Background Febrile seizures are the most common type of convulsions in children. Fever is induced by cytokines release during infection. Recent studies focusing on the identification of a possible role of cytokines in pathogenesis of febrile seizures have contributed conflicting results. Moreover, most of these studies investigated only a few cytokines, such as IL-1β, IL-6 and TNFα. The aim of this study was to investigate multiple cytokine-chemokine profiles that could be potentially associated with the development of febrile seizures. Methods Twenty-four febrile seizure cases (febrile seizure group) and two matched control groups were included in this study. Children with febrile illness without convulsion (febrile control group) and children without seizures and without fever (healthy control group) served as control groups. We investigated serum levels of IL-1β, IL-6, IL-8, IL-10, IL-18, CXCL10/IP-10, CCL2/MCP-1, CXCL13/BLC, TNFα, and fractalkine/CXC3CL1 in all children included in the study. Results The analysis of serum samples revealed a significant elevation of IL-6 (p = 0.0042) in the FS group compared to the febrile controls. Significantly higher levels of cytokines were also found in the FS group compared to healthy controls in IL-10 (p = 0.0039), TNFα (p = 0.0091) and MCP-1 (p = 0.0039). Conclusion Our study supports the hypothesis that IL-6 is involved in the pathogenesis of febrile seizures. We supposed that IL-6 could become a potential biomarker of the development of febrile seizures in children with febrile disease. This knowledge could be used in clinical practice to identify children at risk of developing of febrile convulsions.

INTRODUCTION:Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication, social interaction, and repetitive behavior. The declaration of the COVID-19 pandemic in March 2020 resulted in significant changes in daily life due to restrictive measures. This period posed particular challenges for families with children living with autism, given the limitations in medical care and social services. OBJECTIVE:This study aimed to understand how families with autistic children perceive stress during the pandemic and the coping strategies employed in unexpected situations. METHOD:A total of 44 families with children with ASD and 300 control families, including 44 control families in a matched subsample, were included in the study. To assess stress and parental coping with COVID-19-related stress, the Responses to Stress Questionnaire (Adult Self-Report RSQ-COVID-19) was utilized. RESULTS:Caregivers of autistic children experienced significantly higher stress levels (p = .027, d = 0.479) during the pandemic, with notable stressors such as limited access to medical care and challenges associated with remote work. Despite expectations, coping strategy differences were not statistically significant. CONCLUSION:Families and supporters of children with autism naturally encounter various experiences and challenges stemming from their additional needs. Our study's results highlight an accentuation of stress during challenging situations. As these situations may recur in the future, there is a need to design and implement support plans for these families, appropriate intervention programs, and preparations for the utilization of telemedicine tools.

Our goal was to identify highly accurate empirical models for the prediction of the risk of febrile seizure (FS) and FS recurrence. In a prospective, three-arm, case–control study, we enrolled 162 children (age 25.8 ± 17.1 months old, 71 females). Participants formed one case group (patients with FS) and two control groups (febrile patients without seizures and healthy controls). The impact of blood iron status, peak body temperature, and participants’ demographics on FS risk and recurrence was investigated with univariate and multivariate statistics. Serum iron concentration, iron saturation, and unsaturated iron-binding capacity differed between the three investigated groups (p FWE < 0.05). These serum analytes were key variables in the design of novel multivariate linear mixture models. The models classified FS risk with higher accuracy than univariate approaches. The designed bi-linear classifier achieved a sensitivity/specificity of 82%/89% and was closest to the gold-standard classifier. A multivariate model assessing FS recurrence provided a difference (p FWE < 0.05) with a separating sensitivity/specificity of 72%/69%. Iron deficiency, height percentile, and age were significant FS risk factors. In addition, height percentile and hemoglobin concentration were linked to FS recurrence. Novel multivariate models utilizing blood iron status and demographic variables predicted FS risk and recurrence among infants and young children with fever.

