Monoclonal Antibodies Continue to Excite the Migraine Research Community

LOS ANGELES—Three new experimental treatments targeting calcitonin gene-related peptide (CGRP) receptors for the prevention or reduction of migraine have shown promise in preventing migraine attacks, according to researchers. The new treatments—AMG 334, LY2951742, and ALD403—are selective and potent antibodies targeting human CGRP biology with the potential for migraine prevention.

AMG 334 is an investigational human antibody that targets the CGRP receptor rather than CGRP itself. AMG 334 is in phase II clinical trials for the prevention of migraines. In prior studies of AMG 334 in nonhuman primates, the therapy was found to be a “potent and selective antibody against the human CGRP receptor with potential for migraine prevention,” the authors said.

In the LY2951742 study, 217 subjects with four to 14 migraine headache days per month received biweekly subcutaneous injections of either LY2951742 (a monoclonal antibody that binds to CGRP) or placebo for a total of as many as six doses in a 12-week treatment period. Compared with placebo, treatment with LY2951742 resulted in a significantly greater decrease from baseline in the last 28-day period in the number of migraine headache days, migraine attacks, headache days, and combined probable migraine and migraine headache days. In addition, significantly more patients treated with LY2951742 had a greater than 50% reduction in the last 28-day period in the number of migraine headache days, compared with placebo.

In the ALD403 study, ALD403 was given as a single IV infusion to 81 patients; 82 patients received placebo. Patients were followed for 12 weeks. At the end of 12 weeks, there was, on average, a 66% decrease in migraine days in the ALD403-treated subjects versus a 52% decrease for placebo-treated patients. ALD403 treatment resulted in 16% (0% for placebo) of patients having no migraines, 32% (9% for placebo) of patients having a 75% decrease in their migraine days, and 60% (33% for placebo) having a 50% decrease in their migraine days for the full 12-week study period.

All three CGRP monoclonal antibody treatments were well tolerated and showed no significant adverse events or other safety concerns.

Peter Goadsby, MD, of the University of California, San Francisco, and coinvestigator on two of the CGRP monoclonal antibody studies, stressed that the findings in all three studies are encouraging but preliminary and need larger, longer-term studies to confirm the efficacy and safety of the treatments.

Deployment-Related Brain Injury Is Strongly Associated With Migraine in Iraq and Afghanistan Veterans
Veterans who were deployed to combat zones in the Iraq and Afghanistan wars and experienced traumatic brain injury (TBI) have a strong and highly significant increase in the frequency and intensity of headaches, the majority of which are migraines, according to researchers.

The incidence of chronic daily headache (ie, 15 or more headache days per month) was three times greater, compared with controls, and the incidence of frequent headache (ie, 10 to 14 headache days per month) was 4.5 times greater in these soldiers than in control groups, reported lead author James R. Couch, MD, of the University of Oklahoma School of Medicine in Oklahoma City, and colleagues. “Combat zone deployment by itself is stressful. Since TBI is the signature injury of these wars and occurs in 15% to 20% of deployed soldiers, and both TBI and stress are known to be associated with headache, we sought to evaluate the differences in headache occurrence and severity between those who were deployed and those who were deployed and also experienced a TBI,” Dr. Couch said.

Dr. Couch and his team evaluated 53 pairs of deployed veterans with TBI and a matched group of veterans who were deployed but did not sustain a TBI (controls). All subjects with deployment-related TBI had headache, while 11 (23.9%) controls had no headache. In addition, 89% of headaches in the deployed veterans with TBI were migraine, compared with 40% in the control group. All subjects with deployment-related TBI reported significantly greater frequency and intensity of headache than the control group did.

Adolescents With Chronic Migraine Get More Relief When Their Medications Are Combined With Biofeedback and Relaxation Therapies
Cognitive behavioral therapy (CBT) resulted in greater reductions in headache frequency and migraine-related disability in children and adolescents with chronic migraine, according to researchers.

The study, conducted by Scott W. Powers, PhD, and his team at Cincinnati Children’s Hospital Medical Center found that adding biofeedback, relaxation techniques, and stress reduction to amitriptyline therapy reduced the number of migraine days and disability and had a favorable and clinically meaningful impact on children’s school functioning.

“Now that there is strong evidence for CBT in headache management, we believe it should be offered routinely as a first-line treatment for chronic migraine along with medications, and not only as an add-on if medications are not found to be sufficiently effective,” said Dr. Powers.

