Combined neuromodulation and resection for functional cortex epilepsy: a case series.

OBJECTIVE: Medically refractory epilepsy (MRE) often requires resection of the seizure onset zone (SOZ) for effective treatment. However, when the SOZ is in functional cortex (FC), achieving complete and safe resection becomes difficult, due to the seizure network overlap with function. The authors aimed to assess the safety and outcomes of a combined approach involving partial resection combined with focal neuromodulation for FC refractory epilepsy. METHODS: The authors performed a retrospective analysis of individuals diagnosed with MRE who underwent surgical intervention from January 2015 to December 2022. Patients whose SOZ was located in FC and were treated with resection combined with simultaneous implantation of a focal neuromodulation device (responsive neurostimulation [RNS] device) with more than 12 months of follow-up data were included. All patients underwent a standard epilepsy preoperative assessment including intracranial electroencephalography and extraoperative stimulation mapping. Resections were performed under general anesthesia, followed by the concurrent implantation of an RNS device. RESULTS: Seven patients (4 males, median age 32.3 years, all right-handed) were included. The median interval from seizure onset to surgery was 17.4 years. The epileptogenic network included sensorimotor areas (cases 2, 3, and 6), visual cortex (case 1), language areas (cases 4 and 7), and the insula (case 5). The median follow-up was 3 years (range 1-5.8 years). No significant changes in neuropsychological tests were reported. One permanent nondisabling planned neurological deficit (left inferior quadrantanopia) was observed. Six patients had stimulation activated at a median of 4.7 months after resection. All patients achieved good seizure outcomes (5 with Engel class I and 2 with Engel class II outcomes). CONCLUSIONS: Maximal safe resection combined with focal neuromodulation presents a promising alternative to stand-alone resections for MRE epileptogenic zones overlapping with functional brain. This combined approach prioritizes the preservation of function while improving seizure outcomes.

Systematic 1 Hz direct electrical stimulation for seizure induction: A reliable method for localizing seizure onset zone and predicting seizure freedom.

OBJECTIVE: To prospectively investigate the utility of seizure induction using systematic 1 Hz stimulation by exploring its concordance with the spontaneous seizure onset zone (SOZ) and relation to surgical outcome; comparison with seizures induced by non-systematic 50 Hz stimulation was attempted as well. METHODS: Prospective cohort study from 2018 to 2021 with ≥ 1 y post-surgery follow up at Yale New Haven Hospital. With 1 Hz, all or most of the gray matter contacts were stimulated at 1, 5, and 10 mA for 30-60s. With 50 Hz, selected gray matter contacts outside of the medial temporal regions were stimulated at 1-5 mA for 0.5-3s. Stimulation was bipolar, biphasic with 0.3 ms pulse width. The Yale Brain Atlas was used for data visualization. Variables were analyzed using Fisher's exact, χ2, or Mann-Whitney test. RESULTS: Forty-one consecutive patients with refractory epilepsy undergoing intracranial EEG for localization of SOZ were included. Fifty-six percent (23/41) of patients undergoing 1 Hz stimulation had seizures induced, 83% (19/23) habitual (clinically and electrographically). Eighty two percent (23/28) of patients undergoing 50 Hz stimulation had seizures, 65% (15/23) habitual. Stimulation of medial temporal or insular regions with 1 Hz was more likely to induce seizures compared to other regions [15/32 (47%) vs. 2/41 (5%), p < 0.001]. Sixteen patients underwent resection; 11/16 were seizure free at one year and all 11 had habitual seizures induced by 1 Hz; 5/16 were not seizure free at one year and none of those 5 had seizures with 1 Hz (11/11 vs 0/5, p < 0.0001). No patients had convulsions with 1 Hz stimulation, but four did with 50 Hz (0/41 vs. 4/28, p = 0.02). SIGNIFICANCE: Induction of habitual seizures with 1 Hz stimulation can reliably identify the SOZ, correlates with excellent surgical outcome if that area is resected, and may be superior (and safer) than 50 Hz for this purpose. However, seizure induction with 1 Hz was infrequent outside of the medial temporal and insular regions in this study.

Characteristics and Attendance of Patients Eligible for the PASS Clinic: A Transition of Care Model After Acute Symptomatic Seizures.

Background and Objectives: Most acute symptomatic seizure (ASyS) patients stay on antiseizure medications (ASM) long-term, despite low epilepsy development risk. The Post-Acute Symptomatic Seizure (PASS) clinic is a transition of care model for ASyS patients who individualize ASM management with the goal of a safe deprescription. We evaluated patients discharged on ASMs after a witnessed or suspected ASyS to analyze their PASS clinic visit attendance and its predictors. Methods: A single-center, retrospective cohort study of adults without epilepsy who were discharged from January 1, 2019, to September 30, 2019, on first-time ASMs due to witnessed or suspected ASyS (PASS clinic-eligible). We fit a cause-specific Cox proportional hazards model to analyze factors associated with PASS clinic attendance, which depends on survival in this patient population that has a high early postdischarge mortality (a competing risk). We checked for multicollinearity and the assumption of proportional hazards. Results: Among 307 PASS clinic-eligible patients, 95 (30.9%) attended the clinic and 136 (44.3%) died during a median follow-up of 14 months (interquartile range = 2-34). ASyS occurred in 60.2% (convulsive 47%; electrographic 26.7%) of patients. ASMs were continued in the absence of ASyS or epileptiform abnormalities (EAs) in 27% of patients. Multivariable analysis revealed that the presence of EAs (HR = 1.69, 95% CI 1.10-2.59), PASS clinic appointments provided before discharge (HR = 3.39, 95% CI 2.15-5.33), and less frequently noted ASyS etiologies such as autoimmune encephalitis (HR = 2.03, 95% CI 1.07-3.86) were associated with an increased clinic attendance rate. Medicare/Medicaid insurance (HR = 0.43, 95% CI 0.24-0.78, p = 0.005) and the presence of progressive brain injury (i.e., tumors; HR = 0.55, 95% CI 0.32-0.95, p = 0.032) were associated with reduced rate of PASS clinic attendance. Discussion: Our real-world data highlight the need for appropriate postdischarge follow-up of ASyS patients, which can be fulfilled by the PASS clinic model. Modest PASS clinic attendance can be significantly improved by adhering to a structured discharge planning process whereby appointments are provided before discharge. Future research comparing patient outcomes, specifically safe ASM discontinuation in a PASS clinic model to routine clinical care, is needed.

