1. Quantitative EEG during Sleep in Fibromyalgia Victor Rosenfeld M.D. Director of Neurology, SouthCoast Medical Group Medical Director, SouthCoast Sleep Center Savannah, GA

2. Disclosure Information Victor Rosenfeld MD  Disclosure of Relevant Financial Relationships  I have no financial relationships to disclose.  Disclosure of Off-Label and/or Investigative Uses  I will discuss the following off label use and/or investigational use in my presentation: Sodium Oxybate and Pain

3. Sleep and FMS  Sleep Disorders are common in FMS including Non- restorative sleep, Insomnia, Hypersomnia, Sleep Apnea, and Restless Legs  Non-restorative sleep is a hallmark of FMS and can be identified using qEEG during PSG  Sleep Disorder in FMS are identifiable and treatable.

4. Symptoms in Fibromyalgia SYMPTOMSMean Severity (SD) Morning Stiffness7.2 (2.5) Fatigue7.1 (2.1) Non-Restorative Sleep6.8 (2.0) Pain6.4 (2.0) Forgetfulness5.9 (2.7) Bennet et al: BMC Muscoloskeletal Disorders, 2007; 8:27

5. 2010 Fibromyalgia Clinical Diagnostic Criteria Widespread Pain Index (WPI) In how many areas has the patient had pain in the last week? Score = 0-19 Symptom Severity Scale (SS) What was the level of symptom severity in the last week? Score = 0-12 0 (no problem), 1 (slight), 2 (moderate), 3 (severe) Patient satisfies the 2010 Fibromyalgia Clinical Diagnostic Criteria if WPI ≥7 and SS score ≥5 or WPI between 3-6 and SS score ≥9 Shoulder (L/R); Upper arm (L/R); Lower am (L/R); Jaw (L/R); Neck; Buttock; Hip trochanter (L/R); Upper let (L/R); Lower leg (L/R); Upper back; Lower back; Chest; Abdomen Fatigue; Waking unrefreshed; Cognitive disturbances; General somatic symptoms

6. George Beard (1869)- Neurasthenia  Described “...a disease of the nervous system characterized by enfeeblement of the nervous force. Young women appear to have been particularly susceptible to it and its onset was frequently “triggered” by an infection.”  Also described neurasthenia as a “...condition of nervous exhaustion, characterized by undue fatigue on the slightest exertions, both physical and mental. The chief symptoms are headaches, gastrointestinal disturbances, and subjective sensations of all kinds.”

7. Normal Sleep Architecture After Rechtschaffen & Kale, 1968, Kalat, 2005, Weiten 2004

8. Sleep Architecture in FMS  Non-FMS:  REM 25%  Deep Sleep 20%  In FMS:  REM Sleep decreases  Deep Sleep decreases  Sleep becomes “fractured”  FMS sleep like the elderly

9. Sleep Basics

10. Deep Sleep: Normal

11. Deep Sleep: Alpha Intrusions

15. Fig. 4: The DE/AE Ratio improved significantly for each patient after treatment with Sodium Oxybate. Fig. 5: Improvement in DE/AE Ratio correllates correlates with improvement in VAS Pain Score Delta Events/Alpha Events Visual Analog Scale Alpha/Delta qEEG during Polysomnography in five FMS patients before and after treatment with Sodium Oxybate V. Rosenfeld, MD, Sansum Clinic; D. Ngyuen, Sleepmed; J. Stern, M.D., UCLA

16. VariableTotal Group N = 385 Persons with Fibromyalgia N = 133 Persons without Fibromyalgia and Severe OSA N = 252 Demographic characteristics/health history Gender – Male142 (36.9%)5 (3.8%)137 (54.4%)*** Taking benzodiazepines or benzodiazepine agonist97 (25.2%)61 (45.9%)36 (14.3%)*** Taking antidepressants (tricyclic or SNRIs)100 (26.0%)56 (43.6%)42 (16.7%)*** Age (y)49.2 (12.8) 15 - 75 48.6 (11.1)49.5 (13.6) Body mass index30.1 (6.4) 13.1-52.0 28.9 (5.9)30.7 (6.6)** Epworth Sleepiness Scale10.5 (5.4) 0-26 10.4 (5.4) n = 131 10.5 (5.4) n = 251 Sleep variables Time spent sleeping (min)279.3 (102.8) 59.0-550.0 304.6 (95.8)265.9 (104.1)*** Sleep efficiency (percentage)77.9 (14.2) 22.3 – 98.8 78.5 (12.6)77.5 (15.2) Wake after sleep onset (min)453.1 (44.2) 0-236 55.3 (42.5)51.9 (45.1) Apnea/Hypopnea Index10.2 (11.0) 0-80.2 9.4 (14.8)10.7 (8.3) Respiratory Distress Index (RDI)14.6 (13.7) 0-94.7 13.1 (17.8) n = 132 15.4 (10.9) Periodic limb movement - yes57 (14.8%)16 (12.0%)41 (16.3%) Periodic Limb Movement Index (PLMI)15.2 (18.3).2-99.9 12.8 (13.7) n = 48 16.5 (20.3) n = 82 Periodic Limb Movement Arousal Index (PLMAI)9.3 (15.1).1-83.9 6.8 (14.2) n = 52 10.8 (15.5) n = 89 Narcolepsy or idiopathic hypersomnolence25 (6.5%)10 (7.1%)15 (6.0%) Delta event/alpha event ratio13.3 (26.0) 0.3-231.0 7.4 (11.1)16.5 (30.7)** n = 251 Rosenfeld et al: Journal of Clinical Neurophysiology, 2015; 32:2

17. FMS and Sleep Apnea (n=129)

18. Polysomnographic Variables in FMS

19. qEEG in PSG in pts w/wo FMS  D/A ratio < 1: 98.4% specificity for FMS  D/A ratio < 10: 85% sensitive for FMS  D/A ratio > 11: 89.1% negative predictive value for FMS Rosenfeld et al: Journal of Clinical Neurophysiology, 2015; 32:2

21. qEEG in PSG in pts w/wo FMS  Non-restorative sleep is a hallmark of FMS and can be identified using qEEG during PSG  Sleep Apnea is seen in 45% of FMS patients.  Hypersomnlence is seen in 7% of FMS Patients.  PLMS is probably less common than in the non-FMS population.  Sleep Disorders in FMS are largely identifiable and treatable.