Fatigue has numerous definitions and classifications; however clinically, fatigue is commonly defined asfeelings of physical and/or mental exhaustion during or after usual activities, or feelings of inadequate energy to begin activities.1,2
Fatigue
Overview
Definition
Prevalence
Fatigue is one of the most common symptoms following brain injury, 3 with an estimated prevalence of 32-73% post TBI4-6 relative to 29% in the general population. 6
Etiology
Central Fatigue - Brain Injury factors
- Structural brain damage (i.e. direct injury to reticular activating system and basal ganglia)
- Biochemical brain alterations (i.e. serotonergic pathways)
- Sleep disturbances
- Physiological factors (physical deconditioning, sleep deprivation, excessive energy consumption and depletion of hormones or neurotransmitters)
Central Fatigue - Psychological factors
- Depression
- Anxiety and stress
- Alcohol/drug dependency
- Reduced motivation
Peripheral/Physical or Non-Neurological factors
- Medications
- Other medical conditions
- Pain
Risk Factors
- Sleep hygiene practices
- Exercise and physical activity (too much or too little)
- Substance use or abuse (such as alcohol, nicotine, caffeine, and recreational drugs)
- Medications (such as antiepileptics, antihistamines, antipsychotics, typical and atypical, corticosteroids, antiarrhythmics, antidepressants, antiemetics)
- Untreated medical conditions (such as obstructive sleep apnea, obesity hypoventilation syndrome, hypopituitarism, hydrocephalus, anemia, depression, anxiety, agitation, PTSD, nightmare disorders)
- Untreated pain
Clinical Features
Physical Symptoms
- Yawning
- Heavy eyelids
- Eye-rubbing
- Nodding off or head drooping
- Headaches, nausea, or upset stomach
- Slowed reaction time
- Lack of energy, weakness, or light headedness
Cognitive Symptoms
- Difficulty concentrating
- Lapses of attention
- Failure to communicate important information
- Failure to anticipate events or actions
- Making mistakes on well-practiced tasks
- Forgetfulness
- Difficulty thinking clearly
- Poor decision making
Emotional Symptoms
- More quiet or withdrawn than normal
- Lack of motivation
- Irritable
- Low motivation
- Heightened emotional sensitivity
Assessment
History
- Sleep history
- Review sleep hygiene
- Premorbid sleep disturbance
- Physical activity log
- Medication review
- Cardiopulmonary or other medical disorders
- See Clinical Features
Physical Exam
- Inspect throat/oral cavity for obstructions (sleep apnea)
- Cardiopulmonary exam
- Physical fitness
- Cognitive assessment
Screening
Screening for fatigue involves subjective reporting and careful interpretation, as fatigue is multifaceted in nature. Several scales have been used to screen for fatigue. All of the screening tools have limitations; they are neither diagnostic nor a substitute for a comprehensive clinical assessment.
The most frequently used instruments for evaluating fatigue include:
- Fatigue Severity Scale (FSS)
- Fatigue Impact Scale (FIS)
- Visual Analogue Scale-F (VAS-F)
- Global Fatigue Index (GFI)
- Epworth Sleepiness Scale (ESS)
None of these scales were specifically developed for those with ABI. Of these, only the FSS has been validated in patients with ABI. 7,8
| Scale Author, Year | Initial Population | Specified Fatigue Subscales | Time Frame | Purpose | Score Interpretation |
|---|---|---|---|---|---|
Fatigue Severity Scale 10 | MS, lupus, healthy | None | Not stated | Measures severity of fatigue, impact on activities and lifestyle. | Score range: 1-7 Higher score=more severe fatigue |
Modified Fatigue Impact Scale 11 | MS | Physical, cognitive, psychosocial | Past 4 weeks | Measures impact of fatigue on life function. | Score range: 0-84 Higher score=more severe fatigue |
Visual Analog Scale – Fatigue 12 | Sleep disordered and healthy | Energy, fatigue | Not stated | Measures severity of fatigue. | 0-4 No fatigue 5-44 Mild 45-74 Moderate 75-100 Severe |
Global Fatigue Index 13 | Rheumatoid Arthritis | Degree, severity, distress, impact on ADLs, timing | Not stated | Measures severity and impact of physical and mental fatigue | Score range: 1-50 Higher score=more severe fatigue |
Epworth Sleepiness Scale 14 | Sleep disorders, healthy controls | Daytime sleepiness | Not stated | Measures daytime sleepiness | 0-10 Normal 11-14 Mild Sleepiness 15-17 Moderate 18-24 Severe |
Diagnostic Testing
There is no diagnostic imaging or serology specifically diagnosing fatigue.
Laboratory Investigations
Initial investigations should be determined based on the history and physical examination. Where appropriate, laboratory tests may include:
- Complete blood count (CBC)
- Electrolytes
- Fasting blood glucose or HbA1c
- C-reactive protein (CRP)
- Pregnancy test
- A workup for neuroendocrine causes of fatigue
- Blood levels of anti-seizure medications.
Diagnosis
Fatigue resulting from an ABI is diagnosed on the basis of exclusion of reversible or treatable causes of fatigue. As such, a systematic approach guided by a thorough clinical history should be used to rule out other causes of fatigue.
Diagnostic Criteria
There are no specific criteria for the diagnosis of fatigue.
Differential Diagnosis
Differential diagnosis is immense and this is an incomplete list. For a complete list please refer to the ERABI Clinical Guidebook - Fatigue and Sleep disorders.
Common causes of fatigue include:
- Cardiopulmonary – Congestive Heart Failure, COPD, Obstructive sleep apnea
- Anemia, Vitamin D deficiency
- Diabetes Mellitus, Hypothyroidism, Hypopituitarism
- Depression, Substance abuse
- Chronic Infection – HIV
- Malignancy
- Insomnia, Restless Legs
- Medication-related Fatigue
- Chronic Renal Disease
- Chronic Pain
- Chronic Fatigue Syndrome
Complications
- Decreased functional abilities
- Increased stress and depression
- Decreased physical fitness
Management
The management of fatigue is complicated by its multifaceted nature and as of yet a definitive treatment does not exist. Initial management should begin with addressing comorbidities or contributing causes identified on history, physical examination, and investigations. Following the management of comorbid conditions, non-pharmacological interventions such as behavioural modifications and psychoeducation should be considered next. Once conservative measures fail and modifiable factors have been addressed, pharmacological management should be considered.
Non-pharmacological Interventions
INESSS-ONF Clinical Practice Guideline Recommendations
Non-pharmacological interventions should be considered in the treatment of fatigue and sleep disorders for individuals with traumatic brain injury. Interventions may include: cognitive behavioural therapy (CBT) (for insomnia), light therapy, regular exercise, energy conservation strategies and sleep hygiene.7
Cognitive Behavioural Therapy
The goal of CBT is to modify behavioural factors that perpetuate fatigue. Ngyuen et al. 15 divides CBT for fatigue into six modules that focus on psychoeducation, daily schedule organization, cognitive restructuring, sleep interventions, strategies for physical and mental fatigue, as well as relapse prevention.
Psychoeducation
The goal of psychoeducation is to educate patients and caregivers about the sequelae of ABIs, such as a reduced ability to perform tasks that may result in fatigue. Accordingly, patients may learn compensatory techniques to adjust to their new cognitive and physical limitations.
Pacing
Energy conservation and pacing are two ways an individual is encouraged to overcome or deal with his or her levels of fatigue following brain injury; 16 often training with pacing is grouped under CBT.
Sleep Hygiene
Sleep hygiene involves education about behavioural patterns and environmental factors that disrupt sleep. Sleep support strategies should be provided, including information about avoiding caffeine, screen time before bed and maintaining a daily schedule. A list of suggested strategies from the ONF Guidelines for Concussion/Mild Traumatic Brain Injury & Persistent symptoms is provided below.
Mindfulness-Based Therapy
Mindfulness-based cognitive therapy combines cognitive behavioural therapy methods with mindfulness meditation practices such as yoga, body scan and sitting meditation or mindfulness classes. It is thought to reduce fatigue by lessening the impact of maladaptive coping strategies, behavioural, emotional or cognitive patterns
Lifestyle Management Strategies
Lifestyle changes can include anything from diet modifications to self-care to exercise. Although this approach intuitively makes sense, there are challenges when attempting to compare studies as the breadth of interventions and outcomes is significantly larger than in most areas of research.
Exercise
Exercise may improve fatigue and has significant benefits for cardiovascular health, general well-being, emotional and immune system functioning.
Light Therapy
The goal of light therapy is to shift waking or bedtimes towards a more desirable sleep-wake schedule. Typically, light therapy involves a person being exposed to a short wavelength light (430-475 nm; blue wavelength light) upon awakening. The theoretical basis for light therapy is using light to alter melatonin production and secretion.
