Faculty Bibliography

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.

BACKGROUND/PURPOSE/UNASSIGNED:Downbeat nystagmus (DBN) is an uncommon finding in comatose patients, especially as a manifestation of epileptiform activity. We report a 59-year-old man who developed DBN in the context of myoclonic status epilepticus following anoxic brain injury secondary to cardiac arrest. The DBN was phase-locked with generalized periodic epileptiform discharges (GPDs) on electroencephalography (EEG) and resolved with pharmacologic burst suppression. CONCLUSION/UNASSIGNED:This case suggests a potential link between DBN and cortical epileptiform activity, which we hypothesize may be due to bilateral cortical hyperexcitability and cerebellar disinhibition. The presence of DBN in this setting may indicate a poor prognosis.

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.

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.

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.

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.

BACKGROUND:Diet may influence MS activity, but most studies use a single dietary measure. The stability of diet over time in pediatric-onset MS (POMS) is unclear. OBJECTIVES/OBJECTIVE:To evaluate the reproducibility and short-term temporal stability of dietary intake in youth with POMS using repeated food frequency questionnaires (FFQ). METHODS:This longitudinal study included participants with a baseline FFQ (the Block Kids Food Screener, 2014). Intraclass correlation coefficients (ICCs) were estimated using random-intercept mixed-effects models to quantify the relative contributions of between-person and within-person variability. Temporal trends in intake were assessed by modeling time since baseline as a fixed effect, using log-transformed dietary variables to estimate percent change over time. RESULTS:Of 419 FFQs from 195 participants, 140 (71.8%) completed ≥2 FFQs over a median of 6.5 months (range 2.8-18). ICCs ranged from 0.41 to 0.78 across dietary measures, with the highest reproducibility observed for vegetables and fiber (ICCs 0.78 and 0.72). Log-transformed models showed small declines in several nutrients over time, corresponding to <10% change over a six-month period. CONCLUSIONS:Dietary intake demonstrated moderate to good reproducibility over the 6 to 18 month follow-up period. Vegetable and fiber intake had the strongest reliability. These findings suggest that reported dietary intake assessed by a single or infrequent FFQ may remain reasonably stable over a 6- to 18-month period in longitudinal POMS studies. However, the moderate-to-good reproducibility observed indicates that within-person variability persists and may attenuate diet-disease associations when only a single dietary assessment is available.

BACKGROUND:Public understanding about brain death/death by neurologic criteria (BD/DNC) is generally poor. With the rising popularity of utilization of large language model (LLM) chatbots to answer medical questions, we sought to determine the quality of information about BD/DNC provided by ChatGPT 4o-mini and Gemini 3 Flash (Fast). METHODS:With the assistance of a family advocate, we developed 45 open-ended questions about BD/DNC and submitted them to ChatGPT 4o-mini and Gemini 3 Flash (Fast) in January 2026. We recorded response word count, Flesch-Kincaid Readability Score and source reputability (non-reputable sources were defined as nonmedical, nongovernmental, nonlegal and not affiliated with an organ donation organization). Two authors of the 2023 BD/DNC guidelines independently assessed response accuracy relative to accepted medical standards and a third adjudicated discrepancies. RESULTS:Most responses were ≥ 10th grade level [ChatGPT 4o-mini: 44/45 (98%), Gemini 3 Flash (Fast): 39/45 (86%)]. After adjudication, 22/45 (49%) responses from Gemini 3 Flash (Fast) and 20/45 (44%) from ChatGPT 4o-mini were considered completely correct (p = 0.673). There was no relationship between accuracy and: word count; readability; or citation of at least one non-reputable source. CONCLUSION/CONCLUSIONS:ChatGPT 4o-mini and Gemini 3 Flash (Fast) responses to questions about BD/DNC may include inaccuracies. This could promote confusion and distrust. There is remarkable potential for integration of artificial intelligence in public education about healthcare, but there is a need for improvement to ensure responses are accurate and readable. The healthcare team should be prepared to address misconceptions about BD/DNC based on use of LLMs.