Faculty Bibliography

OBJECTIVE:To compare seizure outcomes during pregnancy in women with epilepsy (WWE) by history of catamenial patterns. BACKGROUND:Catamenial patterns are defined as increased seizure frequency during certain phases of the menstrual cycle (perimenstrual, peri-ovulatory, or luteal in anovulatory cycles). Animal studies suggest seizure improvement occurs with higher progesterone and allopregnanolone concentrations and lower estrogen concentrations. Prior human studies also reported that WWE with catamenial patterns were more likely to have improved seizure frequency during pregnancy, presumably due to higher sensitivity to fluctuations in sex steroid hormones. DESIGN/METHODS/METHODS:Women with epilepsy (WWE), ages 18-40yo, were enrolled in a longitudinal, prospective cohort study at time of attempting conception to compare fertility outcomes to healthy controls. Once enrolled, WWE used a daily diary app for menstrual and seizure tracking from preconception through delivery. For this secondary analysis, participants were excluded if they chose to discontinue the study, if they did not become pregnant, were seizure free preconception, if their diary data was inadequate (defined as <80 % of the days tracked), or if they had <1 month of seizure data tracked prior to conception. Prospective diary data was used to determine if participants met criteria for observed catamenial patterns. Seizure frequency during pregnancy was compared to preconception frequency. RESULTS:Among 89 participants, 13 became pregnant with seizure tracking; 6 (46 %) met criteria for catamenial epilepsy. Focal epilepsy was less common than generalized epilepsy in the catamenial group (33 %) vs the non-catamenial group (86 %, p = 0.10). No significant differences in seizure frequency change from preconception to pregnancy were observed between groups (p = 0.42). During pregnancy, 33 % of the catamenial group and 43 % of the non-catamenial group became seizure-free (p = 0.99). Seizure improvement or stability occurred in 67 % and 86 %, respectively (p = 0.56). CONCLUSIONS:In patients who had preconception seizures, seizure control during pregnancy was generally favorable: many patients' seizure frequency improved or achieved seizure freedom. There was no clear evidence that a pre-conception catamenial pattern immediately before pregnancy altered prognosis. Further research is needed to guide counseling and treatment during pregnancy.

BACKGROUND:Individuals with sensory processing disorders (SPDs) face challenges in wayfinding due to heightened sensitivity to environmental stimuli like noise and lighting. Although sensory maps have aided SPD individuals by aligning navigational routes with sensory needs, standardized protocols for creating these maps are lacking, with current methods largely qualitative. OBJECTIVE:This study aimed to establish a standardized, quantitative protocol for sensory map creation, evaluating sound, brightness, and crowding density in a healthcare setting to enhance map precision and support future automation. METHODS:Sensory data were collected from the 1st and 17th floors of a large urban ambulatory care center in New York City. A qualitative spatial audit was initially conducted, followed by quantitative measurements of sound (decibels), brightness (lux), and crowding density at designated nodes. Using Python, we developed Voronoi diagrams to visualize intensity distributions across floorplans, applying statistical methods to ensure data accuracy and consistency. RESULTS:Qualitative assessments identified high-stimulus areas, particularly in the main lobby and elevator zones, which aligned closely with quantitative findings. Brightness peaked in central, naturally lit areas, while noise levels were highest near heating, ventilation, and air conditioning (HVAC) systems and entry points. The quantitative method enabled a more nuanced representation, enhancing map detail and reliability. CONCLUSIONS:The developed quantitative protocol offers a robust framework for sensory mapping, improving accessibility for individuals with SPDs in complex spaces. This approach holds potential for automation, addressing current reproducibility limitations and advancing inclusive design in public and healthcare settings.

BACKGROUND:Cognitive impairment (CI) is prevalent in people with multiple sclerosis (PwMS) and influences employment outcomes independent of physical disability. Although associations between multi-domain CI and employment have been established, less is known about the relative clinical utility of brief cognitive screening tools versus time-efficient multi-domain computerized assessments that can be implemented in routine care. OBJECTIVES/OBJECTIVE:To compare the Symbol Digit Modality Test (SDMT) and NeuroTrax computerized cognitive battery (NT) as predictors of self-reported employment status in PwMS. METHOD/METHODS:109 PwMS (Mean age = 48 years, SD = 10.4; 74 % female) completed the oral SDMT and NT as part of routine clinical care. Employment status was self-reported as "employed" or "unemployed" (including early retirement if <55 years). RESULTS:(3) = 17.862, p < .001), with executive function and attention most frequently impaired. CONCLUSION/CONCLUSIONS:While the SDMT remains a useful screening tool, the NT appears clinically feasible for use in routine care and provides incremental and domain-specific information beyond processing speed alone. Extending assessment in routine care beyond a single screening measure may better characterize cognitive profiles associated with unemployment and inform individualized vocational interventions in PwMS.