| Intervention | Effect | Level of Evidence |
|---|---|---|
| Cognitive Behavioural Therapy for Fatigue | + | 1b Cognitive behavioural therapy may reduce fatigue and insomnia. |
| Psychoeducation | UC | N/A The effects of psychoeducation have not been studied with this group and as a result treatment effects are not known. |
| Pacing* | UC | N/A Although used clinically, the benefits of pacing have not been studied in a population with moderate to severe ABI. |
| Sleep Hygiene* | UC | N/A Although used clinically, the benefits of sleep hygiene have not been studied in a population with moderate to severe ABI. |
| Mindfulness-based therapy | UC | N/A Although used clinically, the benefits of MBT have not been studied in a population with moderate to severe ABI. |
| Lifestyle Management Strategies | + | 4 Programming focusing on lifestyle factors, adaptive coping, and goal management training may reduce fatigue up to 3 months and sleepiness up to 9 months post intervention. |
| Exercise* | + | 2 Home-based walking program may reduce fatigue up to 24 weeks following treatment compared to a nutritional counselling program. |
| Light Therapy* | C | 1b Blue light therapy, but not yellow light therapy, may be effective in reducing fatigue and daytime sleepiness. |
*Recommended by the INESSS-ONF Clinical Practice Guidelines
Pharmacological Interventions
INESSS-ONF Clinical Practice Guideline Recommendations
Consider short-term treatment with methylphenidate to reduce excess daytime sleepiness in individuals with traumatic brain injury. 7
Methylphenidate
Methylphenidate is a neurostimulant commonly used to treat narcolepsy and attention deficit hyperactivity disorder in children. 17 Methylphenidate increases dopamine and norepinephrine within the brain.
Modafinil
Modafinil, a wakefulness promoting agent, has been approved to address excessive daytime sleepiness (EDS). 18 The precise mechanism of action of modafinil is unknown.
Amantadine
Amantadine, another wakefulness promoting agent may provide some benefit in individuals with fatigue from multiple sclerosis although the results are mixed.
| Intervention | Effect | Level of Evidence |
|---|---|---|
| Methylphenidate* | C | 3 May not have adverse effects on the sleep-wake cycle. |
| Modafinil | - | 1a May not be effective for treating fatigue but may be effective short-term in treating excessive daytime sleepiness. |
| Amantadine | UC | N/A Although used clinically, the benefits of amantadine have not been studied in a population with moderate to severe ABI. |
| (-)-OSU6162 | - | 1b (-)-OSU6162 may not be effective for treating fatigue. |
*Recommended by the INESSS-ONF Clinical Practice Guidelines
Resources
INESSS-ONF Clinical Practice Guidelines
ERABI Clinical Guidebook
ERABI Module
ONF Guidelines for Concussion/Mild Traumatic Brain Injury & Persistent Symptoms
References
1. Chen MK. The epidemiology of self-perceived fatigue among adults. Preventive medicine. 1986;15(1):74-81.
2. Aaronson LS, Teel CS, Cassmeyer V, et al. Defining and measuring fatigue. Image--the journal of nursing scholarship. 1999;31(1):45-50.
3. Duclos C, Dumont M, Wiseman-Hakes C, et al. Sleep and wake disturbances following traumatic brain injury. Pathologie-biologie. 2014;62(5):252-261.
4. 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):1379-1388.
5. Ponsford JL, Ziino C, Parcell DL, et al. Fatigue and sleep disturbance following traumatic brain injury-their nature, causes, and potential treatments. Journal of Head Trauma Rehabilitation. 2012;27(3):224-233.
6. Silver JM, McAllister TW, Arciniegas DB. Textbook of traumatic brain injury. American Psychiatric Pub; 2018.
7. ONF-INESSS. Clinical Practice Guideline for the Rehabilitation of Adults with Moderate to Severe TBI. 2016.
8. Dittner AJ, Wessely SC, Brown RG. The assessment of fatigue: a practical guide for clinicians and researchers. Journal of psychosomatic research. 2004;56(2):157-170.
9. Ziino C, Ponsford J. Measurement and prediction of subjective fatigue following traumatic brain injury. Journal of the International Neuropsychological Society. 2005;11(4):416-425.
10. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Archives of neurology. 1989;46(10):1121-1123.
11. Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clinical Infectious Diseases. 1994;18:S79-S83.
12. Lee KA, Hicks G, Nino-Murcia G. Validity and reliability of a scale to assess fatigue. Psychiatry research. 1991;36(3):291-298.
13. Belza B. Comparison of self-reported fatigue in rheumatoid arthritis and controls. The Journal of Rheumatology. 1995;22(4):639-643.
14. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545.
15. Nguyen S, McKay A, Wong D, et al. Cognitive behavior therapy to treat sleep disturbance and fatigue after traumatic brain injury: a pilot randomized controlled trial. Archives of physical medicine and rehabilitation. 2017;98(8):1508-1517. e1502.
16. Fellus J, Elovic E. Fatigue: assessment and treatment. Brain injury medicine New York: Demos Medical Publishing. 2007:545-555.
17. Weber P, Lutschg J. Methylphenidate treatment. Pediatric neurology. 2002;26(4):261-266.
18. Jha A, Weintraub A, Allshouse A, et al. A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury. The Journal of head trauma rehabilitation. 2008;23(1):52-63.