No previous evidence
Exercise is also frequently recommended as a treatment, though there has not been sufficient scientific evidence that it really has any effect on migraine patients.

In a randomized controlled study researchers from the University of Gothenburg’s Sahlgrenska Academy have now analysed how well exercise works as a preventative treatment for migraines relative to relaxation exercises and topiramate.

40 minutes of exercise
Published in the journal Cephalalgia, the study involved 91 migraine patients, a third of whom were asked to exercise for 40 minutes three times a week under the supervision of a physiotherapist, with another third doing relaxation exercises, and the final third given topiramate. The study lasted for a total of three months, during which the patients’ migraine status, quality of life, aerobic capacity and level of phyical activity were evaluated before, during and after their treatment. Follow-ups were then carried out after three and six months.

Exercise just as effective
The results show that the number of migraines fell in all three groups. Interestingly, there was no difference in the preventative effect between the three treatments.

The researchers concluded that exercise can act as an alternative to relaxations and topiramate when it comes to preventing migraines, and is particularly appropriate for patients who are unwilling or unable to take preventative medicines, says Emma Varkey, the physiotherapist and doctoral student at the Sahlgrenska Academy who carried out the study.

Material adapted from University of Gothenburg.

Reference
Title: Exercise as migraine prophylaxis: A randomized study using relaxation and topiramate as controls
Authors: Emma Varkey, Åsa Cider, Jane Carlsson and Mattias Linde
Published by:Cephalalgia published online 2 September 2011
DOI: 10.1177/0333102411419681

More than 70% of patients who had suffered a TBI reported having headaches during the first year after their injury. This finding is a result of a multi-center study described by Jeanne Hoffman, PhD, Department of Rehabilitation Medicine, University of Washington, Seattle, and a group of colleagues from University of Washington, Craig Hospital (Denver, CO), Mayo Clinic (Rochester, MN), University of Alabama at Birmingham, University of Texas Southwestern Medical School (Dallas), Virginia Commonwealth University (Richmond), and Moss Rehab (Philadelphia, PA).

Females and persons with a pre-injury history of headache were significantly more likely to report headache, but there was no statistical link between incidence of post-injury headache and the severity of the TBI.

Material adapted from Mary Ann Liebert, Inc., Publishers.

Download / Reference
Jeanne M. Hoffman, PhD, Sylvia Lucas, MD, PhD, Sureyya Dikmen, PhD, Cynthia A. Braden, MA, Allen W. Brown, MD, Robert Brunner, MD, Ramon Diaz-Arrastia, MD, William C. Walker, MD, Thomas K. Watanabe, MD & Kathleen R. Bell: “Natural History of Headache Following Traumatic Brain Injury,” Journal of Neurotrauma, doi: 10.1089/neu.2011.1914

Researcher Donald Penzien

He said the costs of prescription prophylactic drugs – the kind chronic migraine sufferers take every day to prevent onset – may not seem much even at several dollars a day.

“But those costs keep adding up with additional doctor visits and more prescriptions,” Penzien said. “The cost of behavioral treatment is front-loaded. You go to a number of treatment sessions but then that’s it. And the benefits last for years.”

Published in the June issue of the journal Headache, the study compared the costs over time of several types of behavioral treatments with prescription-drug treatments. The research team included investigators from Wake Forest University, UMMC and the University of Mississippi.

The researchers found that after six months, the cost of minimal-contact behavioral treatment was competitive with pharmacologic treatments using drugs costing 50 cents or less a day. Minimal-contact treatment is when a patient sees a therapist a few times, but largely practices the behavioral techniques at home, aided by literature or audio recordings.

After one year, the minimal-contact method was nearly $500 cheaper than pharmacologic treatment.

“We have a whole armamentarium of behavioral treatments and their efficacy has been proven. But headache sufferers are only getting a tip of these options,” said Dr. Timothy Houle, associate professor of anesthesiology and neurology at Wake Forest University, and the study’s principal investigator. “One reason is people think behavioral treatment costs a lot. Now with this study, we know that the costs are actually comparable, if not cheaper, in the long run.”

At a time when health-care costs are under national scrutiny, the study offers a framework for comparing costs that researchers can update and use for years to come.

“We thought, ‘Wouldn’t it be fun to model this and see how it comes out over time?’” Penzien said. “All the figures are there so if someone disagrees with it, they can plug in their own numbers.”

The researchers did not compare the effectiveness of methods, nor did they calculate the costs over time of individual drugs, since dosages and prices vary widely. Rather, they figured the per-day costs of each method based on fees of physicians and psychologists. For the physician group, they added in the cost of prescription beta-blocker drugs at various prices.

For instance, among the psychologists surveyed, one-on-one behavioral sessions cost between $70 and $250 for the intake visit and $65 and $200 for follow-up visits. That put the median intake cost at $175 and median follow-up cost at $125 for a median 10 visits.

The researchers calculated the median cost of pharmacologic approaches at $250 for the intake session and a professional fee of $140 per session. Median time to the first follow-up was 52.2 days, rising to 60 for the second with a median five visits per year.

To get information on behavioral treatments, the researchers surveyed members of the Behavioral Issues Group of the American Headache Society. For figures on pharmacologic treatments, the researchers surveyed a group of Headache Society-member physicians they knew treated substantial numbers of headache sufferers.

The most expensive behavioral treatment method – individual sessions with a psychologist in clinic – cost more than pharmacologic treatment with $6-a-day drugs in the first months. But at about five months, individual sessions become competitive. After a year, they are cheaper than all methods except treatment with drugs costing 50 cents or less a day.

Overall, group therapy and minimal-contact behavioral treatment were cost-competitive with even the cheapest medication treatment in the initial months. At one year, they become the least-expensive headache treatment choice.

Material adapted from University of Mississippi Medical Center .

“The incidence and severity of migraines was greatly reduced after bariatric surgery and weight loss, suggesting there are a number of people who are suffering from migraines who otherwise might not but for their excessive weight,” said Isaac Samuel, MD, Associate Professor, University of Iowa (UI) Roy J. and Lucille A. Carver College of Medicine and Director, UI Obesity Surgery Program.

UI researchers reviewed the medical records of 702 patients who had Roux-en-Y gastric bypass (RYGB) surgery between March 2000 and September 2009 who had a diagnosis of migraine for which they were being medically treated. Eighty-one patients qualified for the retrospective study and data were collected from institutional electronic medical records or via telephone. The post-operative follow-up period ranged from 12 months to eight-and-a-half years (patients followed up less than 12 months were excluded from the analysis).

The researchers noted that while gastric bypass generally improved or resolved migraine headaches among all study participants, those who developed their first migraines after becoming obese experienced the most improvement. About 80 percent had total resolution and 14 percent had partial improvement. Of the people who experienced their first migraine before the onset of obesity, 75 percent showed improvement after surgery (46% had total resolutions, 29% had partial improvement).

While many people with morbid obesity have additional medical issues associated with migraines, by analyzing the data, researchers showed that the improvement in migraine symptoms following surgery was independent of the improvement of their migraine-associated issues such as depression, anxiety, or sleep apnea. Women with migraines associated with their menstrual cycles had similar improvement of migraines, as did others in the study.

“The association between migraine headache and obesity is controversial,” added Dr. Samuel. “Although some suggest that obesity is associated with migraine prevalence, others have only found a correlation between the frequency and severity of migraine headache and obesity. The effect of surgical weight loss on morbidly obese patients with migraines provides a unique opportunity to evaluate this association. The higher number of patients identified in this study cohort that developed migraines after obesity onset could suggest that obesity contributes to an increased risk of having migraines rather than merely exacerbating the symptoms.”

Other causes of headache in obese patients could include pseudotumor cerebri, or idiopathic intracranial hypertension, an increase in pressure around the brain that can feel like a migraine and may be caused by obesity, which also responds well to bariatric surgery.(1) The UI retrospective study was unable to differentiate between the two, and researchers relied on the doctor’s diagnosis of migraine.

Bariatric surgery has been shown to be the most effective and long lasting treatment for morbid obesity and many related conditions.(2) People with morbid obesity have BMI of 40 or more, or BMI of 35 or more with an obesity-related disease such as Type 2 diabetes, heart disease, or sleep apnea. Recently the FDA approved the use of an adjustable gastric band for BMI 30 and above, recognizing that there is an increase in mortality and medical complications of obesity at even this level of obesity.

According to the ASMBS, more than 15 million Americans have morbid obesity. Studies have shown patients may lose 30 to 50 percent of their excess weight 6 months after surgery and 77 percent of their excess weight as early as one year after surgery.(3)

The most common methods of bariatric surgery are laparoscopic gastric bypass and laparoscopic adjustable gastric banding (LAGB). Bariatric surgery limits the amount of food the stomach can hold, and/or limits the amount of calories absorbed, by surgically reducing the stomach’s capacity to a few ounces.

The federal government estimated that in 2008, annual obesity-related health spending reached $147 billion,(4) double what it was a decade ago, and projects spending to rise to $344 billion each year by 2018.(5) The Agency for Healthcare Research and Quality (AHRQ) reported significant improvements in the safety of bariatric surgery due in large part to improved laparoscopic techniques and the advent of bariatric surgical centers of excellence. The overall risk of death from bariatric surgery is about 0.1 percent(6) and the risk of major complications is about 4 percent.(7)

In addition to Dr. Samuel, FRCS, FACS, study co-authors include Yusuf Gunay MD, Mohammad Jamal MD, FACS, Alyssa Capper BS, Anas Eid MD, Debi Heitshusen RN, all from the UI Roy J. and Lucille A. Carver College of Medicine.

Material adapted from American Society for Metabolic & Bariatric Surgery.

Reference
*Yusuf Gunay, MD; Mohammad Jamal, MD, FACS; Alyssa Capper, BS; Anas Eid, MD; Debi Heitshusen, RN, Isaac Samuel, MD, FRCS, FACS, The University of Iowa, Roy J. and Lucille A. Carver College of Medicine. PL 111 – Roux-en-Y Gastric Bypass Achieves Substantial Resolution of Migraine Headache in the Severely Obese: a 9-year analysis of 81 patients.

Additional Citations
1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1420807/

2. RA Weiner. “ Indications and Principles of Metabolic Surgery.” U.S. National Library of Medicine. 2010; 81(4):379-94

3. AC Wittgrove et al. “Laparoscopic Gastric Bypass, Roux-en-Y: Technique and Results in 75 Patients With 3-30 Months Follow-up.“ Obesity Surgery. 1996. 6:500-504.

4. EA Finkelstein. “Annual Medical Spending Attributable To Obesity: Payer-And Service-Specific Estimates.” Health Affairs. 2009. 28(5):822-831.

5. K Thorpe. America’s Health Rankings. “The Future Costs of Obesity.” 2009.

6. Agency for Healthcare Research and Quality (AHRQ). Statistical Brief #23. Bariatric Surgery Utilization and Outcomes in 1998 and 2004. Jan. 2007.

7. Flum et al. “Perioperative Safety in the Longitudinal Assessment of Bariatric Surgery.” New England Journal of Medicine. 2009. 361:445-454.http://content.nejm.org/cgi/content/full/361/5/445

Epidemiological studies are pointing out that genetic factors may be an underlying cause. Discrepancies in the way people are reacting to wine intake, and whether or not it triggers migraine, may be potentially explained by genetic polymorphisms in specific enzymes related to metabolism. Alcoholic drinks are a migraine trigger in about one third of patients with migraine in retrospective studies on trigger factors. Many population studies show that patients with migraine consume alcohol in a smaller percentage than the general population. Research has shown a decreased prevalence of headache with increasing number of alcohol units consumed. The classification criteria of alcohol-related headaches remain problematic.

A paper from The Headache Center in Empoli, Italy by Panconesi et al. summarizes the scientific data relating to alcohol and migraine headaches. The factors that trigger an attack of migraine, or of other headaches as well, are poorly understood. While retrospective studies tend to include alcohol as a trigger for an attack, the authors describe that in a recent prospective study (in which information on the factors that could potentially trigger an attack were collected prior to the migraine attack), menstruation, stress, and fatigue were found most commonly to relate to a subsequent attack.

In the present paper, the authors reviewed the role and mechanism of the action of alcohol or other components of alcoholic drinks in relation to alcohol-induced headache. They conclude from their review that reports overestimate the role of alcohol, as well as other foods, in the triggering of migraine.

International Scientific Forum on Alcohol Research members thought that this was a very balanced review of the subject, and that it provided straightforward and sensible advice. Although some individuals surely have the onset of a migraine or other type of headache after the consumption of wine or alcohol, the findings are not consistent (in this study, beer consumption on the previous day reduced the risk of a migraine attack). Forum members suggest that given that subjects reporting migraine headaches have been found to be at increased risk of cardiovascular disease, it would not be appropriate to advise all such sufferers to avoid alcohol.

As suggested by the authors of this paper, it may be reasonable for migraine sufferers to drink small amounts of specific types of alcoholic beverages to see if each beverage is tolerated or not. After seeing the effects, and factoring in symptoms from other dietary or lifestyle elements (sleep, stress, dehydration), a reasonable discussion can be carried out with one’s physician with respect to commencing or continued alcohol use.

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, go to http://www.bu.edu/alcohol-forum/critique-044-the-association-of-alcohol-drinking-with-migraine-headache-12-june-2011

Material adapted from Boston University Medical Center.

Download / Reference
Panconesi A, Bartolozzi ML, & Guidi L. (2011). Alcohol and migraine: What should we tell patients? Curr Pain Headache Rep, 15:177-184. DOI 10.1007/s11916-011-0184-4.

In this paper, lead author B. Lee Peterlin and colleagues review the epidemiology of PTSD and migraine, underscoring the established sex differences. While individually both migraine and PTSD are more common in women than men, a recent study by Peterlin and colleagues — the only study to date to look at sex differences in the PTSD-migraine association — suggests that men with migraines had up to a four-fold greater odds of PTSD than females who experience migraine headaches. This finding suggests that sex hormones play an important role in the PTSD-migraine association.

The age of the traumatic life event resulting in PTSD may also be an important factor for the sex differences in the PTSD-migraine association. When a traumatic life event occurs before 13 years of age, the risk of depression is greater than the risk of PTSD; however, when the traumatic life event occurs after 12 years of age, the risk of PTSD is greater. Although the migraine population has a documented high prevalence of abuse, the peak age of vulnerability for childhood sexual abuse, is under 13 years of age. In contrast, transportation accidents and combat (two of the most common traumatic events reported by migraineurs with PTSD in one study) may be more commonly experienced by those older than 12 years of age. It is therefore possible that in the migraine population, sex differences in the type and age of traumatization contributes to the sex differences in the risk of PTSD.

Studies have also shown that the presence of PTSD in those with migraine is associated with greater headache-related disability than in migraine sufferers without PTSD. Dr. Peterlin explains, “The current data indicate that behavioral PTSD treatment alone can positively influence chronic pain conditions and disability. Therefore, physicians should consider screening migraine sufferers for PTSD, and men in particular. Further, in those migraineurs with PTSD, behavioral therapy should be considered, alone or in combination with pharmacological treatment.” The authors suggest that further research investigating the sex differences in the association between PTSD and migraine is necessary to validate the sex differences found in their study, as well as to determine suitable treatment options in those migraineurs suffering with PTSD.

A second related article published this month in Headache also reviews sex and gender differences in those with headache. Todd Smitherman, PhD, from the University of Mississippi and Thomas Ward, MD, of the Dartmouth Medical School in New Hampshire, reviewed extant medical literature to examine the psychosocial factors of gender and social role expectations, and coping strategies as they relate to sex and gender differences in headache pain.

A distinction was made in this paper between sex — the biologically-based indicators of male or female; and gender — “the traits and behaviors characteristic of and appropriate to members of each sexual category” (Unger, 1976) given that pain-related differences between men and women established in the medical literature cannot be reduced solely to biological determinants.

The authors suggest that women’s pain experiences, multiple role responsibilities, and coping strategies likely influence the sex and gender differences in pain perception and response. “Gender-based differences are not strictly biological and important psychosocial issues are involved with headache pain as well,” Dr. Smitherman concluded. “Further research of the impact of sex and gender on psychosocial variables may help clinicians tailor treatment plans that reduce pain and disability for headache patients.”

Material adapted from Wiley-Blackwell.

References
“Post-Traumatic Stress Disorder and Migraine: Epidemiology, Sex Differences, and Potential Mechanisms.” B. Lee Peterlin, Satnam S. Nijjar, Gretchen E. Tietjen. Headache; Published Online: May 17, 2011 (DOI: 10.1111/j.1526-4610.2011.01907.x). http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2011.01907.x/abstract.

“Psychosocial Factors of Relevance to Sex and Gender Studies in Headache.” Todd A. Smitherman and Thomas N. Ward. Headache; Published Online: June 1, 2011 (DOI: 10.1111/j.1526-4610.2011.01919.x).http://doi.wiley.com/10.1111/j.1526-4610.2011.01919.x.

“Sex Matters: Evaluating Sex and Gender in Migraine and Headache Research.” B. Lee Peterlin, Saurabh Gupta,Thomas N. Ward and E. Anne MacGregor. Headache; Published Online: June 1, 2011 (DOI: 10.1111/j.1526-4610.2011.01900.x). http://doi.wiley.com/10.1111/j.1526-4610.2011.01900.x.

“Sex-Related Differences in Epidemiological and Clinic-Based Headache Studies.” E. Anne MacGregor, Jason D. Rosenberg and Tobias Kurth. Headache; Published Online: June 1, 2011 (DOI: 10.1111/j.1526-4610.2011.01904.x). http://doi.wiley.com/10.1111/j.1526-4610.2011.01904.x.

“Childhood Abuse and Migraine: Epidemiology, Sex Differences, and Potential Mechanisms.” Gretchen E. Tietjen and B. Lee Peterlin. Headache; Published Online: June 1, 2011 (DOI: 10.1111/j.1526-4610.2011.01906.x). http://doi.wiley.com/10.1111/j.1526-4610.2011.01906.x.

“Migraine Genes and the Relation to Gender.” Reinald Shyti, Boukje de Vries and Arn van den Maagdenberg. Headache; Published Online: June 1, 2011 (DOI: 10.1111/j.1526-4610.2011.01913.x). http://doi.wiley.com/10.1111/j.1526-4610.2011.01913.x.

“Sex-Related Differences in Animal Models of Migraine Headache.” Hayrunnisa Bolay, Nancy E. J. Berman and Didem Akcali. Headache; Published Online: June 1, 2011 (DOI: 10.1111/j.1526-4610.2011.01903.x). http://doi.wiley.com/10.1111/j.1526-4610.2011.01903.x.

“Mechanisms of Pain Modulation by Sex Hormones in Migraine.” Saurabh Gupta, Kenneth E. McCarson, K.M.A. Welch and Nancy E.J. Berman. Headache; Published Online: June 1, 2011 (DOI: 10.1111/j.1526-4610.2011.01908.x). http://doi.wiley.com/10.1111/j.1526-4610.2011.01908.x.

The session “Maltreatment in Headache: Epidemiology, Neurobiology, Evaluation and Treatment,” led by Gretchen E. Tietjen, MD, a leading investigator in the field, will be at 11 am, Thursday, June 2 in the Grand Hyatt Washington. Dr. Tietjen is Director of University of Toledo Medical Center’s Headache Treatment and Research Program.

“We are finding an unusually high prevalence of childhood abuse in migraine patients.” Dr. Tietjen said. “This seems to be more than a psychological reaction to maltreatment. We are examining the idea that early abuse – no matter what kind – creates permanent changes in the neurobiological system of abused persons that may make them more prone to migraine pain.”

Dr. Tietjen said there is considerable preclinical and clinical evidence that chronic early life stress results in changes in the neuroendocrine system that controls reactions to stress and regulates many body processes, including the immune system as well as mood, emotions, and sexuality. “We are interested in exploring the idea that treatment with serotonin-specific reuptake inhibitors may actually reverse some of the neurobiological effects of maltreatment, including decreasing the hormonal response to stress.”

Addressing the issue of asking patients about potential abuse will be discussed by Dr. Elliott Schulman, Adjunct Clinical Professor of Neurology at Jefferson School of Medicine in Philadelphia.

Dr. Tietjen said. “Many patients seem relieved when we ask them about abuse, but we need more much more research to tell us if such information can really influence how we treat them.” In some cases patients are referred for psychological counseling which may or may not help their migraine condition, but Dr. Tietjen acknowledged that such questions may not be easy for neurologists to ask.

About Migraine Headaches
Some 36 million Americans suffer from migraine, more than have asthma or diabetes combined. Migraine is characterized by pulsating or throbbing headache pain which can be moderate to severe in intensity. Its severity can be extremely disabling for sufferers, painful enough to cause work loss and absence from activities with family and friends. Migraine costs the United States more than $20 billion each year. Costs are attributed to direct medical expenses (e.g. doctor visits, medications) and indirect expenses (e.g. missed work, lost productivity).

Material adapted from MBooth & Associates.

The session examines the role of the thalamus in regulating pain transmission in migraine, a new understanding of the anatomy of migraine. It will be at 3:15 pm, Thursday, June 3, and is chaired by Michael A. Moskowitz, MD, of the Neuroscience Center at Massachusetts General Hospital and R. Allan Purdy, MD, who is scientific chair of this year’s meeting

“Elegant basic science and clinical experiments have recently demonstrated that the thalamus acts as a sort of railway station and integration center for the transmission of migraine pain,” Dr. Purdy said. “An impulse comes into the ‘station’ and the thalamus regulates how it will be transmitted to the cortex, and the extent to which it is made worse by environmental stimuli, such as light.” We are beginning to understand that the thalamus may be a target for current and future migraine treatments

In a study of blind people, Rami Burstein, professor of anesthesia and critical care medicine at Harvard Medical School in Boston, looked at two groups of blind patients who suffer migraine headaches – the first group included patients totally blind due to eye diseases such as retinal cancer and glaucoma and the second group patients who were legally blind due to retinal degenerative diseases, such as retinitis pigmentosa. Patients in the first group were unable to see images or to sense light and therefore could not maintain normal sleep-wake cycles. Patients in the second group described intensified pain when they were exposed to light, in particular to blue wavelengths.

“This suggested to us that the mechanism of photophobia must involve the optic nerve, because in totally blind individuals, the optic nerve does not carry light signals to the brain,” Dr. Burstein said.

About Migraine Headaches
Some 36 million Americans suffer from migraine, more than have asthma or diabetes combined. Migraine is characterized by pulsating or throbbing headache pain which can be moderate to severe in intensity. Its severity can be extremely disabling for sufferers, painful enough to cause work loss and absence from activities with family and friends. Migraine costs the United States more than $20 billion each year. Costs are attributed to direct medical expenses (e.g. doctor visits, medications) and indirect expenses (e.g. missed work, lost productivity).

Material adapted from MBooth & Associates.

“Although the intention of control and placebo interventions in research studies is to be relatively ineffective, the question rises as to what factors might cause improvement seen in these groups,” commented corresponding investigator Arianne P. Verhagen, PhD, Assistant Professor, Department of General Practice, Erasmus Medical Center, Rotterdam, The Netherlands. “The aim of this study was to analyze the observed effects in the ‘no treatment’ and placebo control groups in clinical trials with TTH and migraine patients.”

In the headache clinical trials studied, the “no treatment” and placebo groups had a high overall recovery rate of 36%. Control groups in pharmacological trials showed a higher response rate than the behavioral (non-pharmacological) trials (38.5% vs. 15.0%). Patients had higher recovery rates in the acute treatments compared with the prophylactic treatments (39.6% vs. 32.8%). Knowing that a substantial portion of patients improve without treatment is important when considering the benefits and risks of daily headache treatment.

Pharmacological treatment typically starts when non-pharmacological treatments like lifestyle changes, relaxation therapy, cognitive therapy, and reassurance do not work. Many of the prescribed or over-the-counter medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), may lead to adverse events and medication overuse headache. Considering the risks of adverse events, the authors recommend that “the prescription of medication needs to be carefully considered and evaluated with each individual patient. Because of the recovery results in ‘no treatment’ control groups in pharmacological trials, the question rises whether or not this way of prescription is always preferable over no treatment (wait and see) especially in the TTH population.”

Material adapted from Elsevier.

Reference
The article is “Headache: The Placebo Effects in the Control Groups in Randomized Clinical Trials; An Analysis of Systematic Reviews” by Femke M. de Groot, BSc, Annieke Voogt-Bode, BSc, Jan Passchier, PhD, Marjolein Y. Berger, MD, Bart W. Koes, PhD, and Arianne P. Verhagen, PhD. It will appear in the Journal of Manipulative and Physiological Therapeutics, Volume 34, Issue 5 (June 2011), DOI 10.1016/j.jmpt.2011.04.007, published by Elsevier.

Headache is a universal experience. At present, there are more than 100 different types of headache and one of the most recurring ones is migraine, which affects approximately 10-12% of the population, being three times more common in women than in men. When migraine becomes chronic –occurring more than 15 days a month–, it can disrupt patients’ daily life in a great degree.

This research study is one of the three studies that have been conducted by Juan Miguel García Leiva –a researcher at the University of Granada Institute for Neuroscience “Federico Oloriz” – and coordinated by professor Elena Pita Calandre.

Trigger Points in Migraine Sufferers
In the first study, researchers examined a sample of healthy subjects and patients with a diagnosis of migraine with any frequency, and analyzed the presence of trigger points and their location, many of the explorations resulting in a migraine crisis. The most interesting findings of this study were: 95% of migraine sufferers have trigger points, while only 25% of healty subjects have them. The most common locations of trigger points are the anterior temporal and the suboccipital region, both billateral, of the head. Furthermore, researchers found a positive correlation among the number of trigger points in a patient, the number of monthly crises and the duration in years of the condition.

The most common locations of trigger points in migraine sufferers.

Subsequently, researchers conducted another study with 52 migraine sufferers (with migraine refractory to common pharmacological treatments). During three months, patients received a weekly subcutaneous injection of 1mL of a local anesthetic into their trigger points.

After the injection of the anesthetic, 18% of patients experienced a 50% or higher reduction in the frequency of migraine crises, as compared with the basal period. Additionally, an 11-49% reduction of frequency was observed in 38% of patients. Two thirds of the patients treated reported to feel “better or much better”.

Few Side Effects
In the third study, 25 patients with chronic migraine were injected with 12.5 doses of botox into each trigger point twice, during a period of 3 months. Frequency (main variable), intensity and scales of migraine crises were recorded one month before and one month after the treatment to compare the changes experienced. In addition, side effects were also recorded during the experiment, and they were found to be mild and temporary.

After the injections, the most significant decrease in crisis frequency was observed at week 20. Similar results were obtained in those crises labelled as “moderate” and in the frequency of analgesic use by patients.

García Leiva specified that this treatment “is not a first-choice treatment for migraine sufferers, but it can only be applied in patients with chronic migraine who have tried several treatments with poor results, and who show peripheral sensitization of muscles. Recently, the Foods and Drugs Administration (USA) has approved botulinum toxin as a therapeutical drug for the treatment of chronic migraine.

Material adapted from University of Granada.

References
1. Trigger point evaluation in migraine patients: an indication of peripheral sensitization linked to migraine predisposition? Calandre EP, Hidalgo J, García-Leiva JM, Rico-Villademoros, F. European Journal of Neurology 2006, 13: 244–249

2. Effectiveness of Ropivacaine Trigger Points Inactivation in the Prophylactic Management of Patients with Severe Migraine. García-Leiva JM, HidalgoJ,Rico-Villademoros F, Moreno V, Pain Medicine 2007, 8 (1): 244-249

3.- Hidalgo J, Rodríguez-López CM, García-Leiva JM, Rico-Villademoros F, Calandre EP. Effectiviness botulinum toxin type A in the prophylaxis of severe and treatment–refractory migraine. J Headache Pain, 2006; 7(S-1): p. S-18.

Joint hypermobility syndrome is a condition where joints easily move beyond their normal range and often affects women. There is a genetic component to the illness, and it tends to run in families. Genes that are responsible for the production of collagen, an important protein that helps glue tissues together, are suspected to play a role.

The syndrome often causes other joint pain, which can lead to misdiagnosis.

“Joint hypermobility syndrome is very common and affects roughly 10 to 15 percent of the entire female population,” says Martin, who also has the syndrome and experiences migraines. “Preliminary studies suggested that headache disorders are more common in patients with joint hypermobility syndrome.

“We wanted to determine if the prevalence, frequency, and disability of migraine differ between female patients with the syndrome and a control population.”

Using interviews and written questionnaires, researchers compared 28 women with the syndrome with 232 women from two primary care practices. They found that 75 percent of patients with joint hypermobility syndrome also got migraines while only 43 percent suffered from migraines in the comparison group. After assessing age and gender differences between the groups, those with joint hypermobility had three times the risk of migraines.

Women in this group also experienced migraines nearly twice as many days each month and were more likely to experience visual disturbances called “aura” preceding the pain of a migraine attack.

“The results show that this common clinical disorder is strongly associated with an increased prevalence, frequency, and disability of migraine in females,” Martin says. “The patients in the study were selected from a specialty connective tissue clinic, so our next step is to test whether or not this is the same in less severe cases by using patients in a regular primary care clinic.

“In bringing attention to this link, we hope that patients can be diagnosed earlier, leading to quicker treatments.”

In addition, individuals who are double-jointed might want to consider seeing a specialist if they have recurrent, debilitating migraines or experience the following:

• Moderate to severe arthritis.
• Dislocation and sprains in joints.
• Fibromyalgia.
• Anxiety and depression.
• Neck pain or herniated discs.
• TMJ (temporomandibular joint disorder), or inflammation of the temporomandibular joint which connects the mandible to the skull.
• Leaky heart valves.

“There are treatments that can greatly improve the quality of life for those with the syndrome, but the correct diagnosis needs to be made first,” Martin says.

Material adapted from University of Cincinnati.

Dr. Rachel McCandless and colleagues from the Primary Children’s Medical Center and the University of Utah studied children 6-18 years old who were diagnosed with migraines between 2008 and 2009. The 109 children enrolled in the study were treated at the Primary Children’s Medical Center, which serves kids from Utah, Idaho, Montana, Nevada, Colorado, and parts of Wyoming.

The researchers took two-dimensional echocardiograms of each child’s heart, looking for a patent foramen ovale (PFO), a common defect in the wall between the two upper chambers of the heart. Although a PFO is not necessarily dangerous, it can allow unfiltered blood to bypass the lungs and circulate throughout the body. As Dr. McCandless explains, “Some adult studies have suggested a link between having a PFO and migraine headaches.”

Of the studied children who had migraines with aura, 50% also had a PFO; this is nearly double the PFO rate of the general population. However, only 25% of children who had migraines without aura had a PFO. Dr. McCandless and colleagues hypothesize that if a causal relationship can be established, closure of a PFO with a catheter device may help in the treatment of certain kinds of migraines, specifically migraines with aura. It is her hope that “our study will help guide future research about this difficult problem.”

Material adapted from Elsevier.

Reference
“Patent Foramen Ovale in Children with Migraine Headaches” by Rachel T. McCandless, MD, Cammon B. Arrington, MD, Douglas C. Nielsen, James F. Bale, Jr., MD, and L. LuAnn Minich, MD, appears in The Journal of Pediatrics, DOI 10.1016/j.jpeds.2011.01.062, published by Elsevier.

This is welcome news for sufferers as the treatment effectiveness of migraine medications is reported to be discouraging. A large majority (84%) of people with migraines state that the drugs do not completely relieve their pain, and sometimes do not even work at all. Another 71% note that their headaches return after treatment, and more than a third report that the drugs are associated with excessive side effects.

Jonathan Walker, M.D., a Dallas, Texas neurologist, recently published a study in the journal Clinical EEG and Neuroscience in which he used quantitative EEG (QEEG) brain imaging to map the brain activity of 71 patients who came for migraine treatment. He discovered a brain activation pattern associated with systemic stress common to every single patient. He then offered to treat anyone in the group using neurofeedback, also known as EEG-biofeedback, instead of drugs. 46 patients elected to undergo neurofeedback and 25 patients decided to remain on medications.

Dr. Walker treated those who opted for neurofeedback with an innovative brain-computer interface developed by BrainMaster Technologies, Inc. of Bedford, Ohio, a leading provider of neurofeedback equipment and technology, for an average of 24 sessions. During treatment sessions, patients were attached to sensors, which tracked their brain waves and delivered real-time visual and auditory information as they entered a specified combination of brainwave conditions associated with relaxation and self-regulation.

At the end of the study, 54% of those participating in neurofeedback experienced a complete elimination of their migraine headaches with no side effects from the neurofeedback therapy. None of those in the pharmaceutical therapy group reported elimination of migraine activity. An additional 39% of the neurofeedback group reported a more than a 50% reduction in migraine frequency, while only 8% of people in the pharmaceutical therapy group reported similar improvement. One person in the neurofeedback group reported no change in headache frequency, while 68% of the pharmaceutical therapy group said their headache frequency had not changed. Statistical analysis reveals a 1 in 100,000 possibility the results were due to chance.

Dr. Walker’s study demonstrates the effectiveness of neurofeedback in treating patients with recurrent migraines with a moderate investment of time and energy, and no apparent risk of side effects.

Material adapted from The Neurotherapy Center of Dallas.

Reference
Walker, Jonathan E. (2011). QEEG-Guided Neurofeedback for Recurrent Migraine Headaches, CLINICAL EEG and NEUROSCIENCE, VOL. 42, NO.1.

Lesions of the brain microvessels
Lesions of the brain microvessels, visible on cerebral MRI images, can be of various kinds: white-matter hyperintensities, and, more rarely, silent infarcts leading to loss of white-matter tissue.

They result from a deterioration of the small cerebral arteries that supply blood to the brain’s white matter – the material which ensures, among other things, the passage of information between different parts of the brain.

These lesions are observed in almost all elderly people. However, their severity varies greatly from one individual to the next. Moreover, it has been shown that they are more severe among hypertension sufferers and diabetics.

