Clinical And Imaging Characteristics Of CADASIL

Objective:CADASIL is a kind of chromosome-induced inherited cerebral arteriovenous disease,which is associated with middle-aged disease caused by Notch3 gene mutation on chromosome 19,Non-arterial sclerosis,hereditary small arteriolar cerebrovascular disease.The clinical symptoms to repeated subcortical ischemic stroke,progressive cognitive disorders,migraine,pseudo-ball paralysis and emotional disorders,and ultimately lead to dementia or even death.Magnetic Resonance Imaging features is a kind of bilateral cerebral hemispheric diffuse white matter lesions and multiple basal ganglia lacunar infarcts.It is of great value in the early diagnosis of this disease.CADASIL is the most common cause of stroke and vascular dementia in adults.Its clinical and neurovascular findings are similar to other small vessel disease,such as cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy,multiple sclerosis,small vessel disease Binswanger disease,central nervous system primary vasculitis,clinical and other clinical manifestations of cerebral hemorrhagic cerebral arterial disease,That is easy to CADASIL caused by misdiagnosis and missed diagnosis clinically,and the course was developed,early diagnosis of the disease and early diagnosis of patients is heip the patients with clinical treatment.In this study,we analyzed the clinical manifestations and imaging features of the autosomal dominant cerebral arterial disease families with two subcortical infarcts and white encephalopathy,with a view to providing a strong basis for further gene diagnosis.Reducing the misdiagnosis and missed diagnosis of the disease.Methods:All the two families in Kunming,Yunnan Province,were clinically suspected of having autosomal dominant arteriopathy with subcortical infarct andLeuco-encephalopathy and their family members.①The CADASIL scale was used to analyze the onset age,the first symptom and the condition of the disease,the imaging features,the blood biochemistry and the cognitive function evaluation scale of the two clinically diagnosed CADASIL patients,and the families were investigated,Completed the family tree.②The peripheral blood of two patients and their family members were drawn and the peripheral blood was extracted.Primer Premier 5.0 software was used to design primers for the exon coding region of nonterukine mutation region 3-6/11-14/18-19.PCR polymerase was amplified by PCR,and then the PCR products were sequenced and compared with the reference sequence to find the possible mutations and mutations.③T1WI,T2WI and T2FLAIR conventional scans and Susceptibility weighted imaging were performed on the two probands and their families by singal.5T MR.④To analyze the genetic test results of two CADASIL probands and their family members,to study their genetic changes,and then to summarize the imaging features and clinical features of the patient with gene mutants.Results:The specific clinical data of 2 probands in 2 families were recorded,including gender,age,age of onset,onset,onset symptoms,family history and vascular risk factors(hypertension,smoking,alcohol intake,diabetes mellitus,Hypercysteinemia,heart disease,etc.),using the CADASIL scale established by Francesca Pescini et al as a screening tool for clinical suspected CADASIL patients,retrospective analysis of the CADASIL score,2 cases of CADASIL The scores were greater than 15 points(family 1:Ⅱ1= 19 points;family 2:Ⅱ2= 22 points),both of which were highly suspected to be CADASIL patients.Consecutive members of the two family were investigated,9 members,for 3 consecutive generations have onset,the incidence of both men and women,no gender ratio differences,consistent with the often dyed dominant genetic disease,but the onset of the existence of individual differences in the situation.2 families of a total of nine members of the line NOTCH3 gene was found in 3 families of family 1 to detect the NOTCH3 gene mutation,located in the exon 4 exon c.421C>T p.(Arg141Cys)heterozygous missense mutation(translation protein in the 141th amino acid residues from the fine Amino acid into cysteine.)The proband had a history of hyperlipidemia,and none of the members of the family had high risk factors such as hypertension,hyperlipidemia and hyperglycemia,and 4 patients in the family 2 detected the NOTCH3 gene mutation(Deletion of the amino acid residue at position 258 in the translation protein from tyrosine to cysteine)in the exon 5 of exon c.773A>G p.(Try258Cys),and 1 case of non-detectable NOTCH3 gene mutations in the family members were no hypertension,hyperlipidemia,hyperglycemia and other risk factors.2 families in the incidence of MRI examination showed bilateral symmetrical extensive multiple white matter lesions and cerebral ischemia,with a certain characteristics.2 cases of proband magnetic susceptibility imaging showed bilateral lateral ventricle white matter and basal ganglia abnormal iron deposition,consider the micro-hemorrhage stool change.Conclusions:1.CADASIL disease is usually inherited by autosomal dominant,and patients with heterozygous mutations have a 50%chance to pass pathogenic mutations to offspring.Almost all of the individuals who carry the mutations will develop disease.But different families,the same family members of the existence of individual differences in the situation.2.The CADASIL scale can be used as a screening tool for clinical use,and patients with highly suspected CADASIL can be selected for patients with highly suspected CADASIL.The NOTCH3 gene assay can improve the diagnosis rate and save unnecessary costs.3.Imaging examination is an indispensable index for clinical diagnosis of CADASIL.CADASIL MRI showed bilateral symmetrical extensive multiple white matter lesions and cerebral ischemia,has a certain characteristics,is one of the necessary means of diagnosis of the disease.4.Hypertension,diabetes mellitus,hyperlipidemia and other cerebrovascular disease risk factors can exist in patients with CADASIL,cerebrovascular risk factors and intracranial aortic stenosis can not be used as a CADASIL exclusion criteria,vascular risk factors control is an important component of CADASIL management section.5.Genetic testing is the gold standard for CADASIL diagnosis.