AIM: The primary goal was to determine the yield of next-generation sequencing (NGS) epilepsy gene panels used for epilepsy etiology diagnosing using a multidisciplinary approach and to demonstrate the importance of genotype-phenotype correlations. The secondary goal was to evaluate the application of precision medicine in selected patients. METHODS: This single-center retrospective study included a total of 175 patients (95 males and 80 females) aged 0-19 years. They were examined between 2015 and 2020 using an NGS epilepsy gene panel (270 genes). A bioinformatic analysis was performed including copy number variation identification. Thorough genotype-phenotype correlation was performed. RESULTS: Out of 175 patients, described pathogenic variants or novel variants with clear pathogenic impact were identified in 30 patients (17.14%). Genotype-phenotype correlations and parental DNA analysis were performed, and genetic diagnosis was confirmed on the basis of the results in another 16 out of 175 patients (9.14%). The diagnostic yield of our study increased from 30 to 46 patients (by 53.33%) by the precise genotype-phenotype correlation. INTERPRETATION: We emphasize a complex genotype-phenotype correlation and a multidisciplinary approach in evaluating the results of the NGS epilepsy gene panel, which enables the most accurate genetic diagnosis and correct interpretation of results.

• MeSH
• epilepsie * diagnóza   genetika   MeSH
• fenotyp MeSH
• genetické asociační studie MeSH
• genetické testování metody   MeSH
• lidé MeSH
• mutace MeSH
• retrospektivní studie MeSH
• variabilita počtu kopií segmentů DNA * MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• epilepsie parciální diagnostické zobrazování   MeSH
• jednofotonová emisní výpočetní tomografie metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• multimodální zobrazování MeSH
• neurozobrazování metody   MeSH
• pozitronová emisní tomografie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: The purpose of the study was to evaluate cerebral morphological changes in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and their relationship to the cerebellum. METHODS: The study cohort included 21 patients with intractable TLE-HS (14 left-sided, 7 right-sided) and 38 healthy controls (HC). All patients later underwent anteromedial temporal lobe resection. All subjects were examined using a 1.5-T magnetic resonance imaging (MRI). Volumes of distinct cerebral and cerebellar structures were measured using voxel-based morphometry. The structural covariance of temporal lobe structures, insula, and thalamus with cerebellar substructures was examined using partial least squares regression. RESULTS: Morphological changes were more significant in the group with left TLE-HS when comparing left-sided with right-sided structures as well as when comparing patients with controls. The gray matter volume (GMV) of the temporal lobe structures was smaller ipsilaterally to the seizure onset side in most cases. There was a significant amygdala enlargement contralateral to the side of hippocampal sclerosis in both patients with right and left TLE-HS as compared with controls. Selected vermian structures in patients with left but not right TLE-HS had significantly larger GMV than the identical substructures in controls. The structural covariance differed significantly between patients with left and right TLE-HS as compared with HC. The analysis revealed significant negative covariance between anterior vermis and mesial temporal structures in the group with left TLE-HS. No significance was observed for the group with right TLE-HS. CONCLUSION: There is significant asymmetry in the GMV of cerebral and cerebellar structures in patients with TLE-HS. Morphological changes are distinctly more pronounced in patients with left TLE-HS. The observed structural covariance between the cerebellum and supratentorial structures in TLE-HS suggests associations beyond the mesial temporal lobe structures and thalamus.

• MeSH
• dospělí MeSH
• epilepsie temporálního laloku diagnostické zobrazování   chirurgie   MeSH
• hipokampus diagnostické zobrazování   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozeček diagnostické zobrazování   MeSH
• mozková kůra diagnostické zobrazování   MeSH
• šedá hmota diagnostické zobrazování   MeSH
• skleróza diagnostické zobrazování   chirurgie   MeSH
• spánkový lalok diagnostické zobrazování   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH