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Objective To develop and implement a customized toolkit within the electronic medical record (EMR) to standardize care of patients with brain tumors. Patients and Methods We built a customized structured clinical documentation support toolkit to capture standardized data at office visits. We detail the process by which this toolkit was conceptualized and developed. Toolkit development was a physician-led process to determine a work flow and necessary elements to support best practices as defined by the neuro-oncology clinical team. Results We have developed in our EMR system a customized work flow for clinical encounters with neuro-oncology patients. In addition to providing a road map for clinical care by our neuro-oncology team, the toolkit is designed to maximize discrete data capture. Several hundred fields of discrete data are captured through the toolkit in the context of our routine office visits. We describe the characteristics of patients seen at our clinic, the adoption of the toolkit, current initiatives supported by the toolkit, and future applications. Conclusion The EMR can be effectively structured to standardize office visits and improve discrete data capture. This toolkit can be leveraged to support quality improvement and practice-based research initiatives at the point of care in a neuro-oncology practice.

Background We developed and implemented a structured clinical documentation support (SCDS) toolkit within the electronic medical record, to optimize patient care, facilitate documentation, and capture data at office visits in a sleep medicine/neurology clinic for patient care and research collaboration internally and with other centers. Methods To build our SCDS toolkit, physicians met frequently to develop content, define the cohort, select outcome measures, and delineate factors known to modify disease progression. We assigned tasks to the care team and mapped data elements to the progress note. Programmer analysts built and tested the SCDS toolkit, which included several score tests. Auto scored and interpreted tests included the Generalized Anxiety Disorder 7-item, Center for Epidemiological Studies Depression Scale, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index, and the International Restless Legs Syndrome Study Group Rating Scale. The SCDS toolkits also provided clinical decision support (untreated anxiety or depression) and prompted enrollment of patients in a DNA biobank. Results The structured clinical documentation toolkit captures hundreds of fields of discrete data at each office visit. This data can be displayed in tables or graphical form. Best practice advisories within the toolkit alert physicians when a quality improvement opportunity exists. As of May 1, 2019, we have used the toolkit to evaluate 18,105 sleep patients at initial visit. We are also collecting longitudinal data on patients who return for annual visits using the standardized toolkits. We provide a description of our development process and screenshots of our toolkits. Conclusions The electronic medical record can be structured to standardize Sleep Medicine office visits, capture data, and support multicenter quality improvement and practice-based research initiatives for sleep patients at the point of care.

Objective: To use the electronic medical record (EMR) to optimize patient care, facilitate documentation, and support quality improvement and practice-based research in a concussion (mild traumatic brain injury; mTBI) clinic.Methods: We built a customized structured clinical documentation support (SCDS) toolkit for patients in a concussion specialty clinic. The toolkit collected hundreds of fields of discrete, standardized data. Autoscored and interpreted score tests include the Generalized Anxiety Disorder 7-item scale, Center for Epidemiology Studies Depression scale, Insomnia Severity Index, and Glasgow Coma Scale. Additionally, quantitative score measures are related to immediate memory, concentration, and delayed recall. All of this data collection occurred in a standard appointment length.Results: To date, we evaluated 619 patients at an initial office visit after an mTBI. We provided a description of our toolkit development process, and a summary of the data electronically captured using the toolkit.Conclusions: The electronic medical record can be used to effectively structure and standardize care in a concussion clinic. The toolkit supports the delivery of care consistent with Best Practices, provides opportunities for point of care decision support, and writes comprehensive progress notes that can be communicated to other providers.

Genetic risk factors for Parkinson's disease (PD) risk and progression have been identified from genome-wide association studies (GWAS), as well as studies of familial forms of PD, implicating common variants at more than 90 loci and pathogenic or likely pathogenic variants at 16 loci. With the goal of understanding whether genetic variants at these PD-risk loci/genes differentially contribute to individual clinical phenotypic characteristics of PD, we used structured clinical documentation tools within the electronic medical record in an effort to provide a standardized and detailed clinical phenotypic characterization at the point of care in a cohort of 856 PD patients. We analyzed common SNPs identified in previous GWAS studies, as well as low-frequency and rare variants at parkinsonism-associated genes in the MDSgene database for their association with individual clinical characteristics and test scores at baseline assessment in our community-based PD patient cohort: age at onset, disease duration, Unified Parkinson's Disease Rating Scale I-VI, cognitive status, initial and baseline motor and non-motor symptoms, complications of levodopa therapy, comorbidities and family history of neurological disease with one or more than one affected family members. We find that in most cases an individual common PD-risk SNP identified in GWAS is associated with only a single clinical feature or test score, while gene-level tests assessing low-frequency and rare variants reveal genes associated in either a unique or partially overlapping manner with the different clinical features and test scores. Protein-protein interaction network analysis of the identified genes reveals that while some of these genes are members of already identified protein networks others are not. These findings indicate that genetic risk factors for PD differentially affect the phenotypic presentation and that genes associated with PD risk are also differentially associated with individual disease phenotypic characteristics at baseline. These findings raise the intriguing possibility that different SNPs/gene effects impact discrete phenotypic characteristics. Furthermore, they support the hypothesis that different gene and protein-protein interaction networks that underlie PD risk, the PD phenotype, and the neurodegenerative process leading to the disease phenotype, and point to the significance of the genetic background on disease phenotype.

