PONE-D-22-00142Definition and surgical timing in CES - A systematic reviewPLOS ONE

Dear Dr. Gillespie,

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.

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We look forward to receiving your revised manuscript.

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Alfio Spina, M.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. 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: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. 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: Yes

Reviewer #2: Yes

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4. 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: Yes

Reviewer #2: Yes

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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: This is an excellent review of a timely topic. If the same language and definition of time is not used then it is impossible to determine the results across studies. This work will highlight that need.

Reviewer #2: This is a very interesting study concerning the definition and surgical timing in cauda equinal syndrome. But the varieties of the syndrome were highly correlated to the etiologies of disease. The surgical timing also depended on the diseases themselves.

The authors should add the parameters of etiologies as a crucial factor for the analysis.

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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.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-22-00142R1Definition and surgical timing in Cauda Equina Syndrome – A systematic reviewPLOS ONE

Dear Dr. Gillespie,

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 02 2023 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Andreas K Demetriades, MBBChir, MPhil, FRCSEd, FEBNS.

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Thanks for your patience.

The handling editor had to change due to previous delays, and reviewers not responding, necessitating a fresh restart of reviews.

There are still significant shortcomings, as per peer review and we hope you find the comments constructive.

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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

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

Reviewer #4: All comments have been addressed

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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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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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: Yes

Reviewer #2: (No Response)

Reviewer #3: Yes

Reviewer #4: Yes

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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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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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: The authors present an acceptable version of their paper. The authors present an acceptable version of their paper. The

Reviewer #2: The authors had already addressed all the response to comments recommended by the reviewer. The manuscript should be published.

Reviewer #3: Thank you for giving me the opportunity to review the present manuscript. The authors performed a systematic review of the literature on the definitions and timing of intervention for cauda equina syndrome. The manuscript has scientific merit as it illustrates the lack of adoption of established knowledge and "guidelines" on the topic, probably due to the lack of a consensus on the subject.

Please find my comments below:

1) Title: I suggest that the title be revised to illustrate that this is an "updated" systematic review

2) Abstract:

a) Study design: narrative review -> please revise

b) Be consistent in your use of "n" for study number and the use of percentages

3) Methods:

a) Search strategy: The literature search is outdated (last update: 30th April 2021). Please re-run the literature search to identify articles published in the last 1.5 years.

b) Search strategy: Although the PRISMA guidelines only require the strategy of at least 1 database to be presented, I suggest that the search strategy for all databases is presented in Table S1.

c) Study screening and selection: Lines 123-126, please revise the sentence.

d) Statistical analysis: please mention the statistical tests that yielded the p values mentioned later in the text

e) Quality assessment: please provide a quality assessment paragraph as mentioned in your PRISMA protocol. A paragraph with the results should also be provided in the "Results" section.

4) Results:

a) I believe that combining some of the data of the supplementary tables to create 1-2 Tables presented in the main text with the basic characteristics of the included studies will help readers better understand the findings. (suggestion)

b) Be consistent in your use of "n" for study number and the use of percentages

c) Please provide statistical significance values when comparing the two periods (1990-2016 & 2016-2021). For example here: "There was an increase in percentage of studies using pre-existing criteria over the time period

205 2016-2021 compared to the ones published in 1990-2016, with 9.4% of studies using criteria

206 between 1990-2016 (n=3), and 38.7% (n=12) of studies using them between the years 2016-

207 2021."

5) Discussion:

a) Make sure to include references consistently when mentioning other studies.

Reviewer #4: Authors present a revised version of the narrative review of definiton and surgical timing in cauda equina syndrome. Methodology of study selection is fairly well described. Authors conclude that there is currently no concensus , either on definiton nor on how early is the early timing in management of cauda equina syndrome.

One major drawback of this study is that it does not discuss one very important aspect of the studies which were analyzed - the etiology. Cauda equina syndrome can appear due to tumor compression - primary or metastasis, due to trauma, infection or degenerative disease. We are sure that there would be certain differences in the management, timing and surgical treatment in general; what authors did in the revision is just information of which etiologies in which percentage led to the syndrome. Furthermore, this review provides a mere description of the evaluated studies, without any comparison between the studies; surgical philosophy is not discussed at all (decompression surgery, decompression + stabilization), and one very important clinical aspect - not only time of the surgery in terms of from onset of symptoms to surgery, but also time of the day of the surgery - were there any studies which analyze this very important aspect and its correlation to timing? - for example:

Baig Mirza A, Velicu MA, Lyon R, Vastani A, Boardman T, Al Banna Q, Murphy C, Kellett C, Vasan AK, Grahovac G. Is Cauda Equina Surgery Safe Out-of-Hours? A Single United Kingdom Institute Experience. World Neurosurg. 2022 Mar;159:e208-e220. doi: 10.1016/j.wneu.2021.12.028. Epub 2021 Dec 14. PMID: 34915208.

Demetriades AK. Cauda equina syndrome - from timely treatment to the timing of out-of-hours surgery. Acta Neurochir (Wien). 2022 May;164(5):1201-1202. doi: 10.1007/s00701-022-05174-1. Epub 2022 Mar 30. PMID: 35352153.

Are there any information of complication rates of these surgeries? To simply describe timing without description of outcome does not make a lot of sense, so I suggest to include outcome assesment following surgery in correlation to time, and to include into Discussion and comment on current literature:

Woodfield J, Lammy S, Jamjoom AA, Fadelalla MA, Copley PC, Arora M, Glasmacher SA, Abdelsadg M, Scicluna G, Poon MT, Pronin S, Leung AH, Darwish S, Demetriades AK, Brown J, Eames N, Statham PF, Hoeritzauer I; UCES Study Collaborators; British Neurosurgical Trainee Research Collaborative. Demographics of Cauda Equina Syndrome: A Population Based Incidence Study. Neuroepidemiology. 2022 Oct 31. doi: 10.1159/000527727. Epub ahead of print. PMID: 36315989.

I urge authors to analyze the following manuscript and compare their results to this review:

Epstein NE. Review/Perspective: Operations for Cauda Equina Syndromes - "The Sooner the Better". Surg Neurol Int. 2022 Mar 25;13:100. doi: 10.25259/SNI_170_2022. PMID: 35399881; PMCID: PMC8986648.

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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

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-22-00142R2Definition and surgical timing in Cauda Equina Syndrome – An updated systematic reviewPLOS ONE

Dear Dr. Gillespie,

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 yet again to submit a revised version of the manuscript that addresses the points raised during the review process. One reviewer has made specific recommendations which we hope can be addressed.

Please submit your revised manuscript by Apr 06 2023 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Andreas K Demetriades, MBBChir, MPhil, FRCSEd, FEBNS.

Academic Editor

PLOS ONE

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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 #3: All comments have been addressed

Reviewer #4: 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 #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #4: N/A

**********

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 #3: Yes

Reviewer #4: Yes

**********

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 #3: Yes

Reviewer #4: Yes

**********

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 #3: (No Response)

Reviewer #4: Authors have provided a revised version of their manuscript on timing of surgery in cases of cauda equine syndrome. Recommended literature has been included and discussed. Authors state that due to the volume of the analyzed studies, further inquiry regarding etiology which led to cauda syndrome as well as the role of surgical therapy could not have been analyzed. I urge authors to go through the studies and look at this issue, even more data of descriptive nature could be of interest and enrich the manuscript. Especially timing in relation to trauma and tumors has a different significance and dynamics.

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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 #3: No

Reviewer #4: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Definition and surgical timing in Cauda Equina Syndrome – An updated systematic review

PONE-D-22-00142R3

Dear Mr Gillespie,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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,

Andreas K Demetriades, MBBChir, MPhil, FRCSEd, FEBNS.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Congratulations on addressing all peer review points during this lengthy process.

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 #3: All comments have been addressed

Reviewer #4: 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 #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #4: Yes

**********

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 #3: No

Reviewer #4: Yes

**********

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 #3: Yes

Reviewer #4: Yes

**********

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 #3: (No Response)

Reviewer #4: Authors provide a revised version of their literature review on definition and surgical timing in cauda equina surgery. Although descriptive, section on underlying etiology has been added to the review. Authors have sufficiently responded to reviewer remarks.

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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 #3: No

Reviewer #4: No

**********