Evaluating Hypersomnolence and Fatigue

Evaluating Hypersomnolence and Fatigue Max Hirshkowitz, PhD, DABSM Consulting Professor Stanford University, School of Medicine, Division of Public Mental Health and Population Sciences, Stanford, CA Full Professor (Emeritus) Baylor College of Medicine, Department of Medicine, Houston, TX Chairman of the Board of Directors National Sleep Foundation, Arlington, VA Photo from W Eugene Smith, Life Magazine

Learning Objectives By the end of this program, the attendee should Be familiar with the conceptual models of sleepiness (hypersomnolence) & fatigue Have improved understanding of neurobiology of underlying sleepiness & fatigue Be more aware of what we measure with tools designed to index sleepiness and/or fatigue

What is hypersomnolence? Fatigue is perceived as a sense of drowsiness or tiredness with a desire to sleep at inappropriate times What Causes Hypersomnolence? 1. Reduced Sleep Quantity 2. Reduced Sleep Quality 3. Mismatched Sleep Timing 4. Sleep Disorders 5. Medical Disorders 6. Neurological Disorders 7. Psychiatric Disorders 8. Drugs or Drug Withdrawal 3

What is fatigue? Fatigue is perceived as a sense of tiredness, exhaustion, and/or lack of energy. Fatigue increases the chance of performance impairment or failure. What Causes Fatigue? 1. Exceeding physical or mental capacity with increasing time-on-task, stress load, or both. 2. Increased External Stress Load from work demand &/or poor workplace design 3. Increased Internal Stress Load from medical, neurological, & psychiatric illness; psychological issues; drugs; & sleepiness). 4

Properties of Fatigue Sleepiness is arguably the most important stressors provoking fatigue in humans. Fatigue can be non-pathological (that is, part of the natural rest-activity cycle). Fatigue can be pathological (evoked by a disease process). Non-pathological fatigue improves with rest. 5

Scales Measuring Self-reported Sleepiness (Relying on Introspection)

Scales Measuring Self-Reported Fatigue BIFS Brain Injury Fatigue Scale (Quinn) Differentiates normal and pathological fatigue BNI- Barrow Neurological Institute Fatigue Scale (Borgaro et al, 2004 & 2005) Used for acute TBI FIS Fatigue Impact Scale (Fisk et al, 1994) Used for MS fatigue FSS Fatigue Severity Scale (Krupp et al, 1989) The most commonly used scale FAS Fatigue Assessment Scale (Mead et al, 2007) Commonly used in CA research Subscales of EBIQ (Bateman et al, 2009) Subscale of Profile of Mood States (McNair et al, 1992)

Fatigue Severity Scale (FSS) The FSS contains nine statements that rate the severity of your fatigue symptoms. Please read each statement and circle a number from 1 to 7, based on how accurately it reflects your condition during the past week and the extent to which you agree or disagree that the statement applies to you. A low value (e.g. 1) indicates strong disagreement with the statement, whereas a high value (e.g. 7) indicates strong agreement. It is important that you circle a number (1 to 7) for every question. During the past week, I have found that: 1. My motivation is lower when I am fatigued 1 2 3 4 5 6 7 2. Exercise brings on my fatigue 1 2 3 4 5 6 7 3. I am easily fatigued 1 2 3 4 5 6 7 4. Fatigue interferes with my physical functioning 1 2 3 4 5 6 7 5. Fatigue causes frequent problems for me 1 2 3 4 5 6 7 6. My fatigue prevents sustained physical functioning 1 2 3 4 5 6 7 7. Fatigue interferes with carrying out certain duties and responsibilities 1 2 3 4 5 6 7 8. Fatigue is among my three most disabling symptoms 1 2 3 4 5 6 7 9. Fatigue interferes with my work, family, or social life 1 2 3 4 5 6 7

Fatigue Assessment Scale The following ten statements refer to how you usually feel. Per statement you can choose one out of five answer categories, varying from Never to Always. Please circle the answer to each question that is applicable to you. Please give an answer to each question, even if you do not have any complaints at the moment. 1 = Never, 2 = Sometimes; 3 = Regularly; 4 = Often and 5 = Always. 1. I am bothered by fatigue 1 2 3 4 5 2. I get tired very quickly 1 2 3 4 5 3. I don t do much during the day 1 2 3 4 5 4. I have enough energy for everyday life 1 2 3 4 5 5. Physically, I feel exhausted 1 2 3 4 5 6. I have problems to start things 1 2 3 4 5 7. I have problems to think clearly 1 2 3 4 5 8. I feel no desire to do anything 1 2 3 4 5 9. Mentally, I feel exhausted 1 2 3 4 5 10. When I am doing something, 1 2 3 4 5 I can concentrate quite well

Fatigue Assessment Interview When did it start? How long has it lasted? Has it got worse over time? Does anything make it feel better or worse? For example, exercise, eating or pain. Does it affect your daily living activities such as washing, cooking or walking? Do you have any problems sleeping? Do you have any other major problems in your life such as relationship or financial problems or work worries? Do you have any other symptoms with your fatigue, such as feeling or being sick, breathlessness or pain? Do you have any other medical conditions? Did you feel fatigued before your stroke/neurological condition was diagnosed? How long since you have had your bowels open? Are you having any problems with passing urine? What medication, herbs, or recreational drugs do you use?

Medication, Drugs, & Substances Fatigue is commonly associated with soporific substances or withdrawal from stimulants

Sleep Promoting Substances Soporifics Chronohypnotics Other GABA A & BZD Receptor Agonists Antihistamines Orexin Antagonists (Suvorexant) Melatonin & Cicadin DA agnoists for RLS Ramelteon (MT agnoist) Agomelatine GHB (Xyrem) Traditional Neuroleptics (Dopamine Antagonists) Adenosine Agonists (in development) Low dose doxepin (Silenor) 5HT 2a Inverse Agonist (Eplivanserin not approved)

Rx with Antihistaminergic Properties Associated with Sleepiness and Fatigue Diphenhydramine (Benedryl) Desyrel (Trazodone) Mirtazepine (Remeron) Amitriptyline (Elevil) Doxepin (Adapin, Sinequan) Quitiapine (Seroquel) Gabapentine (Neurontin)

The image part with relationship ID rid2 was not found in the file. Alcohol & Cannabis

Wake-Promoting Agents Mechanisms Substance Underlying Action Sleep Factor Caffeine Traditional psychostimulants - ampehetamine {1927} - methylphenidate {1959} Modafinil s Adenosine receptor antagonist enhance neurotransmission of DA, NE, & 5-HT mechanisms unclear; likely H1 agonist & DA transport effect Homeostatic and ANS ANS ANS and possible circadian

MSLT- AASM SPC Indications Indicated as part of evaluation of patients suspected of narcolepsy (2 or more SoREMPs has a 0.78 sensitivity and 0.93 specificity for diagnosing narcolepsy) May be indicated to differentiate idiopathic hypersomnia Not indicated for routine evaluation of sleep-related breathing disorders, insomnia, or circadian dysrhythmias Repeat MSLT may be indicated (a) when study conditions were inappropriate during initial test (b) when results are ambiguous (c) when earlier MSLT did not confirm narcolepsy 33

MWT AASM SPC Indications MWT 40 minute protocol may be used to assess an individual s ability to remain awake when it constitutes a public or personal safety issue 59% of normals remain awake entire 40 minutes across all 4 trials (using unequivocal sleep criteria). Latency <8 minutes is abnormal Latency 8-40 is of unknown significance Mean sleep latency (1 st sleep epoch) is 30.4 + 11.2 m Upper 95% confidence interval is 40 min Indicated for assessing response to treatment 43

Measuring Manifest Sleepiness with the Maintenance of Wakefulness Test (MWT) Clinical standard is now 4, 40-minute test sessions at 2 hour intervals 1st test session begins 2 hours after arising Street clothing Sit on bed with bolster pillow Darkened but not pitch black room Concurrent PSG recording Instruction Resist falling asleep Measure sleep latency & note microsleeps 44

MWT TEST SESSION TERMINATION Lights-out Sleep-Onset End T 0 T 1 T E Terminate test at: 1 st unequivocal sleep -or- T 0 + 40 m if no sleep Sleep-onset is: Any epoch of sleep Unequivocal sleep is: 1 epoch of stage 2,3,4 or REM -or- 3 consecutive epochs of stage 1 oran epoch of stage 1 followed by an epoch of 2,3,4 or REM 45

Vigilance & Performance Tests When workload is high, this is a performance task When workload is low, this becomes a vigilance task Vigilance tasks differ from performance tasks with respect to 1. little need for practice 2. little need for ability 3. little intrinsic stimulation

Level Description Our Current Paradigm Label I Inability to remain awake Overwhelmingly Sleepy II Having difficulty remaining Drowsy awake III Feels a desired to sleep Tired (in the sleepy sense) How conscious are we of these ongoing processes? What are associated process that correlate, influence, and/or masquerade? For example: denial, lack of awareness, depression, anxiety, physical fatigue, mental fatigue {from emotional stressors}, boredom, pain, 1 or 2 gain

Making Sense out of the Disconnects Between the Faces of Sleepiness

Learning Objectives The attendee should now Be familiar with the conceptual models of sleepiness (hypersomnolence) & fatigue Have improved understanding of neurobiology of underlying sleepiness & fatigue Be more aware of what we measure with tools designed to index sleepiness and/or fatigue

References: 1. Hirshkowitz M, Sharafkhaneh A. Evaluating Sleepiness. In: Kryger MH, Roth T, Dement WC (Eds). Principles and Practice of Sleep Medicine, 6 th Edition. Elsevier- Sanders: Philadelphia, PA. In Press. 2. Hirshkowitz M. Fatigue, Sleepiness, and Safety: Definitions, Assessment, Methodology. Sleep Med Clin 2013; 8: 183-189. 3. Hirshkowitz M, Sharafkhaneh A. Sleep Medicine Clinics: Fatigue Management. Philadelphia, PA: Elsevier; 2013. 4. Assessment of Fatigue- BMJ Best Practice updated 10/19/15 (Available Online) 68