Michael A. Dimyan

Background: Repetitive task practice reduces mean upper extremity motor impairment in populations of patients with chronic stroke, but individual response is highly variable. A method to predict meaningful reduction in impairment in response to training based on biomarkers and other data collected prior to an intervention is needed to establish realistic rehabilitation goals and to effectively allocate resources. Objectives: To identify prognostic factors and better understand the biological substrate for reductions in arm impairment in response to repetitive task practice among patients with chronic (≥6 months) post-stroke hemiparesis. Methods: The intervention is a form of repetitive task practice using a combination of robot-assisted therapy and functional arm use in real-world tasks. Baseline measures include the Fugl-Meyer Assessment, Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, MRI, transcranial magnetic stimulation, kinematics, accelerometry, and genomic testing. Results: Mean increase in FM-UE was 4.6 ± 1.0 SE, median 2.5. Approximately one-third of participants had a clinically meaningful response to the intervention, defined as an increase in FM ≥ 5. The selected logistic regression model had a receiver operating curve with AUC = .988 (Std Error = .011, 95% Wald confidence limits: .967–1) showed little evidence of overfitting. Six variables that predicted response represented impairment, functional, and genomic measures. Conclusion: A simple weighted sum of 6 baseline factors can accurately predict clinically meaningful impairment reduction after outpatient intensive practice intervention in chronic stroke. Reduction of impairment may be a critical first step to functional improvement. Further validation and generalization of this model will increase its utility in clinical decision-making.

To develop a clinically useful patient-reported screening tool for health care providers to identify patients with spasticity in need of treatment regardless of etiology. Eleven spasticity experts participated in a modified Delphi panel and reviewed and revised 2 iterations of a screening tool designed to identify spasticity symptoms and impact on daily function and sleep. Spasticity expert panelists evaluated items pooled from existing questionnaires to gain consensus on the screening tool content. The study also included cognitive interviews of 20 patients with varying spasticity etiologies to determine if the draft screening tool was understandable and relevant to patients with spasticity. The Delphi panel reached an initial consensus on 21 of 47 items for the screening tool and determined that the tool should have no more than 11 to 15 items and a 1-month recall period for symptom and impact items. After 2 rounds of review, 13 items were selected and modified by the expert panelists. Most patients (n = 16 [80%]) completed the cognitive interview and interpreted the items as intended. Through the use of a Delphi panel and patient interviews, a 13-item spasticity screening tool was developed that will be practical and easy to use in routine clinical practice.

Motor impairment is a common symptom of stroke. Several processes, such as innate neuroplasticity, are considered to underlie gains in motor function after stroke. In this article, Dimyan and Cohen provide a review of neuroplasticity associated with poststroke motor impairment and highlight the latest experimental interventions being developed to manipulate neuroplasticity to enhance motor rehabilitation. Approximately one-third of patients with stroke exhibit persistent disability after the initial cerebrovascular episode, with motor impairments accounting for most poststroke disability. Exercise and training have long been used to restore motor function after stroke. Better training strategies and therapies to enhance the effects of these rehabilitative protocols are currently being developed for poststroke disability. The advancement of our understanding of the neuroplastic changes associated with poststroke motor impairment and the innate mechanisms of repair is crucial to this endeavor. Pharmaceutical, biological and electrophysiological treatments that augment neuroplasticity are being explored to further extend the boundaries of poststroke rehabilitation. Potential motor rehabilitation therapies, such as stem cell therapy, exogenous tissue engineering and brain–computer interface technologies, could be integral in helping patients with stroke regain motor control. As the methods for providing motor rehabilitation change, the primary goals of poststroke rehabilitation will be driven by the activity and quality of life needs of individual patients. This Review aims to provide a focused overview of neuroplasticity associated with poststroke motor impairment, and the latest experimental interventions being developed to manipulate neuroplasticity to enhance motor rehabilitation.

Motor impairments are a major cause of morbidity and disability after stroke. This article reviews evidence obtained using transcranial magnetic stimulation (TMS) that provides new insight into mechanisms of impaired motor control and disability. They briefly discuss the use of TMS in the diagnosis, prognosis, and therapy of poststroke motor disability. Particular emphasis is placed on TMS as a tool to explore mechanisms of neuroplasticity during spontaneous and treatment-induced recovery of motor function to develop more rational and clinically useful interventions for stroke rehabilitation.

The excitability of the human primary motor cortex (M1) as tested with transcranial magnetic stimulation (TMS) depends on its previous history of neural activity. Homeostatic plasticity might be one important physiological mechanism for the regulation of corticospinal excitability and synaptic plasticity. Although homeostatic plasticity has been demonstrated locally within M1, it is not known whether priming M1 could result in similar homeostatic effects in the homologous M1 of the opposite hemisphere. Here, we sought to determine whether down-regulating excitability (priming) in the right (R) M1 with 1-Hz repetitive transcranial magnetic stimulation (rTMS) changes the excitability-enhancing effect of intermittent theta burst stimulation (iTBS) applied over the homologous left (L) M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design with real or sham R M1 1-Hz TMS stimulation always preceding L M1 iTBS or sham by about 10 min. The primary outcome measure was corticospinal excitability in the L M1, as measured by recruitment curves (RCs). Secondary outcome measures included pinch force, simple reaction time, and tapping speed assessed in the right hand. The main finding of this study was that preconditioning R M1 with 1-Hz rTMS significantly decreased the excitability-enhancing effects of subsequent L M1 iTBS on RCs. Application of 1-Hz rTMS over R M1 alone and iTBS over L M1 alone resulted in increased RC in L M1 relative to sham interventions. The present findings are consistent with the hypothesis that homeostatic mechanisms operating across hemispheric boundaries contribute to regulate motor cortical function in the primary motor cortex.

Background and Purpose— Recent work demonstrated that application of peripheral nerve and cortical stimulation independently can induce modest improvements in motor performance in patients with stroke. The purpose of this study was to test the hypothesis that combining peripheral nerve stimulation (PNS) to the paretic hand with anodal direct current stimulation (tDCS) to the ipsilesional primary motor cortex (M1) would facilitate beneficial effects of motor training more than each intervention alone or sham (tDCS _Sham and PNS _Sham ). Methods— Nine chronic stroke patients completed a blinded crossover designed study. In separate sessions, we investigated the effects of single applications of PNS+tDCS, PNS+tDCS _Sham , tDCS+PNS _Sham , and PNS _Sham +tDCS _Sham before motor training on the ability to perform finger motor sequences with the paretic hand. Results— PNS+tDCS resulted in a 41.3% improvement in the number of correct key presses relative to PNS _Sham +tDCS _Sham , 15.4% relative to PNS+tDCS _Sham , and 22.7% relative to tDCS+PNS _Sham . These performance differences were maintained 1 and 6 days after the end of the training. Conclusions— These results indicate that combining PNS with tDCS can facilitate the beneficial effects of training on motor performance beyond levels reached with each intervention alone, a finding of relevance for the neurorehabilitation of motor impairments after stroke.