Narcolepsy and Other Hypersomnias

1. Narcolepsy and Other Hypersomnias Marietta B. Bibbs, RPSGT Morton Plant Mease Healthcare Clearwater, FL

2. Objectives • Discuss etiology and symptoms of narcolepsy • Discuss causes of excessive sleepiness • Define idiopathic hypersomnia • Describe other causes of hypersomnia • Define the three factors that characterize sleepiness • Demonstrate the dangers of drowsy driving

3. What is Narcolepsy? • A neurological disorder caused by deficiency of an excitatory neuro-transmitter leading to excessive sleepiness and other atypical REM-related activity. • It is a chronic disorder characterized by excessive daytime sleepiness despite a restful night of sleep, and sudden and uncontrollable attacks of sleep that are sometimes accompanied by hallucinations and sleep paralysis.

4. Characteristics of Narcolepsy • Excessive sleepiness with cataplexy • Rapid transition from wakefulness to sleep • Early onset REM epochs • Automatic behavior

5. Narcolepsy • Other Symptoms: • Sleep Paralysis (waking with inability to move—a frightening condition). • Hypnagogic hallucinations (perceptual distortions that seem real) • Characterizations: • Repeated naps, lasting 10-20 minutes with sleepiness reappearing in 2-3 hour repetitious patterns. • Waking up refreshed from naps

6. Unique Distinctions of Narcolepsy • Inability to consolidate wakefulness in the day (and sleep at night) • Cataplexy (loss of muscle tone in response to strong, usually positive, emotions) • Short naps are very refreshing • Sleepiness returns within hours after napping • Cataplexy may be localized or general, and vary from mild to very disabling. • Clustered cataplexy episodes may result in status cataplecticus, lasting minutes up to an hour

7. Four Primary Symptoms • Excessive Daytime Sleepiness (with uncontrollable sleep attacks and automatic behavior, and the most prominent symptom of narcolepsy). • Cataplexy (loss of bilateral peripheral muscle tone). • HypnagogicHallucinations (usually occur as vivid dreams at sleep onset). • Sleep Paralysis (usually occurs at sleep onset). • It is rare for a person to have all four symptoms.

8. Sleep Attacks of Narcolepsy • Uncontrollable sleep attacks occur most often in sedentary situations, but can also occur in situations where sleep would normally not occur such as in the middle of conversation, while driving, eating, walking, etc. • Narcoleptics can fight sleep attacks for a while, but eventually lose the fight and give in to the urge to sleep.

9. Cataplexy • The most exclusive feature of narcolepsy. • Cataplexy is always precipitated by powerful emotion, such as laughter, crying, anger, etc. • It is characterized by a sudden, bilateral loss of muscle tone in which consciousness and memory are intact • Respiratory and ocular muscles are not affected.

10. Cataplexy • A catapletic attack can last from a few seconds to several minutes. • The loss of muscle tone in cataplexy can be very mild (jaw dropping, slurred speech) to a complete collapse in which the person can fall to the ground. • Strong emotion can sometimes precipitate episodes of cataplexy that occur in succession, called status cataplecticus).

11. Onset and Diagnosis • Early adolescence is the peak age of onset for narcolepsy, but it can have onset in early childhood and adulthood. • Can be diagnosed with a good sleep and family history of narcolepsy. • Diagnosis confirmed by polysomnography and MSLT.

12. Diagnosis • Clinical findings and characteristic features of polysomnography are key in the diagnosis of narcolepsy • The Multiple Sleep Latency Test (MSLT) confirms the diagnosis and the severity of excessive sleepiness.

13. Automatic Behavior in Narcolepsy • Performing a routine task automatically without conscious awareness. The narcoleptic patient continues to perform the task while falling asleep (microsleep) and without memory of performing the action.

14. Nocturnal Sleep Disturbance • Narcoleptic patients fall asleep easily, but often complain of trouble staying asleep during the night, despite the fact that they may experience sleepiness and fall asleep repeatedly during the day. • Narcoleptics don’t sleep more than normal people over the 24-hour cycle, but they do have frequent awakenings or excessive shifts to stage N1.

15. Diagnostic Criteria….. • Narcolepsy with Cataplexy • Narcolepsy without Cataplexy • Narcolepsy Due to Medical Conditions

16. Diagnostic Criteria…. • A complaints of excessive daytime sleepiness occurring daily for at least 3 months. • EDS cannot be explained by another sleep disorder, medical or neurological disorder, medication use or substance use. • A definite history of cataplexy (sudden and transient episodes of loss of muscle tone triggered by emotions).

17. Diagnostic Criteria….. Confirmation of the disorder through multiple sleep latency testing (MSLT). The MSLT results in a mean sleep latency less than or equal to 8 minutes with two or more sleep onset REM periods (SOREMPS) observed following sufficient nocturnal sleep of a minimum of 6 hours. The Stanford Sleepiness Scale and Epworth Sleepiness Scale can be used to aide in the clinical diagnosis of Narcolepsy.