INTRODUCTION/BACKGROUND:Multiple sclerosis (MS) is a chronic, immune-mediated neurological disease, leading to significant morbidity. Over 25 disease-modifying therapies (DMTs) are approved for MS; however, older patients may benefit less from high-efficacy DMTs. We compared the risk of severe infections (SIs) and annualized relapse rate (ARR) by age (< 45 and ≥ 45 years) between diroximel fumarate (DRF) and anti-CD20 monoclonal antibodies (mAbs) in patients with MS. METHODS:This retrospective study utilized the Komodo Health Claims database to identify patients treated with DRF or anti-CD20 agents. Patients were propensity score matched 1:1 on baseline characteristics and stratified by age (younger: < 45 years; older: ≥ 45 years). Infection-related encounters were identified by diagnosis codes; SIs required hospitalization or intravenous antibiotics. MS relapses were based on inpatient or outpatient claims and associated treatments. RESULTS:Between 2016 and 2025, 2894 propensity score-matched patients with MS who initiated DRF (n = 1447) or anti-CD20s (n = 1447) were included. DRF-treated patients had a lower proportion of SIs at 12 and 24 months compared with anti-CD20-treated patients (p ≤ 0.002 at 24 months). Younger DRF-treated patients had significantly fewer SIs (p = 0.005), while older DRF-treated patients had lower non-SI rates. COVID-19-related SIs were also significantly lower in DRF-treated patients (p < 0.001). ARRs were similar between the two groups. CONCLUSION/CONCLUSIONS:DRF-treated patients with MS had a significantly lower risk of SI compared with anti-CD20-treated patients, with no difference in ARR. More real-world studies are needed to understand the efficacy and safety of DMTs in the setting of de-escalation in aging patients with MS.

Peptidoglycan (PG), the primary load-bearing component of bacterial cell envelopes, is a bio-derived material whose mechanical and hydration properties are central to microbial viability and their environmental responsiveness. PG has been increasingly recognized as a scalable water-responsive (WR) material, capable of converting chemical potential gradients from ambient changes in relative humidity (RH) directly into mechanical work. In this study, we leverage stress-induced PG remodeling pathways in a BB-3 Escherichia coli (E. coli) strain to modulate the architecture of its PG sacculus for enhanced WR performance. Under arabinose-deprived conditions (-Ara), BB-3 PG exhibits a twofold increase in the ratio of crosslinked-to-linear muropeptide stems and a threefold rise in the relative abundance of ③-③ (mDap-mDap) linkages relative to an arabinose-rich (+Ara) control. When responding to RH changes between 10% and 90% RH, these molecular-level modifications translated into a fivefold increase in WR actuation energy density (623.0 kJ/m³) with rapid response times on the order of seconds (τ_d: 1.8 s, τ_h: 0.7 s). The remodeled PG also displays a significant increase in stiffness (E: 8.9 GPa at 10% RH) and an 8% greater uptake of water, driving the PG matrix to generate twofold higher WR strain (ε: 30.2%). The observed increases in water retention and WR behavior of E. coli PG may also carry intriguing evolutionary implications, reflecting adaptive strategies microbes take to restructure PG layers and survive under microenvironmental nutrient scarcity. STATEMENT OF SIGNIFICANCE: Current testing of water responsive (WR) engineered living materials (ELMs) has largely overlooked bacterial species other than Bacillus subtilis. Our work addresses this gap by demonstrating that the peptidoglycan (PG) sacculus of Escherichia coli also exhibits robust WR properties. Through leveraging a combination of genetic and environmental factors during the organism's growth phase, we demonstrate that these properties can be rationally improved to yield enhanced actuator materials. By establishing a connection between PG crosslinking architecture and emergent mechanical and hydration dynamics, we present a promising approach to engineer dynamic and sustainable ELMs that can be employed as active components in high-performance actuators.

OBJECTIVE:This study aimed to understand the factors limiting access to medications for the preventive treatment of migraine and to improve access to evidence-based preventive care. BACKGROUND:For decades, the effective use of medication for the preventive treatment of migraine was limited by slow onset, slow and complex dose titration schedules, modest benefits, drug interactions, frequent side effects, and very low long-term adherence. The calcitonin gene-related peptide (CGRP) targeted preventive medications mitigate some of these limitations and demonstrated substantial therapeutic benefits in a significant proportion of adults with migraine. The American Headache Society considers these medications among the first-line options for migraine prevention, although access to them remains limited. The American Migraine Foundation hosted a single-day, multidisciplinary expert panel discussion to identify barriers to optimal preventive care and developed recommendations to address them. METHODS:Participants identified and prioritized barriers and used a modified nominal group technique to achieve consensus on them. A series of moderated discussions in plenary and breakout sessions was used to create possible solutions. Modified nominal group technique was also employed to achieve consensus on the priorities among these barriers and to achieve whole-group consensus on the recommendations. Ethical issues that inform access were discussed. RESULTS:Participants included eight neurologists and board-certified headache specialists, six representatives of reimbursement decision-makers, six employees of life sciences companies, four patient advocates with lived experience with migraine, and a medical ethicist. Among those who have consulted healthcare professionals and received a diagnosis of migraine, we identified four main barriers to accessing preventive treatment: restrictive prior authorization requirements, the perceived lack of real-world evidence and treatment guidelines, the need for clinician education, and the need for patient education. Consensus recommendations for eliminating barriers centered on using new evidence to evaluate policies that restrict the selection of first-line therapies, initiating/improving collaboration among stakeholders, sharing of data and best practices, and increased training. Participants agreed to explore novel definitions of the value of preventive treatment and to establish the Migraine Prevention Network to facilitate ongoing cooperation and collective action. However, due to financial limitations, staffing changes, and time constraints, post-meeting discussions led to a shift from establishing a broad Migraine Prevention Network to forming smaller task forces focused on the top-priority barriers (real-world evidence and The Patient Playbook) identified through collaborative voting among American Headache Society, American Migraine Foundation, and industry stakeholders. CONCLUSIONS:Adults with migraine face multiple barriers in accessing novel migraine-specific, CGRP-targeted preventive treatment. Stakeholders in the delivery of care, including clinicians, reimbursement decision-makers, life sciences companies, and patient and clinician advocates, may be able to overcome many of these barriers and improve access by working with and on behalf of patients.

BACKGROUND/UNASSIGNED:Tapia's syndrome is a rare neurological condition defined by concurrent unilateral paralysis of the vagus (cranial nerve X) and hypoglossal (cranial nerve XII) nerves. It is most commonly reported as an iatrogenic complication of procedures involving airway manipulation, such as orotracheal intubation. This report describes a unique case of Tapia's syndrome with a temporal association to the initiation of noninvasive continuous positive airway pressure (CPAP) therapy. CASE PRESENTATION/UNASSIGNED:A 66-year-old female presented with a four-day history of acute-onset dysphonia, dysphagia, and right-sided tongue deviation. Her symptoms began shortly after initiating CPAP therapy with a full-face mask for newly diagnosed obstructive sleep apnea. She had also recently received multiple vaccinations. Clinical examination revealed right-sided vagus and hypoglossal nerve palsies, and laryngoscopy confirmed right vocal cord paralysis. Extensive diagnostic evaluation, including magnetic resonance imaging and angiography of the brain and neck, effectively excluded central nervous system pathologies such as stroke, demyelinating disease, or mass lesions and diagnosis of Tapia's syndrome was made. The patient was managed by discontinuing CPAP and administering a course of oral corticosteroids, alongside speech and swallowing therapy. She experienced a near-complete resolution of her symptoms over 6 weeks. CONCLUSION/UNASSIGNED:This case suggests that Tapia's syndrome can be a rare complication of noninvasive airway support. A multifactorial etiology involving mechanical nerve compression from the CPAP apparatus, potentially compounded by an immune-mediated nerve sensitization from recent vaccinations, should be considered in the differential diagnosis of lower cranial neuropathies.

OBJECTIVE:The latest European Medicines Agency (EMA) guideline on the clinical investigation of medicines to treat epileptic disorders was adopted by the EMA Committee for Medicinal Products for Human Use in 2025. We compared this guideline with the previous version (2010), highlighting areas where significant revisions were introduced. METHODS:The 2025 and 2010 versions of the guideline were systematically analyzed to identify significant modifications. RESULTS:The latest EMA guideline incorporated terminology from the 2017 International League Against Epilepsy (ILAE) classification of seizures and epilepsy and the 2022 classification of syndromes and replaced the older term "antiepileptic drug (AED)" with "antiseizure medication (ASM)." Recommendations for add-on studies in common epilepsies have remained substantially unchanged, the main revision being the acceptability of the time-to-event design also for confirmatory trials, provided it is not the only design in the clinical development plan. A major novelty is the feasibility of extrapolating data from add-on trials to the monotherapy indication, provided specific conditions are met. Guidance on pediatric ASM development has been expanded, addressing extrapolation of efficacy from data in adults and older children and options for studies in developmental and epileptic encephalopathies and other rare epilepsies. Compared with the previous guideline, greater emphasis is placed on nonseizure outcomes, including functional, quality of life, and patient-reported outcomes. Two new sections have been introduced, addressing studies in neonates and clinical trials in status epilepticus and other seizure emergencies. Options for innovative designs, including registry-based studies, are also discussed in situations where randomized controlled trials are unfeasible. SIGNIFICANCE/CONCLUSIONS:The updated guideline reflects the changing scenario in epilepsy treatment development, with a greater focus on pediatric epilepsies, rare epilepsies, and other indications with high unmet needs. The updates also reflect the contribution during the consultation process by a wide range of stakeholders, including the ILAE Task Force on Regulatory Affairs.