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      Systematic Review of Parameters of Stimulation, Clinical Trial Design Characteristics, and Motor Outcomes in Non-Invasive Brain Stimulation in Stroke

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          Abstract

          Introduction/Objectives: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation are two powerful non-invasive neuromodulatory therapies that have the potential to alter and evaluate the integrity of the corticospinal tract. Moreover, recent evidence has shown that brain stimulation might be beneficial in stroke recovery. Therefore, investigating and investing in innovative therapies that may improve neurorehabilitative stroke recovery are next steps in research and development. Participants/Materials and Methods: This article presents an up-to-date systematic review of the treatment effects of rTMS and tDCS on motor function. A literary search was conducted, utilizing search terms “stroke” and “transcranial stimulation.” Items were excluded if they failed to: (1) include stroke patients, (2) study motor outcomes, or (3) include rTMS/tDCS as treatments. Other exclusions included: (1) reviews, editorials, and letters, (2) animal or pediatric populations, (3) case reports or sample sizes ≤2 patients, and (4) primary outcomes of dysphagia, dysarthria, neglect, or swallowing. Results: Investigation of PubMed English Database prior to 01/01/2012 produced 695 applicable results. Studies were excluded based on the aforementioned criteria, resulting in 50 remaining studies. They included 1314 participants (1282 stroke patients and 32 healthy subjects) evaluated by motor function pre- and post-tDCS or rTMS. Heterogeneity among studies’ motor assessments was high and could not be accounted for by individual comparison. Pooled effect sizes for the impact of post-treatment improvement revealed consistently demonstrable improvements after tDCS and rTMS therapeutic stimulation. Most studies provided limited follow-up for long-term effects. Conclusion: It is apparent from the available studies that non-invasive stimulation may enhance motor recovery and may lead to clinically meaningful functional improvements in the stroke population. Only mild to no adverse events have been reported. Though results have been positive results, the large heterogeneity across articles precludes firm conclusions.

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          Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke.

          Stroke is a leading cause of adult motor disability. Despite recent progress, recovery of motor function after stroke is usually incomplete. This double blind, Sham-controlled, crossover study was designed to test the hypothesis that non-invasive stimulation of the motor cortex could improve motor function in the paretic hand of patients with chronic stroke. Hand function was measured using the Jebsen-Taylor Hand Function Test (JTT), a widely used, well validated test for functional motor assessment that reflects activities of daily living. JTT measured in the paretic hand improved significantly with non-invasive transcranial direct current stimulation (tDCS), but not with Sham, an effect that outlasted the stimulation period, was present in every single patient tested and that correlated with an increment in motor cortical excitability within the affected hemisphere, expressed as increased recruitment curves (RC) and reduced short-interval intracortical inhibition. These results document a beneficial effect of non-invasive cortical stimulation on a set of hand functions that mimic activities of daily living in the paretic hand of patients with chronic stroke, and suggest that this interventional strategy in combination with customary rehabilitative treatments may play an adjuvant role in neurorehabilitation.
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            Non-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke?

            Motor impairment resulting from chronic stroke can have extensive physical, psychological, financial, and social implications despite available neurorehabilitative treatments. Recent studies in animals showed that direct epidural stimulation of the primary motor cortex surrounding a small infarct in the lesioned hemisphere (M1(lesioned hemisphere)) elicits improvements in motor function. In human beings, proof of principle studies from different laboratories showed that non-invasive transcranial magnetic stimulation and direct current stimulation that upregulate excitability within M1(lesioned hemisphere) or downregulate excitability in the intact hemisphere (M1(intact hemisphere)) results in improvement in motor function in patients with stroke. Possible mechanisms mediating these effects can include the correction of abnormally persistent interhemispheric inhibitory drive from M1(intact hemisphere) to M1(lesioned hemisphere) in the process of generation of voluntary movements by the paretic hand, a disorder correlated with the magnitude of impairment. In this paper we review these mechanistically oriented interventional approaches. WHAT NEXT?: These findings suggest that transcranial magnetic stimulation and transcranial direct current stimulation could develop into useful adjuvant strategies in neurorehabilitation but have to be further assessed in multicentre clinical trials.
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              Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients.

              Motor recovery after stroke depends on the integrity of ipsilesional motor circuits and interactions between the ipsilesional and contralesional hemispheres. In this sham-controlled randomized trial, we investigated whether noninvasive modulation of regional excitability of bilateral motor cortices in combination with physical and occupational therapy improves motor outcome after stroke. Twenty chronic stroke patients were randomly assigned to receive 5 consecutive sessions of either 1) bihemispheric transcranial direct current stimulation (tDCS) (anodal tDCS to upregulate excitability of ipsilesional motor cortex and cathodal tDCS to downregulate excitability of contralesional motor cortex) with simultaneous physical/occupational therapy or 2) sham stimulation with simultaneous physical/occupational therapy. Changes in motor impairment (Upper Extremity Fugl-Meyer) and motor activity (Wolf Motor Function Test) assessments were outcome measures while functional imaging parameters were used to identify neural correlates of motor improvement. The improvement of motor function was significantly greater in the real stimulation group (20.7% in Fugl-Meyer and 19.1% in Wolf Motor Function Test scores) when compared to the sham group (3.2% in Fugl-Meyer and 6.0% in Wolf Motor Function Test scores). The effects outlasted the stimulation by at least 1 week. In the real-stimulation group, stronger activation of intact ipsilesional motor regions during paced movements of the affected limb were found postintervention whereas no significant activation changes were seen in the control group. The combination of bihemispheric tDCS and peripheral sensorimotor activities improved motor functions in chronic stroke patients that outlasted the intervention period. This novel approach may potentiate cerebral adaptive processes that facilitate motor recovery after stroke. This study provides Class I evidence that for adult patients with ischemic stroke treated at least 5 months after their first and only stroke, bihemispheric tDCS and simultaneous physical/occupational therapy given over 5 consecutive sessions significantly improves motor function as measured by the Upper Extremity Fugl-Meyer assessment (raw change treated 6.1 ± 3.4, sham 1.2 ± 1.0).
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                Author and article information

                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                12 November 2012
                2012
                : 3
                : 88
                Affiliations
                [1] 1Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, Harvard Medical School Boston, MA, USA
                [2] 2Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School Boston, MA, USA
                [3] 3Division of Neurology, Santa Casa de São Paulo Medical School São Paulo, Brazil
                [4] 4Hospital das Clínicas da Faculdade de Medicina, University of São Paulo São Paulo, Brazil
                [5] 5Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, MA, USA
                Author notes

                Edited by: Andre R. Brunoni, Universidade de São Paulo, Brazil

                Reviewed by: Kátia K. Monte-Silva, Federal University of Pernambuco, Brazil; Pedro Shiozawa, Santa Casa de Misericórdia de São Paulo, Brazil

                *Correspondence: Felipe Fregni, Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, 125 Nashua Street #727, Boston, MA 02114, USA. e-mail: fregni.felipe@ 123456mgh.harvard.edu ; http://neuromodulationlab.org/

                Marcel Simis and Debora Duarte Macea have contributed equally to this work.

                This article was submitted to Frontiers in Neuropsychiatric Imaging and Stimulation, a specialty of Frontiers in Psychiatry.

                Article
                10.3389/fpsyt.2012.00088
                3495265
                23162477
                e928d9a2-1fbf-461f-853c-64a6cee61bc0
                Copyright © 2012 Adeyemo, Simis, Macea and Fregni.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 31 May 2012
                : 22 September 2012
                Page count
                Figures: 3, Tables: 4, Equations: 0, References: 122, Pages: 27, Words: 18690
                Categories
                Psychiatry
                Review Article

                Clinical Psychology & Psychiatry
                stroke,noninvasive brain stimulation,motor,transcranial magnetic stimulation,repetitive transcranial magnetic stimulation,transcranial direct current stimulation

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