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BackgroundGait and balance impairments are common in neurological diseases, including stroke, and negatively affect patients’ quality of life. Improving balance and gait are among the main goals of rehabilitation. Rehabilitation is mainly performed in clinics, which lack context specificity; therefore, training in the patient’s home environment is preferable. In the last decade, developed rehabilitation technologies such as virtual reality and augmented reality (AR) have enabled gait and balance training outside clinics. Here, we propose a new method for gait rehabilitation in persons who have had a stroke in which mobile AR technology and a sensor-based motion capture system are combined to provide fine-grained feedback on gait performance in real time. ObjectiveThe aims of this study were (1) to investigate manipulation of the gait pattern of persons who have had a stroke based on virtual augmentation during overground walking compared to walking without AR performance feedback and (2) to investigate the usability of the AR system. MethodsWe developed the ARISE (Augmented Reality for gait Impairments after StrokE) system, in which we combined a development version of HoloLens 2 smart glasses (Microsoft Corporation) with a sensor-based motion capture system. One patient with chronic minor gait impairment poststroke completed clinical gait assessments and an AR parkour course with patient-centered performance gait feedback. The movement kinematics during gait as well as the usability and safety of the system were evaluated. ResultsThe patient changed his gait pattern during AR parkour compared to the pattern observed during the clinical gait assessments. He recognized the virtual objects and ranked the usability of the ARISE system as excellent. In addition, the patient stated that the system would complement his standard gait therapy. Except for the symptom of exhilaration, no adverse events occurred. ConclusionsThis project provided the first evidence of gait adaptation during overground walking based on real-time feedback through visual and auditory augmentation. The system has potential to provide gait and balance rehabilitation outside the clinic. This initial investigation of AR rehabilitation may aid the development and investigation of new gait and balance therapies.

BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.

Introduction: Stroke-induced upper limb disabilities can be characterized by both motor impairments and activity limitations, commonly assessed using Fugl-Meyer Motor Assessment for Upper Extremity (FMMA-UE) and Action Research Arm Test (ARAT), respectively. The relationship between the two assessments during recovery is largely unstudied. Expectedly they diverge over time when recovery of impairment (restitution) plateaus, but compensationdriven improvements still occur. The objective of this study is to evaluate the alignment between FMMA-UE and ARAT in defining upper limb functional recovery categories by ARAT scores. We aimed to establish cut-off scores for both measures from the acute/early subacute, subacute and chronic stages of stroke recovery. Methods: Secondary analysis of four prospective cohort studies (acute/early subacute: n = 133, subacute: n = 113, chronic: n = 92) stages post-stroke. Receiver operating characteristic curves calculated the area under the curve (AUC) to establish optimal FMMA-UE cut-offs based on predefined ARAT thresholds distinguishing five activity levels from no activity to full activity. Weighted kappa was used to determine agreement between the two assessments. We used minimally clinically important difference (MCID) and minimal detectable change (MDC95) for comparison. Results: FMMA-UE and ARAT scores showed no relevant divergence across all recovery stages. Results indicated similar cut-off scores in all recovery stages with variability below MCID and MDC95 levels. Cut-off scores demonstrated robust AUC values from 0.77 to 0.86 at every recovery stage. Only in highly functional patients at the chronic stage, we found a reduced specificity of 0.55. At all other times sensitivity ranged between 0.68 and 0.99 and specificity between 0.71 and 0.99. Weighted kappa at the acute/early subacute, subacute and chronic stages was 0.76, 0.83, and 0.81, respectively. Discussion: Our research shows a strong alignment between FMMA-UE and ARAT cut-off scores throughout stroke recovery, except among the subgroup of highly recovered patients at the chronic stage. Discrepancies in specificity potentially stem from fine motor deficits affecting dexterity outcomes that are not captured by FMMA-UE. Additionally, the high congruence of both measures suggests they are not suited to distinguish between restitution and compensation. Calling for more comprehensive assessment methods to better understand upper limb functionality in rehabilitation. [ABSTRACT FROM AUTHOR]

Revascularization surgery for the symptomatic hemisphere with hemodynamic impairment is effective for Moyamoya vasculopathy patients. However, careful patient selection is crucial and ideally supported by advanced quantitative hemodynamic imaging. Recently, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) and quantitative magnetic resonance angiography with non-invasive optimal vessel analysis (qMRA-NOVA) have gained prominence in assessing these patients. This study aims to present the results of BOLD-CVR and qMRA-NOVA imaging along with the changes in cerebral hemodynamics and flow status following flow augmentation with superficial temporal artery–middle cerebral artery (STA-MCA) bypass in our Moyamoya vasculopathy patient cohort. Symptomatic patients with Moyamoya vasculopathy treated at the Clinical Neuroscience Center of the University Hospital Zurich who underwent hemodynamic and flow imaging (BOLD-CVR and qMRA-NOVA) before and after bypass were included in the analysis. Reduced hemispheric volume flow rates, as well as impaired BOLD-CVR, were measured in all 12 patients with Moyamoya vasculopathy before STA-MCA bypass surgery. Following the surgical procedure, post-operative BOLD-CVR demonstrated a non-significant increase in BOLD-CVR values within the revascularized, symptomatic middle cerebral artery territory and cerebral hemisphere. The results of the statistical tests should be viewed as indicative due to the small sample size. Additionally, post-operative qMRA-NOVA revealed a significant improvement in the hemispheric volume flow rate of the affected hemisphere due to the additional bypass flow rate. Our findings affirm the presence of hemodynamic and flow impairments in the symptomatic hemisphere of the Moyamoya vasculopathy patients. Bypass surgery proves effective in improving both BOLD-CVR impairment and the hemispheric volume flow rate in our patient cohort. [ABSTRACT FROM AUTHOR]

