Faculty Bibliography

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps. Subsequently, a consensus-building process was performed to prioritize and rank important LTO domains for further research. The prioritization of LTO domains was qualitative, enabling the expert panel to generate ideas, share opinions, and provide reasons for the rankings. A second round took place to allow expansion and agreement regarding specific details for each domain. Outcomes were classified into eight main domains: (1) Function: Neuropsychological, Neurological (other than seizures), and Psychiatric (mood and behavior); (2) Quality of Life; (3) Epilepsy; (4) Nonneurological (medical); (5) Social; (6) Caregiver Burden; (7) Long-Term Mortality; and (8) Health Care System Impact. In addition, the working group suggested obtaining outcome measures for each domain at 6 months and 1 year after discharge and annually thereafter until stability has been reached. There are no currently established time frames set for when LTO in NORSE begin or plateau, and previously there existed no consensus regarding which LTO should be considered. This consensus process identifies and recommends NORSE LTO domains that should be considered in future research studies to provide more consistent results that can be compared between studies. Survivors of NORSE should be evaluated serially and at fixed points over time to maximize our understanding of the recovery trajectory for all LTO domains. Establishing reliable and standardized data describing LTO (beyond seizures) after NORSE will support discussions with families during the acute stages, prognostication, the development of targeted management strategies for survivors, and future comparative research globally helping to identify biomarkers that may predict LTO.

Since the first antiseizure medication (ASM) was introduced in 1857, more than 30 medications have been approved by the United States Food and Drug Administration (FDA) for the treatment of epilepsy. However, limitations in efficacy and tolerability have led to one-third of patients suffering from uncontrolled seizures. Recent advances in genetics, disease modeling, high-throughput target-based and phenotype-based screening, study design, and identification of novel mechanisms of action or routes of delivery have resulted in more than 200 therapeutics currently under development in the epilepsy pipeline. This study discusses near-to-market drugs in advanced clinical development, with select drugs in earlier stages. Background regarding mechanisms, animal studies, pharmacokinetics, pharmacodynamics, efficacy, tolerability, and safety data are provided for each drug when available.

BACKGROUND:Endovascular thrombectomy (EVT) is the gold standard for acute ischemic stroke (AIS) with large vessel occlusion (LVO). However, concomitant intracranial hemorrhage (ICH) might render AIS-LVO patients ineligible for EVT in real-life practice. OBJECTIVE:To provide robust evidence regarding the outcomes of EVT in AIS-LVO patients with concomitant ICH. METHODS:We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Data analysis was performed using OpenMetaAnalyst software. We assessed the pooled incidence rate with a 95 % confidence interval (CI) for qualitative data and analyzed the pooled mean difference (MD) with a 95 % CI for continuous data. The pooled effect size for all outcomes was calculated using the DerSimonian and Laird random-effects model. RESULTS:Six studies were included in the meta-analysis. The overall incidence rate of successful revascularization was 85.3 % (95 % CI: 75.8 %-94.7 %), with rates of 76.1 % for ipsilateral hemorrhages and 66.1 % for contralateral hemorrhages. Functional independence was achieved in 20 % of patients (95 % CI: 4.8 %-36.8 %), with rates of 23 % for ipsilateral and 27.7 % for contralateral hemorrhages. Mortality was reported at 52 % (95 % CI: 34.9 %-69 %), with a higher rate of 52.6 % for ipsilateral hemorrhages compared to 36.8 % for contralateral hemorrhages. CONCLUSION/CONCLUSIONS:This meta-analysis indicates that EVT is feasible in AIS patients with concurrent ICH, yet it is associated with poor functional outcomes and high mortality rates. Careful patient selection is essential to optimize the outcomes, and further research is needed to enhance outcomes for these high-risk patients.

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.

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.

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.

OBJECTIVE:This study was an open-label single-arm clinical trial evaluating the fidelity, feasibility, acceptability, and clinical signal of abbreviated mindfulness-based cognitive therapy (MBCT-brief) delivered either via telephone (MBCT-T) or by video conferencing (MBCT-V) for people with migraine and comorbid depressive symptoms. BACKGROUND:Migraine is commonly comorbid with elevated depressive symptoms. MBCT reduces depressive symptoms and shows promise to reduce migraine-related disability. An abbreviated and remotely delivered version of MBCT could increase access to care. METHODS:) at baseline, mid-treatment, and post-treatment. Feasibility and acceptability rates were compared to a priori benchmarks. RESULTS:(pre-treatment median [interquartile range] score 8 [5, 13] vs. post-treatment 4 [3, 6], p = 0.003). CONCLUSION/CONCLUSIONS:We found that remotely delivered MBCT-brief for migraine and depressive symptoms was feasible and acceptable to patients in both the telephone and video modalities. Intervention was associated with significant post-treatment reductions in headache-related disability and depressive symptomatology, findings that must be interpreted cautiously in the absence of a control group.

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.