Migraine ICYMI

Key clinical point: Once-daily atogepant at doses of 30 and 60 mg significantly improved the performance of social, work-related, and daily activities compared with placebo in patients with episodic migraine.

Major finding: At week 12, atogepant (30 and 60 mg) vs placebo significantly improved Migraine-Specific Quality of Life Questionnaire version 2.1 Role Function-Restrictive (least-squares mean difference [LSMD] 10.08 and 10.8, respectively; both P < .0001). Atogepant at doses of 30 and 60 mg significantly improved monthly Activity Impairment in Migraine-Diary Performance of Daily Activities (P = .0003 and P < .0001, respectively) and Physical Impairment (P = .001 and P < .0001, respectively) scores across the 12-week treatment.

Study details: Findings are from the phase 3, ADVANCE trial including 873 patients with episodic migraine who were randomly assigned to receive once-daily atogepant (10, 30, or 60 mg) or placebo.

Disclosures: This study was sponsored by AbbVie/Allergan. Four authors declared being current or former employees of or holding stocks in AbbVie. The lead author and several other authors reported ties with various sources, including AbbVie.

Source: Lipton RB et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. 2022 (Nov 17). Doi: 10.1212/WNL.0000000000201568

Key clinical point: Once-daily atogepant at doses of 30 and 60 mg significantly improved the performance of social, work-related, and daily activities compared with placebo in patients with episodic migraine.

Major finding: At week 12, atogepant (30 and 60 mg) vs placebo significantly improved Migraine-Specific Quality of Life Questionnaire version 2.1 Role Function-Restrictive (least-squares mean difference [LSMD] 10.08 and 10.8, respectively; both P < .0001). Atogepant at doses of 30 and 60 mg significantly improved monthly Activity Impairment in Migraine-Diary Performance of Daily Activities (P = .0003 and P < .0001, respectively) and Physical Impairment (P = .001 and P < .0001, respectively) scores across the 12-week treatment.

Study details: Findings are from the phase 3, ADVANCE trial including 873 patients with episodic migraine who were randomly assigned to receive once-daily atogepant (10, 30, or 60 mg) or placebo.

Disclosures: This study was sponsored by AbbVie/Allergan. Four authors declared being current or former employees of or holding stocks in AbbVie. The lead author and several other authors reported ties with various sources, including AbbVie.

Source: Lipton RB et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. 2022 (Nov 17). Doi: 10.1212/WNL.0000000000201568

Key clinical point: Once-daily atogepant at doses of 30 and 60 mg significantly improved the performance of social, work-related, and daily activities compared with placebo in patients with episodic migraine.

Major finding: At week 12, atogepant (30 and 60 mg) vs placebo significantly improved Migraine-Specific Quality of Life Questionnaire version 2.1 Role Function-Restrictive (least-squares mean difference [LSMD] 10.08 and 10.8, respectively; both P < .0001). Atogepant at doses of 30 and 60 mg significantly improved monthly Activity Impairment in Migraine-Diary Performance of Daily Activities (P = .0003 and P < .0001, respectively) and Physical Impairment (P = .001 and P < .0001, respectively) scores across the 12-week treatment.

Study details: Findings are from the phase 3, ADVANCE trial including 873 patients with episodic migraine who were randomly assigned to receive once-daily atogepant (10, 30, or 60 mg) or placebo.

Disclosures: This study was sponsored by AbbVie/Allergan. Four authors declared being current or former employees of or holding stocks in AbbVie. The lead author and several other authors reported ties with various sources, including AbbVie.

Source: Lipton RB et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. 2022 (Nov 17). Doi: 10.1212/WNL.0000000000201568

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This month, we will take a look at three new studies investigating risk factors and treatments for headache in children.

Stress has long been noted to be one of the most consistent triggers for migraine attacks. Much has been written and studied regarding the effect of migraine on mood in adults; however, few studies have done the same in the pediatric and adolescent population. Childhood trauma has been associated with the development of chronic migraine as an adult, and behavioral treatments, such as cognitive-behavioral therapy and biofeedback, are considered as effective or more effective for migraine prevention in children compared with preventive medications. Falla and colleagues have quantified the risk for anxiety and depression in children and adolescents with migraine.

The "internalization of symptoms" is defined by the authors as an individual's tendency to react to stress with physical symptoms, including anxiety and depression. These are thought to be elevated in children and adolescents with many effects, including migraine. However, no correlation has yet been shown. Beyond the internalization of symptoms, specific psychiatric diagnoses may also be more prominent in this population.

This study was a meta-analysis of data pooled from studies that assessed migraine-related symptoms as they relate to disorders on the spectrum of anxiety, depression, and trauma-related disorders. Any studies with participants older than 18 years were excluded from this analysis. A total of 80 studies were included. Anxiety symptoms were seen to be significantly higher in children and adolescents with migraine compared to controls and the odds of having an anxiety disorder were higher among those with migraine compared with controls. Depressive symptoms were also significantly higher; however, this effect size was much smaller. The incidence of migraine was not different than that of other headache disorders.

Many patients describe stress as a trigger for migraine and other headache attacks. Mood disorders and childhood trauma are associated with the development of chronic migraine as an adult. This study reveals a two-way connection between mood disorders and headache diagnoses in children. Screening for the underlying symptoms of depression and anxiety should be done when evaluating children and adolescents for headache disorders, and there should be a focus on the treatment of these conditions in addition to treating the headache symptoms.

There are, unfortunately, very few acute pediatric migraine trials. Only a handful of medications have actually been investigated for the treatment of migraine in children younger than 12 years, and only one migraine-specific medication, rizatriptan, is approved in the United States for pediatric use. Because of this, many argue that children and adolescents with migraines end up overusing over-the-counter medication options, increasing the risk for medication overuse headache. In addition, many patients need nonoral acute migraine treatments due to nausea and vomiting or rapid onset migraine attacks.

