PONE-D-24-27124Severity of peripheral neuropathies among causes in Amazon regionPLOS 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

Reviewer #3: Partly

Reviewer #4: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: 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

Reviewer #4: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: 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: The title of the article is very interesting and very meaningful, This is the first comprehensive study of the diverse causes of neuropathy in a territory undergoing epidemiologic transition in the Amazon region. The content of the article is regular and there are no obvious mistakes. It basically wants to express the content clearly and has a certain popular significance

Reviewer #2: This article is well written.

Here are my few comments:

1. Research title could be "Pattern,causes and functional outcome of peripheral neuropathies in Amazon region.

2. In lines 93 & 94 AND lines 131 to 134 they wrote about mortality of the general underlying illness like diabetes rather than the topic of interest like diabetic neuropathy,Chemotherapy-related neuropathy ,GBS etc.

3. In line 122-123 they wrote the lost to follow up as 369 which is huge number as compared with the sample size i.e. 754.

4. For Table 1 and figures 1-3 , the title is incompletely written.Also, the tables and figures shall all be put under results section or at the end of the article after the references.

Reviewer #3: In this study, Nathalie Deschamps et al. analyze the different peripheral neuropathies present in the Amazon region to elucidate the most frequent etiologies and their correlation with the severity of the neuropathy, based on the Peripheral Neuropathy Disability (PND) functional scores. I believe that Nathalie Deschamps et al. not only perform a very important and necessary analysis, but also that the outcomes of this study could help elucidate the causes leading to most severe symptoms and mortality, and whose study and treatment should thus be prioritized. In addition, the high amount of patients included will help obtaining very robust and reliable results. On the other hand, considering the high amount of patients and the availability of a good statistical method (STATA 18 software), the collection of more information from the patients and the performance of a more thorough analysis would very much improve this manuscript, which at the moment is rather poor. I also believe that this manuscript would benefit from a language revision.

Below please find my comments, which I hope will help improving this study:

- In this study, the authors analyze the correlation between the different etiologies leading to a peripheral neuropathy and their severity. To do this, they use the Peripheral Neuropathy Disability (PND) functional scores. The study would benefit from an analysis of also the pain and sensations related to these neuropathies, with scores such as the Numerical Rating Score (NRS), the Neuropathic Pain Symptom Inventory (NPSI) or the Modified Glasgow Composite Pain Scale (GCPS), for instance. In addition, the authors could use other severity and neuropathy scores, such as the Toronto Clinical Neuropathy Score (TCNS), to validate their results. Since this might not be possible due to lack of information from all patients, this point should be discussed as part of the limitations of the study.

- Through the manuscript, the authors comment on the follow-up of the patients, stating that “Patients without hospital visits by 2023 were considered lost to follow-up.”, that this is the reason for the “unlabeled” group, and that “369 patients were lost to follow-up”. Nevertheless, these 369 are included in Table 1, thus the authors analyze their diagnoses and PND. Why then are the 369 patients “lost”? From where are they excluded? What is the difference between them and the excluded patients due to “insufficient medical information regarding neuropathy characteristics”? In addition, 24 patients were included as unlabeled “because the patients were lost to follow-up.”. Why were these 24 patients not “lost”, like the other 369? The term follow-up means that there would be two time points of analysis, where at the first timepoint there would be 754 patients, and at the second timepoints there would be 385 (because 369 would be lost). Since this study does not include different timepoints, the “lost to follow-up” statement and the inclusion of those 369 patients nonetheless is very confusing. Please resolve this issue.

- In Methods, line 63, the authors state the keywords that they used to find the patients used in the study (“…using keywords such as "neuropathy," "Guillain-Barre syndrome," "chronic inflammatory demyelinating polyneuropathy (CIDP)," "multineuritis," "amyloid," and "amyloidosis".”). In figure 1, however, they show a flow chart of the 754 patients included, where they state that they use the keyword “No neuropathy” to 3746 patients. Please clarify the selection process and change whichever is wrong accordingly.

- In addition, the selection of different neuropathies ("Guillain-Barre syndrome," "chronic inflammatory demyelinating polyneuropathy (CIDP)," "multineuritis," "amyloid," and "amyloidosis") as keywords in the selection of patients creates a bias in the study and in the probability of finding these neuropathies among the total cohort of patients. Please discuss this bias as one of the limitations of the study.

- In Methods, line 73 to 85, “Determining the cause of the neuropathy”, the authors explain the different causes that they studied and how they are categorized ("Guillain-Barre syndrome" (GBS), "alcoholic," "deficiency," "infectious," "chronic renal failure (CRF)," "connective tissue disease (CTD)," "vasculitis," "rheumatism," "hereditary pressure hypersensitivity neuropathy (HNPP)," "CIDP," "FAP," "monoclonal gammopathy," "toxic," or "unlabeled"). In Table 1 and Figure 2, the authors include one cause of neuropathy that has not been discussed or explained in the manuscript: “intensive care”. Please explain the neuropathies present in the two patients that conform this small group.

- In Methods, line 99, the authors state “Assessment of functional severity within each group was conducted through cross-tabulation and Chi-squared tests. Subsequently, ordinal multiple logistic regression was employed to calculate adjusted odds ratios (aOR) compared to diabetes.”. Why were the odds ratios compared to diabetes in particular?

- In Results, the authors analyze the relation between mortality and the different diagnoses, but they do not include this information in Table 1 or in the figures. Thus I cannot judge whether this analysis and its conclusions are correct. Please include that information in the table.

- In Table 1, authors do a good job analyzing the different PND and diagnoses, but in the text, they do not comment on many of the results that they find. In particular, only two sentences correlate the severity (PND) with the diagnoses (line 129-131), and do not give concrete numbers. In addition, the study of PND is of the most important analyses in this study, yet authors do not mention or discuss these results in the Discussion.

- In the Discussion, line 177, the authors state “We may have missed cases from more isolated regions where access to healthcare is limited, potentially leading to an underrepresentation of deficiency-related peripheral neuropathy in our findings.”. Please explain why limited access to healthcare would affect the deficiency-related neuropathies in particular, but not the other ones.

Reviewer #4: This is an interesting study reporting on the frequency of neuropathy and its severity in French Guiana. However, the main concern is how the authors define neuropathy.

The authors simply interpreted the clinical data as diagnostic of neuropathy, including paresthesia, sensorimotor deficits and abolition of reflexes (symmetrical? distal? Please clarify). Also, it is possible misdiagnosis since neuropathy was evaluated by internal medicine, infectious diseases, or intensive care departments (line 77). There are no nerve conduction studies, therefore subclinical neuropathy could be underestimated and misdiagnosis could also exist.

In addition, I would like the authors to discuss the following points:

79. Please, clarify what types of deficiency.

86. Include Peripheral Neuropathy Disability (PND) functional scores in the article.

124. Why do you think toxicity is the second frequent cause of neuropathy? It is not common. Please argue this.

125. Guillain-Barré syndrome is the third cause with 48 cases, could you determine any associated infection?

127. What is “Bita”? Is it a regional plant?

Table 1. It is striking that there are no cases of thyroid disorders, that FAP and HNNP occur more than CMT, and that alcohol consumption is not among the main causes.

86. PND functional scores were determined retrospectively from medical records to quantify functional severity at disease onset and last hospital visit. In Table 1, do the PND score data refer to baseline or last visit? It would be interesting to determine how the PND score evolved over time between the first and last visit.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Pattern, causes and functional outcome of peripheral neuropathies in the Amazon region

PONE-D-24-27124R1

Dear Dr. Nathalie DESCHAMPS,

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.

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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 #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: (No Response)

Reviewer #3: Yes

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

Reviewer #2: (No Response)

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: (No Response)

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: (No Response)

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: (No Response)

Reviewer #3: Thank you for taking into account all of our corrections, comments and suggestions. I believe the manuscript is now ready for publication.

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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: No

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