Ing. Kateřina Macková

Objectives: We comprehensively characterised a large paediatric cohort with focal cortical dysplasia (FCD) type 1 to expand phenotypic spectrum and to identify predictors of postsurgical outcomes. Methods: We included paediatric patients with histopathological diagnosis of isolated FCD type 1 and at least one year of postsurgical follow-up. We systematically re-analysed clinical, electrophysiological, and radiological features. The results of this re-analysis served as independent variables for subsequent statistical analyses of outcome predictors. Results: All children (N=31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient (IQ)/developmental quotient scores: 32–106). Low presurgical IQ was associated with abnormal slow background EEG activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy MRI protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six out of eight MRI-negative cases, fluorodeoxyglucose-PET and subtraction ictal single-photon emission computed tomography co-registered to MRI (SISCOM) helped localise the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median 5 years, interquartile range 3.3–9 years), seizure freedom was achieved in 71% of patients (22/31), including 7 out of 8 MRI-negative patients. Anti-seizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI, and PET findings. Significance: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multi-layered presurgical approach helped localise the epileptogenic zone in many previously non-lesional cases, resulting in improved postsurgical seizure outcomes, which are more favourable than previously reported for FCD type 1 patients.

Neuroimaging of subtle hypometabolic epileptogenic lesions using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is challenging due to its limited spatial resolution, which causes partial volume effects (PVE), leading to image blurring and underestimation of radiotracer activity. Partial volume correction (PVC) post-processing compensates for the blurring, but relies on accurate knowledge of the point spread function (PSF), which must be provided as an input parameter. However, no guidelines exist for determining an appropriate PSF value, which varies with scanner type, reconstruction algorithm, and scanned object properties. We conducted phantom measurements on Siemens Biograph mCT 40 and Vision 600 scanners using a clinical reconstruction protocol to compare two PSF estimation methods: one based on capillary phantom (following NEMA) and another using effective image resolution (EIR) of Hoffman phantom images (following EARL guideline). The impact of the PSF estimation method on PVC performance was assessed using image quality metrics: gray matter recovery coefficient (GMRC), gray matter edge recovery coefficient (GMERC), and gray matter coefficient of variation (GMCOV). PVC with both PSF estimation methods improved image quality compared to the original images. However, PVC with input PSF estimated by EIR showed better performance than PVC with capillary-based estimate: GMRC was 92-94% vs. 85-86%, GMERC was 85-90% vs. 78-79%, and lower GMCOV: 18-22% vs. 20-23%. These findings suggest that the estimation of input PSF by EIR could be a more reliable and practical approach for PVC in clinical FDG-PET brain imaging, especially since it is already used in the EARL F/C Brain PET/CT Accreditation.

Objective: Epilepsy surgery in the operculo-insular cortex is challenging due to the difficult delineation of the epileptogenic zone and the high risk of post-operative deficits following resections in this region. Methods: Pre- and post-surgical data from 30 pediatric patients who underwent opercular-insular cortex surgery at Motol Epilepsy Center Prague from 2010 to 2022 were analyzed. Results: Focal cortical dysplasia (FCD, n = 15, 50%) was the predominant cause of epilepsy in the patients studied, followed by epilepsy-associated tumors (n = 5, 17%) and tuberous sclerosis complex (n = 2, 7%). In eight patients where FCD was the most likely etiology, histology was negative. Seven patients (23%) displayed normal MRI results. Seizures exhibited diverse semiology and propagation patterns (i.e., frontal, perisylvian, and temporal). Ictal and interictal EEG findings observed during video EEG were mostly extensive. Multimodal imaging and advanced post-processing were frequently utilized. Stereoelectroencephalography (SEEG) monitoring was used for localizing the epileptogenic zone and eloquent cortex in 23 patients (77%). Oblique electrodes were used as guides for better orientation of neurosurgeons during resection. The epileptogenic zone was in the dominant hemisphere in 16 patients. At the two-year follow-up, 22 patients (73%) were completely seizure-free, and eight (27%) experienced a seizure frequency reduction of > 50% (ILAE 3 and 4). Fourteen patients (47%) underwent anti-seizure medication tapering; treatment was completely withdrawn in two patients (7%). Nineteen patients (63%) remained seizure-free following the definitive outcome assessment (median: 6 years and 5 months, range: 2 years to 13 years and 5 months post-surgery). Six patients (20 %) experienced corona radiata or basal ganglia ischemia; four (13%) improved to mild hemiparesis, and one (3%) to moderate hemiparesis with ongoing rehabilitation. Two patients (7 %) operated on in the anterior insula, along with fronto-temporal resection experienced major complications - pontine ischemia and post-operative brain edema. Significance: Epilepsy surgery in the opercular-insular cortex can lead to excellent patient outcomes. A comprehensive diagnostic approach is crucial for surgical success. There is a great chance for significant recovery of postoperative deficits with the use of rehabilitation.

Objective: Focal cortical dysplasia (FCD) is the most common malformation causing refractory focal epilepsy. Surgical removal of the entire dysplastic cortex is crucial for achieving a seizure-free outcome. Precise presurgical distinctions between FCD types by neuroimaging are difficult, mainly in patients with normal magnetic resonance imaging findings. However, the FCD type is important for planning the extent of surgical approach and counselling. Methods: This study included patients with focal drug-resistant epilepsy and definite histopathological FCD type I or II diagnoses who underwent intracranial electroencephalography (iEEG). We detected interictal epileptiform discharges (IEDs) and their recruitment into repetitive discharges (RDs) to compare electrophysiological patterns characterizing FCD types. Results: Patients with FCD type II had a significantly higher IED rate (p<0.005), a shorter inter-discharge interval within RD episodes (p<0.003), sleep influence on decreased RD periodicity (p<0.036), and longer RD episode duration (p<0.003) than patients with type I. A Bayesian classifier stratified FCD types with 82% accuracy. Conclusion: Temporal characteristics of IEDs and RDs reflect the histological findings of FCD subtypes and can differentiate FCD types I and II. Significance: Presurgical prediction of FCD type can help to plan a more tailored surgical approach in patients with normal magnetic resonance findings.