PONE-D-24-27948Bright middle cerebellar peduncle sign in multiple system atrophy with predominant cerebellar ataxia is more apparent in double-inversion recovery than in conventional imagingPLOS ONE

Dear Dr. Shiraishi,

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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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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: No

Reviewer #2: Yes

Reviewer #3: No

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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 study reports that DIR is the most useful MRI sequence for evaluating the MCP sign in MSA-C compared to other MRI sequences. The results are reasonable, however, several additional investigations are necessary to enhance it as an original research article.

Major Points:

・The study focuses only on the MCP sign, without evaluating other findings. The imaging diagnosis of MSA-C should be comprehensive. It is worth considering whether the Hot Cross Bun sign is also better visualized with DIR.

・MSA-C is a relatively common condition. It would be preferable to evaluate the utility of DIR in a larger cohort, including cases that are difficult to diagnose in the early stages. The control group in such a study should include patients with Parkinson’s disease and other atypical parkinsonism.

Minor Points:

・Native English editing is recommended.

・Some figures are not correctly aligned with their descriptions.

・For Figure 2, provide continuous slices for Grade 3.

・As this is a retrospective study, the baseline characteristics of the MSA-C patients and controls should be included in the Methods and Subjects section.

・There is some redundancy between the Discussion and Introduction sections.

Reviewer #2: The authors have shown that DIR is useful for visual assessment of the Bright MCP sign. Although the small number of cases studied limits statistical interpretation, the usefulness of DIR is clearly demonstrated.

However, there are some concerns that need to be addressed as listed below.

1. The authors need to explain why they chose multiple sclerosis, neuromyelitis optica, and spinocerebellar atrophy as control groups.

2. In the text and figure legends, 'T2' should be written as 'T2WI' for T2-weighted images.

3. I think the corresponding figure is different from the instructions referring to the figure in the text. Are Figures 2, 3, and 1 in the text really Figures 1, 2, and 3, respectively? Also, I believe that the A, B, B, C listed in the figure legend in Figure 2 are correctly A, B, C, D. Manuscripts must be carefully and meticulously prepared.

Reviewer #3: Comments to the Author

It has been a pleasure to review your manuscript entitled “Bright middle cerebellar peduncle sign in multiple system atrophy with predominant cerebellar ataxia is more apparent in double-inversion recovery than in conventional imaging.”

I find the study to be worthy of publication; however, several concerns must be addressed before it can be considered for final acceptance. Please refer to the following comments:

Major comments:

1. “This study aimed to investigate whether DIR can detect the bright MCP sign in MSA-C patients significantly better than T2 or FLAIR. Furthermore, in cases where we could follow the MRI changes over time, we evaluated the time-course change of the MCP abnormality. ” (P4, line 66-68)

Given the stated aim, would it not be sufficient to analyze only the MSA-C group? Please provide a clear and detailed explanation of the reasons for including control subjects and the results derived from this comparison.

Moreover, as the authors mention in the limitations, the control group consisting of a mixture of demyelinating diseases, astrocytopathy, and degenerative diseases seems inappropriate. Table 1 shows a comparison between the MSA-C group and this control group, but even if significant differences are observed, it is difficult to assess the relevance of these findings when comparing such a mixed group. I recommend reevaluating the control selection.

2. Please include a summary of the MSA-C cases in the manuscript. Information such as initial symptoms, duration of illness, and the timing of MRI scans are crucial to understanding the context of the findings.

3. It appears that Figures 2 and 3 may be reversed. Please carefully review and confirm their correctness.

4. In Figure 6, the authors show the progression of MCP signals in MSA-C patients. When specifically does the MCP signal increase in MSA-C? Is there a noticeable difference between cases with unilateral versus bilateral MCP signals? I recommend discussing and interpreting the results of Figure 6 in greater detail.

Minor comments:

1. The figure legends are lacking detail. For instance, all figures should indicate the MRI sequence used. Additionally, Figure 1D is not sufficiently explained. Please review and enhance the figure legends accordingly.

2. Certain parts of the text are underexplained. For example, is the case presented in Figure 1 included in your overall analysis? Additionally, which specific cases correspond to case 1 (P8, line 141) and Case 2 (P8, line 143)? Please clarify these points with more detail.

3. There is inconsistency in the use of parentheses around figure references, such as Figure 1 (P7, line 122) and (Figure 5) (P8, line 141). Please ensure consistent formatting throughout the manuscript.

4. Proper capitalization needs to be applied throughout the text. For instance, "case" (P8, line 141), "Case" (P8, line 143), "middle" (P16, line 301), and "double" (P16, line 302) should all be capitalized where appropriate. Please carefully proofread the manuscript to correct these and other minor errors.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: AKIO AKAGI

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Bright middle cerebellar peduncle sign in multiple system atrophy with predominant cerebellar ataxia is more apparent in double-inversion recovery imaging than in conventional imaging

PONE-D-24-27948R1

Dear Dr. Shiraishi,

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.

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Kind regards,

Kensaku Kasuga

Academic Editor

PLOS ONE

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: 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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: Yes

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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: 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 #2: Yes

Reviewer #3: 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 #2: The authors have shown that DIR is useful for visual assessment of the Bright MCP sign. They have revised the manuscript appropriately in line with the previous comments.

Reviewer #3: Comments to the author:

It is my pleasure to have the opportunity to review this manuscript once again.

The authors have responded appropriately to the comments. I consider it worthy of publication.

I am praying for all of authors success in the future.

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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 #2: No

Reviewer #3: Yes: AKIO AKAGI

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