Commentary: Pregnancy, photophobia, and stroke in relation to migraine, March 2023

Migraine is the single most common neurologic condition worldwide and is particularly predominant among women during their reproductive years. There are many important questions that arise when women with migraine start pregnancy planning, most of which involve acute and preventive medication use and red flags for headache in pregnancy. As of yet, there have been no large-scale epidemiologic studies looking at pregnancy risks for people with migraine. Specifically, if migraine is a statistically significant vascular risk factor, does it incur additional risks in pregnancy, which is a prothrombotic state?

Purdue-Smithe and colleagues reviewed a large longitudinal study, the Nurses' Health Study II, a biennial questionnaire that took place from 1989 to 2009 and in which the questions changed yearly. Migraine was assessed on the basis of whether the participants had been given a diagnosis of migraine (or migraine with aura) by a medical professional; outcomes of pregnancy were also determined on the basis of participants providing a comprehensive reproductive history, including pregnancy outcome, gestation length, birth weight, and pregnancy complications.

A total of 2234 participants were included in this study; 1989 of them reported a history of physician-diagnosed migraine, with 1078 classified as having migraine with aura and 1156 classified as having migraine without aura. Adverse pregnancy outcomes more frequently affect multiple gestations; a sensitivity analysis was conducted to restrict the data here to singleton pregnancies. Individuals with migraine were more likely to report a history of infertility, obesity, and oral contraceptive use than were those without migraine. A history of migraine was associated with greater risks for preterm delivery, gestational hypertension, and preeclampsia; however, it was not associated with gestational diabetes or low birth weight. Theses outcomes were independent of age during pregnancy.

This wide-ranging study does allow us to better discuss potential risks for our patients with migraine. In addition to discussions about estrogen contraception use and stroke risk, it is worth taking a minute to discuss potential pregnancy risks that are more associated with migraine. This will allow our patients to be better aligned with their obstetricians, who can determine if other factors may further elevate these risks. Highlighting areas of risk can allow for better recognition of these potential negative outcomes much earlier.

There is a well-known association between calcitonin gene related peptide (CGRP) and migraine, but what is less understood is how CGRP affects specific features of migraine. CGRP is found in the gut and is therefore thought to have an association with migraine-related nausea, but other migraine associated symptoms, such as photophobia, are less well understood. Schiano di Cola and colleagues sought to determine the effectiveness of galcanezumab specifically in regard to ictal photophobia pain.

They enrolled 80 patients with either high-frequency episodic migraine or chronic migraine who were taking galcanezumab; 47 were included as expressing photophobia as a significant migraine-associated symptom at baseline. The patients were evaluated after 3 months and again after 6 months of treatment. They were asked to record headache days, migraine days, consumption of acute medication, and pain intensity. Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) scores were also followed up. Improvement with photophobia was determined as either no improvement, slight improvement, moderate improvement, or high improvement. After 3 months of treatment, 68% of patients reported a significant improvement in ictal photophobia, 11 patients reported moderate improvement, and six patients a slight improvement. Two patients reported improvement only after 6 months of treatment.

Post hoc analysis revealed photophobia improvement was not statistically significant in patients who are considered responders to galcanezumab compared with nonresponders. Photophobia improvement was most apparent in patients who were considered triptan responders. It was also more common in people with high-frequency episodic migraine rather than in those with chronic migraine. Migraine disability scores were noted to be higher in participants who did not notice photophobia improvement.

This study highlights the necessity to focus on factors beyond simply migraine frequency and severity. Many of the most disabling characteristics of migraine may not be related to pain directly. More research is currently being undertaken regarding the mechanisms that underlie photophobia in migraine. Ultimately, this will lead to more focused treatment for patients who may have other disabling symptoms associated with their headache disorder.

So much has already been written regarding the association between migraine and vascular risk factors. Migraine is considered a statistically significant risk factor for stroke specifically; migraine with aura has been noted to have a stronger association. Acarsoy and colleagues longitudinally examined the risk for stroke for any cause as it relates to migraine in both middle-aged and older populations.

