Homocysteine as a potential biochemical marker for depression in elderly stroke survivors

Background: Elderly stroke survivors have been reported to be at risk of malnutrition and depression. Vitamin B-related metabolites such as methylmalonic acid and homocysteine have been implicated in depression. Objective: We conducted a study exploring the relationship between homocysteine and post-stroke depression. Design: Three methodologies were used: Observational cohort study of elderly Swedish patients (n=149) 1.5 years post-stroke, assessed using Diagnostic and Statistical Manual of Mental Disorders, Montgomery Åsberg Depression Rating Scale and serum blood levels of methylmalonic acid and homocysteine. Results: Homocysteine significantly correlated with depressive symptomatology in stroke survivors (β = 0.18*). Individuals with abnormal levels of methylmalonic acid and homocysteine were almost twice more likely to show depressive symptomatology than those with normal levels (depressive symptoms 22%; no depressive symptoms 12%). Comparison of methylmalonic acid and homocysteine levels with literature data showed fewer stroke survivors had vitamin deficiency than did reference individuals (normal range 66%; elevated 34%). Conclusions: Homocysteine is significantly associated with depressive symptomatology in elderly Swedish stroke survivors

Scoping review: The trajectory of recovery of participation outcomes following stroke

Participation is a central concept in health and well-being and healthcare, yet operationalizing this concept has been difficult. Its definition, uses in healthcare, and impacts on recovery require ongoing research. Our review question goes like this: from the longitudinal evidence investigating participation among stroke survivors, what are the patterns of participation recovery in stroke survivors over time, and what interventions are used to improve participation? To fully understand these questions, we also ask, how is participation defined in the stroke literature, and what are the measures of participation used in the stroke literature? A systematic scoping review was undertaken using the search terms “stroke,” “longitudinal,” “participation,” and “outcome” in seven databases. Articles included were published until April 2017, written in English, and had at least two longitudinal assessments of participation. Fifty-nine articles met the inclusion criteria. The International Classification of Functioning, Disability and Health was the most frequent definition of participation used (34%). There were 22 different measures of participation. Eight of ten studies demonstrated significant improvements in participation up to 12 months poststroke. Efficacy of interventions and their impact on participation varied. The various definitions, measures, and intervention efficacies of participation highlight the need for further research worldwide into achieving meaningful participation and quality of life among stroke survivors. Future practice should include participation as a main outcome measure

Linking cerebral palsy upper limb measurements to the international classification of functioning disability and health

Background: Intervention studies describe outcomes as meas­uring specific domains of the International Classification of Functioning, Disability and Health (ICF). However, the same measure may be described by different authors as assessing different domains, resulting in considerable confusion and inconsistent reporting of outcomes. Objective: To systematically link the scored items from the Melbourne Assessment of Unilateral Upper Limb Function, Quality of Upper Extremity Skills Test and Assisting Hand Assessment to domain(s) of the ICF. Methods: The meaningful concept for each scored item was defined. Using ICF linking rules, the concepts were assigned ICF codes to determine the outcome’s overall domain of measurement. Results: The Melbourne Assessment predominantly evaluates concepts in the body function domain. Coding of the Quality of Upper Extremity Skills Test indicated that dissociated movement, weight-bearing and protective extension predominantly measure concepts in the body function domain. Grasp was the only domain where concepts were coded in both the body function and activity domains. The Assisting Hand Assessment was the only measure where the majority of items assessed concepts in the activity domain. Conclusion: Measures of upper limb function can be categorized according to ICF domains. These findings should resolve confusion surrounding the classification of these measures and provide a reference for reporting the impact of intervention

Sustained inflammation 1.5 years post-stroke is not associated with depression in elderly stroke survivors

Background: Depression is common in elderly stroke survivors and has been associated with systemic inflammation. We aimed to investigate an elderly population of Swedish stroke patients for evidence of sustained peripheral inflammation 18 months post-stroke and to identify if inflammation is associated with post-stroke depression at 18 months post-stroke. Methods: The Barthel Index was used to measure the level of impairment in activities of daily living at 3 days post-stroke. Serum concentrations of inflammation markers, ie, C-reactive protein and white cell count, were measured in 149 stroke patients (mean age 81 ± 5.33 years, 35% male) at 18 months post-stroke, and a comparison was made with an age-matched sample of elderly Swedish individuals who had not suffered a stroke. At the same visit, clinical depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria. Severity of depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Results: Mean C-reactive protein and white cell count levels in stroke patients were significantly elevated at 18 months post-stroke compared with population probands. Disability scores were associated with MADRS depression scores, but C-reactive protein and white cell count were not. Conclusion: We found evidence for a sustained peripheral inflammatory response at 18 months post-stroke. C-reactive protein and white cell count were not associated with depression in this study

Fish oil supplementation associated with decreased cellular degeneration and increased cellular proliferation 6 weeks after middle cerebral artery occlusion in the rat

Anti-inflammatory long-chain omega-3 polyunsaturated fatty acids (n-3-LC-PUFAs) are both neuroprotective and have antidepressive effects. However the influence of dietary supplemented n-3-LC-PUFAs on inflammation-related cell death and proliferation after middle cerebral artery occlusion (MCAo)-induced stroke is unknown. We have previously demonstrated that anxiety-like and hyperactive locomotor behaviors are reduced in n-3-LC-PUFA-fed MCAo animals. Thus in the present study, male hooded Wistar rats were exposed to MCAo or sham surgeries and examined behaviorally 6 weeks later, prior to euthanasia and examination of lesion size, cell death and proliferation in the dentate gyrus, cornu ammonis region of the hippocampus of the ipsilesional hemispheres, and the thalamus of the ipsilesional and contralesional hemispheres. Markers of cell genesis and cell degeneration in the hippocampus or thalamus of the ipsilesional hemisphere did not differ between surgery and diet groups 6 weeks post MCAo. Dietary supplementation with n-3-LC-PUFA decreased cell degeneration and increased cell proliferation in the thalamic region of the contralesional hemisphere. MCAo–associated cell degeneration in the hippocampus and thalamus positively correlated with anxiety-like and hyperactive locomotor behaviors previously reported in these animals. These results suggest that anti-inflammatory n-3-LC-PUFA supplementation appears to have cellular protective effects after MCAo in the rat, which may affect behavioral outcomes

Longitudinal evaluation of cognition after stroke - A systematic scoping review

BACKGROUND: Cognitive impairment affects up to 80 percent of the stroke population, however, both the available evidence about post-stroke cognition and the measures used to evaluate it longitudinally have not been well described. The aims of this systematic scoping review were: to identify and characterize studies evaluating cognition longitudinally after stroke; to summarize the cognitive instruments used and the domains they target; and to organize cognitive domains assessed using the International Classification of Functioning, Disability and Health (ICF). METHODS: We used a systematic scoping approach to search for peer-reviewed articles involving adults with stroke that evaluated cognition longitudinally. Screening of titles, abstracts, and full reports was completed independently by two reviewers, across six electronic databases (PubMed, PsycInfo, Medline, Cinahl Plus, Embase, and Web of Science). Cognitive domains were mapped to an ICF function independently by the same two reviewers, using a previously tested, standardized approach. RESULTS: A total of 5,540 records were found; 257 were included, representing a total pooled sample of 120,860 stroke survivors. Of these studies, 200 (78%) provided specific cognitive outcomes from the longitudinal evaluations, 57 (22%) reported model predictions, and 77 (30%) included interventions. Cognition was evaluated with 356 unique instruments, targeting 95 distinct cognitive domains, and 17 mental functions from the ICF. The Mini-Mental State Examination was the most frequently used instrument (117 reports, 46%). Other tools used longitudinally were the Trail Making Test (17% of reports), tests of verbal fluency (14%), the Functional Independence Measure (14%), the Montreal Cognitive Assessment (13%), the Digit Span (11%), and the Stroop test (10%). Global cognition was evaluated in 170 reports (66%), followed by higher-level cognitive functioning (29%), memory (28%), language (21%), attention (21%), and perceptual skills (14%). Studies using functional (or performance-based) cognitive assessments over time were scarce (\u3c 1%). CONCLUSION: Our findings indicate that whilst there is a substantial number of studies available that report longitudinal evaluations of cognition after stroke, there is large variability in the measures used and the cognitive domains they target. Nonetheless, the available data for evaluation of cognition over time after stroke can be organized and described systematically

Activation of Bilateral Secondary Somatosensory Cortex With Right Hand Touch Stimulation: A Meta-Analysis of Functional Neuroimaging Studies

