Neurostructural and Neurophysiological Correlates of Multiple Sclerosis Physical Fatigue: Systematic Review and Meta-Analysis of Cross-Sectional Studies.

Fatigue is one of the most debilitating symptoms for people with multiple sclerosis (PwMS). By consolidating a diverse and conflicting evidence-base, this systematic review and meta-analysis aimed to gain new insights into the neurobiology of MS fatigue. MEDLINE, ProQuest, CINAHL, Web of Science databases and grey literature were searched using Medical Subject Headings. Eligible studies compared neuroimaging and neurophysiological data between people experiencing high (MS-HF) versus low (MS-LF) levels of perceived MS fatigue, as defined by validated fatigue questionnaire cut-points. Data were available from 66 studies, with 46 used for meta-analyses. Neuroimaging studies revealed lower volumetric measures in MS-HF versus MS-LF for whole brain (-22.74 ml; 95% CI: -37.72 to -7.76 ml; p = 0.003), grey matter (-18.81 ml; 95% CI: -29.60 to -8.03 ml; p < 0.001), putamen (-0.40 ml; 95% CI: -0.69 to -0.10 ml; p = 0.008) and acumbens (-0.09 ml; 95% CI: -0.15 to -0.03 ml; p = 0.003) and a higher volume of T1-weighted hypointense lesions (1.10 ml; 95% CI: 0.47 to 1.73 ml; p < 0.001). Neurophysiological data showed reduced lower-limb maximum voluntary force production (-19.23 N; 95% CI: -35.93 to -2.53 N; p = 0.02) and an attenuation of upper-limb (-5.77%; 95% CI:-8.61 to -2.93%; p < 0.0001) and lower-limb (-2.16%; 95% CI:-4.24 to -0.07%; p = 0.04) skeletal muscle voluntary activation, accompanied by more pronounced upper-limb fatigability (-5.61%; 95% CI: -9.57 to -1.65%; p = 0.006) in MS-HF versus MS-LF. Results suggest that MS fatigue is characterised by greater cortico-subcortical grey matter atrophy and neural lesions, accompanied by neurophysiological decrements, which include reduced strength and voluntary activation. Prospero registration Prospero registration number: CRD42016017934.

Consumption of Fruitflow® lowers blood pressure in pre-hypertensive males: a randomised, placebo controlled, double blind, cross-over study.

In order to investigate whether the angiotensin converting enzyme-inhibitory tomato extract Fruitflow® would lower blood pressure after consumption, we conducted a randomised, double-blinded, placebo-controlled human intervention study, involving 12 pre-hypertensive people in a crossover design. Consuming a single dose of 150 mg Fruitflow® resulted in a significant reduction in 24-hour average blood pressure as well as average wake-period and sleep-period SBP, compared to placebo. Other parameters related to blood pressure, such as 24-hour average mean arterial pressure, pulse pressure, heart rate, central aortic systolic pressure and radial augmentation index were also reduced. In addition, the platelet aggregation response to ADP, measured 24 hours after consuming Fruitflow®, fell significantly compared to baseline, and compared to placebo. This pilot study clearly shows the beneficial effects of Fruitflow® on two important cardiovascular risk factors, high blood pressure and platelet hyperactivity.

Fruitflow®: the first European Food Safety Authority-approved natural cardio-protective functional ingredient.

Hyperactive platelets, in addition to their roles in thrombosis, are also important mediators of atherogenesis. Antiplatelet drugs are not suitable for use where risk of a cardiovascular event is relatively low. It is therefore important to find alternative safe antiplatelet inhibitors for the vulnerable population who has hyperactive platelets in order to reduce the risk of cardiovascular disease. Potent antiplatelet factors were identified in water-soluble tomato extract (Fruitflow®), which significantly inhibited platelet aggregation. Human volunteer studies demonstrated the potency and bioavailability of active compounds in Fruitflow®. Fruitflow® became the first product in Europe to obtain an approved, proprietary health claim under Article 13(5) of the European Health Claims Regulation 1924/2006 on nutrition and health claims made on foods. Fruitflow® is now commercially available in different countries worldwide. In addition to its reduction in platelet reactivity, Fruitflow® contains anti-angiotensin-converting enzyme and anti-inflammatory factors, making it an effective and natural cardio-protective functional food.

