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的临床特点(附1家系报告)

目的 探讨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)的临床特点.方法 对1例CADASIL患者及其家系的临床资料进行回顾性分析.结果 先证者以大脑皮质下梗死起病,伴有渐进性认知功能障碍.头颅MRI示皮质下多发梗死灶,脑白质疏松.NOTHC3基因检测为第3号外显子Arg110Cys突变,家系调查显示为常染色体显性遗传.结论 CADASIL临床表现主要为缺血性卒中、认知障碍、偏头痛及精神症状.MRI特征性改变是颞极白质T2的异常高信号.NOTCH3基因检查发现突变.     

CADASIL的MRI特征及NOTCH3基因的研究

目的探讨伴皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(CADASIL)的MRI特点和基因突变类型。方法收集5例经临床确诊的CADASIL患者,对其颅脑MRI的特点和基因检测结果进行回顾性分析。结果 MRI显示为双侧大致对称的脑白质病灶,双侧颞极白质病灶(O`sullivan征),外囊T2高信号("人"字征),皮层下腔隙灶(SLLS征),基底节区、丘脑腔隙性梗死,桥脑T2高信号,脑萎缩,微出血灶。4例患者进行了基因检测,其中3例(75%)为Notch3基因外显子4位点突变,1例(25%)为Notch3基因外显子3位点突变。1例患者病理检查证实为血管平滑肌细胞表面出现嗜锇颗粒沉积。结论 MRI结合Notch3基因突变可以诊断CADASIL。     

5个CADASIL家族的核磁共振改变特点

目的　分析来自5个CADASIL家族中8名患者的核磁共振(MRI)表现,总结病变不同时期的MRI变化规律及其诊断价值。方法　研究对象为经过超微病理和Notch3基因检查确诊的5个CADASIL家族中的8个患者,均在成年早期发病,主要表现为反复发作的缺血性卒中和进行性痴呆。对先证者1及其母亲、先证者2及其哥哥、姐姐,先证者3、4和5 ,总计8名患者进行了头部MRI检查,其中4名进行了MRI血管成像检查。结果　8名患者的头部MRI均显示多发腔隙性脑梗死,病灶主要分布在基底节、丘脑和脑室旁白质,6例患者出现了外囊梗死,4例出现了胼胝体梗死,3例出现了脑桥梗死。所有8例患者均存在双侧大脑半球多灶性或弥漫性白质疏松,1例患者MRI确诊1年后随访显示多灶性白质病变进展为弥漫性损害,5例患者出现了双侧颞极等T1 长T2 信号。4例患者的头部MRI血管成像检查未见异常。结论　基底节、丘脑和脑室旁白质是CADASIL腔隙性脑梗死的好发部位,外囊和胼胝体梗死以及双侧颞极长T2 信号对本病具有较高的诊断价值。脑干受累可以出现在病程早期,而白质病灶分布形式的变化可以反映病情的进展。     

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的临床、影像和病理学一例分析

目的探讨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)的临床特点、影像和病理学特征,提高对CADASIL的认识。方法对一例CADASIL患者的临床表现、影像学表现及皮肤活检进行总结。结果患者妊娠晚期发病,表现为反复的缺血性卒中发作,头颅MRI见皮质下梗死和白质脑病的改变,皮肤活检提示微小动脉的平滑肌细胞表面出现颗粒样嗜锇物质(GOM)。结论有阳性家族史,无常见脑血管病危险因素且发病年龄较早的缺血性脑血管病患者要考虑到CADASIL的可能,同时妊娠可能会对促进本病的发展有一定的影响。     

表现为家族性偏头痛的CADASIL家系的影像学特点

目的探讨伴皮层下梗死和白质脑病的常染色体显性遗传性脑病(CADASIL)家系的核磁共振(MRI)特点,提高对本病脑内MRI表现的认识。方法记录该CADASIL家系先证者及其亲属的临床表现及影像学检查,并行NOTCH3基因检测。结果本组6例中5例检出NOTCH3基因第14外显子C2182T突变,其中3例与MRI初诊结果一致。头颅核磁共振显示双侧额叶皮层下与侧脑室旁白质内广泛融合的病灶,基本对称性分布的稍长T1T2信号,T2FLAIR呈高信号者4例;外囊T2WI呈高信号3例;基底节区、丘脑腔隙性梗死4例;脑干T2WI呈高信号2例;脑内微出血3例;未见双侧颞极白质病灶(O’Sullivin征)。结论 CADASIL病例MRI存在特征性的病变,MRI对该病的诊断有重要作用。     