Yonker and colleagues conducted a phase 3, randomized, double-blind, multicenter trial that only enrolled patients aged 6-11 years, all of whom had a diagnosis of episodic migraine (< 15 days of migraine per month). Children that weighed < 50 kg were given a randomly assigned lower dose of 1 mg or 2.5 mg zolmitriptan nasal spray, and those who weighed > 50 kg were randomly assigned to either 2.5 mg or 5 mg, which is the standard adult dose.

The primary outcome was a standard 2-hour pain freedom level; secondary outcomes included the proportion of improvement at 0.5, 1, and 24 hours post-dose, as well as sustained headache response for the following 2-24 hours and time to rescue medication use. Although 300 patients were enrolled and taken through the run-in process, 114 were discontinued either due to placebo response or because they had no treated migraine during the run-in phase. The mean age was 9.2 years and half of the patients were girls (of note, this is considered an appropriate proportion for pediatric migraine).

The primary endpoint of 2-hour pain freedom was not met; however, more patients in the high-dose treatment group were pain-free after 2 hours than in the placebo group. Several secondary endpoints did achieve statistical significance, including pain-free status at 1 hour post-dose, as well as headache response at 0.5, 1, and 2 hours — all of which were lower in the high-dose treatment group. The lower-dose treatment group was statistically similar to placebo for all the timepoints noted above. Treatment-related adverse events were rare in all groups.

This study did not meet its primary efficacy endpoint. However, it does show safety and effectiveness, enough at least to broaden the use of zolmitriptan for pediatric migraine. Many more effective medications for migraine treatment in adults should follow the lead of this group to find better and more specific treatments for children with migraine.

As we noted above, childhood trauma is associated with the development of chronic migraine in adulthood. Prior studies have defined childhood trauma as physical or emotional abuse primarily, and the correlation between childhood illnesses and headache disorder has not previously been determined. Davidsson and colleagues published a study in the Journal of Cancer Epidemiology that reviewed nationwide database registers longitudinally to better understand this potential risk factor.

The Danish Cancer Register was reviewed for the purpose of identifying anyone in the general Danish population who developed a diagnosis of cancer before age 20 years. The individual identification numbers in that register were linked to data in other nationwide registers for the purpose of determining whether those individuals initiated migraine-specific medications or were admitted for an inpatient hospitalization for migraine. Study participants were also grouped based on cancer type, specifically hematologic cancers involving chemotherapy and central nervous system-directed therapies, brain tumors needing intracranial surgery or radiation to the brain, blastomas or other solid tumors outside of the central nervous system, sarcomas treated with an alkylating chemotherapy, and all other carcinomas.

Among all individuals diagnosed with a childhood cancer, there was a significant increase in overall risk for the need to initiate antimigraine medication. Of interest, this was higher in those diagnosed in their teenage years. Migraine hospitalization was also noted to be higher in nearly all strata, with the exception of those diagnosed with cancer prior to the age of 5 years. The highest risk was also noted in individuals with hematologic cancers, blastomas, and brain tumors as opposed to those with sarcomas and other carcinomas. The highest cumulative risk for migraine remains in those who were diagnosed with cancer between ages 15 and 19 years.

This month, we will take a look at three new studies investigating risk factors and treatments for headache in children.

Stress has long been noted to be one of the most consistent triggers for migraine attacks. Much has been written and studied regarding the effect of migraine on mood in adults; however, few studies have done the same in the pediatric and adolescent population. Childhood trauma has been associated with the development of chronic migraine as an adult, and behavioral treatments, such as cognitive-behavioral therapy and biofeedback, are considered as effective or more effective for migraine prevention in children compared with preventive medications. Falla and colleagues have quantified the risk for anxiety and depression in children and adolescents with migraine.

The "internalization of symptoms" is defined by the authors as an individual's tendency to react to stress with physical symptoms, including anxiety and depression. These are thought to be elevated in children and adolescents with many effects, including migraine. However, no correlation has yet been shown. Beyond the internalization of symptoms, specific psychiatric diagnoses may also be more prominent in this population.

This study was a meta-analysis of data pooled from studies that assessed migraine-related symptoms as they relate to disorders on the spectrum of anxiety, depression, and trauma-related disorders. Any studies with participants older than 18 years were excluded from this analysis. A total of 80 studies were included. Anxiety symptoms were seen to be significantly higher in children and adolescents with migraine compared to controls and the odds of having an anxiety disorder were higher among those with migraine compared with controls. Depressive symptoms were also significantly higher; however, this effect size was much smaller. The incidence of migraine was not different than that of other headache disorders.

Many patients describe stress as a trigger for migraine and other headache attacks. Mood disorders and childhood trauma are associated with the development of chronic migraine as an adult. This study reveals a two-way connection between mood disorders and headache diagnoses in children. Screening for the underlying symptoms of depression and anxiety should be done when evaluating children and adolescents for headache disorders, and there should be a focus on the treatment of these conditions in addition to treating the headache symptoms.

There are, unfortunately, very few acute pediatric migraine trials. Only a handful of medications have actually been investigated for the treatment of migraine in children younger than 12 years, and only one migraine-specific medication, rizatriptan, is approved in the United States for pediatric use. Because of this, many argue that children and adolescents with migraines end up overusing over-the-counter medication options, increasing the risk for medication overuse headache. In addition, many patients need nonoral acute migraine treatments due to nausea and vomiting or rapid onset migraine attacks.

Yonker and colleagues conducted a phase 3, randomized, double-blind, multicenter trial that only enrolled patients aged 6-11 years, all of whom had a diagnosis of episodic migraine (< 15 days of migraine per month). Children that weighed < 50 kg were given a randomly assigned lower dose of 1 mg or 2.5 mg zolmitriptan nasal spray, and those who weighed > 50 kg were randomly assigned to either 2.5 mg or 5 mg, which is the standard adult dose.

The primary outcome was a standard 2-hour pain freedom level; secondary outcomes included the proportion of improvement at 0.5, 1, and 24 hours post-dose, as well as sustained headache response for the following 2-24 hours and time to rescue medication use. Although 300 patients were enrolled and taken through the run-in process, 114 were discontinued either due to placebo response or because they had no treated migraine during the run-in phase. The mean age was 9.2 years and half of the patients were girls (of note, this is considered an appropriate proportion for pediatric migraine).

The primary endpoint of 2-hour pain freedom was not met; however, more patients in the high-dose treatment group were pain-free after 2 hours than in the placebo group. Several secondary endpoints did achieve statistical significance, including pain-free status at 1 hour post-dose, as well as headache response at 0.5, 1, and 2 hours — all of which were lower in the high-dose treatment group. The lower-dose treatment group was statistically similar to placebo for all the timepoints noted above. Treatment-related adverse events were rare in all groups.

This study did not meet its primary efficacy endpoint. However, it does show safety and effectiveness, enough at least to broaden the use of zolmitriptan for pediatric migraine. Many more effective medications for migraine treatment in adults should follow the lead of this group to find better and more specific treatments for children with migraine.

As we noted above, childhood trauma is associated with the development of chronic migraine in adulthood. Prior studies have defined childhood trauma as physical or emotional abuse primarily, and the correlation between childhood illnesses and headache disorder has not previously been determined. Davidsson and colleagues published a study in the Journal of Cancer Epidemiology that reviewed nationwide database registers longitudinally to better understand this potential risk factor.

The Danish Cancer Register was reviewed for the purpose of identifying anyone in the general Danish population who developed a diagnosis of cancer before age 20 years. The individual identification numbers in that register were linked to data in other nationwide registers for the purpose of determining whether those individuals initiated migraine-specific medications or were admitted for an inpatient hospitalization for migraine. Study participants were also grouped based on cancer type, specifically hematologic cancers involving chemotherapy and central nervous system-directed therapies, brain tumors needing intracranial surgery or radiation to the brain, blastomas or other solid tumors outside of the central nervous system, sarcomas treated with an alkylating chemotherapy, and all other carcinomas.

Among all individuals diagnosed with a childhood cancer, there was a significant increase in overall risk for the need to initiate antimigraine medication. Of interest, this was higher in those diagnosed in their teenage years. Migraine hospitalization was also noted to be higher in nearly all strata, with the exception of those diagnosed with cancer prior to the age of 5 years. The highest risk was also noted in individuals with hematologic cancers, blastomas, and brain tumors as opposed to those with sarcomas and other carcinomas. The highest cumulative risk for migraine remains in those who were diagnosed with cancer between ages 15 and 19 years.

This month, we will take a look at three new studies investigating risk factors and treatments for headache in children.

Stress has long been noted to be one of the most consistent triggers for migraine attacks. Much has been written and studied regarding the effect of migraine on mood in adults; however, few studies have done the same in the pediatric and adolescent population. Childhood trauma has been associated with the development of chronic migraine as an adult, and behavioral treatments, such as cognitive-behavioral therapy and biofeedback, are considered as effective or more effective for migraine prevention in children compared with preventive medications. Falla and colleagues have quantified the risk for anxiety and depression in children and adolescents with migraine.

The "internalization of symptoms" is defined by the authors as an individual's tendency to react to stress with physical symptoms, including anxiety and depression. These are thought to be elevated in children and adolescents with many effects, including migraine. However, no correlation has yet been shown. Beyond the internalization of symptoms, specific psychiatric diagnoses may also be more prominent in this population.

This study was a meta-analysis of data pooled from studies that assessed migraine-related symptoms as they relate to disorders on the spectrum of anxiety, depression, and trauma-related disorders. Any studies with participants older than 18 years were excluded from this analysis. A total of 80 studies were included. Anxiety symptoms were seen to be significantly higher in children and adolescents with migraine compared to controls and the odds of having an anxiety disorder were higher among those with migraine compared with controls. Depressive symptoms were also significantly higher; however, this effect size was much smaller. The incidence of migraine was not different than that of other headache disorders.

Many patients describe stress as a trigger for migraine and other headache attacks. Mood disorders and childhood trauma are associated with the development of chronic migraine as an adult. This study reveals a two-way connection between mood disorders and headache diagnoses in children. Screening for the underlying symptoms of depression and anxiety should be done when evaluating children and adolescents for headache disorders, and there should be a focus on the treatment of these conditions in addition to treating the headache symptoms.

There are, unfortunately, very few acute pediatric migraine trials. Only a handful of medications have actually been investigated for the treatment of migraine in children younger than 12 years, and only one migraine-specific medication, rizatriptan, is approved in the United States for pediatric use. Because of this, many argue that children and adolescents with migraines end up overusing over-the-counter medication options, increasing the risk for medication overuse headache. In addition, many patients need nonoral acute migraine treatments due to nausea and vomiting or rapid onset migraine attacks.

Yonker and colleagues conducted a phase 3, randomized, double-blind, multicenter trial that only enrolled patients aged 6-11 years, all of whom had a diagnosis of episodic migraine (< 15 days of migraine per month). Children that weighed < 50 kg were given a randomly assigned lower dose of 1 mg or 2.5 mg zolmitriptan nasal spray, and those who weighed > 50 kg were randomly assigned to either 2.5 mg or 5 mg, which is the standard adult dose.

The primary outcome was a standard 2-hour pain freedom level; secondary outcomes included the proportion of improvement at 0.5, 1, and 24 hours post-dose, as well as sustained headache response for the following 2-24 hours and time to rescue medication use. Although 300 patients were enrolled and taken through the run-in process, 114 were discontinued either due to placebo response or because they had no treated migraine during the run-in phase. The mean age was 9.2 years and half of the patients were girls (of note, this is considered an appropriate proportion for pediatric migraine).

The primary endpoint of 2-hour pain freedom was not met; however, more patients in the high-dose treatment group were pain-free after 2 hours than in the placebo group. Several secondary endpoints did achieve statistical significance, including pain-free status at 1 hour post-dose, as well as headache response at 0.5, 1, and 2 hours — all of which were lower in the high-dose treatment group. The lower-dose treatment group was statistically similar to placebo for all the timepoints noted above. Treatment-related adverse events were rare in all groups.

This study did not meet its primary efficacy endpoint. However, it does show safety and effectiveness, enough at least to broaden the use of zolmitriptan for pediatric migraine. Many more effective medications for migraine treatment in adults should follow the lead of this group to find better and more specific treatments for children with migraine.

As we noted above, childhood trauma is associated with the development of chronic migraine in adulthood. Prior studies have defined childhood trauma as physical or emotional abuse primarily, and the correlation between childhood illnesses and headache disorder has not previously been determined. Davidsson and colleagues published a study in the Journal of Cancer Epidemiology that reviewed nationwide database registers longitudinally to better understand this potential risk factor.

The Danish Cancer Register was reviewed for the purpose of identifying anyone in the general Danish population who developed a diagnosis of cancer before age 20 years. The individual identification numbers in that register were linked to data in other nationwide registers for the purpose of determining whether those individuals initiated migraine-specific medications or were admitted for an inpatient hospitalization for migraine. Study participants were also grouped based on cancer type, specifically hematologic cancers involving chemotherapy and central nervous system-directed therapies, brain tumors needing intracranial surgery or radiation to the brain, blastomas or other solid tumors outside of the central nervous system, sarcomas treated with an alkylating chemotherapy, and all other carcinomas.

Among all individuals diagnosed with a childhood cancer, there was a significant increase in overall risk for the need to initiate antimigraine medication. Of interest, this was higher in those diagnosed in their teenage years. Migraine hospitalization was also noted to be higher in nearly all strata, with the exception of those diagnosed with cancer prior to the age of 5 years. The highest risk was also noted in individuals with hematologic cancers, blastomas, and brain tumors as opposed to those with sarcomas and other carcinomas. The highest cumulative risk for migraine remains in those who were diagnosed with cancer between ages 15 and 19 years.

By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.

“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.

Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.

Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
 

Diagnosis

One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.

Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.

Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.

In addition, the headaches should exhibit at least two out of four features:

1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).

2. Be of moderate to severe intensity.

3. Have a pounding or throbbing quality.

4. Grow worse with activity or cause an avoidance of activity.

If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:

1. Are sensitive to light and sounds.

2. Are associated with nausea and/or vomiting.

A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.

“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.

Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.

“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
 

First line of treatment

Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.

“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”

The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.

Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.

Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.

However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.

Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B₂) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.

“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.

For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.

A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.

For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.

Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
 

Lifestyle triggers

Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.

Migraine patients should also be mindful of their screen time, Dr. Kelley added.

“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.

As for other potential triggers of attacks, the evidence is mixed.

“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.

Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.

Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.

As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.

The difference for Mira has been extraordinary.

“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”

It’s only migraine

One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.

“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.

Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.

“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.

Some warning signs that further tests might be warranted, Dr. Kelley said, include:

• Headaches that wake a patient up in the middle of the night.
• Headaches that start first thing in the morning, especially those that include vomiting.
• A headache pattern that suddenly gets much worse.
• Certain symptoms that accompany the headache, such as tingling, numbness or double vision.

Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.

By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.

“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.

Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.

Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
 

Diagnosis

One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.

Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.

Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.

In addition, the headaches should exhibit at least two out of four features:

1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).

2. Be of moderate to severe intensity.

3. Have a pounding or throbbing quality.

4. Grow worse with activity or cause an avoidance of activity.

If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:

1. Are sensitive to light and sounds.

2. Are associated with nausea and/or vomiting.

A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.

“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.

Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.

“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
 

First line of treatment

Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.

“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”

The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.

Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.

Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.

However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.

Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B₂) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.

“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.

For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.

A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.

For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.

Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
 

Lifestyle triggers

Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.

Migraine patients should also be mindful of their screen time, Dr. Kelley added.

“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.

As for other potential triggers of attacks, the evidence is mixed.

“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.

Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.

Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.

As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.

The difference for Mira has been extraordinary.

“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”

It’s only migraine

One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.

“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.

Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.

“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.

Some warning signs that further tests might be warranted, Dr. Kelley said, include:

• Headaches that wake a patient up in the middle of the night.
• Headaches that start first thing in the morning, especially those that include vomiting.
• A headache pattern that suddenly gets much worse.
• Certain symptoms that accompany the headache, such as tingling, numbness or double vision.

Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.

By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.

“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.

Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.

Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
 

Diagnosis

One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.

Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.

Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.

In addition, the headaches should exhibit at least two out of four features:

1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).

2. Be of moderate to severe intensity.

3. Have a pounding or throbbing quality.

4. Grow worse with activity or cause an avoidance of activity.

If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:

1. Are sensitive to light and sounds.

2. Are associated with nausea and/or vomiting.

A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.

“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.

Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.

“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
 

First line of treatment

Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.

“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”

The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.

Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.

Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.

However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.

Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B₂) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.

“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.

For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.

A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.

For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.

Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
 

Lifestyle triggers

Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.

Migraine patients should also be mindful of their screen time, Dr. Kelley added.

“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.

As for other potential triggers of attacks, the evidence is mixed.

“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.

Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.

Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.

As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.

The difference for Mira has been extraordinary.

“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”

It’s only migraine

One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.

“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.

Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.

“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.

Some warning signs that further tests might be warranted, Dr. Kelley said, include:

• Headaches that wake a patient up in the middle of the night.
• Headaches that start first thing in the morning, especially those that include vomiting.
• A headache pattern that suddenly gets much worse.
• Certain symptoms that accompany the headache, such as tingling, numbness or double vision.

Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.

Key clinical point: Once-monthly galcanezumab significantly reduced the frequency of migraine-associated symptoms and migraine headache severity in patients with episodic migraine.

Major finding: Moderate-to-severe migraine headache days (MHD) reduced significantly with 240 mg galcanezumab (difference in least-squares mean change from baseline [Δ] −1.8 days,  95% CI −2.5 to −1.2) and 120 mg (Δ −1.9 days, 95% CI −2.5 to −1.2) vs placebo, with 240 mg galcanezumab also leading to significant reductions in the proportion of monthly MHD during menstrual periods (P = .04), and MHDswith nausea or vomiting (P = .02).

Study details: This was a secondary analysis of a phase 2 trial including 440 patients with episodic migraine who were randomly assigned to receive monthly galcanezumab (240 or 120 mg) or placebo.

Disclosures: This study was funded by Eli Lilly Japan K.K. Two authors declared being employees and minor shareholders of Eli Lilly. Two authors reported receiving personal fees for speaker or consulting services from Eli Lilly Japan K.K. and other sources.

Source: Igarashi H et al. Galcanezumab effects on migraine severity and symptoms in Japanese patients with episodic migraine: Secondary analysis of a phase 2 randomized trial. Neurol Ther. 2022 (Oct 20). Doi: 10.1007/s40120-022-00410-3

Key clinical point: Once-monthly galcanezumab significantly reduced the frequency of migraine-associated symptoms and migraine headache severity in patients with episodic migraine.

Major finding: Moderate-to-severe migraine headache days (MHD) reduced significantly with 240 mg galcanezumab (difference in least-squares mean change from baseline [Δ] −1.8 days,  95% CI −2.5 to −1.2) and 120 mg (Δ −1.9 days, 95% CI −2.5 to −1.2) vs placebo, with 240 mg galcanezumab also leading to significant reductions in the proportion of monthly MHD during menstrual periods (P = .04), and MHDswith nausea or vomiting (P = .02).

Study details: This was a secondary analysis of a phase 2 trial including 440 patients with episodic migraine who were randomly assigned to receive monthly galcanezumab (240 or 120 mg) or placebo.

Disclosures: This study was funded by Eli Lilly Japan K.K. Two authors declared being employees and minor shareholders of Eli Lilly. Two authors reported receiving personal fees for speaker or consulting services from Eli Lilly Japan K.K. and other sources.

Source: Igarashi H et al. Galcanezumab effects on migraine severity and symptoms in Japanese patients with episodic migraine: Secondary analysis of a phase 2 randomized trial. Neurol Ther. 2022 (Oct 20). Doi: 10.1007/s40120-022-00410-3

Key clinical point: Once-monthly galcanezumab significantly reduced the frequency of migraine-associated symptoms and migraine headache severity in patients with episodic migraine.

Major finding: Moderate-to-severe migraine headache days (MHD) reduced significantly with 240 mg galcanezumab (difference in least-squares mean change from baseline [Δ] −1.8 days,  95% CI −2.5 to −1.2) and 120 mg (Δ −1.9 days, 95% CI −2.5 to −1.2) vs placebo, with 240 mg galcanezumab also leading to significant reductions in the proportion of monthly MHD during menstrual periods (P = .04), and MHDswith nausea or vomiting (P = .02).

Study details: This was a secondary analysis of a phase 2 trial including 440 patients with episodic migraine who were randomly assigned to receive monthly galcanezumab (240 or 120 mg) or placebo.

Disclosures: This study was funded by Eli Lilly Japan K.K. Two authors declared being employees and minor shareholders of Eli Lilly. Two authors reported receiving personal fees for speaker or consulting services from Eli Lilly Japan K.K. and other sources.

Source: Igarashi H et al. Galcanezumab effects on migraine severity and symptoms in Japanese patients with episodic migraine: Secondary analysis of a phase 2 randomized trial. Neurol Ther. 2022 (Oct 20). Doi: 10.1007/s40120-022-00410-3

Key clinical point: Adenosine vs placebo infusion increased headaches and short-lasting vasodilation without a significant induction of migraine attacks in patients with migraine without aura.

Major finding: The incidence of migraine attacks was not significantly different after adenosine vs placebo infusion (39% vs 17%; P = .29); however, a higher proportion of patients receiving adenosine vs placebo reported headache (78% vs 33%; P < .01). Adenosine vs placebo increased heart rate (area under the curve [AUC]_{T0-120 min}, P < .001), facial skin blood flow (AUC_{T0-120 min}, P < .05), and left superficial temporal artery diameter (AUC_{T0-20 min}, P = .01), but decreased middle cerebral artery blood flow velocity (AUC_{T0-20 min}, P < .001).

Study details: This randomized controlled trial included 18 patients with migraine without aura who received adenosine or placebo infusion over 20 minutes on two study days separated by a 1 week washout period.

Disclosures: This study received support from the Lundbeck Foundation. M Ashina reported receiving consulting fees, honoraria for lectures and presentations, and royalties from various sources, including Lundbeck.

Source: Thuraiaiyah J et al. Adenosine causes short-lasting vasodilation and headache, but not migraine attacks in migraine patients: A randomized clinical trial. Pain. 2022 (Oct 17). Doi: 10.1097/j.pain.0000000000002804

Key clinical point: Adenosine vs placebo infusion increased headaches and short-lasting vasodilation without a significant induction of migraine attacks in patients with migraine without aura.

Major finding: The incidence of migraine attacks was not significantly different after adenosine vs placebo infusion (39% vs 17%; P = .29); however, a higher proportion of patients receiving adenosine vs placebo reported headache (78% vs 33%; P < .01). Adenosine vs placebo increased heart rate (area under the curve [AUC]_{T0-120 min}, P < .001), facial skin blood flow (AUC_{T0-120 min}, P < .05), and left superficial temporal artery diameter (AUC_{T0-20 min}, P = .01), but decreased middle cerebral artery blood flow velocity (AUC_{T0-20 min}, P < .001).

Study details: This randomized controlled trial included 18 patients with migraine without aura who received adenosine or placebo infusion over 20 minutes on two study days separated by a 1 week washout period.

Disclosures: This study received support from the Lundbeck Foundation. M Ashina reported receiving consulting fees, honoraria for lectures and presentations, and royalties from various sources, including Lundbeck.

Source: Thuraiaiyah J et al. Adenosine causes short-lasting vasodilation and headache, but not migraine attacks in migraine patients: A randomized clinical trial. Pain. 2022 (Oct 17). Doi: 10.1097/j.pain.0000000000002804

Key clinical point: Adenosine vs placebo infusion increased headaches and short-lasting vasodilation without a significant induction of migraine attacks in patients with migraine without aura.

Major finding: The incidence of migraine attacks was not significantly different after adenosine vs placebo infusion (39% vs 17%; P = .29); however, a higher proportion of patients receiving adenosine vs placebo reported headache (78% vs 33%; P < .01). Adenosine vs placebo increased heart rate (area under the curve [AUC]_{T0-120 min}, P < .001), facial skin blood flow (AUC_{T0-120 min}, P < .05), and left superficial temporal artery diameter (AUC_{T0-20 min}, P = .01), but decreased middle cerebral artery blood flow velocity (AUC_{T0-20 min}, P < .001).

Study details: This randomized controlled trial included 18 patients with migraine without aura who received adenosine or placebo infusion over 20 minutes on two study days separated by a 1 week washout period.

Disclosures: This study received support from the Lundbeck Foundation. M Ashina reported receiving consulting fees, honoraria for lectures and presentations, and royalties from various sources, including Lundbeck.

Source: Thuraiaiyah J et al. Adenosine causes short-lasting vasodilation and headache, but not migraine attacks in migraine patients: A randomized clinical trial. Pain. 2022 (Oct 17). Doi: 10.1097/j.pain.0000000000002804

Key clinical point: Individuals diagnosed with childhood cancer were at an increased risk for antimigraine medication and hospitalization due to migraine.

Major finding: Compared with unaffected individuals, those diagnosed with childhood cancer were at an elevated risk for initiating antimigraine therapy (standardized incidence ratios [SIR] 1.22; 95% CI 1.09-1.36) and hospitalization due to migraine (SIR 2.44; 95% CI 1.87-3.12), with the risk for initiating antimigraine therapy being the highest among individuals diagnosed with cancer at 15-19 years of age (SIR 1.48; 95% CI 1.25-1.74).

Study details: This was a population-based cohort study including individuals diagnosed with childhood cancer who had data available for antimigraine prescriptions (n = 6564) and migraine hospitalization (n = 7771).

Disclosures: This study was funded by Danmarks Frie Forskningsfond, Denmark. The authors declared no conflicts of interest.

Source: Davidsson OB et al. Childhood cancer confers increased risk of migraine – A Danish nationwide register study. Cancer Epidemiol. 2022;81:102278 (Oct 13). Doi: 10.1016/j.canep.2022.102278

Key clinical point: Individuals diagnosed with childhood cancer were at an increased risk for antimigraine medication and hospitalization due to migraine.

Major finding: Compared with unaffected individuals, those diagnosed with childhood cancer were at an elevated risk for initiating antimigraine therapy (standardized incidence ratios [SIR] 1.22; 95% CI 1.09-1.36) and hospitalization due to migraine (SIR 2.44; 95% CI 1.87-3.12), with the risk for initiating antimigraine therapy being the highest among individuals diagnosed with cancer at 15-19 years of age (SIR 1.48; 95% CI 1.25-1.74).

Study details: This was a population-based cohort study including individuals diagnosed with childhood cancer who had data available for antimigraine prescriptions (n = 6564) and migraine hospitalization (n = 7771).

Disclosures: This study was funded by Danmarks Frie Forskningsfond, Denmark. The authors declared no conflicts of interest.

Source: Davidsson OB et al. Childhood cancer confers increased risk of migraine – A Danish nationwide register study. Cancer Epidemiol. 2022;81:102278 (Oct 13). Doi: 10.1016/j.canep.2022.102278

Key clinical point: Individuals diagnosed with childhood cancer were at an increased risk for antimigraine medication and hospitalization due to migraine.

Major finding: Compared with unaffected individuals, those diagnosed with childhood cancer were at an elevated risk for initiating antimigraine therapy (standardized incidence ratios [SIR] 1.22; 95% CI 1.09-1.36) and hospitalization due to migraine (SIR 2.44; 95% CI 1.87-3.12), with the risk for initiating antimigraine therapy being the highest among individuals diagnosed with cancer at 15-19 years of age (SIR 1.48; 95% CI 1.25-1.74).

Study details: This was a population-based cohort study including individuals diagnosed with childhood cancer who had data available for antimigraine prescriptions (n = 6564) and migraine hospitalization (n = 7771).

Disclosures: This study was funded by Danmarks Frie Forskningsfond, Denmark. The authors declared no conflicts of interest.

Source: Davidsson OB et al. Childhood cancer confers increased risk of migraine – A Danish nationwide register study. Cancer Epidemiol. 2022;81:102278 (Oct 13). Doi: 10.1016/j.canep.2022.102278

Key clinical point: The presence of seemingly inert calcified lesions of neurocysticercosis (CLN) influences the course of migraine by increasing headache frequency, pain severity, and migraine-associated disability; however, patients with CLN showed a better response to amitriptyline treatment.

Major finding: In patients with vs without CLN, the headache frequency (P < .001), visual analog scale score (P < .001), and Migraine Disability Assessment score (P < .001) were significantly higher at baseline and not significantly different at 3 months after amitriptyline treatment; however, the magnitude of treatment response was significantly higher in patients with vs without CLN (P < .001).

Study details: This case-control study included age- and sex-matched patients with migraine with (n = 78) and without (n = 78) CLN on cranial computed tomography who received preventive treatment with amitriptyline.

Disclosures: The publication expenses were supported by the American Society of Tropical Medicine and Hygiene. RK Garg reported receiving royalties for writing UpToDate articles and an honorarium for writing for MedLink Neurology.

Source: Sharma K et al. Does calcified neurocysticercosis affect migraine characteristics and treatment responsiveness? A case-control study. Am J Trop Med Hyg. 2022 (Oct 10). Doi: 10.4269/ajtmh.22-0335

Key clinical point: The presence of seemingly inert calcified lesions of neurocysticercosis (CLN) influences the course of migraine by increasing headache frequency, pain severity, and migraine-associated disability; however, patients with CLN showed a better response to amitriptyline treatment.

Major finding: In patients with vs without CLN, the headache frequency (P < .001), visual analog scale score (P < .001), and Migraine Disability Assessment score (P < .001) were significantly higher at baseline and not significantly different at 3 months after amitriptyline treatment; however, the magnitude of treatment response was significantly higher in patients with vs without CLN (P < .001).

Study details: This case-control study included age- and sex-matched patients with migraine with (n = 78) and without (n = 78) CLN on cranial computed tomography who received preventive treatment with amitriptyline.

Disclosures: The publication expenses were supported by the American Society of Tropical Medicine and Hygiene. RK Garg reported receiving royalties for writing UpToDate articles and an honorarium for writing for MedLink Neurology.

Source: Sharma K et al. Does calcified neurocysticercosis affect migraine characteristics and treatment responsiveness? A case-control study. Am J Trop Med Hyg. 2022 (Oct 10). Doi: 10.4269/ajtmh.22-0335

Key clinical point: The presence of seemingly inert calcified lesions of neurocysticercosis (CLN) influences the course of migraine by increasing headache frequency, pain severity, and migraine-associated disability; however, patients with CLN showed a better response to amitriptyline treatment.

Major finding: In patients with vs without CLN, the headache frequency (P < .001), visual analog scale score (P < .001), and Migraine Disability Assessment score (P < .001) were significantly higher at baseline and not significantly different at 3 months after amitriptyline treatment; however, the magnitude of treatment response was significantly higher in patients with vs without CLN (P < .001).

Study details: This case-control study included age- and sex-matched patients with migraine with (n = 78) and without (n = 78) CLN on cranial computed tomography who received preventive treatment with amitriptyline.

Disclosures: The publication expenses were supported by the American Society of Tropical Medicine and Hygiene. RK Garg reported receiving royalties for writing UpToDate articles and an honorarium for writing for MedLink Neurology.

Source: Sharma K et al. Does calcified neurocysticercosis affect migraine characteristics and treatment responsiveness? A case-control study. Am J Trop Med Hyg. 2022 (Oct 10). Doi: 10.4269/ajtmh.22-0335

Key clinical point: Autonomic symptoms were prevalent in patients with episodic or chronic migraine but demonstrated no significant correlation with headache frequency, treatment response, or reversion from chronic to episodic migraine.

Major finding: Overall, 60.5% of patients reported a Composite Autonomic Symptom Scale (COMPASS-31) score of ≥30. The median monthly headache days (P = .002) and Migraine Disability Assessment Score (P = .01) reduced significantly during the study period but change in the mean weighted COMPASS-31 score was not significant (P = .885), with no correlation observed between the COMPASS-31 score and monthly headache frequency or reversion from chronic to episodic migraine.

Study details: This was a prospective longitudinal cohort study including 43 patients with episodic or chronic migraine who completed 12 months of treatment and follow-up surveys.

Disclosures: This study did not report the source of funding. Four authors declared receiving funding, grants, or payment for developing educational presentations, serving on advisory boards, or being involved in clinical trials sponsored by various sources.

Source: Ray JC et al. Autonomic symptoms in migraine: Results of a prospective longitudinal study. Front Neurol. 2022;13:1036798 (Nov 3). Doi: 10.3389/fneur.2022.1036798

Key clinical point: Autonomic symptoms were prevalent in patients with episodic or chronic migraine but demonstrated no significant correlation with headache frequency, treatment response, or reversion from chronic to episodic migraine.

Major finding: Overall, 60.5% of patients reported a Composite Autonomic Symptom Scale (COMPASS-31) score of ≥30. The median monthly headache days (P = .002) and Migraine Disability Assessment Score (P = .01) reduced significantly during the study period but change in the mean weighted COMPASS-31 score was not significant (P = .885), with no correlation observed between the COMPASS-31 score and monthly headache frequency or reversion from chronic to episodic migraine.

Study details: This was a prospective longitudinal cohort study including 43 patients with episodic or chronic migraine who completed 12 months of treatment and follow-up surveys.

Disclosures: This study did not report the source of funding. Four authors declared receiving funding, grants, or payment for developing educational presentations, serving on advisory boards, or being involved in clinical trials sponsored by various sources.

Source: Ray JC et al. Autonomic symptoms in migraine: Results of a prospective longitudinal study. Front Neurol. 2022;13:1036798 (Nov 3). Doi: 10.3389/fneur.2022.1036798

Key clinical point: Autonomic symptoms were prevalent in patients with episodic or chronic migraine but demonstrated no significant correlation with headache frequency, treatment response, or reversion from chronic to episodic migraine.

Major finding: Overall, 60.5% of patients reported a Composite Autonomic Symptom Scale (COMPASS-31) score of ≥30. The median monthly headache days (P = .002) and Migraine Disability Assessment Score (P = .01) reduced significantly during the study period but change in the mean weighted COMPASS-31 score was not significant (P = .885), with no correlation observed between the COMPASS-31 score and monthly headache frequency or reversion from chronic to episodic migraine.

Study details: This was a prospective longitudinal cohort study including 43 patients with episodic or chronic migraine who completed 12 months of treatment and follow-up surveys.

Disclosures: This study did not report the source of funding. Four authors declared receiving funding, grants, or payment for developing educational presentations, serving on advisory boards, or being involved in clinical trials sponsored by various sources.

Source: Ray JC et al. Autonomic symptoms in migraine: Results of a prospective longitudinal study. Front Neurol. 2022;13:1036798 (Nov 3). Doi: 10.3389/fneur.2022.1036798

Key clinical point: During acute headaches, patients with migraine had elevated levels of peripheral inflammatory markers (PIM), specifically the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-monocyte ratio (NMR), which could fairly differentiate between the migraine and no headache groups.

Major finding: Patients with migraine had higher NLR, NMR, and monocyte-to-lymphocyte ratio (all P < .001) compared with control individuals without headache and higher NMR (P < .001) and higher NLR (P = .051) compared with patients with non-migraine headaches during acute headache attacks. NLR and NMR could fairly differentiate between the migraine and no headache groups (NLR: area under the curve [AUC] 0.65; NMR: AUC 0.61; P < .001).

Study details: This was a retrospective analysis of 4005 patients with acute headache attack, including those with migraine (n = 1453) or non-migraine (n = 2552) headaches, and 88,586 control individuals without headache.

Disclosures: This study was supported by Basic Science Research Program through the National Research Foundataion of Korea funded by the Ministry of Education and others. The authors declared no conflicts of interest.

Source: Lee S-H et al. Role of peripheral inflammatory markers in patients with acute headache attack to differentiate between migraine and non-migraine headache. J Clin Med. 2022;11(21):6538 (Nov 3). Doi: 10.3390/jcm11216538

Key clinical point: During acute headaches, patients with migraine had elevated levels of peripheral inflammatory markers (PIM), specifically the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-monocyte ratio (NMR), which could fairly differentiate between the migraine and no headache groups.

Major finding: Patients with migraine had higher NLR, NMR, and monocyte-to-lymphocyte ratio (all P < .001) compared with control individuals without headache and higher NMR (P < .001) and higher NLR (P = .051) compared with patients with non-migraine headaches during acute headache attacks. NLR and NMR could fairly differentiate between the migraine and no headache groups (NLR: area under the curve [AUC] 0.65; NMR: AUC 0.61; P < .001).

Study details: This was a retrospective analysis of 4005 patients with acute headache attack, including those with migraine (n = 1453) or non-migraine (n = 2552) headaches, and 88,586 control individuals without headache.

Disclosures: This study was supported by Basic Science Research Program through the National Research Foundataion of Korea funded by the Ministry of Education and others. The authors declared no conflicts of interest.

Source: Lee S-H et al. Role of peripheral inflammatory markers in patients with acute headache attack to differentiate between migraine and non-migraine headache. J Clin Med. 2022;11(21):6538 (Nov 3). Doi: 10.3390/jcm11216538

Key clinical point: During acute headaches, patients with migraine had elevated levels of peripheral inflammatory markers (PIM), specifically the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-monocyte ratio (NMR), which could fairly differentiate between the migraine and no headache groups.

Major finding: Patients with migraine had higher NLR, NMR, and monocyte-to-lymphocyte ratio (all P < .001) compared with control individuals without headache and higher NMR (P < .001) and higher NLR (P = .051) compared with patients with non-migraine headaches during acute headache attacks. NLR and NMR could fairly differentiate between the migraine and no headache groups (NLR: area under the curve [AUC] 0.65; NMR: AUC 0.61; P < .001).

Study details: This was a retrospective analysis of 4005 patients with acute headache attack, including those with migraine (n = 1453) or non-migraine (n = 2552) headaches, and 88,586 control individuals without headache.

Disclosures: This study was supported by Basic Science Research Program through the National Research Foundataion of Korea funded by the Ministry of Education and others. The authors declared no conflicts of interest.

Source: Lee S-H et al. Role of peripheral inflammatory markers in patients with acute headache attack to differentiate between migraine and non-migraine headache. J Clin Med. 2022;11(21):6538 (Nov 3). Doi: 10.3390/jcm11216538