Brain injury frequently causes changes in sleep patterns likely through injury to brainstem functions that affect the daily circadian rhythms. Individuals with brain injury frequently complain of fatigue that is likely partially due to decreased nerve function and connectivity in the brain and the extra effort required for cognition. These issues may be combined with other causes of fatigability such as deconditioning and other concomitant medical conditions. Individuals with complaints of fatigue and sleep disturbance require a medical and sleep workup to rule out treatable causes. People with traumatic brain injury (TBI) should be taught strategies to optimize fatigue (e.g. energy conservation, pacing) and good sleep hygiene. In those with persistent fatigue where TBI is believed to be the main cause medications may be considered. 

The rehabilitation team should have a structured and systematic process for assessing sleep disturbances and fatigue in individuals with traumatic brain injury. Clinicians with expertise in non-pharmacological therapeutic approaches for sleep-related disturbance, particularly cognitive behavioral therapy, should be available early on in the rehabilitation process. The rehabilitation environment and schedule should facilitate adequate sleep hygiene.

Indicators exemples

• Proportion of individuals with TBI formally assessed for fatigue and sleep disorders.

• Proportion of individuals with TBI and fatigue and/or sleep disorder who received at least one of the following five non-pharmacological interventions:

  1. Cognitive behavioural therapy (CBT);

  2. Light therapy;

  3. Regular exercise;

  4. Energy conservation strategies;

  5. Sleep hygiene

The following are suggestions of tools and resources that can be used to support the implementation of the recommendations in this section. Healthcare professionals must respect the legal and normative regulations of the regulatory bodies, in particular with regards to scopes of practice and restricted/protected activities, as these may differ provincially

Clinical Tools:

• Insomnia severity index (Morin, 1993)
• Pittsburgh sleep quality index (Buysse et al., 1989)
  English contact person: Daniel J. Buysse, M.D. at buyssedj@upmc.edu
• Fatigue severity scale (Krupp et al., 1989)
• Multidimensional Fatigue Inventory in Smets, E.M.A. et al. The multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. Journal of Psychosomatic Research, Volume 39, Issue 3, 315 - 325
• Insomnie et fatigue après un traumatisme craniocérébal – Manuel d’évaluation et d’intervention  (Insomnia and Fatigue after a Traumatic Brain Injury: Evaluation and intervention manual) – CIRRIS (in French only, English version due May 2018)
• Indications of use (Health Canada) and insurance coverage (for Quebec only) for the Pharmacological Management of TBI related Impairments

Patient and Family Resources:

• Sleep Comic – TBI Model Systems Knowledge Translation Center
• Fatigue and TBI – TBI Model Systems Knowledge Translation Center

Wiseman-Hakes et al. (2013) states that sleep disturbances associated with TBI can exacerbate cognitive, communication and mood deficits that are trauma-related. Similarly, Bushnik, Englander, and Wright (2008) found that when fatigue worsened over the course of 2 years, it was accompanied by poorer cognitive and motor outcomes as well as reduced levels of general functioning. Dealing with sleep disturbances is necessary for optimal recovery and fatigue and sleep disorders should be assessed. Common objective assessments for fatigue and sleep disorders included questionnaires, polysomnography, actigraphy, multiple sleep latency tests and maintenance of wakefulness tests (Mollayeva, Colantonio, Mollayeva, & Shapiro, 2013).

In terms of treatment, both pharmacological and non-pharmacological options have been studied:

Non-pharmacological interventions may include pacing, cognitive behavioural therapy (CBT), or light therapy, among others. A pre-post case series found that 8 sessions of CBT improved sleep disturbances by improving total wake time (p<0.001), sleep efficacy (p=0.01), fatigue (p<0.012), and insomnia (p<0.01) but not total sleep time (Ouellet & Morin, 2007). No additional significant gains were made once the treatment had concluded, although gains were maintained at a 3-month follow-up.

A RCT conducted by Sinclair, Ponsford, Taffe, Lockley, and Rajaratnam (2014) examined the effectiveness of blue and yellow light therapy versus a control group. The blue light therapy was shown to significantly decrease fatigue (p<0.001) and daytime sleepiness (p<0.01) but yellow light therapy did not show improvements compared to the control group. The improvements measured during the treatment phase did not persist at follow-up (week 8).

Pharmacological treatments to improve sleep quality have also been suggested. In research in cats, Aton et al. (2009) found that trazodone administration did not affect EEG but may have affected cortical plasticity. While trazodone has been found to be commonly prescribed in humans for insomnia, and shown some benefit, in other study populations, the research supporting trazodone’s effects on insomnia among a brain injury population is minimal (Larson & Zollman, 2010). Shan and Ashworth (2004) compared lorazepam with zopiclone to assess the effects of these medications on sleep and cognition in a randomized, double-blinded, crossover trial. There was no difference in average sleep duration or in subjective measures of sleep. Cognition as assessed by the Mini Mental Status Exam revealed no difference in the zopiclone arm compared with the lorazepam arm.

The indolamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin production has been found to be associated with REM sleep (Shekleton et al., 2010). Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties (Naseem & Parvez, 2014). Further, melatonin production levels were lower in individuals with TBI compared to healthy controls which suggests the disruption of the circadian regulation of melatonin synthesis (Shekleton et al., 2010). (Ponsford & Sinclair, 2014; Ponsford, Ziino, et al., 2012) conducted a large cohort study of community-based patients with TBI, recruited from a TBI rehabilitation program, completed measures of subjective fatigue and sleep disturbances, as well as attentional measures. A subgroup of participants completed polysomnography and assessment of dim light melatonin onset. They found that objective sleep studies show reduced sleep efficiency, increased sleep onset latency, and increased time awake after sleep onset. Depression and pain exacerbate but cannot entirely account for these problems. Individuals with TBI show lower levels of evening melatonin production, associated with less rapid-eye movement sleep (Ponsford & Sinclair, 2014; Ponsford, Ziino, et al., 2012). There are, however, limited studies examining the administration of exogenous melatonin among a brain injury population. (Kemp et al., 2004) conducted a RCT cross-over trial comparing melatonin and amitriptyline for a month for those with TBI (n=7). No significant improvements were found for either group on any of the sleep variables examined: latency, duration, quality or daytime alertness; however, it was found that melatonin had a moderate effect on daytime alertness (Kemp et al., 2004).

Pharmacological treatments to reduce fatigue are also an option if sleep disturbances have been ruled out and brain injury is suspected as the cause. Modafinil has been studied in two RCTs and although both studies found no significant difference between groups in fatigue, as measured by the Fatigue Severity Scale, the treatment groups both showed a significantly greater decrease in Epworth Sleepiness Scale scores when compared to controls, representing a greater improvement in excessive daytime sleepiness (Jha et al., 2008; Kaiser et al., 2010).

REFERENCES
Aton, S. J., Seibt, J., Dumoulin, M. C., Coleman, T., Shiraishi, M., & Frank, M. G. (2009). The sedating antidepressant trazodone impairs sleep-dependent cortical plasticity. PLoS One, 4(7), e6078.

Bushnik, T., Englander, J., & Wright, J. (2008). Patterns of fatigue and its correlates over the first 2 years after traumatic brain injury. J Head Trauma Rehabil, 23(1), 25-32.

Evidence-Based Review of Moderate To Severe Acquired Brain Injury (ERABI). (2016). http://www.abiebr.com/.   

Jha, A., Weintraub, A., Allshouse, A., Morey, C., Cusick, C., Kittelson, J., . . . Gerber, D. (2008). A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury. J Head Trauma Rehabil, 23(1), 52-63.

Kaiser, P. R., Valko, P. O., Werth, E., Thomann, J., Meier, J., Stocker, R., . . . Baumann, C. R. (2010). Modafinil ameliorates excessive daytime sleepiness after traumatic brain injury. Neurology, 75(20), 1780-1785.

Kemp, S., Biswas, R., Neumann, V., & Coughlan, A. (2004). The value of melatonin for sleep disorders occurring post-head injury: a pilot RCT. Brain Inj, 18(9), 911-919.

Larson, E. B., & Zollman, F. S. (2010). The effect of sleep medications on cognitive recovery from traumatic brain injury. J Head Trauma Rehabil, 25(1), 61-67.

Mollayeva, T., Colantonio, A., Mollayeva, S., & Shapiro, C. M. (2013). Screening for sleep dysfunction after traumatic brain injury. Sleep Med, 14(12), 1235-1246.

Naseem, M., & Parvez, S. (2014). Role of melatonin in traumatic brain injury and spinal cord injury. ScientificWorldJournal, 2014, 586270.

Ouellet, M. C., & Morin, C. M. (2007). Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic brain injury: a single-case experimental design. Arch Phys Med Rehabil, 88(12), 1581-1592.

Ponsford, J., & Sinclair, K. (2014). Sleep and fatigue following traumatic brain injury. Psychiatr Clin North Am, 37(1), 77-89.

Ponsford, J., Ziino, C., Parcell, D. L., Shekleton, J. A., Roper, M., Redman, J. R., . . . Rajaratnam, S. M. (2012). Fatigue and sleep disturbance following traumatic brain injury--their nature, causes, and potential treatments. J Head Trauma Rehabil, 27(3), 224-233.

Shan, R. S., & Ashworth, N. L. (2004). Comparison of Lorazepam and Zopiclone for Insomnia in Patients with Stroke and Brain Injury: A Randomized, Crossover, Double-Blinded Trial. American Journal of Physical Medicine & Rehabilitation, 83(6), 421-427.

Shekleton, J. A., Parcell, D. L., Redman, J. R., Phipps-Nelson, J., Ponsford, J. L., & Rajaratnam, S. M. (2010). Sleep disturbance and melatonin levels following traumatic brain injury. Neurology, 74(21), 1732-1738.

Sinclair, K. L., Ponsford, J. L., Taffe, J., Lockley, S. W., & Rajaratnam, S. M. (2014). Randomized controlled trial of light therapy for fatigue following traumatic brain injury. Neurorehabil Neural Repair, 28(4), 303-313.

Wiseman-Hakes, C., Murray, B., Moineddin, R., Rochon, E., Cullen, N., Gargaro, J., & Colantonio, A. (2013). Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI. Brain Injury, 27(12), 1364-1376.