Sleep Disorders and Fatigue Issues following TBI

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Sleep Disorders and Fatigue Issues following TBI Presented by Brooke Murtaugh, OTD, OTR/L, CBIST Brain Injury Program Manager Madonna Rehabilitation Hospitals

Objectives OBJECTIVES State the nature and prevalence of sleep disorders and fatigue issues following TBI Describe at least five causes of sleep disorders and fatigue issues following TBI State 4 non-pharmacological and pharmacological treatment options for treatment of sleep disorders and fatigues issues following TBI

Sleep As necessary as food, water and light. Crucial to the development and maturation of the brain. Sleep is a restorative function of the brain. Sleep regulates immune function, endocrine function. Promotes neuroplasticity and brain healing. Normal sleep occurs in organized patterns.

Sleep and TBI Studies show individuals in comatose state have disorganized sleep patterns. Well organized sleep-wake cycle is a positive prognosticator for increased clinical outcome after TBI. Arnaldi, D. (2016). Insomnia is a key variable of perceived disability. Mollayeva, T. (2015). Sleep disturbances can persist for years post injury. Sleep disturbances are more prevalent in those with MTBI.

Sleep and TBI Most Common Sleep Disorders Post TBI: Insomnia Sleep-related breathing disorders Obstructive sleep apnea Central apnea Narcolepsy Rare Post-Traumatic Hypersomnia Increased duration of sleep Circadian Rhythm Sleep Disorders Disorganized sleep-wake patterns

Insomnia Factors contributing to insomnia Neuropathological process Medications Pain Psychological Factors Environmental Factors Life habits

Sleep and Acute Rehabilitation Large numbers of admitted patients have sleep disorders: 2015 ACRM Study indicates 67% of acute rehab patients with BI met diagnostic criteria for a sleep disorder Recent study of 205 consecutive admissions to Acute TBI Rehab unit found 66% had a specific clinical diagnosis (Nakase-Richardson et al 2015) Circadian Rhythm Disorder (>47%) Sleep Apnea (33%)

Sleep Study Findings (Ponsford et al, 2013; Shekelton et al, 2010) 80% of TBI survivors report subjective sleep changes Poorer sleep quality Increased daytime sleepiness Longer sleep onset and more naps TBI patients reported higher levels of pain, depression and anxiety which were associated with some of the changes reported Reports of sleep changes are correlated with reduced REM and increased slow wave sleep even after controlling for the impact of anxiety and depression TBI patients have lower levels of melatonin in the evening which is associated with reduced REM Elevated psychological distress, particularly depression was associated with reduced sleep quality

Sleep Disorders Mathias (2012) Review of Sleep and TBI 12x risk of obstructive sleep apnea following TBI 2/5 had sleep apnea on inpatient admission Trazodone doesn t help sleep apnea Circadian rhythm disorder is the most common problem Studies have show a direct relationship between FIM Cognition score and CPAP compliance

Sleep Disorders Cognitive deficits will appear worse when sleep disorder is present. Daytime sleepiness is associated with reduced cognitive functioning. Experience increased anxiety, depression and fatigue with sleep/wake cycle disturbance. Increased overall pain and chronic headaches.

TBI and Sleep Disturbance Associated with Worse Outcomes Patients with sleep disturbance had Slower reaction time Poor delayed recall scores Executive Dysfunction Longer Duration of PTA Longer Lengths of Stay Decrease in vigliance Daytime somnolence can result in lack of participation and possible early discharge Confused patients are awake at night Increases likelihood of physical restraints More agitation Use of chemical restraints which may slow recovery

Sleep Disorders Depression and Anxiety Common after TBI Vicious cycle Depression and anxiety can cause insomnia and sleep disorders, and sleep disorders can increase depression and anxiety. Hard to know which comes first.

What about kids? Sleep-wake disturbances are common after traumatic brain injury in school aged children regardless of the severity of injury. Fatigue issues are common after TBI in school aged children. Fatigue is one of the most frequent postconcussive symptoms, and can be persistent. There has been no structured study to date of preschool children with TBI.

Sleep is IMPORTANT! Sleep links to participation in rehabilitation. Sleep links to acute cognitive recovery. Sleep links to productivity at one year. Sleep improvement precedes resolution of other confusion symptoms. Early improvement in sleep is associated with earlier resolution of PTA. Strong evidence that sleep promotes brain repair.

