Robert D Brown

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (217)1264.07 Total impact

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    ABSTRACT: The clinical significance of cerebral microbleeds (CMB) in patients hospitalized with atrial fibrillation (AF) and cerebral ischemia is unclear. We aimed to determine the prevalence of CMB in this population and determine the future risk of intracerebral hemorrhage (ICH) and cerebral infarction (CI). The medical records and brain imaging of patients hospitalized with cerebral ischemia due to AF between 2008 and 2011 were reviewed. Followup was obtained through medical record review, mailed survey, and acquisition of death certificates. Prevalence was calculated from those patients with a hemosiderin-sensitive MRI sequence. Recurrent CI and ICH were calculated using Kaplan-Meier curves censored at 3 years. Among 426 patients hospitalized with cerebral ischemia due to AF, 134 had an MRI with hemosiderin-sensitive sequences. The prevalence of CMB was 27.6 %. At 3 years, 90.6 % of CMB-negative patients were overall stroke free (ICH and CI) compared to 78.6 % CMB-positive patients (p = 0.0591). Only one patient in the CMB-positive group had an ICH distant to the CMB. There was a nonsignificant trend toward higher recurrent CI, recurrent overall stroke rate, and mortality in patients with 5 or more CMB compared to 0-4 CMB. The rate of prospective CI in patients with prior cerebral ischemia due to AF is higher than the rate of ICH in patients with CMB. Further study is warranted to assess larger numbers of patients to determine appropriate antithrombotic use in this high-risk population.
    Journal of Neurology 11/2015; DOI:10.1007/s00415-015-7966-2 · 3.38 Impact Factor
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    ABSTRACT: Study objectives: To assess etiology of ischemic stroke in patients with obstructive sleep apnea (OSA) compared with controls. This information may aid in determining how OSA increases stroke risk and facilitate recurrent stroke prevention in patients with OSA. Design: Retrospective, case-control study. Setting: Academic tertiary referral center. Patients: Consecutive patients who underwent polysomnography and had an ischemic stroke within 1 year were identified. Stroke subtype was determined using two validated algorithms. Polysomnographic results were used to separate patients into OSA cases and controls. Information regarding cardiovascular risks, neuroimaging, and echocardiographic data were collected. Interventions: N/A. Measurements and results: In 53 subjects, cardioembolic (CE) strokes were more common among OSA cases than controls (72% versus 33%, P = 0.01). The majority of CE strokes occurred in those with moderate to severe OSA. Atrial fibrillation (AF) was more frequent in OSA cases (59% versus 24%, P = 0.01). The association between OSA and CE stroke remained significant after controlling for AF (P = 0.03, odds ratio 4.5). Conclusions: There appears to be a strong association between obstructive sleep apnea (OSA) and cardioembolic (CE) stroke. In patients with OSA presenting with cryptogenic stroke, high clinical suspicion for CE is warranted. This may lead to consideration of diagnostic studies to identify CE risk factors such as paroxysmal atrial fibrillation (AF). CE strokes are more common in patients with OSA even after adjusting for AF. This finding may reflect a high rate of occult paroxysmal AF in this population; alternatively, OSA may lead to CE strokes through mechanisms independent of AF.
