
H1N1 Vaccination and narcolepsy
2009 H1N1 Flu season
Pandemrix vaccine used in EU, increased reports of narcolepsy
Was an adverse reaction to the vaccine
131
What is the pathophysiology of IH?
Theories include:
abnormal activation of GABA-A receptors
CSF studies
autonomic dysfunction
Circadian dysfunction
peripheral clocks and gene expression
132
Non-pharmacological strategies for Narcolepsy Type 1
```
In addition to stimulant medications:
regular nocturnal sleep times AND short scheduled naps (in those with severe residual EDS)
School/work accommodations:
naps
Counseling/support
safety (driving)
Med side effects
Patient groups (narcolepsy network, wake up narcolepsy)
```
133
Non-pharmacological strategies for IH
```
Naps are not typically helpful
long
unrefreshing
sleep inertia
School/work accommodations
late start time (esp if phase delayed)
Counseling/support
safety
med side effects
patient groups
```
134
What are the current AASM treatment guidelines for Hypersomnias?
Modafanil
Narcolepsy (standard)
IH (option)
KLS (option)
Sodium oxybate
Narcolepsy (standard)
Amphetamines
narcolepsy (guideline)
IH (option)
KLS (option)
Selegiline
narcolepsy (option)
Lithium
KLS (option)
Scheduled naps as adjunctive rx
Narcolepsy (guideline)
135
Current AASM Treatment Guideline for cataplexy (narcolepsy type 1)
```
Sodium oxybate (standard)
TCAs, SSRIs, SSNRIs (Guideline)
```
Standard= highest recommendation
Guideline=next highest recommendation
136
FDA approved treatments for either type of narcolepsy
Non-amphetamine wake-promoting meds:
modafinil (provigil)
armodafinil (Nuvigil), longer half life, better wakefulness effects, once daily dosing, starting dose 150mg
solriamfetol (Sunosi), NE-dopamine reuptake inhibitor
```
Amphetamines/related
methylphenidate (Ritalin)
dextroamphetamine/amphetamine (adderall)
Dextroamphetamine (Dexedrine)
amphetamine
```
Sodium oxybate- sleepiness and cataplexy (Xyrem)
consolidates sleep/effective for cataplexy/ improves EDS
Expensive
Generally well tolerated, but issues about “date rape”
Histaminergic medications
pitolisant (Wakix)
137
Side effects of modafanil/Armodafinil
```
Most common side effects:
nervousness/irritability
palpitations/tachy
headache
nausea
rhinitis/pharyngitis
```
Severe SE:
SJS and other drug rashes
mania, psychosis, hallucinations, SI
abuse/dependence, schedule IV
Must use birth control other than/in addition to OCPs
138
Sodium oxybate for Narcolepsy Type 1
Sodium salt of GHB
restricted distribution
drug diversion/misuse concerns
Dosed at bedtime and 2.5-4 hrs later
Short half-life
Bed wetting, nausea, sleep walking, mood changes/thought changes
Nearly 100% of daily sodium intake
139
Solriamfetol (Sunosi)
```
Dopamine and NE reuptake inhibitor
FDA approved March 2019
Tx of sleepiness assoc. with:
Narcolepsy (type 1 or 2)
OSA
Schedule IV
```
75 mg starting dose
150 mg max dose
140
Pitolisant (Wakix)
```
H3 antagonist/inverse agonist
FDA approved August 2019
Treatment of sleepiness associated with:
Narcolepsy (Type 1/2)
Available in US since Nov. 2019
Unscheduled by FDA
Specialty pharmacy
```
141
What happens in OSA?
Key mechanisms:
Anatomy: small collapsible upper airway
Loop gain: oversensitive ventilatory control system
poor airways dilator muscles response gain and reflex
sleep wake mechanisms-low arousal thresholds
142
What happens in OSA?
Wakefulness: airway latency compensation
Sleep: decreased compensation
airway collapse
This leads to hypoxia/hypercapnia, increased effort
That leads to sympathetic activation
That leads to arousal/sleep fragmentation
Which then leads to hyperventilation, decrease CO2 and increased O2
This cycle continues through the night
End result is sleepiness (hyperactivity/behavioral problems in kids); cognitive impairment CVD
143
What are the characteristics of Snoring?
```
25% of men and 15% of women are habitual snorers
ETOH increases snoring
Consequences:
30-50% of asx snorers have OSA
UARS (snoring related arousals)
Risk factor for HTN, CVA, MI-carotid
atherosclerosis, TIA
Socially unacceptable
```
144
What are characteristics of UARS?
RERA on PSG (respiratory effort related arousal)
Patients with crescendo snoring
EDS w/o apneas or hypopneas
Treat with CPAP
145
What is a possible treatment for snoring?
Nasal strips
| But they will not open the pharynx
146
OSA-Adult
| ICSD-3 diagnostic criteria
(A and B) or C
(A) 1 or more of the following:
Sleepiness/nonrestorative sleep/fatigue
insomnia
observer reports snoring/breathing
interruptions
patient wakes breath holding, gasping,
choking
Dx of mood d/o, HTN, Cognitive dysfunction,
CAD, CHF, Atrial fib, T2 DM
(B) PSG with 5+ obstructive apneas, hypopneas
or RERAs per hour
(C) PSG or OCST with 15+ obstructive respiratory
events per hour
147
What are symptoms of OSA?
Repetitive episodes of complete (apnea) or partial (hypopnea) obstruction of upper airway during sleep
Results in Hypersomnolence (EDS), impaired concentration, increased risk of MVA, decreased QOL
Associated with CV diseases, HTN, metabolic abnormalities, cognitive impairment, Postop CV and respiratory complications, and stroke
148
What are typical clinical characteristics of OSA in adults?
```
Heavy snoring
Witnessed apneas, choking
EDS
Men: nocturnal
Women: night sweats
Obesity/neck size
HTN (esp. poorly controlled)
```
149
What are common physical findings in OSA?
