Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Severe hypoxemia after generalized convulsive seizures (GCSs) can trigger neural injury and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP). Some degree of variability in interbreath interval is normal, but increased variability may suggest dysfunctional breathing control and may be associated with severe postictal hypoxemia. We evaluated the relationship between interictal breathing variability and severity and duration of hypoxemia after GCS. METHODS:nadir), and secondary outcome: occurrence of combined prolonged and pronounced hypoxemia. Univariable and multivariable models were created for primary outcomes, but only univariable analyses were performed for the secondary outcome. RESULTS:= 0.002) was the only variable significantly associated with hypoxemia severity after controlling for duration of postictal generalized EEG suppression, SD-2 of the awake interbreath interval, and body mass index. Univariable analyses for combined prolonged and pronounced hypoxemia showed SD-2 of the awake interbreath interval, temporal lobe epilepsy, ictal central apnea, and a shorter tonic phase duration were significantly associated. DISCUSSION/CONCLUSIONS:Measures of interictal respiratory variability are associated with severe and prolonged hypoxemia after GCS. Increased interictal respiratory variability suggests baseline respiratory dysregulation in some PWE and may be a surrogate for SUDEP risk.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Interactions between cancer cells and their microenvironment are central to tumor formation. Regional microenvironmental variability in the brain may offer insights into essential factors in tumorigenesis. Surprisingly, a granular assessment of regional patterns of gliomagenesis has not been undertaken in the molecular era. The aim of this study was to quantitatively establish the anatomic distribution of the major molecular subtypes of adult diffuse glioma. METHODS:We retrospectively analyzed 204 isocitrate dehydrogenase (IDH)-mutant and 200 IDH-wildtype gliomas. Reproducibility was assessed in an external cohort (190 IDH-mutant, 227 IDH-wildtype), and microarray expressions from Allen Human Brain Atlas were used to compare transcriptomic profiles between IDH-mutant hotspots and coldspots. RESULTS:A total of 50.5% (103/204) of IDH-mutant tumors arose with the superior and middle frontal gyri, indicating a 3.1-fold regional enrichment relative to the volume of these gyri (P < .001). Totally, 9.5% (19/200) of IDH-wildtype tumors arose in the superior temporal gyrus with a 2.1-fold enrichment (P = .01). IDH-mutant and wildtype tumors were enriched by 4 and 4.5-fold, respectively, in the insula (both P < .001). Overall, 23.3% (24/103) of astrocytomas occurred disproportionately higher in the insula compared with oligodendrogliomas (P < .001). Transcriptomic analysis comparing the lobar hotspot (frontal lobe) to the coldspot (occipital lobe) revealed frontal enrichment of cholesterol (normalized enrichment score = 1.78) and fatty acid (normalized enrichment score = 1.94) metabolism pathways, paralleling the observed regional enrichment of IDH-mutant gliomas. CONCLUSION/CONCLUSIONS:This study identifies molecular subtype-specific glioma hotspots and may suggest that regional metabolic differences may underlie the brain's variable vulnerability to gliomagenesis. These findings provide a framework for investigating additional microenvironmental factors that drive human glioma formation.

STUDY DESIGN/METHODS:A national prospective cervical spine surgery registry was developed to archive radiographic studies, patient-reported outcome measures (PROMs), and surgical implant data to assess long-term safety. OBJECTIVE:To describe the design, development, funding, and implementation of a cervical spine data registry for 1000 patients with myelopathy and radiculopathy. SUMMARY OF BACKGROUND DATA/BACKGROUND:While surgery for cervical radiculopathy and myelopathy is safe and effective, there is significant practice variation among spine surgeons. While randomized clinical trials (RCTs) can provide high-quality comparative effectiveness data, RCTs lack the ability to evaluate the safety and effectiveness of various surgical procedures and implants among heterogenous real-world patient populations. The CSRS Registry was designed to collect patient demographics, outcomes, radiographic imaging, surgical approach, and implant data for the purpose of conducting