基于筛查量表的中国常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病患者临床特征分析

目的基于筛查量表,分析中国常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)患者的临床特征。方法回顾性纳入2012年1月-2019年11月在深圳市人民医院经NOTCH3基因检测确诊的CADASIL患者,行CADASIL筛查量表评分测试其敏感度。检索国内外数据库查找中国CADASIL相关文献,汇总中国患者基于筛查量表各项目的出现频率。将本研究数据(A组)、中国患者文献复习数据(B组)、制订CADASIL筛查量表时使用的原始数据(C组)三组的数据进行比较,总结中国患者的临床特征。结果本研究16例CADASIL患者中,筛查量表的敏感性为68.8%(11/16)。其中出现频率较低的项目分别为伴先兆的偏头痛(0/16,0%)、偏头痛(5/16,31.3%)、情绪精神障碍(5/16,31.3%)、脑白质病变累及颞极(7/16,43.8%)、阳性家族史(其中1代家族史阳性7/16,43.8%;2代家族史阳性4/16,25%);TIA或卒中、认知功能下降/痴呆出现率均在一半以上。A、B、C三组进行比较,偏头痛、伴先兆的偏头痛、认知功能下降/痴呆、脑白质病变、脑白质病变累及颞极、阳性家族史在三组间的出现频率均有统计学差异(均P<0.05)。经两两比较,在伴先兆的偏头痛和阳性家族史两个项目中,A组、B组的出现率均明显低于C组(均P<0.001);偏头痛、认知功能下降/痴呆、脑白质病变、脑白质病变累及颞极这几项,B组的出现率均低于C组(均P<0.05)。结论 CADASIL筛查量表应用于中国患者的敏感度不高。制定CADASIL筛查量表时使用的原始数据常见的临床症状伴或不伴先兆的偏头痛、脑白质病变累及颞极、可采集到阳性家族史,在中国患者却很低;中国CADASIL患者最常见的临床特征是TIA或卒中。     

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(附1例报道)

目的　探讨伴有皮层下梗死和白质脑病 (Cerebralautonomicdominantarteriopathywithsubcorti calinfarctsandleukoencephalopathy ,CADASIL)的常染色体显性遣传性脑动脉病的临床特点和诊断方法。 方法　对 1例CADASIL患者的临床表现、影像学 (MRI、CT)特点及皮肤活检等方面进行了探讨。结果　患者临床表现为反复发作的缺血性脑卒中、记忆力减退、假性球麻痹、MRI、CT见皮质下梗死和白质脑病的改变 ,皮肤活检显示小动脉含糖原颗粒 ,管腔狭窄 ,血管内皮下黑色嗜锇颗粒。结论　通过本病的临床特点、影像学和皮肤活检 ,可在生前进行诊断。     

常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病的临床特征及其与头颅磁共振改变的关系

目的 总结常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病(CADASIL)的眼底动脉改变规律,探讨其与临床表现以及头颅MRI改变的关系.方法 7个家系的16例患者(男4例,女12例)经过我院病理和基因检查证实为CADASIL,平均年龄(43.4±8.1)岁,平均病程(4.7±3.4)年.对所有患者进行简易精神状态量表(MMSE)评分、改良Rankin评分、眼底动脉检查和头颅MRI检查,把眼底动脉狭窄程度分为0～Ⅲ级,对头颅MRI改变进行Coulthard评分.计算患者眼底动脉狭窄分级与头颅MRI评分、MMSE、改良Rankin评分以及年龄的相关系数.选择16名健康人(在性别、年龄、视力等方面匹配)作为对照进行眼底血管检查.结果 16例患者中15例出现眼底动脉狭窄,其中4例存在轻度动脉-静脉交叉压迫.出现0级、Ⅰ级、Ⅱ级和Ⅲ级眼底动脉狭窄的患者分别为1例、4例、7例和4例,相应头颅MRI的Coulthard评分平均分按眼底动脉狭窄程度从0到Ⅲ级分别为6.0、19.0、25.1和29.8分.眼底动脉狭窄分级和头颅MRI的Coulthard评分、MMSE、改良Rankin评分、年龄的相关系数分别为0.743(P＜0.001)、-0.429(P＜0.05)、0.437(P＞0.05)和0.299(P＞0.05).对照组有2例出现Ⅰ级眼底动脉狭窄.结论 眼底动脉狭窄是CADASIL常见的视网膜改变;眼底动脉狭窄和头颅MRI改变以及痴呆可能有一定的统计学相关性.     