Background: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, both without prevention or cure. The Mediterranean diet (MeDi) may be neuroprotective by modulating gut microbiota. We aimed to assess the effects of adherence to MeDi on the gut microbiota in relation to AD or PD risk. It was our hypothesis that weak adherence to the MeDi, gut microbial dysbiosis, and AD or PD are in a chain of causality. Methods: A search from inception to November 2020 was conducted in PubMed, CINAHL, EMBASE, Web of Science, Global Health, Biological Abstracts, and Grey Literature Report databases. Two searches were conducted: 1) (MeDi or Microbiota) and (PD or AD) and 2) MeDi and microbiota. Inclusion criteria for papers were specified prior to review. Findings: Of 4,672 studies identified, 65 were eligible for inclusion. These studies were divided into five groups: MeDi and AD risk (n=5), MeDi and PD risk (n=2), MeDi and microbial composition or metabolomics (n=21), AD and microbial composition or metabolomics (n=7), and PD and microbial composition or metabolomics (n=30). Adherence to the MeDi was associated with a lower risk of AD, but the results were conflicting for PD risk due to the limited studies. The gut microbiota of MeDi non-adherers shared commonalities with the gut microbiota of AD or PD cases, while the gut microbiota of MeDi adherers was more similar to the gut microbiota of healthy controls than of cases. Eight genera and two species had an inverse relationship with MeDi and AD, and one family, eight genera and three species had an inverse relationship with MeDi and PD. Interpretation: Adherence to the MeDi is associated with a lower risk for AD, and to a lesser extent PD. MeDi, gut microbiota, and neurodegeneration may be causally related. Registration Details: Prospero (CRD42020221170). Funding Information: There was no funding source for this study. Declaration of Interests: None to declare.

Alzheimer’s disease (AD) and AD-related dementias (ADRD) are a class of neurodegenerative diseases affecting about 5.7 million Americans. There is no cure for AD/ADRD. Current interventions have modest effects and focus on attenuating cognitive impairment. Detection of patients at high risk of AD/ADRD is crucial for timely interventions to modify risk factors and primarily prevent cognitive decline and dementia, and thus to enhance the quality of life and reduce health care costs. This study seeks to investigate both knowledge-driven (where domain experts identify useful features) and data-driven (where machine learning models select useful features among all available data elements) approaches for AD/ADRD early prediction using real-world electronic health records (EHR) data from the University of Florida (UF) Health system. We identified a cohort of 59,799 patients and examined four widely used machine learning algorithms following a standard case-control study. We also examined the early prediction of AD/ADRD using patient information 0-years, 1-year, 3-years, and 5-years before the disease onset date. The experimental results showed that models based on the Gradient Boosting Trees (GBT) achieved the best performance for the data-driven approach and the Random Forests (RF) achieved the best performance for the knowledge-driven approach. Among all models, GBT using a data-driven approach achieved the best area under the curve (AUC) score of 0.7976, 0.7192, 0.6985, and 0.6798 for 0, 1, 3, 5-years prediction, respectively. We also examined the top features identified by the machine learning models and compared them with the knowledge-driven features identified by domain experts. Our study demonstrated the feasibility of using electronic health records for the early prediction of AD/ADRD and discovered potential challenges for future investigations.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent neurodegenerative diseases, both without prevention or cure. The Mediterranean diet (MeDi) may be neuroprotective by modulating gut microbiota. We aimed to assess the effects of adherence to MeDi on the gut microbiota in relation to AD or PD risk. A search from inception to November 2020 was conducted in PubMed, CINAHL, EMBASE, Web of Science, Global Health, Biological Abstracts, and Grey Literature Report databases. Two searches were conducted: 1) (MeDi or Microbiota) and (PD or AD) and 2) MeDi and microbiota. Inclusion criteria for papers were specified prior to review. Of 4672 studies identified, 64 were eligible for inclusion. These studies were divided into five groups: MeDi and AD risk (n = 4), MeDi and PD risk (n = 2), MeDi and microbial composition or metabolomics (n = 21), AD and microbial composition or metabolomics (n = 7), and PD and microbial composition or metabolomics (n = 30). Adherence to the MeDi was associated with a lower risk of AD and PD development. Eight genera and two species of bacteria had an inverse relationship with MeDi and AD, and one family, eight genera and three species of bacteria had an inverse relationship with MeDi and PD. More studies are needed to investigate if MeDi, gut microbiota, and neurodegeneration are causally related.

