Sleep & Wakefulness Disorders in Parkinson s Disease: The Challenge of Getting a Good Night s Sleep

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Sleep & Wakefulness Disorders in Parkinson s Disease: The Challenge of Getting a Good Night s Sleep Helene A. Emsellem, MD March 25, 2017 The Center for Sleep & Wake Disorders PFNCA Symposium

Sleep is mandatory eventually SURVIVAL: water, food, air & SLEEP

What is sleep & what does it do? Restores us physically Resets us psychologically We learn during sleep Mood is dependent on sleep Caloric management is sleep dependent

Sleep?. What happens when we don t get enough? Impaired cognitive function difficulty with FOCUS, ATTENTION & CONCENTRATION irritability impaired memory Impaired inhibitory control subjective sleepiness - prolonged auditory reaction time - prolonged visual reaction time

Impaired motor function Prolonged motor reaction time Tremor Incoordination Blurred vision

Sleep is a dynamic process: Each stage has a unique purpose Must cycle thru all stages adequate time in each stage orderly sequence

Sleep Synaptic Homeostasis Hypothesis During the day we acquire info & build connections... At night we downscale and clean up Sleep is the price we pay for plasticity G. Tononi & C. Cirelli, Sleep Medicine Reviews, Vol. 10, no 1:49-62, 2006

Glial Washing Glial supportive cells in the brain Form the GLYMPHATIC system Enhanced removal of toxic waste Including amyloid proteins assoc with Alzheimer s During slow wave sleep

The more we use a brain region during the day more local slow wave sleep activity is needed to clean up at night

STATES of BEING Wakefulness Sleep.. and many ambiguous states in between.. and sleeprelated phenomena Non-REM Sleep REM Sleep

REM Sleep Dreaming No memories of the dream process formed Cognitive cortex off line Muscle paralysis (atonia) Rapid eye movement (REM) bursts LEARNING & CREATIVITY Positive effect of sleep on learning does not occur if sleep restricted!!!!

Sleep Requirements Adults. including seniors: 7-9 hrs

Medical & Social Implications of Disrupted & Insufficient Sleep in PD Aggravation of underlying PD symptoms Impaired responsiveness to medication Impaired social function irritability, mood disorder hypophonia Difficulty with weight control

Parkinson s & Sleep Disorders Sleep-wake abnormalities are found in >60% of patients More severe PD: sleep disturbance Nocturnal sleep abnormalities: 60-98% Daytime sleepiness: 15-51%

Sleep & Wake Regulation Cortex Thalamus Cortical Activation Sleep Spindle EEG Synchronization Hypothalamus Sleep/Wake Switch Courtesy of E. Mignot, MD. Stanford University. SCN Circadian Clock Brainstem Ascending Cortical Activation REM/SWS Switch

Disorders of Sleep-Wake in PD 1. Insomnia & Fragmentation of sleep 2. Excessive daytime sleepiness 3. Obstructive Sleep Apnea 4. Periodic Limb Movements of Sleep 5. REM Sleep Behavioral Disorder 6. Disturbed Sleep-Wake Timing (?)

1. Insomnia & fragmentation of Sleep Sleep onset difficulty Anxiety Medication side effects Frequent arousals Tremor during sleep Rigidity (may disturb transition into sleep & repositioning during the night) Other sleep disorders: Sleep apnea REM sleep behavioral disorder Periodic limb movements of sleep Concurrent depression Altered sleep timing (circadian rhythm)

Is INSOMNIA due to: A disorder of the brain s ability to initiate or maintain sleep OR A disorder of the brain s ability to turn alertness OFF

Light is a DRUG that promotes WAKEFULNESS Charles A. Czeisler, PhD, MD Director of Sleep Medicine Harvard Medical School

Management of Insomnia in PD Monitor sleep pattern (keep logs) Prioritize sleep Regulate the schedule Add a pre-bed wind-down time Control evening light (orange lenses) Disengage: Turn off electronics Cognitive behavioral therapy (CBT) Judicious use of sleep medication Use of nocturnal PD meds

