Brad A Racette

Brad A Racette
Washington University in St. Louis | WUSTL , Wash U · Department of Neurology

M.D.

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155
Publications
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Publications

Publications (155)
Article
Introduction Prior epidemiologic studies indicate that agricultural work and occupational exposure to pesticides may increase risk of Parkinson disease (PD). Findings may vary by country as well as by type and degree of agricultural exposures. We therefore studied whether work in agriculture, forestry, and fishing is related to the risk of PD in Fi...
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Objective: Studies suggest a greater risk of Parkinson disease (PD) after traumatic brain injury (TBI), but it is possible that the risk of TBI is greater in the prodromal period of PD. We aimed to examine the time-to-TBI in PD patients in their prodromal period compared to population-based controls. Methods: We identified 89,790 incident PD cas...
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Objective: To use administrative medical claims data to identify patients with incident Parkinson disease (PD) prior to diagnosis. Methods: Using a population-based case-control study of incident PD in 2009 among Medicare beneficiaries aged 66-90 years (89,790 cases, 118,095 controls) and the elastic net algorithm, we developed a cross-validated...
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Occupational manganese (Mn) exposure is associated with the development of parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron emission tomography (PET) imaging provides a non-invasive method of assessing dopamineric neuronal function. 6-[¹⁸F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo nigrostriatal function, but results...
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Objectives: Examine associations between pesticide exposure and signs or symptoms of parkinsonism. Methods: Prior to the 2014 pesticide spray season we examined 38 active pesticide handlers age 35-65 (median 43.5) who participated in the State of Washington's cholinesterase monitoring program in the Yakima Valley, where cholinesterase-inhibiting...
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Manganese (Mn) over-exposure in occupational settings is associated with basal ganglia toxicity and a movement disorder characterized by parkinsonism (i.e., the signs and symptoms of Parkinson disease). A simple test to help non-neurologists identify workers with clinical Mn neurotoxicity represents an unmet need. In a cohort of Mn-exposed workers...
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Introduction: Supranuclear gaze palsy (SGP) is a classic clinical feature of progressive supranuclear palsy (PSP) but is not specific for this diagnosis and has been reported to occur in several other neurodegenerative parkinsonian conditions. Our objective was to evaluate the association between SGP and autopsy-proven diagnoses in a large populat...
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Objective: To determine whether the parkinsonian phenotype prevalent in welders is progressive, and whether progression is related to degree of exposure to manganese (Mn)-containing welding fume. Methods: This was a trade union-based longitudinal cohort study of 886 American welding-exposed workers with 1,492 examinations by a movement disorders...
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Background: Chronic exposure to manganese (Mn) is a health concern in occupations such as welding because of well-established motor effects due to basal ganglia dysfunction. We hypothesized that cognitive control (the ability to monitor, manipulate, and regulate ongoing cognitive demands) would also be affected by chronic Mn exposure. Methods: W...
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Purpose of review: While the distinctive motor symptoms of Parkinson disease (PD) have been described for centuries, cognitive impairment has only recently been recognized as a central feature. Studies have yielded clues to the etiology and natural history of cognitive impairment in PD, but much remains unclear and effective therapies are needed....
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Introduction Previous studies have reported a dose-response relationship between occupational manganese (Mn) exposure and decreased motor function, adverse psychological symptoms, attention deficits, and working memory deficits. Residential exposure to Mn has also been associated with depression and anxiety but the relationship with environmental M...
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Importance: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associate...
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Parkinson disease (PD) is a degenerative movement disorder that affects up to 2% of persons older than age 60. The etiology of PD remains poorly understood, despite extensive research during the past 50. years. Some genetic factors are consistently associated with PD risk, as is tobacco smoking, which appears protective. Additional lifestyle factor...
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Importance Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials.Objective To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational St...
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Background Multiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the fi rst prospective natural history study of multiple system atrophy in the USA, and the eff ects of phenotype and autonomic failure on prognosis.
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To examine long-term care facility (LTCF or nursing home) use and end-of-life care for individuals with Parkinson disease (PD). In this nationwide retrospective cohort study, we compared LTCF and hospice utilization among Medicare beneficiaries diagnosed with PD by demographic, clinical, and physician characteristics. We also examined the impact of...
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To evaluate the appropriateness of dopamine receptor antagonist prescriptions in hospitalized patients with dopamine-requiring diseases after implementation of an automated prescription alert system. We examined dopamine receptor antagonist prescriptions in hospitalized patients with dopamine-requiring diseases and physician response to an automate...
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Parkinson disease (PD) is a progressive neurodegenerative disease that is associated with substantial morbidity and early mortality. Disease-related costs exceed $10 billion, not including medications, out-of-pocket expenses, or societal costs. Symptomatic treatment with levodopa, which has been available for over 30 years, and advanced therapies s...
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Manganese is an essential trace element with neurotoxicant properties at high levels that were first described in the mid-nineteenth century. The largest sources of occupational and environmental exposures are mining, fossil fuel combustion, and iron and steel industries. Manganese neurotoxicity has been described in many workers with high levels o...
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Full-text available
Multiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the first prospective natural history study of multiple system atrophy in the USA, and the effects of phenotype and autonomic failure on prognosis. We recruited participants with...
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Manganese (Mn) exposure is associated with increased T1-weighted Magnetic Resonance Imaging (MRI) signal in the basal ganglia. T1 signal intensity has been correlated with occupational Mn exposure but not with clinical symptomatology or neuropathology. This study investigated predictors of ex-vivo T1 MRI basal ganglia signal intensity in neuropatho...
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Long-term, high-level exposure to manganese (Mn) is associated with impaired central nervous system (CNS) function. We quantitatively explored relations between low-level Mn exposure and selected neurological outcomes in a longitudinal inception cohort of asymptomatic welder trainees. Welders with no previous occupational Mn exposure were observed...
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Hormone therapy (HT) is a class of medications widely prescribed to women in the Western world. Evidence from animal models and in vitro studies suggests that estrogen may protect against nigrostriatal system injury and increase dopamine synthesis, metabolism, and transport. Existing epidemiologic research indicates a possible reduced risk of Parki...
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Introduction: Neurologist-assessed parkinsonism signs are prevalent among workers exposed to manganese (Mn)-containing welding fume. Neuroinflammation may possibly play a role. Inducible nitric oxide synthase, coded by NOS2, is involved in inflammation, and particulate exposure increases the gene's expression through methylation of CpG sites in th...
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Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P...
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Despite evidence of adverse health effects resulting from exposure to manganese (Mn), biomarkers of exposure are poorly understood. To enhance understanding, mean blood Mn (MnB) and mean air Mn (MnA) were extracted from 63 exposure groups in 24 published papers, and the relationship was modeled using segmented regression. On a log/log scale, a posi...
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Parkinson disease is a neurodegenerative disease that affects gait and postural stability, resulting in an increased risk of falling. The purpose of this study was to estimate mortality associated with demographic factors after hip or pelvic (hip/pelvic) fracture in people with Parkinson disease. A secondary goal was to compare the mortality associ...
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Manganese (Mn) is a common neurotoxicant associated with a clinical syndrome that includes signs and symptoms referable to the basal ganglia. Despite many advances in understanding the pathophysiology of Mn neurotoxicity in humans, with molecular and structural imaging techniques, only a few case reports describe the associated pathological finding...
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To identify sociodemographic, clinical, and physician/practice factors associated with deep brain stimulation (DBS). DBS is a proven surgical therapy for Parkinson disease (PD), but is recommended only for patients with excellent health, results in significant out-of-pocket costs, and requires substantial physician involvement. Retrospective cohort...
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Since the original description of the health effects of inhaled occupational manganese (Mn) by Couper in 1837, an extensive literature details the clinical syndrome and pathophysiology of what was thought to be a rare condition. In the last decade, conventional wisdom regarding the clinicopathological effects of Mn has been challenged. Past exposur...
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Full-text available
As one of the purposes of anterior cruciate ligament reconstruction (ACLR) is to return athletes to their preinjury activity level, it is critical to understand variables influencing return to sport. Associations between return to sport and variables representing knee impairment, function and psychological status have not been well studied in athle...
