Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy：a Case Report and Literature Review

doi:10.12114/j.issn.1007-9572.2020.00.184

Abstract

Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy（CADASIL） is a monogenic autosomal dominant cerebral small-vessel disorder，mainly manifesting as migraine，subcortical ischemic events，cognitive impairment，and mental symptoms （mood disorders） and so on.The disease aggravates progressively，eventually leading to severe disability and dementia.At present，no therapies have been found to be effective in halting or delaying the disease progression and only empiric treatments can be employed to relieve the main symptoms.This article reports a case of CADASIL with a clear diagnosis，in which the clinical characteristics and management methods are analyzed and summarized，aiming to provide a reference for clinicians to manage the disease.

Key words: Cerebral small vessel diseases, Genetics, Genes, Mutation, Clinical governance, Case reports

摘要： 伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）是一种单源性常染色体显性脑小血管疾病，主要临床表现为偏头痛、皮质下梗死、认知功能下降及精神症状（情感障碍）等，病程呈进行性加重，最终可导致严重的残疾和痴呆。目前尚无有效的CADASIL治疗方法，临床上多为经验性治疗。本文通过报道1例诊断明确的CADASIL患者，分析并总结CADASIL的临床特征及管理方法，旨在为临床医生管理该病提供参考。

关键词: 大脑小血管疾病, 遗传学, 基因, 突变, 临床管理, 病例报告

ZHANG Chunyan,LIU Qingxin,CAO Xiaoyu, et al. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy：a Case Report and Literature Review　[J]. Chinese General Practice, 2020, 23(30): 3864-3869. DOI: 10.12114/j.issn.1007-9572.2020.00.184.
张春燕,刘庆新,曹晓雨等. 伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病一例报道并文献复习[J]. 中国全科医学, 2020, 23(30): 3864-3869. DOI: 10.12114/j.issn.1007-9572.2020.00.184.

References

［1］CAPLAN L R.Lacunar infarction and small vessel disease：pathology and pathophysiology［J］．J Stroke，2015，17（1）：2-6．DOI:10.5853/jos.2015.17.1.2.
［2］JOKINEN H，GOUW A A，MADUREIRA S，et al．Incident lacunes influence cognitive decline：the LADIS study［J］．Neurology，2011，76（22）：1872-1878．DOI:10.1212/WNL.0b013e31821d752f.
［3］SOURANDER P，W?LINDER J.Hereditary multi-infarct dementia［J］．Lancet，1977，309（8019）：1015．DOI:10.1016/s0140-6736（77）92324-8.
［4］JOUTEL A，CORPECHOT C，DUCROS A，et al．Notch3 mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy （CADASIL），a Mendelian condition causing stroke and vascular dementia［J］．Ann N Y Acad Sci，1997，826：213-217．DOI:10.1111/j.1749-6632.1997.tb48472.x.
［5］PAPAKONSTANTINOU E，BACOPOULOU F，BROUZAS D，et al．NOTCH3 and CADASIL syndrome：a genetic and structural overview［J］．EMBnet J，2019，24：e921．DOI:10.14806/ej.24.0.921.
［6］DI DONATO I，BIANCHI S，DE STEFANO N，et al．Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy （CADASIL） as a model of small vessel disease：update on clinical，diagnostic，and management aspects［J］．BMC Med，2017，15（1）：41．DOI:10.1186/s12916-017-0778-8.
［7］LIU X，ZUO Y，SUN W，et al．The genetic spectrum and the evaluation of CADASIL screening scale in Chinese patients with NOTCH3 mutations［J］．J Neurol Sci，2015，354（1/2）：63-69．DOI:10.1016/j.jns.2015.04.047.
［8］OPHERK C.Long-term prognosis and causes of death in CADASIL：a retrospective study in 411 patients［J］．Brain，2004，127（11）：2533-2539．DOI:10.1093/brain/awh282.
［9］DEL RíO-ESPíNOLA A，MENDIóROZ M，DOMINGUES-MONTANARI S，et al．CADASIL management or what to do when there is little one can do［J］．Expert Rev Neurother，2009，9（2）：197-210．DOI:10.1586/14737175.9.2.197.
［10］GOLDSTEIN J，HAGEN M，GOLD M.Results of a multicenter，double-blind，randomized，parallel-group，placebo-controlled，single-dose study comparing the fixed combination of acetaminophen，acetylsalicylic acid，and caffeine with ibuprofen for acute treatment of patients with severe migraine［J］．Cephalalgia，2014，34（13）：1070-1078．DOI:10.1177/0333102414530527.
［11］FERRARI M D，ROON K I，LIPTON R B，et al．Oral triptans （serotonin 5-HT（1B/1D） agonists） in acute migraine treatment：a meta-analysis of 53 trials［J］．Lancet，2001，358（9294）：1668-1675．DOI:10.1016/S0140-6736（01）06711-3.
［12］TFELT-HANSEN P，SAXENA P R，DAHL?F C，et al．Ergotamine in the acute treatment of migraine：a review and European consensus［J］．Brain，2000，123（ Pt 1）：9-18．DOI:10.1093/brain/123.1.9.
［13］MARTIKAINEN M H，ROINE S.Rapid improvement of a complex migrainous episode with sodium valproate in a patient with CADASIL［J］．J Headache Pain，2012，13（1）：95-97．DOI:10.1007/s10194-011-0400-y.
［14］DONNINI I，NANNUCCI S，VALENTI R，et al．Acetazolamide for the prophylaxis of migraine in CADASIL：a preliminary experience［J］．J Headache Pain，2012，13（4）：299-302．DOI:10.1007/s10194-012-0426-9.
［15］PETERS N，HERZOG J，OPHERK C，et al．A two-year clinical follow-up study in 80 CADASIL subjects：progression patterns and implications for clinical trials［J］．Stroke，2004，35（7）：1603-1608．DOI:10.1161/01.STR.0000131546.71733.f1.
［16］LIPPI G，MATTIUZZI C，MESCHI T，et al．Homocysteine and migraine.A narrative review［J］．Clin Chim Acta，2014，433：5-11．DOI:10.1016/j.cca.2014.02.028.
［17］BERSANO A，BEDINI G，OSKAM J，et al．CADASIL：treatment and management options［J］．Curr Treat Options Neurol，2017，19（9）：31．DOI:10.1007/s11940-017-0468-z.
［18］SHOBHA N，FANG J M，HILL M D.Do lacunar strokes benefit from thrombolysis? Evidence from the Registry of the Canadian Stroke Network［J］．Int J Stroke，2013，8（Suppl A100）：45-49．DOI:10.1111/j.1747-4949.2012.00932.x.
［19］DICHGANS M，PETERSEN D.Angiographic complications in CADASIL［J］．Lancet，1997，349（9054）：776-777．DOI:10.1016/S0140-6736（05）60202-4.
［20］ADIB-SAMII P，BRICE G，MARTIN R J，et al．Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype：study in 200 consecutively recruited individuals［J］．Stroke，2010，41（4）：630-634．DOI:10.1161/STROKEAHA.109.568402.
［21］HOLTMANNSP?TTER M，PETERS N，OPHERK C，et al．Diffusion magnetic resonance histograms as a surrogate marker and predictor of disease progression in CADASIL：a two-year follow-up study［J］．Stroke，2005，36（12）：2559-2565．DOI:10.1161/01.STR.0000189696.70989.a4.
［22］VERGHESE J，LIPTON R B，HALL C B，et al．Low blood pressure and the risk of dementia in very old individuals［J］．Neurology，2003，61（12）：1667-1672．DOI:10.1212/01.wnl.0000098934.18300.be.
［23］RUFA A，DOTTI M T，FRANCHI M，et al．Systemic blood pressure profile in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy［J］．Stroke，2005，36（12）：2554-2558．DOI:10.1161/01.STR.0000190832.17620.25.
［24］FLEMMING K D，NGUYEN T T，ABU-LEBDEH H S，et al．Hyperhomocysteinemia in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy （CADASIL）［J］．Mayo Clin Proc，2001，76（12）：1213-1218．DOI:10.4065/76.12.1213.
［25］SINGHAL S，BEVAN S，BARRICK T，et al．The influence of genetic and cardiovascular risk factors on the CADASIL phenotype［J］．Brain，2004，127（Pt 9）：2031-2038．DOI：10.1093/brain/awh223．
［26］中国缺血性脑卒中和短暂性脑缺血发作二级预防指南（2010）［J］．中国临床医生，2011，39（11）：68-74.
［27］LIAN L F，LI D J，XUE Z，et al．Spontaneous intracerebral hemorrhage in CADASIL［J］．J Headache Pain，2013，14：98．DOI:10.1186/1129-2377-14-98.
［28］RINNOCI V，NANNUCCI S，VALENTI R，et al．Cerebral hemorrhages in CADASIL：report of four cases and a brief review［J］．J Neurol Sci，2013，330（1/2）：45-51．DOI:10.1016/j.jns.2013.04.002.
［29］HUANG L，YANG Q D，ZHANG L，et al．Acetazolamide improves cerebral hemodynamics in CADASIL［J］．J Neurol Sci，2010，292（1/2）：77-80．DOI:10.1016/j.jns.2010.01.023.
［30］PETERS N，FREILINGER T，OPHERK C，et al．Effects of short term atorvastatin treatment on cerebral hemodynamics in CADASIL［J］．J Neurol Sci，2007，260（1/2）：100-105．DOI:10.1016/j.jns.2007.04.015.
［31］CHABRIAT H，PAPPATA S，OSTERGAARD L，et al．Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking［J］．Stroke，2000，31（8）：1904-1912．DOI:10.1161/01.str.31.8.1904.
［32］MIZUNO T，KONDO M，ISHIGAMI N，et al．Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine［J］．Clin Neuropharmacol，2009，32（2）：113-116．DOI:10.1097/WNF.0b013e31816c82a6.
［33］SHIN D，OH Y H，EOM C S，et al．Use of selective serotonin reuptake inhibitors and risk of stroke：a systematic review and meta-analysis［J］．J Neurol，2014，261（4）：686-695．DOI:10.1007/s00415-014-7251-9.
［34］KEVERNE J S，LOW W C，ZIABREVA I，et al．Cholinergic neuronal deficits in CADASIL［J］．Stroke，2007，38（1）：188-191．DOI:10.1161/01.STR.0000251787.90695.05.
［35］MANGANELLI F，RAGNO M，CACCHIò G，et al．Motor cortex cholinergic dysfunction in CADASIL：a transcranial magnetic demonstration［J］．Clin Neurophysiol，2008，119（2）：351-355．DOI:10.1016/j.clinph.2007.10.011.
［36］DICHGANS M，MARKUS H S，SALLOWAY S，et al．Donepezil in patients with subcortical vascular cognitive impairment：a randomised double-blind trial in CADASIL［J］．Lancet Neurol，2008，7（4）：310-318．DOI:10.1016/S1474-4422（08）70046-2.
［37］POSADA RODRíGUEZ I J，FERRERO ROS M，LóPEZ VALDéS E，et al．Tratamiento con galantamina en la demencia asociada a CADASIL［J］．Rev Neurol，2008，47（6）：299．DOI:10.33588/rn.4706.2008234.
［38］MCSHANE R，AREOSA SASTRE A，MINAKARAN N.Memantine for dementia［J］．Cochrane Database Syst Rev，2006（2）：CD003154．DOI:10.1002/14651858.CD003154.pub5.
［39］TIKKA S，NG Y P，DI MAIO G，et al．CADASIL mutations and shRNA silencing of NOTCH3 affect actin organization in cultured vascular smooth muscle cells［J］．J Cereb Blood Flow Metab，2012，32（12）：2171-2180．DOI:10.1038/jcbfm.2012.123.
［40］RUTTEN J W，DAUWERSE H G，PETERS D J，et al．Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping：in vitro proof of concept［J］．Brain，2016，139（Pt 4）：1123-1135．DOI:10.1093/brain/aww011.
［41］GONG L，LIU X Y，FANG M.Recent progress on small vessel disease with cognitive impairment［J］．Int J Clin Exp Med，2015，8（5）：7701-7709.
［42］GHEZALI L，CAPONE C，BARON-MENGUY C，et al．Notch3ECD immunotherapy improves cerebrovascular responses in CADASIL mice［J］．Ann Neurol，2018，84（2）：246-259．DOI:10.1002/ana.25284.

[1]	LIU Yu, YUE Ting, YANG Dongyu, ZHAO Zhongting, YANG Jibo, ZHU Tiantian. Research Progress on Mechanism of Autophagy in the Pathogenesis of Rheumatoid Arthritis [J]. Chinese General Practice, 2023, 26(29): 3710-3714.
[2]	REN Yumei, XU Min, YE Meilei, ZHANG Qiu, HU Honglin. A Mutation in the Insulin Receptor Substrate 2 Gene May Be Associated with Maturity-onset Diabetes of the Young: a Case Report with Genetic Analysis [J]. Chinese General Practice, 2023, 26(18): 2301-2305.
[3]	MENG Qizhe, XI Zhi, WANG Ming, WANG Yang, YANG Xiaopeng. Correlation of Blood Glucose Variability with Infarct Burden and Cognitive Impairment in Patients with Type 2 Diabetes Mellitus Complicated with Recent Small Subcortical Infarct [J]. Chinese General Practice, 2023, 26(15): 1885-1891.
[4]	YU Jie, LI Hongling, ZHAO Gang, LI Jingui. Effect of Circling Moxibustion on the Ultrastructure of Wound Tissue in Rats with Pressure Injury [J]. Chinese General Practice, 2023, 26(11): 1375-1381,1388.
[5]	CHAI Yan, ZHAO Yuqing, GUO Xunan, WANG Dongying, BIAN Yunfei. Bioinformatics Analysis of the Role of Epicardial Adipose Tissue in Coronary Artery Disease [J]. Chinese General Practice, 2023, 26(08): 939-950.
[6]	WANG Jing, LIU Yun, HUANG Haoyu, WU Jinting, LIU Chunming, ZHANG Yangping, WANG Wenjuan. Developmental Delay/Mental Retardation of Unknown Origin in Children: Genetic Analysis of 93 Cases [J]. Chinese General Practice, 2023, 26(08): 933-938.
[7]	SUN Tao, PENG Yingchao, SHI Zhuo, GAO Chunlin, XIA Zhengkun. Unilateral Renal Atrophy Due to GREB1L Gene Mutation: a Case Report and Literature Review [J]. Chinese General Practice, 2023, 26(08): 1028-1030.
[8]	ZHANG Sen, BAI Hongying, LI Qianqian, LI Caixia. Total Deep Medullary Veins Score in Cerebral Small Vessel Disease: Association with Imaging Markers and Factors Related to Its Elevation [J]. Chinese General Practice, 2023, 26(06): 681-686.
[9]	HE Xiaoli, LIANG Shuheng, LI Miaoxia, KONG Jinliang, SHAN Qingwen. Hereditary Pancreatitis in Children: Report of One Case with Pedigree Analysis and Literature Review [J]. Chinese General Practice, 2023, 26(05): 641-646.
[10]	Yingmei ZHANG, Fei WANG, Xiaobing REN, Yuelian WANG, Jun CHEN, Ying HU, Xiaoqin HU, Wenge XU. Phenotypic Drug Resistance and Gene Mutation in Mycobacterium Tuberculosis with and without Diabetes: a Prospective Study [J]. Chinese General Practice, 2022, 25(29): 3616-3620.
[11]	Xiaomiao WAN, Ling LI, Changwei LIU, Chaohui SHEN, Liwen WU, Suxian ZHOU. Rubinstein-Taybi Syndrome: Clinical and Genetic Analyses of One Case and Literature Review [J]. Chinese General Practice, 2022, 25(24): 3070-3074.
[12]	Jiansheng LI, Zhenzhen FENG, Yang XIE, Jiajia WANG. Strategy and Development of the TCM Syndrome-based Treatment Effectiveness Assessment Scale Using the Mode of Combination of Disease and Syndrome [J]. Chinese General Practice, 2022, 25(20): 2513-2519.
[13]	Jingjing ZHAO, Yuhong LI, Min YU, Fangfang YANG, Qiaozhi YU, Xiaoyue WANG, Sisi BU, Peipei LIAO. Maternal Physical Activity in the Third Trimester and Delayed Onset of Lactogenesis [J]. Chinese General Practice, 2022, 25(18): 2268-2274.
[14]	Jinxiang WANG, Yuxin DONG, Yibo ZHAO, Xianglong MENG, Yanfen CHAI, Heng JIN. Advances in Diagnosis and Management of Acute Kidney Injury Induced by Crush Syndrome [J]. Chinese General Practice, 2022, 25(15): 1914-1918.
[15]	LI Yong, LONG Yong, ZHAO Chong, ZHANG Guanqing, SU Yanhe. Curative Effect of EGFR-TKIs with Anti-angiogenic Drugs as the Treatment for Patients with Advanced EGFR-mutant Non-small Cell Lung Cancer：a Meta-analysis [J]. Chinese General Practice, 2022, 25(08): 1007-1013.