Jerzy P. Szaflarski

Objective: Intracranial electroencephalography (iEEG) practices and diagnostic testing vary among institutions, limiting standardization and optimization of surgical outcomes. This study estimates resection rates and surgical outcome effect sizes after iEEG and develops individual patient‐level data (IPD) models using the missing‐indicator method to approximate real‐world clinical uncertainties and practice variability in iEEG and surgical decision‐making. Methods: Databases were queried for studies reporting ≥12‐month outcomes after epilepsy surgery in patients with drug‐resistant epilepsy (DRE) who underwent iEEG. Random‐effects meta‐analysis estimated pooled outcome proportions. IPD analysis was performed using multivariable generalized linear regression and logistic regression models with cross‐validation and calibration assessment. Missing values for key predictors were retained as a “not specified” category to evaluate the impact of incorporating uncertainty in common clinical data on outcome prediction. Results: Primary outcomes were seizure freedom (Engel class IA or International League Against Epilepsy [ILAE] 1) and favorable seizure outcomes (Engel I or ILAE 1–2). Of 4975 studies identified, 115 met the inclusion criteria. The pooled frequency of patients undergoing resection after iEEG was 67% (95% confidence interval [CI] 60%–74%), 52% achieved seizure freedom (95% CI 48%–56%), and 58% achieved a favorable outcome (95% CI 54%–62%). IPD analysis included 1305 patients from 29 studies and identified a lesional magnetic resonance imaging (MRI; odds ratio [OR] 1.94, CI 1.48–2.55, p < .0001) and a cortical malformation (OR 1.47, CI 1.08–2.00, p = .01) as independent predictors of a favorable outcome, whereas iEEG implantation strategy (bilateral implantation OR .61, 95% CI .42–.89, p = .01) was an independent predictor of a less favorable outcome. Significance: About two‐thirds of patients undergoing iEEG proceeded to resection, and about half achieved seizure freedom. Multivariable models incorporating clinical uncertainty and practice variability were well calibrated. However, modest discrimination suggests that routinely available clinical variables alone have limited ability to predict individual surgical outcomes. More standardized and granular clinical and practice‐related data may improve individualized prognostication after iEEG.

Objective: This study investigated whether idiopathic generalized epilepsies (IGEs) are associated with neuroinflammation by measuring neurometabolite levels and brain temperature using whole‐brain magnetic resonance spectroscopy imaging (MRSI). We compared patients with IGEs to healthy controls (HCs), and in IGEs examined relationships with seizure control, MRSI markers, epilepsy duration, and cognitive performance. Methods: Seventeen patients with IGEs and 15 HCs underwent 3T‐MRI scans. IGEs were also administered the Montreal Cognitive Assessment (MoCA) and Flanker test. Whole‐brain ¹ H‐MRSI provided metabolite and water maps. Levels for myo‐inositol (MI; glial marker), glutamate‐glutamine complex (Glx), and N‐acetylaspartate (NAA) were normalized to creatine (Cr) levels. Brain temperature was obtained by frequency difference between water and Cr. IGEs were stratified into seizure‐free (IGE−) and treatment‐resistant (IGE+) groups. Group analyses were performed using permutation‐based threshold‐free cluster enhancement (TFCE) within bilateral regions of interest: anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), hippocampus, parietal cortex, and thalami. Results: Compared with HCs, IGEs showed higher MI/Cr in the parietal cortex, PCC, and thalamus; higher hippocampus Glx/Cr; and lower parietal cortex NAA/Cr. Brain temperature did not differ between groups. IGE− exhibited higher hippocampal NAA/Cr and better MoCA scores than IGE+. Longer epilepsy duration was associated with lower NAA/Cr in the ACC and PCC, and parietal cortex, as well as lower Glx/Cr in the ACC, PCC, parietal cortex, and hippocampus. Lower NAA/Cr in the ACC, PCC, hippocampus, and thalamus, together with higher thalamus MI/Cr, was associated with lower MoCA scores in IGEs. Lower NAA/Cr in the ACC, thalamus, and hippocampus was associated with poorer Flanker performance in IGEs. Significance: We provide novel evidence of neurometabolic abnormalities in IGEs. The associations between metabolite levels and clinical and cognitive variables suggest potential biomarkers for disease progression and treatment response. Furthermore, these results highlight the roles of abnormal glial activation, neuronal loss, and hyperexcitability in IGE pathophysiology. Plain Language Summary: We compared patients with idiopathic generalized epilepsies (IGEs) to healthy controls (HCs) to investigate brain chemistry and temperature differences and their relationships to seizure control, epilepsy duration, and cognitive performance. We found group differences in brain N‐acetylaspartate (NAA; neuronal marker), myo‐inositol (MI; glial cell marker), and glutamate/glutamine (Glx; excitatory neurotransmission) levels, but not in brain temperature. Longer epilepsy duration was associated with brain chemistry levels. In IGEs, lower NAA levels and higher MI levels were associated with worse cognitive performance. This study highlights the roles of abnormal glial activation, neuronal loss, and hyperexcitability in epilepsy duration and cognition in IGEs.

Objective: Patients with functional seizures (FS) frequently exhibit deficits in cognitive and functioning measures (CFM) similar in magnitude to those present in epilepsy. An association between glymphatic system function and CFM in various neuropsychiatric conditions has been reported. Our objective was to investigate the relationships between CFM and diffusion tensor imaging analysis along perivascular spaces (DTI‐ALPS) index as a measure of perivascular directional diffusivity related to neurofluid dynamics in FS after traumatic brain injury (TBI‐FS), TBI without functional seizures (TBI‐only), and healthy controls (HCs). Methods: A total of 173 participants (40 HCs, 74 TBI‐FS, 59 TBI‐only) underwent diffusion magnetic resonance imaging at 3 T to establish their DTI‐ALPS index. CFM acquired in patient groups were Montreal Cognitive Assessment, Quality of Life in Epilepsy‐31 (total score and cognitive subscale), and Global Assessment of Functioning (GAF). Group differences were analyzed using linear mixed models with hemisphere as a within‐subject factor. The primary group comparison was adjusted for age and sex. Correlations between CFM and DTI‐ALPS index were examined in patient groups. Results: CFM were significantly worse in TBI‐FS than TBI‐only on all measures. GAF showed a significant positive correlation with DTI‐ALPS index in the combined patient sample ( r = .228, p = .009). In the primary analysis, there was a significant main effect of group on DTI‐ALPS index ( F _{2, 330} = 3.51, p = .031, η ² p = .021). DTI‐ALPS index was lower in TBI‐FS than in TBI‐only ( p = .026), and biological sex was a significant covariate ( F _{1, 330} = 5.71, p = .017; females higher). A significant hemispheric asymmetry was found, with right hemisphere DTI‐ALPS index values lower than left ( F _{1, 340} = 35.30, p < .001, η ² p = .094). Significance: TBI‐FS participants showed reduced CFM across all measures, with lower global functioning associated with lower DTI‐ALPS index values in the combined patient sample, suggesting a positive relationship between perivascular directional diffusivity related to neurofluid dynamics and global functioning. Patients with TBI‐FS showed reduced DTI‐ALPS index compared to TBI‐only participants, suggesting potential differences in perivascular function.

Objective: This study was undertaken to evaluate the safety and effectiveness of responsive thalamic stimulation as adjunctive therapy for drug‐resistant idiopathic generalized epilepsy (IGE) with generalized tonic–clonic seizures (GTCSs). Methods: NAUTILUS is a prospective, multicenter, single‐blind, randomized sham‐controlled pivotal trial. Patients were ≥12 years of age with drug‐resistant IGE and ≥2 GTCSs over a 3‐month baseline. Bilateral depth leads were targeted to the centromedian thalamus. One month later, patients were randomized to Active (responsive stimulation, n = 44) or Sham (no stimulation, n = 43). The effectiveness evaluation period (EEP) began 3 months postimplant through 1 year. After a second GTCS in the EEP, patients transitioned to open‐label active stimulation. The primary safety endpoint was the serious adverse device‐related event (SADE) rate at 84 days postimplant. The primary effectiveness endpoint was time‐to‐second‐GTCS during the EEP. Additional endpoints included median percent change in days with any generalized seizure, GTCS frequency, and responder rate (RR). Results: Eighty‐seven patients were implanted across 23 US centers. The SADE rate was significantly below the performance goal (6.9%, p < .0001), with no adverse effects on cognition, mood, or sleep. The prespecified primary effectiveness endpoint was not significant. However, a post hoc mixed‐effects model considering all EEP days demonstrated greater GTCS reduction in the originally randomized Active group (61%) compared to patients originally randomized to Sham (49%, p = .030). Eighteen‐month outcomes included 76.8% median GTCS reduction, 62.5% RR, 40% GTCS‐free at that timepoint, and 77.8% median reduction in days with any generalized seizure. More than 90% of patients and 86% of physicians reported improvement on Global Impression of Change scales. Significance: NAUTILUS is the first randomized controlled neuromodulation trial in IGE. Responsive thalamic stimulation provided a clinically meaningful and durable reduction in seizures with an acceptable safety profile, offering a much‐needed option for drug‐resistant IGE.

Background and ObjectivesNeuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct bra...

In 2005, the Epilepsy Foundation published an expert consensus ( Epilepsia 2005; 46:1423–1425) on actions to minimize risks of visually‐provoked (photosensitive) seizures (VPS). Since then, technology, scientific information, and experience have greatly expanded. An international expert panel convened by the Epilepsy Foundation collated literature, information, and opinions regarding VPS. Consensus guidelines are divided into advice for: patients and families, clinicians, designers of video games, architects, and regulatory agencies. No attempt was made to develop a formal systematic review. Patients are advised about symptoms and epilepsy syndromes that relate to VPS. Commonly used medications and useful behavioral modifications are reviewed. Clinicians are advised on an approach to events that are concerning for VPS, including how to use history and electroencephalography (EEG) to assess whether an event was a seizure (vs another neurologic symptom) and what visual stimuli (light or patterns) provoked it. The utility of magnetic resonance imaging (MRI) to assess for an epileptogenic lesion, routine blood tests, and genetic studies is discussed. Media designers of video games, movies, TV productions, web videos, and artificial or virtual reality images are advised to avoid bright flashing patterns in the 10–20 Hz range, repetitive color flashes, and oscillating or static stripes of ~1–8 cycles per visual degree. Signal analysis or trained human inspectors can identify provocative visual patterns. Architects and designers of public spaces should be aware that some striped patterns can provoke seizures. Government and regulatory agencies require screening of potentially provocative media in some nations. VPS are both an individual and public health problem. The Epilepsy Foundation encourages further research and efforts to minimize risks of seizures provoked by visual stimuli.