NOTCH3 and migraine disorder: Other plausible mechanisms include the possibility that the vascular abnormalities in CADASIL patients could decrease the threshold for CSD, as demonstrated in mice with mutated or deleted NOTCH3 genes [141], that the brainstem involvement in the disease process in CADASIL patients increases their susceptibility for migraine with auras, or that the NOTCH3 gene is involved in the pathway of migraine auras, since genetic studies have shown that family members of migraine patients have an increased risk of experiencing migraine themselves [44,142].