Basics of Sleep Basics of Sleep Basics of Sleep Basics of Sleep Sleep Architecture and Sleep Stages

- Sleep is divided into 2 independent states: Nono Non-REM Sleep (divided into 3 stages; used to be 4 stages until it

o N1

o N2

o N3 (slow

o REM sleep Noted 60 to 90 minutes after onset of sleep Accounts for about 20-25% of sleep time Characterized by fast rhythms and theta activity Believed that approximately 80% dreams occur during REM sleep (the other 20% occur

Interesting triviadreams are more realistic and rational

Can be divided into 2 stages:

Tonic stage: desynchronized EEG, hypotonia or atonia of major muscle grand polysynaptic reflexes

Phasic stage: Characterized by rapid eye movements in all directions, phasic swings in blood pressure and heart rate, irregular respiration, spontaneous middle

Function of Sleep

- I will not go over this too much as the function of sleep largely remains a mystery - Several theories

o Restorative theory: sleep needed to restore cerebral function after periods of waking (evidence of increased anabolic hormo

levels of catabolic hormones during sleep) During NREM sleep: presence of slow wave sleep after sleep deprivation

o Memory consolidation more recent studies have revealed that new memories can be strengthened by sleep (so remember to get

before FND!) synthesis of new RNA and proteins by neurons during sleep

o Maintenance of synaptic and neuronal network integrity - Some interesting associations: sleep deprivation leads to decreased levels of serum leptin and increased levels

explain the BMI observed with short sleep duration

Sleep Patterns with Age - Sleep requirements change dramatically from infancy to old age

o Newborns: poly-phasic sleep pattern with 16 hours of sleep per day Sleep requirements decrease to about 10 hours per day by ages 3 to 5 years

o Preschool children: sleep assumes biphasic pattern (nap time!)o Adult: mono-phasic sleep pattern (7.5 o Elderly: changes back to biphasic pattern (nap time!)

- Newborn spends 50% of the time in REM sleep; however, duration of the NREMand increasing as they get older; by age 6, time in REM is decreased to about 25% but their NREM

: Non-REM sleep and REM sleep - both alternate and each cycle last about 90

REM Sleep (divided into 3 stages; used to be 4 stages until it was modified in 2007)

Diminishment in alpha rhythms (8-13 Hz), which are characteristics for wakefulness Presence of slower theta rhythms appear (4-7 Hz) and beta waves (> 13 Hz) EMG activity: slow, rolling eye movements Vertex sharp waves noted toward the end of N1

Characteristic EEG findings: sleep spindles (12-18 Hz; most often 14 Hz) and K complexes Also contains theta rhythms and fewer than 20% slow waves (0.5 Lasts for about 30-60 minutes

N3 (slow-wave sleep) Now the slow waves will occupy > 20% up to 100%

Noted 60 to 90 minutes after onset of sleep 25% of sleep time

Characterized by fast rhythms and theta activity Believed that approximately 80% dreams occur during REM sleep (the other 20% occur during NREM)

Interesting trivia: REM sleep dreams are highly emotionally charged, complex and bizarre; whereas NREM dreams are more realistic and rational

Can be divided into 2 stages:

: desynchronized EEG, hypotonia or atonia of major muscle groups and depression of monosynaptic and polysynaptic reflexes

: Characterized by rapid eye movements in all directions, phasic swings in blood pressure and heart rate, irregular respiration, spontaneous middle-ear muscle activity and tongue m

I will not go over this too much as the function of sleep largely remains a mystery

sleep needed to restore cerebral function after periods of waking (evidence of increased anabolic hormolevels of catabolic hormones during sleep)

presence of slow wave sleep after sleep deprivation

more recent studies have revealed that new memories can be strengthened by sleep (so remember to get

synthesis of new RNA and proteins by neurons during sleep Maintenance of synaptic and neuronal network integrity

Some interesting associations: sleep deprivation leads to decreased levels of serum leptin and increased levels BMI observed with short sleep duration

Sleep requirements change dramatically from infancy to old age phasic sleep pattern with 16 hours of sleep per day

ents decrease to about 10 hours per day by ages 3 to 5 years : sleep assumes biphasic pattern (nap time!)

phasic sleep pattern (7.5 - 8 hours) : changes back to biphasic pattern (nap time!)

Newborn spends 50% of the time in REM sleep; however, duration of the NREM-REM cycle is shorter in infants and increasing as they get older; by age 6, time in REM is decreased to about 25% but their NREM-REM cycles are increa

both alternate and each cycle last about 90-100 minutes

13 Hz), which are characteristics for wakefulness 7 Hz) and beta waves (> 13 Hz)

18 Hz; most often 14 Hz) and K complexes Also contains theta rhythms and fewer than 20% slow waves (0.5 - 2 Hz)

during NREM)

: REM sleep dreams are highly emotionally charged, complex and bizarre; whereas NREM

oups and depression of monosynaptic

: Characterized by rapid eye movements in all directions, phasic swings in blood pressure and heart ear muscle activity and tongue movements.

sleep needed to restore cerebral function after periods of waking (evidence of increased anabolic hormones and decreased

more recent studies have revealed that new memories can be strengthened by sleep (so remember to get a lot of sleep

Some interesting associations: sleep deprivation leads to decreased levels of serum leptin and increased levels of ghrelin; which can possibly

REM cycle is shorter in infants -- lasting about 45-50 minutes REM cycles are increased

Approach to and Evaluation of Sleep Disorders Approach to and Evaluation of Sleep Disorders Approach to and Evaluation of Sleep Disorders Approach to and Evaluation of Sleep Disorders Sleep History

- Provided by patient; but when possible, should be supplemented by bed partner, family member or roommate - Different Components of the sleep history

o Presenting sleep-related symptoms (onset, duration, frequency, severity, precipitating factors)o Associated nocturnal symptoms (i.e. abnormal breathing, nocturnal behaviors, nocturnal awakenings)o Time of symptoms o Daytime functioning (sleepiness, concentration, mood do Sleep schedule and sleep hygiene o Any use of sleep aids and/or stimulants?

