CADASIL病

CADASIL(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 )的研究是近年来证实遗传因素参与脑血管病发病的重要进展之一 ,其主要临床特点为家族遗传方式起病、中年发病、逐渐进展的缺血性脑卒中样病程、假性球麻痹、进行性血管性痴呆、先兆症状的偏头痛发作和精神症状。脑内广泛多发的白质灶、明确的MRI白质异常信号以及病理学明确的小动脉病变是本病的基本特征。分子遗传学研究发现 19号染色体Notch3基因突变与本病有关     

Investigating the association between Notch3 polymorphism and migraine

OBJECTIVE: The aim of the present study was to evaluate whether the functional Notch3 polymorphism T6746C, which is not causative for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), might be a risk factor for migraine. BACKGROUND: It has been recently demonstrated that migraine is characterized by subclinical brain infarctions and white matter lesions. Several genetic risk factors have been associated with migraine, but no study has unraveled a possible relationship between migraine and Notch3, which is involved in vascular damage. Mutations in Notch3 gene have been demonstrated to be pathogenetic for CADASIL, a small vessel disease of the brain characterized by migraine. METHODS: A total of 156 migraine patients and 128 nonheadache healthy volunteers entered the study. Demographic and clinical characteristics were carefully recorded, and a neurological work-up was performed. Moreover, each subject underwent a blood sampling for Notch3 genotype determination. RESULTS: Notch3 genotypes as well as allele frequencies did not differ in migraine patients compared to controls, even adjusting for the presence of possible confounds. No difference has been found either in migraine patients with aura or in those without aura. CONCLUSIONS: These findings support the view that functional polymorphism T6746C in Notch3 gene is not involved in increasing the risk of migraine or migraine subtypes.     

Anti-NR2 glutamate receptor antibodies as an early biomarker of cerebral small vessel disease

ObjectivesCerebral small vessel disease (SVD) associated with age and vascular risk factors is one of the leading causes of cognitive disorders as well as ischemic and hemorrhagic strokes. The pathogenesis of this disease has not been fully understood yet. The previously established association of the antibodies against the NR2 subunit of the NMDA receptor (NR2ab) with the mechanisms of SVD such as ischemia and blood–brain barrier (BBB) disruption, might suggest their importance in the brain damage.Design & methodsWe studied the NR2ab serum level in 70 patients (45 females, 61.1 ± 6.3 y.o.) with different severity of cognitive impairment and MRI features of SVD and 20 healthy volunteers (12 females, 58.5 ± 6.4 y.o.).ResultsThe elevated level of NR2ab was associated with subjective cognitive impairment (SCI) (p = 0.028) and mild cognitive impairment (MCI) (p = 0.017), Fazekas grade (F) 2 (p = 0,002) and F3 (p = 0,009) of white matter hyperintensities (WMH) and the numbers of lacunes in the cerebral white matter (less than 5) (p = 0,039).ConclusionThe detected increase in serum NR2ab level in patients with SCI, as well as the minimal amount of white matter lacunes, is most likely caused by hypoxia-induced endothelial damage in the early stage of SVD. Normal NR2ab values in patients with F1 WMH, the increased NR2ab level in patients with F2 and F3 WMH and those with the minimal number of lacunes can indicate that NR2bs are involved in diffuse brain damage due to hypoxia-induced loss of BBB integrity.     

