Intracortical facilitation as a potential biomarker of post-stroke fatigue severity

Abstract Background Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME. Methods In this case–control study, 45 female patients who met the 1994 CDC/Fukuda definition for CFS/ME and 25 age- and gender-matched healthy controls underwent HRV recording-resting state tests. The intervals between consecutive heartbeats (RR) were continuously recorded over three 5-min periods. Time- and frequency-domain analyses were applied to estimate HRV variables. Demographic and clinical features, and self-reported symptom measures were also recorded. Results CFS/ME patients showed significantly higher scores in all symptom questionnaires (p < 0.001), decreased RR intervals (p < 0.01), and decreased HRV time- and frequency-domain parameters (p < 0.005), except for the LF/HF ratio than in the healthy controls. Overall, the correlation analysis reached significant associations between the questionnaires scores and HRV time- and frequency-domain measurements (p < 0.05). Furthermore, separate linear regression analyses showed significant relationships between self-reported fatigue symptoms and mean RR (p = 0.005), RMSSD (p = 0.0268) and HFnu indices (p = 0.0067) in CFS/ME patients, but not in healthy controls. Conclusions Our findings suggest that ANS dysfunction presenting as increased sympathetic hyperactivity may contribute to fatigue severity in individuals with ME/CFS. Further studies comparing short- and long-term HRV recording and self-reported outcome measures with previous studies in larger CFS/ME cohorts are urgently warranted.

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Non-Pharmacological Interventions for Post-Stroke Fatigue: Systematic Review and Network Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm9030621 ◽

2020 ◽

Vol 9 (3) ◽

pp. 621 ◽

Cited By ~ 2

Author(s):

Ya Su ◽

Michiko Yuki ◽

Mika Otsuki

Keyword(s):

Systematic Review ◽

Health Management ◽

Behavioral Therapy ◽

Meta Analysis ◽

Cochrane Library ◽

Pharmacological Intervention ◽

Pharmacological Interventions ◽

Post Stroke ◽

Equivalent Efficacy ◽

Fatigue Severity

Post-stroke fatigue (PSF) is one of the most serious sequelae, which often interferes with the rehabilitation process and impairs the functional recovery of patients. Due to insufficient evidence, it is unclear which specific pharmacological interventions should be recommended. Therefore, in this paper, we compare the effectiveness of non-pharmacological interventions in PSF. A systematic review and network meta-analysis of randomized controlled trials were performed using EMBASE, MEDLINE, CINAHL, Cochrane library, ClinicalTrials.gov, CNKI, and CQVIP, from inception to January 2018, in the English and Chinese languages. RCTs involving different non-pharmacological interventions for PSF with an outcome of fatigue measured using the Fatigue Severity Scale were included. Multiple intervention comparisons based on a Bayesian network are used to compare the relative effects of all included interventions. Ten RCTs with eight PSF non-pharmacological interventions were identified, comprising 777 participants. For effectiveness, most interventions did not significantly differ from one another. The cumulative probabilities of the best non-pharmacological intervention for fatigue reduction included Community Health Management (CHM), followed by Traditional Chinese Medicine (TCM) and Cognitive Behavioral Therapy (CBT). Network meta-analysis based on data from the selected RCTs indicated that the eight PSF non-pharmacological interventions shared equivalent efficacy, but CHM, TCM, and CBT showed potentially better efficacy. In the future, fatigue needs to be recognized and more accurate assessment methods for PSF are required for diagnosis and to develop more effective clinical interventions.

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Early Post-Stroke Infections Are Associated with an Impaired Function of Neutrophil Granulocytes

Journal of Clinical Medicine ◽

10.3390/jcm9030872 ◽

2020 ◽

Vol 9 (3) ◽

pp. 872

Author(s):

Till van Gemmeren ◽

Ramona Schuppner ◽

Gerrit M. Grosse ◽

Jessica Fering ◽

Maria M. Gabriel ◽

...

Keyword(s):

Risk Score ◽

Binary Logistic Regression ◽

Neutrophil Function ◽

Infection Risk ◽

Receptor Expression ◽

Neutrophil Granulocytes ◽

Multivariate Statistical ◽

Phagocytic Capacity ◽

Post Stroke ◽

Potential Biomarker

To investigate whether neutrophil granulocytes’ function relates to post-stroke infections and clinical outcome after stroke, we prospectively recruited 95 patients after ischemic stroke and tested them for their microbiocidal neutrophil functions in this exploratory study. Additionally, 24 age-adjusted controls were examined regarding neutrophil function. Phagocytic capacity and the ability of the neutrophil granulocytes to produce reactive oxygen species (ROS) as well as CD11b and CD16 receptor expression profile were measured by flow cytometry at days 1, 3, 7, and 90 after symptom onset. Primary outcome was the development of an infection within the first week after stroke. Results of neutrophil functional measurements were compared between patients with and without infection as well as between all stroke patients and controls. Further risk factors for the development of infections were summarized in an infection-risk score for the purpose of multivariate statistical analysis. The ROS production in neutrophils after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) was reduced at baseline in patients with post-stroke infections compared to those without (p = 0.013). This difference proved to be independent from the infection-risk score in the binary logistic regression (p = 0.011). Phagocytosis and oxidative bursts were not significantly reduced in the whole stroke patient group compared to controls. Dysfunction of neutrophil granulocytes seems to play a significant role in the development of post-stroke infections. Further studies are warranted to investigate neutrophil granulocytes´ function as a potential biomarker of post-stroke infections.

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The Nottingham Fatigue after Stroke (NotFAST) study: factors associated with severity of fatigue in stroke patients without depression

Clinical Rehabilitation ◽

10.1177/0269215517695857 ◽

2017 ◽

Vol 31 (10) ◽

pp. 1406-1415 ◽

Cited By ~ 11

Author(s):

Avril Drummond ◽

Louise Hawkins ◽

Nikola Sprigg ◽

Nick S Ward ◽

Amit Mistri ◽

...

Keyword(s):

Fatigue Severity Scale ◽

Outcome Variable ◽

Severity Scale ◽

Cross Sectional ◽

Mobility Index ◽

Factors Associated ◽

Post Stroke ◽

Brief Assessment ◽

Fatigue Severity ◽

Anxiety Index

Objective: To identify factors associated with post-stroke fatigue in a sample of stroke survivors without depression. Design: Cross-sectional cohort study. Setting: Recruitment was from four stroke units in the UK. Subjects: Participants were assessed within four to six weeks of first stroke; those with high levels of depressive symptoms (score ⩾7 Brief Assessment Schedule Depression Cards) were excluded. Main measures: Participants were assessed after stroke on the Fatigue Severity Scale of the Fatigue Assessment Inventory, the Rivermead Mobility Index, Nottingham Extended Activities of Daily Living scale, Beck Anxiety Index, Sleep Hygiene Index, 6m walk test, and measures of cognitive ability. Results: Of the 371 participants recruited, 103 were excluded and 268 were assessed. Of the latter, the mean age was 67.7 years (SD 13.5) and 168 (63%) were men. The National Institutes of Health Stroke Scale mean score was 4.96 (SD 4.12). Post-stroke fatigue was reported by 115 (43%) of participants, with 71 (62%) reporting this to be a new symptom since their stroke. Multivariate analysis using the Fatigue Severity Scale as the outcome variable found pre-stroke fatigue, having a spouse/partner, lower Rivermead Mobility Index score, and higher scores on both the Brief Assessment Schedule Depression Cards and Beck Anxiety Index were independently associated with post-stroke fatigue, accounting for approximately 47% of the variance in Fatigue Severity Scale scores. Conclusions: Pre-stroke fatigue, lower mood, and poorer mobility were associated with post-stroke fatigue.

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Inter-hemispheric inhibition in stroke survivors is related to fatigue and cortical excitability

10.1101/831511 ◽

2019 ◽

Cited By ~ 2

Author(s):

Sasha Ondobaka ◽

Nick Ward ◽

Annapoorna Kuppuswamy

Keyword(s):

