Pulvinar Sign, Stroke and Their Relationship with Fabry Disease: A Systematic Review and Metanalysis

Round 1

Reviewer 1 Report

Reviewer Comments

The manuscript by Juan Fernando Ortiz. et al. entitled "Pulvinar sign, stroke, and their relationship with Fabry disease: a systematic review and metanalysis" has been reviewed by the authors. Now, the paper has been ameliorated, but there are still some issues that need to revised by the authors.

 

Comments:

1. Introduction, line 76: Please, correct Creutzfeldt-Jakob instead of Creutzfeldt-Jacob.
2. Results, line 128: it should be written 70%, not “0.70%”. Please, correct.
3. Results, Table 3: the caption of the table still reports “acute” renal failure, which should be erased.
4. Results, Bias analysis, Table 4: The data of table 4 are not discussed in the Discussion section. Would the authors drop this table, whose meaning is not clear?
5. Discussion, lines 159-164: The sentence should be revised. Now, the authors refer not only to genetic diseases, but also to other neurologic diseases with different etiology. I would simplify, by mentioning that the PS can be detected also in other diseases of different etiologies.
6. Discussion, lines 194-218: These three paragraphs need to be extensively revised. Indeed, at the moment the content of the paragraphs is quite confusing.

To current knowledge, there are two clinical phenotypes of Fabry disease: classical and later-onset (non-classical) phenotypes. Later-onset phenotypes include predominantly cardiac types (renal phenotype is not accepted as a specific variant).  Lee’s study refers to a specific later-onset variant (IVS4+919G>C), an intronic variant, common in Asian countries (Taiwan, China and Japan). It is one of the cardiac clinical types, not the only one. This intronic variant is the most frequent cardiac genetic variant in Asia; in Europe the most frequent cardiac genetic variant is the p.Asn215Ser.

The aforementioned sentences should guide the authors to rewrite the three paragraphs.

One more thing, the reference 33 (Hirashio et al.) is not the appropriate one to quote in the first of the three mentioned paragraphs. 

7. Discussion, Additional Clinical Markers: I do not see the necessity to talk about other neuroradiological markers, because the paper is focused on the pulvinar sign. Nevertheless, the discussion is too short and, as it is, is not useful. For example, the authors did not report differences on the basilar artery dolichoectasia between males and females and during aging process, and the same can be said for white matter hyperintensities. Furthermore, there are relevant papers on these two topics that should be quote.

I suggest to leave out this paragraph.

8. Discussion, Limitations, line 255-257: the authors wrote: “For example, Moore et al. include only male patients and Burlina (2012) include only female patients (15,17)”. The sentence should be rephrased. Indeed, the study of Burlina et al. (2012) is a report of four female Fabry patients, it is not a cohort study which includes “only” female patients. Furthermore, the study of Takanashi (2003) included in his cohort a female patient. Then, the references 15 and 17 are not the appropriate ones, please check.
9. Discussion, Limitations, line 257-258: the authors wrote: “Some studies include papers with non-classic phenotype cardiac phenotype”. The studies did not include papers, it should be written: “Some studies included cohorts of non-classical phenotype patients, with cardiac type (or variant)”. The authors should be consistent: they usually wrote non-classical, not non-classic.
10. Discussion, Conclusions, line 267-269: the authors wrote: “Among phenotypes, the sign is more frequent in the classical phenotype than the non-classical phenotypes, the cardiac variant has a higher prevalence of the pulvinar sign”. I suppose the authors wanted to say “but” the cardiac variant has a higher prevalence of the pulvinar sign. Anyway, this is not correct, because the authors analyse only the Asian cardiac variant. The sentence should be reformulated.

Author Response

Dear Reviewer, attached you will find the corrections suggested.

Have a great day!

Juan Fernando Ortiz, M.D.

 

Author Response File: Author Response.pdf

Reviewer 2 Report

This version is fine, you just have to check for few minor English grammatical errors.

Author Response

Dear Reviewer, as suggested the language was improved accordingly.

Have a great day!

Regards,

Juan Fernando Ortiz, M.D.

Reviewer 3 Report

Comments addressed

Author Response

Greetings.

Dear Reviewer, the language has been improved accordingly to your suggestions.

Have a great day!

Regards,

Juan Fernando Ortiz, M.D.

Round 2

Reviewer 1 Report

Reviewer Comments

The manuscript by Juan Fernando Ortiz. et al. entitled "Pulvinar sign, stroke, and their relationship with Fabry disease: a systematic review and metanalysis" has been fully revised by the authors. There are now only few issues that need to be revised.

Comments:

1. Discussion, line 170: The authors wrote: “It is typically associated with a low-intensity signal on MR imaging due to the interaction of calcified tissue and protons”. Please, correct and write: “ On MR imaging, the T1 shortening effect is due to the interaction of calcified tissue and protons “.
2. Discussion, lines 194-195: The authors wrote: “In the later-onset form, there is also a particular late-onset phenotype with a predominant cardiac IVS4+919G>C), an intronic variant, common in Asian countries”. Please, correct the sentence as follows:

“Among the later-onset forms, there is also a particular later-onset phenotype with a predominant cardiac variant, an intronic variant (IVS4+9191G>A), common in Asian countries”.

3. Discussion, lines 205-206: The authors wrote: “…a predominant cardiac IVS4+919G>C)”. Please, correct as follows: “….a predominant cardiac variant (IVS4+919G>A)”.
4. Discussion, line 207: Please, write “cardiac Fabry’s phenotype” instead of “Cardiac Fabry’s phenotype”.
5. Discussion, line 211: Please, write “Burlina et al”, instead of “burlina et al.”
6. Discussion, line 218: Please, write “classical phenotype”, instead of “Classical phenotype.”
7. Discussion, line 233: The abbreviation RF has not been explained before in the text, therefore, please, use the complete words. Write “renal failure” instead of “RF”.
8. Discussion, line 233: The abbreviation RF has not been explained before in the text, therefore, please, use the complete words. Write “renal failure” instead of “RF”.
9. Limitations, lines 254-256: The authors wrote: “While in the case series of Burlina (2012), there was a prevalence of 50% (2/4) in the pulvinar sign, which is very different from other results (22): We believe that case series could be an outliner”. As already pointed out in the previous revision, the Burlina et al. (2012) is not a case series is a clinical report of four female sisters, two of them with the pulvinar sign. Therefore, we cannot talk about prevalence, the sentence should be reformulated as follows: “Regarding the detection of pulvinar sign in female Fabry patients, we should just mention the report of Burlina et al. (2012), where two sisters out of four showed PS at brain MRI”.
10. Limitations, line 261: Please, write “renal failure” instead of “Renal Failure”.

 

Author Response

The changes were made as suggested. You can in the manuscript that all your suggestions were addressed and corrected

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

See the attached file.

Comments for author File: Comments.pdf

Reviewer 2 Report

English must be improved widely. In the introduction you speak about classic FD phenotype prevalence in males, but female one is lacking.

Reviewer 3 Report

The manuscript "Pulvinar Sign, Stroke, and Their Relationship with Fabry
Disease: A Systematic Review and Metanalysis" by Ortíz et al is a manuscript of limited interest.

1. The disease covered is important but the approach and outcome is not promising.
2. The authors have not mentioned any exclusion/inclusion criteria.
3. The use of English is pathetic. The first line of abstract "Fabry disease (FD) is the second most common lysosomal storage disorder
   causing." is incomplete and this is where I lost my ineterest.