Grey matter volume alterations in CADASIL: a voxel-based morphometry study

CADASIL is a hereditary disease characterized by cerebral subcortical microangiopathy leading to early onset cerebral strokes and progressive severe cognitive impairment. Until now, only few studies have investigated the extent and localization of grey matter (GM) involvement. The purpose of our study was to evaluate GM volume alterations in CADASIL patients compared to healthy subjects. We also looked for correlations between global and regional white matter (WM) lesion load and GM volume alterations. 14 genetically proved CADASIL patients and 12 healthy subjects were enrolled in our study. Brain MRI (1.5 T) was acquired in all subjects. Optimized-voxel based morphometry method was applied for the comparison of brain volumes between CADASIL patients and controls. Global and lobar WM lesion loads were calculated for each patient and used as covariate-of-interest for regression analyses with SPM-8. Compared to controls, patients showed GM volume reductions in bilateral temporal lobes (p < 0.05; FDR-corrected). Regression analysis in the patient group revealed a correlation between total WM lesion load and temporal GM atrophy (p < 0.05; uncorrected), not between temporal lesion load and GM atrophy. Temporal GM volume reduction was demonstrated in CADASIL patients compared to controls; it was related to WM lesion load involving the whole brain but not to lobar and, specifically, temporal WM lesion load. Complex interactions between sub-cortical and cortical damage should be hypothesized.     

磁共振弥散张量和波谱成像在缺血性脑小血管疾病中的应用研究

目的探讨磁共振弥散张量成像(diffusion tensor imaging,DTI)联合磁共振波谱成像(magnetic resonance spectroscopy,MRS)对于缺血性脑小血管疾病(small vessel disease,SVD)的影像评估价值。材料与方法对42例缺血性SVD患者进行常规MRI、DTI和MRS扫描,测量病灶及健侧对称正常脑白质区域的平均弥散系数(average diffusion coefficient,DCavg)值、各向异性分数(fractional anisotropy,FA)值,测量病灶及其周围正常脑白质区域的N-乙酰天门冬氨酸(N-acetyl aspartic acid,NAA)、胆碱(choline,Cho)、肌酸(creatine,Cr)、肌醇(myo-inositol,MI)等生化代谢物的浓度值,并计算NAA/Cho、NAA/Cr、Cho/Cr、MI/Cr的比值。将42例SVD患者的缺血性病灶按照影像学显示分组,并对各组上述测量指标进行统计学分析。结果选取42例缺血性SVD患者的42个病灶并分成慢性缺血组(30例)和慢性期梗死灶组(12例)。SVD病灶的DCavg值和FA值分别较健侧镜像区正常脑白质的增高和降低(P0.01),而两组间SVD病灶的DCavg值和FA值差异无统计学意义(P0.05)。SVD病灶的NAA、Cho和Cr的均数都小于周围正常白质(P0.01),而两组间的各项MRS代谢值差异均无统计学意义(P0.05)。Pearson相关性分析,正常脑白质的DCavg值与FA值(r=-0.383,P=0.012)呈负相关,FA值与NAA/Cho(r=0.420,P=0.006)、NAA/Cr(r=0.382,P=0.012)之间均呈正相关,而在SVD病灶组无上述相关性。Spearman相关分析,SVD病灶组的DCavg与高血压呈正相关(r=0.338,P=0.029)。结论对于缺血性SVD,DCavg、FA、NAA、Cho和Cr等检测指标能够共同反映神经髓鞘结构的微观变化及其功能的破坏,联合应用DTI和MRS成像技术对缺血性SVD疾病进行研究,有助于其临床诊断及病理机制的研究。     

白质纤维束成像在颅脑疾病中的初步临床应用研究

目的 评价白质纤维束成像在颅脑疾病中的临床应用价值。方法 11例志愿者、15例缺血性脑卒中患者、3例胶质母细胞瘤及2例脑膜瘤患者行扩散张量成像。应用日本东京大学的dTV软件观察白质纤维束形态；对锥体束和胼胝体进行三维显示。结果 全部志愿者和患者均可清楚地观察白质纤维束形态。15例缺血性脑卒中患者可观察到锥体束不同程度的中断，5例脑肿瘤患者可以观察到锥体束和胼胝体受压、移位。结论 本研究表明，使用扩散张量-白质纤维束成像，可以在活体内清楚、立体地观察锥体束和胼胝体等白质纤维束形态变化以及与颅内病灶之间的关系。     

