Leukoaraiosis Burden Research Articles

Extensive Leukoaraiosis Is Associated With High Early Risk of Recurrence After Ischemic Stroke

The integrity of white matter tracts connecting different parts of the brain is important for rapid compensation for the lost function from ischemic stroke. Impaired white matter reserve capacity secondary to leukoaraiosis may facilitate detection of new symptomatic ischemic events that would otherwise remain inconspicuous after an initial ischemic stroke. We sought to identify whether the extent of leukoaraiosis was a predictor of risk of early stroke recurrence. We used Cox regression analysis in consecutive patients with ischemic stroke to determine the relationship between leukoaraiosis burden and symptomatic stroke recurrence within 90 days. We graded total leukoaraiosis, periventricular leukoaraiosis, and subcortical leukoaraiosis using the Fazekas scale as mild (<2) and extensive (≥2) on fluid-attenuated inversion recovery images obtained within 72 hours of stroke onset in the hemisphere contralateral to acute stroke. There were 106 recurrent events in 2378 patients. The cumulative incidence of recurrence was 5.9% at 90 days. Kaplan-Meier estimate of recurrence-free survival rate was lower in patients with extensive leukoaraiosis (P=0.04) and extensive periventricular leukoaraiosis (P=0.02) but not in extensive subcortical leukoaraiosis (P=0.09). Multivariable Cox regression analysis revealed a hazard ratio of 1.50 (95% confidence interval, 1.00-2.25) for extensive leukoaraiosis, 1.67 (95% confidence interval, 1.11-2.51) for extensive periventricular leukoaraiosis, and 1.42 (95% confidence interval, 0.94-2.12) for extensive subcortical leukoaraiosis. The extent of leukoaraiosis independently predicts 90-day recurrent stroke risk after ischemic stroke. This suggests that leukoaraiosis may be used for risk stratification in ischemic stroke.

Setting a gold standard for quantification of leukoaraiosis burden in patients with ischemic stroke: The Atherosclerosis Risk in Communities Study

BackgroundAccurate and reliable measurement of leukoaraiosis, or MR-detected white, matter hyperintensity (WMH) burden in subjects with acute ischemic stroke (AIS) is important for, ongoing research studies and future models of risk and outcome prediction, but the presence of a, cerebral infarct may complicate measurement. We sought to assess accuracy of a volumetric method, designed to measure WMH in AIS subjects as compared to the previously validated protocol. New methodWe randomly selected and equally sampled 120 brain scans from the Atherosclerosis, Risk in Communities (ARIC) MRI Study individuals within designated mild, moderate, and severe, tertiles of WMH volume (WMHV). T2 FLAIR axial images were analyzed using the AIS WMH volumetric, protocol and compared with the ARIC (gold standard) method. Pearson correlation coefficients, linear, concordance correlation coefficient, and Blant–Altman procedures were used to assess measurement, agreements between the two procedures. ResultsMedian WMHV determined by using the ARIC method was 7.8cm3 (IQR 5.7–13.55) vs. 3.54cm3, (IQR 2.1–7.2) using the AIS WMH method. There was good correlation between the two measurements, (r=0.52, 0.67, and 0.9 for tertiles 1, 2, and 3 respectively) (p<0.001). Comparison with existing methodThe AIS WMH protocol was specific for leukoaraiosis in ischemic, stroke, but it appeared to underestimate WMHV compared to the gold standard method. ConclusionsEstimates of MR-detectable WMH burden using a volumetric protocol designed for, analysis of clinical scans correlate strongly with gold standard measurements. These findings will, facilitate future studies of WMH in normal aging and in patients with stroke and other cerebrovascular, disease.

Diabetes is associated with postural instability and gait difficulty in Parkinson disease

BackgroundComorbid diabetes may be associated with more severe motor impairment in Parkinson disease. In normal elderly individuals, diabetes is associated with parkinsonian features, including gait difficulty and rigidity, though not tremor. Whether diabetes contributes to increased motor dysfunction in Parkinson disease by exacerbating nigrostriatal dopaminergic denervation or through intensification of extranigral pathology is unknown. MethodsWe performed a case–control study (n = 39) involving 13 Parkinson disease subjects (age 66.4yrs ± 5.5; duration of disease 6.9yrs ± 4.4) with diabetes and 26 age, gender, and duration-of-disease-matched Parkinson disease controls without diabetes. All subjects underwent [11C]dihydrotetrabenazine vesicular monoamine transporter type-2 positron emission tomography imaging to assess striatal dihydrotetrabenazine distribution volume ratio and Unified Parkinson disease rating scale motor examination to determine rigidity, bradykinesia, tremor, and postural instability and gait difficulty subscores. Magnetic resonance imaging scans were analyzed to assess leukoaraiosis burden. ResultsAfter controlling for nigrostriatal dopaminergic denervation, Parkinson disease subjects with diabetes displayed greater postural instability and gait difficulty subscores (t = 3.81, p = 0.0005). There were no differences in bradykinesia, rigidity, or tremor subscores between cases and controls. The association between diabetes and postural instability and gait difficulty persisted after controlling for comorbid hypertension and body mass index. Leukoaraiosis, distal vibratory sense, and levodopa dose equivalents did not differ significantly between cases and controls. ConclusionsDiabetes may contribute to postural instability and gait difficulty in Parkinson disease through mechanisms other than nigrostriatal dopaminergic denervation.

Risk of intraparenchymal hemorrhage with magnetic resonance imaging‐defined leukoaraiosis and brain infarcts

To determine whether the burden of leukoaraiosis and the number of brain infarcts, defined by magnetic resonance imaging (MRI), are prospectively and independently associated with intraparenchymal hemorrhage (IPH) incidence in a pooled population-based study. Among 4,872 participants initially free of clinical stroke in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, we assessed white matter grade (range, 0-9), reflecting increasing leukoaraiosis, and brain infarcts using MRI. Over a median of 13 years of follow-up, 71 incident, spontaneous IPH events occurred. After adjustment for other IPH risk factors, the hazard ratios (95% confidence intervals) across white matter grades 0 to 1, 2, 3, and 4 to 9 were 1.00, 1.68 (0.86-3.30), 3.52 (1.80-6.89), and 3.96 (1.90-8.27), respectively (p for trend <0.0001). These hazard ratios were weakened only modestly (p for trend = 0.0003) with adjustment for MRI-defined brain infarcts. The IPH hazard ratios for 0, 1, 2, or ≥3 MRI-defined brain infarcts were 1.00, 1.97 (1.10-3.54), 2.00 (0.83-4.78), and 3.12 (1.31-7.43) (p for trend = 0.002), but these were substantially attenuated when adjusted for white matter grade (p for trend = 0.049). Greater MRI-defined burden of leukoaraiosis is a risk factor for spontaneous IPH. Spontaneous IPH should be added to the growing list of potential poor outcomes in people with leukoaraiosis.

Elevated Admission Blood Pressure and Acute Ischemic Lesions in Spontaneous Intracerebral Hemorrhage

Concomitant acute ischemic lesions are detected in a subset of patients with intracerebral hemorrhage (ICH). In this study, our aim was to analyze the pattern of acute ischemic lesions detected by diffusion-weighted imaging (DWI) in patients with ICH, and to use this information, in combination with clinical characteristics of patients, to understand the underlying mechanisms of these lesions. We retrospectively analyzed patients with a diagnosis of ICH who underwent DWI within 14 days of symptom onset. We compared demographic, clinical, and imaging characteristics in patients with and without acute ischemic lesions. We also assessed the number, location, and topographic distribution of DWI bright lesions. Acute ischemic lesions were detected in 15 of 86 patients (17.4%); the lesions had a small, dot-like appearance in 13 patients (87%) and were located in an arterial territory separate from the incident ICH in 12 patients (80%). Patients with acute ischemic lesions had higher admission systolic, diastolic, and mean arterial blood pressure levels; greater periventricular leukoaraiosis burden; more microbleeds, and lower admission Glasgow Coma Scale score. In multivariate analyses, admission mean arterial blood pressure (P < .01) and Glasgow Coma Scale score (P =.03) remained as the only significant variables associated with DWI lesion positivity. Our findings highlight the role of elevated admission blood pressure in the development of concomitant acute ischemic lesions in patients with ICH. The pattern of DWI bright lesions, together with a trend toward an increased burden of leukoaraiosis and microbleeds in patients with acute ischemic lesions, suggest an underlying dysfunctional cerebral microvasculature in the etiology of these lesions.

Small vessel stroke and white matter lesions

Damage to small penetrating vessels is an important unifying cause of ischemic and hemorrhagic strokes. Both types of stroke involve tiny arterioles and are often pathologic twins, arteriolosclerosis and lipohyalinosis being the predominant underlying causes.1 Another entity increasingly linked to small vessel damage is extensive leukoaraiosis: white matter lesions frequently seen on T2-weighted magnetic resonance scans of older people. In this issue of Neurology ®, Rost et al.2 report hospital-based findings from 3 stroke registries showing a greater burden of leukoaraiosis in participants with small vessel stroke (including both ischemic and hemorrhagic forms) compared to other ischemic stroke subtypes, supporting a link among these 3 entities. Thought of together, as peas in a pod, ischemic and hemorrhagic small vessel damage accounts for about one-third of all strokes and represents an important cause of morbidity and mortality. Ischemic small vessel stroke, often referred to as “lacunar,” is usually manifested as infarctions less than 1.5 cm in diameter on CT or MRI, and attributed to thrombosis of a penetrating vessel in the basal ganglia, thalamus, deep white matter, or brainstem. Studies suggest that lacunar strokes are associated with lower short-term disability and mortality than other ischemic stroke subtypes, and reported 1-year case-fatality rates are low, near 3%. …