Migraine and Endothelial Dysfunction – a brain magnetic resonance (MR) imaging case-control study (MED-MRI)

• Applicant: Dr. Thomas Liman, since 5/2022
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 491524754

Migraine is a relevant risk factor for stroke, particularly in women with migraine with aura. However, the underlying mechanisms are still unclear. Endothelial dysfunction (ED) has been proposed as a possible link between migraine and cardiovascular disease, but data from observational studies investigating ED in migraine is scarce. Previously, we could show that levels of endothelial microvesicles (EMV) and arterial stiffness are increased in women with migraine with aura. EMV are novel surrogate markers for endothelial function and activation. The aim of the proposed project is to investigate novel blood-based markers for endothelial activation such as EMVs, stromal-derived factor 1alpha (SDF-1alpha) and activating endothelial autoantibodies (endo-Ab) in a larger case-control study in migraine patients with (MA) and without aura (MO) and age-, and sex-matched controls in relation to advanced brain MRI imaging markers.The following main hypothesis should be tested in migraine patients:1. To test whether biomarkers for endothelial activation (EMV, SDF-1alpha, endo-AK) are associated with severity of cerebral small vessel disease as well as with structural changes of the white matter2. To test whether biomarkers for endothelial activation are increased in migraine patients compared to controls3. To test whether biomarkers for endothelial activation are associated with reduced peripheral endothelial function and increased arterial stiffness4. To test whether peripheral endothelial function and arterial stiffness are correlated with the severity of white matter lesions and structural changes in white matterSixty patients with MO and 60 patients with MA will be enrolled as well as 100 controls. Inclusion criteria are at least more one migraine attack per month and age over 18 years. Exclusion criteria are pregnancy, neuro- or cardiovascular diseases, BMI <18 or> 30kg / m2, arterial hypertension, diabetes mellitus, drug abuse and statins, anticoagulant or triptans <24 hours,The analysis of structural changes of the white matter will be performed by diffusion tensor imaging (DTI), the quantification of WML by the Wahlund Score and recent DTI based analysis in cooperation with Dr. med. Düring (Institute for Stroke and Dementia Research Munich). Arterial stiffness will be assessed by pulse wave velocity and augmentation index, peripheral endothelial function with pulse amplitude tonometry (EndoPAT). The blood-based biomarkers are assessed with different methods such as flow cytometry (EMV) and ELISA (endo-AK) in the laboratories of our cooperation partners.To the best of our knowledge, no study has examined the relationship between endothelial markers and MRI markers for endothelial alterations in migraine. The proposed study, which sets out to investigate various aspects of vascular function and endothelial integrity in migraine, could change our understanding of migraine pathophysiology and lead to novel therapeutic approaches.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Privatdozent Dr. Lars Neeb, until 5/2022