Faculty Bibliography

BACKGROUND:Health insurance in the United States varies in coverage of essential diagnostic tests, therapies, and specialists. Health disparities between privately and publicly insured patients with MS have not been comprehensively assessed. The objective of this study is to evaluate the impact of public versus private insurance on longitudinal brain outcomes in MS. METHODS:Lesional, thalamic, and gray and white matter volumes were extracted from longitudinal MRI of 710 MS patients. Baseline volumes and atrophy rates of lesional, thalamic, and gray and white matter volumes were compared across insurance groups. RESULTS:After image quality assessment, 376 (284 private / 92 public), 638 (499 / 139), and 331 (250 / 81), patients were in MS lesion, thalamic, gray and white matter analyses respectively. Baseline lesion volume was higher for publicly insured patients but increased at a slightly higher rate in those privately insured (p = 0.01). Baseline gray matter measurements were lower for patients with public insurance, but thalamic (p < 0.01) and gray matter (p < 0.01) atrophy rates were slightly higher in the private insurance group. CONCLUSION/CONCLUSIONS:Insurance type was associated with lesion, thalamic, and gray matter volumes. The results suggest that patients with public insurance may present with more advanced disease.

Epilepsy affects approximately 1% of the world population. Patients have recurrent seizures, increased physical and psychiatric comorbidities, and higher mortality rate than the general population. Over the last 40 years, research has resulted in 20 new antiseizure medications (ASMs) approved between 1990 and 2018. In spite of this, up to one-third of patients (~ 1 million patients in the USA) have drug-resistant epilepsy (DRE), with little change between 1982 and 2018, a period of intense new ASM development. A minority of patients with DRE may benefit from surgical treatment, but this specialized care remains challenging to scale. Therefore, the greatest hope for breakthroughs for patients with DRE is in pharmacologic therapies. Recently, several advances promise to change the outcomes for patients with DRE. Cenobamate, a drug with dual mechanisms of modulating sodium channel currents and GABA-A receptors, achieves 90-100% seizure reduction in 25-33% of patients with focal DRE, a response not observed with other ASMs. Fenfluramine, a serotonin-acting drug, dramatically reduces the frequency of convulsive seizures in Dravet syndrome, a devastating developmental epileptic encephalopathy with severe DRE. Both drugs reduce mortality. In addition, the possibility of DRE prevention was recently raised in patients with tuberous sclerosis complex, a relatively common genetic form of epilepsy. A paradigm shift is emerging in the treatment of epilepsy. Seizure freedom has become attainable in a significant proportion of patients with focal DRE, and dramatic seizure reduction has been achieved in a developmental encephalopathy. Coupled with a rich pipeline of new compounds under clinical development, the long sought-after breakthrough in the treatment of epilepsy may finally be in sight.

The replication crisis in experimental psychology and neuroscience has received much attention recently. This has led to wide acceptance of measures to improve scientific practices, such as preregistration and registered reports. Less effort has been devoted to performing and reporting the results of systematic tests of the functioning of the experimental setup itself. Yet, inaccuracies in the performance of the experimental setup may affect the results of a study, lead to replication failures, and importantly, impede the ability to integrate results across studies. Prompted by challenges we experienced when deploying studies across six laboratories collecting electroencephalography (EEG)/magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), and intracranial EEG (iEEG), here we describe a framework for both testing and reporting the performance of the experimental setup. In addition, 100 researchers were surveyed to provide a snapshot of current common practices and community standards concerning testing in published experiments' setups. Most researchers reported testing their experimental setups. Almost none, however, published the tests performed or their results. Tests were diverse, targeting different aspects of the setup. Through simulations, we clearly demonstrate how even slight inaccuracies can impact the final results. We end with a standardized, open-source, step-by-step protocol for testing (visual) event-related experiments, shared via protocols.io. The protocol aims to provide researchers with a benchmark for future replications and insights into the research quality to help improve the reproducibility of results, accelerate multicenter studies, increase robustness, and enable integration across studies.

BACKGROUND AND OBJECTIVES/UNASSIGNED:Previous research has demonstrated that simulation-based medical education (SBME) can improve neurology trainees' confidence, knowledge, and competence. However, a general needs assessment and review of current SBME used within neurology are needed to guide SBME curriculum development. The objective of this study was to describe the current use of SBME in resident education and to assess perceived barriers to expanding SBME interventions. METHODS/UNASSIGNED:We surveyed adult neurology residency program directors (PDs) listed in the Accreditation Council for Graduate Medical Education directory using a Qualtrics-based survey platform. Survey questions addressed current utilization of SBME and barriers to SBME growth. RESULTS/UNASSIGNED:Seventy-five PDs of 171 contactable PDs responded to our survey (response rate 44%). Of the respondents, 84% (64/75) report using SBME in their adult neurology residencies. Of those using SBME, 87% (55/64) programs create their own cases. Most programs use simulation to teach neurocritical care topics (63%) and vascular neurology (78%); few use simulation to teach outpatient topics and teleneurology. Among programs that use SBME, there was variability in the frequency of the SBME interventions and in the target trainee cohort. Among responding programs, most expressed interest in expanding SBME in their curriculum (69%, 52/64), but frequently cited lack of faculty protected time (55%), funding (35%), and resident availability (32%) as barriers to doing so. DISCUSSION/UNASSIGNED:Most responding programs use SBME. However, the frequency and target learner for SBME interventions varied between programs. Many programs wish to expand SBME at their institutions but are constrained by limited protected time and institutional financial support. We discuss potential solutions to the perceived barriers to SBME, including intra-institutional collaboration to advance SBME use and case diversity for learners and help innovate neurology medical education.

Dementia prevention in Africa is critically underexplored, despite the continent's high prevalence of modifiable risk factors. With a predominantly young and middle-aged population, Africa presents a prime opportunity to implement evidence-based strategies that could significantly reduce future dementia cases and mitigate its economic impact. The multinational Africa-FINGERS program offers an innovative solution, pioneering culturally sensitive, multidomain interventions tailored to the unique challenges of the region.  Leveraging insights from landmark global studies such as Worldwide-FINGERS and Alzheimer's Disease Neuroimaging Initiative, the program employs a multideterminant precision prevention framework, grounded in community based systems dynamics. Africa-FINGERS further integrates cutting-edge state-of-the-art multimodal biomarker evaluations tailored to regional contexts, with the goal of advancing brain health and establishing a global standard for dementia prevention. This groundbreaking initiative highlights the potential for scalableand sustainable interventions, thus is poised to transform dementia risk reduction efforts across the continent. HIGHLIGHTS: Dementia rates are escalating in Africa, largely due to longer life spans and increased prevalence of modifiable risk factors. Yet, few regional interventions have directly targeted lifestyle factors to reduce dementia risk. The multinational Africa-FINGERS study will address this gap by adapting the successful FINGERS lifestyle intervention to African populations. Africa-FINGERS will pioneer a culturally informed, multidomain dementia risk reduction intervention in the African region through feasibility dementia prevention trials in rural and urban sites across Kenya and Nigeria in the first instance, enrolling 600 at-risk adults (≥ 50 years). The program adopts participatory research methods to develop culturally appropriate interventions and build infrastructure to evaluate dementia biomarkers from ante and post mortem samples. A cost-effectiveness analysis will be conducted to guide the strategic implementation of Africa-FINGERS into regional health systems. The Africa-FINGERS strategy aligns with the Worldwide-FINGERS framework and integrates the global Alzheimer's Disease Neuroimaging Initiative approach, emphasizing multimodal analysis.

BACKGROUND/UNASSIGNED:Bone regeneration following a fracture is dependent on multiple factors including skeletal stem cells (SSCs). Recruitment, proliferation, and differentiation of the SSCs is guided by the proteins and metabolites found within the fracture microenvironment. Understanding how intrinsic factors affect the fracture microenvironment has been a topic of ongoing investigation. This study sought to determine whether the levels of select proteins and metabolites within the fracture hematoma would be differentially expressed depending on the age of the patient. We hypothesized that a distinct set of proteins and metabolites found within the fracture hematoma microenvironment would be present at varying levels depending on patient age. METHODS/UNASSIGNED:The research study was reviewed and approved by an Institutional Review Board. Hematomas were collected from subjects aged 18 years old or older undergoing surgical intervention for a fracture. Hematoma samples were selected from the biorepository and assigned to one of two fracture groups including young ankle/hindfoot and aged ankle/hindfoot. Protein and metabolite levels within each hematoma were analyzed by liquid chromatography-mass spectrometry. RESULTS/UNASSIGNED:A total of seven hematomas were included in each the young ankle/hindfoot and aged ankle/hindfoot groups. From the global metabolomic analysis, creatine, 2-methylindoline, and acetyl-L-carnitine were identified as being differentially expressed between both groups. An untargeted metabolomic analysis of the two groups identified significant differences in the levels of an additional 66 metabolites. Proteomic analysis identified 34 proteins that were expressed at significantly different levels. CONCLUSIONS/UNASSIGNED:The level of metabolites and proteins found within the local fracture environment vary by patient age. Future investigations will focus on identifying a role for these proteins and metabolites in bone homeostasis and fracture healing. LEVEL OF EVIDENCE/UNASSIGNED:N/A, basic science investigation. SUPPLEMENTARY INFORMATION/UNASSIGNED:The online version contains supplementary material available at 10.1007/s43465-024-01284-3.

