Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

BACKGROUND: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. METHODS: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 µs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. FINDINGS: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. INTERPRETATION: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. FUNDING: MicroTransponder.

Estimated Regional White Matter Hyperintensity Burden, Resting State Functional Connectivity, and Cognitive Functions in Older Adults.

OBJECTIVE: White matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural, and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: Fifty-eight cognitively-healthy older adults. MEASUREMENTS: Tasks of cognitive control and memory, structural MRI, and resting state fMRI. We estimated the disruption to white matter fiber tracts from WMH and its impact on gray matter regions in the cortical and subcortical frontoparietal network, default mode network, and ventral attention network by overlaying each subject's WMH mask on a normative tractogram dataset. We calculated RSFC between nodes in those same networks. We evaluated the interaction of regional WMH burden and RSFC in predicting cognitive control and memory. RESULTS: The interaction of estimated regional WMH burden and RSFC in cortico-striatal regions of the default mode network and frontoparietal network was associated with delayed recall. Models predicting working memory, cognitive inhibition, and set-shifting were not significant. CONCLUSION: Findings highlight the role of network-level structural and functional alterations in resting state networks that are related to WMH and impact memory in older adults.

The Structural and Functional Neuroanatomy of Post-Stroke Depression and Executive Dysfunction: A Review of Neuroimaging Findings and Implications for Treatment.

Post-stroke depression and executive dysfunction co-occur and are highly debilitating. Few treatments alleviate both depression and executive dysfunction after stroke. Understanding the brain network changes underlying post-stroke depression with executive dysfunction can inform the development of targeted and efficacious treatment. In this review, we synthesize neuroimaging findings in post-stroke depression and post-stroke executive dysfunction and highlight the network commonalities that may underlie this comorbidity. Structural and functional alterations in the cognitive control network, salience network, and default mode network are associated with depression and executive dysfunction after stroke. Specifically, post-stroke depression and executive dysfunction are both linked to changes in intrinsic functional connectivity within resting state networks, functional over-connectivity between the default mode and salience/cognitive control networks, and reduced cross-hemispheric frontoparietal functional connectivity. Cognitive training and noninvasive brain stimulation targeted at these brain network abnormalities and specific clinical phenotypes may help advance treatment for post-stroke depression with executive dysfunction.

Detecting change in community participation with the Enfranchisement scale of the community participation indicators.

OBJECTIVE: This study determined the sensitivity to change of the Enfranchisement scale of the Community Participation Indicators in people with stroke. DATA SOURCES: We analyzed data from two studies of participants with stroke: an intervention study and an observational study. MAIN MEASURES: The Enfranchisement Scale contains two subscales: the Importance subscale (feeling valued by and contributing to the community; range: 14-70) and the Control subscale (choice and control: range: 13-64). DATA ANALYSIS: Assessments were administered 6 months apart. We calculated minimum detectable change and minimal clinically important difference. RESULTS: The Control subscale analysis included 121 participants with a mean age of 61.2 and mild-moderate disability (Functional Independence Measure, mean = 97.9, SD = 24.7). On the Control subscale, participants had a mean baseline score of 51.4 (SD = 10.4), and little mean change (1.3) but with large variation in change scores (SD = 11.5). We found a minimum detectable change of 9 and a minimum clinically important difference of 6. The Importance subscale analysis included 116 participants with a mean age of 60.7 and mild-moderate disability (Functional Independence Measure, mean = 98.9, SD = 24.5). On the Importance subscale, participants had a mean baseline score of 44.1 (SD = 12.7), and again demonstrated little mean change (1.08) but with large variation in change scores (SD = 12.6). We found a minimum detectable change of 11 and a minimum clinically important difference 7. CONCLUSIONS: The Control subscale required 9 points of change, and the Importance subscale required 11 points of change, to achieve statistically and clinically meaningful changes, suggesting adequate sensitivity to change.

Changes in the Activity Measure for Post-Acute Care Domains in Persons With Stroke During the First Year After Discharge From Inpatient Rehabilitation.

