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      Repetitive transcranial magnetic stimulation in stroke rehabilitation: review of the current evidence and pitfalls

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          Abstract

          Acute brain ischemia causes changes in several neural networks and related cortico-subcortical excitability, both in the affected area and in the apparently spared contralateral hemisphere. The modulation of these processes through modern techniques of noninvasive brain stimulation, namely repetitive transcranial magnetic stimulation (rTMS), has been proposed as a viable intervention that could promote post-stroke clinical recovery and functional independence. This review provides a comprehensive summary of the current evidence from the literature on the efficacy of rTMS applied to different clinical and rehabilitative aspects of stroke patients. A total of 32 meta-analyses published until July 2019 were selected, focusing on the effects on motor function, manual dexterity, walking and balance, spasticity, dysphagia, aphasia, unilateral neglect, depression, and cognitive function after a stroke. Only conventional rTMS protocols were considered in this review, and meta-analyses focusing on theta burst stimulation only were excluded. Overall, both HF-rTMS and LF-rTMS have been shown to be safe and well-tolerated. In addition, the current literature converges on the positive effect of rTMS in the rehabilitation of all clinical manifestations of stroke, except for spasticity and cognitive impairment, where definitive evidence of efficacy cannot be drawn. However, routine use of a specific paradigm of stimulation cannot be recommended yet due to a significant level of heterogeneity of the studies in terms of protocols to be set and outcome measures that have to be used. Future studies need to preliminarily evaluate the most promising protocols before going on to multicenter studies with large cohorts of patients in order to achieve a definitive translation into daily clinical practice.

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            Cortical plasticity: from synapses to maps.

            It has been clear for almost two decades that cortical representations in adult animals are not fixed entities, but rather, are dynamic and are continuously modified by experience. The cortex can preferentially allocate area to represent the particular peripheral input sources that are proportionally most used. Alterations in cortical representations appear to underlie learning tasks dependent on the use of the behaviorally important peripheral inputs that they represent. The rules governing this cortical representational plasticity following manipulations of inputs, including learning, are increasingly well understood. In parallel with developments in the field of cortical map plasticity, studies of synaptic plasticity have characterized specific elementary forms of plasticity, including associative long-term potentiation and long-term depression of excitatory postsynaptic potentials. Investigators have made many important strides toward understanding the molecular underpinnings of these fundamental plasticity processes and toward defining the learning rules that govern their induction. The fields of cortical synaptic plasticity and cortical map plasticity have been implicitly linked by the hypothesis that synaptic plasticity underlies cortical map reorganization. Recent experimental and theoretical work has provided increasingly stronger support for this hypothesis. The goal of the current paper is to review the fields of both synaptic and cortical map plasticity with an emphasis on the work that attempts to unite both fields. A second objective is to highlight the gaps in our understanding of synaptic and cellular mechanisms underlying cortical representational plasticity.
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              Post-Stroke Depression: A Review.

              Poststroke depression (PSD) has been recognized by psychiatrists for more than 100 years, but controlled systematic studies did not begin until the 1970s. Meta-analyses addressing almost all major clinical issues in the field have emerged because of the relatively small number of patients included in some stroke studies. In order to build large databases, these meta-analyses have merged patients with rigorously assessed mood disorders with major depressive features with patients scoring above arbitrary cutoff points on depression rating scales, thus missing important findings such as cognitive impairment associated with major but not minor depression. Nevertheless, PSD occurs in a significant number of patients and constitutes an important complication of stroke, leading to greater disability as well as increased mortality. The most clinically important advances, however, have been in the treatment and prevention of PSD. Recent meta-analyses of randomized controlled trials for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, randomized controlled trials for prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early antidepressant treatment of PSD appears to enhance both physical and cognitive recovery from stroke and might increase survival up to 10 years following stroke. There has also been progress in understanding the pathophysiology of PSD. Inflammatory processes might be associated with the onset of at least some depressive symptoms. In addition, genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission might be relevant etiological factors. Further elucidation of the mechanism of PSD may ultimately lead to specific targeted treatments.
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                Author and article information

                Contributors
                Journal
                Ther Adv Neurol Disord
                Ther Adv Neurol Disord
                TAN
                sptan
                Therapeutic Advances in Neurological Disorders
                SAGE Publications (Sage UK: London, England )
                1756-2856
                1756-2864
                25 September 2019
                2019
                : 12
                : 1756286419878317
                Affiliations
                [1-1756286419878317]Department of Medical and Surgical Sciences and Advanced Technologies, Section of Neurosciences, University of Catania, Catania, Italy
                [2-1756286419878317]Department of Surgery and Medical-Surgery Specialties, University of Catania, Via Santa Sofia, 78, Catania, 95125, Italy
                [3-1756286419878317]Department of Neurology IC, Oasi Research Institute – IRCCS, Troina, Italy
                [4-1756286419878317]Department of Surgery and Medical-Surgery Specialties, University of Catania, Catania, Italy
                [5-1756286419878317]Department of Surgery and Medical-Surgery Specialties, University of Catania, Catania, Italy
                [6-1756286419878317]Department of Medical and Surgical Sciences and Advanced Technologies, Section of Neurosciences, University of Catania, Catania, Italy
                [7-1756286419878317]Department of Clinical Neurophysiology, University Medical Center, Georg August University, Göttingen, Germany
                [8-1756286419878317]Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
                Author notes
                Author information
                https://orcid.org/0000-0002-5659-662X
                Article
                10.1177_1756286419878317
                10.1177/1756286419878317
                6763938
                31598137
                bf0629c2-4814-4539-960a-124fd67c9dab
                © The Author(s), 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 4 January 2019
                : 28 August 2019
                Categories
                Review
                Custom metadata
                January-December 2019

                neuroplasticity,neurorehabilitation,noninvasive brain stimulation,stroke

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