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Objective:To examine temporal trends and geographic variations and predict inpatient rehabilitation (IPR) length of stay (LOS) and home discharge for stroke patients.Methods:Patients aged ≥18 years who were admitted to an IPR facility in Alberta, Canada, between 04/2014 and 03/2018 (years 2014–2017) were included. Predictors of LOS and home discharge were examined using 2014–2016 data and validated using 2017 data. Multivariable linear regression (MLR), multivariable negative binomial (MNB), and multivariable quantile regressions (MQR) were used to examine LOS, and logistic regression was used for home discharge.Results:We included 2686 rehabilitation admissions between 2014 and 2017. The mean LOS decreased (2014: 71 days; 2017: 62.1 days; p = 0.003) during the study period and was shortest in Edmonton (59.1 days) compared to Calgary (66 days) or other localities (70.8 days; p < 0.001). Three-quarters of patients were discharged home and this proportion remained unchanged between 2014 and 2017. Calgary patients were more likely to be discharged home than those in Edmonton (OR = 0.62; p = 0.019) or other localities (OR = 0.39; p = 0.011). The MLR and MNB models provided accurate prediction for the mean LOS (predicted = 59.9 and 60.8 days, respectively, vs. actual = 62.1 days; both p > 0.5), while the MQR model did so for the median LOS (predicted = 44.3 days vs. actual = 44 days; p = 0.09). The logistic regression resulted in 82.4% of correct prediction, a sensitivity of 91.6%, and a specificity of 50.7% for home discharge.Conclusions:Rehabilitation LOS decreased while the proportion of home discharge remained unchanged during the study period. Both varied across health zones. Identifiable statistical models provided accurate prediction with a separate patient cohort.

Background Analysis of fluid metabolites has the potential to provide insight into the neuropathophysiology of injury in patients with traumatic brain injury (TBI). Objective Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined (1) if urinary metabolites change during recovery in patients with mild to severe TBI; (2) whether changes in urinary metabolites correlate to injury severity; (3) whether biological pathway analysis reflects mechanisms that mediate neural damage/repair throughout TBI recovery. Methods Urine samples were collected within 7 days and at 6-months post-injury in male participants (n = 8) with mild-severe TBI. Samples were analyzed with NMR-based quantitative spectroscopy for metabolomic profiles and analyzed with multivariate statistical and machine learning-based analyses. Results Lower levels of homovanillate (R = −0.74, p ≤ 0.001), L-methionine (R = −0.78, p, Highlights • NMR-based metabolomics of urine can identify metabolic fingerprints associated with functional recovery following TBI. • Metabolic profiles in urine correlate to injury severity. • Biological pathway analysis reflects mechanisms that mediate neural damage and repair processes throughout recovery. • Metabolomics provides insight into the neuropathophysiology of injury in TBI patients.

Perinatal ischemic stroke results in focal brain injury and life-long disability. Hemiplegic cerebral palsy and additional sequelae are common. With no prevention strategies, improving outcomes depends on understanding brain development. Reactive astrogliosis is a hallmark of brain injury that has been associated with outcomes but is unstudied in perinatal stroke. In this article, we hypothesized that gliosis was quantifiable and its extent would inversely correlate with clinical motor function. This was a population-based, retrospective, and cross-sectional study. Children with perinatal arterial ischemic stroke (AIS) or periventricular venous infarction (PVI) with magnetic resonance (MR) imaging were included. An image thresholding technique based on image intensity was utilized to quantify the degree of chronic gliosis on T2-weighted sequences. Gliosis scores were corrected for infarct volume and compared with the Assisting Hand and Melbourne Assessments (AHA and MA), neuropsychological profiles, and robotic measures. In total, 42 children were included: 25 with AIS and 17 with PVI (median = 14.0 years, range: 6.3–19 years, 63% males). Gliosis was quantifiable in all scans and scores were highly reliable. Gliosis scores as percentage of brain volume ranged from 0.3 to 3.2% and were comparable between stroke types. Higher gliosis scores were associated with better motor function for all three outcomes in the AIS group, but no association was observed for PVI. Gliosis can be objectively quantified in children with perinatal stroke. Associations with motor outcome in arterial but not venous strokes suggest differing glial responses may play a role in tissue remodeling and developmental plasticity following early focal brain injury.

Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to aid with prognosticating outcomes following SCI. Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolomics approach of urine samples, the objectives were to determine (a) if alterations in metabolic profiles reflect the extent of recovery of individual SCI patients, (b) whether changes in urine metabolites correlate to patient outcomes, and (c) whether biological pathway analysis reflects mechanisms of neural damage and repair. An inception cohort exploratory pilot study collected morning urine samples from male SCI patients (n=6) following injury and again at 6-months post-injury. A 700 MHz Bruker Avance III HD NMR spectrometer was used to acquire the metabolic signatures of urine samples, which were used to derive metabolic pathways. Multivariate statistical analyses were used to identify changes in metabolic signatures, which were correlated to clinical outcomes in the Spinal Cord Independence Measure (SCIM). Among SCI-induced metabolic changes, biomarkers which significantly correlated to patient SCIM scores included caffeine (R = -0.76, p, Highlights • 1H nuclear magnetic resonance (NMR) spectroscopy identified robust urine biomarkers in patients with spinal cord injury (SCI). • Quantitative NMR-based metabolomics identified metabolic profiles linked to the extent of recovery among SCI patients. • Changes in urine metabolites correlated with patient functional outcomes. • Metabolomic biomarker analysis addresses the need for reliable prognostic biomarkers of spinal cord injury.

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival1–3, impairs neurological recovery4,5, increases the risk of cardiovascular disease6,7, and reduces quality of life8,9. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord10, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury11, and restored walking after paralysis12. Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This ‘neuroprosthetic baroreflex’ controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI. An epidural spinal cord stimulation system regulates blood pressure in the acute and chronic phases of spinal cord injury.

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.

Background. Understanding potential sex differences in stroke recovery is important for prognosis, ensuring appropriate allocation of health care resources, and for stratification in research studies. Previously, functional measures have shown poorer outcomes for females, however, little is known about sex differences that may exist in specific motor and sensory impairments. Objective. The aim of this study was to utilize robotic assessments of motor and sensory impairments to determine if there are sex differences at the impairment level in stroke recovery over the first 6 months poststroke. Methods. We used robotic and clinical assessments of motor and sensory impairments at 1, 6, 12, and 26 weeks poststroke in 108 males and 52 females. Linear mixed models were used to examine the effect of sex on recovery poststroke, controlling for age and lesion volume. Results. In general, we did not find significant sex differences across a range of assessments. The exception to this was a sex × age interaction for the Purdue Pegboard Assessment, where we found that females had better performance than males at younger ages (

Background While motor deficits are the hallmark of hemiparetic cerebral palsy, children may also experience impairments in visuospatial attention that interfere with participation in complex activities, including sports or driving. In this study, we used a robotic object hitting task to assess bilateral sensorimotor control and visuospatial skills in children with hemiparesis due to perinatal arterial ischemic stroke (AIS) or periventricular venous infarct (PVI). We hypothesized that performance would be impaired bilaterally and be related to motor behavior and clinical assessment of visuospatial attention. Methods Forty-nine children with perinatal stroke and hemiparetic cerebral palsy and 155 typically developing (TD) children participated in the study. Participants performed a bilateral object hitting task using the KINARM Exoskeleton Robot, in which they used virtual paddles at their fingertips to hit balls that fell from the top of the screen with increasing speed and frequency over 2.3 min. We quantified performance across 13 parameters including number of balls hit with each hand, movement speed and area, biases between hands, and spatial biases. We determined normative ranges of performance accounting for age by fitting 95% prediction bands to the TD children. We compared parameters between TD, AIS, and PVI groups using ANCOVAs accounting for age effects. Lastly, we performed regression analysis between robotic and clinical measures. Results The majority of children with perinatal stroke hit fewer balls with their affected arm compared to their typically developing peers. We also found deficits with the ipsilesional (“unaffected”) arm. Children with AIS had greater impairments than PVI. Despite hitting fewer balls, we only identified 18% of children as impaired in hand speed or movement area. Performance on the Behavioral Inattention Test accounted for 21–32% of the variance in number of balls hit with the unaffected hand. Conclusions Children with perinatal stroke-induced hemiparetic cerebral palsy may have complex bilateral deficits reflecting a combination of impairments in motor skill and visuospatial attention. Clinical assessments and interventions should address the interplay between motor and visuospatial skills.

