Fatigue following brain injury

Author:  Jennie Ponsford



A significant proportion of people with brain injury (32-73%) reportedly experience  fatigue (1, 2).   Whereas fatigue resolves within days or weeks for most people with mild injuries,  it can persist over many years following moderate to severe injuries and  impact negatively on participation in numerous activities, including work, study, leisure and social pursuits. Despite its common occurrence, causes of fatigue are not well understood and there are no established treatments.

Defining  fatigue

Fatigue is subjective and is experienced by everyone. There are no established methods of measuring it.  Aaronson and colleagues (3) define fatigue as “The awareness of a decreased capacity for physical and/or mental activity due to an imbalance in the availability, utilization, and/or restoration of resources needed to perform activity”  (p. 46).  Resources may be physiological or psychological.  At a physiological level, fatigue may be caused by  loss of energy, hormones, neurotransmitters or  neural connections, due to brain injury. This type of fatigue results directly from the injury. Fatigue may also be associated with muscle weakness or injuries in the peripheral nervous system. This type of fatigue may be assessed using motor tasks, such as grip strength, thumb pressing or speed of finger tapping. However  these  measures are not sensitive to fatigue originating in the central nervous system, such as occurs with a brain injury. Psychological fatigue is defined as, “A state of weariness related to reduced motivation, prolonged mental activity, or boredom that occurs in situations such as chronic stress, anxiety or depression.”(4) (p.291).  As depression and anxiety are commonly associated with TBI, it is important to consider this aspect of fatigue. 

Causes of fatigue

Fatigue is commonly associated with neuronal injury or dysfunction in conditions such as TBI and multiple sclerosis (MS). Fatigue caused by  injury or disease is  termed Primary fatigue (5). Various  factors may exacerbate fatigue, including  pain, sleep disturbance or stress. Fatigue due to these factors is  termed Secondary fatigue(5). Fatigue may be a symptom of depression and depression may result in early morning wakening. Anxiety may also disturb sleep, more commonly resulting in difficulty falling asleep. Emotional distress may thereby contribute to sleep disturbances and exacerbate fatigue. Fatigue following brain injury is most probably caused by any or all of these influences.  

Measuring  fatigue

There is no single valid and reliable fatigue assessment measure. Scales have been developed for assessment of fatigue in particular health conditions, including  cancer and Multiple Sclerosis.  These scales assess fatigue from a number of perspectives: its severity, its impact on lifestyle  and  associated emotional effects. Aaronson et al. (3)  have recommended that each of these aspects of fatigue be assessed,  as well as associated  secondary factors such as sleep or depression and  biological parameters.  Most measures of fatigue are self-report measures.  Measures used in studies of people with TBI have included: the Visual Analogue Scale for Fatigue (VAS-F) (4) which  subjectively quantifies of fatigue and energy levels on a likert scale at one point in time;  The Fatigue Severity Scale (FSS)(6) ,  a 9-item general fatigue scale used to assess the consequences  of fatigue and its impact  on daily functioning on a 7-point scale;   the Barrow Neurological Institute Fatigue Scale (BNI Fatigue Scale) (7), which  comprises 10 items, relating to daily levels of energy and alertness and  the Global Fatigue Index ( GFI)(8),  derived from 15 of 16 items of the Multidimensional Assessment of fatigue (MAF).  No studies have succeeded in identifying an objective measure of fatigue. Physical tests, such as a thumb pressing task, have not been shown to be sensitive to fatigue in people with brain injuries  (9). Other studies examining performance on complex cognitive tasks over time have found that whilst  level of performance may be lowered by presence of  subjective fatigue,  performance did not decline over time more in people with brain injury than healthy controls  (10, 11). Whilst such group findings may mask individual differences, the search for an “objective “ measure of fatigue continues.

What causes fatigue?

Whilst severity of self-reported fatigue following brain injury has not been closely associated with the age of the person, it has been related to higher education and some research  has suggested  females may report greater impact of fatigue on their lifestyle, perhaps related to their tendency to show lower mood (2, 12).

Fatigue is thought to be caused by diffuse axonal  injury, and particularly injury  in brain regions  which regulate  arousal, attention  and speed of response, including the ascending reticular activating system, limbic system, anterior cingulate, middle frontal and basal ganglia areas  (13).  Due to the presence of impairments of speed of information processing, attention, memory and executive function performance of mentally demanding tasks is more effortful for many people with brain injury, which find most cognitively demanding tasks more effortful.

It has been suggested that fatigue results from the increased effort needed to keep up with complex everyday demands in the presence of  impaired attention, processing speed and other cognitive functions. Fatigue levels are related to severity of attentional problems. Moreover whilst people with brain injury may be able to maintain task performance over time, this is associated with a disproportional increase in blood pressure, consistent with greater effort, and this is associated with fatigue levels, and subsequent emotional distress (11).

Self-reported fatigue has not been shown to be related to  severity of injury  (2, 12) or general  cognitive impairment Fatigue levels may decline somewhat in the first 6-12 months post-injury but thereafter plateau out or rise further over time (2, 14).  There is  variability in the patterns and time-course of  fatigue over time. Whilst it would be reasonable to assume that increasing  fatigue over time may be associated with  increased activity levels, there is no demonstrated association of fatigue with employment status (2, 12) or other major life activities (1). However, the most impaired individuals are also least  likely to be employed, and there have been no studies systematically examining the impact of increased lifestyle demands on fatigue.  Increasing fatigue may also reflect growing emotional distress, with increasing experience of functional limitations over time. Therefore, fatigue levels are likely to be determined by a combination of functional impairment and disability, lifestyle demands and emotional distress. .

It has also been suggested that neuroendocrine abnormalities, such as Growth Hormone deficiency (GHD), present in many people with brain injury,  may underpin fatigue. However,  there has been no evidence to support this (15). Baumann and colleagues (16) have argued that fatigue is caused by lower levels of the wake-promoting neurotransmitter CSF Hypocretin-1, caused by loss of hypocretin neurons.  This may cause daytime sleepiness.   

Secondary causes of fatigue

There is has been no established relationship between fatigue and the presence of orthopaedic injuries. Moreover whilst the taking of medication is not related to greater the impact of fatigue on daily lifestyle, there is a modest association between the experience of fatigue levels at a given point in time and the taking of analgesic medication (2).  Pain levels are significantly related to subjective fatigue (1, 2, 15). Depression and anxiety are also strongly associated with self-reported fatigue in individuals with brain injury (1, 2, 15). The direction of this association remains somewhat unclear. Fatigue is known to be a symptom of depression, but it may also be that the experience of fatigue over an extended period of time may result in the development of depression and anxiety. We (17) found that presence of fatigue was significantly associated with presence of depression six months later, whereas depression was not associated with the subsequent reporting of fatigue. Cantor and colleagues (1) also found that secondary factors accounted for a higher proportion of variance in fatigue in healthy controls than in individuals with brain injury, suggesting that the injury itself may make a unique contribution  to fatigue.

Increased levels of self-reported fatigue have also been associated with poor sleep quality or sleep disturbances in a number of studies (1, 2). This suggests that sleep problems,  which are reported by 30 to 80 percent of individuals with TBI (18) may contribute to fatigue. Reported sleep complaints following TBI include insomnia, hypersomnia and excessive daytime sleepiness. Excessive daytime sleepiness (EDS) is manifested as tiredness or drowsiness during the daytime after insufficient sleep or sleep disruption. People with EDS commonly feel the need to nap when they want to be awake. There is a theoretical distinction between EDS and fatigue, although in practice individuals with brain injury may not differentiate between the symptoms.


Treating fatigue

In assessing patients with brain injury who report fatigue, clinicians should investigate  all potential  contributing factors, including cognitive factors such as  attention and processing speed, sedating effects of medications, pain, emotional state, and sleep disturbances , and apply  necessary treatments.  Adjustments may be made to the individual’s lifestyle to allow for cognitive and physical limitations. This may involve reducing work hours, modifying the pace or demands of activities, reducing distraction and need for multi-tasking, and/or taking frequent rest breaks. Addressing psychological issues related to such lifestyle changes may be necessary. Where there is sufficient self-awareness, strategies may be developed to manage information overload and associated social difficulties in a range of situations. Physical conditioning programs can reduce physical fatigue and promote well-being, although they are not likely to alleviate fatigue arising from central nervous system injury.  Where sleep disturbance is reported it is important to have this objectively evaluated, as subjective reports may not accurately identify the source of the problem. Potential causes of sleep problems, such as pain, anxiety or depression need to assessed and treated as necessary. Instruction in sleep hygiene techniques, including avoidance of naps if this interferes with nighttime sleep, adhering to a regular schedule of time spent in bed, and avoiding time spent in bed awake may be provided along the lines described by Ouellet and Morin (19), who have demonstrated in a case series that such techniques can be effective in individuals with TBI.

 Modafinil  is a wake-promoting drug approved in the United States for treating excessive sleepiness associated with narcolepsy, obstructive sleep apnoea and shift work disorder. It has been used in the treatment of fatigue in individuals with multiple sclerosis and TBI. Randomized controlled trials have shown no impact on subjective fatigue in individuals with TBI, but some evidence of reduced daytime sleepiness  (20)  (21) . 

 Bright Light Therapy also presents a potential treatment for fatigue and daytime sleepiness. Light exerts non-visual effects on many biological functions. In healthy and patient populations light exposure results in reduced sleepiness, has arousing effects on a number of biological parameters, increases vigilance performance, and can improve mood. A pilot trial by our research group found a reduction in subjective fatigue and sleepiness during daily exposure to short wavelength light (22). This research is continuing.


Fatigue and sleep disturbance are common and persistent problems following brain injury. Fatigue and its impact on daily lifestyle may be assessed using a number of measures. Studies suggest that fatigue may be associated with impaired attention and information processing speed, necessitating greater effort in performing tasks. Thus assessment of these aspects of cognitive function is important. It may also be associated with depression, anxiety, and pain, which also require assessment, although the directions of these associations remain unclear. Sleep disturbances are also commonly reported and these contribute to fatigue. It is important to assess for and treat anxiety, depression, pain and sleep disturbances.  The injured person may be supported in making modifications to their lifestyle and daily activities to enable them to more effectively live within their cognitive and physical limitations. Sleep hygiene techniques may assist in minimising sleep disturbance. There is some preliminary evidence that Modafinil may reduce daytime sleepiness. Of non-pharmacological interventions light therapy holds promise as a means of increasing daytime alertness, as well as enhancing vigilance and mood. Further controlled trials of all of these interventions are needed.  


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

15.       Englander J, Bushnik T, Oggins J, Katznelson L. Fatigue after traumatic brain injury: Association with neuroendocrine, sleep, depression and other factors. Brain Injury. 2010;24(12):1379-88.

16.       Baumann CR, Werth E, Stocker R, Ludwig S, Bassetti CL. Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study. Brain. 2007;130(Pt 7):1873-83.

17.       Schönberger M, Herrberg M, Ponsford J. Fatigue as a cause, not a consequence of depression and daytime sleepiness: A cross-lagged analysis

Journal of Head Trauma Rehabilitation. in press;Accepted  28 May 2013.

18.       Mathias JL, Alvaro PK. Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: A meta-analysis Sleep Medicine. 2012;13:898-905.

19.       Ouellet MC, Morin CM. Efficacy of cognitive-behavioural therapy for insomnia associated with traumatic brain injury: a single case experimental design. Archives of Physical Medicine and Rehabilitation. 2007;88(12):1581-92.

20.       Jha A, Weintraub A, Allshouse A, Morey C, Cusick C, Kittelson J, et al. 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. 2008;23(1 ):52-63.

21.       Kaiser PR, Valko PO, Werth E, Thomann J, Meier J, Stocker R, et al. Modafinil ameliorates excessive daytime sleepiness after traumatic brain injury. Neurology. 2010;75(20):1780-5.

22.       Sinclair K, Ponsford J, Taffe J, Lockley SW, Rajaratnam SW. Randomised controlled trial of blue light therapy for fatigue following  traumatic brain injury. NeuroRehabilitation and Neural Repair. in press;Accepted 17 July, 2013.


Author contact information:

Jennie L. Ponsford, BA (Hons), MA (Clin Neuropsych), PhD, MAPsS           

Professor of Neuropsychology, School of Psychological Sciences, Monash University,

Director, Monash-Epworth Rehabilitation Research Centre, Epworth Hospital,

Victoria, Australia

Address for correspondence: School of Psychological Sciences, Building 17, Monash University, Clayton, 3800, Victoria, Australia

Email:  jennie.ponsford@monash.edu

Tel : + 61 3 99051552

Fax : +61 3 99053948


Editor’s note: The views and opinions expressed in the articles contained in the International Neuro-Trauma Letter are those of the authors and contributors alone and do not necessarily reflect the views, policy or position of the International Brain Injury Association or all members of the NTL Editorial Board. The NTL is provided solely as an informational resource and the inclusion of any particular article does not establish or imply IBIA’s endorsement of its contents.