Extreme Variation of Nutritional Composition and Osmolality of Commercially Available Carbohydrate Energy Gels.

The provision of exogenous carbohydrate (CHO) in the form of energy gels is regularly practiced among endurance and team sport athletes. However, in those instances where athletes ingest suboptimal fluid intake, consuming gels during exercise may lead to gastrointestinal (GI) problems when the nutritional composition of the gel is not aligned with promoting gastric emptying. Accordingly, the aim of the current study was to quantify the degree of diversity in nutritional composition of commercially available CHO gels intended for use in the global sports nutrition market. We surveyed 31 product ranges (incorporating 51 flavor variants) from 23 brands (Accelerade, CNP, High5, GU, Hammer, Maxim, Clif, USN, Mule, Multipower, Nectar, Carb- Boom, Power Bar, Lucozade, Shotz, TORQ, Dextro, Kinetica, SiS, Zipvit, Maxifuel, Gatorade and Squeezy). Gels differed markedly in serving size (50 ± 22 g: 29-120), energy density (2.34 ± 0.7 kcal/g: 0.83-3.40), energy content (105 ± 24 kcal: 78-204), CHO content (26 ± 6 g: 18-51) and free sugar content (9.3 ± 7.0 g: 0.6-26.8). Most notably, gels displayed extreme variation in osmolality (4424 ± 2883 mmol/kg: 303-10,135) thereby having obvious implications for both GI discomfort and the total fluid intake likely required to optimize CHO delivery and oxidation. The large diversity of nutritional composition of commercially available CHO gels illustrate that not all gels should be considered the same. Sports nutrition practitioners should therefore consider the aforementioned variables to make better-informed decisions regarding which gel product best suits the athlete's specific fueling and hydration requirements.

Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status.

This study investigated the impact of either type 2 diabetes or obesity, separately or in combination, on the absolute amounts of microparticles (MP) and the pathways by which these are associated with either condition. The concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP) and monocytes (MMP), together with their specific activation markers, were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes. The subjects with type 2 diabetes had elevated concentrations of total PMP (P = 0.003), and PMP that were fibrinogen-positive (P = 0.04), tissue factor-positive (P < 0.001), P-selectin-positive (P = 0.03). Type 2 diabetes did not alter either total or activated LMP or MMP. Obesity per se did not impact on any MP measurement. Elevated concentrations of plasma PMP occurred in subjects with type 2 diabetes, whether they were obese or non-obese. In contrast, obesity in the absence of type 2 diabetes had no effect. The increased concentrations of specific marker-positive PMP in the subjects with diabetes might reflect potential pathways by which PMP may contribute to the pathogenesis of atherosclerosis and type 2 diabetes.

The test-retest reliability of non-navigated transcranial magnetic stimulation (TMS) measures of corticospinal pathway excitability early after stroke.

PURPOSE: Motor evoked potential (MEP) characteristics are potential biomarkers of whether rehabilitation interventions drive motor recovery after stroke. The test-retest reliability of Transcranial Magnetic Stimulation (TMS) measurements in sub-acute stroke remains unclear. This study aims to determine the test-retest reliability of upper limb MEP measures elicited by non-neuronavigated transcranial magnetic stimulation in sub-acute-stroke. METHODS: In two identical data collection sessions, 1-3 days apart, TMS measures assessed: motor threshold (MT), amplitude, latency (MEP-L), silent period (SP), recruitment curve slope in the biceps brachii (BB), extensor carpi radialis (ECR), and abductor pollicis brevis (APB) muscles of paretic and non-paretic upper limbs. Test-retest reliability was calculated using the intra-class correlation coefficient (ICC) and 95% confidence intervals (CI). Acceptable reliability was set at a lower 95% CI of 0.70 or above. The limits of agreement (LOA) and smallest detectable change (SDC) were calculated. RESULTS: 30 participants with sub-acute stroke were included (av 36 days post stroke) reliability was variable between poor to good for the different MEP characteristics. The SDC values differed across muscles and MEP characteristics in both paretic and less paretic limbs. CONCLUSIONS: The present findings indicate there is limited evidence for acceptable test-retest reliability of non-navigated TMS outcomes when using the appropriate 95% CI for ICC, SDC and LOA values. CLINICAL TRIAL REGISTRATION: Current Controlled Trials: ISCRT 19090862, http://www.controlled-trials.com.

This study identified that Non-navigated Transcranial Magnetic Stimulation (TMS) demonstrates low reliability of TMS measures in upper limb with variation between muscles and measures in sub-acute strokeWhen using non-navigated TMS to explore corticospinal pathway excitability the individual target muscle and TMS measure should be taken into considerationNon-navigated TMS may be more useful in exploring group differences rather than individual differences in corticospinal pathway excitabilityNon-navigated TMS could provide a means of measuring recovery in clinical practice and could inform the development of more effective interventions but this needs further development before it can be used as a clinical recovery biomarker.

PREP Plus combined postrehabilitation programme to support upper limb recovery in community-dwelling stroke survivors: protocol for a mixed-methods, cluster-assigned feasibility study.

INTRODUCTION: Poor recovery of the upper limb following a stroke has been recognised as a significant problem in the UK. Although there is good evidence that early, intense rehabilitation can lead to upper limb recovery, often this is not maintained, with less than 50% of people regaining the ability to use their upper limb for independent function at 6 months. Upper limb recovery potential is reported for many years poststroke, yet current long-term provision is insufficient. METHODS AND ANALYSIS: 60 participants will be recruited into this feasibility study, with 30 allocated to a Post Rehabilitation Enablement Programme (PREP) alone and 30 allocated to a combined programme, PREP Plus, consisting of PREP and the Graded Repetitive Arm Supplementary Programme (GRASP). We will aim to complete four iterative waves. Within each wave, the intervention design will be refined, based on participant feedback. Within each wave, there will be one cluster unit (one intervention group ;PREP Plus) and one control group ;PREP alone)). A total of five PREP sites within Northern Ireland Health and Social Care Trusts will be used for this study. PREP Plus will have a home exercise component along with exercises logs and a behaviour contract. Qualitative and quantitative measures will evaluate the acceptability and feasibility to determine how feasible it is to embed the intervention into practice, as well as to determine the feasibility of a larger, mixed-methods, randomised controlled trial to assess intervention efficacy. Clinical endpoints will also be explored. ETHICS AND DISSEMINATION: This study has been approved by the Health and Social Care Research Ethics Committee A, IRAS project ID (278620). Participants will provide informed consent prior to participating in the study. Information outlining the purpose of the study, what data will be collected and how the data will be managed will be provided. Results will be published in peer-reviewed journals and any published data will be available on the university data repository. The project management group will advise on different avenues for dissemination to ensure it reaches appropriate audiences. TRIAL REGISTRATION NUMBER: NCT05090163.

Anti-platelet effects of olive oil extract: in vitro functional and proteomic studies.

PURPOSE: Platelets play a key role in haemostasis and wound healing, contributing to formation of vascular plugs. They are also involved in formation of atherosclerosic plaques. Some traditional diets, like the Mediterranean diet, are associated with a lower risk of cardiovascular disease. Components in these diets may have anti-platelet functions contributing to their health benefits. METHODS: We studied the effects of alperujo extract, an olive oil production waste product containing the majority of polyphenols found in olive fruits, through measurement of effects on platelet aggregation and activation in isolated human platelets, and through identification of changes in the platelet proteome. RESULTS: Alperujo extract (40 mg/L) significantly decreased in vitro ADP- (p = 0.002) and TRAP- (p = 0.02) induced platelet activation as measured by the flow cytometry using the antibody for p-selectin (CD62p), but it did not affect the conformation of the fibrinogen receptor as measured by flow cytometry using the antibodies for anti-fibrinogen, CD42a and CD42b. Alperujo extract (100 mg/L) inhibited both collagen- and TRAP-induced platelet aggregation by 5% (p < 0.05), and a combination of hydroxytyrosol and 3,4-dihydroxyphenylglycol were, at least partly, responsible for this effect. Proteomic analysis identified nine proteins that were differentially regulated by the alperujo extract upon ADP-induced platelet aggregation. These proteins represent important mechanisms that may underlie the anti-platelet effects of this extract: regulation of platelet structure and aggregation, coagulation and apoptosis, and signalling by integrin αIIb/ß3. CONCLUSIONS: Alperujo extract may protect against platelet activation, platelet adhesion and possibly have anti-inflammatory properties.

Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers.

BACKGROUND: Crohn's disease is common in developed nations where the typical diet is low in fibre and high in processed food. Primary lesions overlie Peyer's patches and colonic lymphoid follicles where bacterial invasion through M-cells occurs. We have assessed the effect of soluble non-starch polysaccharide (NSP) and food emulsifiers on translocation of Escherichia coli across M-cells. METHODS: To assess effects of soluble plant fibres and food emulsifiers on translocation of mucosa-associated E coli isolates from Crohn's disease patients and from non-Crohn's controls, we used M-cell monolayers, generated by co-culture of Caco2-cl1 and Raji B cells, and human Peyer's patches mounted in Ussing chambers. RESULTS: E coli translocation increased across M-cells compared to parent Caco2-cl1 monocultures; 15.8-fold (IQR 6.2-32.0) for Crohn's disease E coli (N=8) and 6.7-fold (IQR 3.7-21.0) for control isolates (N=5). Electron microscopy confirmed E coli within M-cells. Plantain and broccoli NSP markedly reduced E coli translocation across M-cells at 5 mg/ml (range 45.3-82.6% inhibition, p<0.01); apple and leek NSP had no significant effect. Polysorbate-80, 0.01% vol/vol, increased E coli translocation through Caco2-cl1 monolayers 59-fold (p<0.05) and, at higher concentrations, increased translocation across M-cells. Similarly, E coli translocation across human Peyer's patches was reduced 45±7% by soluble plantain NSP (5 mg/ml) and increased 2-fold by polysorbate-80 (0.1% vol/vol). CONCLUSIONS: Translocation of E coli across M-cells is reduced by soluble plant fibres, particularly plantain and broccoli, but increased by the emulsifier Polysorbate-80. These effects occur at relevant concentrations and may contribute to the impact of dietary factors on Crohn's disease pathogenesis.

Neurophysiological changes accompanying reduction in upper limb motor impairments in response to exercise-based virtual rehabilitation after stroke: systematic review.

BACKGROUND: Virtual reality-augmented therapist-delivered exercise-based training has promise for enhancing upper limb motor recovery after stroke. However, the neurophysiological mechanisms are unclear. OBJECTIVE: To find if neurophysiological changes are correlated with or accompany a reduction in motor impairment in response to virtual reality-aided exercise-based training. DATA SOURCES: Databases searched from inception to August 2020: MEDLINE, AMED, EMBASE, PUBMED, COCHRANE, CINHAL, PROQUEST and OPEN GREY. ELIGIBILITY CRITERIA: Studies that investigated virtual reality-augmented exercise-based training for the upper limb in adults with stroke, and, measured motor impairment and neurophysiological outcomes. Studies that combined VR with another technology were excluded. DATA EXTRACTION AND SYNTHESIS: Using pre-prepared proformas, three reviewers independently: identified eligible studies, assessed potential risk-of-bias, and extracted data. A critical narrative synthesis was conducted. A meta-analysis was not possible because of heterogeneity in participants, interventions and outcome measures. RESULTS: Of 1387 records identified, four studies were eligible and included in the review. Overall, included studies were assessed as having high potential risk-of-bias. The VR equipment, and control interventions varied between studies. Two studies measured motor impairment with the Fugl-Meyer Assessment but there was no commonality in the use of neurophysiological measures. One study found improvement in neurophysiological measures only. The other three studies found a reduction in motor impairment and changes in neurophysiological outcomes, but did not calculate correlation coefficients. CONCLUSION: There is insufficient evidence to identify the neurophysiological changes that are correlated with, or accompany, reduction in upper limb motor impairment in response to virtual reality-augmented exercise-based training after stroke. Systematic Review Registration Number PROSPERO 2017 CRD42017071312.

Challenges and Opportunities for the Future of Brain-Computer Interface in Neurorehabilitation.

Brain-computer interfaces (BCIs) provide a unique technological solution to circumvent the damaged motor system. For neurorehabilitation, the BCI can be used to translate neural signals associated with movement intentions into tangible feedback for the patient, when they are unable to generate functional movement themselves. Clinical interest in BCI is growing rapidly, as it would facilitate rehabilitation to commence earlier following brain damage and provides options for patients who are unable to partake in traditional physical therapy. However, substantial challenges with existing BCI implementations have prevented its widespread adoption. Recent advances in knowledge and technology provide opportunities to facilitate a change, provided that researchers and clinicians using BCI agree on standardisation of guidelines for protocols and shared efforts to uncover mechanisms. We propose that addressing the speed and effectiveness of learning BCI control are priorities for the field, which may be improved by multimodal or multi-stage approaches harnessing more sensitive neuroimaging technologies in the early learning stages, before transitioning to more practical, mobile implementations. Clarification of the neural mechanisms that give rise to improvement in motor function is an essential next step towards justifying clinical use of BCI. In particular, quantifying the unknown contribution of non-motor mechanisms to motor recovery calls for more stringent control conditions in experimental work. Here we provide a contemporary viewpoint on the factors impeding the scalability of BCI. Further, we provide a future outlook for optimal design of the technology to best exploit its unique potential, and best practices for research and reporting of findings.

Platelet hyperactivity in COVID-19: Can the tomato extract Fruitflow® be used as an antiplatelet regime?

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus is now considered a global public health threat. The primary focus has been on reducing the viral spread and treating respiratory symptoms; as time goes on, the impact of COVID-19 on neurological and haemostatic systems becomes more evident. The clinical data suggest that platelet hyperactivity plays a role in the pathology of COVID-19 from its onset and that platelets may serve critical functions during COVID-19 progression. Hyperactivation of blood platelets and the coagulation system are emerging as important drivers of inflammation and may be linked to the severity of the 'cytokine storm' induced in severe cases of COVID-19, in which disseminated intravascular coagulation, and platelet hyperactivity are associated with poor prognosis and increased risk of mortality. We propose that targeting platelet hyperactivity in the early stages of COVID-19 infection may reduce the immunothrombotic complications of COVID-19 and subdue the systemic inflammatory response. Lowering baseline platelet activity may be of particular importance for higher-risk groups. As an alternative to antiplatelet drugs, an inappropriate intervention in public health, we propose that the dietary antiplatelet agent Fruitflow®, derived from tomatoes, may be considered a suitable therapy. Fruitflow® contains antiplatelet and anti-inflammatory compounds that target the mechanisms of platelet activation specific to COVID-19 and can be considered a safe and natural antiplatelet regime.

Dietary Antiplatelets: A New Perspective on the Health Benefits of the Water-Soluble Tomato Concentrate Fruitflow®.

Our understanding of platelet functionality has undergone a sea change in the last decade. No longer are platelets viewed simply as regulators of haemostasis; they are now acknowledged to be pivotal in coordinating the inflammatory and immune responses. This expanded role for platelets brings new opportunities for controlling a range of health conditions, targeting platelet activation and their interactions with other vascular cells. Antiplatelet drugs may be of wider utility than ever expected but often cause platelet suppression too strong to be used out of clinical settings. Dietary antiplatelets represent a nutritional approach that can be efficacious while safe for general use. In this review, we discuss potential new uses for dietary antiplatelets outside the field of cardiovascular health, with specific reference to the water-soluble tomato extract Fruitflow®. Its uses in different aspects of inflammation and immune function are discussed, highlighting exercise-induced inflammation, mediating the effects of air pollution, and controlling thrombotic aspects of the immune response. Potential future developments in women's health, erectile dysfunction, and the allergic response indicate how broad the utility of dietary antiplatelets can be.

Evaluation of the equivalence of different intakes of Fruitflow in affecting platelet aggregation and thrombin generation capacity in a randomized, double-blinded pilot study in male subjects.