OBJECTIVE: To describe functional changes after inpatient stroke rehabilitation using the Activity Measure for Post-Acute Care (AM-PAC), an assessment measure sensitive to change and with a low risk of ceiling effect. DESIGN: Retrospective, longitudinal cohort study. SETTING: Inpatient rehabilitation unit of an urban academic medical center. PARTICIPANTS: Among 433 patients with stroke admitted from 2012-2016, a total of 269 (62%) were included in our database and 89 of 269 patients (33.1%) discharged from inpatient stroke rehabilitation had complete data. Patients with and without complete data were very similar. The group had a mean age of 68.0±14.2 years, National Institutes of Health Stroke Score of 8.0±8.0, and rehabilitation length of stay of 14.7±7.4 days, with 84% having an ischemic stroke and 22.5% having a recurrent stroke. INTERVENTION: None. MAIN OUTCOME MEASURES: Changes in function across the first year after discharge (DC) were measured in a variety of ways. Continuous mean scores for the basic mobility (BM), daily activity (DA), and applied cognitive domains of the AM-PAC were calculated at and compared between inpatient DC and 6 (6M) and 12 months (12M) post DC. Categorical changes among individuals were classified as "improved," "unchanged," or "declined" between the 3 time points based on the minimal detectable change, (estimated) minimal clinically important difference, and a change ≥1 AM-PAC functional stage (FS). RESULTS: For the continuous analyses, the Friedman test was significant for all domains (P≤.002), with Wilcoxon signed-rank test significant for all domains from DC to 6M (all P<.001) but with no change in BM and DA between 6M and 12M (P>.60) and a decline in applied cognition (P=.002). Despite group improvements from DC to 6M, for categorical changes at an individual level 10%-20% declined and 50%-70% were unchanged. Despite insignificant group differences from 6M-12M, 15%-25% improved and 20%-30% declined in the BM and DA domains. CONCLUSIONS: Despite group gains from DC to 6M and an apparent "plateau" after 6M post stroke, there was substantial heterogeneity at an individual level. Our results underscore the need to consider individual-level outcomes when evaluating progress or outcomes in stroke rehabilitation.

Subgroups Defined by the Montreal Cognitive Assessment Differ in Functional Gain During Acute Inpatient Stroke Rehabilitation.

OBJECTIVE: To validate subgroups of cognitive impairment on the Montreal Cognitive Assessment (MoCA)-defined as normal (score of 25-30), mildly impaired (score of 20-24), and moderately impaired (score less than 19)-by determining whether they differ in rehabilitation gain during inpatient stroke rehabilitation. DESIGN: Observational study. Linear regression models were conducted and predictors included MoCA subgroups and relevant baseline demographic and clinical covariates. Separate models included the cognitive subscale of the FIM instrument as a predictor. SETTING: Inpatient rehabilitation facility of an urban, academic medical center. PARTICIPANTS: Inpatients (N=334) with mild-moderate strokes who were administered the MoCA on admission. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The mean relative functional gain (mRFG) and mean relative functional efficiency (mRFE, which adjusts for length of stay) on the FIM total. RESULTS: MoCA subgroups significantly predicted mRFG and mRFE after accounting for age, sex, education, stroke severity, and recurrent vs first stroke. The normal group exhibited greater mRFG and mRFE than the mildly impaired group, while the moderately impaired group had significantly worse mRFG and mRFE than the mildly impaired group. The moderately impaired group had a significantly smaller proportion of individuals who made a clinically meaningful change on the total-FIM than the mildly impaired and normal groups. MoCA subgroups better accounted for mRFG and mRFE than a standard-of-care cognitive assessment (cognitive-FIM). CONCLUSIONS: Use of MoCA-defined subgroups can assist providers in predicting functional gain in survivors of stroke being treated in inpatient rehabilitation.

The diagnostic accuracy of the Montreal Cognitive Assessment in inpatient stroke rehabilitation.

The Montreal Cognitive Assessment (MoCA) is a commonly used screening measure for cognitive impairment; however, the diagnostic accuracy and optimal cutoff points in inpatients with mild stroke severity is unknown. We examined the diagnostic accuracy of the MoCA in an acute inpatient stroke rehabilitation unit (N = 95). The criterion neuropsychological assessment was the 30-minute National Institute of Neurological Disorders and Stroke-Canadian Stroke Network battery, modified to include the Symbol-Digit Modalities Test and Trail Making Test A & B. The MoCA had moderately strong diagnostic accuracy in receiver operating curve analyses, with areas under the curve ranging from .80 to .89 depending on the threshold for defining cognitive impairment. Sensitivity ranged from .72 to .87, and was generally greater than specificity, which ranged from .60 to .81. The optimal cutoff on the MoCA for detecting mild or greater cognitive impairment was <25/30. The optimal cutoff using more conservative definitions of cognitive impairment ranged from <23-24/30. Exploratory analyses of MoCA subgroups ("normal," "mildly impaired," and "functionally impaired") differed in the frequency and magnitude of impairment on the criterion neuropsychological assessment. These findings inform the clinical use of the MoCA in individuals with mild stroke in an inpatient rehabilitation setting.

Feasibility of an Electromyography-Triggered Hand Robot for People After Chronic Stroke.

IMPORTANCE: Effective treatment of the affected hand after stroke is crucial for improved functional independence and recovery. OBJECTIVE: To determine the feasibility and clinical utility of an electromyography-triggered hand robot. DESIGN: Single-group repeated-measures design. Participants completed training 3×/wk for 6 wk. Feasibility data included participant feedback, adverse events, and compliance rates. Upper extremity outcomes were collected at baseline, discharge, and 6-wk follow-up. SETTING: Outpatient clinic. PARTICIPANTS: Twelve stroke survivors at least 6 mo poststroke living in the community. INTERVENTION: Eighteen sessions of intensive robotic hand therapy over 6 wk. Each 60-min treatment session was personalized to match the participant's ability. OUTCOMES AND MEASURES: Arm Motor Ability Test (AMAT), Stroke Impact Scale Hand subscale (SIS-H), Stroke Upper Limb Capacity Scale (SULCS), Fugl-Meyer Assessment, Box and Block Test, and dynamometer. RESULTS: All participants completed the training phase. Mild skin pinching or rubbing at dorsal proximal interphalangeal joint and proximal arm fatigue were the most common adverse events. Improvements in raw scores were achieved from baseline to discharge for all outcome measures, except the SULCS. Participants significantly improved from baseline to discharge on the AMAT and the SIS-H, and improvements were maintained at 6-wk follow-up. CONCLUSION AND RELEVANCE: Robotic hand training was feasible, safe, and well tolerated. Participants reported and demonstrated improvements in functional use of the affected arm. Thirty percent of participants achieved clinically significant improvements on the AMAT. We recommend further study of the device in a larger study using the AMAT as a primary outcome measure. WHAT THIS ARTICLE ADDS: It is feasible and safe to implement a robotic hand training protocol for people with moderate to severe arm impairment in an outpatient setting. Robotic training may provide a viable option for this group to actively participate in intensive training of the distal hand.

Fully Implantable Peripheral Nerve Stimulation for Hemiplegic Shoulder Pain: A Multi-Site Case Series With Two-Year Follow-Up.

OBJECTIVE: To explore the feasibility and safety of a single-lead, fully implantable peripheral nerve stimulation system for the treatment of chronic shoulder pain in stroke survivors. PARTICIPANTS: Participants with moderate to severe shoulder pain not responsive to conservative therapies for six months. METHODS: During the trial phase, which included a blinded sham introductory period, a percutaneous single-lead peripheral nerve stimulation system was implanted to stimulate the axillary nerve of the affected shoulder. After a three-week successful trial, participants received an implantable pulse generator with an electrode placed to stimulate the axillary nerve of the affected shoulder. Outcomes included pain, pain interference, pain-free external rotation range of motion, quality of life, and safety. Participants were followed for 24 months. RESULTS: Twenty-eight participants underwent trial stimulation and five participants received an implantable pulse generator. The participants who received the implantable generator experienced an improvement in pain severity (p = 0.0002). All five participants experienced a 50% or greater pain reduction at 6 and 12 months, and four experienced at least a 50% reduction at 24 months. There was an improvement in pain interference (p < 0.0001). There was an improvement in pain-free external ROM (p = 0.003). There were no serious adverse events related to the device or to the procedure. CONCLUSIONS: This case series demonstrates the safety and efficacy of a fully implantable axillary PNS system for chronic HSP. Participants experienced reduction in pain, reduction in pain interference, and improved pain-free external rotation ROM. There were no serious adverse events associated with the system or the procedure.

Randomized Trial on the Effects of Attentional Focus on Motor Training of the Upper Extremity Using Robotics With Individuals After Chronic Stroke.

OBJECTIVE: To compare the long-term effects of external focus (EF) and internal focus (IF) of attention after 4 weeks of arm training. DESIGN: Randomized, repeated-measures, mixed analysis of variance. SETTING: Outpatient clinic. PARTICIPANTS: Individuals with stroke and moderate-to-severe arm impairment living in the community (N=33; withdrawals: n=3). INTERVENTIONS: Four-week arm training protocol on a robotic device (12 sessions). MAIN OUTCOME MEASURES: Joint independence, Fugl-Meyer Assessment, and Wolf Motor Function Test measured at baseline, discharge, and 4-week follow-up. RESULTS: There were no between-group effects for attentional focus. Participants in both groups improved significantly on all outcome measures from baseline to discharge and maintained those changes at 4-week follow-up regardless of group assignment (joint independence EF condition: F1.6,45.4=17.74; P<.0005; partial η2=.39; joint independence IF condition: F2,56=18.66; P<.0005; partial η2=.40; Fugl-Meyer Assessment: F2,56=27.83; P<.0005; partial η2=.50; Wolf Motor Function Test: F2,56=14.05; P<.0005; partial η2=.35). CONCLUSIONS: There were no differences in retention of motor skills between EF and IF participants 4 weeks after arm training, suggesting that individuals with moderate-to-severe arm impairment may not experience the advantages of an EF found in healthy individuals. Attentional focus is most likely not an active ingredient for retention of trained motor skills for individuals with moderate-to-severe arm impairment, whereas dosage and intensity of practice appear to be pivotal. Future studies should investigate the long-term effects of attentional focus for individuals with mild arm impairment.

Association Between 2 Measures of Cognitive Instrumental Activities of Daily Living and Their Relation to the Montreal Cognitive Assessment in Persons With Stroke.

OBJECTIVES: To explore the relation between a computer adaptive functional cognitive questionnaire and a performance-based measure of cognitive instrumental activities of daily living (C-IADL) and to determine whether the Montreal Cognitive Assessment (MoCA) at admission can identify those with C-IADL difficulties at discharge. DESIGN: Prospective cohort study. SETTING: Acute inpatient rehabilitation unit of an academic medical center. PARTICIPANTS: Inpatients (N=148) with a diagnosis of stroke (mean age, 68y; median, 13d poststroke) who had mild cognitive and neurological deficits. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission cognitive status was assessed by the MoCA. C-IADL at discharge was assessed by the Executive Function Performance Test (EFPT) bill paying task and Activity Measure of Post-Acute Care (AM-PAC) Applied Cognition scale. RESULTS: Greater cognitive impairment on the MoCA was associated with more assistance on the EFPT bill paying task (ρ=-.63; P<.01) and AM-PAC Applied Cognition scale (ρ=-.43; P<.01). This relation was nonsignificant for higher MoCA scores and EFPT bill paying task scores. The AM-PAC Applied Cognition scale and the EFPT bill paying task had low agreement in classifying functional performance (Cohen's κ=.20). A receiver operating characteristic curve identified optimal MoCA cutoff scores of 20 and 21 for classifying EFPT bill paying task status and AM-PAC Applied Cognition scale status, respectively. For values above 20 and 21, sensitivity increased whereas specificity decreased for classifying functional deficits. Approximately one third of the participants demonstrated C-IADL deficits on at least 1 C-IADL measure at discharge despite having a MoCA score of ≥26 at admission. CONCLUSIONS: Questionnaire and performance-based methods of assessment appear to yield different estimates of C-IADL. Low MoCA scores (<20) are more likely to identify those with C-IADL deficits on the EFPT bill paying task. The results suggest that C-IADL should be assessed in those who have mild or no cognitive difficulties at admission.

