Case report: Insulinoma masquerades as epilepsy - quantitative EEG analysis.

Insulinomas are rare gastrointestinal tumors with an incidence of 1-3 per million inhabitants annually. These tumors result in excessive insulin production, culminating in hypoglycemia. Such hypoglycemia triggers various central nervous system (CNS) manifestations, including headache, confusion, abnormal behavior, and epileptic seizures, which can lead to misdiagnosis as epilepsy. This case report documents a 46-year-old male who presented seizure-like episodes. Episodes occurred mainly during the night, lasting several minutes to hours. Initial seizures were characterized by bizarre behavior and altered responsiveness. Over time, seizure frequency, complexity, and severity escalated. We managed to record two episodes during long-term EEG and report, as the first ones, the detailed quantitative EEG analysis of these hypoglycemia-related events. EEG changes preceded the development of clear-cut pathological motor activity in tens of minutes and were present in all investigated frequency bands. The development of profound motor activity was associated with other increases in EEG power spectra in all frequencies except for delta. The most pronounced changes were found over the left temporal region, which can be the most susceptible to hypoglycemia. In our patient, the seizure-like episodes completely disappeared after the insulinoma removal, which demonstrates their relationship to hypoglycemia.

Low prevalence of neural autoantibodies in perioperative cerebrospinal fluid samples of epilepsy surgery patients: A multicenter prospective study.

OBJECTIVE: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses. METHODS: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed. RESULTS: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]). Five patients' samples displayed CSF-restricted oligoclonal bands (OCBs; 6.6%): three cases with FCD (one with FCD II and two with FCD I), one with HS, and one with negative histology. Importantly, eight patients (one of them with CSF-restricted OCBs) had findings on antibody testing in individual serum and/or CSF tests that could not be confirmed by complementary tests and were thus classified as nonspecific, yet could have been considered specific without confirmatory testing. Of these, two had FCD, two gliosis, and four HS. No inflammatory changes or lymphocyte cuffing was observed histopathologically in any of the 76 patients. SIGNIFICANCE: Neural autoantibodies are a rare finding in perioperatively collected serum and CSF of our cohort of mostly MRI-lesional epilepsy surgery patients. Confirmatory testing is essential to avoid overinterpretation of autoantibody-positive findings.

Interictal high-frequency oscillations, spikes, and connectivity profiles: A fingerprint of epileptogenic brain pathologies.

OBJECTIVE: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for preresective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies. METHODS: Interictal awake stereoelectroencephalographic recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs. RESULTS: Statistically significant differences were found between the individual pathologies in HFO rates, spikes, and their characteristics, together with functional connectivity measures, with the highest values in the case of HS and NG/NT. A model to predict brain pathology based on all interictal measures achieved up to 84.0% prediction accuracy. SIGNIFICANCE: The electrophysiological profile of the various epileptogenic lesions in epilepsy surgery patients was analyzed. Based on this profile, a predictive model was developed. This model offers excellent potential to identify the nature of the underlying lesion prior to resection. If validated, this model may be particularly valuable for counseling patients, as depending on the lesion type, different outcomes are achieved after epilepsy surgery.

Twenty-five years of epilepsy surgery at a Central European comprehensive epilepsy center-Trends in intervention delay and outcomes.

OBJECTIVE: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy. METHODS: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center. RESULTS: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001). Correspondingly, extratemporal resections have become more frequent with a significant increase in surgeries for focal cortical dysplasia (2%-8%-19%, P < 0.001). For resections, better outcomes (ILAE scores 1a-2) have been achieved in extratemporal lesional (0%-21%-61%, P = 0.01, at least 2-year follow-up) patients. In temporal lesional patients, outcomes remained unchanged (at least 77% success rate). A longer duration of epilepsy predicted a less favorable outcome for resective procedures (P = 0.024) in patients with disease duration of less than 25 years. SIGNIFICANCE: The spectrum of epilepsy surgery is shifting toward nonlesional and extratemporal cases. While success rates of extratemporal resections at our center are getting better, the average duration of epilepsy before surgical intervention is still very long and is not improving. This underscores the need for stronger collaboration between epileptologists and outpatient neurologists to ensure prompt and effective treatment for patients with drug-resistant epilepsy.