We studied the long-term risk of depressive and anxiety symptoms in women who underwent bilateral oophorectomy before menopause.We conducted a cohort study among all women residing in Olmsted County, MN, who underwent bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the bilateral oophorectomy cohort was matched by age with a referent woman from the same population who had not undergone an oophorectomy. In total, we studied 666 women with bilateral oophorectomy and 673 referent women. Women were followed for a median of 24 years, and depressive and anxiety symptoms were assessed using a structured questionnaire via a direct or proxy telephone interview performed from 2001 through 2006.Women who underwent bilateral oophorectomy before the onset of menopause had an increased risk of depressive symptoms diagnosed by a physician (hazard ratio = 1.54, 95% CI: 1.04-2.26, adjusted for age, education, and type of interview) and of anxiety symptoms (adjusted hazard ratio = 2.29, 95% CI: 1.33-3.95) compared with referent women. The findings remained consistent after excluding depressive or anxiety symptoms that first occurred within 10 years after oophorectomy. The associations were greater with younger age at oophorectomy but did not vary across indications for the oophorectomy. In addition, treatment with estrogen to age 50 years in women who underwent bilateral oophorectomy at younger ages did not modify the risk.Bilateral oophorectomy performed before the onset of menopause is associated with an increased long-term risk of depressive and anxiety symptoms.

Objective To use the electronic medical record (EMR) to optimize patient care, facilitate documentation, and support quality improvement and practice-based research, in a headache specialty clinic. Background Many physicians enter data into the EMR as unstructured free text and not as discrete data. This makes it challenging to use data for quality improvement or research initiatives. Methods We describe the process of building a customized structured clinical documentation support toolkit, specific for patients seen in a headache specialty clinic. The content was developed through frequent physician meetings to reach consensus on elements that define clinical Best Practices. Tasks were assigned to the care team and data mapped to the progress note. Results The toolkit collects hundreds of fields of discrete, standardized data. Auto scored and interpreted score tests include the Generalized Anxiety Disorder 7-item, Center for Epidemiology Studies Depression Scale, Migraine Disability Assessment questionnaire, Insomnia Sleep Index, and Migraine-Specific Quality of Life. We have developed Best Practice Advisories (BPA) and other clinical documentation support tools that alert physicians, when appropriate. As of April 1, 2018, we have used the toolkits at 4346 initial patient visits. We provide screenshots of our toolkits, details of data fields collected, and diagnoses of patients at the initial visit. Conclusions The EMR can be used to effectively structure and standardize headache clinic visits for quality improvement and practice-based research. We are sharing our proprietary toolkit with other clinics as part of the Neurology Practice-Based Research Network. These tools are also facilitating clinical research enrollment and a pragmatic trial of comparative effectiveness at the point-of-care among migraine patients.

ObjectivesTo demonstrate the feasibility of pragmatic clinical trials comparing the effectiveness of treatments using the electronic medical record (EMR) and an adaptive assignment design.MethodsWe have designed and are implementing pragmatic trials at the point-of-care using custom-designed structured clinical documentation support and clinical decision support tools within our physician’s typical EMR workflow. We are applying a subgroup based adaptive design (SUBA) that enriches treatment assignments based on baseline characteristics and prior outcomes. SUBA uses information from a randomization phase (phase 1, equal randomization, 120 patients), to adaptively assign treatments to the remaining participants (at least 300 additional patients total) based on a Bayesian hierarchical model. Enrollment in phase 1 is underway in our neurology clinical practices for 2 separate trials using this method, for migraine and mild cognitive impairment (MCI).ResultsWe are successfully collecting structured data, in the context of the providers’ clinical workflow, necessary to conduct our trials. We are currently enrolling patients in 2 point-of-care trials of non-inferior treatments. As of March 1, 2018, we have enrolled 36% of eligible patients into our migraine study and 63% of eligible patients into our MCI study. Enrollment is ongoing and validation of outcomes has begun.DiscussionThis proof of concept article demonstrates the feasibility of conducting pragmatic trials using the EMR and an adaptive design.ConclusionThe demonstration of successful pragmatic clinical trials based on a customized EMR and adaptive design is an important next step in achieving personalized medicine and provides a framework for future studies of comparative effectiveness.

