Biomarkers of Motor Outcomes After Stroke.

Predicting motor outcomes after stroke based on clinical judgment alone is often inaccurate and can lead to inefficient and inequitable allocation of rehabilitation resources. Prediction tools are being developed so that clinicians can make evidence-based, accurate, and reproducible prognoses for individual patients. Biomarkers of corticospinal tract structure and function can improve prediction tool performance, particularly for patients with initially moderate to severe motor impairment. Being able to make accurate predictions for individual patients supports rehabilitation planning and communication with patients and families.

Accuracy and Reliability of Remote Categorization of Upper Limb Outcome After Stroke.

BACKGROUND: There is an increasing need for motor assessments after stroke that can be performed quickly and remotely. The Fast Outcome Categorization of the Upper Limb after Stroke-4 (FOCUS-4) assessment remotely classifies upper limb outcome into 1 of 4 categories after stroke and was developed via retrospective analysis of Action Research Arm Test (ARAT) scores. OBJECTIVE: The aim of this study was to prospectively evaluate the accuracy and reliability of FOCUS-4 assessments for categorizing upper limb outcome after stroke when administered remotely during a videocall compared to an in-person ARAT. METHODS: Data were collected from 26 participants at 3 months post-stroke (3M), 27 participants at 6 months post-stroke (6M), and 56 participants at the chronic stage of stroke (>6M). Participants performed an in-person ARAT and a remote FOCUS-4 assessment administered during a videocall, and accuracy was evaluated by comparing the upper limb outcome categories. Participants at the chronic stage of stroke also performed a second remote FOCUS-4 assessment to assess between-day reliability. RESULTS: Overall accuracy of the remote FOCUS-4 assessment was 88% at 3M and 96% at 6M. Overall accuracy of the first and second remote FOCUS-4 assessments at the chronic stage was 75% and 79%, respectively. Reliability of the FOCUS-4 assessment at the chronic stage was 82%. The remote FOCUS-4 assessment was most accurate and reliable for participants with mild or severe upper limb functional impairment. CONCLUSIONS: The remote FOCUS-4 assessment has potential to classify upper limb functional capacity or to screen possible participants for stroke trials, but external validation is required.

Resting-state EEG connectivity recorded before and after rTMS treatment in patients with treatment-resistant depression.

Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy and tolerability in Major Depressive Disorder (MDD). However, the underlying mechanisms of its antidepressant effects remain unclear. This open-label study investigated electroencephalography (EEG) functional connectivity markers associated with response and the antidepressant effects of rTMS. Resting-state EEG data were collected from 28 participants with MDD before and after a four-week rTMS course. Source-space functional connectivity between 38 cortical regions was compared using an orthogonalised amplitude approach. Depressive symptoms significantly improved following rTMS, with 43 % of participants classified as responders. While the study's functional connectivity findings did not withstand multiple comparison corrections, exploratory analyses suggest an association between theta band connectivity and rTMS treatment mechanisms. Fronto-parietal theta connectivity increased after treatment but did not correlate with antidepressant response. Notably, low baseline theta connectivity was associated with greater response. However, due to the exploratory nature and small sample size, further replication is needed. The findings provide preliminary evidence that EEG functional connectivity, particularly within the theta band, may reflect the mechanisms by which rTMS exerts its therapeutic effects.

Do lower limb motor-evoked potentials predict walking outcomes post-stroke?

BACKGROUND: This observational study examined whether lower limb (LL) motor-evoked potentials (MEPs) 1 week post-stroke predict recovery of independent walking, use of ankle-foot orthosis (AFO) or walking aid, at 3 and 6 months post-stroke. METHODS: Non-ambulatory participants were recruited 5 days post-stroke. Transcranial magnetic stimulation was used to determine tibialis anterior MEP status and clinical assessments (age, National Institutes of Health Stroke Scale (NIHSS), ankle dorsiflexion strength, LL motricity index, Berg Balance Test) were completed 1 week post-stroke. Functional Ambulation Category (FAC), use of AFO and walking aid were assessed 3 months and 6 months post-stroke. MEP status, alone and combined with clinical measures, and walking outcomes at 3 and 6 months were analysed with Pearson χ2 and multivariate binary logistic regression. RESULTS: Ninety participants were included (median age 72 years (38-97 years)). Most participants (81%) walked independently (FAC ≥ 4), 17% used an AFO, and 49% used a walking aid 3 months post-stroke with similar findings at 6 months. Independent walking was better predicted by age, LL strength and Berg Balance Test (accuracy 92%, 95% CI 85% to 97%) than MEP status (accuracy 73%, 95% CI 63% to 83%). AFO use was better predicted by NIHSS and MEP status (accuracy 88%, 95% CI 79% to 94%) than MEP status alone (accuracy 76%, 95% CI 65% to 84%). No variables predicted use of walking aids. CONCLUSIONS: The presence of LL MEPs 1-week post-stroke predicts independent walking at 3 and 6 months post-stroke. However, the absence of MEPs does not preclude independent walking. Clinical factors, particularly age, balance and stroke severity, more strongly predict independent walking than MEP status. LL MEP status adds little value as a biomarker for walking outcomes.

Applications of Repetitive Transcranial Magnetic Stimulation to Improve Upper Limb Motor Performance After Stroke: A Systematic Review.

BACKGROUND: Noninvasive brain stimulation (NIBS) is a promising technique for improving upper limb motor performance post-stroke. Its application has been guided by the interhemispheric competition model and typically involves suppression of contralesional motor cortex. However, the bimodal balance recovery model prompts a more tailored application of NIBS based on ipsilesional corticomotor function. OBJECTIVE: To review and assess the application of repetitive transcranial magnetic stimulation (rTMS) protocols that aimed to improve upper limb motor performance after stroke. METHODS: A PubMed search was conducted for studies published between 1st January 2005 and 1st November 2022 using rTMS to improve upper limb motor performance of human adults after stroke. Studies were grouped according to whether facilitatory or suppressive rTMS was applied to the contralesional hemisphere. RESULTS: Of the 492 studies identified, 70 were included in this review. Only 2 studies did not conform to the interhemispheric competition model, and facilitated the contralesional hemisphere. Only 21 out of 70 (30%) studies reported motor evoked potential (MEP) status as a biomarker of ipsilesional corticomotor function. Around half of the studies (37/70, 53%) checked whether rTMS had the expected effect by measuring corticomotor excitability (CME) after application. CONCLUSION: The interhemispheric competition model dominates the application of rTMS post-stroke. The majority of recent and current studies do not consider bimodal balance recovery model for the application of rTMS. Evaluating CME after the application rTMS could confirm that the intervention had the intended neurophysiological effect. Future studies could select patients and apply rTMS protocols based on ipsilesional MEP status.

Clinical utility of trans-sacral magnetic stimulation-evoked sphincter potentials and high-density electromyography in pelvic floor assessment: Technical evaluation.

AIM: Faecal incontinence is common and of multifactorial aetiologies, yet current diagnostic tools are unable to assess nerve and sphincter function objectively. We developed an anorectal high-density electromyography (HD-EMG) probe to evaluate motor-evoked potentials induced via trans-sacral magnetic stimulation (TSMS). METHOD: Anorectal probes with an 8 × 8 array of electrodes spaced 1 cm apart were developed for recording HD-EMG of the external anal sphincter. These HD-EMG probes were used to map MEP amplitudes and latencies evoked via TSMS delivered through the Magstim Rapid2 (MagStim Company). Patients undergoing pelvic floor investigations were recruited for this IDEAL Stage 2a pilot study. RESULTS: Eight participants (median age 49 years; five female) were recruited. Methodological viability, safety and diagnostic workflow were established. The test was well tolerated with median discomfort scores ≤2.5/10, median pain scores ≤1/10 and no adverse events. Higher Faecal Incontinence Severity Index scores correlated with longer MEP latencies (r = 0.58, p < 0.001) and lower MEP amplitudes (r = -0.32, p = 0.046), as did St. Mark's Incontinence Scores with both MEP latencies (r = 0.49, p = 0.001) and MEP amplitudes (r = -0.47, p = 0.002). CONCLUSION: This HD-EMG probe in conjunction with TSMS presents a novel diagnostic tool for anorectal function assessment. Spatiotemporal assessment of magnetically stimulated MEPs correlated well with symptoms and offers a feasible, safe and patient-tolerable method of evaluating pudendal nerve and external anal sphincter function. Further clinical development and evaluation of these techniques is justified.

Reliability of a TMS-derived threshold matrix of corticomotor function.

