Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. METHODS:We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. RESULTS:Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). DISCUSSION/CONCLUSIONS:In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.

Extensive neuroimaging research in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) has identified brain atrophy as a disease phenotype. While it is also related to a complex genetic architecture, the transition from genetic risk factors to brain vulnerabilities remains unclear. Using a population-based approach, we examined the associations between epilepsy-related polygenic risk for HS (PRS-HS) and brain structure in healthy developing children, assessed their relation to brain network architecture, and evaluated its correspondence with case-control findings in TLE-HS diagnosed patients relative to healthy individuals We used genome-wide genotyping and structural T1-weighted magnetic resonance imaging (MRI) of 3,826 neurotypical children from the Adolescent Brain Cognitive Development (ABCD) study. Surface-based linear models related PRS-HS to cortical thickness measures, and subsequently contextualized findings with structural and functional network architecture based on epicentre mapping approaches. Imaging-genetic associations were then correlated to atrophy and disease epicentres in 785 patients with TLE-HS relative to 1,512 healthy controls aggregated across multiple sites. Higher PRS-HS was associated with decreases in cortical thickness across temporo-parietal as well as fronto-central regions of neurotypical children. These imaging-genetic effects were anchored to the connectivity profiles of distinct functional and structural epicentres. Compared with disease-related alterations from a separate epilepsy cohort, regional and network correlates of PRS-HS strongly mirrored cortical atrophy and disease epicentres observed in patients with TLE-HS, and highly replicable across different studies. Findings were consistent when using statistical models controlling for spatial autocorrelations and robust to variations in analytic methods. Capitalizing on recent imaging-genetic initiatives, our study provides novel insights into the genetic underpinnings of structural alterations in TLE-HS, revealing common morphological and network pathways between genetic vulnerability and disease mechanisms. These signatures offer a foundation for early risk stratification and personalized interventions targeting genetic profiles in epilepsy.

BACKGROUND:Spinocerebellar ataxia type 27 B (SCA27B) caused by GAA trinucleotide repeats in the fibroblast growth factor 14 gene is emerging as a common cause of late-onset ataxia. Oscillopsia due to downbeat nystagmus (DBN) and diplopia are common symptoms, yet the causes of diplopia and strabismus patterns are poorly defined. METHODS:Retrospective chart review of 18 patients diagnosed with SCA27B over the past year. RESULTS:Ten of 18 patients had episodic or persistent oscillopsia or diplopia at disease onset, neurologically isolated in 4. Seventeen had detectable DBN, although it was often delayed in onset and was clinically obvious in only 5. Diplopia was present in 14 patients: vertical due to skew deviation (static and or alternating on lateral gaze) (n = 8) and/or horizontal due to vergence dysfunction (n = 11). Symptomatic vergence dysfunction included convergence insufficiency (CI) (n = 4) and divergence insufficiency (n = 5). Thirteen of 16 patients experienced improvement in oscillopsia or imbalance on 4-aminopyridine (4-AP). CONCLUSIONS:Strabismus patterns causing diplopia in patients with SCA27B are, not unexpectedly, largely attributable to cerebellar dysfunction and are not unique to SCA27B. The exceptions to cerebellar localization were CI, sixth nerve palsy, and slow saccades. Careful assessment for DBN in patients presenting with episodic or persistent diplopia from skew deviation or vergence disorders is important, as this may be key to confirming a cerebellar localization, subtle on examination, and guide toward genetic testing and 4-AP treatment.

BACKGROUND:Efforts to assess concussion-reporting efficacy face logistical challenges relying on behavioral intentions. Self-report surveys often lack correlation with actual behavior. Simulated in-game behavioral observation may offer a better evaluation method when data on actual behavior are not feasibly collected. OBJECTIVE:To examine the association between concussion-reporting intentions and concussion-reporting behavior in a novel simulated in-game experience. DESIGN/METHODS:This study was performed as a secondary analysis of a larger study that assessed the efficacy of concussion education in concussion-reporting intention among high school athletes. High school football players (n = 313) from seven Colorado high schools completed reporting intention questionnaires. Athletes were randomized to either receive standard concussion education from the Centers for Disease Control and Prevention (n = 167) or not (n = 146). Subsequently, all participants were given a baseline assessment in which they were asked to assess concussion-reporting intention. To test concussion-reporting behavior, all participants watched a novel first-person, 2-minute video in which a simulated concussion occurred. When the simulated concussion occurs, participants are then asked whether they would like to seek evaluation or continue playing. Logistic regression assessed the relationship between concussion-reporting intention and concussion-reporting behavior during the simulated game experience. RESULTS:Athletes who reported their concussion in the simulated game had higher baseline concussion-reporting intention (U = 8669.5, p < .001). Across both the educated and noneducated groups, each one-point increase in baseline reporting intention was associated with 1.99× (95% confidence interval [CI]: 1.11-3.60, p = .02) and 1.53× (95% CI: 1.07-2.30, p = .026) increased odds of reporting the simulated concussion, respectively. CONCLUSIONS:Concussion-reporting behavior in a novel, first-person simulated in-game experience is higher among individuals with higher baseline concussion-reporting intention. This approach may offer promise for evaluating concussion-reporting intention and concussion-reporting behavior via interactive video simulation.

BACKGROUND:The Drivewire 24 (DW24) is a newly FDA-cleared 0.024 inch steerable guidewire. Its proximally controlled deflectable tip allows for intravascular steering to facilitate selective navigation of diagnostic or therapeutic catheters. We present the first clinical experience with the DW24. METHODS:All neurointerventional procedures using the DW24 from October 2024 to April 2025 were retrospectively reviewed. Indications, procedural details, DW24 performance, wire-related complications, and operator feedback were assessed. RESULTS:27 procedures were performed utilizing the DW24. Indications included aneurysm (n=16), stroke (n=5), arteriovenous fistula or malformation (n=4), and diagnostic venography (n=2). Technical success was achieved in 92.6% of cases. Target vessels included the MCA, anterior cerebral artery, posterior cerebral artery, internal carotid artery segments, transverse sinus, and torcula. The device's radiopaque, hydrophilic distal tip aided fluoroscopic visibility, and the variable support enabled articulation across a range of aspiration and delivery catheters without requiring additional support devices. The DW24's steerability enabled access to challenging cerebrovascular anatomy, including one stroke case where conventional guidewires failed to reach a distal M2 occlusion. The DW24's intravascular steering also allowed for the delivery of catheters for Pipeline Embolization Device (PED) deployment and facilitated PED post-processing to improve wall apposition without requiring wire removal, reshaping, or balloon angioplasty. Operators observed a short learning curve. There were no device-related complications, though the wire's response to rotational force was a limitation. CONCLUSION/CONCLUSIONS:The DW24 demonstrated a high technical success rate with no device-related complications. Its versatility across catheter sizes and precise controllability facilitate navigating complex cerebrovasculature. Further studies should assess efficacy in larger cohorts across additional clinical scenarios.

OBJECTIVE:To validate the carotid web (CW) risk stratification assessment described in previous works within a larger cohort of patients with symptomatic and incidentally found asymptomatic CWs. METHODS:A retrospective analysis of our institution's electronic medical records identified all patients with a diagnosis of CW from 2017 to 2024. We included symptomatic patients and those with asymptomatic CWs, that is, incidentally found webs without history of stroke or transient ischemic attack. Patient charts were reviewed for demographics, imaging, comorbidities, and a diagnosis of stroke after diagnosis of asymptomatic CW. All angles were measured as described in previous work on a sagittal reconstruction of neck CT angiography in which the common carotid artery (CCA), external carotid artery, and internal carotid artery (ICA) were well visualized, together with the CW itself. Principal component analysis and logistic regression were performed to evaluate the association between high-risk angles and stroke risk.  RESULTS: Twenty-six symptomatic and 26 asymptomatic patients were identified. Of note, the number of patients with hypertension, hyperlipidemia, and smoking history was 17 (65.0%), 16 (62.0%), and 8 (31.0%) for symptomatic patients and 18 (69.0%), 17 (65.0%), and 15 (58.0%) for asymptomatic patients. All angular measurements showed statistically significant associations with stroke status. The CCA-web-pouch angle showed the strongest association (p=2.07×10⁻⁴), followed by the CCA-pouch-tip angle (p=3.23×10⁻⁴), ICA-web-pouch angle (p=0.004), and ICA-pouch-tip angle (p=0.005). Each additional high-risk angle increased the odds of stroke by 9.47-fold (p<0.0001). The associated probability of stroke increased from 6.3% with no high-risk angles to 39.1% with one high-risk angle and further to 85.9% with two high-risk angles. The model demonstrated high sensitivity, correctly identifying 84.6% of positive cases, and high specificity, correctly identifying 88.5% of negative cases. The F1 score was 0.863, indicating good overall model performance.  CONCLUSION: Given this successful stratification of CWs into high- and low-risk groups, the utilization of geometric CW parameters may play a role in improving patient selection for intervention in the setting of incidentally diagnosed CW. .

Sleep disturbances are prominent across neurodevelopmental disorders (NDDs) and may reflect specific abnormalities in brain development and function. Overnight polysomnography (PSG) allows for detailed investigation of sleep architecture, offering a unique window into neurocircuit function. Analysis of existing pediatric PSGs from clinical studies could enhance the availability of sleep studies in pediatric patients with NDDs towards a better understanding of mechanisms underlying abnormal development in NDDs. Here, we introduce and characterize a retrospective collection of 1527 clinical pediatric overnight PSGs across five different sites. We first developed an automated stager trained on independent pediatric sleep data, which yielded better performance compared to a generic stager trained primarily on adults. Using consistent staging across cohorts, we derived a panel of EEG micro-architectural features. This unbiased approach replicated broad trajectories previously described in typically developing sleep architecture. Further, we found sleep architecture disruptions in children with Down's Syndrome (DS) that were consistent across independent cohorts. Finally, we built and evaluated a model to predict age from sleep EEG metrics, which recapitulated our previous findings of younger predicted brain age in children with DS. Altogether, by creating a resource pooled from existing clinical data we expanded the available datasets and computational resources to study sleep in pediatric populations, specifically towards a better understanding of sleep in NDDs. This Retrospective Analysis of Sleep in Pediatric (RASP) cohorts dataset, including staging annotation derived from our automated stager, is deposited at https://sleepdata.org/datasets/rasp.

Machine learning (ML) on structural MRI data shows high potential for classifying Alzheimer's disease (AD) progression, but the specific contribution of brain regions, demographics, and proteinopathy remains unclear. Using Alzheimer's Disease Neuroimaging Initiative (ADNI) data, we applied an extreme gradient-boosting algorithm and SHAP (SHapley Additive exPlanations) values to classify cognitively normal (CN) older adults, those with mild cognitive impairment (MCI) and AD dementia patients. Features included structural MRI, CSF status, demographics, and genetic data. Analyses comprised one cross-sectional multi-class classification (CN vs. MCI vs. AD dementia, n = 568) and two longitudinal binary-class classifications (CN-to-MCI converters vs. CN stable, n = 92; MCI-to-AD converters vs. MCI stable, n = 378). All classifications achieved 70-77% accuracy and 61-83% precision. Key features were CSF status, hippocampal volume, entorhinal thickness, and amygdala volume, with a clear dissociation: hippocampal properties contributed to the conversion to MCI, while the entorhinal cortex characterized the conversion to AD dementia. The findings highlight explainable, trajectory-specific insights into AD progression.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Dural arteriovenous fistula (dAVF) surgery is a microsurgical procedure that requires confirmation of obliteration using formal cerebral angiography, but the lack of intraoperative angiogram or need for postoperative angiogram in some settings necessitates a search for alternative, less invasive methods to verify surgical success. This study evaluates the use of indocyanine green videoangiography FLOW 800 hemodynamic intraoperatively during cranial and spinal dAVF obliteration to confirm obliteration and predict surgical success. METHODS:A retrospective analysis was conducted using indocyanine green videoangiography FLOW 800 to intraoperatively measure 4 hemodynamic parameters-Delay Time, Speed, Time to Peak, and Rise Time-across venous drainage regions of interest pre/post-dAVF obliteration. Univariate and multivariate statistical analyses to evaluate and visualize presurgical vs postsurgical state hemodynamic changes included nonparametric statistical tests, logistic regression, and Bayesian analysis. RESULTS:A total of 14 venous drainage regions of interest from 8 patients who had successful spinal or cranial dAVF obliteration confirmed with intraoperative digital subtraction angiography were extracted. Significant hemodynamic changes were observed after dAVF obliteration, with median Speed decreasing from 13.5 to 5.5 s-1 (P = .029) and Delay Time increasing from 2.07 to 7.86 s (P = .020). Bayesian logistic regression identified Delay Time as the strongest predictor of postsurgical state, with a 50% increase associated with 2.16 times higher odds of achieving obliteration (odds ratio = 4.59, 95% highest density interval: 1.07-19.95). Speed exhibited a trend toward a negative association with postsurgical state (odds ratio = 0.62, 95% highest density interval: 0.26-1.42). Receiver operating characteristic-area under the curve analysis using logistic regression demonstrated a score of 0.760, highlighting Delay Time and Speed as key features distinguishing preobliteration and postobliteration states. CONCLUSION/CONCLUSIONS:Our findings demonstrate that intraoperative FLOW 800 analysis reliably quantifies and visualizes immediate hemodynamic changes consistent with dAVF obliteration. Speed and Delay Time emerged as key indicators of surgical success, highlighting the potential of FLOW 800 as a noninvasive adjunct to traditional imaging techniques for confirming dAVF obliteration intraoperatively.

BACKGROUND AND IMPORTANCE/BACKGROUND:Rhino-orbital cerebral mucormycosis (ROCM) is an aggressive fungal infection involving the paranasal sinuses, orbit, and intracranial cavity, with a propensity for vascular invasion. This can lead to complications such as internal carotid artery (ICA) thrombosis and occlusion, presenting major neurosurgical challenges. Although surgical debridement and antifungal therapy are the mainstays of treatment, cases with significant neurovascular involvement require specialized intervention. We report a case of ROCM with severe flow-limiting ICA stenosis treated by direct extracranial-intracranial bypass. CLINICAL PRESENTATION/METHODS:tA 65-year-old man with diabetes presented with progressive left-sided blindness and facial numbness. Imaging revealed a left orbital mass extending into the paranasal sinuses and intracranially. Empiric antifungal therapy was started. Pathology confirmed Rhizopus species. Despite extensive surgical debridement and antifungal therapy, the patient developed progressive severe cavernous ICA stenosis, leading to watershed territory strokes. To restore cerebral perfusion, protect from distal emboli, and prepare for potential aggressive debridement, a flow-replacing direct (superficial temporal artery-middle cerebral artery (M2)) bypass was performed, and the supraclinoid carotid was trapped. Intraoperative angiography confirmed robust flow through the bypass. The patient was discharged on antifungal therapy and aspirin. At 6-month follow-up, the patient was neurologically intact with an modified Rankin Scale score of 1. Computed tomography angiography and transcranioplasty Doppler ultrasonography confirmed good flow through the bypass. CONCLUSION/CONCLUSIONS:In addition to antifungal therapy and surgical debridement, superficial temporal artery-middle cerebral artery bypass can be a lifesaving intervention in the management of ROCM with severe cerebrovascular compromise. This case highlights the critical role of cranial bypass in preserving cerebral perfusion in patients with flow-limiting ROCM-associated ICA invasion.