Correlation Between Cerebrovascular Reactivity And White Matter Lesions In Migraine Patients With Right-to-Left Shunts

Background and purpose:White matter lesions(WML)were the common neurodegenerative disease,often associated with aging and vascular risk factors.Recently,several studies have shown that the generation of WML in migraineurs is significantly higher than the health.Migraine is a chronic attack of nervous system disease,which seriously affects people’s daily life.The incidence of migraines in the population is about 10-15%.Several studies have shown that migraineurs were more likely to have right-to-left shunts(RLS).In addition,some studies have shown that migraine was associated with changes of CVR.It was not clear whether changes of CVR in migraineurs were caused by migraine itself or by RLS.Our study aims to explore the changes of cerebrovascular reactivity(CVR)in migraineurs with right-to-left shunts(RLS),and further evaluate the association between CVR and the occurrence of white matter lesions(WML).Methods: A total of 327 migraine patients who visited the Department of Neurology outpatient department of Qingdao University Affiliated Hospital from January 2016 to December 2020 were enrolled in this study.The diagnostic criteria of International Classification of Headache Disorders-Ⅲ Beta existed all patients.All migraineurs underwent a standardized questionnaire for family and personal history and for detailed migraine features.Which includes age,sex,hypertension,hyperlipidemia,diabetes,age of onset,frequency and duration of headache.In addition,patients who met the diagnosis of migraine underwent craniocerebral MRA,cervical vascular ultrasound or cervical CTA to exclude intracranial and extracranial large vessel stenosis.The controls consisted of 81 healthy volunteers with no history of migraine.RLS was further completed in patients who met the diagnostic criteria for migraine in the proposed study.RLS was diagnosed based on a contrast enhancement transcranial Doppler(c-TCD)examination.According to the degree of RLS,grade 0: no microbubble(MB);grade 1: 1-10MBs;grade 2:11-25 MBs;grade 3: more than 25 MBs with no “curtain effect”;grade 4:more than 25 MBs with “curtain effect”.In this study,grade 1-2 was defined as mild-RLS,and grade 3-4 was defined as large-RLS.The breath holding index(BHI),which represents CVR,was measured from the middle cerebral artery(MCA)using a TCD with the breath-holding method.The mean cerebral blood flow velocity(MFVmean)and maximum cerebral blood flow velocity(MFVmax)were monitored by transcranial Doppler,breath holding index(BHI)was calculated,which was an indirect reflection of CVR.WMHs was defined as clearly hyperintense areas in 3T magnetic resonance imaging(MRI).The migraineurs who completed RLS screening were further examined by MRI.MRI showed patchy or diffuse fusion around the upper ventricle and subcortical region,and T1-weighted sequence(T1WI)showed iso-signal or hypo-signal.Abnormal intensification of T2 weighted sequence(T2WI)and T2 fluid attenuation inversion recovery(T2-FLAIR)is defined as white matter hypersignal(WMH).According to the results of MRI,the patients who completed the MRI were divided into WML group and no-WML group.The BHI between controls and migraineurs has been compared,as well as in migraineurs with and without RLS.In addition,the BHI in patients who completed the MRI between WML group and no-WML group has also been compared.Univariate and multivariate Logistic regression analysis was used to analyze the influencing factors of WML.All statistical analyses were carried out in SPSS 25.0 software.Results:A total of 327 migraineurs and 81 controls were included in this study.The average age of the migraineurs was 38.2±12.64 years,including 227 females(69.6%)and100 males(30.4%).The BHI was significantly lower in migraineurs than in controls(0.545±0.68 vs.0.786±0.48,P=0.000).In migraineurs,225(68.8%)were RLS+ and 102(31.2%)were RLS-.And,migraineurs with RLS have lower BHI than those without RLS(0.481±0.64 vs.0.687±0.73,P=0.011).However,there was no difference between subgroups with different shunt degrees(0.525±0.67 vs.0.405±0.07,P=0.176).There were also no intergroup differences in age,sex,or vascular risk factors(including smoking,hypertension and diabetes)between migraine and control,migraineurs with RLS or without,and different degrees of RLS shunts.In addition,migraineurs with WMHs had lower BHI than those without(0.34±0.58 vs.0.72±0.44,P=0.001).Moreover,the reduced BHI was an independent influencing factor for WMHs in our study(OR=0.264;95% CI = 0.115-0.603,P= 0.002).Conclusion:Compared with healthy controls,migraineurs had lower CVR.In migraineurs,RLS was associated with reduced CVR,but there was no difference in RLS subgroups.In addition,reduced CVR was associated with WML in migraineurs.The decrease of CVR in migraine patients may be related to RLS,and the decreased CVR may be related to the occurrence of WML.