OBJECTIVE: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy. METHODS: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing. We searched for predictors of surgical outcome and positive result of germline genetic testing. RESULTS: Ninety-five patients were enrolled in epilepsy surgery program and 64 underwent resective epilepsy surgery. We ascertained germline genetic diagnosis in 13/74 patients having underwent germline gene testing (pathogenic or likely pathogenic variants in CHRNA4, NPRL3, DEPDC5, FGF12, GRIA2, SZT2, STXBP1) and identified three copy number variants. Thirty-five patients underwent somatic gene testing; we detected 10 pathogenic or likely pathogenic variants in genes SLC35A2, PTEN, MTOR, DEPDC5, NPRL3. Germline genetic diagnosis was significantly associated with the diagnosis of focal epilepsy with unknown seizure onset. SIGNIFICANCE: Germline and somatic gene testing can ascertain a definite genetic diagnosis in a significant subgroup of patients in epilepsy surgery programs. Diagnosis of focal genetic epilepsy may tip the scales against the decision to proceed with invasive EEG study or surgical resection; however, selected patients with genetic focal epilepsies associated with MCD may benefit from resective epilepsy surgery and therefore, a genetic diagnosis does not disqualify patients from presurgical evaluation and epilepsy surgery.

• MeSH
• dítě MeSH
• epilepsie parciální * komplikace   MeSH
• epilepsie * genetika   chirurgie   komplikace   MeSH
• fibroblastové růstové faktory genetika   MeSH
• genetické testování MeSH
• lidé MeSH
• malformace mozkové kůry * genetika   MeSH
• prospektivní studie MeSH
• proteiny aktivující GTPasu genetika   MeSH
• proteiny nervové tkáně genetika   MeSH
• refrakterní epilepsie * diagnóza   genetika   chirurgie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: In order to introduce a complex system of monitoring and evaluation of the heath-related quality of life (HRQoL) of children and adolescents with epilepsy (CWE) and their families in the Czech Republic, we aimed to validate the Czech versions of two appropriate instruments - the Impact of Pediatric Epilepsy Scale (IPES) and the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48). METHODS: The verification of the 11-item IPES was carried out in the group of parents of 248 CWE aged 2-18 years. One hundred and thirty-five CWE from the given group aged 11-18 years then completed the 48-item QOLIE-AD-48. Internal consistency, test-retest reliability (with a three-month interval) and the factorial structure of the Czech versions were determined and compared with the original instruments. RESULTS: We found that the Czech version of the IPES exhibited very good psychometric properties including high internal consistency (Cronbach's alpha, α, of 0.93), high test-retest reliability (intraclass correlation coefficient, ICC, of 0.76) and the same 3-factor structure as the original instrument. The superiority of this 3-factor solution over the alternate 2-factor model proposed for some language versions of the IPES was determined using confirmatory factor analysis. We found 8 items in the Czech version of the QOLIE-AD-48 belonging to original Attitudes towards epilepsy and Social support subscales that do not fit well with the Czech version due to their low correlation with the total score and insufficient test-retest reliability and should be omitted. For the remaining 40 items, we have determined high internal consistency (α = 0.95) and test-retest reliability (ICC = 0.82). Confirmatory factor analysis revealed that the 6-factor solution derived from the original instrument (without two removed subscales) was appropriate for the Czech version. The individual subscales exhibited high internal consistency with α = 0.61-0.91. The external validation of both instruments was confirmed based on a significant correlation between test results and physicians' reports of the characteristics of the child's epilepsy. CONCLUSIONS: The Czech versions of both instruments studied are reliable and valid, and can be used in the next research focusing on the effect of different treatment approaches on the HRQoL of CWE and their families.

• MeSH
• dítě MeSH
• doxorubicin analogy a deriváty   MeSH
• epilepsie * diagnóza   MeSH
• jazyk (prostředek komunikace) MeSH
• kvalita života * MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• průzkumy a dotazníky MeSH
• psychometrie MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

OBJECT: Epilepsy surgery is an effective treatment for selected patients with focal intractable epilepsy. Complete removal of the epileptogenic zone significantly increases the chances for postoperative seizure-freedom. In complex surgical candidates, delineation of the epileptogenic zone requires a long-term invasive video/EEG from intracranial electrodes. It is especially challenging to achieve a complete resection in deep brain structures such as opercular-insular cortex. We report a novel approach utilizing intraoperative visual detection of stereotactically implanted depth electrodes to inform and guide the extent of surgical resection. METHODS: We retrospectively reviewed data of pediatric patients operated in Motol Epilepsy Center between October 2010 and June 2020 who underwent resections guided by intraoperative visual detection of depth electrodes following SEEG. The outcome in terms of seizure- and AED-freedom was assessed individually in each patient. RESULTS: Nineteen patients (age at surgery 2.9-18.6 years, median 13 years) were included in the study. The epileptogenic zone involved opercular-insular cortex in eighteen patients. The intraoperative detection of the electrodes was successful in seventeen patients and the surgery was regarded complete in sixteen. Thirteen patients were seizure-free at final follow-up including six drug-free cases. The successful intraoperative detection of the electrodes was associated with favorable outcome in terms of achieving complete resection and seizure-freedom in most cases. On the contrary, the patients in whom the procedure failed had poor postsurgical outcome. CONCLUSION: The reported technique helps to achieve the complete resection in challenging patients with the epileptogenic zone in deep brain structures.

• MeSH
• dítě MeSH
• elektroencefalografie MeSH
• epilepsie * chirurgie   MeSH
• implantované elektrody MeSH
• insulární kortex MeSH
• lidé MeSH
• refrakterní epilepsie * chirurgie   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Patients with tuberous sclerosis complex (TSC) present with drug-resistant epilepsy in about 60% of cases, and evaluation for epilepsy surgery may be warranted. Correct delineation of the epileptogenic zone (EZ) among multiple dysplastic lesions on MRI represents a challenging step in pre-surgical evaluation. METHODS: Two experienced neuroradiologists evaluated pre- and post-surgical MRIs of 28 epilepsy surgery patients with TSC, assessing characteristics of tubers, cysts, calcifications, and focal cortical dysplasia (FCD)-resembling lesions. Utilizing multiple metrics, we compared MRI features of the EZ-defined as the resected area in TSC patients who achieved seizure-freedom 2 years after epilepsy surgery-with features of other brain areas. Using combinatorial analysis, we identified combinations of dysplastic features that are most frequently observed in the epileptogenic zone in TSC patients. RESULTS: All TSC-associated dysplastic features were more frequently observed in the EZ than in other brain areas (increased cortical thickness, gray-white matter blurring, transmantle sign, calcifications, and tubers; Kendal's tau 0.35, 0.25, 0.27, 0.26, and 0.23, respectively; P value <.001 in all). No single feature could reliably and independently indicate the EZ in all patients. Conversely, the EZ was indicated by the presence of the combination of three of the following features: tubers, transmantle sign, increased cortical thickness, calcifications, and the largest FCD-affected area. Out of these, the largest FCD-affected area emerged as the most reliable indicator of the EZ, combined either with calcifications or tubers. SIGNIFICANCE: The epileptogenic zone in TSC patients harbors multiple dysplastic features, consistent with focal cortical dysplasia. A specific combination of these features can indicate the EZ and aid in pre-surgical MRI evaluation in epilepsy surgery candidates with TSC.

• MeSH
• dítě MeSH
• epilepsie * komplikace   etiologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• malformace mozkové kůry * komplikace   diagnostické zobrazování   patologie   MeSH
• mozek patologie   MeSH
• tuberózní skleróza * komplikace   diagnostické zobrazování   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Variants of GATOR1-genes represent a recognised cause of focal cortical dysplasia (FCD), the most common structural aetiology in paediatric drug-resistant focal epilepsy. Reports on familial cases of GATOR1-associated FCD are limited, especially with respect to epilepsy surgery outcomes. METHODS: We present phenotypical manifestations of four unrelated patients with drug-resistant focal epilepsy, FCD and a first-degree relative with epilepsy. All patients underwent targeted gene panel sequencing as a part of the presurgical work up. Literature search was performed to compare our findings to previously published cases. RESULTS: The children (probands) had a more severe phenotype than their parents, including drug-resistant epilepsy and developmental delay, and they failed to achieve seizure freedom post-surgically. All patients had histopathologically confirmed FCD (types IIa, IIb, Ia). In Patient 1 and her affected father, we detected a known pathogenic NPRL2 variant. In patients 2 and 3 and their affected parents, we found novel likely pathogenic germline DEPDC5 variants. In family 4, we detected a novel variant in NPRL3. We identified 15 additional cases who underwent epilepsy surgery for GATOR1-associated FCD, with a positive family history of epilepsy in the literature; in 8/13 tested, the variant was inherited from an asymptomatic parent. CONCLUSION: The presented cases displayed a severity gradient in phenotype with children more severely affected than the parents. Although patients with GATOR1-associated FCD are considered good surgical candidates, post-surgical seizure outcome was poor in our familial cases, suggesting that accurate identification of the epileptogenic zone may be more challenging in this subgroup of patients.

• MeSH
• dítě MeSH
• fenotyp MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• malformace mozkové kůry genetika   chirurgie   MeSH
• mladiství MeSH
• nádorové supresorové proteiny genetika   MeSH
• proteiny aktivující GTPasu genetika   MeSH
• refrakterní epilepsie genetika   MeSH
• retrospektivní studie MeSH
• zárodečné mutace MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: Neurodegeneration with brain iron accumulation constitutes a group of rare progressive movement disorders sharing intellectual disability and neuroimaging findings as common denominators. Beta-propeller protein-associated neurodegeneration (BPAN) represents approximately 7% of the cases, and its first signs are typically epilepsy and developmental delay. We aimed to describe in detail the phenotype of BPAN with a special focus on iron metabolism. MATERIAL AND METHODS: We present a cohort of paediatric patients with pathogenic variants of WD-Repeat Domain 45 gene (WDR45). The diagnosis was established by targeted panel sequencing of genes associated with epileptic encephalopathies (n = 9) or by Sanger sequencing of WDR45 (n = 1). Data on clinical characteristics, molecular-genetic findings and other performed investigations were gathered from all participating centres. Markers of iron metabolism were analysed in 6 patients. RESULTS: Ten children (3 males, 7 females, median age 8.4 years) from five centres (Prague, Berlin, Vogtareuth, Tubingen and Cologne) were enrolled in the study. All patients manifested first symptoms (e.g. epilepsy, developmental delay) between 2 and 31 months (median 16 months). Seven patients were seizure-free (6 on antiepileptic medication, one drug-free) at the time of data collection. Neurological findings were non-specific with deep tendon hyperreflexia (n = 4) and orofacial dystonia (n = 3) being the most common. Soluble transferrin receptor/log ferritin ratio was elevated in 5/6 examined subjects; other parameters of iron metabolism were normal. CONCLUSION: Severity of epilepsy often gradually decreases in BPAN patients. Elevation of soluble transferrin receptor/log ferritin ratio could be another biochemical marker of the disease and should be explored by further studies.

• MeSH
• biologické markery krev   MeSH
• dítě MeSH
• epilepsie krev   genetika   metabolismus   MeSH
• fenotyp MeSH
• lidé MeSH
• mentální retardace krev   genetika   metabolismus   MeSH
• neurodegenerativní nemoci krev   genetika   metabolismus   MeSH
• pohybové poruchy krev   genetika   metabolismus   MeSH
• poruchy metabolismu železa krev   genetika   metabolismus   MeSH
• transportní proteiny genetika   MeSH
• železo krev   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To evaluate the impact of generalized quasiperiodic epileptiform discharges ("hurdles") observed in non-rapid eye movement (NREM) sleep on cognitive function in children with intractable focal epilepsy. "Hurdles" pattern does not meet the criteria of the electrical status epilepticus in slow-wave sleep (ESES). METHODS: In a retrospective analysis, 24 patients with "hurdles" and their 24 peers matched for demographic and epilepsy-related variables were compared in terms of neuropsychological domains and electroencephalography (EEG)-derived quantifiers. Both "hurdles" and controls were children between 2 and 19 years of age who had intractable focal epilepsy evaluated as candidates of resective epilepsy surgery. RESULTS: Full-scale intelligence quotient/developmental quotient (FSIQ/DQ) (P = .002) and visuoconstructional skills (P = .004) were significantly lower in children with "hurdles" compared to controls. Patients with "hurdles" presented with higher interictal spike indexes in sleep (P < .001, median difference -0.9, 95% confidence interval [CI] -1.4, -0.6) and wakefulness (P < .001, median difference -0.3, 95% CI -0.5, -1). Relative time of sleep spindles in NREM sleep was significantly reduced (P < .001, median difference 0.1, 95% CI 0.0, 0.1) in the "hurdles" group. The time proportion of sleep spindles represented a significant positive (P = .008) and spike index of generalized spikes in sleep a significant negative explanatory variable (P = .004) of FSIQ/DQ scores. The proportion of seizure-free patients 2 years after epilepsy surgery did not differ significantly between the two groups (P = .19). SIGNIFICANCE: Although the "hurdles" pattern does not fulfill the criteria of ESES, it is associated with a pronounced cognitive dysfunction. Disturbed sleep structure marked by reduced sleep spindles and generalized spiking in sleep is associated with worse cognitive performance. Despite having a generalized nature, we did not find a lower probability of postsurgical seizure freedom in patients with "hurdles" pattern.

• MeSH
• bdění fyziologie   MeSH
• dítě MeSH
• elektroencefalografie trendy   MeSH
• epilepsie parciální diagnóza   patofyziologie   psychologie   MeSH
• kognitivní dysfunkce diagnóza   patofyziologie   psychologie   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• refrakterní epilepsie diagnóza   patofyziologie   psychologie   MeSH
• retrospektivní studie MeSH
• spánek fyziologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

Background: We aimed first to describe trends in cognitive performance over time in a large patient cohort (n = 203) from a single tertiary centre for paediatric epilepsy surgery over the period of 16 years divided in two (developing-pre-2011 vs. established-post-2011). Secondly, we tried to identify subgroups of epilepsy surgery candidates with distinctive epilepsy-related characteristics that associate with their pre- and post-surgical cognitive performance. Thirdly, we analysed variables affecting pre-surgical and post-surgical IQ/DQ and their change (post- vs. pre-surgical). Methods: We analysed IQ/DQ data obtained using standardized neuropsychological tests before epilepsy surgery and one year post-surgically, along with details of patient's epilepsy, epilepsy surgery and outcomes in terms of freedom from seizures. Using regression analysis, we described the trend in post-operative IQ/DQ. Cognitive outcomes and the associated epilepsy- and epilepsy surgery-related variables were compared between periods before and after 2011. Using multivariate analysis we analysed the effect of individual variables on pre- and post-operative IQ/DQ and its change. Results: Epilepsy surgery tends to improve post-surgical IQ/DQ, most significantly in patients with lower pre-surgical IQ/DQ, and post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ (Rho = 0.888, p < 0.001). We found no significant difference in pre-, post-surgical IQ/DQ and IQ/DQ change between the periods of pre-2011 and post-2011 (p = 0.7, p = 0.469, p = 0.796, respectively). Patients with temporal or extratemporal epilepsy differed in their pre-surgical IQ/DQ (p = 0.001) and in IQ/DQ change (p = 0.002) from those with hemispheric epilepsy, with no significant difference in post-surgical IQ/DQ (p = 0.888). Groups of patients with different underlying histopathology showed significantly different pre- and post-surgical IQ/DQ (p < 0.001 and p < 0.001 respectively) but not IQ/DQ change (p = 0.345).Variables associated with severe epilepsy showed effect on cognitive performance in multivariate model. Discussion: Post-surgical IQ/DQ strongly correlates with pre-surgical IQ/DQ and greatest IQ/DQ gain occurs in patients with lower pre-surgical IQ/DQ scores. Cognitive performance was not affected by changes in paediatric epilepsy surgery practice. Pre- and post-operative cognitive performances, as well as patients' potential for cognitive recovery, are highly dependent on the underlying aetiology and epileptic syndrome.

