EvolvRehab-MoveWell telerehabilitation for stroke survivors: study protocol for a feasibility with embedded initial proof-of-concept study.

INTRODUCTION: Stroke is a leading cause of disability throughout the world. Unilateral upper limb impairment is common in people who have had a stroke. As a result of impaired upper limb function, people who have had a stroke often employ abnormal 'compensatory' movements. In the short term, these compensatory movements allow the individual to complete tasks, though long-term movement in this manner can lead to limitations. Telerehabilitation offers the provision of rehabilitation services to patients at a remote location using information and communication technologies. 'EvolvRehab' is one such telerehabilitation system, which uses activities to assess and correct compensatory upper body movements, although the feasibility of its use is yet to be determined in National Health Service services. Using EvolvRehab, we aim to assess the feasibility of 6 weeks telerehabilitation in people after a stroke. METHODS AND ANALYSIS: A multisite feasibility study with embedded design phase. Normally distributed data will be analysed using paired samples t-tests; non-normally distributed data will be analysed using related samples Wilcoxon signed rank tests. Thematic content analysis of interview transcripts will be used to investigate the usability and perceived usefulness of the EvolvRehab kit. ETHICS AND DISSEMINATION: This study has received ethical approval from Solihull Research Ethics Committee (REC reference: 23/WM/0054). Dissemination will be carried out according to the dissemination plan co-written with stroke survivors, including academic publications and presentations; written reports; articles in publications of stakeholder organisations; presentations to and publications for potential customers. TRIAL REGISTRATION NUMBER: NCT05875792.

Task selection for a sensor-based, wearable, upper limb training device for stroke survivors: a multi-stage approach.

PURPOSE: Post-stroke survivors report that feedback helps to increase training motivation. A wearable system (M-MARK), comprising movement and muscle sensors and providing feedback when performing everyday tasks was developed. The objective reported here was to create an evidence-based set of upper-limb tasks for use with the system. MATERIALS AND METHODS: Data from two focus groups with rehabilitation professionals, ten interviews with stroke survivors and a review of assessment tests were synthesized. In a two-stage process, suggested tasks were screened to exclude non-tasks and complex activities. Remaining tasks were screened for suitability and entered into a categorization matrix. RESULTS: Of 83 suggestions, eight non-tasks, and 42 complex activities were rejected. Of the remaining 33 tasks, 15 were rejected: five required fine motor control; eight were too complex to standardize; one because the role of hemiplegic hand was not defined and one involved water. The review of clinical assessment tests found no additional tasks. Eleven were ultimately selected for testing with M-Mark. CONCLUSIONS: Using a task categorization matrix, a set of training tasks was systematically identified. There was strong agreement between data from the professionals, survivors and literature. The matrix populated by tasks has potential for wider use in upper-limb stroke rehabilitation. IMPLICATIONS FOR REHABILITATIONRehabilitation technologies that provide feedback on quantity and quality of movements can support independent home-based upper limb rehabilitation.Rehabilitation technology systems require a library of upper limb tasks at different levels for people with stroke and therapists to choose from.A user-defined and evidence-based set of upper limb tasks for use within a wearable sensor device system have been developed.

Working Memory Impairment in Transient Ischaemic Attack: N-back as a Sensitive Measure for Detection.

BACKGROUND: Transient ischaemic attack (TIA) can lead to lasting changes in brain structure and function resulting in cognitive impairment. Cognitive screening tools may lack sensitivity for detecting cognitive impairments, particularly executive function, which tends to be the earliest affected domain in vascular cognitive impairment. AIM: In this preliminary study, we examine a working memory (WMem) task as a sensitive measure of cognitive impairment in TIA. METHOD: Patients referred to a TIA clinic for transient neurological symptoms completed a general cognitive screening tool (Montreal Cognitive Assessment; MoCA), and a WMem task (2-N-back) in a cross-sectional design. RESULTS: TIA patients (n = 12) showed significantly reduced WMem performance on the N-back compared to patients diagnosed with mimic clinical conditions with overlapping symptoms (n = 16). No group differences were observed on the MoCA. CONCLUSIONS: Assessing WMem may provide a sensitive measure of cognitive impairment after TIA, with implications for cognitive screening in TIA services to triage patients for further neuropsychological support, or for interventions to prevent vascular dementia.

Optimising acute stroke pathways through flexible use of bed capacity: a computer modelling study.

