Sleep Disorders Flashcards
Insomnia: epidemiology
o Prevalence: 10-15% population
• ~10% cases = primary
• ~90% = comorbid (associated with co-occurring medical, psychiatric, or sleep disorders)
Insomnia: pathophysiology
Biological factors
• CNS hyperarousal
• Higher proportions of short allele of 5-HTTPR gene
Psychological factors
• More reactive to stressors
• Worries and intrusive thoughts prior to sleep
• Over time may develop negative associations with bedtime/environment
• Maladaptive responses may perpetuuate insomnia
Insomnia: Risk factors
o Age (greater prevalence in older individuals) o Female gender (especially post- and perimenopausal) o Divorce/separation/widowhood o Psychiatric illness o Medical conditions o Cigarette smoking o Alcohol and coffee consumption o Certain prescription drugs
Insomnia: common causes/comorbidities
Medical • Cardiac, pulmonary, rheumatologic, neurologic, endocrine, gastrointestinal, renal, pain syndromes • Medication effects: Stimulants (modafinil, amphetamine, methylphenidate) Antidepressants (SSRIs, bupropion) Theophylline and caffeine Decongestants (pseudoephedrine) Diuretics Corticosteroids Antihypertensives Alcohol (esp in 2nd half of night) Withdrawal from sedative-hypnotics
Psychiatric
• Mood disorders, anxiety disorders, substance abuse
• Most psychiatric disorders are associated with insomnia
• Chronic insomnia = 2x risk of developing depression
Sleep
• Circadian rhythm disorders
• Sleep-disordered breathing
• Restless legs syndrome (Willis-Ekbom Disease)
Parasomnias: pathophysiology
Definition:
o Undesirable physical, experiential or behavior phenomena that occur during sleep or are exacerbated by sleeping
Pathophysiology: o Typically arise from Short wave sleep (SWS) = First 1-2 hrs of sleep period o Behaviors and mood states • Not under conscious control • Not remembered on awakening
Arise when elements of specific brain states occur simultaneously:
NREM sleep
REM sleep
Wake
REM vs NREM sleep
NREM Sleep
• Increased parasympathetic activity
• Decreased HR, CO, BP
• Decreased EMG activity (but not as great as REM)
REM Sleep • Increased sympathetic activity • Dreaming • Paralysis of skeletal muscle • Rapid eye movements
Parasomnias: types
o Confusional arousals o Sleepwalking o Sleep terrors o REM behavior disorder o Variants: Sleep-related violence, sexual activity, eating disorder
Parasomnias: prognosis
Often common in children and most tend to grow out of them
Parasomnias: evaluation
For NON-REM parasomnias: PSG not routinely indicated • Unless co-morbid sleep disorder suspected • Dangerous or atypical parsomnia Differential diagnosis • Nocturnal panic attacks • Nocturnal frontal lobe seizures • Delirium • Nocturnal dissociative episodes • REM Sleep Behavior Disorder Treatment Risk-Benefit analysis for each person
For REM Behavior disorder:
• PSG needed to confirm diagnosis:
• Elevated muscle tone
• Increased submental or ant tibialis EMG
Parasomnias: treatment
For NON-REM parasomnias: Three-Step Model • Modify predisposing/precipitating factors • Avoid sleep deprivation, stress • Improve safety of sleeping environment Pharmacotherapy • No controlled trials • Benzodiazepines typically used
For REM Behaviro disorder:
• Treat co-morbid sleep disorders
• Remove iatrogenic causes of RBD (ex: antidepressants)
• Behavioral management = Optimize safety of sleeping environment
Pharmacologic management:
• Benzodiazepines
• Alternatives melatonin, pramipexole
Sleepwalking
- Common in children (10-20%)
- Ususally resolves by adolescence
- 1-4% of adults (80% had behaviors in childhood)
- Strong genetic component:
- Twin studies, HLA-DQB1*0501
- Higher risk with family history
Sleep terrors
Motoric behavior with affective discharge
• In children = piercing scream, followed by fear, crying and inconsolability
• Increased autonomic activity (HR, Resp rate, sweating)
Prevalence: 5% of children, 1-2% of adults
Amnesia is rule
• But simple mentation may be recalled
• Caution confronting = can morph into sleep-related violence
REM behavior disorder
Features:
• Loss of paralysis during REM sleep → Individuals act out their dreams
• Eyes closed; unresponsive to environment
• On awakening = rapid alertness with dream recall
• (Self)-injury often prompts evaluation
Prevalence ~ 0.4-0.5% in elderly
• 70-80% are men
• ~5 years from onset to diagnosis
Risks:
• Associated with narcolepsy in young
• In older men, higher risk of developing Parkinson’s Disease or dementia
Circadian rhythm disorders: pathophysiology
o Misalignment of internal clock with environment
Circadian rhythm disorders: clinical presentation
Combination of difficulty initiating sleep and daytime sleepiness
Types:
Exogenous
• Chronic misalignment between the body’s natural circadian rhythms and environment
• Ex: Shift work sleep disorder