Objective: Millions of sport-related concussions (SRC) occur annually in North America, and current diagnosis of concussion is based largely on clinical evaluations. The objective of this study was to determine whether urinary metabolites are significantly altered post-SRC compared to pre-injury.Setting: Outpatient sports medicine clinic.Participants: Twenty-six male youth sport participants.Methods: Urine was analyzed pre-injury and after SRC by 1H NMR spectroscopy. Data were analyzed using multivariate statistics, pairwise t-test, and metabolic pathway analysis. Variable importance analysis based on random variable combination (VIAVC) was applied to the entire data set and resulted in a panel of 18 features. Partial least square discriminant analysis was performed exploring the separation between pre-injury and post-SRC groups. Pathway topography analysis was completed to identify biological pathway involvement. Spearman correlations provide support for the relationships between symptom burden and length of return to play and quantifiable metabolic changes in the human urinary metabolome.Results: Phenylalanine and 3-indoxysulfate were upregulated, while citrate, propylene glycol, 1-methylhistidine, 3-methylhistidine, anserine, and carnosine were downregulated following SRC. A receiver operator curve (ROC) tool constructed using the 18-feature classifier had an area under the curve (AUC) of 0.887. A pairwise t-test found an additional 19 altered features, 7 of which overlapped with the VIAVC analysis. Pathway topology analysis indicated that aminoacyl-tRNA biosynthesis and beta-alanine metabolism were the two pathways most significantly changed. There was a significant positive correlation between post-SRC 2-hydroxybutyrate and the length of return to play (ρ = 0.482, p = 0.02) as well as the number of symptoms and post-SRC lactose (ρ = 0.422, p = 0.036).Conclusion: We found that 1H NMR metabolomic urinary analysis can identify a set of metabolites that can correctly classify SRC with an accuracy of 81.6%, suggesting potential for a more objective method of characterizing SRC. Correlations to both the number of symptoms and length of return to play indicated that 2-hydroxybutyrate and lactose may have potential applications as biomarkers for sport-related concussion.

Evidence supports establishing a continuum of care from stroke rehabilitation (SR) to cardiac rehabilitation programs (CRPs). It is not known to what extent people poststroke are being integrated. This study aimed to determine the proportion of CRPs that accept referrals poststroke, barriers/facilitators, and eligibility criteria.A web-based questionnaire was sent to CRPs across Canada.Of 160 questionnaires sent, 114 representatives (71%) of 130 CRPs responded. Of respondents, 65% (n = 74) reported accepting people with a diagnosis of stroke and doing so for a median of 11 years, 11 offering stroke-specific classes and an additional 6 planning inclusion. However, 62.5% of CRPs reported that11 patients participated in the last calendar year despite 88.5% reporting no limit to the number they could enroll. Among CRPs, 25% accepted only patients with concurrent cardiac diagnoses, living in the community (47.8%), and without severe mobility (70.1%), communication (80.6%), or cognitive (85.1%) deficits. The 2 most influential barriers and facilitators among all CRPs were funding and staffing. The fourth greatest barrier was lack of poststroke referrals, and third to sixth facilitators were SR/CRP collaboration to ensure appropriate referrals (third) and to increase referrals (sixth), toolkits for prescribing resistance (fourth), and aerobic training (fifth). CRP characteristics associated with accepting stroke were a hybrid program model, a medium program size, and having a falls prevention component.Most CRPs accept patients poststroke, but few participate. Therefore, establishing SR/CRP partnerships to increase appropriate referrals, using a toolkit to help operationalize exercise components, and allocating funding/resources to CRPs may significantly increase access to secondary prevention strategies.Les données recueillies appuient la continuité des soins entre les programmes de réadaptation après un accident vasculaire cérébral (PR-AVC) et les programmes de réadaptation cardiaque (PRC). On ne sait toutefois pas dans quelle mesure les patients qui ont subi un accident vasculaire cérébral (AVC) sont intégrés à un PRC. L’étude visait donc à déterminer la proportion de PRC admettant les patients ayant subi un AVC, les obstacles à l’intégration de ces derniers et les éléments qui la facilitent, ainsi que les critères d’admissibilité.Des responsables de PRC de partout au Canada ont été invités à répondre à un questionnaire en ligne.Au total, 160 invitations ont été envoyées et 114 (71 %) responsables rattachés à 130 PRC y ont répondu. Parmi ces répondants, 65 % (n = 74) ont dit que leur programme admettait depuis un nombre médian de 11 ans les patients ayant reçu un diagnostic d’AVC; 11 programmes offraient des cours spécialement destinés aux patients ayant subi un AVC et 6 autres prévoyaient de le faire. Toutefois, 62,5 % des répondants ont souligné que moins de 11 patients avaient participé à leur programme au cours de l’année qui précédait, malgré le fait que dans 88,5 % des cas, il n’y avait pas de limite au nombre de participants admis. Parmi les PRC, 25 % n’admettaient que des patients ayant aussi reçu un diagnostic d’atteinte cardiaque, vivant dans la collectivité (47,8 %) et n’ayant pas de déficit sévère sur les plans de la mobilité (70,1 %), de la communication (80,6 %) ou de la fonction cognitive (85,1 %). Dans tous les cas, les deux facteurs influant le plus (positivement ou négativement, selon le cas) sur l’intégration des patients ayant subi un AVC étaient les ressources financières et les ressources humaines. Le quatrième obstacle en importance était le faible nombre de patients ayant subi un AVC orientés vers les programmes; les autres éléments facilitateurs également recensés étaient la collaboration entre les PR-AVC et les PRC afin d’assurer l’orientation des patients concernés (3Si la plupart des PRC admettent les patients qui ont subi un AVC, ces derniers sont peu nombreux à y participer. L’établissement de partenariats entre les PR-AVC et les PRC afin d’augmenter le nombre de patients orientés, la mise en place d’outils facilitant l’exécution de programmes d’exercice physique et l’affectation de fonds et de ressources aux PRC pourraient donc augmenter considérablement l’accès aux stratégies de prévention secondaire.

Persistent post-traumatic headache (PTH) after mild traumatic brain injury is one of the most prominent and highly reported persistent post-concussion symptoms (PPCS). Non-pharmacological treatments, including non-invasive neurostimulation technologies, have been proposed for use. Our objective was to evaluate headache characteristics at 1 month after repetitive transcranial magnetic stimulation (rTMS) treatment in participants with PTH and PPCS. A double-blind, randomized, sham-controlled, pilot clinical trial was performed on 20 participants (18-65 years) with persistent PTH (International Classification of Headache Disorders, 3rd edition) and PPCS (International Classification of Diseases, Tenth Revision). Ten sessions of rTMS therapy (10 Hz, 600 pulses, 70% resting motor threshold amplitude) were delivered to the left dorsolateral pre-frontal cortex. The primary outcome was a change in headache frequency or severity at 1 month post-rTMS. Two-week-long daily headache diaries and clinical questionnaires assessing function, PPCS, cognition, quality of life, and mood were completed at baseline, post-treatment, and at 1, 3, and 6 months post-rTMS. A two-way (treatment × time) mixed analyisis of variance indicated a significant overall time effect for average headache severity (

