Headache & Migraine

Key clinical point: Resuming anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) therapy was beneficial in patients with migraine who had responded to this treatment previously but relapsed upon discontinuation.

Major finding: The median monthly headache days (MHD) improved from 16 in the month before antibody reintroduction to 8 after 3 months of treatment re-introduction. The majority of patients achieved 30% reduction in MHD (75.3%) and monthly migraine days (80.8%) during the second treatment period with anti-CGRP mAb.

Study details: This observational prospective analytical multicentric study included 360 patients with migraine who had shown prior response to anti-CGRP mAb, with clinical worsening after withdrawal and were re-introduced anti-CGRP mAb therapy.

Disclosures: This study was funded by the Instituto de Salud Carlos III, European Union, and  Fondo Europeo de Desarrollo Regional (FEDER) funds. Several authors declared receiving speaker honoraria, payments or honoraria for lectures, or research support or grants from various sources.

Source: Romero Del Rincón C, Gonzalez-Martinez A, Quintas S et al. RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine. Eur J Neurol. 2024 (Jan 25). doi: 10.1111/ene.16203 Source

Key clinical point: Resuming anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) therapy was beneficial in patients with migraine who had responded to this treatment previously but relapsed upon discontinuation.

Major finding: The median monthly headache days (MHD) improved from 16 in the month before antibody reintroduction to 8 after 3 months of treatment re-introduction. The majority of patients achieved 30% reduction in MHD (75.3%) and monthly migraine days (80.8%) during the second treatment period with anti-CGRP mAb.

Study details: This observational prospective analytical multicentric study included 360 patients with migraine who had shown prior response to anti-CGRP mAb, with clinical worsening after withdrawal and were re-introduced anti-CGRP mAb therapy.

Disclosures: This study was funded by the Instituto de Salud Carlos III, European Union, and  Fondo Europeo de Desarrollo Regional (FEDER) funds. Several authors declared receiving speaker honoraria, payments or honoraria for lectures, or research support or grants from various sources.

Source: Romero Del Rincón C, Gonzalez-Martinez A, Quintas S et al. RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine. Eur J Neurol. 2024 (Jan 25). doi: 10.1111/ene.16203 Source

Key clinical point: Resuming anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) therapy was beneficial in patients with migraine who had responded to this treatment previously but relapsed upon discontinuation.

Major finding: The median monthly headache days (MHD) improved from 16 in the month before antibody reintroduction to 8 after 3 months of treatment re-introduction. The majority of patients achieved 30% reduction in MHD (75.3%) and monthly migraine days (80.8%) during the second treatment period with anti-CGRP mAb.

Study details: This observational prospective analytical multicentric study included 360 patients with migraine who had shown prior response to anti-CGRP mAb, with clinical worsening after withdrawal and were re-introduced anti-CGRP mAb therapy.

Disclosures: This study was funded by the Instituto de Salud Carlos III, European Union, and  Fondo Europeo de Desarrollo Regional (FEDER) funds. Several authors declared receiving speaker honoraria, payments or honoraria for lectures, or research support or grants from various sources.

Source: Romero Del Rincón C, Gonzalez-Martinez A, Quintas S et al. RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine. Eur J Neurol. 2024 (Jan 25). doi: 10.1111/ene.16203 Source

Key clinical point: Body mass index (BMI) was positively correlated with an increased risk for severe headache or migraine, with the association being further increased in patients with diabetes and high BMI.

Major finding: BMI was positively associated with a higher risk for migraine (adjusted odds ratio [aOR] 1.02; P < .001), with participants in the highest (≥30.0 kg/m²) vs lowest (<25.0 kg/m²) BMI groups reporting an increased risk for migraine (aOR 1.30; P = .0022). The positive association between BMI and migraine was further strengthened in patients with diabetes, who had BMI ≥ 29.71 kg/m² (aOR 1.30; P = . 003).

Study details: This cross-sectional study included 10,074 participants, of whom 2004 had migraine and 1020 had diabetes.

