Clinical manifestations

Presentation and course

Head trauma frequently leads to the appearance of wide variety of sleep disturbances, more frequently in those suffering mild head injury (31). Various sleep related disturbances encountered are listed above in Table 1. In all instances, the altered sleep pattern deviates greatly from the pre-head trauma sleep patterns.

One of the more common problems following head injury involves difficulties initiating and maintaining sleep, either with or without subjective daytime sleepiness. A meta-analysis of 21 studies comprising of 1706 traumatic brain injury survivors reported insomnia symptoms (50%), decreased sleep maintenance and sleep efficiency (49% to 50%), delayed sleep onset (36%), early morning awakenings (38%), and nightmares (27%) (35). In some cases, the insomnia is a manifestation of a circadian rhythm sleep disorder, typically delayed sleep-wake phase disorder or irregular sleep-wake rhythm disorder (03).

Among male military personnel, multiple traumatic brain injuries were found to increase the risk of insomnia (09; 36). Nightmares commonly interrupt sleep in veterans with posttraumatic stress disorder (PTSD) and mild traumatic brain injury (50; 04). Veterans of the United States campaigns in Afghanistan (Operation Enduring Freedom [OEF]) and Iraq (Operation Iraqi Freedom [OIF]) complaining of insomnia associated with mild traumatic brain injury and PSTD were found to report subjective sleepiness compared to veterans with insomnia due to PTSD alone (60).

Patients with traumatic brain injury have demonstrated increased prolonged sleep latency, sleep fragmentation, increased wake time after sleep onset, reduced total sleep time and efficiency, reduced REM latency, and decrease in total REM sleep (36; 62). According to a study, younger age, preserved memory, and comorbid depression were predictors of good response to cognitive behavioral therapy for insomnia (CBT-I) (42).

Hypersomnia developing after a head injury can be very disabling for the patient, with significant impact on quality of life. Although it can improve with time to some extent, persists in many cases (16; 62). Features of both hypersomnia and narcolepsy with or without cataplexy can emerge in posttraumatic patients (59). In cases where posttraumatic hypersomnia is present for at least three months (without any other cause such as another sleep or psychiatric disorder and/or medication), multiple sleep latency testing (MSLT) can demonstrate a mean sleep latency of eight minutes or less. The International Classification of Sleep Disorders, third edition (ICSD-3), published by the American Academy of Sleep Medicine classifies this as hypersomnia due to a medical disorder (01). If hypersomnia after a head injury occurs in association with two or more sleep-onset REM periods during MSLT testing, the diagnosis is narcolepsy type 1 or 2 due to a medical condition. Head trauma has also been reported to precipitate cases of Kleine-Levin syndrome, which is a rare disorder consisting of periodic recurrent hypersomnia with cognitive or behavioral disturbances, hypersexuality, and/or compulsive eating during an occurrence with complete resolution in between episodes (02).

A number of other sleep disorders have also been found in patients with head trauma. Masel and colleagues examined a series of 71 brain injury patients in a residential treatment program, all without a prior history of hypersomnia or sleep disturbance (34). Among 33 (46.5%) hypersomnolent patients, four had obstructive sleep apnea, seven had periodic limb movement disorder, and one had narcolepsy (in addition to periodic limb movement disorder). The remaining 21 patients were given a diagnosis of posttraumatic hypersomnia.

In an extensive series of 184 traumatic brain injury patients, Guilleminault and colleagues found that 32% of the patients were discovered to suffer from sleep-disordered breathing (primarily obstructive sleep apnea) (22). The authors noted that all 16 whiplash patients were diagnosed with sleep-disordered breathing. Traumatic brain injury patients with obstructive sleep apnea have greater degree of neurocognitive and attention deficits (63).

