Dotlike Hemosiderin Spots Are Associated With Past Hemorrhagic Strokes in Patients With Lacunar Infarcts

BACKGROUND AND PURPOSE: Dotlike hemosiderin spots ongradient-echo T2(*)-weighted magnetic resonance imaging of the brain have been histologically diagnosed as old microbleeds associated with small vessel disease (SVD). The authors hypothesize that the presence of many dotHSs may be correlated with the fragility of small vessels and the recurrence of SVD, including lacunar infarction and deep intracerebral hemorrhage (ICH). METHODS: To investigate how dotHSs are related to past history of SVD, the number of subcortical or deep dotHSs was investigated in 146 patients with lacunar infarctions (95 men, 51 women, age 38 to 90 [66.6+/-9.4] years). They were divided into 2 subgroups according to history of deep ICHs or lacunar infarctions. The odds ratio (OR) for past history was estimated from logistic regression analyses with the number of subcortical or deep dotHSs as well as other factors. RESULTS: Of 146 patients with lacunar infarctions, 11 had past symptomatic ICHs and 19 had past symptomatic lacunar infarctions. An elevated rate of history of ICH was found for lacunar infarction patients with many deep dotHSs (>or=3; OR, 9.1; 95% confidence interval, 1.6-51, P=.015). However, history of lacunar infarction was not significantly associated with the number of subcortical or deep dotHSs. CONCLUSIONS: Our findings suggest that many deep dotHSs on T2(*)-weighted magnetic resonance imaging may be correlated with deep ICH-lacunar infarction type of SVD recurrence but not lacunar infarction-lacunar infarction type.     

Dot-Like Hemosiderin Deposition on T2*-Weighted MR Imaging Associated with Nonhypertensive Intracerebral Hemorrhage

BACKGROUND AND PURPOSE: Microangiopathy, a disorder often related to hypertension, is an important cause of deep intracerebral hematoma (ICH). The microangiopathy is associated with dot-like low-intensity spots (a dot-like hemosiderin spot: dotHS) on gradient-echo T2*-weighted MR images that have been histologically diagnosed as old microbleeds. The locations of dotHS are consistent with deep ICH. METHODS: To investigate how dotHS or other risk factors contribute to nonhypertensive deep ICH, the number and location of dotHSs, as well as other risk factors were examined in 213 deep ICH patients (106 males, 107 females, age: 37-94 (65.8 +/- 11.2) years) consecutively admitted to Hakodate Municipal Hospital. Patients were divided into two subgroups according to the presence or absence of hypertension. DotHSs were also divided into deep and subcortical dotHS and investigated independently. Odds ratios (ORs) were estimated from logistic regression analyses. Furthermore, nonhypertensive ICH patients were compared with nonhypertensive healthy volunteers matched for age and sex. RESULTS: No risk factors were identified in the 31 nonhypertensive deep ICH patients that differed from those found in the 182 hypertensive deep ICH patients. Deep dotHS > or = 1 (OR: 25.5; 95% CI: 4.76-137; P = .0002), subcortical dotHS > or = 1 (OR: 9.0; 95% CI: 1.79-44.9; P = .046), diabetes mellitus (OR: 9.0; 95% CI: 1.53-52.3; P = .015), and smoking (OR, 9.6; 95% CI; 1.8-49.8, P = .007) significantly elevated the risk of nonhypertensive ICH, compared to the healthy volunteers. CONCLUSIONS: Our findings suggest that deep and subcortical dotHSs may be risk factors for the development of non-hypertensive deep ICH.     

Dynamics of Dot-Like Hemosiderin Spots on T2*-Weighted MRIs Associated with Stroke Recurrence

BACKGROUND AND PURPOSE: Dot-like low-intensity spots (dot-like hemosiderin spots: dotHSs) on gradient echo T2*-weighted (-w) brain magnetic resonance imaging (MRIs) are frequently associated with cerebral small vessel disease (SVD), including deep intracerebral hemorrhages and lacunar infarctions. This study investigated how numbers of newly appeared dotHSs contribute to recurrent SVD. METHODs: We prospectively analyzed numbers of newly appeared dotHSs in 12 patients with prior SVD (8 males, 4 females; mean 67.6 +/- 10.7 years old) readmitted with recurring SVD between October 2001 and March 2003. Numbers of appeared dotHSs per year were counted on T2*-w MRI scans after SVD recurrence and compared to previous MRIs. Seventy-one outpatients (35 males, 36 females; mean 64.3 +/- 9.6 years old) with histories of intracerebral hemorrhages (ICH) that came to the hospital during the study period served as controls. The hazard ratio (HR) for recurrence was estimated from a multivariate logistic regression model, using the number of appeared dotHSs (per year) and other risk factors. RESULTS: Multivariate analyses revealed that an elevated rate of recurrence was found in patients with substantial numbers of appeared dotHSs (>or=5/year) (HR, 7.34; P= 0.0008). We also analyzed factors associated with the numbers of appeared dotHSs. A number of appeared dotHSs (>or=5/year) was significantly and independently associated with the initial number of dotHSs (>or=10) on T2*-w MRIs following the first SVD (HR, 18.6; P= 0.0001). CONCLUSIONS: Though a small sample size limited the power of our analyses, our findings suggest that a number of newly appeared dotHSs may be associated with SVD recurrence.     

Risk factor for cerebral hemorrhage for the patient with lacunar infarction: investigation of 5 cases associated with both of symptomatic hemorrhagic and ischemic strokes]

BACKGROUND AND PURPOSE: Microangiopathy is regarded as an important cause of intracerebral hematoma(ICH) and lacunar infarction. Dot-like low intensity spots on T2-weighted echo planar image(EPI) have been regarded as hemosiderin deposit associated with microangiopathy. However, clinical significance of dot-like hemosiderin spot(dotHS) is still debated. Therefore, we analyzed the number of dotHS on EPI of symptomatic lacunar infarction associated with ICH. METHODS: To investigate how the dotHS or risk factors contributed to hemorrhagic strokes for patients with lacunar infarction, the number of dotHS and various risk factors were made a comparison between 20 cases with symptomatic lacunar infarctions(lacunar group) and 5 cases with both symptomatic lacunar infarction and symptomatic ICH(complicated group). In addition to EPI, fluid attenuated inversion recovery image, and T1- and T2-weighted MR images were performed for differential diagnosis of dot HS. RESULTS: EPI demonstrated that asymptomatic ICH was significantly more frequent in complicated group (60%) than in lacunar group(10%), and dotHS were significantly more frequent in complicated group(100%) than in lacunar group(50%). The number of dotHS of complicated group was 14.6 +/- 4.3, which was significantly larger than that of lacunar group(4.1 +/- 9.2). No significant difference between two groups were founded in other risk factors including hypertension, diabetes mellitus, hyperlipidemia, and smoking. CONCLUSION: These results suggested that dotHS was one of the risk factors for ICH for patients with symptomatic lacunar infarction, and an increasing number of dotHS was one of the predictive factors of symptomatic and/or asymptomatic ICH.     

Hematoma Size in Deep Intracerebral Hemorrhage and its Correlation with Dot-Like Hemosiderin Spots on Gradient Echo T2*-Weighted MRI

BACKGROUND AND PURPOSE: Dot-like low intensity spots (dot-like hemosiderin spots: dotHSs) on gradient echo T2*-weighted MRI have been histologically diagnosed to represent old cerebral microbleeds associated with microangiopathies. They have also been correlated to the fragility of small vessels and the tendency to bleed. Therefore, a substantial number of dotHSs might be associated with a large-sized, deep intracerebral hematoma (ICH). On the other hand, dotHSs may reflect old microbleeds that did not enlarge to symptomatic size. METHODS: To investigate how dotHSs are related to the size (maximal diameter) of primary deep ICH, we analyzed the diameter and the number of dotHSs in 151 patients with deep ICH not associated with subarachnoid hemorrhage or intraventricular hemorrhage (75 males and 76 females, age ranged from 37 to 90 [65.7 +/- 11.3 years old] who were consecutively admitted to Hakodate Municipal Hospital. The hazard ratio (HR) for a maximal diameter of deep ICH < or =2 cm was estimated, using the number of dotHSs and risk factors for stroke. RESULTS: The number of dotHSs associated with the diameter < or =2 cm was 9.2 +/- 11.5, significantly larger than that with the diameter > or =2 cm (4.7 +/- 7.0, P= .012). Multivariate analysis revealed that a maximal diameter of deep ICH of < or =2 cm was found in patients with dotHS (HR, 3.7; 95% confidence interval [CI], 1.4-10.1; P= .009). CONCLUSION: Though small sample size limited the power of our analyses, these findings suggest that the number of dotHSs may be associated with a small diameter of deep ICH.     

