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In the article by Dr. Paul Mathew published in Headache in January 2014, some questions were posed and many accusatory statements were made about our studies that merit clarification and response.[1] Dr. Mathew writes “Given the high prevalence of migraine and inconsistent effectiveness of preventative treatment, a plastic surgeon, Bahman Guyuron, MD, devised 4 surgical procedures intended to deactivate migraine headache trigger sites.” This statement is not accurate. Neither I nor any other plastic surgeon was looking for a more effective migraine headache (MH) treatment. It evolved following the reports by a few patients who noticed that their MH stopped after forehead rejuvenation.

Surgical Techniques

  1. Top of page
  2. Surgical Techniques
  3. Patient Selection
  4. Sham Surgery Study
  5. Five-Year Study
  6. Socioeconomic Factors
  7. Discussion
  8. Conclusion
  9. References

Dr. Mathew has summarized the surgical techniques very accurately.

He questions why the temple region is the only site in which a nerve is being lysed. This small branch of the trigeminal nerve has been sacrificed during craniofacial surgery and forehead rejuvenation procedures for decades. It was the latter procedure that resulted in patient reports of improvement or elimination of MH. We did not want to alter the technique that prompted the patients to report cessation of their MH until we have evidence that decompression will be effective in this site as well. We have just completed a randomized trial comparing avulsion to decompression of the zygomaticotemporal branch of the trigeminal nerve. Our results indicate that decompression and avulsion produce similar results and we have altered our technique.

Patient Selection

  1. Top of page
  2. Surgical Techniques
  3. Patient Selection
  4. Sham Surgery Study
  5. Five-Year Study
  6. Socioeconomic Factors
  7. Discussion
  8. Conclusion
  9. References

Our patient selection and use of headache terminology has been the subject of criticism by Dr. Mathew. He may have failed to realize that some of the terminology was coined after publication of our earlier articles. The patient selection for all of the clinical studies was done by the neurologists in the team. In fact, there were three different neurologists involved in our studies and all three were board certified specializing in headache. It is clearly stated in every publication that they used the International Headache Society criteria and classification for the diagnosis and patient selection. If the patient is diagnosed to have MH by these experts, surely medication overuse headache is ruled out.

Dr. Mathew finds use of botulinum toxin A (BT-A) injection for patients screening flawed. BT-A was used for patient selection in our earlier studies to emulate the surgery effects by eliminating the muscle function through paralyzing the muscle. Since many of our patients are from out of town or out of the country, adherence to our initial algorithm became too cumbersome and often impossible. As Dr. Mathew mentioned, we have demonstrated that the constellation of symptoms can be reliably used for detection of trigger sites. Thus, BT-A is no longer routinely used as a screening tool by our team.

Dr. Mathew states “It is unclear what is implied by therapeutic BTX, and why any patients in the control group received any BTX. In the review, there is no mention of how many units were utilized. The injections were performed at the sites deemed by the evaluating surgeon to be migraine trigger sites.” By therapeutic BT-A, we meant the Food and Drug Administration (FDA)-approved doses used for preventing chronic MH. Prevention with BT-A was not the purpose of our injection of BT-A and it has been indicated in our articles that we used 12.5 to 25 units based on the size of the muscle. The patients in the control group received BT-A for confirmation of their trigger sites and to assure that we had patients with matching trigger sites. His assumption that the decision is made merely based on response to BT-A injection and nerve block is incorrect. The candidacy for surgery is based on a number of factors including the type of MH, the severity and frequency of the headaches, failed previous medical treatments, constellation of symptoms, computed tomography (CT) findings, and, yes, response to a nerve block and BT-A, if indicated. The overwhelming majority of patients who undergo surgery have already undergone preventative BT-A injections following the FDA-approved guidelines for years and nerve blocks by several reputable neurologists prior to their visit to our office. A number of these patients have had a failed nerve stimulator removed and some of them still have the nonfunctional device in place. Regardless, before we proceed with the surgery, the patients will have an additional evaluation by the neurologists of our team to make sure that they have had sufficient medical management before surgery. Only a very small percentage of the patients who are treated in our headache center are referred to have surgery.

