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ObjectiveTo evaluate the effect of intensive rehabilitation on the modified Rankin Scale (mRS), a measure of activities limitation commonly used in acute stroke studies, and to define the specific changes in body structure/function (motor impairment) most related to mRS gains.MethodsPatients were enrolled >90 days poststroke. Each was evaluated before and 30 days after a 6-week course of daily rehabilitation targeting the arm. Activity gains, measured using the mRS, were examined and compared to body structure/function gains, measured using the Fugl-Meyer (FM) motor scale. Additional analyses examined whether activity gains were more strongly related to specific body structure/function gains.ResultsAt baseline (160 ± 48 days poststroke), patients (n = 77) had median mRS score of 3 (interquartile range, 2-3), decreasing to 2 [2-3] 30 days posttherapy (p < 0.0001). Similarly, the proportion of patients with mRS score ≤2 increased from 46.8% at baseline to 66.2% at 30 days posttherapy (p = 0.015). These findings were accounted for by the mRS score decreasing in 24 (31.2%) patients. Patients with a treatment-related mRS score improvement, compared to those without, had similar overall motor gains (change in total FM score, p = 0.63). In exploratory analysis, improvement in several specific motor impairments, such as finger flexion and wrist circumduction, was significantly associated with higher likelihood of mRS decrease.ConclusionsIntensive arm motor therapy is associated with improved mRS in a substantial fraction (31.2%) of patients. Exploratory analysis suggests specific motor impairments that might underlie this finding and may be optimal targets for rehabilitation therapies that aim to reduce activities limitations.Clinical trialClinicaltrials.gov identifier: NCT02360488.Classification of evidenceThis study provides Class III evidence that for patients >90 days poststroke with persistent arm motor deficits, intensive arm motor therapy improved mRS in a substantial fraction (31.2%) of patients.

ImportanceMany patients receive suboptimal rehabilitation therapy doses after stroke owing to limited access to therapists and difficulty with transportation, and their knowledge about stroke is often limited. Telehealth can potentially address these issues.ObjectivesTo determine whether treatment targeting arm movement delivered via a home-based telerehabilitation (TR) system has comparable efficacy with dose-matched, intensity-matched therapy delivered in a traditional in-clinic (IC) setting, and to examine whether this system has comparable efficacy for providing stroke education.Design, setting, and participantsIn this randomized, assessor-blinded, noninferiority trial across 11 US sites, 124 patients who had experienced stroke 4 to 36 weeks prior and had arm motor deficits (Fugl-Meyer [FM] score, 22-56 of 66) were enrolled between September 18, 2015, and December 28, 2017, to receive telerehabilitation therapy in the home (TR group) or therapy at an outpatient rehabilitation therapy clinic (IC group). Primary efficacy analysis used the intent-to-treat population.InterventionsParticipants received 36 sessions (70 minutes each) of arm motor therapy plus stroke education, with therapy intensity, duration, and frequency matched across groups.Main outcomes and measuresChange in FM score from baseline to 4 weeks after end of therapy and change in stroke knowledge from baseline to end of therapy.ResultsA total of 124 participants (34 women and 90 men) had a mean (SD) age of 61 (14) years, a mean (SD) baseline FM score of 43 (8) points, and were enrolled a mean (SD) of 18.7 (8.9) weeks after experiencing a stroke. Among those treated, patients in the IC group were adherent to 33.6 of the 36 therapy sessions (93.3%) and patients in the TR group were adherent to 35.4 of the 36 assigned therapy sessions (98.3%). Patients in the IC group had a mean (SD) FM score change of 8.36 (7.04) points from baseline to 30 days after therapy (P

Many different measures have been found to be related to behavioral outcome after stroke. Preclinical studies emphasize the importance of brain injury and neural function. However, the measures most important to human outcomes remain uncertain, in part because studies often examine one measure at a time or enroll only mildly impaired patients. The current study addressed this by performing multimodal evaluation in a heterogeneous population. Patients (n = 36) with stable arm paresis 3-6 months post-stroke were assessed across 6 categories of measures related to stroke outcome: demographics/medical history, cognitive/mood status, genetics, neurophysiology, brain injury, and cortical function. Multivariate modeling identified measures independently related to an impairment-based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1) identifying measures related to disability (modified Rankin Scale score), describing independence in daily functions and (2) using only patients with mild deficits. Across patients, greater impairment was related to measures of injury (reduced corticospinal tract integrity) and neurophysiology (absence of motor evoked potential). In contrast, (1) greater disability was related to greater injury and poorer cognitive status (MMSE score) and (2) among patients with mild deficits, greater impairment was related to cortical function (greater contralesional motor/premotor cortex activation). Impairment after stroke is most related to injury and neurophysiology, consistent with preclinical studies. These relationships vary according to the patient subgroup or the behavioral endpoint studied. One potential implication of these results is that choice of biomarker or stratifying variable in a clinical stroke study might vary according to patient characteristics.

