Alternating hemiplegia of childhood: An electroclinical study of sleep and hemiplegia

Josephine Poole; Sara Zagaglia; Rita Demurtas; Fiona Farrell; Matthew C. Walker; Sanjay M. Sisodiya; Simona Balestrini; Umesh Vivekananda

doi:10.1371/journal.pone.0268720

Peer Review History

Original SubmissionMay 3, 2022
26 Jul 2022 Decision Letter - Dragan Hrncic, Editor PONE-D-22-12955ALTERNATING HEMIPLEGIA OF CHILDHOOD: AN ELECTROCLINICAL STUDY OF SLEEP AND HEMIPLEGIAPLOS ONE Dear Dr. Vivekananda, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ============================== ACADEMIC EDITOR: Please do follow very useful comments and directions provided by the reviewers. Justify and explain the current sample size. ============================== Please submit your revised manuscript by Sep 09 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: N/A ****** 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: No Reviewer #2: Yes ****** 4. 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 #1: Yes Reviewer #2: Yes ****** 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: This retrospective study assessed EEG spectral analysis in 5 adults with alternating hemiplegia of childhood (AHC) and 12 age-/gender-matched epilepsy controls. The data show two main statistically significant results: hemispheric differences in pre-ictal and ictal spectral power during AHC hemiplegic episodes; reduced beta power and increased delta power during wakefulness in AHC patients, in comparison with controls. Data are clearly reported, statistically analyzed and appropriately discussed. Both AHC patients and epilepsy controls were taking drugs at the time of the study. This represents an insurmountable limit of the paper. I think that the Authors should specify in the text or in a supplementary file which drugs the epilepsy controls were taking. Also in the Table 1 another column could contain the drugs taken by the AHC patients. Reviewer #2: This paper examines the role of sleep in the rare disorder of Alternating Hemiplegia of Childhood in cases studied in adult life. AHC is a fascinating disorder where seizures are frequent but ill-understood other paroxysmal phenomena occur, most prominently hemiplegia, that resolves with sleep. While sleep has been studied in this disorder, the novel aspect of this paper is the examination of adult subjects and the more detailed spectral analysis performed on hemiplegic attacks, although only 2 of the 5 cases had these. The clinical features of the 5 cases are typical of AHC. The description of the telemetry recordings of the events is useful although this was done retrospectively and eye movement monitors were not used preventing scoring of REM sleep. Key findings were lateralization on EEG during the events where this was interpretable and spectral clots documenting the hemispheric asymmetry during events. A change in spectral power between AHC and control groups was found in the awake state only, the significance of this is a little unclear. It would be useful if the lateralization could be more clearly described. For example, in table 3, the hemispheres are divided up in to those with “increased activity” and “reduced activity” but it is not immediately clear whether which hemisphere is relevant to the hemiplegic limb. Similarly, with the topographic maps shown on figure 1, it is not really clear what side of the body was paralysed in relationship to the evolution of the spectral power pre and post event and this should be clarified. Under ‘significance’ the authors state that disrupted sleep is related to SUDEP. It is quite unclear what the data in this paper adsd to the understanding of SUDEP, in general or in AHC and it is nor even properly discussed. I recommend this be deleted Overall this represents a modest but useful addition to the literature on this fascinating syndrome. ****** 6. 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 #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0268720.r001
Revision 1
5 Sep 2022 Author Response Dear Editors, Thank you for sending our manuscript for peer review, and for giving us the opportunity to address the reviewers’ comments. Below we provide detailed answers to the comments made by the reviewers, and tracked all the changes in the manuscript. In addition, we addressed the journal requirements as requested. Reviewer #1: We are grateful that the reviewer found the data clearly reported, statistically analyzed and appropriately discussed. Both AHC patients and epilepsy controls were taking drugs at the time of the study. This represents an insurmountable limit of the paper. I think that the Authors should specify in the text or in a supplementary file which drugs the epilepsy controls were taking. Also in the Table 1 another column could contain the drugs taken by the AHC patients. We thank the reviewer for this important point. We have now added treatment data for both patients and epilepsy controls in Table 1 and Supporting Table 1, respectively. We also wrote in the discussion (page 9): ‘Another potential source of confounding was the complex polytherapy, mostly comprising antiseizure medications, that both the patients with AHC and the epilepsy control group received. This could have affected the EEG power and arousal data.’ Reviewer #2: We agree with the reviewer that AHC is a fascinating disorder where seizures are frequent but ill-understood other paroxysmal phenomena occur, most prominently hemiplegia, that resolves with sleep. While sleep has been studied in this disorder, the novel aspect of this paper is the examination of adult subjects and the more detailed spectral analysis performed on hemiplegic attacks, although only 2 of the 5 cases had these. The clinical features of the 5 cases are typical of AHC. The description of the telemetry recordings of the events is useful although this was done retrospectively and eye movement monitors were not used preventing scoring of REM sleep. Key findings were lateralization on EEG during the events where this was interpretable and spectral clots documenting the hemispheric asymmetry during events. A change in spectral power between AHC and control groups was found in the awake state only, the significance of this is a little unclear. It would be useful if the lateralization could be more clearly described. For example, in table 3, the hemispheres are divided up in to those with “increased activity” and “reduced activity” but it is not immediately clear whether which hemisphere is relevant to the hemiplegic limb. Similarly, with the topographic maps shown on figure 1, it is not really clear what side of the body was paralysed in relationship to the evolution of the spectral power pre and post event and this should be clarified. We thank the reviewer for this important distinction. Even with experienced neurophysiologists reviewing the attacks, due to the complex nature of them, it was challenging to definitively assign clinical lateralisation to the majority. Indeed normal hemi-function was demonstrated in two events where we can be certain about lateralisation. In these two cases the corresponding lateralisation of spectral power (i.e. contralateral to clinical semiology) was demonstrated. What is interesting is that nearly all attacks demonstrated prior spectral lateralisation irrespective of clinical semiology, which argues the possibility that attack onset has a focus. For this reason, we used increased/reduced spectral activity as a comparator in order to permit statistical analysis. For ease of understanding we have outlined each of the attacks in Table 2, and amended Figure 1 and Supplemental Figure 1 to incorporate clinical semiology when possible. Under ‘significance’ the authors state that disrupted sleep is related to SUDEP. It is quite unclear what the data in this paper adds to the understanding of SUDEP, in general or in AHC and it is nor even properly discussed. I recommend this be deleted. We have now removed the statement on SUDEP, as suggested. Attachments Attachment Submitted filename: Response to Reviewers PLOSONE.docx https://doi.org/10.1371/journal.pone.0268720.r002
19 Sep 2022 Decision Letter - Dragan Hrncic, Editor ALTERNATING HEMIPLEGIA OF CHILDHOOD: AN ELECTROCLINICAL STUDY OF SLEEP AND HEMIPLEGIA PONE-D-22-12955R1 Dear Dr. Vivekananda, 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. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Prof. Dr. Dragan Hrncic, MD, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): 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 #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 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 #1: Yes Reviewer #2: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: N/A ****** 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 #1: Yes Reviewer #2: Yes ****** 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 #1: Yes Reviewer #2: Yes ****** 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 #1: The Authors addressed all the reviewers' comments and queries, improving the quality of their paper. Reviewer #2: My concerns have been addressed. My concerns have been addressed. My concerns have been addressed. My concerns have been addressed. ****** 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 #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0268720.r003
Formally Accepted
21 Sep 2022 Acceptance Letter - Dragan Hrncic, Editor PONE-D-22-12955R1 Alternating Hemiplegia of childhood: an electroclinical study of sleep and Hemiplegia Dear Dr. Vivekananda: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Dragan Hrncic Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0268720.r004

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