Migraine ICYMI

Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine, according to a recent study. The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2039 individual human brain cells across 2 published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Researchers found:

• Analysis of single-brain cell RNA sequencing data from 5 major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that greater than 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type.
• Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons.

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing. [Published online ahead of print March 2, 2018]. Cephalalgia. doi:10.1177/0333102418762476.

Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine, according to a recent study. The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2039 individual human brain cells across 2 published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Researchers found:

• Analysis of single-brain cell RNA sequencing data from 5 major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that greater than 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type.
• Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons.

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing. [Published online ahead of print March 2, 2018]. Cephalalgia. doi:10.1177/0333102418762476.

Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine, according to a recent study. The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2039 individual human brain cells across 2 published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Researchers found:

• Analysis of single-brain cell RNA sequencing data from 5 major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that greater than 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type.
• Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons.

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing. [Published online ahead of print March 2, 2018]. Cephalalgia. doi:10.1177/0333102418762476.

Single pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a recent study.  Researchers conducted the eNeura Spring TMS Post-Market Observational US Study of Migraine (ESPOUSE), a multicenter, prospective, open label, observational study. Of the total subjects (n=263), 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The treatment protocol consisted of preventive (4 pulses twice daily) and acute (3 pulses repeated up to 3 times for each attack) treatment. Researchers found:

• The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set.
• For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline compared to the performance goal (-0.63 days).
• There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days).
• The most common adverse events were lightheadedness, tingling, and tinnitus; there were no serious adverse events.

A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE study). [Published online ahead of print March 4, 2018]. Cephalalgia. doi:10.1177/0333102418762525.

Single pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a recent study.  Researchers conducted the eNeura Spring TMS Post-Market Observational US Study of Migraine (ESPOUSE), a multicenter, prospective, open label, observational study. Of the total subjects (n=263), 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The treatment protocol consisted of preventive (4 pulses twice daily) and acute (3 pulses repeated up to 3 times for each attack) treatment. Researchers found:

• The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set.
• For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline compared to the performance goal (-0.63 days).
• There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days).
• The most common adverse events were lightheadedness, tingling, and tinnitus; there were no serious adverse events.

A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE study). [Published online ahead of print March 4, 2018]. Cephalalgia. doi:10.1177/0333102418762525.

Single pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a recent study.  Researchers conducted the eNeura Spring TMS Post-Market Observational US Study of Migraine (ESPOUSE), a multicenter, prospective, open label, observational study. Of the total subjects (n=263), 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The treatment protocol consisted of preventive (4 pulses twice daily) and acute (3 pulses repeated up to 3 times for each attack) treatment. Researchers found:

• The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set.
• For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline compared to the performance goal (-0.63 days).
• There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days).
• The most common adverse events were lightheadedness, tingling, and tinnitus; there were no serious adverse events.

A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE study). [Published online ahead of print March 4, 2018]. Cephalalgia. doi:10.1177/0333102418762525.

Severe headache and migraine remain important public health problems that are more common and burdensome for women, particularly women of childbearing age, and other historically disadvantaged segments of the population, according to a recent study. Researchers searched for the most current publicly available summary statistics from the National Health Interview Survey (NHIS), the National Hospital Ambulatory Medical Care Survey (NHAMCS), and the National Ambulatory Medical Care Survey (NAMCS). They found:

• The prevalence and burden of self-reported migraine and severe headache in the US adult population is high, affecting roughly 1 out of every 6 Americans and 1 in 5 women over a 3-month period (15.3% overall, 9.7% of males, and 20.7% of females).
• The prevalence of migraine or severe headache in 2015 was highest in American Indians or Alaska Natives (18.4%) compared with whites, blacks, or Hispanics, with the lowest prevalence in Asians (11.3%).
• There is a higher burden of migraine in those aged 18-44 (17.9%), people who are unemployed (21.4%), those with family income less than $35,000 per year (19.9%), and the elderly and disabled (16.4%).

The prevalence and impact of migraine and severe headache in the United States: Figures and trends from government health studies. [Published online ahead of print March 12, 2018]. Headache. doi:10.1111/head.13281.

Severe headache and migraine remain important public health problems that are more common and burdensome for women, particularly women of childbearing age, and other historically disadvantaged segments of the population, according to a recent study. Researchers searched for the most current publicly available summary statistics from the National Health Interview Survey (NHIS), the National Hospital Ambulatory Medical Care Survey (NHAMCS), and the National Ambulatory Medical Care Survey (NAMCS). They found:

• The prevalence and burden of self-reported migraine and severe headache in the US adult population is high, affecting roughly 1 out of every 6 Americans and 1 in 5 women over a 3-month period (15.3% overall, 9.7% of males, and 20.7% of females).
• The prevalence of migraine or severe headache in 2015 was highest in American Indians or Alaska Natives (18.4%) compared with whites, blacks, or Hispanics, with the lowest prevalence in Asians (11.3%).
• There is a higher burden of migraine in those aged 18-44 (17.9%), people who are unemployed (21.4%), those with family income less than $35,000 per year (19.9%), and the elderly and disabled (16.4%).

The prevalence and impact of migraine and severe headache in the United States: Figures and trends from government health studies. [Published online ahead of print March 12, 2018]. Headache. doi:10.1111/head.13281.

Severe headache and migraine remain important public health problems that are more common and burdensome for women, particularly women of childbearing age, and other historically disadvantaged segments of the population, according to a recent study. Researchers searched for the most current publicly available summary statistics from the National Health Interview Survey (NHIS), the National Hospital Ambulatory Medical Care Survey (NHAMCS), and the National Ambulatory Medical Care Survey (NAMCS). They found:

• The prevalence and burden of self-reported migraine and severe headache in the US adult population is high, affecting roughly 1 out of every 6 Americans and 1 in 5 women over a 3-month period (15.3% overall, 9.7% of males, and 20.7% of females).
• The prevalence of migraine or severe headache in 2015 was highest in American Indians or Alaska Natives (18.4%) compared with whites, blacks, or Hispanics, with the lowest prevalence in Asians (11.3%).
• There is a higher burden of migraine in those aged 18-44 (17.9%), people who are unemployed (21.4%), those with family income less than $35,000 per year (19.9%), and the elderly and disabled (16.4%).

The prevalence and impact of migraine and severe headache in the United States: Figures and trends from government health studies. [Published online ahead of print March 12, 2018]. Headache. doi:10.1111/head.13281.

More than one-quarter of initial emergency department (ED) visits for migraine are followed by headache revisits in fewer than six months, according to a retrospective study of New York City hospitals. Reporting in the March issue of Headache, Mia T. Minen, MD, MPH, and colleagues found that among patients discharged from the ED with a diagnosis of migraine, 12.5% revisit the same ED for headache more than once within six months. “Targeted interventions might … decrease the frequency of headache revisits,” said Dr. Minen and colleagues. Dr. Minen is Director of Headache Services at NYU Langone Headache Center in New York City.

Migraine causes more than 1.2 million visits to US EDs annually. Many of these visits are revisits among patients who have already been treated in an ED for migraine. Dr. Minen and colleagues sought to determine the frequency of these headache revisits and the sociodemographic factors associated with them.

A Study of New York City EDs

Using the New York City Department of Health and Mental Hygiene Syndromic Surveillance database, Dr. Minen and colleagues conducted a retrospective nested cohort study. They analyzed visits from 18 New York City EDs with discharge diagnoses in the first six months of 2015. They then conducted descriptive analyses to determine the frequency of headache revisits within six months of an index ED visit for migraine and the elapsed time to revisit. Using multivariable logistic regression, the researchers assessed associations between age, sex, poverty, and revisit.

Of 1,052 ED visits with a discharge diagnosis of migraine during the first six months of 2015, 277 (26.3%) had a headache revisit within six months of their initial migraine visit, and 131 (12.5%) had two or more revisits at the same hospital. Of the revisits for headache, 9% occurred within 72 hours, and 46% occurred within 90 days of the initial migraine visit. Sex, age, and poverty were not associated with an ED revisit.

Noting that the revisit rate in New York City EDs was similar to the 30.3% revisit rate in a prior study in Maine EDs, the researchers said that frequent revisits for headache are not surprising. “Migraine is a recurrent headache disorder, and 80% of headache patients in the ED do not visit a clinic, primary care physician, or specialist before visiting the ED. In one urban ED, nearly 60% of ED patients were not instructed to follow-up with a physician, and approximately 40% were not prescribed medications.”

Potentially Preventable

Several approaches could decrease headache revisits, the researchers said. “Within the ED, the use of evidence-based algorithms can aid in the standardization of headache diagnosis and treatment. These should include the use of dexamethasone, an evidence-based intervention to decrease the frequency of moderate or severe headache within 48 hours of ED discharge.” On discharge from the ED, patients should be advised about local headache treatment facilities. “Because ED patients with migraine and psychiatric comorbidities have higher health care utilization rates than migraine patients without psychiatric comorbidities, migraine patients with comorbid psychiatric disorders could be referred to an ED case manager to ensure further intervention.” Finally, “ED revisits for headache could be mitigated by increasing the availability and access to urgent care appointments or walk-in outpatient appointments, especially during off-hour nights and weekends,” they said.

—Glenn S. Williams

Suggested Reading

Minen MT, Boubour A, Wahnich A, et al. A retrospective nested cohort study of emergency department revisits for migraine in New York City. Headache. 2018;58(3):399-406.

More than one-quarter of initial emergency department (ED) visits for migraine are followed by headache revisits in fewer than six months, according to a retrospective study of New York City hospitals. Reporting in the March issue of Headache, Mia T. Minen, MD, MPH, and colleagues found that among patients discharged from the ED with a diagnosis of migraine, 12.5% revisit the same ED for headache more than once within six months. “Targeted interventions might … decrease the frequency of headache revisits,” said Dr. Minen and colleagues. Dr. Minen is Director of Headache Services at NYU Langone Headache Center in New York City.

Migraine causes more than 1.2 million visits to US EDs annually. Many of these visits are revisits among patients who have already been treated in an ED for migraine. Dr. Minen and colleagues sought to determine the frequency of these headache revisits and the sociodemographic factors associated with them.

A Study of New York City EDs

Using the New York City Department of Health and Mental Hygiene Syndromic Surveillance database, Dr. Minen and colleagues conducted a retrospective nested cohort study. They analyzed visits from 18 New York City EDs with discharge diagnoses in the first six months of 2015. They then conducted descriptive analyses to determine the frequency of headache revisits within six months of an index ED visit for migraine and the elapsed time to revisit. Using multivariable logistic regression, the researchers assessed associations between age, sex, poverty, and revisit.

Of 1,052 ED visits with a discharge diagnosis of migraine during the first six months of 2015, 277 (26.3%) had a headache revisit within six months of their initial migraine visit, and 131 (12.5%) had two or more revisits at the same hospital. Of the revisits for headache, 9% occurred within 72 hours, and 46% occurred within 90 days of the initial migraine visit. Sex, age, and poverty were not associated with an ED revisit.

Noting that the revisit rate in New York City EDs was similar to the 30.3% revisit rate in a prior study in Maine EDs, the researchers said that frequent revisits for headache are not surprising. “Migraine is a recurrent headache disorder, and 80% of headache patients in the ED do not visit a clinic, primary care physician, or specialist before visiting the ED. In one urban ED, nearly 60% of ED patients were not instructed to follow-up with a physician, and approximately 40% were not prescribed medications.”

Potentially Preventable

Several approaches could decrease headache revisits, the researchers said. “Within the ED, the use of evidence-based algorithms can aid in the standardization of headache diagnosis and treatment. These should include the use of dexamethasone, an evidence-based intervention to decrease the frequency of moderate or severe headache within 48 hours of ED discharge.” On discharge from the ED, patients should be advised about local headache treatment facilities. “Because ED patients with migraine and psychiatric comorbidities have higher health care utilization rates than migraine patients without psychiatric comorbidities, migraine patients with comorbid psychiatric disorders could be referred to an ED case manager to ensure further intervention.” Finally, “ED revisits for headache could be mitigated by increasing the availability and access to urgent care appointments or walk-in outpatient appointments, especially during off-hour nights and weekends,” they said.

—Glenn S. Williams

Suggested Reading

Minen MT, Boubour A, Wahnich A, et al. A retrospective nested cohort study of emergency department revisits for migraine in New York City. Headache. 2018;58(3):399-406.

More than one-quarter of initial emergency department (ED) visits for migraine are followed by headache revisits in fewer than six months, according to a retrospective study of New York City hospitals. Reporting in the March issue of Headache, Mia T. Minen, MD, MPH, and colleagues found that among patients discharged from the ED with a diagnosis of migraine, 12.5% revisit the same ED for headache more than once within six months. “Targeted interventions might … decrease the frequency of headache revisits,” said Dr. Minen and colleagues. Dr. Minen is Director of Headache Services at NYU Langone Headache Center in New York City.

Migraine causes more than 1.2 million visits to US EDs annually. Many of these visits are revisits among patients who have already been treated in an ED for migraine. Dr. Minen and colleagues sought to determine the frequency of these headache revisits and the sociodemographic factors associated with them.

A Study of New York City EDs

Using the New York City Department of Health and Mental Hygiene Syndromic Surveillance database, Dr. Minen and colleagues conducted a retrospective nested cohort study. They analyzed visits from 18 New York City EDs with discharge diagnoses in the first six months of 2015. They then conducted descriptive analyses to determine the frequency of headache revisits within six months of an index ED visit for migraine and the elapsed time to revisit. Using multivariable logistic regression, the researchers assessed associations between age, sex, poverty, and revisit.

Of 1,052 ED visits with a discharge diagnosis of migraine during the first six months of 2015, 277 (26.3%) had a headache revisit within six months of their initial migraine visit, and 131 (12.5%) had two or more revisits at the same hospital. Of the revisits for headache, 9% occurred within 72 hours, and 46% occurred within 90 days of the initial migraine visit. Sex, age, and poverty were not associated with an ED revisit.

Noting that the revisit rate in New York City EDs was similar to the 30.3% revisit rate in a prior study in Maine EDs, the researchers said that frequent revisits for headache are not surprising. “Migraine is a recurrent headache disorder, and 80% of headache patients in the ED do not visit a clinic, primary care physician, or specialist before visiting the ED. In one urban ED, nearly 60% of ED patients were not instructed to follow-up with a physician, and approximately 40% were not prescribed medications.”

Potentially Preventable

Several approaches could decrease headache revisits, the researchers said. “Within the ED, the use of evidence-based algorithms can aid in the standardization of headache diagnosis and treatment. These should include the use of dexamethasone, an evidence-based intervention to decrease the frequency of moderate or severe headache within 48 hours of ED discharge.” On discharge from the ED, patients should be advised about local headache treatment facilities. “Because ED patients with migraine and psychiatric comorbidities have higher health care utilization rates than migraine patients without psychiatric comorbidities, migraine patients with comorbid psychiatric disorders could be referred to an ED case manager to ensure further intervention.” Finally, “ED revisits for headache could be mitigated by increasing the availability and access to urgent care appointments or walk-in outpatient appointments, especially during off-hour nights and weekends,” they said.

—Glenn S. Williams

Suggested Reading

Minen MT, Boubour A, Wahnich A, et al. A retrospective nested cohort study of emergency department revisits for migraine in New York City. Headache. 2018;58(3):399-406.

Migraine is associated with increased risk of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter, according to a study published online ahead of print January 31 in BMJ. The results suggest that “migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women,” the researchers said.

Prior studies have found that migraine is associated with ischemic stroke and ischemic heart disease, especially among women and patients with migraine with aura. Convincing epidemiologic evidence of an association between migraine and other cardiovascular events has been lacking, however, said Kasper Adelborg, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University Hospital in Denmark, and colleagues.

Incidence per 1,000 People

Patients with incident migraine had greater absolute risk of most cardiovascular outcomes, compared with the general population, across most follow-up periods. After 19 years of follow-up, the cumulative incidences per 1,000 people were greater among migraineurs, compared with the general population, for myocardial infarction (25 vs 17), ischemic stroke (45 vs 25), hemorrhagic stroke (11 vs 6), peripheral artery disease (13 vs 11), venous thromboembolism (27 vs 18), atrial fibrillation or atrial flutter (47 vs 34), and heart failure (19 vs 18).

Migraine was associated with myocardial infarction (adjusted hazard ratio [HR], 1.49), ischemic stroke (adjusted HR, 2.26), and hemorrhagic stroke (adjusted HR, 1.94), as well as venous thromboembolism (adjusted HR, 1.59) and atrial fibrillation or atrial flutter (adjusted HR, 1.25). Migraine was not meaningfully associated with peripheral artery disease or heart failure. “The associations, particularly for stroke outcomes, were stronger during the short term (0–1 years) after diagnosis than the long term (up to 19 years),” the researchers said. In addition, associations were stronger in migraine with aura than in migraine without aura, and in women than in men. In a subcohort of patients with additional data, the associations persisted after additional adjustments for BMI and smoking.

The absolute risk of cardiovascular outcomes was low, which was expected, given the young age of the study population, the researchers noted. Although the investigators adjusted for a range of potential confounders, other unknown or residual confounding (eg, by physical activity) is possible.

Multifactorial mechanisms may explain the observed increased risk of cardiovascular disease in migraine, and different mechanisms may be involved in specific cardiovascular outcomes. Migraine and cardiovascular diseases may share genetic, inflammatory, vascular, endothelial, electrical or depolarizing, or coagulable factors, the researchers said. In addition, migraineurs often use NSAIDs, which are associated with increased risk of cardiovascular events. It is also possible that immobilization due to migraine attacks may increase the risk of venous thromboembolism.

Reducing Risk

“Although the magnitude of the increased cardiovascular risk associated with migraine was fairly small at the individual level, it translates into a substantial increase in risk at the population level, because migraine is a common disease,” Dr. Adelborg and colleagues said. Migraine increasingly is recognized as an important cardiovascular risk factor to consider in clinical practice, and the recently developed QRISK3 algorithm, which predicts 10-year risk of cardiovascular disease in men and women ages 25 to 84, is the first cardiovascular risk-stratification tool to incorporate migraine.

“Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder,” the researchers said. “Current migraine guidelines do not recommend use of aspirin and clopidogrel in the prophylaxis of migraine, but clinicians should consider whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment.”

The present study and prior research provide “plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk marker,” and data indicate that migraine is associated with “a measurable risk of cardiovascular death,” said Tobias Kurth, MD, Professor of Public Health and Epidemiology and Director of the Institute of Public Health at the Charité-Universitätsmedizin Berlin, and colleagues, in an accompanying editorial. Strategies to reduce the risk of cardiovascular disease in patients with migraine are urgently needed and long overdue, they said.

Suggested Reading

Adelborg K, Szépligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ. 2018 Jan 31 [Epub ahead of print].

Kurth T, Rohmann JL, Shapiro RE. Migraine and risk of cardiovascular disease. BMJ. 2018 Jan 31 [Epub ahead of print].

Migraine is associated with increased risk of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter, according to a study published online ahead of print January 31 in BMJ. The results suggest that “migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women,” the researchers said.

Prior studies have found that migraine is associated with ischemic stroke and ischemic heart disease, especially among women and patients with migraine with aura. Convincing epidemiologic evidence of an association between migraine and other cardiovascular events has been lacking, however, said Kasper Adelborg, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University Hospital in Denmark, and colleagues.

Incidence per 1,000 People

Patients with incident migraine had greater absolute risk of most cardiovascular outcomes, compared with the general population, across most follow-up periods. After 19 years of follow-up, the cumulative incidences per 1,000 people were greater among migraineurs, compared with the general population, for myocardial infarction (25 vs 17), ischemic stroke (45 vs 25), hemorrhagic stroke (11 vs 6), peripheral artery disease (13 vs 11), venous thromboembolism (27 vs 18), atrial fibrillation or atrial flutter (47 vs 34), and heart failure (19 vs 18).

Migraine was associated with myocardial infarction (adjusted hazard ratio [HR], 1.49), ischemic stroke (adjusted HR, 2.26), and hemorrhagic stroke (adjusted HR, 1.94), as well as venous thromboembolism (adjusted HR, 1.59) and atrial fibrillation or atrial flutter (adjusted HR, 1.25). Migraine was not meaningfully associated with peripheral artery disease or heart failure. “The associations, particularly for stroke outcomes, were stronger during the short term (0–1 years) after diagnosis than the long term (up to 19 years),” the researchers said. In addition, associations were stronger in migraine with aura than in migraine without aura, and in women than in men. In a subcohort of patients with additional data, the associations persisted after additional adjustments for BMI and smoking.