Many different measures have been found to be related to behavioral outcome after stroke. Preclinical studies emphasize the importance of brain injury and neural function. However, the measures most important to human outcomes remain uncertain, in part because studies often examine one measure at a time or enroll only mildly impaired patients. The current study addressed this by performing multimodal evaluation in a heterogeneous population. Patients (n = 36) with stable arm paresis 3-6 months post-stroke were assessed across 6 categories of measures related to stroke outcome: demographics/medical history, cognitive/mood status, genetics, neurophysiology, brain injury, and cortical function. Multivariate modeling identified measures independently related to an impairment-based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1) identifying measures related to disability (modified Rankin Scale score), describing independence in daily functions and (2) using only patients with mild deficits. Across patients, greater impairment was related to measures of injury (reduced corticospinal tract integrity) and neurophysiology (absence of motor evoked potential). In contrast, (1) greater disability was related to greater injury and poorer cognitive status (MMSE score) and (2) among patients with mild deficits, greater impairment was related to cortical function (greater contralesional motor/premotor cortex activation). Impairment after stroke is most related to injury and neurophysiology, consistent with preclinical studies. These relationships vary according to the patient subgroup or the behavioral endpoint studied. One potential implication of these results is that choice of biomarker or stratifying variable in a clinical stroke study might vary according to patient characteristics.

Robots can improve motor status after stroke with certain advantages, but there has been less emphasis to date on robotic developments for the hand. The goal of this study was to determine whether a hand-wrist robot would improve motor function, and to evaluate the specificity of therapy effects on brain reorganization. Subjects with chronic stroke producing moderate right arm/hand weakness received 3 weeks therapy that emphasized intense active movement repetition as well as attention, speed, force, precision and timing, and included virtual reality games. Subjects initiated hand movements. If necessary, the robot completed movements, a feature available at all visits for seven of the subjects and at the latter half of visits for six of the subjects. Significant behavioural gains were found at end of treatment, for example, in Action Research Arm Test (34 +/- 20 to 38 +/- 19, P< 0.0005) and arm motor Fugl-Meyer score (45 +/- 10 to 52 +/- 10, P < 0.0001). Results suggest greater gains for subjects receiving robotic assistance in all sessions as compared to those receiving robotic assistance in half of sessions. The grasp task practiced during robotic therapy, when performed during functional MRI, showed increased sensorimotor cortex activation across the period of therapy, while a non-practiced task, supination/pronation, did not. A robot-based therapy showed improvements in hand motor function after chronic stroke. Reorganization of motor maps during the current therapy was task-specific, a finding useful when considering generalization of rehabilitation therapy.

Robots can improve motor status after stroke with certain advantages, but there has been less emphasis to date on robotic developments for the hand. The goal of this study was to determine whether a hand-wrist robot would improve motor function, and to evaluate the specificity of therapy effects on brain reorganization. Subjects with chronic stroke producing moderate right arm/hand weakness received 3 weeks therapy that emphasized intense active movement repetition as well as attention, speed, force, precision and timing, and included virtual reality games. Subjects initiated hand movements. If necessary, the robot completed movements, a feature available at all visits for seven of the subjects and at the latter half of visits for six of the subjects. Significant behavioural gains were found at end of treatment, for example, in Action Research Arm Test (34 +/- 20 to 38 +/- 19, P< 0.0005) and arm motor Fugl-Meyer score (45 +/- 10 to 52 +/- 10, P < 0.0001). Results suggest greater gains for subjects receiving robotic assistance in all sessions as compared to those receiving robotic assistance in half of sessions. The grasp task practiced during robotic therapy, when performed during functional MRI, showed increased sensorimotor cortex activation across the period of therapy, while a non-practiced task, supination/pronation, did not. A robot-based therapy showed improvements in hand motor function after chronic stroke. Reorganization of motor maps during the current therapy was task-specific, a finding useful when considering generalization of rehabilitation therapy.

Background and purposeIn the rim of tissue surrounding a cortical infarct, animal studies have described an increase in a number of growth-related processes that likely contribute to behavioral recovery. The current study hypothesized that in patients with good outcome after stroke, brain activation in peri-infarct tissue would be greater than normal.MethodsIn 15 patients with good recovery chronically after ischemic cortical stroke, activation within peri-infarct brain tissue was directly compared with activation within the same brain tissue of 13 control subjects.ResultsAlthough most patients did show activation within peri-infarct tissues, their activation compared with controls was reduced rather than increased. Evaluation of the T2*-weighted images underlying functional MRI mapping disclosed a significant gradient of increased T2* signal in peri-infarct tissues, likely attributable to tissue changes such as gliosis.ConclusionsAmong well-recovered stroke patients, cortical activation is present in the area surrounding a cortical infarct but is smaller than normal. A baseline derangement of the T2*-weighted signal underlying functional MRI (fMRI) is also present in this area, which might influence interpretation of fMRI findings. The relationship between increased tissue T2* signal and fMRI activation is not known and requires further study.

Background and purposeIn the rim of tissue surrounding a cortical infarct, animal studies have described an increase in a number of growth-related processes that likely contribute to behavioral recovery. The current study hypothesized that in patients with good outcome after stroke, brain activation in peri-infarct tissue would be greater than normal.MethodsIn 15 patients with good recovery chronically after ischemic cortical stroke, activation within peri-infarct brain tissue was directly compared with activation within the same brain tissue of 13 control subjects.ResultsAlthough most patients did show activation within peri-infarct tissues, their activation compared with controls was reduced rather than increased. Evaluation of the T2*-weighted images underlying functional MRI mapping disclosed a significant gradient of increased T2* signal in peri-infarct tissues, likely attributable to tissue changes such as gliosis.ConclusionsAmong well-recovered stroke patients, cortical activation is present in the area surrounding a cortical infarct but is smaller than normal. A baseline derangement of the T2*-weighted signal underlying functional MRI (fMRI) is also present in this area, which might influence interpretation of fMRI findings. The relationship between increased tissue T2* signal and fMRI activation is not known and requires further study.