Faculty Bibliography

PURPOSE/OBJECTIVE:The Unified Multiple System Atrophy Rating Scale (UMSARS) is widely used as an outcome measure in MSA trials, but it has limitations for clinical trial use. To address these, we developed the Multiple System Atrophy Combined Outcome Assessment (MuSyCA), a comprehensive multimodal tool for disease-modifying MSA trials. The purpose of this manuscript is to describe the development and validation plan for MuSyCA, with emphasis on its structure, intended use, and assessment of reliability, validity, and sensitivity in tracking disease progression. METHODS:The development of MuSyCA followed a multistep process. Candidate outcome assessments were identified through systematic literature review and analysis of longitudinal data from large MSA cohorts. Content was refined through multiple Delphi-like consensus rounds involving MSA experts, patient advocacy groups representatives, and industry stakeholders. Cognitive interviews conducted in 20  patients with MSA evaluated the clarity and clinical relevance of patient- and clinician-reported outcomes; feedback was incorporated into a subsequent version of the MuSyCA. Validation is ongoing and includes assessment of construct validity, internal consistency, test-retest reliability, and responsiveness. Longitudinal analyses to determine sensitivity to change over time are ongoing. RESULTS:MuSyCA combines patient- and clinician-reported outcomes, biomarkers (neurofilament light chain, neuroimaging), and performance-based measures to capture subjective and objective aspects of MSA progression, enhancing its utility  to detect treatment effects in clinical trials. MuSyCa is not intended to be used in clinical practice. CONCLUSIONS:MuSyCA offers a multidimensional approach to MSA assessment, supporting precise, disease-relevant evaluations in trials of putative disease-modifying therapies. Its validation will provide a standardized multimodal outcome measure, advancing MSA therapeutic development.

Tennis is played globally across diverse climates and surfaces, exposing athletes to variable levels of environmental heat stress. With rising global temperatures and more frequent heat events, protecting players' health has become a major priority in the sport. This panel discussion aimed to synthesize current evidence and expert perspectives on measuring, managing, and mitigating heat stress in tennis, with a focus on harmonizing policies across governing bodies and player groups. Experts from sport science, medicine, and tournament operations reviewed recent advances in heat measurement tools, including the limitations of the Wet Bulb Globe Temperature (WBGT) and the emergence of tennis-specific heat stress models. Evidence-based cooling strategies-such as ice towels, shaded recovery, and cold-water immersion-were discussed alongside differentiated policy needs for men, women, juniors, seniors, and wheelchair athletes. The discussion further highlighted challenges in achieving effective heat acclimatisation within professional travel schedules and underscored the importance of proactive medical readiness and player education. Enhanced consistency in heat policies, improved access to cooling resources, and continued collaboration between scientists and governing bodies are essential to safeguard player health and performance under increasing environmental heat stress.

BACKGROUND/UNASSIGNED:The Standard of Care (SOC) for treating significant spinal epidural abscesses (SEA) is STAT surgery for patients with the new-onset of neurological deficits following STAT contrast MR studies confirming significant neural (i.e. mild/moderate, moderate, or marked cord/nerve root) compression. Too many health care professionals, including physicians, and select spine surgeons still wrongly believe delaying "acute" spinal decompressions in patients with SEA for up to 8, 12, and even 24 hours is acceptable even in paralyzed patients. METHODS/UNASSIGNED:Here we review the fact that the standard of care for treating SEA is STAT surgery for patients demonstrating the new-onset of neurological deficits following STAT contrast MR scans confirming significant neural compression. RESULTS/UNASSIGNED:STAT surgery for newly neurologically symptomatic patients with SEA following STAT contrast MR scans documenting significant neural compression yields the best results. Notably, select patients without neural deficits or significant MR neural compression may be considered for non-surgical treatment. The "gold standard" for diagnosing SEA is the contrast MR, while non-contrast CT studies almost uniformly fail to diagnose SEA, and Myelogram-CT studies have significant limitations (i.e. risk of causing meningitis, and may fail to document cephalad extent of SEA if there is a distal total block to intrathecal contrast). CONCLUSION/UNASSIGNED:STAT surgery is the SOC and treatment of choice for patient with SEA demonstrating significant new-onset neurological deficits with significant STAT contrast MR findings of neural compression. Further, STAT means STAT, no waiting period is acceptable (i.e. 8, 12 or up to < 24 hours) particularly in paralyzed patients.

PURPOSE OF REVIEW/OBJECTIVE:This review discusses the current state of the evidence related to the relationship between the cerebellum and epilepsy, highlighting evidence on neurostimulation of the cerebellum for treatment of epilepsy, and placing current knowledge into historical context. RECENT FINDINGS/RESULTS:The cerebellum plays an important role in certain epilepsy types, both as a key part of epileptic networks and an area that can give rise to seizures. Cerebellar stimulation as a potential treatment for drug-resistant epilepsy is a recurring, albeit niche, topic of interest. Over decades of intermittent, often highly limited investigations into this area of research, there are still more questions than answers. However, more recent preclinical insights point the way towards leveraging modern surgical techniques and technology in investigating cerebellar stimulation as a potential viable treatment approach to select types of epilepsy. SUMMARY/CONCLUSIONS:Cerebellar stimulation holds promise for improving seizure control in people with specific types of drug-resistant epilepsy. Future studies should leverage new preclinical data, along with modern technology, neurosurgical techniques, and clinical trial design, to help determine the optimal stimulation parameters, optimal stimulation targets, and optimal patient-selection for this promising area of investigation.

Childhood adversity is increasingly recognized as a critical modifier of neurologic disorder development and disease severity, including in the neuroimmune disorder multiple sclerosis (MS). While previous studies have linked early-life adversity to increased MS susceptibility and more severe disease, the underlying biological mechanisms remain poorly understood. This study investigated associations between childhood adversity and MS clinical features, with a focus on two potential pathogenic mechanisms: allostatic load and epigenetic modifications. We evaluated 60 consecutively enrolled young adults with MS; 30 with paediatric-onset MS (POMS) and 30 with adult-onset MS (AOMS). At time of enrolment in this cross-sectional study, participants had MS disease duration of 6 years on average. POMS participants were mean 22.09 (2.66) years and AOMS participants were mean 32.41 (2.19) years old. 62% of participants were female. Childhood adversity was defined using a composite index of individual, family and socioeconomic measures captured by the adverse childhood experiences questionnaire, parental education level and estimated household income during childhood. Clinical outcomes included patient-reported SymptoMScreen questionnaire regarding MS symptom burden and MS neurologist-assessed disability using the Expanded Disability Status Scale (EDSS) of the participant's neurologic exam at the time of enrolment. Circulating biomarkers of allostatic load and genome-wide epigenetic profiles (DNA methylation via RRBS; reduced representation bisulfite sequencing) were also assessed. A history of high childhood adversity was associated with significantly greater patient-reported MS symptom burden (P = 0.001) and higher neurologist-reported EDSS disability scores (P = 0.028), independent of disease duration or timing of treatment initiation. There were no differences between childhood adversity and circulating biomarkers of allostatic load. While childhood adversity was not associated with global epigenetic changes across the entire cohort, stratified analysis revealed divergent methylation patterns by age of MS onset: POMS participants with childhood adversity had increased DNA methylation, whereas AOMS participants with childhood adversity showed decreased methylation compared to individuals without childhood adversity. None of the observed clinical and biologic differences were explained by differences in disease duration or the interval between symptom onset and treatment initiation. Our findings suggest that childhood adversity is associated with increased MS symptom burden and neurologic disability in young adults with MS. Childhood adversity may differentially shape the epigenome, depending on the age of MS onset, with potential implications for disease trajectory and therapeutic vulnerability. These results support the biological embedding of childhood adversity in MS and highlight the need for age- and exposure-sensitive approaches to understanding MS pathogenesis across the lifespan.

