National Institute of Neurological Disorders and Stroke Clinical Trials Methodology Course: Summary and Accomplishments 2014-2023.

The Clinical Trials Methodology Course (CTMC), given from 2014 to 2023, was conducted to educate early-career clinical investigators from various backgrounds in neurosciences in the design of clinical trials and to provide mentorship to enhance academic careers and retention plus improve research productivity and the likelihood of successful grant applications. This summary describes the rationale, history, structure, and trainee outcomes of the CTMC. The course used small groups, consisting of 1-2 clinical faculty advisor(s), 1 faculty biostatistician, and 2-4 trainees who met remotely approximately weekly over 12 weeks.

Analysis of Faculty Gender and Race in Scholarly Achievements in Academic Neurology.

Intersection of gender and race and/or ethnicity in academic medicine is understudied; we aim to understand these factors in relation to scholarly achievements for neurology faculty. Faculty from 19 US neurology departments completed a survey (2021-2022) to report rank, leadership positions, publications, funded projects, awards, and speaker invitations. Regression analyses examined effects of gender, race, and their intersectionality on these achievements.

The Auxiliary to the American Academy of Neurology.

The American Academy of Neurology (AAN) was founded in 1948, and the Women's Auxiliary to the AAN was founded shortly thereafter. We reviewed historical archives of the AAN and Women's Auxiliary and interviewed past Auxiliary leaders to understand the perception and roles of neurologists' spouses. The Women's Auxiliary to the AAN was originally formed for the wives of neurologist Academy members with the intention of facilitating social and intragroup relationships.

Veni, Vidi, Scribivi: I Came, I Saw, I Wrote.

Narrative medicine talks at the American Academy of Neurology Annual Meeting have included writing prompts to inspire and promote wellness among attendees. The 6-word writing exercise at the 2023 Annual Meeting prompted pithy and powerful stories, which we share in this article.

Visual function resists early neurodegeneration in the visual system in primary progressive multiple sclerosis.

Background: Neurodegeneration in multiple sclerosis (MS) affects the visual system but dynamics and pathomechanisms over several years especially in primary progressive MS (PPMS) are not fully understood.

Methods: We assessed longitudinal changes in visual function, retinal neurodegeneration using optical coherence tomography, MRI and serum NfL (sNfL) levels in a prospective PPMS cohort and matched healthy controls. We investigated the changes over time, correlations between outcomes and with loss of visual function.

Longitudinal changes in white matter as measured with diffusion tensor imaging in adult-onset myotonic dystrophy type 1.

Myotonic dystrophy type 1 is characterized by neuromuscular degeneration. Our objective was to compare change in white matter microstructure (fractional anisotropy, radial and axial diffusivity), and functional/clinical measures. Participants underwent yearly neuroimaging and neurocognitive assessments over three-years.

Challenging Neuromuscular Disease Cases.

The diagnosis of neuromuscular disorders requires a thorough history including family history and examination, with the next steps broadened now beyond electromyography and neuropathology to include genetic testing. The challenge in diagnosis can often be putting all the information together. With advances in genetic testing, some diagnoses that adult patients may have received as children deserve a second look and may result in diagnoses better defined or alternative diagnoses made.

Investigating Late-Onset Pompe Prevalence in Neuromuscular Medicine Academic Practices: The IPaNeMA Study.

Background And Objectives: We investigated the prevalence of late-onset Pompe disease (LOPD) in patients presenting to 13 academic, tertiary neuromuscular practices in the United States and Canada.

Methods: All successive patients presenting with proximal muscle weakness or isolated hyperCKemia and/or neck muscle weakness to these 13 centers were invited to participate in the study. Whole blood was tested for acid alpha-glucosidase (GAA) assay through the fluorometric method, and all cases with enzyme levels of ≤10 pmoL/punch/h were reflexed to molecular testing for mutations in the GAA gene.

Disease Progression in Charcot-Marie-Tooth Disease Related to MPZ Mutations: A Longitudinal Study.

Objective: The paucity of longitudinal natural history studies in MPZ neuropathy remains a barrier to clinical trials. We have completed a longitudinal natural history study in patients with MPZ neuropathies across 13 sites of the Inherited Neuropathies Consortium.

Methods: Change in Charcot-Marie-Tooth Examination Score (CMTES) and Rasch modified CMTES (CMTES-R) were evaluated using longitudinal regression over a 5-year period in subjects with MPZ neuropathy.

Blood-Based Markers of Neuronal Injury in Adult-Onset Myotonic Dystrophy Type 1.

Introduction: The present study had four aims. First, neuronal injury markers, including neurofilament light (NF-L), total tau, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1), were compared between individuals with and without adult-onset myotonic dystrophy type 1 (DM1). Second, the impact of age and CTG repeat on brain injury markers was evaluated.

Contemporary Neuroscience Core Curriculum for Medical Schools.

Medical students need to understand core neuroscience principles as a foundation for their required clinical experiences in neurology. In fact, they need a solid neuroscience foundation for their clinical experiences in all other medical disciplines also because the nervous system plays such a critical role in the function of every organ system. Because of the rapid pace of neuroscience discoveries, it is unrealistic to expect students to master the entire field.