A large quantity of hyperintensities leads to many cerebral complications: cognitive deterioration, increased risk of Alzheimer’s disease, depression, movement disorders and increased risk of stroke. Moreover, according to several studies, the presence of a large quantity of this type of brain lesion increases the risk of cognitive deterioration (reasoning, memory, etc.) and of Alzheimer’s disease.

These factors expalin why the research team coordinated by Christophe Tzourio, director of the Inserm-Université Pierre et Marie Curie Mixed Research Unit 708 “Neuroepidemiology,” advanced the hypothesis that migraines could “damage” the brain.

To test this hypothesis, researchers evaluated the impact of migraine on cognitive function. The team used the EVA study-group of individuals aged over 65 years who were recruited from the general population in Nantes and monitored over a 10-year period. Cerebral MRI was performed on more than 800 of the participants, and these individuals were also questioned about their headaches by a neurologist.

“The advantage of this cohort is that it involves relatively elderly individuals. However, since migraine often begins before age 30, if it did indeed have a deleterious and cumulative effect on the brain, then we should observe cerebral damage and a higher level of cognitive decline among the migraine sufferers,” explains Christophe Tzourio.

The cognitive tests performed involved an evaluation of the volunteers orientation in time and space, their short-term memory, and their capacity and speed to correctly carry out specific tasks.

The results show that 21% of people suffer or have suffered from severe headaches over the course of their lives. For more than 70% of these, this involves migraines, some of which are with aura (see more on this below). The MRI scans for those participants having severe headaches confirm that they are twice as likely to have a large quantity of microvascular brain lesions as subjects without headaches.

In contrast, the cognitive scores were identical for individuals with or without severe headaches and for those having or not having cerebral microvascular lesions.

Among participants having a migraine with aura (2% of the total sample), a specific increase in silent cerebral infarcts and certain lesions was observed; hence, this confirmed previous studies, but without detectable cognitive harm.

“This is a very reassuring result for the many people who suffer from migraine. In spite of the increased presence of lesions of the brain microvessels, this disorder does not increase the risk of cognitive decline. Therefore, we have not observed negative consequences of migraine on the brain, ” concludes Tobias Kurth, lead author of the study, who designed and carried out these analyses.

Migraine and brain lesions: a suspected link
Headaches (or cephalgias) are very common among the general population. This is particularly the case for migraine, which is a very painful, chronic and debilitating variety of headaches. It is estimated that around 12% of adults and 5 to 10% of children are afflicted. This totals 11 million migraine sufferers in France.

There are two types of migraine: (1) migraine without aura, which is by far the most frequent, and (2) migraine with aura (15% of migraines). Migraine aura involves the appearance of, often visual, phenomena (zigzag lines of light, the impression of viewing the world through frosted glass, etc.) in the minutes preceding the appearance of the headache.

The mechanisms of migraine and migraine aura are still largely unknown. However, it is suspected that a transitory contraction of the blood vessels could be responsible for a reduction of blood flow in the brain promoting the appearance of migraine aura. Much research elsewhere has shown that people suffering from migraine with aura have an increased risk of cerebral infarction (or strokes). Extremely fortunately, this risk remains low among migraine sufferers. However, the research confirms the existence of a link between migraine and blood vessels in the brain.

Material adapted from INSERM (Institut national de la santé et de la recherche médicale).

Download / Reference
Tobias Kurth, Shajahal Mohamed, Pauline Maillard, Yi-Cheng Zhu, Hugues Chabriat, Bernard Mazoyer, Marie-Germaine Bousser, Carole Dufouil, & Christophe Tzourio, “Headache, Migraine, and Structural Brain Lesions and Function: the population-based EVA MRI Study.” BMJ 2011; 342:c7357 doi: 10.1136/bmj.c7357 (Published 18 January 2011).

And surprisingly, the increase in confidence in self-management abilities is greatest among those who feel that they have very little control over their condition before treatment starts. Seng’s and Holroyd’s findings are published online in Springer’s journal Annals of Behavioral Medicine.

Seng and Holroyd analyzed data for 176 participants in the US Treatment of Severe Migraine Trial. Treatment programs included acute drug therapy for all, with either β-blockers or placebo – each with or without behavioral migraine management. The behavioral migraine management program consisted of demonstrations of migraine management skills during four monthly clinic visits, which were then applied between sessions by participants through workbooks, audiotape lessons, and guided home practice.

Their analyses showed that the addition of behavioral migraine management to drug therapy dramatically increased participants’ confidence in their ability to effectively self-manage migraine, compared to migraine drug therapy alone. Behavioral management also increased participants’ belief that migraines can be influenced by one’s own behavior and decreased the belief that migraines are primarily influenced by chance or fate.

The authors conclude: “Our exploratory analyses offer an optimistic message: brief psychological interventions for migraine management can effectively increase sufferers’ confidence in self-management and can be long-lasting.” Psychological interventions enhanced drug therapy, enabling participants to take a more active role in their treatment by using behavioral skills to manage migraines.

Material adapted from Springer.

Reference
Seng EK & Holroyd KA (2010). The dynamics of changes in self-efficacy and local of control expectancies in the behavioral and drug treatment of severe migraine. Annals of Behavioral Medicine; DOI 10.1007/s12160-010-9223-3.

Using data from the Adverse Childhood Experiences (ACE) Study of 17,337 adult members of the Kaiser Health Plan in San Diego, Gretchen E. Tietjen, MD of the University of Toledo College Of Medicine and her team found that the number of ACEs showed a graded relationship to the likelihood of experiencing frequent headaches.

“We looked at eight ACEs – emotional, physical, or sexual abuse, witnessing domestic violence, growing up with mental illness in the home, having household members who were incarcerated or were abusing drugs, and experiencing parental separation or divorce,” said Dr. Tietjen. “Each ACE increased the chance of frequent headache, and as the number of ACEs increased, so did the risk of frequent headache. This ‘dose-response’ relationship suggests that ACEs may contribute to the development and frequency of severe headaches later in life.”

“Earlier studies have linked childhood maltreatment to frequent headaches and migraine,” said David Dodick, M.D., president of the AHS. “The biological underpinnings of this relationship should be a target of future research and clinicians should be aware of and evaluate for this important relationship in order to facilitate appropriate management strategies.”

Material adapted from American Headache Society by CFisher.

Paul L. Dunham, Ph.D. and his team at Missouri State University’s Center for Biomedical & Life Sciences sought to understand the mechanisms by which sleep disturbance increases the risk of migraine and may even trigger migraine.

“Previous clinical data support a relationship between sleep quality and migraine,” said Dr. Durham, “so we used an established model of sleep deprivation to measure levels of proteins that lower the activation threshold of peripheral and central nerves involved in pain transmission during migraine. We found that REM sleep deprivation caused increased expression of the proteins p38, PKA, and P2X3, which are known to play an important role in initiating and sustaining chronic pain.”

“So little is known about the biological mechanisms that underlie how certain factors trigger a migraine attack,” said David Dodick, M.D., president of the AHS. “This is important work and this Missouri State team should be applauded for beginning to shed light on an area desperately in need of investigation.”

More than 200 scientific papers and posters are being presented during the AHS meeting which is expected to draw some 500 migraine and headache health professionals including doctors, researchers, and specialists.

Material adapted from American Headache Society by CFisher.

“Migraine has been viewed as a painful condition that affects quality of life, but not as a threat to people’s overall health,” said lead investigator Richard B. Lipton, M.D., senior author of the study and professor and vice chair in The Saul R. Korey Department of Neurology at Einstein. He also directs the Headache Center at Montefiore Medical Center, the University Hospital and Academic Medical Center for Einstein.

Dr. Lipton added, “Our study suggests that migraine is not an isolated disorder and that, when caring for people with migraine, we should also be attentive to detecting and treating their cardiovascular risk factors.”

More than 29 million Americans suffer from migraine, according to the National Headache Foundation. There are two major forms, migraine without aura and migraine with aura. Both forms involve pulsing or throbbing pain, pain on one side of the head, nausea or vomiting, or sensitivity to light or sound. Migraine with aura has additional neurological symptoms including flashing lights, zig-zag lines, or a graying out of vision. Migraine is most common between the ages of 25 and 55; women are affected three times more frequently than men.

Previous population studies found that migraine with aura is associated with heart disease and stroke, particularly in health care professionals over the age of 45. The Einstein study showed that both migraine with aura and migraine without aura are risk factors for heart disease and stroke in a broadly representative sample of the U.S. population, including people from all walks of life between the ages of 18 and 80.

In the study, the researchers analyzed data on 6,102 people with migraine and 5,243 people without migraine. Participants completed questionnaires that asked about general health; headache frequency, severity and symptoms; and a broad range of medically diagnosed cardiovascular symptoms and events. Data was collected as part of The American Migraine Prevalence and Prevention Study, a longitudinal, population-based study of U.S. headache sufferers.

Results showed that migraine sufferers were about twice as likely to have had a heart attack compared with people without migraine (4.1 percent of people with migraine compared with 1.9 percent of those without migraine). The heart-attack risk was higher for those whose migraine is accompanied by aura: a three-fold greater risk compared with people who didn’t suffer migraine.

The data also shows that people with migraine were about 50 percent more likely than controls to have diabetes, hypertension, and elevated cholesterol, all well-known cardiovascular risk factors. The study found that these risk factors may contribute – but do not fully explain – the increased risk of heart attack and stroke in persons with migraine. This finding, according to an editorial accompanying the study, suggests a possible mechanism linking migraine headaches and cardiovascular events: the functioning of the inner layer of blood vessels, known as the endothelium, might be compromised in vessels both inside and outside the brains of migraine sufferers.

“Migraine sufferers should not be alarmed by our findings,” said Dr. Lipton. “While we found an increased risk for cardiovascular problems, the percentage of people actually affected remains small. Overall, for example, only 4.1 percent of migraine sufferers had heart attacks. And while the risk of stroke was 60 percent higher for migraine sufferers than for the rest of the population, the percentage of migraine sufferers experiencing strokes was still quite low – 2 percent.”

The main message of the study, said Dr. Lipton, is that migraine patients and their doctors should be particularly attentive to identifying and managing cardiovascular risk factors, such as high blood pressure, high cholesterol, obesity, and diabetes.

“We hope these findings will motivate migraine sufferers to exercise regularly, to avoid smoking and to address their other health problems,” said Dawn Buse, Ph.D., assistant professor in The Saul R. Korey Department of Neurology and co-author of the study. “It is important to view migraine as more than a series of individual attacks. We need to think about migraine as a chronic disorder with episodic attacks – and between those attacks, migraine sufferers have an enduring predisposition to cardiovascular events. In that sense, migraine has a lot in common with conditions like asthma, where sufferers seem fine between attacks, but there is more going on beneath the surface.”

In follow-up studies, Dr. Lipton and his colleagues aim to assess the importance of headache frequency and severity, aura frequency, and other factors influencing cardiovascular risk. They also hope to assess whether effective migraine treatment reduces that risk.

Video Interview:
Visit the original press release to watch a video interview with the researchers.

Material adapted from Albert Einstein College of Medicine by CFisher.

Introduction/Background
Migraine is a common, disabling and often progressive disorder characterized by increased excitability of the central nervous system [1, 2]. It occurs in 18% of women and 6% of men in the US with peak prevalence in individuals between the ages of 25 and 55 [3]. Economic burden of migraine in the US is estimated to be approximately 13 billion annually [4]. Biofeedback is a common intervention in pain management. For migraine treatment, the most frequently used biofeedback methods have been peripheral skin temperature biofeedback, blood-volume-pulse and electromyography feedback [5].

Neurotherapy is a broad term referring to the many types of biofeedback used to deliver information about the central nervous system which involve blood flow, thermal output from the brain or electrical activity. Neurofeedback (also called neurobiofeedback or EEG biofeedback) usually refers to frequency-based biofeedback that uses an EEG to give clients information about their brainwaves and gradually and subtly teaches people how to alter their brainwave activity. Sensors are attached to the scalp and the raw EEG signal is amplified, the frequency spectrum is extracted via a Fourier transform and selected frequency components are displayed through a user interface such as a video game. Unlike peripheral biofeedback that monitors the status of peripheral aspects of the sympathetic and parasympathetic nervous systems (e.g. respiration, galvanic skin response), neurofeedback monitors central nervous system activity.

Abnormalities in electrophysiological activity have commonly been found in the brains of migraine patients [16-21], therefore it is plausible that interventions involving the EEG might be of benefit [16]. Children afflicted with migraine, those with and without aura, demonstrate increased theta frequencies compared to normal controls [17]. One popular neurofeedback protocol for migraine emphasizes protocols rewarding 12-15 HZ at the temporal lobes at sites T3 and T4 [22]. Siniatchkin and colleagues demonstrated a significant reduction in migraines in 10 young migraineurs after 10 sessions of neurofeedback at midline frontal and central areas teaching them to control slow cortical potential activity representing cortical sensitivity and reactivity [7]. Michael Tansey enabled four migraineurs to eliminate their migraines after neurofeedback training along midline frontal and central areas which showed that low frequencies became less dominant and higher frequencies were augmented [8]. An older study found that thermal biofeedback was no more effective than EEG alpha biofeedback and self hypnosis in treating migraine [9]

Neurofeedback training also includes a newer method called hemoencephalography, which targets the frontal lobe [23]. Passive infrared hemoencephalography (pIR HEG) is a form of biofeedback for the brain that measures and feeds back information on the thermal output of the frontal lobe [10,23]. Unlike electromyographic (EMG) feedback which involves lowering the tension of the frontalis or trapezius muscles, pIR HEG involves increasing the forehead temperature by watching a movie for feedback. The movie is in operation when the measured forehead temperature rises and the movie stops when the temperature drops. The therapist will increase the threshold as the client learns how to raise their forehead temperature. Clients are instructed to calmly concentrate on making the movie continue to play. Increases in the pIR HEG signal reflect a composite of thermal activity generated by vascular supply, vascular return and brain cell activity. 100 International Headache Society (IHS)-diagnosed migraineurs reduced the frequency of their headaches using this form of biofeedback [10, 24,25].

Methods
This is a single group outcome, open label study in a clinical setting where both the patients and those administering treatment were aware of the treatment being given. Patients were given Informed Consent for biofeedback methods administered as well as Informed Consent to Research as put forth by the lead author’s ethics committee of the American Psychological Association and the Association of Applied Psychophysiology and Biofeedback.

Participants
The total sample included 37 migraine patients (29 females and 8 males). Ages ranged from 9 to 79, with the majority (56%) between the ages of 16 and 52, and the remainder evenly split between the younger group (22% were between 9 and 15) and the older group (22% were between 55 and 79). In terms of medical history, most patients had long, stable histories of migraine and had tried multiple pharmaceutical treatments prior to neurotherapy. All were having at least one migraine per month and taking at least one type of medication (preventive, abortive or rescue) for their migraines and were not required to discontinue these during the study (See Table 1).

Table 1 (click to enlarge). Number of patients on each type of migraine medication

Initial Assessments
A personal and family headache history was taken at initial evaluation and a diagnostic interview was performed by a licensed psychologist to confirm the IHS-diagnosis of migraine with or without aura and to assess other symptoms and conditions. For patients who did not have at least two weeks of headache diaries, they were asked to wait two weeks to begin treatment in order to keep a baseline daily diary to record headache frequency and severity. At the first session and every 10 sessions thereafter, clients were asked to complete a non-standardized checklist to indicate changes in headaches as well as other symptoms (e.g., anxiety, insomnia, other pain types, depression, and behavioral problems).

Follow up data collection
The data reported in this study were collected 3 months to 2 years after patients stopped coming to the neurotherapy center, either because they had completed the recommended number of  treatment sessions or because they discontinued treatment on their own.  The data were collected through follow-up telephone surveys conducted by a research consulting firm not affiliated with The Better Brain Center.

Treatment Protocol

neurofeedback
The study involved treatment using EEG biofeedback, pIR HEG biofeedback and hand warming biofeedback for an average total of 40 sessions. Average length of time in treatment was 6 months. Subjects underwent an average of 30 frequency-based neurofeedback sessions and 10 pIR HEG sessions for 30 minutes at least twice weekly. Eleven patients had an interruption in their treatment after the initial 20 sessions of up to several weeks but returned for their remaining sessions.  Previously recorded baseline EEG measures were used to guide neurofeedback training protocols by targeting frequency ranges with the highest amplitude. All migraine patients were trained to reduce the amplitude of the targeted frequencies. The EEG training primarily occurred at 5 sets of homologous sites (T3-T4, C3-C4, F3-F4, FP1-FP2 and P3-P4). These homologous sites were chosen according to the lead author’s training in neurofeedback in which years of clinical experience in treating migraines by other experienced clinicians is taught [22].  Electrode placements at homologous sites were used and training always began as a single channel placement using the first site as the signal and the second site as reference (example: T3-T4).

pIR HEG biofeedback
For most patients 30 minutes of pIR HEG biofeedback was introduced at approximately their tenth visit. This involved the patients wearing a headset which is designed to be worn at FPZ (center of forehead) and watching a movie and being challenged to keep the movie playing as the reward threshold was re-set to higher temperatures.

thermal hand warming
Thermal hand warming biofeedback was also used simultaneously along with the EEG biofeedback during clinic sessions.

