Neurological
Research into the biomarker modalities of migraines
When diagnosing migraines based on clinical criteria, neurologists can overlook genetic and neurobiological factors. The study researchers presented the latest findings on biomarker modalities for migraine and their respective challenges in an article in the Lancet.
The study researchers were able to identify 38 genomic loci that influence the risk of migraine, particularly in genes that are expressed in tissues with vascular and smooth muscle cells. Others found that high polygenic exposure was linked to increased migraine severity, its presence in younger people, and migraines with aura.
They were also able to identify the single gene associated with familial hemiplegic migraine, cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, and familial advanced sleep phase syndrome. Identifying the genes that cause migraines is difficult because multiple variants can have little impact and other factors may be involved.
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Human challenge models have found that calcitonin gene-related peptide (CGRP), Pituitary adenylate cyclase-activating polypeptide (PACAP), glyceryl trinitrate and phosphodiesterase 3 and 5 inhibitors trigger migraine attacks in most patients with migraine via the second messenger systems of cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP). Induction rates reached 100% when patients received a KATP channel opener and 95% when they received a BKCa channel opener.
The origin of migraines can be either peripheral or central. This research has been applied to the development of drugs such as: Such as those that target CGRP or its receptor and capture trigger molecules, but such treatments have not always been successful. Human provocation models may be able to predict treatment response.
Study researchers found conflicting results when examining whether peripheral blood CGRP levels are increased during migraine attacks and whether interictal plasma levels of CGRP are increased in people with episodic or chronic migraines. Two studies on PACAP showed that spontaneous migraine attacks are associated with increased PACAP-like immunoreactivity, while two studies found no increase in PACAP in the interictal phase of migraines. Studies on whether baseline CGRP is higher in migraineurs who benefited from treatment with onabotulinum toxin A were also inconsistent.
In addition, magnetic resonance imaging (MRI) has shown conflicting results on whether white matter hyperintensities with migraines are associated with aura. One study found that women with migraines had thicker cortexes for the visual realm than their peers, while another study found structural changes in pain pathways that may be associated with thalamic changes.
Other studies have shown that the brain structure of migraineurs is slightly different than that of those with tension-type headaches or headaches after a traumatic brain injury. Functional MRI (fMRI) showed that the activity of the dorsal pons increases in the headache phase of migraines.
Ultimately, study researchers were able to combine biomarker modalities. During imaging using magnetic resonance angiography and challenge models in humans, they found that CGRP-induced migraine attacks resulted in dilation of the middle cerebral artery and the middle meningeal artery. “Building on this,” they concluded, “future research should explore precision medicine approaches that improve the diagnosis and treatment of migraines.”
Disclosure: Some of the study’s authors stated links with biotech, pharmaceutical, and / or device companies. For a full list of the authors’ information, see the original reference.
reference
Ashina M., Terwindt GM, Al-Karagholi MAM, et al. Migraines: Disease Characterization, Biomarkers, and Precision Medicine. Lancet. 2021; 397 (10283): 1496-1. 1504. doi: 10.1016 / S0140-6736 (20) 32162-0