Effects of Anti-CGRP Monoclonal Antibodies on Neurophysiological and Clinical Outcomes: A Combined Transcranial Magnetic Stimulation and Algometer Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The results in the abstract do not reflect the obtained findings. It is uncertain to what extent they are significant and practical.

 

The sentences in the introduction are too general, i.e., too many references are attributed to them (e.g., 5-12, etc.). Specifics should be pointed out, knowing what these references indicate.

 

Please indicate the p-value precisely, avoiding styles like p < 0.05 but rather using, for example, 0.02. Do not write p-values in the style .02. Avoid phrases like ns p>.05, but instead use, for instance, p = 0.32.

 

Results for the Mann-Whitney test should be presented appropriately, e.g., U = 23; p = 0.02, while for Friedman's ^χ2_F(2) = 2.571, p = 0.276.

 

It is advisable to calculate appropriate measures of effect size; relying solely on the p-value is insufficient (e.g., Glass rank biserial correlation coefficient and Kendall's W value).

 

Descriptive statistics for such tests should be expanded to include the median and quartiles.

Comments on the Quality of English Language

Minor editing of English language required.

Author Response

Dear reviewer 1

My coauthors and I wish to thank you for the valuable comments and suggestions related to our submission titled “ Effects of Anti-CGRP Monoclonal Antibodies on Neurophysiological and Clinical Outcomes: a Combined TMS and Algometer Study.”.

The suggestions and precious comments have greatly improved our paper’s scientific quality and impact. We have addressed your concerns below, and we have amended the manuscript according to your recommendations.

Please, find all changes highlited in yellow throughout the submitted manuscript.

Responses to Reviewers’ comments are shown in bold below.

Should you have any further requests or comments, please do not hesitate to contact us.

Kind regards,

Manuela Deodato

Reviewer #1

- "The results in the abstract do not reflect the obtained findings. It is uncertain to what extent they are significant and practical."

>>Thank you very much for this comment that improve the quality of our abstract section. Change in the article lines 21-28

"The main findings of this study are the significant effects of anti-CGRP mAbs treatment on TMS parameters of intracortical inhibition and the rise of the resting mo-tor threshold in our group of patients affected by resistant migraine. The clinical effect of therapy on migraine is associated with the increase of short interval intracortical in-hibition (SICI), resting motor threshold (RMT), and Pressure Pain Threshold (PPT). In all patients, all clinical headache parameters improved significantly 3 months after the first injection of mAbs and the improvement was maintained at 1-month follow-up. At baseline, migraineurs and HC had significant differences in all TMS parameters and in PPT, while at follow-up assessment no differences were observed on RMT, SICI and PPT between the two groups. "

-"The sentences in the introduction are too general, i.e., too many references are attributed to them (e.g., 5-12, etc.). Specifics should be pointed out, knowing what these references indicate."

>>Yes we agree and try to better specified and describe the results of the studies that support our introduction section. 

Extensive neurophysiological studies in migraineurs have recognized neurological lesions and damage^5,6, biomarkers associated with inflammation^7,8,an abnormal information processing and functional connectivity⁹,involving habituation and sensitization opposing processes⁴, that change during the migraine phases ^10,11. 

-"Please indicate the p-value precisely, avoiding styles like p < 0.05 but rather using, for example, 0.02. Do not write p-values in the style .02. Avoid phrases like ns p>.05, but instead use, for instance, p = 0.32."

>>Thank you very much for this comment We have changed all the p-values ​​present in the text, you can see the change in the manuscript highlighted in yellow

 - Results for the Mann-Whitney test should be presented appropriately, e.g., U = 23; p = 0.02, while for Friedman's ^χ2_F(2) = 2.571, p = 0.276.-

- Thank you very much for this suggestion that improve the quality of our results section.  You could see the change in the manuscript highlighted in yellow.

- "It is advisable to calculate appropriate measures of effect size; relying solely on the p-value is insufficient (e.g., Glass rank biserial correlation coefficient and Kendall's W value)."

>>Thank you., we calculated the kendall's W values and added it in the text.  You could see the change in the manuscript highlighted in yellow.

"Descriptive statistics for such tests should be expanded to include the median and quartiles."

>> Yes, we agree with your comment. We added the median and quartiles range in all tables. You could see the change in the manuscript highlighted in yellow.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

In migraine – during prodromal phase there is a lack of habituation at repeated stimuli, with abnormal cortical excitability, that could be assessed by TMS (transcranial magnetic stimulation).

On the other hand, during headache phase in migraine there is a sensitization, related to a reduction of Pressure Pain Threshold (PPT)

This is a very interesting paper regarding the electrophysiological changes in migraine patients after using anti-CGRP monoclonal antibodies.

In the study were included 11 migraine patients and 11 health controls (HC).

Neuroelectrophysiological evaluation was performed in HC and also in migraine patients. Migraine patients were evaluated before and after 3 months of treatment with anti CGRP mAbs.

TMS parameters evaluated were: RMT (Rest Motor Threshold), SICI (Short interval Intra Cortical Inhibition), ICF (Intra Cortical facilitation) and MEP (motor evoked potentials).

The authors used Somedic algometer in order to evaluate PPT in cephalic and extracephalic muscles.

They found a significant improvement of TMS parameters after anti-CGRP mAbs treatment in resistant migraine patients, with increase in intracortical inhibition, with increase in RMT.

These findings suggests that anti-CGRP monoclonal antibodies determine a normalization of cortical excitability, a modulation of peripheral and central sensitization to pain.

Author Response

Dear reviewer 2

My coauthors and I wish to thank you for your revision and comments related to our submission titled “ Effects of Anti-CGRP Monoclonal Antibodies on Neurophysiological and Clinical Outcomes: a Combined TMS and Algometer Study.”

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The recommended suggestions were taken into account by the authors.

Comments on the Quality of English Language

Minor editing of English language required.