Faculty Bibliography

RATIONALE/BACKGROUND:The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. METHODS:Neuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. RESULTS:The highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23-40% cognitively intact, 24-29% single domain impairment, 13-20% bi-domain impairment, and 18-33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15-18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. CONCLUSIONS:These results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands.

BACKGROUND AND OBJECTIVES/UNASSIGNED: METHODS/UNASSIGNED:variants were recruited through physicians' practices and patient organization groups. We used standardized questionnaires to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder and adaptive skills of patients. We also assessed caregiver burden. RESULTS/UNASSIGNED:de novo variants. One patient with a partial exon 3 deletion had greater daily living skills and social skills than others with single-nucleotide variants. Ten of 14 (71%) patients had drug-resistant seizures, treated with a median of 2 antiseizure medications. All patients (100%) had abnormal pain processing. Sleep disturbances, social communication disorders, and aggressive/self-injurious behaviors were each reported in 86% of patients. Only half of adults could walk with minimal or no assistance. Toileting was normal in 29%, and 71% had constipation. No adult patients could read or understand verbal material at a sixth-grade level or higher. Aggressive/self-injurious behaviors were leading cause of caregiver burden. The oldest patient was aged 65 years; although nonambulant, she had walked independently when younger. DISCUSSION/UNASSIGNED:-DEE. Only 50% of adults can ambulate with minimal or no assistance. Almost all adult patients depend on caregivers for many activities of daily living. Prompt diagnostic genetic testing of adults with DEE can inform clinical care and guide outcomes of precision therapies.

AIMS/UNASSIGNED:The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach. METHODS/UNASSIGNED:A total of 60 surgeons from 11 countries were invited to develop consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest within patellar instability. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered to be unanimous. RESULTS/UNASSIGNED:Of 27 questions and statements on patellar instability, three achieved unanimous consensus, 14 achieved strong consensus, five achieved consensus, and five did not achieve consensus. CONCLUSION/UNASSIGNED:The statements that reached unanimous consensus were that an assessment of physeal status is critical for paediatric patients with patellar instability. There was also unanimous consensus on early mobilization and resistance training following nonoperative management once there is no apprehension. The statements that did not achieve consensus were on the importance of immobilization of the knee, the use of orthobiologics in nonoperative management, the indications for MPFC repair, and whether a vastus medialis oblique advancement should be performed.

BACKGROUND/UNASSIGNED:Although current programs exist to encourage undergraduate interest in neuroscience and neurology, few students go on to pursue a career in neurology. Thus, there is a need for more neurologists in the US. To assess undergraduate pipeline programs and their goals of garnering interest and knowledge of neurology, we systematically reviewed available literature on existing undergraduate neurology pipeline programs. METHODS/UNASSIGNED:A medical librarian conducted an electronic database search of PubMed, EMBASE, PsycINFO, Education Source, and ERIC based on a search strategy developed with a team of undergraduates and a neurologist. Of the 2,852 articles screened, 33 met the systematic review criteria and were evaluated based on the type and goal of the pipeline program, its delivery, and efficacy. RESULTS/UNASSIGNED:The 33 programs were classified into subtypes of pipeline programs, with focuses ranging from student-led projects to early clinical research opportunities. All programs were found to be successful in attracting student interest in neurology, providing exposure to relevant opportunities, and classroom enrichment. DISCUSSION/UNASSIGNED:The existing literature shows that neurology pipeline programs successfully inspire interest in a career in neurology among undergraduate students. These programs are valuable supplements to undergraduate neuroscience curricula and instrumental in introducing students to various fields.

BACKGROUND/UNASSIGNED:Diroximel fumarate (DRF) is approved for adults with relapsing-remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate (DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF. OBJECTIVE/UNASSIGNED:To report final outcomes from EVOLVE-MS-1. METHODS/UNASSIGNED:EVOLVE-MS-1 was an open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in patients with RRMS. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory. RESULTS/UNASSIGNED:< 0.0001); adjusted annualized relapse rate was 0.13 (95% confidence interval: 0.11-0.15). CONCLUSION/UNASSIGNED:DRF was generally well tolerated over 2 years, with few discontinuations due to AEs; radiological measures indicated decreased disease activity from baseline. These outcomes support DRF as a treatment option in patients with RRMS.

The immunomodulatory effects of disease-modifying therapies for multiple sclerosis might affect the immune response to vaccines for severe acute respiratory syndrome coronavirus 2. We analyzed the severe acute respiratory syndrome coronavirus 2-specific antibody response and lymphocyte profile before and after Ad26.COV2.S (Johnson & Johnson) vaccination in natalizumab-treated patients with multiple sclerosis. There was a 72-fold increase in mean anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G levels 4 weeks after vaccination and a 137-fold increase after 6 months. Other immune signals were within normal ranges. Natalizumab-treated patients with multiple sclerosis had a robust immune response to Ad26.COV2.S vaccine, and other immune signals were not significantly affected.

OBJECTIVE:People with blindness and low vision face substantial challenges when navigating both indoor and outdoor environments. While various solutions are available to facilitate travel to and from public transit hubs, there is a notable absence of solutions for navigating within transit hubs, often referred to as the "middle mile". Although research pilots have explored the middle mile journey, no solutions exist at scale, leaving a critical gap for commuters with disabilities. In this paper, we proposed a novel mobile application, Commute Booster, that offers full trip planning and real-time guidance inside the station. METHODS AND PROCEDURES/METHODS:Our system consists of two key components: the general transit feed specification (GTFS) and optical character recognition (OCR). The GTFS dataset generates a comprehensive list of wayfinding signage within subway stations that users will encounter during their intended journey. The OCR functionality enables users to identify relevant navigation signs in their immediate surroundings. By seamlessly integrating these two components, Commute Booster provides real-time feedback to users regarding the presence or absence of relevant navigation signs within the field of view of their phone camera during their journey. RESULTS:As part of our technical validation process, we conducted tests at three subway stations in New York City. The sign detection achieved an impressive overall accuracy rate of 0.97. Additionally, the system exhibited a maximum detection range of 11 meters and supported an oblique angle of approximately 110 degrees for field of view detection. CONCLUSION/CONCLUSIONS:The Commute Booster mobile application relies on computer vision technology and does not require additional sensors or infrastructure. It holds tremendous promise in assisting individuals with blindness and low vision during their daily commutes. Clinical and Translational Impact Statement: Commute Booster translates the combination of OCR and GTFS into an assistive tool, which holds great promise for assisting people with blindness and low vision in their daily commute.

AIMS/UNASSIGNED:The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process. METHODS/UNASSIGNED:This was the second part of a study dealing with these aspects of management in these patients. As in part I, a total of 60 surgeons from 11 countries contributed to the development of consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered unanimous. RESULTS/UNASSIGNED:Of 41 questions and statements on patellar instability, none achieved unanimous consensus, 19 achieved strong consensus, 15 achieved consensus, and seven did not achieve consensus. CONCLUSION/UNASSIGNED:Most statements reached some degree of consensus, without any achieving unanimous consensus. There was no consensus on the use of anchors in MPFL reconstruction, and the order of fixation of the graft (patella first versus femur first). There was also no consensus on the indications for trochleoplasty or its effect on the viability of the cartilage after elevation of the osteochondral flap. There was also no consensus on postoperative immobilization or weightbearing, or whether paediatric patients should avoid an early return to sport.