    Sleep 11/2015; 38(11):1699-1705. DOI:10.5665/sleep.5146 · 4.59 Impact Factor
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    ABSTRACT: Background and purpose: Seizures are a known complication of ischemic stroke (IS). This study assesses the long-term incidence and characteristics of poststroke seizures in a well-defined population. Methods: Using the Rochester Epidemiology Project medical records-linkage system, we identified all incident cases of IS among Rochester, Minnesota, residents from 1990 to 1994 and followed the patients in the comprehensive medical record through March 2014. All patients with poststroke seizures were identified, and data regarding incident IS, seizures, and status at last follow-up were analyzed. Results: We identified 489 patients with first IS. Mean follow-up was 6.5 (standard deviation 6.3) years. New onset seizures occurred in 35 patients (7.2%). Patients with poststroke seizure did not differ from those without in terms of IS etiologic subtype (P = .44) or IS risk factors (P > .05). Early seizures (within 14 days of index stroke) developed in 14 patients (40%), the majority within the first 24 hours (n = 9, 64.3%). The median time of seizure onset for the remaining 21 patients was 13.8 months. Functional outcome, as measured by modified Rankin Scale (mRS), was worse following development of poststroke seizures (mean mRS score 2.9 after IS, 3.3 following index seizure; P = .005), and mortality was higher as well, even after adjusting for IS etiologic subtype (HR 1.52, 95% confidence interval 1.07-2.16, P = .02). Conclusion: Development of poststroke seizures is an infrequent but significant complication of IS, portending a worse short-term functional outcome and a higher long-term mortality rate. Seizure occurrence did not differ based on IS etiologic subtype or stroke risk factors.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 10/2015; DOI:10.1016/j.jstrokecerebrovasdis.2015.09.008 · 1.67 Impact Factor
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    ABSTRACT: Stroke is a common cause of mortality and morbidity in Eastern Europe. However, detailed epidemiological data are not available. The National Registry of Hospitalized Patients (NRHOSP) is a nationwide registry of prospectively collected data regarding each hospitalization in the Czech Republic since 1998. As a first step in the evaluation of stroke epidemiology in the Czech Republic, we validated stroke cases in NRHOSP. Any hospital in the Czech Republic with a sufficient number of cases was included. We randomly selected 10 of all 72 hospitals and then 50 patients from each hospital in 2011 stratified according to stroke diagnosis (International Classification of Diseases Tenth Revision [ICD-10] cerebrovascular codes I60, I61, I63, I64, and G45). Discharge summaries from hospitalization were reviewed independently by 2 reviewers and compared with NRHOSP for accuracy of discharge diagnosis. Any disagreements were adjudicated by a third reviewer. Of 500 requested discharge summaries, 484 (97%) were available. Validators confirmed diagnosis in NRHOSP as follows: transient ischemic attack (TIA) or any stroke type in 82% (95% confidence interval [CI], 79-86), any stroke type in 85% (95% CI, 81-88), I63/cerebral infarction in 82% (95% CI, 74-89), I60/subarachnoid hemorrhage in 91% (95% CI, 85-97), I61/intracerebral hemorrhage in 91% (95% CI, 85-96), and G45/TIA in 49% (95% CI, 39-58). The most important reason for disagreement was use of I64/stroke, not specified for patients with I63. The accuracy of coding of the stroke ICD-10 codes for subarachnoid hemorrhage (I60) and intracerebral hemorrhage (I61) included in a Czech Republic national registry was high. The accuracy of coding for I63/cerebral infarction was somewhat lower than for ICH and SAH. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 06/2015; 24(9). DOI:10.1016/j.jstrokecerebrovasdis.2015.04.019 · 1.67 Impact Factor
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    ABSTRACT: The aim of this updated statement is to provide comprehensive and evidence-based recommendations for management of patients with unruptured intracranial aneurysms. Writing group members used systematic literature reviews from January 1977 up to June 2014. They also reviewed contemporary published evidence-based guidelines, personal files, and published expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulated recommendations using standard American Heart Association criteria. The guideline underwent extensive peer review, including review by the Stroke Council Leadership and Stroke Scientific Statement Oversight Committees, before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. Evidence-based guidelines are presented for the care of patients presenting with unruptured intracranial aneurysms. The guidelines address presentation, natural history, epidemiology, risk factors, screening, diagnosis, imaging and outcomes from surgical and endovascular treatment. © 2015 American Heart Association, Inc.
    Stroke 06/2015; 46(8). DOI:10.1161/STR.0000000000000070 · 5.72 Impact Factor
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    ABSTRACT: Cardiac myxomas can present with a myriad of neurological complications including stroke, cerebral aneurysm formation and metastatic disease. Our study had two objectives: (1) to describe the neuroimaging findings of patients with cardiac myxomas and (2) to examine the relationship between a history of embolic complications secondary to myxoma and intracranial aneurysm formation, hemorrhage and metastatic disease. We hypothesized that patients who present with embolic complications related to myxoma would be more likely to have such complications. We searched our institutional database for all patients with pathologically proven cardiac myxomas from 1995 to 2014 who received neuroimaging. Neuroimaging findings were categorized as acute ischemic stroke, intracerebral hemorrhage, oncotic aneurysm, and cerebral metastasis. Cardiac myxoma patients were divided into those presenting with embolic complications (i.e. lower extremity emboli or cerebral emboli) and those presenting with non-embolic complications prior to surgical resection of the myxoma. The prevalence of intracranial hemorrhage, myxomatous aneurysm formation, and cerebral metastases was compared in myxoma patients presenting with and without embolic complications using a Chi-squared test. Forty-seven consecutive patients were included in this study. Sixteen patients (34.0%) had imaging evidence of acute ischemic stroke. Of these, 13 had acute ischemic strokes directly attributed to the cardiac myxoma (27.7%) and 3 had acute ischemic strokes secondary to causes other than myxoma (6.4%). Seven patients (14.9%) had aneurysms. Two patients (4.3%) had parenchymal metastatic disease on long-term imaging. Fourteen patients (29.8%) presented with ischemic symptoms that were attributed to cardiac myxoma (1 with lower extremity ischemia, 1 with lower extremity ischemia and ischemic stroke, and 12 with ischemic stroke). Patients presenting with embolic complications related to the myxoma (ischemic stroke or lower extremity ischemia) were more likely to have imaging evidence of intracranial hemorrhage (21.4 vs. 3.0%, p = 0.09), oncotic aneurysm (35.7 vs. 6.1%, p = 0.03), and cerebral metastasis (14.3 vs. 0.0%, p = 0.07) on follow-up imaging. Ischemic stroke and intracranial oncotic aneurysm were found in a substantial proportion of cardiac myxoma patients undergoing neuroimaging. Patients presenting with embolic complications of cardiac myxoma are more likely to have intracranial hemorrhage, intracranial oncotic aneurysms, and cerebral metastatic disease. © 2015 S. Karger AG, Basel.
    Cerebrovascular Diseases 06/2015; 40(1-2):35-44. DOI:10.1159/000381833 · 3.75 Impact Factor
  • Kelly D. Flemming · Robert D. Brown · Michael J. Link ·
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    ABSTRACT: The objective was to determine if there was seasonal variation in the month of symptom onset in patients with intracerebral cavernous malformations (ICM). Patients seen at our institution between 1989 and 1999 with ICM identified from a radiologic database were included. Demographic data and symptoms at onset were abstracted. Symptomatic patients in this ICM database were included if the month of symptom onset was known. Comparison of proportions of patients presenting in fall and winter and during flu season were performed with the chi squared test and Fisher's exact test with significance at p<0.05. Of 292 patients identified, 179 patients had symptomatic ICM. Of these, 135 patients with symptomatic ICM were identified for whom the exact month of symptom onset was known. Eighty-seven (64.4%) presented with intracerebral hemorrhage (ICH) or focal neurologic deficit (FND) and 48 (35.6%) due to seizures. When assessing all 135 patients, 75 (55.5%) presented in the fall and winter compared to the spring and summer (p=0.1962). Eighty-three (61.4%) patients presented during flu season (p=0.0074). When assessing only those initially presenting with ICH or FND, 53 (60.9%) patients presented in the fall and winter compared to spring and summer (p=0.041) and 54 (62.8%) presented during flu season (p=0.017). Patients with recurrent ICH more commonly presented in the fall and winter compared to summer and spring and during flu season. Patients with ICM who presented with FND or ICH or had recurrent ICH tended to present in the fall and winter or during flu season. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Clinical Neuroscience 03/2015; 22(6). DOI:10.1016/j.jocn.2015.01.007 · 1.38 Impact Factor
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    ABSTRACT: Object: The objective of this study was to characterize the clinical features of radiation-induced cavernous malformations (RICMs). Methods: The authors retrospectively reviewed the clinical and radiological characteristics of patients with RICMs. The features of these RICMs were then compared with features of nonradiation cavernous malformations (CMs) in 270 patients. Results: Thirty-two patients with RICMs were identified (56.2% men), with a median age of 31.1 years at RICM diagnosis. The median latency from radiation treatment to RICM diagnosis was 12.0 years (interquartile range 5.0-19.6 years). RICMs were always within the previous radiation port. RICMs were symptomatic at diagnosis in 46.9%, and were associated with symptomatic intracranial hemorrhage at any time in 43.8%. Older age at the time of radiation treatment and higher radiation dose were associated with shorter latency. RICMs tended to be diagnosed at a younger age than nonradiation CMs (median 31.1 vs 42.4 years, respectively; p = 0.054) but were significantly less likely to be symptomatic at the time of diagnosis (46.9% vs 65.8%, respectively; p = 0.036). RICMs were more likely to be multiple CMs than nonradiation CMs (p = 0.0002). Prospectively, the risk of symptomatic hemorrhage was 4.2% for RICMs and 2.3% for nonradiation CMs per person-year (p = 0.556). In the absence of symptoms at presentation, the risk of hemorrhage for RICMs was higher than for nonradiation CMs (4.2% vs 0.35%, respectively; p = 0.118). Conclusions: In this patient population, RICMs occurred within the radiation port approximately 12 years after radiation treatment. Compared with nonradiation CMs, RICMs were more likely to occur as multiple CMs, to present at a younger age, and were at least as likely to cause symptomatic hemorrhage.
    Journal of Neurosurgery 02/2015; 122(5):1-9. DOI:10.3171/2015.1.JNS141452 · 3.74 Impact Factor
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    ABSTRACT: Objective. To describe the treatment and outcomes in primary central nervous system vasculitis (PCNSV). Methods. We retrospectively studied a cohort of 163 consecutive patients with PCNSV seen at the Mayo Clinic over a 29-year period. We analyzed treatments and responses, and factors predictive of outcomes. Results. 85% of patients treated with prednisone alone responded favorably as did 80% of those given prednisone and cyclophosphamide. Relapses were observed in 27% of patients. 25% had discontinued therapy by last follow-up. Treatment with prednisone alone was associated with more frequent relapses (OR, 2.90), while large vessel involvement (OR, 6.14) and cerebral infarcts at diagnosis (OR, 3.32) were associated with poor response to treatment. Prominent gadolinium-enhanced lesions or meninges (OR, 2.28) were linked with continued treatment at last follow-up. Higher disability scores at last follow-up were associated with increasing age at diagnosis (OR, 1.44), and cerebral infarctions (OR, 3.74), while lower disability scores were associated with gadolinium enhanced cerebral lesions or meninges (OR, 0.35) and cerebral amyloid angiopathy (OR, 0.24). Increased mortality was associated with increasing age at diagnosis (HR 1.39), diagnosis by angiography (HR 3.28), cerebral infarction (HR, 4.44), and large cerebral vessel involvement (HR, 4.98), while reduced mortality with gadolinium enhanced cerebral lesions or meninges (HR, 0.20). Conclusion. The majority of patients with PCNSV responded to treatment. Recognition of findings at diagnosis which predict course or outcome may aid decisions regarding therapy. This article is protected by copyright. All rights reserved. Copyright © 2015 American College of Rheumatology.
    Arthritis and Rheumatology 02/2015; 67(6). DOI:10.1002/art.39068
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    ABSTRACT: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in adult primary central nervous system vasculitis (PCNSV). We studied a cohort of 163 patients with PCNSV who were seen at the Mayo Clinic from 1983 to 2011. We compared patients treated with MMF and those receiving other therapies. We identified 16 patients treated with MMF. MMF in combination with GCs achieved a favorable response in most patients. A significant proportion of patients treated with MMF had a less severe disability at last follow-up compared to those receiving other therapies (p = 0.023) and cyclophosphamide and prednisone (p = 0.017). No statistically significant differences were observed regarding relapses and ability to discontinue therapy at last follow-up. A trend to a more favorable treatment response was observed in patients treated with MMF compared to those treated with other therapies (p = 0.075). Only 1 patient suspended MMF for severe leukopenia. MMF seems to be an effective and safe therapy for adult PCNSV. Copyright © 2015 Elsevier Inc. All rights reserved.
    Seminars in Arthritis and Rheumatism 02/2015; 45(1). DOI:10.1016/j.semarthrit.2015.02.008 · 3.93 Impact Factor
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    ABSTRACT: To determine the influence of antithrombotic use on the etiology of primary intracerebral hemorrhage (ICH). We conducted a retrospective review of consecutive patients admitted with primary ICH from 2009 to 2012. Data recorded included age, history of hypertension, and use of antithrombotic medications. Imaging was reviewed to determine hemorrhage location and the presence and the location of any microhemorrhages. Etiologies were classified using a predetermined algorithm, which was based on existing literature. In total, 292 patients were included. Median age was 74 years (range, 18-101), and 52% were male (n = 151). Hemorrhage etiology was hypertension in 50.6% (n = 148), indeterminate in 29.5% (n = 86), and cerebral amyloid angiopathy (CAA) in 19.9% (n = 58). Most patients were on antithrombotics (61.3%, n = 179). Nearly half of the patients (49%) were 75 years of age or older, and the most common etiology in this group was hypertension (n = 77, 53%). There was a nonsignificant trend toward older age and CAA-ICH (median age, 77 years; interquartile range [IQR], 70-82 years) compared with other causes (median age, 74 years; IQR, 61-82 years; P = .07). There was no difference between CAA-ICH and other-cause ICH with respect to proportion of patients on antithrombotics in general (67% versus 60%; P = .367) or anticoagulants in particular (24% versus 25%; P = 1.000). The most common ICH etiology in this study was hypertension, regardless of age. Our findings do not suggest that the higher occurrence of ICH in older patients or in patients with CAA-associated ICH is because of a higher frequency of anticoagulant use. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 01/2015; 24(3). DOI:10.1016/j.jstrokecerebrovasdis.2014.11.009 · 1.67 Impact Factor
