Glymphatic system dysfunction in patients with cluster headache

Abstract

Introduction The aim of this study was to investigate alterations of the glymphatic system function in patients with cluster headache. Methods We enrolled patients with cluster headache and healthy controls, and they underwent brain magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI). We used the MRIcron and DSI studio programs for DTI preprocessing and DTI analysis with perivascular space (DTI‐ALPS) index calculation. Results Fourteen patients with cluster headache and 23 healthy controls were enrolled. The DTI‐ALPS indexes of the groups were significantly different. The DTI‐ALPS index for the patients with cluster headache was lower than that for the healthy controls (1.586 vs. 1.786, p = 0.044). There was a significant negative correlation between the DTI‐ALPS index and age in the patients with cluster headache (r = −0.549, p = 0.042). However, the DTI‐ALPS index was not associated with other clinical characteristics, including disease duration and headache intensity (r = −0.405, p = 0.150; r = −0.048, p = 0.869, respectively). Conclusion Patients with cluster headache had a lower DTI‐ALPS index than the healthy controls; this might indicate glymphatic system dysfunction in the patients with cluster headache. Further research is required to determine whether glymphatic system dysfunction is related to the pathophysiology of cluster headache.

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

“…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.…”

“…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.…”

“…13 Glymphatic system dysfunction has been identified in patients with cluster headache. 14 Additionally, post-traumatic headache is reportedly associated with the glymphatic system. 15 Thus far, the literature suggests a link between the glymphatic system and headache disorders.…”

“…Recently, the temporary closure of perivascular space and impairment of glymphatic flow has been demonstrated in a model of migraine with aura 13 . Glymphatic system dysfunction has been identified in patients with cluster headache 14 . Additionally, post‐traumatic headache is reportedly associated with the glymphatic system 15 .…”

Migraine Pharmacological Treatment and Cognitive Impairment: Risks and Benefits

“…The system’s impairment is implicated in headache disorders [ 253 , 254 ]. In particular, CSD-driven migraine aura is accompanied by a temporary closure of paravascular spaces and the build-up of nociceptive molecules [ 255 ].…”