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Commentary: Comorbidities in Migraine, March 2024

Dr Moawad scans the journals so you don't have to!

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Migraine is a common condition, estimated to affect about 12% of the US population and up to 1 billion people worldwide.[1,2] With such a high prevalence, a number of comorbidities are associated with migraine. Frequently recognized comorbidities include mood disorders, cardiovascular disease, neurologic conditions, and sleep disorders. Given that migraine is a neurologic condition with vascular features, these associations seem like natural areas for research investigation, and several theories have been proposed regarding shared pathophysiology or causes for these links.

Additionally, several recently published reviews have examined the risks of comorbidities that are not neurologic or cardiovascular, such as allergies, inflammatory bowel disease, obesity, and diabetes. Although these types of associations are not inherently obvious in terms of migraine pathophysiology, determining whether there is a link may help shed a light on some contributing factors that could play a role in migraine or in the comorbid disorders.

Authors of a study published in the January 2024 issue of the European Journal of Medical Research sought to examine the relationship between allergic rhinitis and migraine. They noted that several studies, as well as a statement from the American Migraine Prevalence and Prevention Study, published in 2013, reported an increased frequency of migraines in patients with allergic rhinitis. The researchers used data extracted from the UK Biobank, comprising 25,486 patients diagnosed with allergic rhinitis and 87,097 controls and 8547 migraine cases and 176,107 controls. They performed statistical analysis using bidirectional two-sample Mendelian randomization with publicly available summary-level statistics of large genome-wide association studies to estimate the possible causal effects. The researchers did not find any clear causal or genetic association between allergic rhinitis and migraine risk. However, the lack of causation between migraine and allergic rhinitis does not contradict previous studies that point to the prevalence of comorbidity of the two conditions. It's also important to note that congestion is a known migraine trigger, and the results of the study do not contradict that relationship. Given the variability of results from different research studies, the authors suggested that more research is warranted to help untangle the complex association between allergic rhinitis and migraine.

Inflammatory bowel disease (IBD) is another condition with a higher prevalence in patients who have migraine. A January 2024 article in Scientific Reports described the results of a nationwide population-based study that was conducted using data from the Korean National Health Insurance Service database. This study included 10,131,193 individuals. The researchers found that the risk for development of IBD in patients with migraine was significantly higher, by 1.3 times, compared with the general population. These results are similar to previous studies, such as a meta-analysis published in May 2023 in the International Journal of Preventive Medicine, which reported a pooled prevalence of migraine in IBD cases of 19%, with 1.5-fold higher odds of developing migraine in IBD cases when compared with controls.[3] These studies were both aimed at examining epidemiologic data rather than uncovering a physiologic or genetic cause of the link, and neither study described an explanation for this connection.

A Mendelian randomization study published in May 2023 in Headache investigated potential genetic links between migraine and IBD. As with the January 2024 European Journal of Medical Research study that was done to search for a genetic association between migraine and allergic rhinitis, the authors stated that there was no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease.[4] Although the evidence doesn't point to a causal relationship, it's important to note that diet plays a role in migraine management, and diet is especially important in managing IBD. Consideration of dietary factors could be beneficial for preventing symptoms — and is even more important for avoiding exacerbation of symptoms.

A high body mass index (BMI) is correlated with migraine. A study published in January 2024 in BMC Geriatrics analyzed data from people who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 by the Centers for Disease Control and the National Center for Health Statistics, comprising a total of 31,126 participants. The researchers found a linear association between BMI and migraine. They also noted that increased BMI was related to a significantly higher risk for migraine in the group with diabetes, but this positive relationship between BMI and migraine seemed to be smaller in the group without diabetes. The authors considered inflammation associated with obesity as a possible contributing factor for this link but acknowledged that the pathophysiologic mechanism is unknown and suggested that there is a high likelihood of confounding factors. Given that diabetes and obesity are both correlated with an increased risk for vascular disease and migraine is associated with a slight increase in cardiovascular risk, it could be especially important to identify these comorbidities in individual patients.

Migraine is common, and many comorbidities have been verified with population studies. Although there are some explanations for the links between migraine and vascular or neurologic conditions, the cause of associations between migraine and other conditions is not known. Some theories that have begun to be investigated include inflammation and genetics. Eventually, further research and understanding of contributing factors could potentially provide explanations that may help in diagnosing migraine or associated disorders at an early stage — and might even be used to help guide treatment.

Additional References

1. Ashina M, Katsarava Z, Do TP, et al. Migraine: Epidemiology and systems of care. Lancet. 2021;397:1485-1495. doi: 10.1016/S0140-6736(20)32160-7 Source

2. Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, burden, and comorbidity. Neurol Clin. 2019;37:631-649. doi: 10.1016/j.ncl.2019.06.001 Source

3. Olfati H, Mirmosayyeb O, Hosseinabadi AM, Ghajarzadeh M. The prevalence of migraine in inflammatory bowel disease, a systematic review and meta-analysis. Int J Prev Med. 2023;14:66. doi: 10.4103/ijpvm.ijpvm_413_21 Source

4. Welander NZ, Rukh G, Rask-Andersen M, Harder AV, et al and International Headache Genetics Consortium. Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study. Headache. 2023;63:642-651. doi: 10.1111/head.14470 Source

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