CADASIL的影像学表现

目的：研究CADASIL的影像学表现。材料与方法：报告1家系7人中4人患病,介绍了先证者的5年间颅脑CT、MRI表现。结果：颅脑MRI见脑内多发性腔梗灶和脑白质变性,颞叶前部和外囊部病变明显,且随年龄增加而加重,同时伴有脑萎缩。结论：MRI结合临床表现和家族史可诊断本病。     

The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients

Mutations in Notch3 cause CADASIL (cerebral autosomal dominant adult onset arteriopathy), which leads to stroke and dementia in humans. CADASIL arteriopathy is characterized by major alterations of vascular smooth muscle cells and the presence of specific granular osmiophilic deposits. Patients carry highly stereotyped mutations that lead to an odd number of cysteine residues within EGF-like repeats of the Notch3 receptor extracellular domain. Such mutations may alter the processing or the trafficking of this receptor, or may favor its oligomerization. In this study, we examined the Notch3 expression pattern in normal tissues and investigated the consequences of mutations on Notch3 expression in transfected cells and CADASIL brains. In normal tissues, Notch3 expression is restricted to vascular smooth muscle cells. Notch3 undergoes a proteolytic cleavage leading to a 210-kDa extracellular fragment and a 97-kDa intracellular fragment. In CADASIL brains, we found evidence of a dramatic and selective accumulation of the 210-kDa Notch3 cleavage product. Notch3 accumulates at the cytoplasmic membrane of vascular smooth muscle cells, in close vicinity to but not within the granular osmiophilic material. These results strongly suggest that CADASIL mutations specifically impair the clearance of the Notch3 ectodomain, but not the cytosolic domain, from the cell surface.     

Influence of Type 2 Diabetes on Brain Volumes and Changes in Brain Volumes: Results from the Women’s Health Initiative Magnetic Resonance Imaging Studies

OBJECTIVE

To study how type 2 diabetes adversely affects brain volumes, changes in volume, and cognitive function.

RESEARCH DESIGN AND METHODS

Regional brain volumes and ischemic lesion volumes in 1,366 women, aged 72–89 years, were measured with structural brain magnetic resonance imaging (MRI). Repeat scans were collected an average of 4.7 years later in 698 women. Cross-sectional differences and changes with time between women with and without diabetes were compared. Relationships that cognitive function test scores had with these measures and diabetes were examined.

RESULTS

The 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01) but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in gray matter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits.

CONCLUSIONS

Diabetes is associated with smaller brain volumes in gray but not white matter and increasing ischemic lesion volumes throughout the brain. These markers are associated with but do not fully account for diabetes-related deficits in cognitive function.Many interrelated factors adversely affect the brain health of individuals with type 2 diabetes, including energy dysregulation, inflammation, reduced perfusion, and increased oxidative stress and protein deposition (1,2). In cross-sectional studies, type 2 diabetes is often associated with smaller brain volumes and, less consistently, with greater amounts of white matter hyperintensities and other markers of cerebrovascular disease (3,4). Two longitudinal magnetic resonance imaging (MRI) studies have documented increased rates of total brain atrophy, which appeared to be greater among individuals with lower cognitive function, but not increased accumulations of white matter hyperintensities (5,6). The relative increases in atrophy associated with diabetes remained after covariate adjustment for many risk factors for cognitive dysfunction, including age, blood pressures, education, lipid levels, and BMI.This article is organized with three aims. In a large cohort of older women, we first describe the cross-sectional associations that diabetes had with brain tissue volumes and ischemic lesion loads. We do so for the whole brain and separately for white matter, gray matter, and major lobes. Second, among the women assessed longitudinally with MRI, we examine whether changes in brain tissue and ischemic lesion volumes varied according to diabetes status. Finally, we examine associations that brain volumes and ischemic lesion volumes had with global cognitive function and its subdomains and examine the degree to which they account for diabetes-related relative deficits. There has been one report that diabetes is associated with greater adverse effects on changes in brain structure among women than men (5), perhaps because diabetes often co-occurs with relatively more vascular risk factors among women with versus without diabetes than is the case among men (7). We analyze data from the first sufficiently large cohort of women to characterize the extent to which diabetes-related brain changes account for relative cognitive deficits.     

Brain Atrophy in Type 2 Diabetes: Regional distribution and influence on cognition

OBJECTIVE

Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function.

RESEARCH DESIGN AND METHODS

This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures.

RESULTS

T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume.

CONCLUSIONS

Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.Type 2 diabetes (T2DM) is associated with an increased risk of incident cognitive impairment, dementia, and Alzheimer disease as a possible result of cerebrovascular and/or neurodegenerative disease (1–3). T2DM is associated with brain infarcts (4,5) on magnetic resonance imaging (MRI) and less consistently with cerebral white matter hyperintensities (WMHs) (6,7) and cerebral microbleeds (8,9). Lower hippocampal volume (10–12) and total brain volume (13), which are features of Alzheimer disease, are also more likely to occur in T2DM. However, few studies have clarified the regional distribution of brain atrophy attributable to T2DM (14–16). These studies were small, and only one compared people with and without T2DM, with the results suggesting that temporal lobe gray matter may be affected in T2DM (15). Understanding the pattern of brain atrophy in T2DM may provide clues toward the underlying neurodegenerative process. For example, gray matter atrophy occurs early in the temporal, parietal, and limbic cortices before spreading to involve frontal and occipital regions in Alzheimer disease (17). Moreover, although some studies demonstrated associations of T2DM with brain atrophy or cerebrovascular disease, no data describe how MRI measures of atrophy and cerebrovascular disease mediate the difference in cognitive function between those with and without T2DM. Manschot et al. (18) found an association between T2DM and more deep white matter lesions, cortical and subcortical atrophy, and infarcts as well as impaired cognitive performance. In subgroup analysis of only those with T2DM, they found that cognitive performance was inversely associated with deep white matter lesion volume, atrophy, and infarcts. In the current study, we examined the distribution of brain atrophy in older people with T2DM, predicting that MRI measures of brain atrophy and cerebrovascular disease would mediate or modify the association between T2DM and cognitive function.     

CADA7SIL磁共振表现

目的：探讨皮层下梗死伴白质脑病的常染色体显性遗传性脑动脉病（CADASIL）的磁共振表现.材料与方法：回顾性分析有临床症状的一家系三兄弟患者资料,分析其MRI信号改变、发病部位和预后.结果：3名CADSSIL患者具有或轻或重神经缺失,MRI表现均异常.第一,脑室旁周围白质、脑干、基底节区和丘脑出现多发腔隙性梗塞;第二,脑白质病出现在皮层下区域,具有对称并相互融合的趋势,其中以颞叶多见.第三,同时伴有脑萎缩.结论：结合MRI表现（皮层下弥漫对称脱髓鞘和腔隙性脑梗塞）和家族史可诊断CADASIL此病.     

变性高压液相色谱分析在中国家族性CADASIL患者基因筛查中的应用

目的:探讨变性高压液相色谱分析(DHPLC)在伴皮质下梗死及白质脑病的常染色体显性遗传性脑动脉病(CADASIL)患者诊断中的方法和价值。方法:运用DHPLC及DNA直接测序技术,对CADASIL家系先证者、家系成员14例(CADASIL组)及健康对照者100例(对照组)进行Notch3基因检测。结果:CADASIL组发现3种致病性突变,其中Cys134Tyr为新的突变类型,同时发现15种多态类型;对照组中未发现突变。结论:DHPLC技术在筛查Notch3中起重要作用,但在筛查时应进行多个柱温的测试,温度调换以2℃为宜。     

Genetics of cerebrovascular disorders

Physicians must be able to recognize stroke caused by a mendelian or mitochondrial disorder. Some genetic disorders such as sickle cell anemia and Fabry disease have proven disease-specific treatments, whereas others have no effective treatment, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Proper diagnosis of a genetic disorder has prognostic value and prevents patient exposure to unnecessary and potentially harmful therapeutic agents and diagnostic tests. This article reviews the clinical and genetic features of some mendellan and mitochondrial disorders associated with ischemic stroke, hemorrhagic stroke, and cerebrovascular malformations.     

GENETICS

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to accumulating neurologic deficits and dementia. CADASIL has been linked to nucleotide substitutions and deletions in the Notch3 gene. All the mutations described until now lead to unpaired cysteine residue in the epidermal growth factor-like repeats. The authors report a family with CADASIL carrying a deletion in the Notch3 gene that did not involve a cysteine residue.
Comment: At least 400 families from countries around the world have been described with CADASIL. The four classic features are migraine with aura, stroke, dementia, and psychiatric disturbances. Migraine with aura, especially familial hemiplegic migraine and migraine with prolonged aura, is linked genetically to CADASIL on chromosome 19, occurs in up to 30% of patients, and when present is usually the earliest symptom. Definitive diagnosis is by skin biopsy, with characteristic depositions surrounding degenerating smooth muscle cells in the media. —Stewart J. Tepper, MD     

Cerebral Ischemia Enhances Polyamine Oxidation: Identification of Enzymatically Formed 3-Aminopropanal as an Endogenous Mediator of Neuronal and Glial Cell Death

To elucidate endogenous mechanisms underlying cerebral damage during ischemia, brain polyamine oxidase activity was measured in rats subjected to permanent occlusion of the middle cerebral artery. Brain polyamine oxidase activity was increased significantly within 2 h after the onset of ischemia in brain homogenates (15.8 ± 0.9 nmol/h/mg protein) as compared with homogenates prepared from the normally perfused contralateral side (7.4 ± 0.5 nmol/h/mg protein) (P <0.05). The major catabolic products of polyamine oxidase are putrescine and 3-aminopropanal. Although 3-aminopropanal is a potent cytotoxin, essential information was previously lacking on whether 3-aminopropanal is produced during cerebral ischemia. We now report that 3-aminopropanal accumulates in the ischemic brain within 2 h after permanent forebrain ischemia in rats. Cytotoxic levels of 3-aminopropanal are achieved before the onset of significant cerebral cell damage, and increase in a time-dependent manner with spreading neuronal and glial cell death. Glial cell cultures exposed to 3-aminopropanal undergo apoptosis (LD₅₀ = 160 μM), whereas neurons are killed by necrotic mechanisms (LD₅₀ = 90 μM). The tetrapeptide caspase 1 inhibitor (Ac-YVAD-CMK) prevents 3-aminopropanal–mediated apoptosis in glial cells. Finally, treatment of rats with two structurally distinct inhibitors of polyamine oxidase (aminoguanidine and chloroquine) attenuates brain polyamine oxidase activity, prevents the production of 3-aminopropanal, and significantly protects against the development of ischemic brain damage in vivo. Considered together, these results indicate that polyamine oxidase–derived 3-aminopropanal is a mediator of the brain damaging sequelae of cerebral ischemia, which can be therapeutically modulated.     

Cardiac diastolic dysfunction is associated with cerebral white matter lesions in elderly patients with risk factors for atherosclerosis

Cerebral white matter lesions on magnetic resonance imaging (MRI) are considered to be the result of brain ischemic injury and a risk factor for clinical stroke. The purpose of this study was to elucidate the relationship between the cardiac diastolic function and cerebral white matter lesions in elderly patients with risk factors for atherosclerosis. The study subjects were 55 patients (75 +/- 7 years) with risk factors for atherosclerosis including hypertension, diabetes mellitus, and dyslipidemia. Patients with symptomatic cerebrovascular events were excluded from the study. Cerebral white matter lesions, which were defined as exhibiting high intensity regions on brain MRI, were evaluated with the degrees of periventricular hyperintensity (PVH) according to the Japanese Brain Dock Guidelines of 2003. Peak early diastolic mitral annular velocity (E' velocity) was measured by tissue Doppler echocardiography, and was used as a parameter of cardiac diastolic function. The mean value of E' velocity was decreased due to the cardiac diastolic dysfunction (5.2 +/- 1.4 cm/s). In addition, the E' velocity was inversely correlated with the degree of PVH (rho = -0.701, p < 0.001). Stepwise regression analysis showed that the decrease in the E' velocity (beta coefficient = -0.42, p < 0.001) and the presence of hypertension (beta coefficient = 0.31, p = 0.001) were independent determinants of the degree of PVH. Thus, cardiac diastolic dysfunction is correlated to the severity of cerebral white matter lesions, suggesting the cardio-cerebral connection in elderly patients with risk factors for atherosclerosis.     

血清脂蛋白(a)测定在脑梗死患者中的临床意义

为了探讨血清脂蛋白 (a) [Lp(a) ]在脑梗死形成中的作用 ,我们测定了 47例大血管性脑梗死 (LVD)和腔梗 (SVD)病人的血清Lp(a) ,发现与 18例正常对照组相比有显著差异 (P <0 .0 1) ,大血管性脑梗死与腔梗相比也有显著差异 (P <0 .0 1)。提示Lp(a)在大动脉粥样硬化性脑梗死中的作用比小动脉硬化性腔梗中的作用大。     

Magnetic susceptibility anisotropy of human brain in vivo and its molecular underpinnings

Frequency shift of gradient-echo MRI provides valuable information for assessing brain tissues. Recent studies suggest that the frequency and susceptibility contrast depend on white matter fiber orientation. However, the molecular underpinning of the orientation dependence is unclear. In this study, we investigated the orientation dependence of susceptibility of human brain in vivo and mouse brains ex vivo. The source of susceptibility anisotropy in white matter is likely to be myelin as evidenced by the loss of anisotropy in the dysmyelinating shiverer mouse brain. A biophysical model is developed to investigate the effect of the molecular susceptibility anisotropy of myelin components, especially myelin lipids, on the bulk anisotropy observed by MRI. This model provides a consistent interpretation of the orientation dependence of macroscopic magnetic susceptibility in normal mouse brain ex vivo and human brain in vivo and the microscopic origin of anisotropic susceptibility. It is predicted by the theoretical model and illustrated by the experimental data that the magnetic susceptibility of the white matter is least diamagnetic along the fiber direction. This relationship allows an efficient extraction of fiber orientation using susceptibility tensor imaging. These results suggest that anisotropy on the molecular level can be observed on the macroscopic level when the molecules are aligned in a highly ordered manner. Similar to the utilization of magnetic susceptibility anisotropy in elucidating molecular structures, imaging magnetic susceptibility anisotropy may also provide a useful tool for elucidating the microstructure of ordered biological tissues.     

CADASIL伴脑出血的临床和基因分析:3例报告

目的:评估常染色体显性遗传性皮质下梗死和白质脑病(CADASIL)伴脑出血(ICH)的临床表现、影像学和基因特征。方法:CADASIL伴ICH患者3例,在Pubmed数据库纳入另外25例有详细资料的患者,评估出血性CADASIL的临床表现、影像学特征和基因突变特点。结果:共纳入患者28例,男19例、女9例,平均年龄(54.2±13.4)岁。高血压病是最常见的危险因素(18例,64.3%),50%的患者曾接受抗栓治疗。10例患者以ICH为首发表现,最常见的出血部位是基底节和脑叶。11号外显子R544C位点是最常见的突变位点(46.2%)。18例患者(64.3%)发现数量不等的微出血灶。结论:CADASIL可发生ICH且可能是首发临床表现。严格控制高血压和谨慎使用抗血栓药可能有助于防止CADASIL患者发生ICH。