Transcranial magnetic stimulation (TMS) studies typically focus on suprathreshold motor evoked potentials (MEPs), overlooking small MEPs representing subthreshold corticomotor pathway activation. Assessing subthreshold excitability could provide insights into corticomotor pathway integrity and function, particularly in neurological conditions like stroke. The aim of the study was to examine the test-retest reliability of metrics derived from a novel compositional analysis of MEP data from older adults. The study also compared the composition between the dominant (D) and non-dominant (ND) sides and explored the association between subthreshold responses and resting motor threshold. In this proof-of-concept study, 23 healthy older adults participated in two identical experimental sessions. Stimulus-response (S-R) curves and threshold matrices were constructed using single-pulse TMS across intensities to obtain MEPs in four upper limb muscles. S-R curves had reliable slopes for every muscle (Intraclass Correlation Coefficient range = 0.58-0.88). Subliminal and suprathreshold elements of the threshold matrix showed good-excellent reliability (D subliminal ICC = 0.83; ND subliminal ICC = 0.79; D suprathreshold ICC = 0.92; ND suprathreshold ICC = 0.94). By contrast, subthreshold elements of the matrix showed poor reliability, presumably due to a floor effect (D subthreshold ICC = 0.39; ND subthreshold ICC = 0.05). No composition differences were found between D and ND sides (suprathreshold BF01 = 3.85; subthreshold BF01 = 1.68; subliminal BF01 = 3.49). The threshold matrix reliably assesses subliminal and suprathreshold MEPs in older adults. Further studies are warranted to evaluate the utility of compositional analyses for assessing recovery of corticomotor pathway function after neurological injury.

Motor rehabilitation after stroke: European Stroke Organisation (ESO) consensus-based definition and guiding framework.

PURPOSE: To propose a consensus-based definition and framework for motor rehabilitation after stroke. METHODS: An expert European working group reviewed the literature, attaining internal consensus after external feedback. FINDINGS: Motor rehabilitation is defined as a process that engages people with stroke to benefit their motor function, activity capacity and performance in daily life. It is necessary for people with residual motor disability whose goal is to enhance their functioning, independence and participation. Motor rehabilitation operates through learning- and use-dependent mechanisms. The trajectory of motor recovery varies across patients and stages of recovery. Early behavioral restitution of motor function depends on spontaneous biological mechanisms. Further improvements in activities of daily living are achieved by compensations. Motor rehabilitation is guided by regular assessment of motor function and activity using consensus-based measures, including patient-reported outcomes. Results are discussed with the patient and their carers to set personal goals. During motor rehabilitation patients learn to optimize and adapt their motor, sensory and cognitive functioning through appropriately dosed repetitive, goal-oriented, progressive, task- and context-specific training. Motor rehabilitation supports people with stroke to maximize health, well-being and quality of life. The framework describes the International Classification of Functioning, Disability and Health in the context of stroke, describes neurobiological mechanisms of behavioral restitution and compensation, and summarizes recommendations for clinical assessment, prediction tools, and motor interventions with strong recommendations from clinical practice guidelines (2016-2022). CONCLUSIONS: This definition and framework may guide clinical educators, inform clinicians on current recommendations and guidelines, and identify gaps in the evidence base.

Proportional Recovery After Stroke: Addressing Concerns Regarding Mathematical Coupling and Ceiling Effects.

Baseline scores after stroke have long been known as a good predictor of post-stroke outcomes. Similarly, the extent of baseline impairment has been shown to strongly correlate with spontaneous recovery in the first 3 to 6 months after stroke, a principle known as proportional recovery. However, recent critiques have proposed that proportional recovery is confounded, most notably by mathematical coupling and ceiling effects, and that it may not be a valid model for post-stroke recovery. This article reviews the current understanding of proportional recovery after stroke, discusses its supposed confounds of mathematical coupling and ceiling effects, and comments on the validity and usefulness of proportional recovery as a model for post-stroke recovery. We demonstrate that mathematical coupling of the true measurement value is not a real statistical confound, but rather a notational construct that has no effect on the correlation itself. On the other hand, mathematical coupling does apply to the measurement error and can spuriously amplify correlation effect sizes, but should be negligible in most cases. We also explain that compression toward ceiling and the corresponding proportional recovery relationship are consistent with our understanding of post-stroke recovery dynamics, rather than being unwanted confounds. However, while proportional recovery is valid, it is not particularly groundbreaking or meaningful as previously thought, just like how correlations between baseline scores and outcomes are relatively common in stroke research. Whether through proportional recovery or baseline-outcome regression, baseline scores are a starting point for investigating factors that determine recovery and outcomes after stroke.

Predicting Motor Outcomes Using Atlas-Based Voxel Features of Post-Stroke Neuroimaging: A Scoping Review.

BACKGROUND: Atlas-based voxel features have the potential to aid motor outcome prognostication after stroke, but are seldom used in clinically feasible prediction models. This could be because neuroimaging feature development is a non-standardized, complex, multistep process. This is a barrier to entry for researchers and poses issues for reproducibility and validation in a field of research where sample sizes are typically small. OBJECTIVES: The primary aim of this review is to describe the methodologies currently used in motor outcome prediction studies using atlas-based voxel neuroimaging features. Another aim is to identify neuroanatomical regions commonly used for motor outcome prediction. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol was constructed and OVID Medline and Scopus databases were searched for relevant studies. The studies were then screened and details about imaging modality, image acquisition, image normalization, lesion segmentation, region of interest determination, and imaging measures were extracted. RESULTS: Seventeen studies were included and examined. Common limitations were a lack of detailed reporting on image acquisition and the specific brain templates used for normalization and a lack of clear reasoning behind the atlas or imaging measure selection. A wide variety of sensorimotor regions relate to motor outcomes and there is no consensus use of one single sensorimotor atlas for motor outcome prediction. CONCLUSION: There is an ongoing need to validate imaging predictors and further improve methodological techniques and reporting standards in neuroimaging feature development for motor outcome prediction post-stroke.

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee.

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer's disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentato-thalamo-motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity.

Arguments for the biological and predictive relevance of the proportional recovery rule.

The proportional recovery rule (PRR) posits that most stroke survivors can expect to reduce a fixed proportion of their motor impairment. As a statistical model, the PRR explicitly relates change scores to baseline values - an approach that arises in many scientific domains but has the potential to introduce artifacts and flawed conclusions. We describe approaches that can assess associations between baseline and changes from baseline while avoiding artifacts due either to mathematical coupling or to regression to the mean. We also describe methods that can compare different biological models of recovery. Across several real datasets in stroke recovery, we find evidence for non-artifactual associations between baseline and change, and support for the PRR compared to alternative models. We also introduce a statistical perspective that can be used to assess future models. We conclude that the PRR remains a biologically relevant model of stroke recovery.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

The TWIST Tool Predicts When Patients Will Recover Independent Walking After Stroke: An Observational Study.

BACKGROUND: The likelihood of regaining independent walking after stroke influences rehabilitation and hospital discharge planning. OBJECTIVE: This study aimed to develop and internally validate a tool to predict whether and when a patient will walk independently in the first 6 months post-stroke. METHODS: Adults with stroke were recruited if they had new lower limb weakness and were unable to walk independently. Clinical assessments were completed one week post-stroke. The primary outcome was time post-stroke by which independent walking (Functional Ambulation Category score ≥ 4) was achieved. Cox hazard regression identified predictors for achieving independent walking by 4, 6, 9, 16, or 26 weeks post-stroke. The cut-off and weighting for each predictor was determined using ß-coefficients. Predictors were assigned a score and summed for a final TWIST score. The probability of achieving independent walking at each time point for each TWIST score was calculated. RESULTS: We included 93 participants (36 women, median age 71 years). Age < 80 years, knee extension strength Medical Research Council grade ≥ 3/5, and Berg Balance Test < 6, 6 to 15, or ≥ 16/56, predicted independent walking and were combined to form the TWIST prediction tool. The TWIST prediction tool was at least 83% accurate for all time points. CONCLUSIONS: The TWIST tool combines routine bedside tests at one week post-stroke to accurately predict the probability of an individual patient achieving independent walking by 4, 6, 9, 16, or 26 weeks post-stroke. If externally validated, the TWIST prediction tool may benefit patients and clinicians by informing rehabilitation decisions and discharge planning.

Investigating the structure-function relationship of the corticomotor system early after stroke using machine learning.

BACKGROUND: Motor outcomes after stroke can be predicted using structural and functional biomarkers of the descending corticomotor pathway, typically measured using magnetic resonance imaging and transcranial magnetic stimulation, respectively. However, the precise structural determinants of intact corticomotor function are unknown. Identifying structure-function links in the corticomotor pathway could provide valuable insight into the mechanisms of post-stroke motor impairment. This study used supervised machine learning to classify upper limb motor evoked potential status using MRI metrics obtained early after stroke. METHODS: Retrospective data from 91 patients (49 women, age 35-97 years) with moderate to severe upper limb weakness within a week after stroke were included in this study. Support vector machine classifiers were trained using metrics from T1- and diffusion-weighted MRI to classify motor evoked potential status, empirically measured using transcranial magnetic stimulation. RESULTS: Support vector machine classification of motor evoked potential status was 81% accurate, with false positives more common than false negatives. Important structural MRI metrics included diffusion anisotropy asymmetry in the supplementary and pre-supplementary motor tracts, maximum cross-sectional lesion overlap in the sensorimotor tract and ventral premotor tract, and mean diffusivity asymmetry in the posterior limbs of the internal capsule. INTERPRETATIONS: MRI measures of corticomotor structure are good but imperfect predictors of corticomotor function. Residual corticomotor function after stroke depends on both the extent of cross-sectional macrostructural tract damage and preservation of white-matter microstructural integrity. Analysing the corticomotor pathway using a multivariable MRI approach across multiple tracts may yield more information than univariate biomarker analyses.

Decreased salience network fMRI functional connectivity following a course of rTMS for treatment-resistant depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a treatment shown to be effective in treating major depressive disorder (MDD). However, the effect of rTMS therapy on functional connectivity within the brains of patients being treated for MDD remains poorly understood. Few studies have investigated the effects of a course of rTMS on resting-state network activity. METHODS: In an open-label naturalistic study, resting-state fMRI was collected prior to and following a four-week course of rTMS in 24 participants with MDD and 2 with bipolar disorder. Montgomery-Asberg depression rating scale scores showed a response rate of 42%. RESULTS: Clinical response to rTMS was correlated with reduced functional connectivity from baseline to post-rTMS within the salience network (SN). This indicates SN connectivity may be functionally relevant to how rTMS produces antidepressant effects. In an exploratory inter-network analysis, connectivity between the SN and posterior default mode network (pDMN) was higher following treatment. However this difference was not correlated with the antidepressant response. Local BOLD activity within these networks was also assessed using the fractional amplitude of low-frequency fluctuations (fALFF) technique. Local activity increased in both the SN and pDMN following rTMS. However this increase was also not correlated with antidepressant response. LIMITATIONS: The sample population was heterogeneous, continuing current use of medications, and the study lacked a healthy control or sham stimulation comparison group. CONCLUSIONS: Together, these results provide evidence for the involvement of the SN in the antidepressant response to rTMS treatment.

Fast Outcome Categorization of the Upper Limb After Stroke.

BACKGROUND AND PURPOSE: The ARAT (Action Research Arm Test) has been used to classify upper limb motor outcome after stroke in 1 of 3, 4, or 5 categories. The COVID-19 pandemic has encouraged the development of assessments that can be performed quickly and remotely. The aim of this study was to derive and internally validate decision trees for categorizing upper limb motor outcomes at the late subacute and chronic stages of stroke using a subset of ARAT tasks. METHODS: This study retrospectively analyzed ARAT scores obtained in-person at 3 months poststroke from 333 patients. In-person ARAT scores were used to categorize patients' 3-month upper limb outcome using classification systems with 3, 4, and 5 outcome categories. Individual task scores from in-person assessments were then used in classification and regression tree analyses to determine subsets of tasks that could accurately categorize upper limb outcome for each of the 3 classification systems. The decision trees developed using 3-month ARAT data were also applied to in-person ARAT data obtained from 157 patients at 6 months poststroke. RESULTS: The classification and regression tree analyses produced decision trees requiring 2 to 4 ARAT tasks. The overall accuracy of the cross-validated decision trees ranged from 87.7% (SE, 1.0%) to 96.7% (SE, 2.0%). Accuracy was highest when classifying patients into one of 3 outcome categories and lowest for 5 categories. The decision trees are referred to as FOCUS (Fast Outcome Categorization of the Upper Limb After Stroke) assessments and they remained accurate for 6-month poststroke ARAT scores (overall accuracy range 83.4%-91.7%). CONCLUSIONS: A subset of ARAT tasks can accurately categorize upper limb motor outcomes after stroke. Future studies could investigate the feasibility and accuracy of categorizing outcomes using the FOCUS assessments remotely via video call.

Intensive rehabilitation programme for patients with subacute stroke in an inpatient rehabilitation facility: describing a protocol of a prospective cohort study.

INTRODUCTION: Rehabilitation is recognised as a cornerstone of multidisciplinary stroke care. Intensity of therapy is related to functional recovery although there is high variability on the amount of time and techniques applied in therapy sessions. There is a need to better describe stroke rehabilitation protocols to develop a better understanding of current practice increasing the internal validity and generalisation of clinical trial results. The aim of this study is to describe an intensive rehabilitation programme for patients with stroke in an inpatient rehabilitation facility, measuring the amount and type of therapies (physical, occupational and speech therapy) provided and reporting functional outcomes. METHODS AND ANALYSIS: This will be a prospective observational cohort study of patients with subacute stroke admitted to our inpatient rehabilitation facility during 2 years. A therapy recording tool was developed in order to describe the rehabilitation interventions performed in our unit. This tool was designed using the Delphi method, literature search and collaboration with senior clinicians. Therapists will record the time spent on different activities available in our unit during specific therapy sessions. Afterwards, the total time spent in each activity, and the total rehabilitation time for all activities, will be averaged for all patients. Outcome variables were divided into three different domains: body structure and function outcomes, activity outcomes and participation outcomes and will be assessed at baseline (admission at the rehabilitation unit), at discharge from the rehabilitation unit and at 3 and 6 months after stroke. ETHICS AND DISSEMINATION: This study was approved by the Medical Research Committee at Hospital del Mar Research Institute (Project ID: 34/C/2017). The results of this study will be presented at national and international congress and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04191109.

Effect of rTMS on GABA and glutamate levels in treatment-resistant depression: An MR spectroscopy study.

Alterations in levels of neurotransmitters γ-aminobutyric acid (GABA) and glutamate may underlie the mechanism by which repetitive transcranial magnetic stimulation (rTMS) has efficacy as a treatment for major depressive disorder (MDD). This study used proton magnetic resonance spectroscopy (H1MRS) to investigate the effect of rTMS on levels of GABA and combined glutamate/glutamine measure (Glx). Treatment-resistant, currently depressed individuals participated in a naturalistic open-label study with rTMS treatment administered at 10 Hz and 120% of resting motor threshold to the left dorsolateral prefrontal cortex (DLPFC) for 20 sessions. H1 MRS measures were collected at baseline and after four weeks of daily treatment. GABA and Glx were measured from both the left DLPFC and a control region (right motor cortex). Twenty-seven participants completed the study and were included in the analysis. Contrary to previous studies, no difference in GABA was observed following treatment. Glx levels were found to significantly increase in both the left DLPFC and right motor cortex voxels but this increase did not correlate with antidepressant response. Glx levels were found to increase following rTMS, not only underlying the site of stimulation but also at a distant control voxel suggesting a degree of non-specificity in response to therapy.

The effects of unilateral step training and conventional treadmill training on gait asymmetry in patients with chronic stroke.

BACKGROUND: Step length asymmetry is common after stroke. Unilateral step training (UST) can improve step length asymmetry for patients who take a longer step with their paretic leg (P-long). UST has not been tested with patients who take a shorter step with their paretic leg (P-short). RESEARCH QUESTION: Does training patients according to the direction of their asymmetry improve step length asymmetry? METHODS: Adults 18 years and older with asymmetrical gait at least 6 months post-stroke completed three 20 min treadmill training sessions at least 48 h apart: Conventional treadmill; UST with the non-paretic leg stationary on the side of the treadmill and the paretic leg stepping on the moving treadmill belt (P-stepping); and UST with the paretic leg stationary on the side of the treadmill and the non-paretic leg stepping on the moving belt (NP-stepping). Spatiotemporal gait parameters before, immediately, 10 min and 30 min after training were recorded at self-selected and fastest walking pace. Asymmetry values for each parameter were calculated. RmANOVAs were used to investigate the effects of training type on spatiotemporal parameters and paired-samples t-tests used to investigate potential contributors to training effects on asymmetry. RESULTS: Twenty participants (16 male, median age 65 (43-80) years; 11 P-long, 9 P-short) were included. Improvements in step length asymmetry were observed immediately after both Conventional (9.1 %; 95 % CI 2.7-15.4%) and P-stepping (11.6 %; 95 % CI 5.3-17.8 %) treadmill training in participants who take a shorter step with their paretic leg, however effects were only sustained after Conventional training. Step length asymmetry did not improve for P-long participants with any training type. SIGNIFICANCE: The effectiveness of unilateral step training may be related to the direction of step length asymmetry. Further investigation is required before considering using unilateral step training as a rehabilitation tool for gait asymmetry after stroke.