Rebuttal letter

Dear editor, and reviewers.

We would like to thank you for giving us the opportunity to submit a revised version of our manuscript titled “Racial Variations in Sciatic Nerve Anatomy: A Systematic Review and Meta-Analysis”. We are too grateful to you and the reviewers for taking the time and effort to read our manuscript and offer insightful comments. Based on these comments and suggestions, we have made careful modifications to the original manuscript. Your informed and helpful feedback helped us think of potential changes for the current version. We believe the manuscript has improved and hope that it meets your high standards. The authors welcome further constructive comments, if any. Please see below for a point-by-point response to comments and concerns. Comments are shown in black, followed by our answers and responses in dark blue. The changes are shown in the marked copy of the manuscript (highlighted in blue).

Best regards,

Academic Editor’s Comment

Dear Dr. Abdu,

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 Aug 29 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.

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.

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We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Mohsin Khan

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response: Thank you for your guidance. We have carefully revised our manuscript to ensure full compliance with PLOS ONE's style requirements.

2. Please ensure that your PRISMA flow diagram is included in your main manuscript file as Figure 1; please see the PLOS ONE submission guidelines for systematic reviews and meta-analyses at https://journals.plos.org/plosone/s/submission-guidelines#loc-systematic-reviews-and-meta-analyses.

Response: Thank you. We have updated and included the PRISMA flow diagram in the main manuscript file as Figure 1 in page eight, in accordance with PLOS ONE's submission guidelines for systematic reviews and meta-analyses.

3. Please include a caption for figure 1.

Response: Thank you for your critical comment regarding Figure 1. We fully acknowledge the importance of securing appropriate licensing for published figures. Although we contacted the original authors (Tomaszewski et al., 2016) to request permission to reuse their illustration, we have not received a response. As a result, to ensure compliance with copyright guidelines, we have removed the original figure. Instead, we have inserted a detailed textual description of the sciatic nerve variations in relation to the piriformis muscle, following the classification by Tomaszewski et al. (2016), in the revised manuscript [lines 49-59]. This approach preserves the clarity and scientific value of the content while avoiding any potential copyright issues.

Additional Editor Comments (if provided):

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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

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

Reviewer #1: Yes

Reviewer #2: N/A

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: No

Reviewer #2: Yes

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

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: The authors performed a systematic review and meta-analysis of studies related to SN anatomy to quantify the pooled prevalence of sciatic nerve variations per racial subgroup. Overall, this study is of interest, as specific racial considerations of SN anatomy have not been thoroughly investigated.

Response: The authors thank the reviewer for this kind deep insight. We sincerely appreciate your recognition of the relevance of our study and the novelty of addressing racial variations in sciatic nerve anatomy.

This manuscript is overall well-written. There are a few important points related to methods, results, conclusions, and grammar listed below, to which I would appreciate author's attention to.

Methods:

Response: Thank you for your positive assessment of our manuscript and for noting that it is overall well-written. We also appreciate your constructive feedback on the methods, results, conclusions, and grammar. We have carefully reviewed each of your points and made the necessary revisions accordingly. Please see our detailed responses below.

1. Limiting the study to English-language articles may introduce language bias, particularly in a study assessing racial variation. Including non-English studies with translation support would enhance comprehensiveness. Was there a reason only English studies were assessed?

Response: We appreciate the reviewer’s important observation regarding potential language bias. In our study, we did not strictly exclude non-English articles; however, we required at least an English abstract to preliminarily assess the article’s relevance. For articles without English full texts but with abstracts indicating eligibility, we attempted to obtain translations when possible. Unfortunately, due to resource limitations and difficulties in accessing reliable translations for certain full texts, especially in less commonly spoken languages, we were unable to include all non-English studies. We acknowledge that this may introduce some degree of language bias and have addressed this point as a limitation in the Discussion section of the manuscript from line 319 to 322.

2. In general, using website search engine like google and Yahoo is atypical in this setting. Inclusion of specialized medical databases (e.g., Embase, Scopus) is recommended.

Response: Thank you for this helpful comment. We fully agree that specialized medical databases such as Embase and Scopus provide comprehensive coverage and are ideal for systematic reviews. However, due to limited access as we do not have institutional or personal subscriptions to Embase or Scopus we were unable to include them in our current search strategy. To enhance the completeness of our review, we supplemented our primary database search (PubMed, Hinari, and Google Scholar) with manual cross-referencing of all included studies. This approach enabled us to identify additional relevant articles and minimize the risk of missing key studies. As a result, we included over 20 more studies than previous reviews.

3. Please clarify the date range for included studies— is there no predefined earliest date? What does “from their inception” mean?

Response: Thank you for raising this important point. We have clarified the date range in line 79 by adding: “Studies published from the start of each database to June 2024 were included.”

We have also retained the term “inception” in lines 102-103, with a slight rewording, “Moreover, this systematic review and meta-analysis included studies published from the inception of each database up to June 2024.” We would like to note that the term “inception” is widely accepted and frequently used in the context of systematic reviews and meta-analyses. It refers to the earliest date from which each database began indexing records. This terminology is commonly used in high-quality reviews following PRISMA and Cochrane guidelines, making it appropriate and standard in this methodological setting.

3. The “methods” portion of the abstract should mention “a systematic review and meta-analysis was conducted to assess the pooled prevalence of SN variations among racial subgroups." or a variation of this, as it is not written there.

Response: Thank you for this helpful suggestion. We agree with your comment and have revised the “Methods” section of the abstract to clearly indicate the study design and its primary objective. The revised sentence now reads. ” Methods: A systematic review and meta-analysis were conducted to assess the pooled prevalence of SN variations among racial subgroups. A comprehensive literature search was performed using PubMed, Google Scholar, Hinari, and additional sources, including cross-referenced articles. Subgroup analyses by region, and country were also conducted using a random-effects model. Heterogeneity was assessed with the Cochrane Q test and the I² statistic”

Results:

1. Is it possible based on the data collected to compare if there are differences in the most common type of sciatic nerves between races/continents? Although the prevalence of variations is of interest, an important point would be a specific variant is more common in certain races/regions

Response: Thank you for your insightful comment. We agree that identifying whether specific SN variation types are more common in particular racial or regional groups would be valuable. However, the primary studies included in our review did not consistently report the prevalence of each individual variant stratified by race or continent. As a result, we were unable to perform such a detailed comparative analysis.

2. If one conclusion is that regional differences are important, should subgroup analyses be done by grouping regions together and comparing?

Response: Thank you for this view. In our study, we conducted subgroup analyses by continent (Africa, Asia, Europe, and America) and by country, with statistical comparisons based on 95% confidence intervals (CIs). As shown in detailed in the results section and Table 2, the highest prevalence of SN variations was found in Asia (16%), with particularly high rates in East Asian countries such as China (38%) and Japan (30%). While most of the subgroup CIs overlapped, indicating no statistically significant differences between many regions, we observed notable exceptions, such as between East Asian countries and other regions. These differences highlight that regional factors may contribute more significantly to the variation in SN anatomy than racial classifications alone. We agree that further analyses based on more refined regional groupings (e.g., East vs. West Asia) may be valuable and recommend this as an area for future research.

3. Please make all data underlying the findings fully available.

Response: We appreciate the reviewer’s concern. In response, we have ensured that all data underlying our findings are fully available in the manuscript. Specifically, we have provided comprehensive details of the search strategy, including the databases searched, keywords used, inclusion/exclusion criteria, and the selection process. Furthermore, AQUA domain scores have been summarized in the respective figures. If additional raw data are needed, we are happy to include them as supplementary material upon request.

Conclusions:

1. The overall conclusion per my understanding is that based on continents and race, there is only a modest difference in prevalence of SN variation. However, this is not reflected in the conclusion in the abstract. This should be amended to be the primary conclusion.

Response: Thank you for your valuable comment. We agree with your observation that the overall differences in the prevalence of sciatic nerve variations across racial and continental groups are modest and should be clearly reflected in the abstract conclusion. In response, we have revised the conclusion to emphasize this key finding. The updated conclusion now reads:

"This review revealed only modest and statistically non-significant differences in the prevalence of sciatic nerve variations across broad racial and continental groups. In contrast, substantial variation was observed at the regional level, with particularly high prevalence rates in East Asian countries such as China and Japan. These findings suggest that regional factors contribute more to the observed variations than racial factors."

Figures: 1.Was approval obtained by Tomaszewski et al. [6] to use their picture in Figure 1? Please ensure the proper permissions have been obtained from the original authors.

Response: Thank you for raising this important point. Regarding Figure 1, we fully acknowledge the importance of securing appropriate licensing for published figures. Although we contacted the original authors (Tomaszewski et al., 2016) to request permission to reuse their illustration, we have not received a response. As a result, to ensure compliance with copyright guidelines, we have removed the original figure. Instead, we

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Rebuttal letter

Dear editor, and reviewers.

We would like to thank you for giving us the opportunity to submit a second revised version of our manuscript titled “Racial Variations in Sciatic Nerve Anatomy: A Systematic Review and Meta-Analysis”. We are too grateful to you and the reviewers for taking the time and effort to read our manuscript and offer insightful comments. Based on these comments and suggestions, we have made careful modifications to the original manuscript. Your informed and helpful feedback helped us think of potential changes for the current version. We believe the manuscript has improved and hope that it meets your high standards. The authors welcome further constructive comments, if any. Please see below for a point-by-point response to comments and concerns. Comments are shown in black, followed by our answers and responses in dark blue. The changes are shown in the marked copy of the manuscript (track chamges).

Best regards,

PONE-D-24-41926R1

Racial Variations in Sciatic Nerve Anatomy: A Systematic Review and Meta-Analysis

PLOS One

Dear Dr. Abdu,

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 Mar 05 2026 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 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,

Oyelola A. Adegboye, PhD

Academic Editor

PLOS One

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Additional Editor Comments:

1. Given the time elapsed since the original literature search, it would strengthen the manuscript to update the search to include studies published up to the end of 2025, where feasible, to ensure that the findings reflect the most current evidence base.

Response: We thank the editor for the suggestion. In response, we have updated our literature search to include studies published up to the end of 2025. In the initially submitted R1 manuscript, 75 reports were included. During the updated search and careful review, we identified one study that had been published twice at different time points in different journals. To avoid duplication and multiplication bias, we included only the more comprehensive version, reducing the number of reports to 74. With the addition of seven new studies (1-7) identified in the updated search, the total number of included reports increased to 81. These updates are reflected in the revised PRISMA flowchart and throughout the manuscript, ensuring that the findings reflect the most current evidence base. Moreover, to align with best practices for anatomical meta-analyses, as recommended by the anatomy working group, we changed our software from Stata to MetaXL version 5.3 (EpiGear International Pty Ltd., Wilston, Queensland, Australia), which is strongly recommended for multiple pooled analyses. This update is clearly described in the Statistical Analysis subsection of the Methods section (lines 132–141).

2. The meta-analysis reports substantial between-study heterogeneity (high I²). The authors should consider a meta-regression or other exploratory analyses (e.g., subgroup or sensitivity analyses) to examine potential study-level factors contributing to this heterogeneity. Where such analyses are not feasible, a clearer discussion of this limitation would be helpful.

Response: We thank the editor again for these important points. As described in results section lines 234–241, we conducted sensitivity analyses and assessed publication bias using the LFK index from Doi plots, which demonstrated that our pooled estimates remain robust despite heterogeneity and as noted by Henry et al. (2016), high heterogeneity is a common and inherent feature of anatomical meta-analyses. While meta-regression was not feasible due to the limited number of studies in some subgroups, the observed heterogeneity is consistent with the variability inherent in anatomical studies.

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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

________________________________________

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

________________________________________

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

Reviewer #1: 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 #1: 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 #1: 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 #1: The authors have incorporated many earlier concerns, and the manuscript has improved in clarity. The manuscript is technically sound (data are available, methods are reproducible, ethical criteria are satisfied, and the paper is intelligible). The corrections in the graphs are appreciated and the detailed description of the limitations.

Response: We sincerely thank the reviewer for their encouraging comments and positive assessment of our manuscript. We are glad that the clarifications, corrections, and detailed description of limitations have improved the readability and quality of the work. We greatly appreciate the reviewer’s constructive feedback throughout the review process

I have two suggestions:

1) Thank you for clarifying your search methods; Although cross-referencing and Google Scholar were used, the absence of Embase/Scopus remains a limitation. This is acceptable given resource constraints, but the methods could be clearer. Suggestion: Add an explicit sentence noting that “without access to certain subscription databases (e.g., Embase, Scopus), our search may have missed relevant studies, though we mitigated this by cross-referencing extensively.” This will help readers also understand and accept this limitation.

