Yu Hua Fan

Cerebral Microbleeds as a Risk Factor for Subsequent Intracerebral Hemorrhages Among Patients With Acute Ischemic Stroke

Background and Purpose— Cerebral microbleeds (MBs) detected by gradient-echo MRI are considered evidence of advanced microangiopathy with potential for further bleeding. The goal of this study was to determine whether the presence of MBs is a risk factor for subsequent intracerebral hemorrhage among patients with acute ischemic stroke. Methods— We prospectively examined patients hospitalized with acute cerebral infarction with gradient-echo T2*-weighted MRI for the presence of MBs. We recorded demographics, medical history, and stroke severity. Patients were then followed up for the development of stroke, other vascular events, and death. Results— One hundred twenty-one consecutive patients with a mean age of 67.96±10.97 years were recruited. MBs were present in 43 patients (35.5%). During follow-up of 27.15±11.68 months, 16 patients had recurrent stroke. There was no difference between patients with or without MB for the development of ischemic stroke (5 and 6 respectively, P =0.841). However, 4 patients (9.3%) with MBs and 1 patient (1.3%) without an MB had intracerebral hemorrhage during follow-up (P =0.053). Of the 5 patients who developed subsequent intracerebral hemorrhages, 3 were treated with aspirin and 2 with anticoagulation. Two of the intracerebral hemorrhages occurred in the site where asymptomatic MBs were found at baseline. Conclusions— MBs appear to be a risk factor for subsequent intracerebral hemorrhage among patients with ischemic stroke in this small cohort of Chinese stroke patients. A large cohort study is required to confirm this observation.

Risk vs benefit of anti-thrombotic therapy in ischaemic stroke patients with cerebral microbleeds

BackgroundRetrospective studies suggested that cerebral microbleeds (MB) on magnetic resonance images (MRI) increase risk of intracerebral haemorrhage (ICH).ObjectiveTo compare the benefit of anti-thrombotic agents in stroke prevention (absolute risk reduction 2.49 –6 %) versus risk of ICH in ischaemic stroke patients with MB.Materials and methodsWe prospectively studied patients admitted consecutively for acute ischaemic stroke between 1999 and 2004. MB on MRI were documented. Primary end points were subsequent ICH, recurrent cerebral infarct (CI) and mortality.ResultsA total of 908 patients were recruited. MB were identified in 252 (27.8 %) patients. Mean follow-up period was 26.6 ± 15.4 months. Risk of subsequent ICH increased significantly with quantity of MB: 0.6 % (no MB), 1.9 % (1 MB), 4.6 % (2–4 MB) and 7.6 % (≥ 5 MB) (p < 0.001). There was also a significant increase in mortality from ICH: 0.6 %, 0.9 %, 1.5 % and 3.8 % respectively (p = 0.054). Rate of recurrent CI was 9.6 %, 5.6 %, 21.5 % and 15.2 % respectively (p = 0.226). Mortality from CI and myocardial infarction did not increased with quantity of MB. Survival analyses showed that age, presence of MB, mixed cortical-subcortical distribution of MB were independent predictors of subsequent ICH.ConclusionRisk and mortality of ICH increased with quantity of MB. As tendency to recurrent CI exceed that of ICH, anti-thrombotic agents are still warranted. However, in patients with ≥ 5 MB, the high risk and mortality of ICH seem to outweigh the modest benefit of antithrombotic agents. Extra precautions should be taken to minimize risk of ICH. Further studies in patients on Coumadin and assessment of functional outcome are warranted to support these preliminary findings.