BACKGROUND: Optimising capacity along clinical pathways is essential to avoid severe hospital pressure and help ensure best patient outcomes and financial sustainability. Yet, typical approaches, using only average arrival rate and average lengths of stay, are known to underestimate the number of beds required. This study investigates the extent to which averages-based estimates can be complemented by a robust assessment of additional 'flex capacity' requirements, to be used at times of peak demand. METHODS: The setting was a major one million resident healthcare system in England, moving towards a centralised stroke pathway. A computer simulation was developed for modelling patient flow along the proposed stroke pathway, accounting for variability in patient arrivals, lengths of stay, and the time taken for transfer processes. The primary outcome measure was flex capacity utilisation over the simulation period. RESULTS: For the hyper-acute, acute, and rehabilitation units respectively, flex capacities of 45%, 45%, and 36% above the averages-based calculation would be required to ensure that only 1% of stroke presentations find the hyper-acute unit full and have to wait. For each unit some amount of flex capacity would be required approximately 30%, 20%, and 18% of the time respectively. CONCLUSIONS: This study demonstrates the importance of appropriately capturing variability within capacity plans, and provides a practical and economical approach which can complement commonly-used averages-based methods. Results of this study have directly informed the healthcare system's new configuration of stroke services.

FeMA: Feature matching auto-encoder for predicting ischaemic stroke evolution and treatment outcome.

Although, predicting ischaemic stroke evolution and treatment outcome provide important information one step towards individual treatment planning, classifying functional outcome and modelling the brain tissue evolution remains a challenge due to data complexity and visually subtle changes in the brain. We propose a novel deep learning approach, Feature Matching Auto-encoder (FeMA) that consists of two stages, predicting ischaemic stroke evolution at one week without voxel-wise annotation and predicting ischaemic stroke treatment outcome at 90 days from a baseline scan. In the first stage, we introduce feature similarity and consistency objective, and in the second stage, we show that adding stroke evolution information increase the performance of functional outcome prediction. Comparative experiments demonstrate that our proposed method is more effective to extract representative follow-up features and achieves the best results for functional outcome of stroke treatment.

International stroke genetics consortium recommendations for studies of genetics of stroke outcome and recovery.

Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable for multicenter genetic studies of ischemic stroke brain injury and recovery. Our recommendations have been endorsed by the International Stroke Genetics Consortium.

A Comparison of T2 Relaxation-Based MRI Stroke Timing Methods in Hyperacute Ischemic Stroke Patients: A Pilot Study.

BACKGROUND: T2 relaxation-based magnetic resonance imaging (MRI) signals may provide onset time for acute ischemic strokes with an unknown onset. The ability of visual and quantitative MRI-based methods in a cohort of hyperacute ischemic stroke patients was studied. METHODS: A total of 35 patients underwent 3T (3 Tesla) MRI (<9-hour symptom onset). Diffusion-weighted (DWI), apparent diffusion coefficient (ADC), T1-weighted (T1w), T2-weighted (T2w), and T2 relaxation time (T2) images were acquired. T2-weighted fluid attenuation inversion recovery (FLAIR) images were acquired for 17 of these patients. Image intensity ratios of the average intensities in ischemic and non-ischemic reference regions were calculated for ADC, DWI, T2w, T2 relaxation, and FLAIR images, and optimal image intensity ratio cut-offs were determined. DWI and FLAIR images were assessed visually for DWI/FLAIR mismatch. RESULTS: The T2 relaxation time image intensity ratio was the only parameter with significant correlation with stroke duration (r = 0.49, P = .003), an area under the receiver operating characteristic curve (AUC = 0.77, P < .0001), and an optimal cut-off (T2 ratio = 1.072) that accurately identified patients within the 4.5-hour thrombolysis treatment window with sensitivity of 0.74 and specificity of 0.74. In the patients with the additional FLAIR, areas under the precision-recall-gain curve (AUPRG) and F1 scores showed that the T2 relaxation time ratio (AUPRG = 0.60, F1 = 0.73) performed considerably better than the FLAIR ratio (AUPRG = 0.39, F1 = 0.57) and the visual DWI/FLAIR mismatch (F1 = 0.25). CONCLUSIONS: Quantitative T2 relaxation time is the preferred MRI parameter in the assessment of patients with unknown onset for treatment stratification.

Determining T2 relaxation time and stroke onset relationship in ischaemic stroke within apparent diffusion coefficient-defined lesions. A user-independent method for quantifying the impact of stroke in the human brain.

BACKGROUND AND OBJECTIVE: In hyperacute ischaemic stroke, T2 of cerebral water increases with time. Quantifying this change may be informative of the extent of tissue damage and onset time. Our objective was to develop a user-unbiased method to measure the effect of cerebral ischaemia on T2 to study stroke onset time-dependency in human acute stroke lesions. METHODS: Six rats were subjected to permanent middle cerebral occlusion to induce focal ischaemia, and a consecutive cohort of acute stroke patients (n = 38) were recruited within 9 hours from symptom onset. T1-weighted structural, T2 relaxometry, and diffusion MRI for apparent diffusion coefficient (ADC) were acquired. Ischaemic lesions were defined as regions of lowered ADC. The median T2 difference (ΔT2) between lesion and contralateral non-ischaemic control region was determined by the newly-developed spherical reference method, and data compared to that obtained by the mirror reference method. Linear regressions and receiver operating characteristics (ROC) were compared between the two methods. RESULTS: ΔT2 increases linearly in rat brain ischaemia by 1.9 ± 0.8 ms/h during the first 6 hours, as determined by the spherical reference method. In patients, ΔT2 linearly increases by 1.6 ± 1.4 and 1.9 ± 0.9 ms/h in the lesion, as determined by the mirror reference and spherical reference method, respectively. ROC analyses produced areas under the curve of 0.83 and 0.71 for the spherical and mirror reference methods, respectively. CONCLUSIONS: Data from the spherical reference method showed that the median T2 increase in the ischaemic lesion is correlated with stroke onset time in a rat as well as in a human patient cohort, opening the possibility of using the approach as a timing tool in clinics.

Quantifying T 2 relaxation time changes within lesions defined by apparent diffusion coefficient in grey and white matter in acute stroke patients.

The apparent diffusion coefficient (ADC) of cerebral water, as measured by diffusion MRI, rapidly decreases in ischaemia, highlighting a lesion in acute stroke patients. The MRI T 2 relaxation time changes in ischaemic brain such that T 2 in ADC lesions may be informative of the extent of tissue damage, potentially aiding in stratification for treatment. We have developed a novel user-unbiased method of determining the changes in T 2 in ADC lesions as a function of clinical symptom duration based on voxel-wise referencing to a contralateral brain volume. The spherical reference method calculates the most probable pre-ischaemic T 2 on a voxel-wise basis, making use of features of the contralateral hemisphere presumed to be largely unaffected. We studied whether T 2 changes in the two main cerebral tissue types, i.e. in grey matter (GM) and white matter (WM), would differ in stroke. Thirty-eight acute stroke patients were accrued within 9 h of symptom onset and scanned at 3 T for 3D T 1-weighted, multi b-value diffusion and multi-echo spin echo MRI for tissue type segmentation, quantitative ADC and absolute T 2 images, respectively. T 2 changes measured by the spherical reference method were 1.94 ± 0.61, 1.50 ± 0.52 and 1.40 ± 0.54 ms h-1 in the whole, GM, and WM lesions, respectively. Thus, T 2 time courses were comparable between GM and WM independent of brain tissue type involved. We demonstrate that T 2 changes in ADC-delineated lesions can be quantified in the clinical setting in a user unbiased manner and that T 2 change correlated with symptom onset time, opening the possibility of using the approach as a tool to assess severity of tissue damage in the clinical setting.

Sneddon Syndrome: A Case Report Exploring the Current Challenges Faced with Diagnosis and Management.

Sneddon syndrome (SS) is a rare medium-vessel vasculopathy which characteristically presents with livedo racemosa (LR) and complications such as strokes. This case report describes a female presenting acutely with a stroke and, initially, no evidence of LR. Her antiphospholipid antibodies were negative, and her neuroimaging revealed multiple territory strokes with extensive vasculopathy and fragile neo-formed vessel collateralisation. She had progressive memory loss and multiple transient ischaemic attacks on a background of established infarctions. SS should be considered in any idiopathic medium-vessel vasculopathy despite the absence of LR. Medical therapy can be challenging and the importance of antiphospholipid status in risk stratifying anticoagulation against antiplatelet therapy is discussed with a proposed rheumatology management strategy. The medical option of hydroxychloroquine should be considered in all patients in view of its anti-thrombotic properties and efficacy in diseases such as systemic lupus erythematosus and antiphospholipid syndrome with the suggestion that SS may be a forme fruste of these diseases. Neurosurgical options should be considered for recurrent transient neurological symptoms. For our patient, this included an extracranial to intracranial bypass via a radial artery graft for haemodynamic stroke management confirmed on SPECT imaging. The traditional hallmark of SS has previously been LR. This case highlights an atypical presentation stressing the importance of diagnostic vigilance in a patient with an idiopathic medium-vessel vasculopathy, together with balancing the medical risk of antiplatelet therapy, anticoagulation and thrombolysis whilst revealing possible neurosurgical options in select SS patients.

Visual training in hemianopia alters neural activity in the absence of behavioural improvement: a pilot study.

BACKGROUND: Damage to the primary visual cortex (V1) due to stroke often results in permanent loss of sight affecting one side of the visual field (homonymous hemianopia). Some rehabilitation approaches have shown improvement in visual performance in the blind region, but require a significant time investment. METHODS: Seven patients with cortical damage performed 400 trials of a motion direction discrimination task daily for 5 days. Three patients received anodal transcranial direct current stimulation (tDCS) during training, three received sham stimulation and one had no stimulation. Each patient had an assessment of visual performance and a functional magnetic resonance imaging (fMRI) scan before and after training to measure changes in visual performance and cortical activity. RESULTS: No patients showed improvement in visual function due to the training protocol, and application of tDCS had no effect on visual performance. However, following training, the neural response in motion area hMT+ to a moving stimulus was altered. When the stimulus was presented to the sighted hemifield, activity decreased in hMT+ of the damaged hemisphere. There was no change in hMT+ response when the stimulus was presented to the impaired hemifield. There was a decrease in activity in the inferior precuneus after training when the stimulus was presented to either the impaired or sighted hemifield. Preliminary analysis of tDCS data suggested that anodal tDCS interacted with the delivered training, modulating the neural response in hMT+ in the healthy side of the brain. CONCLUSION: Training can affect the neural responses in hMT+ even in the absence of change in visual performance.

Visual contrast sensitivity deficits in 'normal' visual field of patients with homonymous visual field defects due to stroke: a pilot study.

BACKGROUND: Homonymous visual field defects (VFD) are common following stroke, and often recover, partially or fully, by unknown mechanisms. In clinical practice, visual field recovered on perimetry is often considered perceptually normal. However, studies have shown contrast sensitivity (CS) deficits in patients with stroke and homonymous VFD. This study investigated the origin of visual CS loss in patients with VFD due to stroke. We hypothesised that CS deficits would be found in visual field areas appearing normal on perimetry, in patients with ischaemic stroke affecting the retrochiasmal visual system, and that the spatiotemporal properties of this CS loss would be consistent with those of 'blindsight', perhaps suggesting similar underlying mechanisms. METHODS: CS measurements were made in 20 healthy participants, and in 7 patients with stroke causing homonymous VFD sparing foveal vision, measured using Humphrey static perimetry (SITA-Fast 24-2 procedure). Importantly, patients with concomitant visuospatial neglect were excluded. CS measurements were made using a modification of the method of increasing contrast, corrected for reaction time. Three spatial stimuli were used, at several spatial frequencies: (1) large sinusoidal gratings; (2) foveal Gabor patches; and (3) Gabor patches presenting in the putatively recovered visual field, near VFD. Stimuli with different temporal profiles were used to selectively stimulate transient and sustained visual channels, to provide insight into mechanisms of visual loss and/or recovery. Analysis of variance (ANOVA) was used in the analysis of the measurements, allowing for correction for age and stimulus eccentricity. RESULTS: ANOVA for sustained grating stimuli showed orientation-selective (horizontal) CS loss (p = 0.025); no such loss was apparent in the central visual field (foveal Gabor stimuli). Localised CS close to VFD was reduced in stroke-affected hemifields compared with unaffected hemifields (p ≤ 0.005), though these areas appeared normal on perimetry. In these areas, CS was relatively preserved for transient compared with sustained stimuli (Wilcoxon signed rank tests). CONCLUSIONS: The finding of specific CS deficits in the normal-appearing visual field of patients with homonymous VFD due to stroke suggests that static perimetry provides an inadequate assessment of visual function in these patients, with clear implications for testing of vision in clinical practice. The results are consistent with relative sparing of the transient/magnocellular visual channel. These findings demand further investigation. If confirmed in larger, longitudinal studies, this will have important implications for the mechanisms of recovery, and may provide a target for visual rehabilitation - for example, using repeated detection practice ('perceptual learning').

Stroke management.

INTRODUCTION: Stroke is the third most common cause of death in most developed countries. It is a worldwide problem; about 4.5 million people die from stroke each year. Stroke can occur at any age, but half of all strokes occur in people aged over 70 years. About 80% of all acute strokes are ischaemic, usually resulting from thrombotic or embolic occlusion of a cerebral artery. The remainder are caused either by intracerebral or subarachnoid haemorrhage. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of specialised care in people with acute stroke? What are the effects of medical treatment in people with acute ischaemic stroke? What are the effects of decompressive hemicraniectomy in acute ischaemic stroke? What are the effects of surgical evacuation for intracerebral haematomas? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 41 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: acute reduction in blood pressure, aspirin, evacuation (early surgical evacuation, or conservative treatment), decompressive hemicraniectomy, neuroprotective agents (calcium channel blockers, citicoline, gamma-aminobutyric acid agonists, glycine antagonists, lubeluzole, magnesium, N-methyl-D-aspartate antagonists), specialised stroke care, systemic anticoagulation (heparinoids, specific thrombin inhibitors, low molecular weight heparin, oral anticoagulants, unfractionated heparin), and thrombolysis.

Self administered cognitive screening test (TYM) for detection of Alzheimer's disease: cross sectional study.

OBJECTIVE: To evaluate a cognitive test, the TYM ("test your memory"), in the detection of Alzheimer's disease. DESIGN: Cross sectional study. SETTING: Outpatient departments in three hospitals, including a memory clinic. PARTICIPANTS: 540 control participants aged 18-95 and 139 patients attending a memory clinic with dementia/amnestic mild cognitive impairment. INTERVENTION: Cognitive test designed to use minimal operator time and to be suitable for non-specialist use. MAIN OUTCOME MEASURES: Performance of normal controls on the TYM. Performance of patients with Alzheimer's disease on the TYM compared with age matched controls. Validation of the TYM with two standard tests (the mini-mental state examination (MMSE) and the Addenbrooke's cognitive examination-revised (ACE-R)). Sensitivity and specificity of the TYM in the detection of Alzheimer's disease. RESULTS: Control participants completed the TYM with an average score of 47/50. Patients with Alzheimer's disease scored an average of 33/50. The TYM score shows excellent correlation with the two standard tests. A score of

Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory.

Previous data suggest that methylphenidate can have variable effects on different cognitive tasks both within and between individuals. This is thought to be underpinned by inverted U-shaped relationships between cognitive performance and dopaminergic activity in relatively separate fronto-striatal circuits and reflected by individual differences in trait impulsivity. Direct evidence for this is currently lacking. In this study, we demonstrate for the first time that therapeutic doses of oral methylphenidate administered to young healthy subjects result in different sized changes in D(2)/D(3) receptor availability in different regions of the human striatum and that the change in receptor availability within an individual subregion predicts cognitive performance on a particular task. Methylphenidate produced significantly different effects on reversal learning and spatial working memory tasks within individuals. Performance on the reversal learning task was predicted by the drug-induced change in D(2)/D(3) receptor availability in postcommissural caudate, measured using [(11)C]-raclopride radioligand PET imaging, whereas performance on the spatial working memory task was predicted by changes in receptor availability in the ventral striatum. Reversal learning performance was also predicted by subjects' trait impulsivity, such that the most impulsive individuals benefited more from methylphenidate, consistent with this drug's beneficial effects on cognition in attention deficit hyperactivity disorder.

Stroke management.

INTRODUCTION: Stroke is the third most common cause of death in most resource-rich countries. It is a worldwide problem; about 4.5 million people die from stroke each year. Stroke can occur at any age, but half of all strokes occur in people aged over 70 years. About 80% of all acute strokes are ischaemic, usually resulting from thrombotic or embolic occlusion of a cerebral artery. The remainder are caused either by intracerebral or subarachnoid haemorrhage. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of specialised care in people with acute stroke? What are the effects of medical treatment in people with acute ischaemic stroke? What are the effects of surgical treatment for intracerebral haematomas? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 42 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: acute reduction in blood pressure, aspirin, evacuation (early surgical evacuation, or conservative treatment), neuroprotective agents (calcium channel antagonists, citicoline, gamma-aminobutyric acid agonists, glycine antagonists, lubeluzole, magnesium, N-methyl-D-aspartate antagonists, tirilazad), specialised stroke care, systemic anticoagulation (heparinoids, low or specific thrombin inhibitors, molecular weight heparin, oral anticoagulants, unfractionated heparin), and thrombolysis.

Coding of the contrasts in natural images by visual cortex (V1) neurons: a Bayesian approach.

Individual V1 neurons respond dynamically over only limited ranges of stimulus contrasts, yet we can discriminate contrasts over a wide range. Different V1 neurons cover different parts of the contrast range, and the information they provide must be pooled somehow. We describe a probabilistic pooling model that shows that populations of neurons with contrast responses like those in cat and monkey V1 would most accurately code contrasts in the range actually found in natural scenes. The pooling equation is similar to Bayes's equation; however, explicit inclusion of prior probabilities in the inference increases coding accuracy only slightly.