以先兆型偏头痛为主要临床表现的CADASIL(附1例报告)

目的 分析1例以先兆型偏头痛为主要临床表现的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(cerebral autonomic dominant arteriopathy with subcortical infarcts and leucoencephalopathy,CADASIL),探讨该病早期的临床特点.方法 对1例临床表现为先兆型偏头痛患者,进行临床、影像学分析、Notch3基因外显子测序.结果 该患主要表现为有家族史的先兆型偏头痛,头颅MRI见T2加权像和FLAIR像特征性颞极白质异常高信号,与放射冠、半卵圆中心区腔隙性脑梗死灶并存,Notch3基因外显子测序提示杂合突变c.353C→G(p.Ser118Cys).结论 重视先兆型偏头痛患者的头颅MRI表现,颞极异常信号提示CADASIL可能,进一步行Notch3基因外显子测序可提高CADASIL确诊率.     

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（附l例报道）

目的 探讨伴有皮层下梗死和白质脑病(Cerebral autonomic dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)的常染色体显性遗传性脑动脉病的临床特点和诊断方法。方法 对1例CADASIL患者的临床表现、影像学(MRI、CT )特点及皮肤活检等方面进行了探讨。结果 患者临床表现为反复发作的缺血性脑卒中、记忆力减退、假性球麻痹、MRI、CT见皮质下梗死和白质脑病的改变，皮肤活检显示小动脉含糖原颗粒，管腔狭窄，血管内皮下黑色嗜锇颗粒。结论 通过本病的临床特点、影像学和皮肤活检，可在生前进行诊断。     

急性播散性脑脊髓炎与经典多发性硬化的临床对比分析

目的 寻找临床上鉴别急性播散性脑脊髓炎(acute disseminated encephalumyelitis,ADEM)与经典多发性硬化(classical multiple sclerosis,CMS)的方法.方法 回顾性分析20例ADEM和24例CMS患者的流行病学特点、临床症状、实验室检查和MRI,对各定性资料进行卡方检验,定量资料进行两独立样本的Wilcoxon秩和检验.结果 ADEM患者起病年龄[(27±15)岁]较CMS患者[(37±13)岁,Z=-2.218,P=0.027]小.ADEM患者通常有前驱感染史(75%),发热(65%)、脑膜刺激征(40%)、癫痫(25%),较CMS者常见(x2=23.652、18.609、9.189、4.514,均P＜0 05),脑病更多见于ADEM患者.ADEM患者血白细胞[(11 9±5.8)×109/L,Z=-2.030,P=0.042]、C反应蛋白(2.74 mg/L,Z=-3.028,P=0.002)、红细胞沉降率(11.00 mm/h,Z=-2 406,P=0.016)、脑脊液白细胞(9×106/L,Z=-2.781,P=0.005)较CMS患者[上述指标分别为(8.0±3.2)×109/L、0.49 mg/L、7.00 mm/h、2 ×106/L]高,脑脊液蛋白(ADEM组0.19 g/L,CMS组0.17 g/L)及寡克隆带(OCB)阳性率(ADEM组4/20,CMS组11/24)在两者间差异无统计学意义.在MRI上,ADEM患者更多见皮质灰质病灶(14/20,x2=15.213,P=0.000)、基底节区灰质病灶(14/20,x2=8.910,P=0.003)和脑干病灶(14/20,x2=5.867,P=0.015),脊髓病灶多近中央分布(83%,x2=11.542,P=0 001),病灶边界模糊(95%,x2=21.787,P=0.000);CMS患者更多见近皮质白质病灶(21/24,x2=17.628,P=0.000)、侧脑室旁病灶(21/24,x2=15.213,P=0.000)和胼胝体病灶(14/24,x2=8.640,P=0.003),脊髓病灶多呈偏心分布(85%),病灶边界清楚(75%).结论 ADEM与CMS无论在流行病学特点、临床症状,还是在脑脊液和MRI检查方面都有一定差异.

Abstract：

Objective To improve differential diagnosis between acute disseminated encephalomyelitis ( ADEM) and classical multiple sclerosis ( CMS).Methods All 20 cases of ADEM and 24 cases of CMS were examined.Their epidemiological and clinical findings,laboratory features and magnetic resonance imaging ( MRI) data were analyzed using x2 test for categorical variables,Wilcoxon Rank-Sum tests for continuous variables.Results ADEM and CMS showed no sex predominance.Patients with ADEM ((27 ±15) years) were younger than CMS ((37 ±13) years,Z= -2.218,P =0.027).The following findings were more commonly seen in ADEM compared with CMS:predemyelinating infectious disease (75% vs 4%,x2 =23.652,P = 0.000),fever (65% vs 4%,x2 =18.609,P = 0.000),meningeal irritation sign (40% vs 0,x2 = 9.189,P =0.002),seizure (25% vs 0,x2 =4.514,P = 0.034),and encephalopathy.ADEM patients were more likely to present with blood leucocytosis ( (11.9 ± 5.8) ×109/L vs (8.0±3.2) ×109/L,Z= -2.030,P=0.042),high C-reactive protein (2.74 mg/L vs 0.49 mg/L,Z = - 3.028,P = 0.002),increased erythrocyte sedimentation rate (11.00 mm/h vs 7.00 mm/h,Z= -2.406,P =0.016),and cerebrospinal fluid leucocytosis (9 × 106/L vs 2×106/L,Z =- 2.781,P = 0.005).There were no differences in cerebrospinal fluid protein and oligoclonal band between the two groups.The following MRI lesions were more commonly seen in ADEM patients:cortical gray matter lesions (14/20,x2=15.213,P=0.000),basal ganglia gray matter lesions (14/20,x2 =8.910,P = 0.003),and brainstem lesions ( 14/20,x2 = 5.867,P = 0.015).In contrast,lesions in subcortical white matter (21/24,x2 = 17.628,P =0.000),periventricular area (21/24,x2 =15.213,P=0.000) and corpus callosum ( 14/24,x2 = 8.640,P = 0.003 ) were more common in the MRI image of CMS patients.The lesions in spinal cord were usually centrally distributed in ADEM (83% ),while peripherally in CMS (85%,x2 = 11.542,P = 0.001).The lesions had poorly defined margins in ADEM (95%),but well defined margins in CMS (75%,x2 =21.787,P = 0.000).Conclusion There are differences in epidemiological and clinical findings,laboratory features and MRI appearances between ADEM and CMS.     

CADASIL患者脑微出血分布特征及临床意义

目的 探讨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（cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy，CADASIL）患者脑微出血（cerebral microbleeds，CMBs）的分布特征及临床意义。 方法 回顾性纳入2017年6月-2019年12月北京协和医院基因确诊的连续CADASIL患者21例（CADASIL 组），以及性别匹配的高血压动脉硬化性脑小血管病患者21例（高血压脑小血管病组）。所有患者均 行头MRI 检查（含T2 */SWI序列），盲法读片并记录CMBs的数量和部位，分析两组CMBs分布的差异。 结果 CADASIL组年龄和常见血管病危险因素比例均低于高血压脑小血管病组。CADASIL组47.6% 患者检出CMBs（共计115个），而高血压脑小血管病组高达95.2%（共计218个）。CADASIL组CMBs分 布以丘脑最常受累（45.2%），其次是脑叶（皮层/皮层下，35.7%）、基底节（11.3%）。高血压脑小 血管病组则以丘脑以外的基底节CMBs最多见（35.3%），其次是脑叶（26.6%）、丘脑（19.2%）、脑干 （16.1%）。CADASIL患者丘脑CMBs/总CMBs比例、丘脑CMBs/（基底节CMBs+脑干CMBs）比例均高于高 血压脑小血管病组（均P＜0.001）。 结论 CADASIL患者CMBs分布以丘脑最常见，其次是皮层/皮层下区域，而高血压脑小血管病患者 则以丘脑以外的基底节、脑干更常见。     

Cerebral microbleeds in CADASIL

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy leading to recurrent cerebral infarcts and dementia. Intracerebral hemorrhage (ICH) has been described sporadically in patients with CADASIL, suggesting that the affected arteries in CADASIL are not bleed-prone. However, the presence of cerebral microbleeds, which often remain undetected on conventional MRI, has not been determined in CADASIL. OBJECTIVE: To determine whether cerebral vessels in patients with CADASIL are prone to microbleeding. METHODS: T2*-weighted gradient echo MRI, which is highly sensitive for visualizing microbleeds, was performed in patients with CADASIL and their family members (n = 63). Known risk factors for ICH were determined for all individuals. On an exploratory basis, the presence of cerebral microbleeds was correlated with demographic variables, vascular risk factors, disease progression, ischemic MR lesions, and genotype. RESULTS: Cerebral microbleeds were present in 31% of symptomatic CADASIL mutation carriers, predominantly in the thalamus. Vascular risk factors such as hypertension did not account for the microbleeds in these patients. Factors associated with microbleeds were age (p = 0.008), Rankin disability score (p = 0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and the Arg153Cys Notch3 mutation (p = 0.017). After correction for age, only the Arg153Cys mutation remained significantly associated with the presence of microbleeds. CONCLUSION: Patients with CADASIL have an age-related increased risk of intracerebral microbleeds. This implies that they may have an increased risk for ICH, which should be taken into account in CADASIL diagnosis and patient management.     

小脑分水岭梗死患者临床及影像学特点分析

目的分析小脑分水岭梗死患者的临床特点及影像学特征。方法收集房山区第一医院神经内科2011-09-2014-12住院的小脑梗死患者147例,均行头颅MRI、椎动脉彩超、经颅多普勒(TCD)、颅内动脉核磁血管造影(MRA)检查,必要时进行计算机断层摄影血管造影(CTA)和/或数字减影血管造影(DSA)检查。根据小脑梗死部位将患者分为小脑区域性梗死组和小脑分水岭梗死组,比较两组患者的危险因素、临床及影像学特点。结果 (1)小脑区域性脑梗死109例,小脑分水岭梗死38例(25.9%),两组在年龄、性别构成以及合并高血压、糖尿病、高脂血症、吸烟及心房纤颤比例比较无统计学差异。(2)与区域性脑梗死比较,小脑分水岭脑梗死组失水状态、晕厥等前驱症状发生率较高(21.1%比9.2%,P=0.026),后循环多发病灶发生率较低(21.1%比38.5%,P=0.002),NHISS评分低(2.7±1.9比6.1±2.5,P=0.000)。(3)两组小脑梗死患者发生后循环大血管病变比例无统计学差异(52.6%比36.7%,P=0.085);分析非心源性脑梗死病例发现,分水岭梗死存在大动脉狭窄几率高于区域性脑梗死(47.4%比30.2%,P=0.002)。结论小脑分水岭梗死与区域性脑梗死相比危险因素相同,病因略有不同。分水岭梗死患者临床症状轻,但前驱症状发生率高。     

缺血性卒中患者脑微出血的相关因素分析

目的 探讨缺血性卒中患者发牛脑微出血(CMBs)的相关因素. 方法 对85例急性缺血性卒中患者进行磁共振检查,其中包括梯度回波T2加权成像(GE-T2~*WI),并对患者的临床资料和影像学特点进行分析. 结果 26例(30.6%)患者中共检出CMBs 124个,每位患者的CMBs数目在1～16个之间.CMBs在基底节丘脑区和皮质一皮质下区分布较多,在幕下区较少见.发生在脑十的CMBs可有相关症状及体征.CMBs数目与年龄、腔隙性梗死数目及白质疏松程度评分有相关性(r=0.243,P=0.025;r=337,P=0.002;r=0.438,P=0.000).CMBs在GE-T2~*WI上显影良好,部分CMBs可在自旋叫波(SE)T2WI及DWI序列上显影. 结论 CMBs是脑微小血管病变标志,主要预测因素有高龄、多发腔隙性梗塞和白质疏松.     