high-quality research. METHODS:Patients with cervical myelopathy or radiculopathy were enrolled in the CSRS National Registry. De-identified patient data, validated PROMs, radiographic data, and implant data were collected from multiple clinical sites across the United States. RESULTS:One thousand patients [mean age, 58 y; 456 (46%) women] were enrolled, with 31% follow-up at 1 year. Five hundred ninety-two patients were diagnosed with radiculopathy, 252 with myelopathy, and 156 with radiculopathy and myelopathy. Patients had significant improvements in their PROMs after surgery. At 1 year, the mean NDI score improved from 37.2 to 20.9 (P<0.001). The mean self-reported P-mJOA score at baseline was 14.2 and improved to 15.2 by 1 year (P<0.001). Baseline CSDI score was 23.6 and improved with a 1-year decrease to an average score of 13.6 (P<0.001). There was significant improvement in PROMIS-10 Physical Health score from 41.0 to 45.9 (n=311; P<0.001) at 1-year follow-up. CONCLUSIONS:The CSRS Registry has successfully collected clinical outcomes data that is being leveraged for comparative effectiveness research and evaluations of the long-term safety and effectiveness of spinal implants.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The therapeutic approach for small- and medium-sized vestibular schwannoma (VS) with normal hearing function remains controversial, with limited comparative data regarding hearing outcomes after stereotactic radiosurgery (SRS) or observation (OBS). We evaluated the serviceable hearing preservation, loss of American Academy of Otolaryngology-Head and Neck Surgery class A hearing, and tumor control (TC) across individuals with Koos grade I and II VSs and normal hearing at presentation who underwent SRS or OBS. METHODS:In this multicenter international study, we retrospectively analyzed the hearing, radiological, and neurological outcomes of patients who underwent SRS (SRS group) or OBS (OBS group). The cohorts were matched using propensity scores based on age, sex, tumor volume, pure-tone average, and speech discrimination score at a 1:1 ratio without replacement. RESULTS:After matching, each group comprised 57 patients. The median follow-up was 49 and 37 months for the SRS and the OBS groups, respectively (P = .3). The 5- and 9-year serviceable hearing preservation rates in the SRS group were 76.2% and 42.4% vs 56.1% and 16.8% in the OBS group (P = .17). Class A preservation occurred in 57.9% (33/57) of the SRS and 52.6% (30/57) of the OBS cohorts (P = .70). Regarding the TC rates, SRS was associated with significantly higher TC rates (P < .0001). CONCLUSION/CONCLUSIONS:We found that SRS is significantly superior regarding TC and provided noninferior hearing outcomes compared with OBS in VS patients with American Academy of Otolaryngology-Head and Neck Surgery class A hearing at presentation. Therefore, we suggest performing SRS in individuals with VS and normal hearing function.

STUDY DESIGN/METHODS:Prospective, multi-center analysis. OBJECTIVE:Evaluate preoperative and minimum 2-year postoperative health related quality of life (HRQOL) outcomes for adult spine deformity (ASD) using legacy HRQOL measures and computer adaptive testing (CAT) version of the patient reported outcome measurement information system (PROMIS). SUMMARY OF BACKGROUND DATA/BACKGROUND:PROMIS is the NIH recommended measure for patient reported outcomes. No data exists evaluating minimum 2-year ASD surgical outcomes using PROMIS CAT compared to legacy HRQOL measures. METHODS:ASD patients > 18 years of age were enrolled into a prospective, multi-center, observational study. Patients were administered legacy HRQOLs (SRS-22r, ODI, NRS back and leg pain, VR-12) and PROMIS CAT for Pain Interference, Physical Function, Satisfaction with Participation in Social Roles, Satisfaction with Participation in Discretionary Social Activities, Depression, and Anxiety. Preoperative and minimum 2-year postoperative HRQOL scores were compared and ASD PROMIS scores were compared to general population PROMIS values. RESULTS:144 of 190 patients had complete data at minimum 2-year follow-up. Mean preoperative values included: age=62.6 years, scoliosis=34.2°, SVA=74.2mm, PI-LL=16.7. At mean 2.3 year follow-up surgical treatment improved spine alignment (scoliosis=14.7°, SVA=34.5mm, and PI-LL=4.5°; P<0.0001). All legacy HRQOL and PROMIS scores improved from preoperative to minimum 2-year postoperative (P<0.005). Referencing PROMIS scores to normative values demonstrated 50-85% of ASD patients preoperatively reported moderate-severe deficits in all domains. At minimum 2-year postoperative 52-88% of ASD patients reported normal values-mild deficits in all PROMIS domains. PROMIS social health domains demonstrated the greatest improvement. CONCLUSION/CONCLUSIONS:This is the first study evaluating minimum 2-year ASD surgical outcomes using PROMIS CAT. ASD patients demonstrated postoperative improvements in all PROMIS health domains, with the social health domains improving most. The majority of ASD patients reported normal PROMIS values at minimum 2-years postoperative.