BMI
Oropharynx
Retrognathia (2-4% with sx had OSA, 4-9% w/o sx)
more recent-33%
150
Who gets OSA?
| What are the risk factors?
```
Adults:
Middle aged
Overweight
Loud snoring
EDS
Gasping/choking episodes during sleep
Obesity
Retrognathia (recessed chin)
Increased neck size:
17 inches, men
Crowded upper airway
Unrefreshing sleep
Nocturnal
Systemic HTN
Race (Asian)
```
BMI and neck circ are good predictors of AHI
Increase in BMI of one SD assoc w/ 3-4x increased risk of OSA
OSA runs in families: obesity link
2-4 x risk
40% of the variance in the AHI may be explained
by familial factor
16 inches, women
151
What is the genetic basis for OSA?
Altered geometry/structure/craniofacial
Altered function/collapsibility
Respiratory drive
Load compensation
152
What are some populations that have higher risk for OSA?
```
Obesity
Genetic
Craniofacial, cleft
Neuromuscular
Sickle cell
Asthma
```
153
What is a Modified Mallampati score?
Tongue out (class 1-4) - throat restriction
```
Class 1-4
1=normal
2= some crowding
3=only see minute parts of oropharynx
4= only see soft and hard palate
```
Stick tongue out and relax it
154
How do you measure for Retrognathia?
Measuring if bridge of nose, eye and chin are in line
draw imaginary line
chin should normally touch the imaginary line
155
How is the Apnea-hypopnea index (AHI) defined?
AHI = events/sleep time (hrs)
Apnea = >90% reduction in peak signal airflow (cessation of breathing) for >10 sec
Hypopnea: > 30% reduction in peak signal excursion of the airflow sensor >10 sec and associated with 3% O2 desat or arousal (4% per CMS guideline)
156
What is the range for AHI?
AHI: number of apneas + hypopneas/hr of sleep
<5 = normal
=>5, but <15 = mild sleep apnea (treat with sx or comorbidities)
=>15 but < 30= moderate sleep apnea
=>30 = severe sleep apnea
157
What is the definition of sleep apnea?
Sleep apnea is defined as:
AHI > 5 per hr if have a co-morbid condition
AHI> 15 per hr otherwise
Sleep apnea is usually worse during REM sleep and in supine position
158
What are the consequences of untreated OSA?
```
Mood disorder
Cognitive dysfunction
Insulin resistance
HTN
CVD
MI
CVA
Arrhythmias
Death
```
159
What is the association of OSA and stroke in men?
| Sleep Heart Health Study
• Increase risk of developing stroke as intensity increases
• Not found in women
• Compared to men in lowest sleep apnea quartile, men with mod severe OSA had an almost 3-fold increased risk of ischemic stroke
• Risk of stroke in men increased 6% with every unit increase in baseline AHI from 5 to 25 events/hr
• In women, increased risk of stroke is only AHI >25 events per hour
• OSA predicted incident coronary heart disease only in men <70 y/o
o Men between 40-70, AHI>30 were 68% more likely to develop coronary heart disease than those with AHI <5
• OSA predicted incident heart failure in men but not in women
o Men with AHI>30 were 58% more likely to develop heart failure than those with AHI<5
160
What is the workup for sleep apnea?
```
Screen overnight oximetry (optimal)
may be used in hospitalized patient
Overnight PSG (gold standard)
1st night diagnostic
2nd night therapeutic study with CPAP
Split-night PSG- cost effective
Home studies (works when high index of suspicion for osa)
Inpatient sleep studies: esp. cardiac patients
```
161
What is pickwickian syndrome?
Obesity hypoventilation syndrome (OHS)
Triad of obesity, SDB, chronic hypercapnia during wakefulness in absence of other known hypercapnia (increased CO2 in blood stream)
162
OSA in women what is different?
```
Atypical presentation of insomnia/mood
Atypical symptoms
Snoring is strongest predictor
Milder, greater REM-related OSA
Populations: PCOS, pregnancy, post menopausal (2-3x)
```
Treatment PAP: improves function (mood, sleepiness, fatigue)
163
OSA and insomnia
OSA and insomnia are comorbid up to 50%
Insomnia sx decrease with treatment of OSA
Sleep onset insomnia:
Naps effecting process S
continued awakening at sleep onset
increased cortisol
Sleep maintenance insomnia:
if presenting symptom, consider OSA
164
What are the treatment options for OSA?
```
CPAP (most common and efficacious)
CPAP, I level, auto-CPAP
Oral appliance
Surgery
Positional therapy
Weight loss
```
165
CPAP therapy, what are the results seen?
```
Most common and efficacious
Decreases EDS
Improves QOL
Decrease accident risk
Decrease HTN
Increase cognitive functioning
```
166
What to tell a patient starting CPAP?
```
Safer than medication
Not a breathing machine
Just a splint to open the airway
Noise is much less than snoring
Only need to sleep with it
Consider a dementia action program (get used to it, take pictures of yourself)
```
167
What is CPAP tracking?
What are we looking for?
What are problems?
```
Optimal pressure (5-20 cm H20) determined by PSG
Abolish apneas and hypopneas
Abolish snoring and arousals
Maintain oxygen saturation > 90%
Reduction in total arousals
```
Compliance typically 50-60%
Patient acceptability
Avg nightly use 4.8 hrs
168
Oral appliance
| MAD
For mild/mod. OSA
For people with Retrognathia
Done by special DDS
Tongue forward and off the back
169
What is the typical presentation of pediatric OSA?
```
Snoring
Labored/obstructed breathing
Daytime consequences ( EDS, hyperactivity)
```
170
What is the PSG criteria for Dx of OSA in pediatrics?
1 or more obstructive events (obstructive or mixed apnea or hypopnea) per hr of sleep
Obstructive hypoventilation, PaC02 >50 mm Hg for >25% of sleep time, along with snoring, paradoxical thoracoabdominal movement, or flattening of nasal airway pressure waveform
171
What are the risk factors for pediatric OSA?
```
Adenotonsillar hypertrophy
BMI/obesity
Prematurity
Smoke exposure
Comorbid conditions
```
172
What are the clinical features of children with OSA?
Snoring/gasping/choking/pauses in breathing
Sleeping with neck hyperextended or other unusual positioning
Fitful sleep, sweats in sleep
Mouth breathing
Bruxism
Hypo nasal speech (nasal congestion)
Nocturnal enuresis (secondary)
Hyperactive, behavioral problems (not always sleepy)
173
What are consequences of untreated OSA in children?
```
Impaired growth/FTT
Inflammatory
Neurocognitive and behavioral problems
hyperactivity, behavior, learning, mood
EDS, less common
More visceral fat (independent of BMI)
Secondary enuresis, 6% incidence
Cardiac: HTN, cardiac remodeling
Metabolic syndrome, insulin resistance
```
174
What is OSA prevalence by age group?
```
Kids-younger children
10% of children snore, 1-5% OSA
peak age toddler (tonsils)
Teens
2nd peak, related to increased obesity
Adults
moderate OSA (young-old)
3-9% women
10-17% men
>50% mild OSA in obesity (BMI > 30)
many undiagnosed
```
175
How do we screen for OSA in children?
Screen all children for snoring during Well child visit
Guidelines for high risk groups
Down syndrome
Achondroplasia: +central sleep apnea (dwarfism)
176
How do we screen for OSA in adults?
```
STOP-BANG
originally used in anesthesia world
Snore loudly
Tired-during the day
Observed-stop breathing
Pressure: hypertension
BMI >35
Age >50
Neck circ: 17+ inches in men, 16+ inches in women
Gender: male
High risk:
> 2 STOP
>3 STOP-BANG
```
177
How is the STOP-BANG scoring interpreted?
STOP: >2 high risk for OSA, <2 low risk
| STOP-BANG: >3 high risk, <3 low risk
178
What is the testing that’s done to screen for OSA?
```
PSG: gold standard
HSAT (home study): Adults, some teens
Only for OSA
Best for high probability OSA
May miss some mild cases, if neg. And OSA still possible, needs PSG
```
Pediatric screening:
AAP/AASM support PSG prior to T&A for OSA
ENT supports PSG testing prior to T&A for high risk or Comorbid it’s (obesity, age <3, high risk)
CHAT trial (childhood AT trial): 50% who have AT, had primary snoring/mild SDB (no OSA)
179
When is Tx of OSA in adults indicated?
AHI>5-14: mild OSA + symptoms (gasping, EDS, insomnia, uncontrolled HTN, CV)
AHI>15: moderate-severe
180
When is Tx of OSA indicated in pediatrics?
Different cutoffs for kids
Primary snoring
Mild OSA (AHI 1.5-4.9): can do watchful waiting based on CHAT trial
Moderate-severe OSA (AHI>5), want to treat
181
What are the Tx options for OSA in children?
First line treatment is AT
CPAP: for residual OSA, bridge Tx
Milder: nasal steroids (Flonase)
Other: maxillary-mandibular dental (selected cases), maxillary expansion
Weight loss if applicable
Specialty surgeries for craniofacial cases
182
What is Tx options for OSA in adults?
First line Tx is CPAP for all types of apnea
Dental devices (OAT/MAD): Tx for mild/mod. OSA
Surgery (selected cases, multiple types of surgery)
Hypoglossal nerve stimulator (Inspire) for mod/severe OSA, CPAP intolerant, BMI of 32-35 or less
Other: expiratory valve, negative pressure
Adjunctive: lifestyle, exercise, wt. loss, positioning, stop smoking
“When in doubt, pressurize the snout”
183
Aspects of CPAP
```
Pneumatic splinting
Primary therapy for adults
CPAP can be transformative
But many patients inadequately treated due to inconsistent adherence
Some patients “intolerant”
Children can wear CPAP
```
184
What are conservative treatments for children and some adults?
Myofunctional therapy
Medications to improve nasal passage: reduce allergies/inflammation
Nasal steroid sprays, montelukast
Non-surgical dental therapies
Dental appliances
185
What is myofunctional therapy for OSA?
We should breathe through our nose
Train person to not breath through mouth
Retrain to breath through the nose, increase nasal patency
Mouth breathing influences palatal development in growing children, under-developed midface, palatal constriction
In adults: reduces AHI severity
186
What are non-surgical dental therapies for Tx of OSA?
OAT (oral appliance therapy/ MAD (mandibular advancement device)
Rapid maxillary advancement
children
newer modalities for adults
Dental appliances are effective in mild/mod OSA
Must have dentition and completed growth (not for young children)
Sleep study before and after
DDS teams with sleep
Adult outcomes: reduces AHI (not as effective as CPAP), lowers BP and less EDS
187
What are surgical options for OSA?
```
Site specific:
AT
nasal surgery
soft palate
Floppy epiglottis (children)
```
Craniofacial:
maxillomandibular advancement
Most aggressive: tracheostomy (only in malignant OSA)
Hypoglossal nerve stimulator (inspire)
neuromodulation, surgically implanted
produces dose-related increase in airflow by stimulating tongue during inspiration, w/o waking
Effective in mod/severe OSA
188
What is the impact of sleeping position on OSA?
Supine sleep tends to increase risk for OSA
Positional therapy: side sleeping, incline sleeping
189
What is the effect of weight loss on OSA?
For mild OSA: can cure in a dose-dependent manner (more weight loss, more likely)
For more severe OSA:
bariatric surgical weight loss vs diet/exercise
20% weight loss: AHI 65 to 39
5% weight loss: AHI 57 to 43
190
What is the effect of exercise on OSA?
Adults: increase in exercise can decrease AHI by 8 w/o changing BMI
Children: insignificant results, but do have improvements, most do not get the daily requirement of exercise
191
Are medications recommended for OSA?