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Background: Manganese (Mn) is a common component of welding fume. Exposure to Mn fume has been associated with parkinsonism. A simple and reliable screening tool to evaluate Mn exposed workers for neurotoxic injury would have broad occupational health application. Methods: This study investigated 490 occupational welders recruited from a trade u...
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Objective The purpose of this study was to investigate the neuropathology of chronic Mn exposure in South African Mn miners. Methods We performed a neuropathologic study of eight deceased Mn miners and ten deceased, non-Mn reference miners, none of whom had a diagnosis of a Mn- related clinical syndrome. We compared mean cell density in the caudate...
Data
Negative results from a randomized controlled trial of olanzapine for psychosis in Parkinson disease: data, CONSORT checklist and initial study protocol F1000Research. Michelle J Nichols, Johanna M Hartlein, Meredith GA Eicken, Brad A Racette, Kevin J Black Retrieved 18:07, Jul 09, 2013 (GMT) http://dx.doi.org/10.6084/m9.figshare.730446 - See more...
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Background: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use. Objective: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effecti...
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This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague–Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and...
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DJ-1 is a multifunctional protein that plays an important role in oxidative stress, cell death, and synucleinopathies, including Parkinson disease. Previous studies have demonstrated that total DJ-1 levels decrease in the cerebrospinal fluid, but do not change significantly in human plasma from patients with Parkinson disease when compared with con...
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Background: To determine the demographic distribution of Young Onset Parkinson's Disease (YOPD) in the United States and to quantify the burden of neuropsychiatric disease manifestations. Methods: Cross sectional study of 3,459,986 disabled Americans, aged 30-54, who were receiving Medicare benefits in the year 2005. We calculated race and sex d...
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To investigate the impact of neurologist care on Parkinson disease (PD)-related hospitalizations. Recent data indicate that neurologist treatment in PD may be associated with improved survival, yet is underutilized. Factors contributing to this improved survival remain unknown, but may be due in part to optimal disease treatment or avoidance of dis...
Article
Manganese (Mn), an established neurotoxicant, is a common component of welding fume. The neurological phenotype associated with welding exposures has not been well described. Prior epidemiologic evidence linking occupational welding to parkinsonism is mixed, and remains controversial. This was a cross-sectional and nested case-control study to inve...
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Full-text available
Plantar heel pain is a common disorder of the foot. The purpose of this study was to explore the relationship between duration of symptoms in plantar fasciitis patients and demographic factors, the intensity and location of pain, extent of previous treatment, and self-reported pain and function. The charts of patients presenting with plantar heel p...
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Objective To determine the relative contributions of individual pathologic protein deposits associated with dementia in patients with Parkinson disease (PD). Design Autopsied patients were analyzed from February 24, 2005, through July 25, 2010, to determine the distribution and severity of individual pathologic protein deposits (α-synuclein, Aβ, an...
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High forefoot plantar pressure is associated with plantar ulcers in people with diabetes and peripheral neuropathy. The purpose of this pilot study was to determine the safety and efficacy of botulinum toxin A injected into the gastrocnemius-soleus muscles to reduce muscle strength and plantar pressure. This double blind, randomized clinical trial...
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Manganese exposure leads to diffuse cerebral metal deposition with the highest concentration in the globus pallidus associated with increased T1-weighted MRI signal. T1 signal intensity in extra-pallidal basal ganglia (caudate and putamen) has not been studied in occupationally exposed workers. Diffusion weighted imaging is a non-invasive measure o...
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Full-text available
To investigate whether manganese toxicity secondary to end-state liver disease is associated with nigrastriatal dysfunction as measured by 6-[(18)F]fluoro-L-DOPA (FDOPA) positron emission tomographic (PET) imaging. Observational case report. The Movement Disorder Center at Washington University, St Louis, Missouri. An individual with manganese toxi...
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Full-text available
Manganese (Mn) is a common occupational exposure worldwide. Recent studies indicate clinical and imaging evidence of neurotoxicity in chronically exposed workers. The pathologic significance of these findings is unclear. South Africa produces over 80% of the world's Mn from mines from a desert region in the Northern Cape Province. An autopsy progra...