PURPOSE/OBJECTIVE:We previously reported that single doses of the norepinephrine transporter inhibitor, atomoxetine, increased standing blood pressure (BP) and ameliorated symptoms in patients with neurogenic orthostatic hypotension (nOH). We aimed to evaluate the effect of atomoxetine over four weeks in patients with nOH. METHODS:A randomized, double-blind, placebo-controlled crossover clinical trial between July 2016 and May 2021 was carried out with an initial open-label, single-dose phase (10 or 18 mg atomoxetine), followed by a 1-week wash-out, and a subsequent double-blind 4-week treatment sequence (period 1: atomoxetine followed by placebo) or vice versa (period 2). The trial included a 2-week wash-out period. The primary endpoint was symptoms of nOH as measured by the orthostatic hypotension questionnaire (OHQ) assessed at 2 weeks. RESULTS:A total of 68 patients were screened, 40 were randomized, and 37 completed the study. We found no differences in the OHQ composite score between atomoxetine and placebo at 2 weeks (-0.3 ± 1.7 versus -0.4 ± 1.5; P = 0.806) and 4 weeks (-0.6 ± 2.4 versus -0.5 ± 1.6; P = 0.251). There were no differences either in the OHSA scores at 2 weeks (3 ± 1.9 versus 4 ± 2.1; P = 0.062) and at 4 weeks (3 ± 2.2 versus 3 ± 2.0; P = 1.000) or in the OH daily activity scores (OHDAS) at 2 weeks (4 ± 3.0 versus 5 ± 3.1, P = 0.102) and 4 weeks (4 ± 3.0 versus 4 ± 2.7, P = 0.095). Atomoxetine was well-tolerated. CONCLUSIONS:While previous evidence suggested that acute doses of atomoxetine might be efficacious in treating nOH; results of this clinical trial indicated that it was not superior to placebo to ameliorate symptoms of nOH. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov; NCT02316821.

BACKGROUND:The Center for Medicare and Medicaid Services requires Organ Procurement Organizations (OPOs) to verify and document that any potential organ donor has been pronounced dead per applicable legal requirements of local, state, and federal laws. However, OPO practices regarding death by neurologic criteria (DNC) verification are not standardized, and little is known about their DNC verification processes. This study aimed to explore OPO practices regarding DNC verification in the United States. METHODS:An electronic survey was sent to all 57 OPOs in the United States from June to September 2023 to assess verification of policies and practices versus guidelines, concerns about policies and practices, processes to address concerns about DNC determination, and communication practices. RESULTS:Representatives from 12 OPOs across six US regions completed the entire survey; 8 of 12 reported serving > 50 referral hospitals. Most respondents (11 of 12) reported comparing their referral hospital's DNC policies with the 2010 American Academy of Neurology Practice Parameter and/or other (4 of 12) guidelines. Additionally, most (10 of 12) reported independently reviewing and verifying each DNC determination. Nearly half (5 of 12) reported concerns about guideline-discordant hospital policies, and only 3 of 12 thought all referral hospitals followed the 2010 American Academy of Neurology Practice Parameter in practice. Moreover, 9 of 12 reported concerns about clinician knowledge surrounding DNC determination, and most (10 of 12) reported having received referrals for patients whose DNC declaration was ultimately reversed. All reported experiences in which their OPO requested additional assessments (11 of 12 clinical evaluation, 10 of 12 ancillary testing, 9 of 12 apnea testing) because of concerns about DNC determination validity. CONCLUSIONS:Accurate DNC determination is important to maintain public trust. Nearly all OPO respondents reported a process to verify hospital DNC policies and practices with medical society guidelines. Many reported concerns about clinician knowledge surrounding DNC determination and guideline-discordant policies and practices. Educational and regulatory advocacy efforts are needed to facilitate systematic implementation of guideline-concordant practices across the country.