We examined the impact of stroke severity and timing to inpatient rehabilitation admission on length of stay (LOS), functional gains, and discharge destination.Alberta inpatient stroke rehabilitation data between April 2013 and March 2017 were analyzed. We evaluated the impact of stroke severity, as measured by the Functional Independence Measure (FIM), on timing to inpatient rehabilitation, functional gains, LOS, and discharge destination. Further, we examined whether timing to inpatient rehabilitation impacted the latter three factors.The 2404 adults were subcategorized as mild (1237), moderate (1031), or severe (136) based on FIM at inpatient rehabilitation admission. Length of time to rehabilitation admission was not significantly (p = 0.232) different between stroke severities. Mean length of time (days) to rehabilitation admission was 19.79 (20.3 SD) for mild, 27.7 (35.7 SD) for moderate, and 37.70 (56.8 SD) for severe stroke. Mean FIM change for mild (M = 16.3, 9.9 SD) differed significantly (p = 5.1 × 10-9) from moderate (M = 30.4, 16.4 SD) and severe (M = 31.0, 25.7 SD) stroke. The mean LOS for mild stroke (M = 41.3, 31.9 SD) was significantly (p = 5.1 × 10-9) different from moderate stroke (M = 86.8, 76.4 SD) and severe stroke (M = 126.1, 104.2 SD). Time to inpatient rehabilitation admission showed a small, significant impact on FIM change (p = 1.4 × 10-9, partial η2 0.022) and LOS (p = 1.1 × 10-19, partial η2 0.042). Shorter times to rehabilitation admission and mild stroke were associated with discharging home without needing homecare.Stroke severity has a significant impact on the conduct of inpatient rehabilitation. Yet, despite suggestions shortening timing to rehabilitation should improve outcomes, the impact on functional gains and rehabilitation LOS was small.Les soins de réadaptation prodigués à des patients albertains hospitalisés: quelle est l’importance de la gravité des AVC et des délais d’admission en matière de réadaptation? Contexte: Nous nous sommes penchés sur l’impact que la gravité des AVC et les délais d’admission à des soins de réadaptation peuvent avoir sur la durée de séjour de patients hospitalisés, sur leurs gains fonctionnels et sur leur lieu de destination à la suite de leur congé. Méthodes: Nous avons analysé les données portant sur la réadaptation de patients albertains hospitalisés à la suite d’un AVC. Ces données couvraient la période allant d’avril 2013 à mars 2017. À l’aide de la mesure de l’indépendance fonctionnelle (MIF), nous avons ainsi évalué l’impact de la gravité des AVC sur les délais d’admission de patients hospitalisés à des soins de réadaptation, sur leurs gains fonctionnels, sur la durée de leur séjour et sur leur lieu de destination à la suite de leur congé. De plus, nous avons examiné dans quelle mesure les délais d’admission à des soins de réadaptation avaient un impact sur ces trois dernières variables. Résultats: Au total, 2 404 adultes ont été répartis en trois catégories en fonction de leur résultat à la MIF: AVC légers (1237), modérés (1031) ou graves (136). Mentionnons que les délais avant d’être admis à des soins de réadaptation ne se sont pas révélés notablement différents (p = 0,232) selon les niveaux de gravité des AVC. Les délais moyens (en jours) avant d’être admis à des soins de réadaptation ont été de 19,79 (σ 20,3) pour les AVC légers; de 27,7 (σ 35,7) pour les AVC modérés; et de 37,70 (σ 56,8) pour les AVC graves. En se basant sur la MIF, les changements moyens pour les AVC légers (M = 16,3; σ 9,9) ont différé de façon notable (p = 5,1 x 10-9) par rapport à ceux des AVC modérés (M = 30,4; σ 16,4) et des AVC graves (M = 31,0; σ 25,7). La durée moyenne de séjour dans le cas des AVC légers (M = 41,3; σ 31,9) s’est par ailleurs révélée significativement (p = 5,1 x 10-9) différente si on la compare aux autres catégories (AVC modérés M = 86,8; σ 76,4 ou AVC graves M = 126,1; σ 104,2). Les délais d’admission à des soins de réadaptation ont donné à voir un faible, quoique notable, impact sur les changements révélés par la MIF (p = 1,4 x 10-9, eta-carré partiel 0,022) et sur la durée des séjours (p = 1,1 x 10-19, eta-carré partiel 0,042). Enfin, des délais d’admission plus courts à des soins de réadaptation et des AVC légers ont été associés, à la suite d’un congé, à un retour à la maison sans devoir recourir à des soins à domicile. Conclusion: La gravité des AVC a un impact considérable sur la réadaptation de patients ayant été hospitalisés. Bien qu’il ait été suggéré que la réduction des délais d’admission à des soins de réadaptation devrait améliorer l’évolution de leur état de santé, l’impact quant à leurs gains fonctionnels et leur durée de séjour en réadaptation a toutefois été mineur.

Deficits in proprioception, the ability to discriminate the relative position and movement of our limbs, affect ~50% of stroke patients and reduce functional outcomes. Our lack of knowledge of the anatomical correlates of proprioceptive processing limits our understanding of the impact that such deficits have on recovery. This research investigated the relationship between functional impairment in brain activity and proprioception post-stroke. We developed a novel device and task for arm position matching during functional MRI (fMRI), and investigated 16 subjects with recent stroke and nine healthy age-matched controls. The stroke-affected arm was moved by an experimenter (passive arm), and subjects were required to match the position of this limb with the opposite arm (active arm). Brain activity during passive and active arm movements was determined, as well as activity in association with performance error. Passive arm movement in healthy controls was associated with activity in contralateral primary somatosensory (SI) and motor cortices (MI), bilateral parietal cortex, supplementary (SMA) and premotor cortices, secondary somatosensory cortices (SII), and putamen. Active arm matching was associated with activity in contralateral SI, MI, bilateral SMA, premotor cortex, putamen, and ipsilateral cerebellum. In subjects with stroke, similar patterns of activity were observed. However, in stroke subjects, greater proprioceptive error was associated with less activity in ipsilesional supramarginal and superior temporal gyri, and lateral thalamus. During active arm movement, greater proprioceptive error was associated with less activity in bilateral SMA and ipsilesional premotor cortex. Our results enhance our understanding of the correlates of proprioception within the temporal parietal cortex and supplementary/premotor cortices. These findings also offer potential targets for therapeutic intervention to improve proprioception in recovering stroke patients and thus improve functional outcome.

Background: The Montreal Cognitive Assessment (MoCA) is a cognitive screening tool known to accurately measure mild cognitive impairment (MCI) in many different neurological populations. Objective: We aimed to determine whether a sport-related concussion (SRC) history and other concussion modifiers influence global cognitive function in high-performance athletes. Methods: A cross-sectional study of 326 varsity and national team athletes aged 18–36 years was completed at the University of Calgary Sports Medicine Clinic, Calgary, Alberta, Canada. Logistic regression analysis was used to examine the association between the total MoCA score, MoCA subscales, and number of previous SRC, adjusting for age, sex, sport participation (SP), and concussion modifiers. Results: Athletes with a history of three or more SRC were 5.36 times more likely to score less than 26/30 on the MoCA (the cutoff for MCI) compared to athletes with two or less SRC (p = 0.02). Males were 2.23 times more likely to have MCI than females (p = 0.0004). There was a significant relationship between the number of previous concussions and the MoCA subscales of attention (p = 0.05) and abstraction (p = 0.003). Age, SP, and concussion modifiers (migraine, depression, anxiety, and attention deficit and hyperactivity disorder) did not influence the relationship between MoCA and previous concussion history. Conclusion: In the appropriate clinical context, cognitive screening with the MoCA may benefit clinical care in athletes with multiple previous SRC, but should not replace a full neuropsychological assessment. Thus, further research is needed to compare the MoCA to full neuropsychological assessments in this population.

Background and Purpose The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability impairs outcome assessment as well as reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health, we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the modified Rankin Scale and deliver a more thorough understanding of disability following stroke. Methods The initial construct validity of miFUNCTION was 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 modified Rankin Scale and other outcome measures within the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the beneficial effect 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 a clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale.