Please review the original article for a more detailed explanation for treatment rationale, neurofeedback/pIR HEG/biofeedback protocol, and reward/inhibit criteria.

Results
Table 2 shows the age and gender of everyone in the full sample and the pre-treatment and post-treatment migraine frequency estimates. The estimates are based on participant reports of the average number of migraines they experienced per month in the 6 months prior to treatment, and the 6 months immediately preceding the follow-up telephone survey.

The small number of participants (n=7) who had completed treatment only 1 to 5 months before the follow-up interview, reported migraine frequency for this shorter post-treatment time period. The pretreatment mean frequency was 7.6 migraines per month (S.D = 5.1) the post-treatment mean was 2.9 migraines per month (S.D=2.8), and the mean difference was 4.72 (S.D.=4,32) few migraines per month. The standardized effect size (derived by dividing the mean difference score by the standard deviation of the difference scores) is 1.09, an effect size considered in the literature to be very large. Since many migraine studies include only those who experience 2 to 14 migraines per month we also calculated effect size eliminating the 5 patients with 15 to 20 migraines/month and the 4 who experienced only one per month. This produced and even larger effect size: 1.23. We next added in 3 “dummy” cases showing no change to address concerns that those who fail to complete the minimum number of sessions (the minimum was 20, most had at least 40) might have been non-responders. This effort to approximate an “ intention to treat” analysis, assuming a 10% non-completer rate, reduced the 1.23 effect size in the restricted , 2 to 14 migraine sample, to 1.00, still a very large effect size.

Table 2 (click to enlarge). Sample characteristics and average number of migraines per month pre- and post-treatment

For each individual we also calculated the percent reduction in migraine frequency by dividing the difference between that individual’s pre- and post-treatment migraine frequency estimates by the average number of pre-treatment migraines they experienced. As illustrated in Figure 1, 70% of the sample (or 26/37) showed a 50% or greater reduction in the frequency of their migraines, and only 16% (or 6/37) failed to improve at all.

The significance of the observed changes was examined using the Wilcoxon signed ranks test, a non-parametric alternative to the t-test for small sample studies where the dependent variable is not normally distributed. In the Wilcoxon signed ranks test the differences between pre- and post-treatment scores are rank ordered, and the significance test is based on ranks, eliminating the potential biasing effects of large, spurious differences in either direction. If the treatment has no effect the sum of the ranks where the difference is positive should be nearly equal to the sum of the ranks where the difference is negative.

Figure 1 (click to enlarge). Percent reduction of migraine frequency.

In the present case, there was a large difference; in 31 cases post-treatment scores (average number of migraines per month) were less than pre-treatment scores, in 6 cases scores were equivalent, and there were no cases where post-treatment scores were greater than pre-treatment scores. The resulting z-score of -4.86 was statistically significant at the p<.001 level. Although the focus of this study was on migraine headaches, patients seeking neurotherapy are typically experiencing more than one problem, and migraine patients are no exception.

In the follow-up interviews we asked participants to (a) indicate which of several other common symptoms they were experiencing when they first sought treatment, and then (b) use a 5-point scale to rate the level of improvement they experienced following neurotherapy treatment. The response scale options were “no improvement” (0), “slight (10-30%) improvement” (1), “moderate (40%-60%) improvement” (2), “major (70-90%) improvement” (3), and “total (90- 100%) improvement” (4). Table 3 shows the number of individuals rating the 6 most common symptoms (migraine is included and the N of 34 indicates that we did not get ratings from 3 of the migraineurs who provided headache frequency data), and the percent reporting three levels of improvement. The first group includes those who selected either the “No improvement” or the “Slight (10-30%) improvement” response options, the middle group includes those who selected the “Moderate (40-60%) response option, and the third group includes those who selected “Major (70-90%) or Total (100%) improvement. Migraines were the most improved symptom based on this scale, with 62% or 23/37 reporting major or total improvement, followed by “other headaches,” where 50% or 19/37 reported major or total improvement. The percent reporting major or total improvement on other symptoms ranged from 32% to 41%. Sleep problems were least likely to be substantially improved.

Discussion
The concept of an under or over-aroused nervous system was first proposed by Nobel Laureate Walter Rudolph Hess who in the 1950s experimented with electrical stimulation of the brain which led to changes in arousal [26]. It has been theorized that disorders of attention, affect and pain are due either to over or underaroused brain states, and that neurofeedback is effective for a variety of symptoms or symptom clusters because it improves the brain’s ability to regulate these arousal states [13]. Neurofeedback treatment protocols address the underlying arousal problem, obviating separate validation studies for every medical diagnosis [13].

In this study, it appears that the biofeedback enabled the patients to gradually learn to control their susceptibility to getting headaches. Generally, they began to notice gradual improvements early on in treatment, particularly in their ability to manage stress, which was impetus for continuing treatment. This was assessed every 10 sessions by a written checklist and by interviews with a psychologist at each session. By session 20, most began to be aware of their ability to control or prevent their headaches. In most cases, by session 40, patients felt a sense of increased mastery over being better able to recognize when they were at risk (increased autonomic arousal in reaction to stress) and to take appropriate measures to be able to prevent headaches. 40 sessions happened to be the average number of sessions undertaken in the study.

Number of sessions ranged from 20-67 and was determined by what treatment provider and each patient felt they needed in order to ultimately learn to control migraines. These patients described the biofeedback as helping them to acquire the ability to better self-regulate by learning to control their EEG and reducing muscle tension, slowing the rate of their breathing and warming their hands and forehead, all of which were necessary for the types of biofeedback they had undergone. When asked how they thought they were better able to prevent headaches during interviews at each session and on checklists after every 10 sessions, many would explain that during potentially stressful conditions they would imagine hearing or visualizing the neurofeedback games and this appeared to help them invoke the physiological state elicited during the actual sessions.

We have observed that thermal biofeedback devices (pIR HEG machine and the hand warming units) can often be powerful migraine abortives once patients learn to raise their hand or forehead temperatures. All clients, whether or not they were successful at reducing their migraines, demonstrated an ability to warm their hands and foreheads and decrease their elevated EEG amplitudes of both slow and fast-wave activity. Patients related during session interviews that these techniques have eventually enabled them to automatically learn to abort their headaches without having to use the actual devices. Of the 37 patients in the study, five had fifteen or more migraines a month and all five improved significantly which may show promise that these methods can be useful for preventing the progression from episodic to chronic migraine.

Central nervous system dysfunction may play a key role in the pathogenesis of migraine [16-21]. As there are no apparent structural disturbances, clinical neurophysiological methods may be well-suited to study its pathophysiology [16]. In both migraine with and without aura, somatosensory evoked potential studies show that lack of habituation in cortical information processing between attacks is a reproducible central nervous system abnormality with this population [19]. Siniatchkin et al demonstrated the vulnerability of the migraine brain by measuring the effects of experimentally-induced stress on the contingent negative variation (CNV) response, which is a slow cortical potential believed to reflect altered excitability. This study showed a susceptibility to stress-induced migraine provoking agents before an actual attack [20]. Additionally, it has been observed that abnormal behavioral patterns such as hypersensitivity and perfectionism are often characteristic among migraine sufferers yet these psychological features may be the result of an innate cortical hypersensitivity in addition to associated social learning processes [21]. In this study neurofeedback appears to have improved stress resilience and susceptibility to migraines in the migraine participants. This may be due to the increase in self regulation brought about by the process of long term potentiation that may result from the operant conditioning of the EEG during the neurofeedback training [12].

Migraine has a comorbid association with a number of psychiatric conditions, including bipolar disorder, anxiety states, and depression, all of which are associated with perturbations in the serotonin and norepinephrine neurotransmitter substances [27,28]. Depression is often comorbid with migraines and anti-depressants are often used to treat both conditions [29]. Evidence that many neurological conditions are comorbid and alleviated by identical or very similar drugs supports three important principles in the spectrum paradigm: a) different symptoms are often manifestations of the same underlying instability or in balance, b) symptoms manifest differently depending on where they fall along the continuum of the underlying dysfunction, c) treatments need not be “disease specific” to be helpful [13]. Neurologist Oliver Sacks’ speculation that brainwave biofeedback might prove useful for migraines after showing promise in treating seizures supports the spectrum concept of related disorders responding to one mode of treatment [30].