The absolute risk of cardiovascular outcomes was low, which was expected, given the young age of the study population, the researchers noted. Although the investigators adjusted for a range of potential confounders, other unknown or residual confounding (eg, by physical activity) is possible.

Multifactorial mechanisms may explain the observed increased risk of cardiovascular disease in migraine, and different mechanisms may be involved in specific cardiovascular outcomes. Migraine and cardiovascular diseases may share genetic, inflammatory, vascular, endothelial, electrical or depolarizing, or coagulable factors, the researchers said. In addition, migraineurs often use NSAIDs, which are associated with increased risk of cardiovascular events. It is also possible that immobilization due to migraine attacks may increase the risk of venous thromboembolism.

Reducing Risk

“Although the magnitude of the increased cardiovascular risk associated with migraine was fairly small at the individual level, it translates into a substantial increase in risk at the population level, because migraine is a common disease,” Dr. Adelborg and colleagues said. Migraine increasingly is recognized as an important cardiovascular risk factor to consider in clinical practice, and the recently developed QRISK3 algorithm, which predicts 10-year risk of cardiovascular disease in men and women ages 25 to 84, is the first cardiovascular risk-stratification tool to incorporate migraine.

“Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder,” the researchers said. “Current migraine guidelines do not recommend use of aspirin and clopidogrel in the prophylaxis of migraine, but clinicians should consider whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment.”

The present study and prior research provide “plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk marker,” and data indicate that migraine is associated with “a measurable risk of cardiovascular death,” said Tobias Kurth, MD, Professor of Public Health and Epidemiology and Director of the Institute of Public Health at the Charité-Universitätsmedizin Berlin, and colleagues, in an accompanying editorial. Strategies to reduce the risk of cardiovascular disease in patients with migraine are urgently needed and long overdue, they said.

Suggested Reading

Adelborg K, Szépligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ. 2018 Jan 31 [Epub ahead of print].

Kurth T, Rohmann JL, Shapiro RE. Migraine and risk of cardiovascular disease. BMJ. 2018 Jan 31 [Epub ahead of print].

Migraine is associated with increased risk of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter, according to a study published online ahead of print January 31 in BMJ. The results suggest that “migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women,” the researchers said.

Prior studies have found that migraine is associated with ischemic stroke and ischemic heart disease, especially among women and patients with migraine with aura. Convincing epidemiologic evidence of an association between migraine and other cardiovascular events has been lacking, however, said Kasper Adelborg, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University Hospital in Denmark, and colleagues.

Incidence per 1,000 People

Patients with incident migraine had greater absolute risk of most cardiovascular outcomes, compared with the general population, across most follow-up periods. After 19 years of follow-up, the cumulative incidences per 1,000 people were greater among migraineurs, compared with the general population, for myocardial infarction (25 vs 17), ischemic stroke (45 vs 25), hemorrhagic stroke (11 vs 6), peripheral artery disease (13 vs 11), venous thromboembolism (27 vs 18), atrial fibrillation or atrial flutter (47 vs 34), and heart failure (19 vs 18).

Migraine was associated with myocardial infarction (adjusted hazard ratio [HR], 1.49), ischemic stroke (adjusted HR, 2.26), and hemorrhagic stroke (adjusted HR, 1.94), as well as venous thromboembolism (adjusted HR, 1.59) and atrial fibrillation or atrial flutter (adjusted HR, 1.25). Migraine was not meaningfully associated with peripheral artery disease or heart failure. “The associations, particularly for stroke outcomes, were stronger during the short term (0–1 years) after diagnosis than the long term (up to 19 years),” the researchers said. In addition, associations were stronger in migraine with aura than in migraine without aura, and in women than in men. In a subcohort of patients with additional data, the associations persisted after additional adjustments for BMI and smoking.

The absolute risk of cardiovascular outcomes was low, which was expected, given the young age of the study population, the researchers noted. Although the investigators adjusted for a range of potential confounders, other unknown or residual confounding (eg, by physical activity) is possible.

Multifactorial mechanisms may explain the observed increased risk of cardiovascular disease in migraine, and different mechanisms may be involved in specific cardiovascular outcomes. Migraine and cardiovascular diseases may share genetic, inflammatory, vascular, endothelial, electrical or depolarizing, or coagulable factors, the researchers said. In addition, migraineurs often use NSAIDs, which are associated with increased risk of cardiovascular events. It is also possible that immobilization due to migraine attacks may increase the risk of venous thromboembolism.

Reducing Risk

“Although the magnitude of the increased cardiovascular risk associated with migraine was fairly small at the individual level, it translates into a substantial increase in risk at the population level, because migraine is a common disease,” Dr. Adelborg and colleagues said. Migraine increasingly is recognized as an important cardiovascular risk factor to consider in clinical practice, and the recently developed QRISK3 algorithm, which predicts 10-year risk of cardiovascular disease in men and women ages 25 to 84, is the first cardiovascular risk-stratification tool to incorporate migraine.

“Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder,” the researchers said. “Current migraine guidelines do not recommend use of aspirin and clopidogrel in the prophylaxis of migraine, but clinicians should consider whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment.”

The present study and prior research provide “plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk marker,” and data indicate that migraine is associated with “a measurable risk of cardiovascular death,” said Tobias Kurth, MD, Professor of Public Health and Epidemiology and Director of the Institute of Public Health at the Charité-Universitätsmedizin Berlin, and colleagues, in an accompanying editorial. Strategies to reduce the risk of cardiovascular disease in patients with migraine are urgently needed and long overdue, they said.

Suggested Reading

Adelborg K, Szépligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ. 2018 Jan 31 [Epub ahead of print].

Kurth T, Rohmann JL, Shapiro RE. Migraine and risk of cardiovascular disease. BMJ. 2018 Jan 31 [Epub ahead of print].

NAPLES, FL—A growing literature on posttraumatic headache suggests that many of the accepted principles of onset, course, and treatment should be re-examined. Data suggest that pathogenesis is multidimensional, and neurologists still lack evidence-based treatments, according to a lecture delivered at the 45th Annual Meeting of the Southern Clinical Neurological Society.

When Does Onset Occur?

To begin with, research is calling the current definition of posttraumatic headache into question. Data culled from head injuries in the military, professional sports, and everyday trauma show that headache onset more than seven days after the trauma is not the exception it once was believed to be.

“Regarding soldiers in particular, only 37% report posttraumatic headache onset within seven days of their injury,” reported Bert B. Vargas, MD, Director of the Sports Neurology and Concussion Program at the University of Texas Southwestern Medical Center in Dallas. “The rest of them presented up to several weeks later.”

A New Understanding of Phenotype

The accepted phenotypes of posttraumatic headache have also shifted over the past several years, according to Dr. Vargas. Although tension-like headache was considered characteristic of most posttraumatic headache in years past, researchers familiar with International Classification of Headache Disorders (ICHD) criteria for migraine and other headache disorders found that the tension-type phenotype represented only about 20% of posttraumatic headache. Migraine (∼40%) and probable migraine (∼25%) are the most representative phenotypes, Dr. Vargas said. About 10% of patients have a cervicogenic phenotype, while other phenotypes, like cluster headache, are less common.

Prognosis has also been revisited. More rigorous follow-up shows that a one-to-two-week recovery period is not as typical as once was believed, said Dr. Vargas. An examination of military and athletic injuries suggests that half or more patients continue to have recurring headaches at three months, and as much as one-third have them at the end of one year. In one study, 24% of patients still had recurring headaches at four years. A more recent study reported that at five years after injury, as much as 36% of patients may experience headache several times per week or daily.

Research Clarifies Pathophysiology

The close association between posttraumatic headache and migraine is consistent with the underlying pathophysiology derived from experimental models. In these models, the depolarization caused by concussive force produces a shift in ions that can disrupt neuronal metabolic function, Dr. Vargas said. Similar metabolic changes are associated with migraine aura. These changes include potassium efflux and sodium influx. The increased energy demand produced by activation of ion pumps can be complicated by diminished cerebral blood flow, thus impairing the cell’s drive to maintain homeostasis.

In this cascade of events, which includes cortical spreading depression, headache pain for posttraumatic headache and migraine is believed to be generated by activation of glial cells and release of factors such as calcitonin gene-related peptide (CGRP) that are implicated in pain signaling. “If the accepted pathophysiologies are correct, then what is happening on an intracellular level after concussion is similar to what is seen in migraine aura,” said Dr. Vargas.

Potential Changes in Treatment

Regarding medications commonly used for prophylaxis of posttraumatic headache, “we see a great deal of overlap with medications that are commonly used to treat migraine,” Dr. Vargas said. The evidence supporting the benefit of these agents is generally derived from small, retrospective, open-label studies, however. In one retrospective study in soldiers, topiramate outperformed tricyclic antidepressants, propranolol, and valproate with regard to decrease in headache frequency and Migraine Disability Assessment score in patients with posttraumatic headache. In this study, triptans outperformed nontriptans for acute treatment at two hours. The response rate was better, however, for posttraumatic headache associated with blunt trauma, relative to blast trauma (86% vs 66%).

This difference is potentially important, because experimental studies of blunt and blast concussions suggest that they may be different. “In rodent models, blunt force injury has been shown to result in mast cell degranulation and decrease in the actual density of the mast cells on the ipsilateral and contralateral side of the injury within 72 hours,” said Dr. Vargas. Blast injuries in rodents, in contrast, produce “a delayed and bilateral mast cell degranulation at day seven.” Although further degranulation occurs after this point, the persistence in mast cell density suggests that “the cascades of events that ensue after blunt trauma and blast injuries may be different and may have a meaningful influence on treatment and our expectations for recovery timelines,” said Dr. Vargas.

Even if the best treatments for blast and blunt posttraumatic headache differ, however, there is a lack of well-conducted clinical trials for either condition. Based on available evidence and his own experience, Dr. Vargas concluded that all or most of the therapies used for acute treatment and prophylaxis of migraine are effective in at least some patients with posttraumatic headache. As a precaution, “despite excellent evidence that it is an effective migraine prophylactic medication, I find myself avoiding topiramate as a first-line treatment,” due to concern that this agent may exacerbate the cognitive dysfunction frequently associated with concussion, said Dr. Vargas. Despite some headache specialists’ belief that extended-release topiramate has less effect on cognitive function, Dr. Vargas is not aware of any head-to-head study confirming that the drug reduces this risk.

Despite the evidence that migraine medications offer relief in posttraumatic headache, they are not the first choice for many clinicians, said Dr. Vargas. In one study, between 2% and 5% of patients with posttraumatic headache received triptans. In an ongoing concussion registry in Texas that has now enrolled more than 2,000 patients, “we have observed frequent use of either nonsteroidal anti-inflammatory drugs or acetaminophen,” but initial treatment with migraine-specific medications, such as triptans, is not common, said Dr. Vargas. The data from this registry suggest that many patients, particularly those with a migraine phenotype, appear to report suboptimal pain control.

“Our registry data support other studies showing that migraine-specific medications may be underutilized in posttraumatic headache—including those with migrainous features,” said Dr. Vargas, who helped develop the concussion registry. “An important question that we must address is whether more aggressive treatment directed toward headache phenotype leads to better short- and long-term outcomes.

“Additionally, although current expert opinion suggests that treatment of posttraumatic headache should be based on treatment algorithms based on headache phenotype, well-designed prospective studies are needed to address this question.”

More rigorously defined treatment algorithms have become an urgent need in the context of growing evidence that posttraumatic headache can result in significant morbidity. Dr. Vargas cited one study in which 18.7% of soldiers with persistent posttraumatic headache returned to combat. Also, concern about the long-term consequences of posttraumatic headache from sports-related concussion is growing. In the context of the frequency of posttraumatic headache, Dr. Vargas believes there is an urgent need for objective studies to improve care.

Dr. Vargas reported financial relationships with Amgen, Alder, Avanir, Lilly, Pernix, and Upsher-Smith.

—Ted Bosworth

Suggested Reading

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

Evans RW. Posttraumatic headaches in civilians, soldiers, and athletes. Neurol Clin. 2014;32(2):283-303.

Packard RC. Treatment of chronic daily posttraumatic headache with divalproex sodium. Headache. 2000;40(9):736-739.

NAPLES, FL—A growing literature on posttraumatic headache suggests that many of the accepted principles of onset, course, and treatment should be re-examined. Data suggest that pathogenesis is multidimensional, and neurologists still lack evidence-based treatments, according to a lecture delivered at the 45th Annual Meeting of the Southern Clinical Neurological Society.

When Does Onset Occur?

To begin with, research is calling the current definition of posttraumatic headache into question. Data culled from head injuries in the military, professional sports, and everyday trauma show that headache onset more than seven days after the trauma is not the exception it once was believed to be.

“Regarding soldiers in particular, only 37% report posttraumatic headache onset within seven days of their injury,” reported Bert B. Vargas, MD, Director of the Sports Neurology and Concussion Program at the University of Texas Southwestern Medical Center in Dallas. “The rest of them presented up to several weeks later.”

A New Understanding of Phenotype

The accepted phenotypes of posttraumatic headache have also shifted over the past several years, according to Dr. Vargas. Although tension-like headache was considered characteristic of most posttraumatic headache in years past, researchers familiar with International Classification of Headache Disorders (ICHD) criteria for migraine and other headache disorders found that the tension-type phenotype represented only about 20% of posttraumatic headache. Migraine (∼40%) and probable migraine (∼25%) are the most representative phenotypes, Dr. Vargas said. About 10% of patients have a cervicogenic phenotype, while other phenotypes, like cluster headache, are less common.

Prognosis has also been revisited. More rigorous follow-up shows that a one-to-two-week recovery period is not as typical as once was believed, said Dr. Vargas. An examination of military and athletic injuries suggests that half or more patients continue to have recurring headaches at three months, and as much as one-third have them at the end of one year. In one study, 24% of patients still had recurring headaches at four years. A more recent study reported that at five years after injury, as much as 36% of patients may experience headache several times per week or daily.

Research Clarifies Pathophysiology

The close association between posttraumatic headache and migraine is consistent with the underlying pathophysiology derived from experimental models. In these models, the depolarization caused by concussive force produces a shift in ions that can disrupt neuronal metabolic function, Dr. Vargas said. Similar metabolic changes are associated with migraine aura. These changes include potassium efflux and sodium influx. The increased energy demand produced by activation of ion pumps can be complicated by diminished cerebral blood flow, thus impairing the cell’s drive to maintain homeostasis.

In this cascade of events, which includes cortical spreading depression, headache pain for posttraumatic headache and migraine is believed to be generated by activation of glial cells and release of factors such as calcitonin gene-related peptide (CGRP) that are implicated in pain signaling. “If the accepted pathophysiologies are correct, then what is happening on an intracellular level after concussion is similar to what is seen in migraine aura,” said Dr. Vargas.

Potential Changes in Treatment

Regarding medications commonly used for prophylaxis of posttraumatic headache, “we see a great deal of overlap with medications that are commonly used to treat migraine,” Dr. Vargas said. The evidence supporting the benefit of these agents is generally derived from small, retrospective, open-label studies, however. In one retrospective study in soldiers, topiramate outperformed tricyclic antidepressants, propranolol, and valproate with regard to decrease in headache frequency and Migraine Disability Assessment score in patients with posttraumatic headache. In this study, triptans outperformed nontriptans for acute treatment at two hours. The response rate was better, however, for posttraumatic headache associated with blunt trauma, relative to blast trauma (86% vs 66%).

This difference is potentially important, because experimental studies of blunt and blast concussions suggest that they may be different. “In rodent models, blunt force injury has been shown to result in mast cell degranulation and decrease in the actual density of the mast cells on the ipsilateral and contralateral side of the injury within 72 hours,” said Dr. Vargas. Blast injuries in rodents, in contrast, produce “a delayed and bilateral mast cell degranulation at day seven.” Although further degranulation occurs after this point, the persistence in mast cell density suggests that “the cascades of events that ensue after blunt trauma and blast injuries may be different and may have a meaningful influence on treatment and our expectations for recovery timelines,” said Dr. Vargas.

Even if the best treatments for blast and blunt posttraumatic headache differ, however, there is a lack of well-conducted clinical trials for either condition. Based on available evidence and his own experience, Dr. Vargas concluded that all or most of the therapies used for acute treatment and prophylaxis of migraine are effective in at least some patients with posttraumatic headache. As a precaution, “despite excellent evidence that it is an effective migraine prophylactic medication, I find myself avoiding topiramate as a first-line treatment,” due to concern that this agent may exacerbate the cognitive dysfunction frequently associated with concussion, said Dr. Vargas. Despite some headache specialists’ belief that extended-release topiramate has less effect on cognitive function, Dr. Vargas is not aware of any head-to-head study confirming that the drug reduces this risk.

Despite the evidence that migraine medications offer relief in posttraumatic headache, they are not the first choice for many clinicians, said Dr. Vargas. In one study, between 2% and 5% of patients with posttraumatic headache received triptans. In an ongoing concussion registry in Texas that has now enrolled more than 2,000 patients, “we have observed frequent use of either nonsteroidal anti-inflammatory drugs or acetaminophen,” but initial treatment with migraine-specific medications, such as triptans, is not common, said Dr. Vargas. The data from this registry suggest that many patients, particularly those with a migraine phenotype, appear to report suboptimal pain control.

“Our registry data support other studies showing that migraine-specific medications may be underutilized in posttraumatic headache—including those with migrainous features,” said Dr. Vargas, who helped develop the concussion registry. “An important question that we must address is whether more aggressive treatment directed toward headache phenotype leads to better short- and long-term outcomes.

“Additionally, although current expert opinion suggests that treatment of posttraumatic headache should be based on treatment algorithms based on headache phenotype, well-designed prospective studies are needed to address this question.”

More rigorously defined treatment algorithms have become an urgent need in the context of growing evidence that posttraumatic headache can result in significant morbidity. Dr. Vargas cited one study in which 18.7% of soldiers with persistent posttraumatic headache returned to combat. Also, concern about the long-term consequences of posttraumatic headache from sports-related concussion is growing. In the context of the frequency of posttraumatic headache, Dr. Vargas believes there is an urgent need for objective studies to improve care.

Dr. Vargas reported financial relationships with Amgen, Alder, Avanir, Lilly, Pernix, and Upsher-Smith.

—Ted Bosworth

Suggested Reading

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

Evans RW. Posttraumatic headaches in civilians, soldiers, and athletes. Neurol Clin. 2014;32(2):283-303.

Packard RC. Treatment of chronic daily posttraumatic headache with divalproex sodium. Headache. 2000;40(9):736-739.

NAPLES, FL—A growing literature on posttraumatic headache suggests that many of the accepted principles of onset, course, and treatment should be re-examined. Data suggest that pathogenesis is multidimensional, and neurologists still lack evidence-based treatments, according to a lecture delivered at the 45th Annual Meeting of the Southern Clinical Neurological Society.

When Does Onset Occur?

To begin with, research is calling the current definition of posttraumatic headache into question. Data culled from head injuries in the military, professional sports, and everyday trauma show that headache onset more than seven days after the trauma is not the exception it once was believed to be.

“Regarding soldiers in particular, only 37% report posttraumatic headache onset within seven days of their injury,” reported Bert B. Vargas, MD, Director of the Sports Neurology and Concussion Program at the University of Texas Southwestern Medical Center in Dallas. “The rest of them presented up to several weeks later.”

A New Understanding of Phenotype

The accepted phenotypes of posttraumatic headache have also shifted over the past several years, according to Dr. Vargas. Although tension-like headache was considered characteristic of most posttraumatic headache in years past, researchers familiar with International Classification of Headache Disorders (ICHD) criteria for migraine and other headache disorders found that the tension-type phenotype represented only about 20% of posttraumatic headache. Migraine (∼40%) and probable migraine (∼25%) are the most representative phenotypes, Dr. Vargas said. About 10% of patients have a cervicogenic phenotype, while other phenotypes, like cluster headache, are less common.

Prognosis has also been revisited. More rigorous follow-up shows that a one-to-two-week recovery period is not as typical as once was believed, said Dr. Vargas. An examination of military and athletic injuries suggests that half or more patients continue to have recurring headaches at three months, and as much as one-third have them at the end of one year. In one study, 24% of patients still had recurring headaches at four years. A more recent study reported that at five years after injury, as much as 36% of patients may experience headache several times per week or daily.

Research Clarifies Pathophysiology

The close association between posttraumatic headache and migraine is consistent with the underlying pathophysiology derived from experimental models. In these models, the depolarization caused by concussive force produces a shift in ions that can disrupt neuronal metabolic function, Dr. Vargas said. Similar metabolic changes are associated with migraine aura. These changes include potassium efflux and sodium influx. The increased energy demand produced by activation of ion pumps can be complicated by diminished cerebral blood flow, thus impairing the cell’s drive to maintain homeostasis.

In this cascade of events, which includes cortical spreading depression, headache pain for posttraumatic headache and migraine is believed to be generated by activation of glial cells and release of factors such as calcitonin gene-related peptide (CGRP) that are implicated in pain signaling. “If the accepted pathophysiologies are correct, then what is happening on an intracellular level after concussion is similar to what is seen in migraine aura,” said Dr. Vargas.

Potential Changes in Treatment

Regarding medications commonly used for prophylaxis of posttraumatic headache, “we see a great deal of overlap with medications that are commonly used to treat migraine,” Dr. Vargas said. The evidence supporting the benefit of these agents is generally derived from small, retrospective, open-label studies, however. In one retrospective study in soldiers, topiramate outperformed tricyclic antidepressants, propranolol, and valproate with regard to decrease in headache frequency and Migraine Disability Assessment score in patients with posttraumatic headache. In this study, triptans outperformed nontriptans for acute treatment at two hours. The response rate was better, however, for posttraumatic headache associated with blunt trauma, relative to blast trauma (86% vs 66%).

This difference is potentially important, because experimental studies of blunt and blast concussions suggest that they may be different. “In rodent models, blunt force injury has been shown to result in mast cell degranulation and decrease in the actual density of the mast cells on the ipsilateral and contralateral side of the injury within 72 hours,” said Dr. Vargas. Blast injuries in rodents, in contrast, produce “a delayed and bilateral mast cell degranulation at day seven.” Although further degranulation occurs after this point, the persistence in mast cell density suggests that “the cascades of events that ensue after blunt trauma and blast injuries may be different and may have a meaningful influence on treatment and our expectations for recovery timelines,” said Dr. Vargas.

Even if the best treatments for blast and blunt posttraumatic headache differ, however, there is a lack of well-conducted clinical trials for either condition. Based on available evidence and his own experience, Dr. Vargas concluded that all or most of the therapies used for acute treatment and prophylaxis of migraine are effective in at least some patients with posttraumatic headache. As a precaution, “despite excellent evidence that it is an effective migraine prophylactic medication, I find myself avoiding topiramate as a first-line treatment,” due to concern that this agent may exacerbate the cognitive dysfunction frequently associated with concussion, said Dr. Vargas. Despite some headache specialists’ belief that extended-release topiramate has less effect on cognitive function, Dr. Vargas is not aware of any head-to-head study confirming that the drug reduces this risk.

Despite the evidence that migraine medications offer relief in posttraumatic headache, they are not the first choice for many clinicians, said Dr. Vargas. In one study, between 2% and 5% of patients with posttraumatic headache received triptans. In an ongoing concussion registry in Texas that has now enrolled more than 2,000 patients, “we have observed frequent use of either nonsteroidal anti-inflammatory drugs or acetaminophen,” but initial treatment with migraine-specific medications, such as triptans, is not common, said Dr. Vargas. The data from this registry suggest that many patients, particularly those with a migraine phenotype, appear to report suboptimal pain control.

“Our registry data support other studies showing that migraine-specific medications may be underutilized in posttraumatic headache—including those with migrainous features,” said Dr. Vargas, who helped develop the concussion registry. “An important question that we must address is whether more aggressive treatment directed toward headache phenotype leads to better short- and long-term outcomes.

“Additionally, although current expert opinion suggests that treatment of posttraumatic headache should be based on treatment algorithms based on headache phenotype, well-designed prospective studies are needed to address this question.”

More rigorously defined treatment algorithms have become an urgent need in the context of growing evidence that posttraumatic headache can result in significant morbidity. Dr. Vargas cited one study in which 18.7% of soldiers with persistent posttraumatic headache returned to combat. Also, concern about the long-term consequences of posttraumatic headache from sports-related concussion is growing. In the context of the frequency of posttraumatic headache, Dr. Vargas believes there is an urgent need for objective studies to improve care.

Dr. Vargas reported financial relationships with Amgen, Alder, Avanir, Lilly, Pernix, and Upsher-Smith.

—Ted Bosworth

Suggested Reading

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

Evans RW. Posttraumatic headaches in civilians, soldiers, and athletes. Neurol Clin. 2014;32(2):283-303.

Packard RC. Treatment of chronic daily posttraumatic headache with divalproex sodium. Headache. 2000;40(9):736-739.

Assessment and treatment of sleep problems in pediatric patients with chronic headache is important, with several contextual and headache diagnostic factors influencing the severity of sleep disturbance, according to a recent retrospective chart review. Researchers evaluated 527 patients, aged 7-17 years, with a primary headache diagnosis of migraine (n=278), tension-type headache (TTH; n=157), and new daily persistent-headache (NDPH; n=92). Patients completed measures of disability, anxiety, and depression and their parents completed measures of sleep disturbance. They found:

• Sleep disturbance was greater in patients with TTH (10.34 ± 5.94) and NDPH (11.52 ± 6.40) than migraine (8.31 ± 5.89).
• Across patient groups, greater sleep disturbance was significantly associated with higher levels of functional disability, anxiety, and depression.
• Additionally, higher pain levels were significantly associated with greater sleep disturbance among TTH patients, with this association non-significant among the other headache groups.
• When simultaneously examining demographic, pain-related, and emotional distress factors, older age, higher levels of disability and depression, and NDPH diagnosis were all significant predictors of greater sleep disturbance.

Pediatric headache and sleep disturbance: A comparison of diagnostic groups. Headache. 2018;58(2):217-228. doi:10.1111/head.13207.

Assessment and treatment of sleep problems in pediatric patients with chronic headache is important, with several contextual and headache diagnostic factors influencing the severity of sleep disturbance, according to a recent retrospective chart review. Researchers evaluated 527 patients, aged 7-17 years, with a primary headache diagnosis of migraine (n=278), tension-type headache (TTH; n=157), and new daily persistent-headache (NDPH; n=92). Patients completed measures of disability, anxiety, and depression and their parents completed measures of sleep disturbance. They found:

• Sleep disturbance was greater in patients with TTH (10.34 ± 5.94) and NDPH (11.52 ± 6.40) than migraine (8.31 ± 5.89).
• Across patient groups, greater sleep disturbance was significantly associated with higher levels of functional disability, anxiety, and depression.
• Additionally, higher pain levels were significantly associated with greater sleep disturbance among TTH patients, with this association non-significant among the other headache groups.
• When simultaneously examining demographic, pain-related, and emotional distress factors, older age, higher levels of disability and depression, and NDPH diagnosis were all significant predictors of greater sleep disturbance.

Pediatric headache and sleep disturbance: A comparison of diagnostic groups. Headache. 2018;58(2):217-228. doi:10.1111/head.13207.

Assessment and treatment of sleep problems in pediatric patients with chronic headache is important, with several contextual and headache diagnostic factors influencing the severity of sleep disturbance, according to a recent retrospective chart review. Researchers evaluated 527 patients, aged 7-17 years, with a primary headache diagnosis of migraine (n=278), tension-type headache (TTH; n=157), and new daily persistent-headache (NDPH; n=92). Patients completed measures of disability, anxiety, and depression and their parents completed measures of sleep disturbance. They found:

• Sleep disturbance was greater in patients with TTH (10.34 ± 5.94) and NDPH (11.52 ± 6.40) than migraine (8.31 ± 5.89).
• Across patient groups, greater sleep disturbance was significantly associated with higher levels of functional disability, anxiety, and depression.
• Additionally, higher pain levels were significantly associated with greater sleep disturbance among TTH patients, with this association non-significant among the other headache groups.
• When simultaneously examining demographic, pain-related, and emotional distress factors, older age, higher levels of disability and depression, and NDPH diagnosis were all significant predictors of greater sleep disturbance.

Pediatric headache and sleep disturbance: A comparison of diagnostic groups. Headache. 2018;58(2):217-228. doi:10.1111/head.13207.

Associations of migraine severity and presence of associated features with inhibitory control varied by body mass index (BMI) in overweight/obese women with migraine, according to a recent study. These findings, therefore, warrant consideration of weight status in clarifying the role of migraine in executive functioning. Women (n=124) aged 18–50 years with overweight/obesity BMI=35.1 ± 6.4 kg/m² and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period. Researchers found:

• Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time).
• Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT).
• More frequent photophobia, phonophobia, and aura were independently related to slower RT on the Stroop and/or Flanker tests, and BMI moderated the relationship between the occurrence of aura and Stroop RT.

The role of migraine headache severity, associated features and interactions with overweight/obesity in inhibitory control. Int J Neurosci. 2018;128(1):63-70. doi:10.1080/00207454.2017.1366474.

Associations of migraine severity and presence of associated features with inhibitory control varied by body mass index (BMI) in overweight/obese women with migraine, according to a recent study. These findings, therefore, warrant consideration of weight status in clarifying the role of migraine in executive functioning. Women (n=124) aged 18–50 years with overweight/obesity BMI=35.1 ± 6.4 kg/m² and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period. Researchers found:

• Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time).
• Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT).
• More frequent photophobia, phonophobia, and aura were independently related to slower RT on the Stroop and/or Flanker tests, and BMI moderated the relationship between the occurrence of aura and Stroop RT.

The role of migraine headache severity, associated features and interactions with overweight/obesity in inhibitory control. Int J Neurosci. 2018;128(1):63-70. doi:10.1080/00207454.2017.1366474.

Associations of migraine severity and presence of associated features with inhibitory control varied by body mass index (BMI) in overweight/obese women with migraine, according to a recent study. These findings, therefore, warrant consideration of weight status in clarifying the role of migraine in executive functioning. Women (n=124) aged 18–50 years with overweight/obesity BMI=35.1 ± 6.4 kg/m² and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period. Researchers found:

• Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time).
• Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT).
• More frequent photophobia, phonophobia, and aura were independently related to slower RT on the Stroop and/or Flanker tests, and BMI moderated the relationship between the occurrence of aura and Stroop RT.

The role of migraine headache severity, associated features and interactions with overweight/obesity in inhibitory control. Int J Neurosci. 2018;128(1):63-70. doi:10.1080/00207454.2017.1366474.

Typical practices of obtaining new baselines every 2 years in the high school population can be applied to athletes with a history of special education or learning disorders (LD) and headache/migraine treatment, a recent study found. This study examined the test-retest reliability of the 4- and 2-factor structures (ie, memory and speed) of ImPACT (Immediate Post-Concussion Assessment and Cognitive Test) over a 2-year interval across multiple groups with premorbid conditions, including those with a history of special education or LDs (n=114), treatment history for headache/migraine (n=81), and a control group (n= 792).

Researchers found:

• Significant improvement on all 4 composites were observed for the control group over a 2-year interval, whereas significant differences were observed only on visual motor speed for the LD and headache/migraine treatment history groups.
• The 2-factor structure has potential to increase test-retest reliability.

Two-year test-retest reliability in high school athletes using the four- and two-factor ImPACT composite structures: The effects of learning disorders and headache/migraine treatment history. Clin Neuropsychol. 2018;33(2):256-226. doi:10.1093/arclin/acx059.

Typical practices of obtaining new baselines every 2 years in the high school population can be applied to athletes with a history of special education or learning disorders (LD) and headache/migraine treatment, a recent study found. This study examined the test-retest reliability of the 4- and 2-factor structures (ie, memory and speed) of ImPACT (Immediate Post-Concussion Assessment and Cognitive Test) over a 2-year interval across multiple groups with premorbid conditions, including those with a history of special education or LDs (n=114), treatment history for headache/migraine (n=81), and a control group (n= 792).

Researchers found:

• Significant improvement on all 4 composites were observed for the control group over a 2-year interval, whereas significant differences were observed only on visual motor speed for the LD and headache/migraine treatment history groups.
• The 2-factor structure has potential to increase test-retest reliability.

Two-year test-retest reliability in high school athletes using the four- and two-factor ImPACT composite structures: The effects of learning disorders and headache/migraine treatment history. Clin Neuropsychol. 2018;33(2):256-226. doi:10.1093/arclin/acx059.

Typical practices of obtaining new baselines every 2 years in the high school population can be applied to athletes with a history of special education or learning disorders (LD) and headache/migraine treatment, a recent study found. This study examined the test-retest reliability of the 4- and 2-factor structures (ie, memory and speed) of ImPACT (Immediate Post-Concussion Assessment and Cognitive Test) over a 2-year interval across multiple groups with premorbid conditions, including those with a history of special education or LDs (n=114), treatment history for headache/migraine (n=81), and a control group (n= 792).

Researchers found:

• Significant improvement on all 4 composites were observed for the control group over a 2-year interval, whereas significant differences were observed only on visual motor speed for the LD and headache/migraine treatment history groups.
• The 2-factor structure has potential to increase test-retest reliability.

Two-year test-retest reliability in high school athletes using the four- and two-factor ImPACT composite structures: The effects of learning disorders and headache/migraine treatment history. Clin Neuropsychol. 2018;33(2):256-226. doi:10.1093/arclin/acx059.