Objective We describe our experience with routinely capturing and analyzing Mediterranean diet data via structured clinical documentation support tools built into the electronic medical record and describe adherence to the Mediterranean diet in patients at risk for either stroke or dementia in a US neurology clinical practice. Patients and Methods The Mediterranean diet is associated with a reduced risk of stroke and dementia. The Department of Neurology at NorthShore University HealthSystem routinely evaluates patients at initial and annual outpatient visits using structured clinical documentation support (SCDS) tools built into the electronic medical record (EMR). For patient evaluations in our Vascular Neurology and Brain Health subspecialty clinics, SCDS tools in the EMR include the validated 14-item questionnaire for Mediterranean diet adherence (PREvencion con DIeta MEDiterranea [PREDIMED]) that autoscores, auto-interprets, writes to the progress note, and electronically captures data. Our study population includes patients seen at these clinics from July 1, 2015, through November 29, 2017. Results At their initial office visit, 25.5% (95/373) of Brain Health patients scored 10 or more points ("strongly adherent") on the PREDIMED (median, 8; range, 0-14) whereas 6.7% (55/829) of Vascular Neurology patients achieved a score of 10 or more points (median, 6; range, 0-12). By contrast, 34.7% (2586/7447) of individuals in the original PREDIMED cohort were strongly adherent to the Mediterranean diet. Conclusion PREDIMED scores can be electronically captured to tailor nutrition interventions by assessing baseline adherence at the time of their initial neurology clinic visit. Patients in our Midwestern US clinics were weakly adherent to the Mediterranean diet. This suggests a major opportunity for nutrition intervention and education in US neurology clinical practices, toward preserving and improving brain health.

Objective: To determine whether there were differences in clinical outcomes for ioflupane I123 injection (DaTscan) and single photon emission tomography consistent with early Parkinson’s disease (P...

Background: Alzheimer’s disease and aging brain disorders are progressive, often fatal neurodegenerative diseases. Successful aging, modern lifestyles and behaviors have combined to result in an expected epidemic. Risks for these diseases include genetic, medical, and lifestyle factors; over 20 modifiable risks have been reported. Objectives: We aim to primarily prevent Alzheimer’s disease and related disorders through electronic medical record (EMR)-based screening, risk assessments, interventions, and surveillance. Design: We identified modifiable risks; developed human, systems and infrastructural resources; developed interventions; and targeted at-risk groups for the intervention. Setting: A Community Based Health System. Participants: In year one (June 2015 to May 2016), 133 at-risk patients received brain health services with the goal of delaying or preventing Alzheimer’s disease and related disorders. Measurements: We created mechanisms to identify patients at high risk of neurodegenerative disease; EMR-based structured clinical documentation support tools to evaluate risk factors and history; evidence-based interventions to modify risk; and the capacity for annual surveillance, pragmatic trials, and practice-based and genomic research using the EMR. Results: This paper describes our Center for Brain Health, our EMR tools, and our first year of healthy but at-risk patients. Conclusion: We are translating research into primary prevention of Alzheimer’s disease and related disorders in our health system and aim to shift the paradigm in Neurology from brain disease to brain health.

Background and purpose Epilepsy patients are more likely to experience depressive symptoms and cognitive impairment compared to individuals in the general population. As the reasons for this are not definitively known, we sought to determine what factors correlate most strongly with cognition and a screening test for depression in epilepsy patients. Methods Our study population included 379 adult patients diagnosed with epilepsy or seizure in our neurology clinic. We collected detailed demographic and clinical data during patient visits using structured clinical documentation support tools that we have built within our commercial electronic medical records system (Epic), including a depression score (Neurological Disorders Depression Inventory for Epilepsy, NDDIE) and cognition score test measures (specifically in this study, Mini-Mental State Examination [MMSE]). Medication, age, gender, body mass index, duration of epilepsy, seizure frequency, current number of anti-epileptic medications, years of education were assessed in relation to baseline score as well as change in score from initial visit to first annual follow-up. Results Of the analyzed factors, two statistically significant associations were found after correction for multiple testing. Male gender and lower anti-seizure medication count were associated with better mood, as assessed by NDDIE score, at initial visit. Specifically, male gender was associated with a 1.3 decrease in NDDIE and for each additional anti-seizure medication, there was an associated 1.2 increase in NDDIE. Conclusions However, these factors were not associated with change in NDDIE score from initial to first annual follow-up visit. These findings, although interesting, are preliminary. Additionally, these findings were based on a homogenous (mainly Caucasian) clinic-based population and detailed information on previous medication use was lacking. Further work is needed to replicate these findings and to understand any mechanisms that may explain these associations.