Disclosures: This work was supported by the National Natural Science Foundation of China and Jiangxi Province, Jiangxi Provincial Department of Education Science and Technology Program Project, and Jiangxi Province Postgraduate Innovation Special Fund. The authors declared no competing interests.

Source: Tian S, Cheng Z, Zheng H et al. Interaction between diabetes and body mass index on severe headache or migraine in adults: A cross-sectional study. BMC Geriatr. 2024;24:76. doi: 10.1186/s12877-024-04657-3 Source

Key clinical point: Body mass index (BMI) was positively correlated with an increased risk for severe headache or migraine, with the association being further increased in patients with diabetes and high BMI.

Major finding: BMI was positively associated with a higher risk for migraine (adjusted odds ratio [aOR] 1.02; P < .001), with participants in the highest (≥30.0 kg/m²) vs lowest (<25.0 kg/m²) BMI groups reporting an increased risk for migraine (aOR 1.30; P = .0022). The positive association between BMI and migraine was further strengthened in patients with diabetes, who had BMI ≥ 29.71 kg/m² (aOR 1.30; P = . 003).

Study details: This cross-sectional study included 10,074 participants, of whom 2004 had migraine and 1020 had diabetes.

Disclosures: This work was supported by the National Natural Science Foundation of China and Jiangxi Province, Jiangxi Provincial Department of Education Science and Technology Program Project, and Jiangxi Province Postgraduate Innovation Special Fund. The authors declared no competing interests.

Source: Tian S, Cheng Z, Zheng H et al. Interaction between diabetes and body mass index on severe headache or migraine in adults: A cross-sectional study. BMC Geriatr. 2024;24:76. doi: 10.1186/s12877-024-04657-3 Source

Key clinical point: Body mass index (BMI) was positively correlated with an increased risk for severe headache or migraine, with the association being further increased in patients with diabetes and high BMI.

Major finding: BMI was positively associated with a higher risk for migraine (adjusted odds ratio [aOR] 1.02; P < .001), with participants in the highest (≥30.0 kg/m²) vs lowest (<25.0 kg/m²) BMI groups reporting an increased risk for migraine (aOR 1.30; P = .0022). The positive association between BMI and migraine was further strengthened in patients with diabetes, who had BMI ≥ 29.71 kg/m² (aOR 1.30; P = . 003).

Study details: This cross-sectional study included 10,074 participants, of whom 2004 had migraine and 1020 had diabetes.

Disclosures: This work was supported by the National Natural Science Foundation of China and Jiangxi Province, Jiangxi Provincial Department of Education Science and Technology Program Project, and Jiangxi Province Postgraduate Innovation Special Fund. The authors declared no competing interests.

Source: Tian S, Cheng Z, Zheng H et al. Interaction between diabetes and body mass index on severe headache or migraine in adults: A cross-sectional study. BMC Geriatr. 2024;24:76. doi: 10.1186/s12877-024-04657-3 Source

Key clinical point: Eptinezumab vs placebo led to a greater reduction in migraine frequency and an improvement in migraine response in patients with migraine, irrespective of the type of prior treatment failure.

Major finding: Across weeks 1-12, patients receiving eptinezumab vs placebo experienced greater reductions in monthly migraine days (MMD) from baseline in all subgroups, with even greater improvements at weeks 13-24 (all P < .0001). Migraine responder rates (≥50% reduction in MMD) were also higher with eptinezumab vs placebo and increased following a second infusion (all P < .0001).

Study details: Findings are from a post hoc analysis of the DELIVER trial that included 890 patients with migraine who were randomly assigned to receive either 100 mg or 300 mg eptinezumab or placebo.

Disclosures: The study was sponsored and funded by H. Lundbeck A/S. Several authors declared receiving personal fees, research support, or research funding from various sources. Four authors declared being full-time employees of or holding stocks in Lundbeck or one of its subsidiary companies.

Source: Pozo-Rosich P, Ashina M, Tepper SJ et al. Eptinezumab demonstrated efficacy regardless of prior preventive migraine treatment failure type: Post hoc analyses of the DELIVER study. Neurol Ther. 2024 (Jan 18). doi: 10.1007/s40120-023-00575-5  Source

Key clinical point: Eptinezumab vs placebo led to a greater reduction in migraine frequency and an improvement in migraine response in patients with migraine, irrespective of the type of prior treatment failure.

Major finding: Across weeks 1-12, patients receiving eptinezumab vs placebo experienced greater reductions in monthly migraine days (MMD) from baseline in all subgroups, with even greater improvements at weeks 13-24 (all P < .0001). Migraine responder rates (≥50% reduction in MMD) were also higher with eptinezumab vs placebo and increased following a second infusion (all P < .0001).

Study details: Findings are from a post hoc analysis of the DELIVER trial that included 890 patients with migraine who were randomly assigned to receive either 100 mg or 300 mg eptinezumab or placebo.

Disclosures: The study was sponsored and funded by H. Lundbeck A/S. Several authors declared receiving personal fees, research support, or research funding from various sources. Four authors declared being full-time employees of or holding stocks in Lundbeck or one of its subsidiary companies.

Source: Pozo-Rosich P, Ashina M, Tepper SJ et al. Eptinezumab demonstrated efficacy regardless of prior preventive migraine treatment failure type: Post hoc analyses of the DELIVER study. Neurol Ther. 2024 (Jan 18). doi: 10.1007/s40120-023-00575-5  Source

Key clinical point: Eptinezumab vs placebo led to a greater reduction in migraine frequency and an improvement in migraine response in patients with migraine, irrespective of the type of prior treatment failure.

Major finding: Across weeks 1-12, patients receiving eptinezumab vs placebo experienced greater reductions in monthly migraine days (MMD) from baseline in all subgroups, with even greater improvements at weeks 13-24 (all P < .0001). Migraine responder rates (≥50% reduction in MMD) were also higher with eptinezumab vs placebo and increased following a second infusion (all P < .0001).

Study details: Findings are from a post hoc analysis of the DELIVER trial that included 890 patients with migraine who were randomly assigned to receive either 100 mg or 300 mg eptinezumab or placebo.

Disclosures: The study was sponsored and funded by H. Lundbeck A/S. Several authors declared receiving personal fees, research support, or research funding from various sources. Four authors declared being full-time employees of or holding stocks in Lundbeck or one of its subsidiary companies.

Source: Pozo-Rosich P, Ashina M, Tepper SJ et al. Eptinezumab demonstrated efficacy regardless of prior preventive migraine treatment failure type: Post hoc analyses of the DELIVER study. Neurol Ther. 2024 (Jan 18). doi: 10.1007/s40120-023-00575-5  Source

Key clinical point: Patients diagnosed with migraine should be monitored for the potential onset of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC); particularly, men with migraine may require increased monitoring for the development of UC.

Major finding: Patients with migraine had a higher risk for IBD (adjusted hazard ratio [aHR] 1.31; P < .0001), CD (aHR 1.58; P = .0002), and UC (aHR 1.26; P = .0004) than those without migraine. Presence of migraine increased the risk for UC more prominently in men (aHR 1.43; 95% CI 1.20-1.71) than in women (aHR 1.12; 95% CI 0.94-1.34; P_interaction = .042).

Study details: The data come from a nationwide population-based cohort study that included 10,131,193 individuals who had undergone a national health examination conducted by the Korean National Health Insurance Service in 2009, of which 281,144 patients had migraine.

Disclosures: This study did not disclose the funding source. The authors declared no competing interests.

Source: Lee CH, Han K, Lee HJ et al. Migraine is associated with the development of adult patients with inflammatory bowel disease: A nationwide, population-based study. Sci Rep. 2024;14:1157 (Jan 12).  doi: 10.1038/s41598-024-51455-3  Source.

Key clinical point: Patients diagnosed with migraine should be monitored for the potential onset of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC); particularly, men with migraine may require increased monitoring for the development of UC.