Objective: The pathophysiological processes leading to epileptogenesis and pharmacoresistance in epilepsy have been the subject of extensive preclinical and clinical research. The main impact on clinical practice is the development of new targeted therapies for epilepsy. We studied the importance of neuroinflammation in the development of epileptogenesis and pharmacoresistance in childhood epilepsy patients.Methods: A cross-sectional study conducted at two epilepsy centers in the Czech Republic compared 22 phar-macoresistant patients and 4 pharmacodependent patients to 9 controls. We analyzed the ProcartaPlexTM 9-Plex immunoassay panel consisting of interleukin (IL)-6, IL-8, IL-10, IL-18, CXCL10/IP-10, monocyte chemoattractant protein 1 (CCL2/MCP-1), B lymphocyte chemoattractant (BLC), tumor necrosis factor-alpha (TNF-& alpha;), and che-mokine (C-X3-X motif) ligand 1 (fractalkine/CXC3CL1) to determine their alterations in cerebrospinal fluid (CSF) and blood plasma, concurrently.Results: The analysis of 21 paired CSF and plasma samples in pharmacoresistant patients compared to controls revealed a significant elevation of CCL2/MCP-1 in CSF (p < 0.000512) and plasma (p < 0.00.017). Higher levels of fractalkine/CXC3CL1 were revealed in the plasma of pharmacoresistant patients than in controls (p < 0.0704), and we determined an upward trend in CSF IL-8 levels (p < 0.08). No significant differences in CSF and plasma levels were detected between pharmacodependent patients and controls.Conclusion: Elevated CCL2/MCP-1 in CSF and plasma, elevated levels of fractalkine/CXC3CL1 in CSF, and a trend toward elevated IL-8 in the CSF of patients with pharmacoresistant epilepsy indicate these cytokines as potential biomarkers of epileptogenesis and pharmacoresistance. CCL2/MCP-1was detected in blood plasma; this assess-ment may be easily achieved in clinical practice without the invasiveness of a spinal tap. However, due to the complexity of neuroinflammation in epilepsy, further studies are warranted to confirm our findings.

with the Dravet's syndrome phenotype are associated with the detection of a sequence variant in the SCN1A gene (alpha 1 subunit of the voltage-gated sodium channel) (2). However, sequence variants in the SCN1A gene are associated with a very broad clinical spectrum, from asymptomatic carriers to the severe myoclonic epilepsy phenotype with severe disease (3).In the presented work, we retrospectively evaluated a group of 6 patients of the Department of Pediatric Neurology of the Medical Faculty of Masaryk University and the University Hospital in Brno with a proven missense mutation. Based on the specific pathogenic sequence variant, we correlated the patient's phenotype with the location of the sequence variant in the SCN1A gene. The aim of the analysis was to verify the extent, to which the storage of a pathogenic sequence variant in the SCN1A gene corresponds to the clinical picture of the patient (Tab. 2, Fig. 2, Ref. 10). Keywords: Dravet's syndrome, sodium channel, functional analysis, prognosis.

Purpose: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common drug-resistant epilepsy. Despite major advances in epilepsy research, the epileptogenesis of the MTLE-HS is not well understood. The altered neuroimmune response is one of the pathomechanisms linked to progressive epileptogenesis in MTLE-HS, and understanding its role may help design future cures for pharmaco-resistant MTLE-HS. Here, the neuroimmune function was evaluated by the assessment of cytokine-chemokine profiles in brain samples from the hippocampus of patients with MTLE-HS. Methods: Brain samples from patients with MTLE-HS collected during epileptosurgical resection (n = 21) were compared to those obtained from autopsy controls (n = 13). The typing of HS was performed according to ILAE consensus classification, and patients were additionally sorted into subgroups based on the severity of neuronal depletion (Wyler grading system). Differences between patients with MTLE-HS with and without a history of febrile seizures were also assessed. RNA was isolated from native samples, and real-time gene expression analysis of cytokine-chemokine profiles, i.e., levels of IL-1 beta, IL-6, IL-10, IL-18, CCL2, CCL3, CCL4, and STAT3, was carried out by qRT-PCR methodology. Results: Upregulation of IL-1 beta (p = 0.001), IL-18 (p = 0.0018), CCL2 (p = 0,0377), CCL3 (p < 0.001), and CCL4 (p < 0.001) in MTLE-HS patients was detected when compared to the post-mortem hippocampal samples collected from autopsy controls. The STAT3 expression was higher in more severe neuronal loss and glial scaring determined by different Wyler grades in HS patients. Furthermore, cytokine-chemokine profiles were not different in MTLE-HS patients with or without febrile seizures. Conclusion: The upregulation of specific cytokines and chemokines in MTLE-HS provides evidence that the neuroinflammatory process contributes to MTLE epileptogenesis. History of febrile seizures did not alter the immune profiles. Specific immune mediators and related immune pathways represent potential therapeutic targets for seizure control and pharmacoresistancy prevention in MTLE associated with hippocampal sclerosis.