In the study, the team randomized 135 participants ages 10 to 17 diagnosed with chronic migraine with a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points to CBT (n = 64) or headache education (n = 71). Interventions consisted of 10 CBT or 10 headache education sessions involving equivalent time and therapist attention; CBT included training in pain coping, including a biofeedback component. Each group received amitriptyline. Follow-up visits were conducted at three, six, nine, and 12 months. At 12-month follow-up, 86% of CBT participants had a 50% or greater reduction in days with headache versus 69% of the headache education group; 88% of CBT participants had a PedMIDAS of less than 20 points (mild to no disability) versus 76% of the headache education group.

“While this is very good news as a study finding, translating this into clinical practice in treating young people with chronic migraine is an enormous challenge,” said Lawrence Newman, MD, President of the American Headache Society. “Treatment specialists will need to find ways to overcome adolescent resistance to behavioral therapy and insurance coverage issues for add-on treatment,” he said.

Women With Migraine Experience More Headaches During the Menopausal Transition
Migraine attack frequency is higher in women during perimenopause and menopause than in premenopause, according to investigators.

“Ours is the first study to demonstrate that the frequency of migraine attacks increases during the menopausal transition,” said first author Vincent T. Martin, MD, Codirector of the University of Cincinnati Headache and Facial Pain Program and Professor of Medicine in the Department of Internal Medicine, University of Cincinnati, and colleagues.

The research was conducted as part of the American Migraine Prevalence and Prevention (AMPP) study, a longitudinal, mailed questionnaire survey of 120,000 US households selected to be representative of the US population. Based on data from the 2006 AMPP study survey, women with migraine between the ages of 35 and 65 were eligible for these analyses. Women with migraine were classified based on headache frequency into a high frequency group if they experienced 10 or more headache days per month and into a low or moderate frequency episodic migraine group if they had fewer than 10 days per month. Women were also classified as premenopausal, perimenopausal, or postmenopausal (absent menstrual periods for at least 12 months) based on responses to the questionnaire.

Of 3,603 eligible women, the mean age was 45, and 34% were premenopausal, 35% were perimenopausal, and 30% were menopausal. Frequent headache (10 or more days per month) was 50% to 60% more common among perimenopausal (12.2%) and menopausal (12.0%) women, compared with the premenopausal group (8.0%).

“Given that migraines tend to worsen during menstruation, it may seem paradoxical that when periods become irregular during perimenopause or absent during menopause that headache became more frequent,” said Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Center at the Albert Einstein College of Medicine. “We believe that both declining estrogen levels that occur at the time of menstruation, as well as low estrogen levels that are encountered during the menopause, are triggers of migraine in some women,” he said.

“These results validate the belief by many women that their headaches worsen during the transition into menopause,” Dr. Martin said. “We hope that our work spurs researchers to develop novel treatments for migraine during this time period, given that many of the headaches encountered are thought to be hormonally triggered.”

Retired NFL Players With Headache Lack Access to Adequate Treatment
National Football League (NFL) alumni have a significantly higher incidence and frequency of headache, migraine, and chronic migraine when compared with the general population, but lack access to care, investigators reported.

“The players we examined were not receiving standard headache treatment,” said lead author Frank Conidi, DO, MS, Sports Neurologist and Headache and Concussion Specialist at Florida State University College of Medicine and Florida Center for Headache and Sports Neurology in Palm Beach Gardens, Florida, and colleagues. “In fact, they lacked access to both neurologists and headache specialists, despite an increased incidence of concussion and headache frequency.”

Retired players in the study were between the ages of 30 and 43 (mean age 36.67), had played an average of 4.3 years (range, two to nine years), and had an average of 7.33 concussions (± 5.2, maximum 15). They experienced a mean of 24 headache days per month. Of these, 14.6 headaches were rated as severe and met the International Headache Society (IHS) criteria for migraine; 43% met IHS criteria for chronic migraine. Half of the retired players were currently using narcotic pain medication (not specifically for headache), but only one was taking a migraine-specific abortive medication. Neuropsychologic testing demonstrated significant abnormalities in attention and concentration (66%), executive function (50%), learning and memory (50%), and spatial and perceptual function (33%). Three players had abnormalities on advanced brain imaging that indicated permanent brain injury.

Concern about injuries sustained while performing on the field of play in football, hockey, or other contact sports has spurred new regulations within professional and high school sports organizations to protect players. Earlier this year, the NFL reported that the number of concussions in the league had declined by 13% this season because of improved medical diagnoses, stiffer penalties for striking with a helmet, and fewer practices.

“While it’s too late to protect retired players from injury,” Dr. Conidi said, “We must do all we can to ensure that they get the kind of treatment and access to care they need.”

Assessing the Family Burden of Chronic Migraine
Chronic migraine significantly affects family relationships and activities in ways including canceled vacation plans and reduced quality time with partners and children, according to researchers.

Results of the Chronic Migraine Epidemiology and Outcomes (CaMEO) study also revealed that patients with chronic migraine experience feelings of guilt, anger, and annoyance toward family members because of headache and avoid sexual intimacy because of headache.

CaMEO was a web-based study of 994 men and women with chronic migraine. Lead author Dawn C. Buse, PhD, and colleagues said the study’s purpose was to measure the perceived nature and extent of chronic migraine-related burden on family relationships and activities. Dr. Buse is Director of Behavioral Medicine at Montefiore Headache Center and Associate Professor of Clinical Neurology at Albert Einstein College of Medicine, both in the Bronx, New York.

“This study highlights the significant impact of chronic migraine, not only on the person with migraine, but on the entire family,” said Dr. Buse. “Respondents reported missing both routine and special family events on a regular basis and feeling guilty and sad about how this affected their relationships with their spouses and children.”

Almost three-quarters of respondents (73%) thought that they would be better spouses if they did not have chronic migraine. The majority of respondents (64%) felt guilty about being easily angered or annoyed by their partners because of headache, and 67% avoided sexual intimacy with their partners at times because of headache. The majority of respondents (59%) felt that they would be better parents if they did not have chronic migraine. Sixty-one percent of respondents reported that they became easily annoyed with their children because of headache. In addition, 54% of respondents reported that they had reduced participation or enjoyment on a family vacation because of headache in the past year, and 20% canceled or missed a family vacation altogether.

Women consistently reported lower percentage rates of absenteeism across many activities because of headaches than did men. “This may be due to differences in headache severity between genders; differential denominators, in that women may have more activities and responsibilities; or women may feel more obligated to keep commitments despite migraine occurrence,” the researchers said.

“Clearly, the effects of chronic migraine can be devastating and far-reaching. Chronic migraine can be a great burden, not only from the direct effects of the condition on the person with chronic migraine, but also the effects that it has on family members. The effect of chronic migraine on the family is not commonly discussed; however, people who live with chronic migraine may experience substantial emotional distress caused by feeling worried, guilty, and sad about how their condition affects the people they love, adding to the total burden,” said Dr. Buse.

The CaMEO study recruited individuals from a web-based panel, using quota sampling to complete a series of web-based surveys for more than one year. The data were used to characterize migraine and chronic migraine. The current analysis reflects data from respondents meeting study criteria for chronic migraine.

LOS ANGELES—Three new experimental treatments targeting calcitonin gene-related peptide (CGRP) receptors for the prevention or reduction of migraine have shown promise in preventing migraine attacks, according to researchers. The new treatments—AMG 334, LY2951742, and ALD403—are selective and potent antibodies targeting human CGRP biology with the potential for migraine prevention.

AMG 334 is an investigational human antibody that targets the CGRP receptor rather than CGRP itself. AMG 334 is in phase II clinical trials for the prevention of migraines. In prior studies of AMG 334 in nonhuman primates, the therapy was found to be a “potent and selective antibody against the human CGRP receptor with potential for migraine prevention,” the authors said.

In the LY2951742 study, 217 subjects with four to 14 migraine headache days per month received biweekly subcutaneous injections of either LY2951742 (a monoclonal antibody that binds to CGRP) or placebo for a total of as many as six doses in a 12-week treatment period. Compared with placebo, treatment with LY2951742 resulted in a significantly greater decrease from baseline in the last 28-day period in the number of migraine headache days, migraine attacks, headache days, and combined probable migraine and migraine headache days. In addition, significantly more patients treated with LY2951742 had a greater than 50% reduction in the last 28-day period in the number of migraine headache days, compared with placebo.

