Abstract
BACKGROUND: Patent foramen ovale (PFO) is more common in females and often complicates with migraine; however, its mechanism is not completely definite. This study aimed to explore whether a decline of diffusion tensor image analysis along the perivascular space (DTI-ALPS) index exists which partially indicates glymphatic function, examine the relationship between diffusivity parameters, DTI-ALPS index, and visual analogue scales (VAS), and further investigate how the DTI-ALPS index and VAS perform after percutaneous closure in patients with PFO and migraine. METHODS: Female patients with PFO and migraine without aura were prospectively included; they underwent diffusion tensor imaging (DTI) scanning and received VAS scores before and after percutaneous closure. Healthy controls (HC) without migraine were recruited from the community and underwent DTI scanning. Diffusivity parameters in the x-axis, y-axis, and z-axis from association and projection fibers (D(xx-assoc), D(xx-proj), D(yy-proj), and D(zz-assoc)), as well as the DTI-ALPS index were extracted. Diffusivity parameters and DTI-ALPS index were compared between PFO and HC groups using independent sample t-test; the relationships among clinical characteristics, diffusivity parameters, DTI-ALPS index, and VAS were analyzed utilizing linear regression; besides, the above parameters and VAS in patients before and after percutaneous closure were examined with paired sample t-test. RESULTS: A total of 60 female participants were included. Among them, 20 patients with PFO and migraine had a significantly lower DTI-ALPS index in comparison with HC on the left hemisphere (P=0.005) and right hemisphere (P=0.034) as well as average DTI-ALPS index (P=0.003). The areas under the receiver operating characteristic curve (ROC; AUCs) of the DTI-ALPS index were 0.70 on the left hemisphere and 0.66 on the right, and the average DTI-ALPS index covered the largest AUC of 0.73 using a cut-off value of 1.54 with a sensitivity of 0.85 and a specificity of 0.55. Higher D(xx-proj) and D(yy-proj) on both hemispheres and D(xx-assoc) and D(zz-assoc) on the left hemisphere existed in patients with PFO and migraine compared to HC (P<0.05). Further, a positive correlation was detected between D(xx-proj) on the left hemisphere and VAS (b=0.22, t=2.85, P=0.011). After percutaneous closure, the patients showed a significantly higher DTI-ALPS index than before on the left hemisphere (P=0.047) and right hemisphere (P=0.004) as well as average DTI-ALPS index (P=0.006). In addition, the VAS decreased visibly after closure (P<0.001). CONCLUSIONS: Patients with PFO and migraine exhibited a decline of the DTI-ALPS index, which possibly reveals a trend of decreased interstitial fluid (ISF) metabolism and partly indicates glymphatic system dysfunction. Besides, the DTI-ALPS index and VAS improved after percutaneous closure, which might imply an improvement of the glymphatic system and a relief of migraine, which further highlighte the value of the closure surgery. Further, the increase of D(xx-proj) on the left hemisphere may contribute to the aggravation of migraine.