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Bone metastases, affecting more than 4.8% of patients with cancer annually, and particularly spinal metastases require urgent intervention to prevent neurological complications. However, the current process of manually reviewing radiological reports leads to potential delays in specialist referrals. We hypothesized that natural language processing (NLP) review of routine radiology reports could automate the referral process for timely multidisciplinary care of spinal metastases. METHODS:We assessed 3 NLP models-a rule-based regular expression (RegEx) model, GPT-4, and a specialized Bidirectional Encoder Representations from Transformers (BERT) model (NYUTron)-for automated detection and referral of bone metastases. Study inclusion criteria targeted patients with active cancer diagnoses who underwent advanced imaging (computed tomography, MRI, or positron emission tomography) without previous specialist referral. We defined 2 separate tasks: task of identifying clinically significant bone metastatic terms (lexical detection), and identifying cases needing a specialist follow-up (clinical referral). Models were developed using 3754 hand-labeled advanced imaging studies in 2 phases: phase 1 focused on spine metastases, and phase 2 generalized to bone metastases. Standard McRae's line performance metrics were evaluated and compared across all stages and tasks. RESULTS:In the lexical detection, a simple RegEx achieved the highest performance (sensitivity 98.4%, specificity 97.6%, F1 = 0.965), followed by NYUTron (sensitivity 96.8%, specificity 89.9%, and F1 = 0.787). For the clinical referral task, RegEx also demonstrated superior performance (sensitivity 92.3%, specificity 87.5%, and F1 = 0.936), followed by a fine-tuned NYUTron model (sensitivity 90.0%, specificity 66.7%, and F1 = 0.750). CONCLUSION/CONCLUSIONS:An NLP-based automated referral system can accurately identify patients with bone metastases requiring specialist evaluation. A simple RegEx model excels in syntax-based identification and expert-informed rule generation for efficient referral patient recommendation in comparison with advanced NLP models. This system could significantly reduce missed follow-ups and enhance timely intervention for patients with bone metastases.

PURPOSE OF REVIEW/UNASSIGNED:Alzheimer disease (AD) and epilepsy are major causes of neurologic disability and are reciprocally related: epileptiform discharges, subclinical seizures, and epilepsy are more prevalent in patients with AD compared with controls; progressive cognitive impairment commonly afflicts epilepsy patients; and late-onset epilepsy patients have higher rates of new-onset dementia. RECENT FINDINGS/UNASSIGNED:Epidemiologic studies support shared risk factors (e.g., genetic variants, vascular disease, sleep disorders, microbiome) with notable divergences. AD and epilepsy have some overlapping anatomic (e.g., hippocampus, entorhinal, and association cortex), clinical (e.g., memory, attentional, and executive) impairments, and neuropathologic (e.g., amyloid, tau, neurofibrillary tangles) features. Shared clinical and translational challenges include underlying mechanisms (e.g., genetic variants, neuroinflammation, metabolic and mitochondrial dysfunction, excitatory/inhibitory imbalance, microbiome, and sociodemographic factors) and identifying valid and reliable biomarkers (e.g., total tau and phosphorylated tau (p-tau), amyloid deposition, Aβ42/Aβ40 ratio) to assess disease progression, predict outcomes, and assess potentially disease-modifying interventions. SUMMARY/UNASSIGNED:Identifying convergences and divergences between epilepsy and AD may inform our understanding. The clinical, neurophysiologic, neuropathologic, and molecular pathologic changes in AD and epilepsy may reveal pathophysiologic insights and therapeutic opportunities.

