Daniel J. Zhou

Background: In glioblastoma, tumor-related epilepsy (TRE) is paradoxically associated with longer survival, but the mechanism is unclear. We hypothesized that structural connectivity is associated with seizure susceptibility and survival, and tested whether these associations are independent or mediated. Methods: We retrospectively studied glioblastoma patients with preoperative diffusion-weighted MRI. Fractional anisotropy-weighted connectivity matrices were constructed using lesion-aware tractography. Mean edge weight and local efficiency were computed per Yeo 7-network and with global efficiency at hemisphere and whole-brain levels. Associations with TRE, overall survival (OS), and progression-free survival (PFS) were assessed using logistic regression and Cox proportional hazards models with false discovery rate correction. Causal mediation analysis tested whether connectivity and TRE mediate each other’s relationship with overall survival. Results: We included 420 glioblastoma patients. Of 406 classifiable for TRE, 217 (53%) had TRE. TRE was associated with higher local efficiency across all seven contralateral networks ( d= 0.42-0.49, q< 0.010) and five of seven ipsilateral networks ( d =0.44-0.49, q< 0.050). In adjusted models, higher contralateral global efficiency was associated with longer OS (HR 0.84, q= 0.021), with no metric associated with PFS. TRE did not mediate the connectivity-OS relationship. Contralateral local efficiency partially mediated the TRE-OS association when postoperative KPS was excluded from the model (ACME 16.6 days, 7.8% mediated, p =0.029), though this was attenuated when KPS was included ( p =0.074). Conclusions: Structural connectivity may partially mediate the seizure-survival association, suggesting preserved network architecture may contribute to longer survival in glioblastoma patients with TRE, though most of the effect operates through other pathways. Key Points: Tumor-related epilepsy in glioblastoma was associated with relatively greater structural connectivity. Higher contralateral global efficiency related to longer overall survival. Contralateral local efficiency may partly mediate the seizure-survival link. Importance of the Study: Seizures in glioblastoma are paradoxically associated with longer survival, yet the biological basis of this relationship has remained unknown. Using lesion-aware diffusion tractography in 420 patients, we found that the same structural network measures relate to both seizure susceptibility and survival. Patients with tumor-related epilepsy had relatively greater white matter connectivity, and higher contralateral connectivity was independently associated with longer overall survival. Causal mediation analysis showed that connectivity accounted for a small fraction of the seizure-survival association, suggesting that seizures mark, rather than confer, the survival advantage, and that both may reflect a shared upstream driver not captured here. These findings identify structural connectivity as a shared correlate and candidate imaging biomarker for seizure risk and prognosis in glioblastoma.

Objective: We aim to comprehensively analyze how regional tumor and edema characteristics are associated with clinical presentations and survival outcomes in a large cohort of glioblastoma patients. Methods: Patients with IDH ‐wildtype glioblastoma who received brain MRI from 2010 to 2023 were included. The enhancing tumor, necrotic core, and edema/infiltration volumes were automatically segmented across brain regions. Multivariable regression assessed associations between regional volumes, presenting symptomatology, and survival outcomes. Results: Of 526 patients analyzed, initial presentations included seizure (29%), aphasia (26%), confusion (25%), headache (24%), focal weakness (22%), memory problems (20%), ataxia (16%), visual field deficits (11%), personality change (10%), and focal sensory abnormalities (7%). Distinct regional tumor patterns emerged: seizures were associated with smaller overall tumor burden but with relatively greater cortical involvement, headache with increased subcortical volumes, confusion with left hemisphere and temporal involvement, personality changes with frontal‐cingulate‐basal ganglia involvement, and focal neurologic deficits with mostly predictable patterns. While no initial presentation correlated with survival, the presence of postoperative seizures was associated with improved overall survival. Increased volume of enhancing tumor, particularly in the insula and brainstem, was associated with worse overall survival. Interpretation: Anatomical tumor distribution provided prognostic information beyond overall tumor burden in glioblastoma. Regional patterns expand on the anatomical basis of symptoms. The survival benefit associated with postoperative seizures suggests distinct tumor biology or microenvironmental factors. Incorporating regional characteristics into clinical and prognostic models may improve risk stratification and inform treatment planning.

Intracranial electroencephalographic (iEEG) connectivity analysis is a promising method to localize epileptic networks and guide surgical planning in focal drug‐resistant epilepsy. Despite numerous studies exploring its utility, the added value of iEEG connectivity over standard clinical presurgical evaluation remains unclear. We assess the current evidence on the efficacy of iEEG connectivity analyses to improve seizure outcomes following epilepsy surgery through a systematic review and meta‐analysis. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) reporting guidelines, we searched PubMed and Embase for studies (2006–2024) of adult focal drug‐resistant epilepsy patients who underwent surgical resection or ablation, reported outcomes at least 1 year postsurgery, and used iEEG connectivity analysis to localize networks. Reviews, nonhuman studies, and studies lacking iEEG connectivity analysis or network localization were excluded. We derived classification metrics (true/false positives/negatives) based on concordance between iEEG findings, clinical localization, and outcome. Subgroup meta‐analyses and meta‐regressions determined differences by seizure type, lesion status, and analysis approach. Of 2881 studies screened, 25 met criteria ( n = 909). The pooled odds ratio comparing seizure outcome prediction using iEEG connectivity versus standard clinical evaluation was 1.36 (95% confidence interval = 1.10–1.69, p = .004), indicating a significant overall benefit. Subgroup analyses found no significant differences by directionality, modeling method (linear/nonlinear), or iEEG epoch (interictal/peri‐ictal). Meta‐regression revealed greater added value of iEEG connectivity in studies with higher proportions of non‐seizure‐free patients following surgery for temporal lobe or lesional epilepsy. However, no individual study achieved statistical significance on its own, reflecting limited power and lack of individual patient‐level data. Power analysis confirmed that detecting a clinically meaningful effect requires substantially larger, potentially multicenter datasets. iEEG connectivity analysis offers modest but consistent increased value over standard clinical methods to predict seizure freedom in adult patients with focal drug‐resistant epilepsy. For clinical translation, we propose recommendations for future studies to address sample size limitations, standardize reporting, and prioritize individual patient‐level data sharing.

Automated seizure detection and localization from intracranial EEG requires validated benchmark datasets with expert annotations, yet existing open datasets lack multi-expert consensus annotations and exclude stimulation-induced seizures. We present stereotactic EEG recordings from 83 seizures (46 spontaneous, 37 stimulation-induced) across 32 patients (19 from the University of Pennsylvania, 13 from the Children’s Hospital of Philadelphia) with drug-resistant epilepsy. Three board-certified epileptologists independently annotated each seizure for onset time, onset channels, and channels seizing at 10 seconds post-onset using a standardized protocol. Consensus annotations were determined through majority voting. Inter-rater agreement was κ = 0.64 for onset channels and κ = 0.62 for spread channels. Individual rater agreement with consensus was κ = 0.81 for onset and κ = 0.80 for spread. Agreement metrics did not differ between spontaneous and stimulation-induced seizures. All data follow Brain Imaging Data Structure (BIDS) standards and include electrode localizations, patient demographics, and clinical outcomes. This dataset enables the validation of seizure onset and spread detection and localization against human expert performance and supports comparative analysis of seizure networks across spontaneous and stimulation-induced seizures.

Background: Pleomorphic xanthoastrocytomas (PXAs) are rare brain tumors that are often associated with seizures. There are limited data characterizing epilepsy phenotypes in relation to PXA tumor biology and survival outcomes. Methods: This is a retrospective observational study of 35 patients with PXA who received treatment at the University of Pennsylvania or Dana-Farber Cancer Institute. Demographic and clinical features were assessed in PXA patients with or without seizures and with respect to seizure freedom following tumor resection. Results: During their clinical course, 27 (77%) developed tumor-related epilepsy (TRE), with 25 (71%) initially presenting with a seizure. Compared to those without TRE, patients with TRE were more likely to have a BRAF-mutated PXA and less likely to have frontal lobe tumor localization. Patients with TRE who became seizure-free after the initial resection up to the time of progressive disease were found to have a lower age of seizure onset, smaller tumor diameter, and more likely to have BRAF-mutated tumors compared to those who were not seizure-free. However, following the last tumor resection and accounting for tumor recurrences, there were no significant differences in clinical features between those who were seizure-free and those who were not. Overall survival was 88% after 5 years and 59% after 10 years, with similar survival rates between patients with and without TRE. Conclusion: These findings indicate that BRAF-mutated and BRAF-wildtype PXAs have distinct epilepsy phenotypes. Further investigation of the interplay between tumor biology and seizures may help guide counseling and targeted therapeutic strategies for PXA-related epilepsy.

We report two distinct challenging initial presentations of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Case 1 describes a 12-year-old boy who developed headaches refractory to pain medication followed by cranial neuropathies and intracranial hypertension, confirmed by lumbar puncture with an opening pressure >36 cm H₂O. Case 2 describes a 3-year-old boy who developed new-onset seizures refractory to antiseizure medications, a presentation of FLAIR-hyperintense lesions in MOG-antibody associated encephalitis with seizures (FLAMES). On repeat magnetic resonance imaging, both patients were found to have cortical T2 hyperintensities, leptomeningeal contrast enhancement, and bilateral optic nerve enhancement. In the cerebrospinal fluid, both patients had CSF pleocytosis with neutrophilic predominance. The patients were treated with intravenous immunoglobulins, plasma exchange, and high-dose corticosteroids. The first patient achieved disease remission, whereas the second patient required the addition of rituximab for management of seizures. The two cases highlight the pleomorphic clinical phenotypes of MOGAD.

To describe thiamine prescribing patterns and to study the association of thiamine supplementation with clinical outcomes in hospitalized patients with altered mental status (AMS).We conducted a re...

Restless leg syndrome (RLS) is a common neurological disorder with an estimated prevalence of 10–35% in people over 65 years of age. Current clinical practice guidelines include the recommendation to check serum ferritin levels and provide iron supplementation if the ferritin level is ≤75 μg/L. We present a case of an 84-year-old man who developed worsening RLS symptoms over the past year despite up-titration of oral ropinirole to maximum daily dose. As part of his workup for RLS, his serum ferritin level was found to be severely low. He was also previously noted to be anemic, so we recommended that he be worked up for iron deficiency anemia. He later received a colonoscopy, which revealed a cecal polyp with high grade dysplasia, and then underwent right hemicolectomy. The patient reported significant improvement in RLS symptoms following the surgery. This case demonstrates the importance of working up iron deficiency anemia in the setting of worsening RLS symptoms, particularly in the geriatric population.