Jay Chol Choi

Intracerebral hemorrhages in CADASIL

Intracerebral hemorrhage (ICH) has been described only sporadically for patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, cerebral microbleeds (CMBs) were found in 31% to 69% of the patients with CADASIL, and this predicted an increased risk of ICH. In this study, the authors found that 25% of the symptomatic patients with CADASIL had ICHs, and their development was closely related to the number of CMBs.

Case Characteristics, Hyperacute Treatment, and Outcome Information from the Clinical Research Center for Stroke-Fifth Division Registry in South Korea

Characteristics of stroke cases, acute stroke care, and outcomes after stroke differ according to geographical and cultural background. To provide epidemiological and clinical data on stroke care in South Korea, we analyzed a prospective multicenter clinical stroke registry, the Clinical Research Center for Stroke-Fifth Division (CRCS-5). Patients were 58% male with a mean age of 67.2±12.9 years and median National Institutes of Health Stroke Scale score of 3 [1-8] points. Over the 6 years of operation, temporal trends were documented including increasing utilization of recanalization treatment with shorter onset-to-arrival delay and decremental length of stay. Acute recanalization treatment was performed in 12.7% of cases with endovascular treatment utilized in 36%, but the proportion of endovascular recanalization varied across centers. Door-to-IV alteplase delay had a median of 45 [33-68] min. The rate of symptomatic hemorrhagic transformation (HT) was 7%, and that of any HT was 27% among recanalization-treated cases. Early neurological deterioration occurred in 15% of cases and were associated with longer length of stay and poorer 3-month outcomes. The proportion of mRS scores of 0-1 was 42% on discharge, 50% at 3 months, and 55% at 1 year after the index stroke. Recurrent stroke up to 1 year occurred in 4.5% of patients; the rate was higher among older individuals and those with neurologically severe deficits. The above findings will be compared with other Asian and US registry data in this article.

MRI-based Algorithm for Acute Ischemic Stroke Subtype Classification

Background and Purpose In order to improve inter-rater reliability and minimize diagnosis of undetermined etiology for stroke subtype classification, using a stroke registry, we developed and implemented a magnetic resonance imaging (MRI)-based algorithm for acute ischemic stroke subtype classification (MAGIC). Methods We enrolled patients who experienced an acute ischemic stroke, were hospitalized in the 14 participating centers within 7 days of onset, and had relevant lesions on MR-diffusion weighted imaging (DWI). MAGIC was designed to reflect recent advances in stroke imaging and thrombolytic therapy. The inter-rater reliability was compared with and without MAGIC to classify the Trial of Org 10172 in Acute Stroke Treatment (TOAST) of each stroke patient. MAGIC was then applied to all stroke patients hospitalized since July 2011, and information about stroke subtypes, other clinical characteristics, and stroke recurrence was collected via a web-based registry database. Results The overall intra-class correlation coefficient (ICC) value was 0.43 (95% CI, 0.31-0.57) for MAGIC and 0.28 (95% CI, 0.18-0.42) for TOAST. Large artery atherosclerosis (LAA) was the most common cause of acute ischemic stroke (38.3%), followed by cardioembolism (CE, 22.8%), undetermined cause (UD, 22.2%), and small-vessel occlusion (SVO, 14.6%). One-year stroke recurrence rates were the highest for two or more UDs (11.80%), followed by LAA (7.30%), CE (5.60%), and SVO (2.50%). Conclusions Despite several limitations, this study shows that the MAGIC system is feasible and may be helpful to classify stroke subtype in the clinic.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: A Genetic Cause of Cerebral Small Vessel Disease

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disorder of the cerebral small blood vessels caused by mutations in the Notch3 gene. The exact prevalence of this disorder was unknown currently, and the number of reported CADASIL families is steadily increasing as the clinical picture and diagnostic examinations are becoming more widely known. The main clinical manifestations are recurrent stroke, migraine, psychiatric symptoms, and progressive cognitive impairment. The clinical course of CADASIL is highly variable, even within families. The involvement of the anterior temporal lobe and the external capsule on brain magnetic resonance imaging was found to have high sensitivity and specificity in differentiating CADASIL from the much more common sporadic cerebral small-vessel disease (SVD). The pathologic hallmark of the disease is the presence of granular osmiophilic material in the walls of affected vessels. CADASIL is a prototype single-gene disorder that has evolved as a unique model for studying the mechanisms underlying cerebral SVD. At present, the incidence and prevalence of CADASIL seem to be underestimated due to limitations in clinical, neuroradiological, and genetic diagnoses of this disorder.

Evaluation of the Somatotopic Organization of Corticospinal Tracts in the Internal Capsule and Cerebral Peduncle: Results of Diffusion-Tensor MR Tractography

Objective We have used diffusion tensor tractography (DTT) for the evaluation of the somatotopic organization of corticospinal tracts (CSTs) in the posterior limb of the internal capsule (PLIC) and cerebral peduncle (CP). Materials and Methods We imaged the brains of nine healthy right-handed subjects. We used a spin-echo echo-planar imaging (EPI) sequence with 12 diffusion-sensitized directions. DTT was calculated with an angular threshold of 35 degrees and a fractional anistropy (FA) threshold of 0.25. We determined the location of the CSTs by using two regions of interest (ROI) at expected areas of the pons and expected areas of the lateral half of the PLIC, in the left hemisphere of the brain. Fiber tracts crossing these two ROIs and the precentral gyrus (PCG) were defined as CSTs. Four new ROIs were then defined for the PCG, from the medial to lateral direction, as ROI 1 (medial) to ROI 4 (lateral). Finally, we defined each fiber tract of the CSTs between the pons and each ROI in the PCG by using two ROIs methods. Results In all subjects, the CSTs were organized along the long axis of the PLIC, and the hand fibers were located anterior to the foot fibers. The CSTs showed transverse orientation in the CP, and the hand fibers were located usually medial to the foot fibers. Conclusion Corticospinal tracts are organized along the long axis of the PLIC and the horizontal direction of the CP.

Family history and risk for ischemic stroke: sibling history is more strongly correlated with the disease than parental history.

Current data concerning the association between family history and the risk for developing stroke have been controversial. There has been very little data on the influence of family history on intracranial atherosclerosis (ICAS), stroke severity, and recovery, especially among Asian populations. We evaluated the association between family history and the risk for stroke and investigated the relationships between family history and ICAS, stroke severity, and short-term stroke outcome in Korean stroke patients. In this case-control study, we recruited 400 patients with acute ischemic stroke, along with the same number of age- and gender-matched control subjects. Assessments of first-degree family history of stroke, myocardial infarction, hypertension and diabetes mellitus were obtained by structured questionnaires, followed by reviews of the clinical and neuro-radiological findings of the stroke patients. A family history of stroke was associated with an increased risk of ischemic stroke (OR, 2.65; 95% CI, 1.75 to 4.01), and the correlation remained significant after multivariate analysis. The odds ratios of paternal, maternal, and sibling history were 2.07, 2.16, and 4.21, respectively. The risk of stroke did not differ significantly with the presence of ICAS, stroke severity, and stroke outcome. Family history of stroke was an independent risk factor for ischemic stroke. A positive sibling history was more strongly correlated with the incidence of stroke than a positive parental history, and this finding may indicate the possible role of environmental factors in a shared household in addition to the genetic factors involved in family medical history.

Genetics of Cerebral Small Vessel Disease

Cerebral small vessel disease (SVD) is an important cause of stroke and cognitive impairment among the elderly and is a more frequent cause of stroke in Asia than in the US or Europe. Although traditional risk factors such as hypertension or diabetes mellitus are important in the development of cerebral SVD, the exact pathogenesis is still uncertain. Both, twin and family history studies suggest heritability of sporadic cerebral SVD, while the candidate gene study and the genome-wide association study (GWAS) are mainly used in genetic research. Robust associations between the candidate genes and occurrence of various features of sporadic cerebral SVD, such as lacunar infarction, intracerebral hemorrhage, or white matter hyperintensities, have not yet been elucidated. GWAS, a relatively new technique, overcomes several shortcomings of previous genetic techniques, enabling the detection of several important genetic loci associated with cerebral SVD. In addition to the more common, sporadic cerebral SVD, several single-gene disorders causing cerebral SVD have been identified. The number of reported cases is increasing as the clinical features become clear and diagnostic examinations are more readily available. These include cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, COL4A1-related cerebral SVD, autosomal dominant retinal vasculopathy with cerebral leukodystrophy, and Fabry disease. These rare single-gene disorders are expected to play a crucial role in our understanding of cerebral SVD pathogenesis by providing animal models for the identification of cellular, molecular, and biochemical changes underlying cerebral small vessel damage.

Diversity of Stroke Presentation in CADASIL: Study from Patients Harboring the Predominant NOTCH3 Mutation R544C

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disorder of the cerebral small blood vessels caused by mutations in the NOTCH3 gene. Several characteristic population-specific clinical phenotypes and neuroimaging features have been reported in CADASIL. This study investigated the clinical stroke presentation and cranial magnetic resonance imaging (MRI) findings in a group of patients with CADASIL. We reviewed the clinical stroke presentation and brain MRI findings in 73 consecutive Korean patients aged >18 years diagnosed with CADASIL between May 2004 and April 2009. Brain MRI images were also scored for lacunar infarction and cerebral microbleeds. Intracranial atherosclerosis (ICAS) was assessed by magnetic resonance angiography. Disability was measured with the modified Rankin scale (mRS) and classified as good (mRS score 0-2) or poor (mRS score 3-5). In this study, 65 of the 73 patients (90.3%) had the same R544C genotype. A total of 40 episodes of cerebral infarction were confirmed in 31 patients, with a mean age at onset of 58.8 ± 11.4 years (range, 38-76 years). Twelve patients (16.9%) had ICAS, and 5 of these patients had symptomatic stenoses. Intracerebral hemorrhage occurred in 9 patients (12.3%). Both intracerebral hemorrhage and ICAS were associated with poor clinical outcome. Our data demonstrate the diversity of clinical stroke presentation according to ethnicity and vascular risk factors.

Early Outcomes After Carotid Artery Stenting Compared With Endarterectomy for Asymptomatic Carotid Stenosis

Background and Purpose— Despite the absence of definitive data from randomized clinical trials on the comparative effectiveness of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) for asymptomatic carotid stenosis, the use of CAS has been expanding and seems to be displacing the use of CEA in some parts of the United States. Methods— We used comprehensive hospital discharge data from January 2010 to December 2012 to identify patients who had CEA or CAS for asymptomatic carotid stenosis at all academic medical centers that participate in the University HealthSystem Consortium. In-hospital death and postoperative stroke after CAS and after CEA were compared using multivariable logistic regression, propensity score matching, and a grouped-treatment approach using multilevel mixed-effects models to adjust for baseline characteristics of patients selected for these procedures. Results— We identified 17 716 patients with asymptomatic carotid stenosis treated with CEA and 3962 treated with CAS at 186 University HealthSystem Consortium hospitals. Postoperative stroke or in-hospital death was more frequent after CAS (4.0% versus 1.5%; P<0.001), and patients with CAS were more likely to have these adverse outcomes even after adjusting for baseline characteristics using multivariable analysis (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1–3.1; P<0.001) and propensity score matching (OR, 2.5; 95% CI, 1.9–3.4; P<0.001). In a multilevel mixed-effects model, hospitals that performed a higher proportion of all carotid revascularization cases using CAS had significantly higher rates of adverse outcomes (OR, 3.7; 95% CI, 1.8–7.6; P<0.001) after adjusting for patient-level variables. Conclusions— For asymptomatic carotid stenosis, CAS is associated with a substantially higher risk of postoperative stroke or in-hospital death than CEA even after adjustment for baseline differences in hospital and patient characteristics.

Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours A Comparative Effectiveness and Safety Study

Background and Purpose— The low-dose (0.6 mg/kg) alteplase strategy to treat acute ischemic stroke patients became widespread in East Asian countries, without rigorous testing against standard-dose (0.9 mg/kg) alteplase treatment. Our aim was to investigate the comparative effectiveness and safety of the low-dose versus standard-dose intravenous alteplase strategy. Methods— A total of 1526 acute ischemic stroke patients who qualified for intravenous alteplase and treated within 4.5 hours were identified from a prospective, multicenter, and nationwide stroke registry database. Primary outcomes were a modified Rankin scale score of 0 to 1 at 3 months after stroke and occurrence of symptomatic hemorrhagic transformation. Inverse probability of low-dose alteplase weighting by propensity scores was used to remove baseline imbalances between the 2 groups, and variation among centers were also accounted using generalized linear mixed models with a random intercept. Results— Low-dose intravenous alteplase was given to 450 patients (29.5%) and standard-dose intravenous alteplase to 1076 patients (70.5%). Low-dose alteplase treatment was comparable to standard-dose therapy according to the following adjusted outcomes and odds ratios (95% confidence intervals): modified Rankin scale score 0 to 1 at 3 months and 0.95 (0.68–1.32); modified Rankin scale 0 to 2 at 3 months and 0.84 (0.62–1.15); symptomatic hemorrhagic transformation and 1.05 (0.65–1.70); and 3-month mortality and 0.54 (0.35–0.83). The associations were unchanged when the analysis was limited to those without endovascular recanalization. Conclusions— The low-dose alteplase strategy was comparable to the standard-dose treatment in terms of the effectiveness and safety.