The objective of this study was to estimate the direct cost before and after diagnosis assessment in patients with Dravet's syndrome (DS). The basis of the economic study was to calculate the costs of health care before and after diagnosis of DS. We retrospectively evaluated all SCN1A positive patients with phenotype of DS treated in our hospital. Statistical analyses were performed by IBM SPSS Statistics 24.0 software. After the diagnosis of DS, there was a significant decline of health care costs (-85.6%) an average of Euro29.4 +/- 26.1 monthly per patient. We estimated the monthly costs at Euro204.5 +/- 167 (median: Euro193.9, range: Euro35.5-534.4) per patient before DS diagnosis. The major cost was for hospitalization in neurological department: Euro43.3 +/- 52 (median: Euro21.9, range: Euro9.5-179.4) per patient. Minimal cost per patient per months before DS diagnosis was cost of psychological testing/care and complementary rehabilitation (0.13 and 0.6% of total cost). After DS diagnosis, the major cost was focused on nonhospitalization care of patients (64.8%), minimal (Euro0) for genetic testing and major for outpatient care (18%, mean: Euro5.3, median: Euro7). DS results in essential health care utilization and high financial burden before diagnosis elucidation caused by repeated hospitalization and extensive diagnostics tests of "epileptic encephalopathy of unknown etiology." The results of this study point out that early assessment of the diagnosis leads to significant decrease of the financial costs because of adequate therapeutic management and exclusion of redundant diagnostic testing after elucidation of correct diagnosis.

Novorozenecke obdobi představuje nejvulnerabilnějsi periodu pro rozvoj epileptických paroxysmů. Zasadnim predisponujicim faktorem je zvýsena neuronalni excitabilita plynouci z nedokoncene maturace nezraleho mozku. Z tohoto pohledu jsou nejrizikovějsi skupinou pro vznik novorozeneckých zachvatů nedonoseni novorozenci. Vcasne zahajeni racionalnich dia­gnosticko-terapeutických intervenci mnohdy komplikuje vagni až absentni klinicka manifestace novorozeneckých zachvatů. Variabilitu jejich klinickeho obrazu reflektuje nova klasifikace novorozeneckých zachvatů dle Mezinarodni ligy proti epilepsii (International League Against Epilepsy; ILAE) z roku 2018. Vcasne stanoveni dia­gnozy a zahajeni adekvatni terapie s ohledem na etiologii je z prognostickeho hlediska stěžejni. Nejsilnějsim prognostickým prediktorem je etiologie, dale pak gestacni staři, vstupni nalez při neurologickem vysetřeni a EEG iktalni a interiktalni charakteristiky.

Předkladane ucebni texty „Zaklady vývojove neurologie“ podavaji přehledným způsobem zakladni poznatky z vývojove neurologie. Text je cleněn do 8 kapitol, ktere ctenaře postupně převedou přes zaklady vývoje nervoveho systemu, vývojovou reflexologii, zakladni milniky psychomotorickeho vývoje i neuro-vývojove vysetřeni novorozence a kojence. Samostatne kapitoly jsou dale věnovany patologickým vývojovým syndromům, psychomotoricke retardaci a vývojove rehabilitaci. Věřime, že studentům LF MU i lekařům v předatestacni připravě pomohou nacerpat nove znalosti z vývojove neurologie.

Zanět mozku představuje jeden z hlavnich substratů farmakorezistentni epilepsie různe etiologie a může přimo ovlivnit neuronalni excitabilitu. Neuromodulacni schopnosti ně­kte­rých prozanětlivých molekul (cytokinů, chemokinů) mohou být odpovědne za hyperexcitabilitu v neuronalnich sitich. Vztah zanětu a epilepsie je reciprocni. Zanětlive procesy v mozku se mohou ucastnit na spoustěni zachvatove aktivity a zaroveň mohou být nasledkem pokracujicich zachvatů. Farmakologicke studie na zviřecich modelech cilene na systemy IL-1[BETA]/ IL-1R1, HMGB1/ TLR4 a COX-2/ prostaglandiny prokazuji, že tyto zanětlive kaskady maji významný podil na spoustěni a opakovani zachvatove aktivity. Status epilepticus (SE) vede k rozvoji zanětlivých procesů, ktere mohou být detekovany v mozkove tkani, mozkomisnim moku i seru. Prolongovane zachvaty a SE vedou k rychle a dlouhotrvajici aktivaci specifických zanětlivých kaskad v těch oblastech mozku, ktere odpovidaji epileptogenni zoně. Pochopeni komplexni role zanětu při vzniku a exacerbaci epilepsie a rozvoji farmakorezistence je zasadnim předpokladem možnosti identifikace nových molekularnich cilů, ktere by se mohly uplatnit v lecbě těchto pacientů.

Purpose: Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by focal seizures with dominant auditory symptomatology. We present a case report of an 18-year-old patient with acute onset of seizures associated with epilepsy. Based on the clinical course of the disease and the results of the investigation, the diagnosis of ADLTE with a proven mutation in the RELN gene, which is considered causative, was subsequently confirmed. The aim of this study was to use 3 Tesla (3 T) magnetic resonance imaging (MRI) and advanced neuroimaging methods in a patient with a confirmed diagnosis of ADTLE. Methods: 3 T MRI brain scan and advanced neuroimaging methods were used in the standard protocols to analyzse voxel-based MRI, cortical thickness, and functional connectivity. Results: Morphometric MRI analysis (blurred grey-white matter. junctions. voxel-based morphometty, and cortical thickness analysis) did not provide any informative results. The functional connectivity analysis revealed higher local synchrony in the patient in the left temporal ( middle temporal gyrus), left frontal (supplementary motor area, superior frontal gyrus), and left parietal (gyrus angularis, gyms supramarginalis) regions and the cingulate (middle cingulate gyrus) as compared to healthy controls. Conclusions: Evidence of multiple areas of functional connectivity supports the theory of epileptogenic networks in ADTLE. Further studies are needed to elucidate this theory. (C) 2018 The Authors. Published by Elsevier Inc.

Poruchy autistickeho spektra (PAS) se řadi mezi neurovývojove a neuropsychiatricke poruchy s klinickou manifestaci v dětskem věku. V poslednich letech se tato porucha dostava do popředi vědeckeho zajmu, a to předevsim z důvodu narůstajici prevalence až na 1/68 v roce 2014. Odhaluji se geneticke přiciny poruchy a patofyziologicke mechanismy, ktere by se na rozvoji PAS mohly podilet. Komorbidni výskyt s epilepsii je poměrně castý, a to až ve 46% připadů. Prace shrnuje dosavadni poznatky v teto oblasti se zaměřenim na hypotezu excitacně-inhibicni nerovnovahy. Jsou probrany i geneticke přiciny PAS a patofyziologie komorbidniho výskytu PAS a epilepsie je diskutovana z pohledu možných terapeutických intervenci.

Generalizovaný konvulzivni status epilepticus (GCSE) je u děti nejcastějsim emergentnim neurologickým stavem. Jedna se o generalizovaný konvulzivni zachvat trvajici > 5 minut. Kojenecký a zejmena novorozenecký věk představuje nejrizikovějsi obdobi pro rozvoj GCSE. Febrilni status epilepticus je nejcastějsi přicinou. Rozlisuji se 4 stadia GCSE: 1. casný (5–20 minut), 2. rozvinutý (20–40 minut), 3. refrakterni (> 40 minut) a 4. superrefrakterni (> 24 hodin). Generalizovaný konvulzivni zachvat v prvnich pěti minutach býva oznacovan jako hrozici GCSE. Během pěti minut musi být zahajena adekvatni lecba vedouci k terminaci zachvatu. Tato lecba sleduje dvě soucasně probihajici linie: 1. zajistěni vitalnich funkci (podle pravidel A – B – C) a 2. lecbu urcitými antiepileptiky podle stadia GCSE. Soucasně je potřeba řesit přicinu GCSE, je-li zjistěna. Vsechna antiepileptika maji být aplikovana intravenozně. Lekem 1. volby ve fazi casneho GCSE je benzodiazepin: diazepam nebo klonazepam. Pro lecbu 2. volby ve fazi rozvinuteho GCSE mame na výběr jedno z těchto nebenzodiazepinových antiepileptik: fenytoin, kyselina valproova, levetiracetam, eventualně i fenobarbital ci lakosamid. Nedojde-li ke kontrole GCSE, zahajujeme ve fazi refrakterniho GCSE celkovou anestezii jednim ze tři intravenoznich celkových anestetik: midazolam, thiopental, propofol. Celkova anestezie ma trvat 24–48 hodin a jeji hloubka ma být kontinualně monitorovana prostřednictvim EEG. GCSE recidivujici během vyvaděni z > 24 hodin trvajici adekvatni celkove anestezie býva oznacovan jako superrefrakterni a býva spojen s vysokou morbiditou a mortalitou.

Nově vzniklý refrakterni status epilepticus (NORSE- New-onset refractory status epilepticus) je definovan jako status epilepticus, který se rozvinul u pacienta bez aktivni epilepsie nebo jineho neurologickeho onemocněni. Syndrom je charakterizovan refrakternimi epileptickými zachvaty, bez prokazatelne aktivni strukturalni, toxicke nebo metabolicke přiciny. Rozvoji onemocněni ve větsině připadů předchazi mirne febrilni onemocněni. Ve větsině připadů se přicinu NORSE nepodaři prokazat (kryptogenni NORSE). Etiologicky se v mensim procentu upatňuji autoimunitni encefalitidy a virove infekce CNS. Standardni antiepileticka medikace nebýva efektivni. V lecbě se uplatňuje imunoterapie, ketogenni dieta,  resp. dalsi nefarmakologicke možnosti. Dlouhodoba prognoza pacientů je variabilni, ve větsině připadů je přitomno kognitivni postiženi spolecně s epilepsii.

Prezentujeme retrospektivnu analýzu suboru 11 pacientov s Dravetovej syndromom (DS) s preukazanou mutaciou v SCN1A gene (sodium voltage-gated channel alpha subunit 1 – alfa1 podjednotka sodikoveho kanalu). Pacienti boli vysetreni s podozrenim na DS od roku 2010 do februara 2017. Cieľom prace bola analýza epidemiologických a klinických nalezov, ako aj hodnotenie efektivity medikamentoznej terapie a nalezov na MR mozgu a EEG. Zvolenou metodou bola analýza udajov a nalezov v zdravotnickej dokumentacii pacientov s DS s preukazanou mutaciou v SCN1A gene a jeho nasledne statisticke zhodnotenie. Sledovali sme rozvoj ochorenia, pohlavie, typy zachvatových prejavov a ich vekovu vazbu, nalezy na EEG a MR, efekt medikamentoznej terapie. Taktiež sme sa venovali hodnoteniu neurologickeho nalezu a behavioralne-mentalneho statusu pacientov.