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      Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study

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          Abstract

          Background

          Recent studies have shown that patients with disorders of consciousness (DoC) can benefit from repetitive transcranial magnetic stimulation (rTMS) therapy. The posterior parietal cortex (PPC) is becoming increasingly important in neuroscience research and clinical treatment for DoC as it plays a crucial role in the formation of human consciousness. However, the effect of rTMS on the PPC in improving consciousness recovery remains to be studied.

          Method

          We conducted a crossover, randomized, double-blind, sham-controlled clinical study to assess the efficacy and safety of 10 Hz rTMS over the left PPC in unresponsive patients. Twenty patients with unresponsive wakefulness syndrome were recruited. The participants were randomly divided into two groups: one group received active rTMS treatment for 10 consecutive days ( n = 10) and the other group received sham treatment for the same period ( n = 10). After a 10-day washout period, the groups crossed over and received the opposite treatment. The rTMS protocol involved the delivery of 2000 pulses/day at a frequency of 10 Hz, targeting the left PPC (P3 electrode sites) at 90% of the resting motor threshold. The primary outcome measure was the JFK Coma Recovery Scele-Revised (CRS-R), and evaluations were conducted blindly. EEG power spectrum assessments were also conducted simultaneously before and after each stage of the intervention.

          Result

          rTMS-active treatment resulted in a significant improvement in the CRS-R total score ( F = 8.443, p = 0.009) and the relative alpha power ( F = 11.166, p = 0.004) compared to sham treatment. Furthermore, 8 out of 20 patients classified as rTMS responders showed improvement and evolved to a minimally conscious state (MCS) as a result of active rTMS. The relative alpha power also significantly improved in responders ( F = 26.372, p = 0.002) but not in non-responders ( F = 0.704, p = 0.421). No adverse effects related to rTMS were reported in the study.

          Conclusions

          This study suggests that 10 Hz rTMS over the left PPC can significantly improve functional recovery in unresponsive patients with DoC, with no reported side effects.

          Clinical trial registration

          www.ClinicalTrials.gov, identifier: NCT05187000.

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          Most cited references73

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          The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility.

          To determine the measurement properties and diagnostic utility of the JFK Coma Recovery Scale-Revised (CRS-R). Analysis of interrater and test-retest reliability, internal consistency, concurrent validity, and diagnostic accuracy. Acute inpatient brain injury rehabilitation hospital. Convenience sample of 80 patients with severe acquired brain injury admitted to an inpatient Coma Intervention Program with a diagnosis of either vegetative state (VS) or minimally conscious state (MCS). Not applicable. The CRS-R, the JFK Coma Recovery Scale (CRS), and the Disability Rating Scale (DRS). Interrater and test-retest reliability were high for CRS-R total scores. Subscale analysis showed moderate to high interrater and test-retest agreement although systematic differences in scoring were noted on the visual and oromotor/verbal subscales. CRS-R total scores correlated significantly with total scores on the CRS and DRS indicating acceptable concurrent validity. The CRS-R was able to distinguish 10 patients in an MCS who were otherwise misclassified as in a VS by the DRS. The CRS-R can be administered reliably by trained examiners and repeated measurements yield stable estimates of patient status. CRS-R subscale scores demonstrated good agreement across raters and ratings but should be used cautiously because some scores were underrepresented in the current study. The CRS-R appears capable of differentiating patients in an MCS from those in a VS.
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            Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome

            Background Some patients awaken from coma (that is, open the eyes) but remain unresponsive (that is, only showing reflex movements without response to command). This syndrome has been coined vegetative state. We here present a new name for this challenging neurological condition: unresponsive wakefulness syndrome (abbreviated UWS). Discussion Many clinicians feel uncomfortable when referring to patients as vegetative. Indeed, to most of the lay public and media vegetative state has a pejorative connotation and seems inappropriately to refer to these patients as being vegetable-like. Some political and religious groups have hence felt the need to emphasize these vulnerable patients' rights as human beings. Moreover, since its first description over 35 years ago, an increasing number of functional neuroimaging and cognitive evoked potential studies have shown that physicians should be cautious to make strong claims about awareness in some patients without behavioral responses to command. Given these concerns regarding the negative associations intrinsic to the term vegetative state as well as the diagnostic errors and their potential effect on the treatment and care for these patients (who sometimes never recover behavioral signs of consciousness but often recover to what was recently coined a minimally conscious state) we here propose to replace the name. Conclusion Since after 35 years the medical community has been unsuccessful in changing the pejorative image associated with the words vegetative state, we think it would be better to change the term itself. We here offer physicians the possibility to refer to this condition as unresponsive wakefulness syndrome or UWS. As this neutral descriptive term indicates, it refers to patients showing a number of clinical signs (hence syndrome) of unresponsiveness (that is, without response to commands) in the presence of wakefulness (that is, eye opening).
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              Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)

              A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                16 February 2023
                2023
                : 14
                : 1059789
                Affiliations
                [1] 1Department of Rehabilitation Medicine, Joint Research Centre for Disorders of Consciousness, Zhujiang Hospital of Southern Medical University , Guangzhou, China
                [2] 2Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University , Nanchang, China
                [3] 3School of Basic Medical Sciences, Hangzhou Normal University , Hangzhou, China
                Author notes

                Edited by: Shraddha Mainali, Virginia Commonwealth University, United States

                Reviewed by: Xiaoyu Xia, Chinese PLA General Hospital, China; Jianghong He, Capital Medical University, China

                *Correspondence: Yang Bai ✉ baiyang1126@ 123456gmail.com

                This article was submitted to Neurorehabilitation, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2023.1059789
                9978157
                36873436
                c58d6cce-9035-4125-a785-ca332d073f67
                Copyright © 2023 Xu, Wu, Zheng, Liang, Huang, Zhong, Xiao, Lan, Bai and Xie.

                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 October 2022
                : 18 January 2023
                Page count
                Figures: 4, Tables: 4, Equations: 0, References: 73, Pages: 11, Words: 8280
                Funding
                Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;
                Award ID: 81801119
                Award ID: 81974154
                Award ID: 82171174
                Funded by: Guangzhou Municipal Science and Technology Project, doi 10.13039/501100010256;
                The study was supported by grants from the National Natural Science Foundation of China (no. 82171174, 81974154, and 81801119) and the Key Realm R&D Program of Guangzhou (no. 202007030005). The funding organizations played no further role in study design, data collection, analysis, interpretation, or paper writing.
                Categories
                Neurology
                Original Research

                Neurology
                repetitive transcranial magnetic stimulation,disorders of consciousness,unresponsive wakefulness syndrome/vegetative state,randomized control trial,eeg

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