Transfrontal Approach to the Amygdala for Ablation With Laser Interstitial Thermal Therapy: An Epilepsy Case Report.

BACKGROUND AND IMPORTANCE: Stereotactic laser amygdalohippocampotomy (SLAH) using laser interstitial thermal therapy is a minimally invasive surgery used to treat mesial temporal lobe epilepsy. It uses laser probes inserted through occipital and temporo-occipital trajectories to ablate the hippocampus and amygdala. However, these trajectories are limited in their ability to ablate the superior amygdala and entorhinal cortex (ERC). We present a trajectory through the middle frontal gyrus as an alternative to the temporo-occipital trajectory, which provides more complete ablation of the amygdala and anterior ERC through a single pass. CLINICAL PRESENTATION: A 70-year-old woman with seizures characterized by fear were localized to the left superomedial amygdala on intracranial electroencephalography. They developed after resection of a left temporal arteriovenous malformation and were refractory to medication. Her age and prior craniotomy made open resection less desirable. A frontal and occipital SLAH achieved Engel 1a at 1-year follow-up without decline in neuropsychological performance scores. CONCLUSION: Typical SLAH uses trajectories that have limited ability to ablate the superior and medial amygdala and ERC in a single passage. A combined approach using an occipital and frontal trajectory allows more complete ablation of the amygdala, hippocampus, and ERC.

Factors Predicting Outcome After Intracranial EEG Evaluation in Patients With Medically Refractory Epilepsy.

BACKGROUND AND OBJECTIVES: The aim of this study was to identify predictors of a resective surgery and subsequent seizure freedom following intracranial EEG (ICEEG) for seizure-onset localization. METHODS: This is a retrospective chart review of 178 consecutive patients with medically refractory epilepsy who underwent ICEEG monitoring from 2002 to 2015. Univariable and multivariable regression analysis identified independent predictors of resection vs other options. Stepwise Akaike information criteria with the aid of clinical consideration were used to select the best multivariable model for predicting resection and outcome. Discrete time survival analysis was used to analyze the factors predicting seizure-free outcome. Cumulative probability of seizure freedom was analyzed using Kaplan-Meier curves and compared between resection and nonresection groups. Additional univariate analysis was performed on 8 select clinical scenarios commonly encountered during epilepsy surgical evaluations. RESULTS: Multivariable analysis identified the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant as independent predictors of resection (p < 0.0001, area under the receiver operating characteristic curve 0.80, 95% CI 0.73-0.87). Focal ICEEG onset and undergoing a resective surgery predicted absolute seizure freedom at the 5-year follow-up. Patients who underwent resective surgery were more likely to be seizure-free at 5 years compared with continued medical treatment or neuromodulation (60% vs 7%; p < 0.0001, hazard ratio 0.16, 95% CI 0.09-0.28). Even patients thought to have unfavorable predictors (nonlesional MRI or extratemporal lobe hypothesis or dominant hemisphere implant) had ≥50% chance of seizure freedom at 5 years if they underwent resection. DISCUSSION: Unfavorable predictors, including having nonlesional extratemporal epilepsy, should not deter a thorough presurgical evaluation, including with invasive recordings in many cases. Resective surgery without functional impairment offers the best chance for sustained seizure freedom and should always be considered first. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant are independent predictors of resection. Focal ICEEG onset and undergoing resection are independent predictors of 5-year seizure freedom.

Acute epileptiform abnormalities are the primary predictors of post-stroke epilepsy: a matched, case-control study.

Stroke patients who underwent continuous EEG (cEEG) monitoring within 7 days of presentation and developed post-stroke epilepsy (PSE; cases, n = 36) were matched (1:2 ratio) by age and follow-up duration with ones who did not (controls, n = 72). Variables significant on univariable analysis [hypertension, smoking, hemorrhagic conversion, pre-cEEG convulsive seizures, and epileptiform abnormalities (EAs)] were included in the multivariable logistic model and only the presence of EAs on EEG remained significant PSE predictor [OR = 11.9 (1.75-491.6)]. With acute EAs independently predicting PSE development, accounting for their presence may help to tailor post-acute symptomatic seizure management and aid anti-epileptogenesis therapy trials.

Electrical cortical stimulation can impair production of the alphabet without impairing counting.

Neurosurgery has the potential to cure patients with drug-resistant focal epilepsy, but carries the risk of permanent language impairment when surgery involves the dominant hemisphere of the brain. This risk can be estimated and minimized using electrical stimulation mapping (ESM), which uses cognitive and linguistic tasks during cortical ESM to differentiate "eloquent" and "resectable" areas in the brain. One such task, counting, is often used to screen and characterize language during ESM in patients whose language abilities are limited. Here we report a patient with drug-resistant epilepsy arising from the language-dominant hemisphere using fMRI. Our patient experienced loss of the ability to recite or write the alphabet, but not to count, during ESM of the dominant left posterior superior temporal gyrus. This selective impairment extended to both spoken and written production. We suggest the need for caution when using counting as a sole means to screen language function and as a method of testing low functioning patients using ESM.