Efficacy and Safety of OnabotulinumtoxinA for the Treatment of Pediatric Upper and Lower Limb Spasticity: Results From 2 Open-Label, Long-term Extension Trials.

Aim: To evaluate the efficacy and safety of onabotulinumtoxinA for treating upper and lower limb spasticity among pediatric patients in 2 open-label extension trials.

Methods: Patients aged <18 years received ≤5 doses of onabotulinumtoxinA (maximum: 8 U/kg [300 U], cycle 1; 10 U/kg [340 U], cycles 2-5) over 60 weeks. Week 6 efficacy endpoints included mean change from baseline in Modified Ashworth Scale-Bohannon and Modified Tardieu Scale scores, and mean Clinical Global Impression of Overall Change score.

The effect of air pollution on hospitalizations with Parkinson's disease among medicare beneficiaries nationwide.

We examined the effect of annual exposure to fine particulate matter (PM), nitrogen dioxide (NO), and ozone (O), on the rate of first hospitalization with a PD-related diagnosis (hospitalization with PD) among Medicare Fee-for-Service beneficiaries (2001-2016). Machine learning-derived annual air pollution concentrations were linked to residential ZIP codes. For each exposure, we fitted four models: 1) traditional outcome stratification, 2) marginal structural, 3) doubly robust, and 4) generalized propensity score matching Poisson regression models, adjusted for sociodemographic and meteorological confounders and long-term trends.

Adherence to practice parameters in Medicare beneficiaries with amyotrophic lateral sclerosis.

Objective: Physician adherence to evidence-based clinical practice parameters impacts outcomes of amyotrophic lateral sclerosis (ALS) patients. We sought to investigate compliance with the 2009 practice parameters for treatment of ALS patients in the United States, and sociodemographic and provider characteristics associated with adherence.

Methods: In this population-based, retrospective cohort study of incident ALS patients in 2009-2014, we included all Medicare beneficiaries age ≥20 with ≥1 International Classification of Diseases, Ninth Revision, Clinical Modification ALS code (335.

Olfactory tract/bulb metal concentration in Manganese-exposed mineworkers.

Background: Manganese (Mn) is an essential micronutrient as well as a well-established neurotoxicant. Occupational and environmental exposures may bypass homeostatic regulation and lead to increased systemic Mn levels. Translocation of ultrafine ambient airborne particles via nasal neuronal pathway to olfactory bulb and tract may be an important pathway by which Mn enters the central nervous system.

Fine Particulate Matter and Parkinson Disease Risk Among Medicare Beneficiaries.

Background And Objectives: Numerous studies suggest that environmental exposures play a critical role in Parkinson disease (PD) pathogenesis, and large, population-based studies have the potential to advance substantially the identification of novel PD risk factors. We sought to study the nationwide geographic relationship between PD and air pollution, specifically PM (particulate matter with a diameter <2.5 micrometers), using population-based US Medicare data.

Biologic targets of prescription medications and risk of neurodegenerative disease in United States Medicare beneficiaries.

Objective: To identify prescription medications associated with a lower risk of three neurodegenerative diseases: Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis.

Methods: We conducted a population-based, case-control study of U.S.

A predictive algorithm to identify ever smoking in medical claims-based epidemiologic studies.

Purpose: To develop and validate an algorithm to estimate probability of ever smoking using administrative claims.

Methods: Using population-based samples of Medicare-aged individuals (121,278 Behavioral Risk Factor Surveillance System survey respondents and 207,885 Medicare beneficiaries), we developed a logistic regression model to predict probability of ever smoking from demographic and claims data. We applied the model in 1,657,266 additional Medicare beneficiaries and calculated area under the receiver operating characteristic curve (AUC) using presence or absence of a tobacco-specific diagnosis or procedure code as our "gold standard.

Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis spectrum imaging.

Objective: To evaluate in-vivo neuroinflammation and white matter (WM) microstructural integrity in occupational manganese (Mn) exposure.

Methods: We assessed brain inflammation using Diffusion Basis Spectrum Imaging (DBSI) in 26 Mn-exposed welders, 17 Mn-exposed workers, and 26 non-exposed participants. Cumulative Mn exposure was estimated from work histories and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were completed by a movement specialist.

Protective Effects of Lovastatin in a Population-Based ALS Study and Mouse Model.

Objective: The objective of this study was to use a novel combined pharmacoepidemiologic and amyotrophic lateral sclerosis (ALS) mouse model approach to identify potential motor neuron protective medications.

Methods: We constructed a large, population-based case-control study to investigate motor neuron disease (MND) among US Medicare beneficiaries aged 66 to 90 in 2009. We included 1,128 incident MND cases and 56,400 age, sex, race, and ethnicity matched controls.

Neocortical Lewy Body Pathology Parallels Parkinson's Dementia, but Not Always.

Objective: The objective of this study was to evaluate the relationship between Parkinson's disease (PD) with dementia and cortical proteinopathies in a large population of pathologically confirmed patients with PD.

Methods: We reviewed clinical data from all patients with autopsy data seen in the Movement Disorders Center at Washington University, St. Louis, between 1996 and 2019.

Incidence of amyotrophic lateral sclerosis in older adults.

Introduction/aims: We investigated the age- and sex-specific incidence and survival of Medicare beneficiaries with amyotrophic lateral sclerosis (ALS) in patients 66 to 90 years of age.

Methods: We identified all incident ALS cases within a population-based sample of Medicare beneficiaries in 2009 (total: 22 000 177 person-years at risk for ALS). We calculated age- and sex-specific incidence in 2009 according to multiple, progressively more stringent case definitions.

Environmental manganese exposure and cognitive control in a South African population.

Objective: To characterize the association between environmental (residential air) manganese (Mn) exposure and cognitive performance, focusing on cognitive control, in a Black African population.

Methods: We administered the Go-No-Go, Digit Span, and Matrix Reasoning tests to population-based samples age ≥40 from a high Mn (smelter) exposed community, Meyerton (N = 629), and a demographically comparable low (background levels) non-exposed community, Ethembalethu, (N = 96) in Gauteng province, South Africa. We investigated the associations between community and performance on the cognitive tests, using linear regression.

Efficacy and safety of onabotulinumtoxinA with standardized physiotherapy for the treatment of pediatric lower limb spasticity: A randomized, placebo-controlled, phase III clinical trial.

Background: Spasticity is common in cerebral palsy and can result in pain and diminished health-related quality of life.

Objective: To evaluate the safety and efficacy of onabotulinumtoxinA for lower limb spasticity treatment in children with cerebral palsy.

Methods: In this registrational phase 3, multinational, randomized, double-blind, placebo-controlled trial (NCT01603628), children (2-< 17 years) with cerebral palsy and ankle spasticity (Modified Ashworth Scale-Bohannon [MAS] score≥2) were randomized 1 : 1 : 1 to standardized physical therapy and onabotulinumtoxinA (4 or 8 U/kg), or placebo.

A comparison of prediction approaches for identifying prodromal Parkinson disease.

Identifying people with Parkinson disease during the prodromal period, including via algorithms in administrative claims data, is an important research and clinical priority. We sought to improve upon an existing penalized logistic regression model, based on diagnosis and procedure codes, by adding prescription medication data or using machine learning. Using Medicare Part D beneficiaries age 66-90 from a population-based case-control study of incident Parkinson disease, we fit a penalized logistic regression both with and without Part D data.

Solvent exposed occupations and risk of Parkinson disease in Finland.

Introduction: Epidemiologic and toxicology studies suggest that exposure to various solvents, especially chlorinated hydrocarbon solvents, might increase Parkinson disease (PD) risk.

Methods: In a population-based case-control study in Finland, we examined whether occupations with potential for solvent exposures were associated with PD. We identified newly diagnosed cases age 45-84 from a nationwide medication reimbursement register in 1995-2014.

Depression and anxiety in a manganese-exposed community.

Objective: To characterize the association between residential environmental manganese (Mn) exposure and depression and anxiety, given prior associations among occupationally-exposed workers.

Methods: We administered the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) to 697 study participants in their preferred languages. These participants represented a population-based sample of residents aged ≥40 from two predominantly Black African communities in Gauteng province, South Africa: 605 in Meyerton, adjacent to a large Mn smelter, and 92 in Ethembalethu, a comparable non-exposed community.

A Rapid Motor Task-Based Screening Tool for Parkinsonism in Community-Based Studies.

The prevalence of parkinsonism in developing countries is largely unknown due to difficulty in ascertainment because access to neurologists is often limited. Develop and validate a parkinsonism screening tool using objective motor task-based tests that can be administered by non-clinicians. In a cross-sectional population-based sample from South Africa, we evaluated 315 adults, age >40, from an Mn-exposed (smelter) community, using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3), Purdue grooved pegboard, and kinematic-UPDRS3-based motor tasks.

Principal Component Analysis of Striatal and Extrastriatal D2 Dopamine Receptor Positron Emission Tomography in Manganese-Exposed Workers.

The relationships between the neurotoxicant manganese (Mn), dopaminergic pathology, and parkinsonism remain unclear. Therefore, we used [11C](N-methyl)benperidol (NMB) positron emission tomography to investigate the associations between Mn exposure, striatal and extrastriatal D2 dopamine receptors (D2R), and motor function in 54 workers with a range of Mn exposure. Cumulative Mn exposure was estimated from work histories, and all workers were examined by a movement specialist and completed a Grooved Pegboard test (GPT).

Severity of parkinsonism associated with environmental manganese exposure.

Background: Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016-2020.

Herpesvirus Infections and Risk of Parkinson's Disease.

Introduction: Herpesviruses might play a role in the pathogenesis of neurodegenerative disorders. We sought to examine a possible association between alpha herpesvirus infections and Parkinson's disease.

Methods: We conducted a population-based case-control study of incident Parkinson's disease in 2009 Medicare beneficiaries age 66-90 years (89,790 cases, 118,095 randomly selected comparable controls).

Is Levodopa Response a Valid Indicator of Parkinson's Disease?

Background: The clinical diagnosis of Parkinson's disease (PD) requires the presence of parkinsonism and supportive criteria that include a clear and dramatic beneficial response to dopaminergic therapy. Our aim was to test the diagnostic criterion of dopaminergic response by evaluating its association with pathologically confirmed diagnoses in a large population of parkinsonian patients.

Methods: We reviewed clinical data maintained in an electronic medical record from all patients with autopsy data who had been seen in the Movement Disorders Center at Washington University, St.

Validation of Parkinson's Disease-Related Questionnaires in South Africa.

Background: There are very few epidemiological studies investigating Parkinson's disease (PD) in Africa. The hundreds of local languages and dialects make traditional screening and clinical evaluation tools difficult to use.

Objective: The objective of the study was to validate two commonly used PD questionnaires in an African population.

[11C]dihydrotetrabenazine Positron Emission Tomography in Manganese-Exposed Workers.

Objective: To understand the neurotoxic effects of manganese (Mn) exposure on monoaminergic function, utilizing [C]dihydrotetrabenazine (DTBZ) positron emission tomography (PET) to measure vesicular monoamine transporter 2 (VMAT2).

Methods: Basal ganglia and thalamic DTBZ binding potentials (BPND) were calculated on 56 PETs from 41 Mn-exposed workers. Associations between cumulative Mn exposure, regional BPND, and parkinsonism were examined by mixed linear regression.

Fractures in the prodromal period of Parkinson disease.

Objective: To examine the association between fractures and Parkinson disease (PD) during the 5-year prodromal phase as compared to controls.

Methods: We performed a population-based case-control study of Medicare beneficiaries in the United States from 2004 to 2009. We identified 89,632 incident PD cases and 117,760 comparable controls 66-90 years of age in 2009.

Validation of a Parkinson Disease Predictive Model in a Population-Based Study.

Parkinson disease (PD) has a relatively long prodromal period that may permit early identification to reduce diagnostic testing for other conditions when patients are simply presenting with early PD symptoms, as well as to reduce morbidity from fall-related trauma. Earlier identification also could prove critical to the development of neuroprotective therapies. We previously developed a PD predictive model using demographic and Medicare claims data in a population-based case-control study.