Description: Background and Purpose— We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke. Methods— We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.0 years) enrolled consecutively from 11 nationwide stroke centers, from patient (fluid-attenuated-inversion-recovery) MRIs onto a standard brain template set. Using multivariable analyses, we assessed the impact of major (age/hypertension) and minor risk factors on WMH variability. Results— We have produced a large reference data library showing the location and quantity of WMHs as topographical frequency-volume maps. This easy-to-use graphical reference data set allows the quantitative estimation of the severity of WMH as a percentile rank score. For all patients (median age=69 years), multivariable analysis showed that age, hypertension, atrial fibrillation, and left ventricular hypertrophy were independently associated with increasing WMH (0–9.4%, median=0.6%, of the measured brain volume). For younger (≤69) hypertensives (n=819), age and left ventricular hypertrophy were positively associated with WMH. For older (≥70) hypertensives (n=944), age and cholesterol had positive relationships with WMH, whereas diabetes mellitus, hyperlipidemia, and atrial fibrillation had negative relationships with WMH. For younger nonhypertensives (n=578), age and diabetes mellitus were positively related to WMH. For older nonhypertensives (n=328), only age was positively associated with WMH. Conclusions— We have generated a novel graphical WMH grading (Kim statistical WMH scoring) system, correlated to risk factors and adjusted for age/hypertension. Further studies are required to confirm whether the combined data set allows grading of WMH burden in individual patients and a tailored patient-specific interpretation in ischemic stroke-related clinical practice.

Description: Background and Purpose— Several stroke risk scores for prediction of functional outcome have been developed, but rarely validated in Asian populations. We assessed the validity of the iScore, recently developed from Canadian stroke population, in an Asian stroke population from Korea. Methods— We applied the iScore to 4061 eligible participants with acute ischemic stroke in the nationwide multicenter stroke registry in Korea. The main outcome was poor functional outcome defined as having a modified Rankin Scale 3 to 6 at 3 months after stroke onset. The secondary outcome was death at 3 months. C-statistics were calculated to assess performance of the iScore. Results— Poor functional outcome was found in 1496 patients (36.8%), whereas death at 3 months occurred in 294 patients (7.2%). C-statistics were 0.819 (95% confidence interval, 0.805–0.833) for poor functional outcome and 0.861 (95% confidence interval, 0.840–0.883) for death. Overall, there was a high correlation between observed and expected outcomes for poor functional outcome (Pearson correlation coefficient, r =0.990) and for death ( r =0.969) according to risk score. Conclusions— The iScore reliably predicts poor functional outcome or death at 3 months after stroke in Korean patients.

Description: Background and Purpose— An urgent need exists to develop therapies for stroke that have high efficacy, long therapeutic time windows, and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. Methods— Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. Results— Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically relevant therapeutic time windows of 6 hours and 9 hours in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained on 14th day poststroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests, and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust antiexcitotoxic, antioxidant, and mitochondria protecting activity. Conclusions— In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

Description: Background and Purpose— Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion–weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. Methods— Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s T max strata to the entire hypoperfusion volume ( T max≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each T max strata proportion and cerebral blood volumes. Results— Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe T max delays ( T max 16–18 s , T max 18–22 s , T max 22–24 s , and T max 〉24 s ) were associated with poor collaterals. The probability equation model using T max strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682–0.9924). The probability score was negatively correlated with the volume of infarct growth ( P =0.030). Conclusions— Collateral status is associated with more severe T max delays than previously defined. The present T max severity–weighted model can determine good collaterals and subsequent infarct growth.