• Publikační typ
• časopisecké články MeSH

PURPOSE: We assessed trends in spectrum of candidates, diagnostic algorithm, therapeutic approach and outcome of a pediatric epilepsy surgery program between 2000 and 2017. METHODS: All pediatric patients who underwent curative epilepsy surgery in Motol Epilepsy Center during selected period (n = 233) were included in the study and divided into two groups according to time of the surgery (developing program 2000-2010: n = 86, established program 2011-2017: n = 147). Differences in presurgical, surgical and outcome variables between the groups were statistically analyzed. RESULTS: A total of 264 resections or hemispheric disconnections were performed (including 31 reoperations). In the later epoch median age of candidates decreased. Median duration of disease shortened in patients with temporal lobe epilepsy. Number of patients with non-localizing MRI findings (subtle or multiple lesions) rose, as well as those with epileptogenic zone adjacent to eloquent cortex. There was a trend towards one-step procedures guided by multimodal neuroimaging and intraoperative electrophysiology; long-term invasive EEG was performed in fewer patients. Subdural electrodes for long-term invasive monitoring were almost completely replaced by stereo-EEG. The number of focal resections and hemispherotomies rose over time. Surgeries were more often regarded complete. Histopathological findings of resected tissue documented developing spectrum of candidates. 82.0% of all children were seizure-free two years after surgery; major complications occurred in 4.6% procedures; both groups did not significantly differ in these parameters. CONCLUSION: In the established pediatric epilepsy surgery program, our patients underwent epilepsy surgery at younger age and suffered from more complex structural pathology. Outcomes and including complication rate remained stable.

• MeSH
• dítě MeSH
• elektroencefalografie metody   MeSH
• epilepsie patologie   chirurgie   MeSH
• hemisferektomie škodlivé účinky   metody   MeSH
• lidé MeSH
• mladiství MeSH
• mozková kůra chirurgie   MeSH
• neurologie trendy   MeSH
• neurozobrazování metody   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Chirurgická léčba epilepsie představuje významnou terapeutickou alternativu u pacientů s farmakorezistentní epilepsií. Klinika dětské neurologie 2. LF UK a FN Motol se v rámci Centra pro epilepsie Motol zabývá chirurgickou léčbou epilepsie u dětí od roku 2000. K 1. 11. 2017 zde bylo realizováno 263 výkonů u 232 pacientů. V našem článku shrneme základní principy epileptochirurgie, předoperační diagnostiky a představíme výsledky epileptochirurgického programu dětské části Centra pro epilepsie Motol včetně aktuálních trendů. 80,7 % dětí v našem souboru je dva roky po operaci bez záchvatů. Základním předpokladem úspěchu epileptochirurgie zůstává včasné provedení výkonu, které pro dětské pacienty představuje navíc šanci na zachování jejich kognitivního potenciálu.

Surgical treatment of epilepsy represents an important therapeutic option in patients with drug-resistant epilepsy. At Departmentof Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospitalpaediatric epilepsy surgery has been practiced since 2000. Up to 1st November 2017 263 surgeries in 232 patients have beenperformed. This article aims to summarize essential principles both epilepsy surgery and preoperative diagnostic work-up as wellas results of our paediatric epilepsy surgery programme including recent trends. 80,7 % children in our series are seizure-free at 2year follow-up. Candidates undergoing early surgery have better chance gaining both seizure and AED freedom and (in children)their cognitive potential is more likely to be preserved.

• MeSH
• dítě MeSH
• epilepsie diagnostické zobrazování   epidemiologie   farmakoterapie   chirurgie   MeSH
• křeče u dětí diagnostické zobrazování   etiologie   chirurgie   MeSH
• lidé MeSH
• mladiství MeSH
• neurochirurgické výkony metody   statistika a číselné údaje   škodlivé účinky   MeSH
• neurozobrazování metody   statistika a číselné údaje   škodlivé účinky   MeSH
• refrakterní epilepsie * diagnostické zobrazování   epidemiologie   chirurgie   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH