Migraine ICYMI

During the past 20 years, mindfulness-based training has become an increasingly popular treatment for many conditions, including migraine. In the February online issue of the Journal of Headache and Pain, Dr. Grazzi addresses medication overuse chronic migraine (CM-MO) and provides initial evidence for the consideration of mindfulness training to help reduce headache symptoms.

However, the reader should take seriously the authors’ caution that “although our findings are encouraging and suggestive of the independent value of mindfulness for headache care, certain design limitations preclude us [from] making unequivocal claims.”

Since the goal of a noninferiority trial is to assess whether a new therapy is at least as beneficial as standard treatment, extra caution is necessary when interpreting findings from an underpowered feasibility study. In general, a useful approach to noninferiority is to determine whether the confidence intervals include effect sizes that one might consider clinically meaningful. Instead of focusing on whether the mindfulness-based training group performed the same as the comparison group, we should accept the valuable information that is presented. The take away message from this pilot study is threefold. Mindfulness-based training is potentially acceptable to patients with CM-MO. Patients with CM-MO might be amenable to participating in a fully powered randomized controlled trial of mindfulness-based training. Finally, it is possible that mindfulness-based training may show improvement similar in magnitude to pharmaceuticals. Overall, Grazzi et al have laid the groundwork for a fully powered, randomized version of their study.

—Alice R. Pressman, PhD
Director of Analytics and Evaluation
Sutter Health
Walnut Creek, California

During the past 20 years, mindfulness-based training has become an increasingly popular treatment for many conditions, including migraine. In the February online issue of the Journal of Headache and Pain, Dr. Grazzi addresses medication overuse chronic migraine (CM-MO) and provides initial evidence for the consideration of mindfulness training to help reduce headache symptoms.

However, the reader should take seriously the authors’ caution that “although our findings are encouraging and suggestive of the independent value of mindfulness for headache care, certain design limitations preclude us [from] making unequivocal claims.”

Since the goal of a noninferiority trial is to assess whether a new therapy is at least as beneficial as standard treatment, extra caution is necessary when interpreting findings from an underpowered feasibility study. In general, a useful approach to noninferiority is to determine whether the confidence intervals include effect sizes that one might consider clinically meaningful. Instead of focusing on whether the mindfulness-based training group performed the same as the comparison group, we should accept the valuable information that is presented. The take away message from this pilot study is threefold. Mindfulness-based training is potentially acceptable to patients with CM-MO. Patients with CM-MO might be amenable to participating in a fully powered randomized controlled trial of mindfulness-based training. Finally, it is possible that mindfulness-based training may show improvement similar in magnitude to pharmaceuticals. Overall, Grazzi et al have laid the groundwork for a fully powered, randomized version of their study.

—Alice R. Pressman, PhD
Director of Analytics and Evaluation
Sutter Health
Walnut Creek, California

During the past 20 years, mindfulness-based training has become an increasingly popular treatment for many conditions, including migraine. In the February online issue of the Journal of Headache and Pain, Dr. Grazzi addresses medication overuse chronic migraine (CM-MO) and provides initial evidence for the consideration of mindfulness training to help reduce headache symptoms.

However, the reader should take seriously the authors’ caution that “although our findings are encouraging and suggestive of the independent value of mindfulness for headache care, certain design limitations preclude us [from] making unequivocal claims.”

Since the goal of a noninferiority trial is to assess whether a new therapy is at least as beneficial as standard treatment, extra caution is necessary when interpreting findings from an underpowered feasibility study. In general, a useful approach to noninferiority is to determine whether the confidence intervals include effect sizes that one might consider clinically meaningful. Instead of focusing on whether the mindfulness-based training group performed the same as the comparison group, we should accept the valuable information that is presented. The take away message from this pilot study is threefold. Mindfulness-based training is potentially acceptable to patients with CM-MO. Patients with CM-MO might be amenable to participating in a fully powered randomized controlled trial of mindfulness-based training. Finally, it is possible that mindfulness-based training may show improvement similar in magnitude to pharmaceuticals. Overall, Grazzi et al have laid the groundwork for a fully powered, randomized version of their study.

—Alice R. Pressman, PhD
Director of Analytics and Evaluation
Sutter Health
Walnut Creek, California

BOSTON—Erenumab reduces the number of migraine days per month in patients with episodic migraine, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology. The treatment also reduces the use of acute migraine medication and improves function.

Erenumab is a fully human monoclonal antibody developed to block the pathway of calcitonin gene-related peptide (CGRP). The treatment showed promise in a phase II study in patients with episodic migraine and in a phase II study of patients with chronic migraine, according to Peter Goadsby, MD, PhD, Professor of Neurology at the University of California, San Francisco School of Medicine.

A Test of Two Doses

Dr. Goadsby and colleagues conducted a phase III study of 955 participants to examine whether erenumab would be an effective preventive treatment for episodic migraine. Eligible patients had between four and 14 migraine days per month and were allowed to take one concomitant migraine medication. Patients who previously had failed two preventive medications were excluded. After screening, patients underwent a four-week baseline period during which they kept electronic migraine diaries. The investigators then randomized patients in groups of equal size to placebo, 70 mg of subcutaneous erenumab, or 140 mg of subcutaneous erenumab. The treatment period lasted for six months.

As has been the case in many studies of migraine during the past 25 years, the typical patient in this study was a 41-year-old Caucasian woman, said Dr. Goadsby. Slightly more than half of participants had no previous exposure to a preventive therapy. The mean number of migraine days in all treatment groups was eight, and the mean number of headache days was nine. The treatment groups were well balanced.

Treatment Reduced Medication Use

During the last three months of treatment, the mean number of monthly migraine days decreased by 3.2 for patients receiving 70 mg of erenumab and by 3.7 for patients receiving 140 mg of erenumab, compared with 1.8 for patients receiving placebo. The difference between the active and control arms was statistically significant. The rate of participants who had a 50% reduction in migraine attacks was 26.6% for controls, 43% for patients receiving the 70-mg dose, and 50% for patients receiving the 140-mg dose.

The use of acute medicines decreased by 1.1 days for patients receiving 70 mg of erenumab and by 1.6 days for patients receiving 140 mg, compared with a decrease of 0.2 days for patients receiving placebo. Using the Migraine Physical Function Impact Diary, participants in the 70-mg group reported that the impact of migraine on everyday activities decreased by 5.5 points. Participants in the 140-mg group reported a 5.9-point reduction in this end point. Participants in the placebo group reported a 3.3-point reduction. Physical impairment decreased by 4.2 points for the 70-mg group and by 4.8 points for the 140-mg group versus 2.4 points for the placebo group.

Erenumab was well tolerated, and none of the serious adverse events appeared to be related to treatment. The most common adverse event was injection-site reactions. About 6% of the entire cohort developed antibodies to erenumab, including 8% in the 70-mg group and 3.2% in the 140-mg group. One patient receiving 70 mg had a neutralizing antibody, and no patients in the 140-mg group had neutralizing antibodies.

The study results are exciting, said Dr. Goadsby. In the future, treatments that target the CGRP pathway could be provided to migraineurs who do not respond to or cannot tolerate the current therapies, he added.

The trial was sponsored by Amgen, and Dr. Goadsby previously has consulted for the company.

—Erik Greb

BOSTON—Erenumab reduces the number of migraine days per month in patients with episodic migraine, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology. The treatment also reduces the use of acute migraine medication and improves function.

Erenumab is a fully human monoclonal antibody developed to block the pathway of calcitonin gene-related peptide (CGRP). The treatment showed promise in a phase II study in patients with episodic migraine and in a phase II study of patients with chronic migraine, according to Peter Goadsby, MD, PhD, Professor of Neurology at the University of California, San Francisco School of Medicine.

A Test of Two Doses

Dr. Goadsby and colleagues conducted a phase III study of 955 participants to examine whether erenumab would be an effective preventive treatment for episodic migraine. Eligible patients had between four and 14 migraine days per month and were allowed to take one concomitant migraine medication. Patients who previously had failed two preventive medications were excluded. After screening, patients underwent a four-week baseline period during which they kept electronic migraine diaries. The investigators then randomized patients in groups of equal size to placebo, 70 mg of subcutaneous erenumab, or 140 mg of subcutaneous erenumab. The treatment period lasted for six months.

As has been the case in many studies of migraine during the past 25 years, the typical patient in this study was a 41-year-old Caucasian woman, said Dr. Goadsby. Slightly more than half of participants had no previous exposure to a preventive therapy. The mean number of migraine days in all treatment groups was eight, and the mean number of headache days was nine. The treatment groups were well balanced.

Treatment Reduced Medication Use

During the last three months of treatment, the mean number of monthly migraine days decreased by 3.2 for patients receiving 70 mg of erenumab and by 3.7 for patients receiving 140 mg of erenumab, compared with 1.8 for patients receiving placebo. The difference between the active and control arms was statistically significant. The rate of participants who had a 50% reduction in migraine attacks was 26.6% for controls, 43% for patients receiving the 70-mg dose, and 50% for patients receiving the 140-mg dose.

The use of acute medicines decreased by 1.1 days for patients receiving 70 mg of erenumab and by 1.6 days for patients receiving 140 mg, compared with a decrease of 0.2 days for patients receiving placebo. Using the Migraine Physical Function Impact Diary, participants in the 70-mg group reported that the impact of migraine on everyday activities decreased by 5.5 points. Participants in the 140-mg group reported a 5.9-point reduction in this end point. Participants in the placebo group reported a 3.3-point reduction. Physical impairment decreased by 4.2 points for the 70-mg group and by 4.8 points for the 140-mg group versus 2.4 points for the placebo group.

Erenumab was well tolerated, and none of the serious adverse events appeared to be related to treatment. The most common adverse event was injection-site reactions. About 6% of the entire cohort developed antibodies to erenumab, including 8% in the 70-mg group and 3.2% in the 140-mg group. One patient receiving 70 mg had a neutralizing antibody, and no patients in the 140-mg group had neutralizing antibodies.

The study results are exciting, said Dr. Goadsby. In the future, treatments that target the CGRP pathway could be provided to migraineurs who do not respond to or cannot tolerate the current therapies, he added.

The trial was sponsored by Amgen, and Dr. Goadsby previously has consulted for the company.

—Erik Greb

BOSTON—Erenumab reduces the number of migraine days per month in patients with episodic migraine, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology. The treatment also reduces the use of acute migraine medication and improves function.

Erenumab is a fully human monoclonal antibody developed to block the pathway of calcitonin gene-related peptide (CGRP). The treatment showed promise in a phase II study in patients with episodic migraine and in a phase II study of patients with chronic migraine, according to Peter Goadsby, MD, PhD, Professor of Neurology at the University of California, San Francisco School of Medicine.

A Test of Two Doses

Dr. Goadsby and colleagues conducted a phase III study of 955 participants to examine whether erenumab would be an effective preventive treatment for episodic migraine. Eligible patients had between four and 14 migraine days per month and were allowed to take one concomitant migraine medication. Patients who previously had failed two preventive medications were excluded. After screening, patients underwent a four-week baseline period during which they kept electronic migraine diaries. The investigators then randomized patients in groups of equal size to placebo, 70 mg of subcutaneous erenumab, or 140 mg of subcutaneous erenumab. The treatment period lasted for six months.

As has been the case in many studies of migraine during the past 25 years, the typical patient in this study was a 41-year-old Caucasian woman, said Dr. Goadsby. Slightly more than half of participants had no previous exposure to a preventive therapy. The mean number of migraine days in all treatment groups was eight, and the mean number of headache days was nine. The treatment groups were well balanced.

Treatment Reduced Medication Use

During the last three months of treatment, the mean number of monthly migraine days decreased by 3.2 for patients receiving 70 mg of erenumab and by 3.7 for patients receiving 140 mg of erenumab, compared with 1.8 for patients receiving placebo. The difference between the active and control arms was statistically significant. The rate of participants who had a 50% reduction in migraine attacks was 26.6% for controls, 43% for patients receiving the 70-mg dose, and 50% for patients receiving the 140-mg dose.

The use of acute medicines decreased by 1.1 days for patients receiving 70 mg of erenumab and by 1.6 days for patients receiving 140 mg, compared with a decrease of 0.2 days for patients receiving placebo. Using the Migraine Physical Function Impact Diary, participants in the 70-mg group reported that the impact of migraine on everyday activities decreased by 5.5 points. Participants in the 140-mg group reported a 5.9-point reduction in this end point. Participants in the placebo group reported a 3.3-point reduction. Physical impairment decreased by 4.2 points for the 70-mg group and by 4.8 points for the 140-mg group versus 2.4 points for the placebo group.

Erenumab was well tolerated, and none of the serious adverse events appeared to be related to treatment. The most common adverse event was injection-site reactions. About 6% of the entire cohort developed antibodies to erenumab, including 8% in the 70-mg group and 3.2% in the 140-mg group. One patient receiving 70 mg had a neutralizing antibody, and no patients in the 140-mg group had neutralizing antibodies.

The study results are exciting, said Dr. Goadsby. In the future, treatments that target the CGRP pathway could be provided to migraineurs who do not respond to or cannot tolerate the current therapies, he added.

The trial was sponsored by Amgen, and Dr. Goadsby previously has consulted for the company.

—Erik Greb

Stigma in Media and Society

Although neurologists and the general public acknowledge the symptoms and disability associated with a disease, they generally discount or fail to recognize its associated stigma, said Dr. Shapiro. Internalized stigma is a person’s sense that he or she is kept at a social distance, and enacted stigma refers to instances of discrimination on the basis of a person’s condition. Consequences of stigma include psychologic distress, low self-esteem, poor social outcomes, and poor health outcomes.

In a 2006 analysis, Caspermeyer et al examined 1,203 newspaper articles about neurologic conditions. They found that, after articles about epilepsy, articles about migraine contained the highest frequency of stigmatizing language (29%). Although migraine was among the most prevalent diseases in the analysis, it was among the least covered topics in newspaper articles.

To determine whether migraine is associated with stigma, Young and colleagues administered the Stigma Scale for Chronic Illness, a questionnaire, to patients with episodic migraine, chronic migraine, or epilepsy. The investigators observed that patients with chronic migraine and patients with epilepsy faced a similar amount of stigma. They further observed that stigma correlated most strongly with inability to work and was greater for chronic migraine than for epilepsy or episodic migraine.

Level of Stigma by Disease

Following these studies, Dr. Shapiro and colleagues investigated externalized stigma, or the rejection of others because of their condition. They polled adult members of the Amazon Mechanical Turk community, a group of approximately 500,000 people who voluntarily respond to surveys for modest monetary compensation. Compared with the US population, the Amazon Mechanical Turk community includes more women, Caucasians, young people, liberals, educated people, secular people, and people with low incomes. The group better represents the US population, however, than general Internet or university convenience samples do.

The investigators presented each respondent with one of four vignettes about people with a disease that does not respond well to treatment and that sometimes results in missed work or family activities. The vignettes were identical except for the condition named. The four conditions were migraine, epilepsy, panic disorder, and asthma. After reviewing the vignette, each respondent completed a validated stigma-assessment instrument using a Likert scale for each item.

In all, 765 people completed the instrument. Respondents’ mean age was 28, and 60% of the sample was female. There was no difference in the level of stigma attributed to migraine, panic disorder, or epilepsy, but respondents attributed less stigma to asthma than to the other three conditions. Noting the similar level of stigma between migraine and epilepsy, Dr. Shapiro said, “Epilepsy historically has been associated with demonic possession. If ever there were a disease that you would assume would have social distance or stigma attached, it certainly would be epilepsy.”

Disease and Productivity Loss

In a second study, Dr. Shapiro and colleagues presented members of the Amazon Mechanical Turk community with one of five vignettes. The vignettes described the following cases:

• A woman with migraine on four days per month who missed no workdays per year
• A woman with migraine on four days per month who missed two workdays per year
• A woman with migraine on 20 days per month who missed 10 workdays per year
• A man with migraine on four days per month who missed two workdays per year
• A woman with seizures on four days per month who missed two workdays per year.

Respondents then completed a social distance scale that included questions about the respondent’s willingness to socialize with, trust, hire, or allow the person in the vignette to marry into his or her family.

The researchers found that the level of externalized stigma was the same for the woman with migraine who missed two workdays per year as it was for the woman with epilepsy who missed two workdays per year. Respondents believed that the person with epilepsy would care more about whether he or she was a burden on others, compared with the migraineur. Respondents also said that the person with epilepsy would try harder and would be less likely to malinger, compared with the migraineur.

The gender of the person in the vignette was not associated with the level of stigma, said Dr. Shapiro. On the other hand, men were much more likely to stigmatize a man or a woman with migraine than women were.

In addition, the researchers found that the woman with chronic migraine who missed 10 workdays per year was much more likely to be stigmatized than migraineurs who missed fewer workdays. People who missed more workdays were less likely to be seen as trying hard, less likely to be interviewed, more likely to be considered malingerers, and less likely to be considered trustworthy.

Fear of Pain and Social Distance

As part of the same study, respondents completed instruments that measured fear of pain and empathy, and also provided demographic information, including migraine status. Overall, fear of pain was similar between migraineurs and nonmigraineurs. Migraineurs feared migraine as much as they feared falling down a flight of stairs or having a car door slammed on the hand. Nonmigraineurs, however, considered migraine to be less severe than migraineurs did. Among nonmigraineurs, greater fear of pain was associated with greater social distance from migraineurs. But in the same group, greater fear of migraine was associated with less social distance from migraineurs.

Furthermore, Dr. Shapiro’s group noted that the more migraine is part of a person’s experience, the less social distance that person maintains from migraineurs. Similarly, they found that as empathy increased, the social distance to migraine decreased.

Other findings included that younger people were more likely to stigmatize migraine than older people, and that non-Caucasians were more likely to stigmatize migraine than Caucasians. The gender of the stigmatizer was a dominant influence on the amount of stigma.

Reasons for Migraine Stigma

Various hypotheses offer potential reasons for stigmatizing migraine. Approximately 75% of migraineurs are women, and migraine changes with hormonal fluctuations. Hence, sexism against women may be one cause of stigma.

Also, migraine has been considered a behavior problem or conversion disorder for decades, said Dr. Shapiro. One illustration of this point is that a monograph published in 1926 identified migraine as a neurosis. In 1894, Freud described migraine as the result of a failure to find release after sexual stimulation.

Migraine is associated with headache, and headache has various connotations. The type of headache with which most people are familiar is tension-type headache, thus the general public may be likely to minimize the severity or importance of migraine. The word “headache” also connotes “concern” or “annoyance,” which may contribute to a minimization of migraine’s severity.

Whatever its origin, the stigma associated with migraine often is overlooked, said Dr. Shapiro. Neurologists should consider the potential effects of stigma on health outcomes as they treat patients with headache, he concluded.

—Erik Greb

Suggested Reading

Caspermeyer JJ, Sylvester EJ, Drazkowski JF, et al. Evaluation of stigmatizing language and medical errors in neurology coverage by US newspapers. Mayo Clin Proc. 2006;81(3):300-306.

Evans RW, Evans RE. A survey of neurologists on the likeability of headaches and other neurological disorders. Headache. 2010;50(7):1126-1129.

Evans RW, Evans RE, Kell HJ. A survey of family doctors on the likeability of migraine and other common diseases and their prevalence of migraine. Cephalalgia. 2010;30(5):620-623.

Young WB, Park JE, Tian IX, Kempner J. The stigma of migraine. PLoS One. 2013;8(1):e54074.

Stigma in Media and Society

Although neurologists and the general public acknowledge the symptoms and disability associated with a disease, they generally discount or fail to recognize its associated stigma, said Dr. Shapiro. Internalized stigma is a person’s sense that he or she is kept at a social distance, and enacted stigma refers to instances of discrimination on the basis of a person’s condition. Consequences of stigma include psychologic distress, low self-esteem, poor social outcomes, and poor health outcomes.

In a 2006 analysis, Caspermeyer et al examined 1,203 newspaper articles about neurologic conditions. They found that, after articles about epilepsy, articles about migraine contained the highest frequency of stigmatizing language (29%). Although migraine was among the most prevalent diseases in the analysis, it was among the least covered topics in newspaper articles.

To determine whether migraine is associated with stigma, Young and colleagues administered the Stigma Scale for Chronic Illness, a questionnaire, to patients with episodic migraine, chronic migraine, or epilepsy. The investigators observed that patients with chronic migraine and patients with epilepsy faced a similar amount of stigma. They further observed that stigma correlated most strongly with inability to work and was greater for chronic migraine than for epilepsy or episodic migraine.

Level of Stigma by Disease

Following these studies, Dr. Shapiro and colleagues investigated externalized stigma, or the rejection of others because of their condition. They polled adult members of the Amazon Mechanical Turk community, a group of approximately 500,000 people who voluntarily respond to surveys for modest monetary compensation. Compared with the US population, the Amazon Mechanical Turk community includes more women, Caucasians, young people, liberals, educated people, secular people, and people with low incomes. The group better represents the US population, however, than general Internet or university convenience samples do.

The investigators presented each respondent with one of four vignettes about people with a disease that does not respond well to treatment and that sometimes results in missed work or family activities. The vignettes were identical except for the condition named. The four conditions were migraine, epilepsy, panic disorder, and asthma. After reviewing the vignette, each respondent completed a validated stigma-assessment instrument using a Likert scale for each item.

In all, 765 people completed the instrument. Respondents’ mean age was 28, and 60% of the sample was female. There was no difference in the level of stigma attributed to migraine, panic disorder, or epilepsy, but respondents attributed less stigma to asthma than to the other three conditions. Noting the similar level of stigma between migraine and epilepsy, Dr. Shapiro said, “Epilepsy historically has been associated with demonic possession. If ever there were a disease that you would assume would have social distance or stigma attached, it certainly would be epilepsy.”

Disease and Productivity Loss

In a second study, Dr. Shapiro and colleagues presented members of the Amazon Mechanical Turk community with one of five vignettes. The vignettes described the following cases:

• A woman with migraine on four days per month who missed no workdays per year
• A woman with migraine on four days per month who missed two workdays per year
• A woman with migraine on 20 days per month who missed 10 workdays per year
• A man with migraine on four days per month who missed two workdays per year
• A woman with seizures on four days per month who missed two workdays per year.

Respondents then completed a social distance scale that included questions about the respondent’s willingness to socialize with, trust, hire, or allow the person in the vignette to marry into his or her family.

The researchers found that the level of externalized stigma was the same for the woman with migraine who missed two workdays per year as it was for the woman with epilepsy who missed two workdays per year. Respondents believed that the person with epilepsy would care more about whether he or she was a burden on others, compared with the migraineur. Respondents also said that the person with epilepsy would try harder and would be less likely to malinger, compared with the migraineur.

The gender of the person in the vignette was not associated with the level of stigma, said Dr. Shapiro. On the other hand, men were much more likely to stigmatize a man or a woman with migraine than women were.

In addition, the researchers found that the woman with chronic migraine who missed 10 workdays per year was much more likely to be stigmatized than migraineurs who missed fewer workdays. People who missed more workdays were less likely to be seen as trying hard, less likely to be interviewed, more likely to be considered malingerers, and less likely to be considered trustworthy.

Fear of Pain and Social Distance

As part of the same study, respondents completed instruments that measured fear of pain and empathy, and also provided demographic information, including migraine status. Overall, fear of pain was similar between migraineurs and nonmigraineurs. Migraineurs feared migraine as much as they feared falling down a flight of stairs or having a car door slammed on the hand. Nonmigraineurs, however, considered migraine to be less severe than migraineurs did. Among nonmigraineurs, greater fear of pain was associated with greater social distance from migraineurs. But in the same group, greater fear of migraine was associated with less social distance from migraineurs.

Furthermore, Dr. Shapiro’s group noted that the more migraine is part of a person’s experience, the less social distance that person maintains from migraineurs. Similarly, they found that as empathy increased, the social distance to migraine decreased.

Other findings included that younger people were more likely to stigmatize migraine than older people, and that non-Caucasians were more likely to stigmatize migraine than Caucasians. The gender of the stigmatizer was a dominant influence on the amount of stigma.

Reasons for Migraine Stigma

Various hypotheses offer potential reasons for stigmatizing migraine. Approximately 75% of migraineurs are women, and migraine changes with hormonal fluctuations. Hence, sexism against women may be one cause of stigma.

Also, migraine has been considered a behavior problem or conversion disorder for decades, said Dr. Shapiro. One illustration of this point is that a monograph published in 1926 identified migraine as a neurosis. In 1894, Freud described migraine as the result of a failure to find release after sexual stimulation.

Migraine is associated with headache, and headache has various connotations. The type of headache with which most people are familiar is tension-type headache, thus the general public may be likely to minimize the severity or importance of migraine. The word “headache” also connotes “concern” or “annoyance,” which may contribute to a minimization of migraine’s severity.

Whatever its origin, the stigma associated with migraine often is overlooked, said Dr. Shapiro. Neurologists should consider the potential effects of stigma on health outcomes as they treat patients with headache, he concluded.

—Erik Greb

Suggested Reading

Caspermeyer JJ, Sylvester EJ, Drazkowski JF, et al. Evaluation of stigmatizing language and medical errors in neurology coverage by US newspapers. Mayo Clin Proc. 2006;81(3):300-306.

Evans RW, Evans RE. A survey of neurologists on the likeability of headaches and other neurological disorders. Headache. 2010;50(7):1126-1129.

Evans RW, Evans RE, Kell HJ. A survey of family doctors on the likeability of migraine and other common diseases and their prevalence of migraine. Cephalalgia. 2010;30(5):620-623.

Young WB, Park JE, Tian IX, Kempner J. The stigma of migraine. PLoS One. 2013;8(1):e54074.

Stigma in Media and Society

Although neurologists and the general public acknowledge the symptoms and disability associated with a disease, they generally discount or fail to recognize its associated stigma, said Dr. Shapiro. Internalized stigma is a person’s sense that he or she is kept at a social distance, and enacted stigma refers to instances of discrimination on the basis of a person’s condition. Consequences of stigma include psychologic distress, low self-esteem, poor social outcomes, and poor health outcomes.

In a 2006 analysis, Caspermeyer et al examined 1,203 newspaper articles about neurologic conditions. They found that, after articles about epilepsy, articles about migraine contained the highest frequency of stigmatizing language (29%). Although migraine was among the most prevalent diseases in the analysis, it was among the least covered topics in newspaper articles.

To determine whether migraine is associated with stigma, Young and colleagues administered the Stigma Scale for Chronic Illness, a questionnaire, to patients with episodic migraine, chronic migraine, or epilepsy. The investigators observed that patients with chronic migraine and patients with epilepsy faced a similar amount of stigma. They further observed that stigma correlated most strongly with inability to work and was greater for chronic migraine than for epilepsy or episodic migraine.

Level of Stigma by Disease

Following these studies, Dr. Shapiro and colleagues investigated externalized stigma, or the rejection of others because of their condition. They polled adult members of the Amazon Mechanical Turk community, a group of approximately 500,000 people who voluntarily respond to surveys for modest monetary compensation. Compared with the US population, the Amazon Mechanical Turk community includes more women, Caucasians, young people, liberals, educated people, secular people, and people with low incomes. The group better represents the US population, however, than general Internet or university convenience samples do.

The investigators presented each respondent with one of four vignettes about people with a disease that does not respond well to treatment and that sometimes results in missed work or family activities. The vignettes were identical except for the condition named. The four conditions were migraine, epilepsy, panic disorder, and asthma. After reviewing the vignette, each respondent completed a validated stigma-assessment instrument using a Likert scale for each item.

In all, 765 people completed the instrument. Respondents’ mean age was 28, and 60% of the sample was female. There was no difference in the level of stigma attributed to migraine, panic disorder, or epilepsy, but respondents attributed less stigma to asthma than to the other three conditions. Noting the similar level of stigma between migraine and epilepsy, Dr. Shapiro said, “Epilepsy historically has been associated with demonic possession. If ever there were a disease that you would assume would have social distance or stigma attached, it certainly would be epilepsy.”

Disease and Productivity Loss

In a second study, Dr. Shapiro and colleagues presented members of the Amazon Mechanical Turk community with one of five vignettes. The vignettes described the following cases:

• A woman with migraine on four days per month who missed no workdays per year
• A woman with migraine on four days per month who missed two workdays per year
• A woman with migraine on 20 days per month who missed 10 workdays per year
• A man with migraine on four days per month who missed two workdays per year
• A woman with seizures on four days per month who missed two workdays per year.

Respondents then completed a social distance scale that included questions about the respondent’s willingness to socialize with, trust, hire, or allow the person in the vignette to marry into his or her family.

The researchers found that the level of externalized stigma was the same for the woman with migraine who missed two workdays per year as it was for the woman with epilepsy who missed two workdays per year. Respondents believed that the person with epilepsy would care more about whether he or she was a burden on others, compared with the migraineur. Respondents also said that the person with epilepsy would try harder and would be less likely to malinger, compared with the migraineur.

The gender of the person in the vignette was not associated with the level of stigma, said Dr. Shapiro. On the other hand, men were much more likely to stigmatize a man or a woman with migraine than women were.

In addition, the researchers found that the woman with chronic migraine who missed 10 workdays per year was much more likely to be stigmatized than migraineurs who missed fewer workdays. People who missed more workdays were less likely to be seen as trying hard, less likely to be interviewed, more likely to be considered malingerers, and less likely to be considered trustworthy.

Fear of Pain and Social Distance

As part of the same study, respondents completed instruments that measured fear of pain and empathy, and also provided demographic information, including migraine status. Overall, fear of pain was similar between migraineurs and nonmigraineurs. Migraineurs feared migraine as much as they feared falling down a flight of stairs or having a car door slammed on the hand. Nonmigraineurs, however, considered migraine to be less severe than migraineurs did. Among nonmigraineurs, greater fear of pain was associated with greater social distance from migraineurs. But in the same group, greater fear of migraine was associated with less social distance from migraineurs.

Furthermore, Dr. Shapiro’s group noted that the more migraine is part of a person’s experience, the less social distance that person maintains from migraineurs. Similarly, they found that as empathy increased, the social distance to migraine decreased.

Other findings included that younger people were more likely to stigmatize migraine than older people, and that non-Caucasians were more likely to stigmatize migraine than Caucasians. The gender of the stigmatizer was a dominant influence on the amount of stigma.

Reasons for Migraine Stigma

Various hypotheses offer potential reasons for stigmatizing migraine. Approximately 75% of migraineurs are women, and migraine changes with hormonal fluctuations. Hence, sexism against women may be one cause of stigma.

Also, migraine has been considered a behavior problem or conversion disorder for decades, said Dr. Shapiro. One illustration of this point is that a monograph published in 1926 identified migraine as a neurosis. In 1894, Freud described migraine as the result of a failure to find release after sexual stimulation.

Migraine is associated with headache, and headache has various connotations. The type of headache with which most people are familiar is tension-type headache, thus the general public may be likely to minimize the severity or importance of migraine. The word “headache” also connotes “concern” or “annoyance,” which may contribute to a minimization of migraine’s severity.

Whatever its origin, the stigma associated with migraine often is overlooked, said Dr. Shapiro. Neurologists should consider the potential effects of stigma on health outcomes as they treat patients with headache, he concluded.

—Erik Greb

Suggested Reading

Caspermeyer JJ, Sylvester EJ, Drazkowski JF, et al. Evaluation of stigmatizing language and medical errors in neurology coverage by US newspapers. Mayo Clin Proc. 2006;81(3):300-306.

Evans RW, Evans RE. A survey of neurologists on the likeability of headaches and other neurological disorders. Headache. 2010;50(7):1126-1129.

Evans RW, Evans RE, Kell HJ. A survey of family doctors on the likeability of migraine and other common diseases and their prevalence of migraine. Cephalalgia. 2010;30(5):620-623.

Young WB, Park JE, Tian IX, Kempner J. The stigma of migraine. PLoS One. 2013;8(1):e54074.

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].

STOWE, VT—Medication overuse headache is frequent, treatable, and preventable, according to an overview provided at the Headache Cooperative of New England’s 27th Annual Stowe Headache Symposium.

 The first step in treating medication overuse headache is to teach patients about the condition and how they can reduce their intake of acute medication. If patients still overuse medication, neurologists can prescribe a preventive therapy, such as topiramate or botulinum toxin. If preventive therapies fail, patients may require detoxification and integrated headache management, said Hans-Christoph Diener, MD, PhD, Senior Professor of Clinical Neurosciences and Director of the Headache Center at University Hospital Essen in Germany.

The diagnostic criteria for medication overuse headache include headache on 15 or more days per month, a pre-existing headache disorder, and regular overuse for more than three months of one or more acute or symptomatic headache drugs. The worldwide prevalence of medication overuse headache is about 1%, and about 10% of patients in headache centers have medication overuse headache.

Patients May Overuse Medication for Years

A meta-analysis of 29 studies with more than 2,600 patients found that medication overuse headache is more common in women than in men (3.5:1). About 65% of patients have a history of migraine, 27% have a history of tension-type headache, and 8% have a history of cluster headache. At diagnosis, patients’ average age is 40, average duration of primary headache is about 20 years, average duration of drug overuse is about 10 years, and average duration of medication overuse headache is about six years. “It is a slowly developing process,” Dr. Diener said. “Unfortunately, the patients present much too late.”

Risk factors include frequent headache, depression, anxiety, obesity, and other chronic pain conditions (eg, low back pain and fibromyalgia). Low socioeconomic status, being an immigrant, living alone, caffeine overuse, and opioid use also are associated with increased risk of medication overuse headache.

In an effort to treat patients with frequent episodic headache before they develop chronic migraine and medication overuse, Dr. Diener’s headache center evaluates high-risk patients who are referred by insurance companies. “If somebody has enough of these risk factors and frequent prescription of triptans, someone from the insurance company will call the patient and say, ‘Do you have problems with your headache?’” If so, the insurance company refers the patient. “In this way, we now get patients on the way to developing medication overuse, and we can treat them before they have full-blown medication overuse headache,” Dr. Diener said.

Overuse of triptans, ergots, barbiturates, and opioids may cause medication overuse headache, and a combination drug is more likely to cause medication overuse headache, compared with a drug with a single active ingredient. Limmroth et al conducted a prospective study of 98 patients with medication overuse headache to assess headache features associated with overuse of various drugs. With triptan overuse, migraine frequency increased in a majority of patients, and some patients developed a tension-type-like headache. With ergot overuse, patients tended to develop a tension-type-like daily headache. With analgesic overuse, the phenotype changed to a daily headache that resembled tension-type headache.

Start With Patient Education

When treating medication overuse headache, “simple advice is effective in a subgroup of patients,” Dr. Diener said. Grande et al taught 109 patients about medication overuse with the goal of reducing intake of acute medication. After 18 months, mean medication days per month significantly decreased from 22 at baseline to six. Education “worked in the majority of these patients,” Dr. Diener said.

Rossi et al conducted a prospective randomized trial in Italy that included 120 patients with medication overuse headache. The researchers randomized patients to advice, a structured outpatient program, or a one-week inpatient program. “There was basically no difference” between the three groups at four and eight weeks, Dr. Diener said. All three groups experienced a reduction in medication days per month of between 70% and 80%.

Do Preventive Therapies Work?

Neurologists had thought that medication overuse might render preventive medication ineffective, but studies have found that topiramate and onabotulinum toxinA are effective preventive agents in this population. The trials excluded patients who had overused barbiturates or opioids, however. In such cases, “it is not only overuse, it is addiction,” Dr. Diener said. “That is a totally different disease.”

Dr. Diener and colleagues conducted a randomized trial of topiramate in patients with chronic migraine. A majority of the patients overused triptans (ie, they took triptans on at least 10 days per four weeks). Patients had about 16 migraine days per month.

Compared with baseline, patients who received placebo had virtually no change in headache days per month, whereas patients who received topiramate had about five fewer headache days per month at 16 weeks. Two-thirds of patients in the active treatment group no longer overused medication at the end of the study. A parallel study in the United States had similar results. “We should offer this [treatment] to patients prior to drug withdrawal,” Dr. Diener said. “If patients refuse or cannot tolerate the drug,” then neurologists may consider other options, including botulinum toxin.

OnabotulinumtoxinA was evaluated in two trials. About 65% of patients overused medication in the active treatment and placebo groups of each trial, and treatment significantly reduced headache days in patients who did and did not overuse medication. In addition, compared with patients who received placebo, a greater proportion of patients who received onabotulinumtoxinA no longer overused medication for three and six consecutive months. Patients can choose between topiramate tablets and onabotulinumtoxinA injections as preventive therapy, Dr. Diener said.

Detoxification

If preventive medication fails to help patients, the next step is detoxification. Dr. Diener has patients stop acute medications cold turkey and initiates preventive therapy at that time. Patients at Dr. Diener’s center normally undergo detoxification on an outpatient basis.

Chiang et al assessed the evidence for withdrawal, withdrawal with preventive medications, and preventive medications alone. Withdrawal and withdrawal with preventive medications were found to be possibly effective, while the use of preventive medications alone was found to be likely effective. Withdrawal alone has a high failure rate and worsens symptoms in some patients. Withdrawal with preventive medication produced encouraging results in some studies, but the studies lacked control groups.

Studies suggest that the relapse rate for medication overuse headache is about 10% per year, Dr. Diener said.