Cortical Excitability ◽

Effective Connectivity ◽

Self Report ◽

Stroke Survivors ◽

Corticomotor Excitability ◽

Post Stroke ◽

Motor Cortex Excitability ◽

Persistent Fatigue ◽

Fatigue Severity ◽

Exercise Induced

ABSTRACTObjectivePersistent post-stroke fatigue is a major debilitating condition that has been linked to low corticomotor excitability and aberrant attention, both phenomena that are associated with the inter-hemispheric inhibition balance in the brain. In this study, we examined the relationship between inter-hemispheric inhibitory effective connectivity, motor cortex excitability and chronic persistence of post-stroke fatigue.MethodsWe tested eighteen non-depressed stroke survivors with minimal motoric and cognitive impairments using spectral dynamic causal modelling (spDCM) of ‘resting state’ magnetic resonance imaging (rs-fMRI) and transcranial magnetic stimulation (TMS) measures of cortical excitability. We also assessed the levels of non-exercise induced, persistent fatigue using Fatigue Severity Scale (FSS) - a self-report questionnaire which has been widely applied and validated across different conditions. To understand neural effective connectivity mechanisms involved in fatigue and corticomotor excitability we examined the balance in inhibitory connectivity between homologue regions in M1, anterior insula, caudate and thalamus of the resting brain.ResultsInter-hemispheric inhibition balance between left and right M1 accounted for 67% of variability in the reported fatigue (R=.82, p<0.001). Inter-hemispheric inhibition balance in M1 also accounted for 54% of variability in the corticomotor excitability characterised by individual resting motor thresholds (R=.74, p<0.001), a measure that has been associated with subjective fatigue reports. Other examined inter-hemispheric connections did not show significant relationships with either fatigue or cortical excitability measures.ConclusionOur findings suggest that the balance in inter-hemispheric effective connectivity between primary motor regions is involved in regulation of corticomotor excitability and could explain subjective post-stroke fatigue.

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Ability of The Cardiorespiratory System to Adapt to Exercise is Impaired in Individuals With Severe Post-Stroke Fatigue

10.21203/rs.3.rs-112240/v1 ◽

2020 ◽

Author(s):

Kazuaki Oyake ◽

Yasuto Baba ◽

Yuki Suda ◽

Jun Murayama ◽

Ayumi Mochida ◽

...

Keyword(s):

Time Constant ◽

Exercise Test ◽

Constant Load ◽

Rehabilitation Program ◽

Primary Objective ◽

Peak Exercise ◽

Cardiorespiratory System ◽

Post Stroke ◽

Fatigue Severity ◽

Secondary Objective

Abstract Physical deconditioning after stroke may induce post-stroke fatigue. However, research on this association is limited. Our primary objective was to investigate the associations of post-stroke fatigue with oxygen uptake (⩒O2) at peak exercise and the time constant of ⩒O2 kinetics (τ⩒O2) at the onset of exercise. The secondary objective was to examine the associations between fatigue and cardiorespiratory variables potentially affecting ⩒O2 during exercise. Twenty-three inpatients from a subacute rehabilitation ward were enrolled in this study. The median (interquartile range) Fatigue Severity Scale (FSS) score as a measure of fatigue was 32 (27, 42) points. The FSS score was not associated with ⩒O2 at peak exercise during a symptom-limited graded exercise test (rho = −0.264; p = 0.224), while it was significantly associated with τ⩒O2 during a submaximal constant-load exercise test (rho = 0.530; p = 0.009). A higher FSS score was also significantly correlated with a longer time constant of cardiac output kinetics (rho = 0.476, p = 0.022). These results suggest that the ability of the cardiorespiratory system to adapt to exercise is impaired in individuals with severe post-stroke fatigue. Our findings can contribute to the development of an appropriate rehabilitation program for such individuals.

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A cross-sectional study exploring overlap in post-stroke fatigue caseness using three fatigue instruments: Fatigue Severity Scale, Fatigue Questionnaire and the Lynch’s Clinical Interview

Journal of Psychosomatic Research ◽

10.1016/j.jpsychores.2021.110605 ◽

2021 ◽

Vol 150 ◽

pp. 110605

Author(s):

Anita Kjeverud ◽

Stein Andersson ◽

Anners Lerdal ◽

Anne-Kristine Schanke ◽

Kristin Østlie

Keyword(s):

Cross Sectional Study ◽

Clinical Interview ◽

Fatigue Severity Scale ◽

Sectional Study ◽

Severity Scale ◽

Cross Sectional ◽

Post Stroke ◽

Fatigue Severity

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Cardiorespiratory responses to exercise related to post-stroke fatigue severity

Scientific Reports ◽

10.1038/s41598-021-92127-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kazuaki Oyake ◽

Yasuto Baba ◽

Yuki Suda ◽

Jun Murayama ◽

Ayumi Mochida ◽

...

Keyword(s):

Time Constant ◽

Exercise Test ◽

Constant Load ◽

Primary Objective ◽

Peak Exercise ◽

Post Stroke ◽

Exercise Onset ◽

Fatigue Severity ◽

Secondary Objective ◽

Physical Deconditioning

AbstractPhysical deconditioning after stroke may induce post-stroke fatigue. However, research on this association is limited. Our primary objective was to investigate the associations of post-stroke fatigue severity with oxygen uptake ($$\dot{\mathrm{V}}$$ V ˙ O2) at peak exercise and the time constant of $$\dot{\mathrm{V}}$$ V ˙ O2 kinetics (τ$$\dot{\mathrm{V}}$$ V ˙ O2) at exercise onset. The secondary objective was to examine the associations between fatigue and cardiorespiratory variables potentially affecting $$\dot{\mathrm{V}}$$ V ˙ O2 during exercise. Twenty-three inpatients from a subacute rehabilitation ward were enrolled in this study. The median (interquartile range) Fatigue Severity Scale (FSS) score, as a measure of fatigue, was 32 (range 27–42) points. The FSS score was not associated with $$\dot{\mathrm{V}}$$ V ˙ O2 at peak exercise during a symptom-limited graded exercise test (rho = − 0.264; p = 0.224), whereas it was significantly associated with τ$$\dot{\mathrm{V}}$$ V ˙ O2 during a submaximal constant-load exercise test (rho = 0.530; p = 0.009). A higher FSS score also significantly correlated with a longer time constant of cardiac output (CO) kinetics (rho = 0.476; p = 0.022). Our findings suggest that severe post-stroke fatigue is associated with delayed increases in $$\dot{\mathrm{V}}$$ V ˙ O2 and CO at the onset of exercise. Our findings can contribute to the development of an appropriate rehabilitation programme for individuals with post-stroke fatigue.

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Exploring The Views Of Stroke Survivors Around Post Stroke Fatigue In Saudi Arabia: A Qualitative Interview Study

International Journal of Therapy and Rehabilitation ◽

10.12968/ijtr.2019.26.6.6 ◽

2019 ◽

Vol 26 (6) ◽

pp. 6-6

Author(s):

Wafa Alahmari ◽

Ahmed Alhowimel ◽

Mazyad Alotaibi ◽

Eirini Kontou ◽

Pip Logan ◽

...

Keyword(s):

Quality Of Life ◽

Health Care ◽

Saudi Arabia ◽

Standard Deviation ◽

Fatigue Severity Scale ◽

Stroke Survivors ◽

Severity Scale ◽

Post Stroke ◽

Fatigue Severity

Background/Aims Among stroke survivors, post-stroke fatigue is highly prevalent, ranging from 25% to 85% and has a significant impact on their quality of life. The available literature on post-stroke fatigue is still rudimentary, especially from middle-eastern countries such as Saudi Arabia, which is a country with a complex health care system and diverse population. The aim of this study is to explore the post-stroke survivors' experiences and perceptions of their post-stroke fatigue. To our knowledge, this is the first attempt to understand post-stroke fatigue among stroke survivors living in Saudi Arabia. Methods This was a qualitative study where semi-structured interviews were conducted with stroke survivors who were diagnosed to have fatigue based on the Fatigue Severity Scale. A total of eight participants were recruited using a purposive sampling technique for the study. Interviews with the participants were recorded, transcribed verbatim and analysed using inductive thematic analysis. Validity was ensured through data triangulation with participants. Results The 8 participants (male=4; female=4), aged between 27 and 65 years (mean 52, standard deviation 14), were interviewed. Their scores on the Fatigue Severity Scale ranged from 4.5 to 6 (mean 5.3, standard deviation 0.5). On analysing the interview transcripts, 8 over-arching themes were generated: fatigue after stroke; symptomatology of post-stroke fatigue; pre-stroke fatigue levels and lifestyle; stroke survivors' perspectives of post-stroke fatigue; post-stroke fatigue's impact on daily living; coping with post-stroke fatigue; post-stroke fatigue patients' perception on physiotherapy; type of support from family and health care professional. Conclusions The results from this study highlights the lack of awareness about fatigue after stroke among stroke survivors. Also, the themes indicate that there is a need to educate stroke patients and their caregivers about post-stroke fatigue and how they should manage it. Based on patients ‘experiences’, physiotherapy seems to be helpful in reducing fatigue symptoms after stroke, but sill there is a need to design specific physiotherapy interventions with suitable frequency and intensity to target fatigue after stroke. In summary, post-stroke fatigue has a significant impact on their quality of life concerning social participation and their daily life. Stroke survivors did not receive enough support from health care professionals with respect to post-stroke fatigue, and it is highly essential to train health care practitioners to identify and acknowledge post-stroke fatigue appropriately.

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