The electronic medical record (EMR) presents an opportunity to standardize patient data collection based on quality guidelines and conduct practice-based research. We describe the development of a customized EMR “toolkit” that standardizes patient data collection with hundreds of discrete fields that supports Best Practices for treating patients with memory disorders. The toolkit also supports practice-based research. We describe the design and successful implementation of a customized EMR toolkit to support Best Practices in the care of patients with memory disorders. We discuss applications, including quality improvement projects and current research initiatives, using the toolkit. This toolkit is being shared with other departments of Neurology as part of the Neurology Practice-Based Research Network. Data collection is ongoing, including longitudinal follow-up. This toolkit will generate data that will allow for descriptive and hypothesis driven research as well-quality improvement among patients seen in a memory clinic.

Previous studies using verapamil as an adjunct therapy to anti-seizure medications have used doses ranging from 120 to 240mg per day. However, despite showing promising results, there was an increased incidence of side effects. The aim of this study is to assess the efficacy and tolerability of low dose verapamil (20mg p.o. tid) as adjunct therapy to patient's anti-seizure medications irrespective of the type or etiology of the epilepsy. In an open-label pilot study we enrolled 20 adult patients with history of epilepsy who continued to have a minimum of 2 seizures a month despite being on or having tried maximum tolerated doses of 3 or more standard antiepileptic drugs under the supervision of an epileptologist. 10 of the 19 patients (53%) who continued in the study had >50% reduction in seizure frequency. 2 of the patients (10%) had

Gait freezing as a presenting and relatively restricted condition is uncommon but a distinctive disorder. This entity was initially defined as "pure akinesia with gait freezing", and later a neuropathological substrate of progressive supranuclear palsy has been recognized. Limited studies have reported the clinical evolution after presentation, which is important for patient counseling. The objective of this study was to assess the demographic and clinical features, treatment-response, neuroimaging, and evolution of pure akinesia with gait freezing. A retrospective review of patients with this phenotype as previously defined was performed. Patients included had no or minimal limb rigidity and/or bradykinesia and no resting tremor, and all underwent neuroimaging of the brain after onset. Inclusion criteria were met by 30 patients, who were followed up to 21 years after symptom onset. During their course, 28 patients had falls (93 %), 12 patients had dysarthria (40 %), and 13 had handwriting changes (43 %). All patients had progression of their gait disorder over time, but with a variable interval until falls occurred. None of the patients developed vertical gaze palsy or met diagnostic criteria for an alternative parkinsonian disorder. Pure akinesia with gait freezing is a distinctive disorder that can be recognized in the clinic. Despite the previously reported progressive supranuclear palsy-like neuropathology, the clinical course is much less aggressive and disabling than classic Richardson syndrome, although fall risk eventually develops in nearly all patients. Bradykinesia, tremor, and rigidity do not develop, distinguishing pure akinesia with gait freezing from Parkinson's disease and other parkinsonian disorders.

Introduction The MAPT H1 haplotype has been associated with several neurodegenerative diseases. We were interested in exploring the role of MAPT haplotypic variation in risk of dementia with Lewy bodies (DLB). Method We genotyped six MAPT haplotype tagging SNPs and screened 431 clinical DLB cases, 347 pathologically defined high-likelihood DLB cases, and 1049 controls. Result We performed haplotypic association tests and detected an association with the protective H2 haplotype in our combined series (odds ratio [OR] = 0.75). We fine-mapped the locus and identified a relatively rare haplotype, H1G, that is associated with an increased risk of DLB (OR = 3.30, P = .0017). This association was replicated in our pathologically defined series (OR = 2.26, P = .035). Discussion These results support a role for H1 and specifically H1G in susceptibility to DLB. However, the exact functional variant at the locus is still unknown, and additional studies are warranted to fully explain genetic risk of DLB at the MAPT locus.

