Post-stroke fatigue is a common problem, affecting 38-73% of stroke survivors. It can persist for months or years after a stroke and significantly impact quality of life. The document discusses factors that may contribute to post-stroke fatigue like depression, sleep disturbances, lack of exercise, and medications. It also reviews tools to assess fatigue severity and differentiates fatigue from excessive daytime sleepiness. While no pharmacological treatments have proven effective, non-drug interventions like exercise, energy conservation, and sleep management may help manage post-stroke fatigue. A randomized controlled trial found that cognitive therapy combined with graded activity training over 12 weeks can reduce persistent post-stroke fatigue.

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Post Stroke Fatigue
Why Live with It?
Benton Giap, MD MBA
© 2008 Santa Clara Valley Health & Hospital System

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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

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Disclosure
Off-labeled uses of medications for post stroke fatigue.
Employer Anthem Blue Cross, Commercial Health Plan
Lots of cute baby pictures

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In Their own words
 “my head is foggy”
 “life is too overwhelming!”
 hit a “brick wall”
 “exhausted” and failing to meet the

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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]

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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

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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?

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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

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 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

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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

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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

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“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

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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

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Fatigue Severity Scale (FSS)

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Fatigue Pictogram
© 2008 Santa Clara Valley Health & Hospital System

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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

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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

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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

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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

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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

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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

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Zedlitz and colleagues
Stroke. 2012;43:1046-1051
© 2008 Santa Clara Valley Health & Hospital System

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