Dr. Mathew questions the type of pathology that we are looking for in the CT of the nose and assumes that septal deviation and enlarged turbinates are the only types of pathology that we consider as migraine triggering elements. In reality, these two abnormal findings by themselves are not sufficient to make a patient a candidate for surgery on this site. We first confirm the presence of symptoms that are commonly associated with the intranasal trigger sites, such as retrobulbar pain that is triggered with weather change, MHs that awaken the patient in the morning or in the middle of the night, MHs that are aggravated by menstrual periods and worsen with allergies or are orgasmic. We look for contact points as we have indicated in many of the articles and book chapters. Other common pathology includes concha bullosa, Haller's cell, and paradoxical curl of the middle and superior turbinates. These findings on patients who have the diagnosis of MHs based on the criteria set forth by the IHS will lead us to suggest surgery on the septum and turbinates.

Dr. Mathew discusses the value of high-resolution magnetic resonance imaging or ultrasound studies in detecting the trigger sites. These studies may demonstrate some pathology when assessing daily headaches. However, since most episodic headaches seem to be triggered peripherally and may have a dynamic muscle origin, documenting any static pathology may prove difficult. We are currently studying the role of vascular Doppler and infrared thermography in detection of the migraine trigger sites and are hopeful to share our findings with our neurology colleagues in the near future.

Sham Surgery Study

  1. Top of page
  2. Surgical Techniques
  3. Patient Selection
  4. Sham Surgery Study
  5. Five-Year Study
  6. Socioeconomic Factors
  7. Discussion
  8. Conclusion
  9. References

Dr. Mathew questions why out of 317 patients initially screened in our study with a sham surgery group, only half of them received BT-A injection and 76 were included in the study. We were looking for the rare patients with a single trigger site or a single predominant site that required screening of many patients. Additionally, the patients with nasal trigger sites were excluded in this process since a strong placebo effect could not be generated for this group. Also, the patients with medication overuse headaches were excluded by the neurologist in the team. This was the reason that only 76 of the 317 patients qualified for the study.

Dr. Mathew also questions why the number of control group patients was nearly half of the surgical group. This was based on a calculation by our bio-statistician considering the results of our previous studies and satisfaction of sufficient statistical power. He wanted to include the minimum number of patients in the sham surgery group that would still produce strong enough statistical evidence, for obvious reasons. This study indeed had sufficient statistical power, especially for a sham surgery study whereby committing more patients to sham surgery than was absolutely necessary would have been unprincipled.

Dr. Mathew made some puzzling omissions that were important, were clearly stated in the articles, and empowered the study. He failed to mention that there were two neurologists involved in this particular study alone. Additionally, he failed to mention that all three MH components, including the frequency, severity, and duration, were independent end-points along with the Migraine Index. Therefore, Migraine Index being unreliable is not a reasonable argument since we took every major migraine component into consideration independently. Furthermore, Dr. Mathew did not mention that we used three different validated tools including Migraine Disability Assessment (MIDAS), Migraine Specific Quality-of-Life Questionnaire (MSQ), and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) to make sure that we had assessments beyond the patient statements about their MH.

I find Dr. Mathew's argument that the included patients in our studies may have had non-MHs specious since our neurologist strictly adhered to the definition by the IHS, as stated clearly in every article.

Dr. Mathew questions who followed up the patients, and offers an opinion that these patients should have been followed by an independent neurologist. The patients were followed up by both the neurologist and the surgical team. Having an independent specialist follow the patients and collect detailed information for a study is not a common practice in surgery. I wonder if this is routine in neurology. If yes, are the independent physicians reimbursed? Who reimburses them?

Dr. Mathew writes “Although all subjects were blinded as to which intervention they received, the retained movement of the corrugator supercilii, depressor supercilii, and procerus muscles in the sham group likely led to subjects in the sham group becoming aware that they received the sham procedure. In addition, it is assumed that the subjects in the frontal group received bilateral surgery for cosmetic reasons, but it is unclear whether subjects received bilateral or unilateral surgery in the temporal and occipital groups. This also draws into question whether bilateral or unilateral procedures are performed in clinical practice for patients with a unilateral headache origin.” Had Dr. Mathew's theory been correct about the muscle movement, we would not have seen as many positive changes in the sham surgery group as we did. Blinding was complete in the temporal and occipital sites and it was adequate in the frontal region since no matter how hard one tries, complete elimination of muscle function, and thus forehead movement, with the surgery is impossible without violating the nerves. Additionally, the frontalis and orbicularis oculi muscle function were never altered by surgery and, therefore, the patients in the treatment group did not have a completely motionless forehead. Meanwhile, sham surgery often resulted in some swelling and reduction in the muscle function temporarily, which was enough to give an impression of muscle removal to the patients with sham surgery. Regardless, the placebo effect in our sham surgery study was much more reliable than the Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) study where neither the patient nor the treating physician could miss the difference between those who received BT-A vs those who did not. To answer his question about whether the procedures were done unilaterally or bilaterally, none of the patients in this study had unilateral temporal or occipital headaches. However, since no muscle is removed to potentially cause asymmetry during the temple surgery and the removed muscle is insignificant during the occipital surgery, the procedure is performed unilaterally on these two sites in rare patients with unilateral headaches.

Dr. Mathew points out that we did not indicate whether preventative or abortive medications were altered, and he sees post-surgery patients who received BT-A and whose preventative medications were changed postoperatively thus altering the surgical results on patients to whom he attends. The preventative medications were not altered for our study patients except for those who had elimination and no longer needed migraine medications, as indicated earlier, and none of the patients received BT-A injection after surgery while they were the subject of the study.

Dr. Mathew outlines every adverse effect of the surgery and adds “Interestingly, only 2 of the adverse events were specifically cited to last for greater than 1 year, which would lead some readers to assume that the other events lasted for less than 1 year and resolved when in fact some of these adverse events may actually be ongoing.” This kind of distortion of facts is a reflection of a prejudicial assessment of our studies. Any fair reviewer would have concluded that since we recorded and reported every complication throughout the follow-up period, if only two adverse effects were cited to be present at the 1-year follow up, that means the remaining complications were all temporary and resolved over time, which indeed was the reality.

Dr. Mathew's statement that I am attempting to discredit the trigeminovascular theory of MH is baseless. First, there is no such statement in any of our publications. I have advocated the role of peripheral mechanisms based on our findings and the efficacy of surgical procedures and BT-A, without dismissing any other theories. I do not believe that I am qualified to redefine the pathophysiology of the complex MH cascade.

In the discussion paragraph, Dr. Mathew writes “The author once again lumps together these 4 procedures, and uses this collective weak data to reinforce these self-promoting curative surgical interventions.” This type of unsubstantiated remark with a baseless condescending tone is a clear indication of the bias frame within which Dr. Mathew has been expressing his tainted opinion. I have not claimed a cure and I do not need self-promotion.

Five-Year Study

  1. Top of page
  2. Surgical Techniques
  3. Patient Selection
  4. Sham Surgery Study
  5. Five-Year Study
  6. Socioeconomic Factors
  7. Discussion
  8. Conclusion
  9. References

Dr. Mathew states that not including sham surgery in the 5-year follow up is a design flaw. Criticizing the methodology of a surgical study by someone who is not in the field of surgery and has never done a randomized prospective study or sham surgery is improper. In order for patients to participate in the control group (sham surgery), they were promised that they would be surgically treated if they served in the control group for 1 year. To expect the patient to participate in a study and serve as a control for 5 years is totally unrealistic. If Dr. Mathew does a literature search, he would find very few, if any, sham surgery studies being done today due to the extremely perplexing nature of this type of study and the difficulty in obtaining institutional review board approval. To expect a 5-year sham surgery study is unreasonable and no IRB is going to approve that kind of investigation.

Related to our comprehensive study with 25 patients serving as controls, he did not see the value of this control group. He states, “As such, it is not clear why this ‘control group’ was part of the study other than possibly to convince the reader that there was a fair comparison to a ‘control group,’ which would artificially elevate the significance of the results from the active intervention group.” I am not sure why Dr. Mathew does not see the scientific merit in having a randomly selected group of patients who did not undergo surgery to compare with a group of patients who underwent surgery. Validated tools were used on both groups and meaningful data with statistical significance were collected. Had we not had a control group, the scientific value would have been open to more criticism. In an overwhelming majority of surgery-related studies, the control group consists of a number of patients who do not undergo surgery rather than sham surgery, which again is extremely rare.

Dr. Mathew questions who evaluated the patients for our 5-year follow-up study. Here as well, the team, including a biostatistician, the surgeon, and the neurologist, designed the study; the neurologist selected the patients; the surgeon and neurologist detected the trigger sites; the nurse study coordinator collected, compiled, and delivered the data directly to the biostatistician who then analyzed the results without the involvement of the surgeon. Additionally, the surgical team never wrote a prescription for MH medication and therefore the patients who needed medications during the 5-year follow up had to visit the neurologists for medications in addition to the patient obligation to visit the neurologist by the design of the study. Dr. Mathew once more considers the fact that the patients were not followed up by an independent neurologist a flaw. Again, to expect an independent neurologist to follow the surgical patients for 5 years and to collect data is totally unreasonable. This is not what is done in the surgical field and, again, I wonder how often it is done in the neurology field. I sincerely hope that this type of distrust is not ubiquitous in the neurology field. We trust and respect our colleagues in the surgery field who devote their lives to research and believe in the scientific integrity of the researchers unless it is proven otherwise.

Dr. Mathew writes, “Among the 79 patients who presented at the 5-year follow-up, 10 received additional procedures. These 10 subjects were not included in the final analysis. It is interesting to note that these 10 patients had ‘significant improvement’ of their migraines but still opted to proceed with additional procedures. One could assume that these patients had an outcome that would negatively impact the final results, and not surprisingly, these 10 subjects were not included in the final analysis.” I find this blatant claim offensive and this is the first time that the integrity of what I do has been questioned by anyone. I am not sure why he did not notice or chose to ignore our clear statement in the article that the final results were analyzed with and without inclusion of those 10 subjects and there was no statistically significant difference in the final outcome. Those patients who had additional surgery had a significant improvement in the sites where they had the surgery, but they still had residual pain in the non-operated sites and that is why they underwent additional surgery. We were trying to render them pain free by operating on the sites that we had not touched previously. It would have been unfair and totally selfish to deny them additional improvement for 4 more years because of the fact that we needed them to continue having some pain to prove a point to the unfair skeptics. These patients had already served in the initial 1-year phase of the study. Additionally, I wonder how Dr. Mathew would have judged our study had we included the 10 patients who had undergone additional surgery. Would he not have claimed that the study was seriously flawed since some patients underwent additional procedures? Furthermore, had there been any hint of dishonesty in our report, we would not have mentioned anything about the second surgery, since the surgery was not being repeated on the same site. However, this type of disclosure and exclusion of patients who had undergone additional surgery is an obligation of any research team with integrity and should not be used against the researchers.

Dr. Mathew writes “Of the 22 subjects who did not present for follow-up, the reasons for not presenting may have included adequate treatment effect after the procedure, surgical failure to improve the subject's headache, or untreatable complications from the procedure.” Dr. Mathew's claim that 22 subjects did not present for a follow up is inaccurate. We operated on 91 patients and lost 2 patients during the first year follow up and an additional 10 patients in the ensuing 4 years, for a total of 12 patients not being available for a follow up at the end of the 5th year. Again, I find his assumption that they were potentially not included because we wanted to only include patients with favorable results very discourteous. I would understand if he would ask for an explanation. However, unashamedly stating that we may have excluded these patients because they had unfavorable outcomes is an insult to our team. We have included eight patients in the study who did not have a positive response (less than 50% improvement). For anyone who has not done a 5-year study, it would be difficult to understand how challenging it is to keep in touch with close to 89 patients for 5 years. Of the possibilities that he has outlined, the likely reason for losing these patients in follow up is that many of these patients were symptom free and they did not need care. Otherwise, these patients would have needed medication from our neurologists. Why would they not visit the neurologist and receive treatment without cost, had they had pain? But this is not what we claimed in the study nor do we claim it now. Articles and results should be about the facts, not suppositions. One inevitably loses a portion of the committed patients along the way, especially in a 5-year study, and that is a fact.

One more disrespectful statement from Dr. Mathew surrounds his conclusion that our procedures are “self-promoting,” curative interventions. We have never stated during our presentations or publications that the surgery is a cure. To assign such a claim is totally unjustified and is self-serving on his part.

Dr. Mathew writes “Commentary is then made about rebound headache, and subjects taking opiates, which is the only time the author comments on medications that are taken during the study. It is not surprising that the only medications noted by the author are those that may negatively impact study results (medication overuse headache), as there is no mention of preventative and abortive medications that can positively impact statistical analysis.” This is another misrepresentation of the facts to diminish the significance of the study. Had the glorification of the studies by referring to these medications been our aim, we would have referred to them more frequently and not just in the most recent study. The medication use was only elucidated on in our recent studies since we learned during the peer review process that this matter was important to our neurology colleagues.

Socioeconomic Factors

  1. Top of page
  2. Surgical Techniques
  3. Patient Selection
  4. Sham Surgery Study
  5. Five-Year Study
  6. Socioeconomic Factors
  7. Discussion
  8. Conclusion
  9. References

Dr. Mathew disparagingly writes “The improvement of a patient's pain with nerve blocks or BTX could be used to persuade a patient to proceed with an expensive surgical treatment with unclear benefit and potentially irreversible complications including worsening of pain.” He portrays our team as “salespersons” pushing patients to do what they should not be doing. Once more, he discounts the facts that all of these patients are referred to us by their neurologists or examined by our neurologist and found to be a candidate for surgery. These are the patients who are well informed but are invariably at the end of their course. They frequently tell us “you are my last resort, I have no quality of life and I may as well not live.”

Dr. Mathew's claim that the surgeon's charge is $15,000 for a single trigger site is not the norm. There are unprofessional physicians in every field. However, many of these patients have often undergone implantation of nerve stimulators, as I indicated earlier, which have a significant failure rate and much higher costs, and these patients harbor a large permanent foreign body. I do not see Dr. Mathew criticizing this procedure in any of the total of 6 articles that he has published.

Discussion

  1. Top of page
  2. Surgical Techniques
  3. Patient Selection
  4. Sham Surgery Study
  5. Five-Year Study
  6. Socioeconomic Factors
  7. Discussion
  8. Conclusion
  9. References

Dr. Mathew indicates that neurologists have been skeptical about the 4 surgical decompression techniques because of unclear mechanisms of action within the current context of migraine pathophysiological models of migraine and potential irreversible complications. Decompression of the nerves is not an unfamiliar procedure to neurologists and those who have an open mind can see the rationale for the efficacy of the surgical treatment of MH. The mechanism is similar to carpal tunnel surgery or other nerve decompression techniques. With the growing evidence for pericranial sensory communication with the meninges, the pathophysiology is becoming more understandable but we still have a great deal to learn.[2] Dr. Mathew indicates that many of these patients have episodic MH and may not have had adequate preventative treatment. First, I have repeatedly indicated that these patients were selected by neurologists in every article that I have published. Second, the irreversible complications, which are very few, are not serious. In fact, permanent numbness, which is exceedingly rare, is actually a welcomed change and when I describe this complication to the patients, their common response is “If I could pull the nerve out, I would.” The only disturbing complication is deterioration of pain or severe hypersensitivity of the surgical site, and fortunately, this is extremely rare. Many of the patients that I currently operate on have daily pain with an intensity of 10 (on a scale of 1 to 10) and I am not sure how much worse it can get. We are presently studying these uncommon cases, addressing these complications and creating treatment options for these patients. I do not prescribe migraine medications but from reading the related articles, it seems that every migraine medication potentially can result in some serious side effects.[3]

Dr. Mathew's comparison of what we do with Dr. Janetta's surgery for trigeminal neuralgia is fair. His statement that it took 20 years for the neurologists to accept and support Dr. Janetta's procedure is distressing. Although, it has been 14 years since I introduced the peripheral trigger site deactivation concept and the fact that the headache specialty organizations keep denouncing the surgical decompression of migraine trigger sites is very disheartening. I, too, strongly believe that there is tremendous similarity between what we do and what Dr. Janetta offers. The role of a blood vessel in the vicinity of the nerve that triggers MHs, especially in the auriculotemporal and lesser occipital sites, is intriguing and we almost routinely find a Doppler pulse in the most intense pain site in different regions.

