OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis 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 electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize 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 seven of eight MRI-negative patients. Antiseizure 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 multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.

• Klíčová slova
• drug‐resistant epilepsy, epilepsy surgery, focal cortical dysplasia type 1, multilayered diagnostic protocol, pediatric patients,
• MeSH
• dítě MeSH
• elektroencefalografie MeSH
• fokální kortikální dysplazie MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• malformace mozkové kůry, skupina I * komplikace   chirurgie   patofyziologie   diagnostické zobrazování   MeSH
• mladiství MeSH
• následné studie MeSH
• pozitronová emisní tomografie MeSH
• předškolní dítě MeSH
• refrakterní epilepsie * chirurgie   diagnostické zobrazování   patofyziologie   etiologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVES: Malformations of cortical development (MCD), though individually rare, constitute a significant burden of disease. The diagnostic yield of next-generation sequencing (NGS) in these patients varies across studies and methods, and novel genes and variants continue to emerge. METHODS: Patients (n = 123) with a definite radiologic or histopathologic diagnosis of MCD, with or without epilepsy were included in this study. They underwent NGS-based targeted gene panel (TGP) testing, whole-exome sequencing (WES), or WES-based virtual panel testing. Selected patients who underwent epilepsy surgery (n = 69) also had somatic gene testing of brain tissue-derived DNA. We analyzed predictors of positive germline genetic finding and diagnostic yield of respective methods. RESULTS: Pathogenic or likely pathogenic germline genetic variants were detected in 21% of patients (26/123). In the surgical subgroup (69/123), we performed somatic sequencing in 40% of cases (28/69) and detected causal variants in 18% (5/28). Diagnostic yield did not differ between TGP, WES-based virtual gene panel, and open WES (p = 0.69). Diagnosis of focal cortical dysplasia type 2A, epilepsy, and intellectual disability were associated with positive results of germline testing. We report previously unpublished variants in 16/26 patients and 4 cases of MCD with likely pathogenic variants in non-MCD genes. DISCUSSION: In this study, we are reporting genetic findings of a large cohort of MCD patients with epilepsy or potentially epileptogenic MCD. We determine predictors of successful ascertainment of a genetic diagnosis in real-life setting and report novel, likely pathogenic variants in MCD and non-MCD genes alike.

• Publikační typ
• časopisecké články MeSH

Focal cortical dysplasias (FCDs) are a range of malformations of cortical development each with specific histopathological features. Conventional radiological assessment of standard structural MRI is useful for the localization of lesions but is unable to accurately predict the histopathological features. Quantitative MRI offers the possibility to probe tissue biophysical properties in vivo and may bridge the gap between radiological assessment and ex-vivo histology. This review will cover histological, genetic and radiological features of FCD following the ILAE classification and will explain how quantitative voxel- and surface-based techniques can characterise these features. We will provide an overview of the quantitative MRI measures available, their link with biophysical properties and finally the potential application of quantitative MRI to the problem of FCD subtyping. Future research linking quantitative MRI to FCD histological properties should improve clinical protocols, allow better characterisation of lesions in vivo and tailored surgical planning to the individual.

• Klíčová slova
• Biophysical tissue properties, Epilepsy surgery, Focal cortical dysplasia, Histology, MRI, Malformation of cortical development, Quantitative MRI, Quantitative mapping, Radiology, qMRI,
• MeSH
• fenotyp * MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   statistika a číselné údaje   MeSH
• malformace mozkové kůry diagnostické zobrazování   genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH