Management of Trigeminal Neuralgia with Botulinum Toxin Type A: Report of Two Cases
Round 1
Reviewer 1 Report
Dear authors,
in the manuscript, the question is original and well defined. The topic and the new approach are really interesting and could represent a different and effective way to treat these specific problems of neuralgia and pain. Certainly there are insufficient data or results to provide a scientific justification for this method, but the first clinical findings are appreciable.
The clinical cases are clearly presented and the methods are explained in such a way that every doctor can repeat the procedure. However, anatomical and pharmacological information should be explored to help the reader understand the scientific basis of this option. The discussion should be deepened with more information on the molecular mechanism surrounding these phenomena.
Best regards
Author Response
The biggest recommendation was to further develop the discussion with more information regarding the molecular mechanisms involved. The limited discussion regarding molecular mechanisms is due to the mechanism by which botulinum toxin type A inhibits pain transmission in the IAN, particularly after a peripheral nerve injury, are not well understood. The following paper illustrates this point.
Waskitho A, Yamamoto Y, Raman S, Kano F, Yan H, Raju R, Afroz S, Morita T, Ikutame D, Okura K, Oshima M, Yamamoto A, Baba O, Matsuka Y. Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model. Toxins (Basel). 2021 Oct 5;13(10):704. doi: 10.3390/toxins13100704. PMID: 34678997; PMCID: PMC8541196.
However, I added this reference, with a statement that the mechanism is not fully understood into the introduction section.
Reviewer 2 Report
Dear Authors the paper ‘’Management of Trigeminal Neuralgia: Interesting Cases Show- ing Non-Traditional Treatment Approach ‘’is really interesting, well conducted and fits the objectives of the journal; but it is necessary to review some points in order to improve the quality of the paper:
-About the Title of the article,I suggest you to modify it and add the type of article.
-First, i ask you to check the plagiarism of your article using specific sites to get a similitary report
-Please be sure to use only keywords accordingly to medical subject headings (Mesh word) for a better indexing.
- The introduction section is very short and is needed to add other references to increase the quality of the manuscript, Add recent references about the topic of the article, dwelling in the introduction on articles published in 2022 and describing what your article will add compared to the last articles published; Preferably a published articles should be with 90 or more references.
I suggest you some articles (about TMD ) that will help you improve your article.
Efficacy of conservative approaches on pain relief in patients with temporomandibular joint disorders: a systematic review with network meta-analysis. PMID: 36148997.
Teledentistry in the Management of Patients with Dental and Temporomandibular Disorders Doi: https://doi.org/10.1155/2022/7091153
Prosthodontic Treatment in Patients with Temporomandibular Disorders and Orofacial Pain and/or Bruxism: A Review of the Literature https://doi.org/ 10.3390/prosthesis4020025
-You need to review the grammar and English of your article
-I suggest you add a table with the list of abbreviations used in the text.
Regards
Author Response
I changed the title to say “case reports” to meet your recommendation.
An online originality report was conducted, and the only sentence that required revision was the very first sentence of the abstract, which has been changed.
The following keywords were MeSH terms and did not require editing: Trigeminal Neuralgia, pain relief, orofacial pain, and trigeminal neuropathy.
For Botulinum Toxin A we added the word “type,” for mental nerve and mental foramen we replaced them with Inferior Alveolar Nerve and Multiple Sclerosis.
This reviewer also recommended we develop the introduction section focusing on articles published in 2022. I read through the following articles, among many others which were published in either 2021 or 2022:
Valerie Chávez-Pérez, Natalia Felipe-Spada, Javier Roldán-Cubero, Patricia Freire-Nieto & Jordi Tomàs-Aliberas (2021) Current status of the application of botulinum toxin as a treatment option for trigeminal neuralgia, CRANIO®, 39:1, 1-3, DOI: 10.1080/08869634.2020.1849976
Kayani AMA, Silva MS, Jayasinghe M, Singhal M, Karnakoti S, Jain S, Jena R. Therapeutic Efficacy of Botulinum Toxin in Trigeminal Neuralgia. Cureus. 2022 Jul 14;14(7):e26856. doi: 10.7759/cureus.26856. PMID: 35974855; PMCID: PMC9375637.
Tangney T, Heydari ES, Sheldon BL, Shetty A, Argoff CE, Khazen O, Pilitsis JG. Botulinum Toxin as an Effective Treatment for Trigeminal Neuralgia in Surgical Practices. Stereotact Funct Neurosurg. 2022 Aug 9:1-7. doi: 10.1159/000526053. Epub ahead of print. PMID: 35944492.
My takeaway is that these articles either describe botulinum toxin A injections into the temporalis/masseter muscles (first two cited sources), or into the trigeminal ganglion like the neurosurgical journal source (third source). The only study I have found that follows the same technique outlined in this case report is source 21 in the manuscript, which was published in 2021.
Upon reading the two articles you recommended, we feel as though the TMD papers do not strongly relate to the subject matter of this paper due to Trigeminal Neuralgia not involving the temporomandibular joint directly but rather the Inferior Alveolar nerve. For example, occlusal splints are not a widely-accepted first line of treatment for Trigeminal Neuralgia patients.
The grammar and English has been reviewed and we believe it to be acceptable. Some changes that were made include avoiding personal pronouns in the manuscript.
A list of abbreviations was added to the end of the paper.
Reviewer 3 Report
line 19: "One option is to", instead of "These injections are"
line 45: "First line of treatment includes", instead of "Conservative treatment".
line 50-52: There are multiple times in the manuscript where subjective terms are including. Here is an example with "many, and "made difficult".
Before line 68: Source of the diagram?
line 81: Indicate keywords and date of pubmed search.
line 90: the fact that a neurologist did a diagnsis does not imply that is correct. I will mention something such as : "clinical features were consistent with".
Materials and Methods: All this section is a description of procedures but does not include bias or confounding variables. This is a report of two different cases, so the authors should explain why they are presenting them together. Also, the fact that anesthetic was used, the results might be secondary to the anesthetic and not the toxin. Needs to rewrite this section.
Figure 2: Not needed.
Cases: Using a table per case explaining the step by step will be better than the narrative, that seems repetitive.
Avoid personal pronouns in the manuscript.
The second case seems more traumatic neuralgia, so the use of the toxin will have a peripheral effect and not central.
RESULTS: The authors assume that the response is due to the toxin, but if anesthetic was used, that could be the cause of the relief. Include some references.
CONCLUSIONS: This is applicable only to these two cases. A double-blind study is needed to suggest efficacy.
Author Response
The wording changes were made in lines 19, 45, and 50-52. The word “many” was also removed from the paper entirely to avoid subjectivity.
The diagram’s source was added. It is now actually the graphical abstract on the cover page.
The pubmed search was detailed more explicitly using the MeSH terms searched for and date.
Line 90, wording updated to no longer imply that neurologist’s diagnosis is correct.
Materials and Methods: An explanation of why these two cases were presented together was added to the discussion section. I felt that was a more appropriate location since I hadn’t yet presented the cases yet in the materials and methods sections.
As for confounding variables, we performed a mental nerve diagnostic block when both patients first presented for a consultation and the lidocaine plain wore off within 30-60 minutes, after which the pain returned with the same intensity and in the same locations for both patients. Thus, we conclude that the long-term pain relief is not from the anesthetic. However, this step is clearly outlined in lines 184-188 (lines may have shifted now that I’m rewriting sections, but it’s the paragraph that starts with “we administered an IAN block” in case two). I’ll make a note in materials and methods that this process was followed in both cases and mention that it still is a potential confounding variable. I think it’s important to mention all of the limitations of this case report, as our goal is not to change other people’s way of practice, but rather to raise awareness that this non-FDA approved procedure has worked at least for the 2 patients we have attempted it on and to highlight areas that require further study in the future.
Figure 2 has been removed.
Cases: We discussed and determined that because the details of each specific paper and the differences between the two patients are vital parts of the paper, we want to keep the case report sections in narrative form as it is easier to mention how the two patients are different in their etiologies. This is the crux of the paper; both patients experienced long-term pain relief from this non-traditional treatment method despite having very different etiologies of their TN pain.
Personal pronouns were removed except in the actual case presentation sections, where we feel that they outline what was done by our team versus the work done by previous Doctors and thus provide a level of clarity that would not be attained if personal pronouns were removed.
Results: reference 24 outlines the role of nerve blocks in the diagnosis of traumatic trigeminal neuralgia. This statement was added to the materials and methods section, but it supports the short-term nature of the effects of plain lidocaine that these 2 patients experienced.
Conclusion: The conclusion has been revised to emphasize that a double-blind study is needed to suggest efficacy.
Round 2
Reviewer 3 Report
I suggest you change the title to: Management of Trigeminal Neuralgia with Botox: Report of two cases.
Author Response
I changed the title exactly as you suggested, the only difference being that instead of saying botox I wrote "botulinum toxin type A" since botox is a brand name and thus would require permission to use their name to avoid copyright issues. This is avoided by simply mentioning the active ingredient.