Major finding: Patients with migraine had a higher risk for IBD (adjusted hazard ratio [aHR] 1.31; P < .0001), CD (aHR 1.58; P = .0002), and UC (aHR 1.26; P = .0004) than those without migraine. Presence of migraine increased the risk for UC more prominently in men (aHR 1.43; 95% CI 1.20-1.71) than in women (aHR 1.12; 95% CI 0.94-1.34; P_interaction = .042).

Study details: The data come from a nationwide population-based cohort study that included 10,131,193 individuals who had undergone a national health examination conducted by the Korean National Health Insurance Service in 2009, of which 281,144 patients had migraine.

Disclosures: This study did not disclose the funding source. The authors declared no competing interests.

Source: Lee CH, Han K, Lee HJ et al. Migraine is associated with the development of adult patients with inflammatory bowel disease: A nationwide, population-based study. Sci Rep. 2024;14:1157 (Jan 12).  doi: 10.1038/s41598-024-51455-3  Source.

Key clinical point: Patients diagnosed with migraine should be monitored for the potential onset of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC); particularly, men with migraine may require increased monitoring for the development of UC.

Major finding: Patients with migraine had a higher risk for IBD (adjusted hazard ratio [aHR] 1.31; P < .0001), CD (aHR 1.58; P = .0002), and UC (aHR 1.26; P = .0004) than those without migraine. Presence of migraine increased the risk for UC more prominently in men (aHR 1.43; 95% CI 1.20-1.71) than in women (aHR 1.12; 95% CI 0.94-1.34; P_interaction = .042).

Study details: The data come from a nationwide population-based cohort study that included 10,131,193 individuals who had undergone a national health examination conducted by the Korean National Health Insurance Service in 2009, of which 281,144 patients had migraine.

Disclosures: This study did not disclose the funding source. The authors declared no competing interests.

Source: Lee CH, Han K, Lee HJ et al. Migraine is associated with the development of adult patients with inflammatory bowel disease: A nationwide, population-based study. Sci Rep. 2024;14:1157 (Jan 12).  doi: 10.1038/s41598-024-51455-3  Source.

Key clinical point: Patients with chronic migraine may be informed that they should not expect a consistent wearing-off effect when being treated with erenumab or fremanezumab as anxiety regarding attacks toward the end of the month may potentially trigger further migraine episodes.

Major finding: Overall, 62% of patients treated with erenumab and fremanezumab achieved a consistent ≥30% reduction in migraine days over 2 consecutive months (≥30% responders), with no consistent wearing-off effect (ie, an increase of ≥2 weekly migraine days from week 2 to 4 over 2 consecutive treatment months) in the erenumab (P = .194) and fremanezumab (P = .581) groups. Among ≥30% responders, there was no significant wearing-off effect from week 2 to 4 over 2 consecutive months (1.43 vs 1.52 days; P = .573).

Study details: This single-center, real-world, observational study included 100 patients with chronic migraine (age ≥ 18 years) who received either erenumab (n = 60) or fremanezumab (n = 40).

Disclosures: This study was supported by Lundbeck Foundation. Two authors declared receiving personal fees or honoraria from or serving on advisory boards for various sources.

Source: Florescu AM, Lannov LV, Younis S et al. No wearing-off effect of erenumab or fremanezumab for chronic migraine prevention: A single-center, real-world, observational study. Cephalalgia. 2024 (Jan 12). doi: 10.1177/03331024231222 Source.

Key clinical point: Patients with chronic migraine may be informed that they should not expect a consistent wearing-off effect when being treated with erenumab or fremanezumab as anxiety regarding attacks toward the end of the month may potentially trigger further migraine episodes.

Major finding: Overall, 62% of patients treated with erenumab and fremanezumab achieved a consistent ≥30% reduction in migraine days over 2 consecutive months (≥30% responders), with no consistent wearing-off effect (ie, an increase of ≥2 weekly migraine days from week 2 to 4 over 2 consecutive treatment months) in the erenumab (P = .194) and fremanezumab (P = .581) groups. Among ≥30% responders, there was no significant wearing-off effect from week 2 to 4 over 2 consecutive months (1.43 vs 1.52 days; P = .573).

