Faculty Bibliography

IMPORTANCE:Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact exposure. CTE can only be diagnosed post mortem, and the antemortem neuropsychological profile is poorly understood, hindering accurate diagnosis before death. OBJECTIVE:To characterize antemortem neuropsychological test performance of former National Football League (NFL) players with autopsy-confirmed CTE. DESIGN, SETTING, AND PARTICIPANTS:This retrospective case series included former NFL players who completed an antemortem neuropsychological evaluation and had autopsy-confirmed CTE. Data were collected between January 1, 2017, and April 30, 2025. Statistical analysis was performed from September 2025 to June 2026. EXPOSURE:CTE neuropathology, defined by the National Institute of Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering consensus panel. MAIN OUTCOMES AND MEASURES:Neuropsychological test performance, neuropathologic diagnoses, and semiquantitative phosphorylated tau (p-tau) pathology across 11 brain regions were examined. Raw scores were converted to z scores using age, sex, and/or education level-based normative data. Test results with z scores of -1.5 or less were categorized as impaired; domains with 2 or more impaired test results were considered impaired. RESULTS:The primary analytic sample included 33 men (mean [SD] age at death, 65.4 [13.3] years; mean [SD] time between testing and death, 2.4 [1.6] years), 25 with high- and 8 with low-stage CTE. Learning and memory was most impaired (17 of 27 [63.0%]), followed by executive function (15 of 29 [51.7%]) and language (12 of 29 [41.4%]). High-stage CTE participants generally had worse scores than low-stage CTE participants. Greater global p-tau burden was associated with worse learning and memory performance (B = -0.40; 95% CI, -0.70 to -0.09; P = .01). Findings were similar after excluding 9 participants with co-occurring Alzheimer disease or frontotemporal lobar degeneration tau. CONCLUSIONS AND RELEVANCE:In this retrospective case series of NFL players with autopsy-confirmed CTE, memory, executive function, and language impairments were common, and p-tau burden was associated with worse memory performance. Findings provide insight into the expected CTE neuropsychological profile and may help advance diagnosis before death.

PURPOSE/UNASSIGNED:To investigate the short-T1 fraction as a potential biomarker of white matter myelin integrity, using myelin histology as ground truth. METHODS/UNASSIGNED:short-T1 fraction data were acquired from two elderly volunteers with WMHs to demonstrate translational feasibility. RESULTS/UNASSIGNED:significant reductions in short-T1 fractions were detected within WMHs. CONCLUSION/UNASSIGNED:The short-T1 fraction correlated with myelin content in postmortem brain white matter, supporting its potential as a clinically translatable biomarker of myelin integrity.

BACKGROUND:Epstein-Barr virus (EBV) is a key environmental risk factor for multiple sclerosis (MS), and tonsils and adenoids serve as a primary viral reservoir. This study investigates the potential role of adenotonsillectomy in pediatric-onset multiple sclerosis (POMS) risk and relapse rate. OBJECTIVES/OBJECTIVE:status, were collected. Multivariable logistic regression assessed the association between adenotonsillectomy and MS risk. In addition, negative binomial regression offset by follow-up time was used to assess the relationship between adenotonsillectomy and relapse rate in POMS participants with available follow-up data. RESULTS: = 0.013). CONCLUSIONS:Prior adenotonsillectomy was associated with increased risk of MS and greater relapse rate in pediatric patients, suggesting a potential interplay between EBV, immune regulation, and MS pathogenesis.

The neurocritical care treatment team frequently interacts with patient surrogates and Organ Procurement Organizations (OPOs) at the end-of-life. A 2025 survey of Neurocritical Care Society (NCS) members assessing experiences and attitudes related to organ donation identified the need to enhance education for the treatment team about organ donation and opportunities for improvement in palliative interventions after withdrawal of life-sustaining therapies for potential donation after cardiac death/death by circulatory-respiratory criteria. Additionally, members noted concerns regarding blurred boundaries between patient care and care directed towards organ donation; a potential lack of transparency, empathy and cultural sensitivity in communication between OPOs and patient surrogates; and the ethics of first-person authorization for organ donation. In response to these concerns, the NCS Ethics Committee developed this statement to provide education and ethical guidance for organ donation at the end-of-life. Members had an opportunity to share feedback on the statement from April 6-19, 2026. This statement provides an informal narrative review of the literature related to organ donation that is pertinent to the care of potential organ donors at the end-of-life and includes practical guidance related to the legal definitions of death and first-person authorization, collaborative communication, and management of potential conflicts.

BACKGROUND AND OBJECTIVES/OBJECTIVE:This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS:A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, ≥50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS:A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION/CONCLUSIONS:This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

OBJECTIVE:Novel proof-of-concept designs utilizing biomarkers associated with an established clinically meaningful outcome are needed for antiseizure medication (ASM) efficacy assessment in patients with epilepsy, including drug-resistant focal epilepsy. Changes in long episode (LE) frequency, recorded by the responsive neurostimulator (RNS® System), are associated with changes in clinical seizure (CS) frequency following ASM initiation, suggesting that LEs may serve as a valid biomarker. Here, we aimed to establish the LE reduction magnitude associated with a clinically meaningful CS reduction. METHODS:Post hoc retrospective analyses of CS and LE frequencies, responder rate, and receiver operating characteristics from a long-term RNS open-label treatment study in patients who met predefined criteria were performed to evaluate the association between changes in LE and CS frequency and the LE reduction cutpoint associated with a ≥ 50% CS reduction. RESULTS:Patients (N=45) initiated clobazam (n=15), levetiracetam (n=4), or lacosamide (n=26). Patients achieved a median 30% LE and 50% CS reduction. Patients with <50% and ≥50% CS reductions had a median 5.9% LE increase and 52.4% LE reduction, respectively. A positive association between LE and CS frequency reduction across the entire range of responses (0-100%) was observed. A ≥30% LE reduction was associated with a ≥50% CS reduction; AUC=0.765, N=45. SIGNIFICANCE/CONCLUSIONS:If LE reductions may serve as a potential biomarker, a threshold associated with meaningful improvement in CSs is paramount. Results from this hypothesis-generating analysis support the use of a ≥ 30% LE reduction as a biomarker associated with clinically meaningful improvement in focal epilepsy.

Subjective cognitive decline (SCD) refers to cognitive concerns that may occur with or without objective impairment on standardized testing. Studies suggest that SCD may be an early clinical marker of Alzheimer's disease and related dementias, and that it can predict future objective cognitive decline and progression to dementia. However, the research that supports these conclusions is primarily based on samples with homogeneous socioeconomic and cultural backgrounds. The limited studies in samples with more diverse representations of racial, ethnic, gender, and sexual orientation characteristics show varying SCD prevalence, correlates, and outcomes. Here, we review this literature, focusing on how to apply the findings to advance our understanding of SCD. We further evaluate how our findings inform a roadmap for future research. Overall, we conclude that broader investigations across more diverse populations enhance our understanding of the factors that may differentially contribute to SCD and shape its utility as a clinical metric.

INTRODUCTION/BACKGROUND:Repetitive head impacts (RHIs) have been linked to later life neurodegeneration, yet the in vivo structural correlates of cumulative biomechanical loading remain unclear. We examined whether regional ventricular morphology in former American football players reflects exposure burden and traumatic encephalopathy syndrome (TES) classification. METHODS:Participants included 170 male former football players and 54 age-matched asymptomatic male controls from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Subject-specific manual segmentation quantified lateral ventricle, inferior horn, third ventricle, and fourth ventricle volumes. Group and exposure associations were tested using generalized least squares models. RESULTS:Former players showed larger left inferior lateral ventricle volume than controls, with the largest effects among professional players. Greater cumulative linear and rotational acceleration exposure was associated with enlargement across lateral ventricular and inferior horn regions. DISCUSSION/CONCLUSIONS:Regional ventricular enlargement may represent an in vivo marker of cumulative biomechanical loading after RHI exposure.

This practice guideline provides updated evidence-based recommendations regarding the use of pharmacologic migraine prevention in adults. A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies published through June 6, 2024, and is available in a companion publication. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Recommendations are provided on how to decide when it is appropriate to start a pharmacologic migraine preventive medication and how to decide which migraine preventive medication to start. Recommendations address decision making on appropriate choices of migraine preventive medications in specific situations and populations, including patients with fibromyalgia, obesity, or hypertension; considerations for older adults; treatment during pregnancy and lactation; sex-related factors in choosing medications; and treatment for patients with medication overuse. Recommendations on assessment of treatment efficacy, adverse effects, and discontinuing migraine preventive medications are provided.