The Anti-Vaccine Legacy: Re-Emergence of Subacute Sclerosing Panencephalitis in Children

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript presents a case series of seven pediatric patients diagnosed with subacute sclerosing panencephalitis (SSPE) associated with measles infection detected from January 2021 to December 2025. It describes their demographic data, clinical characteristics, history of measles infection and vaccination, onset of symptoms, and diagnosis. All patients presented at a similar disease stage with characteristic EEG findings, while MRI results were variable. The study also outlines treatment approaches, clinical progression, and follow-up outcomes, highlighting the generally poor prognosis despite therapeutic interventions. The demographic, clinical manifestation, diagnosis, treatment, and outcome are clearly described and presented, and the discussion is appropriate. Some comments have been provided as follows.

1. In line 16, please clarify whether the correlation between SSPE incidence and measles vaccination coverage is positive or negative.

2. Please clarify whether this manuscript is intended to be a research article or a case series, as it currently reads more like a case report (series). If so, the article type should be revised accordingly. The main text should present Cases 1–7 individually, with clear diagnostic evidence provided for each case.

3. The Introduction section should more clearly define the study gap. The “epidemiology” and “pathogenesis” sections should be integrated into a single paragraph within the Introduction, and the aim of the manuscript should be clearly stated. 

4. In lines 233–235, please relocate the aim of this study to the introduction section and revise the stated aim of the study to remove redundant terms and ensure alignment with the presented data. For example, terms such as “demographic data” and “including sex and age distribution”, “diagnostic investigations performed” and “management”, “clinical data” and “clinical presentation” may be repetitive or overly broad. Additionally, please exclude any elements that were not actually analyzed in the study.

5. In lines 240-245, the main text that the author provides is not appropriate to use subheading “epidemiological data”. Epidemiological data usually refer to population-level patterns (e.g., incidence, prevalence, trends, risk factors at a broader scale), whereas the context describes patient characteristics. Please clarify.

6. In the treatment section, it would be helpful to present the information in a table for clarity.

7. It would be clearer if the authors presented a table summarizing demographic data, symptom onset, latency period, and measles infection and vaccination history for each case.

8. Lines 253–261 should be relocated to follow Case 7 for better consistency.

9. In line 391, the subheading “Evolution” is not appropriate for the context. Please revise it to “Clinical Outcomes and Follow-up” or “Treatment Response”.

Author Response

Reviewer 1

Comments and Suggestions for Authors

This manuscript presents a case series of seven pediatric patients diagnosed with subacute sclerosing panencephalitis (SSPE) associated with measles infection detected from January 2021 to December 2025. It describes their demographic data, clinical characteristics, history of measles infection and vaccination, onset of symptoms, and diagnosis. All patients presented at a similar disease stage with characteristic EEG findings, while MRI results were variable. The study also outlines treatment approaches, clinical progression, and follow-up outcomes, highlighting the generally poor prognosis despite therapeutic interventions. The demographic, clinical manifestation, diagnosis, treatment, and outcome are clearly described and presented, and the discussion is appropriate. Some comments have been provided as follows.

Thank you for your kind review and for all your valuable comments and suggestions.

Comments 1. In line 16, please clarify whether the correlation between SSPE incidence and measles vaccination coverage is positive or negative.

Response 1: The correlation between the occurrence of PESS and vaccination coverage is negative. Thank you for this observation. We will modify it as follows: 'Its incidence is negatively correlated with measles vaccination coverage'.

Comments 2. Please clarify whether this manuscript is intended to be a research article or a case series, as it currently reads more like a case report (series). If so, the article type should be revised accordingly. The main text should present Cases 1–7 individually, with clear diagnostic evidence provided for each case.

Response 2 Certainly, the submitted work could be classified as a case series, as you rightly point out. However, we decided to classify it as an article because it contains both a significant theoretical section, which aims to present the most recent data regarding the studied pathology, and our original research.

Our research is indeed limited to a very small number of cases, but this is explained by the rarity of this condition. Furthermore, since we have not admitted any child with this disease to our hospital over the past two decades and, according to available data, no cases have been reported in Romania, we considered this work an article rather than a case study. Our goal was to raise awareness of this condition, which, although not new, is resurfacing after a long absence, emphasizing that the global trend of non-vaccination has devastating consequences and that such cases are unfortunately likely to reappear in other regions with insufficient vaccination coverage.

Comments 3. The Introduction section should more clearly define the study gap. The “epidemiology” and “pathogenesis” sections should be integrated into a single paragraph within the Introduction, and the aim of the manuscript should be clearly stated.

Response 3. Thank you for these suggestions. We will clearly specify both the aim and the gaps in the study.

The gaps and limitations of the study are due to the small number of cases and the lack of treatment protocols for SSPE. Further research is needed to obtain a curative treatment for SSPE, and it is very important to increase the vaccination rate as a primary preventive measure.

The aim of this study is to bring SSPE back into discussion—a disease described a century ago that still has no curative treatment, despite advances in medical science.

 

Comments 4. In lines 233–235, please relocate the aim of this study to the introduction section and revise the stated aim of the study to remove redundant terms and ensure alignment with the presented data. For example, terms such as “demographic data” and “including sex and age distribution”, “diagnostic investigations performed” and “management”, “clinical data” and “clinical presentation” may be repetitive or overly broad. Additionally, please exclude any elements that were not actually analyzed

Response 4. Thank you for your comment.

In this section, we aimed to present the cohort of patients studied, as well as the study period, and to mention that this is a descriptive retrospective study based on an analysis of patient medical records.

We aimed to analyze demographic data (age and sex distribution), epidemiology (measles infection and vaccination status), clinical data (latency period, symptomatology on onset, clinical presentation at hospital admission, and clinical stage on admission), paraclinical diagnostic, treatment, and clinical outcome.

We have revised the paragraph in the article in accordance with your suggestion

 

Comments 5. In lines 240-245, the main text that the author provides is not appropriate to use subheading “epidemiological data”. Epidemiological data usually refer to population-level patterns (e.g., incidence, prevalence, trends, risk factors at a broader scale), whereas the context describes patient characteristics. Please clarify.

Response 5. Thank you for your very pertinent question.

Since, when we refer specifically to the epidemiology of PESS, we take into account the fact that it is inversely correlated with vaccination status and that the risk of onset is higher in children who have had measles infection, especially at a young age (as we presented in the theoretical section), we considered it appropriate to mention these aspects under the subheading of ”epidemiological data”, even though, as you pointed out, this term typically also encompasses the factors you mentioned.

Comments 6. In the treatment section, it would be helpful to present the information in a table for clarity.

Response 6. Thank you for your insightful comment. Indeed, the data is much clearer and easier to understand when the therapeutic elements are presented in table form. That is why we chose this approach, which we also find very useful..

 

Comments 7. It would be clearer if the authors presented a table summarizing demographic data, symptom onset, latency period, and measles infection and vaccination history for each case.

Response 7. That is a very valid point; we had also planned to present this data in tabular form. However, because the clinical presentation varied so greatly and was so complex between patients, we chose to describe it in detail for each patient individually. To avoid overloading the article with too many tables, we decided to address the other aspects separately within the text. However, for clarity, we have chosen to include the clinical stage at admission in the table, even though we have described the symptoms separately in the text.

 

Comments 8. Lines 253–261 should be relocated to follow Case 7 for better consistency.

Response 8. Thank you again for sugesstion, we will relocate this part after Case 7.

Comments 9. In line 391, the subheading “Evolution” is not appropriate for the context. Please revise it to “Clinical Outcomes and Follow-up” or “Treatment Response”.

Response 9. This recommendation is very appropriate; we will choose «Clinical Outcomes and Follow-up.” 

Response to Reviewer 1

Thank you for taking the time to read our article, as well as for your extremely valuable comments and suggestions, which definitely add value to the content. We hope that the explanations we have provided regarding the parts that were less clear will help you understand the approach we took in presenting certain aspects.

Reviewer 2 Report

Comments and Suggestions for Authors

In the manuscript « The Anti-Vaccine Legacy: Re-Emergence of Subacute Sclerosing Panencephalitis (SSPE) in Children », Maria-Delia Mihailov et al., followed SSPE diagnosed children in a Hospital for 5 years in order to analyze demographic and epidemiological factors, clinical and paraclinical findings, management, and outcomes. This is a significant study, given that the declining incidence of SSPE has made research increasingly difficult to conduct over the last decades.

Here are my comments and suggestions :

• The authors claim that no children had immunosuppression. However, could the patients have experienced transient immunosuppression due to a concurrent disease ? At the moment of the emergence of SSPE symptoms, is it known if the children contracted COVID-19 of flu ? Were they vaccinated against SARS-CoV-2 and Influenza ? It could be interesting to have these informations.
• How were the treatments chosen? The authors mentioned nucleosid analogs. Do the authors considered these kind of treatments, especially Remdesivir ?
• The addition of a diagram showing the evolution of symptoms over time for each patient (improvement or worsening) in relation to treatment administration would be useful.

Author Response

 

Please see the attachment

 

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

"The pathogenesis of the disease is not fully understood, but it appears that the hy-permutant measles virus, in combination with an abnormal cellular response and genetic susceptibility, is responsible for its onset"

there is literature on abnormalities and mutations in the measles virus, e.g. absence of m protein, etc. that are thought to account for SSPE which could be cited here.  

 

The issue is important but not new.  I leave it to the editors to decide whether this review of new cases warrants publication.  

Author Response

Please see the attachment

Author Response File: Author Response.pdf