Mechanisms of Neurosyphilis-Induced Dementia: Insights into Pathophysiology

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In this review, the Authors explored the fundamental pathophysiology of neurosyphilis-induced dementia, drawing on current research to clarify its mechanisms and impact. By understanding the relationship between treponema pallidum infection and neurodegeneration, the Authors aimed to inform clinical practices and guide future research in this evolving area. 

Overall, I found this expert opinion narrative review timely, straightforward, original and scientifically sound: I have only some minor suggestions aimed at improving the high quality of the paper, and these are outlined below:

1. In the introduction, a brief note on the fact on what are also the most common  psychiatric symptoms in neurosyphilis-induced dementia and how to these are (if any) different or similar to other dementia.
2. However, even if narrative and interesting, I would suggest the Authors introduce a very basic and brief section on Materials and Methods of the review to let the readers know how they conducted the literature searches with relevant key terms.
3. Translating into “real world” clinical practice and medicine, what possible clinical shreds of evidence might arise from the present review and what the Researchers do suggest to improve everyday clinical practice? I suggest to add a box with the most important points pointed out by this review to give an express view to the clinicians.

Comments on the Quality of English Language

The English language should be improved a bit 

Author Response

We very much appreciate the opportunity to resubmit our manuscript, “Mechanisms of Neurosyphilis-Induced Dementia: Insights into Pathophysiology.” First, we thank the Reviewers for their positive and encouraging comments on our m/s and the many valuable suggestions for improvement. We have seriously considered all these concerns, and appropriate changes have been made in the revised m/s.

In this resubmission, we have responded to all the issues raised by the reviewers and made appropriate changes. We have submitted two versions of the m/s: 1) Modified Version: changes have been identified in red color and strikeouts, and 2) Clean Version: does not identify the changes.

Response to reviewer's comments:

 

In this review, the Authors explored the fundamental pathophysiology of neurosyphilis-induced dementia, drawing on current research to clarify its mechanisms and impact. By understanding the relationship between treponema pallidum infection and neurodegeneration, the Authors aimed to inform clinical practices and guide future research in this evolving area. 

 

Overall, I found this expert opinion narrative review timely, straightforward, original, and scientifically sound. I have only some minor suggestions aimed at improving the high quality of the paper, and these are outlined below:

 

1. In the introduction, a brief note on the facts on what are also the most common psychiatric symptoms in neurosyphilis-induced dementia and how these are (if any) different or similar to other dementia.

• Thank you for the suggestion. We have added a paragraph specifically describing the unique clinical features of neurosyphilis in section 6 because another reviewer suggested the same thing.

 

2. However, even if the narrative is interesting, I would suggest the Authors introduce a very basic and brief section on the review's Materials and Methods to let the readers know how they conducted the literature searches with relevant key terms.

• We now added a section regarding Materials and Methods as per the suggestion

 

3. Translating into “real world” clinical practice and medicine, what possible clinical shreds of evidence might arise from the present review, and what do the researchers suggest improving everyday clinical practice? I suggest adding a box with the most essential points pointed out by this review to give an express view to the clinicians.

• We now added a paragraph discussing the real world in clinical practice and future prospective about neurosyphilis and how to prevent development of dementia.

Reviewer 2 Report

Comments and Suggestions for Authors

The present manuscript reported the adverse outcomes, diagnosis, pathophysiology, and treatment of neurosyphilis induced dementia. The following issues to be addressed by authors in the revised manuscript.

·       Line 38 instead agent write it as organism

·       Add at least 2 to 3 references in first paragraph of introduction

·       Line 140-147, 187-193, 194-197, 211-219, 220-22, Section 7 (first three paragraphs) 5,: Provide references

·       Autohrs should provide the reference for the Figure 2

·       Italicize Treponema pallidum

·       Section 7: This section discussing various drugs managing the neurological issues. The cited reference is majorly indicating protective response against neurological diseases, but not neurosyphilis. Therefore, author need to cite the text which are relevant to the neurosyphilis.

·       Discussion on combination of antibiotics and memory enhancing agents would be appreciated

·       Section 6; In detail clinical identification of neurosyphilis dementia is appreciated

·       Section 4 and 8 can be merged

·       Dementia can be identified with imbalances in cholinergic nervous system. Authors need to discuss the relationship between neurosyphilis induced dementia and cholinergic system imbalances, Similarly, discuss amyloid beta aggregation, tau tangles formation, NMDA signalling in the pathophysiology section.