White matter alterations in MR-negative temporal and frontal lobe epilepsy using fixel-based analysis.

This study focuses on white matter alterations in pharmacoresistant epilepsy patients with no visible lesions in the temporal and frontal lobes on clinical MRI (i.e. MR-negative) with lesions confirmed by resective surgery. The aim of the study was to extend the knowledge about group-specific neuropathology in MR-negative epilepsy. We used the fixel-based analysis (FBA) that overcomes the limitations of traditional diffusion tensor image analysis, mainly within-voxel averaging of multiple crossing fibres. Group-wise comparisons of fixel parameters between healthy controls (N = 100) and: (1) frontal lobe epilepsy (FLE) patients (N = 9); (2) temporal lobe epilepsy (TLE) patients (N = 13) were performed. A significant decrease of the cross-section area of the fixels in the superior longitudinal fasciculus was observed in the FLE. Results in TLE reflected widespread atrophy of limbic, thalamic, and cortico-striatal connections and tracts directly connected to the temporal lobe (such as the anterior commissure, inferior fronto-occipital fasciculus, uncinate fasciculus, splenium of corpus callosum, and cingulum bundle). Alterations were also observed in extratemporal connections (brainstem connection, commissural fibres, and parts of the superior longitudinal fasciculus). To our knowledge, this is the first study to use an advanced FBA method not only on the datasets of MR-negative TLE patients, but also MR-negative FLE patients, uncovering new common tract-specific alterations on the group level.

Prediction of Vagal Nerve Stimulation Efficacy in Drug-Resistant Epilepsy (PRECISE): Prospective Study for Pre-implantation Prediction/Study Design.

Background: Vagal nerve stimulation (VNS) can be indicated in patients with drug-resistant epilepsy, who are not eligible for resective epilepsy surgery. In VNS therapy, the responder rate (i.e., percentage of subjects experiencing ≥50% seizure reduction) is ~50%. At the moment, there is no widely-accepted possibility to predict VNS efficacy in a particular patient based on pre-implantation data, which can lead to unnecessary surgery and improper allocation of financial resources. The principal aim of PRediction of vagal nerve stimulation EfficaCy In drug-reSistant Epilepsy (PRECISE) study is to verify the predictability of VNS efficacy by analysis of pre-implantation routine electroencephalogram (EEG). Methods: PRECISE is designed as a prospective multicentric study in which patients indicated to VNS therapy will be recruited. Patients will be classified as predicted responders vs. predicted non-responders using pre-implantation EEG analyses. After the first and second year of the study, the real-life outcome (responder vs. non-responder) will be determined. The real-life outcome and predicted outcome will be compared in terms of accuracy, specificity, and sensitivity. In the meantime, the patients will be managed according to the best clinical practice to obtain the best therapeutic response. The primary endpoint will be the accuracy of the statistical model for prediction of response to VNS therapy in terms of responders and non-responders. The secondary endpoint will be the quantification of differences in EEG power spectra (Relative Mean Power, %) between real-life responders and real-life non-responders to VNS therapy in drug-resistant epilepsy and the sensitivity and specificity of the model. Discussion: PRECISE relies on the results of our previous work, through which we developed a statistical classifier for VNS response (responders vs. non-responders) based on differences in EEG power spectra dynamics (Pre-X-Stim). Trial Registration: www.ClinicalTrials.gov, identifier: NCT04935567.

Development and Validation of the 5-SENSE Score to Predict Focality of the Seizure-Onset Zone as Assessed by Stereoelectroencephalography.

Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified. Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated. Design, Setting, and Participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021. Main Outcomes and Measures: Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample. Results: A total of 128 patients (57 women [44.5%]; median [range] age, 31 [13-58] years) were analyzed for score development and 207 patients (97 women [46.9%]; median [range] age, 32 [16-70] years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity. Conclusions and Relevance: High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

Pregnancy Outcomes in Refractory Epilepsy Patients with Vagus Nerve Stimulation: Long-Term Single-Center Experience.

