Brain Injury Study Guide - Fatigue

18 May 2018

What is fatigue?

Fatigue is a symptom, a subjective phenomenon - not something which can be measured objectively. Depression anxiety or stress may exacerbate or be the cause of fatigue and it is most severe immediately after brain injury.Fatigue is common but often overlooked, presenting as limited energy reserves to accomplish ordinary daily activities, or extreme exhaustion which may appear suddenly during mental activity.

Diagnosing fatigue

Exclude other causes in addition to anxiety, depression and stress, like lack of regular and restorative sleep, chronic pain, seizure related fatigue, hydrocephalus, hormonal abnormalities (e.g. hypothyroidism), nutritional deficiencies (e.g. B12), anaemia, serious illness (e.g. leukaemia, renal failure, hepatitis). If these can be ruled out, then conclude that the fatigue is neurogenic.

Evaluation should include screening for the above, medication, triggers, aggravators, alleviators and in what ways fatigue impacts physically and mentally and when.

Pacing and chunking activities (i.e. putting certain activities together) is helpful. Drugs are certainly not first line treatment, but in resistant cases methylphenidate may help.

How common is fatigue?

It is difficult to be precise about how common fatigue, or particularly mental fatigue, is because of different definitions and study methodologies.

However, in follow-up studies the frequency of prolonged fatigue is from 16 – 73%, and there is no correlation with severity of primary injury, age or time since injury. In those with fatigue three months after injury, it remained stable over prolonged periods.

What are the typical characteristics and symptoms of fatigue?

A typical characteristic of pathological mental fatigue after brain injury is that the mental exhaustion becomes pronounced during sensory stimulation or when cognitive tasks are performed for extended periods without breaks.

There is a drain of mental energy where the environment is noisy and hectic, leading to an invasion of the senses with an overload of impressions. Disproportionally long recovery periods are required after overload.

Fatigue fluctuates during the day, and it can appear very rapidly after which it is not possible for the person to continue with the activity.

Common associated symptoms include:

  • impaired memory and concentration capacity,
  • slowness of thinking,
  • irritability,
  • tearfulness,
  • sound and light sensitivity,
  • sensitivity to stress,
  • sleep problems,
  • lack of initiative and
  • headache.

For many people, this mental fatigue is the dominating factor which limits their ability to lead a normal life with work and social activities. For most people, fatigue subsides after a period of time while, for others, this pathological fatigue persists for several months or years even after the brain injury has healed. Interestingly however, as many as 30% of family or friends interpret fatigue as laziness.

Theories about fatigue

Theories about the mechanism of fatigue suggest that cognitive activities require more resources and are more energy-demanding after brain injury than usual.

There is no robust theory about the mechanism but there is speculation that the symptom may be caused by dysfunction of the astrocytes, the most common supporting cells in the brain. As a consequence, nerve cell communications do not function properly. Following TBI there is a neuroinflammation with down-regulation of astroglial glutamate transport systems.

Glutamate signaling is essential for information processing, including learning and memory formation. Low levels and fine-tuning of extracellular glutamate are necessary to maintain high precision in information processing, and thereby high efficiency in the information handling within the central nervous system.

One way to restore this dysfunction is to stimulate Na+ /K+ -ATPase along the dopaminergic circuits which regulate attention and executive functions. Possible candidates for doing this are methylphenidate and the dopaminergic stabilizer OSU6162.

Assessment can be made using the MFS, a multidimensional questionnaire containing 15 questions. It incorporates affective, cognitive and sensory symptoms, duration of sleep and daytime variation in symptom severity. The questions concern the following: fatigue in general, lack of initiative, mental fatigue, mental recovery, concentration difficulties, memory problems, slowness of thinking, sensitivity to stress, increased tendency to become emotional, irritability, sensitivity to light and noise, decreased or increased sleep as well as 24-hour symptom variations.

It has been found that information processing speed, attention and working memory were significantly reduced after brain injury (both mild TBI and TBI) compared to controls. Among the cognitive functions, processing speed was found to be a significant predictor for the rating on MFS.

Research indicates that mental fatigue and depression must be treated as separate constructs and it is also important to make this distinction for the purposes of therapeutic strategies.

How to recognize long-lasting mental fatigue?

  • • The mental fatigue has persisted for at least 1 month
  • • The sum of scores from the MFS is 10.5 points or above.

Typical symptoms include:

  • • An unusually rapid drain of mental energy upon mental activity
  • • Impaired attention and concentration capacity over time
  • • Following over-exertion, a long recovery time disproportionate to the exertion level
  • • Diurnal variation of the fatigue symptom with the fatigue often being better in the mornings and worse in the afternoons and evenings; variations from one day to the next
  • • Usually one or several associated symptoms
  • • Mood swings, irritability and stress intolerance
  • • Trouble with memory
  • • Sleep problems
  • • Sensitivity to, or intolerance of light and loud noise
• Headaches following over-exertion.

Characteristic symptoms in blue circle and associated symptoms in green circle

There is currently no effective treatment for mental fatigue. For many people, there is an increased risk of doing too much and becoming even more fatigued. Today, the most important recommendations are to adapt to the energy available by doing one thing at a time, resting regularly and not overdoing things.

When mental fatigue is present, it is important to adapt work as well as daily activities to levels that the brain can manage. However, this is challenging for most people and it may take a long time, even years, to adapt to a sustainable level. It may also be difficult for the person to learn by himself/herself and it can take several years of considerable struggle, frustration, despair and depression, to find the right balance between rest and activity. Professional support is required but this can be hard or impossible to find especially when mental fatigue continues for many years.

Treatment strategies include:

  • • Take regular breaks
  • • Encourage rest before becoming over-tired
  • • Try to work at a steady pace, taking one task at a time with short working periods, and prioritize the tasks
• Plan the days’ activities or the activities for the week in a diary or journal. Avoid overexertion.

The use of strategies is important. By resting the brain as much as possible the mental energy will be restored. However, the brain and the individual also need positive experiences and stimulation to ensure wellbeing. It is difficult to achieve this balance between rest and stimulation.

When mental fatigue becomes a prolonged problem, it is essential to be able to alleviate the symptoms.

Options include: the mindfulness-based stress reduction (MBSR) programme, pharmacological treatments, using neurostimulant substances as methylphenidate which affects dopamine and norepinephrine signaling, and potentially a new substance not currently available on the market, OSU6162, which is a dopamine and serotonin stabilizer.

Research results demonstrate that mindfulness practice may be a therapeutic method well-suited to subjects suffering from mental fatigue after brain injury. One reason why MBSR is effective may be that this treatment offers strategies to better handle stressful situations appropriately and economize the use of mental energy.

In an open randomized study, methylphenidate significantly improved mental fatigue dose dependently as assessed with the MFS.

In two randomized, double-blind and placebo-controlled studies, statistically significant alleviation of mental fatigue was found after a stroke or TBI by OSU6162 during 4 weeks’ treatment with active drug. However, the numbers of patients in these studies were small (21 TBI and 19 stroke victims).

Fatigue Study Guide


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