To assume that some or many of the patients who have had a positive outcome from the nerve decompression may have supraorbital neuralgias, as Dr. Mathew proposes, once more casts aside the expertise of our headache specialists of the team and this is not proper. We have performed decompression surgery on those who had the diagnosis of supraorbital neuralgia with success outside the study group.

Dr. Mathew makes a remark about an upcoming article outlining the complications of these surgeries. I strongly caution against the publication of any failed or deteriorated migraine symptoms to which Dr. Mathew has repeatedly inferred, without inclusion of all of the facts. First, this type of anecdotal collection of patients who claim that their symptoms became worse cannot be scientific. Second, the surgical techniques are tremendously subject to the surgeon's capabilities and experience. The fact that a surgeon or a few surgeons do not produce good results does not mean that the surgery is not effective, as much as an improperly prescribed abortive or preventative medication may not work, or worse, may result in serious complications, while the same medication would work in most instances if prescribed properly. Third, there are a number of patients who are dependent on narcotics such that if they do not receive these medications, they may claim that they are worse off in order to obtain more medication. Furthermore, those who have failed the initial surgery or experience worse symptoms could be helped with additional interventions by those of us who have devoted an enormous amount of time in figuring out the complicated matters related to this surgery. Additionally, not reporting success and only referring to failure or deterioration is totally unfair because if out of 1000 patients, a few experience poor results while 90% benefit from surgery, the benefits may outweigh the risks. We need to remember that the majority of the patients who undergo surgery have already been seen and treated by reputable clinics and have exhausted most non-invasive and often invasive possibilities and are undergoing surgery as a last resort. Therefore, the success rate will not be reported. We are investigating the deterioration of pain after migraine surgery and we will report the accurate incidence, the reason for this, and how failure or deterioration can be minimized or managed. I wonder how headache specialists would feel if surgeons would research and write an article about failed preventative and abortive medications or their complications. This will not occur since we consider this kind of report unscientific, egotistical, and totally inappropriate.

Conclusion

  1. Top of page
  2. Surgical Techniques
  3. Patient Selection
  4. Sham Surgery Study
  5. Five-Year Study
  6. Socioeconomic Factors
  7. Discussion
  8. Conclusion
  9. References

In the conclusion, Dr. Mathew criticizes the destructive nature of the treatment of the zygomaticotemporal branch of the trigeminal nerve. As I indicated earlier, this nerve, which is less than 1 mm in diameter, has been the subject of transection in many aesthetic and reconstructive procedures for decades. We are not aware of any patients developing a neuroma or persistent pain after this surgery that was not present prior to the surgery. This nerve will be decompressed from here on based on our recent study results. This will offer a second option for the patients, should decompression fail. His repeated claim that the patients who benefitted from the surgery may have had different types of headaches rather than MH is another reproachful remark against the headache specialists who are integral members of our research team. These highly respected neurologists have been enormously instrumental in serving many patients and allowing them to gain a quality of life they had never had.

Cooperation between plastic surgeons and neurologists can serve a small group of migraine patients who are not benefiting from the available preventative or abortive measures. Plastic surgical decompression of migraine trigger sites is not different from neurosurgical or orthopedic decompression of the different cranial and spinal nerves. The potential complications are extremely low and the benefits are life altering for many of these patients. The patients who are symptom free are not going to call their neurologist to report not having pain or visit their neurologist and pay for the visit when they do not need any care. These neurologists are not going to hear about the success of the surgery, but invariably they will hear about the failures. I warmly invite our neurology colleagues to join forces with us to figure out how we can better help this small group of patients who suffer from such a devastating condition, but do not benefit from the available preventive or abortive medications. Many of these patients who undergo surgery not only have reduced migraine days or less intense pain, but they can often breathe better and commonly look better.

Denouncing the surgery will result in hopeless patients being attracted and persuaded by the advertisements of the few improperly trained and immoral surgeons with unreasonable fees, which will have disappointing and even devastating outcomes. Our neurology colleagues, by accepting this procedure and referring patients to properly trained surgeons, can control the outcomes to some degree and prevent these patients from selecting surgeons who may have financial gain as their sole aim.

References

  1. Top of page
  2. Surgical Techniques
  3. Patient Selection
  4. Sham Surgery Study
  5. Five-Year Study
  6. Socioeconomic Factors
  7. Discussion
  8. Conclusion
  9. References