Faculty Bibliography

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.

OBJECTIVE:Stereotactic radiosurgery (SRS) has long been used for the management of vestibular schwannoma (VS). While the use of SRS as a primary or adjuvant modality for VS has been extensively studied, more effort is needed to clarify the outcomes of SRS as a salvage approach after tumor progression following incomplete resection of VS. The objective of this study was to determine the safety and efficacy of salvage SRS for tumor progression after incomplete resection of VS and to elucidate the factors influencing tumor control and freedom from additional treatment (FFAT). METHODS:Patients with VS who underwent incomplete microsurgical resection followed by salvage SRS for tumor progression were retrospectively reviewed. A total of 64 patients were identified and analyzed. The median patient age at time of SRS was 51.5 years, and 30 (46.9%) patients were males. The median marginal dose was 12.5 Gy at a median isodose of 50%. RESULTS:The 10- and 15-year tumor control rates following salvage SRS were 87.5% (95% CI 76.8-94.4) and 84.4% (95% CI 73.1-92.2), respectively, while the 10- and 15-year FFAT rates were 95.3% (95% CI 86.9-99.0) and 92.2% (95% CI 82.7-97.4), respectively. No factors were significantly associated with tumor control or FFAT in the Cox proportional hazards model. The median time between microsurgical resection and salvage SRS was 38.8 months. Following SRS, the primary complication was worsening or new-onset trigeminal neuropathy (n = 10 [15.6%]). Worsening hearing, measured using Gardner-Robertson class, was reported in 9 cases (14.1%). CONCLUSIONS:Salvage SRS is a safe and effective modality for long-term tumor control and FFAT in VS patients whose tumors progress after initial incomplete microsurgical resection.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Trigeminal schwannomas (TSs) are rare, mostly benign tumors that exhibit an indolent clinical course. The lateral orbitotomy approach (LOA), with or without endoscopic assistance, has emerged as a novel skull base route, particularly for accessing lesions confined to the middle cranial fossa. Herein, we elucidate the advantages and limitations of the LOA for the treatment of TSs. METHODS:All TS cases that underwent LOA through a lateral canthus incision during the past decade in our department were retrospectively reviewed. The operative technique was detailed, and clinical outcomes were analyzed. RESULTS:Eight patients (4 females) with an average age of 37 years underwent LOA for TSs. The mean maximum tumor diameter was 2.7 cm (range: 1.8-3.7 cm). Seven were primary and one was recurrent, the latter in a patient with neurofibromatosis type 2. All tumors were predominantly in the middle cranial fossa, with 4 having either a small or medium posterior fossa component (6: Samii Type A; 2: Type C). Presenting symptoms included trigeminal neuralgia (n = 6), facial hypoesthesia (n = 6), headache (n = 5), and double vision (n = 3). All patients underwent gross (n = 6) or near-total (n = 2) resection. Neuralgia, while not exacerbated, reappeared in 4 patients after surgery and was ameliorated with medication. Two patients sustained new trigeminal hypoesthesia, and preoperative abducens palsy either improved or resolved in all 3 cases. No orbital complications, cerebrospinal fluid leak, or mortalities occurred. Two lesions had minor recurrence during a mean follow-up of 42.9 months. The first underwent radiosurgery 6 years postoperatively and the second is under close surveillance. CONCLUSION/CONCLUSIONS:Minimally invasive LOA stands as a plausible and aesthetically favorable surgical corridor for addressing TSs of the middle cranial fossa, even with extension into the posterior fossa. However, additional study is required as the approach may be limited for tumors with significant posterior or infratemporal fossa involvement.

The ability to quickly learn and generalize is one of the brain's most impressive feats and recreating it remains a major challenge for modern artificial intelligence research. One of the most mysterious one-shot learning abilities displayed by humans is one-shot perceptual learning, whereby a single viewing experience drastically alters visual perception in a long-lasting manner. Where in the brain one-shot perceptual learning occurs and what mechanisms support it remain enigmatic. Combining psychophysics, 7 T fMRI, and intracranial recordings, we identify the high-level visual cortex as the most likely neural substrate wherein neural plasticity supports one-shot perceptual learning. We further develop a deep neural network model incorporating top-down feedback into a vision transformer, which recapitulates and predicts human behavior. The prior knowledge learnt by this model is highly similar to the neural code in the human high-level visual cortex. These results reveal the neurocomputational mechanisms underlying one-shot perceptual learning in humans.

INTRODUCTION/BACKGROUND:There has been a surge in attention to ethical controversies associated with organ donation in the USA. The Neurocritical Care Society (NCS) Ethics Committee sought to understand member experiences and attitudes related to organ donation in the USA. METHODS:We designed a survey of members who practice in the USA and have interacted with an organ procurement organization (OPO)/potential donor. The survey was disseminated by NCS from 1 June 2025 to 1 September 2025. Free-text responses were reviewed to identify themes. RESULTS:Of 2204 NCS members in the USA, there were 71 respondents who completed the survey and 37 respondents who provided free-text comments. Experiences and attitudes varied, but 59% of respondents indicated that they generally think that communication between the OPO and patient surrogates about donation after brain death/death by neurologic criteria seems appropriate, and 34% indicated that they generally think that communication between the OPO and patient surrogates regarding donation after cardiac death/death by circulatory-respiratory criteria (DCD) seems appropriate. Themes included (1) the need to improve education for the treatment team about organ donation; (2) blurred boundaries between patient care and care directed toward organ donation; (3) misalignment between OPOs and treatment team priorities; (4) loss of trust between patient surrogates and the treatment team based on interactions with OPOs; (5) suboptimal timing of communication between OPOs and patient surrogates; (6) concerns regarding a potential lack of transparency, empathy, and cultural sensitivity in communication between OPOs and patient surrogates; (7) opportunities for improvement in preoperative care before donation and palliation after extubation for DCD; and (8) changes in willingness to donate organs based on interactions with OPOs. CONCLUSIONS:Although the results from this survey reflect the experience and attitudes of a small percentage of NCS members in the USA, they indicate that there are opportunities for improvement in organ donation processes. Survey results will guide the NCS Ethics Committee in supporting members navigating ethical controversies related to organ donation.

OBJECTIVE:NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant genetic disorder characterized by the development of schwannomas, meningiomas, and spinal ependymomas. Treatment with bevacizumab, a monoclonal antibody against VEGF, has been shown to result in decreased vestibular schwannoma size and hearing improvement in ~50% of NF2-SWN patients. It is unknown whether the same degree of benefit is seen in younger patients compared with older patients. The objective of this study is to determine the association between age and bevacizumab treatment outcomes in NF2-SWN. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Thirty-seven patients with NF2-SWN. INTERVENTIONS/METHODS:Bevacizumab. MAIN OUTCOME MEASURES/METHODS:Change in tumor size of 20% or more. RESULTS:This study includes 37 patients with NF2-SWN who were treated with bevacizumab at our institution between 2014 and 2024. They were divided into 2 groups: 22 adults over the age of 25 (26 to 71 y) and 15 adolescent and young adult (AYA) patients under the age of 25 (12 to 24 y). The median treatment duration was 2.1 years. A significantly higher proportion of AYA schwannomas (37.5%, n=9) exhibited radiographic tumor progression during the treatment period compared with those of the older patient group (11.9%, n=5) (P=0.026), despite similar pre-treatment growth rates. There was no significant difference in the proportion of older and younger patients with hearing decline, improvement, or stability (P>0.05). CONCLUSIONS:AYA patients were significantly more likely to exhibit progression of tumor growth during bevacizumab treatment compared with older patients, though no significant differences were detected in hearing outcomes.

OBJECTIVE:To characterize patient outcomes after primary stereotactic radiosurgery (SRS) for the management of sporadic facial nerve schwannoma. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Six tertiary referral centers across the United States and United Kingdom. PATIENTS/METHODS:Adults undergoing SRS from 2000 through 2023 for sporadic facial nerve schwannoma along any segment of the facial nerve were included. Patients with NF2-related schwannomatosis were excluded. INTERVENTION/METHODS:Stereotactic radiosurgery. MAIN OUTCOME MEASURE/METHODS:Long-term tumor control. RESULTS:Among 60 patients meeting inclusion, the median age at SRS was 52 years (IQR: 41 to 64) with a median tumor size of 19.5 mm (IQR: 14.7 to 22.8). Tumors commonly involved the internal auditory canal (73%), cisternal (49%), geniculate/labyrinthine (47%), and tympanic segments (22%). Two patients experienced SRS failure and underwent salvage treatment; salvage-free survival rates (95% CI; number still at risk) at 1, 3, 5, and 10 years after SRS were 100% (100 to 100; 55), 100% (100 to 100; 36), 100% (100 to 100; 18), and 87% (72 to 100; 9), respectively. Among 31 (52%) patients with House-Brackmann (HB) grade I facial function at presentation, only 6 demonstrated worse facial function at a median of 3.2 years (IQR: 1.7 to 6.6) after SRS. Of 18 patients with serviceable hearing (AAO-HNS class A/B) at SRS, 13 maintained serviceable hearing at a median of 1.0 years (IQR: 0.5 to 4.9) of post-SRS audiometric follow-up. CONCLUSIONS:Durable tumor control after primary SRS for sporadic facial nerve schwannoma is achieved in most patients. Among those with HB grade I facial function at presentation, treatment with SRS harbors limited additional risk of facial paresis beyond observation alone.

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.