Proprioception encompasses our sense of position and movement of our limbs, as well as the effort with which we engage in voluntary actions. Historically, sense of effort has been linked to centrally generated signals that elicit voluntary movements. We were interested in determining the effect of differences in limb geometry and personal control on sense of effort. In experiment 1, subjects exerted either extension or flexion torques to resist a torque applied by a robot exoskeleton to their reference elbow. They attempted to match this torque by exerting an equal effort torque (in a congruent direction with the reference arm) with their opposite (matching) arm in different limb positions (±15°). Subjects produced greater matching torque when their matching arm exerted effort toward the mirrored position of the reference (e.g., reference/matching arms at 90°/105° elbow flexion) vs. away (e.g., 90°/75° flexion). In experiment 2, a larger angular difference between arms (30°) resulted in a larger discrepancy in matched torques. Furthermore, in both experiments 1 and 2, subjects tended to overestimate the reference arm torque. This motivated a third experiment to determine whether providing more personal control might influence perceived effort and reduce the overestimation of the reference torques that we observed ( experiments 3a and 3b). Overestimation of the matched torques decreased significantly when subjects self-selected the reference torque that they were matching. Collectively, our data suggest that perceived effort between arms can be influenced by signals relating to the relative geometry of the limbs and the personal control of motor output during action. NEW & NOTEWORTHY This work highlights how limb geometry influences our sense of effort during voluntary motor actions. It also suggests that loss of personal control during motor actions leads to an increase in perceived effort.

BackgroundKinarm Standard Tests (KSTs) is a suite of upper limb tasks to assess sensory, motor, and cognitive functions, which produces granular performance data that reflect spatial and temporal aspects of behavior (>100 variables per individual). We have previously used principal component analysis (PCA) to reduce the dimensionality of multivariate data using the Kinarm End-Point Lab (EP). Here, we performed PCA using data from the Kinarm Exoskeleton Lab (EXO), and determined agreement of PCA results across EP and EXO platforms in healthy participants. We additionally examined whether further dimensionality reduction was possible by using PCA across behavioral tasks.MethodsHealthy participants were assessed using the Kinarm EXO (N = 469) and EP (N = 170–200). Four behavioral tasks (six assessments in total) were performed that quantified arm sensory and motor function, including position sense [Arm Position Matching (APM)] and three motor tasks [Visually Guided Reaching (VGR), Object Hit (OH), and Object Hit and Avoid (OHA)]. The number of components to include per task was determined from scree plots and parallel analysis, and rotation type (orthogonal vs. oblique) was decided on a per-task basis. To assess agreement, we compared principal components (PCs) across platforms using distance correlation. We additionally considered inter-task interactions in EXO data by performing PCA across all six behavioral assessments.ResultsBy applying PCA on a per task basis to data collected using the EXO, the number of behavioral parameters were substantially reduced by 58–75% while accounting for 76–87% of the variance. These results compared well to the EP analysis, and we found good-to-excellent agreement values (0.75–0.99) between PCs from the EXO and those from the EP. Finally, we were able to reduce the dimensionality of the EXO data across tasks down to 16 components out of a total of 76 behavioral parameters, which represents a reduction of 79% while accounting for 73% of the total variance.ConclusionPCA of Kinarm robotic assessment appears to capture similar relationships between kinematic features in healthy individuals and is agnostic to the robotic platform used for collection. Further work is needed to investigate the use of PCA-based data reduction for the characterization of neurological deficits in clinical populations.

Background Studies using clinical measures have suggested that proprioceptive dysfunction is related to motor impairment of the upper extremity following adult stroke. We used robotic technology and clinical measures to assess the relationship between position sense and reaching with the hemiparetic upper limb in children with perinatal stroke. Methods Prospective term-born children with magnetic resonance imaging-confirmed perinatal ischemic stroke and upper extremity deficits were recruited from a population-based cohort. Neurotypical controls were recruited from the community. Participants completed two tasks in the Kinarm robot: arm position-matching (three parameters: variability [Varxy], contraction/expansion [Areaxy], systematic spatial shift [Shiftxy]) and visually guided reaching (five parameters: posture speed [PS], reaction time [RT], initial direction error [IDE], speed maxima count [SMC], movement time [MT]). Additional clinical assessments of sensory (thumb localization test) and motor impairment (Assisting Hand Assessment, Chedoke-McMaster Stroke Assessment) were completed and compared to robotic measures. Results Forty-eight children with stroke (26 arterial, 22 venous, mean age: 12.0 ± 4.0 years) and 145 controls (mean age: 12.8 ± 3.9 years) completed both tasks. Position-matching performance in children with stroke did not correlate with performance on the visually guided reaching task. Robotic sensory and motor measures correlated with only some clinical tests. For example, AHA scores correlated with reaction time (R = − 0.61, p Conclusions Robotic technology can quantify complex, discrete aspects of upper limb sensory and motor function in hemiparetic children. Robot-measured deficits in position sense and reaching with the contralesional limb appear to be relatively independent of each other and correlations for both with clinical measures are modest. Knowledge of the relationship between sensory and motor impairment may inform future rehabilitation strategies and improve outcomes for children with hemiparetic cerebral palsy.

Neuroanatomical investigations have associated cortical areas, beyond Primary Somatosensory Cortex (S1), with impaired proprioception. Cortical regions have included temporoparietal (TP) regions (supramarginal gyrus, superior temporal gyrus, Heschl's gyrus) and insula. Previous approaches have struggled to account for concurrent damage across multiple brain regions. Here, we used a targeted lesion analysis approach to examine the impact of specific combinations of cortical and sub-cortical lesions and quantified the prevalence of proprioceptive impairments when different regions are damaged or spared. Seventy-seven individuals with stroke (49 male; 28 female) were identified meeting prespecified lesion criteria based on MRI/CT imaging: 1) TP lesions without S1, 2) TP lesions with S1, 3) isolated S1 lesions, 4) isolated insula lesions, and 5) lesions not impacting these regions (other regions group). Initially, participants meeting these criteria (1–4) were grouped together into right or left lesion groups and compared to each other, and the other regions group (5), on a robotic Arm Position Matching (APM) task and a Kinesthesia (KIN) task. We then examined the behaviour of individuals that met each specific criteria (groups 1–5). Proprioceptive impairments were more prevalent following right hemisphere lesions than left hemisphere lesions. The extent of damage to TP regions correlated with performance on both robotic tasks. Even without concurrent S1 lesions, TP and insular lesions were associated with impairments on the APM and KIN tasks. Finally, lesions not impacting these regions were much less likely to result in impairments. This study highlights the critical importance of TP and insular regions for accurate proprioception. Significance statement This work advances our understanding of the neuroanatomy of human proprioception. We validate the importance of regions, beyond the dorsal column medial lemniscal pathway and S1, for proprioception. Further, we provide additional evidence of the importance of the right hemisphere for human proprioception. Improved knowledge on the neuroanatomy of proprioception is crucial for advancing therapeutic approaches which target individuals with proprioceptive impairments following neurological injury or with neurological disorders.

Much of our understanding of motor control deficits in children with developmental coordination disorder (DCD) comes from upper limb assessments focusing on the dominant limb. Here, using two robotic behavioural tasks, we investigated motor control in both the dominant and non-dominant limbs of children with DCD. Twenty-six children with diagnosed DCD (20 males; mean age 10.6 years ± 1.3 years) and 155 controls were included in this cross-sectional study. Participants completed a visually guided reaching task with their dominant and non-dominant limbs and a bimanual object hitting task. Motor performance was quantified across nine parameters. We determined the number of children with DCD who fell outside of the typical performance range of the controls on these parameters and compared the DCD and control groups using ANCOVAs, accounting for age. Children with DCD demonstrated impairments in six out of nine parameters; deficits were more commonly noted in the non-dominant limb. Interestingly, when looking at individual performance, several children with DCD performed in the range of controls. These findings indicate that children with DCD display deficits in motor control in both the dominant and non-dominant limb and highlight the importance of including detailed assessments of both limbs when investigating children with DCD. They also demonstrate the variability in motor control performance evidenced by children with DCD.

Objective. To develop consensus recommendations for the use of repetitive transcranial magnetic stimulation (rTMS) as an adjunct intervention for upper extremity motor recovery in stroke rehabilitation clinical trials. Participants. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) convened a multidisciplinary team of clinicians and researchers from institutions across Canada to form the CanStim Consensus Expert Working Group. Consensus Process. Four consensus themes were identified: (1) patient population, (2) rehabilitation interventions, (3) outcome measures, and (4) stimulation parameters. Theme leaders conducted comprehensive evidence reviews for each theme, and during a 2-day Consensus Meeting, the Expert Working Group used a weighted dot-voting consensus procedure to achieve consensus on recommendations for the use of rTMS as an adjunct intervention in motor stroke recovery rehabilitation clinical trials. Results. Based on best available evidence, consensus was achieved for recommendations identifying the target poststroke population, rehabilitation intervention, objective and subjective outcomes, and specific rTMS parameters for rehabilitation trials evaluating the efficacy of rTMS as an adjunct therapy for upper extremity motor stroke recovery. Conclusions. The establishment of the CanStim platform and development of these consensus recommendations is a first step toward the translation of noninvasive brain stimulation technologies from the laboratory to clinic to enhance stroke recovery.

Background. Tic disorders may reflect impaired inhibitory control. This has been evaluated using different behavioural tasks, yielding mixed results. Our objective was to test inhibitory control in children with tics through simultaneous presentation of multiple, mobile stimuli. Methods. Sixty-four children with tics (mean age 12.4 years; 7.5-18.5) were evaluated using a validated robotic bimanual exoskeleton protocol (Kinarm) in an object-hit-and-avoid task, in which target and distractor objects moved across a screen and participants aimed to hit only the targets while avoiding distractors. Performance was compared to 146 typically developing controls (mean age 13 years; 6.1-19.9). The primary outcome was the percentage of distractors struck. Results. ANCOVA (age as covariate) showed participants struck significantly more distractors (participants without comorbid ADHD, 22.71% [SE 1.47]; participants with comorbid ADHD, 23.56% [1.47]; and controls, 15.59% [0.68]). Participants with comorbid ADHD struck significantly fewer targets (119.74 [2.77]) than controls, but no difference was found between participants without comorbid ADHD (122.66 [2.77]) and controls (127.00 [1.28]). Participants and controls did not differ significantly in movement speed and movement area. Just over 20% of participants with tics fell below the age-predicted norm in striking distractors, whereas fewer than 10% fell outside age-predicted norms in other task parameters. Conclusions. In children with tics (without comorbid ADHD), acting upon both targets and distractors suggests reduced ability to suppress responses to potential triggers for action. This may be related to increased sensorimotor noise or abnormal sensory gating.

Context Sport-related concussion (SRC) often presents with multidimensional and subtle neurologic deficits that are difficult to detect with standard clinical tests. New assessment approaches that efficiently quantify deficits across multiple neurologic domains are needed. Objective To quantify impairments in postural movements during an assessment of rapid, bimanual motor ability in athletes within 10 days of experiencing an SRC and evaluate relationships between impairments in upper extremity and postural performance. Design Cohort study. Setting Sports medicine clinic. Patients or Other Participants Initial baseline assessments were completed for 711 athletes. Seventy-five athletes (age = 15.8 ± 3.3 years at baseline) sustained SRCs and were reassessed within 10 days. Seventy-eight athletes (age = 15.5 ± 2.0 years) completed 2 assessments in a healthy state. Main Outcome Measure(s) Athletes stood on force plates and performed a rapid, bimanual motor task, termed the object-hit task, delivered using a Kinesiological Instrument for Normal and Altered Reaching Movements endpoint robot. Measures of postural stability that quantified center-of-pressure movements and measures of upper extremity performance were used to characterize task performance. Results Performance changes across assessments were converted to reliable change indices. We observed a difference in reliable change indices values between athletes with SRC and healthy control athletes on the combined postural measures (P = .01). Using measures to evaluate the change in postural movements from the early, easier portion of the task to the later, more difficult portion, we identified the highest levels of impairment (19%–25% of the sample impaired). We also noted a difference between individuals with concussion and healthy individuals on the combined upper extremity measures (P = .003), but these impairments were largely unrelated to those identified in the postural movements. Conclusions Measurement of postural movements during the object-hit task revealed impairments in postural stability that were not related to impairments in upper extremity performance. The findings demonstrated the benefits of using assessments that simultaneously evaluate multiple domains of neurologic function (eg, upper extremity and postural control) after SRC.

Background Robotic rehabilitation after stroke provides the potential to increase and carefully control dosage of therapy. Only a small number of studies, however, have examined robotic therapy in the first few weeks post-stroke. In this study we designed robotic upper extremity therapy tasks for the bilateral Kinarm Exoskeleton Lab and piloted them in individuals with subacute stroke. Pilot testing was focused mainly on the feasibility of implementing these new tasks, although we recorded a number of standardized outcome measures before and after training. Methods Our team developed 9 robotic therapy tasks to incorporate feedback, intensity, challenge, and subject engagement as well as addressing both unimanual and bimanual arm activities. Subacute stroke participants were assigned to a robotic therapy (N = 9) or control group (N = 10) in a matched-group manner. The robotic therapy group completed 1-h of robotic therapy per day for 10 days in addition to standard therapy. The control group participated only in standard of care therapy. Clinical and robotic assessments were completed prior to and following the intervention. Clinical assessments included the Fugl-Meyer Assessment of Upper Extremity (FMA UE), Action Research Arm Test (ARAT) and Functional Independence Measure (FIM). Robotic assessments of upper limb sensorimotor function included a Visually Guided Reaching task and an Arm Position Matching task, among others. Paired sample t-tests were used to compare initial and final robotic therapy scores as well as pre- and post-clinical and robotic assessments. Results Participants with subacute stroke (39.8 days post-stroke) completed the pilot study. Minimal adverse events occurred during the intervention and adding 1 h of robotic therapy was feasible. Clinical and robotic scores did not significantly differ between groups at baseline. Scores on the FMA UE, ARAT, FIM, and Visually Guided Reaching improved significantly in the robotic therapy group following completion of the robotic intervention. However, only FIM and Arm Position Match improved over the same time in the control group. Conclusions The Kinarm therapy tasks have the potential to improve outcomes in subacute stroke. Future studies are necessary to quantify the benefits of this robot-based therapy in a larger cohort. Trial registration: ClinicalTrials.gov, NCT04201613, Registered 17 December 2019—Retrospectively Registered, https://clinicaltrials.gov/ct2/show/NCT04201613.

Background Robotic technologies to measure human behavior are emerging as a new approach to assess brain function. Recently, we developed a robot-based postural Load Task to assess corrective responses to mechanical disturbances to the arm and found impairments in many participants with stroke compared to a healthy cohort (Bourke et al, J NeuroEngineering Rehabil 12: 7, 2015). However, a striking feature was the large range and skewed distribution of healthy performance. This likely reflects the use of different strategies across the healthy control sample, making it difficult to identify impairments. Here, we developed an intuitive “Unload Task”. We hypothesized this task would reduce healthy performance variability and improve the detection of impairment following stroke. Methods Performance on the Load and Unload Task in the KINARM exoskeleton robot was directly compared for healthy control (n = 107) and stroke (n = 31) participants. The goal was to keep a cursor representing the hand inside a virtual target and return “quickly and accurately” if the robot applied (or removed) an unexpected load to the arm (0.5–1.5 Nm). Several kinematic parameters quantified performance. Impairment was defined as performance outside the 95% of controls (corrected for age, sex and handedness). Task Scores were calculated using standardized parameter scores reflecting overall task performance. Results The distribution of healthy control performance was smaller and less skewed for the Unload Task compared to the Load Task. Fewer task outliers (outside 99.9 percentile for controls) were removed from the Unload Task (3.7%) compared to the Load Task (7.4%) when developing normative models of performance. Critically, more participants with stroke failed the Unload Task based on Task Score with their affected arm (68%) compared to the Load Task (23%). More impairments were found at the parameter level for the Unload (median = 52%) compared to Load Task (median = 29%). Conclusions The Unload Task provides an improved approach to assess fast corrective responses of the arm. We found that corrective responses are impaired in persons living with stroke, often equally in both arms. Impairments in generating rapid motor corrections may place individuals at greater risk of falls when they move and interact in the environment.

Background Activities of daily living frequently require children to make rapid decisions and execute desired motor actions while inhibiting unwanted actions. Children with hemiparetic cerebral palsy due to perinatal stroke may have deficits in executive functioning in addition to motor impairments. The objective of this study was to use a robotic object hit and avoid task to assess the ability of children with hemiparetic cerebral palsy to make rapid motor decisions. Methods Forty-five children with hemiparetic cerebral palsy due to perinatal stroke and 146 typically developing children (both groups ages 6–19 years) completed a robotic object hit and avoid task using the Kinarm Exoskeleton. Objects of different shapes fell from the top of the screen with increasing speed and frequency. Children were instructed to hit two specific target shapes with either hand, while avoiding six distractor shapes. The number of targets and distractors hit were compared between children with hemiparetic cerebral palsy and typically developing children, accounting for age effects. We also compared performance to a simpler object hit task where there were no distractors. Results We found that children with hemiparetic cerebral palsy hit a greater proportion of total distractors compared to typically developing children, demonstrating impairments in inhibitory control. Performance for all children improved with age. Children with hemiparetic cerebral palsy hit a greater percentage of targets with each arm on the more complex object hit and avoid task compared to the simpler object hit task, which was not found in typically developing children. Conclusions Children with hemiparetic cerebral palsy due to perinatal stroke demonstrated impairments in rapid motor decision making including inhibitory control, which can impede their ability to perform real-world tasks. Therapies that address both motor performance and executive functions are necessary to maximize function in children with hemiparetic cerebral palsy.

Stroke is the leading cause of neurologic disability not only in adults but perinatal and childhood stroke affect millions of children as well worldwide with deficits that last a lifetime. The rapidly increasing evidence base for how noninvasive neuromodulation may enhance stroke recovery in adults may be applicable to the youngest stroke survivors. In return, how the plasticity of the developing brain contributes to stroke recovery and its modulation may provide equally valuable insight toward mechanisms and opportunities for enhancing recovery in all stroke patients. Despite this synergistic relationship, examinations of stroke recovery and neuromodulation across the life span have rarely been considered. Here, we attempt to amalgamate the worlds of adult, childhood, and perinatal stroke to explore the differences and commonalities between the models and approaches that are driving advances in noninvasive neuromodulation toward better outcomes for stroke patients of all ages.

Rationale A top priority in stroke rehabilitation research is determining the appropriate exercise dose to optimize recovery. Although more intensive rehabilitation very early after stroke may be deleterious to recovery, inpatient rehabilitation, occurring after acute care, may be a more appropriate setting to assess therapeutic dose on neurological recovery. Hypothesis Individuals receiving higher intensity and dose exercise programs will yield greater improvements in walking ability over usual inpatient physical therapy care. Methods and design Seventy-five individuals across seven inpatient rehabilitation sites in Canada will be randomized into one of three treatment programs, each 5 days/week, for four weeks and monitored for exertion (heart rate) and repetitions (step count). Study outcomes The primary outcome measure is the 6 min walk and secondary outcomes include functional independence, cognitive, and quality-of-life measures. Outcome data will be assessed at four time points. Summary This trial will contribute to our knowledge of the therapeutic intensity and dose necessary to maximize functional recovery at a very important stage of rehabilitation and neural recovery poststroke.

Background Stroke is a leading cause of perinatal brain injury with variable outcomes including cerebral palsy and epilepsy. The biological processes that underlie these heterogeneous outcomes are poorly understood. Alterations in developmental myelination are recognized as a major determinant of outcome in preterm brain injury but have not been explored in perinatal stroke. We aimed to characterize myelination in hemiparetic children after arterial perinatal stroke, hypothesizing that ipsilesional myelination would be impaired, the degree of which would correlate with poor outcome. Methods Retrospective, controlled cohort study. Participants were identified through the Alberta Perinatal Stroke Project (APSP), a population-based research cohort (n > 400). Inclusion criteria were: 1) MRI-confirmed, unilateral arterial perinatal stroke, 2) T1-weighted MRI after 6 months of age, 3) absence of other neurological disorders, 4) neurological outcome that included at least one of the following tests - Pediatric Stroke Outcome Measure (PSOM), Assisting Hand Assessment (AHA), Melbourne Assessment (MA), neuropsychological evaluation (NPE), and robotic sensorimotor measurements. FreeSurfer software measured hemispheric asymmetry in myelination intensity (primary outcome). A second method using ImageJ software validated the detection of myelination asymmetry. A repeated measures ANOVA was used to compare perilesional, ipsilesional remote, and contralesional homologous region myelination between stroke cases and typically developing controls. Myelination metrics were compared to clinical outcome measures (t-test, Pearson's correlation). Results Twenty youth with arterial stroke (mean age: 13.4 ± 4.2yo) and 27 typically developing controls (mean age: 12.5 ± 3.7yo) were studied in FreeSurfer. Participants with stroke demonstrated lower myelination in the ipsilesional hemisphere (p, Highlights • Myelination is altered in the lesioned hemisphere after perinatal stroke. • The uninjured, contralesional hemisphere also demonstrates differences in myelination. • Simple software can estimate MRI myelination abnormalities in children with perinatal brain injury.

Proprioceptive deficits are common after stroke and have been associated with poorer recovery. Relatively little is known about the brain regions beyond primary somatosensory cortex that contribute to the percept of proprioception in humans. We examined a large sample (n = 153) of stroke survivors longitudinally to determine which brain regions were associated with persistent post-stroke proprioceptive deficits. A robotic exoskeleton quantified two components of proprioception, position sense and kinesthesia (movement sense), at 2 weeks and again at 6 months post-stroke. A statistical region of interest (sROI) analysis compared the lesion-behaviour relationships of those subjects with cortical and subcortical stroke (n = 136). The impact of damage to brainstem and cerebellum (n = 17) was examined separately. Results indicate that damage to the supramarginal gyrus, the arcuate fasciculus, and Heschl's gyrus are associated with deficits in position sense and kinesthesia at 6 months post-stroke. These results suggest that regions beyond the primary somatosensory cortex contribute to our sense of limb position and movement. This information extends our understanding of proprioceptive processing and may inform personalized interventions such as non-invasive brain stimulation where specific brain regions can be targeted to potentially improve stroke recovery., Highlights • Proprioception is a persistent problem 6 months post-stroke. • Brain regions associated with poor proprioception extend beyond the primary somatosensory cortex. • Damage to the supramarginal gyrus, the arcuate fasciculus, and Heschl's gyrus are associated with deficits in proprioception at 6 months post-stroke.

Robotic technologies can provide objective, reliable tools for assessing a broad range of sensory, motor and cognitive functions. However, as additional tasks are developed on these platforms, the time necessary to assess a patient increases. In this paper, we present a hierarchical task selection strategy for five tasks that form part of the battery of standard tests performed on the KINARM robotic system. The strategy is built using dependencies derived through three types of analyses: 1) non-linear hierarchical ordering theory is applied to determine the ordering of five tasks; 2) the parameters of all tasks are also ranked using non-linear hierarchical ordering theory; and 3) a modeling technique, fast orthogonal search, is applied to assess the predictive power of each robotic task for the estimation of other task parameters. The inferred hierarchical task selection strategy can lead to a reduction of up to 91% of the time required to assess a patient.

Objective: The primary goal of this study was to investigate the feasibility of utilizing intermittent electrical stimulation (IES) in an intensive care environment as a potential method for preventing pressure ulcers. Furthermore, we wished to evaluate the practicality of the innovation and end-user acceptability. Approach: Twenty immobile subjects, age ranging from 19 to 86 years old with a Braden Scale score ranging from 9 to 16 (very high to moderate risk of developing pressure ulcers), were enrolled. Intermittent 35 Hz electrical stimulation was administered through surface electrodes to the gluteal muscles causing them to contract for 10 s every 10 min. Subjects utilized IES on a program that increased from 4 to 24 h per day over 8 days and lasted up to a maximum of 4 weeks. Results: Bedside nurses reported that IES was simple to use, took an average of 6 min to apply, and 2 min to remove. Furthermore, IES could be easily incorporated into routine patient care. No pressure ulcers occurred in any sub...

BackgroundPersistent post-concussive symptoms (PPCS) affect up to 30% of individuals following mild traumatic brain injury. PPCS frequently includes exercise intolerance. Sub-symptom threshold aerobic exercise has been proposed as a treatment option for symptom burden and exercise intolerance in this population. The primary aim of this study is to evaluate whether a progressive, sub-symptom threshold aerobic exercise program can alleviate symptom burden in adults with PPCS.MethodsFifty-six adults (18–65) with PPCS (>3mos-5 yrs) will be randomized into two groups: an immediate start 12-week aerobic exercise protocol (AEP) or delayed start 6-week placebo-like stretching protocol (SP), followed by AEP. Aerobic or stretching activities will be completed 5x/week for 30 mins during the intervention. Online daily activity logs will be submitted. Exercise prescriptions for the AEP will be 70–80% of heart rate at the point of symptom exacerbation achieved on a treadmill test with heart rate monitoring. Exercise prescription will be updated every 3-weeks with a repeat treadmill test. The Rivermead Post-concussion Symptom Questionnaire will be the primary outcome measure at 6 and 12-weeks of intervention. Secondary outcomes include assessments of specific symptoms (headache, quality of life, mood, anxiety, fatigue, dizziness, sleep parameters, daytime sleepiness) in addition to blood biomarkers and magnetic resonance imaging and spectroscopy data for quantification of brain metabolites including γ-aminobutyric acid (GABA), glutathione, glutamate and N-acetyl aspartate (NAA) all measured at 6 and 12-weeks of intervention.DiscussionThis trial will evaluate the use of aerobic exercise as an intervention for adults with PPCS, thus expanding our knowledge of this treatment option previously studied predominantly for adolescent sport-related concussion.Trial registrationClinicalTrials.gov -NCT03895450(registered 2019-Feb-11).

BackgroundNumerous studies have found associations when change scores are regressed onto initial impairments in people with stroke (slopes ≈ 0.7). However, there are important statistical considerations that limit the conclusions we can draw about recovery from these studies.ObjectiveTo provide an accessible “check-list” of conceptual and analytical issues on longitudinal measures of stroke recovery. Proportional recovery is an illustrative example, but these considerations apply broadly to studies of change over time.MethodsUsing a pooled dataset of N = 373 Fugl-Meyer Assessment (FMA) upper extremity scores, we ran simulations to illustrate three considerations: (1) how change scores can be problematic in this context; (2) how “nil” and non-zero null-hypothesis significance tests can be used; and (3) how scale boundaries can create the illusion of proportionality, while other analytical procedures (e.g., post-hoc classifications) can augment this problem.ResultsOur simulations highlight several limitations of common methods for analyzing recovery over time. Critically, we find that uniform recovery (in the population) leads to similar group-level statistics (regression slopes) and individual-level classifications (into fitters and non-fitters) that have been claimed as evidence for the proportional recovery rule.ConclusionsOur results highlight that one cannot identify whether proportional recovery is true or not based on commonly used methods. We illustrate how these techniques (regressing change scores onto baseline values), measurement tools (bounded scales), and post-hoc classifications (e.g., “non-fitters”) can create spurious results. Going forward the field needs to carefully consider the influence of these factors on how we measure, analyze, and conceptualize recovery.

Background Motor impairment after stroke interferes with performance of everyday activities. Upper limb spasticity may further disrupt the movement patterns that enable optimal function; however, the specific features of these altered movement patterns, which differentiate individuals with and without spasticity, have not been fully identified. This study aimed to characterize the kinematic and proprioceptive deficits of individuals with upper limb spasticity after stroke using the Kinarm robotic exoskeleton. Methods Upper limb function was characterized using two tasks: Visually Guided Reaching, in which participants moved the limb from a central target to 1 of 4 or 1 of 8 outer targets when cued (measuring reaching function) and Arm Position Matching, in which participants moved the less-affected arm to mirror match the position of the affected arm (measuring proprioception), which was passively moved to 1 of 4 or 1 of 9 different positions. Comparisons were made between individuals with (n = 35) and without (n = 35) upper limb post-stroke spasticity. Results Statistically significant differences in affected limb performance between groups were observed in reaching-specific measures characterizing movement time and movement speed, as well as an overall metric for the Visually Guided Reaching task. While both groups demonstrated deficits in proprioception compared to normative values, no differences were observed between groups. Modified Ashworth Scale score was significantly correlated with these same measures. Conclusions The findings indicate that individuals with spasticity experience greater deficits in temporal features of movement while reaching, but not in proprioception in comparison to individuals with post-stroke motor impairment without spasticity. Temporal features of movement can be potential targets for rehabilitation in individuals with upper limb spasticity after stroke.

Background Position sense is commonly impaired after stroke. Traditional rehabilitation methods instruct patients to visualize their limbs to compensate for impaired position sense. Objective Our goal was to evaluate how the use of vision influences impaired position sense. Methods We examined 177 stroke survivors, an average of 12.7 days (+/− 10 days (SD)) post-stroke, and 133 neurologically-intact controls with a robotic assessment of position sense. The robot positioned one limb (affected) and subjects attempted to mirror-match the position using the opposite limb (unaffected). Subjects completed the test without, then with vision of their limbs. We examined three measures of position sense: variability (Var), contraction/expansion (C/E) and systematic shift (Shift). We classified stroke survivors as having full compensation if they performed the robotic task abnormally without vision but corrected performance within the range of normal with vision. Stroke survivors were deemed to have partial compensation if they performed the task outside the range of normal without and with vision, but improved significantly with vision. Those with absent compensation performed the task abnormally in both conditions and did not improve with vision. Results Many stroke survivors demonstrated impaired position sense with vision occluded [Var: 116 (66%), C/E: 91 (51%), Shift: 52 (29%)]. Of those stroke survivors with impaired position sense, some exhibited full compensation with vision [Var: 23 (20%), C/E: 42 (46%), Shift: 32 (62%)], others showed partial compensation [Var: 37 (32%), C/E: 8 (9%), Shift: 3 (6%)] and many displayed absent compensation (Var: 56 (48%), C/E: 41 (45%), Shift: 17 (33%)]. Stroke survivors with an affected left arm, visuospatial neglect and/or visual field defects were less likely to compensate for impaired position sense using vision. Conclusions Our results indicate that vision does not help many stroke survivors compensate for impaired position sense, at least within the current paradigm. This contrasts with historical reports that vision helps compensate for proprioceptive loss following neurologic injuries.

Background. Corticospinal tract (CST) damage is considered a biomarker for stroke recovery. Several methods have been used to define CST damage and examine its relationship to motor performance, but which method is most useful remains unclear. Proprioceptive impairment also affects stroke recovery and may be related to CST damage. Methods. Robotic assessment quantified upper-limb motor and proprioceptive performance at 2 weeks and 6 months poststroke (n = 149). Three previously-established CST lesion metrics were calculated using clinical neuroimaging. Diffusion magnetic resonance imaging quantified CST microstructure in a subset of participants (n = 21). Statistical region of interest (sROI) analysis identified lesion locations associated with motor and proprioceptive deficits. Results. CST lesion metrics were moderately correlated with motor scores at 2 weeks and 6 months poststroke. CST fractional anisotropy (FA) was correlated with motor scores at 1 month poststroke, but not at 6 months. The FA ratio of the posterior limb of the internal capsule was not correlated with motor performance. CST lesion metrics were moderately correlated with proprioceptive scores at 2 weeks and 6 months poststroke. sROI analysis confirmed that CST damage was associated with motor and proprioceptive deficits and additionally found that putamen, internal capsule, and corticopontocerebellar tract lesions were associated with poor motor performance. Conclusions. Across all methods used to quantify CST damage, correlations with motor or proprioceptive performance were moderate at best. Future research is needed to identify complementary or alternative biomarkers to address the complexity and heterogeneity of stroke recovery.

Treatment efficacy is established via controlled research trials, but treatment in real-world clinical environments is typically highly variable and may differ from research protocols by necessity. Here, we examined provision of visual retraining for adults after neurological injury at an outpatient rehabilitation program in Calgary, Canada.Retrospective chart audits extracted demographic data, assessment outcomes, and details related to provision of training.Treatment was provided to individuals with both visual field and visual-perceptual impairments due to neurological injury (mostly stroke). Tools and techniques of visual retraining at this program are discussed, the common denominator being repetitive practice of compensatory visual behaviors. Across this multisite program, there was significant variability in the number of treatment sessions, 13.00 (±10.21) sessions for those with visual-perceptual impairments and 14.41 (±9.63) sessions for those with field loss. Descriptive statistics and confidence intervals suggest improved outcomes on some measures for those with visual field and visual perceptual impairments.Our data suggest that visual retraining is feasible in this clinical outpatient setting. Implications for rehabilitation This program of visual retraining was provided to individuals with visual impairment (e.g., hemianopia) and visual perceptual impairment (e.g., unilateral spatial neglect) as a result of neurological injury. In this outpatient program, visual rehabilitation was feasible and appeared to improve outcomes among a heterogeneous clinical population. Fundamental characteristics of visual compensatory training at this program included repetitive practice of adaptive scanning behaviors across multiple contexts to promote automaticity and generalization of skills.

Proprioceptive and motor impairments commonly occur after stroke. Relationships between corticospinal tract (CST) fractional anisotropy (FA) and motor recovery have been identified. However, the relationship between sensory tract microstructure and proprioceptive recovery remains unexplored. Using probabilistic tractography, we examined the relationship between diffusion metrics in three tracts known to contain proprioceptive information (a) dorsal-column medial-lemniscal (DCML), (b) postcentral gyrus to supramarginal gyrus (POCG-SMG), (c) postcentral gyrus to Heschl's gyrus (POCG-HG) and proprioception at 1 (n = 26) and 6 months (n = 19) poststroke. Proprioception was assessed using two robotic tasks. Motor performance was also assessed robotically and compared to CST diffusion metrics. At 1-month poststroke, a nonsignificant relationship (r = -0.43, p = 0.05) was observed between DCML-FA and proprioceptive impairment. A moderate relationship was identified between POCG-SMG FA and POCG-HG FA and proprioceptive impairment (r = -0.47, p = 0.001 and r = -0.51, p = 0.008, respectively). No relationships were significant at 6 months poststroke. Similar to previous studies, lower CST-FA correlated with motor impairment at 1 month poststroke (r = -0.58, p = 0.002). While CST-FA is considered a predictor of motor impairment, our findings suggest that the relationship between FA and tracts containing proprioceptive information is not as straightforward and highlights the importance of sensory association areas in proprioception.

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. Perinatal stroke is the leading cause of hemiparetic cerebral palsy. Motor deficits and their treatment are commonly emphasized in the literature. Sensory dysfunction may be an important contributor to disability, but it is difficult to measure accurately clinically. Objective. Use robotics to quantify position sense deficits in hemiparetic children with perinatal stroke and determine their association with common clinical measures. Methods. Case-control study. Participants were children aged 6 to 19 years with magnetic resonance imaging–confirmed unilateral perinatal arterial ischemic stroke or periventricular venous infarction and symptomatic hemiparetic cerebral palsy. Participants completed a position matching task using an exoskeleton robotic device (KINARM). Position matching variability, shift, and expansion/contraction area were measured with and without vision. Robotic outcomes were compared across stroke groups and controls and to clinical measures of disability (Assisting Hand Assessment) and sensory function. Results. Forty stroke participants (22 arterial, 18 venous, median age 12 years, 43% female) were compared with 60 healthy controls. Position sense variability was impaired in arterial (6.01 ± 1.8 cm) and venous (5.42 ± 1.8 cm) stroke compared to controls (3.54 ± 0.9 cm, P < .001) with vision occluded. Impairment remained when vision was restored. Robotic measures correlated with functional disability. Sensitivity and specificity of clinical sensory tests were modest. Conclusions. Robotic assessment of position sense is feasible in children with perinatal stroke. Impairment is common and worse in arterial lesions. Limited correction with vision suggests cortical sensory network dysfunction. Disordered position sense may represent a therapeutic target in hemiparetic cerebral palsy.

Introduction Stroke survivors frequently experience a range of post-stroke deficits. Specialized stroke rehabilitation improves recovery, especially if it is started early post-stroke. However, resource limitations often preclude early rehabilitation. Mobile technologies may provide a platform for stroke survivors to begin recovery when they might not be able to otherwise. The study objective was to demonstrate the feasibility of RecoverNow, a tablet-based stroke recovery platform aimed at delivering speech and cognitive therapy. Methods We recruited a convenience sample of 30 acute stroke patients to use RecoverNow for up to 3 months. Allied health professionals assigned specific applications based on standard of care assessments. Participants were encouraged to take home the RecoverNow tablets upon discharge from acute care. The study team contacted participants to return for a follow-up interview 3 months after enrollment. The primary outcome of interest was feasibility, defined using 5 facets: recruitment rate, adherence rate, retention rate, the proportion of successful follow-up interventions, and protocol deviations. We tracked barriers to tablet-based care as a secondary outcome. Results We successfully recruited 30 of 62 eligible patients in 15 weeks (48% recruitment rate). Participants were non-adherent to tablet-based therapy inside and outside of acute care, using RecoverNow for a median of 12 minutes a day. Retention was high with 23 of 30 patients participating in follow-up interviews (77% retention rate) and all but 3 of the 23 interviews (87%) were successfully completed. Only 2 major protocol deviations occurred: one enrollment failure and one therapy protocol violation. Barriers to tablet-based care were frequently encountered by study participants with many expressing the assigned applications were either too easy or too difficult. Conclusions Acute stroke patients are interested in attempting tablet-based stroke rehabilitation and are easily recruited early post-stroke. However, tablet-based therapy may be challenging due to patient, device and system-related barriers. Reducing the frequency of common barriers will be essential to keeping patients engaged in tablet-based therapy.

Transcranial direct-current stimulation (tDCS) enhances motor learning in adults. We have demonstrated that anodal tDCS and high-definition (HD) tDCS of the motor cortex can enhance motor skill acquisition in children, but behavioral mechanisms remain unknown. Robotics can objectively quantify complex sensorimotor functions to better understand mechanisms of motor learning. We aimed to characterize changes in sensorimotor function induced by tDCS and HD-tDCS paired motor learning in children within an interventional trial. Healthy, right-handed children (12–18 y) were randomized to anodal tDCS, HD-tDCS, or sham targeting the right primary motor cortex during left-hand Purdue pegboard test (PPT) training over five consecutive days. A KINARM robotic protocol quantifying proprioception, kinesthesia, visually guided reaching, and an object hit task was completed at baseline, posttraining, and six weeks later. Effects of the treatment group and training on changes in sensorimotor parameters were explored. Twenty-four children (median 15.5 years, 52% female) completed all measures. Compared to sham, both tDCS and HD-tDCS demonstrated enhanced motor learning with medium effect sizes. At baseline, multiple KINARM measures correlated with PPT performance. Following training, visually guided reaching in all groups was faster and required less corrective movements in the trained arm (H(2) = 9.250,p=0.010). Aspects of kinesthesia including initial direction error improved across groups with sustained effects at follow-up (H(2) = 9.000,p=0.011). No changes with training or stimulation were observed for position sense. For the object hit task, the HD-tDCS group moved more quickly with the right hand compared to sham at posttraining (χ2(2) = 6.255,p=0.044). Robotics can quantify complex sensorimotor function within neuromodulator motor learning trials in children. Correlations with PPT performance suggest that KINARM metrics can assess motor learning effects. Understanding how tDCS and HD-tDCS enhance motor learning may be improved with robotic outcomes though specific mechanisms remain to be defined. Exploring mechanisms of neuromodulation may advance therapeutic approaches in children with cerebral palsy and other disabilities.

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.