Lost Environmental Sleep Cues BR no longer for Ss sleep & sex only Light from screens Intellectual engagement Noise TV & subliminal messages

2. Excessive Daytime Sleepiness in Parkinson s Disease Sleep attacks may occur Prevalence: 43-56% of PD patients Multifactorial: PD disturbs alerting brainstem pathways Side effect of dopaminergic PD therapy Consequence of other sleep disorders

Measures of Sleepiness Subjective: Epworth Sleepiness Scale 8 point rating scale of sleepiness during key activities over the past week Objective: Daytime Multiple Sleep Latency Test (MSLT) Daytime Maintenance of Wakefulness Test Used to assess alertness & driving safety

Treatment of EDS Optimize nocturnal sleep: Quality, quantity & timing Identify & Treat co-existent sleep disorders Timed naps Stimulants & Wake promoting agents Modafinil, r-modafinil In Study: Jazz JZP-110 specifically being studied for sleepiness in Parkinson s disease

Cardinal Symptoms of OSA Loud snoring. but not always Excessive daytime sleepiness Obesity but not always Less frequent associated symptoms - sleep onset insomnia - multiple nighttime awakenings - fatigue -cognitive impairment

AIRWAY Nose: cartilage Mouth: boney palate Pharynx: jeopardy zone: muscular Trachea: cartilaginous rings

Open Airway Closed Airway

4. Nocturnal movements in PD 28% of PD patients have Restless Leg Syndrome >15% have Periodic Limb Movements of Sleep 15-50% have REM Sleep Behavioral Disorder

RLS & PLMS Dx & RX Clinical history +/- sleep study Check serum iron / ferritin levels Treatments overlap with PD meds Gabapentin Opioids

Failure of normal paralysis of REM sleep Dream enactment behaviors Rx Treat underlying sleep apnea Remove offending medications: SSRIs Rx: Clonazepam, melatonin, gabapentin

Resources

Epworth Sleepiness Scale (ESS) How likely are you to doze off in the following circumstances over the past week? Score 0-3: 0 = no chance of dozing, 1=slight chance, 2=moderate chance, & 3=high probability 1. Sitting & reading 2. Watching TV 3. Sitting inactive in a public place 4. As a passenger in a car for 1 hour

5. Lying down to rest in the afternoon 6. Sitting & talking to someone 7. Sitting quietly after a lunch without alcohol 8. In a car while stopped in traffic Scoring of ESS: <8/24 = normal alertness 8-9/24 = borderline alertness 10/24 = excessive daytime sleepiness Johns, MW. Sleep 1991; 14: 540

Multiple Sleep Latency Test Measures patient s tendency to fall asleep Obtained in setting of regular sleep schedule with preceding in-lab sleep study Patient is given 5, 20-minute opportunities to nap at 2 hour intervals during the day lying down in a darkened room Sleep onset is scored objectively by EEG, eye movements and muscle tone Average sleep latency < 10 minutes is considered abnormal

Resources for Insomnia Sleep logs to track sleep schedule: http://www.sleepdoc.com/pdf/sleep_log.pdf On-line cognitive behavioral therapy http://www.myshuti.com/ $135 for 6 session course On line access for 16 weeks

Light Control Uvex orange lens glasses: to block the alerting blue light portion of the light spectrum in the evening Wear in PM beginning 1.5-2 hours prior to desired bedtime to help initiate sleep www.amazon.com: search UVEX orange lens glasses The standard UVEX S1933x are fine unless you wear glasses in which case you may want the larger S0360x model. $9-12.

Habits to Help You Sleep Better Keep a regular schedule Wind down me time before bedtime Daily exercise Dim screens/reduce ambient light Clear the decks safe sleep environment Avoid late, heavy meals Avoid evening naps Avoid late alcohol No heavy discussions at bedtime Sleep work-up & treat the problems