PONE-D-19-19642

The relation between local and distal muscle fat infiltration in chronic whiplash using magnetic resonance imaging

PLOS ONE

Dear Ms Karlsson,

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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: Yes

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

Reviewer #1: No

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: No

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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: I thank the authors for their work in addressing my comments and believe the paper is now much more focused and streamlined. I have a few additional comments and suggestions primarily related to the discussion of the data and conclusions drawn.

1. Introduction: I am still struggling with the connection between this data and the idea of “complementing the neck images with whole body coverage” for diagnostic purposes. First, you are unable to determine whether the stronger correlation between multifidi and lower extremity MFI in the severe WAD group pre-exists and predicts a worse outcome or is a progressive response to injury. The data that you discuss more strongly support the latter, in which case diagnostic whole body scans would not be useful. Second, to argue for whole body scans, you would have to show that the relationship between multifidi and lower extremity MFI is a better indicator than multifidi MFI on its own. This can be grossly assessed by adding the two tests discussed in the next points.

2. Results: Please perform an ANCOVA on your three regressions to determine whether the slopes are significantly different.

3. Results: Please also include an ANOVA on the multifidi MFI between groups to complement Figure 4.

4. Results: Please report all statistical results in your Results section. The Discussion discusses associations between multifidi MFI and age, BMI and duration since injury and a comparison of multifidi MFI across groups. If these are outcomes of the statistical models, please include more details about the models and their outputs so the reader is aware of the results before the discussion.

5. Discussion: Please discuss additional explanations for the association between multifidi and lower extremity MFI. These are mentioned in the Introduction, but I would like to see a more in-depth treatment in the Discussion. “However, a number of hypotheses around injury severity, pain intensity and/or related disability (9, 10), heightened stress-responses (11-13) central/peripheral neuronal interference (14-16), and/or physical inactivity (17, 18) may be offered to explain the rapid expression and larger magnitude of MFI in patients with more severe self-reported symptoms.”

Reviewer #2: Thank you for the opportunity to review this interesting manuscript for PLOS ONE. Our author colleagues have undertaken a study examining the relationship between cervical multifidus MFI and lower limb MFI in controls, mild WAD and mod-severe WAD patients. Findings indicate a relationship between cervical muscle MFI and lower limb MFI in mod-severe WAD patients.

General comments:

This study provides important insight on the mechanisms underpinning chronic WAD, which I believe represents an advance in our knowledge of this challenging condition.

I see that the authors have already made substantial amendments to the manuscript in response to two prior reviewers’ comments. My impression is that they have adequately addressed prior reviewer concerns.

Specific comments:

Abstract

1) “…to investigate the relation between fat infiltration…” awkward wording, suggest revise to ‘…relationship between…’

Introduction

2) Minor typographic error: “…whiplash from an motor vehicle collision.” Correct to ‘…a motor vehicle…’

3) Paragraph 2: “…reporting lower levels of pain-related disability, those nominating full recovery, idiopathic neck pain, and healthy controls.” Suggest add citation to this paper here: Elliott et al. (2008). Fatty infiltrate in the cervical extensor muscles is not a feature of chronic, insidious-onset neck pain. Clin Radiol. 63, 681-687

4) Paragraph 3: In line with the hypothesis around SCI in WAD, I suggest also mentioning the preliminary publication detailing magnetic resonance spectroscopic evidence of cord injury below, as a complementary study supporting this theory:

Elliott JM, Pedler AR, Cowin G, Sterling M, McMahon K. Spinal cord metabolism and muscle water diffusion in whiplash. Spinal Cord. 2012 Jun;50(6):474-6

Methods

5) “…technique uses foreground and backgrounds seeds and let the segmented mask grow.” Awkward wording, suggest revise.

6) “The segmentation was performed by a musculoskeletal physiotherapist with >6 months experience.” Suggest slight re-wording for clarity that it is 6 months experience doing this particular analysis (or as applicable).

7) Statistics: Was there a power/sample size calculation undertaken?

Discussion

8) The Discussion reads well. My only comment is that it would be good to address the contrasting findings between this study and that of Pedler et al (2018) which did not find increased lower limb MFI in WAD:

Pedler A, McMahon K, Galloway G, Durbridge G, Sterling M (2018) Intramuscular fat is present in cervical multifidus but not soleus in patients with chronic whiplash associated disorders. PLoS ONE 13(5): e0197438. https://doi.org/10.1371/journal.pone.0197438

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Plos1_Review_Karlsson.docx

The relation between local and distal muscle fat infiltration in chronic whiplash using magnetic resonance imaging

PONE-D-19-19642R1

Dear Dr. Karlsson,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Xi Chen

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 #2: All comments have been addressed

Reviewer #3: (No Response)

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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 #2: Yes

Reviewer #3: (No Response)

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

Reviewer #2: Yes

Reviewer #3: (No Response)

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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 #2: Yes

Reviewer #3: (No Response)

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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 #2: Yes

Reviewer #3: (No Response)

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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 #2: Thank you to the authors for their revisions of the manuscript. They have appropriately addressed the comments that I raised in my earlier review.

My only minor comment is that there is a typographic error in the spelling of Shapiro in the first paragraph of the Statistics section of the Method.

Reviewer #3: Previous reviewer's comments were fully addressed by the authors. It has significant improvement over the previous version and would be suitable for publication in the current form.

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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.

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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 #2: Yes: Scott Farrell PhD

Reviewer #3: No