Study details: This single-center, real-world, observational study included 100 patients with chronic migraine (age ≥ 18 years) who received either erenumab (n = 60) or fremanezumab (n = 40).

Disclosures: This study was supported by Lundbeck Foundation. Two authors declared receiving personal fees or honoraria from or serving on advisory boards for various sources.

Source: Florescu AM, Lannov LV, Younis S et al. No wearing-off effect of erenumab or fremanezumab for chronic migraine prevention: A single-center, real-world, observational study. Cephalalgia. 2024 (Jan 12). doi: 10.1177/03331024231222 Source.

Key clinical point: Patients with chronic migraine may be informed that they should not expect a consistent wearing-off effect when being treated with erenumab or fremanezumab as anxiety regarding attacks toward the end of the month may potentially trigger further migraine episodes.

Major finding: Overall, 62% of patients treated with erenumab and fremanezumab achieved a consistent ≥30% reduction in migraine days over 2 consecutive months (≥30% responders), with no consistent wearing-off effect (ie, an increase of ≥2 weekly migraine days from week 2 to 4 over 2 consecutive treatment months) in the erenumab (P = .194) and fremanezumab (P = .581) groups. Among ≥30% responders, there was no significant wearing-off effect from week 2 to 4 over 2 consecutive months (1.43 vs 1.52 days; P = .573).

Study details: This single-center, real-world, observational study included 100 patients with chronic migraine (age ≥ 18 years) who received either erenumab (n = 60) or fremanezumab (n = 40).

Disclosures: This study was supported by Lundbeck Foundation. Two authors declared receiving personal fees or honoraria from or serving on advisory boards for various sources.

Source: Florescu AM, Lannov LV, Younis S et al. No wearing-off effect of erenumab or fremanezumab for chronic migraine prevention: A single-center, real-world, observational study. Cephalalgia. 2024 (Jan 12). doi: 10.1177/03331024231222 Source.

Key clinical point: Women who had menarche at older age had a lower risk for migraine, whereas those who used oral contraceptives and those who had children had a higher risk for migraine.

Major finding: Older age at menarche decreased migraine risk (adjusted hazard ratio [aHR] 0.96; 95% CI 0.95-0.98), whereas oral contraceptive use (aHR 1.12; 95% CI 1.06-1.18) and having children (aHR 1.37; 95% CI 1.29-1.46) increased migraine risk.

Study details: This study evaluated the data of 62,959 women (age 30-70 years) from the Norwegian Women and Cancer Study, of whom 15,635 (24.8%) had migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bugge NS, Grøtta Vetvik K, Alstadhaug KB, Braaten T et al. Cumulative exposure to estrogen may increase the risk of migraine in women. Cephalalgia. 2024 (Jan 12). doi: 10.1177/03331024231225 Source.

Key clinical point: Women who had menarche at older age had a lower risk for migraine, whereas those who used oral contraceptives and those who had children had a higher risk for migraine.

Major finding: Older age at menarche decreased migraine risk (adjusted hazard ratio [aHR] 0.96; 95% CI 0.95-0.98), whereas oral contraceptive use (aHR 1.12; 95% CI 1.06-1.18) and having children (aHR 1.37; 95% CI 1.29-1.46) increased migraine risk.

Study details: This study evaluated the data of 62,959 women (age 30-70 years) from the Norwegian Women and Cancer Study, of whom 15,635 (24.8%) had migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bugge NS, Grøtta Vetvik K, Alstadhaug KB, Braaten T et al. Cumulative exposure to estrogen may increase the risk of migraine in women. Cephalalgia. 2024 (Jan 12). doi: 10.1177/03331024231225 Source.

Key clinical point: Women who had menarche at older age had a lower risk for migraine, whereas those who used oral contraceptives and those who had children had a higher risk for migraine.

Major finding: Older age at menarche decreased migraine risk (adjusted hazard ratio [aHR] 0.96; 95% CI 0.95-0.98), whereas oral contraceptive use (aHR 1.12; 95% CI 1.06-1.18) and having children (aHR 1.37; 95% CI 1.29-1.46) increased migraine risk.

Study details: This study evaluated the data of 62,959 women (age 30-70 years) from the Norwegian Women and Cancer Study, of whom 15,635 (24.8%) had migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bugge NS, Grøtta Vetvik K, Alstadhaug KB, Braaten T et al. Cumulative exposure to estrogen may increase the risk of migraine in women. Cephalalgia. 2024 (Jan 12). doi: 10.1177/03331024231225 Source.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

Key clinical point: Higher dietary intakes of vitamin B₆ and folate were significantly associated with a lower risk for severe headaches or migraines, with a synergistic interaction observed between vitamin B₆ and folate intake and reduced migraine risk.

Major finding: Compared with the lowest quintile of dietary vitamin B₆ (≤1.13 mg/day) and folate (≤240 μg/day) intake, the risk for severe headache or migraine was lower in the highest quintile of vitamin B₆ (≥2.39 mg/day; adjusted odds ratio [aOR] 0.66; P = .01) and folate (≥502.01 μg/day; aOR 0.57; P = .002) intake. A synergistic interaction was observed between the high mass of vitamin B₆ and folate intake and a lower risk for severe headache or migraine (synergy index 0.58; 95% CI 0.40-0.83).

Study details: This cross-sectional study included 7017 adult participants (age ≥ 20 years), of whom 1350 (19.23%) had migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangxi Province, and others. No conflicts of interests were declared.

Source: Tian S et al. Vitamin B₆ and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999-2004. Nutr Res. 2023;121:51-60 (Nov 15). doi: 10.1016/j.nutres.2023.11.008

Key clinical point: Higher dietary intakes of vitamin B₆ and folate were significantly associated with a lower risk for severe headaches or migraines, with a synergistic interaction observed between vitamin B₆ and folate intake and reduced migraine risk.

Major finding: Compared with the lowest quintile of dietary vitamin B₆ (≤1.13 mg/day) and folate (≤240 μg/day) intake, the risk for severe headache or migraine was lower in the highest quintile of vitamin B₆ (≥2.39 mg/day; adjusted odds ratio [aOR] 0.66; P = .01) and folate (≥502.01 μg/day; aOR 0.57; P = .002) intake. A synergistic interaction was observed between the high mass of vitamin B₆ and folate intake and a lower risk for severe headache or migraine (synergy index 0.58; 95% CI 0.40-0.83).

Study details: This cross-sectional study included 7017 adult participants (age ≥ 20 years), of whom 1350 (19.23%) had migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangxi Province, and others. No conflicts of interests were declared.

Source: Tian S et al. Vitamin B₆ and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999-2004. Nutr Res. 2023;121:51-60 (Nov 15). doi: 10.1016/j.nutres.2023.11.008

Key clinical point: Higher dietary intakes of vitamin B₆ and folate were significantly associated with a lower risk for severe headaches or migraines, with a synergistic interaction observed between vitamin B₆ and folate intake and reduced migraine risk.

Major finding: Compared with the lowest quintile of dietary vitamin B₆ (≤1.13 mg/day) and folate (≤240 μg/day) intake, the risk for severe headache or migraine was lower in the highest quintile of vitamin B₆ (≥2.39 mg/day; adjusted odds ratio [aOR] 0.66; P = .01) and folate (≥502.01 μg/day; aOR 0.57; P = .002) intake. A synergistic interaction was observed between the high mass of vitamin B₆ and folate intake and a lower risk for severe headache or migraine (synergy index 0.58; 95% CI 0.40-0.83).

Study details: This cross-sectional study included 7017 adult participants (age ≥ 20 years), of whom 1350 (19.23%) had migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangxi Province, and others. No conflicts of interests were declared.

Source: Tian S et al. Vitamin B₆ and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999-2004. Nutr Res. 2023;121:51-60 (Nov 15). doi: 10.1016/j.nutres.2023.11.008

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source