Effect of White Matter Changes on Cognitive Impairment in Patients With Lacunar Infarcts

Background and Purpose— Cerebral white matter changes (WMC) and lacunar infarct are both believed to be consequence of small vessel disease. Whether the extent of WMC affect the type and degree of cognitive impairment in patients with lacunar infarct is not clear. The study was undertaken to determine if WMC influences cognition in patients with lacunar infarcts. Methods— We recruited consecutive patients who were admitted to the acute stroke unit because of acute lacunar infarcts, mainly documented by diffusion-weighted magnetic resonance imaging. WMC were measured qualitatively and quantitatively. Patients were divided into quartiles according to the distribution of the volume of WMC. Cognition was assessed 12 weeks after stroke by psychometric tests (Chinese version of Mini-Mental State Examination [MMSE], Alzheimer’s Disease Assessment Scale-cognition [ADAS-cog], Mattis Dementia Rating Scale-Initiation/ Perseveration subscale [MDRS I/P]) and was compared between patients with varying severity of WMC. Multivariate linear regression analysis was performed to find variables that influenced performance in the psychometric tests. Results— Among the 94 included patients with acute lacunar infarcts, those patients (n=25) within the highest quartile of WMC were older, had more lacunar infarcts, more severe stroke, and lower prestroke cognitive function compared with those with less WMC. In addition, their performances in psychometric tests were significantly more impaired. Multivariate linear regression analysis revealed that WMC significantly influenced performance in MDRS I/P. WMC did not independently influence performance in MMSE and ADAS-cog. Conclusions— Extent of WMC appears to be associated with executive dysfunction in stroke patients with lacunar infarcts. Further large prospective studies with extensive scales of executive function testing are required to confirm this issue.

Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease

BackgroundHyperhomocysteinemia is associated with cerebral small vessel disease (SVD). We examined the relationship between homocysteine and 1) volumetric measure of white matter change (WMC), 2) silent brain infarcts, 3) cerebral atrophy on MRI and 4) cognition on a consecutive cohort of patients with stroke associated with SVD.Subjects and methodsFifty–seven patients consecutively admitted to the Acute Stroke Unit in a university hospital due to stroke associated with SVD were recruited and assessed three months after the stroke. Non–fasting homocysteine was obtained. Using MRI, the number of infarcts, volume of WMC and cerebral atrophy were measured. General cognitive functions were assessed using the Mini Mental State Examination and Alzheimers disease Assessment Scale. Mattis Dementia Rating Scale – Initiation/Perseveration subset was used to assess executive cognitive functions.ResultsHyperhomocysteinemia (≥ 14.88 μmol/L) significantly accounted for the volume of WMC on MRI in a multivariate stepwise regression model (adjusted R2=0.058, p <0.05) after adjustment for age and folate level. Patients in the highest quartile of WMC volume had significantly higher levels of homocysteine than those in lowest quartile (p <0.001). No significant relationship was found between homocysteine and silent brain infarcts, cerebral atrophy and performance on psychometric tests.ConclusionHyperhomocysteinemia is associated with volumetric measure of WMC among patients with SVD. The role of homocysteine in the development of silent brain infarcts and cerebral atrophy as previously reported cannot be ascertained in this study. No direct relationship was found between homocysteine and cognitive functions.

Multiple acute cerebral infarcts on diffusion-weighted imaging and risk of recurrent stroke.

Multiple acute cerebral infarcts (MACIs) detected by diffusion-weighted imaging (DWI) may indicate an unstable source of thromboembolism. The authors studied 119 consecutive acute ischemic stroke patients within 24 hours of onset with DWI. MACIs were present in 20 patients (16.8%). During the follow-up period, there were 15 recurrent strokes, 3 acute coronary syndromes, and 5 deaths. MACI was the only significant independent predictor for vascular events and death (odd ratio [OR]] = 4.34; p = 0.001) and stroke recurrence (OR = 5.93; p = 0.001).

The age-related white matter changes scale correlates with cognitive impairment

Background and purpose:  Age‐related white matter changes (ARWMC) are closely associated with cognitive impairment. Although the ARWMC scale has been widely used to grade white matter changes (WMC) severity, the correlation between this scale and cognitive impairment has not been studied. We aimed to validate the ARWMC scale against cognition in patients with stroke.

Topographic patterns of small subcortical infarcts associated with MCA stenosis: a diffusion-weighted MRI study.

Background and Purpose. Small subcortical infarcts (SSI, maximum lesion diameter ≤2.0 cm) are usually considered as infarcts caused by small vessel disease. However, SSI can also be associated with large artery occlusive disease such as middle cerebral artery (MCA) stenosis. We performed a prospective study to investigate the relationship between MCA stenosis and SSI distribution and further to investigate the mechanism of SSI caused by MCA stenosis. Methods. Magnetic resonance angiography (MRA) and diffusion‐weighed MRI (DWI) of consecutive acute ischemic stroke patients with recent SSI were studied. The distribution of acute infarcts on DWI was categorized as cortical infarct (CI), border zone infarct (BI), or perforating artery infarct (PAI). Results. Totally, 93 cases were recruited, among which 12 had single SSI with MCA stenosis (group 1) and 26 patients had multiple SSI with MCA stenosis (group 2), while 55 patients without MCA stenosis had single SSI (group 3). For patients with single SSI and MCA stenosis, 6 had BI and 6 had PAI; for patients with multiple SSI and MCA stenosis, 25 had BI, 4 had PAI and 9 had CI (compared with group1: P= .001); for patients with single SSI but without MCA stenosis, 20 had BI and 35 had PAI (compared with group1: P= .58). Conclusion. Multiple acute infarcts along the border zone are the commonest pattern in small infarcts with MCA stenosis, especially among those with multiple acute infarcts. Our data suggest that hemodynamic compromise and artery‐to‐artery embolism may be both important factors for infarcts in patients with MCA stenosis.

Variability and Validity of a Simple Visual Rating Scale in Grading White Matter Changes on Magnetic Resonance Imaging

Background and Purpose. A new simple visual rating scale can be used in magnetic resonance imaging (MRI) to grade the severity of white matter changes (WMC). The authors sought to study the interobserver variability and the validity of this visual rating scale against a computer‐aided quantitative method in measuring WMC. Methods. The authors examined 220 magnetic resonance images from stroke‐free patients with traditional risk factors for atherosclerosis and middle cerebral artery stenosis who were participants in a clinical trial requiring MRI examination. The severity of WMC was graded from 0 (no WMC) to 3 (severe WMC). For the quantitative assessment of WMC, the volume of WMC were measured with a computer‐aided, automated segmentation method. The interobserver variability was also determined. Results. The mean volumes were significantly different among the different groups, which were scored 1, 2, and 3 (1324.59, 6475.48, and 25,440.05 mm3, respectively; 1‐way analysis of variance, P < .001). Interobserver variability for grading WMC was good in different locations of the brain. Excellent results were found in the frontal lobe (κ=0.829) and the parietal‐occipital lobe (κ=0.646), whereas poor results were found in the basal ganglia (κ=0.391). There was perfect agreement between the 2 observers in 89.1% for the frontallobe and 77.0% for the parietal‐occipital lobe. Conclusions. The results suggest that this simple visual rating scale is a valid and reliable method for grading WMC in the lobar region but not in the basal ganglion.

Different distribution patterns of cerebral microbleeds in acute ischemic stroke patients with and without hypertension.

Background: Cerebral microbleeds (CMBs) were found in patients with and without hypertension. We aimed to investigate different distribution patterns of CMBs in patients with and without hypertension. Methods: We examined acute ischemic stroke patients using a standardized MRI protocol that included T1, T2 and gradient-echo T2*. Clinical and imaging characteristics were collected from all patients. Results: Among 998 patients, CMBs were detected in 273 patients (27.3%). Of these, 62 did not have hypertension (22.7%). The incidence of CMBs among patients without hypertension (62/335, 18.5%) was lower than among those with hypertension (211/663, 31.8%; p < 0.01). The location of CMBs in patients without hypertension was limited to the cortical-subcortical (CSC) region in 40.3% (25/62) compared to 20.4% of those with hypertension (43/211; p = 0.01). No significant difference was found between CMB locations within the intra-CSC region in both groups. The severity of white matter changes and systolic blood pressure on admission were found to be independent predictors for CMBs in patients without hypertension. Conclusions: CMBs in patients with and without hypertension have different distribution patterns and may have a different pathogenesis. Blood pressure controlling is important in both groups because systolic blood pressure is an independent predictor of CMBs in patients without hypertension.