One Center’s Experience

At Essen Headache Center, researchers prospectively studied 150 patients who had a diagnosis of migraine and medication overuse headache. A third achieved successful treatment with counseling and education. Another third benefited from topiramate or botulinum toxin. And the remaining third required detoxification. The majority of patients requiring detoxification had comorbidities (eg, chronic low back pain or depression). These patients require integrated headache care, including preventive therapy, exercise and physiotherapy, behavioral therapy (eg, stress management and relaxation), and education.

“The most important part is education,” Dr. Diener said. Headache center staff members tell patients that they will leave the center knowing more about their condition than their general practitioner does. “This is the goal that we want to achieve,” he said.

—Jake Remaly

Suggested Reading

Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia. 2016;36(4):371-386.

Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30(7):804-814.

Diener HC, Dodick DW, Goadsby PJ, et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia. 2009;29(10):1021-1027.

Diener HC, Holle D, Solbach K, Gaul C. Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol. 2016;12(10):575-583.

Grande RB, Aaseth K, Benth JŠ, et al. Reduction in medication-overuse headache after short information. The Akershus study of chronic headache. Eur J Neurol. 2011;18(1):129-137.

Limmroth V, Katsarava Z, Fritsche G, et al. Features of medication overuse headache following overuse of different acute headache drugs. Neurology. 2002;59(7):1011-1014.

Pijpers JA, Louter MA, de Bruin ME, et al. Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure? Cephalalgia. 2016;36(2):122-130.

Rossi P, Di Lorenzo C, Faroni J, et al. Advice alone vs. structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs. Cephalalgia. 2006;26(9):1097-1105.

STOWE, VT—Medication overuse headache is frequent, treatable, and preventable, according to an overview provided at the Headache Cooperative of New England’s 27th Annual Stowe Headache Symposium.

 The first step in treating medication overuse headache is to teach patients about the condition and how they can reduce their intake of acute medication. If patients still overuse medication, neurologists can prescribe a preventive therapy, such as topiramate or botulinum toxin. If preventive therapies fail, patients may require detoxification and integrated headache management, said Hans-Christoph Diener, MD, PhD, Senior Professor of Clinical Neurosciences and Director of the Headache Center at University Hospital Essen in Germany.

The diagnostic criteria for medication overuse headache include headache on 15 or more days per month, a pre-existing headache disorder, and regular overuse for more than three months of one or more acute or symptomatic headache drugs. The worldwide prevalence of medication overuse headache is about 1%, and about 10% of patients in headache centers have medication overuse headache.

Patients May Overuse Medication for Years

A meta-analysis of 29 studies with more than 2,600 patients found that medication overuse headache is more common in women than in men (3.5:1). About 65% of patients have a history of migraine, 27% have a history of tension-type headache, and 8% have a history of cluster headache. At diagnosis, patients’ average age is 40, average duration of primary headache is about 20 years, average duration of drug overuse is about 10 years, and average duration of medication overuse headache is about six years. “It is a slowly developing process,” Dr. Diener said. “Unfortunately, the patients present much too late.”

Risk factors include frequent headache, depression, anxiety, obesity, and other chronic pain conditions (eg, low back pain and fibromyalgia). Low socioeconomic status, being an immigrant, living alone, caffeine overuse, and opioid use also are associated with increased risk of medication overuse headache.

In an effort to treat patients with frequent episodic headache before they develop chronic migraine and medication overuse, Dr. Diener’s headache center evaluates high-risk patients who are referred by insurance companies. “If somebody has enough of these risk factors and frequent prescription of triptans, someone from the insurance company will call the patient and say, ‘Do you have problems with your headache?’” If so, the insurance company refers the patient. “In this way, we now get patients on the way to developing medication overuse, and we can treat them before they have full-blown medication overuse headache,” Dr. Diener said.

Overuse of triptans, ergots, barbiturates, and opioids may cause medication overuse headache, and a combination drug is more likely to cause medication overuse headache, compared with a drug with a single active ingredient. Limmroth et al conducted a prospective study of 98 patients with medication overuse headache to assess headache features associated with overuse of various drugs. With triptan overuse, migraine frequency increased in a majority of patients, and some patients developed a tension-type-like headache. With ergot overuse, patients tended to develop a tension-type-like daily headache. With analgesic overuse, the phenotype changed to a daily headache that resembled tension-type headache.

Start With Patient Education

When treating medication overuse headache, “simple advice is effective in a subgroup of patients,” Dr. Diener said. Grande et al taught 109 patients about medication overuse with the goal of reducing intake of acute medication. After 18 months, mean medication days per month significantly decreased from 22 at baseline to six. Education “worked in the majority of these patients,” Dr. Diener said.

Rossi et al conducted a prospective randomized trial in Italy that included 120 patients with medication overuse headache. The researchers randomized patients to advice, a structured outpatient program, or a one-week inpatient program. “There was basically no difference” between the three groups at four and eight weeks, Dr. Diener said. All three groups experienced a reduction in medication days per month of between 70% and 80%.

Do Preventive Therapies Work?

Neurologists had thought that medication overuse might render preventive medication ineffective, but studies have found that topiramate and onabotulinum toxinA are effective preventive agents in this population. The trials excluded patients who had overused barbiturates or opioids, however. In such cases, “it is not only overuse, it is addiction,” Dr. Diener said. “That is a totally different disease.”

Dr. Diener and colleagues conducted a randomized trial of topiramate in patients with chronic migraine. A majority of the patients overused triptans (ie, they took triptans on at least 10 days per four weeks). Patients had about 16 migraine days per month.

Compared with baseline, patients who received placebo had virtually no change in headache days per month, whereas patients who received topiramate had about five fewer headache days per month at 16 weeks. Two-thirds of patients in the active treatment group no longer overused medication at the end of the study. A parallel study in the United States had similar results. “We should offer this [treatment] to patients prior to drug withdrawal,” Dr. Diener said. “If patients refuse or cannot tolerate the drug,” then neurologists may consider other options, including botulinum toxin.

OnabotulinumtoxinA was evaluated in two trials. About 65% of patients overused medication in the active treatment and placebo groups of each trial, and treatment significantly reduced headache days in patients who did and did not overuse medication. In addition, compared with patients who received placebo, a greater proportion of patients who received onabotulinumtoxinA no longer overused medication for three and six consecutive months. Patients can choose between topiramate tablets and onabotulinumtoxinA injections as preventive therapy, Dr. Diener said.

Detoxification

If preventive medication fails to help patients, the next step is detoxification. Dr. Diener has patients stop acute medications cold turkey and initiates preventive therapy at that time. Patients at Dr. Diener’s center normally undergo detoxification on an outpatient basis.

Chiang et al assessed the evidence for withdrawal, withdrawal with preventive medications, and preventive medications alone. Withdrawal and withdrawal with preventive medications were found to be possibly effective, while the use of preventive medications alone was found to be likely effective. Withdrawal alone has a high failure rate and worsens symptoms in some patients. Withdrawal with preventive medication produced encouraging results in some studies, but the studies lacked control groups.

Studies suggest that the relapse rate for medication overuse headache is about 10% per year, Dr. Diener said.

One Center’s Experience

At Essen Headache Center, researchers prospectively studied 150 patients who had a diagnosis of migraine and medication overuse headache. A third achieved successful treatment with counseling and education. Another third benefited from topiramate or botulinum toxin. And the remaining third required detoxification. The majority of patients requiring detoxification had comorbidities (eg, chronic low back pain or depression). These patients require integrated headache care, including preventive therapy, exercise and physiotherapy, behavioral therapy (eg, stress management and relaxation), and education.

“The most important part is education,” Dr. Diener said. Headache center staff members tell patients that they will leave the center knowing more about their condition than their general practitioner does. “This is the goal that we want to achieve,” he said.

—Jake Remaly

Suggested Reading

Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia. 2016;36(4):371-386.

Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30(7):804-814.

Diener HC, Dodick DW, Goadsby PJ, et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia. 2009;29(10):1021-1027.

Diener HC, Holle D, Solbach K, Gaul C. Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol. 2016;12(10):575-583.

Grande RB, Aaseth K, Benth JŠ, et al. Reduction in medication-overuse headache after short information. The Akershus study of chronic headache. Eur J Neurol. 2011;18(1):129-137.

Limmroth V, Katsarava Z, Fritsche G, et al. Features of medication overuse headache following overuse of different acute headache drugs. Neurology. 2002;59(7):1011-1014.

Pijpers JA, Louter MA, de Bruin ME, et al. Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure? Cephalalgia. 2016;36(2):122-130.

Rossi P, Di Lorenzo C, Faroni J, et al. Advice alone vs. structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs. Cephalalgia. 2006;26(9):1097-1105.

STOWE, VT—Medication overuse headache is frequent, treatable, and preventable, according to an overview provided at the Headache Cooperative of New England’s 27th Annual Stowe Headache Symposium.

 The first step in treating medication overuse headache is to teach patients about the condition and how they can reduce their intake of acute medication. If patients still overuse medication, neurologists can prescribe a preventive therapy, such as topiramate or botulinum toxin. If preventive therapies fail, patients may require detoxification and integrated headache management, said Hans-Christoph Diener, MD, PhD, Senior Professor of Clinical Neurosciences and Director of the Headache Center at University Hospital Essen in Germany.

The diagnostic criteria for medication overuse headache include headache on 15 or more days per month, a pre-existing headache disorder, and regular overuse for more than three months of one or more acute or symptomatic headache drugs. The worldwide prevalence of medication overuse headache is about 1%, and about 10% of patients in headache centers have medication overuse headache.

Patients May Overuse Medication for Years

A meta-analysis of 29 studies with more than 2,600 patients found that medication overuse headache is more common in women than in men (3.5:1). About 65% of patients have a history of migraine, 27% have a history of tension-type headache, and 8% have a history of cluster headache. At diagnosis, patients’ average age is 40, average duration of primary headache is about 20 years, average duration of drug overuse is about 10 years, and average duration of medication overuse headache is about six years. “It is a slowly developing process,” Dr. Diener said. “Unfortunately, the patients present much too late.”

Risk factors include frequent headache, depression, anxiety, obesity, and other chronic pain conditions (eg, low back pain and fibromyalgia). Low socioeconomic status, being an immigrant, living alone, caffeine overuse, and opioid use also are associated with increased risk of medication overuse headache.

In an effort to treat patients with frequent episodic headache before they develop chronic migraine and medication overuse, Dr. Diener’s headache center evaluates high-risk patients who are referred by insurance companies. “If somebody has enough of these risk factors and frequent prescription of triptans, someone from the insurance company will call the patient and say, ‘Do you have problems with your headache?’” If so, the insurance company refers the patient. “In this way, we now get patients on the way to developing medication overuse, and we can treat them before they have full-blown medication overuse headache,” Dr. Diener said.

Overuse of triptans, ergots, barbiturates, and opioids may cause medication overuse headache, and a combination drug is more likely to cause medication overuse headache, compared with a drug with a single active ingredient. Limmroth et al conducted a prospective study of 98 patients with medication overuse headache to assess headache features associated with overuse of various drugs. With triptan overuse, migraine frequency increased in a majority of patients, and some patients developed a tension-type-like headache. With ergot overuse, patients tended to develop a tension-type-like daily headache. With analgesic overuse, the phenotype changed to a daily headache that resembled tension-type headache.

Start With Patient Education

When treating medication overuse headache, “simple advice is effective in a subgroup of patients,” Dr. Diener said. Grande et al taught 109 patients about medication overuse with the goal of reducing intake of acute medication. After 18 months, mean medication days per month significantly decreased from 22 at baseline to six. Education “worked in the majority of these patients,” Dr. Diener said.

Rossi et al conducted a prospective randomized trial in Italy that included 120 patients with medication overuse headache. The researchers randomized patients to advice, a structured outpatient program, or a one-week inpatient program. “There was basically no difference” between the three groups at four and eight weeks, Dr. Diener said. All three groups experienced a reduction in medication days per month of between 70% and 80%.

Do Preventive Therapies Work?

Neurologists had thought that medication overuse might render preventive medication ineffective, but studies have found that topiramate and onabotulinum toxinA are effective preventive agents in this population. The trials excluded patients who had overused barbiturates or opioids, however. In such cases, “it is not only overuse, it is addiction,” Dr. Diener said. “That is a totally different disease.”

Dr. Diener and colleagues conducted a randomized trial of topiramate in patients with chronic migraine. A majority of the patients overused triptans (ie, they took triptans on at least 10 days per four weeks). Patients had about 16 migraine days per month.

Compared with baseline, patients who received placebo had virtually no change in headache days per month, whereas patients who received topiramate had about five fewer headache days per month at 16 weeks. Two-thirds of patients in the active treatment group no longer overused medication at the end of the study. A parallel study in the United States had similar results. “We should offer this [treatment] to patients prior to drug withdrawal,” Dr. Diener said. “If patients refuse or cannot tolerate the drug,” then neurologists may consider other options, including botulinum toxin.

OnabotulinumtoxinA was evaluated in two trials. About 65% of patients overused medication in the active treatment and placebo groups of each trial, and treatment significantly reduced headache days in patients who did and did not overuse medication. In addition, compared with patients who received placebo, a greater proportion of patients who received onabotulinumtoxinA no longer overused medication for three and six consecutive months. Patients can choose between topiramate tablets and onabotulinumtoxinA injections as preventive therapy, Dr. Diener said.

Detoxification

If preventive medication fails to help patients, the next step is detoxification. Dr. Diener has patients stop acute medications cold turkey and initiates preventive therapy at that time. Patients at Dr. Diener’s center normally undergo detoxification on an outpatient basis.

Chiang et al assessed the evidence for withdrawal, withdrawal with preventive medications, and preventive medications alone. Withdrawal and withdrawal with preventive medications were found to be possibly effective, while the use of preventive medications alone was found to be likely effective. Withdrawal alone has a high failure rate and worsens symptoms in some patients. Withdrawal with preventive medication produced encouraging results in some studies, but the studies lacked control groups.

Studies suggest that the relapse rate for medication overuse headache is about 10% per year, Dr. Diener said.

One Center’s Experience

At Essen Headache Center, researchers prospectively studied 150 patients who had a diagnosis of migraine and medication overuse headache. A third achieved successful treatment with counseling and education. Another third benefited from topiramate or botulinum toxin. And the remaining third required detoxification. The majority of patients requiring detoxification had comorbidities (eg, chronic low back pain or depression). These patients require integrated headache care, including preventive therapy, exercise and physiotherapy, behavioral therapy (eg, stress management and relaxation), and education.

“The most important part is education,” Dr. Diener said. Headache center staff members tell patients that they will leave the center knowing more about their condition than their general practitioner does. “This is the goal that we want to achieve,” he said.

—Jake Remaly

Suggested Reading

Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia. 2016;36(4):371-386.

Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30(7):804-814.

Diener HC, Dodick DW, Goadsby PJ, et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia. 2009;29(10):1021-1027.

Diener HC, Holle D, Solbach K, Gaul C. Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol. 2016;12(10):575-583.

Grande RB, Aaseth K, Benth JŠ, et al. Reduction in medication-overuse headache after short information. The Akershus study of chronic headache. Eur J Neurol. 2011;18(1):129-137.

Limmroth V, Katsarava Z, Fritsche G, et al. Features of medication overuse headache following overuse of different acute headache drugs. Neurology. 2002;59(7):1011-1014.

Pijpers JA, Louter MA, de Bruin ME, et al. Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure? Cephalalgia. 2016;36(2):122-130.

Rossi P, Di Lorenzo C, Faroni J, et al. Advice alone vs. structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs. Cephalalgia. 2006;26(9):1097-1105.

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

—Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

—Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

—Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

Multiaxial Assessment

All workups for headache evaluate frequency, intensity, duration, and disability. From a behavioral perspective, Dr. Baskin recommended considering a few more factors—adherence to therapy, stress-related issues, comorbid psychiatric disorders, and factors that transform migraine from episodic to chronic.

“When you talk about adherence, one of the basics of this is readiness to change,” said Dr. Baskin. “Is the patient motivated for treatment? That doesn’t necessarily happen immediately.” For example, a patient who is motivated to have an abortive agent might not be motivated to pursue prevention, lose weight, exercise, or make lifestyle changes. “Over time, that might change,” Dr. Baskin noted. Patient motivation may evolve with a greater understanding of the goals of treatment.

“Has the patient adhered to past therapy regimens? If the answer is no, then the answer will most likely be no again,” Dr. Baskin said. If medication overuse was a problem, it may be again. Whenever possible, ask open-ended questions, such as “how do you decide when to take an acute medication?” Dr. Baskin advised.

Stress and Migraine

High levels of daily stress, even daily stressors that are not catastrophic, can transform migraine from episodic to chronic. “Patients with depression show a greater effect of stress,” Dr. Baskin said. Similarly, victims of trauma or childhood maltreatment can have more disabling headaches that may be more likely to transform into daily headaches. “Many patients do not have the coping skills necessary to manage stress or recurrent headache,” Dr. Baskin said. One of the goals of behavioral therapy for migraine is to increase patients’ self-efficacy and give them the tools and the confidence to manage headaches and stressors.

Psychiatric Comorbidity

Psychiatric comorbidity may complicate differential diagnosis, and nonadherence to medication is greater in people with mood disorders and anxiety disorders. These patients may show a reduced response to pharmacologic and behavioral treatments for headache. Psychiatric comorbidities also can contribute to migraine chronification. “However, if you add a small behavioral component to your headache program, patients with psychiatric comorbidities seem to respond relatively well,” Dr. Baskin said.

Migraineurs have a two- to threefold greater prevalence of depression. There is a bidirectional relationship between migraine and depression in population studies. The relationship between migraine and depression is greater in clinic populations, in chronic migraine, and in medication overuse headache.

There is a significant relationship between migraine and anxiety disorders. Anxiety disorders entail a sense of danger, fear, or worry. “All patients with anxiety disorder have physical symptoms, and they often show avoidance behaviors,” said Dr. Baskin. For example, in generalized anxiety disorder, the object of avoidance is probably the fear of uncertainty. People worry excessively, thinking they are avoiding uncertainty. “Avoidance learning is huge in anxiety,” said Dr. Baskin. People fear unexpected events and perceive things as more unmanageable, dangerous, or threatening than they objectively are. “We see that frequently in migraineurs with anxiety disorders,” he said. Dr. Baskin noted that anxious patients tend to be sensitive to medication side effects and somatic sensations in general.

Patients with headache and anxiety often develop strong fear reactions. They identify a warning signal for headache, real or imagined, and may treat their fear, which they perceive as a headache prodrome, with a medication. “There is a preemptive strike with medicine treating a sensation that may or may not develop into headache,” Dr. Baskin said. That medication reduces their emotional distress and prevents the migraine, a powerful avoidance learning paradigm. That cycle can be a major part of medication overuse headache.

Anxiety disorders are much more prevalent than depression in migraineurs. They are associated with greater long-term persistence of headache, greater headache-related disability, and reduced satisfaction with acute therapy. “Across all emotional disorders, anxiety is the driver of distress,” Dr. Baskin said. “When you add anxiety to any disorder, it becomes much more problematic.”

The concept of interoceptive awareness—an individual’s sensitivity to bodily signals—is important in people with panic disorder. Like people with panic disorder, some migraineurs often have high interoceptive awareness. Anxiety sensitivity—fear that benign physical sensations will have harmful or catastrophic consequences—also may be a factor in panic disorder, as well as migraine. As in panic disorder, highly anxious migraineurs may develop hypervigilance to somatic sensations and conditioned fear to these internal sensations.

Dr. Baskin recommends screening patients for psychiatric comorbidity. He recommends two questions from the Patient Health Questionnaire-9 screener—“Do you have little interest or pleasure in doing things?” and “Are you feeling down, depressed, or hopeless?”—and two additional anxiety questions—“Are you feeling anxious, nervous, or on edge?” and “Are you unable to stop or control worrying?” “With just those four questions, you can capture a good number of people with anxiety or mood issues,” Dr. Baskin said.

Behavioral Therapy

“Our behavioral medicine program is time-limited and goal-oriented,” said Dr. Baskin. “We try to get people to develop self-efficacy and personal responsibility. We monitor and maximize adherence to medications and help patients to regulate their routine activities, including going to bed, getting up, and exercising on a consistent schedule. We offer biofeedback for self-regulation, relaxation and coping skills training utilizing a cognitive behavioral model, and we treat psychiatric issues,” said Dr. Baskin. Many of those things can be done by clinicians who are not behavioral clinicians, he said. “You do not necessarily have to refer all these people. Schedule frequent revisits for complicated or difficult patients. Do not overwhelm patients with too much information. Simplify jargon, provide written instructions, and make sure the patient understands the plan.”

An important component of behavioral treatment is teaching relaxation exercises, which can reduce muscle tension and autonomic arousal. There are many types of relaxation strategies. Dr. Baskin recommended breathing pacer apps, which are designed to encourage slower abdominal breathing. The goal is to gradually reduce the breathing rate to six breaths per minute for five- to 10-minute practice sessions. “If you can teach people diaphragmatic breathing—it takes about 30 seconds to begin the discussion—it is helpful.” Dr. Baskin recommended having patients do it three to five times per day for a few minutes at a time.

“We deliver relaxation training alone, sometimes with biofeedback, and teach it as a self-regulation coping skill. We try to get people to develop an internal locus of control so they can manage some of their own physiology, relax muscles, and learn a nonspecific low-arousal response and use it as a coping skill to apply in different situations,” Dr. Baskin said.

Cognitive behavioral therapy is another tool. It gives people an opportunity to modify distress-related thoughts and to examine their personal danger cognitions, their sense of threat, and the negative predictions that they may have. Dr. Baskin uses cognitive behavioral therapy to help patients develop an action plan based on their prescribed strategy to treat an acute migraine attack as well as manage concomitant emotional reactivity and maintain functionality in the presence of a significant headache disorder.

Trigger Management

Historically, migraineurs have avoided headache triggers. The down side to that strategy is that they can unnecessarily restrict themselves. Studies suggest that avoiding triggers may lead to sensitization to those triggers. Gradual exposure coping models are being developed. “Cope, do not avoid,” Dr. Baskin said.

Biofeedback

Relaxation training, EMG biofeedback, thermal biofeedback, and cognitive behavioral therapy show grade A but modest efficacy. There is recent evidence that combining behavioral therapy with preventive pharmacologic treatment improves outcomes. The behavioral section of the American Headache Society will soon be reviewing the most recent evidence on behavioral interventions in migraine.

Sleep Hygiene

Three main messages regarding sleep are to adopt a routine, consistent bedtime and wake up time, avoid all non–sleep-related activities at bedtime, and employ relaxation strategies to reduce sleep onset latency. In addition, patients should not eat or drink a lot of fluid too close to bedtime, not exercise in the evening, and avoid napping. A patient should be advised that if he or she cannot sleep, the best solution is to get out of bed, go to another room in the house, engage in a relaxing activity, and go back to bed when he or she gets tired. With these strategies, clinicians have converted chronic migraine to episodic migraine for a significant number of patients.

Combination Treatment of Migraine and Psychiatric Disorder

Many doctors support the idea that one drug should treat migraine and associated conditions whenever possible. The idea is to use one agent to treat migraine and associated conditions (“two-fer”) This strategy is simpler and may entail lower cost, fewer adverse events, and fewer potential drug interactions. “It makes sense on one level, however, there’s a risk of treating only one condition optimally or treating none of them optimally,” Dr. Baskin said. “It is important to treat both disorders the way you think they should be treated. Sometimes two drugs are better than one. You want to treat both conditions effectively.”

When treating anxiety disorders with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), prescribers should know that people with anxiety are exceptionally sensitive to side effects. Also, anxiety disorders often require higher doses than treating depression. “You should start dosing incredibly low and titrate slowly,” Dr. Baskin said.

—Glenn S. Williams

Multiaxial Assessment

All workups for headache evaluate frequency, intensity, duration, and disability. From a behavioral perspective, Dr. Baskin recommended considering a few more factors—adherence to therapy, stress-related issues, comorbid psychiatric disorders, and factors that transform migraine from episodic to chronic.

“When you talk about adherence, one of the basics of this is readiness to change,” said Dr. Baskin. “Is the patient motivated for treatment? That doesn’t necessarily happen immediately.” For example, a patient who is motivated to have an abortive agent might not be motivated to pursue prevention, lose weight, exercise, or make lifestyle changes. “Over time, that might change,” Dr. Baskin noted. Patient motivation may evolve with a greater understanding of the goals of treatment.

“Has the patient adhered to past therapy regimens? If the answer is no, then the answer will most likely be no again,” Dr. Baskin said. If medication overuse was a problem, it may be again. Whenever possible, ask open-ended questions, such as “how do you decide when to take an acute medication?” Dr. Baskin advised.

Stress and Migraine

High levels of daily stress, even daily stressors that are not catastrophic, can transform migraine from episodic to chronic. “Patients with depression show a greater effect of stress,” Dr. Baskin said. Similarly, victims of trauma or childhood maltreatment can have more disabling headaches that may be more likely to transform into daily headaches. “Many patients do not have the coping skills necessary to manage stress or recurrent headache,” Dr. Baskin said. One of the goals of behavioral therapy for migraine is to increase patients’ self-efficacy and give them the tools and the confidence to manage headaches and stressors.

Psychiatric Comorbidity

Psychiatric comorbidity may complicate differential diagnosis, and nonadherence to medication is greater in people with mood disorders and anxiety disorders. These patients may show a reduced response to pharmacologic and behavioral treatments for headache. Psychiatric comorbidities also can contribute to migraine chronification. “However, if you add a small behavioral component to your headache program, patients with psychiatric comorbidities seem to respond relatively well,” Dr. Baskin said.

Migraineurs have a two- to threefold greater prevalence of depression. There is a bidirectional relationship between migraine and depression in population studies. The relationship between migraine and depression is greater in clinic populations, in chronic migraine, and in medication overuse headache.

There is a significant relationship between migraine and anxiety disorders. Anxiety disorders entail a sense of danger, fear, or worry. “All patients with anxiety disorder have physical symptoms, and they often show avoidance behaviors,” said Dr. Baskin. For example, in generalized anxiety disorder, the object of avoidance is probably the fear of uncertainty. People worry excessively, thinking they are avoiding uncertainty. “Avoidance learning is huge in anxiety,” said Dr. Baskin. People fear unexpected events and perceive things as more unmanageable, dangerous, or threatening than they objectively are. “We see that frequently in migraineurs with anxiety disorders,” he said. Dr. Baskin noted that anxious patients tend to be sensitive to medication side effects and somatic sensations in general.

Patients with headache and anxiety often develop strong fear reactions. They identify a warning signal for headache, real or imagined, and may treat their fear, which they perceive as a headache prodrome, with a medication. “There is a preemptive strike with medicine treating a sensation that may or may not develop into headache,” Dr. Baskin said. That medication reduces their emotional distress and prevents the migraine, a powerful avoidance learning paradigm. That cycle can be a major part of medication overuse headache.

Anxiety disorders are much more prevalent than depression in migraineurs. They are associated with greater long-term persistence of headache, greater headache-related disability, and reduced satisfaction with acute therapy. “Across all emotional disorders, anxiety is the driver of distress,” Dr. Baskin said. “When you add anxiety to any disorder, it becomes much more problematic.”

The concept of interoceptive awareness—an individual’s sensitivity to bodily signals—is important in people with panic disorder. Like people with panic disorder, some migraineurs often have high interoceptive awareness. Anxiety sensitivity—fear that benign physical sensations will have harmful or catastrophic consequences—also may be a factor in panic disorder, as well as migraine. As in panic disorder, highly anxious migraineurs may develop hypervigilance to somatic sensations and conditioned fear to these internal sensations.

Dr. Baskin recommends screening patients for psychiatric comorbidity. He recommends two questions from the Patient Health Questionnaire-9 screener—“Do you have little interest or pleasure in doing things?” and “Are you feeling down, depressed, or hopeless?”—and two additional anxiety questions—“Are you feeling anxious, nervous, or on edge?” and “Are you unable to stop or control worrying?” “With just those four questions, you can capture a good number of people with anxiety or mood issues,” Dr. Baskin said.

Behavioral Therapy

“Our behavioral medicine program is time-limited and goal-oriented,” said Dr. Baskin. “We try to get people to develop self-efficacy and personal responsibility. We monitor and maximize adherence to medications and help patients to regulate their routine activities, including going to bed, getting up, and exercising on a consistent schedule. We offer biofeedback for self-regulation, relaxation and coping skills training utilizing a cognitive behavioral model, and we treat psychiatric issues,” said Dr. Baskin. Many of those things can be done by clinicians who are not behavioral clinicians, he said. “You do not necessarily have to refer all these people. Schedule frequent revisits for complicated or difficult patients. Do not overwhelm patients with too much information. Simplify jargon, provide written instructions, and make sure the patient understands the plan.”

An important component of behavioral treatment is teaching relaxation exercises, which can reduce muscle tension and autonomic arousal. There are many types of relaxation strategies. Dr. Baskin recommended breathing pacer apps, which are designed to encourage slower abdominal breathing. The goal is to gradually reduce the breathing rate to six breaths per minute for five- to 10-minute practice sessions. “If you can teach people diaphragmatic breathing—it takes about 30 seconds to begin the discussion—it is helpful.” Dr. Baskin recommended having patients do it three to five times per day for a few minutes at a time.

“We deliver relaxation training alone, sometimes with biofeedback, and teach it as a self-regulation coping skill. We try to get people to develop an internal locus of control so they can manage some of their own physiology, relax muscles, and learn a nonspecific low-arousal response and use it as a coping skill to apply in different situations,” Dr. Baskin said.

Cognitive behavioral therapy is another tool. It gives people an opportunity to modify distress-related thoughts and to examine their personal danger cognitions, their sense of threat, and the negative predictions that they may have. Dr. Baskin uses cognitive behavioral therapy to help patients develop an action plan based on their prescribed strategy to treat an acute migraine attack as well as manage concomitant emotional reactivity and maintain functionality in the presence of a significant headache disorder.

Trigger Management

Historically, migraineurs have avoided headache triggers. The down side to that strategy is that they can unnecessarily restrict themselves. Studies suggest that avoiding triggers may lead to sensitization to those triggers. Gradual exposure coping models are being developed. “Cope, do not avoid,” Dr. Baskin said.

Biofeedback

Relaxation training, EMG biofeedback, thermal biofeedback, and cognitive behavioral therapy show grade A but modest efficacy. There is recent evidence that combining behavioral therapy with preventive pharmacologic treatment improves outcomes. The behavioral section of the American Headache Society will soon be reviewing the most recent evidence on behavioral interventions in migraine.

Sleep Hygiene

Three main messages regarding sleep are to adopt a routine, consistent bedtime and wake up time, avoid all non–sleep-related activities at bedtime, and employ relaxation strategies to reduce sleep onset latency. In addition, patients should not eat or drink a lot of fluid too close to bedtime, not exercise in the evening, and avoid napping. A patient should be advised that if he or she cannot sleep, the best solution is to get out of bed, go to another room in the house, engage in a relaxing activity, and go back to bed when he or she gets tired. With these strategies, clinicians have converted chronic migraine to episodic migraine for a significant number of patients.

Combination Treatment of Migraine and Psychiatric Disorder

Many doctors support the idea that one drug should treat migraine and associated conditions whenever possible. The idea is to use one agent to treat migraine and associated conditions (“two-fer”) This strategy is simpler and may entail lower cost, fewer adverse events, and fewer potential drug interactions. “It makes sense on one level, however, there’s a risk of treating only one condition optimally or treating none of them optimally,” Dr. Baskin said. “It is important to treat both disorders the way you think they should be treated. Sometimes two drugs are better than one. You want to treat both conditions effectively.”

When treating anxiety disorders with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), prescribers should know that people with anxiety are exceptionally sensitive to side effects. Also, anxiety disorders often require higher doses than treating depression. “You should start dosing incredibly low and titrate slowly,” Dr. Baskin said.

—Glenn S. Williams

Multiaxial Assessment

All workups for headache evaluate frequency, intensity, duration, and disability. From a behavioral perspective, Dr. Baskin recommended considering a few more factors—adherence to therapy, stress-related issues, comorbid psychiatric disorders, and factors that transform migraine from episodic to chronic.

“When you talk about adherence, one of the basics of this is readiness to change,” said Dr. Baskin. “Is the patient motivated for treatment? That doesn’t necessarily happen immediately.” For example, a patient who is motivated to have an abortive agent might not be motivated to pursue prevention, lose weight, exercise, or make lifestyle changes. “Over time, that might change,” Dr. Baskin noted. Patient motivation may evolve with a greater understanding of the goals of treatment.

“Has the patient adhered to past therapy regimens? If the answer is no, then the answer will most likely be no again,” Dr. Baskin said. If medication overuse was a problem, it may be again. Whenever possible, ask open-ended questions, such as “how do you decide when to take an acute medication?” Dr. Baskin advised.

Stress and Migraine

High levels of daily stress, even daily stressors that are not catastrophic, can transform migraine from episodic to chronic. “Patients with depression show a greater effect of stress,” Dr. Baskin said. Similarly, victims of trauma or childhood maltreatment can have more disabling headaches that may be more likely to transform into daily headaches. “Many patients do not have the coping skills necessary to manage stress or recurrent headache,” Dr. Baskin said. One of the goals of behavioral therapy for migraine is to increase patients’ self-efficacy and give them the tools and the confidence to manage headaches and stressors.

Psychiatric Comorbidity

Psychiatric comorbidity may complicate differential diagnosis, and nonadherence to medication is greater in people with mood disorders and anxiety disorders. These patients may show a reduced response to pharmacologic and behavioral treatments for headache. Psychiatric comorbidities also can contribute to migraine chronification. “However, if you add a small behavioral component to your headache program, patients with psychiatric comorbidities seem to respond relatively well,” Dr. Baskin said.

Migraineurs have a two- to threefold greater prevalence of depression. There is a bidirectional relationship between migraine and depression in population studies. The relationship between migraine and depression is greater in clinic populations, in chronic migraine, and in medication overuse headache.

There is a significant relationship between migraine and anxiety disorders. Anxiety disorders entail a sense of danger, fear, or worry. “All patients with anxiety disorder have physical symptoms, and they often show avoidance behaviors,” said Dr. Baskin. For example, in generalized anxiety disorder, the object of avoidance is probably the fear of uncertainty. People worry excessively, thinking they are avoiding uncertainty. “Avoidance learning is huge in anxiety,” said Dr. Baskin. People fear unexpected events and perceive things as more unmanageable, dangerous, or threatening than they objectively are. “We see that frequently in migraineurs with anxiety disorders,” he said. Dr. Baskin noted that anxious patients tend to be sensitive to medication side effects and somatic sensations in general.

Patients with headache and anxiety often develop strong fear reactions. They identify a warning signal for headache, real or imagined, and may treat their fear, which they perceive as a headache prodrome, with a medication. “There is a preemptive strike with medicine treating a sensation that may or may not develop into headache,” Dr. Baskin said. That medication reduces their emotional distress and prevents the migraine, a powerful avoidance learning paradigm. That cycle can be a major part of medication overuse headache.

Anxiety disorders are much more prevalent than depression in migraineurs. They are associated with greater long-term persistence of headache, greater headache-related disability, and reduced satisfaction with acute therapy. “Across all emotional disorders, anxiety is the driver of distress,” Dr. Baskin said. “When you add anxiety to any disorder, it becomes much more problematic.”

The concept of interoceptive awareness—an individual’s sensitivity to bodily signals—is important in people with panic disorder. Like people with panic disorder, some migraineurs often have high interoceptive awareness. Anxiety sensitivity—fear that benign physical sensations will have harmful or catastrophic consequences—also may be a factor in panic disorder, as well as migraine. As in panic disorder, highly anxious migraineurs may develop hypervigilance to somatic sensations and conditioned fear to these internal sensations.

Dr. Baskin recommends screening patients for psychiatric comorbidity. He recommends two questions from the Patient Health Questionnaire-9 screener—“Do you have little interest or pleasure in doing things?” and “Are you feeling down, depressed, or hopeless?”—and two additional anxiety questions—“Are you feeling anxious, nervous, or on edge?” and “Are you unable to stop or control worrying?” “With just those four questions, you can capture a good number of people with anxiety or mood issues,” Dr. Baskin said.

Behavioral Therapy

“Our behavioral medicine program is time-limited and goal-oriented,” said Dr. Baskin. “We try to get people to develop self-efficacy and personal responsibility. We monitor and maximize adherence to medications and help patients to regulate their routine activities, including going to bed, getting up, and exercising on a consistent schedule. We offer biofeedback for self-regulation, relaxation and coping skills training utilizing a cognitive behavioral model, and we treat psychiatric issues,” said Dr. Baskin. Many of those things can be done by clinicians who are not behavioral clinicians, he said. “You do not necessarily have to refer all these people. Schedule frequent revisits for complicated or difficult patients. Do not overwhelm patients with too much information. Simplify jargon, provide written instructions, and make sure the patient understands the plan.”

An important component of behavioral treatment is teaching relaxation exercises, which can reduce muscle tension and autonomic arousal. There are many types of relaxation strategies. Dr. Baskin recommended breathing pacer apps, which are designed to encourage slower abdominal breathing. The goal is to gradually reduce the breathing rate to six breaths per minute for five- to 10-minute practice sessions. “If you can teach people diaphragmatic breathing—it takes about 30 seconds to begin the discussion—it is helpful.” Dr. Baskin recommended having patients do it three to five times per day for a few minutes at a time.

