Updates in Adult Sleep Medicine 44 th Annual Advances in Internal - - PowerPoint PPT Presentation

6/24/2016 1

Updates in Adult Sleep Medicine

44th Annual Advances in Internal Medicine Bernie Y. Sunwoo, MBBS

Assistant Professor of Clinical Medicine Division of Pulmonary, Allergy, Critical Care and Sleep Medicine

Faculty Disclosures

No relevant commercial interests

Outline

• Insomnia
• Circadian rhythm sleep-wake disorders
• Sleep disordered breathing
• Obstructive sleep apnea
• Obesity hypoventilation disorder
• Central sleep apnea
• Sleep related movement disorders
• Parasomnias
• Hypersomnolence of central origin

Insomnia

AASM ICSD-3 definition: 1) Persistent sleep difficulty

• Sleep initiation
• Sleep maintenance
• Waking earlier than desired

2) Adequate opportunity and circumstances for sleep 3) Associated daytime impairment

• Fatigue or malaise; Impaired attention, concentration or memory; Impaired

social, family, occupational or academic performance; Mood disturbance or irritability; Daytime sleepiness; Behavioral problems; Reduced motivation, energy, initiative; Proneness for errors, accidents; Concerns about or dissatisfaction with sleep

• AASM. International Classification of Sleep Disorders 3rd Edition 2014.

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Insomnia simplified

• A comorbid disease – sleep, medical, psychiatric disorders,

medications and substance use ICSD 2nd Edition ICSD 3rd Edition

• Primary
• Psychophysiological
• Idiopathic
• Inadequate sleep hygiene
• Paradoxical
• Secondary
• Short-term insomnia disorder
• <3 months
• Chronic insomnia disorder ->3

times per week, >3 months

• Other insomnia disorder
• AASM. International Classification of Sleep Disorders 3rd Edition 2014.

The Scope of Chronic Insomnia

• Prevalence varies with the definitions use but you WILL see it –
• 10%
• Symptoms approximately 35%
• Risk factors
• Female sex
• ? Increasing age
• Genetic
• Lower socioeconomic status
• Medical illness
• Psychiatric disorders
• Substance abuse
• Stress
• Shift work
• Personality

Ohayon MM et al. Sleep Med 2009; 10(9): 952-60 Ohayon MM. Sleep Med Rev 2002; 6:97-111 Buysse et al. Primary Psychiatry 2005; 12(8):50-57

Sleep & Psychiatric disorders

Sleep Psychiatric disorders

• Almost 1/3-1/2 of individuals with complaints of insomnia or

hypersomnia have a psychiatric disorder

• ~80% of patients with a depressive episodes describe insomnia
• Sleep complaints are part of the diagnostic criteria of many psychiatric

disorders

Chronic insomnia evaluation

A clinical diagnosis

• Detailed history –
• Sleep – primary complaint, onset, time course, pre-sleep conditions,

sleep-wake schedule, nocturnal symptoms, daytime function, daytime activities

• Medical
• Psychiatric
• Medications, substance use
• A sleep study is not indicated unless concerns for other sleep disorders

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Management

• Treatment is directed at both the insomnia and the comorbidities
• Cognitive and behavioral therapy for insomnia (CBT-I)
• Effective - as effective or better than pharmacotherapy

ACP recommendation: First line therapy for insomnia

• Major barrier is availability and access, “eCBT-I”. Eg. SHUTi (www.shuti.me)
• Pharmacologic treatments
• Combination therapy
• CBT-I and pharmacotherapy, followed by CBT-I alone, shown to produce

better long-term outcomes than either alone

• Can facilitate withdrawal of hypnotic agents

Qaseem A et al. Ann Intern Med 2016; 165 Wilt TJ et al. Ann Intern Med 2016 Schutte-Rodin S et al. J Clin Sleep Med 2008; 4(5):487-504 Morin CM et al. Sleep 2007; 30:1547-1554 Morin CM et al. JAMA 2009; 301:2005

What is CBT-I?

Typically 6-8 individual sessions

• Cognitive therapy –

Changing beliefs and attitude about insomnia

Standard

• Behavioral therapy
• Stimulus control therapy
• Sleep restriction therapy
• Relaxation therapy
• Biofeedback
• Paradoxical intention
• Sleep hygiene education

Standard Standard Guideline Guideline Guideline No recommendation

Good sleep hygiene

No evidence that sleep hygiene education alone is effective for insomnia

Use of bed only for sleep Maintain regular waking times Limited caffeine consumption until noon Quiet, dark and cool environment in the bedroom Avoidance of stimulating activity near bedtime No exercise within 2 hours of bedtime Face of alarm clock should not be visible from bed Avoidance of napping if sleep maintenance is a problem

Question 1

A 60 year old male, with a history of alcohol dependence and benign prostate hypertrophy complains of chronic insomnia. A sleep study did not reveal sleep disordered breathing. Cognitive behavioral therapy for insomnia is suggested. Which is the most appropriate medication for treatment of his insomnia?

• A. Doxepin 25 mg
• B. Zolpidem 5 mg
• C. Diphenhydramine 25 mg
• D. Trazodone 50 mg

17% 54% 13% 17%

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Pharmacologic treatments

• ACP recommendation: Use a shared decision-making approach,

including a discussion of the benefits, harms and costs of short-term use of medications, to decide whether to add pharmacological therapy in adults with chronic insomnia disorder in whom CBT-I alone is unsuccessful

• Little data comparing the effectiveness of different medications
• Little long term efficacy data
• Medications should ideally be used for no longer than 4-5 weeks

Wilt TJ et al. Ann Intern Med 2016

Which drug ?

• Agents
• Benzodiazepine-receptor agonists
• Antidepressants
• Orexin antagonists
• Melatonin agonists
• Others
• Choice depends on:
• Nature of insomnia & duration of medication action
• Co-morbidities
• Drug interactions
• Prior treatment failure and side effects
• Cost

Benzodiazepine receptor agonists

• Shown to decrease sleep latency (10 mins) and depending on duration of action,

potentially increase total sleep time and decrease WASO

• Side effects – sedation, anterograde amnesia, tolerance, dependence, rebound

insomnia, fall risk, sleep behaviors, respiratory depression, dementia (HR 2.34)

Benzodiazepine Nonbenzodiazepine BZRA

• Decrease stage N3 sleep
• Less anxiolytic, myorelaxant and anticonvulsant activity
• Less rebound, respiratory depression or evidence of tolerance
• Triazolam (Halcion) [S]
• Estazolam (Prosom) [S]
• Temazepam (Restoril) [I]
• Alprazolam (Xanax) [L]
• Lorazepam (Ativan) [L]
• Flurazepam (Dalmane) [L]
• Zaleplon (Sonata) [S]
• Zolpidem IR (Ambien, Intermezzo, Zolpimist, Edular) [S-I]
• Zolpidem CR [I]
• Eszopiclone (Lunesta) [I]

Sedating antidepressants & antipsychotics

• Relatively little evidence on effectiveness in patients without

depression

• Lower doses than doses used for antidepressant effects
• Commonly used agents
• Trazodone (25-100 mg)
• Very modest efficacy in patients with depression
• Side effects – postural hypotension, priapism
• Mirtazapine (7.5-15 mg)
• Side effects – weight gain
• Quetiapine (12.5-50 mg)
• Side effects – QT prolongation, weight gain, extrapyramidal side effects, headaches, lens changes, leukopenia
• Doxepin (1-6 mg)
• Shown to decrease wake after sleep onset time
• Only FDA approved antidepressant for the treatment of insomnia
• Side effects - anticholinergic
• Amitriptyline (10-25 mg)
• Side effects - anticholinergic

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Melatonin and MT receptor agonist

• Melatonin
• Hormone produced by the pineal gland during the dark cycle that can decrease the

suprachiasmatic nucleus (SCN) alerting signal

• ACP insufficient evidence on global and sleep outcomes
• Ferracioli-Oda E et al. 2013 meta-analysis suggesting small effect on sleep latency, TST and

sleep quality

• Can cause a phase shift of circadian rhythms
• Ramelteon
• MT1/MT2 receptor agonist and x17 times more potent then melatonin
• Short acting and few studies suggesting small reduction in sleep latency. Approved in the

US for sleep onset insomnia

• Lacks abuse potential
• Side effects – headache, nausea, dizziness, somnolence, nightmares, hallucinations, rarely

suicidal ideation, contraindicated in patients taking fluvoxamine

Ferracioli-Oda E et al. PLoS ONE 8(5) Kuriyama A et al. Sleep Med 2014; 15:385 Wilt JJ et al. Ann Intern Med 2016 Wade AG et al. Curr Med Res Opin. 2011; 27:87-98

Orexin antagonists

• Orexin A and B are neuropeptides that play a key role in regulating

the sleep-wake cycle & promoting wakefulness

• Suvorexant (Belsomra ) is a dual orexin receptor antagonist
• Subjective improvements in sleep latency and total sleep time
• FDA approved in 2014 as a scheduled C-IV controlled substance,

maximum dose 20 mg

• Side effects – somnolence, headache, amnesia, abnormal dreams,

emergence of narcolepsy symptoms, dry mouth, sleep walking, RBD, suicidal ideation, CYP 3A4 metabolism, rebound insomnia, worsening depression

Kishi T et al. PLosOne 2015; 10(8) Michelson D et al. Lancet Neurol 2014; 13:461 Wilt T J. Ann Intern Med 2016

Over the counter medications

• Most are diphenhydramine, a sedating antihistamine
• Limited evidence exists for efficacy
• Side effects

Question 2

A 23 year old male complains of difficulty falling asleep and inability to wake up for his classes in the morning. On weekdays he is unable to fall asleep until 2 AM. He wakes at 6 AM using an alarm and is drinking up to 6 cups of coffee in the mornings to try and stay awake. On weekends he wakes at 11 AM and feels refreshed. He denies snoring. What is the most likely cause for his insomnia ?

• A. Obstructive sleep apnea
• B. Restless legs syndrome
• C. Poor sleep hygiene
• D. Delayed sleep wake phase disorder

0% 54% 46% 0%

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Circadian rhythm disorders

• Disruption or misalignment between the internal circadian rhythm

and the sleep-wake schedule required by the external environment or work schedule

• Delayed sleep-wake phase disorder (DSWPD)
• Advanced sleep-wake phase disorder (ASWPD)
• Non-24-hr sleep wake rhythm disorder
• Irregular sleep-wake rhythm disorder
• Shift-work disorder
• Jet leg disorder
• Sleep log & actigraphy aid diagnosis
• Management includes:
• Timed light and melatonin therapy
• Chronotherapy

Sack RL. N Engl J Med 2010; 362:440-447

Sleep disordered breathing

Obstructive Sleep Apnea

• Disorder of repetitive complete (apnea) or partial (hypopnea) upper

airway obstruction during sleep

• Diagnosis requires a sleep study
• Definition -
• >5 obstructive respiratory events per hour of sleep during a polysomnography

(PSG) or per hour of monitoring during an out-of-center sleep test (OCST) AND

• Symptoms or
• Comorbidities - hypertension, mood disorder, cognitive dysfunction, coronary artery

disease, stroke, CHF, atrial fibrillation or type 2 diabetes mellitus

• >15 obstructive respiratory events per hour on PSG or OCS

OSA in USA

• Prevalence – varies with the definitions used
• Wisconsin cohort study (1993)

AHI >5 – 24% males, 9% females + daytime sleepiness – 4% males, 2% females

• Under-diagnosed
• Risk factors –
• Age, plateaus in the elderly
• Males > females
• Obesity
• Upper airway and craniofacial anatomy
• Genetic factors, family history
• Specific genetic disorders
• Endocrine disorders
• Alcohol, sedatives

Young T et al. NEJM 1993; 328:1230-1235 Peppard PE et al. Am J Epidemiol 2013; 177(9):1006-1014

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The consequences of OSA

• Excessive daytime sleepiness
• Motor vehicle accidents – x2-3 times increased overall risk
• Hypertension – strong evidence
• Modest improvement with CPAP, 2-3 mmHg
• Other cardiovascular outcomes – associations –
• Cerebrovascular accidents
• Cardiac arrhythmias, relapse into atrial fibrillation
• Congestive heart failure
• Coronary artery disease
• Cardiovascular mortality
• Pulmonary hypertension
• Association with insulin resistance and type 2 diabetes mellitus
• Increased perioperative complications described
• Associations described – all cause mortality, GERD, NASH, cancer risk …

Diagnosis

“ No clinical model is recommended to predict the severity of OSA

therefore objective testing is required.” Diagnosis requires a sleep study A problem of access

Epstein LJ et al. J Clin Sleep Med 2009; 5:263-272

Question 3

Which of the following patients is appropriate for out-of-center sleep testing (OCST):

• A. A 50 year old male, BMI 35.2 kg/m2, who complains of

fatigue and loud snoring.

• B. A 25 year old male, BMI 22.1 kg/m2, who complains of

excessive daytime sleepiness and sleep paralysis.

• C. A 40 year old female, BMI 22.6 kg/m2, modified

mallampati grade 2, who complains of insomnia and light snoring.

• D. A 60 year old male, BMI 27.8 kg/m2, with chronic
• bstructive pulmonary disease, FEV1 50% predicted,

who complains of morning headaches and loud snoring.

76% 8% 8% 8%

Types of Sleep Studies

PSG Type 1: Attended Type 2: Unattended Type 3 Type 4 EEG X EOG X Chin EMG X ECG X Nasal Pressure X X X Snoring X X Respiratory Belts X X Pulse oximetry X X X Body position X X Leg movements X

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(Limited channel sleep testing (LCST), home sleep testing (HST), Portable monitoring (PM) Type 3 monitors Type 4 monitors

OCST commonly underestimate the number of obstructive respiratory events per hour as compared to PSG [Respiratory event index (REI) by the AASM or Respiratory disturbance index (RDI) by CMS but the RDI is also used by the AASM to denote the number of apneas, hypopneas, and RERAs per hour of sleep

Current AASM Guidelines for PM

• PM may be used as an alternative to PSG for the diagnosis of OSA in

patients with a high pretest probability of moderate to severe OSA

• PM is not appropriate for the diagnosis of OSA in patients with

significant comorbid medical conditions, including moderate to severe pulmonary disease, neuromuscular disease or congestive heart failure

• PM for the diagnosis of OSA should be performed only in conjunction

with a comprehensive sleep evaluation supervised by a sleep specialist

• If PM is negative for OSA but a high index of suspicion for OSA exists,

a in-laboratory PSG should be performed

Collop NA eg al. J clinic Sleep Med 2007; 3(7):737-747

An ambulatory pathway for OSA management Portable Sleep Testing AutoCPAP

(Autotitrating or Autoadjusting)

Vary the delivered pressure between upper and lower pressure limits to eliminate apnea, hypopnea, snoring and air flow limitation, using proprietary algorithms

Morgenthaler TI et al. Sleep 2008; 31:141

Veterans Sleep Apnea Treatment Trial

Kuna S et al. AJRCCM 2011; 183:1238-44

Sleep Clinic Evaluation

Home sleep study In-lab (split night) PSG In-lab PSG CPAP titration Home APAP titration Set home CPAP to PSG CPAP titration Set home CPAP to APAP titration CPAP adherence Functional Outcomes Medical Care Cost AHI < 15 AHI < 15 Clinic F/U Clinic F/U

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Patient-centered clinical outcomes research testing ambulatory management of OSA

• Non-inferiority studies have shown similar improvements in

symptom scores, self-reported quality of life, CPAP adherence, treatment efficacy (AHI)

• Caveats:
• Restrictive patient selection
• Conducted by highly trained and specialized staff
• Limited endpoints studied

Mulgrew et al. Ann Intern Med 2007: 146:157-66 Berry et al. Sleep 2008; 31:1423-31 Antic et al. AJRCCM 20090; 179: 501-8 Rosen et al. Sleep 2012; 35: 757-67 Chai-Coetzer et al. JAMA 2013; 309 (10):997-1004

Moving forward…

• Increased reliance on home sleep studies
• Auto-titrating PAP is now the preferred treatment
• It is likely that primary care practices and allied health personnel will

play an important role in the future ambulatory management of OSA to provide an adequate work force for chronic disease management

• f a major public health problem

Kuna S et al. 22nd Annual Advances in Diagnosis and Treatment of Sleep Apnea and Snoring, 2016

When to treat ?

OSA Symptomatic Treat Consider comorbidities Consider severity Observation

YES NO Moderate-Severe Mild Significant Minimal

OSA Treatment

Snoring Mild OSA AHI <15/hr Moderate 15 < AHI < 30 Severe AHI >30 Primary Rx Observation Rx nasal congestion Lateral positioning Observation Lateral positioning Oral appliance, or Upper airway surgery PAP PAP Secondary Rx Oral appliance, or Upper airway surgery-1 PAP if symptomatic

• r comorbidities,

and motivated Oral appliance, or Upper airway surgery-2 Upper airway surgery-3, or Oral appliance, or Hypoglossal stimulator Tracheostomy Adjunctive Weight loss Weight loss Lateral positioning Weight loss Lateral positioning Weight loss Lateral positioning

Berry R. Sleep Medicine Pearls. 3rd Ed.

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CPAP is effective

Nasal pillows Nasal mask Full face mask

Check adherence

• It only works if you wear it !
• Adherence is the major challenge to PAP treatment
• Variable PAP adherence reported – 68-85%
• Early adherence is a good predictor for long-term PAP use
• Objective monitoring is possible and should be performed early and

at continuous intervals

• Insurance requirements
• 4 hours/day, at least 70% of nights + face-to-face meeting

Non-PAP treatments

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AASM Surgical Treatment Recommendations

Surgical procedures Indications or Conditions

Tracheostomy

Other options do not exist or have failed. Clinical urgency.

Maxillomandibular advancement (MMA)

Severe OSA. Unwilling or unable to tolerate PAP. OA considered an undesirable or ineffective.

Uvulopalatopharyngoplasty (UPPP)

Snoring, mild OSA. Moderate OSA only after offering PAP and OA. Does not reliably normalize the HAI.

Palatal implants

“may be effective in some patients with mild OSA”. Indicated IF patients cannot tolerate or adhere to PAP or OA

Genioglossus advancement (GA), Hyoid advancement (HA)

No specific recommendations Used for hypopharyngeal narrowing.

Multilevel or Stepwise surgery

Upper airway narrowing at multiple sites. Patients have failed UPPP as sole treatment.

Caples SM et al. Sleep 2010; 33:1396-1407

Obesity Hypoventilation Syndrome (OHS)

Consensus definition: 1) Obesity

• BMI >30 kg/m²

2) Daytime hypoventilation

• Awake daytime hypercapnia on ABG (PaCO2 >45 mmHg)

[Serum HCO3 threshold 27 mEq/L - sensitivity 92%, specificity 50%]

3) Sleep disordered breathing

• 90% obstructive sleep apnea, 10% sleep hypoventilation

4) Exclusion of other causes of hypoventilation

• Pulmonary disease, chest wall disorders, neuromuscular disease,

hypothyroidism, other central hypoventilation syndromes

Mokhlesi B et al. Sleep Breath. 2007. 11:117-124 Macavei V et al. Journal of Clinical Sleep Medicine. 2013. 9(9): 879-884

Bariatric surgery

• Bariatric surgery is more effective than non-surgical weight loss
• Greater weight loss (mean difference -26 kg)
• Greater reduction in comorbidities
• 1991 NIH consensus recommendations for bariatric surgery:
• BMI >40 kg/m2
• BMI >35 kg/m2 + obesity-related comorbid condition (OHS), who

failed non-surgical treatment.

