AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2578-8868/212
1 Department of Neurology - Ain Shams University.
*Corresponding Author: Abdelrahman Atef, Department of Neurology - Ain Shams University.
Citation: Antonis Theofilidis, Filipos Kargopoulos (2021) Effect of Ultrasound Guided Bilateral Greater Occipital Nerve Block on Serum Calcitonin Gene Related Peptide (CGRP) in Chronic Migraine. J. Neuroscience and Neurological Surgery. 9(5); DOI:10.31579/2578-8868/212
Copyright: © 2021 Abdelrahman Atef, This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Received: 06 October 2021 | Accepted: 22 October 2021 | Published: 29 November 2021
Keywords: chronic migraine; GONB; CGRP
Background: The trigeminal ganglion plays a key role in primary headache pathophysiology. Calcitonin gene-related peptide (CGRP) and CGRP receptors are expressed in trigeminal neurons that form C-fibers and A-fibers, respectively. In migraine attacks, there is release of CGRP into the cranial venous outflow, in refractory headache to conventional pharmacologic management, minimally invasive techniques such as greater occipital nerve block (GONB) are feasible for pain relief, and help to decrease the frequency of the attacks, Studies on the ultrasound (US) guided GON injection technique have emphasized that this technique has a higher success rate and should allow for a more precise block of the nerve. Our study will be concerned by correlation of CGRP level as a biomarker for effectiveness and responders of us guided GON block in chronic migraine (CM).
Methods: twenty patients diagnosed with chronic migraine were recruited in this study. All participants underwent ultrasound-guided bilat. GONB by 40 mg triamcinolone and 1 cc leidocaine using a portable ultrasound system with a 7 – 13 MHz multifrequency transducer, blood samples were collected from antecubital vein immediately before and three to five weeks after injection clinical response was evaluated using headache diaries
Results: CGRP levels after ultrasound guided GONB (median, 40 pg/mL; range, 25-60) were significantly lower as compared with CGRP levels obtained before GONB (median, 145 pg/mL; range, 60-380; P =0.001). Pretreatment CGRP levels in non-responders (310 pg/mL) were significantly higher than those seen in responders being in poor responders less than 50% improvement (135 pg/ml) and good responders (140 pg/mL; P = 0.003). One month after treatment. A number of demographic factors, clinical features, and comorbidities were not different in responders as compared with those of nonresponders.
Conclusion: These results suggests that interictal CGRP levels can be of help in predicting the response to GONB and suggest that the mechanism of action of GONB in CM is the reversal of sensitization as a result of the inhibition of CGRP release still more studies needed to highlight CGRP role with GONB .
Migraine is a common, multifactorial, neurovascular disorder with major individual and societal effects. ( Goadsby et al.,2011)
Migraine affects roughly 15% of people and is typically characterised by disabling episodes of severe headache accompanied by nausea, vomiting, and hypersensitivity to light, sound, and smell for up to 3 days (migraine without aura).( Olesen et al.,2013).
In a third of patients, attacks might be associated with transient focal neurological aura symptoms (migraine with aura); it has been suggested that migraine with and without aura are distinct disorders. Once a migraine attack has started, the mechanisms underlying migraine aura and headache are reasonably well understood. Aura is most likely caused by cortical spreading depression, and headache by activation of the trigeminovascular system and associated release of CGRP. ( Messlinger et al.,2011)
Migraine headache is caused by activation of the trigeminovascular system (TVS) The TVS consists of nociceptive trigeminal sensory afferents surrounding cranial blood vessels. Upon activation of these perivascular trigeminal afferents, the signal travels through the trigeminal ganglion to neurons in the trigeminocervical complex, using CGRP as the main neurotransmitter. The signals are then relayed to the thalamus; because all nociceptive inputs are integrated through this structure, it has been named the pain matrix of the brain.( Noseda et al.,2013)
Modulation of the signal occurs through extensive connections with brainstem regions such as the periaqueductal gray and the locus coeruleus.( Akerman et al.,2011)
GON block intervention is found to substantially reduce pain intensity and analgesic medication consumption for migraine patients, with no increase in adverse events. GON block intervention should be recommended to be administrated in migraine patients (zhang et al., 2018).
Once the headaches become refractory to conventional pharmacologic management, minimally invasive techniques such as peripheral nerve blocks are feasible for pain relief, and help to decrease the frequency of the attacks.Various studies have demonstrated that peripheral nerve blocks are safe and effective for the treatment of a variety of headache disorders. These techniques not only provide adequate analgesia but can also help to decrease systemic side effects of pharmacological therapy (Soto et al.,2012).moreover it was found that The US guided GON injection technique has a higher success rate and might allow a more precise block of the nerve (Vanderhoek et al., 2013).
The aim of this study was to to assess the effect of ultrasound guided bilateral GONB on CGRP levels in peripheral blood and outcome in chronic migraine (CM).
This study consecutively recruited 20 participants diagnosed with chronic migraine from headache outpatient clinics at Neurology Department of Ain Shams University Hospitals in the city of Cairo, from August 2018 through March 2021.
This was an interventional study with a convenient sample. Inclusion criteria of our sample were patients with the age above 18 years. Written informed consent was obtained from all participants. Exclusion criteria were patients with severe systemic diseases, infection or injury in occiput and patients with allergy to any of substances used in injection All patients were evaluated by •Clinical history (Detailed history including personal data, past history, history of current illness, antimigraine treatment used). All patients underwent ultrasound-guided bilateral GONB by 40 mg triamcinolone and 1 cc leidocaine using a portable ultrasound transducer. The patient were asked to lie prone on the table. To locate the nerve we searched for the occipital artery in the medial one-third of the superior nuchal line between the occipital tubercle and mastoid process. The scalp was cleaned with iodine; GONB was performed by applying the injection to the medial of the artery. A needle was advanced beneath the lateral border of the probe using real-time ultrasound guidance and an in-plane technique ,Sampling :Blood samples were obtained after an overnight fast before initiating blockade and one month later to avoid the effect of circadian rhythms on biomarkers levels, blood samples were obtained between 9 and 11 a.m. Subjects didn’t consume anti- inflammatory or analgesic medication in the previous 48 hours. A blood sample will be extracted from the nondominant forearm to measure serum CGRP, Efficacy was evaluated evaluated using: Diaries completed by patients in one month following the blockade,
The collected data was revised, coded and introduced to a PC using Statistical package for Social Science (SPSS 25, by IBM: Armonk; New York, US). Data were introduced and suitable analysis was done according to the type of data obtained for each parameter. Mean, standard deviation (±SD) and range for parametric numerical data, while median and interquartile range (IQR) for non-parametric numerical data. Frequency and percentage for non-numerical data. Chi-Square test was used to assess the relationship between two qualitative variables. Student T Test was used to investigate the statistical significance of the difference between two study group means. ANOVA test was used to investigate the statistical significance of the difference between more than two study group means. Correlation analysis (using Spearman's rho and Pearson method) to assess the strength of association between two quantitative variables. P-value level of significance was defined as P >0.05 is non-significant, P < 0>
1. Clinical data:
Forty patients fulfilling the CM criteria were included in this study. Mean age of CM patients 31.125±7.387, only 4 (20%) were males and the rest are females 16 (80%) (. By history, the average time that patients had CM was 7.225±2.869years. The main phenotypes and associated symptoms of the patients that were enrolled in this study are shown in Table 1.
2. CGRP determinations and correlation with clinical response:
CGRP levels after GONB (median, 40 pg/mL; range, 25-60) were significantly lower as compared with CGRP levels obtained before GONB (median, 145 pg/mL; range, 60-380; P =0.001) (Figure. 1).
17 (85%) responded and the remaining 3 patients (15%) did not notice
any significant response to GONB, about 8 patients (40%) showed good response while 9 patients (45%) showed poor response . Pretreatment CGRP levels in non-responders (310 pg/mL) were significantly very high than that seen in responders (135-140 pg/mL; P = 0.001). One month after treatment (table 2).while CGRP level after GONB wasn’t significantly correlated to clinical response.
An increasedCGRP level has been proposed as the first biomarker to aid in obtaining a more objective diagnosis of CM, in the context of a patient with daily or almost daily headaches and a history of migraine. Cernuda-Morollón, E. et al. (2013) We show here that treatment with GONB significantly decreases interictal CGRP levels measured in peripheral blood samples in patients with CM.These results contribute to clarifying the mechanism of action of GONB in CM and suggest that the measurement of interictal CGRP levels can be of help in predicting the response to GONB.
As regard headache days we considered decrease after injection by >50% good response ,Less than 50% poor response and if no difference considered no response , our study showed that there was statistical significant reduction in headache days before and after injection with the mean (19.35±3.1) before and after block it was (12.30±5.46) with 40% showing good response , 45% poor response and 15% showing no response, Similar results were found in study by Ashkenazi and colleagues (Ashkenazi et al., 2008),
On the other hand Bovim and Sand (1992) examined the diagnostic value and effects of GON block and found only 6% in the migraine group showed good response and this may be attributed to blockade type as they used injection of 0.5 to 1.5 mL of lidocaine 2%, with adrenaline 12.5 μg/mL, also using ultrasound guided technique added more accuracy and precise localization of the nerve which improved response among our patients.
We found that CGRP levels were highly elevated before GONB and this comes in concordance with study conducted by Goadsby PJ and Edvinsson L(1993) in which they conducted studied on both cats and humans with stimulation and found that CGRP level is elevated in migraneur patients and levels normalize after receiving sumatripatans and dihydroergotamine with relief of symptoms.
In our study we aimed to detect if there are changes in CGRP level after GONB and if it can be used as a biomarker predictor for response to GONB and we found that there was a significant reduction of CGRP level after GONB although There are no previous studies in the literarure measured the change in CGRP level after GONB but there were few studies measured CGRP level changes after botulinum toxin injection Cernuda-Morollón, etal.,(2015).
In our study we found that 45% of the patients showed good response ,40% showed poor response and about 15% showed no response at all , here we show not only that CGRP levels are decreased after GONB, but also that this reduction correlates with its efficacy rate. In fact, CGRP levels decreased significantly, and very homogenously in almost each individuals but we found that pretreatment CGRP levels were high but in responders it was high but level didn’t exceed 200
pg/ml (median, 135 pg/mL; range, 100-200 in poor responder and median, 140 pg/mL;range, 80-150 in good responders ; P = 0.003), while in non-responders it was very high exceeding 200pg/ml (median, 310 pg/mL; range, 262.5-350; P = 0.003) which again supports a role of CGRP levels in predicting response to this treatment , And these findings may support the need for repeated GONB to tackle resitant chronic migraine which didn’t show initial response to GONB , Gul, H. L et al., (2017) conducted a study in which they included 44 CM patients and randomly divide the patients into two groups, as group A (bupivacaine) and group B (placebo) , GON blockade was administered four times (once per week) and they found significant reduction in headache severity and frequency in group A compared to placebo group. Moreover In the RCT undertaken by Inan et al.,(2015) GON blocks were applied four times weekly. There was a significant decrease in the number of headaches and VAS scores.
In our study we found that percentage of change in both responders and non-responders was significant ( P =0.010) while CGRP levels after injection was insignificant (P=0.577 ) raising the possibility that clinical improvement may be non CGRP mechanism these findings in nonresponders could be explained by limitations of this study, such as the absence of a control group, the fact that most of these patients remained on oral preventives, the relatively low numbers of nonresponders in our series, or the intrinsic and subjective variability of migraine, our results might indicate that some patients with a “CM” phenotype could suffer from other headaches (eg, psychogenic, tension-type headache or other secondary headaches) in which CGRP does not seem to be involved. This may be due to in some patients with migraine, pain could be secondary to a predominant activation of the parasympathetic arm of the TVS (Strassman AM et al ,1997) .This could explain the fact that the efficacy of pure CGRP antagonists “gepants” seems to belower than that seen for triptans, which are known to inhibit both CGRP and VIP release by the TVS (Olesen J, etal 2009).
At the end we found that CGRP level before GONB may play a role as a predictor for response for the GONB as the higher the level of CGRP exceeding 200 pg/ml showed no response while lower levels than 200 pg/ml showed respose ranging from poor (<50>50%) although both responders and non-responders showed significant reduction in CGRP levels and this may raise the importance of repeated GONB in non-responders while CGRP levels after injection didn’t show significant correlation raising the possibility that improvement may be non CGRP mechanism moreover Our study has several limitations. First, the size of the sample is relatively small. Patients come from a selected clinical population. Many of them were using other preventive medications due to ethical reasons and this could work as a cofounder. The use of other drugs could also reduce levels of biomarkers related to inflammation, also a controlled trial would give more insight on CGRP changes.
Our current results suggest that the primary mechanism of action of GONB in CM is the reversal of peripheral and central sensitization as a result of the inhibition of the release of CGRP
The fact that we are the first study in the literature to assess the changes of CGRP levels with GONB gave us little chances to correlate our work with the others, hopefully in the future there will more studies regarding CGRP changes with peripheral intervention as they are feasible with less side effect and affordable.
CM……………………………...Chronic migraine
GONB……………………………….Greater occipital nerve block
HIT6……………………………….Headache impact score
MIDAS……………………………….Migraine disability assessment scale
REM………………………………Rapid eye movement
SD…………………………………Standard deviation
SPSS………………………………Statistical package for Social Science
TVS…………………………….Trigemino vascul
VAS…………………………………Visual analogue scale
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