In the ALD403 study, ALD403 was given as a single IV infusion to 81 patients; 82 patients received placebo. Patients were followed for 12 weeks. At the end of 12 weeks, there was, on average, a 66% decrease in migraine days in the ALD403-treated subjects versus a 52% decrease for placebo-treated patients. ALD403 treatment resulted in 16% (0% for placebo) of patients having no migraines, 32% (9% for placebo) of patients having a 75% decrease in their migraine days, and 60% (33% for placebo) having a 50% decrease in their migraine days for the full 12-week study period.

All three CGRP monoclonal antibody treatments were well tolerated and showed no significant adverse events or other safety concerns.

Peter Goadsby, MD, of the University of California, San Francisco, and coinvestigator on two of the CGRP monoclonal antibody studies, stressed that the findings in all three studies are encouraging but preliminary and need larger, longer-term studies to confirm the efficacy and safety of the treatments.

Deployment-Related Brain Injury Is Strongly Associated With Migraine in Iraq and Afghanistan Veterans
Veterans who were deployed to combat zones in the Iraq and Afghanistan wars and experienced traumatic brain injury (TBI) have a strong and highly significant increase in the frequency and intensity of headaches, the majority of which are migraines, according to researchers.

The incidence of chronic daily headache (ie, 15 or more headache days per month) was three times greater, compared with controls, and the incidence of frequent headache (ie, 10 to 14 headache days per month) was 4.5 times greater in these soldiers than in control groups, reported lead author James R. Couch, MD, of the University of Oklahoma School of Medicine in Oklahoma City, and colleagues. “Combat zone deployment by itself is stressful. Since TBI is the signature injury of these wars and occurs in 15% to 20% of deployed soldiers, and both TBI and stress are known to be associated with headache, we sought to evaluate the differences in headache occurrence and severity between those who were deployed and those who were deployed and also experienced a TBI,” Dr. Couch said.

Dr. Couch and his team evaluated 53 pairs of deployed veterans with TBI and a matched group of veterans who were deployed but did not sustain a TBI (controls). All subjects with deployment-related TBI had headache, while 11 (23.9%) controls had no headache. In addition, 89% of headaches in the deployed veterans with TBI were migraine, compared with 40% in the control group. All subjects with deployment-related TBI reported significantly greater frequency and intensity of headache than the control group did.

Adolescents With Chronic Migraine Get More Relief When Their Medications Are Combined With Biofeedback and Relaxation Therapies
Cognitive behavioral therapy (CBT) resulted in greater reductions in headache frequency and migraine-related disability in children and adolescents with chronic migraine, according to researchers.

The study, conducted by Scott W. Powers, PhD, and his team at Cincinnati Children’s Hospital Medical Center found that adding biofeedback, relaxation techniques, and stress reduction to amitriptyline therapy reduced the number of migraine days and disability and had a favorable and clinically meaningful impact on children’s school functioning.

“Now that there is strong evidence for CBT in headache management, we believe it should be offered routinely as a first-line treatment for chronic migraine along with medications, and not only as an add-on if medications are not found to be sufficiently effective,” said Dr. Powers.

In the study, the team randomized 135 participants ages 10 to 17 diagnosed with chronic migraine with a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points to CBT (n = 64) or headache education (n = 71). Interventions consisted of 10 CBT or 10 headache education sessions involving equivalent time and therapist attention; CBT included training in pain coping, including a biofeedback component. Each group received amitriptyline. Follow-up visits were conducted at three, six, nine, and 12 months. At 12-month follow-up, 86% of CBT participants had a 50% or greater reduction in days with headache versus 69% of the headache education group; 88% of CBT participants had a PedMIDAS of less than 20 points (mild to no disability) versus 76% of the headache education group.

“While this is very good news as a study finding, translating this into clinical practice in treating young people with chronic migraine is an enormous challenge,” said Lawrence Newman, MD, President of the American Headache Society. “Treatment specialists will need to find ways to overcome adolescent resistance to behavioral therapy and insurance coverage issues for add-on treatment,” he said.

Women With Migraine Experience More Headaches During the Menopausal Transition
Migraine attack frequency is higher in women during perimenopause and menopause than in premenopause, according to investigators.

“Ours is the first study to demonstrate that the frequency of migraine attacks increases during the menopausal transition,” said first author Vincent T. Martin, MD, Codirector of the University of Cincinnati Headache and Facial Pain Program and Professor of Medicine in the Department of Internal Medicine, University of Cincinnati, and colleagues.

The research was conducted as part of the American Migraine Prevalence and Prevention (AMPP) study, a longitudinal, mailed questionnaire survey of 120,000 US households selected to be representative of the US population. Based on data from the 2006 AMPP study survey, women with migraine between the ages of 35 and 65 were eligible for these analyses. Women with migraine were classified based on headache frequency into a high frequency group if they experienced 10 or more headache days per month and into a low or moderate frequency episodic migraine group if they had fewer than 10 days per month. Women were also classified as premenopausal, perimenopausal, or postmenopausal (absent menstrual periods for at least 12 months) based on responses to the questionnaire.

Of 3,603 eligible women, the mean age was 45, and 34% were premenopausal, 35% were perimenopausal, and 30% were menopausal. Frequent headache (10 or more days per month) was 50% to 60% more common among perimenopausal (12.2%) and menopausal (12.0%) women, compared with the premenopausal group (8.0%).

“Given that migraines tend to worsen during menstruation, it may seem paradoxical that when periods become irregular during perimenopause or absent during menopause that headache became more frequent,” said Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Center at the Albert Einstein College of Medicine. “We believe that both declining estrogen levels that occur at the time of menstruation, as well as low estrogen levels that are encountered during the menopause, are triggers of migraine in some women,” he said.

“These results validate the belief by many women that their headaches worsen during the transition into menopause,” Dr. Martin said. “We hope that our work spurs researchers to develop novel treatments for migraine during this time period, given that many of the headaches encountered are thought to be hormonally triggered.”

Retired NFL Players With Headache Lack Access to Adequate Treatment
National Football League (NFL) alumni have a significantly higher incidence and frequency of headache, migraine, and chronic migraine when compared with the general population, but lack access to care, investigators reported.

“The players we examined were not receiving standard headache treatment,” said lead author Frank Conidi, DO, MS, Sports Neurologist and Headache and Concussion Specialist at Florida State University College of Medicine and Florida Center for Headache and Sports Neurology in Palm Beach Gardens, Florida, and colleagues. “In fact, they lacked access to both neurologists and headache specialists, despite an increased incidence of concussion and headache frequency.”

Retired players in the study were between the ages of 30 and 43 (mean age 36.67), had played an average of 4.3 years (range, two to nine years), and had an average of 7.33 concussions (± 5.2, maximum 15). They experienced a mean of 24 headache days per month. Of these, 14.6 headaches were rated as severe and met the International Headache Society (IHS) criteria for migraine; 43% met IHS criteria for chronic migraine. Half of the retired players were currently using narcotic pain medication (not specifically for headache), but only one was taking a migraine-specific abortive medication. Neuropsychologic testing demonstrated significant abnormalities in attention and concentration (66%), executive function (50%), learning and memory (50%), and spatial and perceptual function (33%). Three players had abnormalities on advanced brain imaging that indicated permanent brain injury.

Concern about injuries sustained while performing on the field of play in football, hockey, or other contact sports has spurred new regulations within professional and high school sports organizations to protect players. Earlier this year, the NFL reported that the number of concussions in the league had declined by 13% this season because of improved medical diagnoses, stiffer penalties for striking with a helmet, and fewer practices.

“While it’s too late to protect retired players from injury,” Dr. Conidi said, “We must do all we can to ensure that they get the kind of treatment and access to care they need.”

Assessing the Family Burden of Chronic Migraine
Chronic migraine significantly affects family relationships and activities in ways including canceled vacation plans and reduced quality time with partners and children, according to researchers.

Results of the Chronic Migraine Epidemiology and Outcomes (CaMEO) study also revealed that patients with chronic migraine experience feelings of guilt, anger, and annoyance toward family members because of headache and avoid sexual intimacy because of headache.

CaMEO was a web-based study of 994 men and women with chronic migraine. Lead author Dawn C. Buse, PhD, and colleagues said the study’s purpose was to measure the perceived nature and extent of chronic migraine-related burden on family relationships and activities. Dr. Buse is Director of Behavioral Medicine at Montefiore Headache Center and Associate Professor of Clinical Neurology at Albert Einstein College of Medicine, both in the Bronx, New York.

“This study highlights the significant impact of chronic migraine, not only on the person with migraine, but on the entire family,” said Dr. Buse. “Respondents reported missing both routine and special family events on a regular basis and feeling guilty and sad about how this affected their relationships with their spouses and children.”

