Faculty Bibliography

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.

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.

OBJECTIVE:Interictal epileptiform discharges (IEDs) are transients observed on the electroencephalogram (EEG) of patients with epilepsy. IEDs have traditionally been recorded from scalp or intracranial EEG macrocontacts, which coarsely sample neural activity. Here, we investigated the use of flexible, high-resolution microelectrocorticographic (μECoG) arrays for measuring IEDs with greater spatiotemporal precision to test whether there exist microscale patterns of IED activity that may be missed on standard intracranial EEG. METHODS:) to record from seven patients undergoing surgical treatment of epilepsy. We identified IEDs by a combination of expert review and automated detection. We quantified the spatial extent of IEDs, mapped patterns of repeated IED activity, and quantified IED propagation direction using multilinear fit models. We also compared IED detection rates and propagation measurements between μECoG arrays and simulated macroarrays (10-mm spacing, 2.3-mm diameter). RESULTS:We demonstrated successful use of μECoG arrays to map intraoperative microscale patterns of IEDs. The majority of patients (5/7) exhibited elevated IED activity that was highly localized (subcentimeter localization). Across all patients, 40% of detected IEDs were observed within a 4-mm radius of cortex. μECoG arrays also mapped the direction of IED propagation. An average of 39% (range = 4.2%-96.5%, SD = ±36.8%) of the IED events captured by the μECoG arrays were not detectable by simulated macrocontacts. SIGNIFICANCE/CONCLUSIONS:These intraoperative data demonstrate that μECoG arrays can map the microscale spatiotemporal activity of IEDs. These patterns of IEDs may be poorly captured by standard, macroscale recording devices. Our findings support the use of high-resolution, large area coverage μECoG arrays for the presurgical and intraoperative mapping of epileptic cortex.

INTRODUCTION/BACKGROUND:This study aimed to explore the experience of living with amyotrophic lateral sclerosis (ALS) and to develop a conceptual model for this rare disease. METHODS:Concept elicitation interviews were conducted (January-September 2024) with people living with ALS (PLwALS; n = 31), caregivers (n = 20), and clinicians (n = 10). Qualitative data were analyzed separately to develop a conceptualization of the experience of living with ALS. Concept saturation was assessed every 5-6 interviews, and a conceptual model was developed. RESULTS:The mean age of PLwALS was 42.4 years (standard deviation [SD] 11.5), 81% were female, 84% were white, and 23% had SOD1-ALS. The mean time since diagnosis was 4.6 years (SD 4.2); mean normed Rasch Overall ALS Disability Scale score was 76 (SD 17.16). Signs, symptoms, and functions reported during PLwALS interviews included neuromuscular, bulbar, speech, neurocognitive (e.g., memory issues), and a range of physical functioning issues (e.g., motor coordination). PLwALS also reported impacts on a range of activities and psychosocial interactions (e.g., eating, depressed mood, and relationships), alongside management strategies they employed. Interviews with caregivers and clinicians supported findings from the PLwALS interviews. Caregivers also identified signs such as drooling/excess salivation, and impacts related to ALS management (e.g., need for writing aids). Clinicians additionally considered loss of speech and neurocognitive signs (e.g., behavior/personality change) as ALS clinical manifestations. Concept saturation was reached, and a consolidated, comprehensive conceptual model was developed. CONCLUSION/CONCLUSIONS:This research provides a holistic understanding of the experience of living with ALS and is the first conceptual model based on in-depth concept elicitation interviews. The findings highlight the range of signs, symptoms, and impacts that PLwALS experience, emphasizing its serious humanistic impact and high unmet need, and will help to guide patient-centric evaluation of clinical outcome assessments in future ALS studies.

PURPOSE/OBJECTIVE:Cannabidiol has well described drug interactions including inhibition of clobazam metabolism. Phenytoin is known to induce metabolism of cannabidiol. Cannabidiol inhibition of phenytoin metabolism is predicted but not well described. METHODS:We present the cases of two individuals with Lennox Gastaut Syndrome which demonstrate the clinical relevance of cannabidiol inhibition of phenytoin metabolism. RESULTS:In the first case, the addition of cannabidiol led to increased levels of phenytoin and clobazam which resulted in freedom from previously refractory tonic-clonic seizures. This was sustained for one year. The phenytoin dose was later lowered due to concern for liver function and this led to recurrent seizures despite continued elevation of N-desmethylclobazam levels, suggesting the higher phenytoin was responsible for the seizure control. In the second case, the addition of cannabidiol led to phenytoin toxicity with ataxia and falls. Lowering phenytoin dose led to resolution of these symptoms. CONCLUSION/CONCLUSIONS:Physicians should be aware of the interactions between phenytoin and cannabidiol in the management of epilepsy.

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.

PURPOSE/OBJECTIVE:Responsive neurostimulation (RNS) is an effective therapeutic option for drug-resistant focal epilepsy, especially when the seizure onset zone lies in an eloquent cortex. However, the safety, tolerability, efficacy, as well as optimal stimulation and detection settings for RNS therapy in the primary motor cortex are poorly understood. METHODS:We performed a multi-center retrospective cohort study to assess the safety and efficacy of treatment with RNS targeting the primary motor cortex in patients with drug-resistant focal motor epilepsy. RESULTS:A total of 20 patients were included in the study. Overall, 79 % of the patients achieved ≥ 50 % seizure reduction at a mean follow-up time of 58.4 months, while 53 % of the patients achieved ≥ 90 % seizure reduction. None of the patients had any complications from the surgical implantation of the RNS device. There were no reported adverse side effects from neurostimulation therapy of the primary motor cortex. CONCLUSION/CONCLUSIONS:For individuals with drug-resistant focal motor epilepsy, treatment with RNS of the primary motor cortex is safe, effective, and well-tolerated.

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.

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.