Inpatient Rehab: What can we do? Raise awareness of the importance of sleep for our patients. Staff, physicians, family awareness Monitor patient sleep cycles Actigraphy Nurse Sleep Logs Sound/Light Monitors PSG/Sleep studies Limit night time noise on the unit Limit night time vitals and cares Limit night time audio/visual stimulation from personal electronics Use light darkening shades, dimmed lights at bedside Use bright lights in the morning, use of light boxes Limit daytime sleep periods No Caffeine Schedule toileting before sleep

Treatment of Sleep Disorders Prescription drugs are a short term fix. Even in short term, not very effective. Conduct an objective sleep assessment. Self report is not always accurate Management of pain. Treat mood disturbance. Cognitive-behavioral therapy. Target mal-adaptive sleep behaviors

CBT Limited studies on efficacy of CBT to treat sleep disorders post TBI. Conclusive evidence that CBT does positively impact insomnia secondary to depression and anxiety, thus positively impacting depression and anxiety symptoms. Ashworth, 2015

Fatigue and TBI

Sleep and Fatigue as a Long-term Issue

Fatigue and TBI Most common symptom and can be longstanding after TBI. Difficulty to treat, wide range of symptoms and descriptions of fatigue and every person experiences fatigue differently. Frequently referred to as Post-Traumatic Fatigue (PTF) or pathological fatigue.

Fatigue and TBI Hypothesis Fatigue is the product of poor neuronal processing, impaired by a combination of primary, secondary and tertiary effects, decreasing the effectiveness of coordinated cognitive out put. Henri, 2013

What is Fatigue? A universal symptom, also present in healthy individuals. Defining fatigue is difficult as it is a subjective and multidimensional construct. the failure to initiate and/or sustain attentional tasks and physical activities requiring selfmotivation (Chauduri & Behan, 2000). Distinction between physiological and psychological resources.

Fatigue and TBI Pathological Fatigue A state that refers to a weariness unrelated to a previous exertion level, and not ameliorated by rest.

Fatigue Pathophysiology TBI can impact the areas of the brain responsible for our arousal. Reticular activating system Medulla Pons Basal Ganglia Can lead to decreased initiation, motivation and decreased activation of arousal centers.

The Problem: Fatigue and TBI Numerous studies examining outcomes following mild, moderate and severe TBI have found fatigue to be a common and persistent problem, reported between 21-72% of patients. (Borgaro et al, 2005; Bushnik et al, 2007,2008; Kempf et al, 2010; Ponsford et al, 2000; Olver et al, 1996; Ponsford et al, 2012, Henrie, 2013)

Physiological Fatigue Physiologically, fatigue is defined as functional organ failure, generally caused by excessive injury consumption. Depletion of essential substrates of physiological functioning (e.g. hormones, neurotransmitters) and/or a diminished ability to contract muscles.

Physiological Fatigue: Central vs. Peripheral Fatigue Central Fatigue: Arises from impairment within the CNS (e.g. hypothalamus, reticular formation) or impaired transmission between the CNS and PNS Peripheral Fatigue: Results from malfunction of the peripheral nervous system, such as impaired neuromuscular transmission at the motor end plate, not related to the CNS

Psychological Fatigue A state of weariness related to reduced motivation, prolonged mental activity, or boredom that occurs in situations such as chronic stress, anxiety or depression. (Lee et al., 1991, p. 291) A high proportion of TBI patients develop depression and anxiety.

Predictors of Fatigue Psychiatric symptoms Sleep disturbances Post-traumatic amnesia Loss of consciousness Schiehser, 2016

Factors Impacting Fatigue Systematic Review demonstrated consistent factors contributing to fatigue post TBI: Earlier fatigue severity Genetic disposition History of mental health issue Medical disability Marital status (widowed, divorced, separated) Litigation Depression

Measurement of Fatigue Numerous measures developed No single valid and reliable measure exists Many fatigue scales are specific to a particular illness (e.g. cancer) Existing scales address differing aspects of fatigue it s characteristics, it s consequences and the associated subjective feelings

Measurement of Fatigue Aaronson et al (1999) recommend assessment of: Subjective quantification of fatigue levels Subjective distress because of fatigue Subjective assessment of the impact of fatigue on activities of daily living Correlates of fatigue with other associated factors (e.g. sleep and depression) Biological parameters