Migraine and tension type headache were linked after both types showed a significant response to sumatriptan. A convergence hypothesis was proposed speculating that the entire clinical spectrum of headache may share a common physiological pathway based on one type of medication exerting an effect on two distinctly different types of headache [31,32]. Similarly, an older study shows that neurofeedback was effective for tension type headache [11] and our study finds that several types of biofeedback have an effect on migraines, other types of headache and other comorbidities. Biofeedback used with medications appears to outperform medications alone [5, 33,34]. In our study involving biofeedback with clients using medications, we saw the frequency of usage of the abortive and rescue medications drop along with the frequency of headaches.

Conclusions
Migraine may be progressive disorder with an excellent response to preventive early interventions [33,34]. Yet none of the pharmaceutical options are exceptionally effective or without side effects. The best result that medication has achieved has been only about a 50% reduction in approximately 50% of migraine patients [34]. Our study outperforms this by achieving a 50% or more reduction in 70% of the participants based on follow-up data collected on average, 14 months after patients had completed at least the minimum recommended 20 treatment sessions. The treatment effect sizes we obtained (1.09) are greater than those reported in a recent meta-analysis for either EEG-biofeedback (about .4) or temperature training feedback (about .5) or blood volume pulse feedback (about .7) alone, or temperature feedback plus electromyographic feedback (about .6) [5]. Although we did not have a control group, and thus cannot completely rule out placebo effects in this study, it may be unusual for a placebo effect to last 6 months to two years.

Despite the different types of intervention used in our study (manipulation of the EEG, forehead temperature or hand temperature), the retrospective reports of migraine frequency and the absence of a control group, the statistically and clinically significant improvements observed in this patient population attests to the promise biofeedback based treatment modalities hold for migraine patients. It is our hope that this study will generate an interest in performing larger scale controlled studies in the non-invasive neurotherapies to treat migraine and other chronic and/ or progressive disorders.

Citation:
Material adapted by CFisher from:

Stokes, D., & Lappin, M. (2010). Neurofeedback and biofeedback with 37 migraineurs: A clinical outcome study. Behavioral and Brain Functions, 6(9).

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The study involved 2,652 people who took part in the larger Erasmus Rucphen Family study. All of the participants are descendants of 22 couples who lived in Rucphen in the 1850s to 1900s. “Genealogical information has shown them all to be part of a large extended family, which makes this type of genetic study possible,” said study author Gisela M. Terwindt, MD, PhD, of Leiden University Medical Center in the Netherlands.

Of the participants, 360 had migraine. Of those, 151 had migraine with aura, which is when headaches are preceded by sensations that affect vision, such as seeing flashing lights, and 209 had migraine with no aura. A total of 977 people had depression, with 25 percent of those with migraine also having depression, compared to 13 percent of those without migraine.

The researchers then estimated the relative contribution of genetic factors for both of the disorders. They found that for both types of migraine, the heritability was estimated at 56 percent, i.e., 56 percent of the trait is explained by genetic effects. For migraine with aura, the estimate was 96 percent. “This finding shows that migraine with aura may be a promising avenue to search for migraine genes,” Terwindt said.

Comparing the heritability scores for depression between those with migraine and those without showed a shared genetic component in the two disorders, particularly with migraine with aura. “This suggests that common genetic pathways may, at least partly, underlie both of these disorders, rather than that one is the consequence of the other,” Terwindt said.

Material adapted from American Academy of Neurology Press by CFisher.

Overall, biofeedback (all combined) produced a robust moderate effect size of .58 (95% CI=.52-.64) in pre vs. post headache conditions. In treatment specific comparisons, biofeedback (all combined) achieved a moderate effect size (.45) compared to a no-treatment (wait-list) control condition, but did not exhibit superiority (nor was biofeedback inferior) over known beneficial treatments (relaxation and pharmacotherapy). The authors noted a “trend” toward significance for biofeedback over pharmacotherapy, as well as few, if any, reported side effects in the biofeedback treatments. Importantly, biofeedback therapies failed to achieve statistical significance when compared to placebo control groups, despite a .25 effect size. This is because the confidence interval (0.00-.49) included zero.

The researchers also compared each biofeedback treatment to another (e.g. EMG vs TEMP, etc.). All biofeedback treatment were equally effective (statistically speaking), though HRV obtained the highest numerical effect size at .68 (medium to large effect size). Another important finding is that biofeedback treatment effects endured at 1 year or more follow-up. Concurrent patient home training sessions improved treatment effect sizes at study completion and at extended follow-up. Additionally, biofeedback significantly reduced anxiety and depression, and significantly improved beliefs of self-efficacy. In fact, gains in self-efficacy were higher than pain improvements.

The authors mentioned how impressed they were with these results given that the participants reported chronic migraines (average of 16 years). They further stated that, “Thus, based on the present results BFB can be recommended to therapists, physicians and healthcare providers as an efficacious non-medical treatment alternative for highly chronified migraine patients; suitable also for the long-term prevention of migraine attacks” (pg. 122).

In my opinion, a well designed randomized, double-blind, placebo controlled study with a large number of participants is warranted and could help clarify the benefits of biofeedback for migraine headache.

Summary of Important Highlights From The Current Study:

• Study Design: meta-analysis
• Primary Inclusion Criteria: migraine headache (average years suffering: 16.9 years)
• Number of Participants: 2,229 (experimental = 1,718; control = 511)
• Participants’ Average Age: 37.1 (SD=10.0)
• Participants’ Gender: 88.6% female
• Primary Outcome: overall moderate effect size of .58 (95% CI=.52-.64) in pre vs post headache and .45 (95% CI=.26-.63) wait-list control comparisons
• Limitations: biofeedback did not produce statistically meaningful gains over placebo conditions.

CFisher

Reference:

*Nestoriuc, Y., & Martin, A. (2007). Efficacy of biofeedback for migraine: A meta-analysis. Pain, 128, 111-127.

One important distinction must first be made. EEG biofeedback, better known as neurofeedback, has been frequently discussed at BMED Report.  The current TTH study mostly involves peripheral biofeedback.  The basic principles of peripheral biofeedback are very similar to neurofeedback except that instead of the patient monitoring his or her EEG (in neurofeedback), the patient receives feedback and reinforcement of their body signals.  Biofeedback can include a number of different measures, such as heart rate variability (HRV), skin temperature, electromyography (EMG; muscle electricity), and electrodermal response (sweat).  These signals are indirect measures of autonomic nervous system activity and/or muscular activity.  Similar to neurofeedback, the biofeedback therapist encourages certain desired states with visual and auditory reinforcements. 

53 studies involving 1532 patients, ages 10.3 to 66.7, with TTH were identified for inclusion in this meta-analysis.  EMG biofeedback was the most frequently used modality across all studies; however, studies using temperature (2), electrodermal (1), and EEG (1) biofeedback, as well as combined relaxation (9) were also included. Please review the original article for a more comprehensive overview of inclusion criteria and descriptions of each study.

An overall medium-to-large effect size of .73 was found across all 53 studies for pre/post comparisons of symptom improvement (or lack thereof) following biofeedback treatment.  Statistically significant medium-to-large effect sizes were reported for headache reduction (frequency, intensity, duration, and headache index).  Interestingly, patient anxiety, depression, and self-efficacy also significantly improved across 19 studies. Biofeedback treatment compared no-treatment or placebo control groups again produced statistically significant improvements with medium-to-large effect sizes (.81, .50 respectively).  Biofeedback also improved patient outcome over and above relaxation modalities as evidenced a by small, but statistically significant, effect size (.20).  Combined EMG biofeedback and relaxation therapy were the most effective treatment for TTH.   Children and adolescents had the best results, though adults did very well too.  Adults with chronic (long term) TTH actually fared better than those with acute (short-term) TTH. Geriatric patients did not realize significant treatment effects, but only 2 groups comprising a total of 12 participants were included in the analysis. Importantly, treatment gains were found to persist for years at follow up, with an average follow up period of 15 months.

Unfortunately, only a handful of studies were located to allow for adequate comparison of biofeedback to pharmacotherapy and traditional behavioral/talk therapies; however, researchers noted that in 2 of the 3 studies biofeedback treatment was favored over pharmacotherapy with large effect sizes.

Remember that a meta-analysis is not a “cause and effect” experiment. Nonetheless, it does provide a statistically valid and reliable way to make standardized comparisons across studies (subject to statistician error and bias of course), and provides reasonable estimates of a treatment effectiveness in a number of different settings with different populations.

In summary, the results of this meta-analysis suggest that peripheral biofeedback may represent an efficacious treatment of TTH for many people.

Reference:
*Nestoriuc, Y., Rief, W., Martin, A. (2008).  Meta-analysis of biofeedback for tension-type headache: Efficacy, specificity, and treatment moderators. Journal of Consulting and Clinical Psychology, 76(3), 379-396.