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University of Michigan - Ann Arbor
Lecture 21: Causes and Consequences of Excessive Daytime Sleepiness
Lecture 21: Causes and Consequences of Excessive Daytime Sleepiness
University of Michigan - Ann Arbor
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What regions of the brain regulate the two main states of brain consciousness?
Arousal centers (TMN, LC, Raphe)
Sleep centers (VLPO)
What regions of the brain monitor the transition of control from one brain center to the other?
Transition centers (PeF)
What is involved in the sleep switch to the sleep state?
Mutual inhibition of orexin and LC/TMN/Raphe neurons by VLPO and eVLPO
What is involved in the sleep switch to the awake state?
Orexin activate LC/TMN/Raphe
LC/TMN/Raphe inhibit VLPO and eVLPO
What are the two opposing processes in the sleep-wake cycle?
Circadian and homeostatic regulation of sleep
-longer stay awake, greater propensity to sleep
-stay asleep, dissipate homeostatic drive
What are some of the most common sleep-inducing situations in apnea patients?
Watching TV, reading riding in a car
What does an Epworth Sleepiness Scale (ESS) score greater than or equal to 10 indicate?
Excessive daytime sleepiness or sleep disorder
What is the mean ESS score for narcolepsy?
What is the mean ESS score for severe untreated OSA?
What is the mean ESS score for Parkinson's disease?
What is the mean ESS score for seasonal affective disorder?
What is the mean ESS score for MDD with ES/fatigue?
What is the mean ESS score for untreated depression?
What is the mean ESS score for depression with partial response to antidepressants?
What is the mean ESS score for multiple sclerosis?
What are some conditions that fall within the moderate to severe sleepiness range?
Narcolepsy, severe untreated OSA, Parkinson's disease, seasonal affective disorder, MDD with ES/fatigue, untreated depression
What are some different measurement of daytime sleepiness behavior?
Psychomotor performance (long, monotonous, externally paced, no feedback)
What is a good test of psychomotor performance?
Driving on a highway
What is the effect of sleep restriction on reaction time in a vigilance task?
Significantly higher in 5hr in bed group than 8hr in bed
What effects are there in regards to an increase in reaction time on stopping distance at 70mph?
50 msec stop at 5 feet
100 msec stop at 10 feet
150 msec stop at 15 feet
Give an overview of the interactions occurring during the wakeful sleep state.
Ascending arousal centers in the brainstem, hypothalamus, and basal forebrain excite sensory and motor regions in the cerebral cortex and thalamus
What arousal centers are involved with thalamocortical transmission?
What arousal centers are involved with activation of the cerebral cortex?
LC, Raphe nucleus, TMN, vPAG
What do the lateral hypothalamus (LH) and basal forebrain (BF) contribute to?
What does the SCN modulate?
The balance between periods of high and low sleep propensity
What is one of the main jobs of the waking centers?
To increase neuronal and cortical activities
What effect does sleep deprivation have on cortical activity?
Decrease in activity
-Occipital cortex, inferior parietal cortex, thalamus, prefrontal cortex
What are some different physiological measurements of daytime sleepiness?
P300-ERP, rolling eye movements, pupillometry, EEG spectral measures (alpha activity), sleep propensity
What are some different measurements of sleep propensity?
MSLT (multiple sleep latency test)
Maintenance of wakefulness test
What is pupillometry a measure of?
Measure of ANS and sleepiness
What effect does fatigue have on cortical activity?
Decreases cortical activity
-Reduced glucose metabolism in the bilateral prefrontal cortex and basal ganglia
How does baseline MSLT vary throughout the day?
Higher latency at 9am and 5pm (~15.3 min)
Lowest around 1pm (~9.3 min)
What is the average American sleep latency?
What is the average sleep latency in sleep apnea?
What is the average sleep latency in college students?
What is the average sleep latency in children?
How does sleepiness affect psychomotor performance?
MSLT score (<6) significantly more likely to doze off while driving in comparison to those with MSLT score >10
What relationship is there between crashes and the MSLT?
Significantly higher number of crashes in MSLT group of less than 5 minutes in comparison to 5-10 min and >10 min groups
How can one tell if an accident was sleep-related?
Look at braking patterns
-Often no brake marks or very delayed
-Tend to occur 2-6am in younger people and 2-4pm in older populations
What percent of people have an ESS score over 12?
What percent of people suffer from excessive daytime sleepiness as indicated by MSLT?
What percent of people suffer from moderate sleepiness as indicated by MSLT?
What is 0hr TIB for 1 night comparable to?
MSLT of narcoleptic individual
Where do anesthesia residents fall on MSLT?
~5 minutes (on par with sleep apnea)
What populations are at risk for sleepiness?
Transportation workers (truck/train drivers, commuters)
Younger age groups
Sleep, medical and psychiatric disorders patients
What are some behavioral/mood consequences of sleep loss?
Sleepiness, psychomotor impairment, accidents, decreased work productivity, reduced quality of life, deficits in learning/memory, stimulant seeking, alcohol interaction, mood effects, lack of awareness, risk taking behavior
What are some physiologic consequences of sleep loss?
Hypoxemia, insulin resistance, increase sympathetic activity, blunted arousal response (hypoxemia, CO2, EEG), increase pain sensitivity, decreased antibody production
What is the number one CNS stimulant drug in the US?
How does apnea correlate with number of crashes?
Increasing severity of apnea results in higher instances of apnea
What did the Wayne state study of ER residents that drove post-call show?
17% had MVAs
6.7x more likely to fall asleep driving prior to residency
What did the UPenn survey of anesthesia residents that drove post-call show?
17% had MVAs, all between 8-9am
72% had near-miss MVAs
How does sleepiness affect the recognition of words?
Cannot consolidate memory when sleepy
What relationship is there between sleepiness and school achievement?
Correlation between decreasing grades and increasing sleepiness
What were the results of delaying school time by 1 hour in Minneapolis, MN?
Delayed school time by 1 hour, dramatically reduced accident rates and increased grades
How does sleep deprivation affect genioglossal EMG readings?
Decreased genioglossal EMG
What effects did extending sleep in mild to moderate sleep apnea syndrome have on minutes and times SO2 below 90% per hr sleep?
When people start studying the relationship between sleep apnea and sleepiness, what do they look at?
Correlate blood gases with degree of sleepiness
What is noted in more sleepy individuals?
What effects do sleep and REM sleep loss have on finger withdrawal latency?
Decreasing latency with decreased time in bed
What are some metabolic effect of sleep deprivation?
Decreased glucose clearance and effectiveness in sleep deprived individuals (within diabetic range)
What is reduced total sleep time associated with?
Increased prevalence of obesity
What are some real world consequences of sleep loss?
-Ex: train conductor took 20 seconds from train stop signal to applying the brake
How did response requirements and point loss probabilities in alert and sleepy subjects compare?
Response requirements: sleepy showed higher rate at 50
Point loss probability: sleepy showed higher rate
-More likely to make poorer decision
What are some causes of excessive daytime sleepiness?
Sleep at night (reduced sleep length, sleep continuity)
CNS acting drugs
What mammal requires one of the least total daily sleep times?
How long does the average American sleep?
Which MSLT group showed the highest amount of weekend oversleeping?
MSLT <5 mins
Which country consumes the most caffeine?
How does caffeinated beverage consumption compare with MSLT?
Increase consumption in lower MSLT
How does methylphenidate self-administration compare between sleep-deprived and normal individuals?
Increased consumption of MD in sleep-deprived individuals
How do mean MSLT latency and TIB correlate?
Decreasing MSLT latency with decreased time in bed
What did experiments on chronic restriction of sleep from 1-2 weeks reveal?
Cumulative increases in lapse rates in a sleep-dose response matter
How does sleep fragmentation affect mean sleep latency?
