Faculty Bibliography

Brain health is crucial to optimizing both the function and well-being of every person at each stage of life and is key to both individual and social progress. As a concept, brain health is complex and requires a multidisciplinary collaborative approach between many professional and public organizations to bring into effect meaningful change. Neurologists are uniquely positioned to serve as specialists in brain health and to advance the newly evolving field of preventive neurology, which aims to identify individuals at high risk of brain disorders and other neurologic conditions and offer strategies to mitigate disease emergence or progression. For decades, the American Academy of Neurology (AAN) has demonstrated a commitment to brain health through its public outreach and advocacy. The AAN's Brain Health Initiative launched in 2022 with a strategic plan prioritizing brain health as a key aspect of public engagement and positioning the AAN and neurologists as champions of brain health in collaboration with a broad range of other brain health providers. In this study, we present (1) the new definition of brain health developed by the AAN for neurologists, patients, partners in health care, and the public; (2) the strategic objectives of the AAN Brain Health Initiative; and (3) the AAN Brain Health Platform and Action Plan framework, including key positions on brain health, its 3 ambitious goals, and a national brain health vision. The top-line priorities of the AAN Brain Health Action Plan highlight the need for research, education, public policy, and direct-to-public messaging across the individual's life span and will serve as a catalyst for future cross-disciplinary collaborations within each epoch and longitudinally. The AAN Brain Health Platform is designed to communicate the AAN's vision for brain health and provide a blueprint toward achieving the future of optimal brain health across the life span for all. Through this position statement, we call upon neurologists and other stakeholders in brain health to join our collective efforts to accomplish the ultimate goal of transforming the current trajectory of public health of an increasing burden of neurologic disorders-from both illness and injury-to achieving optimal brain health for all.

INTRODUCTION AND PROBLEM STATEMENT/UNASSIGNED:As the role of teleneurology expands, it is important to prepare trainees to perform virtual encounters proficiently. OBJECTIVES/UNASSIGNED:We created a comprehensive multimodality teleneurology curriculum for residents to teach key aspects of telehealth encounters including the virtual examination and skill development across several environments. METHODS AND CURRICULUM DESCRIPTION/UNASSIGNED:We developed and implemented a teleneurology curriculum focused on teaching the virtual neurologic examination, measuring teleneurology competency, and providing opportunities for trainees to perform telehealth encounters in multiple settings. Residents (N = 22) were first surveyed on what methods would be most helpful to learn teleneurology. Trainees observed a faculty member conducting a teleneurology visit with another faculty member playing a patient. Residents then practiced a teleneurology encounter during a 10-minute objective structured clinical examination (OSCE) at a simulation center. After positive feedback from the fall of 2020, we adapted the OSCE to be completely remote in the spring of 2021 for senior residents. Trainees then performed teleneurology visits during their continuity clinics and subspecialty clinic rotations. RESULTS AND ASSESSMENT DATA/UNASSIGNED:< 0.05) and requested more access to simulations during training. Sensorimotor assessment and adequate visualization of the affected limb were identified as areas for improvement. DISCUSSION AND LESSONS LEARNED/UNASSIGNED:Our multimodal 3-year teleneurology curriculum provides opportunities for residents to learn and apply teleneurology. Survey tools helped strengthen the curriculum to optimize educational potential. We implemented a teleneurology simulation with and without the use of a simulation center. We plan to expand our teleneurology clinical and simulation experiences to trainees based on our data and further developments in teleneurology and to track the progress of teleneurology skills as residents advance through training.

Mitigating the substantial public health impact of concussion is a particularly difficult challenge. This is partly because concussion is a highly prevalent condition, and diagnosis is predominantly symptom-based. Much of contemporary concussion management relies on symptom interpretation and accurate reporting by patients. These types of reports may be influenced by a variety of factors for each individual, such as preexisting mental health conditions, headache disorders, and sleep conditions, among other factors. This can all be contributory to non-specific and potentially misleading clinical manifestations in the aftermath of a concussion. This review aimed to conduct an examination of the existing literature on emerging approaches for objectively evaluating potential concussion, as well as to highlight current gaps in understanding where further research is necessary. Objective assessments of visual and ocular motor concussion symptoms, specialized imaging techniques, and tissue-based concentrations of specific biomarkers have all shown promise for specifically characterizing diffuse brain injuries, and will be important to the future of concussion diagnosis and management. The consolidation of these approaches into a comprehensive examination progression will be the next horizon for increased precision in concussion diagnosis and treatment.

PURPOSE/OBJECTIVE:Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGF-β coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs. EXPERIMENTAL DESIGN/METHODS:ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models. RESULTS:ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis. CONCLUSIONS:Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease.

This study investigated the individual and combined utility of 10 embedded validity indicators (EVIs) within executive functioning, attention/working memory, and processing speed measures in 585 adults referred for an attention-deficit/hyperactivity disorder (ADHD) evaluation. Participants were categorized into invalid and valid performance groups as determined by scores from empirical performance validity indicators. Analyses revealed that all of the EVIs could meaningfully discriminate invalid from valid performers (AUCs = .69-.78), with high specificity (≥90%) but low sensitivity (19%-51%). However, none of them explained more than 20% of the variance in validity status. Combining any of these 10 EVIs into a multivariate model significantly improved classification accuracy, explaining up to 36% of the variance in validity status. Integrating six EVIs from the Stroop Color and Word Test, Trail Making Test, Verbal Fluency Test, and Wechsler Adult Intelligence Scale-Fourth Edition was as efficacious (AUC = .86) as using all 10 EVIs together. Failing any two of these six EVIs or any three of the 10 EVIs yielded clinically acceptable specificity (≥90%) with moderate sensitivity (60%). Findings support the use of multivariate models to improve the identification of performance invalidity in ADHD evaluations, but chaining multiple EVIs may only be helpful to an extent.

CSF1R-related leukoencephalopathy is an autosomal dominant neurological disorder causing microglial dysfunction with a wide range of neurologic complications, including motor dysfunction, dementia and seizures. This case report highlights an unusual presentation of CSF1R-related leukoencephalopathy with radiographic spinal cord involvement initially diagnosed as multiple sclerosis. The case highlights the importance of considering adult-onset neurogenetic disorders in the setting of white matter disease. Genetic testing provides a confirmatory diagnosis for an expanding number of adult-onset leukoencephalopathies and informs therapeutic decision-making.

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https : //neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.

STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS:We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS:Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS:Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.

A 74-year-old man with chronic obstructive pulmonary disease, glaucoma, and Stage IIIB squamous cell lung cancer experienced several minutes of flashing lights in his right visual hemifield, followed by onset of a right visual field defect. On examination, the patient had a right homonymous hemianopsia that was most dense inferiorly by confrontation testing. Emergent CT scan of the head revealed a 2.5 × 3 cm hypodensity in the left occipital lobe, which was interpreted as an acute stroke. Continuous EEG monitoring captured left posterior quadrant seizures that were temporally correlated to the positive visual phenomena. Subsequent MRI of the brain with and without contrast revealed a conglomerate of centrally necrotic and peripherally enhancing mass lesions. On biopsy, a thick purulent material was drained and Gram stain of the sample revealed gram-positive beaded rods, which speciated to Nocardia farcinica. The patient was treated with a six-week course of intravenous meropenem and a one-year course of oral trimethroprim-sulfamethoxazole. On follow-up, the patient experienced resolution of the right visual field deficit.