“We deliver relaxation training alone, sometimes with biofeedback, and teach it as a self-regulation coping skill. We try to get people to develop an internal locus of control so they can manage some of their own physiology, relax muscles, and learn a nonspecific low-arousal response and use it as a coping skill to apply in different situations,” Dr. Baskin said.

Cognitive behavioral therapy is another tool. It gives people an opportunity to modify distress-related thoughts and to examine their personal danger cognitions, their sense of threat, and the negative predictions that they may have. Dr. Baskin uses cognitive behavioral therapy to help patients develop an action plan based on their prescribed strategy to treat an acute migraine attack as well as manage concomitant emotional reactivity and maintain functionality in the presence of a significant headache disorder.

Trigger Management

Historically, migraineurs have avoided headache triggers. The down side to that strategy is that they can unnecessarily restrict themselves. Studies suggest that avoiding triggers may lead to sensitization to those triggers. Gradual exposure coping models are being developed. “Cope, do not avoid,” Dr. Baskin said.

Biofeedback

Relaxation training, EMG biofeedback, thermal biofeedback, and cognitive behavioral therapy show grade A but modest efficacy. There is recent evidence that combining behavioral therapy with preventive pharmacologic treatment improves outcomes. The behavioral section of the American Headache Society will soon be reviewing the most recent evidence on behavioral interventions in migraine.

Sleep Hygiene

Three main messages regarding sleep are to adopt a routine, consistent bedtime and wake up time, avoid all non–sleep-related activities at bedtime, and employ relaxation strategies to reduce sleep onset latency. In addition, patients should not eat or drink a lot of fluid too close to bedtime, not exercise in the evening, and avoid napping. A patient should be advised that if he or she cannot sleep, the best solution is to get out of bed, go to another room in the house, engage in a relaxing activity, and go back to bed when he or she gets tired. With these strategies, clinicians have converted chronic migraine to episodic migraine for a significant number of patients.

Combination Treatment of Migraine and Psychiatric Disorder

Many doctors support the idea that one drug should treat migraine and associated conditions whenever possible. The idea is to use one agent to treat migraine and associated conditions (“two-fer”) This strategy is simpler and may entail lower cost, fewer adverse events, and fewer potential drug interactions. “It makes sense on one level, however, there’s a risk of treating only one condition optimally or treating none of them optimally,” Dr. Baskin said. “It is important to treat both disorders the way you think they should be treated. Sometimes two drugs are better than one. You want to treat both conditions effectively.”

When treating anxiety disorders with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), prescribers should know that people with anxiety are exceptionally sensitive to side effects. Also, anxiety disorders often require higher doses than treating depression. “You should start dosing incredibly low and titrate slowly,” Dr. Baskin said.

—Glenn S. Williams

OJAI, CA—Spontaneous CSF leaks are treatable, often misdiagnosed, and can cause a neurologic syndrome that may include headache, nausea, and tinnitus. Spinal fluid leaks also can lead to serious complications, including seizures. Patients may have a CSF leak for years or decades before it is diagnosed.

Although CSF leaks may not be readily apparent on imaging, a suspected CSF leak is important to consider because it is fixable, said Dr. Carroll, Assistant Professor of Anesthesiology and Perioperative and Pain Medicine at Stanford University Medical Center in California and a member of the Stanford CSF leak program.

Postdural Puncture Headache Versus Spontaneous CSF Leaks

A spontaneous CSF leak and the clinical syndrome that it causes may be confused with a postdural puncture headache.

With a postdural puncture headache, a patient usually has a single leak site in the dorsal dura. “There is up to a 90% response to a single epidural blood patch. Its natural history is generally well understood and benign. It is rarely mysterious, and it is ultimately fixable,” said Dr. Carroll. In contrast, “a spontaneous CSF leak is often mysterious in terms of the onset, cause, and diagnosis.”

The natural history of CSF leaks is poorly understood. The percentage of patients whose spontaneous leaks seal on their own or whose leaks cause a catastrophe (eg, coma, seizures, or hematomas) is not known. Between 30% and 40% of patients with spontaneous leaks have leaks from multiple sites at diagnosis. “With a spontaneous leak a dural rent is more likely in the ventral dura, anterior to the spinal cord or at the nerve root, making the dura less amenable to patching. A single patch at the correct spinal level will fix the problem only 30% of the time. With multiple patches, the success rate can approach 65% to 75%.” If the first epidural blood patch fails, it should be repeated. Directed epidural blood patches, placement of fibrin sealant, and surgical treatment are other treatment options.

Headaches

Most patients with post-puncture CSF leaks have classic orthostatic headaches. The orthostatic headaches from spontaneous leaks are often atypical, however, in that patients may not feel better immediately when they lie down and worse when they stand, Dr. Carroll said. Headaches may occur late in the day after prolonged upright time or with exertion. In addition, patients may “go from having an orthostatic headache to having a terrible headache all the time, regardless of what position they are in.”

Nausea and Vomiting

Nausea and vomiting can be the main symptom of a CSF leak. Dr. Carroll described a patient with complex regional pain syndrome who underwent a spinal cord stimulation trial. Afterward, she had a postdural puncture headache and received an epidural blood patch. “After that, she developed vomiting up to nine times a day.” A CSF leak was not visible on the first CT myelogram but was apparent on the second. The leak was “so small it was missed by the slice thickness” of the first CT myelogram, said Dr. Carroll. She ultimately required surgery to fix the leak. The patient improved, although she continued vomiting three times per day.

Tinnitus

CSF leaks may cause tinnitus. “You can get ringing in the ears when you have migraine,” Dr. Carroll said. But if patients have tinnitus when they are not having headaches, “you should be thinking that there is something else going on.” Data suggest that CSF fluid is connected to inner ear fluid so a change of pressure in CSF changes inner ear pressure, and patients with high or low CSF pressure may get tinnitus.

Other symptoms may include neck pain and fatigue. “I have had the parents of patients tell me that the most remarkable thing that they see when we patch their sons or daughters is how they are bouncing around the house,” he said. Many patients complain of difficulty with concentrating, task persistence, and other nondescript, nonfocal neurologic symptoms.

Imaging Limitations

Imaging of patients with CSF leaks often initially is read as normal, and MRI is not an adequate evaluation in the high clinical suspicion of a leak, Dr. Carroll said. “It is a good place to start, because if you see a leak on your MRI, maybe you do not have to get a CT myelogram,” he said. “But if you have a clinical suspicion of a leak … you should pursue that in the face of your radiologist telling you that there is nothing.”

Schievink et al in 2007 looked at several years of data from an emergency department to assess how often imaging findings consistent with CSF leaks were missed. They reviewed MRIs of patients with headache to look for evidence of intracranial hypotension, and then compared the number of CSF leaks with the number of subarachnoid hemorrhages seen during the same time. They found that for every subarachnoid hemorrhage, there were approximately 0.5 CSF leaks (23 subarachnoid hemorrhages and 11 CSF leaks). The results suggested that spontaneous intracranial hypotension is more common than previously thought and its diagnosis in emergency departments is problematic. The 11 people with MRI evidence of intracranial hypotension subsequently were diagnosed with CSF leaks and treated.  None were diagnosed at the time of the MRI while in the emergency department.

Causes of Leaks

The four main causes of CSF leaks are medical procedures; whiplash; bony, sharp calcifications penetrating the dura; and genetic disorders of connective tissue.

Webb et al conducted a study to evaluate headaches in patients who had a known wet tap (ie, unintentional dural puncture) after a labor epidural. The researchers reviewed quality assurance data in an obstetrics anesthesia division and identified 40 patients who had known wet taps and 40 controls who had received an epidural without a wet tap during the same week and were matched for age and weight. Investigators contacted patients between 12 and 24 months later (mean, 18 months) and asked them about the incidence of chronic headache. The incidence of chronic headache in controls was 5% versus nearly 30% in patients who had had a wet tap. The investigators then compared patients who were managed conservatively (ie, they did not receive an epidural blood patch) versus patients who were managed with a blood patch. “If you got a blood patch, your risk of having a chronic headache 18 months later was only half as much as if you did not get a blood patch,” he said.

Connective Tissue Disorders and Calcifications

Because connective tissue disorders are associated with CSF leaks, headache physicians should determine patients’ Beighton Hypermobility Scores, Dr. Carroll said. The score is derived from a simple test that assesses joint hypermobility. For instance, patients receive a point if they can touch their thumb to their wrist or straighten their elbow more than 10° beyond 180°. A score between 3 and 5 raises suspicion that the patient might have a hereditary disorder of connective tissue. Cataracts at an early age, being unusually tall or short, degenerative disc disease, and history of aneurysm also are associated with an increased risk of CSF leaks.

With regard to calcifications, Dr. Carroll described a patient whose main complaint was confusion upon standing too long. The patient also had neck pain. They determined that he had a calcified bone spur that was puncturing the spinal cord, causing a leak.

Whiplash

Trauma and whiplash can cause leaks. Researchers in Japan studied 66 patients with chronic whiplash-associated disorders (ie, they had a whiplash accident and complained of neck and head pain, as well as difficulty with fatigue or memory). The patients were given a radionuclide cisternogram. Thirty-seven of the 66 patients had imaging that was positive for a CSF leak. “After being patched, roughly half the people who were found to have a leak went back to work, whereas they had not been working before,” he said. Another study found that 10% of people with brachial plexus injuries have spinal fluid leaks.

Overlap With POTS

The fact that Ehlers-Danlos also is associated with postural orthostatic tachycardia syndrome (POTS) raises the possibility that patients with CSF leaks may be misdiagnosed as having POTS.

“Why should a hereditary disorder of connective tissue be associated with the only two known conditions that are associated with feeling worse when you are up?” Dr. Carroll asked. Among patients with POTS, 60% have headaches, and many have dizziness and nausea. Dr. Carroll asked the POTS clinics at Stanford to refer patients with POTS, headache, and Ehlers-Danlos syndrome to him. The first referred patient’s history was consistent with a CSF leak. She had been passing out and had severe headaches for more than 10 years. Although her initial imaging was read as negative for CSF leaks, and an MRI showed no signs of intracranial hypotension, “when we patched her, in fact, she got better.” Subsequently, more patients diagnosed with POTS have been referred to the CSF leak program.

Patients initially may be diagnosed as having chronic fatigue syndrome, fibromyalgia, or irritable bowel syndrome when a CSF leak is causing their symptoms. It is a tragedy when patients “have a fixable leak and … nothing is done to treat that underlying problem,” Dr. Carroll said.

—Jake Remaly

Suggested Reading

Ishikawa S, Yokoyama M, Mizobuchi S, et al. Epidural blood patch therapy for chronic whiplash-associated disorder. Anesth Analg. 2007;105(3):809-814.

Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295(19):2286-2296.

Schievink WI, Maya MM, Moser F, et al. Frequency of spontaneous intracranial hypotension in the emergency department. J Headache Pain. 2007;8(6):325-328.

Webb CA, Weyker PD, Zhang L, et al. Unintentional dural puncture with a Tuohy needle increases risk of chronic headache. Anesth Analg. 2012;115(1):124-132.

OJAI, CA—Spontaneous CSF leaks are treatable, often misdiagnosed, and can cause a neurologic syndrome that may include headache, nausea, and tinnitus. Spinal fluid leaks also can lead to serious complications, including seizures. Patients may have a CSF leak for years or decades before it is diagnosed.

Although CSF leaks may not be readily apparent on imaging, a suspected CSF leak is important to consider because it is fixable, said Dr. Carroll, Assistant Professor of Anesthesiology and Perioperative and Pain Medicine at Stanford University Medical Center in California and a member of the Stanford CSF leak program.

Postdural Puncture Headache Versus Spontaneous CSF Leaks

A spontaneous CSF leak and the clinical syndrome that it causes may be confused with a postdural puncture headache.

With a postdural puncture headache, a patient usually has a single leak site in the dorsal dura. “There is up to a 90% response to a single epidural blood patch. Its natural history is generally well understood and benign. It is rarely mysterious, and it is ultimately fixable,” said Dr. Carroll. In contrast, “a spontaneous CSF leak is often mysterious in terms of the onset, cause, and diagnosis.”

The natural history of CSF leaks is poorly understood. The percentage of patients whose spontaneous leaks seal on their own or whose leaks cause a catastrophe (eg, coma, seizures, or hematomas) is not known. Between 30% and 40% of patients with spontaneous leaks have leaks from multiple sites at diagnosis. “With a spontaneous leak a dural rent is more likely in the ventral dura, anterior to the spinal cord or at the nerve root, making the dura less amenable to patching. A single patch at the correct spinal level will fix the problem only 30% of the time. With multiple patches, the success rate can approach 65% to 75%.” If the first epidural blood patch fails, it should be repeated. Directed epidural blood patches, placement of fibrin sealant, and surgical treatment are other treatment options.

Headaches

Most patients with post-puncture CSF leaks have classic orthostatic headaches. The orthostatic headaches from spontaneous leaks are often atypical, however, in that patients may not feel better immediately when they lie down and worse when they stand, Dr. Carroll said. Headaches may occur late in the day after prolonged upright time or with exertion. In addition, patients may “go from having an orthostatic headache to having a terrible headache all the time, regardless of what position they are in.”

Nausea and Vomiting

Nausea and vomiting can be the main symptom of a CSF leak. Dr. Carroll described a patient with complex regional pain syndrome who underwent a spinal cord stimulation trial. Afterward, she had a postdural puncture headache and received an epidural blood patch. “After that, she developed vomiting up to nine times a day.” A CSF leak was not visible on the first CT myelogram but was apparent on the second. The leak was “so small it was missed by the slice thickness” of the first CT myelogram, said Dr. Carroll. She ultimately required surgery to fix the leak. The patient improved, although she continued vomiting three times per day.

Tinnitus

CSF leaks may cause tinnitus. “You can get ringing in the ears when you have migraine,” Dr. Carroll said. But if patients have tinnitus when they are not having headaches, “you should be thinking that there is something else going on.” Data suggest that CSF fluid is connected to inner ear fluid so a change of pressure in CSF changes inner ear pressure, and patients with high or low CSF pressure may get tinnitus.

Other symptoms may include neck pain and fatigue. “I have had the parents of patients tell me that the most remarkable thing that they see when we patch their sons or daughters is how they are bouncing around the house,” he said. Many patients complain of difficulty with concentrating, task persistence, and other nondescript, nonfocal neurologic symptoms.

Imaging Limitations

Imaging of patients with CSF leaks often initially is read as normal, and MRI is not an adequate evaluation in the high clinical suspicion of a leak, Dr. Carroll said. “It is a good place to start, because if you see a leak on your MRI, maybe you do not have to get a CT myelogram,” he said. “But if you have a clinical suspicion of a leak … you should pursue that in the face of your radiologist telling you that there is nothing.”

Schievink et al in 2007 looked at several years of data from an emergency department to assess how often imaging findings consistent with CSF leaks were missed. They reviewed MRIs of patients with headache to look for evidence of intracranial hypotension, and then compared the number of CSF leaks with the number of subarachnoid hemorrhages seen during the same time. They found that for every subarachnoid hemorrhage, there were approximately 0.5 CSF leaks (23 subarachnoid hemorrhages and 11 CSF leaks). The results suggested that spontaneous intracranial hypotension is more common than previously thought and its diagnosis in emergency departments is problematic. The 11 people with MRI evidence of intracranial hypotension subsequently were diagnosed with CSF leaks and treated.  None were diagnosed at the time of the MRI while in the emergency department.

Causes of Leaks

The four main causes of CSF leaks are medical procedures; whiplash; bony, sharp calcifications penetrating the dura; and genetic disorders of connective tissue.

Webb et al conducted a study to evaluate headaches in patients who had a known wet tap (ie, unintentional dural puncture) after a labor epidural. The researchers reviewed quality assurance data in an obstetrics anesthesia division and identified 40 patients who had known wet taps and 40 controls who had received an epidural without a wet tap during the same week and were matched for age and weight. Investigators contacted patients between 12 and 24 months later (mean, 18 months) and asked them about the incidence of chronic headache. The incidence of chronic headache in controls was 5% versus nearly 30% in patients who had had a wet tap. The investigators then compared patients who were managed conservatively (ie, they did not receive an epidural blood patch) versus patients who were managed with a blood patch. “If you got a blood patch, your risk of having a chronic headache 18 months later was only half as much as if you did not get a blood patch,” he said.

Connective Tissue Disorders and Calcifications

Because connective tissue disorders are associated with CSF leaks, headache physicians should determine patients’ Beighton Hypermobility Scores, Dr. Carroll said. The score is derived from a simple test that assesses joint hypermobility. For instance, patients receive a point if they can touch their thumb to their wrist or straighten their elbow more than 10° beyond 180°. A score between 3 and 5 raises suspicion that the patient might have a hereditary disorder of connective tissue. Cataracts at an early age, being unusually tall or short, degenerative disc disease, and history of aneurysm also are associated with an increased risk of CSF leaks.

With regard to calcifications, Dr. Carroll described a patient whose main complaint was confusion upon standing too long. The patient also had neck pain. They determined that he had a calcified bone spur that was puncturing the spinal cord, causing a leak.

Whiplash

Trauma and whiplash can cause leaks. Researchers in Japan studied 66 patients with chronic whiplash-associated disorders (ie, they had a whiplash accident and complained of neck and head pain, as well as difficulty with fatigue or memory). The patients were given a radionuclide cisternogram. Thirty-seven of the 66 patients had imaging that was positive for a CSF leak. “After being patched, roughly half the people who were found to have a leak went back to work, whereas they had not been working before,” he said. Another study found that 10% of people with brachial plexus injuries have spinal fluid leaks.

Overlap With POTS

The fact that Ehlers-Danlos also is associated with postural orthostatic tachycardia syndrome (POTS) raises the possibility that patients with CSF leaks may be misdiagnosed as having POTS.

“Why should a hereditary disorder of connective tissue be associated with the only two known conditions that are associated with feeling worse when you are up?” Dr. Carroll asked. Among patients with POTS, 60% have headaches, and many have dizziness and nausea. Dr. Carroll asked the POTS clinics at Stanford to refer patients with POTS, headache, and Ehlers-Danlos syndrome to him. The first referred patient’s history was consistent with a CSF leak. She had been passing out and had severe headaches for more than 10 years. Although her initial imaging was read as negative for CSF leaks, and an MRI showed no signs of intracranial hypotension, “when we patched her, in fact, she got better.” Subsequently, more patients diagnosed with POTS have been referred to the CSF leak program.

Patients initially may be diagnosed as having chronic fatigue syndrome, fibromyalgia, or irritable bowel syndrome when a CSF leak is causing their symptoms. It is a tragedy when patients “have a fixable leak and … nothing is done to treat that underlying problem,” Dr. Carroll said.

—Jake Remaly

Suggested Reading

Ishikawa S, Yokoyama M, Mizobuchi S, et al. Epidural blood patch therapy for chronic whiplash-associated disorder. Anesth Analg. 2007;105(3):809-814.

Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295(19):2286-2296.

Schievink WI, Maya MM, Moser F, et al. Frequency of spontaneous intracranial hypotension in the emergency department. J Headache Pain. 2007;8(6):325-328.

Webb CA, Weyker PD, Zhang L, et al. Unintentional dural puncture with a Tuohy needle increases risk of chronic headache. Anesth Analg. 2012;115(1):124-132.

OJAI, CA—Spontaneous CSF leaks are treatable, often misdiagnosed, and can cause a neurologic syndrome that may include headache, nausea, and tinnitus. Spinal fluid leaks also can lead to serious complications, including seizures. Patients may have a CSF leak for years or decades before it is diagnosed.

Although CSF leaks may not be readily apparent on imaging, a suspected CSF leak is important to consider because it is fixable, said Dr. Carroll, Assistant Professor of Anesthesiology and Perioperative and Pain Medicine at Stanford University Medical Center in California and a member of the Stanford CSF leak program.

Postdural Puncture Headache Versus Spontaneous CSF Leaks

A spontaneous CSF leak and the clinical syndrome that it causes may be confused with a postdural puncture headache.

With a postdural puncture headache, a patient usually has a single leak site in the dorsal dura. “There is up to a 90% response to a single epidural blood patch. Its natural history is generally well understood and benign. It is rarely mysterious, and it is ultimately fixable,” said Dr. Carroll. In contrast, “a spontaneous CSF leak is often mysterious in terms of the onset, cause, and diagnosis.”

The natural history of CSF leaks is poorly understood. The percentage of patients whose spontaneous leaks seal on their own or whose leaks cause a catastrophe (eg, coma, seizures, or hematomas) is not known. Between 30% and 40% of patients with spontaneous leaks have leaks from multiple sites at diagnosis. “With a spontaneous leak a dural rent is more likely in the ventral dura, anterior to the spinal cord or at the nerve root, making the dura less amenable to patching. A single patch at the correct spinal level will fix the problem only 30% of the time. With multiple patches, the success rate can approach 65% to 75%.” If the first epidural blood patch fails, it should be repeated. Directed epidural blood patches, placement of fibrin sealant, and surgical treatment are other treatment options.

Headaches

Most patients with post-puncture CSF leaks have classic orthostatic headaches. The orthostatic headaches from spontaneous leaks are often atypical, however, in that patients may not feel better immediately when they lie down and worse when they stand, Dr. Carroll said. Headaches may occur late in the day after prolonged upright time or with exertion. In addition, patients may “go from having an orthostatic headache to having a terrible headache all the time, regardless of what position they are in.”

Nausea and Vomiting

Nausea and vomiting can be the main symptom of a CSF leak. Dr. Carroll described a patient with complex regional pain syndrome who underwent a spinal cord stimulation trial. Afterward, she had a postdural puncture headache and received an epidural blood patch. “After that, she developed vomiting up to nine times a day.” A CSF leak was not visible on the first CT myelogram but was apparent on the second. The leak was “so small it was missed by the slice thickness” of the first CT myelogram, said Dr. Carroll. She ultimately required surgery to fix the leak. The patient improved, although she continued vomiting three times per day.

Tinnitus

CSF leaks may cause tinnitus. “You can get ringing in the ears when you have migraine,” Dr. Carroll said. But if patients have tinnitus when they are not having headaches, “you should be thinking that there is something else going on.” Data suggest that CSF fluid is connected to inner ear fluid so a change of pressure in CSF changes inner ear pressure, and patients with high or low CSF pressure may get tinnitus.

Other symptoms may include neck pain and fatigue. “I have had the parents of patients tell me that the most remarkable thing that they see when we patch their sons or daughters is how they are bouncing around the house,” he said. Many patients complain of difficulty with concentrating, task persistence, and other nondescript, nonfocal neurologic symptoms.

Imaging Limitations

Imaging of patients with CSF leaks often initially is read as normal, and MRI is not an adequate evaluation in the high clinical suspicion of a leak, Dr. Carroll said. “It is a good place to start, because if you see a leak on your MRI, maybe you do not have to get a CT myelogram,” he said. “But if you have a clinical suspicion of a leak … you should pursue that in the face of your radiologist telling you that there is nothing.”

Schievink et al in 2007 looked at several years of data from an emergency department to assess how often imaging findings consistent with CSF leaks were missed. They reviewed MRIs of patients with headache to look for evidence of intracranial hypotension, and then compared the number of CSF leaks with the number of subarachnoid hemorrhages seen during the same time. They found that for every subarachnoid hemorrhage, there were approximately 0.5 CSF leaks (23 subarachnoid hemorrhages and 11 CSF leaks). The results suggested that spontaneous intracranial hypotension is more common than previously thought and its diagnosis in emergency departments is problematic. The 11 people with MRI evidence of intracranial hypotension subsequently were diagnosed with CSF leaks and treated.  None were diagnosed at the time of the MRI while in the emergency department.

Causes of Leaks

The four main causes of CSF leaks are medical procedures; whiplash; bony, sharp calcifications penetrating the dura; and genetic disorders of connective tissue.

Webb et al conducted a study to evaluate headaches in patients who had a known wet tap (ie, unintentional dural puncture) after a labor epidural. The researchers reviewed quality assurance data in an obstetrics anesthesia division and identified 40 patients who had known wet taps and 40 controls who had received an epidural without a wet tap during the same week and were matched for age and weight. Investigators contacted patients between 12 and 24 months later (mean, 18 months) and asked them about the incidence of chronic headache. The incidence of chronic headache in controls was 5% versus nearly 30% in patients who had had a wet tap. The investigators then compared patients who were managed conservatively (ie, they did not receive an epidural blood patch) versus patients who were managed with a blood patch. “If you got a blood patch, your risk of having a chronic headache 18 months later was only half as much as if you did not get a blood patch,” he said.

Connective Tissue Disorders and Calcifications

Because connective tissue disorders are associated with CSF leaks, headache physicians should determine patients’ Beighton Hypermobility Scores, Dr. Carroll said. The score is derived from a simple test that assesses joint hypermobility. For instance, patients receive a point if they can touch their thumb to their wrist or straighten their elbow more than 10° beyond 180°. A score between 3 and 5 raises suspicion that the patient might have a hereditary disorder of connective tissue. Cataracts at an early age, being unusually tall or short, degenerative disc disease, and history of aneurysm also are associated with an increased risk of CSF leaks.

With regard to calcifications, Dr. Carroll described a patient whose main complaint was confusion upon standing too long. The patient also had neck pain. They determined that he had a calcified bone spur that was puncturing the spinal cord, causing a leak.

Whiplash

Trauma and whiplash can cause leaks. Researchers in Japan studied 66 patients with chronic whiplash-associated disorders (ie, they had a whiplash accident and complained of neck and head pain, as well as difficulty with fatigue or memory). The patients were given a radionuclide cisternogram. Thirty-seven of the 66 patients had imaging that was positive for a CSF leak. “After being patched, roughly half the people who were found to have a leak went back to work, whereas they had not been working before,” he said. Another study found that 10% of people with brachial plexus injuries have spinal fluid leaks.

Overlap With POTS

The fact that Ehlers-Danlos also is associated with postural orthostatic tachycardia syndrome (POTS) raises the possibility that patients with CSF leaks may be misdiagnosed as having POTS.

“Why should a hereditary disorder of connective tissue be associated with the only two known conditions that are associated with feeling worse when you are up?” Dr. Carroll asked. Among patients with POTS, 60% have headaches, and many have dizziness and nausea. Dr. Carroll asked the POTS clinics at Stanford to refer patients with POTS, headache, and Ehlers-Danlos syndrome to him. The first referred patient’s history was consistent with a CSF leak. She had been passing out and had severe headaches for more than 10 years. Although her initial imaging was read as negative for CSF leaks, and an MRI showed no signs of intracranial hypotension, “when we patched her, in fact, she got better.” Subsequently, more patients diagnosed with POTS have been referred to the CSF leak program.

Patients initially may be diagnosed as having chronic fatigue syndrome, fibromyalgia, or irritable bowel syndrome when a CSF leak is causing their symptoms. It is a tragedy when patients “have a fixable leak and … nothing is done to treat that underlying problem,” Dr. Carroll said.

—Jake Remaly

Suggested Reading

Ishikawa S, Yokoyama M, Mizobuchi S, et al. Epidural blood patch therapy for chronic whiplash-associated disorder. Anesth Analg. 2007;105(3):809-814.

Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295(19):2286-2296.

Schievink WI, Maya MM, Moser F, et al. Frequency of spontaneous intracranial hypotension in the emergency department. J Headache Pain. 2007;8(6):325-328.

Webb CA, Weyker PD, Zhang L, et al. Unintentional dural puncture with a Tuohy needle increases risk of chronic headache. Anesth Analg. 2012;115(1):124-132.

Vertigo is a normal response to certain stimuli, such as looking down from heights and abnormal head movements. In addition, any dysfunction along the pathway that processes balance and gravity information (eg, the semicircular canals, acoustic nerve, and brainstem vestibular centers) can cause vertigo.

Migraine is significantly more common in patients with vertigo, and vertigo is significantly more common in migraineurs than in the general population. In addition, migraineurs are predisposed to motion sickness, which often includes vertigo. Migraineurs’ vestibular systems are more sensitive to stimuli than those of nonmigraine controls, and migraineurs experience vestibular stimulation as more unpleasant and more likely to cause emesis, compared with nonmigraine controls, Dr. Levin said.

The reasons for these correlations are unknown. It may be that heightened vestibular sensitivity in migraine is due to migraineurs perceiving all stimuli more intensely, or migraineurs may be more keenly aware of early signs of vestibulopathy. Vertigo may be a migraine trigger, or a subset of patients may have a type of migraine that includes vertigo as a key symptom, he said. This last possibility is the so-called vestibular migraine.

Recognizing Vestibular Migraine

Vestibular migraine, which also has been known as migraine-associated vertigo, migraine-associated dizziness, and migraine-associated vestibulopathy, has been difficult to define. The current generally accepted definition requires two basic diagnostic criteria: current or previous history of migraine and migraine features (eg, headache, photophobia, phonophobia, or visual aura) with at least half of the spells of vertigo.

Vestibular migraine is estimated to affect about 1% of the general population, 7% of patients at dizziness clinics, and 9% of patients at headache centers.

The duration of vertigo in vestibular migraine varies. About a third of the episodes last for minutes, a third for hours, and a third for days. Vertigo can occur between migraine attacks, prior to them, during, or after, and it tends to be spontaneous. Vestibular migraine is common in children and more common in women than in men. It generally arises years after migraines begin.

Unsteadiness and balance problems are common in vestibular migraine, and audiologic disturbances occur in a minority of patients. Migraine with brainstem aura (formerly called basilar migraine) can include vertigo, but the diagnosis also requires at least one other brainstem symptom (eg, tinnitus or dysarthria).

Evaluating Patients

When seeing patients, neurologists’ first step might be to try to distinguish between vertigo and other similar symptoms, such as presyncope, disorientation, or disequilibrium. “A sense of motion is the best indication of vertigo, though even that might be lacking,” Dr. Levin said.

Neurologists can determine whether position triggers vertigo and identify evidence of peripheral biologic problems (eg, tinnitus, changes in vision, or other focal neurologic signs and symptoms). Family history of migraine in people with episodic vertigo may be a clue that the patient has vestibular migraine versus other causes of vertigo, Dr. Levin said. A history of syncope or other signs may suggest that a patient’s symptoms are related to light-headedness instead of vertigo. Psychiatric illness, time course, drug exposure, and stroke or stroke risk factors also should be considered.

Diagnostic tests may help neurologists distinguish between vestibular migraine and other causes of vertigo. Audiograms can assess for hearing loss, and MRIs may rule out masses or other lesions. Brainstem auditory evoked responses, electronystagmography (ENG), and videonystagmography (VNG), which typically includes saccade, tracking, positional, and caloric testing, also can be useful.

Similar Conditions

One diagnostic entity that can be mistaken for vestibular migraine is mal de debarquement, which is marked by a persistent feeling of vertigo after a cruise or other motion experience. Patients with this condition also may experience symptoms such as blurred vision, inability to focus, cognitive changes, headaches, nausea, feelings of pressure, and trouble sleeping. “It can actually start sounding like migraine,” Dr. Levin said. “Strangely enough, patients may not mention their disembarkation from a trip. …You have to sometimes draw it out.”

Vestibular testing is normal in these patients, and oddly, they often feel better when they ride in a car or otherwise experience motion. Migraine treatment does not work for these patients. Benzodiazepines may help, but patients may become tolerant. Mal de debarquement tends to dampen and resolve in many patients.

Other causes of vertigo include Meniere’s disease, benign paroxysmal positional vertigo, meningeal infection or inflammation, labyrinthine or brainstem ischemia, perilymph fistula, and benign positional vertigo of childhood.

In the end, some diagnostic entities may be part of a spectrum, Dr. Levin said. Thirty-eight percent of vestibular migraines have auditory symptoms as in Meniere’s disease, and the prevalence of migraine in patients with Meniere’s disease is twice that of the general population. Many patients fit diagnostic criteria for vestibular migraine and Meniere’s disease.

The pathophysiology of vestibular migraine is unknown. Connections between vestibular nuclei in the brainstem and the trigeminal nuclei may underlie the condition. Vestibular and trigeminal nociceptive pathways may be activated in parallel. Alternatively, structural brain lesions in the temporal lobes or elsewhere may cause vestibular migraine.

Like other migraine auras, vestibular migraine may be a manifestation of focal or generalized cortical spreading depression. “There are cortical centers for vertigo,” Dr. Levin said. When these cortical centers are affected in patients with epilepsy, patients may experience “tornado seizures,” he said.

Treatment Approaches

Some studies suggest that migraine treatments might help patients with vestibular migraine. Zolmitriptan and rizatriptan at the time of vertigo have been tried, with some suggestion that they may provide benefit.

The best evidence for pharmacologic prevention exists for flunarizine, propranolol, and lamotrigine. Other trials suggest that vestibular rehabilitation and combined caffeine cessation, nortriptyline, and topiramate may be effective.

Limitations of trials in vestibular migraine have included small numbers of patients, noncontrolled designs, and inconsistent definitions of vestibular migraine. In addition, case reports have suggested that benzodiazepines, cinnarizine, selective serotonin reuptake inhibitors, pizotifen, dothiepin, acetazolamide, and behavioral modification may benefit patients. Investigators are enrolling patients in a double-blind, placebo-controlled trial that will evaluate the use of metoprolol for the preventive treatment of vestibular migraine.

If occurrences of vertigo are infrequent, symptomatic vertigo treatments are Dr. Levin’s first choice. “I have had good luck with scopolamine, for example,” he said. Dopamine antagonists, neuroleptics, sedatives, and benzodiazepines are also useful symptomatic treatments for vertigo. The Epley maneuver and other canalith repositioning maneuvers may benefit some patients. For acute treatment, it makes sense to try a triptan, Dr. Levin said. “Sometimes it does work. Other times it does not, and you have to resort to symptomatic medication,” he said.

—Jake Remaly

Suggested Reading

Akdal G, Ozge A, Ergör G. The prevalence of vestibular symptoms in migraine or tension-type headache. J Vestib Res. 2013;23(2):101-106.

Dieterich M, Brandt T. Episodic vertigo related to migraine (90 cases): vestibular migraine? J Neurol. 1999;246(10):883-892.

Dieterich M, Obermann M, Celebisoy N. Vestibular migraine: the most frequent entity of episodic vertigo. J Neurol. 2016;263 Suppl 1:S82-89.

Furman JM, Marcus DA, Balaban CD. Vestibular migraine: clinical aspects and pathophysiology. Lancet Neurol. 2013;12(7):706-715.

Lepcha A, Amalanathan S, Augustine AM, et al. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol. 2014;271(11):2931-2936.

Mikulec AA, Faraji F, Kinsella LJ. Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology. Am J Otolaryngol. 2012;33(1):121-127.

Murdin L, Davies RA, Bronstein AM. Vertigo as a migraine trigger. Neurology. 2009;73(8):638-642.

Neuhauser HK, Radtke A, von Brevern M, et al. Migrainous vertigo: prevalence and impact on quality of life. Neurology. 2006;67(6):1028-1033.

Salviz M, Yuce T, Acar H, et al. Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope. 2016;126(1):169-174.

Van Ombergen A, Van Rompaey V, Van de Heyning P, Wuyts F. Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness. Otol Neurotol. 2015;36(1):133-138.

Vitkovic J, Winoto A, Rance G, et al. Vestibular rehabilitation outcomes in patients with and without vestibular migraine. J Neurol. 2013;260(12):3039-3048.

Vertigo is a normal response to certain stimuli, such as looking down from heights and abnormal head movements. In addition, any dysfunction along the pathway that processes balance and gravity information (eg, the semicircular canals, acoustic nerve, and brainstem vestibular centers) can cause vertigo.

Migraine is significantly more common in patients with vertigo, and vertigo is significantly more common in migraineurs than in the general population. In addition, migraineurs are predisposed to motion sickness, which often includes vertigo. Migraineurs’ vestibular systems are more sensitive to stimuli than those of nonmigraine controls, and migraineurs experience vestibular stimulation as more unpleasant and more likely to cause emesis, compared with nonmigraine controls, Dr. Levin said.

The reasons for these correlations are unknown. It may be that heightened vestibular sensitivity in migraine is due to migraineurs perceiving all stimuli more intensely, or migraineurs may be more keenly aware of early signs of vestibulopathy. Vertigo may be a migraine trigger, or a subset of patients may have a type of migraine that includes vertigo as a key symptom, he said. This last possibility is the so-called vestibular migraine.

Recognizing Vestibular Migraine

Vestibular migraine, which also has been known as migraine-associated vertigo, migraine-associated dizziness, and migraine-associated vestibulopathy, has been difficult to define. The current generally accepted definition requires two basic diagnostic criteria: current or previous history of migraine and migraine features (eg, headache, photophobia, phonophobia, or visual aura) with at least half of the spells of vertigo.

Vestibular migraine is estimated to affect about 1% of the general population, 7% of patients at dizziness clinics, and 9% of patients at headache centers.

The duration of vertigo in vestibular migraine varies. About a third of the episodes last for minutes, a third for hours, and a third for days. Vertigo can occur between migraine attacks, prior to them, during, or after, and it tends to be spontaneous. Vestibular migraine is common in children and more common in women than in men. It generally arises years after migraines begin.

Unsteadiness and balance problems are common in vestibular migraine, and audiologic disturbances occur in a minority of patients. Migraine with brainstem aura (formerly called basilar migraine) can include vertigo, but the diagnosis also requires at least one other brainstem symptom (eg, tinnitus or dysarthria).

Evaluating Patients

When seeing patients, neurologists’ first step might be to try to distinguish between vertigo and other similar symptoms, such as presyncope, disorientation, or disequilibrium. “A sense of motion is the best indication of vertigo, though even that might be lacking,” Dr. Levin said.

Neurologists can determine whether position triggers vertigo and identify evidence of peripheral biologic problems (eg, tinnitus, changes in vision, or other focal neurologic signs and symptoms). Family history of migraine in people with episodic vertigo may be a clue that the patient has vestibular migraine versus other causes of vertigo, Dr. Levin said. A history of syncope or other signs may suggest that a patient’s symptoms are related to light-headedness instead of vertigo. Psychiatric illness, time course, drug exposure, and stroke or stroke risk factors also should be considered.

Diagnostic tests may help neurologists distinguish between vestibular migraine and other causes of vertigo. Audiograms can assess for hearing loss, and MRIs may rule out masses or other lesions. Brainstem auditory evoked responses, electronystagmography (ENG), and videonystagmography (VNG), which typically includes saccade, tracking, positional, and caloric testing, also can be useful.

Similar Conditions

One diagnostic entity that can be mistaken for vestibular migraine is mal de debarquement, which is marked by a persistent feeling of vertigo after a cruise or other motion experience. Patients with this condition also may experience symptoms such as blurred vision, inability to focus, cognitive changes, headaches, nausea, feelings of pressure, and trouble sleeping. “It can actually start sounding like migraine,” Dr. Levin said. “Strangely enough, patients may not mention their disembarkation from a trip. …You have to sometimes draw it out.”

Vestibular testing is normal in these patients, and oddly, they often feel better when they ride in a car or otherwise experience motion. Migraine treatment does not work for these patients. Benzodiazepines may help, but patients may become tolerant. Mal de debarquement tends to dampen and resolve in many patients.

Other causes of vertigo include Meniere’s disease, benign paroxysmal positional vertigo, meningeal infection or inflammation, labyrinthine or brainstem ischemia, perilymph fistula, and benign positional vertigo of childhood.

In the end, some diagnostic entities may be part of a spectrum, Dr. Levin said. Thirty-eight percent of vestibular migraines have auditory symptoms as in Meniere’s disease, and the prevalence of migraine in patients with Meniere’s disease is twice that of the general population. Many patients fit diagnostic criteria for vestibular migraine and Meniere’s disease.

The pathophysiology of vestibular migraine is unknown. Connections between vestibular nuclei in the brainstem and the trigeminal nuclei may underlie the condition. Vestibular and trigeminal nociceptive pathways may be activated in parallel. Alternatively, structural brain lesions in the temporal lobes or elsewhere may cause vestibular migraine.

Like other migraine auras, vestibular migraine may be a manifestation of focal or generalized cortical spreading depression. “There are cortical centers for vertigo,” Dr. Levin said. When these cortical centers are affected in patients with epilepsy, patients may experience “tornado seizures,” he said.

Treatment Approaches

Some studies suggest that migraine treatments might help patients with vestibular migraine. Zolmitriptan and rizatriptan at the time of vertigo have been tried, with some suggestion that they may provide benefit.

The best evidence for pharmacologic prevention exists for flunarizine, propranolol, and lamotrigine. Other trials suggest that vestibular rehabilitation and combined caffeine cessation, nortriptyline, and topiramate may be effective.

Limitations of trials in vestibular migraine have included small numbers of patients, noncontrolled designs, and inconsistent definitions of vestibular migraine. In addition, case reports have suggested that benzodiazepines, cinnarizine, selective serotonin reuptake inhibitors, pizotifen, dothiepin, acetazolamide, and behavioral modification may benefit patients. Investigators are enrolling patients in a double-blind, placebo-controlled trial that will evaluate the use of metoprolol for the preventive treatment of vestibular migraine.

If occurrences of vertigo are infrequent, symptomatic vertigo treatments are Dr. Levin’s first choice. “I have had good luck with scopolamine, for example,” he said. Dopamine antagonists, neuroleptics, sedatives, and benzodiazepines are also useful symptomatic treatments for vertigo. The Epley maneuver and other canalith repositioning maneuvers may benefit some patients. For acute treatment, it makes sense to try a triptan, Dr. Levin said. “Sometimes it does work. Other times it does not, and you have to resort to symptomatic medication,” he said.

—Jake Remaly

Suggested Reading

Akdal G, Ozge A, Ergör G. The prevalence of vestibular symptoms in migraine or tension-type headache. J Vestib Res. 2013;23(2):101-106.

Dieterich M, Brandt T. Episodic vertigo related to migraine (90 cases): vestibular migraine? J Neurol. 1999;246(10):883-892.

Dieterich M, Obermann M, Celebisoy N. Vestibular migraine: the most frequent entity of episodic vertigo. J Neurol. 2016;263 Suppl 1:S82-89.

Furman JM, Marcus DA, Balaban CD. Vestibular migraine: clinical aspects and pathophysiology. Lancet Neurol. 2013;12(7):706-715.

Lepcha A, Amalanathan S, Augustine AM, et al. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol. 2014;271(11):2931-2936.

Mikulec AA, Faraji F, Kinsella LJ. Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology. Am J Otolaryngol. 2012;33(1):121-127.

Murdin L, Davies RA, Bronstein AM. Vertigo as a migraine trigger. Neurology. 2009;73(8):638-642.

Neuhauser HK, Radtke A, von Brevern M, et al. Migrainous vertigo: prevalence and impact on quality of life. Neurology. 2006;67(6):1028-1033.

Salviz M, Yuce T, Acar H, et al. Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope. 2016;126(1):169-174.

Van Ombergen A, Van Rompaey V, Van de Heyning P, Wuyts F. Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness. Otol Neurotol. 2015;36(1):133-138.

Vitkovic J, Winoto A, Rance G, et al. Vestibular rehabilitation outcomes in patients with and without vestibular migraine. J Neurol. 2013;260(12):3039-3048.

Vertigo is a normal response to certain stimuli, such as looking down from heights and abnormal head movements. In addition, any dysfunction along the pathway that processes balance and gravity information (eg, the semicircular canals, acoustic nerve, and brainstem vestibular centers) can cause vertigo.

Migraine is significantly more common in patients with vertigo, and vertigo is significantly more common in migraineurs than in the general population. In addition, migraineurs are predisposed to motion sickness, which often includes vertigo. Migraineurs’ vestibular systems are more sensitive to stimuli than those of nonmigraine controls, and migraineurs experience vestibular stimulation as more unpleasant and more likely to cause emesis, compared with nonmigraine controls, Dr. Levin said.

The reasons for these correlations are unknown. It may be that heightened vestibular sensitivity in migraine is due to migraineurs perceiving all stimuli more intensely, or migraineurs may be more keenly aware of early signs of vestibulopathy. Vertigo may be a migraine trigger, or a subset of patients may have a type of migraine that includes vertigo as a key symptom, he said. This last possibility is the so-called vestibular migraine.

Recognizing Vestibular Migraine

Vestibular migraine, which also has been known as migraine-associated vertigo, migraine-associated dizziness, and migraine-associated vestibulopathy, has been difficult to define. The current generally accepted definition requires two basic diagnostic criteria: current or previous history of migraine and migraine features (eg, headache, photophobia, phonophobia, or visual aura) with at least half of the spells of vertigo.

Vestibular migraine is estimated to affect about 1% of the general population, 7% of patients at dizziness clinics, and 9% of patients at headache centers.

The duration of vertigo in vestibular migraine varies. About a third of the episodes last for minutes, a third for hours, and a third for days. Vertigo can occur between migraine attacks, prior to them, during, or after, and it tends to be spontaneous. Vestibular migraine is common in children and more common in women than in men. It generally arises years after migraines begin.

Unsteadiness and balance problems are common in vestibular migraine, and audiologic disturbances occur in a minority of patients. Migraine with brainstem aura (formerly called basilar migraine) can include vertigo, but the diagnosis also requires at least one other brainstem symptom (eg, tinnitus or dysarthria).

Evaluating Patients

When seeing patients, neurologists’ first step might be to try to distinguish between vertigo and other similar symptoms, such as presyncope, disorientation, or disequilibrium. “A sense of motion is the best indication of vertigo, though even that might be lacking,” Dr. Levin said.

Neurologists can determine whether position triggers vertigo and identify evidence of peripheral biologic problems (eg, tinnitus, changes in vision, or other focal neurologic signs and symptoms). Family history of migraine in people with episodic vertigo may be a clue that the patient has vestibular migraine versus other causes of vertigo, Dr. Levin said. A history of syncope or other signs may suggest that a patient’s symptoms are related to light-headedness instead of vertigo. Psychiatric illness, time course, drug exposure, and stroke or stroke risk factors also should be considered.

Diagnostic tests may help neurologists distinguish between vestibular migraine and other causes of vertigo. Audiograms can assess for hearing loss, and MRIs may rule out masses or other lesions. Brainstem auditory evoked responses, electronystagmography (ENG), and videonystagmography (VNG), which typically includes saccade, tracking, positional, and caloric testing, also can be useful.

Similar Conditions

One diagnostic entity that can be mistaken for vestibular migraine is mal de debarquement, which is marked by a persistent feeling of vertigo after a cruise or other motion experience. Patients with this condition also may experience symptoms such as blurred vision, inability to focus, cognitive changes, headaches, nausea, feelings of pressure, and trouble sleeping. “It can actually start sounding like migraine,” Dr. Levin said. “Strangely enough, patients may not mention their disembarkation from a trip. …You have to sometimes draw it out.”

Vestibular testing is normal in these patients, and oddly, they often feel better when they ride in a car or otherwise experience motion. Migraine treatment does not work for these patients. Benzodiazepines may help, but patients may become tolerant. Mal de debarquement tends to dampen and resolve in many patients.

Other causes of vertigo include Meniere’s disease, benign paroxysmal positional vertigo, meningeal infection or inflammation, labyrinthine or brainstem ischemia, perilymph fistula, and benign positional vertigo of childhood.

In the end, some diagnostic entities may be part of a spectrum, Dr. Levin said. Thirty-eight percent of vestibular migraines have auditory symptoms as in Meniere’s disease, and the prevalence of migraine in patients with Meniere’s disease is twice that of the general population. Many patients fit diagnostic criteria for vestibular migraine and Meniere’s disease.

The pathophysiology of vestibular migraine is unknown. Connections between vestibular nuclei in the brainstem and the trigeminal nuclei may underlie the condition. Vestibular and trigeminal nociceptive pathways may be activated in parallel. Alternatively, structural brain lesions in the temporal lobes or elsewhere may cause vestibular migraine.

Like other migraine auras, vestibular migraine may be a manifestation of focal or generalized cortical spreading depression. “There are cortical centers for vertigo,” Dr. Levin said. When these cortical centers are affected in patients with epilepsy, patients may experience “tornado seizures,” he said.

Treatment Approaches

Some studies suggest that migraine treatments might help patients with vestibular migraine. Zolmitriptan and rizatriptan at the time of vertigo have been tried, with some suggestion that they may provide benefit.

The best evidence for pharmacologic prevention exists for flunarizine, propranolol, and lamotrigine. Other trials suggest that vestibular rehabilitation and combined caffeine cessation, nortriptyline, and topiramate may be effective.

Limitations of trials in vestibular migraine have included small numbers of patients, noncontrolled designs, and inconsistent definitions of vestibular migraine. In addition, case reports have suggested that benzodiazepines, cinnarizine, selective serotonin reuptake inhibitors, pizotifen, dothiepin, acetazolamide, and behavioral modification may benefit patients. Investigators are enrolling patients in a double-blind, placebo-controlled trial that will evaluate the use of metoprolol for the preventive treatment of vestibular migraine.

If occurrences of vertigo are infrequent, symptomatic vertigo treatments are Dr. Levin’s first choice. “I have had good luck with scopolamine, for example,” he said. Dopamine antagonists, neuroleptics, sedatives, and benzodiazepines are also useful symptomatic treatments for vertigo. The Epley maneuver and other canalith repositioning maneuvers may benefit some patients. For acute treatment, it makes sense to try a triptan, Dr. Levin said. “Sometimes it does work. Other times it does not, and you have to resort to symptomatic medication,” he said.

—Jake Remaly

Suggested Reading

Akdal G, Ozge A, Ergör G. The prevalence of vestibular symptoms in migraine or tension-type headache. J Vestib Res. 2013;23(2):101-106.

Dieterich M, Brandt T. Episodic vertigo related to migraine (90 cases): vestibular migraine? J Neurol. 1999;246(10):883-892.

Dieterich M, Obermann M, Celebisoy N. Vestibular migraine: the most frequent entity of episodic vertigo. J Neurol. 2016;263 Suppl 1:S82-89.

Furman JM, Marcus DA, Balaban CD. Vestibular migraine: clinical aspects and pathophysiology. Lancet Neurol. 2013;12(7):706-715.

Lepcha A, Amalanathan S, Augustine AM, et al. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol. 2014;271(11):2931-2936.

Mikulec AA, Faraji F, Kinsella LJ. Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology. Am J Otolaryngol. 2012;33(1):121-127.

Murdin L, Davies RA, Bronstein AM. Vertigo as a migraine trigger. Neurology. 2009;73(8):638-642.

Neuhauser HK, Radtke A, von Brevern M, et al. Migrainous vertigo: prevalence and impact on quality of life. Neurology. 2006;67(6):1028-1033.

Salviz M, Yuce T, Acar H, et al. Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial. Laryngoscope. 2016;126(1):169-174.

Van Ombergen A, Van Rompaey V, Van de Heyning P, Wuyts F. Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness. Otol Neurotol. 2015;36(1):133-138.

Vitkovic J, Winoto A, Rance G, et al. Vestibular rehabilitation outcomes in patients with and without vestibular migraine. J Neurol. 2013;260(12):3039-3048.

RIVIERA BEACH, FL—Neurologists sometimes encounter patients with headaches that have not responded to prior treatment. These patients may be demoralized, and neurologists may be at a loss for a way to relieve their pain. Effective treatment is possible for many of these patients, according to Thomas N. Ward, MD, Emeritus Professor of Neurology at Dartmouth College in Hanover, New Hampshire. He described the process of differential diagnosis, as well as outpatient and inpatient therapeutic options for refractory headache, at the 44th Annual Meeting of the Southern Clinical Neurological Society.

Confirm the Diagnosis

When faced with a patient with refractory headache, a neurologist should first verify the diagnosis and rule out the possibility of secondary headache. These steps will improve the likelihood of a positive outcome. “If you follow the fundamentals and treat the type of headache it is, you usually get a pretty good result,” said Dr. Ward.

A patient with headache on 15 days per month or more has chronic daily headache. The duration of the headaches can provide the basis for a more specific diagnosis. Headaches of short duration (ie, less than four hours) may be symptoms of cluster headache, chronic paroxysmal hemicrania, hypnic headache, or trigeminal neuralgia. Headaches of long duration (ie, more than four hours) may indicate chronic migraine, chronic tension-type headache, hemicrania continua, or new daily persistent headache.

A patient with headache on 15 or more days per month, and for whom headaches on at least eight days per month meet the criteria of migraine, has chronic migraine. The two best-supported treatments for chronic migraine are topiramate and onabotulinumtoxinA. In patients with chronic migraine, what appears to be a tension-type headache may eventually declare its true nature and become a migraine headache with accompanying pounding and photophobia. What looks like a tension-type headache in a migraineur may respond to a triptan, said Dr. Ward.

Stop Medication Overuse

Medication overuse can confound the diagnosis and alter the headache itself. Many patients with refractory headache overuse medication but may fail to mention this to a neurologist. The overused medication may be a prescription or an over-the-counter drug such as ibuprofen, acetaminophen, or a combination that includes caffeine. Drugs with short half-lives appear to be particularly likely to cause medication overuse headache.

Some patients may be overusing opioids for their headache. “Opioids for headache are not a good idea,” said Dr. Ward. “Nothing good will come of it.” These drugs may cause central sensitization and reduce the efficacy of other headache remedies.

The risk of medication overuse headache increases if the patient uses combination analgesics, ergotamine, or triptans on 10 or more days per month, or simple analgesics on more than 15 days per month. “The clinical question I always ask patients is, ‘Are you taking more pills and having more headaches?’ If the answer is ‘yes,’ then they have medication overuse headache,” said Dr. Ward.

If patients stop taking the overused medication, they may have a withdrawal headache that is worse than their normal headache. Medication overuse headache usually resolves itself after the overuse is stopped, and bridge therapies such as steroids, nonsteroidal anti-inflammatory drugs, or dihydroergotamine may alleviate pain during withdrawal. “If you can get the patient over that hump, which can be several days of bad headache, they often do remarkably better,” said Dr. Ward.

Get Back to Basics

Taking a careful history is essential to successful treatment. “If you do not get the original history, you could miss the diagnosis,” said Dr. Ward. The neurologist must know about the mode of onset of the patient’s headache, and also know all about his or her prior headaches.

A patient with refractory headache should undergo a thorough head and neck examination, but physicians sometimes neglect to perform it. An MRI of the brain with gadolinium generally is warranted. About 90% of patients with low CSF pressure have pachymeningeal enhancement, which is visible on MRI performed with gadolinium, said Dr. Ward. Blood work, however, usually reveals little and appears normal. Sometimes thyroid tests, a Lyme test, a blood count, and a serum creatinine test are helpful, and a serum erythrocyte sedimentation rate test in those over age 50 is important to obtain.

Lumbar punctures may be underused, said Dr. Ward. Although it is uncommon, some patients present with high intracranial pressure, but without papilledema. The correct diagnosis can lead to effective treatment for these patients.

Effective treatment also is more likely when the neurologist gets to know the patient. He or she can use preventive medications to reduce the number of headache days. The literature suggests that successful preventive therapy should achieve a target of four headache days or fewer per month.

Neurologists also should treat the patient’s comorbid conditions, which often are psychiatric in people with refractory headache. It is unusual to see a patient with chronic migraine who does not have anxiety and depression, said Dr. Ward. Patients with refractory headache also may have phobias, bipolar disorder, or posttraumatic stress disorder, which is a significant confounder.

To Admit or Not to Admit?

A neurologist may have to decide whether to admit to the hospital a patient with chronic headache who is not doing well. First, the neurologist and patient should agree on a therapeutic target. Outpatient treatment works well if the patient is motivated and compliant and does not have confounding conditions. If the therapeutic target cannot be met through outpatient treatment, the neurologist should consider hospital admission. Insurance companies generally will cover three days of inpatient treatment, said Dr. Ward.

Neurologists have many options for inpatient treatment of refractory headache. Repetitive dihydroergotamine, known as the Raskin protocol, is highly effective if administered correctly. Dihydroergotamine should be given three times per day. “If you order it q. 8 h., the nurse will wake your patient up in the middle of the night, and waking up a patient with benign headaches is not a good idea,” said Dr. Ward. The dose must not be sufficient to cause nausea, because nauseating the patient can exacerbate headaches. “We usually premedicate with metoclopramide or prochlorperazine for nausea, but both of those drugs … also are good headache remedies.”

