Differentiating epileptic from functional seizures is a clinical challenge; while smartphone videos can aid diagnosis, they often require expert review, causing delays. We evaluated the accuracy of four successive multimodal large language models (LLMs), Gemini 1.5 Pro, 2.0 Flash, 2.5 Flash, and 2.5 Pro, in differentiating seizure types from smartphone videos without clinical context. In this prospective diagnostic study at a tertiary epilepsy center, 24 videos from 15 patients were analyzed, with video-electroencephalography monitoring as the gold standard. Of the 24 events (19 epileptic, 5 functional), diagnostic accuracy improved with successive models: Gemini 1.5 Pro (33.3%), Gemini 2.0 Flash (25.0%), and both Gemini 2.5 Flash and Pro (54.2%). In exploratory pairwise comparisons, Gemini 2.5 pro showed higher accuracy than Gemini 1.5 Pro (p = 0.01) and Gemini 2.0 Flash (p = 0.003). Performance was influenced by video features; for example, diagnosis was more accurate for the Gemini 2.5 models when videos focused on the upper body/face (80.0%-90.0%) compared to a whole-body view (28.6%-35.7%). All models reported high confidence scores (median 8.0–9.0) that were poorly aligned and did not correlate with correctness. Successive LLMs show improved yet modest accuracy for seizure classification from video alone, highlighting the need for domain-specific fine-tuning before clinical implementation.

Chimeric antigen receptor T-cell (CAR T-cell) therapy is associated with neurotoxicity, which may include acute symptomatic seizures (ASySs). Specific risk factors and short-term and long-term outcomes of ASyS associated with CAR T-cell therapy have not been well investigated. This retrospective cohort study evaluated incidence and risk factors for ASyS during CAR T-cell therapy. We included patients treated at Mayo Clinic in Minnesota, Florida, and Arizona who underwent CAR T-cell therapy for hematologic malignancies from October 2019 to November 2023. Pretreatment demographics, clinical information, type of CAR T-cell therapy, neuroimaging, laboratories during treatment, and clinical features during admission were analyzed. Data on treatment and prevalence of seizures, EEG, and survival at the last follow-up were assessed. T-tests and nonparametric testing were performed on categorical and continuous data, respectively. Multivariable analysis was also performed. We included 180 patients (mean age 62.3 years, 57.2% women) with 8 (4.4%) developing ASyS at a mean of 8.0 ± 5.3 days after therapy. Earlier onset of cytotoxic release syndrome (odds ratio [OR] 1.81, 95% CI 0.62-2.99, p = 0.007), higher grade immune effector cell-associated neurotoxicity syndrome (ICANS) (OR -1.43, 95% CI -1.86 to -1.00, p < 0.001), focal neurologic deficits (OR 7.15, 95% CI 1.60-32.14, p = 0.007), and cefepime (OR 0.58, 95% CI 0.51-0.65, p = 0.022) exposure were significantly associated with a higher risk of ASyS. A multivariable model accounting for age and sex fit best using the lowest minimum immune effector cell encephalopathy score and highest ICANS grade (R2 = 0.555, χ2 = 28.507, p < 0.001). ASyS was associated with death at the last follow-up (OR 0.48, 95% CI 0.41-0.56, p = 0.007), although short-term outcomes were not affected by ASyS. Nonprotocolized antiseizure medication (ASM) prophylaxis did not affect ASyS incidence. This study suggests a low risk of ASyS because of CAR T-cell therapy, with certain risk factors that may be predictive of ASyS and lack of a definitive and direct association of ASyS with outcomes. The current approach to ASM prophylaxis should be reconsidered when ICANS is encountered. This study is limited by its retrospective nature and the use of ASM prophylaxis in all patients with ICANS, which requires further study to assess its necessity.

PURPOSE:Cenobamate is approved for treating focal epilepsy and has potential for treating tumor-related epilepsy (TRE) based on potential anti-tumor effects, though there is little data on efficacy and safety in this patient population. METHODS:This was a retrospective, multi-center study of patients with TRE who were prescribed cenobamate as adjunctive treatment between January 2020 and November 2024 at Mayo Clinic in Florida, Minnesota, and Arizona. Drug efficacy was assessed, and factors that were predictive of response to treatment were analyzed. RESULTS:A total of 17 patients were included, with 12 being drug resistant. The median seizure frequency for the entire group before starting cenobamate treatment was 12 (IQR = 4-64) per month, and after treatment at last follow-up was 3 (IQR = 1-15) per month, with an overall 56.3% reduction. Four patients (23.5%) were seizure-free, and 7 (41.1%) patients were responders (at least 50% seizure reduction). No adverse events were reported for patients on concurrent chemotherapy. Responders had significantly fewer seizures per month compared to non-responders (5.72 ± 10.29 vs. 27.33 ± 30.17; p = .030). No clinical factors were predictive of responsiveness (or lack thereof) to cenobamate. CONCLUSIONS:This study demonstrates that adjunctive therapy with cenobamate treatment for TRE is a feasible and potentially effective option. Clinical history, including drug resistance, did not predict drug efficacy. No adverse effects were reported in those treated with chemotherapy. Further studies are needed to validate treatment response and safety.

BACKGROUND AND OBJECTIVES:Chimeric antigen receptor T-cell (CAR T-cell) therapy is associated with neurotoxicity, which may include acute symptomatic seizures (ASySs). Specific risk factors and short-term and long-term outcomes of ASyS associated with CAR T-cell therapy have not been well investigated. METHODS:This retrospective cohort study evaluated incidence and risk factors for ASyS during CAR T-cell therapy. We included patients treated at Mayo Clinic in Minnesota, Florida, and Arizona who underwent CAR T-cell therapy for hematologic malignancies from October 2019 to November 2023. Pretreatment demographics, clinical information, type of CAR T-cell therapy, neuroimaging, laboratories during treatment, and clinical features during admission were analyzed. Data on treatment and prevalence of seizures, EEG, and survival at the last follow-up were assessed. T-tests and nonparametric testing were performed on categorical and continuous data, respectively. Multivariable analysis was also performed. RESULTS:We included 180 patients (mean age 62.3 years, 57.2% women) with 8 (4.4%) developing ASyS at a mean of 8.0 ± 5.3 days after therapy. Earlier onset of cytotoxic release syndrome (odds ratio [OR] 1.81, 95% CI 0.62-2.99, p = 0.007), higher grade immune effector cell-associated neurotoxicity syndrome (ICANS) (OR -1.43, 95% CI -1.86 to -1.00, p < 0.001), focal neurologic deficits (OR 7.15, 95% CI 1.60-32.14, p = 0.007), and cefepime (OR 0.58, 95% CI 0.51-0.65, p = 0.022) exposure were significantly associated with a higher risk of ASyS. A multivariable model accounting for age and sex fit best using the lowest minimum immune effector cell encephalopathy score and highest ICANS grade (R2 = 0.555, χ2 = 28.507, p < 0.001). ASyS was associated with death at the last follow-up (OR 0.48, 95% CI 0.41-0.56, p = 0.007), although short-term outcomes were not affected by ASyS. Nonprotocolized antiseizure medication (ASM) prophylaxis did not affect ASyS incidence. DISCUSSION:This study suggests a low risk of ASyS because of CAR T-cell therapy, with certain risk factors that may be predictive of ASyS and lack of a definitive and direct association of ASyS with outcomes. The current approach to ASM prophylaxis should be reconsidered when ICANS is encountered. This study is limited by its retrospective nature and the use of ASM prophylaxis in all patients with ICANS, which requires further study to assess its necessity.

OBJECTIVE:To compare the signal detection performance of a circular grid versus a strip electrode during intraoperative electrocorticography (iECoG) for Functional Brain Mapping (FBM). METHODS:We performed a single center retrospective evaluation of signal detection by recording intraoperative ECoG comparing two intraoperative recording devices and techniques during awake craniotomy for FBM. A circular grid and linear strip evaluated stimulation artifact, afterdischarges (ADs), and epileptiform activity. RESULTS:142 patients underwent awake craniotomy, and 26 (18.3 %) had reoperations with repeat iECoG performed during their subsequent procedure. A total of 71 patients underwent iECoG using circular grids and 71 with linear strip electrodes. Max and min Signal amplitudes were higher with the circular grid (p < 0.01). The minimum (2.3 vs. 2.8 mA) and maximum (4.9 vs. 6.3 mA) currents required to evoke visible stimulation artifact were lower with the circular grid (p < 0.01), suggesting increased sensitivity to stimulation-related signals. Physiological signals represented by ADs were detected in 59.2 % of circular-grid patients vs 40.8 % of strip-electrode patients (Fisher's exact p = 0.044). When adjusting for stimulation trials in a Negative Binomial model with an offset, AD rates per stimulation were 2.5 × higher with circular grids (rate ratio 2.51; 95 % CI 1.61-3.91; p < 0.0001). Total stimulation counts were 2,786 (circular) and 2,209 (strip). Notably, the circular grid also involved more electrodes (5.06 vs. 0.95,p < 0.001). CONCLUSIONS:High-density circular grids enhance intraoperative detection of artifacts and ADs with lower stimulus currents. SIGNIFICANCE:The high-density circular grid offered more interpretable contacts and higher sensitivity.

Surgery remains a critical and often necessary intervention for a subset of patients with epilepsy. The overarching objective of surgical treatment has consistently been to enhance the quality of life for these individuals, either by achieving seizure freedom or by eliminating debilitating seizure types. This review specifically examines minimally invasive surgical approaches for epilepsy. Contemporary advancements have introduced a range of treatments that offer increased safety and efficacy compared to traditional open resective epilepsy surgeries. This manuscript provides a comprehensive review of these techniques and technologies.

Early postoperative seizures (EPS) are a common complication of brain tumor surgery. EPS can lead to hemorrhage, cerebral hypoxia, increased intracranial pressure, longer hospitalization, reduced quality of life, decreased overall survival, and increased morbidity. However, there are no formal guidelines on perioperative antiseizure medication (ASM) management in patients with tumor-related epilepsy who are deemed high risk for EPS. In this study, we describe the case of a 38-year-old man with isocitrate dehydrogenase-mutant mixed glioma and two episodes of EPS manifesting with status epilepticus during prior tumor surgeries and who presented with tumor progression. The Tumor Board recommended awake craniotomy with direct electrical stimulation (DES). The patient was administered aggressive preoperative “prophylactic” ASMs by increasing the maintenance doses of lacosamide and levetiracetam by 25% 48 h before surgery. An intravenous load of fosphenytoin (20 mg/kg) was administered in the operating room before DES, followed by a maintenance dosing of 300 mg/day for 14 days. EPS did not occur, and he was discharged home on postoperative day 4. Our case illustrates that aggressive perioperative prophylactic ASM therapy beyond the maintenance ASM regimen can be considered in patients with tumor-related epilepsy at risk of EPS.

Objective Rapid EEG devices (REDs) have demonstrated substantial benefit regarding reduced time to performance of study and diagnosis in cases where urgent EEG is needed to evaluate patients for potentially revealing nonconvulsive status epilepticus and seizures. However, urgent EEG is also important in identifying cases regarding the need for initiation of antiseizure medication as well as triaging the use of continuous EEG monitoring. Some forms of REDs have a reduced montage (RRME) with electrode derivations that are one-half of standard recordings. This could impact spatial resolution and therefore potentially limit recovery of epileptiform abnormalities. Methods In this study we evaluated the use of the Ceribell® rapid response EEG system and compared it to conventional video EEG (CvEEG). After applying inclusion and exclusion criteria, a total of 20 subjects were included in our analysis. Results RRME was highly sensitive in detecting abundant and periodic discharges (p = 0.013) as well as discharges with a broad spatial distribution on CvEEG (p = 0.039). Sensitivity for detecting less prevalent discharges or those with more restricted spatial distribution was lower. Significance Given the possibility of less frequent and more restricted epileptiform discharges eluding detection on RRME, we propose a protocol for the approach of using RRME and when to consider CvEEG when RRME is negative for epileptiform activity and highlight that urgent CvEEG may still be warranted following RRME.

Temporal lobe epilepsy is a common form of epilepsy that is often associated with hippocampal sclerosis (HS). Although HS is commonly considered a binary assessment in radiologic evaluation, it is known that histopathologic changes occur in distinct clusters. Some subtypes of HS only affect certain subfields, resulting in minimal changes to the overall volume of the hippocampus. This is likely a major reason why whole hippocampal volumetrics have underperformed versus expert readers in the diagnosis of HS. With recent advancements in MRI technology, it is now possible to characterize the substructure of the hippocampus more accurately. However, this is not consistently addressed in radiographic evaluations. The histologic subtype of HS is critical for prognosis and treatment decision-making, necessitating improved radiologic classification of HS. The International League Against Epilepsy (ILAE) has issued a consensus classification scheme for subtyping HS histopathologic changes. This review aims to explore how the ILAE subtypes of HS correlate with radiographic findings, introduce a grading system that integrates radiologic and pathologic reporting in HS, and outline an approach to detecting HS subtypes by using MRI. This framework will not only benefit current clinical evaluations, but also enhance future studies involving high-resolution MRI in temporal lobe epilepsy.

PURPOSE:Awake craniotomy (AC) is a procedure often performed concomitantly with direct electrical cortical stimulation (DES) and electrocorticography (ECoG) during functional brain mapping. Patients undergoing AC are at risk of acute symptomatic seizures, including intraoperative (IS) and early postoperative seizures (EPS) which can lead to higher risk of morbidity. Predicting those who are at risk of IS and EPS could alert clinicians and provide the ability to closely monitor and consider management changes in the acute setting to prevent seizures. MATERIALS AND METHODS:This is a narrative review of previous studies on IS and EPS during awake craniotomy, including a summary of studies from our center using a novel circular grid electrode. RESULTS AND CONCLUSIONS:There are a number of clinical features with variable association with a higher risk of EPS and IS. Surgeries involving the anterior and central head regions are a risk factor for IS. EPS is more likely to occur in patients with perioperative intracranial hemorrhage. Improving grid/electrode technology for ECoG can allow for better sensitivity of detecting epileptiform activity which can help to diagnose and predict perioperative seizures.

Cefepime is a fourth-generation cephalosporin that is widely used to treat sepsis but is associated with a potentially dangerous neurotoxicity syndrome, cefepime-induced neurotoxicity (CIN). As a result, patients treated with cefepime may be at higher risk for morbidity, including seizures, and mortality. Though the recent ACORN trial concluded that cefepime does not increase the risk of mortality, most of these patients were not critically ill or elderly, two of the most at risk populations for CIN. Further, diagnosis may be difficult in the critical care setting as patients may have multiple reasons for encephalopathy. Therefore, this population in particular should be studied and monitored closely for CIN. Importantly, there are not well defined diagnostic criteria for CIN to guide evaluation and management. Defining the risk factors for CIN and using laboratory and EEG to help support the clinical diagnosis could be helpful in early recognition of CIN to help institute treatment and to rule out seizures. In this mini review, we highlight risk factors for CIN, discuss the possible value of EEG, and propose a diagnostic and management approach in the evaluation and management of CIN.

Pupillary changes can be an important semiologic feature in focal epilepsy. Though the subcortical networks involving pupillomotor function have been described, cortical generators of pupillary dilation and constriction in humans are not well known. In this report, we describe a case of pupillary constriction occurring during seizures in a patient with drug resistant focal epilepsy. On stereoelectroencephalography, onset was noted within the posterior segment of the right intraparietal sulcus and direct cortical electrical stimulation of these electrode contacts reproduced pupillary constriction associated with habitual seizures. This is the first case report to describe ictal pupillary constriction during SEEG with confirmation of the cortical localization by direct cortical electrical stimulation. The posterior segment of the right intraparietal sulcus localization of pupillary constriction may aid in surgical evaluation patients with drug resistant focal epilepsy.

3D-Edge Enhancing Gradient Echo MRI (EDGE) is a promising method for identifying focal cortical dysplasia (FCD) because of its superior contrast-to-noise ratio. Gains in signal-to-noise ratio (SNR) and spatial resolution using 7T MRI should further enhance the utility of EDGE; however, the exquisite sensitivity to the optimal inversion time makes translation to 7T challenging given the extreme nonuniformities in the transmit field (B1+). By utilizing a combined MP2RAGE-EDGE sequence, the efficiency of the acquisition can be optimized to improve B1+ transmit uniformity and SNR. Using this approach, we report the first experience of using 7T EDGE MRI for the diagnosis of FCD in epilepsy, showing the feasibility of achieving high spatial resolution, SNR, and image contrast uniformity. EDGE-MP2RAGE sequence improves the detection of gray-white matter junction abnormalities associated with FCD and is a valuable, time-efficient addition to a 7T MR protocol in patients with focal epilepsy.

BACKGROUND AND PURPOSE:Cerebral amyloid angiopathy (CAA) is a common cause of intracranial hemorrhage (ICH), which is a risk factor for seizures. The incidence and risk factors of seizures associated with a heterogeneous cohort of CAA patients have not been studied.METHODS:We conducted a retrospective study of patients with CAA treated at Mayo Clinic Florida between 1 January 2015 and 1 January 2021. CAA was defined using the modified Boston criteria version 2.0. We analyzed electrophysiological and clinical features, and comorbidities including lobar ICH, nontraumatic cortical/convexity subarachnoid hemorrhage (cSAH), superficial siderosis, and inflammation (CAA with inflammation [CAA-ri]). Cognition and mortality were secondary outcomes. Univariate and multivariate analyses were performed to determine risk of seizures relative to clinical presentation.RESULTS:Two hundred eighty-four patients with CAA were identified, with median follow-up of 35.7 months (interquartile range = 13.5-61.3 months). Fifty-six patients (19.7%) had seizures; in 21 (37.5%) patients, seizures were the index feature leading to CAA diagnosis. Seizures were more frequent in females (p = 0.032) and patients with lobar ICH (p = 0.002), cSAH (p = 0.030), superficial siderosis (p < 0.001), and CAA-ri (p = 0.005), and less common in patients with microhemorrhage (p = 0.006). After controlling for age and sex, lobar ICH (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.1-4.2), CAA-ri (OR = 3.8, 95% CI = 1.4-10.3), and superficial siderosis (OR = 3.7, 95% CI = 1.9-7.0) were independently associated with higher odds of incident seizures.CONCLUSIONS:Seizures are common in patients with CAA and are independently associated with lobar ICH, CAA-ri, and superficial siderosis. Our results may be applied to optimize clinical monitoring and management for patients with CAA.