Robert D Brown

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (183)1050.18 Total impact

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    ABSTRACT: Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with cerebral amyloid angiopathy. The annual incidence rate of PCNSV was estimated at 2.4 cases per 1,000,000 person-years. PCNSV appears to consist of several subsets defined by the size of the vessels involved, the clinical characteristics at presentation, MRI findings, and histopathological patterns on biopsy. Early recognition and treatment may reduce poor outcomes.
    Medicine 05/2015; 94(21):e738. DOI:10.1097/MD.0000000000000738 · 4.87 Impact Factor
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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 · 1.32 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 · 3.23 Impact Factor
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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; DOI:10.1016/j.semarthrit.2015.02.008 · 3.63 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.
    02/2015; DOI:10.1002/art.39068
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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 · 1.99 Impact Factor
  • Stroke 01/2015; 46(4). DOI:10.1161/STROKEAHA.114.007771 · 6.02 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. © 2015 S. Karger AG, Basel.
    Cerebrovascular Diseases 01/2015; 39(2):82-86. DOI:10.1159/000369961 · 3.70 Impact Factor
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    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.
  • Kelly B Mahaney, Robert D Brown, James C Torner
    Journal of Neurosurgery 11/2014; 121(5):1022-3. · 3.23 Impact Factor
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    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; DOI:10.1212/WNL.0000000000000942 · 8.30 Impact Factor
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    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.
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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 · 3.23 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. · 2.97 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 · 6.02 Impact Factor
  • Robert D Brown, Joseph P Broderick
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    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. DOI:10.1016/S1474-4422(14)70015-8 · 21.82 Impact Factor
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    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; DOI:10.1161/STROKEAHA.114.004519 · 6.02 Impact Factor
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    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; DOI:10.3171/2014.1.JNS131619 · 3.15 Impact Factor
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    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; 82(14). DOI:10.1212/WNL.0000000000000293 · 8.30 Impact Factor

Publication Stats

4k Citations
1,050.18 Total Impact Points

Institutions

  • 1988–2015
    • Mayo Clinic - Rochester
      • • Department of Neurology
      • • Department of Cardiovascular Diseases
      Рочестер, Minnesota, United States
  • 2012
    • Mayo Foundation for Medical Education and Research
      • Division of Epidemiology
      Jacksonville, FL, United States
    • Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia
      Reggio nell'Emilia, Emilia-Romagna, Italy
    • Indiana University-Purdue University Indianapolis
      • Department of Neurology
      Indianapolis, IN, United States
  • 2011
    • The University of Arizona
      • Department of Surgery
      Tucson, AZ, United States
  • 2007
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
  • 2003
    • University of Virginia
      • Department of Neurology
      Charlottesville, VA, United States