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Central Disorders of Hypersomnia and Narcolepsy Lynn Liu, MD, FAASM, FACNS, FAAN February 10, 2021 Objectives • Describe the prototypical clinical features of Narcolepsy 1 • Differentiate between NT1 and NT2 • Compare and contrast different hypersomnia syndromes CHEST 2014; 146 ( 5 ): 1387 - 1394 Narcolepsy • Chronic neurological disorder – Inability to control sleep-wake cycles – Excessive daytime sleepiness – Refreshing naps • Consequences of untreated, narcolepsy – Psychological, social, and cognitive function and development – Inhibit academic, work, and social activities. Prevalence • Symptoms start at any age often in childhood (ages 7 to 25) • Affects males and females equally • ~135,000 to 200,000 people in the US • Often goes undiagnosed or misdiagnosed Symptoms Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley and Sons, Inc.; 2006:145-149. Symptoms • Most specific symptom of narcolepsy type 1 • Sudden, brief (<2 min) loss of muscle tone with retained consciousness • Triggered by strong emotions, such as laughter, surprise, or anger N Engl J Med 2015; 373:2654-2662 DOI: 10.1056/NEJMra1500587 Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley and Sons, Inc.; 2006:145-149. Symptoms • Vivid dreamlike experiences that occur while falling asleep or waking Leschziner G Narcolepsy: a clinical review Practical Neurology 2014;14:323-331 Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley and Sons, Inc.; 2006:145-149. Symptoms • Hallmark symptom, 100% of patients with narcolepsy • Inability to stay awake and alert during the day Leschziner G Narcolepsy: a clinical review Practical Neurology 2014;14:323-331 Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley and Sons, Inc.; 2006:145-149. Symptoms • Disturbing, temporary inability to move voluntary muscles or speak during sleep-wake transitions Leschziner G Narcolepsy: a clinical review Practical Neurology 2014;14:323-331 Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley and Sons, Inc.; 2006:145-149. Symptoms • Most specific symptom of narcolepsy type 1 • Sudden, brief loss of muscle tone with retained consciousness • Triggered by strong emotions, such as laughter, surprise, or anger • Vivid dreamlike experiences that occur while falling asleep or waking • 100% of patients with narcolepsy • Inability to stay awake and alert during the day • Disturbing, temporary inability to move voluntary muscles • Frequent awakenings due to sleep-wake state instability Pelayo R, Lopes MC. Narcolepsy. In: Lee-Chiong TL, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley and Sons, Inc.; 2006:145-149. Types of Narcolepsy • Narcolepsy Type 1 – Excessive daytime sleepiness daily for ≥3 months – One or both of the following: • Cataplexy and mean sleep latency ≤8 minutes and ≥2 SOREMPs on MSLT; – SOREMP (≤15 min after sleep onset) on preceding nocturnal PSG may replace one of the SOREMPs on MSLT • Low or absent CSF hypocretin-1 levels • Narcolepsy Type 2 – Excessive daytime sleepiness and MSLT findings as above, but without cataplexy – CSF hypocretin-1 levels are unknown or are above the threshold for narcolepsy type 1 – The hypersomnolence and/or MSLT findings are not better explained by other causes • Insufficient sleep, OSA, delayed sleep phase disorder, or the effect of medications/substances or withdrawal. • Secondary narcolepsy – Injury to the hypothalamus – Typical symptoms of narcolepsy – Severe neurological problems and sleep for long periods (more than 10 hours) each night. American Academy of Sleep Medicine . International Classification of Sleep Disorders. 3rd ed. Darien, IL : American Academy of Sleep Medicine; 2014. Etiology • Autoimmune disorders – Loss of brain cells that produce hypocretin/orexin due to a combination of genetic and environmental factors Thannickal, T, Moore, R, Nienhuis, R, et al. Reduced Number of Hypocretin Neurons in Human Narcolepsy, Neuron, Vol 27, Issue 3, 2000, Pages 469-474. Etiology • Autoimmune disorders • Family history – Most cases of narcolepsy are sporadic – There are clusters in families • Up to 10 percent of individuals diagnosed with narcolepsy with cataplexy have a close relative with similar symptoms. C. Capittini et al. / Sleep Medicine 52 (2018) 150e157 Etiology • Autoimmune disorders – Loss of brain cells that produce hypocretin due to a combination of genetic and environmental factors. • Family history – Most cases of narcolepsy are sporadic – There are clusters in families • Up to 10 percent of individuals diagnosed with narcolepsy with cataplexy have a close relative with similar symptoms. • Brain injuries – Rarely, traumatic brain injury to areas that regulate wakefulness and REM sleep – Tumors – Multiple Sclerosis Pediatric Neurology 2018 8427-31DOI: (10.1016/j.pediatrneurol.2017.12.016) Diagnosis • Clinical evaluation – Detailed medical history – Major symptoms specific to narcolepsy • Cataplexy is the most specific symptom – Physical exam • Identify other neurological conditions – Sleep journal • Sleep habits for 1-2 weeks Diagnosis • Polysomnogram (PSG) • Overnight recording • Identify early REM sleep • Exclude other conditions – Obstructive sleep apnea – Periodic Limb Movements – Adequate sleep Leschziner G. Pract Neurol 2014;14:323–331. doi:10.1136/practneurol-2014-000837 Diagnosis • Multiple sleep latency test (MSLT): • Assesses daytime sleepiness • Sleep Onset REM Periods (SOREMP) • Five short naps separated by two hours Richardson GS, Carskadon MA, Flagg W: Excessive daytime sleepiness in man: multiple sleep latency measurements in narcoleptic and control subjects. Electroencephalogr Clin Neurophysiol 1978;45:621–627. Diagnosis • CSF hypocretin/orexin level • Lumbar puncture – Measure CSF levels of hypocretin-1 The Lancet Neurology 2008 7649-662DOI: (10.1016/S1474-4422(08)70140-6) Treatment • Medications • Lifestyle Changes • Safety Precautions N Engl J Med 2015; 373:2654-2662 DOI: 10.1056/NEJMra1500587 Treatments • Lifestyle changes – Take short naps. Regularly scheduled naps at times when they tend to feel sleepiest. – Maintain a regular sleep schedule. Going to bed and waking up at the same time every day, even on the weekends, can help people sleep better. – Avoid caffeine or alcohol before bed. Individuals should avoid alcohol and caffeine for several hours before bedtime. – Avoid smoking, especially at night. – Exercise daily. Exercising for at least 20 minutes per day at least 4 or 5 hours before bedtime also improves sleep quality and can help people with narcolepsy avoid gaining excess weight. – Avoid large, heavy meals right before bedtime. Eating very close to bedtime can make it harder to sleep. – Relax before bed. Relaxing activities such as a warm bath before bedtime can help promote sleepiness. Also make sure the sleep space is cool and comfortable. Safety precautions • Safety – Sleep attacks or cataplexy can result in injuries such as stairs, cooking or swimming • Driving – Untreated symptoms can result in automobile accidents • Americans with Disabilities Act – Employers must provide reasonable accommodations – Negotiate with employers to modify their work schedules so they can take naps – Children and adolescents with narcolepsy should work with school administrators • Support groups – Develop better coping strategies – Reduce social isolation and embarrassment about their symptoms – Promote a network of social contacts who can help and provide emotional support Covid-19 and Narcolepsy • Brazilian study – On-line survey of 78 people with narcolepsy • 25% fewer still going to work, 43% more working from home, 60% lost jobs • Irregular sleep wake schedules • Increased use of stimulants • Italian study – Telephone interviews with 50 consecutive NT1 patients • 3 Groups: 40% no changes in schedule, 44% work/study at home, 8% lost job • Increased nocturnal awakenings – Group 1 and 3 • Increased naps and nocturnal sleep and BMI – Group 2 Rodrigues Aguilar AC, et al The effects of the COVID-19 pandemic on patients with narcolepsy. J Clin Sleep Med. 2020 Oct 30. doi: 10.5664/jcsm.8952. PMID: 33124977. Postiglione E, et al. Impact of COVID-19 pandemic lockdown on narcolepsy type 1 management. Brain Behav. 2020 Nov 28:e01955. doi: 10.1002/brb3.1955. PMID: 33247632 Idiopathic Hypersomnia • Hypersomnia for at least 3 months • No cataplexy • Sleep paralysis and Hypnagogic Hallucinations uncommon • Sleep Drunkenness/Inertia • Longer and unrefreshing naps CHEST 2015; 148 ( 1 ): 262 - 273 Idiopathic Hypersomnia • Prevalence unclear • Etiology unknown – Genetic – Low histamine levels – Altered cytokines – Altered GABAA receptors CHEST 2015; 148 ( 1 ): 262 - 273 PSG and MSLT • TST of 12-14 hours by PSG or actigraphy • High sleep efficiency of >90% • MSL < 8 minutes • Fewer than 2 SOREMP CHEST 2015; 148 ( 1 ): 262 - 273 Central Disorders of Hypersomnia NT1 NT2 IH Clinical Symptoms Hypersomnia >3 months Yes Yes Yes Cataplexy Yes No No Naps Refreshing Refreshing Long and not refreshing Labs Hypocretin levels Very low Low to normal Normal PSG TST >11 hours per 24 hours Sleep Efficiency Poor >90% MSLT MSL < 8 minutes < 8 minutes < 8 minutes SOREMP > 2 > 2 < 2 Modified from SleepJ, 2020,Vol.43, No.8 Kleine-Levin Syndrome • Rare disorder of relapsing and remitting symptoms at least once a year – Hypersomnia - up to 20 hours per day lasting a few days to
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