Telerehabilitation Following Stroke.

Stroke remains a major cause of disability. Intensive rehabilitation therapy can improve outcomes, but most patients receive limited doses. Telehealth methods can overcome obstacles to delivering intensive therapy and thereby address this unmet need. A specific example is reviewed in detail, focused on a telerehabilitation system that targets upper extremity motor deficits after stroke. Strengths of this system include provision of daily therapy associated with very high patient compliance, safety and feasibility in the inpatient or home setting, comparable efficacy to dose-matched therapy provided in-clinic, and a holistic approach that includes assessment, education, prevention, and activity-based therapy.

Genome-Wide Association Studies of 3 Distinct Recovery Phenotypes in Mild Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Stroke genetic research has made substantial progress in the past decade. Its recovery application, however, remains behind, in part due to its reliance on the modified Rankin Scale (mRS) score as a measure of poststroke outcome. The mRS does not map well to biological processes because numerous psychosocial factors drive much of what the mRS captures. Second, the mRS contains multiple disparate biological events into a single measure further limiting its use for biological discovery. This led us to investigate the effect of distinct stroke recovery phenotypes on genetic variation associations with Genome-Wide Association Studies (GWASs) by repurposing the NIH Stroke Scale (NIHSS) and its subscores. METHODS: In the Vitamin Intervention for Stroke Prevention cohort, we estimated changes in cognition, motor, and global impairments over 2 years using specific measures. We included genotyped participants with a total NIHSS score greater than zero at randomization and excluded those with recurrent stroke during the trial. A GWAS linear mixed-effects model predicted score changes, with participant as a random effect, and included initial score, age, sex, treatment group, and the first 5 ancestry principal components. RESULTS: In total, 1,270 participants (64% male) were included with a median NIHSS score of 2 (interquartile range [IQR] 1-3) and median age 68 (IQR 59-75) years. At randomization, 20% had cognitive deficits (NIHSS Cog-4 score >0) and 70% had ≥1 motor deficits (impairment score >1). At 2 years, these percentages improved to 7.2% with cognitive deficits and 30% with motor deficits. GWAS identified novel suggestive gene-impairment associations (p < 5e-6) for cognition (CAMK2D, EVX2, LINC0143, PTPRM, SGMS1, and SMAD2), motor (ACBD6, KDM4B, MARK4, PTPRS, ROBO1, and ROBO2), and global (MSR1 and ROBO2) impairments. DISCUSSION: Defining domain-specific stroke recovery phenotypes and using longitudinal clinical trial designs can help detect novel genes associated with chronic recovery. These data support the use of granular endpoints to identify genetic associations related to stroke recovery.

Making Sense of Vagus Nerve Stimulation for Stroke.

Implantable vagus nerve stimulation, paired with high-dose occupational therapy, has been shown to be effective in improving upper limb function among patients with stroke and received regulatory approval from the US Food and Drug Administration and the Centers for Medicare & Medicaid Services. Combining nonsurgical and surgical approaches of vagus nerve stimulation in recent meta-analyses has resulted in misleading reports on the efficacy of each type of stimulation among patients with stroke. This article aims to clarify the confusion surrounding implantable vagus nerve stimulation as a poststroke treatment option, highlighting the importance of distinguishing between transcutaneous auricular vagus nerve stimulation and implantable vagus nerve stimulation. Recent meta-analyses on vagus nerve stimulation have inappropriately combined studies of fundamentally different interventions, outcome measures, and participant selection, which do not conform to methodological best practices and, hence, cannot be used to deduce the relative efficacy of the different types of vagus nerve stimulation for stroke rehabilitation. Health care providers, patients, and insurers should rely on appropriately designed research to guide well-informed decisions.

Post-Stroke Brain Health Monitoring and Optimization: A Narrative Review.