Objective: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. Methods: This was a post hoc exploratory analysis based on the per‐protocol dataset from TREAT‐CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. Results: All 173 (100%) per‐protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07–0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04–0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07–0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11–0.97) had decreased odds of events when treated with anticoagulation. Interpretation: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886–897 [ABSTRACT FROM AUTHOR]

Introduction: The Fugl-Meyer Motor Assessment (FMMA) is recommended for evaluating stroke motor recovery in clinical practice and research. However, its widespread use requires refined reliability data, particularly across different health professions. We therefore investigated the interrater reliability of the FMMA scored by a physical therapist and a physician using video recordings of stroke patients. Methods: The FMMA videos of 50 individuals 3 months post stroke (28 females, mean age 71.64 years, median National Institutes of Health Stroke Scale score 3.00) participating in the ESTREL trial (Enhancement of Stroke Rehabilitation with Levodopa: a randomized placebo-controlled trial) were independently scored by two experienced assessors (i.e., a physical therapist and a physician) with specific training to ensure consistency. As primary endpoint, the interrater reliability was calculated for the total scores of the entire FMMA and the total scores of the FMMA for the upper and lower extremities using intraclass correlation coefficients (ICC). In addition, Spearman’s rank order correlation coefficients (Spearman’s rho) were calculated for the total score and subscale levels. Secondary endpoints included the FMMA item scores using percentage agreement, weighted Cohen’s kappa coefficients, and Gwet’s AC1/AC2 coefficients. Results: ICCs were 0.98 (95% confidence intervals (CI) 0.96–0.99) for the total scores of the entire FMMA, 0.98 (95% CI 0.96–0.99) for the total scores of the FMMA for the upper extremity, and 0.85 (95% CI 0.70–0.92) for the total scores of the FMMA for the lower extremity. Spearman’s rho ranged from 0.61 to 0.94 for total and subscale scores. The interrater reliability at the item level of the FMMA showed (i) percentage agreement values with a median of 77% (range 44–100%), (ii) weighted Cohen’s kappa coefficients with a median of 0.69 (range 0.00–0.98) and (iii) Gwet’s AC1/AC2 coefficients with a median of 0.84 (range 0.42–0.98). Discussion and conclusion: The FMMA appears to be a highly reliable measuring instrument at the overall score level for assessors from different health professions. The FMMA total scores seem to be suitable for the quantitative measurement of stroke recovery in both clinical practice and research, although there is potential for improvement at the item level. [ABSTRACT FROM AUTHOR]

Tissue tolerance to ischemia can be achieved by noxious stimuli that are below a threshold to cause irreversible damage ('preconditioning'). Understanding the mechanisms underlying preconditioning may lead to the identification of novel therapeutic targets for diseases such as stroke. We here used the oxidative chain inhibitor 3-nitropropionic acid (NPA) to induce ischemia tolerance in a rat middle cerebral artery occlusion (MCAO) stroke model. Cerebral blood flow (CBF) and structural integrity were characterized by longitudinal magnetic resonance imaging (MRI) in combination with behavioral, histologic, and biochemical assessment of NPA-preconditioned animals and controls. Using this approach we show that the ischemia-tolerant state is characterized by a lower energy charge potential and lower CBF, indicating a reduced baseline metabolic demand, and therefore a cellular mechanism of neural protection. Blood vessel density and structural integrity were not altered by NPA treatment. When subjected to MCAO, preconditioned animals had a characteristic MRI signature consisting of enhanced CBF maintenance within the ischemic territory and intraischemic reversal of the initial cytotoxic edema, resulting in reduced infarct volumes. Thus, our data show that tissue protection through preconditioning occurs early during ischemia and indicate that a reduced cellular metabolism is associated with tissue tolerance to ischemia.

The membrane protein Nogo-A is known as an inhibitor of axonal outgrowth and regeneration in the CNS. However, its physiological functions in the normal adult CNS remain incompletely understood. Here, we investigated the role of Nogo-A in cortical synaptic plasticity and motor learning in the uninjured adult rodent motor cortex. Nogo-A and its receptor NgR1 are present at cortical synapses. Acute treatment of slices with function-blocking antibodies (Abs) against Nogo-A or against NgR1 increased long-term potentiation (LTP) induced by stimulation of layer 2/3 horizontal fibers. Furthermore, anti-Nogo-A Ab treatment increased LTP saturation levels, whereas long-term depression remained unchanged, thus leading to an enlarged synaptic modification range. In vivo, intrathecal application of Nogo-A-blocking Abs resulted in a higher dendritic spine density at cortical pyramidal neurons due to an increase in spine formation as revealed by in vivo two-photon microscopy. To investigate whether these changes in synaptic plasticity correlate with motor learning, we trained rats to learn a skilled forelimb-reaching task while receiving anti-Nogo-A Abs. Learning of this cortically controlled precision movement was improved upon anti-Nogo-A Ab treatment. Our results identify Nogo-A as an influential molecular modulator of synaptic plasticity and as a regulator for learning of skilled movements in the motor cortex.