First Ponsford Study Mild-Severe TBI Ages 16-67, living in the community, no prior TBI, neurological or psychiatric illness Average time since injury ranged from 21-1153 days 139 TBI, 77 normals, similar in demographics TBI individuals experience greater subjective fatigue which impacts on their daily lifestyle Used the causes of fatigue questionnaire and found that everything was more fatiguing for patients with TBI except watching TV and taking a shower Found that injury severity and age were not predictive of fatigue Time since injury did predict fatigue severity with some scores increasing over time Higher levels of anxiety and depression were highly significant predictors of fatigue but don t know which is causal

First Ponsford Study (continued) Later studies have shown that feeling fatigued made people feel more depressed and anxious. No significant association between taking any medication and Fatigue Severity Scores. No significant association between the presence/absence of orthopedic injuries and scores on the fatigue scales. TBI patients showed significantly higher pain severity ratings and pain severity and fatigue ratings are moderately associated. Fatigue levels did not decrease over time and in some areas they increased.

Second Ponsford Study Investigation of the impact of subjective fatigue on cognitive performance Attention Higher levels of subjective fatigue were associated with slowed information processing and poorer performances on tasks with higher working memory or dual task demands Vigilance Higher ratings of subjective fatigue associated with slower and more errors on performance Sustaining performance on measures of vigilance were associated with: Increases in blood pressure greater than controls The Impact A Bad Cycle Greater increases in blood pressure resulted in greater subjective fatigue Greater errors on Vigilance task and increase in systolic BP was associated with higher levels of anxiety and depression Greater need for mental effort may increase systemic stress including both physical and psychological stress

Implications TBI patients need to have the attentional demands of their daily activities modified. TBI patients can potentially benefit from management of mood disturbances which will further impact attention difficulties.

Implications Fatigue and impact on employment: Study by Palm, 2017 found that those with fatigue post TBI had a reduced employment status. Higher level of rated mental fatigue correlated with lower employment status. Employment status was not dependent upon age or TBI severeity. Higher rating of depression and anxiety also correlated with lower employment status.

Distinguishing Fatigue from Sleep Disorders Excessive daytime sleepiness is different from fatigue. Excessive daytime sleepiness is defined as drowsiness, feeling the need to nap when they want to be awake, after insufficient sleep or sleep disruption In practice, patients may not be able to differentiate sleepiness from fatigue but as the clinician it will help if you can. Excessive daytime sleepiness is usually from sleep apnea or circadian rhythm disorder.

Organic Basis of Fatigue? In TBI patients, fatigue was predictive of depression and sleepiness however, depression and sleepiness did not predict fatigue. Results support the view of fatigue after TBI as primary fatigue -that is a consequence of the structural brain injury rather than a secondary consequence of depression or daytime sleepiness Schoenberger et al (2014)

Is there an organic basis for fatigue? Schonberger, M. JHTR 29(5) 427-431. Primary fatigue is not just a consequence of depression. Lower visible brain stem volume. Neuroendocrine abnormalities including lower growth hormone levels 2005 Study Orexin in TBI (Hypocretin) -95% of patients with mod-severe TBI had low levels of Orexin Hypothalamic injury?

Other Possible Causes of Fatigue Neuroendocrine abnormalities including lower growth hormone levels (Bushnik et al, 2007; Englander et al, 2010) 2005 Study Orexin in TBI (Hypocretin) -95% of patients with mod-severe TBI had low levels of Orexin Baumann et al (2007) make a case for lower CSF Hypocretin-1 caused by loss of hypocretin neurons causing excessive daytime sleepiness. Found fewer hypocretin neurons in the brains of 4 deceased TBI cases postulating the role of hypothalamic injury in fatigue

Fatigue Management Need to assess contributors/ differential diagnosis. Rule out any other medical issues. Attention issues Medications Pain levels Mood concerns

Fatigue Management Work on regulation of lifestyle Decrease work hours? Modify pace/demands of work Energy Conservation Prioritize activities Decrease distraction/need for multi-tasking Allow time to rest Address psychological issues, cognitive behavioral therapy Modify cognitive demands of tasks.