This prospective population-based trial was embedded in a large Netherlands-based study among middle-aged and older community residents of Rotterdam. A total of 7266 participants were interviewed; 6925 participants had both migraine and stroke information available. Migraine was assessed with a questionnaire based on The International Classification of Headache Disorders (ICHD) criteria. Stroke status was assessed based on World Health Organization criteria and verified from medical records. Participants in this study were continuously monitored for incident stroke through an automatic linking of the study database to national health database files.

Other risk factors selected were body mass index (BMI), smoking history, education level, and physical activity, as well as any history of coronary artery disease, hypertension, or hypercholesterolemia. The average age of the study population was 65.7 years. Among participants with migraine, 20% had a history of migraine with aura. Among all stroke events, 84% were ischemic, and 11% were hemorrhagic. There was no significant difference in stroke-free survival probability between people with and without migraine. Although there was an association between migraine and stroke risk in middle and older ages, this was not statistically significant.

This study highlights, the appropriateness of educating migraine patients in regard to stroke risk. Specifically, patients should not be overly concerned regarding their migraine history. However, this study suggests that there does remain an association, but that this still remains somewhat unclear and less statistically significant in relation to age. When weighing vascular risk factors, more appropriate risks, such as elevated BMI, smoking history, hypertension, and the like should be highlighted, much more so than a history of migraine.

Migraine is the single most common neurologic condition worldwide and is particularly predominant among women during their reproductive years. There are many important questions that arise when women with migraine start pregnancy planning, most of which involve acute and preventive medication use and red flags for headache in pregnancy. As of yet, there have been no large-scale epidemiologic studies looking at pregnancy risks for people with migraine. Specifically, if migraine is a statistically significant vascular risk factor, does it incur additional risks in pregnancy, which is a prothrombotic state?

Purdue-Smithe and colleagues reviewed a large longitudinal study, the Nurses' Health Study II, a biennial questionnaire that took place from 1989 to 2009 and in which the questions changed yearly. Migraine was assessed on the basis of whether the participants had been given a diagnosis of migraine (or migraine with aura) by a medical professional; outcomes of pregnancy were also determined on the basis of participants providing a comprehensive reproductive history, including pregnancy outcome, gestation length, birth weight, and pregnancy complications.

A total of 2234 participants were included in this study; 1989 of them reported a history of physician-diagnosed migraine, with 1078 classified as having migraine with aura and 1156 classified as having migraine without aura. Adverse pregnancy outcomes more frequently affect multiple gestations; a sensitivity analysis was conducted to restrict the data here to singleton pregnancies. Individuals with migraine were more likely to report a history of infertility, obesity, and oral contraceptive use than were those without migraine. A history of migraine was associated with greater risks for preterm delivery, gestational hypertension, and preeclampsia; however, it was not associated with gestational diabetes or low birth weight. Theses outcomes were independent of age during pregnancy.

This wide-ranging study does allow us to better discuss potential risks for our patients with migraine. In addition to discussions about estrogen contraception use and stroke risk, it is worth taking a minute to discuss potential pregnancy risks that are more associated with migraine. This will allow our patients to be better aligned with their obstetricians, who can determine if other factors may further elevate these risks. Highlighting areas of risk can allow for better recognition of these potential negative outcomes much earlier.

There is a well-known association between calcitonin gene related peptide (CGRP) and migraine, but what is less understood is how CGRP affects specific features of migraine. CGRP is found in the gut and is therefore thought to have an association with migraine-related nausea, but other migraine associated symptoms, such as photophobia, are less well understood. Schiano di Cola and colleagues sought to determine the effectiveness of galcanezumab specifically in regard to ictal photophobia pain.

They enrolled 80 patients with either high-frequency episodic migraine or chronic migraine who were taking galcanezumab; 47 were included as expressing photophobia as a significant migraine-associated symptom at baseline. The patients were evaluated after 3 months and again after 6 months of treatment. They were asked to record headache days, migraine days, consumption of acute medication, and pain intensity. Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) scores were also followed up. Improvement with photophobia was determined as either no improvement, slight improvement, moderate improvement, or high improvement. After 3 months of treatment, 68% of patients reported a significant improvement in ictal photophobia, 11 patients reported moderate improvement, and six patients a slight improvement. Two patients reported improvement only after 6 months of treatment.

Post hoc analysis revealed photophobia improvement was not statistically significant in patients who are considered responders to galcanezumab compared with nonresponders. Photophobia improvement was most apparent in patients who were considered triptan responders. It was also more common in people with high-frequency episodic migraine rather than in those with chronic migraine. Migraine disability scores were noted to be higher in participants who did not notice photophobia improvement.

This study highlights the necessity to focus on factors beyond simply migraine frequency and severity. Many of the most disabling characteristics of migraine may not be related to pain directly. More research is currently being undertaken regarding the mechanisms that underlie photophobia in migraine. Ultimately, this will lead to more focused treatment for patients who may have other disabling symptoms associated with their headache disorder.

So much has already been written regarding the association between migraine and vascular risk factors. Migraine is considered a statistically significant risk factor for stroke specifically; migraine with aura has been noted to have a stronger association. Acarsoy and colleagues longitudinally examined the risk for stroke for any cause as it relates to migraine in both middle-aged and older populations.

This prospective population-based trial was embedded in a large Netherlands-based study among middle-aged and older community residents of Rotterdam. A total of 7266 participants were interviewed; 6925 participants had both migraine and stroke information available. Migraine was assessed with a questionnaire based on The International Classification of Headache Disorders (ICHD) criteria. Stroke status was assessed based on World Health Organization criteria and verified from medical records. Participants in this study were continuously monitored for incident stroke through an automatic linking of the study database to national health database files.

Other risk factors selected were body mass index (BMI), smoking history, education level, and physical activity, as well as any history of coronary artery disease, hypertension, or hypercholesterolemia. The average age of the study population was 65.7 years. Among participants with migraine, 20% had a history of migraine with aura. Among all stroke events, 84% were ischemic, and 11% were hemorrhagic. There was no significant difference in stroke-free survival probability between people with and without migraine. Although there was an association between migraine and stroke risk in middle and older ages, this was not statistically significant.

This study highlights, the appropriateness of educating migraine patients in regard to stroke risk. Specifically, patients should not be overly concerned regarding their migraine history. However, this study suggests that there does remain an association, but that this still remains somewhat unclear and less statistically significant in relation to age. When weighing vascular risk factors, more appropriate risks, such as elevated BMI, smoking history, hypertension, and the like should be highlighted, much more so than a history of migraine.

Migraine is the single most common neurologic condition worldwide and is particularly predominant among women during their reproductive years. There are many important questions that arise when women with migraine start pregnancy planning, most of which involve acute and preventive medication use and red flags for headache in pregnancy. As of yet, there have been no large-scale epidemiologic studies looking at pregnancy risks for people with migraine. Specifically, if migraine is a statistically significant vascular risk factor, does it incur additional risks in pregnancy, which is a prothrombotic state?

Purdue-Smithe and colleagues reviewed a large longitudinal study, the Nurses' Health Study II, a biennial questionnaire that took place from 1989 to 2009 and in which the questions changed yearly. Migraine was assessed on the basis of whether the participants had been given a diagnosis of migraine (or migraine with aura) by a medical professional; outcomes of pregnancy were also determined on the basis of participants providing a comprehensive reproductive history, including pregnancy outcome, gestation length, birth weight, and pregnancy complications.

A total of 2234 participants were included in this study; 1989 of them reported a history of physician-diagnosed migraine, with 1078 classified as having migraine with aura and 1156 classified as having migraine without aura. Adverse pregnancy outcomes more frequently affect multiple gestations; a sensitivity analysis was conducted to restrict the data here to singleton pregnancies. Individuals with migraine were more likely to report a history of infertility, obesity, and oral contraceptive use than were those without migraine. A history of migraine was associated with greater risks for preterm delivery, gestational hypertension, and preeclampsia; however, it was not associated with gestational diabetes or low birth weight. Theses outcomes were independent of age during pregnancy.

