Headache & Migraine

Patients with migrane are more sensitive to all colors of light during the ictal phase than the during interictal phase, according to a recent study, but control subjects do not experience pain when exposed to different colors of light. In order to identify the origin of this photophobia in migraineurs, researchers compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual evoked potential paradigms. They found:

• Unexpectedly, it was the amplitude of the retinal rod-driven b-wave, which was consistently larger in the migraineurs than in the controls, rather than the retinal cone-driven a-wave or the visual evoked potentials that differ most strikingly between the 2 groups.
• Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex.

Clinically, these findings may explain why migraineurs complain that the light is too bright even when it is dim.

Bernstein CA, N R-R, Noseda R, et al. The migraine eye: distinct rod-driven retinal pathways’ response to dim light challenges the visual cortex hyperexcitability theory. [Published online ahead of print October 29, 2018]. Pain. doi:10.1097/j.pain.0000000000001434.

Patients with migrane are more sensitive to all colors of light during the ictal phase than the during interictal phase, according to a recent study, but control subjects do not experience pain when exposed to different colors of light. In order to identify the origin of this photophobia in migraineurs, researchers compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual evoked potential paradigms. They found:

• Unexpectedly, it was the amplitude of the retinal rod-driven b-wave, which was consistently larger in the migraineurs than in the controls, rather than the retinal cone-driven a-wave or the visual evoked potentials that differ most strikingly between the 2 groups.
• Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex.

Clinically, these findings may explain why migraineurs complain that the light is too bright even when it is dim.

Bernstein CA, N R-R, Noseda R, et al. The migraine eye: distinct rod-driven retinal pathways’ response to dim light challenges the visual cortex hyperexcitability theory. [Published online ahead of print October 29, 2018]. Pain. doi:10.1097/j.pain.0000000000001434.

Patients with migrane are more sensitive to all colors of light during the ictal phase than the during interictal phase, according to a recent study, but control subjects do not experience pain when exposed to different colors of light. In order to identify the origin of this photophobia in migraineurs, researchers compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual evoked potential paradigms. They found:

• Unexpectedly, it was the amplitude of the retinal rod-driven b-wave, which was consistently larger in the migraineurs than in the controls, rather than the retinal cone-driven a-wave or the visual evoked potentials that differ most strikingly between the 2 groups.
• Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex.

Clinically, these findings may explain why migraineurs complain that the light is too bright even when it is dim.

Bernstein CA, N R-R, Noseda R, et al. The migraine eye: distinct rod-driven retinal pathways’ response to dim light challenges the visual cortex hyperexcitability theory. [Published online ahead of print October 29, 2018]. Pain. doi:10.1097/j.pain.0000000000001434.

Parental migraine impacts children aged 11 to 17 living in the home, particularly in the domains of global well‐being and the parent/child relationship, according to a recent study. This cross‐sectional observational study included parents who met International Classification of Headache Disorders criteria for migraine and their 11- to 17‐year‐old children currently living with the parent with migraine recruited from neurologist offices and online. Researchers found:

• Children (n=40) reported the greatest impact of their parent’s migraine on the Global Well‐Being and Parent/Child Relationship subscales.
• There were no significant differences between the average child and parent rating of parental migraine impact on children.
• Correlations between parent and child ratings of parental migraine impact were strongest for the Social Impact subscale, and non‐significant for the Parent/Child Relationship and Friends Reactions subscales.

Seng EK, Mauser ED, Marzouk N, Patel ZS, Rosen N, Buse DC. When mom has migraine: An observational study of the impact of parental migraine on adolescent children. [Published online ahead of print October 31, 2018]. Headache. doi:10.1111/head.13433.

Parental migraine impacts children aged 11 to 17 living in the home, particularly in the domains of global well‐being and the parent/child relationship, according to a recent study. This cross‐sectional observational study included parents who met International Classification of Headache Disorders criteria for migraine and their 11- to 17‐year‐old children currently living with the parent with migraine recruited from neurologist offices and online. Researchers found:

• Children (n=40) reported the greatest impact of their parent’s migraine on the Global Well‐Being and Parent/Child Relationship subscales.
• There were no significant differences between the average child and parent rating of parental migraine impact on children.
• Correlations between parent and child ratings of parental migraine impact were strongest for the Social Impact subscale, and non‐significant for the Parent/Child Relationship and Friends Reactions subscales.

Seng EK, Mauser ED, Marzouk N, Patel ZS, Rosen N, Buse DC. When mom has migraine: An observational study of the impact of parental migraine on adolescent children. [Published online ahead of print October 31, 2018]. Headache. doi:10.1111/head.13433.

Parental migraine impacts children aged 11 to 17 living in the home, particularly in the domains of global well‐being and the parent/child relationship, according to a recent study. This cross‐sectional observational study included parents who met International Classification of Headache Disorders criteria for migraine and their 11- to 17‐year‐old children currently living with the parent with migraine recruited from neurologist offices and online. Researchers found:

• Children (n=40) reported the greatest impact of their parent’s migraine on the Global Well‐Being and Parent/Child Relationship subscales.
• There were no significant differences between the average child and parent rating of parental migraine impact on children.
• Correlations between parent and child ratings of parental migraine impact were strongest for the Social Impact subscale, and non‐significant for the Parent/Child Relationship and Friends Reactions subscales.

Seng EK, Mauser ED, Marzouk N, Patel ZS, Rosen N, Buse DC. When mom has migraine: An observational study of the impact of parental migraine on adolescent children. [Published online ahead of print October 31, 2018]. Headache. doi:10.1111/head.13433.

Headache disorders, and migraine in particular, are important causes of disability worldwide, and deserve greater attention in health policy debates and research resource allocation. This according to a recent investigation that used data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache. Prevalence for gender and 5-year age group interval at different time points from 1990 and 2016 in all countries and GBD regions were estimated using a Bayesian meta-regression model. Researchers found:

• Almost 3 billion individuals were estimated to have a migraine or tension-type headache in 2016: 1.89 billion with tension-type headache and 1.04 billion with migraine.
• However, because migraine had a much higher disability weight than tension-type headache, migraine caused 45.1 million and tension-type headache only 7.2 million YLDs globally in 2016.
• The headaches were most burdensome in women between ages 15 and 49 years, with migraine causing 20.3 million and tension-type headache 2.9 million YLDs in 2016, which was 11.2% of all YLDs in this age group and sex.

Stovner LJ, Nichols E, Steiner TJ, et al. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954-976. doi:10.1016/S1474-4422(18)30322-3.

Headache disorders, and migraine in particular, are important causes of disability worldwide, and deserve greater attention in health policy debates and research resource allocation. This according to a recent investigation that used data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache. Prevalence for gender and 5-year age group interval at different time points from 1990 and 2016 in all countries and GBD regions were estimated using a Bayesian meta-regression model. Researchers found:

• Almost 3 billion individuals were estimated to have a migraine or tension-type headache in 2016: 1.89 billion with tension-type headache and 1.04 billion with migraine.
• However, because migraine had a much higher disability weight than tension-type headache, migraine caused 45.1 million and tension-type headache only 7.2 million YLDs globally in 2016.
• The headaches were most burdensome in women between ages 15 and 49 years, with migraine causing 20.3 million and tension-type headache 2.9 million YLDs in 2016, which was 11.2% of all YLDs in this age group and sex.

Stovner LJ, Nichols E, Steiner TJ, et al. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954-976. doi:10.1016/S1474-4422(18)30322-3.

Headache disorders, and migraine in particular, are important causes of disability worldwide, and deserve greater attention in health policy debates and research resource allocation. This according to a recent investigation that used data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache. Prevalence for gender and 5-year age group interval at different time points from 1990 and 2016 in all countries and GBD regions were estimated using a Bayesian meta-regression model. Researchers found:

• Almost 3 billion individuals were estimated to have a migraine or tension-type headache in 2016: 1.89 billion with tension-type headache and 1.04 billion with migraine.
• However, because migraine had a much higher disability weight than tension-type headache, migraine caused 45.1 million and tension-type headache only 7.2 million YLDs globally in 2016.
• The headaches were most burdensome in women between ages 15 and 49 years, with migraine causing 20.3 million and tension-type headache 2.9 million YLDs in 2016, which was 11.2% of all YLDs in this age group and sex.

Stovner LJ, Nichols E, Steiner TJ, et al. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954-976. doi:10.1016/S1474-4422(18)30322-3.

The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.

Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.

After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.

In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.

“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”

The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.

The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.

“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”

In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.

Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.

The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).

The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.

However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.

The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.

SOURCE: Sen S et al. Neurology. 2018;91:1-9.

This article was updated 12/12/18.