Decreasing sleep latency with more frequent sleep interruptions
During what times is mean sleep latency lowest throughout the day?
When were the highest occurrences of meter reading errors?
When are the highest occurrences of fatigue-related accidents?
Midnight-4am, smaller spike around 2pm
How does alcohol consumption affect sleep latency?
Increasing dose = decreased sleep latency
How does sleep restriction impact BrEC levels?
Increasing sleep loss corresponded with higher BrEC levels
What were the results of the study looking at the combined effects of sleep deprivation and alcohol consumption?
Gave people 4 and 8 hours of sleep
-2 beers will increase number of times the subject drives off the highway, even higher in sleep deprived individuals
How is sleep latency affected after alcohol consumption between 8 and 10 hr TIB?
Increased ethanol sleep latency in 10 hr TIB
How does caffeine impact reaction time?
Decreases reaction time
What are some common sources of caffeine?
Cola, Mountain Dew, Orange soda, Red Bull, iced tea, drip coffee, Starbucks, Vivarin/NoDoz
What are some sleep disorders with secondary excessive sleepiness?
Shift work sleep disorder (SWSD), obstructive sleep apnea (OSA), narcolepsy, restless legs syndrome (RLS), circadian rhythm disorders, parasomnias
What are some medical diseases with secondary excessive sleepiness?
Parkinson's disease, cerebrovascular disease, endocrine disorders, pain, residual symptoms associated with medication
What are some psychiatric diseases with secondary excessive sleepiness?
Depression (disease-related, residual symptoms of antidepressants), anxiety, bipolar disorder
What cortical activity levels are associated with depression?
Decreased cortical activity levels
When does the onset of narcolepsy typically occur?
In teen years, often earlier
What are some signs of narcolepsy?
Excessive sleepiness, cataplexy (pathognomonic) hypnagogic hallucinations, sleep paralysis, disrupted nighttime sleep
What is the prevalence of narcolepsy?
5 in 10,000
What was discovered in narcoleptic individuals undergoing fMRI BOLD scans?
Mental fatigue--decreased activation seen at last scan in anterior executive network
What are some FDA-approved treatments for sleepiness in narcolepsy?
Modafinil, stimulants, sodium oxybate
What are some FDA-approved treatments for cataplexy in narcolepsy?
What are some FDA-approved treatments for RLS/PLMD?
What can recurrent episodes of airway obstruction during sleep result in?
-Arousals and fragmented sleep
-Fluctuations in blood pressure and heart rate
What is the prevalence of mild OSA?
1 in 5 adults
-Up to 24% of men and 9% of women
What is the prevalence of moderate to severe OSA?
1 in 15 adults
-Up to 9% of men and 4% of women
What percent of women and men aren't diagnosed with moderate to severe OSA?
93% of women and 82% of men
What is part of the reason for the prevalence of OSA?
Rising obesity levels
What does OSA appear to be a risk factor for?
Independent risk factor for increased mortality
Multiple comorbid conditions (hypertension, diabetes, stroke, heart attack, etc.)
What are some primary physiologic events in OSA?
Hypoxemia, reoxygenation, hypercapnia, intrathoracic pressure changes, arousals
What are some systemic effects of OSA?
Sympathetic activation, endothelial dysfunction, vascular oxidative stress, inflammation, increased coagulation, leptin/insulin resistance and obesity
Why does airway obstruction occur?
Fall asleep -> airway collapses -> apnea/hypopnea -> arousal from sleep -> airway opens, breathing resumes -> Fall asleep
What are some causes of class 1 OSA?
Excess body weight, large neck circumference
What are some causes of class 2 OSA?
Excess body weight, large neck circumference, localized structural abnormalities
What are some causes of class 3 OSA?
Smoking, alcohol or sedative intake, nasal congestion, familial association
What are some features of the STOP questionnaire for OSA screening?
Height, weight, age, male/femal, BMI, collar size, neck cirumference
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