BACKGROUND AND STUDY AIMS: Vagus nerve stimulation (VNS) has been employed worldwide as an adjunctive therapy in drug-resistant epilepsy patients. However, the mechanisms of VNS action potentially increase the risk of obstetric complications. The study presents the long-term single-center experience with pregnancies and childbirth in women with VNS for refractory epilepsy based on prospectively collected epileptologic data and a retrospective analysis of pregnancy, childbirth, and data about long-term child development. MATERIAL AND METHODS: From a group of patients with VNS implanted for refractory epilepsy between October 1999 and January 2018, all the women of childbearing age (younger than 40 years) were identified. After checking their hospital records for data about any pregnancies, the women with confirmed childbirth during active VNS stimulation and their general practitioners were interviewed based on a prepared questionnaire regarding their gynecologic history, the course of pregnancy and childbirth, gestational week, birth weight and length, any congenital anomalies of the child, and the child's psychomotor development, school performance, and somatic health problems. RESULTS: From the group of 257 patients implanted with VNS for refractory epilepsy, 4 women (1.5%) became pregnant and gave birth (all on polypharmacotherapy). The mean interval from VNS implantation to birth was 44.3 months. Slight seizure worsening during the last trimester was reported in one woman. In one patient, acute caesarean section was required due to placental separation. Planned birth induction and caesarean section were used in the other two women because of their seizure disorder. No malfunction of the stimulation system was detected during pregnancy or after birth. No congenital malformations were observed. The two children who were of school age at the time of this study require special schooling. CONCLUSIONS: The study results confirmed a high rate of obstetric interventions in patients with VNS. Although no teratogenic effect of VNS has been proven, the higher incidence of children exposed to VNS needing special education requires attention.

Automated fusion of multimodal imaging data for identifying epileptogenic lesions in patients with inconclusive magnetic resonance imaging.

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand-alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR-negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel-wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue. We found a subset of two classes specific to tissue located in resected areas. The average classification accuracy (i.e., the probability of correct classification) was significantly higher than the level of chance in the training group (0.73) and even better in the validation surgery subgroup (0.82). Nuclear imaging, diffusion-weighted imaging, and source localization of interictal epileptic discharges were the strongest methods for classification accuracy. We showed that the automatic fusion of results can identify brain areas that show epileptogenic gray matter tissue features. The method might enhance the presurgical evaluations of MR-negative epilepsy patients.

Arterial Spin Labeling is a Useful MRI Method for Presurgical Evaluation in MRI-Negative Focal Epilepsy.

Arterial spin labeling (ASL) is an MRI technique measuring brain perfusion using magnetically labeled blood as a tracer. The clinical utility of ASL for presurgical evaluation in non-lesional epilepsy as compared with the quantitative analysis of interictal [18F] fluorodeoxyglucose PET (FDG-PET) was studied. In 10 patients (4 female; median age 29 years) who underwent a complete presurgical evaluation followed by surgical resection, the presurgical FDG-PET and ASL scans were compared with the resection masks using asymmetry index (AI) maps. The positive predictive value (PPV) and sensitivity (SEN), were calculated from the number of voxels inside the mask (true positive), and outside the mask (false positive). The comparison of the PPVs showed better PPV in 6 patients using ASL and in 2 patients with PET. SEN was better in 4 patients using ASL and in 5 patients with PET. According to the Wilcoxon signed rank test for PPV (p = 0.74) and for SEN (p = 0.43), these methods have similar predictive power. ASL is a useful method for presurgical evaluation in non-lesional epilepsy. The main benefits of ASL over PET are that it avoids radiation exposure for patients, and it offers lower costs, higher availability, and better time efficiency.

Single-center long-term results of vagus nerve stimulation for epilepsy: A 10-17 year follow-up study.