Physical Examination (in addition to the routine things we check, i.e. vitals, weight, BMI) - Neck circumference - Detailed examination of the head/neck

o Facial morphology (looking for nasal symmetry, mandibular retrognathia)o Oral cavity

There are different classifications including the modified Mallampati classification where it's an assessment of the oral airway which was originally developed for tracheal

Tonsils should be classified by the degree of hypertrophy

4 different grades; the higher grades signify enlarged tonsils Subjective Assessment

- Most well-known and widely used is the Epworth Sleepiness Scale (subjective assessment of the patient's daytime sleep propensity) o 4-point Likert scale (0, 1, 2, or 3) to indicate likelihood of dozing in eight distinct sedentary conditions o If total score 10 (out of 24) suggests excessive dao Scale can be used to follow the patient's self

Objective Measures

- Nocturnal Polysomnography (NPSG) o Basic recording montage should include the following

EEG: central, frontal, and occipital Left/right eye electro-oculograms Mental/submental surface EMG EKG leads

o 4 basic types (keep in mind that there are several other portable types and usually attended nocturnal polysomnography is indicated if the portable yields either negative or a technically inadequate result)

Type 1: standard, attended, in Type 2: comprehensive, portable, unattended polysomnography Type 3: modified portable sleep apnea testing Type 4: continuous single or dual bioparameter recording (i.e. pulse oximetry)

- Multiple sleep latency test (MSLT) o Similar to NPSG but in addition, can measure thoracic and abdominal effort, oxygen saturationo Can used to objectively assess excessive daytime sleepiness o Protocol for testing would be the following:

Five 20-minute nap opportunities held at 2 If sleep is observed during

from the start of the nap trial to the first epoch of sleep Mean sleep latency is then calculated as the average sleep latency across all nap trials Presence and number of sleep Values to consider:

Mean sleep latency > 10 minutes

Mean sleep latency between 8

Mean sleep latency < 8 minutes: can be normal in about 30% of theo If comb

Approach to and Evaluation of Sleep Disorders Approach to and Evaluation of Sleep Disorders Approach to and Evaluation of Sleep Disorders Approach to and Evaluation of Sleep Disorders

Provided by patient; but when possible, should be supplemented by bed partner, family member or roommate

related symptoms (onset, duration, frequency, severity, precipitating factors) Associated nocturnal symptoms (i.e. abnormal breathing, nocturnal behaviors, nocturnal awakenings)

Daytime functioning (sleepiness, concentration, mood disturbances)

Any use of sleep aids and/or stimulants? (in addition to the routine things we check, i.e. vitals, weight, BMI)

(looking for nasal symmetry, mandibular retrognathia)

There are different classifications including the modified Mallampati classification where it's an assessment of the oral airway which was originally developed for tracheal intubation. I don't think this is important to know the details of thisTonsils should be classified by the degree of hypertrophy

4 different grades; the higher grades signify enlarged tonsils

Epworth Sleepiness Scale (subjective assessment of the patient's daytime sleep propensity) point Likert scale (0, 1, 2, or 3) to indicate likelihood of dozing in eight distinct sedentary conditions

10 (out of 24) suggests excessive daytime sleepiness. Scale can be used to follow the patient's self-assessment of sleepiness and also an indicator of treatment response

Basic recording montage should include the following EEG: central, frontal, and occipital (full 16 lead EEG is not needed unless nocturnal seizures are suspected)

oculograms Mental/submental surface EMG (leg surface EMG can be used if history suggestive of motor behaviors during sleep)

(keep in mind that there are several other portable types and usually attended nocturnal polysomnography is indicated if the portable yields either negative or a technically inadequate result):

Type 1: standard, attended, in-laboratory Type 2: comprehensive, portable, unattended polysomnography Type 3: modified portable sleep apnea testing Type 4: continuous single or dual bioparameter recording (i.e. pulse oximetry)

on, can measure thoracic and abdominal effort, oxygen saturation Can used to objectively assess excessive daytime sleepiness Protocol for testing would be the following:

minute nap opportunities held at 2-hour intervals If sleep is observed during these opportunities, patient is allowed to sleep and the sleep latency is measured as the time from the start of the nap trial to the first epoch of sleep Mean sleep latency is then calculated as the average sleep latency across all nap trials

nd number of sleep-onset REM periods can be determined (SOREMPs)

Mean sleep latency > 10 minutes: normal

Mean sleep latency between 8-10 minutes: physiologic gray zone

Mean sleep latency < 8 minutes: can be normal in about 30% of the population mbined with 2 or more SOREMPs - would meet part of the diagno

Provided by patient; but when possible, should be supplemented by bed partner, family member or roommate

Associated nocturnal symptoms (i.e. abnormal breathing, nocturnal behaviors, nocturnal awakenings)

There are different classifications including the modified Mallampati classification where it's an assessment of the oral intubation. I don't think this is important to know the details of this

Epworth Sleepiness Scale (subjective assessment of the patient's daytime sleep propensity) point Likert scale (0, 1, 2, or 3) to indicate likelihood of dozing in eight distinct sedentary conditions

assessment of sleepiness and also an indicator of treatment response

(full 16 lead EEG is not needed unless nocturnal seizures are suspected)

(leg surface EMG can be used if history suggestive of motor behaviors during sleep)

(keep in mind that there are several other portable types and usually attended nocturnal polysomnography is indicated if

these opportunities, patient is allowed to sleep and the sleep latency is measured as the time

population nostic criteria for narcolepsy

- Maintenance of Wakefulness (MWT) o Measures patient's ability to remain awake (rather than the tendency to fall asleep like MSLT) o Protocol for testing would be the following:

Four 40 minute trials that begin at 2-hour intervals (the first should start about 1.5-3 hours after the patient wakes up) Each trial is terminated after 40 minutes if no sleep occurs OR after sleep onset (measured by EEG evidence of stage N1)

o Limited amounts of normative data available unfortunately

Sleep DisorSleep DisorSleep DisorSleep Disorddddersersersers We will review the following common sleep disorders:

- Insomnia - Narcolepsy and Idiopathic Hypersomnia - Sleep Apnea syndrome - Sleep-related Movement Disorders - Circadian Rhythm Sleep Disorders - Parasomnias

INSOMNIA - International Classification of Sleep Disorders: Diagnostic and Coding Manual, 2nd Edition: Diagnostic and Coding Manual (ICSD-2)

o Long list of criteria which I will not include here but essentially, it requires night-time and day-time elements Night-time elements: difficulty falling asleep, staying asleep, awakening excessively or sense of sleep that is not refreshing Day-time elements: fatigue, poor concentration, poor motivation, low energy, various physical symptoms, prone to making

mistakes, headaches, poor performance o Acute: few days to weeks; typically associated with a stressful situation o Chronic: persisting at least 1 month

- Women and older adults at greater risk for insomnia - Can be described as either

o Primary insomnia (an independent disorder without concomitant disorders) o Comorbid type of Insomnia

Primary Insomnia

- Examples: psychophysiological, paradoxical, and idiopathic insomnias - Idiopathic insomnia

o Begins during childhood o Generally have lifelong difficulty with initiating or maintaining sleep o Diagnosis depends on exclusion of concomitant comorbid medical, neurological, psychiatric or psychological disturbances o Typically continues into adulthood

- Psychophysiological insomnia o Begins during young adulthood o Typically these patients are over-concerned and over-focused on sleep problems but typically do NOT have generalized anxiety o Insomnia could have been initiated by a stressor but it persisted even after initial stress is gone o Chronic insomnia with tension or agitation that results from learned sleep-preventing associations such as:

Fear and frustration about being unable to initiate and maintain sleep Identification of the bedroom as an arousal sign

- Paradoxical insomnia o This is a sleep state misperception characterized by subjective complaints of sleeplessness without any objective evidence i.e. PSG

recording documents normal sleep patterns Co-morbid type of Insomnia (I will not go into much detail about this as it is pretty extensive and some of them are pretty self-explanatory)

- Examples: inadequate sleep hygiene, insomnia comorbid with psychiatric disorders, with general medical disorders, with neurological disorders, or insomnia due to drug or other substance abuse

Evaluation of Insomnia

- General advice: think very broadly about the etiology and expect multiple factors that can predispose someone to sleep difficulty - Typically, whatever triggered the sleep difficulty is NOT necessarily what is currently contributing to the persistent symptoms - As mentioned before under "Approach and Evaluation to Sleep Disorders," history should also be obtained from sleep partners if possible - Ask about daytime activities and functioning and sleep-wake schedule routines; is it the difficulty primarily sleep onset or sleep maintenance? - Have them keep a sleep log - Sleep laboratory testing (not routinely done) can be useful when suspicion that a concomitant sleep disorder is contributing to symptoms (i.e.

obstructive sleep apnea) Treatment

- For co-morbid type of insomnia, it is obvious that you would address the underlying cause - Educating on healthy sleep habits

- Cognitive-behavioral therapy for insomnia can help address factors that regulate sleepsleep and cognitive distortions that can be contributing to the perpetuation of insomnia

o Can also include relaxation therapy, biofeedback, "stimulus control therapy"

- Pharmacologic approach o As you already know, there are tons of overo Insomnia medications approved by US FDA include:

-amniobutyric acid response modulators

There are several medications that can be used; I will not list all of them here but to name a few:o Non-BZD: Ambien, Zaleplono BZD: Flurazepam, Temazepam

melatonin receptor agonistconcentrated in the hypothalamic suprachiasmatic nuclei and by doing so,

Use for insomnia characterized by histamine H1 receptor antagonist

Low dose doxepin is approved for insomnia characterized by difficulty with sleep maintenance

should NOT be prescribed for patients w/ untreated narrowwho are taking monoamine oxidase inhibitors

No abuse potential with doxepin o Off-labeled Rx: many anti-depressants, anti

these can be effective at times; but there is little evidence to guide treatment plan

To name a few that we use a lot: trazodone, amitriptyline, quetiapine,

behavioral therapy for insomnia can help address factors that regulate sleep-wake cycle, psychological processes that can affect

sleep and cognitive distortions that can be contributing to the perpetuation of insomnia therapy, biofeedback, "stimulus control therapy" - see below as an example

As you already know, there are tons of over-the-counter medications out there. I wanted to focus on the FDA approved medicationsInsomnia medications approved by US FDA include:

amniobutyric acid response modulators

There are several medications that can be used; I will not list all of them here but to name a few:BZD: Ambien, Zaleplon

BZD: Flurazepam, Temazepam receptor agonist (only one that has been approved: Ramelteon - activated melatonin type receptors that are

concentrated in the hypothalamic suprachiasmatic nuclei and by doing so, the SCN-driven wake

Use for insomnia characterized by difficulty with sleep onset; not beneficial for maintaining sleep histamine H1 receptor antagonist

Low dose doxepin is approved for insomnia characterized by difficulty with sleep maintenance

should NOT be prescribed for patients w/ untreated narrow-angle glaucoma or severe urinary retention or those who are taking monoamine oxidase inhibitors

No abuse potential with doxepin depressants, anti-psychotics, and anti-epileptic have been used to treat insomnia;

these can be effective at times; but there is little evidence to guide treatment plan

To name a few that we use a lot: trazodone, amitriptyline, quetiapine,

wake cycle, psychological processes that can affect

as an example

counter medications out there. I wanted to focus on the FDA approved medications

There are several medications that can be used; I will not list all of them here but to name a few:

activated melatonin type receptors that are driven wake-promoting stimulus)

difficulty with sleep onset; not beneficial for maintaining sleep

Low dose doxepin is approved for insomnia characterized by difficulty with sleep maintenance

angle glaucoma or severe urinary retention or those

leptic have been used to treat insomnia;

NARCOLEPSY - Disorder of REM sleep; this is a classic hypersomnia of central origin - Onset in most cases: adolescents and young adults with peak incidence between ages 15 and 30- Pathophysiology:

o association with HLA-DR with narcolepsy and other HLA types most closely linked being: HLA

o Hypocretin-1 has been implicated in human narcolepsy hypocretin is a neurotransmitter that regulates arousal, wakefulness and appetite hypocretin peptides bind to their own specific receptors (i.e. histaminergic tuberomamillary

nucleus, cholinergic pedunculopontine nucleus) patients with narcolepsy tend to have low or undetectable CSF hypocretin levels

- Three types: o Narcolepsy without Cataplexy o Narcolepsy with Cataplexy o Secondary Narcolepsy

- Narcolepsy without Cataplexy (Criteria)

- Narcolepsy with Cataplexy (Criteria)

- Major clinical manifestations: o Narcoleptic sleep attacks / excessive daytime sleepiness

heralding feature of narcolepsy Irresistible urge to sleep w/o warning Naps are often refreshing and often recommended as part of the treatment plan

o Disturbed night sleep (70-80%) usually not considered as part of the classic tetrad; it is an essential symptom of narcolepsy many experience sleep fragmentation due to multiple arousals, early morning awakenings, nocturnal eating and un

refreshing nocturnal sleep o Cataplexy (60-70%)

defined as a the sudden, involuntary loss or decrease of muscle tone Most commonly precipitated These can either be profound with generalized atonia resulting in falls and injuries OR localized loss of muscle tone that ca

be misdiagnosed or not considered

Subtle weakness incluo slurring of speech

o Sleep paralysis (25%-50%) Characterized by inability to move while being totally aware of one's surroundings occur either at arousal or at sleep onset; rarely lass more than a few minutes this is NOT pathognomonic of narcolepsy (can occur in those who are sleep deprived)

persomnia of central origin Onset in most cases: adolescents and young adults with peak incidence between ages 15 and 30

DR with narcolepsy and other HLA types most closely linked being: HLA-DQB1*0602 1 has been implicated in human narcolepsy

hypocretin is a neurotransmitter that regulates arousal, wakefulness and appetite hypocretin peptides bind to their own specific receptors (i.e. histaminergic tuberomamillary nucleus, cholinergic pedunculopontine nucleus) patients with narcolepsy tend to have low or undetectable CSF hypocretin levels

Narcoleptic sleep attacks / excessive daytime sleepiness (100%) heralding feature of narcolepsy Irresistible urge to sleep w/o warning

are often refreshing and often recommended as part of the treatment plan

usually not considered as part of the classic tetrad; it is an essential symptom of narcolepsy many experience sleep fragmentation due to multiple arousals, early morning awakenings, nocturnal eating and unrefreshing nocturnal sleep

defined as a the sudden, involuntary loss or decrease of muscle tone Most commonly precipitated by laughter or other intense positive emotions These can either be profound with generalized atonia resulting in falls and injuries OR localized loss of muscle tone that cabe misdiagnosed or not considered

Subtle weakness includes: slurring of speech | buckling of knees | jaw dropping | nodding of head

Characterized by inability to move while being totally aware of one's surroundings occur either at arousal or at sleep onset; rarely lass more than a few minutes

pathognomonic of narcolepsy (can occur in those who are sleep deprived)

hypocretin peptides bind to their own specific receptors (i.e. histaminergic tuberomamillary nucleus, ventrolateral preoptic

usually not considered as part of the classic tetrad; it is an essential symptom of narcolepsy many experience sleep fragmentation due to multiple arousals, early morning awakenings, nocturnal eating and un-

