White matter hyperintensities in migraine are not mediated by a dysfunction of the glymphatic system—A diffusion tensor imaging magnetic resonance imaging study

Abstract

ObjectiveWe assessed whether brain magnetic resonance imaging (MRI) markers of glymphatic function are altered in patients with migraine and brain white matter hyperintensities (WMHs).BackgroundThe glymphatic system is responsible for the outflow of waste products from the brain. An impaired glymphatic system has been associated with WMH; however, this impairment has not been shown in patients with migraine.MethodsThe present cross‐sectional study included consecutive patients with migraine from a single tertiary headache center. Glymphatic function was assessed by measuring the diffusion tensor imaging along the perivascular space (DTI‐ALPS) technique, resulting in an index value. WMHs were assessed and quantified by using the Scheltens semi‐quantitative score.ResultsWe included 147 patients (120 women [81.6%]) with a median (interquartile range [IQR]) age of 45 (36–50) years. In all, 74 (50.3%) patients had WMHs. The median (IQR) ALPS index was similar in patients with WMHs compared with those without, at 2.658 (2.332–3.199) versus 2.563 (2.222–3.050) (p = 0.344). The Scheltens score did not correlate with ALPS index (rho = 0.112, p = 0.268).ConclusionsOur results suggest that the presence of WMHs is not associated with an impairment in the glymphatic system in patients with migraine. Although negative and worthy of further confirmation, our finding has implications for the understanding of the nature of WMH in patients with migraine.

Dynamic changes in glymphatic function in reversible cerebral vasoconstriction syndrome

“…Our data further support the potential use of the DTI-ALPS index in the evaluation of subjects with RCVS regarding clinical impacts and implicate the potential role of glymphatics in pain modulation. Several recent studies also enhanced the roles of glymphatic system in headache disorders (Supplementary Table 9 in Additional file 1 ) [ 19 , 31 , 32 , 49 – 55 ]. Nevertheless, since some studies depicted normal glymphatic functions in certain headache disorders, including episodic migraine [ 19 , 52 ] and new daily persistent headache, [ 24 ] and some demonstrated contradictory findings, [ 32 ] the potential mechanism of glymphatics in pain or headache modulation remains to be explored.…”

Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS): Revisiting the Meaning and Significance of the Method

“…182 However, the median ALPS-index was reported to be similar in patients with and without white matter hyperintensities. 183 Another major problem with the DTI-ALPS method is that it can only evaluate the white matter outside the lateral ventricles in an image section that includes the body of the lateral ventricles. The ALPS method cannot evaluate perivascular diffusivity in other regions where the PVS does not run in the x-, y-, or z-axis directions.…”

The glymphatic system in migraine and other headaches

“…It has been suggested that CSD, the surrogate of migraine aura could determine, through the vasoconstriction of pial and penetrating arteries, a spreading ischemia and the appearance of WMHs at MR [ 93 ]. For these reasons, it could be postulated that the WMHs in patients suffering from migraine represent a consequence of the dysfunction of the GS [ 94 ]. To evaluate whether WMHs in migraineurs are associated with the GS dysfunction, Ornello et al used the DTI-ALPS index.…”

“…To evaluate whether WMHs in migraineurs are associated with the GS dysfunction, Ornello et al used the DTI-ALPS index. Using this technique, the authors did not find that GS dysfunction was associated with WMHs in patients with migraine [ 94 ].…”