Significant advancements have been made in recent years in the acute treatment and secondary prevention of stroke. However, a large proportion of stroke survivors will go on to have enduring physical, cognitive, and psychological disabilities from suboptimal post-stroke brain health. Impaired brain health following stroke thus warrants increased attention from clinicians and researchers alike. In this narrative review based on an open timeframe search of the PubMed, Scopus, and Web of Science databases, we define post-stroke brain health and appraise the body of research focused on modifiable vascular, lifestyle, and psychosocial factors for optimizing post-stroke brain health. In addition, we make clinical recommendations for the monitoring and management of post-stroke brain health at major post-stroke transition points centered on four key intertwined domains: cognition, psychosocial health, physical functioning, and global vascular health. Finally, we discuss potential future work in the field of post-stroke brain health, including the use of remote monitoring and interventions, neuromodulation, multi-morbidity interventions, enriched environments, and the need to address inequities in post-stroke brain health. As post-stroke brain health is a relatively new, rapidly evolving, and broad clinical and research field, this narrative review aims to identify and summarize the evidence base to help clinicians and researchers tailor their own approach to integrating post-stroke brain health into their practices.

Lifetime and Acute Stress Predict Functional Outcomes Following Stroke: Findings From the Longitudinal STRONG Study.

BACKGROUND: Stroke is a sudden-onset, uncontrollable event; stroke-related stress may impede rehabilitation and recovery. Lifetime stress may sensitize patients to experiencing greater stroke-related stress and indirectly affect outcomes. We examine lifetime stress as predictor of poststroke acute stress and examine lifetime and acute stress as predictors of 3- and 12-month functional status. We also compare acute stress and baseline National Institutes of Health Stroke Scale as predictors of poststroke functional status. METHODS: Between 2016 and 2020 the STRONG Study (Stroke, Stress, Rehabilitation, and Genetics) enrolled adults with new radiologically confirmed stroke 2 to 10 days poststroke onset at 28 acute care US hospitals. Participants were interviewed 3 times: acute admission (acute stress; Acute Stress Disorder Interview), 3 months (Fugl-Meyer Upper Extremity motor impairment [Fugl-Meyer Upper Arm Assessment; N=431], modified Rankin Scale [3 months; N=542], Stroke Impact Scale-Activities of Daily Living [3 months; N=511], Lifetime Stress Exposure Inventory), and 12 months (modified Rankin Scale, N=533; Stroke Impact Scale 3.0 Activities of Daily Living; N=485; Telephone Montreal Cognitive Assessment; N=484) poststroke. Structural equation models examined whether acute stress predicted 3- and 12-month functional outcomes, and mediated an association between lifetime stress and outcomes controlling for demographics and initial National Institutes of Health Stroke Scale. Standardized betas are reported. RESULTS: Sample (N=763) was 19 to 95 years old (mean=63; SD=14.9); 448 (58.7%) were male. Acute stress scores ranged from 0 to 14 (mean, 3.52 [95% CI, 3.31-3.73]). Controlling for age, gender, baseline National Institutes of Health Stroke Scale, and race and ethnicity, higher lifetime stress predicted higher acute stress (ß=0.18, P<0.001), which predicted lower 3-month Fugl-Meyer Upper Arm Assessment scores (ß=-0.19, P<0.001), lower Stroke Impact Scale 3.0 Activities of Daily Living scores at 3 months (ß=-0.21, P<0.001) and 12 months (ß=-0.21, P<0.001), higher modified Rankin Scale scores at 3 months (ß=0.23, P<0.001) and 12 months (ß=0.22, P<0.001), and lower 12-month Telephone Montreal Cognitive Assessment scores (ß=-0.20, P<0.001). Acute stress predicted 12-month tMoCA (χ2[1]=5.29, P=0.022) more strongly, 3-month and 12-month modified Rankin Scale and SIS scores as strongly (all Ps>0.18), but Fugl-Meyer scores (χ2[1]=7.01, P=0.008) less strongly than baseline National Institutes of Health Stroke Scale. CONCLUSIONS: Lifetime stress/trauma is associated with more poststroke acute stress, which is associated with greater motor and cognitive impairment and disability 3 and 12 months poststroke. Poststroke interventions for acute stress may help mitigate stroke-related disability.

Data-driven biomarkers outperform theory-based biomarkers in predicting stroke motor outcomes.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9±18.0 years; time since stroke 12.2±0.2 months; normalised motor score 0.7±0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.

Distinguishing Distinct Neural Systems for Proximal vs Distal Upper Extremity Motor Control After Acute Stroke.

