Focal cortical dysplasia (FCD) represents the most common cause of drug-resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug-resistant epilepsy evolving in super-refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood- and brain-derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole-exome sequencing of blood-derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection-induced acute necrotizing encephalopathy. No combination of anti-seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high-dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right-sided hemispherotomy that rendered the patient temporarily seizure-free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant. PLAIN LANGUAGE SUMMARY: We report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life-threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient.
- MeSH
- dítě MeSH
- DNA MeSH
- epilepsie * komplikace MeSH
- fokální kortikální dysplazie * MeSH
- komplex proteinů jaderného póru * MeSH
- lidé MeSH
- midazolam MeSH
- molekulární chaperony * MeSH
- nemoci mozku * MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- refrakterní epilepsie * genetika chirurgie MeSH
- status epilepticus * genetika chirurgie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Syndrom Dravetové je závažnou vývojovou a epileptickou encefalopatií se začátkem v kojeneckém věku, která se projevuje farmakorezistentní epilepsií a četnými komorbiditami. Typická je provokace záchvatů zvýšenou teplotou. Léčba onemocnění je obtížná. V chronické medikaci by měl být první volbou valproát, dalšími přidanými léky klobazam, stiripentol, fenfluramin, kanabidiol, topiramát. Pacienti musí být vybaveni SOS medikací pro zvládnutí záchvatů v domácím prostředí. V léčbě je nutné se vyhnout blokátorům sodíkových kanálů, aplikace fenytoinu v epileptickém statu je však přípustná. Kromě protizáchvatové léčby je nutné věnovat pozornost i nefarmakologické léčbě komorbidit.
Dravet syndrome is a developmental and epileptic encephalopathy starting in infancy and its main features are drug -resistant epilepsy and several co-morbidities. Seizures are typically provoked by increased temperature. The treatment of Dravet syndrome is challenging. The first antiseizure drug should be valproic acid, while clobazam, stiripentol, fenfluramine, canabidiol or topiramate are usually added later. All the patients must have rescue medication for home management of seizures. Sodium channel blockers should not be used for chronic treatment, but phenytoin can be administered to stop status epilepticus. Non-pharmacological treatment of co-morbidities should be addressed as well.
- Klíčová slova
- stiripentol, fenfluramin,
- MeSH
- dioxolany aplikace a dávkování farmakologie terapeutické užití MeSH
- epilepsie myoklonické * farmakoterapie patologie MeSH
- kanabidiol aplikace a dávkování farmakologie terapeutické užití MeSH
- klobazam aplikace a dávkování farmakologie terapeutické užití MeSH
- komorbidita MeSH
- kyselina valproová aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- selektivní inhibitory zpětného vychytávání serotoninu aplikace a dávkování farmakologie terapeutické užití MeSH
- topiramat aplikace a dávkování farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
Tato případová studie se zaměřuje na dlouhodobé kognitivní důsledky epilepsie temporálního laloku (temporal lobe epilepsy; TLE) v dětském věku a jejich ovlivnění chirurgickou léčbou. Studie sleduje čtyři dětské pacienty s TLE, kteří v Centru pro epilepsie Motol podstoupili úspěšný resekční epileptochirurgický výkon. Ačkoli je standardním měřítkem úspěchu epileptochirurgie pooperační kompenzace záchvatů, snížení množství medikace a zlepšená kvalita života, naše práce zdůrazňuje také význam sledování celkového neuropsychologického profilu a poskytování další klinicko--psychologické péče. Samotné sledování inteligenční výkonnosti je pro plné pochopení kognitivního vývoje po epileptochirurgii nedostatečné. U námi referovaných případů jsme v dlouhodobém horizontu zdokumentovali postupnou konsolidaci kognitivních funkcí. Pro dosažení celkově příznivého výsledku epileptochirurgie jsou klíčové komplexní péče, mezioborová spolupráce a časná indikace k epileptochirurgii. Včasné referování farmakorezistentních pacientů do specializovaných center a brzká efektivní terapie epileptických záchvatů jsou zásadní pro předcházení dlouhodobým negativním důsledkům neléčené epilepsie, vč. kognitivních obtíží a psychosociálních problémů. Zároveň je však nezbytný další výzkum v oblasti neuropsychologie TLE u dětí a vývoj efektivnějších strategií léčby a podpory pro tyto pacienty a jejich rodiny.
This case study focuses on the long-term cognitive sequelae of temporal lobe epilepsy (TLE) in childhood and their influence by surgical treatment. The study follows four pediatric patients with TLE who underwent successful resectional epilepsy surgery at the Motol Epilepsy Center. While the standard measure of success of epilepsy surgery is postoperative seizure cessation, reduced medication, and improved quality of life, our study also underscores the importance of monitoring the overall neuropsychological profile and providing additional clinical-psychological care. Monitoring of intelligence performance alone is insufficient to fully understand cognitive development after epilepsy surgery. In the cases reported, we documented a gradual consolidation of cognitive functions over time. Comprehensive care, interdisciplinary collaboration, and early indication for epilepsy surgery are crucial to achieve an overall favorable outcome. Early referral of pharmacoresistant patients to specialized centers and prompt effective treatment of epileptic seizures are essential to prevent long-term negative consequences of untreated epilepsy, including cognitive difficulties and psychosocial problems. Simultaneously, further research into the neuropsychology of TLE in children and the development of more effective treatment and support strategies for these patients and their families are essential.
- MeSH
- dítě MeSH
- epilepsie temporálního laloku * chirurgie diagnóza etiologie patologie MeSH
- fokální kortikální dysplazie chirurgie diagnóza patologie MeSH
- kognice * MeSH
- lidé MeSH
- nádory mozku chirurgie diagnóza patologie MeSH
- neurochirurgické výkony metody MeSH
- přední temporální lobektomie MeSH
- refrakterní epilepsie chirurgie diagnóza etiologie patologie MeSH
- vývoj dítěte MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
Antagonistic activity of brain networks likely plays a fundamental role in how the brain optimizes its performance by efficient allocation of computational resources. A prominent example involves externally/internally oriented attention tasks, implicating two anticorrelated, intrinsic brain networks: the default mode network (DMN) and the dorsal attention network (DAN). To elucidate electrophysiological underpinnings and causal interplay during attention switching, we recorded intracranial EEG (iEEG) from 25 epilepsy patients with electrode contacts localized in the DMN and DAN. We show antagonistic network dynamics of activation-related changes in high-frequency (> 50 Hz) and low-frequency (< 30 Hz) power. The temporal profile of information flow between the networks estimated by functional connectivity suggests that the activated network inhibits the other one, gating its activity by increasing the amplitude of the low-frequency oscillations. Insights about inter-network communication may have profound implications for various brain disorders in which these dynamics are compromised.
- MeSH
- dospělí MeSH
- elektroencefalografie MeSH
- elektrofyziologické jevy MeSH
- epilepsie patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mozek * fyziologie patofyziologie MeSH
- nervová síť * fyziologie MeSH
- pozornost * fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Cílem této práce bylo zjistit distribuci a rozsah péče o děti s podezřením na získaný demyelinizační syndrom (zahrnující akutní diseminovanou encefalomyelitidu, klinicky izolovaný syndrom, roztroušenou sklerózu a okruh neuromyelitis optica) a identifikovat oblasti ke zkvalitnění péče v ČR. Soubor a metodika: Elektronické dotazníkové šetření na všech lůžkových pracovištích dětské neurologie (n = 7) a pediatrie (n = 22) na úrovni krajů a fakultních nemocnic. Odpovědi jsme získali ze všech oslovených nemocnic. Výsledky: Na péči se podílí všech sedm pracovišť dětské neurologie a deset pediatrií. Všichni disponují potřebnými diagnostickými možnostmi, alw terapeutické možnosti se liší. Identifikovali jsme konkrétní rozdíly v diagnostickém přístupu – v indikaci a interpretaci vyšetření a ve využití aktuálních diagnostických kritérií. V šesti krajích je péče primárně směřována na lůžka dětské neurologie, v ostatních osmi krajích na lůžka pediatrická s konziliárním dětským neurologem. Složitější případy jsou překládány na dětské neurologie, kde je diagnostický přístup komplexnější a terapeutické možnosti rozsáhlejší. Závěr: Péče o děti se získaným demyelinizačním syndromem je v ČR na vysoké úrovni, ale není standardizována. Nejlépe zajištěná onemocnění jsou RS a okruh neuromyelitis optica, pro která fungují centra vysoce specializované péče. Vzhledem k distribuci péče musí specializovaná edukace cílit i na pediatry a konziliární dětské neurology.
Aim: The aim of this study was to investigate the distribution and extent of healthcare provided to children with a suspected acquired demyelinating syndrome (including acute disseminated encephalomyelitis, clinically isolated syndrome, multiple sclerosis and neuromyelitis optica spectrum disorder) and to identify areas for care improvement in the Czech Republic. Patients and methodology: Electronic questionnaire survey at all inpatient departments of pediatric neurology (N = 7) and pediatric departments (N = 22) at the regional and university hospital level. Responses were obtained from all contacted hospitals. Results: All inpatient departments of pediatric neurology and 10 pediatric departments are involved in the care of patients. All have the necessary diagnostic methods available, but therapeutic options differ. We identified specific differences in the diagnostic approach -in the indication and interpretation of examinations and in the use of current diagnostic criteria. In six regions, care is provided primarily by departments of pediatric neurology. In the remaining eight regions, patients are admitted to pediatric departments with an available pediatric neurology consultant. More complex cases are transferred to pediatric neurology departments, where the diagnostic approach is more comprehensive and the therapeutic options are more extensive. Conclusion: In the Czech Republic, healthcare for children with an acquired demyelinating syndrome is at a high level, but it is not standardized. The most appropriate standard of care is provided in specialized care centers for multiple sclerosis and neuromyelitis optica spectrum disorders. Given the distribution of care, specialized education must also include pediatricians and pediatric neurology consultants.
- MeSH
- demyelinizační nemoci * terapie MeSH
- dítě MeSH
- lidé MeSH
- management nemoci MeSH
- management péče o pacienta * organizace a řízení MeSH
- neuromyelitis optica terapie MeSH
- průzkumy a dotazníky MeSH
- roztroušená skleróza terapie MeSH
- terciární prevence organizace a řízení MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
This study presents an in-depth analysis of mitochondrial enzyme activities in Friedreich's ataxia (FA) patients, focusing on the Electron Transport Chain complexes I, II, and IV, the Krebs Cycle enzyme Citrate Synthase, and Coenzyme Q10 levels. It examines a cohort of 34 FA patients, comparing their mitochondrial enzyme activities and clinical parameters, including disease duration and cardiac markers, with those of 17 healthy controls. The findings reveal marked reductions in complexes II and, specifically, IV, highlighting mitochondrial impairment in FA. Additionally, elevated Neurofilament Light Chain levels and cardiomarkers were observed in FA patients. This research enhances our understanding of FA pathophysiology and suggests potential biomarkers for monitoring disease progression. The study underscores the need for further clinical trials to validate these findings, emphasizing the critical role of mitochondrial dysfunction in FA assessment and treatment.
- MeSH
- biologické markery * metabolismus MeSH
- citrátsynthasa metabolismus MeSH
- dospělí MeSH
- Friedreichova ataxie * diagnóza MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondrie metabolismus MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ubichinon * analogy a deriváty 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
BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.
- MeSH
- elektroencefalografie MeSH
- epilepsie parciální * diagnostické zobrazování chirurgie MeSH
- epilepsie temporálního laloku * chirurgie MeSH
- epilepsie * diagnostické zobrazování chirurgie MeSH
- kohortové studie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- záchvaty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
Fetal intracranial hemorrhage represents a rare event with an estimated prevalence of 1:10 000 pregnancies. We report a patient diagnosed prenatally with intracranial hemorrhage and ventriculomegaly carrying a novel, previously unreported, likely pathogenic variant in COL4A1. At the gestational age of 27 weeks, dilation of lateral ventricles was detected during a routine prenatal ultrasound scan, confirmed by prenatal MRI at 30 + 3 weeks of gestation. Prenatal examinations included amniocentesis with conventional G-band karyotyping and arrayCGH, and maternal testing for TORCH and parvovirus B19 infections. Virtual gene panel based on whole-exome sequencing data was performed postnatally. At the age of 2.5 months, the patient manifested epileptic seizures that remain difficult to control. Postnatal MRI showed partial thalamic fusion and polymicrogyria, in addition to severe enlargement of lateral ventricles, multiple deposits of hemosiderin in cerebral and cerebellar hemispheres, and thin optic nerve and chiasma. Virtual gene panel based on whole-exome sequencing data led to a detection of a de novo previously unreported in-frame deletion NM_001845.5:c.4688_4711del in COL4A1 located in the highly conserved NC1 domain initiating collagen helix assembly. The presented case lies one a more severe end of the COL4A1 mutation-related disease spectrum, manifesting as fetal intracranial bleeding, malformation of cortical development, drug-resistant epilepsy, and developmental delay.
- MeSH
- hydrocefalus * MeSH
- intrakraniální krvácení MeSH
- kojenec MeSH
- kolagen typu IV genetika MeSH
- lidé MeSH
- mutace MeSH
- plod MeSH
- polymikrogyrie * genetika MeSH
- těhotenství MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a group of severe, early-onset epilepsies characterised by refractory seizures, developmental delay, or regression and generally poor prognosis. DEE are now known to have an identifiable molecular genetic basis and are usually examined using a gene panel. However, for many patients, the genetic cause has still not been identified. The aims of this study were to identify causal variants for DEE in patients for whom the previous examination with a gene panel did not determine their genetic diagnosis. It also aims for a detailed description and broadening of the phenotypic spectrum of several rare DEEs. METHODS: In the last five years (2015-2020), 141 patients from all over the Czech Republic were referred to our department for genetic testing in association with their diagnosis of epilepsy. All patients underwent custom-designed gene panel testing prior to enrolment into the study, and their results were inconclusive. We opted for whole exome sequencing (WES) to identify the cause of their disorder. If a causal or potentially causal variant was identified, we performed a detailed clinical evaluation and phenotype-genotype correlation study to better describe the specific rare subtypes. RESULTS: Explanatory causative variants were detected in 20 patients (14%), likely pathogenic variants that explain the epilepsy in 5 patients (3.5%) and likely pathogenic variants that do not fully explain the epilepsy in 11 patients (7.5%), and variants in candidate genes in 4 patients (3%). Variants were mostly de novo 29/40 (72.5%). SIGNIFICANCE: WES enables us to identify the cause of the disease in additional patients, even after gene panel testing. It is very important to perform a WES in DEE patients as soon as possible, since it will spare the patients and their families many years of a diagnostic odyssey. In particular, patients with rare epilepsies might significantly benefit from this approach, and we propose using WES as a new standard in the diagnosis of DEE instead of targeted gene panel testing.
- MeSH
- epilepsie generalizovaná * genetika MeSH
- epilepsie * diagnóza genetika MeSH
- fenotyp MeSH
- genetické asociační studie MeSH
- genetické testování MeSH
- lidé MeSH
- sekvenování exomu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
