Trends in presurgical diagnostics and surgical treatment of epilepsy

Cloppenborg T, Bien C. Trends in der prächirurgischen Diagnostik und der operativen Epilepsiebehandlung. Clinical Epileptology . 2023;36(2):85-90.This article presents the major trends in epilepsy surgery based on experiences at the Bethel Epilepsy Center. In addition, the frequencies and influencing factors on freedom from seizures of nonlesional patients in epilepsy surgery series are discussed.Trends in der Epilepsiechirurgie werden anhand der Erfahrungen des Epilepsiezentrums Bethel zusammenfassend dargestellt. Zudem werden Häufigkeiten und Einflussfaktoren auf Anfallsfreiheit nonläsioneller Patienten in epilepsiechirurgischen Serien diskutiert

Reading and the visual word form area (VWFA)-Management and clinical experience at one epilepsy surgery center

Cloppenborg T, Mertens M, Hopf J, et al. Reading and the visual word form area (VWFA)-Management and clinical experience at one epilepsy surgery center. Epilepsy & Behavior. 2021;124: 108274.Objective: Presurgical evaluation has no established routine to assess reading competence and to identify essential "not to resect" reading areas. Functional models describe a visual word form area (VWFA) located in the midfusiform gyrus in the dominant ventral occipito-temporal cortex (vOTC) as essential for reading. We demonstrate the relevance and feasibility of invasive VWFA-mapping. Methods: Four patients with epilepsy received invasive VWFA-mapping via left temporo-basal strip electrodes. Co-registration of the results and additional data from the literature led to the definition of a region of interest (ROI) for a retrospective assessment of postoperative reading deficits by a standardized telephone-interview in patients with resections in this ROI between 2004 and 2018. Results: Electrical cortical stimulation disturbed whole word recognition and reading in four patients with structural epilepsy. Stimulation results showed distribution in the basal temporal lobe (dorsal mesencephalon to preoccipital notch). We identified 34 patients with resections in the ROI of the dominant hemisphere. Of these, 15 (44.1%) showed a postoperative reading deficit with a mean duration of 18.2 months (+/-32.4, 0.5-122). Six patients suffered from letter-by-letter (LBL) reading. Two patients had permanent LBL reading after resection in the ROI. Significance: We present evidence on the functional relevance of the vOTC for reading by (1) extra operative cortical stimulation of the VWFA and by (2) a retrospective case study of reading deficits in patients operated in this area. Reading assessments and data concerning essential reading structures should be included in the presurgical evaluation of patients with lesions in the left vOTC. (c) 2021 Elsevier Inc. All rights reserved

Clinical characteristics and postoperative seizure outcome in patients with mild malformation of cortical development and oligodendroglial hyperplasia

Gaballa A, Woermann FG, Cloppenborg T, et al. Clinical characteristics and postoperative seizure outcome in patients with mild malformation of cortical development and oligodendroglial hyperplasia. Epilepsia. 2021.OBJECTIVE: We describe for the first time clinical characteristics in a series of 20 pre-surgically investigated patients with mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) who were operated on in our epilepsy center. We aimed to better diagnose this entity and help surgical planning.; METHODS: Data on 20 patients with histologically confirmed MOGHE were retrospectively evaluated as to age at epilepsy onset and operation, seizure semiology, magnetic resonance imaging (MRI) localization, electroencephalography (EEG) patterns, extent of the operative resection, and postoperative seizure outcome.; RESULTS: Epilepsy began mainly in early childhood; however, symptoms did not manifest until adolescence or adulthood in 30% of patients. All patients had pathologic MRI findings. In 45% of patients the lesion was initially overlooked. Most commonly, the lesion was seen in the frontal lobe. Seizure semiology was characterized as follows: (1) epileptic spasms at epilepsy onset were common and (2) nocturnal hyperkinetic seizures during the course of the disease were rare. EEG always showed frequent interictal epileptic discharges. Two peculiar patterns were observed: (1) during sleep stage I-II, sub-continuous repetitive (0.5-1.5/s) unilateral plump spike/polyspike slow waves were seen and (2) during wakefulness, unilateral paroxysms of 2-2.5/s spike-wave complexes occurred. In total, 60% of patients were seizure-free 1year postoperatively. Postoperative seizure outcome was positively correlated with the extent of resection, age at epilepsy onset, and age at operation. Postoperative long-term outcomes remained stable in patients undergoing larger operations.; SIGNIFICANCE: MRI, EEG, and semiology already contribute to the diagnosis of probable MOGHE preoperatively. Because postoperative seizure outcomes depend on the extent of the resection, prior knowledge of a probable MOGHE helps to plan the resection and balance the risks and benefits of such an intervention. In patients undergoing larger operations, epilepsy surgery achieved good postoperative results; the first long-term outcome data were stable in these patients. © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy

Electric Source Imaging in Presurgical Evaluation of Epilepsy: An Inter-Analyser Agreement Study

Mattioli P, Cleeren E, Hadady L, et al. Electric Source Imaging in Presurgical Evaluation of Epilepsy: An Inter-Analyser Agreement Study. Diagnostics. 2022;12(10): 2303.Electric source imaging (ESI) estimates the cortical generator of the electroencephalography (EEG) signals recorded with scalp electrodes. ESI has gained increasing interest for the presurgical evaluation of patients with drug-resistant focal epilepsy. In spite of a standardised analysis pipeline, several aspects tailored to the individual patient involve subjective decisions of the expert performing the analysis, such as the selection of the analysed signals (interictal epileptiform discharges and seizures, identification of the onset epoch and time-point of the analysis). Our goal was to investigate the inter-analyser agreement of ESI in presurgical evaluations of epilepsy, using the same software and analysis pipeline. Six experts, of whom five had no previous experience in ESI, independently performed interictal and ictal ESI of 25 consecutive patients (17 temporal, 8 extratemporal) who underwent presurgical evaluation. The overall agreement among experts for the ESI methods was substantial (AC1 = 0.65; 95% CI: 0.59-0.71), and there was no significant difference between the methods. Our results suggest that using a standardised analysis pipeline, newly trained experts reach similar ESI solutions, calling for more standardisation in this emerging clinical application in neuroimaging

Hemispherotomy in Children: A Retrospective Analysis of 152 Surgeries in a Single Center and Predictors for Long-Term Seizure Outcome.

Kalbhenn T, Cloppenborg T, Woermann FG, et al. Hemispherotomy in Children: A Retrospective Analysis of 152 Surgeries in a Single Center and Predictors for Long-Term Seizure Outcome. Epilepsia. 2023.OBJECTIVE: Completeness as a predictor of seizure freedom is broadly accepted in epilepsy surgery. We focused on the requirements for a complete hemispherotomy and hypothesized that the disconnection of the insula contributes to a favorable postoperative seizure outcome. We analyzed surgical and non-surgical predictors influencing long-term seizure outcome before and after a modification of our hemispherotomy technique.; METHODS: We retrospectively studied surgical procedures, electro-clinical parameters, MRI results, and follow-up data in all children who had undergone hemispherotomy between 2001 and 2018 at our institution. We used logistic regression models to analyze the influence of different factors on seizure outcome.; RESULTS: 152 patients were eligible for seizure outcome analysis only. Of these, 140 cases had complete follow-up data for ≥24 months and provide the basis for the following results. The median age at surgery was 4.3years (range 0.3-17.9years). Complete disconnection (including the insular tissue) was achieved in 63.6% (89/140). At two-year follow-up, seizure freedom (Engel class IA) was observed in 34.8% (8/23) with incomplete insular disconnection while this was achieved in 88.8% (79/89) with complete surgical disconnection (p<0.001, OR=10.41). In the latter group (N=89), a potentially epileptogenic contralateral MRI lesion was the strongest predictor for postoperative seizure recurrence (OR=22.20).; SIGNIFICANCE: Complete surgical disconnection is the most important predictor of seizure freedom following hemispherotomy and requires disconnection of the insular tissue at the basal ganglia level. Even if the hemispherotomy is performed completely surgically, a potentially epileptogenic contralateral lesion on preoperative MRI significantly reduces the chances of postoperative seizure freedom. This article is protected by copyright. All rights reserved

T cell numbers correlate with neuronal loss rather than with seizure activity in medial temporal lobe epilepsy

Troscher AR, Sakaraki E, Mair KM, et al. T cell numbers correlate with neuronal loss rather than with seizure activity in medial temporal lobe epilepsy. Epilepsia. 2021.OBJECTIVE: Medial temporal lobe epilepsy (MTLE) is a drug-resistant focal epilepsy that can be caused by a broad spectrum of different inciting events, including tumors, febrile seizures, and viral infections. In human epilepsy surgical resections as well as in animal models, an involvement of the adaptive immune system was observed. We here analyzed the presence of T cells in various subgroups of MTLE. We aimed to answer the question of how much inflammation was present and whether the presence of T cells was associated with seizures or associated with hippocampal neurodegeneration.; METHODS: We quantified the numbers of CD3+ T cells and CD8+ cytotoxic T cells in the hippocampus of patients with gangliogliomas (GGs; intrahippocampal and extrahippocampal, with and without sclerosis), febrile seizures, and postinfectious encephalitic epilepsy and compared this with Rasmussen encephalitis, Alzheimer disease, and normal controls.; RESULTS: We could show that T cell numbers were significantly elevated in MTLE compared to healthy controls. CD3+ as well as CD8+ T cell numbers, however, varied highly among MTLE subgroups. By comparing GG patients with and without hippocampal sclerosis (HS), we were able to show that T-cell numbers were increased in extrahippocampal GG patients with hippocampal neuronal loss and HS, whereas extrahippocampal GG cases without hippocampal neuronal loss (i.e., absence of HS) did not differ from healthy controls. Importantly, T cell numbers in MTLE correlated with the degree of neuronal loss, whereas no correlation with seizure frequency or disease duration was found. Finally, we found that in nearly all MTLE groups, T cell numbers remained elevated even years after the inciting event.; SIGNIFICANCE: We here provide a detailed histopathological investigation of the involvement of T cells in various subgroups of MTLE, which suggests that T cell influx correlates to neuronal loss rather than seizure activity. © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy

Development and Validation of Prediction Models for Developmental and Intellectual Outcome Following Pediatric Epilepsy Surgery

Cloppenborg T, van Schooneveld M, Hagemann A, et al. Development and Validation of Prediction Models for Developmental and Intellectual Outcome Following Pediatric Epilepsy Surgery. Neurology. 2021: 10.1212/WNL.0000000000013065.**Background and Objectives:** To (1) identify predictors of postoperative intelligence and developmental quotients (IQ/DQ) and (2) develop and validate clinically applicable IQ/DQ prediction models. **Methods:** We retrospectively analyzed neuropsychological outcomes and their possible determinants for children treated in Bethel and Utrecht since 1990. We performed separate analyses for patients with IQ and those with only DQ available. We developed prediction models based on presurgical determinants to predict dichotomized levels of performance (IQ≥85, IQ≥70, DQ≥50). **Results:** IQ/DQ data before and two years after surgery were available for 492 patients (IQ n=365, DQ n=127). At a cutoff-level ±10 points, the chance of improvement was considerably higher than the chance of deterioration (IQ 37.3% vs. 6.6% and DQ 31.5% vs. 15.0%, respectively). Presurgical IQ/DQ was the strongest predictor of postoperative cognition (IQ r=0.85, p<.001, DQ: r=0.57, p<.001). Two IQ models were developed in the Bethel cohort (n=258) and externally validated in the Utrecht cohort (n=102). For DQ, we developed the model in the Bethel cohort and used 10-fold cross-validation. Models allowed good prediction at all three cutoff-levels (correct classification for IQ≥85=86%, IQ≥70=91%, DQ≥50=76%). External validation of the IQ models showed high accuracy (IQ≥85: 0.82, CI 0.75-0.91, IQ≥70: 0.84, CI 0.77-0.92) and excellent discrimination (ROC curves IQ≥85: AUC 0.90, CI 0.84-0.96; IQ≥70: AUC 0.92, CI 0.87-0.97). **Discussion:** After epilepsy surgery in children, the risk of cognitive deterioration is very low. Presurgical development has a strong impact on the postoperative trajectory. The presented models can improve presurgical counseling of patients and parents by reliably predicting cognitive outcomes. **Classification of Evidence:** This study provides Class II evidence that for children undergoing epilepsy surgery presurgical IQ/DQ was the strongest predictor of postoperative cognition

Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014

Cloppenborg T, May TW, Blümcke I, et al. Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014. Epilepsia. 2019;60(2):233-245

Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014

Cloppenborg T, May TW, Blümcke I, et al. Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014. Epilepsia. 2019;60(2):233-245

Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes

Cloppenborg T, May TW, Blümcke I, et al. Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes. Journal of Neurology, Neurosurgery &amp; Psychiatry. 2016;87(12):1322-1329