Gloy VL et al. BMJ. 2013; 347:f5934 Colquitt J et al. Cochrane Database Syst Rev. 2009. 4:CD003641 Sjostrom L et at. N Engl J Med. 2004. 351:2683-03 NIH Consensus Development Conference statement. Am J Clin Nut. 1992. 55:Suppl 2:615S-619S

Central sleep apnea (CSA)

• Characterized by repetitive cessation of airflow lasting > 10 seconds in

the absence of respiratory effort during sleep

• May co-exist with OSA

Obstructive Central

Airflow Respiratory effort

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Non-hypercapnic CSA Hypercapnic CSA

• High or irregular central drive to breathe
• Low central drive to breathe
• No daytime hypoventilation
• Hypoventilation during day and night
• Examples
• Cheyne-Stokes respiration

· Congestive heart failure, CVA

• Idiopathic
• High altitude
• Treatment emergent CSA
• Examples
• CNS disease
• Neuromuscular disorders
• Pulmonary disorders
• Drugs, substances

· Narcotics, narcotics, narcotics

Types of CSA

Malhotra A et al. Respir Care 2010; 55(9): 1168-1178

The SERVE-HF study

• Multi-center RCT of 1325 patients with systolic CHF and predominantly CSA,

investigating the effects of adaptive servo-ventilation to guideline-based CHF medical treatment alone

• No significant effect on the primary composite end point in a time-to-event

analysis of death from any cause, lifesaving cardiovascular intervention or unplanned hospitalization for worsening CHF, but there was an unexpected increase in all-cause and cardiovascular mortality

Cowie MR et al. N Engl J Med 2015; 373:1095-105

More questions than answers …

• AASM updated ASV Recommendations 2016 - “These data support a

Standard level recommendation against the use of ASV to treat CHF- associated CSAS in patients with an LVEF <45% and moderate or severe CSAS, and an Option level recommendation for the use of ASV in the treatment CHF-associated CSAS in patients with an LVEF >45% and mild CSAS. ” Systolic CHF and predominantly CSA on ASV, consider referral back to Sleep Medicine

Aurora RN et al. J Clin Sleep Med 2016 Apr 12

Question 4

A 36 year old female describes a sensation of ants crawling under her skin in her legs before bed. She finds some relief stretching and rubbing her legs. Which of the following factors has been associated with this sensation?

• A. Pregnancy
• B. Alcohol
• C. High iron stores
• D. Nonsedating antihistamines

9% 18% 41% 32%

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Sleep Related Movement Disorders

• Relatively simple, usually stereotyped movements, associated with

sleep disturbance or complaints of daytime sleepiness or fatigue

• Includes
• Restless Legs Syndrome
• Periodic limb Movement Disorder
• Sleep related leg cramps
• Sleep related Bruxism
• Sleep related rhythmic movement disorder
• Benign sleep myoclonus of infancy
• Propriospinal myoclonus at sleep onset
• Others – excessive fragmentary myoclonus, hypnagogic foot tremor and alternating

leg muscle activation, sleep starts

• AASM. International Classification of Sleep Disorders 3rd Edition 2014.

Restless Legs Syndrome (Willis-Ekbom Disease)

• Common, 5-10%
• A clinical diagnosis - (URGE)
• Urge to move the legs, usually accompanied by uncomfortable sensations
• Rest induced
• Gets better with activity
• Evening worse

Not solely accounted for as symptoms of another medical or behavioral disorder

• Symptoms of RLS cause significant distress or impairment in social,
• ccupational, educational, behavioral or other important areas of

functioning

Periodic Limb Movements

• Periodic limb movements in sleep (PLMS) is a polysomnography (PSG)

finding

• Common but often asymptomatic
• 80-90% of RLS patients

Associated with narcolepsy, REM behavior disorder, OSA

• ? clinical significance. Not highly correlated with measures of sleep

disturbance in most studies of RLS patients

• Periodic limb movement disorder (PLMD) – PLMS cause clinically

significant sleep complaints not better explained by another sleep disorder RLS PLMS PLMD A diagnosis of RLS excludes a diagnosis of PLMD

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RLS/WED Risk Factors

• Female sex (x1.5-2)
• Pregnancy (x2-3)
• Age, up to 60-70 years
• Family history (30-50%)
• Iron deficiency, serum ferritin <50 ug/L
• Chronic renal failure (x2-5)
• Medications – sedating antihistamines, some centrally active dopamine

receptor antagonists, most antidepressants

• Neuropathy
• Multiple sclerosis

RLS Treatment

• Varies with symptom severity - various tools (IRLS)
• Intermittent – symptoms on avg <2/week for the past year, with >5

lifetime events

• Chronic persistent – symptoms on average >2/week for the past year
• Non-pharmacologic – insufficient evidence
• Behavioral
• Avoidance of aggravating factors – medication, caffeine
• Pharmacologic
• Iron - goal ferritin >50 mcg/mL
• Guided by symptom severity, comorbidities, medication side effect profile,

patient preference

RLS Pharmacologic treatments

• First-line
• Dopaminergic medications– (levodopa), dopamine agonists
• Alpha-2 receptor ligands
• Second-line
• Opioids – failure of other treatments, contraindication of dopaminergic

therapy, pain disorder requiring pharmacologic therapy, refractory RLS

• Others or combination therapy

Non-ergotamine dopamine agonists

• Effective First-line therapy for daily moderate to severe RLS
• Side effects – nausea, headaches, light-headedness, somnolence, peripheral

edema, nasal congestion, augmentation 30% short term but long-term common, loss of effectiveness, dopamine dysregulation syndrome, impulse control disorders, category C

Berry R. Sleep Medicine Pearls 3rd Ed.

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Alpha-2-delta Ligands

• As effective as DA and may improve sleep quality.
• Consider first line in patients with comorbid pain syndrome, insomnia,

generalized anxiety disorder, neuropathy, history of recurrent impulse control disorder

• Side effects – sedation, fatigue, ataxia, nausea, weight gain, peripheral edema,

leukopenia, thrombocytopenia, depression

• Augmentation not described

Berry R. Sleep Medicine Pearls 3rd Ed.

Question 5

A 62 year old male describes violent behaviors during sleep. His wife describes being hit on several occasions. When she manages to awaken her husband during episodes he reports dreaming and fighting with an

• attacker. The episodes tend to occur between 4-6 AM. What is the

likely diagnosis?

• A. Nocturnal seizures
• B. Sleep terrors
• C. Periodic limb movement disorder
• D. REM behavior disorder

0% 68% 4% 28%

Parasomnias

• Undesirable physical events or experiences that occur during entry into

sleep, within sleep or during arousal from sleep, due to state dissociation.

• Overlap exists

Non-REM parasomnia REM Parasomnia

• Confusional arousals
• Sleep walking
• Sleep terror
• Sleep related eating disorder
• REM Sleep Behavior Disorder
• Nightmare disorder
• Recurrent isolated sleep paralysis

Others: exploding head syndrome, sleep related hallucinations, sleep enuresis

• AASM. International Classification of Sleep Disorders 3rd Edition 2014.

NREM Parasomnia

• Disorders of arousal
• More frequently seen in children
• Typically arise from stage N3 sleep during the first half of the night
• Diagnosis is largely clinical.

Consider a sleep study if suspicion of seizures, atypical presentation, suspicion of another sleep disorder, not responsive to conventional therapy, potentially violent or dangerous behaviors, medicolegal cases

• Treatment – Reassurance, ensure a safe environment, avoid

aggravating factors, rarely medications

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REM Behavior Disorder (RBD)

• Abnormal behaviors during REM sleep (dream enactment), due to loss of normal

muscle atonia associated with REM, that may cause injury or sleep disruption

• 0.5% population, males, >50 years
• Clinical
• Complex, non-stereotypical behaviors, + dream recall, often violent
• Second half the night
• Can result in injury to self and bed partner
• Risk factors
• Alpha-synucleopathies disorders - Parkinson disease, multiple system atrophy, lewy body dementia
• Narcolepsy
• Medications, especially antidepressants
• Diagnosis requires demonstration of REM sleep without atonia on video-PSG
• Treatment
• Safe environment
• Clonazepam (0.25-1 mg), melatonin (3-12 mg)

Question 6

A 21 year old male presents complaining of severe daytime sleepiness and transient bilateral leg weakness lasting 1 minute when embarrassed for the past 9 months. He typically sits during these episodes of weakness. He sleeps for 8 hours per night. He takes no medications. His BMI is 19 kg/m2 and his neurological examination is normal. His sleep study showed no sleep disordered breathing or unusual limb movements. What is the most likely diagnosis?

• A. Seizures
• B. Narcolepsy
• C. Idiopathic hypersomnia
• D. Depression

7% 7% 19% 67%

Excessive Daytime Sleepiness

• AASM definition: Inability to stay awake and alert during the major

waking episodes of the day, resulting in periods of irrepressible need for sleep or unintended lapses into sleep (vs. fatigue)

• Subjective measures
• Epworth Sleepiness Scale
• Stanford Sleepiness Scale
• Objective measures
• Multiple sleep latency test (MSLT)
• Maintenance of wakefulness test (MWT)
• Poor correlation

EPWORTH SLEEPINESS SCALE What is your chance of dozing 0 = NEVER dose 1 = SLIGHT chance 2 = MODERATE chance 3 = HIGH chance 1. Sitting and Reading 2. Watching TV 3. Sitting, inactive in a public place 4. As a passenger in a car for an hr without break 5. Lying down to rest in the afternoon 6. Sitting talking to someone 7. Sitting quietly after a lunch without EtOh 8. In a car while s topped for a few min in traffic TOTAL = ____________ 0-24 (0-10 normal)

• AASM. International Classification of Sleep Disorders 3rd Edition 2014.

Central Disorders of Hypersomnolence

• ICSD-3 Classification
• Narcolepsy, Type 1
• Narcolepsy, Type 2
• Idiopathic Hypersomnia
• Kleine-Levin Syndrome
• Hypersomnia due to a medical disorder
• Hypersomnia due to a medication or substance
• Hypersomnia associated with a psychiatric disorder
• Insufficient Sleep Syndrome
• AASM. International Classification of Sleep Disorders 3rd Edition 2014.

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Narcolepsy

• 1 in 2000 but underdiagnosed
• Classification

1) Type 1 (cataplexy) – CSF hypocretin-1 <110 pg/mL or <1/3 mean value 2) Type 2

• Secondary narcolepsy – neurological disorders
• Clinical
• Excessive sleepiness (100%), >3 months
• Cataplexy (60-70%)
• Sleep related hallucinations (33-80%) - hypnogogic, hypnopompic
• Sleep paralysis

Narcolepsy

• Diagnosis:
• CSF hypocretin-1
• MSLT – mean sleep latency <8 mins and >2 SOREMPs
• Treatment
• Behavioral
• Pharmacologic

· EDS – wake promoting medications, stimulants, sodium oxybate · Cataplexy – antidepressant, sodium oxybate

What is the future of sleep medicine in the US?

“The number of board-certified sleep specialists is dwindling rapidly. The numbers probably peaked around 2013. However, in the 2013 sleep medicine fellowship match….About one-fourth of these positions went unfilled, and an even higher percentage went unfilled in 2014.” “Something needs to change.” “The comfort level of primary care physicians and nonspecialists needs to continue to improve, with enhanced education around sleep and its disorders in medical schools and other levels of training.”

Phillips B. et al. Am J Respir Crit Care Med 2015; 192(8):915-7