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Post-stroke fatigue and return to work a 2-year follow-up, does ear ringing medicine work - Within Minutes

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Defining and therefore operationalising fatigue is challenging as there are many confounding factors associated with it.
Confounding factors contributing towards fatigue following brain injury incorporate pathophysiological, physical, mood and cognitive elements, including slowed speed of processing and difficulty sustaining attention,10 executive dysfunction,11 reward and effort perception,9 anxiety and depression,12,13 sleep disturbance12 and pain.14,15 Clinically these interacting elements may be considered as ‘vulnerability factors’ for fatigue as they are common consequences of an acquired brain injury and so addressing these factors may lead to a reduction in fatigue experienced and enhance levels of social participation. There are numerous self-report fatigue scales available, though few valid and reliable measures have been developed for people with ABI. Figure 1: Clinical model for understanding responses to fatigue following acquired brain injury.
In terms of clinical management, given that fatigue is considered a multidimensional construct, attention should be paid to the variety of factors which may contribute to both performance fatigability (objective signs) and perception of fatigue (subjective symptoms). There is an acknowledged discrepancy between objective signs (performance fatigability) and subjective experience (perception) of fatigue in the literature, which has led to a proposal for a unified taxonomy to guide assessment and intervention.25 Several models of fatigue have been proposed in the literature.
The clinical model proposed provides guidance on domains of functioning to assess and support fatigue management. Assessment and management of fatigue remains complex and challenging for both clinicians and researchers. ICD 10: International Statistical Classification of Diseases and Related Health (ICD-10-SE). It is now widely accepted as a multidimensional, biopsychosocial construct, authors describing both primary and secondary, or physiological (central and peripheral) fatigue and psychological fatigue impacting resultant behaviour, felt experience and its presentation within societal and cultural contexts.2 Central fatigue is considered to result from impairment to structures within the central nervous system and is characterised by depletion of hormones and neurotransmitters.
Pathological fatigue, which may indicate need for clinical intervention, does not necessarily dissipate with rest and is of greater intensity and duration compared to ‘normal fatigue’ experienced following exertion, with a corresponding impact on ability to undertake functional activities. Such scales include the Barrow Neurological Institute Fatigue Scale18 for acute stages post-injury, the Mental Fatigue Scale19 which has been developed for the ABI population, the Neurological Fatigue Index – Stroke20 which has been developed for Stroke.
This involves identifying and addressing both personal and injury-related factors (primary causes and secondary consequences) that make an individual vulnerable to fatigue following ABI.
However, to date, none of these have been found to be clinically useful for understanding fatigue following acquired brain injury, to capture all aspects of this challenging construct and an individual’s potential responses to it.
A review of personal factors, including coping styles and co-morbid illness, is recommended, with evaluation of injury-related vulnerability factors that could be contributing to fatigue based on pathology and assessment of associated physical, cognitive and psychological factors. A clinically useful model to aid a shared understanding and response to fatigue and thereby reduce an individual’s vulnerability to fatigue is proposed. Fatigue & Sleep Disturbance Following Traumatic Brain Injury – Their Nature, Causes, and Potential Treatments.
Unique Contribution of Fatigue to Disability in Community-Dwelling Adults with Traumatic Brain Injury. Fatigue and pain: Relationships with physical performance and patient beliefs after stroke. A self-assessment questionnaire for mental fatigue and related symptoms after neurological disorders and injuries.
Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. The fatigue severity scale: application to patients with multiple sclerosis and systemic lupus erythematosus.
An evaluation of a fatigue management intervention for people with acquired brain injury: an exploratory study. Mindfulness-based stress reduction (MBSR) improves long-term mental fatigue after stroke or traumatic brain injury. Schematic drawing of a synapse with glutamate as the transmitter and an astrocyte with processes surrounding the synaptic terminal.
Rating on separate items on the Mental Fatigue Scale for controls and brain injured subjects.
Correlation with age and rating on MFS for healthy controls and subjects with long-lasting mental fatigue after brain injury.
Correlation between Mental Fatigue Scale and information processing speed (Digit Symbol-Coding).5. The figure illustrates levels and fluctuations in mental fatigue measured with the MFS after TBI and variations over time.
Peripheral fatigue is considered as a diminished ability to contract muscles, involving the peripheral motor and sensory systems.2,7 Brain structures and networks thought to be involved include the hypothalamic-pituitary axis, ascending reticular activating system, frontal cortex and basal ganglia. People experiencing pathological fatigue following ABI frequently refer to their brain as “shutting off”, with an intolerance to sensory stimuli and struggle to think and communicate effectively.
Awareness of indicators of fatigue for that individual, mediating factors affecting behaviour (e.g.
The following model has therefore been developed by our clinical team, inspired by the fatigue model proposed for multiple sclerosis [cited in 26], current evidence and clinical experience, and it has been found useful when working with people with fatigue following ABI. This may indicate medical referral if physiological or psychiatric conditions are suspected which require further assessment and intervention e.g. Use of analogies in fatigue management, such as recharging a phone battery, can be helpful. Mindfulness-Based Stress Reduction has also been demonstrated as effective when delivered as an eight week group programme.29 Sinclair and colleagues30 have identified short wave (blue) light therapy as a potentially useful intervention. The green line represents a full recovery while the blue and red lines represent impaired recovery in terms of the mental energy levels. If this state is not restored completely, there will be an impaired extracellular glutamate clearing with slightly increased extracellular glutamate levels, slight astrocyte swelling and impaired glucose uptake.
Characteristic symptoms are seen on the blue circle and associated symptoms on the green circle. Most mild TBI victims recover completely (green field) and do not exceed 10 points on the MFS. But for people fighting their fatigue after brain injury day after day, fatigue is a major problem. Polatajko, Long term symptoms and limitations of activity of people with traumatic brain injury: a ten-year follow-up. Wright, Patterns of fatigue and its correlates over the first 2 years after traumatic brain injury. Johansson, Long-Lasting Mental Fatigue After Recovery from Meningitis or Encephalitis - A Disabling Disorder Hypothetically Related to Dysfunction in the Supporting Systems of the Brain in Essential Notes in Psychiatry, V.
Azouvi, Subjective fatigue, mental effort, and attention dificits after severe traumatic brain injury. Ponsford, Selective attention deficits and subjective fatigue following traumatic brain injury. For example, neural circuits involved in the regulation of attention and executive function may contribute to development of tiredness and aversion to effort leading to fatigue,8 whilst other authors9 note involvement of the ventro-medial pre-frontal cortex following penetrating traumatic brain injury. In our experience, when people begin to feel less fatigued, they naturally attempt to engage in more activity and so their overall level of fatigue may not reduce significantly, as measured on a fatigue scale.
One important aspect of clinical intervention for people with ABI is to notice signs and symptoms of fatigue before they perceive their brain as ‘shutting down’ or fully ‘draining their battery’. Cognitive and environmental strategies and mood management all contribute towards reducing effort involved in completing activities and associated errors, which may then contribute towards reducing rumination and self criticism. Further research is required to operationalise and validate fatigue assessment tools and to identify specific interventions that may reduce an individual’s vulnerability to fatigue following ABI.
This post-injury mental fatigue is characterized by limited energy reserves to accomplish ordinary daily activities. They consider fatigue after brain injury as an “umbrella term” describing “different symptom clusters with potentially heterogeneous aetiologies and consequences” 6 [p. However, it is possible to capture changes in their felt experience, such as a reduction in level of worry about their fatigue, an increase in their sense of control or self efficacy, an increase in their perceived quality of life or an increase in their awareness and understanding of fatigue. Fatigue management aims to increase a person’s ability to participate in their desired activities more effectively, improve their quality of life and improve their sense of control over their fatigue. Self-monitoring of fatigue levels can be challenging following ABI secondary to dysexecutive syndrome, or as a consequence of reduced interoception.

Adequate hydration, nutrition and physical exercise, implementing good sleep hygiene and having an understanding of preferences and challenges in sensory processing will also aid fatigue management depending on vulnerability factors identified. Given the multiple factors and interventions that may be involved, a specialist neurological multidisciplinary rehabilitation team are likely best placed to support people with fatigue following ABI.
On their return to work and daily activities, they are not able to manage and they become exhausted.
Glutamate is converted to glutamine in the astrocyte and transported back to the presynaptic terminal where glutamine is converted back to glutamate. Persons who have not experienced this extreme exhaustion which may appear suddenly, and without previous warning during mental activity, do not understand the problem.
This change can be captured through using a recognised scale of these constructs or for example using an individualised likert scale before and after intervention.
Identifying personal signs and symptoms of fatigue, through discussion, observation and asking others for signs of fatigue they notice will enable creation of a personalised ‘fatigue scale’ to indicate signs and symptoms of fatigue at an early enough stage to take action. Use of behavioural experiments to test out the impact of coping strategies and beliefs about the self has been useful in fatigue management intervention within our neuropsychological rehabilitation setting.
Persons whose recovery follows the red line do not recover and are not able to return to work and daily activities.2. During this process, and with decreasing ATP levels as the signal, glucose is taken up from the blood to supply neurons and astrocytes with energy.
This is especially difficult to understand as the fatigue may appear even after seemingly trivial mental activities which, for uninjured persons, are regarded as relaxing and pleasant, as reading a book or having a conversation with friends.
Patients report that fatigue significantly impacts upon their ability to participate in rehabilitation and daily living activities and influences their mood, relationships and quality of life. It is recommended to identify helpful coping responses to both reduce effort involved and to re-energise oneself, both ‘in the moment’ and ‘in anticipation’ of certain triggers when planning to support an individual to pace themselves. A normal, well-functioning, brain performs mental activities simultaneously throughout the day, but after a brain injury, it takes greater energy levels to deal with cognitive and emotional situations.In this chapter, we highlight mental fatigue after TBI.
Eilertsen, Ormstad and Kirkevold17 identified the need for acknowledgement of this distressing symptom from others as a key factor influencing coping as it presented as a ‘hidden dysfunction’ which could be misinterpreted by others. Through creation of a personalised fatigue formulation and management plan, based on the proposed clinical model, a shared understanding and validation of the fatigue experience can be facilitated. In the case of long-lasting mental fatigue, it could be the only factor that keeps people from returning to the full range of activities that they pursued prior to their injury with work, studies and social activities.
We describe mental fatigue and suggest diagnostic criteria and we also give a theoretical explanation for this. At the end of the chapter, we discuss treatment strategies and give some examples of possible therapeutic alternatives which may alleviate the mental fatigue.Normally, the brain works in an energy-efficient manner and prominent energy reserves are present. This is due to well-functioning ion channel and amino acid transport systems and other effective physiological processes.
After brain injury, some of these systems are down-regulated, and when mental energy requirements are high the physiological processes do not function to their full capacity; these cease to function efficiently with a resultant energy loss.
A majority of patients recover within one to three months following mild TBI [2, 3].Fatigue is one of the most important long-lasting symptoms following TBI, and is most severe immediately after head injury. However it is difficult to arrive at any clear figure as to how common fatigue or, in particular, mental fatigue is. The reason for this is that different results have been obtained, and these are attributable to differences in definitions and differences in the methodology in the various studies. There is no correlation between persistent fatigue and severity of the primary injury, age of the person at injury or time since injury [7, 8]. For those suffering from fatigue 3 months after the accident the fatigue remained relatively stable during longer periods [9].
Mental fatigue is not a separate diagnostic entityMental fatigue is not an illness, rather it represents a mental sequel, probably due to a disturbance of higher brain functions, either physical or psychological in origin.
Typical characteristics of mental fatigueA typical characteristic of pathological mental fatigue after TBI 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 upon mental activity in situations in which there is an invasion of the senses with an overload of impressions, and in noisy and hectic environments. The mental fatigue is also dependent on the total activity level as well as the nature of the demands of daily activities. The fatigue can appear very rapidly and, when it does, it is not possible for the affected person to continue the ongoing activity. 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 is that as many as 30% of family or friends interpreted fatigue as laziness [9].Theories as to the mechanisms accounting for mental fatigue including our own theory, suggest that cognitive activities require more resources and are more energy-demanding after brain injury than usual [13, 14]. Persons whose recovery follows the red line do not recover and are not able to return to work and daily activities.Therapist Luann Jacobs describes mild TBI and the lack of energy and lack of endurance that many can experience. 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 CNS. Our hypothesis implies that such dysfunction could underlie the mental fatigue at the cellular level. Assessment of mental fatigueThere is an abundance of scales for assessing fatigue in general and several of these scales are designed for use in different diseases [21, 22]. The scales include questions relating to feelings of fatigue, perceived impact on activities, affective feelings and mental or cognitive effects.
We decided to construct this scale since we were not able to find an assessment scale adapted to mental fatigue. 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. The questions in the scale are based on common activities and we have related the estimation to exemplified alternatives. The intention was to make the scale more consistent between individuals and also between ratings for the same individual.
The exemplified alternatives can help the person to respond in a similar way despite the present state of fatigue or emotional state. The CPRS also includes exemplified alternatives and it is used to record changes in psychopathology over a comparatively short period [23]. The questions included in the MFS are based on symptoms described following longitudinal studies of patients with TBI, brain tumours, infections or inflammations in the nervous system, vascular brain diseases, and other brain disorders, which indicates that an acquired brain injury or disorder can result in similar symptoms [24-26]. The use of MFS and results from the studies The rating on MFS by healthy controls and people who suffered mild TBI or TBI did not reveal any significant differences between females and males, and there was no correlation between the results on MFS and age or education of the TBI victims (figure 5). Furthermore, we did not find any correlation for the TBI participants concerning time since injury and their rating on MFS. We have, in our studies worked with participants with mental fatigue lasting for six months or periods greater than six months. This accounts for the fact that the rating may lack correlation to time since injury.The control group rated MFS significantly lower than mild TBI and TBI victims. The participants included for the analysis were healthy controls and participants who had suffered mild TBI or TBI without major depression. A score of 10.5 on the MFS was found to deviate significantly from the control sample and is also above the 99th percentile for the control group.
Mental fatigue and connection to cognitive functionsIt has been proposed that subjective mental fatigue after TBI or mild TBI correlates to poor performance in attention tests and reduced processing speed [13, 27, 29-34]. We also found that information processing speed, attention and working memory were significantly reduced for the brain injury victims (both mild TBI and TBI) compared to controls. Mental fatigue and connection to emotional functionsIn the population of TBI victims, depression is elevated although there is a wide variation in frequency, depending on methodological differences [35-37].

In our studies, we have included participants who complained of mental fatigue after TBI and we excluded subjects affected by major depression, as it was our intention to explore the mental fatigue component. The overlapping items include the following: lack of initiative, concentration difficulties, irritability and decreased sleep.
With a factor analysis, the items were separated into a mental fatigue component and a depression and anxiety component. Irritability was placed in the depression-anxiety component and the other three items in the mental fatigue component.
With an analysis using the new components, we found that by adjusting the mental fatigue component this removed the difference observed between the brain injured subjects and controls in the depression-anxiety component. However, by removing the depression-anxiety component this did not have an effect on the difference observed between the brain injured subjects and controls in the mental fatigue component.In this subject sample, we were able to demonstrate that a significant effect on the difference observed between the brain injured subjects and controls in the scores for depression can result in an overestimation if the effect of the mental fatigue component is not taken into consideration.
This 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.6. Definition and diagnostic criteria for long-lasting mental fatigueThe diagnostic criteria for posttraumatic brain syndrome include most of the symptoms that are often present along with mental fatigue. However, we suggest mental fatigue to be a central symptom after a brain injury reflecting an inefficient support to the neuronal networks.Mental fatigue is a lack of mental energy with impaired cognitive, emotional and sensory functioning. Situations which involve high levels of external cues and an overload of impressions are strenuous.
If the person becomes more mentally fatigued, the sleep will most often become worse, and if the person rests for some days the sleep can become improved again. The emotional load may increase the severity of the fatigue, but if mental fatigue exists, it will remain even once the emotional components, as depression or anxiety have been treated. 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. However, the brain and the individual also need positive experiences and stimulation to ensure wellbeing.
Treatment studies for alleviating mental fatigueWhen mental fatigue becomes a prolonged problem, it is essential to be able to alleviate the symptoms.
We have reported on significantly reduced mental fatigue after treatment using the mindfulness-based stress reduction (MBSR) program [40, 41]. We have also reported on possible therapeutic strategies to reduce mental fatigue by means of pharmacological treatments, using neurostimulant substances as methylphenidate [42] which affects dopamine and norepinephrine signaling. We have also reported on a new substance not currently available on the market, (-)-OSU6162, which is a dopamine and serotonin stabilizer [43].
MindfulnessThe MBSR program was tested on TBI and stroke victims suffering from long-term mental fatigue [40].