Fatigue Management Dietary Lifestyle Weight reduction Foods to boost energy Sleep Hygiene Energy Conservation Strategies Community participation Physical Activity-Walking» Kolakowsky-Hayner, 2016

Fatigue Management Physical conditioning programs can decrease fatigue (Sullivan, Richer & Laurent, 1990; Wolman, Cormail, Fulcher & Greenwood, 1994; Jankowski & Sullivan, 1990) Pharmacological Interventions Modafinil-2 Randomized Controlled Trials Helps with daytime sleepiness but not helping with subjective fatigue Sleep Hygiene Techniques Avoiding naps if this interferes with nighttime sleep Adhering to a regular schedule Avoid time spent in bed awake Outlet and Morin (2007) CBT for insomnia

Fatigue Management Light Therapy for Fatigue and Daytime Sleepiness 2014, Sinclair et al, Neurorehabilitation and Neural Repair, 28(4), 303-313. 30 persons with TBI RCT utilizing 4 week treatment phase of morning use (45 minutes per day) Showing promise Blue Light is the most effective, yellow light and placebo not helpful Projects on the back of the retina Releases melanopsin to the suprachiasmatic nucleaus Increases arousal Blue light therapy following TBI helps with subjective fatigue and daytime sleepiness Trend towards increase in psychomotor vigilance-lots of individual variability Study is ongoing, soon to analyze larger sample size

Summary Sleep and Fatigue shouldn t be ignored There is considerable evidence that sleep disorders are highly prevalent following brain injury both in the acute stages and longterm. Sleep issues impact our patient s outcomes. Patients with brain injury also suffer from fatigue that is separate and distinct from sleep issues. Fatigue appears to be a direct result of the brain injury and cannot be explained as a secondary effect of mood disorders, medications or pain but can be exacerbated by those factors. Treatment of both issues is multifaceted but should be addressed as part of our rehabilitation program.

Thank You! Questions? bmurtaugh@madonna.org

References Ashworth, DK., et al. (2015). A randomized controlled trial of cognitive behavioral therapy for insomnia: an effective treatment for comorbid insomnia and depression. Journal of Counseling Psychology; 62(2): 115-123. Arnaldi, D., Terzaghi, M., et al. (2016). The prognostic value of sleep patterns in disorders of consciousness in the sub-acute phase. Clinical Neurophysiology, 127; 1445-1451. Gagner, C., Landry-Roy, C., Laine, F., & Beauchamp, M.H. (2015). Sleepwake disturbances and fatigue after Pediatric Traumatic Brain Injury: A Systematic Review of the Literature. Journal of Neurotrauma, 32: 1-14. Gardani, M., Morfiri, E., Thomson, A., et al. (2015). Evaluation of sleep disorders in patients with severe traumatic brain injury during rehabilitation. Archives of Physical Medicine and Rehabilitation, e-pub ahead of print. Henri, M, Elovic, E. (2013). Fatigue: Assessment and Treatment. In Brain Injury Medicine. Zasler (Eds). DemosMedical, New York, NY.

References Kolakowsky-Hayner, s., et. Al. (2016). A randomized control trial of walking to ameliorate brain injury fatigue: a NIDRR TBI model system centre-based study. Neuropsychological Rehabilitation; 13: 1-17. Mathias, J.L. & Alvaro, P.K. (2012). Prevalence of sleep disturbances, disorderrs, and problems following traumatic brain injury: A metaanalysis. Sleep Medicine (13); 898-905. Mollayeva, T., Pratt, B., & Mollayeva, S. et al. (2015). The relationship between insomnia and disability in workers with mild traumatic brain injury/concussion. Sleep Medicine; 1-10. Mollayeva, T., et al. (2014). A systematic review of fatigue in patients with traumatic brain injury: the course, predictors and consequences. Neuroscience and Behavioral Reviews. 47:684-716. Nakase-Richardson, R., (2015). Brain Injury Sleep Wake Cycle Disorders. Presentation at the Brain Injury Summit, Vail, CO.

References Ouellet, M., Beaulieu-Bonneau, S., & Morin, C.M. (2015). Sleep-wake disturbances after traumatic brain injury. Lancet Neurol, 14; 746-757. Ouellet, M., Beaulieu-Bonneau, S., & Morin, C. (2013). Sleep-wake disturbances. In Brain Injury Medicine. N.Zasler (Eds). 707-725. Palm, S., Ronnback, L, & Johansoon, B. (2017). Long-term mental fatigue after traumatic brain injury and impact on employment status. Journal of Rehabilitation Medicine; 49; 228-233. Ponsford, J., (2015). Post-traumatic fatigue; Creating an evidence base for efficacious treatments. Presentation at the Brain Injury Summit, Vail, CO. Schiehser, D., et. Al. (2016). Predictors of cognitive and physical fatigue in postacute mild-moderate traumatic brain injury. Neuropsychological Rehabilitation; 18: 1-16.