BACKGROUND: The water-soluble tomato extract, Fruitflow® is a dietary antiplatelet which can be used to lower platelet aggregability in primary preventative settings. We carried out a pilot study to investigate the range of intakes linked to efficacy and to make an initial assessment of variability in response to Fruitflow®. METHODS: Platelet response to adenosine diphosphate (ADP) agonist and thrombin generation capacity were monitored at baseline and 24 h after consuming 0, 30, 75, 150 or 300 mg of Fruitflow® in a randomized, double-blinded crossover study in male subjects 30-65 years of age (N = 12). Results were evaluated for equivalence to the standard 150 mg dose. RESULTS: Results showed that the changes from baseline aggregation and thrombin generation observed after the 75 mg, 150 mg, and 300 mg supplements were equivalent. Aggregation was reduced from baseline by - 12.9 ± 17.7%, - 12.0 ± 13.9% and - 17.7 ± 15.7% respectively, while thrombin generation capacity fell by - 8.6 ± 4.1%, - 9.2 ± 3.1% and - 11.3 ± 2.3% respectively. Effects observed for 0 mg and 30 mg supplements were non-equivalent to 150 mg and not different from baseline (aggregation changed by 3.0 ± 5.0% and - 0.7 ± 10.2% respectively, while thrombin generation changed by 0.8 ± 3.0% and 0.8 ± 3.1% respectively). CONCLUSIONS: The data suggest that the efficacious range for Fruitflow® lies between 75 mg and 300 mg, depending on the individual. It may be pertinent to personalize the daily intake of Fruitflow® depending on individual platelet response. TRIAL REGISTRATION: ISRCTN53447583 , 24/02/2021.

Soluble Non-Starch Polysaccharides From Plantain (Musa x paradisiaca L.) Diminish Epithelial Impact of Clostridioides difficile.

Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea. Adhesion of this Gram-positive pathogen to the intestinal epithelium is a crucial step in CDI, with recurrence and relapse of disease dependent on epithelial interaction of its endospores. Close proximity, or adhesion of, hypervirulent strains to the intestinal mucosa are also likely to be necessary for the release of C. difficile toxins, which when internalized, result in intestinal epithelial cell rounding, damage, inflammation, loss of barrier function and diarrhoea. Interrupting these C. difficile-epithelium interactions could therefore represent a promising therapeutic strategy to prevent and treat CDI. Intake of dietary fibre is widely recognised as being beneficial for intestinal health, and we have previously shown that soluble non-starch polysaccharides (NSP) from plantain banana (Musa spp.), can block epithelial adhesion and invasion of a number of gut pathogens, such as E. coli and Salmonellae. Here, we assessed the action of plantain NSP, and a range of alternative soluble plant fibres, for inhibitory action on epithelial interactions of C. difficile clinical isolates, purified endospore preparations and toxins. We found that plantain NSP possessed ability to disrupt epithelial adhesion of C. difficile vegetative cells and spores, with inhibitory activity against C. difficile found within the acidic (pectin-rich) polysaccharide component, through interaction with the intestinal epithelium. Similar activity was found with NSP purified from broccoli and leek, although seen to be less potent than NSP from plantain. Whilst plantain NSP could not block the interaction and intracellular action of purified C. difficile toxins, it significantly diminished the epithelial impact of C. difficile, reducing both bacteria and toxin induced inflammation, activation of caspase 3/7 and cytotoxicity in human intestinal cell-line and murine intestinal organoid cultures. Dietary supplementation with soluble NSP from plantain may therefore confer a protective effect in CDI patients by preventing adhesion of C. difficile to the mucosa, i.e. a "contrabiotic" effect, and diminishing its epithelial impact. This suggests that plantain soluble dietary fibre may be a therapeutically effective nutritional product for use in the prevention or treatment of CDI and antibiotic-associated diarrhoea.

Predictors of upper limb spasticity after stroke? A systematic review and meta-analysis.