Not recommended
Minimal effects on OSA with side effects.
Presumable effect on REM
192
What are the outcomes for OSA treatment?
Decreased health care utilization
Improved QOL, sleepy scales, BP
Better BG control in DM
Adherence w/ CPAP is challenging
Overall average is 50%, better in sleep clinics
Doesn’t reverse CV mortality. In RCTs likely due to poor adherence
193
What is the definition of central sleep apnea?
```
No effort
Absence of airflow>10 sec with absence of respiratory effort
No breathing
Normal CO2
High altitude
Cheyne-stokes resp (CHF, ESRD)
transitioning around arousal from sleep
High CO2
Ventilatory control abnormalities
opioids, obesity, OHS
neuromuscular disease: impaired resp. Motor control (ALS)
```
194
What is seen in respiratory effort with central sleep apnea?
Use of measurements of chest and abdominal motion to assess resp. Effort
“absent” motion
No paradoxical movements
Can misclassify obstructive as central events
For Cheyne-Stokes, it is the overall pattern that one recognizes
195
What is hypercapnic central sleep apnea?
Chronic congenital hypoventilation (Ondine’s curse), hypoventilation sleep.
breathe normally awake, but as they go to sleep, don’t respond to CO2.
Central hypoventilation syndrome, often fatal
Shy-Drager Syndrome (dysautonomia, movement d/o referred to as Parkinson plus syndrome or Multiple system atrophy (MSA)
Brain stem lesions (stroke, vascular malformations, MS)
Cord lesions-trauma, etc.
196
What is hypocapnic (low CO2) central sleep apnea?
Hypoventilation syndrome (not necessary to have apnea)
Dx criteria- must fulfill A and B
A-one: cor pulmonale, plum HTN, EDS, erythrocytosis, awake PCO2>45
B: increase in PCO2 during sleep >10, O2 desat (sustained) not explained by events
Predisposing factors:
morbid obesity (BMI>35)
chest wall restrictive disorders
Neuromuscular disease
Brainstem or high cord lesions
idiopathic central hypoventilation
obstructive lung disease
hypothyroidism
medications that suppress ventilatory drive (opioids)
197
Hypocapnic (normcapnic) central apnea
Idiopathic central sleep apnea
Apnea at high altitude
Cheyne-stokes respiration
198
Idiopathic central sleep apnea syndrome
```
Uncommon
Apneas > 5/hr, 85% central
EDS
Lower PCO2 awake and sleep
Increased ventilatory response to CO2
```
199
What is Cheyne-stokes respiration?
Rare abnormal breathing pattern that can occur while awake, but usually during sleep
Pattern=fast, shallow breathing followed by slow, heavier breathing and moments w/o any breathing at all (apneas)
Occurs in CHF
Occurs in stroke
3+ consecutive cycles crescendo-decrescendo change in breathing cycle length typically 60 sec.
Can count events or % time with Cheyne-stokes
200
What are the treatments for Cheyne-stokes breathing?
```
Oxygen administration
Inhalation of CO2
Theophylline
CPAP
Auto-CS (now called ASV)
```
201
What are characteristics of Central sleep apnea at high altitude?
Periodic breathing with central apnea at high altitude is extremely common
Cycle time is short- 20 to 30 seconds (compared to classic Cheyne-stokes, 60-90 sec)
Some studies show relationship of AHI to hypoxia ventilatory response but other studies do not
202
What is complex sleep apnea?
Central apneas/Cheyne-stokes in patients with OSA w/obstructive events relieved by CPAP
203
What is the diagnostic criteria for Delayed Sleep Wake Phase disorder (DSWPD)
Significant delay in phase of major sleep period (>2 hrs relative to socially acceptable time)
Symptoms present for at least 3 months
Ad lib. sleep improves quality, quantity, consistency (i.e. vacation)
Not better explained by medication use, SUD, etc
DSPD subtype: motivated DSPD (particularly with teens)
Typical schedule is 2am-10am
204
What are some associated features of DSWPD?
Sleep initiation insomnia
ETOH and hypnotic use at bedtime common
Delay during adolescence, teen to age 25 natural delay
7% of population (behaviorally induced)
Longer tau (longer period/delay intrinsically, like adolescence)
205
What is treatment for DSWPD?
Align sleep schedule to natural delayed phase first
Dim light 2 hrs prior to bedtime
Bright light only after CBTmin (2 hrs before habitual wake time)
0.3-0.5 mg melatonin 2-6 hrs prior to bedtime
Start melatonin to start 5 hrs before bedtime, can shift depending on response
206
What are the recommended assessments for circadian rhythm disorders?
```
Sleep logs (gold standard)
Actigraphy
Questionnaires: MEQ, Munich chronotype
Melatonin: DLMO (from saliva)
Core Body Temp (CBT)
PSG (not indicated)
```
207
What are the Diagnostic criteria for Advanced Sleep Wake Phase Disorder (ASWPD)?
Significant advance in phase of major sleep period (>2 hrs relative to socially acceptable time)
Symptoms present at least 3 months
Ad lib sleep improves sleep quality, quantity, consistency
6-8pm to 2am typical schedule
208
What are associated features of ASWPD?
Early morning awakening (8pm to 2am)
Estimated incidence 1% of population likely low (less likely to perceive as problem)
Tau < 24 hrs, just shorter than 24 hr cycle of the day
More socially acceptable, “early bird gets the worm”
209
What is the treatment for ASWPD?
Bright light in the evening from 7-9 pm (tablet, computer, TV)
Avoid bright light in the morning
Avoid outside light till 10am or later (use sunglasses)
Keep activity low in the morning, delay timing of exercise to avoid light
Reassurance: adapt life to circadian rhythm
Stop taking naps
210
What is the diagnostic criteria for Irregular Sleep Wake Rhythm disorder (ISWRD)?