The Raskin protocol requires the withdrawal of other analgesics. The protocol typically lasts for three days, and most patients have good outcomes at this point. Extending the protocol to six or seven days may increase the number of patients with good outcomes. The success rate for the Raskin protocol is between 60% and 70%, said Dr. Ward. Patients who are pregnant or who have coronary artery disease should not receive dihydroergotamine, however.

Another option for inpatient treatment is IV chlorpromazine. The goal of this treatment is to induce a light sleep and maintain it for two or three days. The neurologist may start with a dose of 10 mg t.i.d. and monitor the patient’s response. The drug effectively suppresses narcotic withdrawal symptoms, so the neurologist may withdraw overused medications while the patient is asleep. Chlorpromazine may cause QT prolongation, so the patient should undergo cardiac monitoring. The drug also causes orthostatic hypotension, so patients should remain on bed rest and receive prophylaxis for deep venous thrombosis, said Dr. Ward.

IV valproate is an excellent choice if the patient has cardiac problems or bipolar disease, he added. The drug can be administered in a single dose of between 300 mg and 500 mg run in rapidly. “You can run in a whole loading dose in five or 10 minutes with virtually no side effects,” said Dr. Ward. Treatment can be administered b.i.d. or t.i.d. for two or three days. Pregnant patients should not receive valproate, however. Yet another option is IV magnesium, although the evidence for its efficacy is mostly anecdotal. A protocol of 1 to 2 g administered over 10 to 20 minutes, repeated several times per day, may be effective. It is advisable to monitor the patient’s serum magnesium levels to ensure that they do not become excessive. Magnesium may adversely affect fetal bone development, so neurologists should exercise caution when considering the drug for a pregnant patient. IV magnesium is “an excellent choice for hemiplegic migraine,” said Dr. Ward.

If the patient’s occipital nerves are tender, occipital nerve blockade may relieve pain. IV ketorolac, in 30-mg doses t.i.d. or q.i.d., may alleviate breakthrough headaches. Lidocaine patches can reduce back or neck pain for as long as 12 hours daily.

Abruptly withdrawing butalbital entails a risk of seizures and delirium. Neurologists may wish to administer phenobarbital in its place, as a single bedtime dose, while they are tapering or stopping butalbital. A 30-mg dose of phenobarbital may be substituted for every 100 mg of butalbital, said Dr. Ward.

Suggested Reading

Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache. 1997;37(3):129-136.

Lai TH, Wang SJ. Update of inpatient treatment for refractory chronic daily headache. Curr Pain Headache Rep. 2016;20(1):5.

Levin M. Opioids in headache. Headache. 2014;54(1):12-21.

Lipton RB, Silberstein SD, Saper JR, et al. Why headache treatment fails. Neurology. 2003;60(7):1064-1070.

RIVIERA BEACH, FL—Neurologists sometimes encounter patients with headaches that have not responded to prior treatment. These patients may be demoralized, and neurologists may be at a loss for a way to relieve their pain. Effective treatment is possible for many of these patients, according to Thomas N. Ward, MD, Emeritus Professor of Neurology at Dartmouth College in Hanover, New Hampshire. He described the process of differential diagnosis, as well as outpatient and inpatient therapeutic options for refractory headache, at the 44th Annual Meeting of the Southern Clinical Neurological Society.

Confirm the Diagnosis

When faced with a patient with refractory headache, a neurologist should first verify the diagnosis and rule out the possibility of secondary headache. These steps will improve the likelihood of a positive outcome. “If you follow the fundamentals and treat the type of headache it is, you usually get a pretty good result,” said Dr. Ward.

A patient with headache on 15 days per month or more has chronic daily headache. The duration of the headaches can provide the basis for a more specific diagnosis. Headaches of short duration (ie, less than four hours) may be symptoms of cluster headache, chronic paroxysmal hemicrania, hypnic headache, or trigeminal neuralgia. Headaches of long duration (ie, more than four hours) may indicate chronic migraine, chronic tension-type headache, hemicrania continua, or new daily persistent headache.

A patient with headache on 15 or more days per month, and for whom headaches on at least eight days per month meet the criteria of migraine, has chronic migraine. The two best-supported treatments for chronic migraine are topiramate and onabotulinumtoxinA. In patients with chronic migraine, what appears to be a tension-type headache may eventually declare its true nature and become a migraine headache with accompanying pounding and photophobia. What looks like a tension-type headache in a migraineur may respond to a triptan, said Dr. Ward.

Stop Medication Overuse

Medication overuse can confound the diagnosis and alter the headache itself. Many patients with refractory headache overuse medication but may fail to mention this to a neurologist. The overused medication may be a prescription or an over-the-counter drug such as ibuprofen, acetaminophen, or a combination that includes caffeine. Drugs with short half-lives appear to be particularly likely to cause medication overuse headache.

Some patients may be overusing opioids for their headache. “Opioids for headache are not a good idea,” said Dr. Ward. “Nothing good will come of it.” These drugs may cause central sensitization and reduce the efficacy of other headache remedies.

The risk of medication overuse headache increases if the patient uses combination analgesics, ergotamine, or triptans on 10 or more days per month, or simple analgesics on more than 15 days per month. “The clinical question I always ask patients is, ‘Are you taking more pills and having more headaches?’ If the answer is ‘yes,’ then they have medication overuse headache,” said Dr. Ward.

If patients stop taking the overused medication, they may have a withdrawal headache that is worse than their normal headache. Medication overuse headache usually resolves itself after the overuse is stopped, and bridge therapies such as steroids, nonsteroidal anti-inflammatory drugs, or dihydroergotamine may alleviate pain during withdrawal. “If you can get the patient over that hump, which can be several days of bad headache, they often do remarkably better,” said Dr. Ward.

Get Back to Basics

Taking a careful history is essential to successful treatment. “If you do not get the original history, you could miss the diagnosis,” said Dr. Ward. The neurologist must know about the mode of onset of the patient’s headache, and also know all about his or her prior headaches.

A patient with refractory headache should undergo a thorough head and neck examination, but physicians sometimes neglect to perform it. An MRI of the brain with gadolinium generally is warranted. About 90% of patients with low CSF pressure have pachymeningeal enhancement, which is visible on MRI performed with gadolinium, said Dr. Ward. Blood work, however, usually reveals little and appears normal. Sometimes thyroid tests, a Lyme test, a blood count, and a serum creatinine test are helpful, and a serum erythrocyte sedimentation rate test in those over age 50 is important to obtain.

Lumbar punctures may be underused, said Dr. Ward. Although it is uncommon, some patients present with high intracranial pressure, but without papilledema. The correct diagnosis can lead to effective treatment for these patients.

Effective treatment also is more likely when the neurologist gets to know the patient. He or she can use preventive medications to reduce the number of headache days. The literature suggests that successful preventive therapy should achieve a target of four headache days or fewer per month.

Neurologists also should treat the patient’s comorbid conditions, which often are psychiatric in people with refractory headache. It is unusual to see a patient with chronic migraine who does not have anxiety and depression, said Dr. Ward. Patients with refractory headache also may have phobias, bipolar disorder, or posttraumatic stress disorder, which is a significant confounder.

To Admit or Not to Admit?

A neurologist may have to decide whether to admit to the hospital a patient with chronic headache who is not doing well. First, the neurologist and patient should agree on a therapeutic target. Outpatient treatment works well if the patient is motivated and compliant and does not have confounding conditions. If the therapeutic target cannot be met through outpatient treatment, the neurologist should consider hospital admission. Insurance companies generally will cover three days of inpatient treatment, said Dr. Ward.

Neurologists have many options for inpatient treatment of refractory headache. Repetitive dihydroergotamine, known as the Raskin protocol, is highly effective if administered correctly. Dihydroergotamine should be given three times per day. “If you order it q. 8 h., the nurse will wake your patient up in the middle of the night, and waking up a patient with benign headaches is not a good idea,” said Dr. Ward. The dose must not be sufficient to cause nausea, because nauseating the patient can exacerbate headaches. “We usually premedicate with metoclopramide or prochlorperazine for nausea, but both of those drugs … also are good headache remedies.”

The Raskin protocol requires the withdrawal of other analgesics. The protocol typically lasts for three days, and most patients have good outcomes at this point. Extending the protocol to six or seven days may increase the number of patients with good outcomes. The success rate for the Raskin protocol is between 60% and 70%, said Dr. Ward. Patients who are pregnant or who have coronary artery disease should not receive dihydroergotamine, however.

Another option for inpatient treatment is IV chlorpromazine. The goal of this treatment is to induce a light sleep and maintain it for two or three days. The neurologist may start with a dose of 10 mg t.i.d. and monitor the patient’s response. The drug effectively suppresses narcotic withdrawal symptoms, so the neurologist may withdraw overused medications while the patient is asleep. Chlorpromazine may cause QT prolongation, so the patient should undergo cardiac monitoring. The drug also causes orthostatic hypotension, so patients should remain on bed rest and receive prophylaxis for deep venous thrombosis, said Dr. Ward.

IV valproate is an excellent choice if the patient has cardiac problems or bipolar disease, he added. The drug can be administered in a single dose of between 300 mg and 500 mg run in rapidly. “You can run in a whole loading dose in five or 10 minutes with virtually no side effects,” said Dr. Ward. Treatment can be administered b.i.d. or t.i.d. for two or three days. Pregnant patients should not receive valproate, however. Yet another option is IV magnesium, although the evidence for its efficacy is mostly anecdotal. A protocol of 1 to 2 g administered over 10 to 20 minutes, repeated several times per day, may be effective. It is advisable to monitor the patient’s serum magnesium levels to ensure that they do not become excessive. Magnesium may adversely affect fetal bone development, so neurologists should exercise caution when considering the drug for a pregnant patient. IV magnesium is “an excellent choice for hemiplegic migraine,” said Dr. Ward.

If the patient’s occipital nerves are tender, occipital nerve blockade may relieve pain. IV ketorolac, in 30-mg doses t.i.d. or q.i.d., may alleviate breakthrough headaches. Lidocaine patches can reduce back or neck pain for as long as 12 hours daily.

Abruptly withdrawing butalbital entails a risk of seizures and delirium. Neurologists may wish to administer phenobarbital in its place, as a single bedtime dose, while they are tapering or stopping butalbital. A 30-mg dose of phenobarbital may be substituted for every 100 mg of butalbital, said Dr. Ward.

Suggested Reading

Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache. 1997;37(3):129-136.

Lai TH, Wang SJ. Update of inpatient treatment for refractory chronic daily headache. Curr Pain Headache Rep. 2016;20(1):5.

Levin M. Opioids in headache. Headache. 2014;54(1):12-21.

Lipton RB, Silberstein SD, Saper JR, et al. Why headache treatment fails. Neurology. 2003;60(7):1064-1070.

RIVIERA BEACH, FL—Neurologists sometimes encounter patients with headaches that have not responded to prior treatment. These patients may be demoralized, and neurologists may be at a loss for a way to relieve their pain. Effective treatment is possible for many of these patients, according to Thomas N. Ward, MD, Emeritus Professor of Neurology at Dartmouth College in Hanover, New Hampshire. He described the process of differential diagnosis, as well as outpatient and inpatient therapeutic options for refractory headache, at the 44th Annual Meeting of the Southern Clinical Neurological Society.

Confirm the Diagnosis

When faced with a patient with refractory headache, a neurologist should first verify the diagnosis and rule out the possibility of secondary headache. These steps will improve the likelihood of a positive outcome. “If you follow the fundamentals and treat the type of headache it is, you usually get a pretty good result,” said Dr. Ward.

A patient with headache on 15 days per month or more has chronic daily headache. The duration of the headaches can provide the basis for a more specific diagnosis. Headaches of short duration (ie, less than four hours) may be symptoms of cluster headache, chronic paroxysmal hemicrania, hypnic headache, or trigeminal neuralgia. Headaches of long duration (ie, more than four hours) may indicate chronic migraine, chronic tension-type headache, hemicrania continua, or new daily persistent headache.

A patient with headache on 15 or more days per month, and for whom headaches on at least eight days per month meet the criteria of migraine, has chronic migraine. The two best-supported treatments for chronic migraine are topiramate and onabotulinumtoxinA. In patients with chronic migraine, what appears to be a tension-type headache may eventually declare its true nature and become a migraine headache with accompanying pounding and photophobia. What looks like a tension-type headache in a migraineur may respond to a triptan, said Dr. Ward.

Stop Medication Overuse

Medication overuse can confound the diagnosis and alter the headache itself. Many patients with refractory headache overuse medication but may fail to mention this to a neurologist. The overused medication may be a prescription or an over-the-counter drug such as ibuprofen, acetaminophen, or a combination that includes caffeine. Drugs with short half-lives appear to be particularly likely to cause medication overuse headache.

Some patients may be overusing opioids for their headache. “Opioids for headache are not a good idea,” said Dr. Ward. “Nothing good will come of it.” These drugs may cause central sensitization and reduce the efficacy of other headache remedies.

The risk of medication overuse headache increases if the patient uses combination analgesics, ergotamine, or triptans on 10 or more days per month, or simple analgesics on more than 15 days per month. “The clinical question I always ask patients is, ‘Are you taking more pills and having more headaches?’ If the answer is ‘yes,’ then they have medication overuse headache,” said Dr. Ward.

If patients stop taking the overused medication, they may have a withdrawal headache that is worse than their normal headache. Medication overuse headache usually resolves itself after the overuse is stopped, and bridge therapies such as steroids, nonsteroidal anti-inflammatory drugs, or dihydroergotamine may alleviate pain during withdrawal. “If you can get the patient over that hump, which can be several days of bad headache, they often do remarkably better,” said Dr. Ward.

Get Back to Basics

Taking a careful history is essential to successful treatment. “If you do not get the original history, you could miss the diagnosis,” said Dr. Ward. The neurologist must know about the mode of onset of the patient’s headache, and also know all about his or her prior headaches.

A patient with refractory headache should undergo a thorough head and neck examination, but physicians sometimes neglect to perform it. An MRI of the brain with gadolinium generally is warranted. About 90% of patients with low CSF pressure have pachymeningeal enhancement, which is visible on MRI performed with gadolinium, said Dr. Ward. Blood work, however, usually reveals little and appears normal. Sometimes thyroid tests, a Lyme test, a blood count, and a serum creatinine test are helpful, and a serum erythrocyte sedimentation rate test in those over age 50 is important to obtain.

Lumbar punctures may be underused, said Dr. Ward. Although it is uncommon, some patients present with high intracranial pressure, but without papilledema. The correct diagnosis can lead to effective treatment for these patients.

Effective treatment also is more likely when the neurologist gets to know the patient. He or she can use preventive medications to reduce the number of headache days. The literature suggests that successful preventive therapy should achieve a target of four headache days or fewer per month.

Neurologists also should treat the patient’s comorbid conditions, which often are psychiatric in people with refractory headache. It is unusual to see a patient with chronic migraine who does not have anxiety and depression, said Dr. Ward. Patients with refractory headache also may have phobias, bipolar disorder, or posttraumatic stress disorder, which is a significant confounder.

To Admit or Not to Admit?

A neurologist may have to decide whether to admit to the hospital a patient with chronic headache who is not doing well. First, the neurologist and patient should agree on a therapeutic target. Outpatient treatment works well if the patient is motivated and compliant and does not have confounding conditions. If the therapeutic target cannot be met through outpatient treatment, the neurologist should consider hospital admission. Insurance companies generally will cover three days of inpatient treatment, said Dr. Ward.

Neurologists have many options for inpatient treatment of refractory headache. Repetitive dihydroergotamine, known as the Raskin protocol, is highly effective if administered correctly. Dihydroergotamine should be given three times per day. “If you order it q. 8 h., the nurse will wake your patient up in the middle of the night, and waking up a patient with benign headaches is not a good idea,” said Dr. Ward. The dose must not be sufficient to cause nausea, because nauseating the patient can exacerbate headaches. “We usually premedicate with metoclopramide or prochlorperazine for nausea, but both of those drugs … also are good headache remedies.”

The Raskin protocol requires the withdrawal of other analgesics. The protocol typically lasts for three days, and most patients have good outcomes at this point. Extending the protocol to six or seven days may increase the number of patients with good outcomes. The success rate for the Raskin protocol is between 60% and 70%, said Dr. Ward. Patients who are pregnant or who have coronary artery disease should not receive dihydroergotamine, however.

Another option for inpatient treatment is IV chlorpromazine. The goal of this treatment is to induce a light sleep and maintain it for two or three days. The neurologist may start with a dose of 10 mg t.i.d. and monitor the patient’s response. The drug effectively suppresses narcotic withdrawal symptoms, so the neurologist may withdraw overused medications while the patient is asleep. Chlorpromazine may cause QT prolongation, so the patient should undergo cardiac monitoring. The drug also causes orthostatic hypotension, so patients should remain on bed rest and receive prophylaxis for deep venous thrombosis, said Dr. Ward.

IV valproate is an excellent choice if the patient has cardiac problems or bipolar disease, he added. The drug can be administered in a single dose of between 300 mg and 500 mg run in rapidly. “You can run in a whole loading dose in five or 10 minutes with virtually no side effects,” said Dr. Ward. Treatment can be administered b.i.d. or t.i.d. for two or three days. Pregnant patients should not receive valproate, however. Yet another option is IV magnesium, although the evidence for its efficacy is mostly anecdotal. A protocol of 1 to 2 g administered over 10 to 20 minutes, repeated several times per day, may be effective. It is advisable to monitor the patient’s serum magnesium levels to ensure that they do not become excessive. Magnesium may adversely affect fetal bone development, so neurologists should exercise caution when considering the drug for a pregnant patient. IV magnesium is “an excellent choice for hemiplegic migraine,” said Dr. Ward.

If the patient’s occipital nerves are tender, occipital nerve blockade may relieve pain. IV ketorolac, in 30-mg doses t.i.d. or q.i.d., may alleviate breakthrough headaches. Lidocaine patches can reduce back or neck pain for as long as 12 hours daily.

Abruptly withdrawing butalbital entails a risk of seizures and delirium. Neurologists may wish to administer phenobarbital in its place, as a single bedtime dose, while they are tapering or stopping butalbital. A 30-mg dose of phenobarbital may be substituted for every 100 mg of butalbital, said Dr. Ward.

Suggested Reading

Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache. 1997;37(3):129-136.

Lai TH, Wang SJ. Update of inpatient treatment for refractory chronic daily headache. Curr Pain Headache Rep. 2016;20(1):5.

Levin M. Opioids in headache. Headache. 2014;54(1):12-21.

Lipton RB, Silberstein SD, Saper JR, et al. Why headache treatment fails. Neurology. 2003;60(7):1064-1070.