Multimodal therapy and use of adjunctive therapies to BoNT-A in spasticity management: defining terminology to help enhance spasticity treatment.

Spasticity management should be provided within the context of a comprehensive person-centered rehabilitation program. Furthermore, active goal setting for specific spasticity interventions is also important, with a well-established "more is better" approach. It is critical to consider adjunctive therapy and multimodal approaches if patients are not attaining their treatment goals. Often used interchangeably, there may be confusion between the terms adjunctive and multimodal therapy. Yet it is imperative to understand the differences between these approaches to achieve treatment goals in spasticity management. Addition of a secondary pharmacologic or non-pharmacologic treatment to optimize the efficacy of the initial modality, such as adding electrical stimulation or casting to BoNT-A, is considered an adjunctive therapy. Adjunctive therapy is time-specific and requires the added therapy be initiated within a specific period to enhance the primary treatment; usually within 2 weeks. Multimodal therapy is an integrated, patient-centric program of pharmacologic and non-pharmacologic strategies utilized in a concurrent/integrated or sequential manner to enhance the overall treatment effect across a variety of spasticity-associated impairments (e.g., neural and non-neural components). Moreover, within a multimodal approach, adjunctive therapy can be used to help enhance the treatment effect of one specific modality. The objectives of this paper are to clarify the differences between adjunctive and multimodal therapies, provide a brief evidence-based review of such approaches, and highlight clinical insights on selecting multimodal and adjunctive therapies in spasticity management.

Foot drop stimulation versus ankle foot orthosis after stroke: 30-week outcomes.

BACKGROUND AND PURPOSE: Drop foot after stroke may be addressed using an ankle foot orthosis (AFO) or a foot drop stimulator (FDS). The Functional Ambulation: Standard Treatment versus Electric Stimulation Therapy (FASTEST) trial was a multicenter, randomized, single-blinded trial comparing FDS and AFO for drop foot among people ≥ 3 months after stroke with gait speed ≤ 0.8 m/s. METHODS: Participants (n=197; 79 females and 118 males; 61.14 ± 11.61 years of age; time after stroke 4.55 ± 4.72 years) were randomized to 30 weeks of either FDS or a standard AFO. Eight dose-matched physical therapy sessions were provided to both groups during the first 6 weeks of the trial. RESULTS: There was significant improvement within both groups from baseline to 30 weeks in comfortable gait speed (95% confidence interval for mean change, 0.11-0.17 m/s for FDS and 0.12-0.18 m/s for AFO) and fast gait speed. However, no significant differences in gait speed were found in the between-group comparisons. Secondary outcomes (standard measures of body structure and function, activity, and participation) improved significantly in both groups, whereas user satisfaction was significantly higher in the FDS group than in the control group. CONCLUSIONS: Using either an FDS or an AFO for 30 weeks yielded clinically and statistically significant improvements in gait speed and other functional outcomes. User satisfaction was higher in the FDS group. Although both groups did receive intervention, this large clinical trial provides evidence that FDS or AFO with initial physical therapy sessions can provide a significant and clinically meaningful benefit even years after stroke. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01138995.

Stroke Rehabilitation and Motor Recovery.

OBJECTIVE: Up to 50% of the nearly 800,000 patients who experience a new or recurrent stroke each year in the United States fail to achieve full independence afterward. More effective approaches to enhance motor recovery following stroke are needed. This article reviews the rehabilitative principles and strategies that can be used to maximize post-stroke recovery. LATEST DEVELOPMENTS: Evidence dictates that mobilization should not begin prior to 24 hours following stroke, but detailed guidelines beyond this are lacking. Specific classes of potentially detrimental medications should be avoided in the early days poststroke. Patients with stroke who are unable to return home should be referred for evaluation to an inpatient rehabilitation facility. Research suggests that a substantial increase in both the dose and intensity of upper and lower extremity exercise is beneficial. A clinical trial supports vagus nerve stimulation as an adjunct to occupational therapy for motor recovery in the upper extremity. The data remain somewhat mixed as to whether robotics, transcranial magnetic stimulation, functional electrical stimulation, and transcranial direct current stimulation are better than dose-matched traditional exercise. No current drug therapy has been proven to augment exercise poststroke to enhance motor recovery. ESSENTIAL POINTS: Neurologists will collaborate with rehabilitation professionals for several months following a patient's stroke. Many questions still remain about the ideal exercise regimen to maximize motor recovery in patients poststroke. The next several years will likely bring a host of new research studies exploring the latest strategies to enhance motor recovery using poststroke exercise.

Feasibility and Acceptability of a Remotely Delivered Executive Function Intervention That Combines Computerized Cognitive Training and Metacognitive Strategy Training in Chronic Stroke.

Executive dysfunction after stroke is associated with limitations in daily activities and disability. Existing interventions for executive dysfunction show inconsistent transfer to everyday activities and require frequent clinic visits that can be difficult for patients with chronic mobility challenges to access. To address this barrier, we developed a telehealth-based executive function intervention that combines computerized cognitive training and metacognitive strategy. The goal of this study was to describe intervention development and to provide preliminary evidence of feasibility and acceptability in three individuals who completed the treatment protocol. The three study participants were living in the community and had experienced a stroke >6 months prior. We assessed satisfaction (Client Satisfaction Questionnaire-8 [CSQ-8]), credibility (Credibility and Expectancy Questionnaire), and feasibility (percent of sessions completed). All three subjects rated the treatment in the highest satisfaction category on the CSQ-8, found the treatment to be credible, and expected improvement. Participants completed a median of 96% of computerized cognitive training sessions and 100% of telehealth-delivered metacognitive strategy training sessions. Individuals with chronic stroke may find a remotely delivered intervention that combines computerized cognitive training and metacognitive strategy training to be feasible and acceptable. Further evaluation with larger samples in controlled trials is warranted.

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.

Ecosystem focused therapy in poststroke depression: a preliminary study.

OBJECTIVE: Poststroke depression (PSD) occurs in the context of abrupt, often catastrophic disability that finds the patient and his or her family unprepared. We developed the ecosystem focused therapy (EFT), a systematic intervention aimed to increase the PSD patient's and his or her ecosystem's abilities to address the "psychosocial storm" of PSD and utilize available treatments effectively and efficiently. This is a preliminary study of its efficacy. DESIGN: A total of 24 PSD patients were randomly assigned to receive weekly sessions of EFT or a comparison condition consisting of systematic Education on Stroke and Depression and their treatment for 12 weeks. RESULTS: Ecosystem Focused Therapy may be more efficacious than Education on Stroke and Depression in reducing depressive symptoms and signs, in leading to a higher remission rate, and in ameliorating disability in PSD. Reduction of disability in the early part of the trial mediated later improvement in depressive symptomatology. Similarly, reduction in depressive symptoms and signs early on mediated later improvement in disability. CONCLUSION: These encouraging findings require replication. Beyond its potential direct benefits in PSD, EFT may provide an appropriate context for efficient and timely administration of pharmacotherapy and of physical, speech, and occupational therapy thus maximizing their efficacy.

Recovery in glioblastoma multiforme during inpatient rehabilitation is equivalent in first versus repeat resection: A 10-year retrospective analysis.

