SPHYNCS: The Use of the Swiss Narcolepsy Scale in a New Cohort of Patients with Narcolepsy and Its Borderland and Review of the Literature

Response to Reviewer

1. Summary

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files. We strived to address all comments and suggestions.

2. Point-by-point response to Comments and Suggestions for Authors

Comments 1: “There are some grammatical errors, such as missing commas in complex sentences. For example: "We analyzed data of the first n = 156 participants included in the iSPHYNCS study and identified n = 122 participants, in whom the results of the SNS and ESS scores at enrollment visit were available..."

Inconsistent use of verb tenses. For instance, "The original SNS score, updated SNS score, and sSNS score showed a high sensitivity and at the same time high specificity..." could be made clearer by maintaining consistency in tenses.

Some sentences are confusing (english language must be improved).”

Response 1: Thank you for pointing this out. We significantly altered the narrative of the paper, including the correction of missing commas, the restructuring of complex sentences, and improvements in the use of the English language. These changes were implemented/approved by a co-author of the manuscript, who is a native English speaker. Regarding the statement about confusing sentences, could you please specify any that are unclear?

Comments 2: “The introduction could be improved by more clearly stating the research objectives and the context of the study. The objectives of the study are not explicitly mentioned.”

Response 2: Thank you for the comment. We have revised the introduction, emphasizing the context of the study specifically the lack of awareness of narcolepsy leading to a significant diagnostic delay in both adults and the pediatric population. The objectives are explicitly stated within the introductory section of the manuscript.

Comments 3: “The study does not discuss ethical considerations or approval by an ethics review board. Ethical oversight and informed consent procedures are vital in human research studies.”

Response 3: Institutional Review Board Statement & Informed Consent Statement are mentioned separately in the lines 337-340 of the revised manuscript (according to the CTN submission form).

Comments 4: “The conclusion should reiterate the key findings of the study, their implications, and potential directions for future research. The current conclusion is quite general, and more specific findings should be highlighted.”

Response 4: We appreciate your comment, and in response, we have revised the conclusion in line with your suggestions.

Comments 5: “Line 147: What is "liquor hypocretin measurement"? It appears that the authors employed a rudimentary translation tool.”

Response 5: We appreciate your comment, and in response, we have changed this to “cerebrospinal fluid hypocretin-1 (CSF Hcrt-1)”, in accordance with ICSD-III.

Comments 6: “Line 151-152: "narcolepsy borderland patients" should be "narcoleptic borderland" (the phrasing should be corrected too)”

Response 6: We appreciate your comment, and in response, we have changed “narcolepsy borderland” to “narcoleptic borderland “.

Comments 7: “A ROC analysis is needed for evaluating the performance of this diagnostic test. In addition, the results must be compared against the gold standard for diagnosis (hypocretin levels in CSF).”

Response 7: We fully agree with your comment. We performed additionally a ROC analysis and added a description, respectively.

We greatly appreciate your comment on comparing the questionnaire results to CSF hypocretin-1 measurements. However, in our study cohort, not all patients with narcolepsy type 1 underwent CSF analysis. Nevertheless, all narcolepsy type 1 patients in our study fulfilled the ICSD-III criteria for NT1, diagnosed based on the presence of cataplexy and SOREMs. We have detailed our patient cohort in the 'Characteristics of the Study Population' section (lines 145-173)."

3. Response to Comments on the Quality of English Language

Comment: “Some paragraphs are quite long and could be divided into smaller, more focused sections to enhance readability and clarity. Use subheadings to organize the text, making it easier for readers to navigate through the study.

The introduction could be improved by more clearly stating the research objectives and the context of the study. The objectives of the study are not explicitly mentioned.

The narrative and use of english language must be improved”

Response: Thank you for pointing this out. We significantly changed the narrative of the paper, including the correction of missing commas, the restructuring of complex sentences, dividing paragraphs and improvements in the use of the English language. These changes were implemented/approved by a co-author of the manuscript, who is a native English speaker. The manuscript contains subheadings to improve readability of the paper.

4. Additional clarifications

Other reviewers recommended enhancing the background by discussing the diagnostic delay, particularly in young adults and children. Additionally, they suggested addressing the apparent diagnostic delay during the H1N1 influenza vaccination in 2009/10 and suggested several papers for citation. We have made efforts to incorporate these suggestions into the manuscript.

Response to Reviewer

1. Summary

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files. We strived to address all comments and suggestions.

2. Point-by-point response to Comments and Suggestions for Authors

Comments 1: “This is an important paper on a new diagnostic instrument in short form which will be valuable in the future.

I miss some aspects in your background in order to deepen the understanding of the complex diagnostic problems, first of all ignorance of the health care when investigating especially young people with EDS, including insufficient knowledge on narcolepsy. I suggest the authors may introduce  this topic which has a bearing on facilitating a diagnose using applicable tests for example your new instrument (the authors may cite doi 10.3389/fneur.2014.00140)”

Response 1: We greatly appreciate your comment on the diagnostic delay in young adults. Thank you for suggesting a relevant paper. In response, we have included an additional paragraph in the introduction, emphasizing the significance of recognizing excessive daytime sleepiness in young adults.

Comments 2: “In many countries who suffered from an increased narcolepsy morbidity due the H1N1 vaccination 2009/10 (at least thousand patients), the risk of delayed diagnosis is apparent. Please mention this important scenario briefly, and chose references by for example Partinen and Sarkanen (doi: 10.1016/S1474-4422(14)70075-4, DOI: 10.21668/health.risk/2020.3.22.eng). It has direct association to the need of simple diagnostics instruments like yours available in general practice and in pediatrics.”

Response 2: Thank you for highlighting the relevant issue of apparent diagnostic delay after the influenza vaccination in 2009/10. We find this aspect highly interesting. Consequently, we have incorporated this scenario into our manuscript, citing the papers you suggested. Additionally, we proposed another potential scenario involving diagnostic delay after COVID-19 infection or vaccination (lines 278-288).

Comments 3: “I also would like the authors to comment on the possibility to use this new scale in monitoring patients over time. ESS is evidently insufficient here, and not appreciated by the patients.”

4. Additional clarifications

Other reviewers required major improvements to the manuscript. These include enhancements to the introduction and conclusion, incorporating a ROC analysis to assess the diagnostic accuracy of the scales, and an overall improvement of the English language. We have made efforts to incorporate these suggestions into the manuscript.

Response to Reviewer

1. Summary

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files.

2. Point-by-point response to Comments and Suggestions for Authors

Comments 1: “The latest draft exhibits a considerable enhancement. I would suggest that the authors consider excluding abbreviations from the abstract, adhering to the journal's stylistic preferences, and presenting tables and figures in high quality formats.”

Response 1: We greatly appreciate your review. We have incorporated a few minor changes into the manuscript. Concerning the abbreviations, the abstract is limited to 200 words (according to the CTN stylistics), and we have already exceeded this limit. Therefore, it is essential to condense the text.

We have carefully re-read the entire paper, making improvements to the English language.

Additionally, we have downloaded the tables and figures separately in better quality. We will kindly request the editor to use them when publishing.