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