Background: Brain regions involved in processing somatosensory information have been well documented through lesion, post-mortem, animal, and more recently, structural and functional neuroimaging studies. Functional neuroimaging studies characterize brain activation related to somatosensory processing; yet a meta-analysis synthesis of these findings is currently lacking and in-depth knowledge of the regions involved in somatosensory-related tasks may also be confounded by motor influences.Objectives: Our Activation Likelihood Estimate (ALE) meta-analysis sought to quantify brain regions that are involved in the tactile processing of the right (RH) and left hands (LH) separately, with the exclusion of motor related activity.Methods: The majority of studies (n = 41) measured activation associated with RH tactile stimulation. RH activation studies were grouped into those which conducted whole-brain analyses (n = 29) and those which examined specific regions of interest (ROI; n = 12). Few studies examined LH activation, though all were whole-brain studies (N = 7).Results: Meta-analysis of brain activation associated with RH tactile stimulation (whole-brain studies) revealed large clusters of activation in the left primary somatosensory cortex (S1) and bilaterally in the secondary somatosensory cortex (S2; including parietal operculum) and supramarginal gyrus (SMG), as well as the left anterior cingulate. Comparison between findings from RH whole-brain and ROI studies revealed activation as expected, but restricted primarily to S1 and S2 regions. Further, preliminary analyses of LH stimulation studies only, revealed two small clusters within the right S1 and S2 regions, likely limited due to the small number of studies. Contrast analyses revealed the one area of overlap for RH and LH, was right secondary somatosensory region.Conclusions: Findings from the whole-brain meta-analysis of right hand tactile stimulation emphasize the importance of taking into consideration bilateral activation, particularly in secondary somatosensory cortex. Further, the right parietal operculum/S2 region was commonly activated for right and left hand tactile stimulation, suggesting a lateralized pattern of somatosensory activation in right secondary somatosensory region. Implications for further research and for possible differences in right and left hemispheric stroke lesions are discussed

Task-specific training versus usual care to improve upper limb function after stroke: The “Task-AT Home” randomised controlled trial protocol

Background: Sixty percent of people have non-functional arms 6 months after stroke. More effective treatments are needed. Cochrane Reviews show low-quality evidence that task-specific training improves upper limb function. Our feasibility trial showed 56 h of task-specific training over 6 weeks resulted in an increase of a median 6 points on the Action Research Arm test (ARAT), demonstrating the need for more definitive evidence from a larger randomised controlled trial. Task-AT Home is a two-arm, assessor-blinded, multicentre randomised, controlled study, conducted in the home setting. Aim: The objective is to determine whether task-specific training is a more effective treatment than usual care, for improving upper limb function, amount of upper limb use, and health related quality of life at 6 weeks and 6 months after intervention commencement. Our primary hypothesis is that upper limb function will achieve a ≥ 5 point improvement on the ARAT in the task-specific training group compared to the usual care group, after 6 weeks of intervention. Methods: Participants living at home, with remaining upper limb deficit, are recruited at 3 months after stroke from sites in NSW and Victoria, Australia. Following baseline assessment, participants are randomised to 6 weeks of either task-specific or usual care intervention, stratified for upper limb function based on the ARAT score. The task-specific group receive 14 h of therapist-led task-specific training plus 42 h of guided self-practice. The primary outcome measure is the ARAT at 6 weeks. Secondary measures include the Motor Activity Log (MAL) at 6 weeks and the ARAT, MAL and EQ5D-5 L at 6 months. Assessments occur at baseline, after 6 weeks of intervention, and at 6 months after intervention commencement. Analysis will be intention to treat using a generalised linear mixed model to report estimated mean differences in scores between the two groups at each timepoint with 95% confidence interval and value of p. Discussion: If the task-specific home-based training programme is more effective than usual care in improving arm function, implementation of the programme into clinical practice would potentially lead to improvements in upper limb function and quality of life for people with stroke. Clinical Trial Registration: ANZCTR.org.au/ACTRN12617001631392p.asp

Fish oil diet associated with acute reperfusion related hemorrhage, and with reduced stroke-related sickness behaviors and motor impairment

Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFAs). However, the potential protective effects of PUFA supplementation on affective behaviors after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioral effects of PUFA supplementation over a 6-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute hemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined 6 weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment, and longer-term locomotor hyperactivity and depression/anxiety-like behavior