·       Write future scope and limitations of the present study

·       It is unclear how TP induces neuroinflammation. In general bacteria releases endotoxins that could be responsible for the pathogenesis. Therefore, authors are advised to identify the potential excretory products of TP that could cause brain damage.

·       References 53-56 are not pertaining to neurosyphilis induced dementia. Therefore, authors need to add the suitable references. If these are speculations, authors need to mention that future studies should investigate it. Similarly, 18-25 references are not relevant to neurosyphilis induced dementia.

·       Cite the clinical studies that are investigating neurosyphilis induced dementia

·       Conclusion can be improved. Write clearly, what is existed and what is required

·       Majority of the references are not pertaining to syphilis and its mediated neuronal complications. Therefore, authors need to find the relevant literature.

Author Response

We very much appreciate the opportunity to resubmit our manuscript, “Mechanisms of Neurosyphilis-Induced Dementia: Insights into Pathophysiology.” First, we thank the Reviewers for their positive and encouraging comments on our m/s and the many valuable suggestions for improvement. We have seriously considered all these concerns, and appropriate changes have been made in the revised m/s.

In this resubmission, we have responded to all the issues raised by the reviewers and made appropriate changes. We have submitted two versions of the m/s: 1) Modified Version: changes have been identified in red color and strikeouts, and 2) Clean Version: does not identify the changes.

Response to reviewer's comments:

The present manuscript reported the adverse outcomes, diagnosis, pathophysiology, and treatment of neurosyphilis-induced dementia. The authors will address the following issues in the revised manuscript.

• Line 38, instead of an agent, write it as an organism
• Corrected
• Add at least 2 to 3 references in the first paragraph of the introduction
• References have been added accordingly
• Line 140-147, 187-193, 194-197, 211-219, 220-22, Section 7 (first three paragraphs) 5, Provide references
• Added to the revised manuscript
• Authors should provide the reference for Figure 2
• Kindly, this figure is an original figure.
• Italicize Treponema pallidum
• Corrected
• Section 7: This section discusses various drugs for managing neurological issues. The cited reference majorly indicates a protective response against neurological diseases but not neurosyphilis. Therefore, the author must cite the texts relevant to neurosyphilis.
• The only treatment available to treat neurosyphilis is penicillin IV. No other treatment options were effective to stop this bacterium. Therefore, if no treatment is provided at the right time, dementia will develop, and once the dementia starts, none of the medications are good enough to regress the pathology. Therefore, only slowing the progression.
• Discussion on a combination of antibiotics and memory-enhancing agents would be appreciated
• A paragraph added to the treatment section as per the suggestion
• Section 6: In detail, clinical identification of neurosyphilis dementia is appreciated
• Added as per the suggestion
• Sections 4 and 8 can be merged
• We now merge those paragraphs as per the valuable suggestion
• Dementia can be identified with imbalances in the cholinergic nervous system. The authors need to discuss the relationship between neurosyphilis-induced dementia and cholinergic system imbalances; similarly, they discuss amyloid beta aggregation, tau tangles formation, and NMDA signaling in the pathophysiology section.
• A paragraph was added to the pathology section as per the suggestion.
• Write the future scope and limitations of the present study
• We added a paragraph discussing the future scope and limitations to the revised manuscript.
• It is unclear how TP induces neuroinflammation. In general, bacteria release endotoxins that could be responsible for pathogenesis. Therefore, authors are advised to identify the potential excretory products of TP that could cause brain damage.
• We now added a paragraph describing the pathophysiology as per your valuable comment. Thank you
• References 53-56 are not about neurosyphilis-induced dementia. Therefore, authors need to add suitable references. If these are speculations, the authors must mention that future studies should investigate them. Similarly, 18-25 references are not relevant to neurosyphilis-induced dementia.
• We now changed all the references as per the suggestions. Thank you
• Cite the clinical studies that are investigating neurosyphilis-induced dementia
• Unfortunately, there are no clinical studies. We hope this manuscript with highlights the importance of such preventable dementia to focus on more studies in the future.
• Conclusion can be improved. Write clearly, what exists and what is required
• We rewrote the conclusion as per the suggestion.
• The majority of the references are not about syphilis and its mediated neuronal complications. Therefore, authors need to find the relevant literature.
• We now changed/added new references as per the suggestions.

In closing, we are most grateful to you and the reviewers for the very insightful, detailed, and helpful comments, all of which we have dealt within this letter, text and in figures. We hope that in its present form you will now find the manuscript suitable for publication in the Journal of Neurology international.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Authors have satisfactorily addressed all the issues.