Endogenous • Delayed sleep phase syndrome o Most common = adolescents o Initial insomnia and difficulty waking in morning o Daytime sleepiness • Advanced sleep phase syndrome o Most common = elderly o Early morning waking
Circadian rhythm disorders: evaluation
o Clinical history = key
o Supplemental data:
• Sleep logs
• Actigraphy (wrist-worn accelerometer that measures rest-activity patterns
Circadian rhythm disorders: treatment
Exogenous Increase sleep duration • Sleep hygiene education • Hypnotic medication Increase alertness • Prophylactic naps • Caffeine • Wake-promoting drugs Re-align circadian rhythm • Adjusting light exposure • Melatonin
Endogenous
• Appropriately timed light exposure
• Regularizing sleep-wake patterns
• Appropriately timed melatonin
Narcolepsy: epidemiology
o Onset = children, teens, young adults
o Prevalence ~0.05%
Narcolepsy: clinical presentation
Features: • Excessive daytime sleepiness • Sleep paralysis • Hypnagogic/hypnopomic imagery (hallucinations at sleep onset and/or offset) • Cataplexy • Loss of muscle tone in response to emotional stimuli • Highly specific for narcolepsy • Automatic behaviors
2 types: 1) Narcolepsy with cataplexy • Loss of hypocretin/orexin neurons in lateral hypothalamus o Normally serve as “finger on switch” to maintain sleep vs. wake state • Likely autoimmune reaction • Associated with HLA DGB1*0602 2) Narcolepsy without cataplexy • Less clear causes
Narcolepsy: evaluation
o PSG test
o Multiple sleep latency test (MSLT)
• Typically shows mean sleep latency <8 min
• Greater than 2 sleep onset REM episodes
Narcolepsy: treatment
o Avoid sleep deprivation
o Scheduled naps
o Stimulants = promote wakefulness (Modafinil, methylhenidate, amphetamines)
o Antidepressants = reduce cataplexy
o Sodium Oxybate = treats excessive daytime sleepiness and cataplexy
• Highly controlled drug
Restless legs syndrome: epidemiology
o Prevalence ~3-5%
Restless legs syndrome: pathophysiology
Primary
• Thought to be from dysfunction of CNS iron metabolism
• However = most present with normal iron levels in periphery
Secondary • Iron deficiency anemia • Renal failure • Pregnancy • Medication induced: antidepressants, antiemetics, antipsychotics, antihistamines
Restless legs syndrome: risk factors
o Female
o Elderly
o Northern European descent
Restless legs syndrome: clinical presentation
o Sensorimotor disorder that disrupts sleep initiation, maintenance, and or causes excessive daytime sleepiness
Restless legs syndrome: diagnosis
o Made clinically
o Associated with periodic limb movements of sleep during PSG (but not specific)
Minimal Criteria: (URGE) Urge to move legs Rest-induced (onset or worsening of symptoms at rest) Gets better with movement Evening predominance
Other features: Sleep disturbance Involuntary leg movements Positive RLS family history Response to dopaminergic therapy
Restless legs syndrome: treatment
Non-pharmacologic
• Abstinence from caffeine, nicotine, alchohol
• Evaluate medications that may worsen RLS
• Iron replacement if ferritin <50 ng/mL
Pharmacologic
• 1st line: dopamine agonists (pramipexole, ropinirole)
• 2nd/3rd line: Gabapentin, Low-potency opioids
List the pharmacologic treatments available for sleep disorders (insomnia treatment)
Benzodiazepine receptor agonists • Agonist on GABAA receptor Adverse effects: • Daytime sedation • Cognitive impairment • Anterograde amnesia • Motor impairment • Rebound insomnia upon discontinuation • Parasomnias = Somnambulism, sleep-eating, sleep-driving • Tolerance/dependence/abuse • Other: headache, GI (nausea, diarrhea)
Melatonin agonists (Rameleon)
• MT1/2 receptor agonist
• Approved for insomnia treatment
• No cognitive impairment or abuse liability
• Rapid absorption and short ½ life = better for sleep initiation than maintenance
Sedating antidepressants (mirtazapine, trazodone, nefazodone, amitriptyline, doxepin, trimipramine)
• Cholinergic, histaminergic, adrenergic, and serotonergic antagonism
• Little abuse liability
• Probably not as effective as benzodiazepines
Adverse effects:
• Daytime sedation
• Weight gain
• Anticholinergic side effects
• Switch into mania in bipolar disorder
Anticonvulsants (gabapentin, tiagabine, pregabalin)
• Good: little abuse liability, may be helpful with co-morbid RLS
• Probably not as effective as benzodiazepines
Adverse effects:
• Cognitive impairment
• Daytime sedation
• Weight gain
• Edema
Atypical antipsychotics (olanzapine, quetiapine, risperidone, ziprasidone) • Dopaminergic, cholinergic, histaminergic, and serotonergic antagonism • Used off-label to treat insomnia Advantages: • Anxiolytic • Mood stabilizing in bipolar disorder • Little abuse liability Disadvantages • Less effective than benzodiazepines • Daytime sedation • Weight gain • Risks of extrapyramidal symptoms • Glucose + lipid abnormalities