Faculty Bibliography

INTRODUCTION/UNASSIGNED:Seizures are common in autoimmune encephalitis (AE), but identifying patients at risk of chronic epilepsy in the post-acute phase remains challenging. This study aims to identify risk factors of treatment-resistant postencephalitic epilepsy. METHODS/UNASSIGNED:This retrospective cohort study included patients with AE who experienced new-onset seizures within one year of symptom onset from two tertiary care centers in New York. EEG findings were analyzed separately based on whether the EEG recording was obtained in the acute (<3 months from symptom onset) or subacute phase. A multivariate logistic regression model was used to identify independent predictors of postencephalitic epilepsy. RESULTS/UNASSIGNED:Eighty-nine patients were included (median age: 33 years). Neural antibodies were present in 73% of patients (NMDAR: 35, LGI1: 19, GAD65: 9, Hu: 1, AGNA-1: 1). Over a median follow-up of 4.9 years, 29.2% developed treatment-resistant postencephalitic epilepsy. Independent predictors of postencephalitic epilepsy included focal slowing on acute EEG (OR 0.15, CI 0.02-0.90), interictal epileptiform discharges (IEDs) or periodic discharges (PDs) on subacute EEG (OR 20.01, CI 1.94-206.44), and cell surface antibodies (OR 0.21, CI 0.05-0.89). Immunotherapy within three months of onset was associated with decreased epilepsy development in patients with neural antibodies (OR 4.16, CI 1.11-16.30). CONCLUSIONS/UNASSIGNED:Nearly one-third of patients with AE and acute seizures developed treatment-resistant postencephalitic epilepsy, with significant predictors including absence of focal slowing on acute EEG, presence of IEDs and PDs on subacute EEG, absence of cell surface antibodies, and absence of early immunotherapy treatment of patients with positive neural antibodies.

Subjective cognitive decline (SCD) is associated with preclinical Alzheimer's disease (AD). Suboptimal sleep is also a risk factor for cognitive decline, but with unclear relationship to SCD. We conducted a retrospective cross-sectional study in a biracial research cohort of 148 cognitively normal older adults who underwent quantification of SCD (Cognitive Change Index; CCI), sleepiness (Epworth Sleepiness Scale; ESS), depression (Geriatric Depression Scale; GDS), and amyloid/tau PET. ESS score was associated with total, amnestic, and non-amnestic CCI scores, after adjustment for GDS, amyloid/tau burden, and race. This supports future longitudinal work on how sleepiness impacts SCD outcomes.

Presence of focal to bilateral tonic-clonic seizures (FBTCS) in focal epilepsy is associated with increased morbidity and mortality. Risk factors for FBTCS are poorly understood, and little is known regarding FBTCS recurrence after treatment initiation. This study aimed to investigate factors related to FBTCS in newly diagnosed focal epilepsy and their recurrence after starting antiseizure medications (ASMs) in the Human Epilepsy Project (HEP) cohort. HEP was an international, prospective cohort study that enrolled people with newly diagnosed focal epilepsy within 4 months of treatment initiation and followed them for up to 6 years. Baseline characteristics, treatment choices, and seizure outcomes were collected. Descriptive and inferential statistical analysis was conducted to assess the differences between study participants who had FBTCS and those who never experienced FBTCS. A total of 443 participants were included in this analysis; 77% (n = 342) had FBTCS at some point prior to or within the study period. In participants with FBTCS, regardless of initial seizure type, diagnosis was mostly made after FBTCS (335/342, 98%). After treatment initiation, FBTCS did not recur in 57% (n = 194/342) of cases. A higher number of total pretreatment seizures (median = 16 vs. 11, p = .048, Mann-Whitney U-test), predominantly focal aware seizures (FAS) or focal impaired awareness seizures (FIAS; median = 15 vs. 10, p = .049, Mann Whitney U-test), was associated with no recurrence in FBTCS after treatment initiation. Of 108 participants without FBTCS prior to treatment, only seven (6%) developed FBTCS after treatment initiation. There was no significant difference in choice of initial ASM class (levetiracetam vs. sodium channel blockers) between participants who experienced FBTCS and those who did not. This study highlights the significance of FBTCS among individuals with newly diagnosed focal epilepsy. The majority of participants who experienced FBTCS were diagnosed with epilepsy after experiencing their first FBTCS despite preceding FAS/FIAS. The more frequent FAS/FIAS in participants whose FBTCS resolved may be a characteristic of their epilepsy.

BACKGROUND AND OBJECTIVES/UNASSIGNED:Neurosarcoidosis poses a diagnostic and management challenge due to its rarity, phenotypic variability, and lack of randomized controlled studies to guide treatment selection. Recommendations for management based on expert opinion are useful in clinical practice and provide a framework for designing prospective studies. METHODS/UNASSIGNED:In this Delphi survey study, specialists with experience in managing patients with neurosarcoidosis were invited to anonymously complete 2 surveys about key elements of evaluation, diagnosis, treatment, monitoring, and long-term management of neurosarcoidosis. Expert consensus recommendations were adopted if >80% threshold of agreement was reached. RESULTS/UNASSIGNED:Of the 41 invited expert clinicians across the United States, 32 (78%) participated in the study. All round 1 respondents self-identified as neuroimmunologists (except for 1 pulmonologist). Consensus was reached regarding the need to consider neurosarcoidosis phenotype and severity to guide the choice of initial immunosuppression in both the acute (relapse) and maintenance phases. Experts endorsed the use of TNF-α inhibitors as first-line agents in selected phenotypes with poor prognosis. Neuroimaging was recommended to complement clinical surveillance for treatment response. DISCUSSION/UNASSIGNED:There was agreement on several key issues, most importantly on the need to consider neurosarcoidosis phenotype and severity when deciding initial treatment. No consensus was achieved on the dosing and duration of specific immunosuppressants, nor regarding the management of the peripheral nervous system manifestation of neurosarcoidosis. These topics warrant further investigation.

Seizures associated with low-grade tumors in pediatric patients can be drug resistant and associated with significant morbidity. There are several low-grade tumor types associated with epilepsy in this population with the majority localized to the temporal lobe and some extra-temporal locations (frontal, parietal, and occipital lobes). The primary treatment of low-grade epilepsy-associated tumors is surgical resection, though the surgical approach and the use of intraoperative techniques remain controversial. Newer treatments are under investigation as primary and/or adjunctive therapy, including non-invasive surgical options and gene-targeted therapy. A multimodal approach to treatment may improve long-term outcomes and quality of life.

The mechanisms behind comorbid symptoms of depression in persons with epilepsy (PWE) remain largely unknown. Our study aimed to learn whether seizures moderate fluctuations in depressive symptoms in PWE when controlling for preictal symptoms of depression. We enrolled 57 adult PWE admitted to the New York University (NYU) Langone Epilepsy Monitoring Unit (EMU) from 2021 to 2024. Thirty-seven participants had a seizure. Twenty of the admitted patients did not have seizures during the admission period and therefore served as controls. All participants were seizure free for > 7 days prior to participation. Upon admission, all participants completed the Montgomery-Asberg Depression Rating Scale (MADRS) to evaluate baseline mood. The MADRS was repeated acutely (4-24 h post seizure or admission) and subacutely (2-7 days post seizure or discharge) for both groups. Linear regression models revealed that individuals with higher baseline MADRS scores (indicating higher depressive symptoms) experienced worse mood acutely post-seizure, while lower baseline MADRS scores were associated with acute mood improvement (R² = 0.59, p < 0.001). Experiencing a seizure was not associated with subacute mood outcomes, which were instead driven by acute mood state (R² = 0.56, p < 0.001). In conclusion, we found that seizures exacerbate pre-ictal depressive symptoms and that post-ictal depressive symptoms persist up to 7 days after seizure resolution. This study may provide evidence for a bidirectional relationship and demonstrate a vicious cycle between depression and epilepsy.

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

OBJECTIVES/BACKGROUND/OBJECTIVE:This study was undertaken to synthesize evidence on the benefits and harms of behavioral interventions for migraine prevention in children and adults. The efficacy and safety of behavioral interventions for migraine prevention have not been tested in recent systematic reviews. METHODS:An expert panel including clinical psychologists, neurologists, primary care physicians, researchers, funders, individuals with migraine, and their caregivers informed the scope and methods. We searched MEDLINE, Embase, PsycINFO, PubMed, the Cochrane Database of Systematic Reviews, clinicaltrials.gov, and gray literature for English-language randomized trials (January 1, 1975 to August 24, 2023) of behavioral interventions for preventing migraine attacks. Primary outcomes were migraine/headache frequency, migraine disability, and migraine-related quality of life. One reviewer extracted data and rated the risk of bias, and a second verified data for completeness and accuracy. Data were synthesized with meta-analysis when deemed appropriate, and we rated the strength of evidence (SOE) using established methods. RESULTS:For adults, we included 50 trials (77 publications, N = 6024 adults). Most interventions were multicomponent (e.g., cognitive behavioral therapy [CBT], biofeedback, relaxation training, mindfulness-based therapies, and/or education). Most trials were at high risk of bias, primarily due to possible measurement bias and incomplete data. For adults, we found that any of three components (CBT, relaxation training, mindfulness-based therapies) may reduce migraine/headache attack frequency (SOE: low). Education alone that targets behavior may improve migraine-related disability (SOE: low). For three other interventions (biofeedback, acceptance and commitment therapy, and hypnotherapy), evidence was insufficient to permit conclusions. We also found that mindfulness-based therapies may reduce migraine disability more than education, and relaxation + education may improve migraine-related quality of life more than propranolol (SOE: low). For children/adolescents, we included 13 trials (16 publications, N = 1444 children), but the evidence was only sufficient to conclude that CBT + biofeedback + relaxation training may reduce migraine attack frequency and disability more than education alone (SOE: low). CONCLUSION/CONCLUSIONS:Results suggest that for adults, CBT, relaxation training, and mindfulness-based therapies may each reduce the frequency of migraine/headache attacks, and education alone may reduce disability. For children/adolescents, CBT + biofeedback + relaxation training may reduce migraine attack frequency and disability more than education alone. Evidence consisted primarily of underpowered trials of multicomponent interventions compared with various types of control groups. Limitations include semantic inconsistencies in the literature since 1975, differential usage of treatment components, expectation effects for subjectively reported outcomes, incomplete data, and unclear dosing effects. Future research should enroll children and adolescents, standardize intervention components when possible to improve reproducibility, consider smart study designs and personalized therapies based on individual characteristics, use comparison groups that control for expectation, which is a known challenge in behavioral trials, enroll and retain larger samples, study emerging digital and telehealth modes of care delivery, improve the completeness of data collection, and establish or update clinical trial conduct and reporting guidelines that are appropriate for the conduct of studies of behavioral therapies.

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the GRADE approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

INTRODUCTION/BACKGROUND:This study investigates whether midlife cortisol levels predict Alzheimer's disease (AD) biomarker burden 15 years later, with particular attention to sex differences and menopausal status. METHODS:F]Flortaucipir) positron emission tomography (PET) imaging conducted 15 years later. We performed multivariable regression analyses adjusted for confounders including, apolipoprotein E4 (APOE4) status. RESULTS:Elevated midlife cortisol correlated with increased amyloid deposition, specifically in post-menopausal women, predominantly in posterior cingulate, precuneus, and frontal-lateral regions (p < 0.05). No significant associations were observed with tau burden or in males. DISCUSSION/CONCLUSIONS:These findings reveal post-menopausal women with high midlife cortisol are at increased risk of AD. Results highlight the importance of identifying early risk factors when biomarkers are detectable but cognitive impairment is absent. HIGHLIGHTS/CONCLUSIONS:High midlife cortisol is linked to increased amyloid deposition in post-menopausal women. Cortisol showed no association with tau pathology. Post-menopausal hormone changes may amplify cortisol's effects on amyloid.