Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analyses

Aline Alves de Souza; Stephano Tomaz da Silva; Amanda Mayra Pereira Régis; Diogo Neres Aires; Karen de Medeiros Pondofe; Luciana Protásio de Melo; Ricardo Alexsandro de Medeiros Valentim; Ana Raquel Rodrigues Lindquist; Lorenna Raquel Dantas de Macedo; Tatiana Souza Ribeiro

doi:10.1371/journal.pone.0320788

Peer Review History

Original SubmissionSeptember 25, 2024
25 Sep 2024 Author Response https://doi.org/10.1371/journal.pone.0320788.r001
27 Dec 2024 Decision Letter - Masoud Rahmati, Editor PONE-D-24-42912Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analysesPLOS ONE Dear Dr. Souza, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Feb 10 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear Authors I have read your manuscript in which you have investigated the effectiveness of Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis. The paper is well written and provides important information about individuals with ALS. Nevertheless, there are some considerations need to be addressed here. • Could gender have an impact on the results? And why aren’t gender differences thoroughly addressed in the discussion? • Given the significant variations in duration of interventions, and other key factors in previous studies, does it raise concerns about the foundation of your research? • The aforementioned concern is also associated with the discrepancy in intervention of previous researches. • Why have exercises like dumbbells and electrostimulation exercises been studied together? • Since increasing age can affect strength training results, doesn't these age differences in previous studies affect the results of your study? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? 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Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0320788.r002
Revision 1
14 Feb 2025 Author Response First of all, we would like to thank the reviewer for his availability and for his very pertinent comments, which helped us to improve our work and clarify essential issues within the research. Below you will find the questions raised by the reviewer and the answers to all of them, with clarifications and indications of the changes made to the text. • Could gender have an impact on the results? And why aren’t gender differences thoroughly addressed in the discussion? In fact, gender differences in muscle strengthening treatments for people with ALS should be considered to optimize results. Individualized interventions that consider biological, clinical, and social factors can offer more significant benefits and improve patients' quality of life; however, this is not a reality found in the scientific evidence available to date. Regarding the studies included in our review, all selected references had their samples composed of both genders, making it impossible to perform a more in-depth analysis of the impact of gender differences on the outcomes evaluated. We appreciate this pertinent comment and have included a paragraph in the discussion addressing this topic in the discussion (paragraph 15 of the discussion, lines 5 to 10). • Given the significant variations in duration of interventions, and other key factors in previous studies, does it raise concerns about the foundation of your research? The heterogeneity of the primary studies, which includes the different interventions applied and their durations, in fact, limited the level of confidence in the results of our systematic review. However, this was well specified in the discussion (paragraph 14, lines 6 and 12; paragraph 16, lines 7 to 11) and conclusion of the present study. However, this same concern consists of an important result, which highlights the need for more robust studies related to peripheral muscle strength in ALS, which present better standardization in the evaluation of the outcome, in the characteristics of the interventions and in the presentation of data, so that, in this way, new analyses can be performed and the levels of evidence and confidence can be increased. • The aforementioned concern is also associated with the discrepancy in intervention of previous researches. Exactly. As previously stated, the heterogeneity of the studies was also verified in terms of discrepant interventions applied. It is likely that the different interventions for muscle strengthening in the included studies reflect the diversity of approaches currently adopted for individuals with ALS, which, in turn, may be linked to the lack of a standardized protocol in the literature for this purpose, for this population. It is important to emphasize, however, that in the present review additional analyses (or subanalyses) were performed, grouping studies with similar characteristics, in an attempt to greater homogenize the sample, allowing a more precise evaluation of the effects of the interventions on the outcomes. (paragraph 16 of the discussion, lines 2 to 7) • Why have exercises like dumbbells and electrostimulation exercises been studied together? We sought to include different types of interventions because this is a topic that has been little discussed in the literature to date, with scarce and sometimes controversial results. For this reason, we included several possibilities for muscle strengthening, using accessories, techniques and devices, in order to broaden the search range of primary studies that investigated peripheral muscle strengthening in this population. Aware of the heterogeneity that this could cause, we considered conducting additional analyses with subgroups that performed strengthening with body weight/functional exercises or that used external loads, such as dumbbells, ankle weights, etc., in order to identify whether there was a difference between these interventions. Comments on this analysis are in paragraph 15 of the discussion, lines 1 to 5. • Since increasing age can affect strength training results, doesn't these age differences in previous studies affect the results of your study? Age is a crucial factor in the progression of ALS and directly impacts the results of exercise interventions, with studies suggesting that younger individuals with ALS may benefit more from muscle strengthening interventions due to greater muscle reserve and neural plasticity. In the studies included in this review, the mean age range of participants was assessed and, following the natural course of development of the disease, where individuals are often diagnosed after the age of 60, the age range varied between 50 and 62, with no significant discrepancies in the age range observed in the included studies. In addition, we included a subgroup analysis considering the studies with participants under and over 60 years old, and no statistically significant differences were found, as demonstrated in the results and discussed in paragraph 14 of the discussion, lines 12 to 17. Attachments Attachment Submitted filename: Response to reviewer.docx https://doi.org/10.1371/journal.pone.0320788.r003
25 Feb 2025 Decision Letter - Masoud Rahmati, Editor Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analyses PONE-D-24-42912R1 Dear Dr. Souza, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Masoud Rahmati Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: (No Response) ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: (No Response) ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: (No Response) ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No ******** https://doi.org/10.1371/journal.pone.0320788.r004
Formally Accepted
Acceptance Letter - Masoud Rahmati, Editor PONE-D-24-42912R1 PLOS ONE Dear Dr. Souza, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Masoud Rahmati Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0320788.r005

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