BACKGROUND AND OBJECTIVES: The classic and singular pattern of distal greater than proximal upper extremity motor deficits after acute stroke does not account for the distinct structural and functional organization of circuits for proximal and distal motor control in the healthy CNS. We hypothesized that separate proximal and distal upper extremity clinical syndromes after acute stroke could be distinguished and that patterns of neuroanatomical injury leading to these 2 syndromes would reflect their distinct organization in the intact CNS. METHODS: Proximal and distal components of motor impairment (upper extremity Fugl-Meyer score) and strength (Shoulder Abduction Finger Extension score) were assessed in consecutively recruited patients within 7 days of acute stroke. Partial correlation analysis was used to assess the relationship between proximal and distal motor scores. Functional outcomes including the Box and Blocks Test (BBT), Barthel Index (BI), and modified Rankin scale (mRS) were examined in relation to proximal vs distal motor patterns of deficit. Voxel-based lesion-symptom mapping was used to identify regions of injury associated with proximal vs distal upper extremity motor deficits. RESULTS: A total of 141 consecutive patients (49% female) were assessed 4.0 ± 1.6 (mean ± SD) days after stroke onset. Separate proximal and distal upper extremity motor components were distinguishable after acute stroke (p = 0.002). A pattern of proximal more than distal injury (i.e., relatively preserved distal motor control) was not rare, observed in 23% of acute stroke patients. Patients with relatively preserved distal motor control, even after controlling for total extent of deficit, had better outcomes in the first week and at 90 days poststroke (BBT, ρ = 0.51, p < 0.001; BI, ρ = 0.41, p < 0.001; mRS, ρ = 0.38, p < 0.001). Deficits in proximal motor control were associated with widespread injury to subcortical white and gray matter, while deficits in distal motor control were associated with injury restricted to the posterior aspect of the precentral gyrus, consistent with the organization of proximal vs distal neural circuits in the healthy CNS. DISCUSSION: These results highlight that proximal and distal upper extremity motor systems can be selectively injured by acute stroke, with dissociable deficits and functional consequences. Our findings emphasize how disruption of distinct motor systems can contribute to separable components of poststroke upper extremity hemiparesis.

Essential information for neurorecovery clinical trial design: trajectory of global disability in first 90 days post-stroke in patients discharged to acute rehabilitation facilities.

BACKGROUND: Many stroke recovery interventions are most beneficial when started 2-14d post-stroke, a time when patients become eligible for inpatient rehabilitation facilities (IRF) and neuroplasticity is often at its peak. Clinical trials focused on recovery need to expand the time from this plasticity to later outcome timepoints. METHODS: The disability course of patients with acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) enrolled in Field Administration of Stroke Therapy Magnesium (FAST-MAG) Trial with moderate-severe disability (modified Rankin Scale [mRS] 3-5) on post-stroke day4 who were discharged to IRF 2-14d post-stroke were analyzed. RESULTS: Among 1422 patients, 446 (31.4%) were discharged to IRFs, including 23.6% within 2-14d and 7.8% beyond 14d. Patients with mRS 3-5 on day4 discharged to IRFs between 2-14d accounted for 21.7% (226/1041) of AIS patients and 28.9% (110/381) of ICH patients, (p < 0.001). Among these AIS patients, age was 69.8 (± 12.7), initial NIHSS median 8 (IQR 4-12), and day4 mRS = 3 in 16.4%, mRS = 4 in 50.0%, and mRS = 5 in 33.6%. Among these ICH patients, age was 62.4 (± 11.7), initial NIHSS median 9 (IQR 5-13), day 4 mRS = 3 in 9.4%, mRS = 4 in 45.3%, and mRS = 5 in 45.3% (p < 0.01 for AIS vs ICH). Between day4 to day90, mRS improved ≥ 1 levels in 72.6% of AIS patients vs 77.3% of ICH patients, p = 0.3. For AIS, mRS improved from mean 4.17 (± 0.7) to 2.84 (± 1.5); for ICH, mRS improved from mean 4.35 (± 0.7) to 2.75 (± 1.3). Patients discharged to IRF beyond day14 had less improvement on day90 mRS compared with patients discharged between 2-14d. CONCLUSIONS: In this acute stroke cohort, nearly 1 in 4 patients with moderate-severe disability on post-stroke day4 were transferred to IRF within 2-14d post-stroke. ICH patients had nominally greater mean improvement on mRS day90 than AIS patients. This course delineation provides a roadmap for future rehabilitation intervention studies.

Identifying the neural correlates of anticipatory postural control: A novel fMRI paradigm.

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the thigh remains supported. For the unsupported leg raise (ULR) the leg is raised from the hip, requiring postural muscle activation in the abdominal/hip extensor musculature. Significant brain activation during the SLR task occurred predominantly in the right primary and secondary sensorimotor cortical regions. Brain activation during the ULR task occurred bilaterally in the primary and secondary sensorimotor cortical regions, as well as cerebellum and putamen. In comparison with the SLR, the ULR was associated with significantly greater activation in the right premotor/SMA, left primary motor and cingulate cortices, primary somatosensory cortex, supramarginal gyrus/parietal operculum, superior parietal lobule, cerebellar vermis, and cerebellar hemispheres. Cortical and subcortical regions activated during the ULR, but not during the SLR, were consistent with the planning, and execution of a task involving multisegmental, bilateral postural control. Future studies using this paradigm will determine mechanisms underlying impaired postural control in patients with neurological and musculoskeletal dysfunction.

Downward adjustment of rehabilitation goals may facilitate post-stroke arm motor recovery.

Objective: Patients starting with physical rehabilitation often hold unrealistically high expectations for their recovery. Because of a lower-than-expected rate of recovery, such unrealistic goals have been linked to adverse effects on mental health. Additionally, overtraining due to overly ambitious goals can lead to suboptimal recovery. We investigated the effectiveness of adjusting rehabilitation goals to a more realistic level as a strategy to select appropriate exercise intensity and achieve better recovery outcomes. Design: Patients with arm paralysis from recent stroke were recruited and went through 6-8 weeks of telerehabilitation and in-clinic rehabilitation programme conducted at 11 US sites (N = 124). Main Outcome Measures: Adjustment of recovery goal was assessed in two timepoints during the rehabilitation programme and arm motor function was assessed before and after the clinical trial. Results: Greater use of goal adjustment strategies predicted better recovery of arm motor function, independent from therapy compliance. This pattern was observed only when the choice of exercises is patient-regulated rather than directed by a physical therapist. Conclusion: Benefits from goal adjustment were more pronounced among patients who entered the programme with poorer motor functions, suggesting that goal adjustment is the most beneficial when goals of complete recovery are most unrealistic.

EMAGINE-Study protocol of a randomized controlled trial for determining the efficacy of a frequency tuned electromagnetic field treatment in facilitating recovery within the subacute phase following ischemic stroke.

Stroke is a leading cause of disability with limited effective interventions that improve recovery in the subacute phase. This protocol aims to evaluate the safety and efficacy of a non-invasive, extremely low-frequency, low-intensity, frequency-tuned electromagnetic field treatment [Electromagnetic Network Targeting Field (ENTF) therapy] in reducing disability and promoting recovery in people with subacute ischemic stroke (IS) with moderate-severe disability and upper extremity (UE) motor impairment. Following a sample-size adaptive design with a single interim analysis, at least 150 and up to 344 participants will be recruited to detect a 0.5-point (with a minimum of 0.33 points) difference on the modified Rankin Scale (mRS) between groups with 80% power at a 5% significance level. This ElectroMAGnetic field Ischemic stroke-Novel subacutE treatment (EMAGINE) trial is a multicenter, double-blind, randomized, sham-controlled, parallel two-arm study to be conducted at approximately 20 United States sites, and enroll participants with subacute IS and moderate-severe disability with UE motor impairment. Participants will be assigned to active (ENTF) or sham treatment, initiated 4-21 days after stroke onset. The intervention, applied to the central nervous system, is designed for suitability in multiple clinical settings and at home. Primary endpoint is change in mRS score from baseline to 90 days post-stroke. Secondary endpoints: change from baseline to 90 days post-stroke on the Fugl-Meyer Assessment - UE (lead secondary endpoint), Box and Block Test, 10-Meter Walk, and others, to be analyzed in a hierarchical manner. EMAGINE will evaluate whether ENTF therapy is safe and effective at reducing disability following subacute IS. Trial registration: www.ClinicalTrials.gov, NCT05044507 (14 September 2021).

Telerehabilitation Initiated Early in Post-Stroke Recovery: A Feasibility Study.

BACKGROUND: Enhanced neural plasticity early after stroke suggests the potential to improve outcomes with intensive rehabilitation therapy. Most patients do not get such therapy, however, due to limited access, changing rehabilitation therapy settings, low therapy doses, and poor compliance. OBJECTIVE: To examine the feasibility, safety, and potential efficacy of an established telerehabilitation (TR) program after stroke initiated during admission to an inpatient rehabilitation facility (IRF) and completed in the patient's home. METHODS: Participants with hemiparetic stroke admitted to an IRF received daily TR targeting arm motor function in addition to usual care. Treatment consisted of 36, 70-minute sessions (half supervised by a licensed therapist via videoconference), over a 6-week period, that included functional games, exercise videos, education, and daily assessments. RESULTS: Sixteen participants of 19 allocated completed the intervention (age 61.3 ± 9.4 years; 6 female; baseline Upper Extremity Fugl-Meyer [UEFM] score 35.9 ± 6.4 points, mean ± SD; NIHSS score 4 (3.75, 5.25), median, IQR; intervention commenced 28.3 ± 13.0 days post-stroke). Compliance was 100%, retention 84%, and patient satisfaction 93%; 2 patients developed COVID-19 and continued TR. Post-intervention UEFM improvement was 18.1 ± 10.9 points (P < .0001); Box and Blocks, 22.4 ± 9.8 blocks (P = .0001). Digital motor assessments, acquired daily in the home, were concordant with these gains. The dose of rehabilitation therapy received as usual care during this 6-week interval was 33.9 ± 20.3 hours; adding TR more than doubled this to 73.6 ± 21.8 hours (P < .0001). Patients enrolled in Philadelphia could be treated remotely by therapists in Los Angeles. CONCLUSIONS: These results support feasibility, safety, and potential efficacy of providing intense TR therapy early after stroke. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov; NCT04657770.

Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Stroke: 2- and 3-Year Follow-up From the Pilot Study.

OBJECTIVE: To assess whether a long-term home-based intervention using Paired VNS therapy is feasible and whether the benefits of Paired VNS therapy are maintained beyond 1 year. DESIGN: A long-term follow-up study. SETTING: Three centers in the United States and 1 in the United Kingdom. PARTICIPANTS: Adults with chronic ischemic stroke (n=15) with moderate to severe arm and hand impairment. INTERVENTIONS: Participants were implanted with a VNS device followed by 6 weeks of in-clinic therapy with Paired (Active) or control VNS followed by home-based rehabilitation through day 90 (blinded phase). The control VNS group then crossed over to receive 6 weeks of in-clinic Active VNS. Participants in both groups then continued a long-term home exercise program with self-administered Active VNS. MAIN OUTCOME MEASURES: Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT) Functional scores were evaluated at the end of in-clinic therapy and day 90. Since both groups were subsequently receiving home-based rehabilitation with Active VNS during the long term, follow-up outcome assessments were pooled for the analyses at 6, 9, and 12 months, as previously reported. Here, we report pooled analysis of outcomes beyond 1 year. RESULTS: One year after Paired VNS therapy, FMA-UE improved by an average of 9.2±8.2 points, as previously reported. Overall, the 2- and 3-year FMA-UE gain from baseline was 11.4±8.7 (P<.001) and 14.8±10.2 points (P<.001), respectively. At years 2 and 3, FMA-UE improved by an additional 2.9 (P=.03 for change vs year 1, n=14) and 4.7 (P=.02 for change vs year 1, n=14) points, respectively. At year 1, 73% (11/15) of participants were responders (FMA-UE change ≥6) and by year 3, 85.7% (12/14) were responders. At years 2 and 3, the WMFT score improved by an additional 0.21 points (P=.03 for change vs year 1, n=15) and 0.42 points (P=.01 for change vs year 1, n=13), respectively. Responder rate (WMFT change ≥0.4) was 46.6% (7/15), 73.3% (11/15), and 69.2% (9/13) at years 1, 2, and 3, respectively. Long-term significant improvements were also observed for Motor Activity Log (MAL) and Stroke Impact Scale, Hand section (SIS-Hand). There were no serious long-term adverse events from the stimulation. CONCLUSIONS: Significant effects of Paired VNS therapy at 1 year were maintained at years 2 and 3, and further improvements in both impairment and function were observed in years 2 and 3. These changes were associated with improvements in measures of activity and participation.

