Sleep disorders and concussion

Handbook of Clinical Neurology, Vol. 158 (3rd series) Sports Neurology B. Hainline and R.A. Stern, Editors https://doi.org/10.1016/B978-0-444-63954-7.00013-6 Copyright © 2018 Elsevier B.V. All rights reserved

Chapter 13

Sleep disorders and concussion ANNE MARIE MORSE1 AND SANJEEV V. KOTHARE2* Department of Child Neurology and Sleep Medicine, Geisinger Medical Center, Danville, PA, United States

1 2

Pediatric Neurology and Pediatric Sleep Program, Department of Pediatrics, Cohen Children’s Medical Center, Lake Success, NY, United States

Abstract Sleep disorders are a common sequel of sports-related concussion. Sleep–wake dysfunction can vary among patients, independent of cause or severity of concussive injury. The pathogenesis of postconcussive sleep disorder is unclear, but may be related to impaired signaling in neurons involved in normal sleep– wake control and circadian rhythm maintenance. Standardized methods of assessment for sleep disorders following concussion are important for diagnosis and management. Appropriate management is key because sleep dysfunction can have deleterious effects on concussion recovery. Management is patientspecific, based on sleep pathology and comorbid postconcussive symptomatology.

INTRODUCTION

PATHOGENESIS OF SLEEP DISORDERS

Sports-related concussion may manifest in any combination of the following clinical domains: somatic, cognitive and/or emotional symptoms; visible physical signs; balance/vestibular impairment; behavioral changes; cognitive impairment; and sleep–wake disturbance (McCrory et al., 2017). Sleep disorders are a common but underrecognized manifestation of concussion (Borgaro et al., 2005; Ouellet et al., 2006; Baumann et al., 2007); the importance of assessing for and managing postconcussive sleep disorders is the focus of this chapter. Sleep disorders following concussion can vary among patients (Table 13.1) (Singh et al., 2016). The most common sleep disorders associated with concussion are insomnia and sleep apnea (Castriotta and Murthy, 2011; Mathias and Alvaro, 2012). Despite variations in causes, excessive daytime sleepiness may be either the primary or only subjective sleep–wake complaint. A comprehensive sleep evaluation is an important diagnostic and management consideration following sportsrelated concussion.

The sleep–wake cycle is a tightly regulated process that results from integration of input from circadian rhythms, sleep–wake homeostasis, and external environmental factors (i.e., food, drugs, stress). Sleep–wake homeostasis is the increasing drive to sleep based on the number of sequential hours spent awake. In other words, the longer a person spends awake, the stronger the drive to sleep becomes. The circadian rhythm is an innate, genetically influenced, biologic clock that runs on a 24-hour cycle, commonly considered the body’s master clock. In healthy sleep, there is a complementary overlap between sleep–wake homeostasis and the circadian rhythm resulting in a regular predictable sleep– wake cycle. However, external factors, such as drugs, stress, or injuries such as concussion, can derange this cycle and cause sleep–wake disorders (Chaput et al., 2009; Gosselin et al., 2009; Hou et al., 2013; Tkachenko et al., 2016) (Table 13.2). Postconcussive sleep disorders may result from any combination of direct linear forces, acceleration– deceleration forces, or rotational forces to the brain that

*Correspondence to: Sanjeev V. Kothare, MD, Cohen Children’s Medical Center, Northwell Health, 2001 Marcus Avenue, Suite W290, Lake Success NY 11042, United States. Tel: +1-516-465-5255, Fax: +1-718-347-2240, E-mail: [email protected]

128

A.M. MORSE AND S.V. KOTHARE Table 13.1 Differential diagnosis of sleep disturbances after concussion Frequency (%) Primary sleep disorders Obstructive sleep apnea Central sleep apnea Hypersomnia Circadian rhythm sleep disorder Narcolepsy Insomnia Parasomnias Periodic limb movement disorder/restless-leg syndrome Secondary causes of sleep disruption Posttraumatic stress disorder Pain Depression/anxiety Fatigue Medications

25 10 28 36 4 30 25 25 15 25 20 55 a

Modified from Singh K, Morse AM, Tkachenko N, et al. (2016) Sleep disorders associated with traumatic brain injury – a review. Pediatr Neurol 60: 30–36. a Frequency varies.