Castriotta and colleagues prospectively studied 87 adults at least three months after traumatic brain injury. Polysomnography and multiple sleep latency tests were administered to all subjects. Forty-six percent of the patients had abnormal sleep studies. The authors diagnosed 23% with obstructive sleep apnea, 11% with posttraumatic hypersomnia, 7% with periodic limb movements in sleep, and 6% with narcolepsy (12).

Head trauma occasionally precipitates parasomnias, NREM (such as sleepwalking), and REM sleep behavior disorder (59). Lesion of subcoeruleus nucleus of brainstem can cause increase in muscle tone during REM with dream enactment behavior (37).

Fatigue is another complaint associated with traumatic brain injury with untoward consequences on quality of life. In a study of 119 patients at least one year after traumatic brain injury, up to 53% reported fatigue, which was more prevalent in women or those with symptoms of depression, pain, or sleep disturbance (17). Studies have shown consequential improvement in mood, both depression and anxiety, upon treating sleep and fatigue in traumatic brain injury patients (42). According to one study, cognitive-behavioral treatment for insomnia (CBTI) was effective in improving fatigue in 55% of patients.

Psychiatric disorders like anxiety and depression add further layers of complexity to the posttraumatic sleep disturbances. Patients with mild traumatic brain injury and sleep complaints were more likely to report feeling depressed at 10 days and six weeks after their injury (13). In a large study of military personnel, a positive screening for traumatic brain injury and sleep problems were found to be early indicators of risk for developing PTSD, or depression, or both (30). New-onset anxiety after head injury is a significant predictor of sleep disturbance, though the cause-effect relationship is unclear (48).

Prognosis and complications

There are few longitudinal studies of patients with posttraumatic sleep disorders. The general clinical impression is that once stabilized, sleep disturbance related to organic brain damage shows little further change, other than a response to treatment (TBI). A prospective cohort study examined sleepiness in 514 traumatic brain injury patients one month after the injury, and then at one year. At one month, 55% endorsed at least one item on a four-item sleepiness questionnaire. At one year, only 27% endorsed one or more of the sleepiness items (61). Another prospective study of 51 patients with traumatic brain injury showed that at three years post-injury, 67% of the patients continued to complain of sleep-wake disturbances, especially fatigue and hypersomnia (27). Disturbed nocturnal sleep may be a marker of more severe injury in patients with closed head injury (32). Improved sleep efficiency is correlated with resolution of posttraumatic amnesia (33). One study also indicated that sustaining a traumatic brain injury in childhood can also increase risk of sleep wake disorders in young adulthood, especially after moderate traumatic brain injury (07). The same investigators also demonstrated that in moderate traumatic brain injury survivors, poor subjective sleep was associated with poor sleep, fatigue, and poor perception of general health (08).

In persons with traumatic brain injury, the presence of obstructive sleep apnea is associated with further impairment of sustained attention and memory than in patients with comparable severity traumatic brain injury without obstructive sleep apnea (63; 20). Traumatic brain injury patients with excessive daytime sleepiness have slower reaction times and poorer performance on the Psychomotor Vigilance Test than nonsleepy patients (12).

Clinical vignette

Case 1. BJ was a 55-year-old man who had experienced sleepiness since a motor vehicle accident five years prior to presentation. An electroencephalogram one year after his accident showed evidence of moderate diffuse cerebral dysfunction. Since the injury, he had experienced a number of neuropsychiatric symptoms, including depression, sleepiness, mood lability, headaches, memory impairment, executive dysfunction, and impulsivity. A polysomnogram performed three years prior to presentation showed mild obstructive sleep apnea with an apnea-hypopnea index of 14. Treatment for obstructive sleep apnea was not initiated due to lack of follow-up at the sleep clinic. His neuropsychiatrist initiated modafinil due to sleepiness. His medications included valproic acid, escitalopram, fentanyl, galantamine, and modafinil 100 mg per day. He was later referred to the sleep clinic for reevaluation.

