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Background and Purpose: We investigated the effect of higher therapeutic exercise doses on walking during inpatient rehabilitation, typically commencing 1 to 4 weeks poststroke. Methods: This phase II, blinded-assessor, randomized controlled trial recruited from 6 Canadian inpatient rehabilitation units, between 2014 and 2018. Subjects (n=75; 25/group) were randomized into: control (usual care) physical therapy: typically, 1 hour, 5 days/week; Determining Optimal Post-Stroke Exercise (DOSE1): 1 hour, 5 days/week, more than double the intensity of Control (based on aerobic minutes and walking steps); and DOSE2: 2 hours, 5 days/week, more than quadruple the intensity of Control, each for 4 weeks duration. The primary outcome, walking endurance at completion of the 4-week intervention (post-evaluation), was compared across these groups using linear regression. Secondary outcomes at post-evaluation, and longitudinal outcomes at 6 and 12-month evaluations, were also analyzed. Results: Both DOSE1 (mean change 61 m [95% CI, 9–113], P =0.02) and DOSE2 (mean change 58 m, 6–110, P =0.03) demonstrated greater walking endurance compared with Control at the post-evaluation. Significant improvements were also observed with DOSE2 in gait speed (5-m walk), and both DOSE groups in quality of life (EQ-5D-5 L) compared with Control. Longitudinal analyses revealed that improvements in walking endurance from the DOSE intervention were retained during the 1-year follow-up period over usual care. Conclusions: This study provides the first preliminary evidence that patients with stroke can improve their walking recovery and quality of life with higher doses of aerobic and stepping activity within a critical time period for neurological recovery. Furthermore, walking endurance benefits achieved from a 4-week intervention are retained over the first-year poststroke. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01915368.

Objective To investigate the use of a robotic assessment tool to quantify sensorimotor, visuospatial attention, and executive function impairments in individuals with traumatic brain injury (TBI). Setting Foothills Hospital (Calgary, Canada). Participants Twenty-three subjects with first-time TBI in the subacute to chronic phase participated in this study. Normative data were collected from 275 to 494 neurologically intact control subjects for each robotic task. Design A prospective observational case series. Subjects with TBI completed brief clinical cognitive and motor assessments followed by robotic assessments of upper limb reaching, position sense, bimanual motor ability, attention, and visuospatial skills. Scores of subjects with TBI were compared with normative data. Main measures Robotic task performance was computed for each subject on each task, as well as performance on specific task parameters. Clinical assessments included the Montreal Cognitive Assessment, Fugl-Meyer upper extremity assessment, and Purdue Peg Board. Results Subjects with TBI demonstrated a variety of deficits on robotic tasks. The proportion of TBI subjects who were significantly different from controls ranged from 36% (dominant arm reaching) to 60% (bimanual object hitting task). Conclusion Robotic measures allowed us to quantify a range of impairments specific to each subject, and offer an objective tool with which to examine these abilities after TBI.

Background and Purpose: The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial inter-observer variability impairs outcome assessment and reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health (ICF), we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the mRS and deliver a more thorough understanding of disability following stroke (figure 1). Methods: The construct validity of miFUNCTION was initially established in a pilot study of patients at an outpatient stroke prevention clinic that had been diagnosed with stroke within 60 days. To further assess criterion validity, miFUNCTION was compared against the mRS and other outcome measures within the ESCAPE trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the benefit of endovascular treatment. Results: The pilot study showed moderate inter-observer agreement (k=0.585, p Conclusions: miFUNCTION is strongly associated with the degree of disability following stroke both in an outpatient setting and clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale.

Proprioception is our sense of limb position and movement without vision. Impaired proprioception leads to difficulty performing activities of daily living. While proprioceptive deficits are common after stroke, the neural correlates underlying them are relatively unknown. Recent voxel based lesion analysis evidence suggests that a cluster of regions is implicated in these deficits, including the supramarginal gyrus (SMG) and S1. Using a case series approach, we assessed the impact of different lesion combinations on proprioception, encapsulating SMG with and without S1 and other brain regions in this network. Robotic assessments of proprioception (position matching and kinaesthesia) and MRI/CT scans were acquired for 217 individuals around 1-week post stroke. Across both robotic assessments, performance was compared to a normative model of healthy controls to detect the presence of proprioceptive deficits. Lesions on scans were marked by a trained assessor and then verified by a neurologist. Individuals with lesions to combinations of SMG, S1, insula and operculum were extracted. The extent of damage to each region was determined using the Automated Anatomical Labelling and Catani atlases. A total of 62 subjects with lesion combinations of interest were identified and analysed in more detail (13 SMG lesions). The extent of SMG damage was small, ranging from 0.03% to 25.95%. Position sense deficits were common for both right (6/6) and left SMG (6/7) lesions. Even in the absence of S1 lesions, these deficits remained prevalent. Deficits in kinaesthesia were more common in individuals with combined SMG and S1 lesions than in those without concurrent S1 lesions. Deficits in both proprioceptive assessments were uncommon in those with left S1 lesions in the absence of SMG lesions. Those with right S1 lesions displayed greater deficits than those with left S1 lesions. Results indicate that brain areas beyond S1 must be considered to better understand proprioceptive deficits and develop better strategies for improving proprioceptive function after stroke. The contributory influence of each area should be further explored in isolation.

Background Understanding how the size of acute lesions and white matter hyperintensities ( WMH ) impact stroke recovery can improve our ability to predict outcomes and tailor treatments. The aim of this exploratory study was to investigate the role of acute lesion volume and WMH volume on longitudinal recovery of specific sensory, motor, and cognitive impairments after stroke using robotic and clinical measures. Methods and Results Eighty‐two individuals were assessed at 1, 6, 12, and 26 weeks poststroke with robotic tasks and commonly used clinical measures. The volumes of acute lesions and WMH were measured on fluid‐attenuated inversion recovery images. Linear mixed models were used to investigate the role of acute lesions and WMH on parameters derived from the robotic tasks and clinical measures. Regression analysis determined the added value of acute lesion and WMH volumes along with measures of initial performance to predict outcomes at 6 months. Acute lesion volume has widespread effects on sensory, motor, and overall functional recovery poststroke. The impact of WMH was specific to cognitive impairments. Apart from the robotic position sense task, neither lesion volume nor WMH measure had significant ability to predict outcomes at 6 months over using initial impairment as measured by robotic assessments alone. Conclusions While acute lesion volume and WMH may impact different impairments poststroke, their clinical utility in predicting outcomes at 6 months poststroke is limited.

Background and Purpose— Developing a better understanding of the trajectory and timing of stroke recovery is critical for developing patient-centered rehabilitation approaches. Here, we quantified proprioceptive and motor deficits using robotic technology during the first 6 months post stroke to characterize timing and patterns in recovery. We also make comparisons of robotic assessments to traditional clinical measures. Methods— One hundred sixteen subjects with unilateral stroke were studied at 4 time points: 1, 6, 12, and 26 weeks post stroke. Subjects performed robotic assessments of proprioceptive (position sense and kinesthesia) and motor function (unilateral reaching task and bimanual object hit task), as well as several clinical measures (Functional Independence Measure, Purdue Pegboard, and Chedoke-McMaster Stroke Assessment). Results— One week post stroke, many subjects displayed proprioceptive (48% position sense and 68% kinesthesia) and motor impairments (80% unilateral reaching and 85% bilateral movement). Interindividual recovery on robotic measures was highly variable. However, we characterized recovery as early (normal by 6 weeks post stroke), late (normal by 26 weeks post stroke), or incomplete (impaired at 26 weeks post stroke). Proprioceptive and motor recovery often followed different timelines. Across all time points, robotic measures were correlated with clinical measures. Conclusions— These results highlight the need for more sensitive, targeted identification of sensory and motor deficits to optimize rehabilitation after stroke. Furthermore, the trajectory of recovery for some individuals with mild to moderate stroke may be much longer than previously considered.

Robotic technology is commonly used to quantify aspects of typical sensorimotor function. We evaluated the feasibility of using robotic technology to assess visuomotor and position sense impairments following traumatic brain injury (TBI). We present results of robotic sensorimotor function testing in 12 subjects with TBI, who had a range of initial severities (9 severe, 2 moderate, 1 mild), and contrast these results with those of clinical tests. We also compared these with robotic test outcomes in persons without disability.For each subject with TBI, a review of the initial injury and neuroradiologic findings was conducted. Following this, each subject completed a number of standardized clinical measures (Fugl-Meyer Assessment, Purdue Peg Board, Montreal Cognitive Assessment, Rancho Los Amigos Scale), followed by two robotic tasks. A visually guided reaching task was performed to assess visuomotor control of the upper limb. An arm position-matching task was used to assess position sense. Robotic task performance in the subjects with TBI was compared with findings in a cohort of 170 person without disabilities.Subjects with TBI demonstrated a broad range of sensory and motor deficits on robotic testing. Notably, several subjects with TBI displayed significant deficits in one or both of the robotic tasks, despite normal scores on traditional clinical motor and cognitive assessment measures.The findings demonstrate the potential of robotic assessments for identifying deficits in visuomotor control and position sense following TBI. Improved identification of neurologic impairments following TBI may ultimately enhance rehabilitation.

Objective: Perinatal stroke causes most hemiplegic cerebral palsy. Sensory dysfunction has been ignored and objective measurement tools are limited. Robotic technology can quantify complex sensory function in adult stroke but has not been applied to kids. Methods: Children from the Alberta Perinatal Stroke Project had MR confirmed unilateral perinatal stroke and upper extremity functional deficit. A bilateral exoskeletal robot (KINARM) capable of testing planar upper limb movements in an augmented reality environment was employed. Primary robotic outcomes were 2 dimensional variability, shift, and contraction/expansion scores of a position-matching task (Figure). Blinded clinical measures of sensory function (touch, proprioception, graphesthesia, stereognosis) were scored. Matched controls (age/gender) were tested. Results: Five children (median 14 yrs, 3 male) with perinatal stroke (3 PVI, 2 arterial) were compared to 7 controls. Stroke children demonstrated marked impairment in position matching including variability (6.48±1.4 vs 3.89±0.7cm, p= 0.001) and shift (5.05±2.2 vs 2.00±1.3cm). Contraction/expansion ratios were also abnormal (0.56±0.27 vs 0.31±0.22; p=0.09). Clinical sensory scores were lower but correlated poorly with robotic measures and motor function. Assessments were well tolerated with no adverse events. Conclusion: Robotic quantification of proprioception is feasible in perinatal stroke. Sensitivity and quantification appear superior to clinical exam. Disordered proprioception is an under-recognized component of disability and a novel therapeutic target.

Stroke can lead to damage of brain regions and pathways involved in sensory processing of limb afferent and visual signals. While stroke rehabilitation research often focuses on motor recovery, there is limited knowledge about the prevalence of proprioceptive deficits and their impact on sensorimotor capabilities. The present study characterizes the presence of kinaesthetic (sense of motion) deficits and the ability of individuals to correct for these deficits with vision after stroke. Individuals with subacute stroke (N = 107, median age = 59) and non-disabled controls (N = 101, median age = 47.5) performed a kinaesthetic matching task with and without vision using a robotic exoskeleton. The robotic exoskeleton passively moved the stroke patients’ affected arm at a preset speed, direction and magnitude of movement. Subjects were instructed to mirror-match the speed, direction and magnitude of the movement as soon as they felt the robot begin to move their affected arm. Stroke subjects also completed a standardized clinical assessment including vision screening, Behavioural Inattention Test (median ± SD = 141 ± 29.71), Chedoke McMaster Stroke Assessment - Impairment Inventory of Arm (5 ± 2.61) and Hand (5 ± 2.49) and Functional Independence Measure (FIM) (95.21 ± 23.54). As compared to controls, 49% of subjects with stroke displayed larger initial direction errors when performing the task without vision. When vision was provided 25% of these subjects now performed within the control range. Surprisingly, 24% of subjects performed worse with vision. A similar pattern of impairments were observed for movement reaction time. As a group, subjects with field defects and/or hemineglect displayed significantly greater impairments than the rest of the subjects with stroke. Our results suggest that kinaesthetic deficits are highly prevalent amongst patients who have had a stroke. The quantification and identification of these sensory deficits using the robotic technology has significant potential for improving diagnosis and prognosis of sensory and motor deficits and performance in daily activities.