These can either be profound with generalized atonia resulting in falls and injuries OR localized loss of muscle tone that can

nodding of head

o Hallucinations (20-40%) - Simple or complex visual hallucinations (auditory and tactile hallucinations can occur) Can be either hypnagogic (transition from wakefulness to sleep) or hypnopompic (sleep to wakefulness) Typically hypnagogic hallucination is commonly associated with narcolepsy this is NOT pathognomonic of narcolepsy

o Automatic behavior (20-40%) described as act of pursuing purposeful behavior with no reminiscence of it Patients either seem awake and alert or appear inattentive during the episode Intrusion of microsleep into wakefulness is believed to be the cause of this symptom Sleep deprivation can precipitate these symptoms this is NOT pathognomonic of narcolepsy

- Can be associated with: o Periodic limb movements of sleep

characterized as cluster of limb movements occurring during sleep that resemble a triple flexion response more prevalent as patient gets older tend to occur during REM sleep

- Evaluation: o Can use the epworth sleepiness scale to assess subjective daytime sleepiness o On polysomnogram, you would find:

decrease in total sleep time a short sleep-onset latency sleep fragmentation REM without atonia REM sleep occurring within 15 minutes of sleep onset

o Genetic testing to look for serum HLA-DQB1*0602 is available; typically do this for patients with narcolepsy with cataplexy o Hypocretin level in CSF can be measured as well

- Treatment: o For the excessive daytime sleepiness:

Typically can use stimulants (i.e. d-amphetamines) or wake-promoting agents (i.e. modafinil) encourage scheduled naps throughout the day

o For cataplexy At the moment, nothing is FDA approved Can try the following:

Tricyclic: imipramine

SSRI: fluoxetine

SNRI: Venlafaxine IDIOPATHIC HYPERSOMNIA (I won't spend too much time on this; but wanted to make you aware of it)

- Unknown etiology - Characterized by:

o Non-refreshing sleep with difficulty waking up (either in the morning or from a nap) o Feel sleepy during the day o Typically show a depressed mood o Normal total sleep time o Absence of sleep-disordered breathing o Normal sleep architecture

- Diagnosis of exclusion - Poorly understood so the precise prevalence of this disorder remains unknown - Treatment

o Behavioral interventions o Pharmacologic approach is similar to narcolepsy

Recurrent Hypersomnia (under the umbrella term of hypersomnia)

- Klein-Levin Syndrome o Triad of: hyperphagia, hypersomnia, hypersexuality o Clinical diagnosis; work-up is mainly to rule out other causes of hypersomnia o Prevalence: 1 in 1 million so very rare o Typically occur during second decade of life; but can really occur at any point o Clinical presentation:

usually preceded by a precipitating factor; most common complaint is an infection or high fever Patients report periods of excessive sleepiness that range from 2 days to 4 weeks with recurrence of these symptoms at

least 1x per year Typically have normal cognitive function Men tend to have more symptoms of hypersexuality than women

o Work-up for these patients are typically normal including polysomnogram, imaging, etc)o Treatment:

Valproic acid, lithium, amantadine or lamotrigine have been tried and showed good responses in a few patients Modafinil has been tried -

SLEEP APNEA SYNDROME

- Broadly divided into two types: o Upper airway obstructive sleep apnea syndrome o Central sleep apnea syndrome

Obstructive Sleep Apnea Syndrome (I will only highlight the

- Obesity is associated with 70% of the cases; so that also means 30% of the cases it's not so it's important to not miss these- Upper airway anatomical abnormalities that can cause reduction of the upper airway space

o Low-hanging soft palate o Large edematous uvula o Large tonsils and adenoids (typically seen in children)

- Consequences of untreated OSA: o Increased morbidity and mortality due to both short term consequences (falling asleep behind the wheel) and long term consequo Associated with systemic HTN o Pulmonary hypertension (can occur 15o Cardiac arrhythmias o Heart failure (mostly systolic heart failure) o Stroke, TIA o Cognitive dysfunction o Depression o Insomnia

- Treatment: positive airway pressure (CPAP or BiPAP), surgery (i.e. adenoidectomy, tonsillectomy, etc) o Can typically use the AHI score to determine the effectiveness of the treatment

AHI: apnea-hypopnea index score; measures the number of apnea and hypopn

Hypopneas: defined as a reduction in the airflow sensor signal by 30% or more of the baseline amplitude for at least 10 seconds accompanied by oxygen desaturation of 4% or more from the pre

Typically AHI > 10 is considered significant

Central Sleep Apnea - Defined as at least a 10-second period of loss of airflow with the absence of respiratory effort indicative of brief loss of ventilatory drive- Normal physiology:

o During sleep: respiration is primarily driven by partial pressure of arterial COo Normally, there is a level of PaCO2 below which a pause in breathing will occur (this is called the apneic threshold)o Apneic threshold is higher during wake than sleep; so can be normal to have brief central ap

- Cheyne-Stokes breathing is noted in patients with congestive heart failure o Characterized by cyclical changes in breathing with a crescendoo In heart failure, CSA can develop because of chronic hypocapnia related to changes in the hemodynamics in the left heart

result of these changes, peripheral and central chemosensitivity are augmented This hypersensitivity of the receptors can l