The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.

Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.

After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.

In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.

“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”

The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.

The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.

“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”

In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.

Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.

The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).

The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.

However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.

The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.

SOURCE: Sen S et al. Neurology. 2018;91:1-9.

This article was updated 12/12/18.

The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.

Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.

After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.

In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.

“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”

The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.

The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.

“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”

In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.

Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.

The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).

The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.

However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.

The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.

SOURCE: Sen S et al. Neurology. 2018;91:1-9.

This article was updated 12/12/18.

Use of anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) may benefit children with more than 8 headache days each month, a high Pediatric Migraine Disability Assessment (PedMIDAS) score, and failure of other treatments; however, researchers cautioned that long-term safety outcomes for the treatment are not yet known, according to a recent set of recommendations published in the journal Headache.

Christina L. Szperka, MD, MSCE, of the division of neurology at the Children’s Hospital of Philadelphia and members of the Pediatric and Adolescent Headache special interest group of the American Headache Society discussed the topic of anti-CGRP mAbs at the 2018 Annual Scientific Meeting of the American Headache Society. They noted clinical outcomes for anti-CGRP mAbs in pediatric patients will likely not be available for several years and created a set of recommendations based on expert opinion of anti-CGRP mAb use in children and adolescents.

Their recommendations support using anti-CGRP mAbs for children with migraine if patients meet the following criteria: headache frequency exceeding 8 headache days per month; a PedMIDAS score of 30 or greater; failure of two or more therapies, such as pharmacologic, nonpharmacologic, or nutraceutical ones; and in patients who are past puberty.

The special interest group recommended against use of anti-CGRP mAbs in children and adolescents with recent meningitis, recent peripheral nerve injury, neurosurgery, or a central nervous system injury caused by a potentially compromised blood-brain barrier. Children and adolescents with immunodeficiency, receiving immunosuppressive medications, with structural heart defects, with pulmonary hypertension, with coronary artery disease, with cardiomyopathy, or at risk for stroke should also avoid use of anti-CGRP mAbs. Anti-CGRP mAbs are also potentially teratogenic and should not be used by adolescents or women who are pregnant, breastfeeding, or have a pregnancy wish.

Pediatric patients with significant osteoporosis or bone disease should be monitored when prescribed anti-CGRP mAbs, and the recommendations specified monitoring height and linear growth or waiting until after puberty to prescribe anti-CGRP mAbs. Although there is currently no evidence that use of anti-CGRP mAb requires pituitary hormone monitoring, the recommendations noted that weight and body mass index should also be observed.

“Pediatric and adolescent trials of anti-CGRP mAbs should be designed to maximize the chances of determining efficacy in these age groups and should focus on those who have not been successful with current multidisciplinary care,” Dr. Szperka and her colleagues wrote in the recommendations. “In the interim, the use of anti-CGRP mAbs for the treatment of headache disorders in children and adolescents may be considered in appropriate cases but should be done with close follow-up and attention to patient characteristics such as age, pubertal state, and medical comorbidities.”

Dr. Szperka receives grant support from Pfizer and Amgen and research funding from NIH. Other authors have reported grants, consulting fees, speaking fees, royalties, advisory board memberships, speaker’s bureau memberships and travel funds from Alder, Allergan, American Academy of Neurology, Amgen, Aralez, Avanir, Autonomic Technologies Inc., Biohaven, Cambridge University Press, Curelator, Depomed, Dr. Reddy’s Laboratories, Electrocore, eNeura, Genentech, Healint, Impax, JAMA Neurology, Journal Watch, Lilly, Massachusetts Medical Society, MedDay, MedicoLegal, Merck, NIH, Novartis, Oxford University Press, Quest Diagnostics, Scion, Supernus, Teva, Trigemina Inc., Upsher-Smith, UpToDate, Wolters Kluwer and Zosano.

SOURCE: Szperka CL et al. Headache. 2018. doi: 10.1111/head.13414.

Use of anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) may benefit children with more than 8 headache days each month, a high Pediatric Migraine Disability Assessment (PedMIDAS) score, and failure of other treatments; however, researchers cautioned that long-term safety outcomes for the treatment are not yet known, according to a recent set of recommendations published in the journal Headache.

Christina L. Szperka, MD, MSCE, of the division of neurology at the Children’s Hospital of Philadelphia and members of the Pediatric and Adolescent Headache special interest group of the American Headache Society discussed the topic of anti-CGRP mAbs at the 2018 Annual Scientific Meeting of the American Headache Society. They noted clinical outcomes for anti-CGRP mAbs in pediatric patients will likely not be available for several years and created a set of recommendations based on expert opinion of anti-CGRP mAb use in children and adolescents.

Their recommendations support using anti-CGRP mAbs for children with migraine if patients meet the following criteria: headache frequency exceeding 8 headache days per month; a PedMIDAS score of 30 or greater; failure of two or more therapies, such as pharmacologic, nonpharmacologic, or nutraceutical ones; and in patients who are past puberty.

The special interest group recommended against use of anti-CGRP mAbs in children and adolescents with recent meningitis, recent peripheral nerve injury, neurosurgery, or a central nervous system injury caused by a potentially compromised blood-brain barrier. Children and adolescents with immunodeficiency, receiving immunosuppressive medications, with structural heart defects, with pulmonary hypertension, with coronary artery disease, with cardiomyopathy, or at risk for stroke should also avoid use of anti-CGRP mAbs. Anti-CGRP mAbs are also potentially teratogenic and should not be used by adolescents or women who are pregnant, breastfeeding, or have a pregnancy wish.

Pediatric patients with significant osteoporosis or bone disease should be monitored when prescribed anti-CGRP mAbs, and the recommendations specified monitoring height and linear growth or waiting until after puberty to prescribe anti-CGRP mAbs. Although there is currently no evidence that use of anti-CGRP mAb requires pituitary hormone monitoring, the recommendations noted that weight and body mass index should also be observed.

“Pediatric and adolescent trials of anti-CGRP mAbs should be designed to maximize the chances of determining efficacy in these age groups and should focus on those who have not been successful with current multidisciplinary care,” Dr. Szperka and her colleagues wrote in the recommendations. “In the interim, the use of anti-CGRP mAbs for the treatment of headache disorders in children and adolescents may be considered in appropriate cases but should be done with close follow-up and attention to patient characteristics such as age, pubertal state, and medical comorbidities.”

Dr. Szperka receives grant support from Pfizer and Amgen and research funding from NIH. Other authors have reported grants, consulting fees, speaking fees, royalties, advisory board memberships, speaker’s bureau memberships and travel funds from Alder, Allergan, American Academy of Neurology, Amgen, Aralez, Avanir, Autonomic Technologies Inc., Biohaven, Cambridge University Press, Curelator, Depomed, Dr. Reddy’s Laboratories, Electrocore, eNeura, Genentech, Healint, Impax, JAMA Neurology, Journal Watch, Lilly, Massachusetts Medical Society, MedDay, MedicoLegal, Merck, NIH, Novartis, Oxford University Press, Quest Diagnostics, Scion, Supernus, Teva, Trigemina Inc., Upsher-Smith, UpToDate, Wolters Kluwer and Zosano.

SOURCE: Szperka CL et al. Headache. 2018. doi: 10.1111/head.13414.

Use of anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) may benefit children with more than 8 headache days each month, a high Pediatric Migraine Disability Assessment (PedMIDAS) score, and failure of other treatments; however, researchers cautioned that long-term safety outcomes for the treatment are not yet known, according to a recent set of recommendations published in the journal Headache.

Christina L. Szperka, MD, MSCE, of the division of neurology at the Children’s Hospital of Philadelphia and members of the Pediatric and Adolescent Headache special interest group of the American Headache Society discussed the topic of anti-CGRP mAbs at the 2018 Annual Scientific Meeting of the American Headache Society. They noted clinical outcomes for anti-CGRP mAbs in pediatric patients will likely not be available for several years and created a set of recommendations based on expert opinion of anti-CGRP mAb use in children and adolescents.

Their recommendations support using anti-CGRP mAbs for children with migraine if patients meet the following criteria: headache frequency exceeding 8 headache days per month; a PedMIDAS score of 30 or greater; failure of two or more therapies, such as pharmacologic, nonpharmacologic, or nutraceutical ones; and in patients who are past puberty.

The special interest group recommended against use of anti-CGRP mAbs in children and adolescents with recent meningitis, recent peripheral nerve injury, neurosurgery, or a central nervous system injury caused by a potentially compromised blood-brain barrier. Children and adolescents with immunodeficiency, receiving immunosuppressive medications, with structural heart defects, with pulmonary hypertension, with coronary artery disease, with cardiomyopathy, or at risk for stroke should also avoid use of anti-CGRP mAbs. Anti-CGRP mAbs are also potentially teratogenic and should not be used by adolescents or women who are pregnant, breastfeeding, or have a pregnancy wish.

Pediatric patients with significant osteoporosis or bone disease should be monitored when prescribed anti-CGRP mAbs, and the recommendations specified monitoring height and linear growth or waiting until after puberty to prescribe anti-CGRP mAbs. Although there is currently no evidence that use of anti-CGRP mAb requires pituitary hormone monitoring, the recommendations noted that weight and body mass index should also be observed.

“Pediatric and adolescent trials of anti-CGRP mAbs should be designed to maximize the chances of determining efficacy in these age groups and should focus on those who have not been successful with current multidisciplinary care,” Dr. Szperka and her colleagues wrote in the recommendations. “In the interim, the use of anti-CGRP mAbs for the treatment of headache disorders in children and adolescents may be considered in appropriate cases but should be done with close follow-up and attention to patient characteristics such as age, pubertal state, and medical comorbidities.”

Dr. Szperka receives grant support from Pfizer and Amgen and research funding from NIH. Other authors have reported grants, consulting fees, speaking fees, royalties, advisory board memberships, speaker’s bureau memberships and travel funds from Alder, Allergan, American Academy of Neurology, Amgen, Aralez, Avanir, Autonomic Technologies Inc., Biohaven, Cambridge University Press, Curelator, Depomed, Dr. Reddy’s Laboratories, Electrocore, eNeura, Genentech, Healint, Impax, JAMA Neurology, Journal Watch, Lilly, Massachusetts Medical Society, MedDay, MedicoLegal, Merck, NIH, Novartis, Oxford University Press, Quest Diagnostics, Scion, Supernus, Teva, Trigemina Inc., Upsher-Smith, UpToDate, Wolters Kluwer and Zosano.

SOURCE: Szperka CL et al. Headache. 2018. doi: 10.1111/head.13414.

Pediatric headache and migraine are associated with a variety of conditions including respiratory, gastrointestinal, neurologic, and mood disorders, according to findings published in the Journal of Pediatrics.

Marta Ortiz/iStock/Getty Images Plus

In a study of 9,329 pediatric patients from the Philadelphia Neurodevelopmental Cohort, at the University of Pennsylvania, children with any headache type were more likely to have cardiovascular (odds ratio, 1.4; 95% confidence interval, 1.1-1.7) and gastrointestinal (OR, 1.2; 95% CI, 1.1-1.4) problems than did those without headache. In addition, they were more likely to have attention deficit hyperactivity disorder (OR, 1.2; 95% CI, 1.1-1.4), wrote Tarannum M. Lateef, MD, MPH, of the Center for Neuroscience and Behavioral Medicine at Children’s National Medical Center in Washington, and her coauthors.

Study participants were aged 8-21 years and were enrolled in the cohort from November 2009 to November 2011. Physical conditions were identified using EMRs and interviews and were later grouped together by general category.

Patients were asked about lifetime headache and migraine symptoms including sensitivity to light and noise, gastrointestinal symptoms, unilateral pain, throbbing and pulsation, and interference at school or work. Migraine was defined as headache accompanied by any three of these symptoms. Mental disorders were identified using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, reported Dr. Lateef and her associates.

Lifetime prevalence of any headache was 45.5%, and 22.6% for migraine. Migraine was more common in female patients (25.5%) than in male patients (19.4%).

Compared with nonmigraine headache patients, those with migraine more frequently had neurologic/central nervous system disorders (OR, 1.7; 95% CI, 1.4-2.0), developmental disorders (OR, 1.3; 95% CI, 1.1-1.6), respiratory problems (OR, 1.3; 95% CI, 1.1-1.6), anxiety (OR, 1.6; 95% CI, 1.3-2), mood disorders (OR, 2; 95% CI, 1.6-2.3), and behavioral disorders (OR, 1.3; 95% CI, 1.1-1.6).

The results suggest that “headache, particularly migraine, is associated with respiratory and other neurologic and developmental disorders, as well as with anxiety and mood disorders,” the authors wrote.

“Comorbidity may be an important index of heterogeneity … that can guide clinical management, genetic investigation, and future research on shared pathophysiology” with other disorders, they concluded.

No disclosures were reported.
 

SOURCE: Lateef T et al. J Pediatr. 2018 Oct 29. doi: 10.1016/j.jpeds.2018.09.033.

Pediatric headache and migraine are associated with a variety of conditions including respiratory, gastrointestinal, neurologic, and mood disorders, according to findings published in the Journal of Pediatrics.

Marta Ortiz/iStock/Getty Images Plus

In a study of 9,329 pediatric patients from the Philadelphia Neurodevelopmental Cohort, at the University of Pennsylvania, children with any headache type were more likely to have cardiovascular (odds ratio, 1.4; 95% confidence interval, 1.1-1.7) and gastrointestinal (OR, 1.2; 95% CI, 1.1-1.4) problems than did those without headache. In addition, they were more likely to have attention deficit hyperactivity disorder (OR, 1.2; 95% CI, 1.1-1.4), wrote Tarannum M. Lateef, MD, MPH, of the Center for Neuroscience and Behavioral Medicine at Children’s National Medical Center in Washington, and her coauthors.

Study participants were aged 8-21 years and were enrolled in the cohort from November 2009 to November 2011. Physical conditions were identified using EMRs and interviews and were later grouped together by general category.

Patients were asked about lifetime headache and migraine symptoms including sensitivity to light and noise, gastrointestinal symptoms, unilateral pain, throbbing and pulsation, and interference at school or work. Migraine was defined as headache accompanied by any three of these symptoms. Mental disorders were identified using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, reported Dr. Lateef and her associates.

Lifetime prevalence of any headache was 45.5%, and 22.6% for migraine. Migraine was more common in female patients (25.5%) than in male patients (19.4%).

Compared with nonmigraine headache patients, those with migraine more frequently had neurologic/central nervous system disorders (OR, 1.7; 95% CI, 1.4-2.0), developmental disorders (OR, 1.3; 95% CI, 1.1-1.6), respiratory problems (OR, 1.3; 95% CI, 1.1-1.6), anxiety (OR, 1.6; 95% CI, 1.3-2), mood disorders (OR, 2; 95% CI, 1.6-2.3), and behavioral disorders (OR, 1.3; 95% CI, 1.1-1.6).

The results suggest that “headache, particularly migraine, is associated with respiratory and other neurologic and developmental disorders, as well as with anxiety and mood disorders,” the authors wrote.

“Comorbidity may be an important index of heterogeneity … that can guide clinical management, genetic investigation, and future research on shared pathophysiology” with other disorders, they concluded.

No disclosures were reported.
 

SOURCE: Lateef T et al. J Pediatr. 2018 Oct 29. doi: 10.1016/j.jpeds.2018.09.033.

Pediatric headache and migraine are associated with a variety of conditions including respiratory, gastrointestinal, neurologic, and mood disorders, according to findings published in the Journal of Pediatrics.

Marta Ortiz/iStock/Getty Images Plus

In a study of 9,329 pediatric patients from the Philadelphia Neurodevelopmental Cohort, at the University of Pennsylvania, children with any headache type were more likely to have cardiovascular (odds ratio, 1.4; 95% confidence interval, 1.1-1.7) and gastrointestinal (OR, 1.2; 95% CI, 1.1-1.4) problems than did those without headache. In addition, they were more likely to have attention deficit hyperactivity disorder (OR, 1.2; 95% CI, 1.1-1.4), wrote Tarannum M. Lateef, MD, MPH, of the Center for Neuroscience and Behavioral Medicine at Children’s National Medical Center in Washington, and her coauthors.

Study participants were aged 8-21 years and were enrolled in the cohort from November 2009 to November 2011. Physical conditions were identified using EMRs and interviews and were later grouped together by general category.

Patients were asked about lifetime headache and migraine symptoms including sensitivity to light and noise, gastrointestinal symptoms, unilateral pain, throbbing and pulsation, and interference at school or work. Migraine was defined as headache accompanied by any three of these symptoms. Mental disorders were identified using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, reported Dr. Lateef and her associates.

Lifetime prevalence of any headache was 45.5%, and 22.6% for migraine. Migraine was more common in female patients (25.5%) than in male patients (19.4%).

Compared with nonmigraine headache patients, those with migraine more frequently had neurologic/central nervous system disorders (OR, 1.7; 95% CI, 1.4-2.0), developmental disorders (OR, 1.3; 95% CI, 1.1-1.6), respiratory problems (OR, 1.3; 95% CI, 1.1-1.6), anxiety (OR, 1.6; 95% CI, 1.3-2), mood disorders (OR, 2; 95% CI, 1.6-2.3), and behavioral disorders (OR, 1.3; 95% CI, 1.1-1.6).

The results suggest that “headache, particularly migraine, is associated with respiratory and other neurologic and developmental disorders, as well as with anxiety and mood disorders,” the authors wrote.

“Comorbidity may be an important index of heterogeneity … that can guide clinical management, genetic investigation, and future research on shared pathophysiology” with other disorders, they concluded.

No disclosures were reported.
 

SOURCE: Lateef T et al. J Pediatr. 2018 Oct 29. doi: 10.1016/j.jpeds.2018.09.033.

Migraine is a common neurovascular disorder with episodic attacks of throbbing headache, nausea/vomiting, photophobia, and phonophobia. Migraine symptoms will lessen in up to 70% of pregnant women, usually during the second and third trimesters, but will worsen in 4%-8%, and new-onset migraine may account for as many as 16% of all cases of the disorder in pregnancy.

Prevention of migraines

baona/E+/Getty Images

A 2002 review by Goadsby PJ et al. (N Engl J Med. 2002 Jan 24;346[4]:257-70) identified 11 drugs or drug classes for the prevention of migraine attacks. Four agents that are available in the United States were thought to have proven efficacy or were well accepted: metoprolol, propranolol, amitriptyline, and valproate. Valproate should not be used during pregnancy because it is a known teratogen and can cause other fetal problems throughout gestation. Metoprolol, a cardioselective beta-blocker, is a risk for intrauterine growth restriction (IUGR) in the second/third trimesters.

Three other agents are not available in the United States: flunarizine (an agent with calcium channel blocking activity) and two serotonin antagonists, pizotifen and methysergide (a semisynthetic ergot alkaloid). Based on the drug class, flunarizine probably is compatible with pregnancy. Ergot alkaloids, including methysergide, are contraindicated in pregnancy.

Verapamil (Calan, Isoptin) and the selective serotonin reuptake inhibitors (SSRIs) were widely used, but the reviewers concluded that there was poor evidence of benefit.

Use of the SSRI antidepressants in the third trimester may cause newborn toxicity.

Only amitriptyline, verapamil, and low-dose propranolol (30-40 mg/day) have sufficient data to classify as compatible throughout pregnancy, but higher doses of propranolol may cause IUGR and other fetal/neonatal toxicity.

Two agents, gabapentin (Neurontin) and topiramate (Topamax), were considered promising agents for migraine prophylaxis. However, topiramate is best avoided in pregnancy. There are inadequate human data to assess the risk of gabapentin and topiramate, therefore both agents should be avoided in the first trimester.

Breastfeeding: Prevention therapy

Based on their potential for harm, topiramate and valproate should not be used during breastfeeding. All of the other drugs probably are compatible with breastfeeding, but the nursing infant should be monitored for adverse effects common in nonpregnant adults.

Acute treatment of migraines

There are 11 single-agent drugs that are indicated for the acute treatment of migraine.

Almotriptan (Axert) is available as an oral tablet. There are no human pregnancy data and the animal data suggest low risk. However, there is a possible risk of preterm birth.

Dihydroergotamine (Migranal, D.H.E. 45) is available for injection and nasal spray. It is contraindicated, especially near term (it has oxytocic properties), and the animal data suggest risk of IUGR.

Eletriptan (Relpax) is an oral tablet. There are no human data and the animal data suggest low risk. There is a possible risk of preterm birth.

Ergotamine (Ergomar), an oral tablet, is contraindicated in pregnancy and breastfeeding (see above and below).

Methysergide (Sansert) is contraindicated but is not available in United States.

Frovatriptan (Frova) has no human pregnancy data. The animal data suggests low risk but there is the possibility of preterm birth.

There are 93 cases in pregnancy for naratriptan (Amerge) but none during breastfeeding. The drug did not cause major defects in animals but did produce dose-related embryo and fetal development toxicity. In addition, the data did suggest a possible increase in preterm births.

For the rizatriptan (Maxalt, Maxalt-MLT) tablet, animal data suggest low risk. There was exposure to the drug in more than 81 human pregnancy cases. Although there was no evidence of birth defects, the data raised the concern of preterm birth.

There is no evidence that sumatriptan (Alsuma, Imitrex, Imitrex Statdose, Sumavel DosePro, Zecuity) is a human teratogen but there is a possible increase in preterm birth. The drug was teratogenic in one animal species. This agent is available as a tablet and for injection.

There is no human pregnancy data for zolmitriptan (Zomig; Zomig-ZMT) but, as with all triptans, there is a possible risk of preterm birth. The animal data suggest low risk. It is available as an oral tablet.

There are three multiagent products that can be used to treat migraines. There are no published human pregnancy data for these combination products. The combination oral drug sumatriptan and naproxen (Treximet) is best avoided in pregnancy because first trimester exposure to the NSAID naproxen may cause embryo-fetal harm (structural anomalies and abortion) or close to term (premature closure of the ductus arteriosus) and other newborn toxicities.

Caffeine and ergotamine (Cafergot, Migergot) tablets should be considered contraindicated in pregnancy and breastfeeding. Although small, infrequent doses of this product do not appear to be fetotoxic or teratogenic, idiosyncratic responses may occur with ergotamine that endanger the fetus.

The third product, acetaminophen, dichloralphenazone, and isometheptene (Epidrin, LarkaDrin, Migragesic IDA) is an over-the-counter tablet. It does not appear to be related to embryo-fetal harm, but its effectiveness is unknown.

Breastfeeding: Acute treatment

Consistent with their relatively low molecular weights, all of the acute treatment agents most likely are excreted into breast milk. With the exception of the two ergotamine products, both of which should be considered contraindicated, all of the other agents probably are compatible during breastfeeding.

Summary

Migraine headaches are common but can be prevented and/or treated safely in pregnancy and when nursing. In addition to the review mentioned above, three other reviews are well worth reading: Becker WJ. Continuum (Minneap Minn). 2015 Aug;21(4 Headache):953-72; Becker WJ. Headache. 2015 Jun;55(6):778-93; Hutchinson S et al. Headache. 2013 Apr;53(4):614-27.

Mr. Briggs is a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

Migraine is a common neurovascular disorder with episodic attacks of throbbing headache, nausea/vomiting, photophobia, and phonophobia. Migraine symptoms will lessen in up to 70% of pregnant women, usually during the second and third trimesters, but will worsen in 4%-8%, and new-onset migraine may account for as many as 16% of all cases of the disorder in pregnancy.

Prevention of migraines

baona/E+/Getty Images

A 2002 review by Goadsby PJ et al. (N Engl J Med. 2002 Jan 24;346[4]:257-70) identified 11 drugs or drug classes for the prevention of migraine attacks. Four agents that are available in the United States were thought to have proven efficacy or were well accepted: metoprolol, propranolol, amitriptyline, and valproate. Valproate should not be used during pregnancy because it is a known teratogen and can cause other fetal problems throughout gestation. Metoprolol, a cardioselective beta-blocker, is a risk for intrauterine growth restriction (IUGR) in the second/third trimesters.

Three other agents are not available in the United States: flunarizine (an agent with calcium channel blocking activity) and two serotonin antagonists, pizotifen and methysergide (a semisynthetic ergot alkaloid). Based on the drug class, flunarizine probably is compatible with pregnancy. Ergot alkaloids, including methysergide, are contraindicated in pregnancy.

Verapamil (Calan, Isoptin) and the selective serotonin reuptake inhibitors (SSRIs) were widely used, but the reviewers concluded that there was poor evidence of benefit.

Use of the SSRI antidepressants in the third trimester may cause newborn toxicity.

Only amitriptyline, verapamil, and low-dose propranolol (30-40 mg/day) have sufficient data to classify as compatible throughout pregnancy, but higher doses of propranolol may cause IUGR and other fetal/neonatal toxicity.

Two agents, gabapentin (Neurontin) and topiramate (Topamax), were considered promising agents for migraine prophylaxis. However, topiramate is best avoided in pregnancy. There are inadequate human data to assess the risk of gabapentin and topiramate, therefore both agents should be avoided in the first trimester.

Breastfeeding: Prevention therapy

Based on their potential for harm, topiramate and valproate should not be used during breastfeeding. All of the other drugs probably are compatible with breastfeeding, but the nursing infant should be monitored for adverse effects common in nonpregnant adults.

Acute treatment of migraines

There are 11 single-agent drugs that are indicated for the acute treatment of migraine.

Almotriptan (Axert) is available as an oral tablet. There are no human pregnancy data and the animal data suggest low risk. However, there is a possible risk of preterm birth.

Dihydroergotamine (Migranal, D.H.E. 45) is available for injection and nasal spray. It is contraindicated, especially near term (it has oxytocic properties), and the animal data suggest risk of IUGR.

Eletriptan (Relpax) is an oral tablet. There are no human data and the animal data suggest low risk. There is a possible risk of preterm birth.

Ergotamine (Ergomar), an oral tablet, is contraindicated in pregnancy and breastfeeding (see above and below).

Methysergide (Sansert) is contraindicated but is not available in United States.

Frovatriptan (Frova) has no human pregnancy data. The animal data suggests low risk but there is the possibility of preterm birth.

There are 93 cases in pregnancy for naratriptan (Amerge) but none during breastfeeding. The drug did not cause major defects in animals but did produce dose-related embryo and fetal development toxicity. In addition, the data did suggest a possible increase in preterm births.

For the rizatriptan (Maxalt, Maxalt-MLT) tablet, animal data suggest low risk. There was exposure to the drug in more than 81 human pregnancy cases. Although there was no evidence of birth defects, the data raised the concern of preterm birth.

There is no evidence that sumatriptan (Alsuma, Imitrex, Imitrex Statdose, Sumavel DosePro, Zecuity) is a human teratogen but there is a possible increase in preterm birth. The drug was teratogenic in one animal species. This agent is available as a tablet and for injection.

There is no human pregnancy data for zolmitriptan (Zomig; Zomig-ZMT) but, as with all triptans, there is a possible risk of preterm birth. The animal data suggest low risk. It is available as an oral tablet.

There are three multiagent products that can be used to treat migraines. There are no published human pregnancy data for these combination products. The combination oral drug sumatriptan and naproxen (Treximet) is best avoided in pregnancy because first trimester exposure to the NSAID naproxen may cause embryo-fetal harm (structural anomalies and abortion) or close to term (premature closure of the ductus arteriosus) and other newborn toxicities.

Caffeine and ergotamine (Cafergot, Migergot) tablets should be considered contraindicated in pregnancy and breastfeeding. Although small, infrequent doses of this product do not appear to be fetotoxic or teratogenic, idiosyncratic responses may occur with ergotamine that endanger the fetus.

The third product, acetaminophen, dichloralphenazone, and isometheptene (Epidrin, LarkaDrin, Migragesic IDA) is an over-the-counter tablet. It does not appear to be related to embryo-fetal harm, but its effectiveness is unknown.

Breastfeeding: Acute treatment

Consistent with their relatively low molecular weights, all of the acute treatment agents most likely are excreted into breast milk. With the exception of the two ergotamine products, both of which should be considered contraindicated, all of the other agents probably are compatible during breastfeeding.

Summary

Migraine headaches are common but can be prevented and/or treated safely in pregnancy and when nursing. In addition to the review mentioned above, three other reviews are well worth reading: Becker WJ. Continuum (Minneap Minn). 2015 Aug;21(4 Headache):953-72; Becker WJ. Headache. 2015 Jun;55(6):778-93; Hutchinson S et al. Headache. 2013 Apr;53(4):614-27.

Mr. Briggs is a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

Migraine is a common neurovascular disorder with episodic attacks of throbbing headache, nausea/vomiting, photophobia, and phonophobia. Migraine symptoms will lessen in up to 70% of pregnant women, usually during the second and third trimesters, but will worsen in 4%-8%, and new-onset migraine may account for as many as 16% of all cases of the disorder in pregnancy.

Prevention of migraines

baona/E+/Getty Images

A 2002 review by Goadsby PJ et al. (N Engl J Med. 2002 Jan 24;346[4]:257-70) identified 11 drugs or drug classes for the prevention of migraine attacks. Four agents that are available in the United States were thought to have proven efficacy or were well accepted: metoprolol, propranolol, amitriptyline, and valproate. Valproate should not be used during pregnancy because it is a known teratogen and can cause other fetal problems throughout gestation. Metoprolol, a cardioselective beta-blocker, is a risk for intrauterine growth restriction (IUGR) in the second/third trimesters.

Three other agents are not available in the United States: flunarizine (an agent with calcium channel blocking activity) and two serotonin antagonists, pizotifen and methysergide (a semisynthetic ergot alkaloid). Based on the drug class, flunarizine probably is compatible with pregnancy. Ergot alkaloids, including methysergide, are contraindicated in pregnancy.

Verapamil (Calan, Isoptin) and the selective serotonin reuptake inhibitors (SSRIs) were widely used, but the reviewers concluded that there was poor evidence of benefit.

Use of the SSRI antidepressants in the third trimester may cause newborn toxicity.

Only amitriptyline, verapamil, and low-dose propranolol (30-40 mg/day) have sufficient data to classify as compatible throughout pregnancy, but higher doses of propranolol may cause IUGR and other fetal/neonatal toxicity.

Two agents, gabapentin (Neurontin) and topiramate (Topamax), were considered promising agents for migraine prophylaxis. However, topiramate is best avoided in pregnancy. There are inadequate human data to assess the risk of gabapentin and topiramate, therefore both agents should be avoided in the first trimester.

Breastfeeding: Prevention therapy

Based on their potential for harm, topiramate and valproate should not be used during breastfeeding. All of the other drugs probably are compatible with breastfeeding, but the nursing infant should be monitored for adverse effects common in nonpregnant adults.

Acute treatment of migraines

There are 11 single-agent drugs that are indicated for the acute treatment of migraine.

Almotriptan (Axert) is available as an oral tablet. There are no human pregnancy data and the animal data suggest low risk. However, there is a possible risk of preterm birth.

Dihydroergotamine (Migranal, D.H.E. 45) is available for injection and nasal spray. It is contraindicated, especially near term (it has oxytocic properties), and the animal data suggest risk of IUGR.

Eletriptan (Relpax) is an oral tablet. There are no human data and the animal data suggest low risk. There is a possible risk of preterm birth.

Ergotamine (Ergomar), an oral tablet, is contraindicated in pregnancy and breastfeeding (see above and below).

Methysergide (Sansert) is contraindicated but is not available in United States.

Frovatriptan (Frova) has no human pregnancy data. The animal data suggests low risk but there is the possibility of preterm birth.

There are 93 cases in pregnancy for naratriptan (Amerge) but none during breastfeeding. The drug did not cause major defects in animals but did produce dose-related embryo and fetal development toxicity. In addition, the data did suggest a possible increase in preterm births.

For the rizatriptan (Maxalt, Maxalt-MLT) tablet, animal data suggest low risk. There was exposure to the drug in more than 81 human pregnancy cases. Although there was no evidence of birth defects, the data raised the concern of preterm birth.

There is no evidence that sumatriptan (Alsuma, Imitrex, Imitrex Statdose, Sumavel DosePro, Zecuity) is a human teratogen but there is a possible increase in preterm birth. The drug was teratogenic in one animal species. This agent is available as a tablet and for injection.

There is no human pregnancy data for zolmitriptan (Zomig; Zomig-ZMT) but, as with all triptans, there is a possible risk of preterm birth. The animal data suggest low risk. It is available as an oral tablet.

There are three multiagent products that can be used to treat migraines. There are no published human pregnancy data for these combination products. The combination oral drug sumatriptan and naproxen (Treximet) is best avoided in pregnancy because first trimester exposure to the NSAID naproxen may cause embryo-fetal harm (structural anomalies and abortion) or close to term (premature closure of the ductus arteriosus) and other newborn toxicities.

Caffeine and ergotamine (Cafergot, Migergot) tablets should be considered contraindicated in pregnancy and breastfeeding. Although small, infrequent doses of this product do not appear to be fetotoxic or teratogenic, idiosyncratic responses may occur with ergotamine that endanger the fetus.

The third product, acetaminophen, dichloralphenazone, and isometheptene (Epidrin, LarkaDrin, Migragesic IDA) is an over-the-counter tablet. It does not appear to be related to embryo-fetal harm, but its effectiveness is unknown.

Breastfeeding: Acute treatment

Consistent with their relatively low molecular weights, all of the acute treatment agents most likely are excreted into breast milk. With the exception of the two ergotamine products, both of which should be considered contraindicated, all of the other agents probably are compatible during breastfeeding.

Summary

Migraine headaches are common but can be prevented and/or treated safely in pregnancy and when nursing. In addition to the review mentioned above, three other reviews are well worth reading: Becker WJ. Continuum (Minneap Minn). 2015 Aug;21(4 Headache):953-72; Becker WJ. Headache. 2015 Jun;55(6):778-93; Hutchinson S et al. Headache. 2013 Apr;53(4):614-27.

Mr. Briggs is a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scientific Meeting of the Southern Headache Society.

“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.

Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”

The Migraine–Stroke Connection

Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.

Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.

Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.

Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.

Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.

A Retrospective Cohort Study

Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.

The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).

The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.

Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.

In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.

Prediction Models

In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.

Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.

Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”

—Jake Remaly

Suggested Reading

Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.

Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.

Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.

ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scientific Meeting of the Southern Headache Society.

“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.

Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”

The Migraine–Stroke Connection

Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.

Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.

Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.

Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.

Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.

A Retrospective Cohort Study

Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.

The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).

The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.

Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.

In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.

Prediction Models

In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.

Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.

Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”

—Jake Remaly

Suggested Reading

Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.

Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.

Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.

ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scientific Meeting of the Southern Headache Society.

“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.

Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”

The Migraine–Stroke Connection

Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.

Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.

Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.

Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.

Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.

A Retrospective Cohort Study

Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.

The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).

The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.

Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.

In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.

Prediction Models

In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.

Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.

Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”

—Jake Remaly

Suggested Reading

Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.

Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.

Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.

ASHEVILLE, NC—Patients with intractable cluster headache present an urgent challenge to neurologists. The disorder is associated with “the worst pain you can experience,” and most patients have suicidal ideation, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. To help these patients, it is necessary to confirm the diagnosis, conduct proper evaluations for secondary mimics, and choose the most appropriate and effective treatments, he said at the Eighth Annual Scientific Meeting of the Southern Headache Society.

Making the Diagnosis

The current diagnostic criteria for cluster headache include severe unilateral orbital, supraorbital, or temporal pain that lasts for 15 minutes to 180 minutes when untreated. Patients may have conjunctival injection, lacrimation, rhinorrhea, or a sense of restlessness. Most patients have between one and three attacks per day, and the average attack lasts from 60 minutes to 75 minutes, said Dr. Rozen. Migrainous features such as photophobia, phonophobia, and nausea are common in cluster headache, but should not affect the diagnosis. If the duration and frequency of attacks are consistent with cluster headache, then that is the correct diagnosis, said Dr. Rozen.

Like migraine, cluster headache may be episodic or chronic. Episodic cluster headache is more likely to remit than chronic cluster headache, but the former may transition to the latter.

The European Headache Fed­er­ation has defined treatment-refractory cluster headache as cluster headache that fails to respond to more than three typical preventive medicines. Regardless of whether the disorder is episodic or chronic for a given patient, it may become intractable, said Dr. Rozen.

Reasons for Intractability

One potential reason for intractability is an incorrect diagnosis. Cluster headache is a trigeminal autonomic cephalalgia (TAC), and a person with a diagnosis of intractable cluster headache may in fact have a different TAC. The TACs form a spectrum, and a patient’s disorder may change from cluster headache to paroxysmal hemicrania, for example, said Dr. Rozen. “Always think of [attack] duration and frequency to make your diagnosis.”

Another potential reason for intractability is that the headache is secondary to a lesion. The secondary headache disorders often mimic the primary headache disorders, but do not respond to typical medications. The three most common causes of secondary cluster headache are secretory pituitary tumors, carotid dissections, and cavernous sinus lesions. “Every cluster patient … deserves a brain MRI with or without the pituitary cuts, an MR angiogram (both head and neck with dissection protocol), and pituitary hormones,” said Dr. Rozen.

Established and Emerging Acute Treatments

The most common acute treatments for cluster headache are sumatriptan injection or nasal spray and high-flow oxygen. Most patients respond to these treatments, but for those who do not, neurologists may consider options such as dihydroergotamine (DHE) injection, ergotamines, intranasal lidocaine, olanzapine, chlorpromazine suppository, and indomethacin suppository. Data from the US Cluster Headache Survey, however, indicate that less than 45% of patients respond to these treatments.

Most patients with cluster headache do not respond to oral acute medications because they have slow onsets of action. An exception is zolmitriptan, which is administered in a 10-mg dose, as opposed to the traditional 5-mg oral dose. Another acute nonmedicinal therapy is a suboccipital nerve block, which often terminates a headache within a minute, said Dr. Rozen.

In addition, new acute treatments for cluster headache have emerged. One is the delivery of oxygen by demand valve, which provides oxygen according to the user’s respiration rate and tidal volume. Unlike previous delivery methods, which deliver a small amount of ambient air, the demand valve delivers 100% pure oxygen. The demand valve also allows hyperventilation, which may be crucial for effective treatment, said Dr. Rozen. Several studies have suggested that demand-valve oxygen may be more effective than the typically prescribed continuous-flow oxygen administered through a nonrebreather face mask.

In 2017, the FDA cleared gamma­Core, a noninvasive vagus nerve stimulation (VNS) device, for the acute treatment of episodic cluster headache. Patients can use the device to deliver two-minute doses of stimulation through a conductive gel applied to the neck. The treatment may be considered for patients who have not responded to other acute medications, said Dr. Rozen.

In a study by Schoenen and colleagues, 67% of patients with chronic cluster headache who were treated with on-demand sphenopalatine ganglion stimulation achieved pain relief. In comparison, 7% of patients who received sham treatment achieved pain relief. Sphenopalatine ganglion stimulation is not approved in the United States, however.

Preventive Treatment Is Essential

“It is absolutely key to treat cluster headaches with preventives unless [the patients] have two- to three-week cycles [of attacks],” said Dr. Rozen. Verapamil, lithium, valproic acid, daily corticosteroids, topiramate, melatonin, and methylergonovine can be used for the prevention of cluster headache attacks. Daily corticosteroids are appropriate if the patient’s cycles last for two to three weeks, said Dr. Rozen. Topiramate appears to be more effective in women with cluster headache than men.

Until a patient has failed to respond to all of these preventive treatments, it may be inappropriate to describe his or her disorder as refractory, said Dr. Rozen. If a patient partially responds to one preventive therapy, another can be added. Combination therapy for cluster headache is common, and as many as three medications can be administered concomitantly, said Dr. Rozen. Unlike for other headache disorders, doses for cluster headache can be raised to high levels.

Data from the US Cluster Headache Survey, though, show that less than half of patients respond to preventive treatments. In addition, more than 70% of respondents had never received any preventive treatment, “which is quite scary for such a horrible disorder,” said Dr. Rozen.

Other Treatments May Be Effective

The literature provides a small amount of evidence to support additional treatments for cluster headache. Three studies have indicated a benefit of daily treatment with triptans, particularly frovatriptan, said Dr. Rozen. Data also support transdermal clonidine, indomethacin, and intranasal civamide. “Gabapentin is a wonderful add-on therapy. It is not good as a primary therapy,” said Dr. Rozen. Neurologists also may choose baclofen or mycophenolate mofetil.

Reports indicate that sodium oxybate can alleviate episodic and chronic cluster headache, especially if the patient has multiple nocturnal headaches, said Dr. Rozen. Three trials have examined hyperbaric oxygen, and a placebo-controlled trial found a benefit of warfarin. Rozen, and later Nobre et al, reported that clomiphene was effective and could change the pattern of cluster headache attacks.

Between 40% and 50% of patients respond to a single suboccipital nerve block as preventive therapy. Dr. Rozen has reported on high-volume suboccipital nerve blocks that administer 9 cm3 of 1% lidocaine and a small amount of corticosteroid. This treatment has “an excellent preventive effect in chronic refractory cluster headache,” he added. “Most of these patients have failed eight to 10 preventive [treatments]…. If you fail block one, you will most likely not respond to blocks.” Many patients who respond to this block could respond well to greater occipital nerve stimulation, but it is not easy to get insurance coverage for this treatment, said Dr. Rozen.

Finally, a new class of medications may be approved for cluster headache prevention. The monoclonal calcitonin gene-related peptide antibodies, which have been approved for migraine prevention, appear to be effective for episodic cluster headache in clinical trials. These treatments may not show efficacy for chronic cluster headache, however.

—Erik Greb

Suggested Reading

Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.

Nobre ME, Peres MFP, Moreira PF Filho, Leal AJ. Clomiphene treatment may be effective in refractory episodic and chronic cluster headache. Arq Neuropsiquiatr. 2017;75(9):620-624.

Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012;52(1):99-113.

Rozen TD, Fishman RS. Demand valve oxygen: a promising new oxygen delivery system for the acute treatment of cluster headache. Pain Med. 2013;14(4):455-459.

Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.

ASHEVILLE, NC—Patients with intractable cluster headache present an urgent challenge to neurologists. The disorder is associated with “the worst pain you can experience,” and most patients have suicidal ideation, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. To help these patients, it is necessary to confirm the diagnosis, conduct proper evaluations for secondary mimics, and choose the most appropriate and effective treatments, he said at the Eighth Annual Scientific Meeting of the Southern Headache Society.

Making the Diagnosis

The current diagnostic criteria for cluster headache include severe unilateral orbital, supraorbital, or temporal pain that lasts for 15 minutes to 180 minutes when untreated. Patients may have conjunctival injection, lacrimation, rhinorrhea, or a sense of restlessness. Most patients have between one and three attacks per day, and the average attack lasts from 60 minutes to 75 minutes, said Dr. Rozen. Migrainous features such as photophobia, phonophobia, and nausea are common in cluster headache, but should not affect the diagnosis. If the duration and frequency of attacks are consistent with cluster headache, then that is the correct diagnosis, said Dr. Rozen.

Like migraine, cluster headache may be episodic or chronic. Episodic cluster headache is more likely to remit than chronic cluster headache, but the former may transition to the latter.

The European Headache Fed­er­ation has defined treatment-refractory cluster headache as cluster headache that fails to respond to more than three typical preventive medicines. Regardless of whether the disorder is episodic or chronic for a given patient, it may become intractable, said Dr. Rozen.

Reasons for Intractability

One potential reason for intractability is an incorrect diagnosis. Cluster headache is a trigeminal autonomic cephalalgia (TAC), and a person with a diagnosis of intractable cluster headache may in fact have a different TAC. The TACs form a spectrum, and a patient’s disorder may change from cluster headache to paroxysmal hemicrania, for example, said Dr. Rozen. “Always think of [attack] duration and frequency to make your diagnosis.”

Another potential reason for intractability is that the headache is secondary to a lesion. The secondary headache disorders often mimic the primary headache disorders, but do not respond to typical medications. The three most common causes of secondary cluster headache are secretory pituitary tumors, carotid dissections, and cavernous sinus lesions. “Every cluster patient … deserves a brain MRI with or without the pituitary cuts, an MR angiogram (both head and neck with dissection protocol), and pituitary hormones,” said Dr. Rozen.

Established and Emerging Acute Treatments

The most common acute treatments for cluster headache are sumatriptan injection or nasal spray and high-flow oxygen. Most patients respond to these treatments, but for those who do not, neurologists may consider options such as dihydroergotamine (DHE) injection, ergotamines, intranasal lidocaine, olanzapine, chlorpromazine suppository, and indomethacin suppository. Data from the US Cluster Headache Survey, however, indicate that less than 45% of patients respond to these treatments.

Most patients with cluster headache do not respond to oral acute medications because they have slow onsets of action. An exception is zolmitriptan, which is administered in a 10-mg dose, as opposed to the traditional 5-mg oral dose. Another acute nonmedicinal therapy is a suboccipital nerve block, which often terminates a headache within a minute, said Dr. Rozen.

In addition, new acute treatments for cluster headache have emerged. One is the delivery of oxygen by demand valve, which provides oxygen according to the user’s respiration rate and tidal volume. Unlike previous delivery methods, which deliver a small amount of ambient air, the demand valve delivers 100% pure oxygen. The demand valve also allows hyperventilation, which may be crucial for effective treatment, said Dr. Rozen. Several studies have suggested that demand-valve oxygen may be more effective than the typically prescribed continuous-flow oxygen administered through a nonrebreather face mask.

In 2017, the FDA cleared gamma­Core, a noninvasive vagus nerve stimulation (VNS) device, for the acute treatment of episodic cluster headache. Patients can use the device to deliver two-minute doses of stimulation through a conductive gel applied to the neck. The treatment may be considered for patients who have not responded to other acute medications, said Dr. Rozen.

In a study by Schoenen and colleagues, 67% of patients with chronic cluster headache who were treated with on-demand sphenopalatine ganglion stimulation achieved pain relief. In comparison, 7% of patients who received sham treatment achieved pain relief. Sphenopalatine ganglion stimulation is not approved in the United States, however.

Preventive Treatment Is Essential

“It is absolutely key to treat cluster headaches with preventives unless [the patients] have two- to three-week cycles [of attacks],” said Dr. Rozen. Verapamil, lithium, valproic acid, daily corticosteroids, topiramate, melatonin, and methylergonovine can be used for the prevention of cluster headache attacks. Daily corticosteroids are appropriate if the patient’s cycles last for two to three weeks, said Dr. Rozen. Topiramate appears to be more effective in women with cluster headache than men.

Until a patient has failed to respond to all of these preventive treatments, it may be inappropriate to describe his or her disorder as refractory, said Dr. Rozen. If a patient partially responds to one preventive therapy, another can be added. Combination therapy for cluster headache is common, and as many as three medications can be administered concomitantly, said Dr. Rozen. Unlike for other headache disorders, doses for cluster headache can be raised to high levels.

Data from the US Cluster Headache Survey, though, show that less than half of patients respond to preventive treatments. In addition, more than 70% of respondents had never received any preventive treatment, “which is quite scary for such a horrible disorder,” said Dr. Rozen.

Other Treatments May Be Effective

The literature provides a small amount of evidence to support additional treatments for cluster headache. Three studies have indicated a benefit of daily treatment with triptans, particularly frovatriptan, said Dr. Rozen. Data also support transdermal clonidine, indomethacin, and intranasal civamide. “Gabapentin is a wonderful add-on therapy. It is not good as a primary therapy,” said Dr. Rozen. Neurologists also may choose baclofen or mycophenolate mofetil.

Reports indicate that sodium oxybate can alleviate episodic and chronic cluster headache, especially if the patient has multiple nocturnal headaches, said Dr. Rozen. Three trials have examined hyperbaric oxygen, and a placebo-controlled trial found a benefit of warfarin. Rozen, and later Nobre et al, reported that clomiphene was effective and could change the pattern of cluster headache attacks.

Between 40% and 50% of patients respond to a single suboccipital nerve block as preventive therapy. Dr. Rozen has reported on high-volume suboccipital nerve blocks that administer 9 cm3 of 1% lidocaine and a small amount of corticosteroid. This treatment has “an excellent preventive effect in chronic refractory cluster headache,” he added. “Most of these patients have failed eight to 10 preventive [treatments]…. If you fail block one, you will most likely not respond to blocks.” Many patients who respond to this block could respond well to greater occipital nerve stimulation, but it is not easy to get insurance coverage for this treatment, said Dr. Rozen.

Finally, a new class of medications may be approved for cluster headache prevention. The monoclonal calcitonin gene-related peptide antibodies, which have been approved for migraine prevention, appear to be effective for episodic cluster headache in clinical trials. These treatments may not show efficacy for chronic cluster headache, however.

—Erik Greb

Suggested Reading

Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.

Nobre ME, Peres MFP, Moreira PF Filho, Leal AJ. Clomiphene treatment may be effective in refractory episodic and chronic cluster headache. Arq Neuropsiquiatr. 2017;75(9):620-624.

Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012;52(1):99-113.

Rozen TD, Fishman RS. Demand valve oxygen: a promising new oxygen delivery system for the acute treatment of cluster headache. Pain Med. 2013;14(4):455-459.

Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.

ASHEVILLE, NC—Patients with intractable cluster headache present an urgent challenge to neurologists. The disorder is associated with “the worst pain you can experience,” and most patients have suicidal ideation, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. To help these patients, it is necessary to confirm the diagnosis, conduct proper evaluations for secondary mimics, and choose the most appropriate and effective treatments, he said at the Eighth Annual Scientific Meeting of the Southern Headache Society.

Making the Diagnosis

The current diagnostic criteria for cluster headache include severe unilateral orbital, supraorbital, or temporal pain that lasts for 15 minutes to 180 minutes when untreated. Patients may have conjunctival injection, lacrimation, rhinorrhea, or a sense of restlessness. Most patients have between one and three attacks per day, and the average attack lasts from 60 minutes to 75 minutes, said Dr. Rozen. Migrainous features such as photophobia, phonophobia, and nausea are common in cluster headache, but should not affect the diagnosis. If the duration and frequency of attacks are consistent with cluster headache, then that is the correct diagnosis, said Dr. Rozen.

Like migraine, cluster headache may be episodic or chronic. Episodic cluster headache is more likely to remit than chronic cluster headache, but the former may transition to the latter.

The European Headache Fed­er­ation has defined treatment-refractory cluster headache as cluster headache that fails to respond to more than three typical preventive medicines. Regardless of whether the disorder is episodic or chronic for a given patient, it may become intractable, said Dr. Rozen.

Reasons for Intractability

One potential reason for intractability is an incorrect diagnosis. Cluster headache is a trigeminal autonomic cephalalgia (TAC), and a person with a diagnosis of intractable cluster headache may in fact have a different TAC. The TACs form a spectrum, and a patient’s disorder may change from cluster headache to paroxysmal hemicrania, for example, said Dr. Rozen. “Always think of [attack] duration and frequency to make your diagnosis.”

Another potential reason for intractability is that the headache is secondary to a lesion. The secondary headache disorders often mimic the primary headache disorders, but do not respond to typical medications. The three most common causes of secondary cluster headache are secretory pituitary tumors, carotid dissections, and cavernous sinus lesions. “Every cluster patient … deserves a brain MRI with or without the pituitary cuts, an MR angiogram (both head and neck with dissection protocol), and pituitary hormones,” said Dr. Rozen.

Established and Emerging Acute Treatments

The most common acute treatments for cluster headache are sumatriptan injection or nasal spray and high-flow oxygen. Most patients respond to these treatments, but for those who do not, neurologists may consider options such as dihydroergotamine (DHE) injection, ergotamines, intranasal lidocaine, olanzapine, chlorpromazine suppository, and indomethacin suppository. Data from the US Cluster Headache Survey, however, indicate that less than 45% of patients respond to these treatments.

Most patients with cluster headache do not respond to oral acute medications because they have slow onsets of action. An exception is zolmitriptan, which is administered in a 10-mg dose, as opposed to the traditional 5-mg oral dose. Another acute nonmedicinal therapy is a suboccipital nerve block, which often terminates a headache within a minute, said Dr. Rozen.

In addition, new acute treatments for cluster headache have emerged. One is the delivery of oxygen by demand valve, which provides oxygen according to the user’s respiration rate and tidal volume. Unlike previous delivery methods, which deliver a small amount of ambient air, the demand valve delivers 100% pure oxygen. The demand valve also allows hyperventilation, which may be crucial for effective treatment, said Dr. Rozen. Several studies have suggested that demand-valve oxygen may be more effective than the typically prescribed continuous-flow oxygen administered through a nonrebreather face mask.

In 2017, the FDA cleared gamma­Core, a noninvasive vagus nerve stimulation (VNS) device, for the acute treatment of episodic cluster headache. Patients can use the device to deliver two-minute doses of stimulation through a conductive gel applied to the neck. The treatment may be considered for patients who have not responded to other acute medications, said Dr. Rozen.

In a study by Schoenen and colleagues, 67% of patients with chronic cluster headache who were treated with on-demand sphenopalatine ganglion stimulation achieved pain relief. In comparison, 7% of patients who received sham treatment achieved pain relief. Sphenopalatine ganglion stimulation is not approved in the United States, however.

Preventive Treatment Is Essential

“It is absolutely key to treat cluster headaches with preventives unless [the patients] have two- to three-week cycles [of attacks],” said Dr. Rozen. Verapamil, lithium, valproic acid, daily corticosteroids, topiramate, melatonin, and methylergonovine can be used for the prevention of cluster headache attacks. Daily corticosteroids are appropriate if the patient’s cycles last for two to three weeks, said Dr. Rozen. Topiramate appears to be more effective in women with cluster headache than men.

Until a patient has failed to respond to all of these preventive treatments, it may be inappropriate to describe his or her disorder as refractory, said Dr. Rozen. If a patient partially responds to one preventive therapy, another can be added. Combination therapy for cluster headache is common, and as many as three medications can be administered concomitantly, said Dr. Rozen. Unlike for other headache disorders, doses for cluster headache can be raised to high levels.

Data from the US Cluster Headache Survey, though, show that less than half of patients respond to preventive treatments. In addition, more than 70% of respondents had never received any preventive treatment, “which is quite scary for such a horrible disorder,” said Dr. Rozen.

Other Treatments May Be Effective

The literature provides a small amount of evidence to support additional treatments for cluster headache. Three studies have indicated a benefit of daily treatment with triptans, particularly frovatriptan, said Dr. Rozen. Data also support transdermal clonidine, indomethacin, and intranasal civamide. “Gabapentin is a wonderful add-on therapy. It is not good as a primary therapy,” said Dr. Rozen. Neurologists also may choose baclofen or mycophenolate mofetil.

Reports indicate that sodium oxybate can alleviate episodic and chronic cluster headache, especially if the patient has multiple nocturnal headaches, said Dr. Rozen. Three trials have examined hyperbaric oxygen, and a placebo-controlled trial found a benefit of warfarin. Rozen, and later Nobre et al, reported that clomiphene was effective and could change the pattern of cluster headache attacks.

Between 40% and 50% of patients respond to a single suboccipital nerve block as preventive therapy. Dr. Rozen has reported on high-volume suboccipital nerve blocks that administer 9 cm3 of 1% lidocaine and a small amount of corticosteroid. This treatment has “an excellent preventive effect in chronic refractory cluster headache,” he added. “Most of these patients have failed eight to 10 preventive [treatments]…. If you fail block one, you will most likely not respond to blocks.” Many patients who respond to this block could respond well to greater occipital nerve stimulation, but it is not easy to get insurance coverage for this treatment, said Dr. Rozen.

Finally, a new class of medications may be approved for cluster headache prevention. The monoclonal calcitonin gene-related peptide antibodies, which have been approved for migraine prevention, appear to be effective for episodic cluster headache in clinical trials. These treatments may not show efficacy for chronic cluster headache, however.

—Erik Greb

Suggested Reading

Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.

Nobre ME, Peres MFP, Moreira PF Filho, Leal AJ. Clomiphene treatment may be effective in refractory episodic and chronic cluster headache. Arq Neuropsiquiatr. 2017;75(9):620-624.

Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012;52(1):99-113.

Rozen TD, Fishman RS. Demand valve oxygen: a promising new oxygen delivery system for the acute treatment of cluster headache. Pain Med. 2013;14(4):455-459.

Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.

Researchers did not find any difference in number of self-reported premenstrual syndrome (PMS) symptoms between migraineurs with and without menstrual migraine (MM), according to a recent study. A total of 237 women from the general population who self-reported migraine in at least 50% of their menstrual periods were invited to a clinical interview and diagnosed by a neurologist. All women were asked to complete a self-administered form containing 11 questions about PMS symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS). They found:

• 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n=61) or because they did not fulfill the ICHD-criteria for migraine (n=6).
• Among the remaining 126 migraineurs, 78 had MM and 48 had non-menstrually related migraine.
• PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs 5.9).
• Women with MM reported more migraine days/month, longer lasting migraine attacks, and higher HIT-6 scores than those without MM, but MIDAS scores were similar.

Vetvik KG, MacGregor EA, Lundqyist C, Russell MB. Symptoms of premenstrual syndrome in female migraineurs with and without menstrual migraine. [Published online ahead of print October 17, 2018]. J Headache Pain. doi:10.1186/s10194-018-0931-6.

Researchers did not find any difference in number of self-reported premenstrual syndrome (PMS) symptoms between migraineurs with and without menstrual migraine (MM), according to a recent study. A total of 237 women from the general population who self-reported migraine in at least 50% of their menstrual periods were invited to a clinical interview and diagnosed by a neurologist. All women were asked to complete a self-administered form containing 11 questions about PMS symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS). They found:

• 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n=61) or because they did not fulfill the ICHD-criteria for migraine (n=6).
• Among the remaining 126 migraineurs, 78 had MM and 48 had non-menstrually related migraine.
• PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs 5.9).
• Women with MM reported more migraine days/month, longer lasting migraine attacks, and higher HIT-6 scores than those without MM, but MIDAS scores were similar.

Vetvik KG, MacGregor EA, Lundqyist C, Russell MB. Symptoms of premenstrual syndrome in female migraineurs with and without menstrual migraine. [Published online ahead of print October 17, 2018]. J Headache Pain. doi:10.1186/s10194-018-0931-6.

Researchers did not find any difference in number of self-reported premenstrual syndrome (PMS) symptoms between migraineurs with and without menstrual migraine (MM), according to a recent study. A total of 237 women from the general population who self-reported migraine in at least 50% of their menstrual periods were invited to a clinical interview and diagnosed by a neurologist. All women were asked to complete a self-administered form containing 11 questions about PMS symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS). They found:

• 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n=61) or because they did not fulfill the ICHD-criteria for migraine (n=6).
• Among the remaining 126 migraineurs, 78 had MM and 48 had non-menstrually related migraine.
• PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs 5.9).
• Women with MM reported more migraine days/month, longer lasting migraine attacks, and higher HIT-6 scores than those without MM, but MIDAS scores were similar.

Vetvik KG, MacGregor EA, Lundqyist C, Russell MB. Symptoms of premenstrual syndrome in female migraineurs with and without menstrual migraine. [Published online ahead of print October 17, 2018]. J Headache Pain. doi:10.1186/s10194-018-0931-6.