Absence of a well-defined circadian pattern to the sleep-wake cycle
TST comparable to health same-aged peer but lacks major sleep period across 24 hr day
3 or more sleep episodes (1-4 hr each) with the longest period typically occurring 2-6 am
Symptoms present for at least 3 months
211
What are associated features of ISWRD?
Most commonly associated with Alzheimer’s disease, other neurodegenerative disorders
Environmental disruptions: ICUs, hospitals, rehab units
212
What is treatments for ISWRD?
Increase circadian amplitude: sleep hygiene, meal timing, social activities, AM bright light
Melatonin as a mono therapy may have negative effects on mood
Hypnotics contraindicated
213
What are the diagnostic criteria for Non-24 hr Sleep-Wake Disorder (N24SWD), (“free running”)
Pattern of circadian misalignment will typically present as a relatively steady, continual delay in the sleep-wake timing
Can sometimes have 1-2 “weeks of alignment” followed by difficulty
Symptoms present for at least 3 months
214
What are associated features of N24SWD?
Can present as periods of insomnia, EDS, or asx depending upon when person is trying to sleep relative to his/her circadian period
Most commonly found in people who are blind (13-50%)
Rare/controversial in sighted individuals (possibly DSWPD with long tau?)
215
What is treatment for N24SWD?
Sighted individuals with N24SWD: same as for DSWPD
Melatonin receptor agonist (Ramelteon, Tasimelteon, AKA Rozerem/Hetlioz) or melatonin (<0.3mg):
Administer 1-2 hrs before desired bedtime
Once entrainment is established over course of a month, can switch to melatonin (<0.5mg)
2-6 hrs before bedtime to maintain entrainment
216
What is the diagnostic criteria for Jet Lag Disorder?
Complaints of insomnia or EDS and reduced TST associated with jet travel across at least two time zones.
Associated daytime impairment (fatigue, general malaise; impairment of decision making, reaction times and athletic performance) and/or somatic complaints (GI disruptions)
Occurs within one to two days after travel
217
What are associated features of Jet Lag disorder?
Limited data suggests increased difficulties for middle to older adults (>50 years) vs younger (<30 y)
Limited data suggests that jet lag could precipitate a relapse of a depressive episode (for Westward travel) or a hypo manic episode (for eastward travel)
218
What is treatment for Jet Lag disorder?
As a general rule for infrequent travelers: maximize daytime light
For Westward travel: strategies for delaying sleep
evening light approaching CBTmin to provide the greatest delaying effects
Avoid bright light in the morning for the first few days
For Eastward travel: strategies for advancing sleep
Avoid bright light in the evening, seek bright light in the morning
When eastward travel exceeds 9 time zones, it becomes more advantageous to make any
adjustments as if the trip were a 14 hr westward journey
219
What is the diagnostic criteria for Shift Work Disorder (SWD)?
Complaints of insomnia and/or EDS along with insufficient TST
Difficulties caused by a work schedule that routinely occurs during habitual sleep time
Symptoms present for at least 3 months
220
What is most harmful to least harmful in SWD?
Most harmful to least:
night shift, rotating, early morning, afternoon/evening, daytime
Duration shift work:
Hrs per shift (>12 hrs per shift)
No. of years engaged in regular shift work (in a dose-dependent response)
Direction of rotation (counterclockwise worse than clockwise)
Speed of rotating shift work:
Faster rotation( i.e. multiple rotations within 1 week, may be worse than slower rotation)
221
What are associated features of SWD?
2004: 13.5% US engage in shift work
Current estimates: 22 million shift workers in the US alone (2018)
Increased risk for metabolic, CV, Reproduction, GI, mood, substance use and other sleep d/o
Known probable carcinogen per WHO, IARC
222
What is Treatment for SWD?
Best treatment= stop shift work if possible
Stimulants (Modafinil) approved to increase alertness during shift work
Match work shift with circadian profile of employees
Align as close to natural sleep-wake rhythm as possible
Use of sedatives not recommended
Timing of naps and bright light therapy during shift
Increase amplitude of circadian signals
Estimate CBTmin (2 hrs before habitual wake time) for strategic light therapy
223
Overview of CRSD treatment options:
1. Understand homeostatic and circadian contributions to sleep/wake complaints
2. Fight the EDS:
Caffeine (not great for children)
stimulants/“alerting agents” (some concern)
prevent or encourage napping
3. Put you to sleep:
melatonin/ramelteon
hypnotics
4. Shift circadian phase:
melatonin
phototherapy
sleep scheduling (e.g. chronotherapy, naps, no naps)
5. Phototherapy
224
Exact criteria for diagnosis of Narcolepsy Type 1
Daily periods of hypersomnolence > 3 months (gradual or sleep attacks)
One or both of the following:
cataplexy and MSL <=8 min and >=2 SOREMPs on MSLT; SOREMP (<= 15min after sleep onset)
on preceding nocturnal PSG may replace one of the SOREMPs on MSLT
low or absent CSF orexin levels, <110 pg/ml or <1/3 of healthy controls (have to do LP)
225
Other specific details of MSLT protocol
Epoch = 30 sec interval
Full day test that consists of 5 scheduled naps separated by 2 hr breaks
Look at 1st epoch of sleep, look for REM
Once fall asleep, carry test for 15 min. And stop.
If no sleeping; stop nap at 20 min.
But if patient falls asleep at minute 12, carry test for another 15 min and then stop minute 27
If patient never falls asleep with nap, then SL = 20 min. (Not zero)
SOL tends to be shortest 3rd/4th naps, longest 5th naps
Propensity for REM greatest in 1st nap
226
What are other reasons for short Sleep onset latency (SOL)?
| When doing MSLT
```
Sleep deprivation
DSWPD
OSA
PLMD
Acute w/d of stimulants
Use of long-acting hypnotics on night preceding MSLT
```
227
What is the definition of a SOREMP?
| What are possible causes for SOREMPs?
SOREM is an abnormal sleep phenomenon characterized by having REM sleep occurrence within 15 minutes from the onset of night time sleep or daytime napping
```
Possible causes for SOREMPs:
Narcolepsy
OSA
DSWPD
Withdrawal from REM suppressants
ETOH withdrawal
Sleep deprivation
1-3% of healthy adults
```
228
What is the range for Sleep latency to Stage 1?
15-20 min = normal
5-10 min = grey zone
0-5 min = pathological EDS
> 2 REM onsets- think of narcolepsy
229
Overview of Idiopathic hypersomnolence (IH)
Chronic sleepiness without cataplexy, not well understood
Long periods of EDS that impair performance
Nocturnal sleep is long and often undisturbed
sleep drunkenness in the morning (sleep inertia)
Automatic behaviors
Short latency to stage 1 sleep on MSLT w/o REM
Age of onset usually in 2nd decade
Treat with modafanil/armodafinil
230
What are NREM-related disorders of arousal (parasomnias)?
Confusional arousal: 17% children, 3-4 % adults
Sleep walking: 18% lifetime prev, 4% adults
Sleep terrors: sudden arousal associated with terror, patient may jump or run
1-6.5% children, 2% adults
231
What are common features of all arousal disorders?
```
Arise in first 3rd of night (out of SWS)
Strong family history
More common in childhood
Recurrent episodes of incomplete awakening from sleep
Min. Response from other people
Min. Recall of episodes
```
232
What are factors that exacerbate arousal disorders?
```
Stress
Sleep deprivation
OSA
PLM
GERD
Medications/ETOH
```
233
What is treatment for arousal disorders?
```
Reassurance (often to parents)
Secure environment
Warning device
Avoid precipitating factors
Treat co-morbid sleep disorders
Medication if needed: BZD or TCA
```
234
What are subcategories of arousal?
Sleep related violence
Sleep related sexual behaviors
Hypnotic induced behaviors
Sleep related eating disorder
235
Characteristics of Sleep Walking (somnambulism) ?
```
Usually occurs in childhood or adolescence
Episodes occur during SWS
Episodes last <10 min
+ family history
Confusion on waking
Minimal recall of events
Patients are able to maneuver around obstacles and perform simple tasks
High risk for injury
```
236
what are characteristics of Sleep Related Eating disorder
Timing of food intake: after initiation of sleep and prior to final awakening
Level of consciousness during feeding: unconscious to fully awake
Unusual food intake (inedible): common
Associated disorders: sleep walking, RLS, OSA, obesity, depression
Medication assoc: zolpidem, triazolam, olanzapine, risperidone
Reported Txs: dopaminergics, topiramate, Benzos
237
Review of Night eating syndrome
Timing of food intake: after last meal and prior to final awakening
Level of consciousness during feeding: fully awake
Unusual food intake: rare
Associated disorders: obesity, depression, substance abuse
Medication assoc: none reported
Reported Tx: sertraline
238
What are REM-related disorders?
Nightmares (dream anxiety)
Sleep paralysis
REM Sleep Behavior Disorder
239
What is the diagnostic criteria for RBD?
Repeated episodes of sleep-related vocalization and/or complex motor behaviors (either documented to arise from REM or presumed based on reports of dream enactment
AND evidence of REM sleep without Antonia on PSG (as defined in scoring manual)
Disturbance not better explained by another disorder, med/substance use
240
What group typically presents with RBD?
Occurs in older men
May be related to a neurodegenerative disease
? Related to/precipitate Parkinson’s disease and Lewy Body dementia
Multi-system atrophy (MSA)
Rare in AD
Mild, mod, severe
Send to neurologist to be followed over time
241
What are possible treatments for RBD?
Clonazepam is treatment of choice (but will worsen sleep apnea)
~90% effective in large series
suppresses behavior, atonia not restored
Melatonin may help: effective at 3mg in 5/6 patients, 2-12 mg in 12/14 patients
Secure environment
242
What is characteristics of Sleep paralysis?
Paralysis of skeletal muscles at sleep onset or awakening
Associated with anxiety
Lasts seconds
Isolated sleep paralysis can occur in normal individuals
243
What are characteristics of somniloquy (sleep talking)
Can occur in any stage
Can be associated with d/o of arousal or RBD
Can be increased in setting of medical/psych stress
Generally does not require treatment
244
Characteristics of sleep-related hallucinations
Hypnogogic (sleep onset) or hyponopompic (sleep offset)
May occur following sudden arousal
Hallucinations primarily visual
Not associated with prior dream
Often involved images of people or animals
May misidentify objects in bedroom, resolving with increased illumination
Can be associated with other medical conditions
245
What is catherenia (sleep related groaning) ?
4 cases of natural expiratory groaning described by Bologna group
No awareness of sleep complaints
NREM (stage 2) and REM
Normal neurological and ENT exams
No evidence of seizure or apnea per original description
246
Bruxism
```
Tooth grinding
Jaw clenching
Headaches
TMJ dysfunction
High prevalence in children
Treatment: night guard
```
247
Rhythmic movement disorder
Stereotype head banging or body rocking
Rare in adults
Often in transition from wake to sleep
Mechanism unknown
248
Myoclonus
| Propriospinal myoclonus
Fragmentary myoclonus: brief, small amplitude twitches, occur in any stage of sleep
Benign sleep myoclonus of infancy
Epileptic typically present in both wakefulness and sleep
Propriospinal myoclonic: large amplitude jerk, arise in wakefulness, disappear in sleep
249
What are sleep starts?
Brief sudden motor or sensory phenomena which occur at wake-sleep transition
May manifest with asymmetric muscle contraction
May be associated with or consist of sensations of falling, loud noise or flash of light
250
What are secondary parasomnias?
| From another disorder
```
Seizure
Headache
Nocturnal asthma
GE reflux
Sleep related dissociate disorders
Nocturnal panic attack
```
251
What are the ICSD3 parasomnias?
```
NREM-related parasomnias:
confusional arousals
sleepwalking
sleep terrors
sleep related eating disorder
REM-related parasomnias:
RBD
Recurrent isolated sleep paralysis
nightmare disorder
Other parasomnias:
exploding head syndrome
sleep-related hallucinations
sleep enuresis
parasomnia due to medical disorder
parasomnia due to medication or substance
parasomnia, unspecified
```
Primary (from sleep) vs secondary (from another disorder)
252
What are the Sleep-related Movement disorders?
```
RLS
PLMD
Sleep-related leg cramps
Sleep-related Bruxism
Sleep-related rhythmic movement d/o
Benign sleep myoclonus of infancy
Propriospinal myoclonus at sleep onset
Sleep-related movement d/o due to medication or substance
Sleep -related movement d/o, unspecified
```
253
Overview of RLS
Estimated to affect 3-5% of population
Prevalence of PLM correlated with age-most common in pts >50 yrs old
43% develop RLS before age 20
RLS autosomal dominant trait, 60% of pts w/RLS have first degree relative with RLS
Common cause of EDS
Bed partner often complains of being kicked-sheets “messed up” in the morning
254
What is the diagnostic criteria for RLS?
| Also called Willis Ekbom disease
Urge to move the legs, often accompanied by uncomfortable or unpleasant sensations in the legs
These sensations are worsened by rest or inactivity
Improved by movement
Worse in evening or overnight
RLS is not pain!
```
URGE is pneumonic used:
Urge to move legs
Rest worsens sx
Gets better w/movement
Evening worsening or night time appearance of sx
```
255
Other details about RLS
80% of patients with RLS will have PLMs during sleep
RLS is a clinical dx, PSG not needed
RLS rating scale, score 0-40, use to evaluate effectiveness of Tx
Associated with iron deficiency in substantia nigra, decreased ferritin, decreased iron in brain
256
What are diagnostic criteria for PLMD?
May be diagnosed when frequency of limb movements (AASM), >15/hr in adults and >5/hr children
Recurrent stereotypic movements of legs during sleep
rhythmic extension of big toe and dorsiflexion of ankle
Must be accompanied by sleep disturbance or other functional impairment to establish dx
80% of patients with RLS manifest PLMD
PLMD should not be used in conjunction with dx of RLS, narcolepsy, RBD, or untreated OSA,
because the movement disturbance is a common finding in these disorders
257
PLMD, Dx with PSG
EEG arousals related to increased EMG on leg channels
Each movement (0.5-10 sec)
Interval between movements (5-90 seconds)
Frequency decreases during delta/REM sleep
Treat if >5-10 arousals per hr and clinical symptoms
258
What are other conditions associated with RLS/PLMD?
Iron deficiency anemia- primary RLS
25% of RLS population is iron deficient
ferritin level >75 is goal; question repeat blood donors
In a stable patient whose RLS abruptly worsens evaluate for GI bleed
Uremia
Neuropathy/spinal cord pathology
Pregnancy- typically worse 2nd half
Medications: TCA, lithium, dopamine antagonists (seroquel, reglan, phenergan, risperdal), anti nausea drugs, antipsychotics, SSRI’s, antihistamines (diphenhydramine)
Use of alcohol, nicotine, caffeine
259
RLS evaluation
If worried about PLMS in sleep, do PSG
If worried about RLS: then no PSG
Medical history: iron status, ferritin level >75 is goal
Check vitamin D levels, low levels related to increased risk for RLS
260
What are treatment options for RLS, nonpharmacological?
```
Behavioral management, get them moving
Avoid long periods of inactivity
sleep hygiene
regular activity
Treat medical problems that exacerbate RLS
Check and Tx iron and vitamin D status
Mental alerting activities
Reduce caffeine intake
Soak affected limbs
Leg massage
```
261
What are Tx options for intermittent RLS?
Leg compression
Warm bath
Movement
Intermittent medications: levodopa, Benzo’s
262
Iron therapy for RLS
check iron status, ferritin level >75 is goal
Iron therapy is first line treatment if iron deficient
325mg BID-TID, with vitamin C to improve absorption
If intolerant oral Fe or refractory to oral Fe, consider IV iron infusion
Sx improvement expected within 6 weeks of IV iron and within 2-3 months of starting oral iron.
263
What are treatments for chronic persistent RLS?
| Dopamine agonists?
Dopamine agonist:
pramipexole (mirapex): start with 0.125mg
ropinirole (requip): 0.25-2.0mg (1-2 hrs Qhs)
rotigotine patch
Can cause nausea, nightmares, fatigue, sleepiness
9% of patients at risk for impulse control disorders (ICD), increased shopping, gambling, sexual activities
264
What is the first line Treatment for RLS?
Alpha 2 ligands:
Gabapentin
Pregabalin (lyrica)
Gabapentin encarbil (horizont): extended release, 600mg at 5pm, once a day and same dosage for all
Preferred treatment now , no risk for augmentation
Risk of augmentation with dopamine agonists
```
Contraindications are:
Obesity
Past or present mod/severe depression
Gait instability
Resp. Failure
Hx of substance abuse
```
265
What is second line treatment for RLS?
Carbidopa 50mg/levodopa 200mg (sinemet)
Clonazepam (klonopin) 0.5-2mg at night
may worsen OSA, increase risk of falls at night
Opiates: codeine, methadone, Tylenol #3
266
What is treatment options for refractory RLS?
Check iron stores, replenish iron as needs, IV if needed
Correct other exacerbating factors
Consider combination treatment:
dopamine agonist, alpha 2 ligand, opioid, benzos
Consider high potency opiates (methadone)
267
What is Rotigotine?
New drug treatment for RLS
Neupro is brand name
Dopamine agonist patch
268
What are medications that can exacerbate RLS?
```
Antiemetics (reglan, phenergan)
Antihistamines (sedating, i.e. Benadryl)
Antipsychotics (seroquel) block dopamine
SSRI’s
SNRI’s
TCA’s
Mianserin and mirtazapine (tetracyclic)
Lithium
ETOH
```
Consider that RLS symptoms started after starting medication
269
What are the characteristics seen with Augmentation?
```
Augmentation refers to overall worsening of sx severity while on DA (mirapex, requip)
Earlier onset of sx
Shorter sx latency w/rest
Shorter duration of action of drugs
Spread of sx to trunk/arms
```
Typically with mirapex
Sx start earlier in the day
Sx worsen
More body parts involved
Normal response of MD is to increase dose of mirapex, but makes Sx worse!
If Sx mild, keep same DA or switch to Rotigine patch or alpha 2 ligand
Wash out first, then switch to alpha 2 ligand
270
Diagnostic criteria for PLMD
PSG to make Dx
Need to have daytime Sx: EDS, insomnia
PLMs > 15/hr on PSG in Adults
PLMs > 5/hr on PSG in children
80% of patients with RLS will have PLMs on PSG
Often present with insomnia, look at arousals with PLMs on PSG
271
Nightmares
```
Peak age 6-10
Frightening dreams final 1/3 of night
Memory of dream detailed and vivid
Precipitating factors in adults:
antidepressants
amphetamines
sedatives
beta blockers
stress
```
272
Sleep terrors
```
Timing: first 1/3 (SWS)
Movements: common
Severity: severe
Vocalizations: common
Autonomic discharge: severe, intense
Amnesia: present
State on waking: confused
Injuries: common
Displacement from bed: common
Can happen with nocturnal sleep, but also during naps
```
273
Nightmares
```
Timing: last 1/3 of night (REM)
Movements: rare
Severity: mild
Vocalizations: rare
Autonomic discharge: mild
Amnesia: absent
State on waking: function well
Injuries: rare
Violence: rare
Displacement from bed: very rare
```
274
What are treatments for Nightmares?
Prazosin: Alpha 1 adrenoreceptor blocker
only drug recommended
Psychotherapeutic approaches: IRT, lucid dreaming
275
Iron therapy for RLS patients with low ferritin
IV iron is good idea if no response with oral iron x 3 months
Bariatric surgery patients: low iron common
Multiparous women: low iron common
often need ~ 3 cycles IV iron
If respond to iron infusions: can decrease Gabapentin dose
Often want to continue Gabapentin since good for insomnia, causes sedation
276
How to choose which alpha ligand to use for RLS?
Choose based on factors that include pharmacokinetics
Symptom pattern
Cost
Sx mostly evening/night: start with lyrica or Gabapentin (but Gabapentin often cheaper)
RLS symptoms most of the day and night, prefer Horizant because provides 24hr coverage, convenient once daily dosing
277
What is the FEO?
The food-entrainable oscillator (FEO) is a mysterious circadian clock because its anatomical location(s) and molecular timekeeping mechanism are unknown. Food anticipatory activity (FAA), which is defined as the output of the FEO, emerges during restricted feeding.
278
What is the PAP Nap procedure?
The “PAP-NAP” is a daytime sleep study conducted to desensitize patients to PAP therapy, especially patients who have acute anxiety about using PAP due to insomnia or other anxiety conditions. The procedure contemplates the patient’s presence in the sleep lab or physician office for individual PAP coaching, an attended cardiopulmonary recording involving at least four channels, and instruction and fitting of the PAP equipment. The patient is then left to sleep briefly with the PAP to familiarize the patient with the equipment and pressure sensations in a controlled setting.
The entire procedure is attended by a sleep technologist and ranges from 3 to 5 hours in length, including patient check-in, instruction, approximately 1 to 3 hours of sleep time, and discharge.
Abbreviated cardio-resp sleep study which aims to enhance PAP adherence. Includes 100 min. Nap period: exposure to PAP with emotion-focused therapy to overcome aversive emotional reactions, mask and pressure desensitization, mental imagery to divert pt. Attention from mask or pressure sensations
279
Psychoeducation on sleep terrors: reassurance and prevention
Most outgrow by adolescence
Genetic predisposition
Not thought to be related to emotional trauma
Very stressful for parents, not so for children
Appropriate parental response
First line Tx: increase sleep duration
Drug Tx options recommended for severe cases
Factors that increase incidence:
Sleep deprivation/ insufficient sleep time
Irregular sleep schedule
Illness/fever
Temporary increase in stress or anxiety
Caffeine
Internal (e.g. cough, full bladder) and external (noise, movement) events during transition from SWS
280
Pediatric OSA- What’s different?
```
Lower prevalence: 1-5%
Severity:
Normal: AHI<1
Mild: AHI >1-4.9
Moderate: AHI >5-9.9
Severe: AHI >10
First line Tx: T and A
Split night studies less common
Most common cause: adenotonsillar hypertrophy
Hyperactivity as a sx
Can cause enuresis (especially secondary)
```
281
What are the AAP Guidelines for Dx and management of pediatric OSA?
All children should be screened for snoring
If snoring (>3 times/wk) and signs/sx of OSA, child should be referred for further evaluation (PSG, ENT, Sleep)
If child is determined to have OSA and has adenotonsillar hypertrophy, 1st line TX is T & A
After OSA Tx, clinically reassess all patients w/OSA for residual signs and sx.
CPAP for residual OSA
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What is AASM guidelines for shift work disorder
Standard: planned nap before or during night shift
Guideline: timed light exposure in work environment and light restriction in the morning
Guideline: melatonin prior to daytime sleep
Guideline: hypnotic to promote daytime sleep, consider adverse consequences
Guideline: Modafinil to enhance alertness
Option: Caffeine to enhance alertness
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Jet lag, other details
Sx worse w/ eastward travel (because attempting to sleep when alerting signal is hight)
Two basic strategies for Tx:
Realign to new circadian clock (start either before journey or upon arrival at destination)
Treat the Symptoms
Melatonin is a “standard” treatment and light is a treatment “option”