  • Jonathan Graff-Radford · Christopher J Boes · Robert D Brown ·

    Stroke 01/2015; 46(4). DOI:10.1161/STROKEAHA.114.007771 · 5.72 Impact Factor
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    ABSTRACT: Background and purpose: Very few cases of intracranial aneurysms (IAs) in twins have been reported. Previous work has suggested that vulnerability to IA formation is heritable. Twin studies provide an opportunity to evaluate the impact of genetics on IA characteristics, including IA location. We therefore sought to examine IA location concordance, multiplicity, and rupture status within affected twin-pairs. Methods: The Familial Intracranial Aneurysm study was a multicenter study whose goal was to identify genetic and other risk factors for formation and rupture of IAs. The study required at least three affected family members or an affected sibling pair for inclusion. Subjects with fusiform aneurysms, an IA associated with an AVM, or a family history of conditions known to predispose to IA formation, such as polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome were excluded. Twin-pairs were identified by birth date and were classified as monozygotic (MZ) or dizygotic (DZ) through DNA marker genotypes. In addition to zygosity, we evaluated twin-pairs by smoking status, major arterial territory of IAs, and rupture status. Location concordance was defined as the presence of an IA in the same arterial distribution (ICA, MCA, ACA, and vertebrobasilar), irrespective of laterality, in both members of a twin-pair. The Fisher exact test was used for comparisons between MZ and DZ twin-pairs. Results: A total of 16 affected twin-pairs were identified. Location concordance was observed in 8 of 11 MZ twin-pairs but in only 1 of 5 DZ twin-pairs (p = 0.08). Three MZ subjects had unknown IA locations and comprised the three instances of MZ discordance. Six of the 11 MZ twin-pairs and none of the 5 DZ twin-pairs had IAs in the ICA distribution (p = 0.03). Multiple IAs were observed in 11 of 22 MZ and 5 of 10 DZ twin-pairs. Thirteen (13) of the 32 subjects had an IA rupture, including 10 of 22 MZ twins. Conclusions: We found that arterial location concordance was greater in MZ than DZ twins, which suggests a genetic influence upon aneurysm location. The 16 twin-pairs in the present study are nearly the total of affected twin-pairs that have been reported in the literature to date. Further studies are needed to determine the impact of genetics in the formation and rupture of IAs.
    Cerebrovascular Diseases 01/2015; 39(2):82-86. DOI:10.1159/000369961 · 3.75 Impact Factor
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    ABSTRACT: Background and purpose: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. Results: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). Conclusions: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
    Stroke 11/2014; 45(12). DOI:10.1161/STROKEAHA.114.007362 · 5.72 Impact Factor
  • Kelly B Mahaney · Robert D Brown · James C Torner ·

    Journal of Neurosurgery 11/2014; 121(5):1022-3. · 3.74 Impact Factor
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    ABSTRACT: Objective: The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems. Methods: Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems. Results: The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; κ = 0.59, 95% confidence interval [CI] 0.58-0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (κ = 0.71, 95% CI 0.69-0.73) and lowest for small-artery occlusion (κ = 0.56, 95% CI 0.54-0.58). Conclusion: Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner.
    Neurology 09/2014; 83(18). DOI:10.1212/WNL.0000000000000942 · 8.29 Impact Factor
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    ABSTRACT: Background and purpose: Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. Methods: Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. Results: Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-8)). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10(-10)). Conclusions: We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.
    Stroke 09/2014; 45(11). DOI:10.1161/STROKEAHA.114.006096 · 5.72 Impact Factor
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    ABSTRACT: Object: The aim of this study was to determine age-related differences in short-term (1-year) outcomes in patients with unruptured intracranial aneurysms (UIAs). Methods: Four thousand fifty-nine patients prospectively enrolled in the International Study of Unruptured Intracranial Aneurysms were categorized into 3 groups by age at enrollment: < 50, 50-65, and > 65 years old. Outcomes assessed at 1 year included aneurysm rupture rates, combined morbidity and mortality from aneurysm procedure or hemorrhage, and all-cause mortality. Periprocedural morbidity, in-hospital morbidity, and poor neurological outcome on discharge (Rankin scale score of 3 or greater) were assessed in surgically and endovascularly treated groups. Univariate and multivariate associations of each outcome with age were tested. Results: The risk of aneurysmal hemorrhage did not increase significantly with age. Procedural and in-hospital morbidity and mortality increased with age in patients treated with surgery, but remained relatively constant with increasing age with endovascular treatment. Poor neurological outcome from aneurysm- or procedure-related morbidity and mortality did not differ between management groups for patients 65 years old and younger, but was significantly higher in the surgical group for patients older than 65 years: 19.0% (95% confidence interval [CI] 13.9%-24.4%), compared with 8.0% (95% CI 2.3%-13.6%) in the endovascular group and 4.2% (95% CI 2.3%-6.2%) in the observation group. All-cause mortality increased steadily with increasing age, but differed between treatment groups only in patients < 50 years of age, with the surgical group showing a survival advantage at 1 year. Conclusions: Surgical treatment of UIAs appears to be safe, prevents 1-year hemorrhage, and may confer a survival benefit in patients < 50 years of age. However, surgery poses a significant risk of morbidity and death in patients > 65 years of age. Risk of endovascular treatment does not appear to increase with age. Risks and benefits of treatment in older patients should be carefully considered, and if treatment is deemed necessary for patients older than 65 years, endovascular treatment may be the best option.
    Journal of Neurosurgery 08/2014; 121(5):1-15. DOI:10.3171/2014.6.JNS121179 · 3.74 Impact Factor
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    ABSTRACT: Primary central nervous system vasculitis (PCNSV) is an uncommon condition that affects the brain and the spinal cord. It is heterogeneous in presenting characteristics and outcomes. We report a patient with a catastrophic rapidly progressive course refractory to intensive treatment with pulses of methylprednisolone and iv cyclophosphamide. The condition rapidly deteriorated and the patient died 6 weeks after presentation. Rapidly progressive PCNSV represents the worst end of the clinical spectrum of PCNSV. These patients are characterised by bilateral, multiple, large cerebral vessel lesions on angiograms and multiple bilateral cerebral infarctions.
    Clinical and experimental rheumatology 05/2014; 32(3 Suppl 82):3-4. · 2.72 Impact Factor
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    ABSTRACT: The chronological development and natural history of cerebral aneurysms (CAs) remain incompletely understood. We used (14)C birth dating of a main constituent of CAs, that is, collagen type I, as an indicator for biosynthesis and turnover of collagen in CAs in relation to human cerebral arteries to investigate this further. Forty-six ruptured and unruptured CA samples from 43 patients and 10 cadaveric human cerebral arteries were obtained. The age of collagen, extracted and purified from excised CAs, was estimated using (14)C birth dating and correlated with CA and patient characteristics, including the history of risk factors associated with atherosclerosis and potentially aneurysm growth and rupture. Nearly all CA samples contained collagen type I, which was <5 years old, irrespective of patient age, aneurysm size, morphology, or rupture status. However, CAs from patients with a history of risk factors (smoking or hypertension) contained significantly younger collagen than CAs from patients with no risk factors (mean, 1.6±1.2 versus 3.9±3.3 years, respectively; P=0.012). CAs and cerebral arteries did not share a dominant structural protein, such as collagen type I, which would allow comparison of their collagen turnover. The abundant amount of relatively young collagen type I in CAs suggests that there is an ongoing collagen remodeling in aneurysms, which is significantly more rapid in patients with risk factors. These findings challenge the concept that CAs are present for decades and that they undergo only sporadic episodes of structural change.
    Stroke 04/2014; 45(6). DOI:10.1161/STROKEAHA.114.005461 · 5.72 Impact Factor

Publication Stats

5k Citations
1,264.07 Total Impact Points


  • 1988-2015
    • Mayo Clinic - Rochester
      • Department of Neurology
      Рочестер, Minnesota, United States
  • 2012
    • Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia
      Reggio nell'Emilia, Emilia-Romagna, Italy
  • 2001-2012
    • Mayo Foundation for Medical Education and Research
      • Division of Epidemiology
      Jacksonville, FL, United States
  • 2011
    • The University of Arizona
      • Department of Surgery
      Tucson, AZ, United States
  • 2008
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 2007
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
    • Columbia University
      New York, New York, United States