Table 13.2 Relationship between concussion and sleep disorders Reference

Study design

Patients evaluated

Significant findings

Hou et al. (2013)

Observational study

Adults (47  13 years) with acute, first-ever TBI, and positive findings on cranial CT scans

● ● ● ●

Gosselin et al. (2009)

Case-control study

Concussed and nonconcussed athletes

● ●

Chaput et al. (2009)

Case series

Patients with mild TBI based on retrospective chart review

●

● ● ●

Tkachenko et al. (2016)

Retrospective chart review

Patients with mild TBI based on retrospective chart review

●

●

38% had sleep disturbance following TBI Insomnia twice as common as hypersomnia Hypersomnia associated with severe TBI Somatic symptoms have a strong association with insomnia No differences between groups on polysomnography or quantitative EEG Discrepancy between subjective and objective measures of sleep quality in concussed athletes Sleep complaints three times more frequent in patients with headaches in first 6 weeks following mild TBI Sleep complaints are a possible risk factor for headache and mood disturbance Acutely impaired sleep is related to pain Subacutely impaired sleep is related to frequent awakenings Patients with moderate/severe headache, dizziness, and psychiatric symptoms have a higher likelihood of moderate/severe sleep disorders following mild TBI Sleep symptoms became more severe with increased time between mild TBI and SCAT-3 administration

CT, computed tomography; EEG, electroencephalogram; SCAT3, Sport Concussion Assessment Tool-3; TBI, traumatic brain injury.

SLEEP DISORDERS AND CONCUSSION may cause shear injuries and axonal damage. Alternatively, delayed injury from cellular and biochemical excitotoxicity may incite sleep–wake disruption. The brainstem and posterior hypothalamus provide arousal signaling throughout the forebrain, regulating activity of the cortex and hypothalamus directly (Saper et al., 2001). Orexin neurons in the lateral hypothalamus further activate these brainstem arousal pathways, as well as directly excite the cortex and basal forebrain. The ventrolateral and median preoptic nuclei are the main sleep-promoting pathways that inhibit ascending arousal pathways in both the hypothalamus and brainstem (Saper et al., 2010). Interactions between sleepand wake-promoting brain regions provide reciprocal activation and inhibition that result in an effective “flip-flop switch” for sleep–wake regulation (Saper et al., 2010). Orexin neurons may provide stability to the switch, preventing sudden rapid transitions between sleep and wake (Saper et al., 2010; De Lecea and Huerta, 2014). These brain regions may be susceptible to concussion (Baumann et al., 2007; Shekleton et al., 2010; Valko et al., 2015). For instance, in contrecoup injuries, the inferior frontal and anterior temporal lobes, including the basal forebrain, may be injured due to brain collision with the bony prominences of sphenoid ridge of the base of the skull. Excessive daytime sleepiness is the most common postconcussive sleep complaint, and it results from impaired orexin (hyprocretin) production and signaling (Baumann et al., 2007). Orexin deficiency may also contribute to symptoms of excessive daytime sleepiness via reduced cortical excitability, as measured by transcranial magnetic stimulation (Nardone et al., 2011). Pleiosomnia (increased sleep need across 24 hours) and excessive daytime sleepiness have also been associated with loss of wake-promoting histaminergic neurons in the tuberomammillary nuclei following severe traumatic brain injury (Valko et al., 2015). Circadian rhythm disorders can result from injury of the suprachiasmatic nuclei in the hypothalamus. Although dim-light melatonin onset is considered the most accurate marker for assessing the circadian pacemaker (Pandi-Perumal et al., 2007), there is no evidence of change in dim-light melatonin onset after concussion. However, total melatonin production differs in patients with concussion versus controls; melatonin production increases acutely, but decreases after 6 months or more after concussive injury (Seifman et al., 2008; Shekleton et al., 2010). Melatonin may increase acutely because it has a neuroprotective role as an antioxidant in areas of injured cerebral tissue (Seifman et al., 2008). Chronically, reduced melatonin may be related to structural damage, impaired neurogenesis, and decreased cell proliferation, resulting in delayed sleep phase syndrome, irregular sleep–wake

129

patterns, and reduced rapid eye movement (REM) sleep (Shekleton et al., 2010).

ASSESSMENT OF SLEEP DISORDERS AFTER CONCUSSION Standardized comprehensive head injury instruments, such as the Acute Concussion Evaluation (ACE) recommended by the Centers for Disease Control and Prevention, (https://www.cdc.gov/headsup/pdfs/providers/ ace-a.pdf), include sleep evaluation screening in patients following concussion (Gioia and Collins, 2007). Screening questions include an assessment for a history of a sleep disorder plus evaluation for postconcussive complaints such as drowsiness, excessive daytime sleepiness, sleep disruption, and difficulty falling asleep. High-yield sleep screening questions like these are a helpful first step in the evaluation for sleep disturbance following sports-related concussion. Patients with highrisk responses, such as positive history of sleep disturbance prior to injury, or new symptoms of excessive daytime sleepiness or sleep disruption, should undergo further evaluation for a sleep disorder. A comprehensive sleep evaluation (Table 13.3) entails a detailed history to help determine the patient’s sleep–wake habits and patterns before and after concussive injury. Such history includes pre- and postinjury bedtime, sleep latency, waking time, and any additional time spent in bed that is not for sleep, for both weekdays and weekends. Pathology-specific questions, such as number and cause of nocturnal awakenings, presence of snoring and apneas, sleep-related hallucinations, or presence of cataplexy will increase the likelihood of correctly identifying a specific sleep pathology. The sleep history is complemented by standardized inventories, such as the Epworth Sleepiness Scale (Johns, 1991) STOP-BANG sleep apnea questionnaire (Abrishami et al., 2010), Pittsburgh Sleep Quality Index (Backhaus et al., 2002), and Insomnia Severity Index (Bastien et al., 2001). Investigations and objective data collection are not uniform (Fig. 13.1), but rather based on the most likely sleep pathology. For example, patients with suspected insomnia may be asked to complete sleep diaries and actigraphy, whereas those suspected of having sleep apnea, REM behavior disorder, or narcolepsy will require sleep studies. Subjective complaints (e.g., excessive daytime sleepiness, sleep fragmentation) may not be captured in results of objective testing such as polysomnography (Gosselin et al., 2009). Polysomnography is not a routine requirement in postconcussive patients. Several studies have demonstrated various findings of altered sleep architecture and quality following concussion, including increased sleep onset latency (Schreiber et al., 2008), increased

130

A.M. MORSE AND S.V. KOTHARE

Table 13.3 Comprehensive sleep assessment tools following sports-related traumatic brain injury Clinical interview ● Document preinjury and current sleep–wake patterns for week days and weekends (include bedtime, wake time, any variations, frequency, and duration of any naps) ● Evaluate frequency, duration, severity, development, and fluctuations of nighttime sleep difficulties or reported daytime sleepiness ● Assess possible contributing factors (e.g., pain, environmental factors, and comorbid psychiatric and medical conditions) ● Evaluate for effects of sleep–wake disturbances (e.g., fatigue, sleepiness, mood, cognition, physical functioning) ● Document use of medication and other substances (e.g., natural products, caffeine, alcohol, or recreational drugs) ● Evaluate for symptoms of specific sleep disorders (e.g., snoring, apneas, sleep-related hallucinations, nightmares, limb movements) Sleep diary ● Patient-recorded report, generally over 14 days or more, of nature, severity, and frequency of sleep difficulties

Self-reported questionnaires ● Assess nature and severity of symptoms ● Insomnia: Insomnia Severity Index or Pittsburgh Sleep

Quality Index ● Excessive daytime sleepiness: Epworth Sleepiness Scale

or Stanford Sleepiness Scale ● Circadian rhythms: Morningness–Eveningness

Polysomnography (PSG) Considered gold standard to diagnose obstructive sleep apnea, periodic limb movement disorder, and narcolepsy Nighttime PSG ● Standard combination of EEG, electro-oculography, and electromyography used to assess patients’ sleep and sleep staging ● Measures of air flow, heart rate, blood oxygenation, and muscle movements provide additional information for diagnosis of specific sleep disorders (e.g., sleep-related breathing disorders or periodic limb movements) Daytime PSG Used to objectively assess daytime sleepiness Multiple Sleep Latency Test Measures time to fall asleep (i.e., sleep onset latency), as well as if REM sleep occurs, over four or five 20-minute nap opportunities (every 2 hours). Patient is asked to fall asleep Maintenance of Wakefulness Test Measures time to fall asleep (i.e., sleep onset latency), over four to five 40-minute periods (every 2 hours). Patient is asked to remain awake ● Evaluates ability to remain awake with minimal external stimulation Actigraphy Watch-like device generally worn at the wrist to monitor motor activity to measure duration of time being asleep or awake and variations in the sleep–wake schedule ● Can be used in combination with sleep diaries ● Concept similar to many commercially available fitness trackers that monitor sleep

Questionnaire or Sleep Timing Questionnaire Modified from Ouellet M, Beaulieu-Bonneau S, Morin CM (2015) Sleep–wake disturbances after traumatic brain injury. Lancet Neurol 14: 746–757. EEG, electroencephalogram; REM, rapid eye movement.

sleep fragmentation (Kaufman et al., 2001; Ouellet et al., 2006), and REM sleep changes (increased or decreased REM and reduced REM onset) (Schreiber et al., 2008). However, such findings have not been consistent; some studies have identified no differences on polysomnography between postconcussive patients and controls (Williams et al., 2008; Gosselin et al., 2009).

SLEEP DISORDERS AND COMORBID POSTCONCUSSIVE SYMPTOMS Sleep–wake dysfunction may cause or aggravate comorbid postconcussive symptoms such as fatigue, pain, depression, anxiety, irritability, and cognitive and functional impairment (Fichtenberg et al., 2002;

Chaput et al., 2009; Hou et al., 2013; Sufrinko et al., 2015). Patients with subjective sleep complaints are three times more likely to develop comorbid postconcussive symptoms (Chaput et al., 2009). The inverse also occurs, where comorbid postconcussive symptoms, such as pain, anxiety, and depression exacerbate sleep–wake dysfunction, creating a vicious cycle. Postconcussive cognitive deficits can be exacerbated by sleep–wake dysfunction. Athletes who sleep less than 7 hours prior to baseline testing perform worse on three of four Immediate Postconcussion Assessment and Cognitive Test (ImPACT) scores, and are also more likely to report associated postconcussive symptoms (McClure et al., 2014). Sleep times exceeding 9 hours

SLEEP DISORDERS AND CONCUSSION Prolonged sleep latency, reduced hours of sleep

Sleep onset different than desired, but appropriate sleep hours

Snoring, apnea, open mouth breather, morning headache/ thirst, bedwetting Fragmented sleep, sleep paralysis, cataplexy, sleep related hallucinations

Regular delayed (or early) sleep onset, normal sleep hours

AHI < 5

Insomnia

Circadian Rhythm Disorder

Sleep Related Breathing Disorder

AHI > 5

+ MSLT

COMPLAINT Excessive Daytime Sleepiness/ Fatigue/Impaired Attention

Irregular sleep onset, reduced sleep hours

Sleep diary +/actigraphy

polysomnography

Head Injury

COMPLAINT Sleep Initiation/Sleep Maintenance Difficulties

131

MSL < 8 mins 2 SOREMS

Narcolepsy

Repetitive rhythmic limb movements every 20-40 sec

PMLD/RLS

Increased tone, movements or activity during REM

REM Parasomnia (RBD)

COMPLAINT Sleep Behavior Changes

Sleep walking, Sleep talking, night terrors, confusional arousal

Violent, dream enactment behavior Stereotyped nocturnal behavior, tongue biting, bedwetting

Polysomnography with extended parasomnia montage versus seizure montage

Frequent limb movement, +/- limb discomfort

Activity (walking, talking, terror) during SWS

NREM Parasomnia

Stereotyped behavior and abnormal EEG findings

Seizure

LTM EEG, MRI

Fig. 13.1. Postconcussive sleep evaluation. AHI, apnea hypopnea index; EEG, electroencephalogram; LTM, long-term monitoring; MRI, magnetic resonance imaging; MSL, mean sleep latency; MSLT, multiple sleep latency test; NREM, nonrapid eye movement; PMLD, periodic limb movement disorder; RBD, REM behavior disorder; REM, rapid eye movement; RLS, restless leg syndrome; SOREMS, sleep onset rapid eye movement sleep; SWS, slow-wave sleep.

are associated with poor visual memory, visual motor speed, and reaction time (Kostyun et al., 2015). Sleep–wake disturbances may also be associated with a mental health disorder. Sleep disturbances experienced less than 3 months after concussion predict development of neuropsychiatric symptoms 1 year after concussive injury (Rao et al., 2014). Patients who experience poor sleep following concussion are more likely to have symptoms of depression or anxiety, and experience worse functional outcomes (Fogelberg et al., 2012). Pain has become recognized as a clinical subtype following concussion, especially chronic headache, and can be associated with sleep disorders (Chaput et al., 2009; Tkachenko et al., 2016). Most studies evaluating postconcussive patients tend to evaluate the contribution of pain on the development and persistence of sleep disruption (Lavigne et al., 2015). However, sleep disturbances and pain frequently exhibit a bidirectional relationship (Smith and Haythornthwaite, 2004a; Ohayon, 2005).

MANAGEMENT OF SLEEP DISORDERS FOLLOWING CONCUSSION Targeted management of postconcussive sleep disorders (Table 13.4) can result in rapid improvement in quality of life (Barlow, 2014). However, numerous factors may influence return to a normalized sleep–wake pattern, including injury severity, prior concussions, genetic factors, presence of medicolegal issues, and premorbid conditions. The current expert consensus is for 24–48 hours of rest after concussion before consideration of exercise and stepwise return to activity (see Chapter 19). Exercise following concussion may protect against development of postconcussive features (Grool et al., 2016). Brain rest can prohibit recovery by contributing to development of depression, anxiety, social isolation, sleep–wake disruption, and physiologic deconditioning (Annesi, 2005; Willer and Leddy, 2006; Howie and Pate, 2012; Thomas et al., 2015). Physical activity encourages

132

A.M. MORSE AND S.V. KOTHARE

Table 13.4 Treatment considerations for sleep disorders in patients following traumatic brain injury Sleep disorder Insomnia Primary Secondary Due to PTSD Due to pain Due to depression Due to medication Nightmare disorder Hypersomnia Obstructive sleep apnea Central sleep apnea Periodic limb movements of sleep/ restless-leg syndrome Circadian rhythm disorder Delayed sleep phase Advanced sleep phase

Parasomnia Narcolepsy

Treatment options Sleep hygiene, cognitive behavioral therapy (CBT)  melatonin, sedative/hypnotics, acupuncture SSRIs, psychologic counseling, pain management counsel, CBT, sleep hygiene  melatonin Remove offending medication, adjust dosing or time administered, consider offer sedating medication at bedtime Imagery rehearsal therapy, systematic desensitization, progressive deep-muscle relaxation training, prazosin Stimulant medications (i.e., methylphenidate, dextroamphetamine, modafinil, armomodafinil)53, strategic caffeine and naps Positive airway pressure (PAP) devices, surgical interventions, mandibular devices, weight loss PAP devices (including assisted servoventilation) Iron supplementation, dopamine agonists, gabapentin

Melatonin supplementation  stimulant medication in daytime,a  hypnotic medication in evening,a bright light therapy in morning/reduced light exposure in evening, prescribed sleep–wake scheduling, sleep hygiene education Advanced chronotherapy (bright light therapy in evening/reduced light exposure in morning)  melatonin,a sleep hygiene education, prescribed sleep–wake scheduling Safe sleep environment, scheduled awakenings, maintain a regular sleep schedule, benzodiazepines, anticonvulsant drugs Stimulant medications (i.e., methylphenidate, dextroamphetamine, modafinil, armodafinil), strategic caffeine and naps, sodium oxybate

Modified from Singh K, Morse AM, Tkachenko N, et al. (2016) Sleep disorders associated with traumatic brain injury – a review. Pediatr Neurol 60: 30–36. a Insufficient evidence to support the efficacy or safety of these medications in these disorders. PTSD, posttraumatic stress disorder; SSRIs, selective serotonin reuptake inhibitors.

maintenance of circadian rhythm and regular sleep–wake schedules and may prevent development of secondary fatigue (Bessot, 2017). In addition, forced rest in young athletes often disrupts normal sleep–wake cycles, with more time spent at night with electronic devices and social media, and more sleep in the daytime (Thomas et al., 2015). All patients recovering from concussion should be educated on the importance of sleep hygiene and maintaining a regular sleep–wake schedule. Cognitive behavioral therapy can improve a patient’s sleep by identifying and changing behaviors that compromise the ability to fall and/or stay asleep (Sullivan et al., 2018). This technique is especially useful in patients with insomnia, but can also be effective in patients with other sleep disorders, or comorbid postconcussive psychiatric and pain symptoms (Edinger et al., 2001; Smith and Haythornthwaite, 2004b; Manber et al., 2008). Patients who suffer from recurrent nightmares potentially related to the injury can be treated

using imagery rehearsal therapy, a form of cognitive behavioral therapy that reduces the frequency and severity of nightmares (Aurora et al., 2010). Patients with sleepdisordered breathing, such as obstructive sleep apnea, may be treated with a positive-pressure airway device (Epstein et al., 2009). Alternatively, depending on the anatomy and severity of symptoms, they may be treated with a mandibular advancement device, otolaryngology intervention, or positional therapy to reduce time spent in supine sleep (Epstein et al., 2009). There are limited studies assessing the safety and efficacy of pharmacologic treatments for postconcussive sleep disorders (Ouellet et al., 2015). Pharmacologic intervention is generally reserved for posttraumatic narcolepsy, symptoms that fail to improve with nonpharmacologic intervention, and sleep disorders with other comorbid symptoms requiring sedating or wakefulness-promoting medication (Castriotta et al., 2009; Castriotta and

SLEEP DISORDERS AND CONCUSSION Murthy, 2011; Menn et al., 2014; Lettieri et al., 2016). Treatment recommendations in postconcussive sleep disorders are therefore generally based on studies that have evaluated the medication’s efficacy in the primary sleep disorder (e.g., benzodiazepine receptor agonists in primary insomnia) (Castriotta and Murthy, 2011). The role of genetics as either a contributory or protective factor for postconcussive sleep disorders is unclear. Clock genes regulate the circadian rhythm (LakinThomas, 2000). There is evidence that specific polymorphisms of some of these genes can contribute to recovery of sleep disturbance after TBI (Hong et al., 2015). On the other hand, genes that function independent of sleep– wake regulation may also be important to consider. For instance, individuals with the APOE4 allele, a predisposition gene for Alzheimer disease, have an increased risk for poor cognitive outcome 6 months following traumatic brain injury (Zhou et al., 2008). Additionally, the same patients with the APOE4 gene are at increased risk for sleep disorders. The overlap of sleep disruption, cognitive deficits, and APOE4 allele following concussion has not been explored, but could potentially reveal a unique risk profile for cognitive sequelae.

CONCLUSION Sleep disorders are an important sequela of concussion. Prompt recognition and management improve recovery and mitigate prolonged postconcussive impairment. Future research should seek to improve understanding of the pathophysiology and genetic factors of postconcussive sleep dysfunction, the evolution of postconcussive symptoms over time, and additional therapeutic interventions. Finally, sleep assessment should be incorporated into return-to-activity decision making following concussion.

REFERENCES Annesi JJ (2005). Correlations of depression and total mood disturbance with physical activity and self-concept in preadolescents enrolled in an after-school exercise program. Psychol Rep 96: 891–898; 3_suppl. Abrishami A, Khajehdehi A, Chung F (2010). A systematic review of screening questionnaires for obstructive sleep apnea. Can J Anaesth 57 (5): 423–438. Aurora RN, Zak RS, Auerbach SH et al. (2010). Best practice guide for the treatment of nightmare disorder in adults. JCSM 6: 389–401. Backhaus J, Junghanns K, Broocks A et al. (2002). Test–retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. J Psychosom Res 53 (3): 737–740. Barlow KM (2014). Postconcussion syndrome: a review. J Child Neurol 31: 57–67.

133

Bastien CH, Vallie`res A, Morin CM (2001). Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med 2 (4): 297–307. Baumann CR, Werth E, Stocker R et al. (2007). Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study. Brain 130: 1873–1883. Bessot N (2017). Effects of physical activity on circadian rhythms in the elderly. In: Circadian rhythms and their impact on aging, Springer, Cham, pp. 323–335. Borgaro SR, Baker J, Wethe JV et al. (2005). Subjective reports of fatigue during early recovery from traumatic brain injury. J Head Trauma Rehabil 20: 416–425. Castriotta RJ, Murthy JN (2011). Sleep disorders in patients with traumatic brain injury. CNS Drugs 25: 175–185. Castriotta RJ, Atanasov S, Wilde MC et al. (2009). Treatment of sleep disorders after traumatic brain injury. JCSM 5: 137–144. Chaput G, Gigue`re J, Chauny J et al. (2009). Relationship among subjective sleep complaints, headaches, and mood alterations following a mild traumatic brain injury. Sleep Med 10: 713–716. De Lecea L, Huerta R (2014). Hypocretin (orexin) regulation of sleep-to-wake transitions. Front Pharmacol 5: 16. Edinger JD, Wohlgemuth WK, Radtke RA et al. (2001). Cognitive behavioral therapy for treatment of chronic primary insomnia: a randomized controlled trial. JAMA 285: 1856–1864. Epstein LJ, Kristo D, Strollo Jr PJ et al. (2009). Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. JCSM 5: 263–276. Fichtenberg NL, Zafonte RD, Putnam S et al. (2002). Insomnia in a post-acute brain injury sample. Brain Inj 16: 197–206. Fogelberg DJ, Hoffman JM, Dikmen S et al. (2012). Association of sleep and co-occurring psychological conditions at 1 year after traumatic brain injury. Arch Phys Med Rehabil 93: 1313–1318. Gioia G, Collins M (2007). Acute concussion evaluation (ACE). Heads Up: brain injury in sport: your practice tool kit. Available online at: www.cdc.gov/ncipc/pub-res/ tbi_toolkit/tbi/ACE. Gosselin N, Lassonde M, Petit D et al. (2009). Sleep following sport-related concussions. Sleep Med 10: 35–46. Grool AM, Aglipay M, Momoli F et al. (2016). Association between early participation in physical activity following acute concussion and persistent postconcussive symptoms in children and adolescents. JAMA 316: 2504–2514. Hong C, Wong C, Ma H et al. (2015). PERIOD3 polymorphism is associated with sleep quality recovery after a mild traumatic brain injury. J Neurol Sci 358: 385–389. Hou L, Han X, Sheng P et al. (2013). Risk factors associated with sleep disturbance following traumatic brain injury: clinical findings and questionnaire based study. PLoS One 8: e76087. Howie EK, Pate RR (2012). Physical activity and academic achievement in children: a historical perspective. JSHS 1: 160–169. Johns MW (1991). A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14 (6): 540–545.

134

A.M. MORSE AND S.V. KOTHARE

Kaufman Y, Tzischinsky O, Epstein R et al. (2001). Long-term sleep disturbances in adolescents after minor head injury. Pediatr Neurol 24: 129–134. Kostyun RO, Milewski MD, Hafeez I (2015). Sleep disturbance and neurocognitive function during the recovery from a sport-related concussion in adolescents. Am J Sports Med 43: 633–640. Lakin-Thomas PL (2000). Circadian rhythms: new functions for old clock genes. Trends Genet 16: 135–142. Lavigne G, Khoury S, Chauny JM et al. (2015). Pain and sleep in post-concussion/mild traumatic brain injury. Pain 156 (Suppl 1): S75–S85. Lettieri CJ, Williams SG, Collen JF (2016). OSA syndrome and posttraumatic stress disorder: clinical outcomes and impact of positive airway pressure therapy. Chest 149: 483–490. Manber R, Edinger JD, Gress JL et al. (2008). Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia. Sleep 31: 489–495. Mathias J, Alvaro P (2012). Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: a meta-analysis. Sleep Med 13: 898–905. McClure DJ, Zuckerman SL, Kutscher SJ et al. (2014). Baseline neurocognitive testing in sports-related concussions: the importance of a prior night’s sleep. Am J Sports Med 42: 472–478. McCrory P, Meeuwisse W, Dvorak J et al. (2017). Consensus statement on concussion in sport—the 5th international conference on concussion in sport held in Berlin, October 2016. Br J Sports Med 51 (11): 838–847. Menn SJ, Yang R, Lankford A (2014). Armodafinil for the treatment of excessive sleepiness associated with mild or moderate closed traumatic brain injury: a 12-week, randomized, double-blind study followed by a 12-month open-label extension. JCSM 10: 1181–1191. Nardone R, Bergmann J, Kunz A et al. (2011). Cortical excitability changes in patients with sleep-wake disturbances after traumatic brain injury. J Neurotrauma 28: 1165–1171. Ohayon MM (2005). Relationship between chronic painful physical condition and insomnia. J Psychiatr Res 39: 151–159. Ouellet MC, Beaulieu-Bonneau S, Morin CM (2006). Insomnia in patients with traumatic brain injury: frequency, characteristics, and risk factors. J Head Trauma Rehabil 21: 199–212. Ouellet M, Beaulieu-Bonneau S, Morin CM (2015). Sleep– wake disturbances after traumatic brain injury. Lancet Neurol 14: 746–757. Pandi-Perumal SR, Smits M, Spence W et al. (2007). Dim light melatonin onset (DLMO): a tool for the analysis of circadian phase in human sleep and chronobiological disorders. Prog Neuropsychopharmacol Biol Psychiatry 31: 1–11. Rao V, McCann U, Han D et al. (2014). Does acute TBI-related sleep disturbance predict subsequent neuropsychiatric disturbances? Brain Inj 28: 20–26.

Saper CB, Chou TC, Scammell TE (2001). The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 24: 726–731. Saper CB, Fuller PM, Pedersen NP et al. (2010). Sleep state switching. Neuron 68: 1023–1042. Schreiber S, Barkai G, Gur-Hartman T et al. (2008). Long-lasting sleep patterns of adult patients with minor traumatic brain injury (mTBI) and non-mTBI subjects. Sleep Med 9: 481–487. Seifman MA, Adamides AA, Nguyen PN et al. (2008). Endogenous melatonin increases in cerebrospinal fluid of patients after severe traumatic brain injury and correlates with oxidative stress and metabolic disarray. J Cereb Blood Flow Metab 28: 684–696. Shekleton JA, Parcell DL, Redman JR et al. (2010). Sleep disturbance and melatonin levels following traumatic brain injury. Neurology 74: 1732–1738. Singh K, Morse AM, Tkachenko N et al. (2016). Sleep disorders associated with traumatic brain injury – a review. Pediatr Neurol 60: 30–36. Smith MT, Haythornthwaite JA (2004a). How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature. Sleep Med Rev 8: 119–132. Smith MT, Haythornthwaite JA (2004b). How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature. Sleep Med Rev 8: 119–132. Sufrinko A, Pearce K, Elbin RJ et al. (2015). The effect of preinjury sleep difficulties on neurocognitive impairment and symptoms after sport-related concussion. Am J Sports Med 43: 830–838. Sullivan KA, Blaine H, Kaye S et al. (2018). A systematic review of psychological interventions for sleep and fatigue after mild traumatic brain injury. J Neurotrauma 35: 195–209. Thomas DG, Apps JN, Hoffmann RG et al. (2015). Benefits of strict rest after acute concussion: a randomized controlled trial. Pediatrics 135: 213–223. Tkachenko N, Singh K, Hasanaj L et al. (2016). Sleep disorders associated with mild traumatic brain injury using Sport Concussion Assessment Tool 3. Pediatr Neurol 57: 46–50; e1. Valko PO, Gavrilov YV, Yamamoto M et al. (2015). Damage to histaminergic tuberomammillary neurons and other hypothalamic neurons with traumatic brain injury. Ann Neurol 77: 177–182. Willer B, Leddy JJ (2006). Management of concussion and post-concussion syndrome. Curr Treat Options Neurol 8: 415–426. Williams BR, Lazic SE, Ogilvie RD (2008). Polysomnographic and quantitative EEG analysis of subjects with long-term insomnia complaints associated with mild traumatic brain injury. Clin Neurophysiol 119: 429–438. Zhou W, Xu D, Peng X et al. (2008). Meta-analysis of APOE 4 allele and outcome after traumatic brain injury. J Neurotrauma 25: 279–290.