Robert D Brown

Mayo Clinic - Rochester, Rochester, Minnesota, United States

Are you Robert D Brown?

Claim your profile

Publications (163)949.84 Total impact

  • 01/2015;
  • Jason Mackey, Robert D Brown, Laura Sauerbeck, Richard Hornung, Charles J Moomaw, Daniel L Koller, Tatiana Foroud, Ranjan Deka, Daniel Woo, Dawn Kleindorfer, Matthew L Flaherty, Irene Meissner, Craig Anderson, Guy Rouleau, E Sander Connolly, John Huston, Joseph P Broderick
    [Show abstract] [Hide abstract]
    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. © 2015 S. Karger AG, Basel.
    Cerebrovascular diseases (Basel, Switzerland). 01/2015; 39(2):82-86.
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    11/2014;
  • Kelly B Mahaney, Robert D Brown, James C Torner
    Journal of neurosurgery. 11/2014; 121(5):1022-3.
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Neurology 09/2014; · 8.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    09/2014;
  • [Show abstract] [Hide abstract]
    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;
  • [Show abstract] [Hide abstract]
    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. · 2.97 Impact Factor
  • [Show abstract] [Hide abstract]
    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; · 6.02 Impact Factor
  • Robert D Brown, Joseph P Broderick
    [Show abstract] [Hide abstract]
    ABSTRACT: Intracranial saccular or berry aneurysms are common, occurring in about 1-2% of the population. Unruptured intracranial aneurysms are increasingly being detected as cross-sectional imaging techniques are used more frequently in clinical practice. Once an unruptured intracranial aneurysm is detected, decisions regarding optimum management are made on the basis of careful comparison of the short-term and long-term risks of aneurysmal rupture with the risk associated with the intervention, whether that be surgical clipping or endovascular management. Several factors need to be carefully considered, including aneurysm size and location, the patient's family history and medical history, and the availability of an interventional option that has an acceptable risk. The patient's knowledge that they have an unruptured intracranial aneurysm can lead to substantial stress and anxiety, and their perspective regarding treatment, after hearing an unbiased appraisal of the rupture risks and the risk of interventional treatment, is of the utmost importance. Controversy remains regarding optimum management, and thorough assessments of the risks and benefits of contemporary management options, specific to aneurysm size, location, and many other aneurysm and patient factors, are needed.
    The Lancet Neurology 04/2014; 13(4):393-404. · 21.82 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.
    Stroke 03/2014; · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Object The aim of this study was to determine the prospective hemorrhage rate in a group of retrospectively identified patients in whom symptoms had an unclear relationship to an intracerebral cavernous malformation (ICM) or the malformation itself was an incidental finding. Methods Patients with incidentally discovered ICMs diagnosed between 1989 and 1999 were identified from a previously published cohort. Those with ICMs having an unclear relationship with existing symptoms were also eligible for analysis. Updated clinical and radiographic data pertaining to symptomatic intracerebral hemorrhage related to the ICM or new seizures were obtained through medical chart review and mail survey. In select patients, phone calls were made and death certificates were obtained when possible. The prospective hemorrhage rate was calculated as the number of prospective hemorrhages divided by the number of patient-years of follow-up. Results There were 1311 patient-years of follow-up among the 107 patients (49.5% male; mean age at diagnosis 52 years) eligible for this study. Forty-four patients died in the follow-up period, and the cause of death could be determined in 34 (77%). Two patients had a prospective hemorrhage, which was definitively related to the ICM in only one. Thus, the definitive prospective bleed rate was 0.08% per patient-year. No new seizures developed in any of the patients during the follow-up period. Conclusions The risk of prospective hemorrhage in patients presenting asymptomatically with ICM is very low. This information can be useful in managing such patients and may be most applicable to those with a single ICM.
    Journal of Neurosurgery 03/2014; · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary CNS vasculitis (PCNSV) is an uncommon disorder of unknown cause that is restricted to brain and spinal cord. Glucocorticoids alone or in combination with cyclophosphamide achieve a favorable response in most patients.(1,2) However, some patients are intolerant or respond poorly to cyclophosphamide, therefore there is the need for new treatment options. We report a patient with PCNSV who appeared to respond to treatment with corticosteroids and rituximab. This study was approved by the Mayo Clinic Institutional Review Board and written informed patient consent to perform the study was obtained.
    Neurology 03/2014; · 8.30 Impact Factor
  • Clinical and experimental rheumatology 02/2014; · 2.97 Impact Factor
  • Giuseppe Lanzino, Robert D Brown
    Neurosurgical FOCUS 01/2014; 36(1):Introduction. · 2.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The decision of whether to treat incidental intracranial saccular aneurysms is complicated by limitations in current knowledge of their natural history. We combined individual patient data from prospective cohort studies to determine predictors of aneurysm rupture and to construct a risk prediction chart to estimate 5-year aneurysm rupture risk by risk factor status. We did a systematic review and pooled analysis of individual patient data from 8382 participants in six prospective cohort studies with subarachnoid haemorrhage as outcome. We analysed cumulative rupture rates with Kaplan-Meier curves and assessed predictors with Cox proportional-hazard regression analysis. Rupture occurred in 230 patients during 29 166 person-years of follow-up. The mean observed 1-year risk of aneurysm rupture was 1·4% (95% CI 1·1-1·6) and the 5-year risk was 3·4% (2·9-4·0). Predictors were age, hypertension, history of subarachnoid haemorrhage, aneurysm size, aneurysm location, and geographical region. In study populations from North America and European countries other than Finland, the estimated 5-year absolute risk of aneurysm rupture ranged from 0·25% in individuals younger than 70 years without vascular risk factors with a small-sized (<7 mm) internal carotid artery aneurysm, to more than 15% in patients aged 70 years or older with hypertension, a history of subarachnoid haemorrhage, and a giant-sized (>20 mm) posterior circulation aneurysm. By comparison with populations from North America and European countries other than Finland, Finnish people had a 3·6-times increased risk of aneurysm rupture and Japanese people a 2·8-times increased risk. The PHASES score is an easily applicable aid for prediction of the risk of rupture of incidental intracranial aneurysms. Netherlands Organisation for Health Research and Development.
    The Lancet Neurology 11/2013; · 21.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To analyze the clinical findings, response to therapy, and outcomes of patients with cerebral vascular amyloid-β (Aβ) deposition with and without inflammatory vascular infiltration. We report 78 consecutive patients with cerebral vascular Aβ deposition examined at Mayo Clinic Rochester over 25 years (1987 through 2011). Specimens reviewed by a neuropathologist showed 40 with vascular Aβ peptide without inflammation (cerebral amyloid angiopathy [CAA]), 28 with granulomatous vasculitis (Aβ-related angiitis or ABRA), and 10 with perivascular CAA-related inflammation. We also matched findings in 118 consecutive patients with primary CNS vasculitis (PCNSV) without Aβ seen over 25 years (1983 through 2007). Compared to the 40 with CAA, the 28 with ABRA were younger at diagnosis (p = 0.05), had less altered cognition (p = 0.02), fewer neurologic deficits (p = 0.02), and fewer intracranial hemorrhages (<0.001), but increased gadolinium leptomeningeal enhancement (p = 0.01) at presentation, and less mortality and disability at last follow-up (p < 0.001). Compared with PCNSV, the 28 patients with ABRA were older at diagnosis (p < 0.001), had a higher frequency of altered cognition (p = 0.05), seizures/spells (p = 0.006), gadolinium leptomeningeal enhancement (p < 0.001), and intracerebral hemorrhage (p = 0.02), lower frequency of hemiparesis (p = 0.01), visual symptoms (p = 0.04), and MRI evidence of cerebral infarction (p = 0.003), but higher CSF protein levels (p = 0.03). Results of treatment and outcomes in ABRA and PCNSV were similar. ABRA appears to represent a distinct subset of PCNSV.
    Neurology 09/2013; · 8.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations within the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL mutations appear to be restricted to the first twenty-four exons, resulting in the gain or loss of a cysteine amino acid. The role of other exonic NOTCH3 variation not involving cysteine residues and mutations in exons 25-33 in ischemic stroke remains unresolved. All 33 exons of NOTCH3 were sequenced in 269 Caucasian probands from the Siblings With Ischemic Stroke Study (SWISS), a 70-center North American affected sibling pair study and 95 healthy Caucasian control subjects. Variants identified by sequencing in the SWISS probands were then tested for association with ischemic stroke using US Caucasian controls collected at the Mayo Clinic (n=654), and further assessed in a Caucasian (n=802) and African American (n=298) patient-control series collected through the Ischemic Stroke Genetics Study (ISGS). Sequencing of the 269 SWISS probands identified one (0.4%) with small vessel type stroke carrying a known CADASIL mutation (p.R558C; Exon 11). Of the 19 common NOTCH3 variants identified, the only variant significantly associated with ischemic stroke after multiple testing adjustment was p.R1560P (rs78501403; Exon 25) in the combined SWISS and ISGS Caucasian series (Odds Ratio [OR] 0.50, P=0.0022) where presence of the minor allele was protective against ischemic stroke. Although only significant prior to adjustment for multiple testing, p.T101T (rs3815188; Exon 3) was associated with an increased risk of small-vessel stroke (OR: 1.56, P=0.008) and p.P380P (rs61749020; Exon 7) was associated with decreased risk of large-vessel stroke (OR: 0.35, P=0.047) in Caucasians. No significant associations were observed in the small African American series. Cysteine-affecting NOTCH3 mutations are rare in patients with typical ischemic stroke, however our observation that common NOTCH3 variants may be associated with risk of ischemic stroke warrants further study.
    PLoS ONE 09/2013; 8(9):e75035. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10 296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14 549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research-generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived. The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.
    Stroke 09/2013; · 6.02 Impact Factor

Publication Stats

3k Citations
949.84 Total Impact Points

Institutions

  • 2002–2014
    • Mayo Clinic - Rochester
      • • Department of Neurology
      • • Department of Radiology
      Rochester, Minnesota, United States
  • 2013
    • Vanderbilt University
      Nashville, Michigan, United States
  • 2012
    • Indiana University-Purdue University Indianapolis
      • Department of Neurology
      Indianapolis, IN, United States
    • Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia
      Reggio nell'Emilia, Emilia-Romagna, Italy
    • University of Florida
      • Department of Emergency Medicine
      Gainesville, FL, United States
  • 2005–2012
    • University of Cincinnati
      • Department of Neurology
      Cincinnati, OH, United States
    • Mayo Foundation for Medical Education and Research
      • • Division of Epidemiology
      • • Department of Neurology
      • • Department of Emergency Medicine
      Jacksonville, FL, United States
  • 2011
    • The University of Arizona
      • Department of Surgery
      Tucson, AZ, United States
  • 2010
    • Rowe Neuroscience Institute
      Lenexa, Kansas, United States
  • 2007–2009
    • National Institutes of Health
      • • Section on Mammalian Molecular Genetics
      • • Section on Molecular Genetics of Immunity
      Bethesda, MD, United States
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
  • 2008
    • National Institute on Aging
      • Laboratory of Neurogenetics (LNG)
      Baltimore, Maryland, United States
  • 2003–2008
    • University of Virginia
      • • Department of Public Health Sciences
      • • Department of Neurology
      Charlottesville, VA, United States