PURPOSE: The paper presents a long-term follow-up study of VNS patients, analyzing seizure outcome, medication changes, and surgical problems. METHOD: 74 adults with VNS for 10 to 17 years were evaluated yearly as: non-responder - NR (seizure frequency reduction <50%), responder - R (reduction ≥ 50% and <90%), and 90% responder - 90R (reduction ≥ 90%). Delayed R or 90R (≥ 4 years after surgery), patients with antiepileptic medication changes and battery or complete system replacement were identified. Statistical analysis of potential outcome predictors (age, seizure duration, MRI, seizure type) was performed. RESULTS: The rates of R and 90R related to the patients with outcome data available for the study years 1, 2, 10, and 17 were for R 38.4%, 51.4%, 63.6%, and 77.8%, and for 90R 1.4%, 5.6%, 15.1%, and 11.1%. The absolute numbers of R and 90R increased until years 2 and 6. Antiepileptic therapy was changed in 62 patients (87.9%). There were 11 delayed R and four delayed 90R, with medication changes in the majority. At least one battery replacement was performed in 51 patients (68.9%), 49 of whom R or 90R. VNS system was completely replaced in 7 patients (9.5%) and explanted in 7 NR (9.5%). No significant predictor of VNS outcome was found. CONCLUSIONS: After an initial increase, the rate of R and 90R remains stable in long-term follow-up. The changes of antiepileptic treatment in most patients potentially influence the outcome. Battery replacements or malfunctioning system exchange reflect the patient's satisfaction and correlate with good outcomes.

Older Age and Longer Epilepsy Duration Do Not Predict Worse Seizure Reduction Outcome after Vagus Nerve Stimulation.

INTRODUCTION: We analyzed the results of vagus nerve stimulation (VNS) on older patients and patients with long-lasting epilepsy and included severely intellectually disabled patients. PATIENTS AND METHODS: A total of 103 adults with VNS implanted from 2005 to 2014 were studied. The responder rates, that is, the percentage of VNS patients who responded to VNS, classified as seizure reduction ≥ 50% (50R) and seizure reduction ≥ 90% (90R), were compared in defined age groups (< 40 and ≥ 40 years, and < 50 and ≥ 50 years) and epilepsy duration groups (< 20 and ≥ 20 years, < 30 and ≥ 30 years, and < 40 and ≥ 40 years) at the 1-year follow-up visit and the last follow-up visit (at least 2 years after surgery). The age distributions and responder rates were also studied in patients with an intellectual disability. RESULTS: The analysis did not confirm a significantly lower 50R or 90R rate in patients ≥ 40, ≥ 50, or ≥ 60 years when compared with their younger counterparts, but the 50R rate increase during follow-up care was the lowest in patients ≥ 50 and ≥ 60 years. The highest percentage of patients with an intellectual disability in the group < 40 years of age did not adversely affect the 50R rate. Longer epilepsy duration was not confirmed as a negative predictor of VNS outcome. There was a significantly higher 50R rate in patients with epilepsy duration ≥ 20 years (at the last follow-up visit) and a higher 90R rate in patients with epilepsy duration ≥ 30 years (at the 1-year follow-up visit). The increase in the 50R rate during follow-up care was lower in patients with epilepsy durations ≥ 30 and ≥ 40 years. CONCLUSIONS: The study did not find worse VNS outcomes, as defined by the 50R or 90R rate, in older adult patients or in patients with a longer epilepsy duration. The increasing stimulation effect over time is less marked in older patients and in patients with longer epilepsy duration.

Temporal lobe epilepsy? Things are not always what they seem.

Temporal lobe epilepsy is the most frequent form of drug-resistant epilepsy referred to epilepsy surgery centres. The vast majority of lesional cases can be operated on without invasive investigation which is often not the case for non-lesional cases. Invasive investigation in non-lesional cases, however, may lead to unexpected results, as illustrated in the following case report. [Published with video sequence on www.epilepticdisorders.com].

Effect of partial drug withdrawal on the lateralization of interictal epileptiform discharges and its relationship to surgical outcome in patients with hippocampal sclerosis.

OBJECTIVE: To assess changes in the relative lateralization of interictal epileptiform discharges (IEDs) and interictal EEG prognostic value in terms of surgical outcome between periods with full medication (FMP) and reduced medication (RMP) in patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS). METHODS: Interictal scalp EEGs of 43 patients were evaluated for the presence of IEDs separately in a waking state (WS) and sleeping state (SS) during FMP and RMP. In each period, patients were categorized as having unitemporal or bitemporal IEDs. Surgical outcome was classified at year 1 after surgery and at last follow-up visit as Engel I or Engel II-IV; and alternatively as completely seizure-free or not seizure-free. RESULTS: There were significant changes in relative IED lateralization between FMP and RMP during SS. The representation of patients with unitemporal IEDs declined from 37 (86%) in FMP during SS to 25 (58%) in RMP during SS (p=0.003). At year 1 after surgery, the relative IED lateralization is a predictive factor for surgical outcome defined as Engel I vs. Engel II-IV in both FMP during WS (p=0.037) and during SS (p=0.007), and for surgical outcome defined as completely seizure-free vs. not seizure-free in FMP during SS (p=0.042). At last follow up visit, the relative IED lateralization is a predictor for outcome defined as Engel I vs. Engel II-IV in FMP during SS (p=0.020), and for outcome defined as completely seizure-free vs. not seizure-free in both FMP during WS (p=0.043) and in FMP during SS (p=0.015). When stepwise logistic regression analysis was applied, only FMP during SS was found to be an independent predictor for surgical outcome at year 1 after surgery (completely seizure-free vs. not seizure-free p=0.032, Engel I vs. Engel II-IV p=0.006) and at last follow-up visit (completely seizure-free vs. not seizure-free p=0.024, Engel I vs. Engel II-IV p=0.017). Gender was found to be independent predictor for surgical efficacy at year 1 if the outcome was defined as completely seizure-free vs. not seizure-free (p=0.036). CONCLUSION: The predictive value of relative IED lateralization with respect to surgical outcome in interictal EEG is present only during FMP; the predictive value decreases with the reduction of AEDs caused by the change of relative IED lateralization.

Syncope with atypical trunk convulsions in a patient with malignant arrhythmia.

Syncope is a condition often misdiagnosed as epilepsy. Syncope caused by cardiac disturbance is a life-threatening condition and accurate diagnosis is crucial for patient outcome. We present a case study of a 71-year-old woman who was referred to our epilepsy centre with a diagnosis of refractory epilepsy. We diagnosed convulsive syncope caused by malignant cardiac arrhythmia based on the presence of cardiac asystole lasting for 20-30 seconds, which was caused by sick sinus syndrome combined with third-degree atrioventricular block. The most prominent feature of this syncope was atypical trunk (abdominal or thoracoabdominal) convulsions, which were accompanied by other motor signs (head and eye deviation and brief jerks of the extremities). In the periods between attacks, all investigations, including standard 12-lead ECG and 24-hour ECG monitoring, were normal. This case study highlights the challenge in differential diagnosis of sudden loss of consciousness. [Published with video sequences].

Intracranial EEG seizure onset patterns in unilateral temporal lobe epilepsy and their relationship to other variables.

OBJECTIVE: We performed a retrospective study to determine the different types of seizure onset patterns (SOP) in invasive EEG (IEEG) in patients with temporal lobe epilepsy (TLE). METHODS: We analyzed a group of 51 patients (158 seizures) with TLE who underwent IEEG. We analyzed the dominant frequency during the first 3s after the onset of ictal activity. The cut-off value for distinguishing between fast and slow frequencies was 8 Hz. We defined three types of SOPs: (1) fast ictal activity (FIA) - frequency ≥8 Hz; (2) slow ictal activity (SIA) - frequency <8 Hz; and (3) attenuation of background activity (AT) - no clear-cut rhythmic activity during the first 3s associated with changes of IEEG signal (increase of frequency, decrease of amplitude). We tried to find the relationship between different SOP types and surgery outcome, histopathological findings, and SOZ localization. RESULTS: The most frequent SOP was FIA, which was present in 67% of patients. More patients with FIA were classified postoperatively as Engel I than those with SIA and AT (85% vs. 31% vs. 0) (P < 0.001). There were no statistically significant differences in the type of SOP, in the histopathological findings, or in the SOZ localization. CONCLUSION: In patients with refractory TLE, seizure onset frequencies ≥8 Hz during the first 3s of ictal activity are associated with a better surgical outcome than frequencies <8 Hz. SIGNIFICANCE: Our study suggests that very early seizure onset frequencies in IEEG in patients with TLE could be the independent predictive factor for their outcome, regardless of the localization and etiology.