BACKGROUND: Inpatient rehabilitation improves function in people with brain tumors, including glioblastoma multiforme (GBM) but there are limited data on the impact of multiple resections on outcomes. We hypothesize that outcomes will be more favorable for those patients with a single resection when compared to those with more than one resection. OBJECTIVE: To examine functional outcomes in inpatient rehabilitation for people with GBM who underwent one or more resections prior to admission. DESIGN: Retrospective analysis. SETTING: Inpatient rehabilitation unit within a large, urban, academic medical center. PARTICIPANTS: Patients who were admitted to our institution for the treatment of initial GBM or GBM recurrence necessitating surgical resection or repeat resection. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Total FIM Change, Total Functional Independence Measure (FIM) Efficiency, Motor and Cognitive FIM efficiency, and proportion discharged home. RESULTS: From 2006 to 2016, 94 persons with GBM were admitted. Eight were readmissions classified as "repeat" and another seven transferred to the medical floor and excluded. Of the 79 patients included, 56 were first and 23 second resections, with a group mean age of 62.7 + 12.2 years and were 51% male. On analysis of covariance, change in FIM score from admission to discharge was insignificant between groups, adjusted for age and acute care length of stay (17.1 vs. 17.4, F[1, 75] = 0.027, P = .871). Likewise, the proportion of home discharge was not significant between groups (chi-square, 75.0% vs. 78.3%, P = .758). CONCLUSIONS: Patients who have undergone second resections for GBM are reasonable candidates for admission to the inpatient rehabilitation units despite carrying a poor prognosis and having multiple exposures to surgical morbidity. Factors to take into account are that candidates considered for a second resection may be relatively younger or healthier and therefore may perform better from a functional standpoint. In addition, postoperative steroid administration may play a role in the similarities the authors noted. A larger, multicenter study should validate our findings (limited by sample size and a single location) and identify factors predicting a successful outcome.

Cognitive impairment predicts engagement in inpatient stroke rehabilitation.

Patient engagement during inpatient rehabilitation is an important component of rehabilitation therapy, as lower levels of engagement are associated with poorer outcomes. Cognitive deficits may impact patient engagement during inpatient stroke rehabilitation. Here, we assess whether patient performance on the cognitive tasks of the 30-min National Institute of Neurologic Disorders and Stroke - Canadian Stroke Network (NINDS-CSN) screening battery predicts engagement in inpatient stroke rehabilitation. Prospective data from 110 participants completing inpatient stroke rehabilitation at an academic medical center were utilized for the present analyses. Cognitive functioning was assessed at inpatient stroke rehabilitation admission using the NINDS-CSN cognitive battery. Patient engagement was evaluated at discharge from an inpatient rehabilitation unit using the Hopkins Rehabilitation Engagement Rating Scale. The results demonstrate that the NINDS-CSN cognitive battery, specifically subtests measuring executive functioning, attention and processing speed, predicts patient engagement in inpatient stroke rehabilitation. Cognitively impaired patients undergoing rehabilitation may benefit from modifications and interventions to increase engagement and improve functional outcomes.

Discharge Rehabilitation Measures Predict Activity Limitations in Patients With Stroke 6 Months After Inpatient Rehabilitation.

OBJECTIVE: The aim of this study was to identify rehabilitation measures at discharge from acute inpatient stroke rehabilitation that predict activity limitations at 6 mos postdischarge. DESIGN: This is a retrospective analysis of a prospective, longitudinal, observational cohort study. It was conducted in an acute inpatient rehabilitation unit at an urban, academic medical center. Activity limitations in patients ( N = 141) with stroke of mild-moderate severity were assessed with the activity measure for post-acute care at inpatient stroke rehabilitation discharge and 6-mo follow-up. Rehabilitation measures at discharge were investigated as predictors for activity limitations at 6 mos. RESULTS: Measures of balance (Berg Balance Scale), functional limitations in motor-based activities (functional independence measure-motor subscore), and motor impairment (motricity index), in addition to discharge activities measure for post-acute care scores, strongly predicted activity limitations in basic mobility and daily activities at 6 mos (51% and 41% variance explained, respectively). Functional limitations in cognition (functional independence measure-cognitive subscore) and executive function impairment (Trail Making Test-part B), in addition to the discharge activities measure for post-acute care score, modestly predicted limitations in cognitively based daily activities at 6 mos (12% of variance). CONCLUSIONS: Standardized rehabilitation measures at inpatient stroke rehabilitation discharge can predict future activity limitations, which may improve prediction of outcome post-stroke and aid in postdischarge treatment planning.