Clinical And Imaging Characteristics Of CADASIL Patients

Objective: Cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy(CADASIL)is the most common monogenic cerebral small vessel disease,the majority of East Asian patients with CADASIL carry the same R544 C mutation.This study collects clinical and imaging information of CADASIL patients,aims at analyzing the clinical and imaging characteristics of CADASIL patients with different mutation,summarizing the clinical and imaging characteristics of CADASIL patients with intracerebral hemorrhage(ICH),and elucidating possible relationship between phenotype and genotype.Methods: We enrolled 102 genetically confirmed CADASIL patients from 2014 to2020 at the First Affiliated Hospital of Fujian Medical University,the demographic information,risk factors,family history and imaging characteristics were recorded.Patients were divided into groups depending on the NOTCH3 gene result(patients with R544 C mutation and patients with other mutations),presentation(patients with ICH and patients without ICH)and hypertension(patients with hypertension and patients without hypertension),the clinical and neuroimaging features were compared between groups.Results:1.A total of 102 patients were enrolled.Ischemic stroke/Transient Ischemic Attacks(TIA)was the most common initial presentation.The incidence of migraine(10.8%)and involvement of temporal pole(43.1%)in this study were lower than in the Caucasian population.2.Comparison of clinical characteristics between the R544 C mutation group and other mutations group showed that the incidence of ICH(40.8% VS 3.2%,P<0.001),the prevalence of hypertension(50.7% VS 25.8%,P=0.02),the incidence of cognitive impairment(73.2% VS 93.5%,P=0.02)and the involvement of temporal pole(31.0%VS 71.0%,P<0.001)between two groups were statistically significant different.3.R544 C mutation accounted for 81.8% and 60.3% in the hypertension group and the non-hypertension group,respectively,with statistically significant difference(P=0.02).Logistic regression analysis suggested that R544 C mutation(OR=2.870,95%Confidence interval:1.091-7.550,P=0.033)was an independent risk factor for hypertension.4.A total of 50 ICH lesions were identified in 30 patients with CADASIL.The basal ganglia(48%)was the most common site,followed by thalamus(32%).5.the prevalence of hypertension(73.3% VS 30.6%,P<0.001),the proportion of R544 C mutation(96.7% VS 58.3%,P<0.001)and the involvement of temporal pole(23.3% VS 51.4%,P=0.009)between the ICH group and non-ICH group was statistically significant different.Logistic regression analysis suggested that R544 C mutation(OR=17.722,95%CI:1.911-164.315,P=0.011)and hypertension(OR=5.217,95%CI:1.736-15.680,P=0.003)were independently associated with the presence of ICH.6.Comparison of imaging features between R544 C mutation group and other mutations group showed that there were significant differences in the number of cerebral microbleed(CMB)(P=0.006),CMB count ≥9(58.8% VS 23.1%,P=0.021),basal ganglia CMB(58.8% VS 15.4%,P=0.005)and thalamus CMB(80.4% VS 38.5%,P=0.008)between the two groups.After adjusting for gender and age,the differences were still statistically significant.7.Comparison of imaging features between ICH group and non-ICH group showed that there were significant differences in the number of CMB(P = 0.002),CMB count≥9(70.8% VS 40.0%,P = 0.017),lobar CMB(83.3% VS 52.5%,P = 0.002),cerebellum CMB(62.5% VS 30.0%,P=0.011),basal ganglia CMB(75.0% VS 35.0%,P=0.002)and thalamus CMB(91.7% VS 60.0%,P=0.006)between the two groups.After adjusting for gender and age,the differences were still statistically significant.Conclusion:1.Patients with CADASIL in this region have a lower incidence of migraine and involvement of temporal pole compared to Caucasian populations.2.Compared with the other mutations group,patients with R544 C mutation had lower incidence of cognitive impairment and involvement of temporal pole,but higher amount of CMB,greater burden of CMB,and higher frequency of CMB in basal ganglia and thalamus.3.R544C mutation was an independent risk factor for hypertension in CADASIL patients.4.The incidence of ICH in CADASIL patients in this region is significantly higher than in the Caucasian population.5.R544C mutation and hypertension were independently associated with the presence of ICH in CADASIL.Patients with ICH in CADASIL had greater burden of CMB,and higher frequency of CMB in lobar,cerebellum,basal ganglia and thalamus.