Term
sleep
basic def (conceptual) |
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Definition
a REVERSIBLE behavioral state of perceptual disengagement from and unresponsiveness to the environment
well-controlled |
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Term
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Definition
a state in which subjects lies with eyes closed and demonstrate no conscious response to external stimuli, even after vigorous attempts to rouse them
pathologic conditions with unawareness of environment
NOT regulated |
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Term
sleep
operational definition |
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Definition
-a physiologic state defined by behavioral and physiologic criteria
-consists of an orderly pattern of transitions between discrete stats of brain activity
-people can be aroused from sleep
-respond to meaningful stimuli more readily than non-meaningful stimuli
-cognitive activity occurs (dreams) |
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Term
consciousness
sleep vs. coma |
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Definition
consciousness is awareness of self and the environment, with the ability to react to internal and external stimuli
sleep = REGULATED state of reduced consciousness
come = UNCONTROLLED state of unconsciousness |
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Term
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Definition
non-REM (NREM) (~75%/night)
-stage N1
-stage N2
-stage N3
REM (~25%/night)
these 2 states alternate at about 90-minute intervals; 4-6 cycles in all |
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Term
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Definition
sleep onset: N1->N2->N3->N2->first REM period
N1, N2: slight sleep
N3: deep sleep/slow wave/delta wave |
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Term
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Definition
brain is less active; body can move
normal EEG with progressive slowing and increased synchronization of EEG activity as get into deeper sleep stages
NO rapid eye movements |
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Term
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Definition
brain is active, but body is paralyzed (limb atonia)
EMG supression
EEG is irregular/desynchronized, low voltage activity - resembles awake state
rapid eye movements |
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Term
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Definition
first 2 cycles dominated by stage N3/NREM sleep
NREM later in night is primarily N2, with brief N1
periods of REM sleep grow longer as night progresses
first 1/3 of night, more slow wave sleep
final 1/3 of night dominated by REM sleep |
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Term
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Definition
ongoing thalamic input to the cortex
stimulus-dependent, non-rhythmic cortical activity (desynchronized EEG)
thalamus receives input from ARAS network
awake state is associated with increased activity in monoamingerigc and cholinergic systems |
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Term
ascending reticular activating system
ARAS |
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Definition
network of pathways that originate in the brainstem (especially midbrain) and project to thalamus
receives input from cortex, thalamus and sensory fibers
excites thalamocortical projections leading to EEG desynch and behavioral arousal --> elevated ARAS levels of NTs |
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Term
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Definition
monoaminergic and cholenergic
norepinephrine, acetylcholine, serotonin, histamine |
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Term
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Definition
initiated by GABA-ergic "hypnogenic neurons" in the basal forebrain nuclei and pre-optic area of the hypothalamus inhibit ARAS
ARAS inhibition results in reduced thalamocortical activity
inhibition of output target leads thalamus and cortex unable to respond to environment
slower, more synchronized EEG activity...NREM sleep |
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Term
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Definition
the cortex is effectively deafferented (closed off from most sensory stimuli)
relative decrease in activity of NE, ACh, 5HT, and histamine pathways |
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Term
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Definition
at some point during slow wave sleep, cholinergic cells in the tegmentum of pons and midbrain begin to fire
these are the REM-on cells
REM-on cells stimulate the thalamus and basal forebrain --> renewed EEG desynchronization (looks like awake EEG) |
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Term
| projections of REM-on neurons |
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Definition
thalamus
spinal interneurons
reticular formation
LGN/occipital cortex
brainstem nuclei
ARAS REM-off cells |
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Term
| REM-on neuronal projection to thalamus |
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Definition
REM-on --> thalamus
EEG DESYNCHRONIZATION |
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Term
| REM-on neuronal projection to spinal interneurons |
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Definition
REM-on --> reticulospinal tract (via reticulospinal tract)
synapse on glycinergic spinal interneurons to cause inhibition of alpha motor neurons in spinal cord
ATONIA |
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Term
| REM-on neuronal projection to reticular formation |
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Definition
REM-on --> reticular formation of pons and midbrain
SACCADIC EYE MOVEMENTS |
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Term
| REM-on neuronal projection to LGN/occipital cortex |
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Definition
REM-on --> lateral geniculate and occicipatl cortex
PGO WAVES that may be related to the visual content of dreams |
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Term
| REM-on neuronal projection to brainstem nuclei |
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Definition
REM-on --> other brainstem nuclei
maintain VITAL FUNCTIONS: respiratory, cardiovascular, etc |
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Term
| REM-on neuronal projection to REM-off |
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Definition
REM-on --> REM-off neurons of the ARAS
inhibition of REM off cells |
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Term
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Definition
subset of neuron in ARAS
serotonergic cells in the dorsal raphe nuclei of the brainstem, NE-containing cells in locus ceruleus or pons, histaminergic neurons in posterior hypothalamus
reciprocal inhibitory projection to REM-on cells
silent during REM sleep (reduction of 5HT, NE, histamine) |
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Term
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Definition
REM-off cells become active at some point in REM to terminate REM sleep
trigger unknown; there may be (in addition to the mutually inhibitory connection between REM-on/off cells) an excitatory cholinergic projection to the REM-off cells from REM-on cells that slowly excites them (gradually building up during REM sleep)
inhibition of REM-on neurons leads to return to NREM sleep and burst EEG activity |
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Term
| NT activity in awake state |
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Definition
+ monoamines (NE, 5HT, histamine)
+ ACh |
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Term
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Definition
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Term
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Definition
- monoaminergic
+ ACh
overall increase in cholinergic activity |
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Term
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Definition
peptide located in certain hypothalamic neurons near the fornix
factor in the regulation of REM/NREM/wakefulness
project widely, including to ALL ARAS nuclei
acts at a NT to stim REM-off cells - inhibit REM sleep
promote wakefulness, stimulate feeding and motor activity |
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Term
| triggers for entire sleep-wake cycle |
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Definition
derives from interplay of two processes
process S: "sleepiness"
process C: "circadian" |
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Term
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Definition
the duration of prior wakefulness influences the timing of sleep onset
homeostatic process related to time since last (deep/slow wave) sleep - increases exponentially as a function of time awake; "sleep debt"
possibly adenosine driven (caffeine blocks adenosine receptors) |
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Term
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Definition
"internal clock" in the SCN of hypothalamus keeps body on an intrinsic 24.2 hour sleep-wake cycle
regulated by intrinsic clock (SCN) and external cues (esp. light)
circadian rhythms are operating at the level of certain "clock genes"
pineal gland has reciprocal connections with SCN and releases melatonin (rises in evening, decreases during the day) |
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Term
| *neurotransmitters of arousal* |
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Definition
monoaminergic;
-5HT
-NE
-histamine
cholinergic
-Ach |
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Term
| *sleep-promoting transmitters and substances* |
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Definition
GABA - released by basal forebrain to start things off
melatonin - released by pineal gland
adenosine - role in "process S" |
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Term
| cholinergic and monoaminergic cells |
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Definition
ACh, 5HT, NE, histamine
celss in ARAS
maintain wakefulness |
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Term
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Definition
| GABA-ergic basal forebrain and preoptic centers that promote sleep |
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Term
| classification of sleep disorders |
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Definition
3 broad categories: trouble staying awake, trouble sleeping, abnormal behaviors during sleep
American Academy of Sleep Medicine catergories (8): insomnias, sleep-related breathing disorders, hypersomnias not due to a sleep-related breathing disorder, circadian rhythm disorders, parasomnias, sleep-related movement disorders, olther sleep disorders, isolated symptoms/apparently normal variants/unresolved issues |
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Term
sleep disorders
trouble staying awake |
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Definition
insufficient sleep
obstructive sleep apnea
narcolepsy
other (meds, encephalopathy, central sleep apnea) |
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Term
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Definition
usually unrecognized, self-imposed sleep deprivation
clue to dx: asking is patient in less sleepy on weekends or whenever they can sleep in
managed by good "sleep hygiene" education |
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Term
obstructive sleep apnea (OSA)
clinical features |
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Definition
patient periodically stops breathing while asleep; usually caused by temporary obstruction of the upper airway
can result in hypersomnia because sleep is disruptive, not going through orderly cycles |
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Term
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Definition
OSA is due to narrowing of upper airways at the level of the soft palate and the base of the tongue
normal pharyngeal muscle relaxation during sleep results in partial or complete occlusion of airway
reduced inspiratory airflow and increased respiratory effort, culminating in partial awakening (to activate muscles and breath, then return to sleep) |
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Term
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Definition
CPAP is most effective (continuous positive airway pressure)
raises the pressure in the oropharynx/upper airway, reversing the pressure gradient across the wall of the airway and propping it open
beneficial in 80-90% of patients |
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Term
narcolepsy
clinical features |
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Definition
excesive daytime somnolence and disordered regulation of REM sleep, resulting in intrusion of components of REM into NREM and waking state
4 cardinal symptoms (not all exhibited by all patients):
1. chronic excessive daytime somnolnce; 2. cataplexy; 3. sleep paralysis; 4. hypnagogic (or hypnopompic) hallucinations |
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Term
cardinal symptoms of narcolepsy:
chronic excessive daytime somnolence |
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Definition
their sleep is always non-restorative, so always sleeps
this sleepiness cannot be relieved by any amount of normal sleep |
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Term
cardinal symptoms of narcolepsy:
cataplexy |
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Definition
sudden loss of postural tone
identical to the atonia of REM sleep but occurs while the patient is awake
may involve only a single muscle group, or generalized and lead to complete body collapse and paralysis
does not involve eye movements or respiratory muscles
associated with areflexia |
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Term
cardinal symptoms of narcolepsy:
sleep paralysis |
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Definition
atonia at sleep onset or immediately upon wakening
patient is half-conscious/awake but unable to move
often accompanied by intense fear and a sense of being unable to breathe |
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Term
cardinal symptoms of narcolepsy:
hypnagogic (or hynopomic) hallucinations |
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Definition
| vivid auditory or visual dream-like experiences that occur at the ONSET of sleep (or on awakening) |
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Term
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Definition
multiple sleep latency test has a mean sleep latency of 5 minutes or less (compared to >10 min for controls)
go into REM sleep sooner |
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Term
narcolepsy
pathophysiologic factors |
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Definition
hypocretin abnormalities
HLA accociation |
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Term
narcolepsy
hypocretin abnormalities |
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Definition
90% of patients WITH cataplexy have undetectable/very low CSF levels of hypocretin
autopsies show depletion of hypocretin-containing neurons
(precise role of hypocretin in the pathogenesis of narcolepsy is unknown) |
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Term
narcolepsy
HLA association |
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Definition
>95% of Asian and Causcasin narc patients have 2 specific HLA antigens
suggests an autoimmune process as an underlying cause |
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Term
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Definition
| medications for excessive daytime somnolence and cataplexy |
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Term
| medications for excessive daytime somnolence |
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Definition
modafinil, armodafinil
dextroamphetamine
methylphenidate
gamma-hydroxybutyrate |
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Term
| medications for cataplexy |
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Definition
tricyclic antidepressants
gamma-hydroxybutyrate |
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Term
sleep disorders
trouble sleeping |
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Definition
sleep onset delay
early morning arousal
sleep fragmentation |
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Term
sleep onset delay
2 flavors |
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Definition
1. psychophysiologic insomnia
2. delayed sleep phase syndrome |
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Term
psychophysiologic insomnia
clinical features |
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Definition
unconscious association of getting into bed and not being able to sleep
multiple potential triggers (anxiety, depression, medical, environmental...)
establishes a conditioned association between bedroom and inability to sleep |
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Term
psychophysiologic insomnia
management |
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Definition
behavioral interventions
good sleep hygiene |
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Term
| CBT for treatment of insomnia |
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Definition
set bed/wake time
no daytime naps
no caffeine after noon
no exercise after dinner
dark, quiet, comfortable bedroom
leave bedroom is unable to fall asleep |
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Term
delayed sleep phase syndrome
clinical features |
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Definition
a circadian rhythm disorder
able to fall asleep readily and for normal amount of time, but do so at "wrong times"
do not feel sleepy at bedtime, stay up until ~3AM and awaken after short interval due to demands of work or school |
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Term
| other circadian rhythm disorders |
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Definition
(delayed sleep phase syndrome)
advance sleep phase syndrome
jet lag
shift work |
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Term
early morning awakening
3 flavors |
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Definition
1. psychiatric and psychologic causes (depression, alcohol)
2. psychophysiologic factors
3. advanced sleep phase syndrome |
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Term
advanced sleep phase syndrome
clinical features |
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Definition
patients fall asleep and wake up too early
sometimes familial |
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Term
advanced sleep phase syndrome
pathophysiology |
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Definition
2 families found with specific clock gene mutations in which advanced sleep phase syndrome was prevalent
-point mutation in Per2 gene coding for phosphorylation site in a casein kinase binding domain
-missense mutation in a casein kinase gene |
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Term
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Definition
sleep that is frequently interrupted is not sufficiently restorative
interruptions may arise from: nocturia, GERD, orthopnea, cluster HA, apnea, PLMs, med schedule, ...)
may initiate the same psychophysiologic cycle that leads to delayed sleep onset or early morning awakening |
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Term
| pharmacologic therapy for treatment of insomnia |
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Definition
BZDs
-temazepam, estazolam, triazolam
non-BZD BZD receptor agonists
-eszopiclone (Lunesta), zolpidem (Ambien), zaleplon
melatonin agonists
-ramelteon |
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Term
sleep disorders
abnormal behavior during sleep |
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Definition
REM sleep parasomnias
NREM sleep parasomnias |
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Term
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Definition
REM sleep behavior disorder
nightmares |
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Term
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Definition
night terrors
sleepwalking/talking
PLMs
misc (bruxism, enuresis, head-banging, and other rhythmic movements) |
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Term
REM sleep behavior disorder
clinical features |
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Definition
REM sleep WITHOUT atonia
patient "act out" their dreams
vigorous, complex motor activity that lasts seconds - minutes with varibale frequency |
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Term
REM sleep behavior disorder
mangement |
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Definition
safety
eval for associated neurologic disease
1st line med = clonazepam
2nd line meds = melatonin, donepezil, dopamine agonist |
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Term
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Definition
| particularly vivid and disturbing dreams that often are associated with arousal from REM sleep |
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Term
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Definition
sudden arousal from deep sleep
scream/terror/confusion
extreme autonomic arousal
variable motor activity |
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Term
sleep terrors
vs.
nightmare |
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Definition
terror: NREM sleep, no plot, amnesia of event, autonomic arousal
mare: REM sleep, dream with plot, details often remembered |
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Term
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Definition
reassurance
meds only if it gets very disruptive
-TCA, BZD |
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Term
sleepwalking/talking
clinical features |
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Definition
during NREM sleep, first 1/3 of the night
wide range of complex, automatic behaviors
most common ages 4-6 years; family hx
duration 1-5 minutes, but can be longer than an hour when behaviors are more complex |
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Term
sleepwalking/talking
management |
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Definition
ensure safety
if frequent and disruptive/dangerous
-BZD |
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Term
periodic leg movements
PLM |
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Definition
stereotyped, period movements of legs
typically dorsiflexion of ankles and small toes, flexion of knee and hip |
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Term
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Definition
(during wakefulness)
creeping, crawling sensation; associated with desire to move legs
mainly while lying or sitting, worse at night
more common in patients with anemia or renal failure |
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Term
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Definition
80-90% of RLS patients have PLMs of sleep
only a minority of patients with PLMs have RLS |
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Term
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Definition
same for both PLM and RLS
levodopa, dopamine agonists, clonazepam, gabapentin |
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Term
| diagnostic tests for sleep disorders |
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Definition
polysomnogram
multiple sleep latency test (MSLT) |
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Term
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Definition
all-night recording of eye movements, EEG, EKG, EMG, oximetry, airflow at nose and mouth, thoracic and abdominal wall motion
may include video monitoring |
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Term
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Definition
measure of daytime sleepiness
subject takes 4 or 5 brief naps at 2-hour intervals on the day after an adequate night's sleep
EEG, EMG and eye movements monitored to determine the mean time the subject takes to fall asleep |
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