Response: We thank the reviewer for this helpful suggestion. We have added a statement to clarify the limitations of our literature search: “Moreover, without access to certain subscription databases (e.g., Embase, Scopus), our search may have missed relevant studies, though we mitigated this by cross-referencing extensively.” This statement has been included in the manuscript in lines 327–329, alongside our explanation of how race was classified, to provide transparency and help readers understand the methods and potential limitations of our study.

2) The meta-analyses yield I² > 90% in nearly all cases. The current discussion mentions this but still presents pooled prevalence as if they are broadly generalizable. Suggestion: Consider a sensitivity analysis (e.g., removing East Asia) to show how much these values drive overall prevalence.

Response: We thank the reviewer for this important comment. To address the concern, we conducted sensitivity analyses, including assessing the influence of studies from East Asia on the overall pooled prevalence. These analyses showed that excluding East Asian studies did not significantly alter the overall prevalence or the estimates for Asia. For clarity, we have added a new paragraph in lines 234–241 to present these findings and highlight that the pooled prevalence remains robust despite high heterogeneity.

3) Minor grammatical suggestions for clarity

Abstract

- “Subgroup analyses by region, and country”—remove the comma after “region”

Response: We thank the reviewer for the suggestion. The comma after “region” has been removed, and the phrase now reads: “Subgroup analyses by region and country.

- To improve understanding amongst a broad audience, in the abstract results, I would recommend rearranging to first mention “The Type A pattern, considered normal, had the highest pooled prevalence at 85.7%. Among the variations...”

Response: We thank the reviewer for this helpful suggestion. In line with the recommendation, the abstract results have been revised to begin with the normal Type A pattern, followed by the variations. We have also updated the prevalence estimates in accordance with the latest analysis. The revised text now reads: Type A, considered the normal pattern, had the highest pooled prevalence at 86%. The remaining 14% represented variations of the sciatic nerve (SN). Among these, Type B was the most common at 7%, followed by Type C and G each observed in 2% of limbs, while less frequent variations included Type Type D (1%), Type E (0%), and Type F (0% (0-1)).

Introduction:

- Line 73: Would say, “…how race and region influence….”

Response: We thank the reviewer for the suggestion. The text has been updated to read “…how race and region influence…,” as recommended.

- Line 118: “thorough,” not “through”

Response: We thank the reviewer for pointing this out. The text has been corrected to “thorough” in line 121.

- Lin 249: Please change comma locations as sown: “Our research reveals that Type A variations, considered the normal branching pattern of the SN where the nerve passes undivided under the PM, are the most commonly observed”

Response: We thank the reviewer for the helpful suggestion. The sentence has been revised for clarity and now reads: “our review reveals that Type A variations, considered the normal branching pattern of the SN where the nerve passes undivided under the PM, are the most commonly observed.” This revised sentence can be found in lines 215–217 of the manuscript.

________________________________________

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

1. Yadav SK, Yadav R, Adhikari RK. Composite anatomical variations of the sciatic nerve in relation to the piriformis muscle observed in cadaveric studies. Journal of Chitwan Medical College. 2025;15(6):101-7.

2. Khan GA, Gautam A, Shakya S, Shrestha A. Study of a variation of lumbosacral plexus: sciatic nerve and its clinical significance. Journal of Chitwan Medical College. 2022;12(4):51-4.

3. Kegoye ES, Ojewale AO, Ezekiel W, Usman IM, Aigbogun EO, Adewale AO, et al. Morphologic and morphometric bilateral analysis and sexual dimorphism in sciatic nerves of adult cadaveric specimens in Uganda. BMC Musculoskeletal Disorders. 2025;26(1):422.

4. Jyothi J, Praveen V, Sarada T. Anatomical Variations of High Division of Sciatic Nerve and its Relation to Piriformis–A Cadaveric Study. International Journal of Medical and Pharmaceutical Research. 2025;6:1595-600.

5. Habumuremyi S, Kubwimana O, Archibong V, Gashegu J. Sciatic nerve variations around the piriformis muscle and bifurcation level: An anatomical study. East African Orthopaedic Journal. 2024;18(2):58-64.

6. Ghosh D, Anandi S, Bandyopadhyay D, Jamwal V. Sciatic Nerve: Morphological Diversification in the Cadavers and Its Clinical Relevance: A Descriptive Observational Study. Journal of Medical Academics. 2025;8(2):95-102.

7. Amasiatu V, Oyakhire M, Oladipo G. Termination pattern of sciatic nerve in Nigeria: A cadaver dissection study. JIRMEPS. 2017;12(1):1-6.

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