Normal sleep and sleep disorders (no sketch)

ACh in sleep

Cholinergic activation system, through projections to the thalamus, is important in EEG desynchronization characteristics of waking and REM sleep. REM-on neurons (selective activity during REM sleep) in brainstem use ACh as neurotransmitter. Activity of this group of neurons activity in effector neurons for REM sleep phenomena. Many peptides (ex: substance P) are co-localized with ACh in brainstem neurons, they may modify responsiveness of ACh and may have independent actions.

Nightmare disorder

Form of REM sleep parasomnia Deam anxiety This condition consists of repeated awakenings with detailed recall of extended and very frightening dreams. The awakenings are more frequent in the second half of the sleep period. On awakening, the person rapidly becomes alert and oriented.

Sleep promoting factors

muramyl peptides (found in bacterial cell walls), lipopolycaccharides, prostaglandins, IL-1, IF-alpha-2, tumor necrosis factor, delta sleep-inducing peptide and vasoactive intestinal peptide. *besides enhancing sleep, all also expert effects on body temp & immune response.

Sleep apnea

2 forms = obstructive & central. Obstructive is most common. obstruction in upper airway. Polysomatography used to confirm and quantify severity. Treatment = CPAP (continuous positive airway pressure).

Parasomnias

Abnormal behavior during sleep Undesirable movements or behaviors during sleep usually in children. 2 categories (NREM & REM) most associated with NREM sleep cuz of atonia in REM *ex may rep disorder of arousal from slow wave sleep resulting in episodes of only partial awakening.

Pathogenesis of narcolepsy-cataplexy

Both genetic predisposition and environmental triggers are involved. There is an association between major histocompatibility complex (MHC) genes and narcolepsy-cataplexy, which is hypothesized to involve an autoimmune component. Hypocretin deficiency (demonstrated by low CSF hypocretin-1 levels) is the cause of most narcolepsy-cataplexy cases in animals and humans. Autopsy studies have shown a selective loss of posterior hypothalamic neurons that produce the neuropeptide hypocretin (orexin). (Hypocretins (orexins) are synthesized in the hypothalamus with widespread projections, especially to brainstem nuclei containing norepinephrine, histamine, serotonin and dopamine neurons. Hypocretin neurons integrate metabolic and sleep- and wake-related inputs. ) Additional models hypothesize hyperactivity in the cholinergic system with hypoactivity in the catecholaminergic system.

sleep-wake cycle

Controlled by circadian rhythms regulated by the SCN (suprachiasmatic nucleus) of the hypothalamus. Light is biggest factor in controlling rhythms & NMDA is involved.

Narcolepsy-cataplexy

Daytime somnolence + cataplexy (sudden loss of postural tone that occurs while pt is awake but identical to atonia that occurs in REM) "sleep attacks" often occur at times of strong emotion Sleepiness can not be overcome with any amount of normal sleep. Atonia may be of a single muscle group or generalized leading to collapse though consciousness is preserved. Starts in adolecnece with narcolepsy followed by cataplexy.

Narcolepsy Narcolepsy without cataplexy Idiopathic hypersomnia disorders

Excessive daytime sleepiness. Disordered regulation of REM sleep resulting in intrusion of components of REM sleep into NREM sleep and waking state. Diagnostic = sleep-onset REM period (period of REM sleep that occurs in first 15 mins of sleep) excessive daytime sleepiness & mul sleep-onset REM periods (SOREMPs) on the MLST poorly defined conditions characterized by excessive daytime sleepiness and not diagnosed as narcolepsy (no REM abnormalities during the MSLT)

Physiologic events of REM sleep

Have effector neurons in brainstem reticular formation. (ex: pontine reticular formation). These neurons are important for rapid eye movements & muscle atonia of REM sleep.

Histamine in wake-sleep regulation

Histamine-containing neurons are localized in the posterior hypothalamus and are REM-off. Histamine system conceptualized as 1 of the wakefulness-promoting system. (think that drowsiness is common side effect of antihistamines!)

Cycle of stages in sleep

N1 (sleep drowsiness) --> N2 --> N3 (deep sleep)(mins-1hr) --> N2 --> Stage R (15-20 mins) --> non-REM cycle *Alternating pattern continues through night, but as night progresses periods of N3 gets shorter and REM gets longer.

What is RBD closely associated with?

Narcolepsy-cataplexy. There are pts with overlapping parasomnias, demonstrating motor-behavioral dyscontrol extending across NREM & REM sleep

NREM sleep parasomnias

Parasomnia = Abnormal behavior during sleep Night terrors = usually don't fully awaken & have no recall. partial arousal from delta sleep. Sleepwalking (somnambulism) = disorder of impaired arousal.

Diagnostic testing of sleep

Polysomnogram = all-night recording of eye movements, EEG, EKG, EMG, ear oximetry, airflow at nose and mouth & thoracic and abd wall motion. MSLT (multiple sleep latency test) = measure of daytime sleepiness. Measures time needed to fall asleep for brief naps during day.

Probable cause of RBD

Pontine tegmental lesions, involving serotoneric, monoaminergic & cholinergic neurotransmission. It is thought that the emergence of RBD results from lesion localization related to any underling neurological disorder, explaining how an array of etiologically different CNS disorders could trigger RBD.

RLS pathogenesis

Probably involves abnormalities in subcortical CNS dopaminergic systems, with DA receptor dysfunction and increased DA production. Dopaminergic agonists and levodopa provide effective treatment for RLS. (The mechanism of this is not known, the effect is paradoxical, but it works. DA synaptic effects are complex and may be excitatory or inhibitory depending on the receptor. Also the amount of DA released may be dependent on stimulus frequency.) The pathophysiology may involve iron deficiency leading to brain DA abnormalities. Also there is evidence for involvement of hypocretin-1 (orexin-A) and histamine.

Primary insomnia

Pt's with this have been shown to have less diurnal (during the day/daily) sleepiness, higher heart rates, higher core body temps, and greater metabolic activity. Most severe case has an insidious (gradual but harmful) onset during childhood & follows chronic course

2 main stages of sleep in normal adult

REM (rapid eye movement) = brain is active and body paralyzed (except eye movements, middle ear ossicles and resp). Dreams occur. NREM (non-REM) = brain less active but body can move. stages categorized on EEG. -Stage W (wake) -Stages N1-N3 (N3 = deep sleep = delta waves on EEG) -Stage R (REM sleep)

REM sleep behavior disorder (RBD)

REM motor atonia breaks down and pts act out dreams usually affects middle-aged or older men Can be acute (drug withdrawal or intoxication) or chronic. Chronic has been show to be associated with synucleinopathies (parkinson, dementia with Lewy bodies, & mul system atrophy) & marked decrease of pigmented neurons in locus coeruleus & substantia nigra.

Restless leg syndrome

Sensorimotor disorder often severely affecting sleep. PLM (periodic leg movements) may occur during sleep (PLMS) and/or while lying or sitting up awake (PLMW). Involves a disorder of transition states between wake and sleep. -Early-onset RLS (before 45) caused by pervasive iron metabolism abnormality producing brain iron insufficiency. This produces hyperdopaminergic state with exaggerated circadian pattern of DA release. Prob also disrupts other neurotransmitter systems (orexin/hypocretin & histamine). -Late-onset RLS (after 45) = more diverse causes though also DA abnormalities. Genetic component more important here than env. esp for late-onset.

Serotonin in sleep-wake cycle

Serotonin acts as a modulatory neurotransmitter; serotonergic input from the dorsal raphe nucleus in the midbrain periaqueductal gray area will act to inhibit the effects of light on the system and is associated with different aspects of the sleep-wake cycle. There is minimal serotonergic input during REM sleep, and maximal input directly following REM. Thus these neurons may normally inhibit phasic REM events and their silence during REM sleep indicates a termination of this inhibition.

Sleep disorders have high comorbidity with?

Sleep and psychiatric disorders are highly comorbid with the highest rates being with anxiety and depression. Studies suggest that the presence of a sleep disturbance may delay recovery from depression. Many antidepressant medications, particularly SSRI's have been found to improve sleep disturbances in addition to relieving depressive symptoms.

3 main patterns of insomnia

Sleep-onset delay (trouble falling asleep) Early morning arousal (trouble staying asleep) Sleep fragmentation (repeating awakenings)

3 kinds of complaints regarding sleep Most common sleep disorders

Trouble staying awake (hypersomnia) Trouble sleeping (insomnia) Abnormal sensations or behavior during sleep (parasomnias) Obstructive sleep apnea Insomnia Restless leg syndrome Narcolepsy and idiopathic hypersomia

Atonia during REM sleep

Under control of the magnocellular nucleus of the medulla; maintained via the reticulospinal tract which mediates inhibition of motor neurons

Orexin in wake-sleep regulation

a hypocretin that has been previously associated with feeding behaviors, has also been found to have a role is sleep behavior. Many areas of the brain associated with the sleep-wake cycle, specifically the lateral and dorsal hypothalamus, have orexin neurons and receptors. Orexin A has been found to activate NE neurons in the locus coeruleus, which are believed to play a role in promoting wakefulness.