18. Other Diagnostic Tools • HLA typing can be used since there is a strong correlation of narcolepsy in individuals with cataplexy when human leukocyte antigen typing is positive for DQB*0602 or DR2.

19. HLA Typing • Although the test can be used to confirm narcolepsy diagnosis, it is not very useful in ruling out narcolepsy. • If presence of DR2 or DQB1*602 are positive, this does not directly indicate narcolepsy, but indicates that the person has a genetic predisposition to develop the disease. • HLA typing assists in determining the risk level in families of narcoleptic patients. • Almost all narcoleptic patients will have presence of HLA-DR2 and DQ1. • In narcoleptics with cataplexy, 90-100% of them will have the DQB1*602 allele regardless of their race .

20. Developments on Narcolepsy • The etiology of narcolepsy is now better understood, and the pathophysiology of narcolepsy is recognized and linked to defects in the orexin (hypocretin) neuropeptide system resulting in impaired control of sleep and wakefulness. • Most cases of narcolepsy in humans have been associated with low or absent cerebrospinal fluid levels of hypocretin.

21. The Orexin Connection… • Patients who have Narcolepsy with cataplexy are associated with loss of approximately 50,000-100,000 hypothalamic neurons containing Orexin. • Hypocretin(Orexin) levels in CSF <= 100 p/mL.

22. The Orexin Connection… • The discovery that orexin/hypocretin dysfunction causes narcolepsy indicates a major role for this system in sleep regulation and integrating metabolic, circadian and sleep debt . • When orexin A/hypocretin-1 is administered, it promotes wakefulness, increases body temperature, and elicits a strong increase in energy expenditure.

23. Narcolepsy Research • When a person is sleep deprived, transmission of orexin A/hypocretin-1 increases and it is now thought that this system is more important in the regulation of energy expenditure than in food intake. • Narcoleptic patients who are deficient in orexin/hypocretin have increased obesity rather than decreased BMI, as would be expected if orexin/hypocretin were primarily an appetite stimulating peptide.

24. Differential Diagnosis • Patients with symptoms of narcolepsy without cataplexy should be distinguished from those with narcolepsy. • When narcolepsy is suspected, but cataplexy is NOT present, other disorders with similar symptoms should be ruled out. These include: • idiopathic hypersomnia • obstructive sleep apnea • periodic limb movement disorder/restless legs syndrome • depression • inadequate sleep secondary to medical disorders or medications

25. Differential Diagnosis • Patients with Idiopathic hypersomnia will not have the REM related features of narcolepsy (sleep paralysis, hypnagogic hallucinations or three out of five REM onset periods during MSLT). • Patients with OSA will not wake from naps feeling refreshed, but narcoleptic patients will feel refreshed following naps.

26. Differential Diagnosis • There is a group of patients with all the symptoms of narcolepsy, including HLA-DR2 positivity, along with two or more sleep-onset REM periods during MSLT, and may also have hypnagogic hallucinations and/or sleep paralysis but they DO NOT have cataplexy. • These patients may be classified as having narcolepsy, essential hypersomnia, primary hypersomnia, ambiguous narcolepsy or atypical narcolepsy.

27. PolysomnographicFeatures • Sleep latency of less than 10 minutes. • Sleep onset REM period (occurring within 20 minutes after sleep onset). • Hypnagogic hallucinations or sleep paralysis associated with sleep onset REM. • Increased N1 sleep. • Sleep disturbance with frequent awakenings.

28. Polysomnography in the Narcolepsy Diagnosis • Patient must be free of drugs that influence sleep, particularly REM sleep, for at least 15 days. • Patient must have an established sleep/wake schedule for 7 days, which can be accomplished through sleep logs. • Polysomnography should be performed on the night immediately before the MSLT in order to rule out other disorders that could have similarities to narcolepsy.

29. Polysomnography in the Narcolepsy Diagnosis • The PSG should consist of EEG (frontal, central, occipital derivations), EOG, EMG (chin, tibialis), respiratory (airflow and effort), ECG, and oximetry. • The recording should reflect the patient’s normal bedtime and wake time. • Patients SHOULD NOT be awakened during the last REM period of the morning.

30. Differential Diagnosis • When other sleep disorders are present, such as apnea, periodic limb movement disorder, it is more difficult to confirm a narcolepsy diagnosis.

31. Multiple Sleep Latency Testing • An objective measure of excessive sleepiness. • A MSLT is positive for narcolepsy when: • there is presence of thee or more sleep onset REM periods during five nap opportunities • sleep latencies are <10 minutes, typically below 5 minutes • A good sleep-wake schedule and good sleep hygiene are essential for MSLT accuracy.

32. MSLT vs MWT • The MSLT is used to measure sleepiness. • The MWT (maintenance of Wakefulness test) is used to measure alertness—ability to stay awake. • The MSLT is the gold standard for confirming the narcolepsy diagnosis. • The MWT is often used to assess the level of alertness after treatment for sleep disorders, such as sleep apnea.

33. The MSLT • Measures the physiological tendency to fall asleep since the tendency to fall asleep increasesas physiological sleepiness increases. • To measure physiological sleepiness, alerting factors must not be present. • The test is based on the hypothesis that sleep latency is a reflection of the degree of sleepiness.

34. MSLT Protocol • Five nap opportunities performed in two-hour intervals. • Four nap opportunities are only reliable if the patient has two sleep onset REM periods during the first four naps. • The first nap opportunity should begin 1.5 to 3 hours after the patient is awakened from the night’s sleep. • Tests should always be performed immediately following polysomnography in the sleep center.

35. MSLT Protocol • REM suppressing medications should be discontinued two weeks prior to the test. • Drug screening may be performed in some cases to rule out pharmacologically induced sleepiness. • Tests should be performed by experienced technologists.

36. MSLT Protocol • In order for the MSLT results to be valid, the patient should have a minimum of 6 hours of sleep during polysomnography . • MSLT should not be performed following split-night polysomnography, but it can be performed following full-night PAP titration.

37. MSLT Protocol • The testing environment should be standardized in order to obtain valid test results. • Sleep rooms should be dark and quiet and temperature should be set to the patient’s comfort.

38. MSLT Protocol • Smoking should cease at least 30 minutes prior to each nap. • Vigorous physical activity should be avoided on the day of the test, and stimulating activities should be discontinued 15 minutes prior to start of each nap. • Caffeinated beverages and exposure to bright sunlight should be avoided during testing. • Meals should occur at least 1 hour prior to the first test and after termination of the second noon trial.

39. Recording Montage • Standard recording procedures for PSG should be followed, with electrode derivations including, central, occipital and frontal leads. • EOG mental/submental EMG and EKG is also recorded. • The patient should use the restroom (if indicated) prior to the start of each test. • The patient should remain out of bed and refrain from sleeping between naps.

40. MSLT Recording Procedure • Standardized physiological calibrations should be performed before each nap opportunity: • “Lie quietly with your eyes open for 30 seconds” • “Close both eyes for 30 seconds” • “Without moving your head, look to the right, then left, then right, then left” • “Blink your eyes slowly 5 times” • “Clench or grit your teeth tightly together” • Following physiological calibrations, the patient should be instructed: • “Please lie quietly, assume a comfortable position, keep your eyes closed and try to fall asleep”

41. MSLT Recording Procedure • Turn lights off immediately after instructions are given. • Determine sleep onset latency: • The time from lights out to the first epoch of ANY stage of sleep • The epoch counted as sleep onset must have 15 seconds of cumulative sleep in a 30-second epoch. • If no sleep occurs during a nap opportunity, the sleep latency is counted as 20 minutes • REM sleep latency: • Calculated from the first epoch of sleep to the first epoch of REM sleep regardless of intervening sleep or wake stages

42. MSLT Recording Procedure • When sleep onset occurs during a nap opportunity, the recording should continue for 15 minutes after the first epoch of sleep. Calculate 15 minutes using “clock time”, not by sleep time. • The 15-minutes of recording allows for occurrence of REM sleep. • In calculating mean sleep latency, ALL naps are included, even the ones in which there is no sleep occurrence.

43. MSLT Recording Procedure • The following data is reported: • the start and end times • latency from lights out to the first epoch of sleep • number of sleep onset REM periods • Mean sleep latency, calculated from data of all naps • End the nap after 20 minutes if no sleep occurs. • End the nap after 15 minutes of “clock time” sleep following sleep onset.

44. The Danger of Hypersomnia and Drowsy Driving • Almost Home

45. Hypersomnias of Central Origin Not due to a Circadian Rhythm Sleep Disorder, Sleep Related Breathing Disorder, or Other Cause of Disturbed Nocturnal Sleep.

46. HYPERSOMNIAS Primary complaint is daytime sleepiness. Cause is NOT one of those previously listed. Subjective measures of EDS: Epworth Sleepiness Scale, MSLT, MWT 12 Disorders in the one category Narcolepsy is described in this category With cataplexy without cataplexy

47. What is Sleep? • Sleep is a reversible state of decreased consciousness that is recurrent and associated with characteristic biophysiologicalterations. • Sleep is a very complex amalgam of physiological and behavioral processes. • Sleep is a process, unlike coma, this is physiologic, recurrent and reversible.

48. Sleep Medicine—Accepted Facts • Sleep is necessary for healing and recovery. • When sleep is abnormal, there can be psychological and physical illness and even death. • Treating sleep disorders improves physical well-being and can be instrumental in treating medical and psychiatric illness.

49. Why is sleep important? Restorative to mind and body Essential for physiological functions Hormone secretion Growth and “Maintenance” Essential to maintain proper mental processes Memory – both long and short term Decision making Socially acceptable personality traits

50. Sleep Requirements • Average adults require about 8 hours of sleep regardless of environmental or cultural differences. • People who sleep less than 4 hours or more than 9 hours have increased risk for coronary artery disease, cancer and stroke. • Whether a person is a “long” sleeper or a “short” sleeper is most likely determined by heredity. • Long sleepers spend more time asleep but have less deep sleep and more stage N2 sleep than do short sleepers.