Cognitive Deficits, Apathy, and Hypersomnolence Represent the Core Brain Symptoms of Adult-Onset Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults, and is primarily characterized by muscle weakness and myotonia, yet some of the most disabling symptoms of the disease are cognitive and behavioral. Here we evaluated several of these non-motor symptoms from a cross-sectional time-point in one of the largest longitudinal studies to date, including full-scale intelligence quotient, depression, anxiety, apathy, sleep, and cerebral white matter fractional anisotropy in a group of 39 adult-onset myotonic dystrophy type 1 participants (27 female) compared to 79 unaffected control participants (46 female). We show that intelligence quotient was significantly associated with depression ( < 0.

MicroRNAs as Biomarkers of Charcot-Marie-Tooth Disease Type 1A.

Objective: To determine whether microRNAs (miRs) are elevated in the plasma of individuals with the inherited peripheral neuropathy Charcot-Marie-Tooth disease type 1A (CMT1A), miR profiling was employed to compare control and CMT1A plasma.

Methods: We performed a screen of CMT1A and control plasma samples to identify miRs that are elevated in CMT1A using next-generation sequencing, followed by validation of selected miRs by quantitative PCR, and correlation with protein biomarkers and clinical data: Rasch-modified CMT Examination and Neuropathy Scores, ulnar compound muscle action potentials, and motor nerve conduction velocities.

Results: After an initial pilot screen, a broader screen confirmed elevated levels of several muscle-associated miRNAs (miR1, -133a, -133b, and -206, known as myomiRs) along with a set of miRs that are highly expressed in Schwann cells of peripheral nerve.

Neurocognitive Features of Motor Premanifest Individuals With Myotonic Dystrophy Type 1.

Objective: The goal of the study was to identify brain and functional features associated with premanifest phases of adult-onset myotonic dystrophy type 1 (i.e., PreDM1).

White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden.

Deficits in white matter (WM) integrity and motor symptoms are among the most robust and reproducible features of myotonic dystrophy type 1 (DM1). In the present study, we investigate whether WM integrity, obtained from diffusion-weighted MRI, corresponds to quantifiable motor outcomes (e.g.

Funding the Educational Mission in Neurology.

Although it is self-evident that education in neurology is important and necessary, how to fund the educational mission is a frequent challenge for neurology departments and clinicians. Department chairs often resort to a piecemeal approach, cobbling together funding for educators from various sources, but frequently falling short. Here, we review the various sources available to fund the educational mission in neurology, understanding that not every department will have access to every source.

Quantitative muscle MRI as a sensitive marker of early muscle pathology in myotonic dystrophy type 1.

Background: Quantitative muscle MRI as a sensitive marker of early muscle pathology and disease progression in adult-onset myotonic dystrophy type 1. The utility of muscle MRI as a marker of muscle pathology and disease progression in adult-onset myotonic dystrophy type 1 (DM1) was evaluated.

Methods: This prospective, longitudinal study included 67 observations from 36 DM1 patients (50% female), and 92 observations from 49 healthy adults (49% female).

Fully automated 3D segmentation of MR-imaged calf muscle compartments: Neighborhood relationship enhanced fully convolutional network.

Automated segmentation of individual calf muscle compartments from 3D magnetic resonance (MR) images is essential for developing quantitative biomarkers for muscular disease progression and its prediction. Achieving clinically acceptable results is a challenging task due to large variations in muscle shape and MR appearance. In this paper, we present a novel fully convolutional network (FCN) that utilizes contextual information in a large neighborhood and embeds edge-aware constraints for individual calf muscle compartment segmentations.

Encoding of facial expressions in individuals with adult-onset myotonic dystrophy type 1.

Emotional issues are often reported among individuals with myotonic dystrophy type 1 (DM1) and some studies have suggested that deficits in ability to quickly encode emotions may contribute to these problems. However, poor performance on emotion encoding tasks could also be explained by a more general cognitive deficit (Full Scale IQ [FSIQ]), rather than a specific deficit in emotional processing. Since individuals with DM1 are known to exhibit difficulties in general cognitive abilities, it is important to account for FSIQ when evaluating emotion encoding.

Training in Neurology: Feedback from Graduates About the Psychiatry Component of Residency Training.

Objective: To obtain feedback from early career adult and pediatric neurologists about the psychiatry component of residency training.

Methods: A survey was developed and administered electronically to 4 cohorts of recently certified American Board of Psychiatry and Neurology diplomates.

Results: The response rate was 16% (431/2,677) and included 330 adult neurologists and 101 pediatric neurologists.

Variant repeats within the CTG expansion protect function in myotonic dystrophy type 1.

Objective: We tested the hypothesis that variant repeat interruptions (RIs) within the CTG repeat tract lead to milder symptoms compared with pure repeats (PRs) in myotonic dystrophy type 1 (DM1).

Methods: We evaluated motor, neurocognitive, and behavioral outcomes in a group of 6 participants with DM1 with RI compared with a case-matched sample of 12 participants with DM1 with PR and a case-matched sample of 12 unaffected healthy comparison participants (UA).

Results: In every measure, the RI participants were intermediate between UA and PR participants.

Subspecialization in clinical neurophysiology: Development and current status.

Objective: To describe the development and current status of training and certification in clinical neurophysiology (CNP); to explore the impact of the newer subspecialties in sleep medicine, neuromuscular medicine, and epilepsy; and to obtain information about aspects of practice in the subspecialty.

Methods: Information about training programs and certification was obtained from the records of the Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology, and diplomates were surveyed about their CNP practice activities and attitudes toward certification/recertification.

Results: In the years since the first examination was administered, a robust number of CNP training programs developed, but recently, there has been a decrease in the number of programs and fellows, although the number of programs and fellows in the subspecialties of epilepsy, neuromuscular medicine, and sleep medicine has increased.