Background and Purpose: Standardized electronic medical record tools provide an opportunity to efficiently provide care that conforms to Best Practices and supports quality improvement and practice-based research initiatives. Methods: We describe the development of a customized structured clinical documentation “toolkit” that standardizes patient data collection to conform to Best Practices for treating patients with stroke. The toolkit collects patients’ demographic information, relevant score test measures, and captures information on disability, treatment, and outcomes. Results: We describe here our creation and implementation of the toolkits and provide example screenshots. As of August 1, 2018, we have evaluated 2332 patients at an initial visit for a possible stroke. We provide basic descriptive data gathered from the use of the toolkits, demonstrating their utility in collecting patient data in a manner that supports both quality clinical care and research initiatives. Conclusions: We have developed an EMR toolkit to support Best Practices in the care of patients with stroke. We discuss quality improvement projects and current research initiatives using the toolkit. This toolkit is being shared with other Departments of Neurology as part of the Neurology Practice-Based Research Network.

Background In 2017, the International Parkinson and Movement Disorder Society put forward new clinical criteria for the diagnosis of PSP, recognizing diverse PSP phenotypes. In this study, we compared the sensitivity and specificity of the new criteria with the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria at different times. Methods Patients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP, were identified from the Society for Progressive Supranuclear Palsy brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at 1 of the 3 Mayo Clinic sites, in Florida, Arizona, and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3-year cutoff. Results A total of 129 patients were included, of whom 66 had PSP pathology (51%). The remainder had other neurodegenerative diseases. The overall sensitivity of the International Parkinson and Movement Disorder Society criteria was 87.9%, compared with 45.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the International Parkinson and Movement Disorder Society probable PSP criteria was 85.7%, compared with 90.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy. Individual patients were noted to have features of multiple PSP phenotypes. Conclusion The International Parkinson and Movement Disorder Society criteria recognize several phenotypes of progressive supranuclear palsy and hence have higher sensitivity than the previous criteria. © 2019 International Parkinson and Movement Disorder Society.

The improved use of Electronic Health Record (EHR) Systems provides an opportunity to improve the overall efficiency and quality of care of patients with epilepsy. Tools and strategies that may be incorporated into the use of EHRs include utilizing patient generated data, clinical decision support systems and natural language processing systems. Standardization of data from EHR systems may lead to improvement in clinical research through the creation of data collections and multi-center collaborations. Challenges to collaborative use of EHR Systems across centers include costs and the diversity of EHR systems.

To determine whether there were differences in clinical outcomes for ioflupane IWe performed a case-control study among patients presenting to the Emergency Room (ER) during 2006-2013 with mTBI (cases, n = 34) or without mTBI (controls, n = 33). We performed clinical and imaging measurements in cases and controls at least 1-year post-presentation to the ER (average three years four months).All DaTscans obtained were qualitatively normal. There were no qualitative DaTscan differences between cases and controls. There was, however, a significant increase in caudate asymmetry in controls versus cases (p = 0.02), but this finding was no longer significant after correction for multiple comparisons. There was a suggestion of a trend of poorer clinical score test measures among those with mTBI, although the overall mean score difference between cases and controls was not clinically significant.Our small study does not provide support for DaTscan changes suggestive of PD in the one to seven years following mTBI. A trend towards poorer clinical measures was seen but was not clinically relevant in our small sample. Further work in a large population is necessary to support these findings.

α-Synuclein gene (SNCA) multiplications cause familial parkinsonism and allele-length polymorphisms within the SNCA dinucleotide repeat REP1 increase the risk for developing Parkinson's disease (PD). Since SNCA multiplications increase SNCA expression, and REP1 genotypes that increase the risk of developing PD show increased SNCA expression in cell-culture systems, animal models, and human blood and brain, PD therapies seek to reduce SNCA expression. We conducted an observational study of 1098 PD cases to test the hypothesis that REP1 genotypes correlated with reduced SNCA expression are associated with better motor and cognitive outcomes. We evaluated the association of REP1 genotypes with survival free of Hoehn and Yahr stages 4 or 5 (motor outcome) and of Modified Telephone Interview for Cognitive Status score ≤27 or Alzheimer's Disease Dementia Screening Interview score ≥2 (cognitive outcome). Median disease duration at baseline was 3.3 years and median lag time from baseline to follow-up was 7.8 years. Paradoxically, REP1 genotypes associated with increased risk of developing PD and increased SNCA expression were associated with better motor (HR = 0.87, p = 0.046, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.020, covariate-adjusted time-scale analysis) and cognitive outcomes (HR = 0.90, p = 0.12, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.023, covariate-adjusted time-scale analysis). Our findings raise the possibility that SNCA has a dual, opposing, and time-dependent role. This may have implications for the development of therapies that target SNCA expression.

