Review Reports

Round 1

Reviewer 1 Report

Your Review show that you performed ‘‘The ATP1A2 Mutation Associated with Hemiplegic Migraine Case Report and Literature Review’’. 

This paper contains very important and useful information with the ATP1A2 mutation associated with hemiplegic migraine. However, you need to prepare the answer for some information as described below. 

              

1 Mutations in ATP1A2 usually cause seizures starting at about age 10. In this case, the symptoms started at about age 30. Is the later onset time related to the genetic mutation?

 

2 The timing of onset of the headache seizures and the epilepsy is unclear. A time-course diagram should be created to show how many seizures occur in a month.

 

3 Is there an association between ATP1A2 mutations and clinical phenotypes of epileptic and headache seizures?

 

4 NMDA receptors have been described as a mechanism of CSD caused by ATP1A2 gene abnormalities.　Are antiepileptic drugs that suppress NMDA receptors a good therapeutic choice for this outcome?

Author Response

Dear reviewer:

Thank you for your letter and for the reviewers’ comments concerning our manuscript entitled ‘The ATP1A2 Mutation Associated with Hemiplegic Migraine: Case Report and Literature Review’(ctn-1989023).

Those comments are all valuable and very helpful for revising and improving our paper, as well as for their important guidance significance for our research. We have studied comments carefully and have made correction and we hope to meet with approval. The point-to-point responses to the reviewer’s comments has upload as a Word file. Thank you.

 

Yours sincerely,

Changyue Liu

Author Response File: Author Response.pdf

Reviewer 2 Report

Punctuation, grammar and spelling need to be significantly improved to make this a readable paper published in the english language. The sense of the case report time course and scientific theories are confused by the language issues. 

The role of CSD in seizures and obtundation are interesting but by 11 days into the event with seizure activity, there are other processes in action- was it considered that recurrent seizures may have caused some of the imaging findings? 

Author Response

Dear Reviewer:

Thank you for your letter and for the reviewers’ comments concerning our manuscript entitled ‘The ATP1A2 Mutation Associated with Hemiplegic Migraine: Case Report and Literature Review’(ctn-1989023).

Those comments are all valuable and very helpful for revising and improving our paper, as well as for their important guidance significance for our research. We have studied comments carefully and have made correction and we hope to meet with approval. The point-to-point responses to the reviewer’s comments are listed as follows. Thank you.

Yours sincerely,

Changyue Liu

Pont 1: Punctuation, grammar and spelling need to be significantly improved to make this a readable paper published in the english language. The sense of the case report time course and scientific theories are confused by the language issues.

Response 1: Thank you for your instructive suggestions. According to the reviewer’s comment, we have carefully corrected the manuscript. Furthermore, the manuscript been reviewed and corrected by the MDPI editorial team on the 12/11/2022. The spelling errors and grammatical issues in our manuscript were also revised in our revised manuscript.

 

Point 2: The role of CSD in seizures and obtundation are interesting but by 11 days into the event with seizure activity, there are other processes in action- was it considered that recurrent seizures may have caused some of the imaging findings?

Response 2: Thank you very much for your helpful advice. Dreier et al. have proposed that the edema on imaging presentation was vasogenic, the blood-brain barrier (BBB) opening as its cause [1] and Vazana et al. reported that seizures resulted in BBB opening [2]. Rempe et al. further lighted on the mechanism leading to seizure-mediated BBB dysfunction in epilepsy, they demonstrated that seizures increase MMP-2 and MMP-9 levels, leading to reduced levels of tight junction proteins and subsequent barrier leakage. also showed that glutamate signals through cPLA2 to trigger these changes in vitro and in vivo. Therefore, we also think that recurrent seizures caused some of the imaging findings [3].

 

[1]   Dreier, J P et al. “Opening of the blood-brain barrier preceding cortical edema in a severe attack of FHM type II.” Neurology vol. 64,12 (2005): 2145-7. doi:10.1212/01.WNL.0000176298.63840.99.

[2] Vazana, Udi et al. “Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.” The Journal of neuroscience : the official journal of the Society for Neuroscience vol. 36,29 (2016): 7727-39. doi:10.1523/JNEUROSCI.0587-16.2016.

[3]   Rempe, Ralf G et al. “Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy.” The Journal of neuroscience : the official journal of the Society for Neuroscience vol. 38,18 (2018): 4301-4315. doi:10.1523/JNEUROSCI.2751-17.2018.

Round 2

Reviewer 1 Report

I would like to accept that  the manuscript has been  sufficiently improved to warrant publication in CTN.