OBJECTIVE: To determine the predictive markers for the occurrence of upper limb spasticity in the first 12 months after stroke. DATA SOURCES: A systematic review was undertaken of the databases MEDLINE, EMBASE, CINAHL and PEDRO to 31st December 2017. STUDY SELECTION: Non-experimental or experimental studies that included a control group with spasticity who did not receive an experimental intervention which investigated at least one variable (explanatory variable) measured at baseline against the development (or not) of spasticity at a future time point within 12 months post stroke were selected independently by two reviewers. Eleven papers met the selection criteria. STUDY APPRAISAL: Data were extracted into tabular format using predefined data fields by two reviewers. Study quality was evaluated using the modified Downs and Black tool. Data were analysed using a meta-analysis or narrative review. RESULTS: Ten studies, including 856 participants were analysed. The predictive markers of upper limb spasticity at one month post stroke were: motor 11.25 (odds ratio, OR); [95% CI:2.48, 51.04] and sensory impairments 4.91 (OR); [1.24, 19.46]; haemorrhagic stroke 3.70 (OR); [1.05, 12.98] and age 0.01 (OR) [0.00, 69.89]. Only motor impairment was found as a significant predictor at six months post stroke 30.68 (OR); [1.60, 587.06]. LIMITATIONS: Low number of studies exploring biomechanical and neurophysiological in addition to behavioural predictors of spasticity were included. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: Using the results, the identified predictive markers have potential to better inform clinical decision-making and to plan specific rehabilitation interventions by physiotherapists for stroke survivors with upper limb spasticity. Systematic Review Registration Number PROSPERO (ID: CRD42016027642).

The effect of simultaneous contractions of ipsilateral muscles on changes in corticospinal excitability induced by paired associative stimulation (PAS).

Consideration was given to means of increasing the reliability and muscle specificity of paired associative stimulation (PAS) by utilising the phenomenon of crossed-facilitation. Eight participants completed three separate sessions: isometric flexor contractions of the left wrist at 20% of maximum voluntary contraction (MVC) simultaneously with PAS (20s intervals; 14 min duration) delivered at the right median nerve and left primary motor cortex (M1); isometric contractions at 20% of MVC; and PAS only (14 min). Eight further participants completed two sessions of longer duration PAS (28 min): either alone or in conjunction with flexion contractions of the left wrist. Thirty motor potentials (MEPs) were evoked in the right flexor (rFCR) and extensor (rECR) carpi radialis muscles by magnetic stimulation of left M1 prior to the interventions, immediately post-intervention, and 10 min post-intervention. Both 14 and 28 min of combined PAS and (left wrist flexion) contractions resulted in reliable increases in rFCR MEP amplitude, which were not present in rECR. In the PAS only conditions, 14 min of stimulation gave rise to unreliable increases in MEP amplitudes in rFCR and rECR, whereas 28 min of PAS induced small (unreliable) changes only for rFCR. These results support the conclusion that changes in the excitability of the corticospinal pathway induced by PAS interact with those associated with contraction of the muscles ipsilateral to the site of cortical stimulation. Furthermore, focal contractions applied by the opposite limb increase the extent and muscle specificity of the induced changes in excitability associated with PAS.

Muscle-specific variations in use-dependent crossed-facilitation of corticospinal pathways mediated by transcranial direct current (DC) stimulation.

The tendency for contractions of muscles in the upper limb to give rise to increases in the excitability of corticospinal projections to the homologous muscles of the opposite limb is well known. Although the suppression of this tendency is integral to tasks of daily living, its exploitation may prove to be critical in the rehabilitation of acquired hemiplegias. Transcranial direct current (DC) stimulation induces changes in cortical excitability that outlast the period of application. We present evidence that changes in the reactivity of the corticospinal pathway induced by DC stimulation of the motor cortex interact systematically with those brought about by contraction of the muscles of the ipsilateral limb. During the application of flexion torques (up to 50% of maximum) applied at the left wrist, motor evoked potentials (MEPs) were evoked in the quiescent muscles of the right arm by magnetic stimulation of the left motor cortex (M1). The MEPs were obtained prior to and following 10 min of anodal, cathodal or sham DC stimulation of left M1. Cathodal stimulation counteracted increases in the crossed-facilitation of projections to the (right) wrist flexors that otherwise occurred as a result of repeated flexion contractions at the left wrist. In addition, cathodal stimulation markedly decreased the excitability of corticospinal projections to the wrist extensors of the right limb. Thus changes in corticospinal excitability induced by DC stimulation can be shaped (i.e. differentiated by muscle group) by focal contractions of muscles in the limb ipsilateral to the site of stimulation.

Kinematic Components of the Reach-to-Target Movement After Stroke for Focused Rehabilitation Interventions: Systematic Review and Meta-Analysis.

