Normal glymphatic system function in patients with migraine: A pilot study

Abstract

Objective No studies have evaluated the glymphatic system function in patients with migraine. In this pilot study, we evaluated and compared the alterations in the glymphatic system function in patients with migraine with healthy controls using a diffusion tensor imaging (DTI) analysis along the perivascular space (DTI‐ALPS) method. We also investigated the differences in the glymphatic system function table between patients with migraine with and without aura using the ALPS method. Methods This field study used a cross‐sectional study design. We prospectively enrolled patients with migraine and healthy controls. All brain magnetic resonance imaging (MRI), including DTI, in participants, patients with migraine, and healthy controls were obtained using the same MRI scanner. We calculated and compared the ALPS index between patients with migraine and healthy controls, and between patients with migraine with and without aura. In addition, we investigated the association between the glymphatic system function and the clinical characteristics of migraine. Results We enrolled 92 patients with migraine and 80 healthy controls. There were no significant differences in the ALPS index between patients with migraine and healthy controls (1.655 ± 0.335 [patients with migraine] vs. 1.713 ± 0.297 [controls], difference = 0.058, 95% confidence interval [CI] of difference = −0.037 to 0.154, p = 0.233), and between patients with migraine with and without aura (1.690 ± 0.380 [with aura] vs. 1.645 ± 0.323 [without aura], difference = −0.044, 95% CI of difference = −0.213 to 0.124, p = 0.601). There was no significant correlation between the ALPS index and clinical characteristics of migraine, including age (r = −0.07, p = 0.507), age at onset (r = 0.07, p = 0.552), disease duration (r = −0.12, p = 0.306), attack frequency (r = −0.05, p = 0.668), and headache intensity (r = 0.00, p = 0.976). Conclusions There was no glymphatic system dysfunction in patients with migraine. Moreover, there were no differences in the glymphatic system function between patients with migraine with and without aura. We also demonstrated the feasibility of the ALPS method, which can be used for research on various neurological diseases. Further studies are needed to confirm our findings.

Normal glymphatic system function in patients with new daily persistent headache using diffusion tensor image analysis along the perivascular space

“…Although the exact pathogenesis and pathophysiology of NDPH are not fully understood, headache attacks in patients with NDPH may be related to chronic neurological inflammation, cytokine production, and persistent glial activation in response to the triggering events mentioned above 16 . Consistent with our findings, a recent study using the ALPS index revealed normal glymphatic function in patients with migraine 34 . Although NDPH and migraine are distinct types of headache, there is no evidence that either type has an underlying association with neurodegenerative disease 37,38 .…”

“…16 Consistent with our findings, a recent study using the ALPS index revealed normal glymphatic function in patients with migraine. 34 Although NDPH and migraine are distinct types of headache, there is no evidence that either type has an underlying association with neurodegenerative disease. 37,38 This difference in the nature of the disorders explains that the glymphatic system may not be directly involved in the pathophysiology of headaches.…”

“…Notably, we assessed the ALPS index separately in both hemispheres, rather than in the left hemisphere alone (as in previous studies). 14,34 Although a previous study showed that the fibers on one side were sufficiently thick for ROI delineation, 19 we performed separate analyses of the left and the right hemispheres, considering that the glymphatic system is built on the vascular network that is connected and partly independent in both hemispheres. Contrary to our hypothesis, glymphatic system dysfunction was not present in patients with NDPH by means of the ALPS method.…”

“…Moreover, this non‐invasive assessment is more likely to be implemented in clinical settings because it does not require dozens of hours spent on multiple dynamic imaging to monitor tracer clearance. Notably, we assessed the ALPS index separately in both hemispheres, rather than in the left hemisphere alone (as in previous studies) 14,34 . Although a previous study showed that the fibers on one side were sufficiently thick for ROI delineation, 19 we performed separate analyses of the left and the right hemispheres, considering that the glymphatic system is built on the vascular network that is connected and partly independent in both hemispheres.…”

Prevalence and clinical characteristics of white matter hyperintensities in Migraine: A meta-analysis

“…Fourthly, impaired glymphatic clearance function is related to WMHs in patients with cerebral small vessel disease ( Xu et al, 2022 , Zhang et al, 2021 ). However, the current evidence does not find glymphatic dysfunction in migraineurs compared to healthy controls ( Lee et al, 2022 ). Finally, blood–brain barrier damage is a fundamental disease mechanism in WMHs ( Wardlaw et al, 2019 ).…”