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Objective: To identify and compare clinical and neuroimaging predictors of primary lobar intracerebral hemorrhage (ICH) recurrence, assessing their relative contributions to recurrent ICH.Methods: Subjects were consecutive survivors of primary ICH drawn from a single-center prospective cohort study. Baseline clinical, imaging, and laboratory data were collected. Survivors were followed prospectively for recurrent ICH and intercurrent aspirin and warfarin use, including duration of exposure. Cox proportional hazards models were used to identify predictors of recurrence stratified by ICH location, with aspirin and warfarin exposures as time-dependent variables adjusting for potential confounders.Results: A total of 104 primary lobar ICH survivors were enrolled. Recurrence of lobar ICH was associated with previous ICH before index event (hazard ratio [HR] 7.7, 95% confidence interval [CI] 1.4 -15.7), number of lobar microbleeds (HR 2.93 with 2-4 microbleeds present, 95% CI 1.3-4.0; HR ϭ 4.12 when Ն5 microbleeds present, 95% CI 1.6 -9.3), and presence of CTdefined white matter hypodensity in the posterior region (HR 4.11, 95% CI 1.01-12.2). Although aspirin after ICH was not associated with lobar ICH recurrence in univariate analyses, in multivariate analyses adjusting for baseline clinical predictors, it independently increased the risk of ICH recurrence (HR 3.95, 95% CI 1.6 -8.3, p ϭ 0.021). Conclusions:Recurrence of lobar ICH is associated with previous microbleeds or macrobleeds and posterior CT white matter hypodensity, which may be markers of severity for underlying cerebral amyloid angiopathy. Use of an antiplatelet agent following lobar ICH may also increase recurrence risk. Neurology ® 2010;75:693-698 GLOSSARY CAA ϭ cerebral amyloid angiopathy; CI ϭ confidence interval; CT-WMH ϭ CT-defined white matter hypodensity; HR ϭ hazard ratio; ICH ϭ intracerebral hemorrhage; VIF ϭ variance inflation factor.Intracerebral hemorrhage (ICH), although accounting for only 15% of acute strokes in the United States, 1 carries the worst prognosis of all acute cerebrovascular diseases. 2,3 Lobar ICH location (selective involvement of the cerebral cortex and underlying white matter) is associated with greater risk for recurrence than deep ICH location [4][5][6] and is associated with different clinical features and risk factors. 7,8 Nonfamilial cerebral amyloid angiopathy (CAA), caused by ␤-amyloid deposition in cerebral arteries and arterioles, is a major cause of lobar ICH but not deep ICH, as shown by autopsy investigations, 9 as well as studies linking lobar ICH with several hallmarks of CAA, such as the APOE ⑀2 and ⑀4 alleles, 5,9,10 asymptomatic microbleeds detected on gradient-echo MRI, 11,12 and white matter lesions. 13 Based on recent evidence, there is some suggestion that asymptomatic CAA may be highly prevalent in the elderly. 14,15 Although several predictors of lobar ICH recurrence have been described, little is known regarding the relative contribution or interaction of each of these predictors. For examp...

Objective In addition to its role in hemorrhagic stroke, advanced cerebral amyloid angiopathy (CAA) is also associated with ischemic lesions and vascular cognitive impairment. We used functional MRI techniques to identify CAA-associated vascular dysfunction. Methods Functional MRI was performed on 25 nondemented subjects with probable CAA (mean ± standard deviation age 70.2±7.8) and 12 healthy elderly controls (age 75.3±6.2). Parameters measured were reactivity to visual stimulation (quantified as blood oxygen level-dependent [BOLD] response amplitude, time to peak response, and time to return to baseline after stimulus cessation) and resting absolute cerebral blood flow in the visually activated region (measured by arterial spin labeling). Results CAA subjects demonstrated reduced response amplitude (percent change in BOLD signal 0.65±0.28 vs 0.89±0.14, p<0.01), prolonged time to peak (11.1±5.1 vs 6.4±1.8 sec, p<0.001) and prolonged time to baseline (16.5±6.7 vs 11.6±3.1 sec, p<0.001) relative to controls. These differences were independent of age, sex, and hypertension in multivariable analysis and were also present in secondary analyses excluding nonresponsive voxels or voxels containing chronic blood products. Within the CAA group, longer time to peak correlated with overall volume of white matter T2 hyperintensity (Pearson correlation 0.53, p=0.007). Absolute resting blood flow in visual cortex, in contrast, was essentially identical between the groups (44.0±12.6 vs 45.0±10.0 ml/100g/min, p=0.8). Interpretation Functional MRI identifies robust differences in both amplitude and timing of the response to visual stimulation in advanced CAA. These findings point to potentially powerful approaches for identifying the mechanistic links between vascular amyloid deposits, vascular dysfunction, and CAA-related brain injury.

Objective: To investigate whether the topography of dilated perivascular spaces (DPVS) corresponds with markers of particular small-vessel diseases such as cerebral amyloid angiopathy and hypertensive vasculopathy.Methods: Patients were recruited from an ongoing single-center prospective longitudinal cohort study of patients evaluated in a memory clinic. All patients underwent structural, high-resolution MRI, and had a clinical assessment performed within 1 year of scan. DPVS were rated in basal ganglia (BG-DPVS) and white matter (WM-DPVS) on T1 sequences, using an established 4-point semiquantitative score. DPVS degree was classified as high (score . 2) or low (score # 2). Independent risk factors for high degree of BG-DPVS and WM-DPVS were investigated.Results: Eighty-nine patients were included (mean age 72.7 6 9.9 years, 57% female). High degree of WM-DPVS was more frequent than low degree in patients with presence of strictly lobar microbleeds (45.5% vs 28.4% of subjects). High BG-DPVS degree was associated with older age, hypertension, and higher white matter hyperintensity volumes. In multivariate analysis, increased lobar microbleed count was an independent predictor of high degree of WM-DPVS (odds ratio HV 5 hypertensive vasculopathy; ICC 5 intracranial compartment; ICH 5 intracerebral hemorrhage; ISF 5 interstitial fluid; MB 5 microbleeds; MCI 5 mild cognitive impairment; MPRAGE 5 magnetization-prepared rapid gradient echo; nWMH 5 normalized volume of white matter hyperintensity; OR 5 odds ratio; SVD 5 small-vessel diseases; SWI 5 susceptibilityweighted imaging; TE 5 echo time; TR 5 repetition time; WM 5 white matter; WM-DPVS 5 dilated perivascular spaces in the white matter; WMH 5 white matter hyperintensity.[