Abstract
The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (responders; n = 11), as evidenced by a reversal in disease status (defined by at least a 50% reduction in migraine frequency and <15 headache days/month), compared to CM patients whose migraine frequency remained unchanged (non-responders; n = 12), showed differences in cortical thickness using surface-based morphometry. We also investigated whether areas showing group differences in cortical thickness displayed altered resting-state functional connectivity (RS-FC) using seed-to-voxel analyses. Migraine characteristics measured across groups included disease duration, pain intensity and headache frequency. Patient reports of headache frequency over the 4 weeks prior to (pre-treatment) and following (post-treatment) prophylaxis were compared (post minus pre) and this measure served as the clinical endpoint that determined group assignment. All patients were scanned within 2 weeks of the post-treatment visit. Results revealed that responders showed significant cortical thickening in the right primary somatosensory cortex (SI) and anterior insula (aINS), and left superior temporal gyrus (STG) and pars opercularis (ParsOp) compared to non-responders. In addition, disease duration was negatively correlated with cortical thickness in fronto-parietal and temporo-occipital regions in responders but not non-responders, with the exception of the primary motor cortex (MI) that showed the opposite pattern; disease duration was positively associated with MI cortical thickness in responders versus non-responders. Our seed-based RS-FC analyses revealed anti-correlations between the SI seed and lateral occipital (LOC) and dorsomedial prefrontal cortices (DMPFC) in responders, whereas non-responders showed increased connectivity between the ParsOp seed and LOC. Overall, our findings revealed distinct morphometric and functional brain changes in CM patients that reverted to EM following prophylactic treatment compared to CM patients that showed no change in disease status. Elucidating the CNS changes involved in disease reversal may be critical to discovering interventions that prevent or slow the progression of CM. Such changes may aid in the evaluation of treatments as well as provide markers for disease “de-chronification”.
Highlights
Migraine continues to be a common and debilitating condition, associated with significant economic, societal and personal burden
Patients were deemed eligible for inclusion if they met diagnostic criteria for chronic migraine (CM) according to the International Classification of Headache Disorders-II (ICHD-II) guidelines at the initial clinical visit, prior to any treatment with BoNT-A (Headache Classification Subcommittee of the International Headache Society, 2004); diagnostic criteria included a history of recurring migraine headaches for at least the last 3 months and a headache frequency ≥15 days/month
We found that patients with CM who were responsive to the treatment intervention, as evidenced by reversal from a chronic to an EM state, showed distinct structural and functional alterations in brain areas previously implicated in migraine pathophysiology, compared to CM patients that were unresponsive to treatment
Summary
Migraine continues to be a common and debilitating condition, associated with significant economic, societal and personal burden. While the majority of migraineurs experience low to moderate episodic migraine (EM ≥15 headache days/month), in many patients this condition progresses in frequency to chronic migraine (CM), defined as ≥15 headache days/month (Headache Classification Subcommittee of the International Headache Society, 2004; Olesen et al, 2006). 3% of individuals in the general population with infrequent episodic headache progress to CM each year (Lipton et al, 2015). Given a 1-year prevalence of EM in the US of nearly 12% (Lipton et al, 2007), these percentages translate into millions of patients at risk for progression or transformation. Any intervention that could impede disease progression or reverse a chronic state to episodic would significantly impact the lives of patients. Little is known about the neurobiology that mediates CM disease progression, or that accompanies disease reversal
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