Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Traditional medical board examinations present clinical information in static vignettes with multiple-choices (MC), fundamentally different from how physicians gather and integrate data in practice. Recent advances in large language models (LLMs) offer promising approaches to creating more realistic clinical interactive conversations. However, these approaches are limited in neurosurgery, where patient communication capacity varies significantly and diagnosis heavily relies on objective data such as imaging and neurological examinations. We aimed to develop and evaluate a multi-artificial intelligence (AI) agent conversation framework for neurosurgical case assessment that enables realistic clinical interactions through simulated patients and structured access to objective clinical data. METHODS:We developed a framework to convert 608 Self-Assessment in Neurological Surgery first-order diagnosis questions into conversation sessions using 3 specialized AI agents: patient AI for subjective information, system AI for objective data, and clinical AI for diagnostic reasoning. We evaluated generative pretrained transformer 4o's (GPT-4o's) diagnostic accuracy across traditional vignettes, patient-only conversations, and patient + system AI interactions, with human benchmark testing from 10 neurosurgery residents. RESULTS:= .0030) using fewer interactions and reported high educational value of the interactive format. CONCLUSION/CONCLUSIONS:This multi-AI agent framework provides both a more challenging evaluation method for LLMs and an engaging educational tool for neurosurgical training. The significant performance drops in conversational formats suggest that traditional MC testing may overestimate LLMs' clinical reasoning capabilities, while the framework's interactive nature offers promising applications for enhancing medical education.

Stroke recovery outcomes vary across individuals, motivating the search for biomarkers that can improve prediction. White matter hyperintensities (WMH) volume is a leading biomarker candidate, with FLAIR MRI typically used for WMH segmentation; however, T1-weighted (T1) MRI is often more available. Therefore, we evaluated the performance of two automated WMH segmentation methods (WMH-SynthSeg, SAMSEG) to determine whether WMH volume can be reliably estimated using T1 alone. We analyzed imaging data from 227 stroke patients across three datasets spanning early subacute to chronic recovery, with gold-standard WMH masks and stroke lesion masks manually traced on available T1 and FLAIR scans. WMH was segmented using T1 only as input to WMH-SynthSeg and SAMSEG, as well as using both T1 and FLAIR as input to SAMSEG, as previously implemented in stroke recovery research. Automated WMH segmentations were compared to the gold-standard WMH mask: spatial accuracy was assessed using Dice similarity index (SI) and cluster-level false negative ratio, while volumetric agreement was assessed using intraclass correlation, Pearson's correlation, and volume ratio. We used linear mixed-effects models to evaluate whether SI was influenced by factors such as WMH volume, stroke lesion volume, WMH contrast, age, sex, and days since stroke, with dataset as a random effect. WMH-SynthSeg using T1-only input produced more accurate and reliable WMH segmentations compared to SAMSEG with T1-only input and performed comparably to SAMSEG using both T1 and FLAIR input. WMH-SynthSeg using T1-only input may be used for WMH volume estimation in stroke recovery research in the absence of multimodal imaging.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Implementation of telemedicine expanded options for outpatient neurology care. It remains uncertain which new neurology patients can be appropriately evaluated virtually. We compared subsequent health care utilization after virtual vs in-person new patient neurology visits across 3 academic medical centers. METHODS:We conducted a retrospective multicenter cohort study of adults with a new outpatient neurology visit from September 2020 through December 2021 using the Vizient Clinical Data Base and Clinical Practice Solutions Center databases. Virtual and in-person patients were matched 1:1 using propensity scores incorporating demographics, clinical characteristics, time period, and previous health care utilization. Outcomes were analyzed overall and stratified by neurologic chief complaint category and institution. We compared rates of subsequent neurologic clinic follow-up, emergency department (ED) visits, and hospitalizations after virtual and in-person encounters. Testing and all-cause ED visits/hospitalizations were also assessed. RESULTS:= 0.13, respectively). Analyses by chief complaint found that 90-day follow-up was higher after in-person visits for dementia, whereas 30- and 90-day follow-up was higher after virtual visits for Parkinson disease and multiple sclerosis, and 90-day follow-up was higher after virtual visits for headache. Testing was more frequent after in-person visits for certain chief complaints. DISCUSSION/CONCLUSIONS:In this propensity score-matched multicenter cohort, new neurology patients seen virtually had similar downstream utilization as those seen in-person, including comparable 90-day follow-up and similar neurologic and all-cause ED visits and hospitalizations. Although follow-up varied modestly by chief complaint and testing was more frequent after some in-person visits, no major differences emerged overall.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT. METHODS:This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will be conducted at 5 years. RESULTS:). DISCUSSION/CONCLUSIONS:This prospective real-world study contributes to the body of evidence that adjunctive direct brain-responsive neurostimulation provides significant and sustained reductions in the frequency of focal seizures. Seizure reductions were greater and were achieved faster than in the RCT and long-term treatment trials but were similar to a more recent retrospective multicenter real-world study. As in the preapproval studies, treatment was well-tolerated and safe, and the SUDEP rate was low. The RNS System showed similar safety and improved seizure outcomes in real-world use compared with the RCT. Improvements in efficacy may reflect changes in programming practices. Future research efforts will focus on using the brain data obtained by the device to optimize detection and stimulation paradigms for each patient. TRIAL REGISTRATION INFORMATION/UNASSIGNED:ClinicalTrials.gov, NCT02403843, submitted March 26, 2015. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class IV evidence that in adults with refractory focal-onset seizures, direct brain-responsive neurostimulation reduces seizure frequency without serious adverse events up to 3 years.

Seizure frequency has been the primary endpoint in epilepsy trials, with enrollment usually requiring ≥4 seizures per month. This threshold is more and more misaligned with clinical reality, as the availability of more treatment options has reduced baseline seizure burden, with a risk of excluding a proportion of patients from trials. Although cognitive and developmental outcomes are gaining prominence, seizure control remains essential due to its impact on morbidity and mortality. We have tools to study all types of seizure frequency: Time-to-event designs, including time-to-pre-randomization seizure count or time to the Nth seizure, offer a validated alternative by enabling inclusion across a wider range of seizure frequencies while maintaining methodological rigor. Future trial designs should study cognitive outcomes, while studies focusing on anti-seizure efficacy remain critical.

BACKGROUND:There is significant heterogeneity related to the use of prophylactic antiseizure medications (ASM) following supratentorial craniotomy. METHODS:We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized following supratentorial neurosurgery with no prior seizure history. The following population, intervention, comparator, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used as seizure prophylaxis in adult patients undergoing supratentorial neurosurgery? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT) be preferentially used? and (3) Should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes. We utilized Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate recommendations. RESULTS:The initial literature search yielded 1988 articles, and 16 formed the basis of the recommendations. PICO 1: while meta-analysis of randomized controlled trials (RCTs) demonstrated a significant benefit for early seizure prevention, meta-analyses including all study designs was nonsignificant. Further, there were no differences in late seizure or mortality rates, and there was a trend toward higher adverse event rates with ASM. PICO 2: LEV was associated with significantly lower early seizure rates than PHT, and there were trends toward fewer late seizures and adverse events with LEV. PICO 3: only three studies examined the duration of ASM treatment, and there was no significant difference in seizure events between subjects treated for a short versus long duration. CONCLUSIONS:We suggest that either prophylactic ASM or no ASM be used for seizure prophylaxis in patients undergoing supratentorial neurosurgery (conditional recommendation, low quality of evidence). If an ASM is used, we suggest LEV over PHT (conditional recommendation, very low quality of evidence) for a short duration (conditional recommendation, very low quality of evidence).

BACKGROUND AND PURPOSE/OBJECTIVE:Mild traumatic brain injury (MTBI) is a common public health concern with potential long-term consequences, yet its underlying pathophysiology remains poorly understood. Clinical heterogeneity of individuals having diverse extent and array of symptoms has impeded the identification of reliable imaging biomarkers. Traditional group-level analyses may obscure biologically meaningful subtypes. This study uses latent class analysis (LCA) to classify MTBI subjects into symptom-defined subgroups and examines corresponding WM microstructural alterations using advanced diffusion MRI. MATERIALS AND METHODS/METHODS:Sixty-one MTBI patients within one month of injury completed the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). LCA was used to identify symptom-based subgroups. Of these, 54 MTBI patients underwent multi-shell diffusion MRI and were compared with 31 controls. WM changes were assessed across subgroups using ROI-based diffusion analyses. RESULTS:LCA identified three distinct MTBI subgroups: those with minimal to no symptoms (31.5%), the cognitively symptomatic (38.9%), and the more globally symptomatic (29.6%). The three groups were associated with different patterns of diffusion MRI differences compared with controls. The cognitively symptomatic subgroup showed predominantly central WM differences, the globally symptomatic subgroup exhibited more peripheral differences with right-hemisphere predominance and sparing the corpus callosum, marked by reduced fractional anisotropy and kurtosis and elevated diffusivities, the less symptomatic subgroup demonstrated focal differences in the callosal genu, with increased fractional anisotropy and kurtosis and decreased diffusivity measures. CONCLUSIONS:MTBI comprises biologically distinct phenotypes with subgroup-specific WM signatures on diffusion MRI. Even individuals with minimal to no symptoms show WM differences compared with controls, underscoring the limitations of symptom reporting alone. Integrating symptom-based classification with advanced diffusion MRI may improve diagnostic precision to help risk stratification and provide insight into mechanisms of injury. ABBREVIATIONS/BACKGROUND:LCA = latent class analysis; MTBI = mild traumatic brain injury; RPQ = Rivermead post-concussion symptoms questionnaire.

PURPOSE/OBJECTIVE:We describe a case of bilateral, multiple, branch retinal artery occlusions (BRAO) associated with carotid webs. METHODS:A thorough chart review was conducted for the patient. Relevant literature was systematically reviewed. RESULTS:Eight cases of fibromuscular dysplasia (FMD) associated with retinal artery occlusions have been reported. Two additional cases of FMD with other ocular involvement have been described. No cases of carotid webs associated with retinal artery occlusions were found. CONCLUSION/CONCLUSIONS:Carotid webs, an uncommon variant of FMD, are a recognized causative etiology of arterial, ischemic stroke. The case described here of bilateral, multifocal BRAOs represents a unique manifestation of this variant of FMD. This diagnosis should be considered in the setting of an otherwise unrevealing BRAO workup, as recognition of this association may be sight and life-saving.

OBJECTIVE:A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN/METHODS:Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING/METHODS:Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS/METHODS:A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS/RESULTS:A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS:A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.