(PaO2) and rise in PaCO2PaCO2 below the apneic threshold

up for these patients are typically normal including polysomnogram, imaging, etc)

Valproic acid, lithium, amantadine or lamotrigine have been tried and showed good responses in a few patients shown to decrease the duration of the episodes but no effect on the recurrence rate

Upper airway obstructive sleep apnea syndrome

(I will only highlight the importance features) Obesity is associated with 70% of the cases; so that also means 30% of the cases it's not so it's important to not miss theseUpper airway anatomical abnormalities that can cause reduction of the upper airway space

Large tonsils and adenoids (typically seen in children)

Increased morbidity and mortality due to both short term consequences (falling asleep behind the wheel) and long term consequ

Pulmonary hypertension (can occur 15-20% of the cases)

Heart failure (mostly systolic heart failure) -- tend to occur more in central sleep apneas

Treatment: positive airway pressure (CPAP or BiPAP), surgery (i.e. adenoidectomy, tonsillectomy, etc) Can typically use the AHI score to determine the effectiveness of the treatment

hypopnea index score; measures the number of apnea and hypopnea episodes occur per hour of sleep

Hypopneas: defined as a reduction in the airflow sensor signal by 30% or more of the baseline amplitude for at least 10 seconds accompanied by oxygen desaturation of 4% or more from the pre

I > 10 is considered significant

second period of loss of airflow with the absence of respiratory effort indicative of brief loss of ventilatory drive

y driven by partial pressure of arterial CO2 Normally, there is a level of PaCO2 below which a pause in breathing will occur (this is called the apneic threshold)Apneic threshold is higher during wake than sleep; so can be normal to have brief central apnea during transition to sleepStokes breathing is noted in patients with congestive heart failure Characterized by cyclical changes in breathing with a crescendo-decrescendo sequence separated by apneas or hypopneas In heart failure, CSA can develop because of chronic hypocapnia related to changes in the hemodynamics in the left heart result of these changes, peripheral and central chemosensitivity are augmented

This hypersensitivity of the receptors can lead to an exaggerated response to the fall in partial pressure of arterial oxygen

2 seen during a single apnea --> leading to hyperventilation --> which will again decrease the below the apneic threshold --> leading to hypoventilation

Valproic acid, lithium, amantadine or lamotrigine have been tried and showed good responses in a few patients duration of the episodes but no effect on the recurrence rate

Obesity is associated with 70% of the cases; so that also means 30% of the cases it's not so it's important to not miss these cases

Increased morbidity and mortality due to both short term consequences (falling asleep behind the wheel) and long term consequences

ea episodes occur per hour of sleep

Hypopneas: defined as a reduction in the airflow sensor signal by 30% or more of the baseline amplitude for at least 10 seconds accompanied by oxygen desaturation of 4% or more from the pre-event baseline

second period of loss of airflow with the absence of respiratory effort indicative of brief loss of ventilatory drive

Normally, there is a level of PaCO2 below which a pause in breathing will occur (this is called the apneic threshold) nea during transition to sleep

decrescendo sequence separated by apneas or hypopneas In heart failure, CSA can develop because of chronic hypocapnia related to changes in the hemodynamics in the left heart -- an as a

ead to an exaggerated response to the fall in partial pressure of arterial oxygen > which will again decrease the

SLEEP-RELATED MOVEMENT DISORDERS Restless Leg Syndrome

- MC movement disorder but uncommonly recognized and treated- No single diagnostic test for RLS - Lifelong sensory-motor neurological disorder that begins at a very young age but doesn't get diag

o the sensory manifestations are described as: creeping, crawling, tingling, burning, aching, cramping, knifelike, or itching s- In order to make the diagnosis; you need all four essential diagnostic criteria (see

- Most of movements (early stages) are noted to in the evening while the patient is resting in bed o in severe cases, can occur during the day (at least 80% of RLS patients have periodic

- Pathophysiology o likely related to abnormalities in the body's use and storage of iron and dopamine dysfunction o Iron is an important cofactor for tyrosine hydroxylase (rate

there may be a decrease number of dopamine D2 receptor binding sites o So remember to check your ferritin in suspected RLS

- Investigation/Management of RLS o Check iron panel; particularly ferritin as it is the most sensitive measure of iron stores

remember, ferritin is also an acute phase reactant so it may be falsely elevated in acute infections

in these cases, also check the total irono Polysomnography is not routinely indicated o Treatment

If ferritin is low, iron therapy can Dopaminergic agents (i.e. pramipexole, ropinirole)

Maximum dose for RLSo Pramipexole 0.75 mg (should start out with 0.125 mg and titrate up slowly)o Ropinirole 4 mg (should start out at 0.5 mg and titrate up)

Important: long term use of these agents can lead to syndrome earlier in the day)

o Augmentation: augmentation; in order to treat this is to discontinue the medication

o Excessive daytime sleepinesso Impulse control disorder:

to 17%) Benzodiazepines (clonazepam, zolpidem) Opioids - good for severely refractory cases; though these are addictive and exacerbate sleep apnea

Periodic Limb Movement of Sleep Disorder

- Characterized by periodically recurring stereotyped limb movements , particularly dorsiflexion of the ankles and sometimes flexion of theand hips at the average interval of 20 to 40 seconds

o For adults: has to occur more than 15 per houro For children: occur more than 5 per hour

