Category: Statistics

Epilepsy Behav. 2026 Apr 30;181:111074. doi: 10.1016/j.yebeh.2026.111074. Online ahead of print.

ABSTRACT

We aimed to assess differences in auditory deviance detection and the underlying sources’ effective connectivity between participants with juvenile myoclonic epilepsy (JME) (N = 60) and healthy controls (N = 39). 256-channel EEG data were recorded during an auditory roving oddball paradigm. Dynamic causal modeling (DCM) was used to estimate effective connectivity between brain regions involved in generation of auditory mismatch negativity (MMN) and P3a component of event-related potentials (ERPs). Between-group statistics were used to compare the MMN and P3a amplitudes. DCM and Parametric Empirical Bayes (PEB) were used to model experimental perturbations in cortical connectivity and assess between-group differences. Hypothesis-driven correlation tests between the sensor space MMN and P3a amplitudes, as well as DCM connectivity estimates, with heavy executive function load cognitive tests were also evaluated. MMN and P3a amplitudes were significantly smaller in the JME patients group compared to controls. DCM and PEB analyses revealed group-level differences in cortical connectivity as the result of experimental effects (i.e., differential response to the deviant stimuli in relation to the standard ones): (1) Significantly reduced extrinsic connectivity for JME participants versus controls between right superior temporal gyrus (r-STG) and right inferior frontal gyrus (r-IFG), as well as (2) Increase in intrinsic (within a region) excitability in left STG. Weak-to-moderate associations were found between the electrophysiological variables under study and neuropsychological tests of executive function. Reduced auditory deviance detection, as well as a decreased right-sided feedforward connectivity in our JME cohort, correlated with cognitive test performance. These findings reflect aberrant neurophysiology underlying JME warranting potential interventions.

PMID:42066395 | DOI:10.1016/j.yebeh.2026.111074

Epilepsy Behav. 2026 Apr 30;181:111065. doi: 10.1016/j.yebeh.2026.111065. Online ahead of print.

ABSTRACT

The primary aim of this systematic review and meta-analysis is to evaluate the impact of educational programs for children with epilepsy and/or their parents on disease management. A comprehensive literature search was performed across eight electronic databases from inception to January 20, 2026, to identify studies evaluating educational interventions for children with epilepsy and/or their parents or caregivers. Following screening and eligibility assessment, ten studies were included in the final systematic review and meta-analysis. Study selection, data extraction, and risk of bias assessment were independently performed by two reviewers using standardized tools. Meta-analyses were conducted using RevMan software, applying fixed- or random-effects models based on heterogeneity, and the certainty of evidence was assessed using the GRADE approach. This meta-analysis included ten randomized controlled trials evaluating educational programs for children with epilepsy and/or their parents. In the analysis of seizure frequency, educational programs showed an effect in reducing the likelihood of seizures, but the result was not statistically significant (OR = 0.62; 95% CI: 0.37-1.03; p = 0.07; I² = 0%). Educational programs significantly improved parental quality of life (SMD = 0.71; 95% CI: 0.15-1.27; p = 0.01; I² = 69%). Strong trends were found towards decreased parental anxiety (SMD = – 0.82; 95% CI: -1.68-0.04; p = 0.06; I² = 93%) and increased self-efficacy (SMD = 2.63; 95% CI: -0.18-5.44; p = 0.07; I² = 98%), but these findings did not reach statistical significance. Knowledge level regarding epilepsy significantly increased with educational programs (SMD = 1.29; 95% CI: 0.56-2.02; p = 0.0005; I² = 87%). Epilepsy management significantly improved with educational programs (MD = 0.48; 95% CI: 0.21-0.76; p = 0.0005; I² = 0%). This meta-analysis demonstrates consistent and significant benefits of educational programs on epilepsy management, knowledge level, and parental quality of life. While the effects on seizure frequency, parental anxiety, and self-efficacy were not statistically conclusive, the observed effect trends point to clinically positive potential. It supports the inclusion of education-based interventions as a complementary and empowering component in epilepsy care.

PMID:42066394 | DOI:10.1016/j.yebeh.2026.111065

Comput Biol Chem. 2026 Apr 22;124(Pt 1):109086. doi: 10.1016/j.compbiolchem.2026.109086. Online ahead of print.

ABSTRACT

Non-small cell lung cancer (NSCLC) contains rare cancer stem cells (CSCs) that contribute to relapse and drug resistance. Bulk RNA-seq overlooks these cells due to its averaging of expression across all cell types, whereas standard single-cell RNA-seq (scRNA-seq) analyses often struggle to reliably identify these rare CSC states. To address this, we developed an scRNA-seq pipeline that integrates machine learning with explainable AI (XAI) to detect CSC-like epithelial cells in NSCLC (GSE198099, n = 2 patients; analyses supported by effect size-based validation despite limited statistical power). Patient-derived scRNA-seq profiles underwent quality control and batch correction using scVI, and annotated using CellTypist. A 45-gene stemness score was used to identify candidate CSC-like states. Four machine learning models (Logistic Regression, LightGBM, XGBoost, and CatBoost) were trained to refine the CSC-like state identification. SHAP-based feature attribution analyses converged on six key biomarkers: DLL1, ITGA6, ATXN2, NOTCH1, DCLK1, and PUM1. These biomarkers are involved in regulating transcription, adhesion, cytoskeletal dynamics, and post-transcriptional control. Pathway analysis and validation using TCGA validation data provided supportive evidence for the biological relevance of these biomarkers. This framework provides a methodologically reproducible approach to reveal rare CSC-like states with improved mechanistic clarity, providing candidate biomarkers for studying NSCLC tumor plasticity.

PMID:42066389 | DOI:10.1016/j.compbiolchem.2026.109086

Neurosurg Focus. 2026 May 1;60(5):E8. doi: 10.3171/2025.12.FOCUS25941.

ABSTRACT

OBJECTIVE: Surgical intervention is a standard treatment for severe cervical spondylotic myelopathy (CSM), but postoperative outcomes can vary based on socioeconomic characteristics such as insurance status. The aim of this study was to investigate the influence of insurance on patient-reported outcomes (PROs) at 60 months postoperatively.

METHODS: In this prospective cohort study, the Spine CORe™ study group analyzed data from the Quality Outcomes Database (QOD) database. Chi-square and Kruskal-Wallis tests were performed to identify the associations between sociodemographic and clinical variables and insurance type. The chi-square test was also used to examine the influence of insurance type on the achievement of minimal clinically important difference (MCID) for each outcome measure. Statistically significant covariates (p < 0.001) were used in a multivariate linear regression model measuring the influence of insurance type on 60-month changes in scores for neck and arm pain numeric rating scale (NRS), Neck Disability Index (NDI), EQ-5D, and modified Japanese Orthopaedic Association (mJOA) scores.

RESULTS: From a dataset of 1085 patients who underwent CSM surgery, 106 patients died during the 5-year follow-up period and 793 had an NDI score at the 5-year follow-up. The follow-up rate was 83% ([793 with NDI + 106 died]/1085 patients). Of the 1085 patients, the authors excluded patients with Veterans Affairs insurance, no insurance, or who were missing baseline PROs, which left 1030 patients with Medicare (n = 408), Medicaid (n = 75), and private (n = 547) insurance with 60-month PROs. Insurance status varied based on demographics and medical comorbidities (each p < 0.05). Medicaid patients had significantly worse scores at baseline and 60 months for arm and neck NRS, NDI, EQ-5D, and mJOA (each p < 0.05). In multivariate analysis after adjustment for relevant covariates, compared with private insurance, only Medicare insurance was associated with lower 60-month EQ-5D scores (β -0.05, 95% CI -0.09 to -0.01; p < 0.05). Otherwise, there was no significant difference in PROs. Medicaid insurance was not significantly associated with differences in any of the outcomes after covariate adjustment compared to private insurance.

CONCLUSIONS: Despite having worse baseline scores, patients with Medicaid insurance coverage had similar rates of achievement of MCID compared with those with private insurance. These results suggest that patients with CSM who underwent surgery had improvement in PROs for all insurance types.

PMID:42066370 | DOI:10.3171/2025.12.FOCUS25941

J Neurosurg. 2026 May 1:1-11. doi: 10.3171/2025.12.JNS251528. Online ahead of print.

ABSTRACT

OBJECTIVE: Surgical procedures involving varying tissue depths present challenges to surgeons regarding accessibility and precision, restricting instrument movement and increasing the risk of tissue injury. Understanding how experts navigate varying depths is essential, yet research on this issue is limited. Artificial intelligence (AI)-powered systems enable real-time analysis of 3D psychomotor performance during virtual reality simulation tasks. In this study, the authors evaluated performance in a complex brain tumor resection simulation, testing two hypotheses: 1) neurosurgeons’ performance scores would remain at an expert level across varying depths, and 2) trainees’ scores would decline as they navigated into deeper and more challenging areas.

METHODS: Participants included neurosurgeons (n = 14), senior trainees (n = 14), junior trainees (n = 10), and medical students (n = 12). Five left-handed participants were excluded to avoid confounding due to hand dominance, resulting in a final analyzed sample of 45 participants. The Intelligent Continuous Expertise Monitoring System, an AI-powered real-time performance assessment system, assessed surgical performance and measured metrics such as instrument tip separation distance, bleeding risk, healthy tissue injury risk, aspirator force applied, bipolar cautery force applied, and an overall composite score. An average score for each metric at each depth interval (0-15 mm) was calculated across expertise levels for statistical comparison in a retrospective single-center analysis.

RESULTS: Neurosurgeons maintained their performance score across varying depths, demonstrating their expertise. Senior trainees had lower scores with increased depth. Surprisingly, increased depth resulted in higher composite scores among medical students and junior trainees, as they had to adapt better instrument techniques in deeper surgical sites. However, their scores remained in the novice spectrum. There was an increasing trend in bleeding risk with greater depth regardless of the expertise level, indicating the more challenging nature of deeper sites.

CONCLUSIONS: The unique responses observed at varying depths at each expertise level indicate the necessity for adaptive training modules that accommodate trainee skill set levels and individual learning curves, ensuring development of the competencies required for mastering challenging tasks.

PMID:42066367 | DOI:10.3171/2025.12.JNS251528

J Neurosurg. 2026 May 1:1-11. doi: 10.3171/2025.12.JNS252197. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to compare the long-term risk of hemorrhagic stroke and death between conservative management and monotherapy intervention in patients with Spetzler-Martin (SM) grade I and II brain arteriovenous malformations (AVMs).

METHODS: The authors included AVMs that underwent conservative management and monotherapy intervention between August 2011 and December 2021 from a nationwide multicenter prospective collaboration registry. Patients were categorized into unruptured and ruptured cohorts for comparison of long-term outcomes, with hemorrhagic stroke and death defined as primary outcomes and neurological status as a secondary outcome. The efficacy of various intervention strategies, including resection, embolization, and stereotactic radiosurgery (SRS), was also evaluated. Stratified analyses based on intervention strategies and different SM grade subtypes were conducted.

RESULTS: Of 4286 AVMs in the registry, 1013 patients were eligible for inclusion (387 with unruptured AVMs and 626 with ruptured AVMs). Overall, the intervention group showed a lower incidence of long-term hemorrhagic stroke and death compared with the conservative management group (0.43 vs 0.88 per 100 patient-years; adjusted HR [aHR] 0.61 [95% CI 0.24-1.52]), although this difference did not reach statistical significance. The results were similar in the two subgroups: aHR 0.95 (95% CI 0.28-3.18) for unruptured AVMs and aHR 0.29 (95% CI 0.06-1.32) for ruptured AVMs. Stratified analyses based on different intervention strategies and different SM grade subtypes showed that resection might benefit both unruptured (0.00 vs 0.79 per 100 patient-years, p = 0.006) and ruptured (aHR 0.12 [95% CI 0.03-0.53], p = 0.033) AVMs, while SRS might only benefit ruptured AVMs (aHR 0.04 [95% CI 0.01-0.34], p = 0.163). Embolization and SRS might not be beneficial for unruptured low-grade AVMs.

CONCLUSIONS: In this observational prospective cohort study, intervention demonstrated benefit over conservative management in preventing long-term hemorrhagic stroke or death in patients with SM grade I or II AVMs. Among specific monotherapy interventions, resection proved favorable for both unruptured and ruptured SM grade I and II AVMs, while SRS might serve as a reasonable alternative in ruptured cases.

PMID:42066362 | DOI:10.3171/2025.12.JNS252197

J Neurosurg. 2026 May 1:1-11. doi: 10.3171/2025.12.JNS252065. Online ahead of print.

ABSTRACT

OBJECTIVE: Adamantinomatous craniopharyngioma (ACP) is a rare type of brain tumor that affects a wide age range, from children to older adults. Due to the rarity of the disease, existing studies are predominantly limited to single-center or single-surgeon experiences, often lacking statistical power and generalizability. The aim of this study was to address this gap by providing a comprehensive analysis of ACP outcomes based on a large multicenter cohort from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID).

METHODS: This multicenter retrospective cohort study was conducted via the RAPID consortium and assessed patients with histologically confirmed ACP treated surgically between August 2000 and November 2024 at high-volume pituitary centers across the United States.

RESULTS: Among the 359 patients (206 male, median age at primary surgery of 47 years) included in the analysis, 76% underwent endoscopic transsphenoidal surgery and 22% underwent craniotomy. Gross-total resection was achieved in 45% and subtotal resection in 47%. Notably, 120 of 311 patients (39%) presented with preoperative hypothalamic-pituitary axis dysfunction. Following all treatments, permanent hypothyroidism was reported in 40% of patients, adrenal insufficiency in 33%, and arginine vasopressin deficiency in 19%. Of 263 patients who underwent primary surgery, radiation therapy was administered in 84 (32%). Progression-free survival (PFS) declined from 66% at 1 year to 31% at 6 years. In the multivariable analysis, independent predictors of worse PFS included subtotal resection (HR 0.22, 95% CI 0.11-0.42; p = 0.001), partial resection (HR 0.11, 95% CI 0.04-0.28, p = 0.001), larger tumor size (HR 0.77, 95% CI 0.64-0.94; p = 0.009), and tumor extension beyond the sella and suprasellar regions (HR 0.21, 95% CI 0.06-0.74; p = 0.016). Primary surgery and salvage surgery groups showed comparable PFS.

CONCLUSIONS: In this large multicenter cohort study, gross-total resection was achieved in fewer than half of patients and was independently associated with improved PFS. Approximately one-third of patients underwent radiation therapy after primary surgery. These findings provide robust evidence supporting the prognostic value of extent of resection and inform contemporary treatment algorithms for ACP. The high incidence of postoperative endocrinopathy underscores the need for individualized multidisciplinary long-term care. While the retrospective design is a limitation, the multicenter approach enhances the generalizability of these results.

PMID:42066361 | DOI:10.3171/2025.12.JNS252065

Neurosurg Focus. 2026 May 1;60(5):E7. doi: 10.3171/2025.12.FOCUS25940.

ABSTRACT

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a common cause of spinal cord dysfunction worldwide and can be treated through anterior or posterior approaches. Both strategies achieve acceptable results, but the growing prevalence of obesity poses unique challenges. Data directly comparing outcomes across body mass index (BMI) strata are limited. Here, the authors examined rates of achieving minimal clinically important differences (MCIDs) in patient-reported outcomes (PROs) between anterior and posterior approaches relative to BMI.

METHODS: This was a post hoc analysis of prospectively collected data from the 14-site Spine CORe™ study group of the Quality Outcomes Database (QOD). Baseline data and PROs-including numeric rating scale (NRS) neck and arm pain, Neck Disability Index (NDI), EQ-5D, and modified Japanese Orthopaedic Association (mJOA) scores-were collected through 60 months. Patients were stratified by an a priori BMI threshold of 30 kg/m2 and by surgical approach (anterior vs posterior). Multivariable regression was used to compare achievement of MCID across approaches within each BMI group. In parallel, unsupervised clustering of baseline-adjusted PROs was combined with a doubly robust estimation framework to assess approach-specific probabilities of achieving optimal outcomes across the continuous BMI spectrum.

RESULTS: Among 1085 patients, 759 (70.0%) underwent anterior and 326 (30.0%) underwent posterior surgery. Anterior approaches were associated with shorter length of stay and fewer nonhome discharges (p < 0.001). For patients with BMI < 30 kg/m2, anterior surgery conferred higher odds of achieving MCID in NRS arm pain (OR 0.45, p = 0.032). For those with BMI ≥ 30 kg/m2, anterior surgery was associated with greater odds of achieving MCID in mJOA (OR 0.32, p = 0.007) and NDI (OR 0.42, p = 0.031) scores. The results were consistent in sensitivity analyses. The doubly robust model identified a BMI range of 29.1-36.7 kg/m2, where anterior approaches significantly increased the probability of optimal outcomes (risk difference > 8.1%; lower confidence interval > 0). Anterior approaches also demonstrated greater probability of achieving optimal outcomes at higher BMIs, though without statistical significance.

CONCLUSIONS: For BMI < 30 kg/m2, both approaches improved disability and quality of life, with anterior surgery offering added relief of arm pain. For BMI ≥ 30 kg/m2, anterior surgery provided superior functional and disability outcomes. Most importantly, anterior surgery became significantly more advantageous beginning at BMI 29.1 kg/m2. However, approach selection remains multifactorial, as anterior and posterior cohorts differed in mean age (anterior 58.7 vs posterior 64.5 years) and mean operated levels (anterior 1.9 vs posterior 4.2 levels). While anterior approaches may be most commonly employed for younger patients or for one- and two-level pathology, posterior approaches remain an important option for multilevel cervical stenosis or in the elderly to avoid dysphagia. Thus, this study highlights BMI as just one of many key factors in approach selection for CSM, but should not replace individualized clinical decision-making.

PMID:42066358 | DOI:10.3171/2025.12.FOCUS25940

Neurosurg Focus. 2026 May 1;60(5):E14. doi: 10.3171/2025.12.FOCUS25945.

ABSTRACT

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a common cause of spinal cord dysfunction, and anterior cervical discectomy and fusion (ACDF) is the gold standard treatment. Cervical disc arthroplasty (CDA) is a relatively novel, motion preserving alternative to ACDF. The aim of this study was to assess CDA versus ACDF in the surgical treatment of CSM at a 5-year follow-up.

METHODS: This study used the 14-site Spine CORe™ study group cervical module of the Quality Outcomes Database (QOD), which included 1085 patients. Baseline demographics, clinical variables, and surgical parameters were collected. Patient-reported outcome measures (PROMs) included the EQ-5D, Neck Disability Index (NDI), and numeric rating scale (NRS) for neck pain and arm pain. Of the 1085 patients, 22 patients who underwent CDA with baseline and 5-year follow-up PROMs data who met the inclusion/exclusion criteria were selected. Nearest-neighbor propensity score matching was performed using a 4:1 matching ratio. Five-year PROMs were compared between the CDA and ACDF groups using the 2-sample t-test for continuous variables. Multivariable linear regression was performed to identify predictors of 5-year myelopathy severity.

RESULTS: There were 1085 patients in the 14-site Spine CORe™ study group’s QOD cervical module; 110 matched patients were analyzed, including 22 who underwent CDA (mean age 47.73 years) and 88 who underwent ACDF (mean age 48.89 years). The subcohort had 100% of PROMs data (NDI, NRS, EQ-5D, and mJOA) at the 5-year follow-up. There were no significant differences for 1- and 2-level operations between the CDA and ACDF groups (p = 0.34). There were no significant differences in 5-year PROMs between the two groups. Patients improved in each PROM category in both treatment groups when comparing baseline with 5-year PROMs. While the rate of reoperation at 5 years was higher in the ACDF group compared with the CDA group, there was no statistically significant difference (17.0% vs 9.1%, p = 0.52).

CONCLUSIONS: In appropriately selected patients with CSM, CDA can provide comparable outcomes to ACDF while preserving cervical motion.

PMID:42066356 | DOI:10.3171/2025.12.FOCUS25945

J Neurosurg. 2026 May 1:1-12. doi: 10.3171/2025.12.JNS25176. Online ahead of print.

ABSTRACT

OBJECTIVE: Communicating hydrocephalus may occur following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs), yet identifying individual patient risk factors associated with this post-SRS complication remains a challenge. This study examined predictors of nonobstructive ventricular enlargement and symptomatic communicating hydrocephalus following primary SRS treatment for VS via a single-center institutional cohort review and meta-analysis of the literature.

METHODS: A retrospective single-institution cohort study and systematic literature review and meta-analysis examining post-SRS communicating hydrocephalus in VS was performed.

RESULTS: The institutional cohort consisted of 634 patients who received primary SRS as treatment for VS. The cohort was 51.6% female, with a median age of 64 (range 18-89) years. Following SRS treatment, 364 patients (57.4%) experienced tumor shrinkage, 218 (34.4%) had no change in the size of their lesion, and 52 (8.2%) experienced tumor growth. Nonobstructive ventricular enlargement was observed in 23 patients (3.6%) following SRS treatment, of whom 9 (39.1%) remained asymptomatic and 14 (60.9%) required placement of a ventriculoperitoneal (VP) shunt, with a median time to shunt placement of 8 months. In the multivariate analysis, patients ≥ 65 years old (p = 0.038), SRS target volume ≥ 5 cm3 (p < 0.001), maximum SRS dose ≥ 26 Gy (p = 0.015), and tumor growth at the most recent follow-up (p = 0.002) were associated with an increased risk of post-SRS ventricular enlargement. Similarly, patients with older age (p = 0.049), increased SRS target volume (p = 0.002), and tumor growth (p = 0.016) were at an increased risk of symptomatic communicating hydrocephalus requiring VP shunt placement. Twenty-nine studies, including the cohort in this study, met inclusion criteria in the meta-analysis. Of the pooled 7825 patients, the overall incidence of hydrocephalus following SRS was 5%, and a subanalysis of 7081 patients demonstrated the incidence of symptomatic hydrocephalus requiring a VP shunt to be 4%. In this subanalysis, the overall shunting rate in patients who experienced post-SRS ventriculomegaly was 92%. Among individual studies in the literature, increased tumor size was most commonly found to be a statistically significant risk factor for post-SRS hydrocephalus.

CONCLUSIONS: Approximately 5% of patients may experience nonobstructive ventricular enlargement following primary SRS treatment for VS. However, not all patients may be symptomatic and require shunting. Patients who are older (≥ 65 years), those with larger tumor volumes, and those with post-SRS tumor growth may be at increased risk of communicating hydrocephalus and may benefit from closer clinical monitoring.

PMID:42066355 | DOI:10.3171/2025.12.JNS25176