Domain-Specific Outcome Measures in Clinical Trials of Therapies Promoting Stroke Recovery: A Suggested Blueprint.

Different deficits recover to different degrees and with different time courses after stroke, indicating that plasticity differs across the brain's neural systems after stroke. To capture these differences, domain-specific outcome measures have received increased attention. Such measures have potential advantages over global outcome scales, which combine recovery across many domains into a single score and so blur the ability to capture individual measures of stroke recovery. Use of a global end point to rate disability can overlook substantial recovery in specific domains, such as motor or language, and may not differentiate between good and poor recovery for specific neurological domains. In light of these points, a blueprint is proposed for using domain-specific outcome measures in stroke recovery trials. Key steps include selecting a domain in the context of preclinical data, picking a domain-specific clinical trial end point, anchoring inclusion criteria to this end point, scoring this end point both before and after treatment, and then pursuing regulatory approval on the basis of the domain-specific results. This blueprint is intended to foster clinical trials that, by using domain-specific end points, are able to demonstrate favorable results in clinical trials of therapies that promote stroke recovery.

Rehabilitation Therapy Doses Are Low After Stroke and Predicted by Clinical Factors.

BACKGROUND: Stroke is a leading cause of long-term disability. Greater rehabilitation therapy after stroke is known to improve functional outcomes. This study examined therapy doses during the first year of stroke recovery and identified factors that predict rehabilitation therapy dose. METHODS: Adults with new radiologically confirmed stroke were enrolled 2 to 10 days after stroke onset at 28 acute care hospitals across the United States. Following an initial assessment during acute hospitalization, the number of physical therapy, occupational therapy, and speech therapy sessions were determined at visits occurring 3, 6, and 12 months following stroke. Negative binomial regression examined whether clinical and demographic factors were associated with therapy counts. False discovery rate was used to correct for multiple comparisons. RESULTS: Of 763 patients enrolled during acute stroke admission, 510 were available for follow-up. Therapy counts were low overall, with most therapy delivered within the first 3 months; 35.0% of patients received no physical therapy; 48.8%, no occupational therapy, and 61.7%, no speech therapy. Discharge destination was significantly related to cumulative therapy; the percentage of patients discharged to an inpatient rehabilitation facility varied across sites, from 0% to 71%. Most demographic factors did not predict therapy dose, although Hispanic patients received a lower cumulative amount of physical therapy and occupational therapy. Acutely, the severity of clinical factors (grip strength and National Institutes of Health Stroke Scale score, as well as National Institutes of Health Stroke Scale subscores for aphasia and neglect) predicted higher subsequent therapy doses. Measures of impairment and function (Fugl-Meyer, modified Rankin Scale, and Stroke Impact Scale Activities of Daily Living) assessed 3 months after stroke also predicted subsequent cumulative therapy doses. CONCLUSIONS: Rehabilitative therapy doses during the first year poststroke are low in the United States. This is the first US-wide study to demonstrate that behavioral deficits predict therapy dose, with patients having more severe deficits receiving higher doses. Findings suggest directions for identifying groups at risk of receiving disproportionately low rehabilitation doses.

A Measure of Neural Function Provides Unique Insights into Behavioral Deficits in Acute Stroke.

BACKGROUND: Clinical and neuroimaging measures incompletely explain behavioral deficits in the acute stroke setting. We hypothesized that electroencephalography (EEG)-based measures of neural function would significantly improve prediction of acute stroke deficits. METHODS: Patients with acute stroke (n=50) seen in the emergency department of a university hospital from 2017 to 2018 underwent standard evaluation followed by a 3-minute recording of EEG at rest using a wireless, 17-electrode, dry-lead system. Artifacts in EEG recordings were removed offline and then spectral power was calculated for each lead pair. A primary EEG metric was DTABR, which is calculated as a ratio of spectral power: [(Delta*Theta)/(Alpha*Beta)]. Bivariate analyses and least absolute shrinkage and selection operator (LASSO) regression identified clinical and neuroimaging measures that best predicted initial National Institutes of Health Stroke Scale (NIHSS) score. Multivariable linear regression was then performed before versus after adding EEG findings to these measures, using initial NIHSS score as the dependent measure. RESULTS: Age, diabetes status, and infarct volume were the best predictors of initial NIHSS score in bivariate analyses, confirmed using LASSO regression. Combined in a multivariate model, these 3 explained initial NIHSS score (adjusted r2=0.47). Adding any of several different EEG measures to this clinical model significantly improved prediction; the greatest amount of additional variance was explained by adding contralesional DTABR (adjusted r2=0.60, P<0.001). CONCLUSIONS: EEG measures of neural function significantly add to clinical and neuroimaging for explaining initial NIHSS score in the acute stroke emergency department setting. A dry-lead EEG system can be rapidly and easily implemented. EEG contains information that may be useful early after stroke.

Cognitive Deficits After Stroke.

Cognition is a central feature of human existence and brain function. Cognitive deficits are common after stroke and may strongly impact functional outcome. Recent years have seen substantial advances in our understanding of cognitive functions in the healthy state, and this new body of knowledge promises to open new avenues for understanding and treating poststroke impairments, including cognitive deficits. The 5 reviews in this Focused Update from an international cast of experts provide excellent updates on cognitive syndromes that commonly contribute to poststroke disability: neglect, aphasia, apraxia, loss of executive function, and memory disorders. Cognitive impairment remains a major source of morbidity after stroke; these reviews approach this problem by considering clinical presentations, pathophysiology, measurement tools, and treatment approaches. In doing so, they highlight a number of key questions and critical gaps. A number of issues emerge as common across cognitive domains poststroke and are summarized herein. There is a need for improved methods to measure cognitive impairments, as well as for improved insights into pathophysiology of symptom onset and mechanisms of recovery after stroke, including validated biomarkers. These 5 state of the art summaries are sure to prove useful toward these goals.

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial.

BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke. OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury. METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS treatment by sex, age (≥62 years), time from stroke (>2 years), severity (baseline FMA-UE score >34), paretic side of body, country of enrollment (USA vs UK) and presence of cortical involvement of the index infarction. We assessed whether there was any interaction with treatment. FINDINGS: The primary outcome increased by 5.0 points (SD 4.4) in the VNS group and by 2.4 points (SD 3.8) in the Control group (P = .001, between group difference 2.6, 95% CI 1.03-4.2). The between group difference was similar across all subgroups and there were no significant treatment interactions. There was no important difference in rates of adverse events across subgroups. CONCLUSION: The response was similar across subgroups examined. The findings suggest that the effects of paired VNS observed in the VNS-REHAB trial are likely to be consistent in wide range of stroke survivors with moderate to severe upper extremity impairment.

Therapies Targeting Stroke Recovery.

Stroke recovery therapeutics include many classes of intervention and numerous treatment targets. Stroke is a very heterogeneous disease. As such, stroke recovery therapeutics benefit from a personalized medicine approach that considers intersubject differences, such as in infarct location or stroke severity, when assigning treatment. Prediction of treatment responders can be improved by incorporating biological measures, such as neural injury and neural function, as the bedside behavioral phenotype has an incomplete relationship with the biological events underlying stroke recovery. Another ramification of high variability between patients is the need to examine effects of restorative therapies in relation to dose, time poststroke, and stroke severity in clinical trials. For example, enrollment across a wide time interval poststroke or in a population with a very broad range of deficits means high variance across patients in the biological state of the brain. The doses of rehabilitation therapy being studied are often low; it takes substantial practice to acquire a skill in the healthy brain; this is more, not less, pronounced after a stroke. Recognition and treatment of poststroke depression represents a major unmet need. These points are considered in the context of a review of recent advances in stroke recovery therapeutics.