Citations

Abstract This paper provides a practical guide to applying the updated seizure classification in clinical settings. The updated classification, published by the International League Against Epilepsy in 2025, builds on the operational classification introduced in 2017. It aims to enhance clarity, clinical relevance, and consistency in seizure terminology across various healthcare settings. The classification system distinguishes between four main seizure classes: focal, generalized, unknown whether focal or generalized, and unclassified. The basic version allows for application even in resource‐limited or primary care environments, while the expanded version offers detailed semiological descriptors and supports advanced diagnostic and surgical decision‐making. Consciousness, defined through awareness (recall) and responsiveness, is now considered a classifier. The paper also highlights the importance of distinguishing observable from non‐observable features and integrates semiology into the expanded classification with attention to temporal sequence and somatotopic detail. Generalized seizures are categorized into seizure types having a direct impact on syndrome diagnosis and treatment decisions. Epileptic spasms are given special attention because of their unique presentation and the urgency of early intervention, particularly in infants. To support clinical implementation, this paper includes a comprehensive table of semiological descriptors, definitions of generalized seizure types, and a series of real‐world case vignettes illustrating the application of the updated seizure classification. Supplementary figures and videos further support the educational aims of the paper. This practical guide is intended for healthcare professionals managing patients with epilepsy, providing a clear, structured approach to seizure classification that is adaptable to varying levels of clinical expertise and diagnostic resources.

PURPOSE Recent studies reveal that 5%-18% of children with cancer harbor pathogenic variants in known cancer-predisposing genes. However, DNA damage repair (DDR) genes, which are frequently somatically altered in pediatric tumors, have not been systematically examined as a source of novel cancer-predisposing signals. METHODS To address this gap, we interrogated 189 DDR genes for presence of germline predisposing variants (PV) among 5,993 childhood cancer cases and 14,477 adult noncancer controls (discovery cohort). PV were determined using a tiered approach incorporating ClinVar annotations, InterVar classification, and in silico tools (REVEL, CADD, and MetaSVM). Using logistic and firth regression, we identified genes with PV statistically enriched in the germline of children with tumors and replicated findings among 1,497 additional childhood cancer cases across three independent cohorts. RESULTS Analysis across all cases with cancer revealed enrichment of TP53 PV. Cancer-specific analyses confirmed known associations including germline TP53 PV in adrenocortical carcinoma, high-grade glioma (HGG), and medulloblastoma (MB), PMS2 in HGG and non-Hodgkin lymphoma (NHL), MLH1 in HGG, BRCA2 in NHL, and BARD1 in neuroblastoma. In addition, four novel associations were uncovered, including BRCA1 in ependymoma, SPIDR in HGG, SMC5 in MB, and SMARCAL1 in osteosarcoma (OS). Importantly, the SMARCAL1 :OS association was significant in the discovery (6/230, 2.6%, false discovery rate [FDR] logistic = 0.0189) as well as all three replication cohorts (Childhood Cancer Survivor Study: 8/275, 2.9%; P Fisher < .0001; Cancer Predisposition Syndrome-German Childhood Cancer Registry: 4/135, 3%, P Fisher = .002; Individualized Therapy for Relapsed Malignancies in Childhood: 4/217, 1.8%, P Fisher = .012). The remaining wild-type SMARCAL1 allele was deleted in three of four OS tumors with available data. CONCLUSION Our study confirms the relevance DDR genetic variation in pediatric cancer risk and establishes SMARCAL1 as a novel OS predisposing gene, providing insights into tumor biology and creating opportunities to optimize care for patients with this challenging tumor.

The treatment landscape of B-cell lymphomas has significantly evolved in recent years with approval of novel targeted therapies. CD3 × CD20 bispecific antibodies and CD19-directed monoclonal antibodies and antibody–drug conjugates have demonstrated efficacy in relapsed/refractory follicular lymphoma (FL). Bruton tyrosine kinase (BTK) inhibitor–based regimens are emerging as effective treatment options for patients with TP53-mutated classical mantle cell lymphoma (MCL). Results from ongoing clinical trials suggest that the addition of CD3 × CD20 bispecific antibodies to chemoimmunotherapy improves outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, MCL, and DLBCL.

Abstract BACKGROUND Ovarian cancer rarely metastasises to the brain, thus studies reporting the outcomes of affected patients are lacking. Stereotactic radiosurgery (SRS) is now the mainstay of management for patients with brain metastases (BM) from most primary sites, but little evidence of its efficacy in ovarian cancer is available. The current study was undertaken to provide guidance for SRS management using pooled data from multiple institutions. MATERIAL AND METHODS Centers participating in the IRRF (International Radiosurgery Research Foundation) were asked to provide outcome data for patients who had SRS for ovarian cancer brain metastases between 2020 and 2024 and at least one clinical and imaging follow-up after the procedure. Primary endpoints included survival from SRS, local tumor response according to RANO-BM criteria and occurrence of adverse radiation effects (ARE). Cox regression analyses were performed to identify variables impact each endpoint. RESULTS 128 patients had SRS for a total of 532 BM treated. Epithelial histology was the most common (91%). Median age at SRS was 62 years (IQR 56-70). Median KPS was 80% (IQR 80-90%) and 71.9% of patients had neurological symptoms at presentation. Other active systemic metastases were present in 41.4%. The median number of treated BM was 2 (IQR1-3) and the median cumulative treatment volume was 6 cc (IQR 2-12.9). The median margin dose was 18 Gy (IQR 16-20). At last follow-up, 19.5% of patients were still alive. The median overall survival (OS) after SRS was 27 months, and 6-, 12- and 24-month OS was 83.8%, 74.2% and 52.2%, respectively. Multivariate analyses revealed that increasing age at SRS (HR 1.02, p=0.05), active systemic metastases (HR 2, p=0.005) and increasing number of brain metastases (HR 1.05, p=0.04) were associated with worse survival, while repeating SRS (HR 0.4, p=0.002) led to improved survival. Local failure occurred in 12.8% of treated BM. Actuarial progression-free survival (PFS) at 6, 12 and 24 months was 92.3%, 86.6% and 70.3%, respectively. Only prior WBRT (HR 4.36, p=0.03) led to worse local control on multivariate analyses. New remote BM appeared in 49.5% of patients and 14.5% suffered from leptomeningeal dissemination. ARE were seen in 12.1% of BM but were symptomatic in only 3.2%. On multivariate analyses, prior SRS (HR 3.13, p=0.002) was associated with increased risk of ARE. CONCLUSION Ovarian cancer brain metastases can be safely and effectively managed with SRS as the primary treatment modality in most patients.

With the first series of PRRX1 -rearranged tumors published in 2019, the spectrum of these so-called fibroblastic tumors has been expanded. Since then, several smaller case series have been published; however, our understanding of them continues to be quite limited given their rarity. We herein studied 18 additional cases, the largest series to date. Eighteen tumors present in 9 male, 8 female, and 1 nonbinary patient with a median age of 35 years (range: 11 to 70 y) and involved the neck (5), the chest region (4), thigh (3), back (1), shoulder (1), forehead (1), lower leg (1), axilla (1), and the parapharyngeal region (1). Clinical follow-up (9/18 tumors; 50%; median: 10 mo; range: 4 to 40 mo) showed consistent indolent behavior without local recurrences or distant metastases. On morphology, these tumors were characterized by well-circumscription and distinctive peripheral crescent-shaped vessels. They were composed of uniform spindle and round cells growing in short fascicles within often densely hyalinized collagen lacking significant mitotic activity, necrosis, or cytologic atypia. Immunohistochemically, about half of the tested tumors expressed focal to rarely diffuse S100 with occasional co-expression of SOX10. Interestingly, almost half of the tested cases also showed complete loss of RB expression. All but 1 tumor harbored a PRRX1::NCOA1 fusion, while 1 case harbored a novel PRRX1::EP300 fusion. We herein provide additional data on these exceptionally uncommon tumors, expand their molecular spectrum, and compare them to their close morphologic mimics to aid in accurate diagnosis and avoid confusion with potentially more aggressive neoplasms.

ABSTRACT Background Patients with hypertrophic obstructive cardiomyopathy (HOCM) were excluded from all major trials for transcatheter aortic valve replacement (TAVR). “Suicide left ventricle” occurring after TAVR is postulated to occur as a result of chronic pressure overload from fixed obstruction that is acutely relieved after the valve deployment resulting in worsening left ventricular outflow tract obstruction. Aims The aim of this study was to determine the clinical and readmission outcomes in HOCM patients undergoing TAVR. Methods Data was extracted from the National Inpatient and National Readmission 2016−2020 Databases. We performed multivariable Logistic regression analysis to determine the odds of in‐hospital mortality and other relevant clinical outcomes in patients undergoing TAVR with and without comorbid HOCM. Multivariable Cox regression analysis was used to assess 30‐day hospital readmission in HOCM patients undergoing TAVR. Results We identified 296,670 patients who underwent TAVR, of whom 534 (0.2%) had comorbid HOCM. The patients undergoing TAVR with comorbid HOCM had more than threefold higher risk of in‐hospital mortality (adjusted odds ratio: 3.47, 95% CI 1.37–8.81, p = 0.009) when compared to patients without HOCM. Additionally, patients undergoing TAVR with comorbid HOCM had a higher risk of atrioventricular blocks, cardiogenic shock, acute kidney injury, and the need for intubation. There was no difference in readmission outcomes post‐TAVR among patients with and without HOCM. Conclusion Our analysis of a large, real‐world cohort of patients undergoing TAVR showed that patients with HOCM have a significantly higher risk of in‐hospital mortality and procedural complications when compared to patients without HOCM.

BACKGROUND Septic facet cysts are a rare phenomenon reported in the literature among immunocompromised hosts and may require operative intervention for appropriate source and symptomatic control. OBSERVATIONS A 70-year-old male with a past medical history of immunoglobulin A lambda smoldering myeloma degenerative lumbar disease who presented with low back and radicular lower extremity pain was found to have a left L4–5 septic facet cyst with extension to the epidural space. Intraoperative cultures were positive for Nocardia species. Staging workup revealed progression to high-risk-profile multiple myeloma. LESSONS Patients with septic facet cysts may require operative intervention for appropriate source control. Nocardia spine infections and septic facet cysts are rare and require investigation of preexisting risk factors and any potential underlying immunocompromise. https://thejns.org/doi/10.3171/CASE25220

Objectives Directly compare the brain glucose patterns seen with [F‐18] fluorodeoxyglucose (FDG) positron emission tomography (PET) between 2 genetically determined forms of Alzheimer's disease: Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD). Methods Cross‐sectional analyses of FDG were performed in individuals with DS (n = 76) from the Alzheimer Biomarker Consortium‐Down Syndrome (ABC‐DS), ADAD (n = 297), and neurotypical familial controls (n = 188) from the Dominantly Inherited Alzheimer Network (DIAN). Within‐group linear regression models and generalized additive models were performed for select regional FDG uptake measures (isthmus cingulate and inferior parietal, precuneus, middle temporal gyrus, and precentral gyrus). Age, sex, apolipoprotein (APOE) ε4 carrier status, and cortical amyloid burden were included within these analyses. Results Even 20 years before expected onset of clinical symptoms, FDG uptake was lower for DS compared to neurotypical familial controls ( p < 0.01). ADAD baseline FDG was similar to neurotypical familial controls until 7 years before expected symptom onset. Both symptomatic individuals with DS and ADAD had lower FDG compared to neurotypical familial controls ( p < 0.01). A higher amyloid burden was associated with lower FDG for both genetic forms, with similar rates of decline in FDG uptake for DS and ADAD who were amyloid positive. Interpretation Brain glucose metabolism is substantially lower for people with DS, even in individuals who are cognitively stable. The patterns of FDG decline are distinct in these 2 genetically determined forms of AD. The diagnostic utility of FDG‐PET is specific to the genetic form of AD. ANN NEUROL 2025;98:1237–1248

Objective To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework. Methods Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD‐related cognitive decline was estimated primarily by baseline cognitive symptoms plus SVD risk factors. Adjudicated risk status was estimated by cognitive symptoms plus presence of moderate‐to‐severe white matter hyperintensities, microbleeds, or lacunes on baseline MRI. Results MarkVCID2 enrolled 1883 individuals age 73.4 ± 7.5 years, 65.0% female, 24.2% Hispanic, and 27.1% non‐Hispanic Black. Among enrollees, 44.8% were provisionally designated high‐risk. After baseline MRI, 48.5% were categorized as adjudicated high‐risk status, with substantial recategorization both from low‐ to high‐risk (primarily because of MRI lesions without SVD risk factors) and high‐ to low‐risk (primarily suspected cognitive impairment at screening not confirmed by baseline testing). Interpretation MarkVCID2 baseline data indicate successful enrollment of diverse individuals enriched in factors associated with SVD‐related cognitive decline. Changes over 3 years of longitudinal follow‐up will be analyzed to validate the candidate biomarkers for 2 projected contexts of use: subject selection (identifying likelihood of future SVD progression) and study outcome (efficiently measuring SVD progression). ANN NEUROL 2026;99:449–458