Symptoms of Narcolepsy
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1 Symptoms of Narcolepsy v Sleep attacks Brief episodes of sleep that occur many times a day May occur without warning or be preceded by drowsiness Patient usually feels refreshed afterwards Refractory period of 1+ hrs before next attack v Excessive daytime sleepiness (EDS) Most disabling symptoms Waxing and waning of alertness and attention 1
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3 Symptoms of Narcolepsy (con t) v Cataplexy Bilateral loss of muscle tone with consciousness maintained Lasts a few seconds to a couple of minutes Severity ranges from a mild sensation of muscle weakness to complete postural collapse Wide range in frequency Episodes are precipitated by a sudden emotional stimulus (laughter, anger, surprise) 3
4 Symptoms of Narcolepsy (con t) v Nocturnal sleep disruption Fragmented and shortened, with multiple awakenings Abnormal timing of REM sleep (at sleep onset) v Hypnagogic hallucinations Visual, auditory, or tactile hallucinations (vivid sensory experiences) lasting 1 to 15 min Experienced upon going to sleep, when person is still conscious 4
5 Symptoms of Narcolepsy (con t) v Sleep paralysis Inability to move voluntary (striated) muscles Experienced upon falling asleep or waking up Temporary condition lasting a few minutes May be accompanied by hypnagogic hallucinations 5
6 SINTOMI ASSOCIATI CON LA NARCOLESSIA 6
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9 ELECTRICAL RECORDINGS taken from the brain and neck muscles of a dog with narcolepsy show that cells in the locus coeruleus are inactive during the muscle paralysis of a cataplexy attack, whereas those in the medial medulla are active. The brain recordings (blue) were obtained using tiny electrodes; the muscle ones (red), with an electromyograph. 9
10 Brain Circuits in Narcolepsy 10
11 New Ideas on Narcolepsy v Animal models Doberman pinschers v Neurochemical Basis Defect in Hypocretins or Orexins (HO) Narcoleptic people have little HO v Genetic basis Defective gene found in dogs No genetic abnormality in people 11
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14 Narcolepsy vs. Hypersomnia Narcolepsy Cataplexy (late appearing) 70% Sudden daytime sleep attacks (by definition) Sleep-related hallucinations, sleep paralysis (REM sleep) 20-40% Primary hypersomnia Longer/less disrupted nocturnal sleep than narcolepsy More trouble waking up More pervasive daytime sleepiness Longer/less refreshing daytime naps, little/no dreaming Kleine-Levin syndrome: EEG slowing, decreased REM latency, bursts of theta activity 14
15 Course of Narcolepsy v Symptomatic course Usually begins in adolescence with onset of EDS and sleep attacks Cataplexy, sleep paralysis, and hypnagogic hallucinations may occur immediately or develop several years later Nocturnal sleep disruption may appear several years after onset of EDS Auxiliary symptoms may wax and wane, but EDS is chronic and unrelenting EDS is not exacerbated by age-related sleep changes 15
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17 Social Impact of Narcolepsy v Half of patients have difficulties in work, relationships, and social lives due to symptoms v Drowsiness, impaired attention, and poor concentration interfere with education and employment v Friends and family may misattribute symptoms to boredom, laziness, or psychological problems v Attempts to control cataplexy by avoiding emotional situations can affect relationships 17
18 Assessment of Narcolepsy v No standardized measures of cataplexy v Objective measures of daytime sleepiness MSLT (Multiple Sleep Latency Test) MWT (Maintenance of Wakefulness Test) 24hr PSG v Subjective measures of daytime sleepiness Stanford Sleep Scale, Epworth Sleepiness Scale Useful for assessing baseline measures of sleepiness and treatment response, but not sufficient for diagnosing narcolepsy 18
19 Assessment of Narcolepsy (con t) v MSLT min daytime nap trials given at 2hr intervals in laboratory Patients instructed to fall asleep Sleep latencies are averaged across nap trials Mean sleep latencies < 5 min are typical > 2 sleep onset REM periods are suggestive but not necessarily diagnostic of narcolepsy 19
20 Assessment of Narcolepsy (con t) v MWT Patients instructed to stay awake Sensitive to effects of treatment v Improvements in sleep latencies on MWT or MSLT may not predict improved functional abilities outside the lab setting 20
21 Pharmacologic Management v Stimulants (modafinil, methylphenidate, pemoline, dextroamphetamine) Effective in reducing or eliminating EDS Improves daytime performance Modafinil is preferred due to less frequent side effects 40% of patients are able to remain awake during the day Many patients are non-compliant 21