Modafinil partially improved his sleepiness, but higher doses precipitated manic episode in which he could not sleep for several days. His wife reported that he used to snore loudly, but this had subsided recently. In addition to chronic sleepiness, BJ also reported sudden sleep attacks. History of cataplexy was not elicited. A repeat polysomnography did not demonstrate significant sleep apnea, and an MSLT was recommended, but he did not follow through. He was later lost to follow-up.

Case 2. RW suffered a closed head injury at work in which an object struck his right parietotemporal region. He developed symptoms of sleep apnea, including snoring, sleepiness, and witnessed apneas, about one month after the accident. He denied sleep apnea symptoms prior to the injury. Examination was remarkable for obesity, an enlarged neck circumference, a thickened tongue base, and a long soft palate.

Polysomnography demonstrated an apnea-hypopnea index of 132, consisting mainly of obstructive apneas and hypopneas, but also included a moderate number of central and mixed apneas, with a brief period of periodic respiratory pattern in the early portion of the study. He was given a diagnosis of severe sleep apnea, predominantly obstructive but with a central component.

Subsequent continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) titrations demonstrated that these modalities were ineffective for treating his sleep apnea. BiPAP therapy in the spontaneous timed mode (BiPAP-ST®) prevented most respiratory events, but sleep fragmentation and significant arousals remained. RW was prescribed BiPAP-ST at 20/12 cm H2O with a backup rate of 12. This improved his sleepiness, but he continued to have frequent nocturnal awakenings despite use of eszopiclone. An adaptive servo ventilation titration was recommended to assess if respiratory disturbances and sleep fragmentation could improve.

These two cases illustrate the challenges of treating sleepiness resulting from head injuries.

Biological basis

Etiology and pathogenesis

Closed head injury is most commonly caused by falls (28%), motor vehicle accidents (20%), impact from an object (19%), and assaults (11%) (28). The mechanism of injury is less important than the site. Past studies failed to show correlation between severity of traumatic brain injury and resultant sleep disturbances, but new emerging evidence demonstrates strong association of intracranial hemorrhage and low Glasgow coma scales with increased sleep (24).

Depending on the impact intensity, direction, and duration of the acceleration/deceleration, different types and extent of damage can occur. Closed head injury is known to lead to "shearing" forces along the direction of main fiber pathways, causing microhemorrhages in these areas.

Various pathophysiological mechanisms have been postulated for different manifestation of posttraumatic sleep disturbances (52). Damage to areas involved in maintenance of wakefulness, including brainstem reticular formation and posterior hypothalamus, can lead to emergence of hypersomnia. High cervical cord lesions have also been known to cause sleepiness and sleep attacks (23).

Most patients with moderate to severe traumatic brain injury have low or intermediate hypocretin-1 levels in the acute phase of injury, which tend to improve by six months (05). Postmortem analysis of traumatic brain injury patients have revealed reduction in wake promoting hypocretinergic and histaminergic neurons (58).

Countercoup brain lesions following head injury most frequently occur at the base of the skull and may result in organic posttraumatic insomnia. They occur in areas of bony irregularities (especially the sphenoid ridges), with consequent damage to the inferior frontal and anterior temporal regions, including the basal forebrain, an area involved in sleep initiation. Sleep-wake disturbances after mild traumatic brain injury are associated with a longer tentorial length and flatter tentorial angle (the angle formed between the tentorium and a line through the foramen magnum) compared to patients with mild traumatic brain injury without sleep-wake disturbances. The authors postulated that direct impact involving the tentorium and pineal gland leads to pineal gland injury in mild trauma, which results in disruption of melatonin homeostasis and sleep-wake disturbances (66). Studies on mice with traumatic brain injury, have shown low concentration of melatonin-1 (MT1) and melatonin-2 (MT2) receptors (43).