MBSR is a clinically-effectivemethod for a wide range of conditions as stress, depression, pain, and fatigue after cancer, with the potential to help individuals to cope with their difficulties [44-47]. MBSR is also suggested to be linked to improvements in attention and cognitive flexibility [48] and also to changes in brain neuronal connectivity [49]. Cullen 2011 [51] and these include gentle Hatha yoga with an emphasis on mindful awareness of the body, a body scan designed to systematically, region by region, cultivate an awareness of the body without the tensing and relaxing of muscle groups associated with progressive relaxation, and sitting meditation with an awareness of the breath as well as a systematic widening of the field of awareness to include all four foundations of mindfulness: awareness of the body, feeling tone, mental states and mental contents.
The program consists of eight weekly group sessions which are each approximately 2.5 hours long, one day-long silent-led retreat between sessions six and seven and home practice of about 45 minutes, six days a week. We found a significantly reduced mental fatigue after the MBSR program and participants improved their processing speed significantly compared to control on waitlist [40]. Another recent study with MBSR for mild TBI patients showed a similar result with significant improvement in quality of life, perceived self-efficacy, working memory and attention [52]. Furthermore, a small-scale study of 10 mild TBI subjects included in the MBSR program over a 12-week period also showed a significantly improved quality of life and decreased depression rating [53]. However, after TBI, a short MBSR program over a 4-week period did not result in any cognitive or emotional changes [55].The 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 was effective may be that this treatment offers strategies to better handle stressful situations appropriately and economize with mental energy.
MethylphenidateMethylphenidate inhibits dopamine and noradrenalin reuptake resulting in increased extracellular concentration of dopamine and noradrenalin [56]. Methylphenidate has been used for many years in the treatment of ADHD in children, in the first instance to increase wakefulness, attention and concentration capacity. Methylphenidate has also been tested on TBI victims with positive effects on information processing speed and, to some extent on working memory and attention [57-63]. Guidelines for use of methylphenidate for deficits of attention and processing speed after TBI have been suggested [64], while no such guidelines exist for fatigue following TBI. In an open randomized study, methylphenidate significantly improved mental fatigue dose-dependently as assessed with the MFS [42]. The item, pain was also studied and we found that this item was rated high by most of the subjects in our study as the participants were recruited on the basis of the items, TBI and pain.
However, it is important to note that pain can hide posttraumatic brain injury symptoms or mental fatigue which is not always connected to the actual pain. We also found that there was no interaction between the pain and the mental fatigue in those participants treated with methylphenidate. These findings indicate that, not only is it necessary to treat patients for the pain for which they are primarily referred to the clinic, but also for the mental fatigue, if present. However, tolerance of methylphenidate differed between subjects and we therefore recommend starting treatment with an initial low dose.
However, the numbers of patients in these studies were small (21 TBI and 19 stroke victims). Further studies are needed, with a larger number of patients and, in particular longer treatment periods as mental fatigue may be long-lasting. Several patients experiencing such adverse reactions expressed the wish to receive continued treatment with the drug.Similar results were detected for methylphenidate and OSU6162. These drugs were shown to have the effect of both alleviating mental fatigue and increasing information processing speed.8. ConclusionsMental fatigue can become a prolonged and distressing problem after TBI having considerable effect on life and wellbeing.
It is important to acknowledge and assess mental fatigue when discussing the options regarding therapeutic methods as the mental fatigue has been the result of a TBI. Suitably-adapted and energy-saving strategies are important and most patients need support in order to achieve an enduring balance between activities and rest as this is difficult, it takes a long time and may be frustrating.The treatment studies we reported on are aimed at helping the person to manage their life better. The reason for this is that, most often they want to carry out activities in a similar way as before the injury and have been longing for the chance to be able to do this. The problem is that, for most persons suffering from long-term mental fatigue after TBI, the activity levels are close to the threshold of what they are able to sustain. With mindfulness most participants reported on more energy, but they also became more pleased and happy with life. Mindfulness also gave them a tool to use and they could take command over their own lives; how it is here and now, not longing for a better life or ruminating over what has been.
A combination with neurostimulants and mindfulness may be a good therapeutic strategy.In the future, research is warranted for early treatment with the intention to reduce the development of long-term mental fatigue.

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