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Post Stroke Fatigue
Why Live with It?
Benton Giap, MD MBA
© 2008 Santa Clara Valley Health & Hospital System
2
Today’s Overview
 Increase awareness of
manifestations and common
factors in developing of PSF
 Review the evidence for
assessment and treatment of
fatigue after stroke
 Management –outline practical
non-pharmacological tools for
managing this condition
3
Disclosure
Off-labeled uses of medications for post stroke fatigue.
Employer Anthem Blue Cross, Commercial Health Plan
Lots of cute baby pictures
4
In Their own words
 “my head is foggy”
 “life is too overwhelming!”
 hit a “brick wall”
 “exhausted” and failing to meet the
5
Definition of Fatigue
“a subjective experience of extreme and persistent tiredness,
weakness or exhaustion after stroke, which can present
itself mentally, physically or both and is unrelated to
previous exertion levels.
[Lerdal and colleagues]
6
Scope of the Problem
 Prevalence – 38 - 73 %
 PSF often does not diminish even years after stroke
 can be present within weeks and persist for many months or even years afterwards
 identified by 40% as amongst their worst symptoms impacting function, QOL, safety
7
Fatigue following Stroke: Frequency,
characteristics and associated factors
 Not associated with lesion size
 Location-fatigue associated lacunar infarcts located within the basal
ganglia, internal capsule, and infra-tentorial areas
 greater fatigue was related consistently to a poorer physical function
and symptoms of depression
 Pre-morbid level of functioning
 Multiple medications effect?
8
Fatigue is well appreciated in other
conditions
 multiple sclerosis
 post-polio syndrome
 traumatic brain injury
 cardiovascular disease
 pulmonary disease (COPD)
 depression
 thyroid disease
 obesity
 HIV/AIDs
 diabetes mellitus
9
 Depression
 Sleep problems, such as sleep
apnea
 Lack of physical exercise
 Vitamin deficiency/poor nutrition
 Anemia
 Pain
 Infection-acute , chronic
 Physical impairments from stroke
 Medications -anti-hypertensive,
spasmolytics, antidepressants,
pain medication
10
Differentiating fatigue from sleepiness
 Subjective feeling of
weariness, depleted energy
 Multidimensional(e.g.
mental, physical)
 No real objective measure
 Physiological drive to sleep
 Measurable signs: Yawning
 Eyes drooping
 Reduced alertness
 Can be measured in a sleep
laboratory(MSLT)
 FATIGUE  EXCESSIVE DAYTIME
SLEEPINESS
11
Mechanisms
 Activation of an
inflammatory response with
secretion of various
cytokines necessary for
immune signaling including
 interleukin-6 (IL-6)
 interleukin-1 beta (IL-1 )β
 tumor necrosis factor
alpha (TNF )α
 the exact mechanisms of origin
and persistence of PSF are still
elusive
 Contribution by hypothalamic-
pituitary-adrenal (HPA) axis
 modulated by cytokines
 Hypo-activity of the HPA axis owing to
decreased corticotrophin releasing
hormone has been accordingly found in
CFS and in chronic autoimmune conditions
 Hyperactivity results in a blunting of the
normal diurnal cortisol secretion curve with
reduced gluco-corticoid production and
onset of fatigue and depressive symptoms
© 2008 Santa Clara Valley Health & Hospital System
12
“Sickness Behavior”
mediated through
neural, immune, and endocrine mechanisms following stroke
 “neurovegetative “
syndrome (early)
 poor appetite
 sleep disturbances
 psychomotor slowing
 fatigue
[Rothwell and colleagues]
 “mood and cognitive”
syndrome (later)
 depression
 anxiety
 impairment of memory, attn
 lowered libido
© 2008 Santa Clara Valley Health & Hospital System
13© 2008 Santa Clara Valley Health & Hospital System
14
7-step approach toward a diagnosis
 Characterize the fatigue
 Assess presence of complaints suggesting organic illness
associated with fatigue
 Evaluate medicines used and/or substances abused
 Perform psychiatric screening
 Ask questions on sleep quantity and/or quality
 Perform a physical examination
 Undertake investigations
15
Fatigue Severity Scale (FSS)
16
Fatigue Pictogram
© 2008 Santa Clara Valley Health & Hospital System
17
Management
 No effective pharmacological option has been identified
 insufficient evidence existed to recommend any single
treatment for PSF
 no evidence-based treatments are currently available to
alleviate fatigue.
© 2008 Santa Clara Valley Health & Hospital System
18
Fatigue: pharmacological options ?
 Anecdotal reports with : amantadine, methylphenidate, modafinil,
Fluoxetine
 Randomized DB controlled trials: One
 N=83, consecutive outpatient stroke survivors (average 14 months
post stroke)
 randomly assigned to either fluoxetine 20 mg/day (n=40) or
placebo (n=43) given over 3 months.
 Follow-up evaluations at 3 and 6 months after the beginning of the
treatment, included the Visual Analogue Scale (mean score 5.4±2 at
baseline) and Fatigue Severity Scale (mean score 4.4±1.2 at
baseline).
© 2008 Santa Clara Valley Health & Hospital System
19
IS EXERCISE THE SOLUTION?
 Design- multicenter, randomized, controlled trial , 8 rehabilitation centers.
 Participants – 83 participants with stroke (4 months after stroke) were randomly
assigned to 12 weeks of cognitive therapy (CO) or cognitive therapy and graded activity
training (COGRAT) after qualification.
 Aim - to compare the effectiveness of a combined intervention (COGRAT) with that of
CO alone on fatigue and associated psychological and physical variables.
 Graded Activity Training (GRAT) consisted of walking on a treadmill, strength training,
and physical fitness home work assignments.
 Outcomes -Seventy-three patients completed treatment and 68 were available at follow-
up.
 Primary outcomes (Checklist Individual Strength–subscale Fatigue (CIS-f); self-observation list–
fatigue (SOL-f))
 Findings - Group cognitive therapy combined with graded activity training during a
12-week period reduces persistent PSF
[Zedlitz and colleagues, 2012]
© 2008 Santa Clara Valley Health & Hospital System
20
Intervention
 Cognitive Behavioral
Intervention
 Sleep Management
 Sleep Hygiene
 Caffeine Intake
 Alcohol Intake
 Medication Use
 Energy Conservation
 Plan
 Prioritize
 Pacing
 Elimination
 Cardiovascular
Conditioning
© 2008 Santa Clara Valley Health & Hospital System
21© 2008 Santa Clara Valley Health & Hospital System
22
Key points
 Stroke patients often present with complex needs.
 Fatigue can truly be disabling
 Fatigue can be challenging to quantify because of its multi-dimensionality (physical,
mental and psychological).
 Comprehensive intervention includes physical, informational, emotional, cognitive,
communication and practical aspects to support.
 Cardiovascular exercise is an important tool and highly recommended intervention.
Exercise offers one of the most effective interventions to enhance neurocognitive
functioning. It also may decrease depression and improve sleep.
 Modafinil is not effective in treating fatigue but has shown to be effective in treating
excessive daytime sleepiness post TBI.
 Practicing energy conservation principles and by prioritizing, planning, pacing for those
important tasks of the day is very often helpful.
© 2008 Santa Clara Valley Health & Hospital System
23
Reference
 Lerdal A, Bakken L, Kouwenhoven S, Pedersen G, Kirkevold M, Finset A, et al. Poststroke fatigue: a review. J Pain
Symptom Manage. 2009;38:928–949.
 Ouellet M, Morin C. Fatigue following traumatic brain injury: frequency, characteristics, and associated factors.
Rehabil Psychol. 2006; 51:140–9.
 Barritt AW, Smithard DG. Review Article: Targeting Fatigue in Stroke Patients. International Scholarly Research
Network ISRN Neurology, Volume 2011, Article ID
 Levine J, Greenwald B; Fatigue in Parkinson disease, stroke and TBI. Phys Med Rehabil clin N Am 2009; 20; 347-61
 Rothwell NJ, Luheshi G, Toulmond S. Cytokines and their receptors in the central nervous system: physiology,
pharmacology, and pathology,” Pharmacology and Therapeutics, vol. 69, no. 2, pp. 85–95, 1996.
 Zedlitz AMEE, Rietveld TCM, Geurts AC, Fasotti L. Randomized, Controlled Trial Cognitive and Graded Activity
Training Can Alleviate Persistent Fatigue After Stroke: Stroke. 2012;43:1046-1051; originally published online February
2, 2012
 Mathiowetz V, Matuska K, Murphey M. Efficacy of an energy conservation course for patients with multiple sclerosis.
Arch Phys Med Rehabil. 2001;82:449.
 Harbison JA, Walsh S , Kenny RA. Hypertension and daytime hypotension found on ambulatory blood pressure is
associated with fatigue following stroke and TIA. Q J Med 2009; 102:109–115
 Barker-Collo S, Feigin VL, Dudley M. Post-stroke fatigue—where is the evidence to guide practice? Journal of the New
Zealand Medical Association, 26-October-2007, Vol 120 No 1264
© 2008 Santa Clara Valley Health & Hospital System
24
Zedlitz and colleagues
Stroke. 2012;43:1046-1051
© 2008 Santa Clara Valley Health & Hospital System
25

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2015: Post Stroke Fatigue - Why Live With It?-Giap

  • 1. 1 Post Stroke Fatigue Why Live with It? Benton Giap, MD MBA © 2008 Santa Clara Valley Health & Hospital System
  • 2. 2 Today’s Overview  Increase awareness of manifestations and common factors in developing of PSF  Review the evidence for assessment and treatment of fatigue after stroke  Management –outline practical non-pharmacological tools for managing this condition
  • 3. 3 Disclosure Off-labeled uses of medications for post stroke fatigue. Employer Anthem Blue Cross, Commercial Health Plan Lots of cute baby pictures
  • 4. 4 In Their own words  “my head is foggy”  “life is too overwhelming!”  hit a “brick wall”  “exhausted” and failing to meet the
  • 5. 5 Definition of Fatigue “a subjective experience of extreme and persistent tiredness, weakness or exhaustion after stroke, which can present itself mentally, physically or both and is unrelated to previous exertion levels. [Lerdal and colleagues]
  • 6. 6 Scope of the Problem  Prevalence – 38 - 73 %  PSF often does not diminish even years after stroke  can be present within weeks and persist for many months or even years afterwards  identified by 40% as amongst their worst symptoms impacting function, QOL, safety
  • 7. 7 Fatigue following Stroke: Frequency, characteristics and associated factors  Not associated with lesion size  Location-fatigue associated lacunar infarcts located within the basal ganglia, internal capsule, and infra-tentorial areas  greater fatigue was related consistently to a poorer physical function and symptoms of depression  Pre-morbid level of functioning  Multiple medications effect?
  • 8. 8 Fatigue is well appreciated in other conditions  multiple sclerosis  post-polio syndrome  traumatic brain injury  cardiovascular disease  pulmonary disease (COPD)  depression  thyroid disease  obesity  HIV/AIDs  diabetes mellitus
  • 9. 9  Depression  Sleep problems, such as sleep apnea  Lack of physical exercise  Vitamin deficiency/poor nutrition  Anemia  Pain  Infection-acute , chronic  Physical impairments from stroke  Medications -anti-hypertensive, spasmolytics, antidepressants, pain medication
  • 10. 10 Differentiating fatigue from sleepiness  Subjective feeling of weariness, depleted energy  Multidimensional(e.g. mental, physical)  No real objective measure  Physiological drive to sleep  Measurable signs: Yawning  Eyes drooping  Reduced alertness  Can be measured in a sleep laboratory(MSLT)  FATIGUE  EXCESSIVE DAYTIME SLEEPINESS
  • 11. 11 Mechanisms  Activation of an inflammatory response with secretion of various cytokines necessary for immune signaling including  interleukin-6 (IL-6)  interleukin-1 beta (IL-1 )β  tumor necrosis factor alpha (TNF )α  the exact mechanisms of origin and persistence of PSF are still elusive  Contribution by hypothalamic- pituitary-adrenal (HPA) axis  modulated by cytokines  Hypo-activity of the HPA axis owing to decreased corticotrophin releasing hormone has been accordingly found in CFS and in chronic autoimmune conditions  Hyperactivity results in a blunting of the normal diurnal cortisol secretion curve with reduced gluco-corticoid production and onset of fatigue and depressive symptoms © 2008 Santa Clara Valley Health & Hospital System
  • 12. 12 “Sickness Behavior” mediated through neural, immune, and endocrine mechanisms following stroke  “neurovegetative “ syndrome (early)  poor appetite  sleep disturbances  psychomotor slowing  fatigue [Rothwell and colleagues]  “mood and cognitive” syndrome (later)  depression  anxiety  impairment of memory, attn  lowered libido © 2008 Santa Clara Valley Health & Hospital System
  • 13. 13© 2008 Santa Clara Valley Health & Hospital System
  • 14. 14 7-step approach toward a diagnosis  Characterize the fatigue  Assess presence of complaints suggesting organic illness associated with fatigue  Evaluate medicines used and/or substances abused  Perform psychiatric screening  Ask questions on sleep quantity and/or quality  Perform a physical examination  Undertake investigations
  • 16. 16 Fatigue Pictogram © 2008 Santa Clara Valley Health & Hospital System
  • 17. 17 Management  No effective pharmacological option has been identified  insufficient evidence existed to recommend any single treatment for PSF  no evidence-based treatments are currently available to alleviate fatigue. © 2008 Santa Clara Valley Health & Hospital System
  • 18. 18 Fatigue: pharmacological options ?  Anecdotal reports with : amantadine, methylphenidate, modafinil, Fluoxetine  Randomized DB controlled trials: One  N=83, consecutive outpatient stroke survivors (average 14 months post stroke)  randomly assigned to either fluoxetine 20 mg/day (n=40) or placebo (n=43) given over 3 months.  Follow-up evaluations at 3 and 6 months after the beginning of the treatment, included the Visual Analogue Scale (mean score 5.4±2 at baseline) and Fatigue Severity Scale (mean score 4.4±1.2 at baseline). © 2008 Santa Clara Valley Health & Hospital System
  • 19. 19 IS EXERCISE THE SOLUTION?  Design- multicenter, randomized, controlled trial , 8 rehabilitation centers.  Participants – 83 participants with stroke (4 months after stroke) were randomly assigned to 12 weeks of cognitive therapy (CO) or cognitive therapy and graded activity training (COGRAT) after qualification.  Aim - to compare the effectiveness of a combined intervention (COGRAT) with that of CO alone on fatigue and associated psychological and physical variables.  Graded Activity Training (GRAT) consisted of walking on a treadmill, strength training, and physical fitness home work assignments.  Outcomes -Seventy-three patients completed treatment and 68 were available at follow- up.  Primary outcomes (Checklist Individual Strength–subscale Fatigue (CIS-f); self-observation list– fatigue (SOL-f))  Findings - Group cognitive therapy combined with graded activity training during a 12-week period reduces persistent PSF [Zedlitz and colleagues, 2012] © 2008 Santa Clara Valley Health & Hospital System
  • 20. 20 Intervention  Cognitive Behavioral Intervention  Sleep Management  Sleep Hygiene  Caffeine Intake  Alcohol Intake  Medication Use  Energy Conservation  Plan  Prioritize  Pacing  Elimination  Cardiovascular Conditioning © 2008 Santa Clara Valley Health & Hospital System
  • 21. 21© 2008 Santa Clara Valley Health & Hospital System
  • 22. 22 Key points  Stroke patients often present with complex needs.  Fatigue can truly be disabling  Fatigue can be challenging to quantify because of its multi-dimensionality (physical, mental and psychological).  Comprehensive intervention includes physical, informational, emotional, cognitive, communication and practical aspects to support.  Cardiovascular exercise is an important tool and highly recommended intervention. Exercise offers one of the most effective interventions to enhance neurocognitive functioning. It also may decrease depression and improve sleep.  Modafinil is not effective in treating fatigue but has shown to be effective in treating excessive daytime sleepiness post TBI.  Practicing energy conservation principles and by prioritizing, planning, pacing for those important tasks of the day is very often helpful. © 2008 Santa Clara Valley Health & Hospital System
  • 23. 23 Reference  Lerdal A, Bakken L, Kouwenhoven S, Pedersen G, Kirkevold M, Finset A, et al. Poststroke fatigue: a review. J Pain Symptom Manage. 2009;38:928–949.  Ouellet M, Morin C. Fatigue following traumatic brain injury: frequency, characteristics, and associated factors. Rehabil Psychol. 2006; 51:140–9.  Barritt AW, Smithard DG. Review Article: Targeting Fatigue in Stroke Patients. International Scholarly Research Network ISRN Neurology, Volume 2011, Article ID  Levine J, Greenwald B; Fatigue in Parkinson disease, stroke and TBI. Phys Med Rehabil clin N Am 2009; 20; 347-61  Rothwell NJ, Luheshi G, Toulmond S. Cytokines and their receptors in the central nervous system: physiology, pharmacology, and pathology,” Pharmacology and Therapeutics, vol. 69, no. 2, pp. 85–95, 1996.  Zedlitz AMEE, Rietveld TCM, Geurts AC, Fasotti L. Randomized, Controlled Trial Cognitive and Graded Activity Training Can Alleviate Persistent Fatigue After Stroke: Stroke. 2012;43:1046-1051; originally published online February 2, 2012  Mathiowetz V, Matuska K, Murphey M. Efficacy of an energy conservation course for patients with multiple sclerosis. Arch Phys Med Rehabil. 2001;82:449.  Harbison JA, Walsh S , Kenny RA. Hypertension and daytime hypotension found on ambulatory blood pressure is associated with fatigue following stroke and TIA. Q J Med 2009; 102:109–115  Barker-Collo S, Feigin VL, Dudley M. Post-stroke fatigue—where is the evidence to guide practice? Journal of the New Zealand Medical Association, 26-October-2007, Vol 120 No 1264 © 2008 Santa Clara Valley Health & Hospital System
  • 24. 24 Zedlitz and colleagues Stroke. 2012;43:1046-1051 © 2008 Santa Clara Valley Health & Hospital System
  • 25. 25

Editor's Notes

  1. In our peer support group meetings for stroke survivors that we host at The Valley, this fatigue theme comes up a lot. The activities that are normally part of life now has become more effortful after stroke. Throughout a normal day, such as concentrating, reading, planning the day’s activities, attending to two conversations at once or conversing with background noise. Described as “sensory overload”, individuals with PSF could become even more error prone, distractible, become more uncoordinated without cognitive breaks.
  2. Defining post-stroke fatigue (PSF) is really difficult. Fatigue is a symptom and represents a complex interaction of biological, psychosocial, and behavioral phenomena. It is often accompanied by distress and decreased functional status related to reduced energy.
  3. The frequency of self-reported fatigue is roughly twice as high in patients post stroke as it is in matched controls, and 27% of stroke survivors experience fatigue every day. In regards to the time course of PSF, a recent study of 167 survivors of first-ever stroke, assessed fatigue at admission, 6-months post-stroke, and 1-year post stroke and found it to be present in 51.5%, 64.1%, and 69.5%, respectively.
  4. It has been proposed that the ascending reticular activating system attributed with maintaining tonic attention may become damaged by brainstem and sub-cortical lesions leading to PSF.
  5. Fatigue is also distinctive from sleepiness. Disorders of sleep have been mentioned as part of sickness behavior and are commonly seen after stroke. They have also been linked to PSF which may be improved when sleep issues are corrected.
  6. The exact mechanisms of origin and persistence of PSF are still elusive. Acute stroke causes secretion of cytokines, chemokines, and proteases from activated microglia at the infarct epicenter accompanied by release of cytotoxic-free radicals. The common denominator is activation of an inflammatory response with production of further cytokines. Disordered sympathetic control, therefore, results and may underpin the observations by Harbison and colleagues that systemic hypertension above 145/90mmHg and diastolic dips below 50mmHg on ambulatory blood pressure monitoring in chronic stroke patients is associated with PSF.
  7. The Inflammatory response is thought to induce the so-called “sickness behaviour” of decreased mood, lowered libido, poor appetite, sleep disturbances, psychomotor slowing, and, importantly, fatigue. Treating depressive symptoms may make a valuable difference to the emotional state and motivation of the patient.
  8. There is huge difficulty in quantifying fatigue, the causes of post-stroke fatigue differ from person to person and may include physical causes such as spasticity, paralysis, pain, inactivity, or other health problems. It has been proposed that post-stroke fatigue may result from the combined effects of organic brain lesions and psychosocial stress related to changes in life situation.
  9. Many scales have been developed attempting to measure the nature, severity, and impact of fatigue in a range of clinical populations. Different scales purport to measure different aspects of fatigue and it has been suggested that measures developed to measure fatigue in one clinical condition may not be justified for other clinical conditions. However, it has also been suggested that “since fatigue is an unspecific symptom there should not be need for adopting disease specific fatigue scales for each individual disease.” While there is no consensus on which fatigue scales are most appropriate for use in the assessment of fatigue in stroke survivors, the most commonly used in stroke populations include the Visual Analogue Scale (used in three studies); Fatigue Severity Scale (used in five studies); Furthermore, while there are a number of measures specific to fatigue that can be used, none of these have been validated in stroke populations. FSS is a common scale- designed initially for pts with MS and SLE. The average score for healthy adult is 2.3 and total score of 20.7. Fatigue Impact Scale (FIS)-40-item multidimensional instrument designed to measure how fatigue affects specific aspects of physical, cognitive, and psychosocial functioning
  10. For patients with aphasia or communication impairments following stroke, visuals can be helpful. This pictogram has two questions with five figures representing each response option. The items assess the intensity of fatigue and the impact of fatigue on daily activities. Since it is very short, simple and easy-to-use.
  11. Despite the high prevalence of post-stroke fatigue and its detrimental effects, studies for post-stroke fatigue interventions are scarce. Indeed, a search of the United Kingdom’s National Clinical Guidelines for Stroke (2nd edition)37 and its tables of evidence reveals no evidence on treatments for fatigue, nor is there any mention of fatigue as a condition requiring treatment. Because the causes of fatigue are multidimensional and interrelated, a considerable range of fatigue management options are available, including cause-specific treatments, pharmacological intervention, and non-pharmacological interventions, including educational programs. For example, stroke patients who have been inactive and/or ill for periods of time may have nutritional or metabolic deficits resulting in fatigue.
  12. In a study where all the patients had PSF on two assessment scales, the selective serotonin reuptake inhibitor antidepressant fluoxetine failed to make any change to the fatigue scores after three months’ therapy, yet dutifully improved post stroke depression and emotional disturbance . Percent change in the fatigue scales and the proportion of patients with fatigue did not differ between the treatment groups at either follow-up assessments. However, fluoxetine significantly improved post-stroke emotional incontinence and depression in patients with fatigue. The authors concluded that post-stroke fatigue may be associated with diverse aetiologies (but not closely related to serotonergic dysfunction), and that further studies are required to elucidate the causative factors to find an appropriate treatment for post-stroke fatigue.
  13. We have been focused on research in the role of exercise and nutritional coaching post traumatic brain injury fatigue. Based on data collected in studies of exercise-induced fatigue, it has been proposed that it is the relative predominance of serotonin compared to dopamine which precipitates fatigue and that exercise training increases plasticity of dopaminergic circuitry leading to a more delayed onset over time.
  14. Given these multiple potential causes of post-stroke fatigue, any assessment of fatigue must be multidimensional, and treatment approaches are likely to be differentially beneficial in different etiologically defined subgroups. Evidence from other patient populations with chronic fatigue suggests that tailored cognitive behavioral therapy, exercise therapy, and teaching energy conservation strategies are effective means to alleviate chronic fatigue and related psychological and physical symptoms. Despite there being no literature on its efficacy, patient and family education/counseling has been identified as an important rehabilitation intervention for the management of stroke-related fatigue. Comprehensive-holistic neuropsychological rehabilitation is centered on the goals of fostering patients’ awareness of their functional potential and adapting to the chronic limitations imposed by their injury, in order to alleviate disability in everyday, social functioning. Principles of energy conservation can be very crucial in addressing symptoms of fatigue. This set of principles has been noted to be beneficial in other medical conditions such as post polio syndrome and multiple sclerosis. As part of their rehabilitation, individuals may be taught or re-taught how to prioritize their commitments and are encouraged to recognize their abilities and limitations.