- Appear most commonly in RLS - On PSG: findings of PLMS without associated

MC movement disorder but uncommonly recognized and treated

motor neurological disorder that begins at a very young age but doesn't get diagnosed until middle or later years the sensory manifestations are described as: creeping, crawling, tingling, burning, aching, cramping, knifelike, or itching s

In order to make the diagnosis; you need all four essential diagnostic criteria (see below)

Most of movements (early stages) are noted to in the evening while the patient is resting in bed

in severe cases, can occur during the day (at least 80% of RLS patients have periodic-limb movement syndrome as well)

likely related to abnormalities in the body's use and storage of iron and dopamine dysfunction Iron is an important cofactor for tyrosine hydroxylase (rate-limiting enzyme in dopamine synthesis); therefore, in an iron deficiency,

umber of dopamine D2 receptor binding sites So remember to check your ferritin in suspected RLS

Check iron panel; particularly ferritin as it is the most sensitive measure of iron stores is also an acute phase reactant so it may be falsely elevated in acute infections

in these cases, also check the total iron-binding capacity and percent saturation Polysomnography is not routinely indicated

If ferritin is low, iron therapy can be considered (add vitamin C to each dose to enhance absorption) Dopaminergic agents (i.e. pramipexole, ropinirole) - approved by FDA for treatment of RLS

Maximum dose for RLS Pramipexole 0.75 mg (should start out with 0.125 mg and titrate up slowly)

pinirole 4 mg (should start out at 0.5 mg and titrate up)

Important: long term use of these agents can lead to augmentation (worsening of the restless leg syndrome earlier in the day), impulse control disorder and daytime sleepiness

Augmentation: in one study, at least 42% of patients treated with pramipexole developed augmentation; in order to treat this is to discontinue the medication Excessive daytime sleepiness: can develop in about 50% of patients Impulse control disorder: typically includes pathologic gambling and compulsive shopping (occur in 6 to 17%)

Benzodiazepines (clonazepam, zolpidem) good for severely refractory cases; though these are addictive and exacerbate sleep apnea

d by periodically recurring stereotyped limb movements , particularly dorsiflexion of the ankles and sometimes flexion of theand hips at the average interval of 20 to 40 seconds

For adults: has to occur more than 15 per hour For children: occur more than 5 per hour

ed RLS causing repeated awakenings and sleep fragmentations

nosed until middle or later years the sensory manifestations are described as: creeping, crawling, tingling, burning, aching, cramping, knifelike, or itching sensations

limb movement syndrome as well)

limiting enzyme in dopamine synthesis); therefore, in an iron deficiency,

is also an acute phase reactant so it may be falsely elevated in acute infections

binding capacity and percent saturation

be considered (add vitamin C to each dose to enhance absorption) approved by FDA for treatment of RLS

Pramipexole 0.75 mg (should start out with 0.125 mg and titrate up slowly)

augmentation (worsening of the restless leg , impulse control disorder and daytime sleepiness

study, at least 42% of patients treated with pramipexole developed

: can develop in about 50% of patients ologic gambling and compulsive shopping (occur in 6

good for severely refractory cases; though these are addictive and exacerbate sleep apnea

d by periodically recurring stereotyped limb movements , particularly dorsiflexion of the ankles and sometimes flexion of the knees

- Significance of this diagnosis has been debated o typically occur in 80 to 88% of patients with RLS; however, there are still up to 20% of the cases where it is not associated with RLS o No definite relationship has been detected between the presence of PLMS and symptoms of insomnia or hypersomnia o Other studies have shown no association between PLMS and PSG measures i.e. total sleep time, wake time after sleep onset,

arousal index and sleep deficiency

- Treatment o Levodopa eliminates the movements; but arousals may still persist during sleep o Optimal treatment for PLMD is uncertain; at this time dopaminergic agonists may be the drug of choice but there has been no

controlled trials of any agents for pure PLMD CIRCADIAN RHYTHM SLEEP DISORDERS

- Result from mismatch between body's internal clock and geophysical environment either from malfunction of biological clock or a shift in environment causing this to be out phase

- Some of the more obvious ones: i.e. jet lag or shift-work sleep disorders (this one we know all too well) - I won't talk about this - instead I'll focus more of the disorders where the biological clock is malfunctioning

Delayed Sleep-Phase Disorder

- Characterized by chronic or recurrent inability to fall asleep and wake up at socially acceptable times o by definition: there is more than 2 hour delay in the major sleep period o typically when these patients are allowed to sleep at their biologically preferred time, they function well o Typically sleep between 1 AM - 6 AM and wake up late morning or early afternoon

- Prevalence: 0.2 to 10% severe cases; milder cases are more prevalent, typically among adolescents and young adults - Pathogenesis: several mechanisms have been postulated

o Decreased response to the phase-advancing effect of light in the morning o Increased sensitivity to the phase delay response of the evening light o Longer than normal time to complete one circadian cycle

- Diagnosis: o careful history and sleep diary for at least 7 days o more of a clinical diagnosis

- Treatment: o Recommend appropriately timed morning light exposure and evening exogenous melatonin either alone or in combination

Bright light in the morning for 2 hours help advance the circadian rhythms in these patients Melatonin given 5 to 6.5 hours before sleep can help advance sleep and rise times Effectiveness can lasts up to 1 year with daily melatonin intake but relapses can occur in up to 90% if they stop

