Brown, Robert D.

Background and Purpose— The best management of patients with unruptured brain arteriovenous malformations (BAVM) is controversial. In this study, we analyzed the stroke rate and functional outcomes of patients having stereotactic radiosurgery (SRS) for unruptured BAVM using the same eligibility criteria and primary end points as the ARUBA trial. Methods— Retrospective observational study of 174 ARUBA-eligible patients having SRS from 1990 to 2005. Results— The median follow-up after SRS was 64 months. Fifteen patients (8.7%) had a hemorrhagic stroke at a median of 21 months after SRS. Six patients (3.5%) had a focal neurological deficit and 4 patients died (2.3%). The risk of stroke or death was 10.3% at 5 years and 11.5% at 10 years. Twelve additional patients (6.9%) had a focal neurological deficit from either radiation-related complications (n=7) or subsequent resection (n=5). The risk of patients’ having clinical impairment (modified Rankin Score ≥2) was 8.4% at 5 years and 12.0% at 10 years. Increasing BAVM volume was associated with both stroke or death (hazard ratio=1.06; 95% confidence interval, 1.0–1.11; P =0.04) and clinical impairment (hazard ratio=1.06; 95% confidence interval, 1.01–1.09; P =0.01). The 10-year risk of stroke or death and clinical impairment for patients with BAVM ≤5.6 cm 3 was 5% and 4%, respectively. Conclusions— The observed risk of stroke or death after SRS was approximately 2% per year for the first 5 years after SRS, declining to 0.2% annually for years 6 to 10. Patients with small volume BAVM may benefit from SRS compared with the natural history of unruptured BAVM over the planned follow-up interval of the ARUBA trial (5–10 years).

Object The goal of this study was to determine the risk of using antithrombotic agents in patients with established intracerebral cavernous malformations (ICMs). Methods From a previously described cohort of 292 patients with radiographically defined ICMs, 40 required an antithrombotic after the ICM was diagnosed. Patients underwent follow-up to determine the incidence of hemorrhage. Results The mean age of these 40 patients was 62.4 years; there were 21 male and 19 female patients. Five (12.5%) of the 40 patients initially presented with hemorrhage and 4 (10%) had multiple ICMs. Of these patients, 32 were placed on an antiplatelet agent alone, 6 on an anticoagulant alone, and 2 were placed on both. In patients necessitating any antithrombotic agent, 1 patient developed a prospective hemorrhage over the 258 person-years of follow-up (prospective hemorrhage rate 0.41% per person-year). Conclusions Antithrombotics likely do not precipitate hemorrhage in patients with known ICMs. However, caution should be exercised in the use of antithrombotics in patients with ICMs at high risk for hemorrhage. The risks and benefits of antithrombotics in each situation should be carefully weighed against the natural history of ICM.

Introduction. Etiology of acute ischemic stroke (AIS) is known to significantly influence management, prognosis, and risk of recurrence.Objective. To determine if ischemic stroke subtype based on TOAST criteria influences mortality.Methods. We conducted an observational study of a consecutive cohort of patients presenting with AIS to a single tertiary academic center.Results. The study population consisted of 500 patients who resided in the local county or the surrounding nine-county area. No patients were lost to followup. Two hundred and sixty one (52.2%) were male, and the mean age at presentation was 73.7 years (standard deviation, SD = 14.3). Subtypes were as follows: large artery atherosclerosis 97 (19.4%), cardioembolic 144 (28.8%), small vessel disease 75 (15%), other causes 19 (3.8%), and unknown 165 (33%). One hundred and sixty patients died: 69 within the first 30 days, 27 within 31–90 days, 29 within 91–365 days, and 35 after 1 year. Low 90-, 180-, and 360-day survival was seen in cardioembolic strokes (67.1%, 65.5%, and 58.2%, resp.), followed for cryptogenic strokes (78.0%, 75.3%, and 71.1%). Interestingly, when looking into the cryptogenic category, those with insufficient information to assign a stroke subtype had the lowest survival estimate (57.7% at 90 days, 56.1% at 180 days, and 51.2% at 1 year).Conclusion. Cardioembolic ischemic stroke subtype determined by TOAST criteria predicts long-term mortality, even after adjusting for age and stroke severity.

Background and Purpose— Ischemic stroke has a strong familial component to risk. The Siblings With Ischemic Stroke Study (SWISS) is a genome-wide, family-based analysis that included use of imputed genotypes. The Siblings With Ischemic Stroke Study was conducted to examine the associations between single-nucleotide polymorphisms (SNPs) and risk of stroke and stroke subtypes within pairs. Methods— The Siblings With Ischemic Stroke Study enrolled 312 probands with ischemic stroke from 70 US and Canadian centers. Affected siblings were ascertained by centers and confirmed by central record review; unaffected siblings were ascertained by telephone contact. Ischemic stroke was subtyped according to Trial of Org 10172 in Acute Stroke Treatment criteria. Genotyping was performed with an Illumina 610 quad array (probands) and an Illumina linkage V array (affected siblings). SNPs were imputed by using 1000 Genomes Project data and MACH software. Family-based association analyses were conducted by using the sibling transmission-disequilibrium test. Results— For all pairs, the correlation of age at stroke within pairs of affected siblings was r =0.83 (95% CI, 0.78–0.86; P <2.2×10 −16 ). The correlation did not differ substantially by subtype. The concordance of stroke subtypes among affected pairs was 33.8% (kappa=0.13; P =5.06×10 −4 ) and did not differ by age at stroke in the proband. Although no SNP achieved genome-wide significance for risk of ischemic stroke, there was clustering of the most associated SNPs on chromosomes 3p and 6p. Conclusions— Stroke subtype and age at stroke in affected sibling pairs exhibit significant clustering. No individual SNP reached genome-wide significance. However, 2 promising candidate loci were, although these risk loci warrant further examination in larger sample collections.

Background and Purpose —There is scant population-based information on functional outcome, survival, and recurrence for ischemic stroke subtypes. Methods —We identified all residents of Rochester, Minnesota, with a first ischemic stroke from 1985 through 1989 using the resources of the Rochester Epidemiology Project medical records linkage system. After reviewing medical records and imaging studies, we assigned patients to 4 major ischemic stroke categories based on National Institute of Neurological Diseases and Stroke Data Bank criteria: large-vessel cervical or intracranial atherosclerosis with stenosis (ATH, n=74), cardioembolic (CE, n=132), lacunar (LAC, n=72), and infarct of uncertain cause (IUC, n=164). We used the Rankin disability score to assess functional outcome and the Kaplan-Meier product-limit method and Cox proportional hazards regression analysis with bootstrap validation to estimate rates and identify predictors of survival and recurrent stroke among these patients. Results —Rankin disabilities were different across stroke subtypes at the time of stroke and 3 months and 1 year later ( P =0.001). LAC was associated with milder deficits compared with other subtypes. Mean follow-up among the 442 patients in the cohort was 3.2 years. Estimated rates of recurrent stroke at 30 days were significantly different ( P <0.001): ATH, 18.5% (95% CI 9.4% to 27.5%); CE, 5.3% (95% CI 1.2% to 9.6%); LAC, 1.4% (95% CI 0.0% to 4.1%); and IUC, 3.3% (95% CI 0.4% to 6.2%). After adjusting for age, sex, and stroke severity, infarct subtype was an independent determinant of recurrent stroke within 30 days ( P =0.0006; eg, risk ratio for ATH compared with CE=3.3, 95% CI 1.2 to 9.3) but not long term ( P =0.07). Four of 25 recurrent strokes within 30 days were procedure-related, each in patients with ATH. Five-year death rates were significantly different ( P <0.001): ATH, 32.2% (95% CI 21.1% to 43.2%); CE, 80.4% (95% CI 73.1% to 87.6%); LAC, 35.1% (95% CI 23.6% to 46.0%); and IUC, 48.6% (95% CI 40.5% to 56.7%). With adjustment for age, sex, cardiac comorbidity, and stroke severity, the subtype of ischemic stroke was an independent determinant of long-term ( P =0.018; eg, risk ratio for ATH compared with cardioembolic=0.47, 95% CI 0.29 to 0.77) but not 30-day survival ( P =0.2). Conclusions —Early recurrence rates for ischemic stroke caused by ATH are higher than those for other subtypes and higher than previous non–population-based studies have reported. Some of the increased risk of early recurrence among patients with ATH may be iatrogenic. Patients with LAC have better poststroke functional status than those with other subtypes. Survival is poorest among those with ischemic stroke with a cardiac source of embolism.