Almost three-quarters of respondents (73%) thought that they would be better spouses if they did not have chronic migraine. The majority of respondents (64%) felt guilty about being easily angered or annoyed by their partners because of headache, and 67% avoided sexual intimacy with their partners at times because of headache. The majority of respondents (59%) felt that they would be better parents if they did not have chronic migraine. Sixty-one percent of respondents reported that they became easily annoyed with their children because of headache. In addition, 54% of respondents reported that they had reduced participation or enjoyment on a family vacation because of headache in the past year, and 20% canceled or missed a family vacation altogether.

Women consistently reported lower percentage rates of absenteeism across many activities because of headaches than did men. “This may be due to differences in headache severity between genders; differential denominators, in that women may have more activities and responsibilities; or women may feel more obligated to keep commitments despite migraine occurrence,” the researchers said.

“Clearly, the effects of chronic migraine can be devastating and far-reaching. Chronic migraine can be a great burden, not only from the direct effects of the condition on the person with chronic migraine, but also the effects that it has on family members. The effect of chronic migraine on the family is not commonly discussed; however, people who live with chronic migraine may experience substantial emotional distress caused by feeling worried, guilty, and sad about how their condition affects the people they love, adding to the total burden,” said Dr. Buse.

The CaMEO study recruited individuals from a web-based panel, using quota sampling to complete a series of web-based surveys for more than one year. The data were used to characterize migraine and chronic migraine. The current analysis reflects data from respondents meeting study criteria for chronic migraine.

LOS ANGELES—Three new experimental treatments targeting calcitonin gene-related peptide (CGRP) receptors for the prevention or reduction of migraine have shown promise in preventing migraine attacks, according to researchers. The new treatments—AMG 334, LY2951742, and ALD403—are selective and potent antibodies targeting human CGRP biology with the potential for migraine prevention.

AMG 334 is an investigational human antibody that targets the CGRP receptor rather than CGRP itself. AMG 334 is in phase II clinical trials for the prevention of migraines. In prior studies of AMG 334 in nonhuman primates, the therapy was found to be a “potent and selective antibody against the human CGRP receptor with potential for migraine prevention,” the authors said.

In the LY2951742 study, 217 subjects with four to 14 migraine headache days per month received biweekly subcutaneous injections of either LY2951742 (a monoclonal antibody that binds to CGRP) or placebo for a total of as many as six doses in a 12-week treatment period. Compared with placebo, treatment with LY2951742 resulted in a significantly greater decrease from baseline in the last 28-day period in the number of migraine headache days, migraine attacks, headache days, and combined probable migraine and migraine headache days. In addition, significantly more patients treated with LY2951742 had a greater than 50% reduction in the last 28-day period in the number of migraine headache days, compared with placebo.

In the ALD403 study, ALD403 was given as a single IV infusion to 81 patients; 82 patients received placebo. Patients were followed for 12 weeks. At the end of 12 weeks, there was, on average, a 66% decrease in migraine days in the ALD403-treated subjects versus a 52% decrease for placebo-treated patients. ALD403 treatment resulted in 16% (0% for placebo) of patients having no migraines, 32% (9% for placebo) of patients having a 75% decrease in their migraine days, and 60% (33% for placebo) having a 50% decrease in their migraine days for the full 12-week study period.

All three CGRP monoclonal antibody treatments were well tolerated and showed no significant adverse events or other safety concerns.

Peter Goadsby, MD, of the University of California, San Francisco, and coinvestigator on two of the CGRP monoclonal antibody studies, stressed that the findings in all three studies are encouraging but preliminary and need larger, longer-term studies to confirm the efficacy and safety of the treatments.

Deployment-Related Brain Injury Is Strongly Associated With Migraine in Iraq and Afghanistan Veterans
Veterans who were deployed to combat zones in the Iraq and Afghanistan wars and experienced traumatic brain injury (TBI) have a strong and highly significant increase in the frequency and intensity of headaches, the majority of which are migraines, according to researchers.

The incidence of chronic daily headache (ie, 15 or more headache days per month) was three times greater, compared with controls, and the incidence of frequent headache (ie, 10 to 14 headache days per month) was 4.5 times greater in these soldiers than in control groups, reported lead author James R. Couch, MD, of the University of Oklahoma School of Medicine in Oklahoma City, and colleagues. “Combat zone deployment by itself is stressful. Since TBI is the signature injury of these wars and occurs in 15% to 20% of deployed soldiers, and both TBI and stress are known to be associated with headache, we sought to evaluate the differences in headache occurrence and severity between those who were deployed and those who were deployed and also experienced a TBI,” Dr. Couch said.

Dr. Couch and his team evaluated 53 pairs of deployed veterans with TBI and a matched group of veterans who were deployed but did not sustain a TBI (controls). All subjects with deployment-related TBI had headache, while 11 (23.9%) controls had no headache. In addition, 89% of headaches in the deployed veterans with TBI were migraine, compared with 40% in the control group. All subjects with deployment-related TBI reported significantly greater frequency and intensity of headache than the control group did.

Adolescents With Chronic Migraine Get More Relief When Their Medications Are Combined With Biofeedback and Relaxation Therapies
Cognitive behavioral therapy (CBT) resulted in greater reductions in headache frequency and migraine-related disability in children and adolescents with chronic migraine, according to researchers.

The study, conducted by Scott W. Powers, PhD, and his team at Cincinnati Children’s Hospital Medical Center found that adding biofeedback, relaxation techniques, and stress reduction to amitriptyline therapy reduced the number of migraine days and disability and had a favorable and clinically meaningful impact on children’s school functioning.

“Now that there is strong evidence for CBT in headache management, we believe it should be offered routinely as a first-line treatment for chronic migraine along with medications, and not only as an add-on if medications are not found to be sufficiently effective,” said Dr. Powers.

In the study, the team randomized 135 participants ages 10 to 17 diagnosed with chronic migraine with a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points to CBT (n = 64) or headache education (n = 71). Interventions consisted of 10 CBT or 10 headache education sessions involving equivalent time and therapist attention; CBT included training in pain coping, including a biofeedback component. Each group received amitriptyline. Follow-up visits were conducted at three, six, nine, and 12 months. At 12-month follow-up, 86% of CBT participants had a 50% or greater reduction in days with headache versus 69% of the headache education group; 88% of CBT participants had a PedMIDAS of less than 20 points (mild to no disability) versus 76% of the headache education group.

“While this is very good news as a study finding, translating this into clinical practice in treating young people with chronic migraine is an enormous challenge,” said Lawrence Newman, MD, President of the American Headache Society. “Treatment specialists will need to find ways to overcome adolescent resistance to behavioral therapy and insurance coverage issues for add-on treatment,” he said.

Women With Migraine Experience More Headaches During the Menopausal Transition
Migraine attack frequency is higher in women during perimenopause and menopause than in premenopause, according to investigators.

“Ours is the first study to demonstrate that the frequency of migraine attacks increases during the menopausal transition,” said first author Vincent T. Martin, MD, Codirector of the University of Cincinnati Headache and Facial Pain Program and Professor of Medicine in the Department of Internal Medicine, University of Cincinnati, and colleagues.

The research was conducted as part of the American Migraine Prevalence and Prevention (AMPP) study, a longitudinal, mailed questionnaire survey of 120,000 US households selected to be representative of the US population. Based on data from the 2006 AMPP study survey, women with migraine between the ages of 35 and 65 were eligible for these analyses. Women with migraine were classified based on headache frequency into a high frequency group if they experienced 10 or more headache days per month and into a low or moderate frequency episodic migraine group if they had fewer than 10 days per month. Women were also classified as premenopausal, perimenopausal, or postmenopausal (absent menstrual periods for at least 12 months) based on responses to the questionnaire.

Of 3,603 eligible women, the mean age was 45, and 34% were premenopausal, 35% were perimenopausal, and 30% were menopausal. Frequent headache (10 or more days per month) was 50% to 60% more common among perimenopausal (12.2%) and menopausal (12.0%) women, compared with the premenopausal group (8.0%).

“Given that migraines tend to worsen during menstruation, it may seem paradoxical that when periods become irregular during perimenopause or absent during menopause that headache became more frequent,” said Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Center at the Albert Einstein College of Medicine. “We believe that both declining estrogen levels that occur at the time of menstruation, as well as low estrogen levels that are encountered during the menopause, are triggers of migraine in some women,” he said.

“These results validate the belief by many women that their headaches worsen during the transition into menopause,” Dr. Martin said. “We hope that our work spurs researchers to develop novel treatments for migraine during this time period, given that many of the headaches encountered are thought to be hormonally triggered.”

Retired NFL Players With Headache Lack Access to Adequate Treatment
National Football League (NFL) alumni have a significantly higher incidence and frequency of headache, migraine, and chronic migraine when compared with the general population, but lack access to care, investigators reported.

“The players we examined were not receiving standard headache treatment,” said lead author Frank Conidi, DO, MS, Sports Neurologist and Headache and Concussion Specialist at Florida State University College of Medicine and Florida Center for Headache and Sports Neurology in Palm Beach Gardens, Florida, and colleagues. “In fact, they lacked access to both neurologists and headache specialists, despite an increased incidence of concussion and headache frequency.”

Retired players in the study were between the ages of 30 and 43 (mean age 36.67), had played an average of 4.3 years (range, two to nine years), and had an average of 7.33 concussions (± 5.2, maximum 15). They experienced a mean of 24 headache days per month. Of these, 14.6 headaches were rated as severe and met the International Headache Society (IHS) criteria for migraine; 43% met IHS criteria for chronic migraine. Half of the retired players were currently using narcotic pain medication (not specifically for headache), but only one was taking a migraine-specific abortive medication. Neuropsychologic testing demonstrated significant abnormalities in attention and concentration (66%), executive function (50%), learning and memory (50%), and spatial and perceptual function (33%). Three players had abnormalities on advanced brain imaging that indicated permanent brain injury.

Concern about injuries sustained while performing on the field of play in football, hockey, or other contact sports has spurred new regulations within professional and high school sports organizations to protect players. Earlier this year, the NFL reported that the number of concussions in the league had declined by 13% this season because of improved medical diagnoses, stiffer penalties for striking with a helmet, and fewer practices.

“While it’s too late to protect retired players from injury,” Dr. Conidi said, “We must do all we can to ensure that they get the kind of treatment and access to care they need.”

Assessing the Family Burden of Chronic Migraine
Chronic migraine significantly affects family relationships and activities in ways including canceled vacation plans and reduced quality time with partners and children, according to researchers.

Results of the Chronic Migraine Epidemiology and Outcomes (CaMEO) study also revealed that patients with chronic migraine experience feelings of guilt, anger, and annoyance toward family members because of headache and avoid sexual intimacy because of headache.

CaMEO was a web-based study of 994 men and women with chronic migraine. Lead author Dawn C. Buse, PhD, and colleagues said the study’s purpose was to measure the perceived nature and extent of chronic migraine-related burden on family relationships and activities. Dr. Buse is Director of Behavioral Medicine at Montefiore Headache Center and Associate Professor of Clinical Neurology at Albert Einstein College of Medicine, both in the Bronx, New York.

“This study highlights the significant impact of chronic migraine, not only on the person with migraine, but on the entire family,” said Dr. Buse. “Respondents reported missing both routine and special family events on a regular basis and feeling guilty and sad about how this affected their relationships with their spouses and children.”

Almost three-quarters of respondents (73%) thought that they would be better spouses if they did not have chronic migraine. The majority of respondents (64%) felt guilty about being easily angered or annoyed by their partners because of headache, and 67% avoided sexual intimacy with their partners at times because of headache. The majority of respondents (59%) felt that they would be better parents if they did not have chronic migraine. Sixty-one percent of respondents reported that they became easily annoyed with their children because of headache. In addition, 54% of respondents reported that they had reduced participation or enjoyment on a family vacation because of headache in the past year, and 20% canceled or missed a family vacation altogether.

Women consistently reported lower percentage rates of absenteeism across many activities because of headaches than did men. “This may be due to differences in headache severity between genders; differential denominators, in that women may have more activities and responsibilities; or women may feel more obligated to keep commitments despite migraine occurrence,” the researchers said.

“Clearly, the effects of chronic migraine can be devastating and far-reaching. Chronic migraine can be a great burden, not only from the direct effects of the condition on the person with chronic migraine, but also the effects that it has on family members. The effect of chronic migraine on the family is not commonly discussed; however, people who live with chronic migraine may experience substantial emotional distress caused by feeling worried, guilty, and sad about how their condition affects the people they love, adding to the total burden,” said Dr. Buse.

The CaMEO study recruited individuals from a web-based panel, using quota sampling to complete a series of web-based surveys for more than one year. The data were used to characterize migraine and chronic migraine. The current analysis reflects data from respondents meeting study criteria for chronic migraine.