Advanced Sleep-Phase Disorder

- Characterized by an advance in phase of the major sleep episode in relation to the desired or required sleep and wake-up times o Typically these patients are sleepy and struggle to stay awake between 6 PM and 9 PM and wake-up earlier than desired between 2

AM and 5 AM - Prevalence: less common than DSPD (about 1%); occur during middle age - Pathogenesis:

o shortened circadian period has been postulated o 2 gene mutations have been identified: gene hPer2 and the casein kinase I delta gene -- these mutations result in a shortened

circadian period - Diagnosis:

o Again, based on clinical history and a sleep diary - Treatment:

o Timed light exposure in the evening and avoiding light in early morning hours o Melatonin may be beneficial for sleep maintenance o Bright light administered before the nadir of body core temperature is potent stimulus for delaying circadian phase

Early-evening light therapy between 7 PM and 9 PM This has been shown to improve sleep duration and sleep maintenance

Irregular Sleep-Wake Rhythm Disorder

- Characterized by temporally disorganized sleep and wake pattern such that multiple sleep and wake periods occur throughout the 24 hr period - Prevalence: MC among institutionalized older adults particularly those with Alzheimer disease; been described in patients with head trauma,

children with developmental delay, and patients with schizophrenia - Pathogenesis:

o Most likely include central degeneration of SCN neurons and decreased exposure or input of external synchronizing agents such as light and activity that result in a weakened central circadian oscillation and temporal disorganization of circadian rhythm

o This problem is perpetuated by a variety of factors inherent in the lifestyle of older adults in nursing homes, etc. - Clinical presentation:

o sleep bouts occur in 3+ short intervals of approximately 1 to 4 hours each spread over 24 hours o typically the overall amount of sleep per 24-hour period is relatively normal for the patient's age

- Diagnosis o Clinical history and history of a minimum of 3 irregular sleep-wake cycles in a 24 hour period for 14 days evident by sleep diary

- Treatment:

o Creating a cognitively enriched environment with structured social and physical activity during the day is probably the best treatment modality to help these patients

i.e. minimizing noise and light during the scheduled sleep period and addressing issues such as nocturia and enuresis to reduce sleep disturbances

exposure to bright lights for 2 hours every morning to improve daytime alertness, decrease napping and consolidate nighttime sleep and reduce nocturnal agitation

PARASOMNIAS - defined as abnormal movements or behaviors that occur in sleep or during arousals from sleep - Can be broken down into 3 broad categories

o Disorders of arousal (from NREM sleep) confusional arousals, sleepwalking (somnambulism), sleep terrors

o Parasomnias associated with REM sleep sleep paralysis, RBD (REM sleep behavior disorder)

o Other parasomnias including sleep-related dissociative disorders, sleep enuresis, sleep-related groaning Disorders of Arousal from Non-REM Sleep

- these parasomnias typically arise from slow-wave sleep in the 1st half of the nocturnal sleep - Confusional arousals:

o episodes of mental confusion or confusional behavior during an arousal or awakening from nocturnal sleep or daytime nap o responsiveness to environmental stimuli is reduced o speech is generally slow and devoid of content o affected individuals typically appear bewildered and have little to no memory of the event

- Sleepwalking o characterized by sequence of complex behaviors in sleep, including ambulation that is more elaborate and seemingly goal-directed o ambulation is typically slow and quiet with eyes open o Occur more often in children than adults; peak between ages 8 and 12

- Sleep terrors o sudden arousal and sitting up in bed associated with a cry or vocalization and intense autonomic system activation o affected individuals appear frightened and confused and are inconsolable; no recollection of the events the following AM

Parasomnias associated with REM sleep

- REM sleep behavior disorder o REM sleep parasomnia that presents with complex nocturnal behaviors o Presenting complaint: recurrent dream-enacting behaviors including vocalization and motor activity in relation to altered dream

mentation o sleep-related injuries to affected person or bed partner occur about 1/3 of the cases o different from those that occur during non-REM sleep is that the patients typically wake-up abruptly at the end of an episode and are

alert and able to recount a coherent dream of being confronted, chased or attacked o important to know that this is the ONLY parasomnia that REQUIRES polysomnographic confirmation

PSG: shows that patient is in REM sleep without atonia in the chin or limb EMG o Occur later in life (typically after age 50) o More common in men than women (9x) o Pathophysiology: requires bilateral pontine tegmental lesions resulting in loss of REM atonia and disinhibition of locomotor pathways;

thereby facilitating dream enactment o several drugs/medications have been shown to exacerbate or cause RBD

anti-depressants i.e. SSRI, SNRI (venlafaxine) and trcyclics o Treatment:

modifying sleep environment to protect the patient and bed partner Clonazepam is remarkably effective in treating RBD

Sleep-Related Dissociative Disorders

- emerge at the transition from wake to sleep or shortly following awakening - most patients have psychiatric co-morbidities including mood disorders, PTSD, history sexual abuse - Episodes are non-stereotyped and feature screaming, running and even self-mutilating, violent behaviors that may represent re-enactment of

prior traumatic events - psychogenic non-epileptic seizures occurring in relation to sleep may be considered a form of sleep-related dissociative disorder

o difficult to differentiate from frontal lobe seizures o Characterized by waxing and waning patterns and long durations o Motor manifestations include: asynchronous movements, side-to-side head movements, pelvic thrusting, opisthotonic posturing and

prolonged body flaccidity and preserved awareness during bilateral motor activity