Association of Left Ventricular Hypertrophy and Atrial Fibrillation with Hemorrhagic Evolution of Small Vessel Disease

ObjectivesCerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood.Materials and MethodsThis retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography.ResultsIn multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18–0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated.ConclusionsMost SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).     

急性腔隙性脑梗死患者脑白质疏松磁共振影像分层研究

目的 通过分析腔隙性脑梗死患者脑白质疏松磁共振成像（magnetic resonance imaging,MRI）特点并结合脑白质血液供应,探讨影像学分层的临床价值。 方法 连续选取北京天坛医院住院的合并脑白质疏松的急性腔隙性脑梗死患者61例,按其脑白质疏松部位不同分为3组（皮层下组、室旁组和混合组）,按其脑白质疏松的严重程度分为3级,分析各组患者临床一般资料的特点及各组、各级脑白质疏松MRI特点。 结果 皮层下组患者年龄较室旁组及混合组小,其差异具有统计学意义（P<0.05）。腔隙性脑梗死患者中,深部、室旁白质疏松及深部合并室旁白质疏松共占88.50%,而皮层下白质疏松占11.50%。深部/室旁白质疏松以2级常见,皮层下白质疏松以1级最常见。 结论 腔隙性脑梗死患者脑白质疏松随年龄增加而加重,而且其脑白质疏松多发生在深部和或室旁白质。     

Increased brachial-ankle pulse wave velocity is independently associated with risk of cerebral ischemic small vessel disease in elderly hypertensive patients

OBJECTIVE: Increased arterial stiffness is an independent predictor of cardiovascular diseases in hypertensive patients. Hypertension and aging can cause similar damage to small vessel walls. The objective of this study was to determine relationship between arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) and the risk of cerebral small vessel disease (SVD) in elderly people with hypertension. METHODS: We studied 196 elderly subjects with hypertension (> or =50 years of age) who had neither large vessel stroke nor cardiac embolism. These patients were divided into three groups based on the results of brain MRI: (1) those with first-ever small vessel stroke; (2) those with asymptomatic subcortical ischemia; and (3) a control group with hypertension. RESULTS: The baPWV was significantly increased in the patients with first-ever small vessel stroke or asymptomatic subcortical infarction when compared to the control group, after adjusting for systolic blood pressure (SBP), pulse pressure (PP), and hs-CRP (p=0.005). Among subjects with SVD on MRI, the number of lacunar infarcts (LIs)> or =5 was significantly related to a higher baPWV (p=0.02). The relationship between the severity of periventricular white matter hyperintensities (PWMH) and the degree of baPWV became insignificant after adjustment for age. CONCLUSION: Increased baPWV was significantly associated with the risk of SVD in elderly persons with hypertension. Therefore, the measurement of baPWV could be used to predict SVD.     

Microvascular retinal abnormalities in acute intracerebral haemorrhage and lacunar infarction

Background

Retinal microvascular changes have been previously associated with cerebral MRI markers of small vessel disease (SVD). Whether retinal changes differ between patient with intracerebral haemorrhage (ICH) and patients with lacunar infarction (LI) caused by small vessel disease has been poorly investigated.

Objective

The study aims to compare the frequency of retinal changes between patients with LI and patients with ICH at the acute stage of stroke-related SVD.

Methods

Microvascular wall signs (arteriolar occlusion, arteriovenous nicking, focal arterial narrowing) and retinopathy lesions (microanevrysms, cotton wool spots, retinal haemorrhages, hard exudates) were assessed by retinography up to three months after stroke onset.

Results

Forty-eight non-diabetic patients with acute stroke-related to SVD (26 LI, 22 ICH) were recruited prospectively in the study. Retinal wall signs (arteriovenous nicking, and focal arterial narrowing) were found in more than three quarters of subjects and most often bilaterally in both groups. Retinopathy lesions (cotton wool spots, retinal haemorrhages) were found more frequently in ICH patients than in LI patients (22.2% vs. 15.4%, 50% vs. 34% respectively, P > 0.005). The frequency of bilateral cotton wool spots and of bilateral retinal haemorrhages was significantly higher in ICH patients than in LI patients (12.5% vs. 0%, P = 0.012, 41.2% vs. 7.7%, P = 0.029 respectively).

Conclusion

These results confirm the high frequency of microvascular alterations in patients with hypertension-related SVD leading to LI or ICH and suggest that retinal tissue alterations are more frequent in ICH than in LI. Further investigations are needed to investigate the mechanisms underlying this difference.     

Correlation study between small vessel disease and early neurological deterioration in patients with mild/moderate acute ischemic stroke

Aims: Cerebral small vessel disease (SVD) refers to a group of pathological processes that affect small arteries, arterioles, venules, and capillaries of the brain. We hypothesized that imaging markers of SVD could be associated with neurological deterioration during acute phase of mild/moderate ischemic stroke. Methods: We performed a prospective cohort with 687 consecutive patients with acute ischemic stroke and also with admission NIHSS score below 12 points. Imaging markers of SVD include silent lacunar infarction, deep cerebral microbleeds (CMBs), brain atrophy, periventricular and semiovale white matter hyperintensities, basal ganglia and semiovale enlarged perivascular spaces as well as SVD burden rating scale, which were evaluated and calculated, respectively. Early neurology deterioration (END) was defined as an increment of NIHSS score ≥2 points in the first 72 h after admission. Results: None of these imaging markers and rating scale of SVD significantly correlated with END after adjusted for major confounders. Post hoc analysis indicated similar negative results in different age, TOAST classification and infarction location subgroups. Only silent infarction (OR 2.42, 95%CI 1.33–5.10) and deep CMBs (OR 2.10, 95%CI 1.08–3.72) seemed to be predictors for END in female patients. However, due to the increased type I error in multiple comparisons, these relationships should not be regarded as statistically significant. Conclusion: In patients with mild/moderate acute ischemic stroke, imaging markers of SVD did not correlate with END.     

Is 15 mm size criterion for lacunar infarction still valid? A study on strictly subcortical middle cerebral artery territory infarction using diffusion-weighted MRI

BACKGROUND AND PURPOSE: The 'lacunar hypothesis' has been challenged, since small (diameter <15 mm) subcortical infarcts can be produced by middle cerebral artery disease (MCAD) or cardioembolism (CE), while a larger infarct can occur without evidence of MCAD or CE. We sought to assess whether the lacunar hypothesis based on size is still valid. METHODS: We studied 118 patients who were admitted within 72 h after stroke onset and had acute deep subcortical MCA territory infarcts detected by diffusion-weighted MRI, and who had undergone angiography (mostly MR angiography). Stroke mechanisms were arbitrarily categorized regardless of lesion size: (1) MCAD when there was a corresponding MCA lesion; (2) internal carotid artery disease (ICAD) when there was a significant (>50%) ipsilateral ICAD; (3) CE when there was emboligenic heart disease without MCAD or ICAD, and (4) small vessel disease (SVD) when there was neither CE nor MCAD. SVD was further divided into definite SVD (dSVD, longest diameter <15 mm) or probable SVD (pSVD, longest diameter > or =15 mm). RESULTS: Seventy-three patients (62%) had SVD, of which 38 (32%) had pSVD and 35 (30%) dSVD. Thirty-three patients (28%) had MCAD, five (4%) CE, and seven (6%) ICAD. The infarct diameter in MCAD was not larger than in SVD (p = 0.35), and there was no difference in clinical features or risk factors between MCAD and SVD, or between pSVD and dSVD. CE was distinguished from SVD by its larger size and cortical symptoms. CONCLUSIONS: There are no clinical and lesion-size differences between MCAD and SVD, suggesting that there seems to be no rationale for the 15 mm size criterion for lacunar or small-vessel infarction.     

缺血性脑白质疏松症危险因素的临床研究

目的基于头部MRI检查,通过分析伴发和不伴发脑白质疏松症(Leukoaraiosis,LA)的腔隙性脑梗死患者常见临床危险因素之间的差异,探讨LA可能的发病机制。方法经1.5TMRI检查证实的腔隙性脑梗死患者386例,分为单纯腔隙性脑梗死组(Isolated lacunar infarction,LI组)和伴发脑白质疏松症组(Lacunar infarctionwith leukoaraiosis,LA组),对两组的临床资料进行回顾性分析,详细记录两组的年龄、性别,有无高血压、2型糖尿病、冠心病、心房颤动、颈动脉粥样硬化、脑动脉硬化、高甘油三酯血症、高胆固醇血症、高尿酸血症和贫血等病史。结果LI组212例(54.9%),年龄32~91岁,平均61.05±11.95岁,LA组174例(45.1%),年龄38~98岁,平均68.52±9.59岁。在单因素分析中,LA组高龄、高血压、脑动脉硬化和2型糖尿病的发生率与LI组相比均有高度显著性差异(P<0.01)。在多因素Logistic回归分析中,脑动脉硬化、高血压、高龄为LA独立的危险因素,2型糖尿病不是独立危险因素。结论脑动脉硬化、高血压、高龄与LA的发病机制有着...     

Heterogeneity of single small subcortical infarction can be reflected in lesion location

Single small subcortical infarction (SSSI), also called lacunar infarction, has been regarded as a different entity with distinct pathogenesis, either lipohyalinosis and fibrinoid degeneration or atherosclerosis. The aim of our study is to identify the heterogeneity of SSSI by comparing the characteristics and imaging features according to lesion location. We retrospectively studied 203 patients with acute SSSIs (diameter ≤20 mm) demonstrated by diffusion-weighted imaging in the perforator territory of the middle cerebral artery, basilar artery, or vertebral artery. We divided the 203 patients according to the lesion location in relation to the parent artery into a distal infarction (dSSSI) group and a proximal infarction (pSSSI) group. We evaluated and compared the imaging features and clinical characteristics between the groups. The evaluated characteristics included indicators of lipohyalinosis [leukoaraiosis and silent brain infarction (SBI)], indicators of atherosclerosis [parent artery disease (PAD) and atherosclerosis of other cerebral arteries (AOCA)], lesion size, and some vascular risk factors. Between the two groups, the pSSSI group had larger lesion size, higher prevalence of PAD and AOCA, and greater frequency of diabetes mellitus, while the dSSSI group had smaller lesion size, higher prevalence of leukoaraiosis and SBI, and lower serum folic acid. Diversity of the SSSIs in imaging features and clinical characteristics according to lesion location suggests the heterogeneity of SSSIs; distal infarction is closely associated with lipohyalinosis, while proximal infarction seems to be related with atherosclerosis.     

Impaired cerebrovascular reactivity as a risk marker for first-ever lacunar infarction: A case-control study.

BACKGROUND AND PURPOSE: Functional assessment of small arteries and arterioles could provide valuable information regarding the extent of diffuse arteriolosclerosis in patients with small-vessel disease. Therefore we attempted to clarify the role of cerebrovascular reactivity (CVR) as a risk marker for first-ever symptomatic lacunar infarction. METHODS: Forty-six patients with lacunar infarction and 46 sex- and age-matched control subjects were prospectively evaluated. Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. CVR was examined by calculating the percent increase in mean flow velocity occurring after 15 mg/kg acetazolamide administration (Diamox test). RESULTS: CVR was significantly (P<0.0001, Student's t test) lower in cases (50.0+/-12. 7%) as compared with control subjects (65.2+/-12.4%). A multiple logistic regression analysis identified male sex (odds ratio [OR] 2. 3, P=0.02), age (OR 3.6, P<0.005), and the presence of lacunar infarction on magnetic resonance imaging (OR 5.3, P<0.001) as significant and independent factors associated with a reduction of CVR. Moreover, a cut-point of 55.6% (sensitivity 67%, specificity 82%) was established as the threshold value for distinguishing between pathological and normal CVR. CVR was significantly (P=0.02) lower in patients with multiple (46.38+/-12.6%) than with single (54. 83+/-11.58%) lacunar infarction. In addition, a trend of negative correlation was found between CVR and the number of lacunar infarctions (r=-0.26, P=0.08). In the multiple logistic model, history of hypertension (OR 7.24; 95% confidence interval 2.95 to 17. 79) and CVR (OR 0.8; 95% confidence interval 0.81 to 0.93) emerge as significant and independent predictors of first-ever lacunar infarction. CONCLUSIONS: These data suggest that impaired CVR is a risk marker for first-ever lacunar infarction.     

脑梗死后出血转化与脑微出血及其它危险因素的相关性研究

目的 研究急性脑梗死后出血转化(HT)与脑微出血(CMB)及其它危险因素的相关性,并探讨其预防方法。 方法 选择自2009年6月至2010年12月在广州中医药大学中山附属医院及南方医科大学附属南方医院神经内科连续住院、资料完整的急性脑梗死患者348例,登记患者的基线资料,行MRIGRE-T2*WI扫描,检查CMB的患病率和HT的发生率。以HT为因变量,其它因素为自变量,进行Logistic回归分析以探索HT的影响因素。 结果 急性脑梗死348例患者中发生HT 35例(10.06％),其中大动脉粥样硬化性脑梗死213例患者中发生HT 19例(8.92％),心源性脑栓塞28例患者中发生HT11例(39.29％),不明病因脑梗死19例患者中发生HT5例(26.32％),腔隙性脑梗死88例患者中无HT发生。Logistic回归分析显示,HT的危险因素为心源性脑栓塞(OR=5.338,95％CI:1.926～14.796,P=.001)、不明病因脑梗死(OR=6.843,95％CI:1.848～25.346,P=0.004)及NIHSS评分(OR=1.181,95％CI：1.085～1.284,P=0.000),低密度脂蛋白为保护性因素(OR=0.637,95％CI:0.414～0.979,P=0.040)。 结论 急性脑梗死后HT在不同亚型脑梗死中发病率不同,心源性脑栓塞中HT发病率最高。HT的危险因素为心源性脑栓塞、不明病因脑梗死及NIHSS评分,低密度脂蛋白为HT的保护性因素,CMB与HT没有明显相关性。     

Clinical classification for lacunar infarct. An investigation of 130 consecutive cases of lacunar infarctions]

A lacunar infarct is defined as the occlusion of a single perforating artery. Certain researchers have proposed that patients with lacunar infarcts can be classified into two clinically distinct entities: patients with a single, symptomatic lacunar infarct, and patients with multiple lacunar infarcts together with hypertension and leukoaraiosis. The present study attempted to delineate the characteristics of lacunar infarcts and evaluate the validity of the aforementioned hypothesis. A total of 130 consecutive patients with first-time symptomatic lacunar infarct were studied. All patients were dichotomized into two groups according to two different kinds of models as follows. Model-1: patients with a single lacune and patients with multiple lacunes; and Model-2: patients with large lacune and patients with small lacune. Associated factors for the multiple lacune group compared with the single lacune group as well as the large lacune group compared with the small lacune group, were analyzed by multivariate logistic regression analysis. Associated factors included age, sex, hypertension, diabetes mellitus, dyslipidemia, smoking, extracranial and intra-cranial vascular lesions, extent of lacunes and white matter lesions, progression status and blood pressure in the acute stage, and coagulation markers such as fibrinogen, thrombin-antithrombin complex, D-dimer, beta-thromboglobulin, platelet factor 4. Results for Model-1: hypertension (age-and sex-adjusted OR: 2.58, p = 0.017) and elevated systolic blood pressure (>160mmHg for the mean value during the first post-ictal week; OR: 2.55, p = 0.016) were significantly associated with the multiple lacune group. Large lacunes (>10mm in diameter) were negatively associated with the multiple lacune group (OR: 0.38, p = 0.017). Association between confluent white matter lesions and the multiple lacune group approached significance (OR: 2.16, p = 0.056). Results for Model-2: female sex (OR: 0.39, p = 0.021), mild stenosis of intracranial and extracranial arteries (<25%) (intracranial; OR: 5.42, p = 0.0042, extracranial; OR: 3.30, p = 0.016), progressing stroke (OR: 6.77, p<0.0001), and high levels of TAT (>3ng/ml) (OR: 2.80, p = 0.039) were significantly associated with the large lacune group. Multiple lacunes (OR: 0.38, p = 0.016) and confluent white matter lesions (OR: 0.28, p = 0.007) exhibited a significant negative association with the large lacune group. In conclusion, underlying vasculopathy in the presence of multiple lacunes may correspond to lipohyalinosis resulting from hypertension. Moreover, large lacune may correspond to microatheroma at the orifice of penetrating arteries.     

The renin-angiotensin-aldosterone system in cerebral small vessel disease

INTRODUCTION: Cerebral small vessel disease (SVD) appears on magnetic resonance imaging (MRI) as leukoaraiosis (LA), état criblé (EC), and multiple lacunar infarctions (MLI). Although the pathophysiology of SVD is poorly understood, there is evidence of a genetic contribution. We sought to analyze the influence of the renin-angiotensin-aldosterone system (RAAS) on SVD in symptomatic patients from the Génétique de l'Infarctus Cérébral (GENIC) study, including RAAS polymorphisms and circulating angiotensin converting enzyme (ACE). METHODS: Caucasian patients (n=510) with acute brain infarction (BI) were recruited and MRIs were evaluated for SVD, including LA, EC, and MLI. We considered ACE levels and several polymorphisms, including ACE, angiotensinogen, aldosterone synthase CYP11B2, and angiotensin II receptor type I. RESULTS: Among the polymorphisms, there were marginal negative associations between aldosterone synthase CYP11B2 -344C against severe EC (adjusted OR, 0.57; 95% CI, 0.31-1.05) and severe LA (adjusted OR, 0.54; 95% CI, 0.30-0.95), both considering -344C dominant. In addition, the frequency of -344C decreased with the number of SVD abnormalities (p=0.016). Mean plasma ACE was elevated in patients with MLI, but not with LA or EC. The risk of MLI increased gradually with increasing plasma ACE (adjusted OR, 1.25; 95% CI, 1.02-1.53). CONCLUSIONS: This exploratory study found no strong evidence for RAAS involvement in severe SVD in this population. The whole spectrum of SVD, including EC, MLI, and LA, can be considered as phenotypes for genetic studies.     

White matter lesions and season of birth of patients with bipolar affective disorder

OBJECTIVE: It is established that patients with bipolar disorder have an excess of births in winter or early spring. The authors investigated a link between season of birth and white matter lesions with magnetic resonance imaging (MRI). METHOD: T(2)-weighted and proton density MRI scans were examined for 79 patients with bipolar disorder (DSM-IV) for the presence of deep subcortical and periventricular white matter lesions. The birth seasons of patients with white matter lesions were compared with those of the general population. RESULTS: Thirteen subjects exhibited deep subcortical white matter lesions, of whom nine (69.2%) were born in the winter months (January to March). Seven of these patients remained symptomatic, despite adequate treatment for more than 2 years. CONCLUSIONS: Birth season, illness outcome, and deep subcortical white matter lesions appear to be closely linked. Deep subcortical white matter lesions may be a marker of a toxic or infective insult in utero.     

Risk factor profile of cerebral small vessel disease and its subtypes

Background

The mechanisms of cerebral small vessel disease (SVD) are unclear. Both atherosclerosis and a non‐atherosclerotic diffuse arteriopathy have been reported pathologically. Two pathological and radiological subtypes have been suggested: localised atherosclerotic disease in larger perforating arteries causing larger lacunar infarcts without leukoaraiosis, and diffuse disease in smaller arterioles causing multiple smaller lacunar infarcts with leukoaraiosis. If atherosclerosis were important in SVD as a whole or in one particular subtype, one would expect the risk factor profile to be similar to that of cerebral large vessel disease (LVD).

Methods

Risk factor profiles were compared in Caucasian stroke patients with SVD (n = 414), LVD (n = 471) and 734 stroke‐free Caucasian population controls. Patients with SVD were subdivided according to the presence or absence of confluent leukoaraiosis, into isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA).

Results

Hypertension was commoner in SVD than LVD (odds ratio (OR) 3.43 (2.32 to 5.07); p<0.001) whereas hypercholesterolaemia (OR 0.34 (0.24 to 0.48); p<0.001), smoking (OR 0.63 (0.44 to 0.91); p = 0.012), myocardial infarction (OR 0.35 (0.20 to 0.59); p<0.001) and peripheral vascular disease (OR 0.32 (0.20 to 0.50); p<0.001) were commoner in LVD. Among SVD patients, age (OR 1.11 (1.09 to 1.14); p<0.001) and hypertension (OR 3.32 (1.56 to 7.07); p = 0.002) were associated with ILA and hypercholesterolaemia (OR 0.45 (0.28 to 0.74); p = 0.002), diabetes (OR 0.42 (0.21 to 0.84); p = 0.014) and myocardial infarction (OR 0.18 (0.06 to 0.52); p = 0.001) with ILI.

Conclusion

SVD has a different risk factor profile from the typical atherosclerotic profile found in LVD, with hypertension being important. There are differences in the risk factor profile between the SVD subtypes; the association of ILI with hypercholesterolaemia, diabetes and myocardial infarction may be consistent with a more atherosclerotic aetiology.The pathogenesis of cerebral small vessel disease (SVD) is incompletely understood. Hypertension is a major risk factor but fails to account for all of the risk.¹ Neuropathological data, particularly soon after a lacunar stroke, are limited because of low case fatality. Pathological vascular abnormalities reported include both a diffuse arteriopathy of the perforating arteries with hyaline deposition, an appearance referred to as lipohyalinosis, and microatheroma.²Based on pathological studies, it has been suggested that there may be two types of SVD that can be differentiated on brain imaging.³ The first involves atheroma at the origins or proximal portions of the larger (200–800 μm diameter) perforating arteries. This is associated with single or a few larger lacunar infarcts without leukoaraiosis. The second involves a diffuse arteriopathy of the smaller perforating arteries, 40–200 μm in diameter, resulting in multiple smaller lacunar infarcts with leukoaraiosis. Endothelial dysfunction may play an important role in the pathogenesis of this SVD subtype. A reduction in white matter cerebral blood flow⁴ and autoregulation,⁵ both dependent on nitric oxide released from the endothelium, has been reported in lacunar infarction with leukoaraiosis. Furthermore, circulating markers of endothelial activation are elevated in lacunar infarction with leukoaraiosis,⁶ and specific associations have been reported with homocysteine, which is toxic to the endothelium.⁷One way of obtaining information on pathogenesis is to compare the risk factor profile between different stroke subtypes. If atherosclerosis plays an important role in SVD, one would expect the risk factor profile to be similar to that seen in patients with large artery atherosclerotic stroke. Furthermore, as suggested by pathological studies in SVD, if atherosclerosis is more important in lacunar infarction without leukoaraiosis compared with lacunar infarction with leukoaraiosis, one might expect differences in the risk factor profile between the two proposed subtypes of lacunar stroke, with a more atherosclerotic profile seen in lacunar infarction without leukoaraiosis.A meta‐analysis of four community based clinical studies demonstrated that there are differences in the risk factor profile between ischaemic stroke subtypes.⁸ Large vessel disease (LVD) stroke was associated with male sex, smoking and raised cholesterol, while SVD was associated with hypertension. However, there were several limitations to these studies, including small SVD and LVD sample sizes, lack of MRI imaging in all studies, variability in risk factor definition between studies, inclusion of hypertension and diabetes in the SVD definition by some studies which may result in biased risk factor–stroke subtype associations, and failure to prospectively subtype patients using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria in one large stroke cohort used in the meta‐analysis. In this same cohort, a significant proportion of patients did not have carotid imaging. It has been shown that subtyping based on clinical presentation alone without imaging of the large arteries cannot reliably distinguish SVD from LVD.⁹ Studies have also suggested there may be differences in the risk factor profile between the two subtypes of cerebral SVD but data are limited and most studies have been small,^{3,10,11,12,13,14} and this was not covered in the meta‐analysis above.In this study, we used a large well‐phenotyped group of patients with SVD and LVD to determine differences in the risk factor profile between the two groups. All patients had brain imaging and imaging of the extracranial cerebral arteries. In addition, differences in the risk factor profile between the two proposed subtypes of SVD were determined.