脑小血管病

目的探讨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(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)患者脑微出血(cerebral microbleeds,CMBs)的分布特征及临床意义。方法回顾性纳入2017年6月-2019年12月北京协和医院基因确诊的连续CADASIL患者21例(CADASIL组),以及性别匹配的高血压动脉硬化性脑小血管病患者21例(高血压脑小血管病组)。所有患者均行头MRI检查(含T2^*/SWI序列),盲法读片并记录CMBs的数量和部位,分析两组CMBs分布的差异。结果CADASIL组年龄和常见血管病危险因素比例均低于高血压脑小血管病组。CADASIL组47.6%患者检出CMBs(共计115个),而高血压脑小血管病组高达95.2%(共计218个)。CADASIL组CMBs分布以丘脑最常受累(45.2%),其次是脑叶(皮层/皮层下,35.7%)、基底节(11.3%)。高血压脑小血管病组则以丘脑以外的基底节CMBs最多见(35.3%),其次是脑叶(26.6%)、丘脑(19.2%)、脑干(16.1%)。CADASIL患者丘脑CMBs/总CMBs比例、丘脑CMBs/(基底节CMBs+脑干CMBs)比例均高于高血压脑小血管病组(均P<0.001)。结论CADASIL患者CMBs分布以丘脑最常见,其次是皮层/皮层下区域,而高血压脑小血管病患者则以丘脑以外的基底节、脑干更常见。     

抗震救灾官兵256例心理亚健康调查分析与康复疗养对策

目的 对参与5.12汶川大地震抗震救灾的官兵进行心理亚健康评测并评价康复疗养效果。 方法 采用症状自评量表SCL-90对2008年5月12日汶川大地震后执行抗震救灾任务的256名解放军官兵进行测评,根据测评结果制定并实施相应康复疗养措施;分别于康复疗养10、20d末再次进行测评,对上述评定结果进行比较分析。 结果 抗震救灾官兵中出现不同程度的躯体化、焦虑、抑郁症状,心理干预前躯体化67例(29.00％),焦虑42例(18.18％),抑郁25例(10.82％);干预第10天末躯体化47例(19.58％),焦虑25例(10.41％),抑郁13例(5.41％),与干预前比较差异均有统计学意义(x2=5.695,P=0.017;x2=5.630,P=0.018;x2=4.638,P=0.031）,干预第20天躯体化10例(4.01％),焦虑7例(2.81％),抑郁2例(0.8％),与干预前比较差异均有统计学意义(x2=55.556,P=0.000;x2=30.509,P=0.000;x2=22.660,P=0.000)。 结论 对处于心理亚健康的抗震救灾官兵及时有效地进行康复疗养,可减轻或消除救援人员在抗震救灾过程中所产生的心理亚健康状态。     

New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature.

A survey was carried out on a large family presenting the symptoms of familial arteriopathy (CADASIL) recently mapped to chromosome 19. This is characterised clinically by recurrent subcortical infarcts developing into pseudobulbar palsy and subcortical dementia, and radiologically by early MRI abnormalities. To characterise this familial condition, 43 members older than 20 years and spreading over four generations were studied clinically (31 living, 12 deceased), genetically, and radiologically by MRI (n = 31). Twenty out of 43 were found to be clinically symptomatic and of these 13 out of 31 had MRI abnormalities. Genetic studies mapped this condition to the locus of CADASIL (lod score > 3). The natural history suggests a chronological clinicoradiological staging of this phenotype of CADASIL: stage I between 20 and 40 years with frequent migraine-like episodes and well delineated lesions of the white matter; stage II between 40 and 60 years with stroke-like episodes, bipolar or monopolar-like psychotic disorders, coalescent lesions of the white matter, and well delineated lesions of the basal ganglia; and stage III over 60 years with subcortical dementia, pseudobulbar palsy, diffuse leukoencephalopathy, and multiple well delineated lesions of the basal ganglia. This phenotype differs from the other two previously described by high frequency of migraine, frequency of psychotic disorders, and early neurological manifestations. The new acronym "cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and migraine" (CADASILM) is proposed to better describe this particular subvariety of CADASIL.