Objectives: To determine whether alpha-synuclein dinucleotide repeat (REP1) genotypes are associated with survival in Parkinson's disease (PD). Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium provided REP1 genotypes and baseline and follow-up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival. Results: Twenty-one sites contributed data for 6,154 cases. There was no significant association between alpha-synuclein REP1 genotypes and survival in PD. However, there was a significant association between REP1 genotypes and age at onset of PD (hazard ratio: 1.06; 95% confidence interval: 1.01-1.10; P value = 0.01). Conclusions: In our large consortium study, alpha-synuclein REP1 genotypes were not associated with survival in PD. Further studies of alpha-synuclein's role in disease progression and long-term outcomes are needed. (C) 2014 International Parkinson and Movement Disorder Society

BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society (Less)

Background Prior studies causally linked mutations in SNCA , MAPT , and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. Methods Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or “VNTRs”) in SNCA , MAPT and LRRK2 , were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. Results Five pairwise interactions had uncorrected P -values SNCA rs3775423 or MAPT rs4792891, coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. Conclusions This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing.

SummaryObjective Using the electronic medical record (EMR) to capture structured clinical data at the point of care would be a practical way to support quality improvement and practice-based research in epilepsy. Methods We describe our stepwise process for building structured clinical documentation support tools in the EMR that define best practices in epilepsy, and we describe how we incorporated these toolkits into our clinical workflow. Results These tools write notes and capture hundreds of fields of data including several score tests: Generalized Anxiety Disorder-7 items, Neurological Disorders Depression Inventory for Epilepsy, Epworth Sleepiness Scale, Quality of Life in Epilepsy–10 items, Montreal Cognitive Assessment/Short Test of Mental Status, and Medical Research Council Prognostic Index. The tools summarize brain imaging, blood laboratory, and electroencephalography results, and document neuromodulation treatments. The tools provide Best Practices Advisories and other clinical decision support when appropriate. The tools prompt enrollment in a DNA biobanking study. We have thus far enrolled 231 patients for initial visits and are starting our first annual follow-up visits and provide a brief description of our cohort. Significance We are sharing these EMR tools and captured data with other epilepsy clinics as part of a Neurology Practice Based Research Network, and are using the tools to conduct pragmatic trials using subgroup-based adaptive designs.

A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted. (C) 2016 Elsevier Inc. All rights reserved.

Background Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease. Although additional missense variants were described, their pathogenic role yet remains inconclusive. Methods and results We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort. Conclusions Our study apart from identifying the p. Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.

Lewy pathology occurs in 8–17% of neurologically normal people age >60, termed incidental Lewy body disease (iLBD). It is often assumed to represent preclinical Parkinson disease (PD). However, some iLBD cases have diffuse pathology inconsistent with preclinical PD. We analyzed iLBD cases (α-synuclein immunohistochemistry) using the Braak PD staging scheme and determined if some had a neuropathological pattern suggestive of preclinical dementia with Lewy bodies (DLB). Of the 235 brains examined, 34 had iLBD (14.5%) and all but one could be assigned a Braak PD stage. The distribution of α-synuclein pathology in the 33 cases fell into three patterns: (1) diffuse cortical and subcortical α-synuclein pathology; (2) no cortical α-synuclein pathology, but a caudal-to-rostral ascending pattern, primarily involving brainstem; and (3) intermediate between these two categories. Also, 6/33 cases failed to follow the pattern of contiguous spread proposed by Braak. These findings suggest dichotomy in the distribution of iLBD: some cases fit the Braak ascending scheme, conceptually consistent with preclinical PD, whereas others displayed prominent cortical involvement that might represent preclinical DLB.

The purpose of this paper is to provide the rationale for therapeutic silencing of the alpha-synuclein gene (SNCA) in Parkinson’s disease (PD). The paper reviews the public health significance of PD; the causal links between rare SNCA variants and familial PD; the association of common SNCA variants and PD susceptibility; the association of SNCA variants also with age at onset and motor and cognitive outcomes in PD; therapeutic strategies targeting SNCA in PD; and preliminary findings and considerations on small interfering RNA-based therapies and PD.

