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      Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3

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          Abstract

          Background

          Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia, and, thus far, effective treatment remains low. Repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of spinal cerebellar ataxia, but the mechanism is unclear; in addition, whether any improvement in the symptoms is related to cerebellar metabolism has not yet been investigated. Therefore, the purpose of this study was to investigate the effects of low-frequency rTMS on local cerebellar metabolism in patients with SCA3 and the relationship between the improvement in the symptoms and cerebellar metabolism.

          Methods

          A double-blind, prospective, randomized, sham-controlled trial was carried out among 18 SCA3 patients. The participants were randomly assigned to the real stimulation group (n = 9) or sham stimulation group ( n = 9). Each participant in both the groups underwent 30 min of 1 Hz rTMS stimulation (a total of 900 pulses), differing only in terms of stimulator placement, for 15 consecutive days. To separately compare pre- and post-stimulation data (magnetic resonance spectroscopy (MRS) data and the International Cooperative Ataxia Rating Scale (ICARS) score) in the real and sham groups, paired-sample t-tests and Wilcoxon’s signed-rank tests were used in the analyses. The differences in the ICARS and MRS data between the two groups were analyzed with independent t-tests and covariance. To explore the association between the changes in the concentration of cerebellar metabolism and ICARS, we applied Pearson’s correlation analysis.

          Results

          After 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group ( p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group ( F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group ( p < 0.05), but no significant differences were found in the sham stimulation group ( p > 0.05). The analysis of covariance also confirmed the greater change in the real stimulation group. This study also demonstrated that there was a negative correlation between NAA/Cr in the right cerebellar hemisphere and ICARS in the real stimulation group (r = − 0.831, p = 0.02).

          Conclusion

          The treatment with rTMS over the cerebellum was found to induce changes in the cerebellar local metabolism and microenvironment in the SCA3 patients. The alterations may contribute to the improvement of the symptoms of ataxia in SCA3 patients.

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          Most cited references42

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          Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion

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            International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology.

            Despite the involvement of cerebellar ataxia in a large variety of conditions and its frequent association with other neurological symptoms, the quantification of the specific core of the cerebellar syndrome is possible and useful in Neurology. Recent studies have shown that cerebellar ataxia might be sensitive to various types of pharmacological agents, but the scales used for assessment were all different. With the long-term goal of double-blind controlled trials-multicentric and international-an ad hoc Committee of the World Federation of Neurology has worked to propose a one-hundred-point semi-quantitative International Cooperative Ataxia Rating Scale (ICARS). The scale proposed involves a compartimentalized quantification of postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders, in order that a subscore concerning these symptoms may be separately studied. The weight of each symptomatologic compartment has been carefully designed. The members of the Committee agreed upon precise definitions of the tests, to minimize interobserver variations. The validation of this scale is in progress.
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              Randomization in clinical studies

              Randomized controlled trial is widely accepted as the best design for evaluating the efficacy of a new treatment because of the advantages of randomization (random allocation). Randomization eliminates accidental bias, including selection bias, and provides a base for allowing the use of probability theory. Despite its importance, randomization has not been properly understood. This article introduces the different randomization methods with examples: simple randomization; block randomization; adaptive randomization, including minimization; and response-adaptive randomization. Ethics related to randomization are also discussed. The study is helpful in understanding the basic concepts of randomization and how to use R software.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                25 April 2022
                2022
                : 14
                : 827993
                Affiliations
                [1] 1Department of Rehabilitation Medicine, The First Affiliated Hospital of Fujian Medical University , Fuzhou, China
                [2] 2The School of Health, Fujian Medical University , Fuzhou, China
                [3] 3Department of Neurology, The First Affiliated Hospital of Fujian Medical University , Fuzhou, China
                [4] 4Department of Radiology, The First Affiliated Hospital of Fujian Medical University , Fuzhou, China
                [5] 5Department of Neurology, The 900th Hospital of Joint Logistics Support Force of PLA , Fuzhou, China
                Author notes

                Edited by: Wei Wu, Alto Neuroscience, United States

                Reviewed by: Ullrich Wüllner, University Hospital Bonn, Germany; Junhong Zhou, Harvard Medical School, United States

                *Correspondence: Qun-Lin Chen, fychenqunlin@ 123456126.com

                These authors have contributed equally to this work and share first authorship

                This article was submitted to Neuroinflammation and Neuropathy, a section of the journal Frontiers in Aging Neuroscience

                Article
                10.3389/fnagi.2022.827993
                9082263
                35547622
                50c3997f-00ff-4e9e-b358-8341ec228419
                Copyright © 2022 Chen, Lian, Liu, Sikandar, Li, Xu, Hu, Chen and Gan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 December 2021
                : 14 March 2022
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 42, Pages: 9, Words: 6370
                Categories
                Neuroscience
                Original Research

                Neurosciences
                cerebellar metabolism,magnetic resonance spectroscopy,repetitive transcranial magnetic stimulation,spinocerebellar ataxia type 3,international cooperative ataxia rating scale

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