This wide-ranging study does allow us to better discuss potential risks for our patients with migraine. In addition to discussions about estrogen contraception use and stroke risk, it is worth taking a minute to discuss potential pregnancy risks that are more associated with migraine. This will allow our patients to be better aligned with their obstetricians, who can determine if other factors may further elevate these risks. Highlighting areas of risk can allow for better recognition of these potential negative outcomes much earlier.

There is a well-known association between calcitonin gene related peptide (CGRP) and migraine, but what is less understood is how CGRP affects specific features of migraine. CGRP is found in the gut and is therefore thought to have an association with migraine-related nausea, but other migraine associated symptoms, such as photophobia, are less well understood. Schiano di Cola and colleagues sought to determine the effectiveness of galcanezumab specifically in regard to ictal photophobia pain.

They enrolled 80 patients with either high-frequency episodic migraine or chronic migraine who were taking galcanezumab; 47 were included as expressing photophobia as a significant migraine-associated symptom at baseline. The patients were evaluated after 3 months and again after 6 months of treatment. They were asked to record headache days, migraine days, consumption of acute medication, and pain intensity. Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) scores were also followed up. Improvement with photophobia was determined as either no improvement, slight improvement, moderate improvement, or high improvement. After 3 months of treatment, 68% of patients reported a significant improvement in ictal photophobia, 11 patients reported moderate improvement, and six patients a slight improvement. Two patients reported improvement only after 6 months of treatment.

Post hoc analysis revealed photophobia improvement was not statistically significant in patients who are considered responders to galcanezumab compared with nonresponders. Photophobia improvement was most apparent in patients who were considered triptan responders. It was also more common in people with high-frequency episodic migraine rather than in those with chronic migraine. Migraine disability scores were noted to be higher in participants who did not notice photophobia improvement.

This study highlights the necessity to focus on factors beyond simply migraine frequency and severity. Many of the most disabling characteristics of migraine may not be related to pain directly. More research is currently being undertaken regarding the mechanisms that underlie photophobia in migraine. Ultimately, this will lead to more focused treatment for patients who may have other disabling symptoms associated with their headache disorder.

So much has already been written regarding the association between migraine and vascular risk factors. Migraine is considered a statistically significant risk factor for stroke specifically; migraine with aura has been noted to have a stronger association. Acarsoy and colleagues longitudinally examined the risk for stroke for any cause as it relates to migraine in both middle-aged and older populations.

This prospective population-based trial was embedded in a large Netherlands-based study among middle-aged and older community residents of Rotterdam. A total of 7266 participants were interviewed; 6925 participants had both migraine and stroke information available. Migraine was assessed with a questionnaire based on The International Classification of Headache Disorders (ICHD) criteria. Stroke status was assessed based on World Health Organization criteria and verified from medical records. Participants in this study were continuously monitored for incident stroke through an automatic linking of the study database to national health database files.

Other risk factors selected were body mass index (BMI), smoking history, education level, and physical activity, as well as any history of coronary artery disease, hypertension, or hypercholesterolemia. The average age of the study population was 65.7 years. Among participants with migraine, 20% had a history of migraine with aura. Among all stroke events, 84% were ischemic, and 11% were hemorrhagic. There was no significant difference in stroke-free survival probability between people with and without migraine. Although there was an association between migraine and stroke risk in middle and older ages, this was not statistically significant.

This study highlights, the appropriateness of educating migraine patients in regard to stroke risk. Specifically, patients should not be overly concerned regarding their migraine history. However, this study suggests that there does remain an association, but that this still remains somewhat unclear and less statistically significant in relation to age. When weighing vascular risk factors, more appropriate risks, such as elevated BMI, smoking history, hypertension, and the like should be highlighted, much more so than a history of migraine.