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Objective To determine the life expectancy of patients with Parkinson disease (PD) in the United States and identify demographic, geographic, and clinical factors that influence survival. Design Retrospective cohort study of 138 000 Medicare beneficiaries with incident PD who were identified in 2002 and followed up through 2008. Main Outcome Measur...
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Full-text available
Multiple system atrophy is a late, adult-onset α-synucleinopathy with no data on the effect of pregnancy on the disease course. Early stage multiple system atrophy can be difficult to distinguish from Parkinson's disease. We describe the case of an Irish woman with parkinsonism starting at age 31, initially diagnosed as having dopa-responsive, idio...
Article
Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide (Couper, 1837). Although the description did not use modern clinical terminology, a parkinsonian illness characterize...
Article
Objectives Manganese, an established neurotoxicant, is a common component of welding fumes. Symptoms of manganese poisoning include parkinsonism (PS). Prior epidemiologic evidence regarding occupational welding and PS is mixed, and remains highly controversial. Methods This study investigated the prevalence of PS among 581 active male shipyard wel...
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Full-text available
Welders are frequently exposed to Manganese (Mn), which may increase the risk of neurological impairment. Historical exposure estimates for welding-exposed workers are needed for epidemiological studies evaluating the relationship between welding and neurological or other health outcomes. The objective of this study was to develop and validate a mu...
Article
Objectives Manganese exposure leads to diffuse cerebral metal deposition with the highest concentration in the globus pallidus associated with increased T1-weighted MRI signal. T1 signal intensity in extra-pallidal basal ganglia (caudate and putamen) has not been studied in occupationally exposed workers. Diffusion weighted imaging (DWI) is a non-i...
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Objectives Historical exposure estimates for welding-exposed workers are needed for studies evaluating the relationship between welding and neurologic or other health outcomes. The objective of this study was to develop and validate a multivariate model to estimate quantitative levels of welding fume exposures based on welding particulate mass (PM)...
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To investigate the utilization of neurologist providers in the treatment of patients with Parkinson disease (PD) in the United States and determine whether neurologist treatment is associated with improved clinical outcomes. This was a retrospective observational cohort study of Medicare beneficiaries with PD in the year 2002. Multilevel logistic r...
Article
Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Subjects included 394 active workers exposed to we...
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Welding exposes workers to manganese (Mn) fumes, but it is unclear if this exposure damages dopaminergic neurons in the basal ganglia and predisposes individuals to develop parkinsonism. PET imaging with 6-[(18)F]fluoro-l-dopa (FDOPA) is a noninvasive measure of nigrostriatal dopaminergic neuron integrity. The purpose of this study is to determine...
Article
Sequence variants in coding and noncoding regions of THAP1 have been associated with primary dystonia. In this study, 1,446 Caucasian subjects with mainly adult-onset primary dystonia and 1,520 controls were genotyped for a variant located in the 5'-untranslated region of THAP1 (c.-237_236GA>TT). Minor allele frequencies were 62/2892 (2.14%) and 55...
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Full-text available
Parkinson disease associated with farming and exposure to agricultural chemicals has been reported in numerous studies; little is known about Parkinson disease risk factors for those living in urban areas. The authors investigated the relation between copper, lead, or manganese emissions and Parkinson disease incidence in the urban United States, s...
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The use of intramuscular injections of Botulinum neurotoxin A (BoNT-A) is common in the treatment of hypertonicity and movement disorders. Although most side effects are mild, systemic effects, manifested by generalized weakness distant from the site of injection, have been reported. Previously reported occurrences are discussed, and 3 new cases of...
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Full-text available
Parkinson disease is a common neurodegenerative disease. The racial, sex, age, and geographic distributions of Parkinson disease in the US are unknown. We performed a serial cross-sectional study of US Medicare beneficiaries aged 65 and older from the years 1995, and 2000-2005. Using over 450,000 Parkinson disease cases per year, we calculated Park...
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THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites. Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence...