Prediction of WMH in Migraine Using a BOLD-CVR Map

Brief Summary: Brain white matter hyperintensities (WMHs) are prevalent in migraineurs, of which the mechanism is still unclear. The investigators aimed to test the spatial association between areas with reduced cerebrovascular reactivity (CVR) to hypercapnic stimuli and consequent development of WMHs.

Detailed Description: A whole-brain map of CVR will be created in patients with migraine and normal controls. Hypercapnic stimuli for CVR will be delivered by prospective end-tidal CO2 targeting device. Hemodynamic responses will be determined by BOLD signal changes using fMRI. WMHs will be determined by high-resolution 3D FLAIR imaging. Patients and controls will undergo serial MRIs with 1 year interval. Associations between areas of reduced CVR and consequent WMH development will be tested in both patients and controls.

Recruitment & Eligibility

Inclusion Criteria

Migraineurs(patients) :
- age 18-50 years
- migraine with or without aura as defined by the third edition of the International Classification of Headache Disorders (ICHD-3 beta)
- migraine duration > 6 months
- episodic migraine feature headache (< 15 attacks/m)
- not any preventive medications for migraine
Control:
- age 18-50 years
- no headache disorder requiring painkillers within the past year
- no more than moderate intensity of headache within the past year
- no headache disorder other than Infrequent episodic tension-type headache as defined by the ICHD-3 beta

Exclusion criteria:

chronic migraine within last month (≥15 attacks/m)
medication overuse headache as defined by ICHD-3 beta
other comorbid disease that may affect vascular function (Hypertension, diabetes, hyperlipidemia, cerebral infarction, smoking etc)
can not breath 20 L for 1 minute because of basal cardiopulmonary disease (chronic obstructive pulmonary disease, heart failure etc)
a disease that can be exacerbated by elevated PCO2 in blood (Interstitial lung disease, amyotrophic lateral sclerosis etc)
predicted to be unable to write the headache diary due to cognitive decline
contraindications to MRI
pregnancy
refusal to informed consent

Arm && Interventions

Group	Intervention	Description
Migraineurs	BOLD MRI	Patients diagnosed with migraine based on the ICHD-3 beta will undergo BOLD MRI with prospective CO2 targeting
Control	BOLD MRI	Normal controls without headaches will undergo BOLD MRI with prospective CO2 targeting

Primary Outcome Measures

Name	Time	Method
CVR association with WMH development	1-year follow-up (2nd year)	The investigators will obtain a CVR map using BOLD MR signal in the first year of study and also obtain changes in WMH during 2 years of follow-up period in patients and controls, respectively. Then the investigators will test whether CVR-map predicts consequent WMH development in patients and controls, respectively.

Secondary Outcome Measures

Name	Time	Method
Spatial pattern of CVR	baseline(1st year)	The investigators will obtain a CVR map for each voxel using BOLD MR signal in response to % increase in EtCO2 respectively in patients and controls. Spatial pattern of CVR will be compared between patients and controls.