Background: Better upper limb recovery after stroke could be achieved through tailoring rehabilitation interventions directly at movement deficits. Aim: To identify potential; targets for therapy by synthesizing findings of differences in kinematics and muscle activity between stroke survivors and healthy adults performing reach-to-target tasks. Methods: A systematic review with identification of studies, data extraction, and potential risk of bias was completed independently by two reviewers. Online databases were searched from their inception to November 2017 to find studies of reach-to-target in people-with-stroke and healthy adults. Potential risk-of-bias was assessed using the Down's and Black Tool. Synthesis was undertaken via: (a) meta-analysis of kinematic characteristics utilizing the standardized mean difference (SMD) [95% confidence intervals]; and (b), narrative synthesis of muscle activation. Results: Forty-six studies met the review criteria but 14 had insufficient data for extraction. Consequently, 32 studies were included in the meta-analysis. Potential risk-of-bias was low for one study, unclear for 30, and high for one. Reach-to-target was investigated with 618 people-with-stroke and 429 healthy adults. The meta-analysis found, in all areas of workspace, that people-with-stroke had: greater movement times (seconds) e.g., SMD 2.57 [0.89, 4.25]; lower peak velocity (millimeters/second) e.g., SMD -1.76 [-2.29, -1.24]; greater trunk displacement (millimeters) e.g. SMD 1.42 [0.90, 1.93]; a more curved reach-path-ratio e.g., SMD 0.77 [0.32, 1.22] and reduced movement smoothness e.g., SMD 0.92 [0.32, 1.52]. In the ipsilateral and contralateral workspace, people-with-stroke exhibited: larger errors in target accuracy e.g., SMD 0.70 [0.39, 1.01]. In contralateral workspace, stroke survivors had: reduced elbow extension and shoulder flexion (degrees) e.g., elbow extension SMD -1.10 [-1.62, -0.58] and reduced shoulder flexion SMD -1.91 [-1.96, -0.42]. Narrative synthesis of muscle activation found that people-with-stroke, compared with healthy adults, exhibited: delayed muscle activation; reduced coherence between muscle pairs; and use of a greater percentage of muscle power. Conclusions: This first-ever meta-analysis of the kinematic differences between people with stroke and healthy adults performing reach-to-target found statistically significant differences for 21 of the 26 comparisons. The differences identified and values provided are potential foci for tailored rehabilitation interventions to improve upper limb recovery after stroke.

Getting a kinematic handle on reach-to-grasp: a meta-analysis.

BACKGROUND AND OBJECTIVES: Reach-to-grasp is an essential everyday activity that is often impaired after stroke. The objectives of this review are: (1) identify differences in the kinematic characteristics of reach-to-grasp between individuals with and without stroke, and (2) determine the influence of object location on kinematics. DATA SOURCES: MEDLINE, AMED, and Embase databases. ELIGIBILITY CRITERIA: Studies investigating individuals with stroke and neurologically intact control participants completing reach-to-grasp (paretic upper limb) of an object assessed via kinematic assessment (motion analysis). REVIEW METHODS: Following Cochrane Collaboration guidelines a meta-analysis comparing kinematic characteristics of reach-to-grasp between individuals with and without stroke. Potential risk of bias was assessed using the Down's and Black Tool. Data were synthesised by calculating the standardised mean difference (SMD) in kinematic characteristics between adults with and without stroke. RESULTS: Twenty-nine studies met the review criteria, mainly of observational design; 460 individuals with stroke and 324 control participants. Kinematic differences in reach-to-grasp were identified in the central and ipsilateral workspace for example, individuals with stroke exhibited significantly lower peak velocity SMD -1.48 (95% CI -1.94, -1.02), and greater trunk displacement SMD 1.55 (95% CI 0.85, 2.25) than control participants. Included studies were assessed as demonstrating unclear or high potential risk-of-bias. CONCLUSIONS: Differences in kinematic characteristics between individuals with and without stroke were identified which may be different reaching in the ipsilateral and central workspace. Suggesting, that object location may influence some kinematic characteristics and not others which may be pertinent when re-training reach-to-grasp. PROSPERO: CRD42014009479.