The convergence of artificial intelligence (AI) and neuroscience represents one of medicine's most profound intellectual partnerships. Neuronal architecture has inspired computational methods, while computational models, evolving from theoretical constructs to transformative clinical tools, are reshaping neurological practice. As AI systems attempt to augment diagnostic accuracy, treatment planning, and patient care, neurologists must develop fluency in these technologies to harness their potential while navigating their limitations and dangers. AI-related publications have exponentially increased in recent years, yet many neurologists lack the foundational computer science background needed to critically evaluate and most safely and effectively implement these tools in clinical practice. This article serves to outline the historical foundations linking neuroscience to computing, examine core concepts of the past and current AI landscape in neurology, and describe methodologies that aim to revolutionize neurological care.

INTRODUCTION/BACKGROUND:We examined obstructive sleep apnea (OSA) severity's association with Alzheimer's disease (AD) plasma biomarkers, independent or synergistic with cerebrospinal fluid (CSF) amyloid, and as a proof of concept, whether plasma amyloid beta (Aβ)42/Aβ40 with OSA severity improves detection of amyloidosis and tau pathology. METHODS:In 120 cognitively normal older adults (70 with CSF data) from New York University sleep and aging studies (2013-2021), OSA severity was measured using apnea/hypopnea index with 4% desaturation; plasma Aβ40, Aβ42, tau, and neurofilament light chain (NfL) via single molecule array; CSF amyloid and tau via enzyme-linked immunosorbent assay. Associations evaluated adjusted correlations and generalized models; receiver operating characteristic analyses evaluated diagnostic accuracy. RESULTS:OSA severity correlated with plasma Aβ40 (r = 0.21), Aβ42 (r = 0.26), and Aβ42/Aβ40 (r = 0.20). Plasma tau and NfL associations depended on CSF-Aβ42. OSA severity with Aβ42/Aβ40 improved CSF amyloidosis (area under the curve [AUC] = 0.78) and tau pathology (AUC = 0.71) detection. DISCUSSION/CONCLUSIONS:OSA severity relates to elevated plasma Aβ and, with CSF amyloid, to tau/NfL. Combined plasma and OSA measures aid non-invasive AD associations' detection.

BACKGROUND:Ischemic/anoxic brain injury is often assumed to occur within minutes of severe cerebral ischemia. However, emerging evidence suggests brain tissue may be more resilient, with important implications for resuscitation. We hypothesized that during prolonged cardiac arrest, cortical electrical activity may be restorable if cerebral oxygenation thresholds are met and may be associated with return of spontaneous circulation (ROSC). METHODS:) during cardiopulmonary resuscitation (CPR). RESULTS:≥16%, and alpha at >40%. Alpha activity was seen up to 35 min, and delta/theta up to 60 min into CPR. Suppression reverted to near-normal in 12% of transitions. Alpha activity was associated with ROSC (OR 5.4; 95% CI 1.08-29.20; p = 0.045), while suppression predicted lower ROSC odds (OR 0.12; 95% CI 0.02-0.53; p = 0.002). Survival analysis was limited by small sample size. CONCLUSION/CONCLUSIONS:Near-physiologic brain activity may be restored during prolonged CPR if oxygenation thresholds are met and is associated with ROSC. Further research is needed to evaluate survival outcomes.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The link between repetitive head impact (RHI) exposure, later-life cognitive decline, and neurobehavioral dysregulation (NBD) is not well understood. Recent work has implicated inflammation and limbic dysfunction as relevant RHI correlates. Our goal was to integrate plasma and CSF inflammatory biomarkers, structural brain imaging, and clinical measures in former elite American football players to better understand reasons for RHI-related cognitive and neurobehavioral changes. METHODS: RESULTS: DISCUSSION/CONCLUSIONS:In former elite football players, elevated plasma and CSF inflammatory markers were associated with poorer limbic WM microstructure, which in turn related to worse cognition. Given the limbic system's role in cognition and behavior, inflammation may be a modifiable target for RHI-related neurodegeneration. Limitations include the cross-sectional design and limited generalizability to other contact sports, lower levels of play, female athletes, or other RHI sources.