Abstract
BackgroundThe increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10–30 headache days/month).MethodsWe prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥50% reduction of baseline headache days and poor outcome was defined as reduction < 50% or frequency increase. Voxel-based morphometry was used to study gray matter volume (GMV), and structural covariance was used to investigate structural connectivity.ResultsAmong 56 patients with HFM, 37 had good outcome and 19 poor outcome. Compared to the healthy controls (n = 37), patients with poor outcome had decreased GMV over the left posterior cingulate gyrus, and increased GMV over the bilateral cerebellum and the right precentral gyrus. Further, patients with poor outcome had greater GMV over the right and the left cerebella compared to patients with good outcome, and the GMVs of the cerebella were correlated to 2-year headache frequencies (right: r = 0.38, P = 0.005; left: r = 0.35, P = 0.009). Structural connectivity were increased between the cerebellum and the cuneus, the calcarine cortex, and the temporal lobe, respectively, in patients with poor outcome, and was decreased between the cerebellum and the prefrontal cortex in patients with poor outcome. The structural covariance integrities between the right cerebellum and the right cuneus were correlated to 2-year headache frequencies (r = 0.36, P = 0.008).ConclusionsStructural volume and connectivity changes of the cerebellum may underlie headache persistence in patients with HFM.
Highlights
Migraine is a recurrent headache disorder, with its attack frequency fluctuating during the disease course [1,2,3]
We evaluated mood based on severity of depression and anxiety using the HADS [14] and functional disability caused by migraine using the Migraine Disability Assessment Scale (MIDAS) [15]
The 44 patients with chronic migraine (CM) and the 12 patients with high frequency episodic migraine did not differ in demographics, headache features, impacts, and outcome, except for a higher score of Hospital Anxiety and Depression Scale-Depression (HADS-D) and baseline headache frequency in those with CM (Supplement Table 1)
Summary
Migraine is a recurrent headache disorder, with its attack frequency fluctuating during the disease course [1,2,3]. Baseline high-frequency headaches, medication overuse, and depression are associated with migraine progression [5, 6], while medication overuse and chronic musculoskeletal complaints are predictors of chronic headache persistence [2]. In the field of neuroimage, altered brain volumes and activities have been demonstrated in patients with CM compared to the patients with episodic migraine or the healthy controls (HC). Whether such changes reflect the current status of frequent attacks, the longitudinal consequences of migraine attacks, or are pathogenic and involved in headache chronification is not clearly understood [7,8,9]. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10–30 headache days/month)
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