Restless Sleep Disorder and the Role of Iron in Other Sleep-Related Movement Disorders and ADHD

Round 1

Reviewer 1 Report

-The authors have planned a review in two parts; first about restless sleep disorder (RSD), and second about the role of iron in sleep-related movement disorders. However, the whole aspects of RSD are not fully covered. The review may be on the role iron in RSD and sleep-related movement disorders. 

-After giving a small data about hepcidin and transferrin, one or two sentence should be added to explain the ferritin and its role in the iron homeostasis. 

-Some of the sentences are very long and difficult to understand. Plus, some needs revision; ie, "... that DAT and D2R reduced expression would decrease the information...". 

-The sentence "Ferritin levels in the age groups...." requires a reference.

-Sleep-related movement disorders other than RLS and PLMD are not covered. After RLS and PLMD comes a section subtitled as "Sleep-related-movement disorders and the role of iron in ADHD patients". Reading the title of the review, it is difficult to expect for this data. I believe the title and the organization of the review should be revised for a better comprehensive presentation.

Minor editing of English language is required.

Author Response

-The authors have planned a review in two parts; first about restless sleep disorder (RSD), and second about the role of iron in sleep-related movement disorders. However, the whole aspects of RSD are not fully covered. The review may be on the role iron in RSD and sleep-related movement disorders.

-After giving a small data about hepcidin and transferrin, one or two sentence should be added to explain the ferritin and its role in the iron homeostasis. 

We thank the reviewer for the comment.

We added two sentences to explain the role of ferritin in iron homeostasis

-Some of the sentences are very long and difficult to understand. Plus, some needs revision; ie, "... that DAT and D2R reduced expression would decrease the information...".

We agree we reduced the length and simplified the paragraph

-The sentence "Ferritin levels in the age groups...." requires a reference.

Thanks for this. We added a reference

-Sleep-related movement disorders other than RLS and PLMD are not covered. After RLS and PLMD comes a section subtitled as "Sleep-related-movement disorders and the role of iron in ADHD patients". Reading the title of the review, it is difficult to expect for this data. I believe the title and the organization of the review should be revised for a better comprehensive presentation.

We edited the title in order include ADHD.

Minor editing of English language is required.

We fully edited the file to avoid errors

Reviewer 2 Report

Comments to the authors:

Thank you for inviting me to review the manuscript entitled “Restless Sleep Disorder and the Role of Iron in Other Sleep-Related Movement Disorders”.
This is a literature review focused on the role of iron at the basis of important sleep-related disorders, such as PLMD, RLS and RSD. The review concludes by identifying the link between iron deficiency and ADHD.
The review is comprehensive and very well written. It highlights an important topic that cross-bridges different sleep-related disorders. It presents data on the epidemiology, diagnostic criteria, provides evidence of the pathophysiology and the mechanisms of action of iron as treatment.
Here’s some major and minor comments that might improve the quality of the manuscript.

Major comments:
- I would find useful to explain why iron might be beneficial and used among the first line of treatment for children diagnosed with RLS and PLMD.
- the authors present a well-described section on the role of iron for RLS and PLMD. What is the current state of the art of implementing iron for RSD?
- I suggest that the authors include a short paragraph where they state their conclusion, that summarizes the insight of this article, and future direction and what future studies should address

Minor comments:

Abstract: this is well written. Minor suggestion: replace the period instead of the semi-comma from lines 19-23, otherwise the sentence is unnecessarily long and complex.

Introduction: This is well explained. To increase the clarify for the reader, especially those that are not that familiar with the topic, I suggest that the authors include a table that briefly summarize what distinguish RLS from RSD, in clinical symptoms and also in pathogenesis. This table should summarize the points explain in the first two sections of 1. Restless Sleep Disorder and 1.1. RSD Pathophysiology

The remaining sections are well explained. I identified above some of the points that might benefit a further speculation or more details.

Author Response

Thank you for inviting me to review the manuscript entitled “Restless Sleep Disorder and the Role of Iron in Other Sleep-Related Movement Disorders”.
This is a literature review focused on the role of iron at the basis of important sleep-related disorders, such as PLMD, RLS and RSD. The review concludes by identifying the link between iron deficiency and ADHD.

The review is comprehensive and very well written. It highlights an important topic that cross-bridges different sleep-related disorders. It presents data on the epidemiology, diagnostic criteria, provides evidence of the pathophysiology and the mechanisms of action of iron as treatment.

Here’s some major and minor comments that might improve the quality of the manuscript.

We thank the reviewer for the appreciation and for the constructive comments.

Major comments:

- I would find useful to explain why iron might be beneficial and used among the first line of treatment for children diagnosed with RLS and PLMD.

We added a sentence to better explain the beneficial effect of iron in RLS and RSD.

- the authors present a well-described section on the role of iron for RLS and PLMD. What is the current state of the art of implementing iron for RSD?

We specified in a new paragraph that “To date, no guidelines are available concerning RSD treatment in children; however, in clinical practice, iron supplementation has been applied to the management of pediatric RSD patients with successful outcomes. [29]”

- I suggest that the authors include a short paragraph where they state their conclusion, that summarizes the insight of this article, and future direction and what future studies should address
Thanks, we added a conclusions paragraph

Minor comments:

Abstract: this is well written. Minor suggestion: replace the period instead of the semi-comma from lines 19-23, otherwise the sentence is unnecessarily long and complex.

Thanks we modified as suggested

Introduction: This is well explained. To increase the clarify for the reader, especially those that are not that familiar with the topic, I suggest that the authors include a table that briefly summarize what distinguish RLS from RSD, in clinical symptoms and also in pathogenesis. This table should summarize the points explain in the first two sections of 1. Restless Sleep Disorder and 1.1. RSD Pathophysiology
Thanks we added the table

The remaining sections are well explained. I identified above some of the points that might benefit a further speculation or more details.

Round 2

Reviewer 1 Report

Revisions are satisfactory. Thanks