Closed head injury may involve the nucleus suprachiasmaticus or its output. This can lead to disturbance of the circadian rhythm and, subsequently, a combination of hypersomnia and insomnia. A complete reversal of the circadian rhythmicity has also been reported (06). In one case, a 20-year-old man suffered mild to moderate traumatic brain injury and penetrating eye injury after an improvised explosive device blast (10). He developed a free-running type of circadian rhythm and was successfully treated with evening melatonin. Disruption of retinohypothalamic tract, which regulates circadian pacemaker, can lead to sleep wake rhythm disturbances (19). One study revealed 42% reduction in melatonin secretion and delay in dim light melatonin onset by 1.5 hours in traumatic brain injury patients as compared to controls (19).

Epidemiology

In the United States, approximately 1.4 million people each year receive medical attention for a new traumatic brain injury (56), causing over one million emergency department visits, 290,000 hospitalizations, and 51,000 deaths (51). The exact prevalence of resulting posttraumatic sleep disorders is unknown but has been cited to be greater than 50% (35). In a prospective study, Baumann and colleagues found that approximately three out of four patients who were initially hospitalized for traumatic brain injury developed sleep-wake disturbances by six months after the injury (05). Insomnia is the most common sleep impairment noted with a prevalence varying between 30% to 65%, with a relatively higher prevalence in mild traumatic brain injury cases (16; 62).

After head injuries, 42% to 85% of patients report excessive sleepiness acutely (16; 15), which remits to 10% to 53% over time (05; 12; 62). A study of moderate to severe traumatic brain injury patients in rehabilitation revealed that 84% had sleep apnea-wake cycle disorder (SWCD) on admission with 63% having moderate to severe sleep apnea-wake cycle disorder after three weeks. Fifty-nine percent still had sleep apnea-wake cycle disorder at four weeks, half with moderate to severe sleep disruption (41).

Obstructive sleep apnea has been reported in 35% to 61% of patients according to various studies (16; 62)

Prevention

Prevention of posttraumatic sleep disorders is best achieved by prevention of the original trauma.

Differential diagnosis

The primary differential diagnosis involves ascertaining the etiology of symptoms and determining their temporal association to head injury. In many cases, especially those developing directly out of recovery from coma, the association is clear. However, a careful history must always exclude prior sleep disturbance of similar type. Occult causes of somnolence must be considered (ie, hydrocephalus, subdural hematoma, arachnoid cysts, meningitis, and epileptic seizures), as well as the possible use of central nervous system depressant medications. Comorbid medical, psychiatric, and behavioral conditions like pain, depression, anxiety, and cognitive impairment may pose challenges in clinical management of these patients. Psychogenic insomnia related to head injury must be ruled out, as should cases in which secondary gain is involved, especially when in a medicolegal context. To date, there is enough information to indicate that subjects with anatomical risk factors for sleep-disordered breathing (ie, snoring or sleep apnea) may abruptly develop evidence of overt sleepiness following head trauma. Similarly, clear-cut narcolepsy with cataplexy has been shown to follow head trauma in subjects found to be HLA-DQB1*0602 positive. The recognition that head trauma can be a precipitating factor leading to excessive daytime sleepiness is important, as it has medicolegal implications. An appropriate work-up is necessary to confirm the appearance of the problem post-head trauma.

Diagnostic workup

A detailed account of a patients sleep history obtained with assistance of caregiver is crucial in order to (1) document the association of the sleep disorder with the trauma, (2) rule out any preexisting sleep disorder, (3) assess the evolution of course after the head injury, and (4) and measure the impact of interventions. Physical examination greatly assists in clinical decision making.

Out of numerous questionnaires, 16 have been studied in the traumatic brain injury population (39). Although there are inherent limitations in obtaining subjective data, Epworth Sleepiness Score (ESS) and Pittsburgh Sleep Quality Index (PSQI) have been validated against objective parameters in traumatic brain injury patients (18; 34). In terms of the latter, global PSQI score of 8 or better delineated the patients with clinically significant insomnia in traumatic brain injury (18). Fatigue severity score (FSS) can be used to assess and monitor changes in fatigue after CBT-I intervention (42). Some other questionnaires employed in this population include Morning-Eveningness Questionnaire (MEQ), Insomnia Severity Index (ISI), and the Swiss Narcolepsy Scale (SNS) (39). A sleep and concussion questionnaire (SCQ) has been proposed for mild TBI cases, which demonstrated convergent validity with objective parameters obtained through polysomnography and other self-reported measures such as insomnia severity index (ISI) and Epworth Sleepiness Score (ESS) (57).

Polysomnography should be done to determine the nature of the posttraumatic nocturnal sleep disturbance, as well as rule out coexistent sleep pathologies, such as sleep apnea and periodic movements in sleep.

Cases with posttraumatic hypersomnia have generally shown an increase in nightly sleep duration with or without changes in other sleep measures (21; 37). In patients with posttraumatic insomnia, sleep architecture has shown long sleep latencies, low sleep efficiency, a decrease in nightly sleep duration, and increased stage 1 sleep (45; 36; 62). Compared to controls, patients with moderate to severe traumatic brain injury had increased slow wave sleep, a reduction in REM sleep, and more frequent nocturnal awakenings (19).

Continuous polysomnography has confirmed an increase in total sleep per 24 hours in some patients with posttraumatic hypersomnia (21). From a historical perspective, it is of interest that polysomnography during the comatose period has prognostic value for the development of full recovery without posttraumatic sleep disturbance. Normal amounts of sleep spindles, K-complexes, and normal non-NREM and REM cyclicity within sleep are favorable prognostic signs (29). Young age, relatively better cognitive status, and higher depression scores predict good clinical response to CBT-I (42). Actigraphy may be a helpful adjunct to a sleep diary in those who have suffered a brain injury (54).

If daytime sleepiness is a major complaint, a multiple sleep latency test following polysomnography may be helpful to determine if a central hypersomnia is present. In posttraumatic hypersomnia with daytime sleepiness, sleep latency may be markedly shortened (21). On the other hand, patients with posttraumatic insomnia exhibit prolonged sleep latencies on multiple sleep latency tests, as well as in nocturnal sleep studies. As already mentioned, the presence of sleep-disordered breathing and sleep-onset REM periods does not eliminate the possibility that the head trauma was the precipitating factor in the development of the sleep disorder. Because a driving accident also may be due to prior existing sleepiness, a thorough inquiry is needed to appropriately compensate victims of secondary sleep disorders, even in the presence of preexisting risk factors. The medical workup should include assessment of the activity of the individual prior to the accident. This assessment should also include: (1) interviews of bed partners and coworkers; (2) investigation of employer records, prior health reports, driving records; and (3) employment history, including absenteeism.

Management

The approach to management should involve focused intervention, based on the specific type of sleep disturbance experienced by the individual.

Insomnia

Non-pharmacological intervention. Although pharmacological treatment of insomnia has been challenging, cognitive behavioral therapy for insomnia (CBTI) has demonstrated promising results (42). Behavioral techniques should be utilized for all insomnia patients. Psychological therapies are beneficial and include stimulus control, therapy, relaxation training, and cognitive behavioral therapy. Other modalities likely used with these are sleep restriction, therapy, biofeedback, and sleep hygiene education (40; 42). These therapies can improve nocturnal sleep quality as well as reduce daytime fatigue in those with insomnia related to traumatic brain injury (46). In addition, acupuncture may also be a viable treatment in improving sleep quality following traumatic brain injury (67). Daily morning blue light therapy has also demonstrated increase in total sleep duration (47).

Pharmacological Intervention. There are lack of scientific data regarding use of sedative agents in this specific population. Current guidelines recommend against the use of benzodiazepines due to adverse effects on cognition, risk of dependency, and/or abuse. The nonbenzodiazepine receptor agonists are extensively used, including zolpidem, the longer-acting eszopiclone, and the shorter-acting zaleplon. Although these medications are often helpful with initiating and/or maintaining sleep, they are associated with some concerning side effects, including complex sleep-related behaviors (ie, sleepwalking and sleep-related eating disorder). One paper reported increased risk of dementia with use of hypnotics in traumatic brain injury patients (14). Additionally, many sedating antidepressants are used for insomnia, especially when comorbid depression exists. These medications include trazodone, mirtazapine, and doxepin. These are also associated with many side effects and should be used with caution in elderly patients. Suvorexant is a newer agent approved for the treatment of insomnia, which acts by blocking the binding of wake-promoting neuropeptides (orexin A and B) to receptors (OX1R and OX2R) to suppress the wake drive. This medication should be used with care as it can lead to impaired motor coordination, complex sleep-related behaviors, mood/behavioral/cognitive changes, sleep paralysis, and/or cataplexy-like symptoms. Furthermore, patients are often treated with many other medications off-label (ie, gabapentin, quetiapine, or olanzapine) due to well-known side effect of sleepiness. Over-the-counter medications are often used to aid sleep, such as diphenhydramine, doxylamine, and hydroxyzine (all first-generation antihistamines). Melatonin and various herbal supplements are also frequently utilized, including valerian, gamma-aminobutyric, 5-L-5-hydroxytryptophan, kava, and many others. When using any of these medications, the prescriber should caution the patient not to drive (or do any other activity that could be of danger to self or others) after taking the medication. The patient should not use these medications with alcohol and use restraint when taking these with other sedating medications.

Selective serotonin reuptake inhibitors for depression or anxiety should be taken in the morning because they can induce insomnia when taken at bedtime. Lastly, tricyclic antidepressants are frequently used to treat chronic pain issues and may also help with insomnia due to their sedating effects.

Hypersomnia

Non-pharmacological intervention. Patients with hypersomnolence should be educated regarding strategic napping, caffeine, and driving precautions. Blue light therapy has shown promise in improving daytime sleepiness, fatigue, and quality of life with recovery in post-concussion symptoms and depression severity. Studies have shown improvement in Epworth Sleepiness Score, Beck Depression Inventory, and functional outcome of sleep questionnaire scores (47; 55).

Pharmacological Intervention. Patients with posttraumatic narcolepsy or hypersomnia may benefit from the use of an alerting agent. Modafinil may be the medication of first intention because it has fewer side effects than other stimulants. The dosage is usually 200 to 400 mg, administered in two divided doses in the morning and at lunchtime. A prospective, double-blind, randomized, placebo-controlled trial found that modafinil (100 to 200 mg given each morning) significantly improved sleepiness measured by the Epworth Sleepiness Scale and the maintenance of wakefulness test. Modafinil was not found to be effective for fatigue (26). However, another study found modafinil to be of limited effectiveness for sleepiness associated with traumatic brain injury (25). Armodafinil, the R-enantiomer of modafinil, is dosed only once per day (38). Methylphenidate and amphetamines are also used in those with narcolepsy (or hypersomnia) related to head injury. Patients with severe head trauma who complain of intellectual slowness may benefit more from amphetamine-based medications because these have a general activating effect that is not solely devoted to sleepiness. When cataplexy is present in narcolepsy, sodium oxybate may be prescribed because it is effective not only for the treatment of sleepiness, but also can reduce the frequency of cataplexy and consolidates sleep. A tricyclic antidepressant, selective serotonin reuptake inhibitor, or venlafaxine can also be prescribed to reduce disabling cataplexy, if present (40).

Restless leg syndrome

Management of restless leg syndrome associated with traumatic brain injury is the same as restless leg syndrome in general population. The dopamine agonists (ie, ropinirole or pramipexole) or alpha2 Delta ligands (gabapentin, pregabalin, and gabapentin enacarbil) are commonly used to treat this disorder. Levodopa has been proven effective but due to the risk of augmentation, it is utilized less frequently. Narcotics and benzodiazepines are only reserved for more significant cases not responsive to other medications. Importantly, iron storage levels should be investigated in these patients to ensure a ferritin level greater than 75 ng/mL. In the event of low ferritin, iron supplementation is the treatment of choice.

Sleep related disordered breathing

Cases of sleep apnea resulting from a head injury are treated in the usual manner with various modes of positive airway pressure, continuous (CPAP), or bilevel (bilevel PAP) therapy. Sometimes the spontaneous/timed mode of BiPAP therapy or adaptive-servo ventilation is necessary for central sleep apnea or when both obstructive and central sleep apnea are present.

Other treatments alternatives for obstructive sleep apnea include mandibular advancement devices. These are used when mild or moderate obstructive sleep apnea is present and have a success rate around 50%. They are less effective for severe obstructive sleep apnea and in those with a higher body mass index.

Surgical procedures are considered at times, especially in those with severe obstructive sleep apnea in those who have difficulty tolerating positive airway pressure. Surgical procedures can include tonsillectomy, septoplasty, turbinate reduction, uvulopalatopharyngoplasty, genioglossus advancement, and hyoid myotomy and/or maxillomandibular advancement. Tracheostomy is rarely used for obstructive sleep apnea; it is reserved for life-threatening cases. Weight reduction surgeries are another surgical consideration in morbidly obese patients with obstructive sleep apnea. In addition, a surgically implanted hypoglossal nerve stimulation contraption is used to treat obstructive sleep apnea (53).

Finally, conservative treatments for obstructive sleep apnea include weight loss, avoiding the supine position during sleep, and maintaining nasal patency with the use of saline spray or prescribed nasal steroid spray, if needed. One should also avoid alcohol and medications that may reduce muscle tone or influence the respiratory drive (ie, narcotics and benzodiazepines) prior to bedtime (40).

When approaching a patient with a posttraumatic brain injury sleep disorder, the clinician must also attend to underlying pain, depression, and anxiety, as these issues can greatly impact sleep. Therapy for posttraumatic stress disorder could also be helpful in ameliorating the sleep disturbances. Those self-medicating posttraumatic brain injury symptoms with alcohol risk sleep disruption, nightmares, reduction in REM sleep, and worsening sleep apnea; thus, counselling regarding sleep practices is vitally important.

Outcomes

Unfortunately, there is a dearth of clinical data regarding treatment of sleep disorders associated with traumatic brain injury. Although targeted management of sleep disorders might improve objective measures in few cases, clinical outcomes have remained poor in terms of subjective sleep and neuropsychological function (11; 26; 37). Encouragingly, an Australian study demonstrated significant clinical improvement in insomniac patients in sleep measures with mean PSQI <5 with cognitive behavioral therapy for insomnia (CBT-I). Seventy percent of the patients showed drastic improvement in sleep scores, and 55% showed positive trend in fatigue measurement (42). Another observational study focusing on CBT-I treatment of insomnia demonstrated decrease in C-reactive protein, an inflammatory marker in patients who had improvement in sleep (04). Contradictory to these, in a group of 57 patients with traumatic brain injury, Castriotta and colleagues polysomnographically documented sleep disorders in 22 subjects (39%) where treatment did not lead to significant changes in quality of life, mood, or cognitive performance. Treatment of obstructive sleep apnea (13 subjects, 23%) with CPAP did not lead to improvement in sleepiness, as measured by the Epworth Sleepiness Scale and MSLT. According to a few other studies, modafinil and armodafinil improve subjective and objective sleepiness but did not have much improvement in functional outcome due to fatigue, which underscores the multifaceted nature of the posttraumatic sleep disturbances (26; 38). Studies regarding use of daily blue light have shown substantial improvement in not only subjective scores of Epworth Sleepiness Score, Beck Depression Inventory, and post-concussion symptom questionnaire, but also normalized wake after sleep onset and greater total sleep time. These findings led to improvement of functional outcome of sleep questionnaire scores (47).