Chronic Migraine Linked With Disruption of Normal White Matter Integrity, Study Finds

Chronic migraine (CM) may be associated with widespread disruption of normal white matter (WM) integrity in the brain, according to a study published in The Journal of Headache and Pain.

Chronic migraine (CM) may be associated with widespread disruption of normal white matter (WM) integrity in the brain, according to a study published in The Journal of Headache and Pain.

Although only a small percentage of individuals with episodic migraine (MO) later develop into chronic migraineurs, research has shown an association between MO and CM and abnormalities in density and thickness of the brain’s grey matter, in addition to functional connectivity at rest or following painful stimulation.

“Some studies have found anomalies in the microstructure of the WM of migraineurs,” authors write. “Two studies reported there to be no remarkable differences in the integrity of WM microstructure between patients with CM and healthy controls (HCs). However, patients were scanned during prevention and/or medication overuse.”

To better understand the relationship between WM and migraine, researchers investigated intracerebral fiber bundles using a tract-based spatial (TBSS) analysis of diffusion tensor imaging (DTI) data to verify microstructural integrity in patients with MO and CM.

“Among the various techniques used to acquire MRI data, DTI is the most sensitive to microstructural changes by estimating the diffusivity of water molecules along the fiber bundles of WM in the 3 main orthogonal directions of diffusion,” authors write.

The study cohort included 19 individuals with MO, 18 patients with CM without any history of drug abuse, and 18 healthy controls. Based on DTI, researchers calculated diffusion metrics including fractional anisotropy (FA), axial diffusion (AD), radial diffusion (RD) and mean diffusion (MD).

“All patients were tested during the interictal period, which was defined as the period at which it had been at least 3 days since the last attack and 3 days before the subsequent attack for the MO group,” authors write.

Analyses showed:

  • TBSS revealed no significant differences in the FA, MD, RD, and AD maps between the MO and HC groups
  • Compared with the HC group, the CM group exhibited widespread increased RD (bilateral superior [SCR] and posterior corona radiata [PCR], bilateral genu of the corpus callosum [CC], bilateral posterior limb of internal capsule [IC], bilateral superior longitudinal fasciculus [LF]) and MD values (tracts of the right SCR and PCR, right superior LF, and right splenium of the CC)
  • Compared with the MO group, the CM group showed decreased FA (bilateral SCR and PCR, bilateral body of CC, right superior LF, right forceps minor) and increased MD values (bilateral SCR and right PCR, right body of CC, right superior LF, right splenium of CC, and right posterior limb of IC)
  • WM tracts that overlapped between the 2 patient groups indicated increases in FA and decreases in MD were located in the right CC and right PCR
  • Diffusive metrics of patients correlated significantly with the subjective perception of headache intensity

“This study found widespread differences in the organization of WM between patients with CM and HCs,” researchers said, while “the diffusive metrics of episodic migraineurs, which did not differ significantly from those of HCs, also differed significantly from those of patients with CM.”

Small sample sizes may have biased results, acting as a limitation to the study. However, it is difficult to recruit patients with pure CM and without preventive treatment or a history of drug abuse, authors note.

The peculiar microstructural patterns of CM patients may indicate axonal abnormalities, decreased cellular density, and/or loss of directional organization in the WM fiber bundles, researchers hypothesize.

However, “further studies are needed to verify whether this reorganization of WM of the CM brain can be normalized by pharmacological and non-pharmacological interventions.”


Coppola G, Di Renzo A, Tinelli E, et al. Patients with chronic migraine without history of medication overuse are characterized by a peculiar white matter fiber bundle profile. J Headache Pain. 2020;21(1):92. doi:10.1186/s10194-020-01159-6

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