STUDY DESIGN/METHODS:Retrospective review. OBJECTIVE:Determine if patients with different degrees of incidence (PI) have the capacity to compensate via pelvic retroversion before initiating lower extremity compensation. SUMMARY OF BACKGROUND DATA/BACKGROUND:Compensatory mechanisms in the spine are thought to help patients with deformities maintain sagittal alignment. Pelvic retroversion and thoracic hypokyphosis are key mechanisms that help maintain balance. When these mechanisms are exhausted, patients often flex their hips and bend their knees. METHODS:This was a retrospective radiographic analysis of the EOS images at a single institution. Various spinal sagittal parameters and lower extremity knee flexion measurements were performed. Patients were subcategorized according to PI. Knee flexion in these groups was correlated with various sagittal parameters to determine whether there were differences when knee flexion occurred based on the PI. RESULTS:Knee flexion was independently correlated with PI, pelvic tilt (PT), PI-lumbar lordosis mismatch (PI-LL), and T1 pelvic inclination angle (TPA) in multiple regression analyses (P < 0.05). In patients with lower PI, knee flexion occurred at a PT of 10-15 degrees, PI-LL mismatch of -5-0 degrees, and TPA of about 10-15 degrees. In those with high PI, knee flexion occurred at a PT of ∼25-30 degrees, PI-LL mismatch of ∼15-20 degrees, and TPA about 25 degrees. Those with a lower PI also more rapidly increased knee flexion with further increases in PI-LL mismatch and TPA compared with those with a higher PI. CONCLUSION/CONCLUSIONS:This study demonstrates that patients with different PI have different capacities to compensate for increasing sagittal plane deformity before initiating knee flexion lower extremity compensation. Those with a lower PI retroverted their pelvis less and begin knee compensation earlier than those with a higher PI. These findings are important for surgical planning in patients with differing PI who are compensating for knee flexion.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Molecular markers such as isocitrate dehydrogenase (IDH) and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) status are essential for glioma classification and treatment planning, but their manual extraction from pathology reports creates significant research bottlenecks. This study evaluated 3 Natural Language Processing approaches with increasing computational complexity: deterministic Regular Expressions (RegEx), statistical Term Frequency-Inverse Document Frequency (TF-IDF) with logistic regression, and contextual deep learning Bidirectional Encoder Representations from Transformers (BERT). We address whether more intensive approaches provide sufficient performance benefits over simpler approaches in computational pathology research. METHODS:We analyzed pathology reports from 404 patients with glioma at Institution A and 197 at Institution B for external validation. IDH analysis included 399 (Institution A) and 193 (Institution B) patients; ATRX analysis included 361 and 130 patients, respectively. All approaches underwent identical preprocessing steps, including text normalization, terminology standardization, and context extraction. Performance was evaluated using standard classification metrics and memory usage benchmarks on internal and external validation data sets. RESULTS:Simpler approaches outperformed more intensive approaches on external validation. For IDH, Regex achieved near-perfect accuracy (99%, area under the curve [AUC] 1.000) and TF-IDF performed exceptionally (94.2%, AUC 0.984), while BlueBERT underperformed (85.2%, AUC 0.934). For ATRX, Regex achieved perfect accuracy (100%, AUC 1.000) and TF-IDF maintained high accuracy (98.0%, AUC 0.998), outperforming BERT-large (84.6%, AUC 0.931). BERT-based approaches required 1825-1953 MB of memory vs Regex (0.82-5.52 MB) and TF-IDF (17.27-34.89 MB). CONCLUSION/CONCLUSIONS:Simple Natural Language Processing approaches effectively automate molecular marker extraction from pathology reports with near-perfect accuracy while requiring minimal computational resources. This enables expanded sample sizes in retrospective studies, multi-institutional analyses of rare molecular subgroups, and accelerated biomarker research. Future work will focus on validation across larger data sets, infrastructure integration, and expansion to additional molecular markers.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Normal pressure hydrocephalus (NPH) is characterized by the classic triad of cognitive decline, gait instability, and urinary incontinence in the setting of ventriculomegaly with normal intracranial pressure. Cerebrospinal fluid diversion is the current standard treatment, yet it carries a risk of overdrainage, resulting in subdural hematoma or hygroma. Different valves have been developed to mitigate this risk, yet consensus remains unclear regarding optimal valve for NPH. METHODS:We performed a retrospective cohort study on all patients with NPH who underwent cerebrospinal fluid shunting or revision between January 2014 and September 2025 at our institution. Demographic, clinical, and radiological data were collected from the electronic health record. Kaplan-Meier survival analysis, univariate logistic regression, and multivariate modeling were used to identify predictors of subdural collections and the need for surgical treatment. RESULTS:Since our change in practice from the Integra NPH Low Flow Valve (Low Flow OSV) to other valves in 2022, we observed a rise in symptomatic subdural collections. Programmable valves were associated with a markedly increased 1-year risk of both subdural collection formation and need for surgical intervention compared with the Low Flow OSV. Overall, Certas and Strata valves demonstrated higher rates of subdural collections requiring surgery than the Low Flow OSV (14.6% vs 2.1%, P < .001; 10.5% vs 2.1%, P = .005, respectively). On multivariate analysis, both the Strata and Certas valves were independently associated with increased odds of developing any subdural collection and necessitating surgery. Vascular disease and dual antiplatelet therapy also increased risk. CONCLUSION/CONCLUSIONS:In this large single-center cohort study, programmable valves, specifically the Certas and Strata, were associated with an increased rate and severity of subdural collections compared with the Low Flow OSV. The use of low-flow designs may mitigate complications for the NPH population, and the use of lower programmable valve settings should be carefully considered.