To identify the neurocognitive mechanisms underpinning the social difficulties that characterize autism, we performed functional magnetic resonance imaging on pairs of autistic and non-autistic adults simultaneously whilst they interacted with one another on the iterated Ultimatum Game (iUG)-an interactive task that emulates the reciprocal characteristic of naturalistic interpersonal exchanges. Two age-matched sets of male-male dyads were investigated: 16 comprised an autistic Responder and a non-autistic Proposer, and 19 comprised non-autistic pairs of Responder and Proposer. Players' round-by-round behavior on the iUG was modeled as reciprocal choices, and dynamic functional connectivity (dFC) was measured to identify the neural mechanisms underpinning reciprocal behaviors. Behavioral expressions of reciprocity were significantly reduced in autistic compared with non-autistic Responders, yet no such differences were observed between the non-autistic Proposers in either set of dyads. Furthermore, we identified latent dFC states with temporal properties associated with reciprocity. Autistic interactants spent less time in brain states characterized by dynamic inter-network integration and segregation among the Default Mode Network and cognitive control networks, suggesting that their reduced expressions of social-emotional reciprocity reflect less efficient reconfigurations among brain networks supporting flexible cognition and behavior. These findings advance our mechanistic understanding of the social difficulties characterizing autism.

• Klíčová slova
• autism, dynamic functional connectivity, reciprocity, social interaction,
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• adaptace psychologická * MeSH
• COVID-19 * psychologie   epidemiologie   MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• osoby pečující o pacienty psychologie   MeSH
• pandemie MeSH
• poruchy autistického spektra * psychologie   MeSH
• předškolní dítě MeSH
• průzkumy a dotazníky MeSH
• psychický stres * psychologie   MeSH
• rodiče * psychologie   MeSH
• SARS-CoV-2 MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The COVID-19 pandemic revealed the need to develop the field of remote assessment for autism spectrum disorders (ASD). The purpose of the study was to evaluate an online assessment protocol that includes the Brief Observation of Symptoms of Autism (BOSA). The online protocol consisting of BOSA and the Autism Diagnostic Interview-Revised (ADI-R) was administered by experienced examiners to 29 children with suspected ASD. The participants were then evaluated by clinical psychologists in a standard clinical setting using the Autism Diagnostic Observation Schedule-2 (ADOS-2) and other methods, and the ASD diagnosis was confirmed or ruled out. The results show substantial to moderate inter-rater agreement between the online and face-to-face raters with the value of Cohen's Kappa = 0.66 (P < 0.001); this corresponds with 79.8% agreement. The sensitivity of the protocol was approx. 94.7%, the specificity was 70%, the positive predictive value was 85.7%, and the negative predictive value was 87.5%. Further, direct false positive or false negative diagnostic conclusions based on the online protocol were absent when the possible conclusion of "I cannot decide" was included. The items B9 Showing, B10 Spontaneous Initiation of Joint Attention, B1 Unusual Eye Contact, B3 Facial Expressions Directed to Others, and C2 Imagination/Creativity were shown to be well observable in BOSA when related to ADOS-2 scoring. The results indicate that the protocol consisting of BOSA and ADI-R administered by an experienced examiner is a promising combination of tools for remote autism assessment.

• Klíčová slova
• Assessment tools, Autism, Autism assessment, Autism spectrum disorders, Neurodevelopmental disorders, Psychodiagnostics, Telehealth, Telehealth assessment,
• Publikační typ
• časopisecké články MeSH

Limb girdle muscular dystrophies (LGMD) are a genetically heterogeneous group of muscular dystrophies. The study presents an overview of molecular characteristics of a large cohort of LGMD patients who are representative of the Czech LGMD population. We present 226 LGMD probands in which 433 mutant alleles carrying 157 different variants with a supposed pathogenic effect were identified. Fifty-four variants have been described only in the Czech LGMD population so far. LGMD R1 caplain3-related is the most frequent subtype of LGMD involving 53.1% of patients with genetically confirmed LGMD, followed by LGMD R9 FKRP-related (11.1%), and LGMD R12 anoctamin5-related (7.1%). If we consider identified variants, then all but five were small-scale variants. One large gene deletion was identified in the LAMA2 gene and two deletions in each of CAPN3 and SGCG. We performed comparison our result with other published studies. The results obtained in the Czech LGMD population clearly differ from the outcome of other LGMD populations in two aspects-we have a more significant proportion of patients with LGMD R1 calpain3-related and a smaller proportion of LGMD R2 dysferlin-related.

• Klíčová slova
• LGMD, genetic diagnostics, limb girdle muscular dystrophy, next generation sequencing,
• Publikační typ
• časopisecké články MeSH

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 (pFWE < 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 (pFWE < 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.

• MeSH
• deficit železa * MeSH
• febrilní křeče * diagnóza   etiologie   MeSH
• horečka komplikace   MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• studie případů a kontrol MeSH
• železo MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• železo MeSH

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 pharmacoresistant patients and 4 pharmacodependent patients to 9 controls. We analyzed the ProcartaPlex™ 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-α), and chemokine (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 assessment 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.

• Klíčová slova
• Chemokine, Cytokine, Epileptogenesis, Interleukin, Pharmacodependent, Pharmacoresistant,
• MeSH
• biologické markery mozkomíšní mok   MeSH
• chemokin CCL2 * mozkomíšní mok   MeSH
• chemokin CX3CL1 MeSH
• epilepsie * diagnóza   farmakoterapie   MeSH
• interleukin-8 mozkomíšní mok   MeSH
• lidé MeSH
• neurozánětlivé nemoci MeSH
• průřezové studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• CCL2 protein, human MeSH Prohlížeč
• chemokin CCL2 * MeSH
• chemokin CX3CL1 MeSH
• interleukin-8 MeSH

This work presents a case series of four children diagnosed with severe cerebrovascular disease in association with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet no patient from the group met typical diagnostic criteria for multisystem inflammatory syndrome in children. Our aim was to highlight the possible vascular involvement and coagulopathies associated with SARS-CoV-2 infection in the pediatric population. Further data are needed to better understand the pathophysiological basis of this condition in children and to ensure its optimal management.

• Klíčová slova
• Brain vasculopathy, COVID-19, Children, SARS-CoV-2, Stroke,
• MeSH
• COVID-19 * komplikace   MeSH
• dítě MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• syndrom systémové zánětlivé reakce MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• Children, Epilepsy, Genetic testing, Next-generation sequencing, Precise medicine,
• 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

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-1β, IL-6, IL-10, IL-18, CCL2, CCL3, CCL4, and STAT3, was carried out by qRT-PCR methodology. RESULTS: Upregulation of IL-1β (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.

• Klíčová slova
• Chemokine, Cytokine, Epileptogenesis, Hippocampal sclerosis, Immune response, Interleukin, Pharmaco-resistant, Temporal lobe epilepsy,
• MeSH
• chemokiny metabolismus   MeSH
• cytokiny metabolismus   MeSH
• epilepsie temporálního laloku * komplikace   MeSH
• hipokampus patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• skleróza patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokiny MeSH
• cytokiny MeSH

Although many new antiseizure drugs have been developed in the past decade, approximately 30%-40% of patients remain pharmacoresistant. There are no clinical tools or guidelines for predicting therapeutic response in individual patients, leaving them no choice other than to try all antiseizure drugs available as they suffer debilitating seizures with no relief. The discovery of predictive biomarkers and early identification of pharmacoresistant patients is of the highest priority in this group. MicroRNAs (miRNAs), a class of short noncoding RNAs negatively regulating gene expression, have emerged in recent years in epilepsy, following a broader trend of their exploitation as biomarkers of various complex human diseases. We performed a systematic search of the PubMed database for original research articles focused on miRNA expression level profiling in patients with drug-resistant epilepsy or drug-resistant precilinical models and cell cultures. In this review, we summarize 17 publications concerning miRNAs as potential new biomarkers of resistance to antiseizure drugs and their potential role in the development of drug resistance or epilepsy. Although numerous knowledge gaps need to be filled and reviewed, and articles share some study design pitfalls, several miRNAs dysregulated in brain tissue and blood serum were identified independently by more than one paper. These results suggest a unique opportunity for disease monitoring and personalized therapeutic management in the future.

• Klíčová slova
• biomarkers, drug-resistant epilepsy, intractable epilepsy, noncoding RNA, refractory epilepsy,
• MeSH
• antikonvulziva farmakologie   terapeutické užití   MeSH
• biologické markery MeSH
• epilepsie * farmakoterapie   genetika   MeSH
• léková rezistence genetika   MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• refrakterní epilepsie * farmakoterapie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antikonvulziva MeSH
• biologické markery MeSH
• mikro RNA * MeSH