Faculty Bibliography

INTRODUCTION/UNASSIGNED:To ensure Alzheimer's disease-modifying treatments can be initiated in diverse populations, efficient pathways to obtain timely diagnoses are required. METHODS/UNASSIGNED:This interim sub-analysis of a multicenter US study included cross-sectional surveys and interviews with neurologists at 12 diverse sites to assess real-world lecanemab use. RESULTS/UNASSIGNED:testing to inform risk/benefit decisions. Infusions usually started within 6 months of diagnosis. Delayed/incomplete referrals were identified as the most significant barrier in the current patient pathway. DISCUSSION/UNASSIGNED:These findings demonstrate the feasibility of lecanemab integration in diverse clinical settings and highlight the importance of primary care physician engagement, optimization of referral pathways, and expanding BBM use in improving timely diagnosis, equitable access, and early treatment initiation.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused significant global harm. Seroprevalence studies detected antibody increases from SARS-CoV-2 infection, assessing transmission and risk from infection. These studies and epidemiological modeling informed public health policy and behavior. Biases in early seroprevalence analyses caused underestimation of fatality risk, including the risk posed to pediatric populations and to those in lower-income nations. The scope of the pandemic was clarified by seroprevalence studies that better assessed at-risk groups and by adjustment of seroprevalence data for known data biases. Reassessment of seroprevalence data confirms the accuracy of early modeling. Public health authorities should inform the public of this modeling success and of the limitations of early seroprevalence analyses. This will prepare the public to better assess global health risk during future pandemics.

OBJECTIVE:Diagnostic and treatment delays in infantile epileptic spasms syndrome (IESS) increase the risk of poor neurodevelopmental outcomes. Early clinical recognition of IESS is essential, especially in regions lacking expedited access to electroencephalograms (EEG). This study aimed to determine clinicians' accuracy at recognizing infantile epileptic spasms (ES) based on smartphone videos, and the impact of brief IESS education on accuracy, diagnostic confidence, and willingness to treat without EEG. METHODS:This multicenter prospective cohort study took place over seven sessions globally from 2022 to 2023. Smartphone videos of children from the US and South Africa with EEG-confirmed diagnoses of IESS (6 videos) and non-epileptic ES-mimickers (3 videos) were obtained. Staff physicians and trainee participants from multiple subspecialties worldwide viewed videos three times: (1) baseline viewing, (2) after brief IESS training, and (3) with clinical history. Surveys on diagnosis and management were completed after each viewing. RESULTS:Of 187 participants who attended a session and initiated a survey, 180 (80 trainees [44%]) met the inclusion criteria. Initial diagnostic accuracy averaged 64% (95% confidence interval [CI]: 62-66%) and improved to 72% (69-74%) after IESS training and clinical history (V + T + CHx). Area under the curve for diagnostic performance of smartphone videos was 0.80 (0.78-0.82), and sensitivity was 0.85 (0.83-0.88) after V + T + CHx. The odds of making a correct diagnosis increased by 86% (OR 1.86, CI 1.59-2.18, p < 0.001) after V + T + CHx. Diagnostic confidence and clinician comfort level treating ES without EEG also improved significantly after V + T + CHx (by 0.36 points and 0.45 points, respectively, on 5-point Likert scales, p < 0.001). Diagnostic accuracy correlated strongly with increased diagnostic confidence and increased clinician comfort level managing patients without an EEG (p < 0.001). Staff physicians had a 24% higher likelihood of making a correct diagnosis than trainees. SIGNIFICANCE/CONCLUSIONS:Smartphone videos, especially when enhanced by brief IESS training, can facilitate triage and early identification of infantile ES, reducing diagnostic delays in this time-sensitive condition. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:Infantile epileptic spasms syndrome is associated with severe developmental impacts, which can be worsened by delayed treatment. Rapid diagnosis is critical, especially in resource-limited settings lacking specialists and timely access to diagnostic tests. Our study found that clinician participants identified epileptic spasms, the hallmark seizure type of this condition, based on video alone with moderately high accuracy, and accuracy improved after education and clinical information. Thus, smartphone videos, particularly when enhanced by brief training, may be an effective tool to triage movements concerning for epileptic spasms, potentially improving resource allocation and reducing diagnostic delays in this urgent childhood epilepsy condition.

BACKGROUND/UNASSIGNED:"Never Events" (<1/1000) likely never occur without a breach in the standard of care (SOC), while "Near Never Events" (<1/100) are typically not far behind. METHODS/UNASSIGNED:"Never Events" are described as "Harmful hospital-acquired conditions that the Center for Medicare and Medicaid Services identified in 2008." Here, we focused on wrong-site spine surgery (WSSS)/wrong-level spine surgery (WLSS), 3 select cases of Caspar Distraction Screws causing hematomas, and one medicolegal case involving multiple simultaneous "Never Events." RESULTS/UNASSIGNED:The spine literature documented the following frequencies of wrong-site spine surgery WSSS/"Never Events" as occurring in 4.5/10,000 lumbar, 6.8/10,000 cervical, and 2.2/10,000 cranial procedures; other series focused on the incidence of wrong-level spine surgery (WLSS). Three "Never Events" consisting of cervical epidural hematomas were attributed to Caspar Distraction Screws. A medicolegal case is also presented in which a spine surgeon caused multiple simultaneous "Never Events" (i.e., ipsilateral surgical errors) during an anterior cervical fusion. Finally, the definition of "Never Events" was newly expanded to better assess "Near Never Events", as the latter applied to varied frequencies of esophageal perforations, plate/screw migration/erosions/displacement, cerebrospinal fluid leaks, infection, and other factors. CONCLUSION/UNASSIGNED:"Never Events" (<1/1000) likely never occur without a breach in the SOC, while "Near Never Events" (<1/100) are typically not far behind.

BackgroundFew studies have examined which patients with migraine might be responders for mind-body interventions. Thus, we examined whether certain baseline mindfulness traits and interest in physical exercise might predict response to treatment.MethodsThis is a planned exploratory analysis of a phase 2 randomized controlled study (N  =  50; 25 per arm) comparing a 6-week physical therapist (PT)-delivered biofeedback-assisted relaxation (BAR) program vs. an Enhanced Usual Care (EUC) migraine self-management program (diary tracking and emailed migraine-related educational materials). We conducted moderation analyses to determine whether the Multidimensional Assessment of Interoceptive Awareness (MAIA), Difficulties in Emotion Regulation Scale (DERS) and Physical Activity Enjoyment Scale (PACES) at baseline influenced the effect of BAR on migraine-related outcomes (Migraine-Specific Quality of Life Role Function Restrictive (MSQv2.1-RFR) and Migraine-Related Disability (MIDAS)) at 6 months.ResultsAmong the n = 40 participants (BAR = 19; EUC = 21), the majority were female (95%), non-Hispanic (77.5%) and white (67.5%). Mean (SD) age was 45.6 (11.2) years. For the MAIA Not-Worrying subscale, BAR produced the greatest improvement in 6-month MSQv2.1-RFR scores among participants with low baseline Not-Worrying scores (those who tended to worry about bodily sensations/discomfort more) (BAR = 77.1 ± 6.6 vs. EUC = 48.9 ± 5.0; p = 0.002, g = 4.75). The benefit diminished at average levels (p = 0.060, g = 2.72) and was absent at high baseline Not-Worrying (p = 0.528, g =  -0.91). For the MAIA Self-Regulation subscale, BAR was most effective among those low in baseline self-regulation (BAR = 71.7 ± 5.3 vs. EUC = 44.3 ± 7.2; p = 0.004, g = 4.27). The DERS total score showed that BAR demonstrated little benefit among participants with better baseline emotion regulation (i.e. lower DERS score; p = 0.907, g = 0.17) but was more effective as baseline emotion regulation difficulties increased, showing a moderate benefit at average levels (BAR = 69.2 ± 4.2 vs. EUC = 55.8 ± 4.0, p = 0.027, g = 3.25) and a large, significant difference at high levels (BAR = 70.6 ± 6.3 vs. EUC = 44.7 ± 5.7; p = 0.004, g = 4.22). The PACES total score indicated that BAR benefits were strongest among those with low (BAR = 76.1 ± 7.0 vs. EUC = 47.1 ± 5.3, p = 0.002, g = 4.60) to average (BAR = 71.2 ± 4.2 vs. EUC = 58.6 ± 4.0, p = 0.035, g = 3.07) enjoyment of physical activity.ConclusionsWe found subgroups of individuals with migraine who may be better responders to PT-delivered BAR, specifically those who tend to worry more about bodily sensations (lower MAIA Not-Worrying score), those with low self-regulation (lower MAIA Self-Regulation score), those with worse emotion regulation (higher DERS score) and those with lower levels of physical activity enjoyment (lower PACES score) at baseline. This may help us determine who may benefit most from BAR.Trial RegistrationClinicalTrials.gov Identifier: NCT06077812.

OBJECTIVE:This study was undertaken to evaluate the safety and effectiveness of responsive thalamic stimulation as adjunctive therapy for drug-resistant idiopathic generalized epilepsy (IGE) with generalized tonic-clonic seizures (GTCSs). METHODS:NAUTILUS is a prospective, multicenter, single-blind, randomized sham-controlled pivotal trial. Patients were ≥12 years of age with drug-resistant IGE and ≥2 GTCSs over a 3-month baseline. Bilateral depth leads were targeted to the centromedian thalamus. One month later, patients were randomized to Active (responsive stimulation, n = 44) or Sham (no stimulation, n = 43). The effectiveness evaluation period (EEP) began 3 months postimplant through 1 year. After a second GTCS in the EEP, patients transitioned to open-label active stimulation. The primary safety endpoint was the serious adverse device-related event (SADE) rate at 84 days postimplant. The primary effectiveness endpoint was time-to-second-GTCS during the EEP. Additional endpoints included median percent change in days with any generalized seizure, GTCS frequency, and responder rate (RR). RESULTS:Eighty-seven patients were implanted across 23 US centers. The SADE rate was significantly below the performance goal (6.9%, p < .0001), with no adverse effects on cognition, mood, or sleep. The prespecified primary effectiveness endpoint was not significant. However, a post hoc mixed-effects model considering all EEP days demonstrated greater GTCS reduction in the originally randomized Active group (61%) compared to patients originally randomized to Sham (49%, p = .030). Eighteen-month outcomes included 76.8% median GTCS reduction, 62.5% RR, 40% GTCS-free at that timepoint, and 77.8% median reduction in days with any generalized seizure. More than 90% of patients and 86% of physicians reported improvement on Global Impression of Change scales. SIGNIFICANCE/CONCLUSIONS:NAUTILUS is the first randomized controlled neuromodulation trial in IGE. Responsive thalamic stimulation provided a clinically meaningful and durable reduction in seizures with an acceptable safety profile, offering a much-needed option for drug-resistant IGE.

Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.

BACKGROUND/UNASSIGNED:The placement of Spinal Cord Stimulator (SCS) trial or permanent electrodes carries a 31.9-43% morbidity/adverse event (AE) rate. Most AEs are attributed to electrode migration (EM: device-related AE 26.7% older cohort vs. 9.7% newer cohort), spinal epidural hematomas (SEHs: 0.81-2.6%), infection (3.4% older vs. 1.9% recent cohort), SCI (spinal cord injury: percutaneous 0.45% vs. 0.36% paddle electrodes), dural tears (DT/ cerebrospinal fluid leaks (CSF leaks)), foreign body/fibrous reactions, or syrinx formation. METHODS/UNASSIGNED:SCSs are typically applied to address chronic neuropathic pain syndromes. Here, we evaluated 20 articles focusing on patients who developed postoperative myelopathy/radiculopathy, variously attributed to MR-documented AE warranting medical or surgical intervention. RESULTS/UNASSIGNED:Postoperative symptoms/signs of AE typically included the acute development of new/increased weakness, sensory loss, and/or sphincter dysfunction. Requisite STAT MR scans usually confirmed the etiology of AE including electrode migration, SEH, DT, SCI, and/or postoperative scarring/fibrosis. Most patients warranted STAT surgery, while a small subset could be managed conservatively. CONCLUSION/UNASSIGNED:The AE rate for spinal cord stimulators ranges from 31.9 to 43%. While the majority are due to electrode migration, other etiologies include SEH, SCI, DT, and foreign body reactions. Those who become acutely myelopathic usually warrant STAT MR scans with the majority additionally necessitating STAT surgical intervention to limit short/long-term neurological morbidity.