22 Pharmacologic Management (con t) v REM sleep suppressants TCAs (clomipramine, imipramine, protriptyline) and SSRIs o o TCAs are more effective than SSRIs for treating cataplexy Anticholinergic side effects may limit use v Pharmacologic treatment is not usually prescribed for other REM dissociation phenomena Treatment of cataplexy usually reduces severity of hypnagogic hallucinations and sleep paralysis 22
23 Behavioral Approaches v Scheduled naps and sleep hygiene strategies are the only approaches that have been tested v Most patients combine medications with behavioral techniques to: Maintain alertness (exercise, caffeine, sugar, stress management, altering schedule, avoiding social situations) Control cataplexy (napping, taking vitamins, avoiding sweets, stress management, avoiding emotional situations) 23
24 Sleep-wake Scheduling for Treating EDS v Efforts to consolidate nocturnal sleep Benzodiazepines and gamma hydroxybutyrate do not improve EDS Stimulants improve nocturnal sleep and EDS Large dose of nighttime sleep (12 hrs) resulted in a small increase in MSLT sleep latency Sleep hygiene program combined with stimulants reduced perceived symptom severity but did not reduce daytime sleep 24
25 Sleep-wake Scheduling for Treating EDS (con t) v Efforts to consolidate nocturnal sleep (con t) Nap studies: o o o o Naps can briefly increase alertness Nap effects are transient A long nap instead of multiple short naps may be the best strategy for patients who are on a stimulant holiday or who want to limit their use of stimulants Most advantageous time to schedule nap is earlier in the day instead of post-lunch Summary: Extending sleep period at night and adding scheduled nap periods can increase daytime alertness 25
26 Sleep-wake Scheduling for Treating EDS (con t) v Combining prescribed sleep periods with stimulants Patients keeping a regular sleep schedule and taking scheduled naps had less EDS and less severe symptoms compared to nap-only group and regular sleep schedule group o o All groups showed reduction in daytime sleep if EDS levels were high pre-treatment Efficacy of scheduled sleep periods is highly associated with pre-treatment levels of daytime sleepiness 26
27 Sleep-wake Scheduling for Treating EDS (con t) v Combining prescribed sleep periods with stimulants (con t) Summary: Schedule manipulations (adding naps, extending sleep periods, regularizing sleep schedules) can produce improvements in daytime alertness at least for short periods. Regardless, patients may remain quite sleepy 27
28 Dietary Approaches for Managing EDS v Manipulations such as restricting sugars, taking supplements, and avoiding meals are popular among patients but research has not supported their efficacy Narcoleptic patients may consume more snacks than controls (due to longer time spent out of bed), but caloric/nutritional intake is similar Narcoleptic patients have a higher BMI and slower metabolic rate than controls (hypocretin system) 28
29 v Caffeine Dietary Approaches for Managing EDS (con t) Has not been investigated as a treatment for EDS in narcoleptic patients Most patients find it ineffective for controlling EDS v L-tyrosine One study showed this to increase alertness, but this effect has not been replicated Studies of dietary intake of other neurotransmitter precursors involved in alertness have not been effective 29
30 Other Behavioral Approaches v Case studies Hypnosis for controlling EDS, cataplexy, and sleep paralysis Progressive muscle relaxation and fluid restriction to improve nocturnal sleep These approaches have not been scientifically proven to be viable treatments v Bright light therapy Ineffective in treating symptoms of narcolepsy 30
31 Future Directions v Medication use Examine patient attitudes towards use of medications Improve compliance with medications Combat patients fears about addiction to stimulants Discuss problems and safety issues with non- compliance to medications 31
32 Future Directions (con t) v Efforts to find a cure Human narcolepsy is associated with a deficiency in the hypocretin/orexin system Deficit may be associated with damage to the hyopthalamic centers where peptide receptors are located 32
33 Future Directions (con t) v Summary Stimulants help maintain wakefulness but do not bring patient to the level of normal controls with respect to sustained performance Stimulants are more effective than behavioral strategies 33
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