Incidence rates of Parkinson's disease are higher in men than in women at all ages, and these differences may be a result of the neuroprotective effects of estrogen on the nigrostriatal pathway. We investigated the association of common variants in 4 estrogen-related genes with Parkinson's disease. Tagging single-nucleotide polymorphisms in the CYP19A1, ESR1, ESR2, and PRDM2 genes were selected from the International Haplotype Map and genotyped in 1103 Parkinson's disease cases from the upper Midwest of the United States and in 1103 individually matched controls (654 unaffected siblings, and 449 unrelated controls from the same region). Of 137 informative single-nucleotide polymorphisms, 2 PRDM2 single-nucleotide polymorphisms were significantly associated with an increased risk of Parkinson's disease at the Bonferroni-corrected significance level of 0.0004 (rs2744690: OR, 1.54; SE(logOR), .109; 99.96% CI, 1.05-2.26; uncorrected P = .0001; rs2744687: OR, 1.53; SE(logOR), .113; 99.96% CI, 1.03-2.29, uncorrected P = .0002); the association was significant in the women-only stratum but not in the men-only stratum. An additional 6 single-nucleotide polymorphisms in PRDM2, 2 in ESR1, 1 in ESR2, and 1 in CYP19A1 had significant P values in the overall sample before Bonferroni correction. None of the single-nucleotide polymorphisms were significantly associated with age at onset of Parkinson's disease after Bonferroni correction. Our results confirm the association of PRDM2 variants with Parkinson's disease susceptibility, especially in women.

Background Many physicians enter data into the electronic medical record (EMR) as unstructured free text and not as discrete data, making it challenging to use for quality improvement or research initiatives. Objectives The objective of this research paper was to develop and implement a structured clinical documentation support (SCDS) toolkit within the EMR to facilitate quality initiatives and practice-based research in a multiple sclerosis (MS) practice. Methods We built customized EMR toolkits to capture standardized data at office visits. Content was determined through physician consensus on necessary elements to support best practices in treating patients with demyelinating disorders. We also developed CDS tools and best practice advisories within the toolkits to alert physicians when a quality improvement opportunity exists, including enrollment into our DNA biobanking study at the point of care. Results We have used the toolkit to evaluate 541 MS patients in our clinic and begun collecting longitudinal data on patients who return for annual visits. We provide a description and example screenshots of our toolkits, and a brief description of our cohort to date. Conclusions The EMR can be effectively structured to standardize MS clinic office visits, capture data, and support quality improvement and practice-based research initiatives at the point of care.

We studied the association of three personality traits related to neuroticism with the subsequent risk of Parkinson's disease (PD) using a historical cohort study. We included 7,216 subjects who resided within the 120-mile radius centered in Rochester, MN, at the time they completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 to 1965. We considered three MMPI personality scales (pessimistic, anxious, and depressive traits). A total of 6,822 subjects (94.5%) were followed over four decades either actively or passively. During follow-up, 227 subjects developed parkinsonism (156 developed PD). An anxious personality was associated with an increased risk of PD [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.16-2.27]. A pessimistic personality trait was also associated with an increased risk of PD but only in men (HR = 1.92; 95% CI = 1.20-3.07). By contrast, a depressive trait was not associated with increased risk. Analyses combining scores from the three personality scales into a composite neuroticism score showed an association of neuroticism with PD (HR = 1.54; 95% CI = 1.10-2.16). The association with neuroticism remained significant even when the MMPI was administered early in life (ages 20-39 years). By contrast, none of the three personality traits was associated with the risk of non-PD types of parkinsonism grouped together. Our long-term historical cohort study suggests that an anxious personality trait may predict an increased risk of PD developing many years later.

Objective: Parkinson disease (PD) may affect the autonomic nervous system and may cause constipation; however, few studies have explored constipation preceding the motor onset of PD. We investigated constipation preceding PD using a case-control study design in a population-based sample. Methods: Using the medical records-linkage system of the Rochester Epidemiology Project, we identified 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to ascertain the occurrence of constipation preceding the onset of PD (or index year). Results: Constipation preceding PD or the index year was more common in cases than in controls (odds ratio [OR] 2.48; 95% confidence interval [CI] 1.49 to 4.11; p = 0.0005). This association remained significant after adjusting for smoking and coffee consumption (ever vs never), and after excluding constipation possibly induced by drugs. In addition, the association remained significant in analyses restricted to constipation documented 20 or more years before the onset of motor symptoms of PD. Although the association was stronger in women than in men and in patients with PD with rest tremor compared with patients with PD without rest tremor, these differences were not significant. Conclusions: Our findings suggest that constipation occurring as early as 20 or more years before the onset of motor symptoms is associated with an increased risk of Parkinson disease.