Dataset Information

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II.

ABSTRACT:

Objective

Favorable seizure outcome is reported following resection of bottom-of-sulcus dysplasia (BOSD). We assessed the distribution of epileptogenicity and dysplasia in and around BOSD to better understand this clinical outcome and the optimal surgical approach.

Methods

We studied 27 children and adolescents with magnetic resonance imaging (MRI)-positive BOSD who underwent epilepsy surgery; 85% became seizure-free postresection (median = 5.0 years follow-up). All patients had resection of the dysplastic sulcus, and 11 had additional resection of the gyral crown (GC) or adjacent gyri (AG). Markers of epileptogenicity were relative cortical hypometabolism on preoperative ¹⁸ F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and spiking, ripples, fast ripples, spike-high-frequency oscillation cross-rate, and phase amplitude coupling (PAC) on preresection and postresection electrocorticography (ECoG), all analyzed at the bottom-of-sulcus (BOS), top-of-sulcus (TOS), GC, and AG. Markers of dysplasia were increased cortical thickness on preoperative MRI, and dysmorphic neuron density and variant allele frequency of somatic MTOR mutations in resected tissue, analyzed at similar locations.

Results

Relative cortical metabolism was significantly reduced and ECoG markers were significantly increased at the BOS compared to other regions. Apart from spiking and PAC, which were greater at the TOS compared to the GC, there were no significant differences in PET and other ECoG markers between the TOS, GC, and AG, suggesting a cutoff of epileptogenicity at the TOS rather than a tapering gradient on the cortical surface. MRI and tissue markers of dysplasia were all maximal in the BOS, reduced in the TOS, and mostly absent in the GC. Spiking and PAC reduced significantly over the GC after resection of the dysplastic sulcus.

Significance

These findings support the concept that dysplasia and intrinsic epileptogenicity are mostly limited to the dysplastic sulcus in BOSD and support resection or ablation confined to the MRI-visible lesion as a first-line surgical approach. ¹⁸ F-FDG PET and ECoG abnormalities in surrounding cortex seem to be secondary phenomena.

SUBMITTER: Macdonald-Laurs E

PROVIDER: S-EPMC10952144 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II.

Macdonald-Laurs Emma E Warren Aaron E L AEL Lee Wei Shern WS Yang Joseph Yuan-Mou JY MacGregor Duncan D Lockhart Paul J PJ Leventer Richard J RJ Neal Andrew A Harvey A Simon AS

Epilepsia 20221227 2

<h4>Objective</h4>Favorable seizure outcome is reported following resection of bottom-of-sulcus dysplasia (BOSD). We assessed the distribution of epileptogenicity and dysplasia in and around BOSD to better understand this clinical outcome and the optimal surgical approach.<h4>Methods</h4>We studied 27 children and adolescents with magnetic resonance imaging (MRI)-positive BOSD who underwent epilepsy surgery; 85% became seizure-free postresection (median = 5.0 years follow-up). All patients had r ...[more]

PMID: 36527426

Similar Datasets

Project description:Purpose: The superior frontal sulcus (SFS), located in the prefrontal and premotor cortex, is considered as one of the common locations of focal cortical dysplasia (FCD). However, the characteristics of seizures arising from this area are incompletely known. The primary purpose of this study was to investigate the clinical features and the epileptic networks of seizures originating from the SFS. Methods: We included seventeen patients with type II FCD within the SFS. SFS was identified both visually and automatically. Semiological features were evaluated and grouped. Interictal 18FDG-PET imaging in all patients was compared to controls using statistical parametric mapping (SPM-PET). In those subjects with stereoelectroencephalography (SEEG), two different quantitative intracranial electroencephalography analyses were applied. Finally, the locations of the SFS-related hypometabolic regions and epileptogenic zones (EZs) were transformed into standard space for group analysis. Results: We identified two semiological groups. Group 1 (9/17) showed elementary motor signs (head version and tonic posturing), while group 2 (8/17) exhibited complex motor behavior (fear, hypermotor, and ictal pouting). Based on SPM-PET, an SFS-supplementary motor area (SMA) epileptic propagation network was found in group 1, and an SFS-middle cingulate cortex (MCC)-pregenual anterior cingulate cortex (pACC) propagation network was discovered in group 2. Intracranial EEG analysis suggested similar affected structures with high epileptogenicity. The SFS-related hypometabolic regions and EZs in these groups showed a posterior-anterior spatial relationship. Conclusions: Even though originating from the spatially restricted cortex, SFS seizures can be divided into two groups based on semiological features. The SFS-SMA and SFS-MCC-pACC epileptic propagation networks may play pivotal roles in the generation of different semiologies. The posterior-anterior spatial relationship of both hypometabolic regions and EZs provides potentially useful information for distinguishing different types of SFS seizures and surgical evaluation.

Project description:We aimed to differentiate between the interictal and preictal states in epilepsy patients with focal cortical dysplasia (FCD) type-II using deep learning-based classifiers based on intracranial electroencephalography (EEG). We also investigated the practical conditions for high interictal-preictal discriminability in terms of spatiotemporal EEG characteristics and data size efficiency. Intracranial EEG recordings of nine epilepsy patients with FCD type-II (four female, five male; mean age: 10.7 years) were analyzed. Seizure onset and channel ranking were annotated by two epileptologists. We performed three consecutive interictal-preictal classification steps by varying the preictal length, number of electrodes, and sampling frequency with convolutional neural networks (CNN) using 30 s time-frequency data matrices. Classification performances were evaluated based on accuracy, F1 score, precision, and recall with respect to the above-mentioned three parameters. We found that (1) a 5 min preictal length provided the best classification performance, showing a remarkable enhancement of >13% on average compared to that with the 120 min preictal length; (2) four electrodes provided considerably high classification performance with a decrease of only approximately 1% on average compared to that with all channels; and (3) there was minimal performance change when quadrupling the sampling frequency from 128 Hz. Patient-specific performance variations were noticeable with respect to the preictal length, and three patients showed above-average performance enhancements of >28%. However, performance enhancements were low with respect to both the number of electrodes and sampling frequencies, and some patients showed at most 1-2% performance change. CNN-based classifiers from intracranial EEG recordings using a small number of electrodes and efficient sampling frequency are feasible for predicting the interictal-preictal state transition preceding seizures in epilepsy patients with FCD type-II. Preictal lengths affect the predictability in a patient-specific manner; therefore, pre-examinations for optimal preictal length will be helpful in seizure prediction.

Project description:Dendritic spines are the postsynaptic sites for most excitatory glutamatergic synapses. We previously demonstrated a severe spine loss and synaptic reorganization in human neocortices presenting Type II focal cortical dysplasia (FCD), a developmental malformation and frequent cause of drug-resistant focal epilepsy. We extend the findings, investigating the potential role of complement components C1q and C3 in synaptic pruning imbalance. Data from Type II FCD were compared with those obtained in focal epilepsies with different etiologies. Neocortical tissues were collected from 20 subjects, mainly adults with a mean age at surgery of 31 years, admitted to epilepsy surgery with a neuropathological diagnosis of: cryptogenic, temporal lobe epilepsy with hippocampal sclerosis, and Type IIa/b FCD. Dendritic spine density quantitation, evaluated in a previous paper using Golgi impregnation, was available in a subgroup. Immunohistochemistry, in situ hybridization, electron microscopy, and organotypic cultures were utilized to study complement/microglial activation patterns. FCD Type II samples presenting dendritic spine loss were characterized by an activation of the classical complement pathway and microglial reactivity. In the same samples, a close relationship between microglial cells and dendritic segments/synapses was found. These features were consistently observed in Type IIb FCD and in 1 of 3 Type IIa cases. In other patient groups and in perilesional areas outside the dysplasia, not presenting spine loss, these features were not observed. In vitro treatment with complement proteins of organotypic slices of cortical tissue with no sign of FCD induced a reduction in dendritic spine density. These data suggest that dysregulation of the complement system plays a role in microglia-mediated spine loss. This mechanism, known to be involved in the removal of redundant synapses during development, is likely reactivated in Type II FCD, particularly in Type IIb; local treatment with anticomplement drugs could in principle modify the course of disease in these patients.

Dataset Information

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II.

Objective

Methods

Results

Significance

Publications

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets