A current view of mitochondria damage and the diversity of lipopigment inclusions in neuronal ceroid lipofuscinose type 2 from rectal biopsy.

Neuronal ceroid lipofuscinoses (NCLs) are a growing group of neurodegenerative storage diseases, in which specific features are sought to facilitate the creation of a universal diagnostic algorithm in the future. In our ultrastructural studies, the group of NCLs was represented by the CLN2 disease caused by a defect in the TPP1 gene encoding the enzyme tripeptidyl-peptidase 1. A 3.5-year-old girl was affected by this disease. Due to diagnostic difficulties, the spectrum of clinical, enzymatic, and genetic tests was extended to include analysis of the ultrastructure of cells from a rectal biopsy. The aim of our research was to search for pathognomonic features of CLN2 and to analyse the mitochondrial damage accompanying the disease. In the examined cells of the rectal mucosa, as expected, filamentous deposits of the curvilinear profile (CVP) type were found, which dominated quantitatively. Mixed deposits of the CVP/fingerprint profile (FPP) type were observed less frequently in the examined cells. A form of inclusions of unknown origin, not described so far in CLN2 disease, were wads of osmophilic material (WOMs). They occurred alone or co-formed mixed deposits. In addition, atypically damaged mitochondria were observed in muscularis mucosae. Their deformed cristae had contact with inclusions that looked like CVPs. Considering the confirmed role of the c subunit of the mitochondrial ATP synthase in the formation of filamentous lipopigment deposits in the group of NCLs, we suggest the possible significance of other mitochondrial proteins, such as mitochondrial contact site and cristae organizing system (MICOS), in the formation of these deposits. The presence of WOMs in the context of searching for ultrastructural pathognomonic features in CLN2 disease also requires further research.

SCN1A-Characterization of the Gene's Variants in the Polish Cohort of Patients with Dravet Syndrome: One Center Experience.

The aim of this study was to characterize the genotype and phenotype heterogeneity of patients with SCN1A gene mutations in the Polish population, fulfilling the criteria for the diagnosis of Dravet syndrome (DRVT). Particularly important was the analysis of the clinical course, the type of epileptic seizures and the co-occurrence of additional features such as intellectual disability, autism or neurological symptoms such as ataxia or gait disturbances. Based on their results and the available literature, the authors discuss potential predictors for DRVT. Identifying these early symptoms has important clinical significance, affecting the course and disease prognosis. 50 patients of the Pediatric Neurology Clinic of the Institute of Mother and Child in Warsaw clinically diagnosed with DRVT and carriers of SCN1A pathogenic variants were included. Clinical data were retrospectively collected from caregivers and available medical records. Patients in the study group did not differ significantly in parameters such as type of first seizure and typical epileptic seizures from those described in other studies. The age of onset of the first epileptic seizure was 2-9 months. The co-occurrence of intellectual disability was confirmed in 71% of patients and autism in 18%. The study did not show a correlation between genotype and phenotype, considering the severity of the disease course, clinical symptoms, response to treatment, the presence of intellectual disability, autism symptoms or ataxia. From the clinical course, a significant problem was the differentiation between complex febrile convulsions and symptoms of DRVT. The authors suggest that parameters such as the age of the first seizure, less than one year of age, the onset of a seizure up to 72 h after vaccination and the presence of more than two features of complex febrile seizures are more typical of DRVT, which should translate into adequate diagnostic and clinical management. The substantial decrease in the age of genetic verification of the diagnosis, as well as the decline in the use of sodium channel inhibitors, underscores the growing attention of pediatric neurologists in Poland to the diagnosis of DRVT.

Enhancing autism spectrum disorder classification in children through the integration of traditional statistics and classical machine learning techniques in EEG analysis.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder hallmarked by challenges in social communication, limited interests, and repetitive, stereotyped movements and behaviors. Numerous research efforts have indicated that individuals with ASD exhibit distinct brain connectivity patterns compared to control groups. However, these investigations, often constrained by small sample sizes, have led to inconsistent results, suggesting both heightened and diminished long-range connectivity within ASD populations. To bolster our analysis and enhance their reliability, we conducted a retrospective study using two different connectivity metrics and employed both traditional statistical methods and machine learning techniques. The concurrent use of statistical analysis and classical machine learning techniques advanced our understanding of model predictions derived from the spectral or connectivity attributes of a subject's EEG signal, while also verifying these predictions. Significantly, the utilization of machine learning methodologies empowered us to identify a unique subgroup of correctly classified children with ASD, defined by the analyzed EEG features. This improved approach is expected to contribute significantly to the existing body of knowledge on ASD and potentially guide personalized treatment strategies.

Genetic Risk Factors for Neurological Disorders in Children with Adverse Events Following Immunization: A Descriptive Study of a Polish Case Series.

Studies conducted on large populations show a lack of connection between vaccination and serious neurological symptoms. However, there are isolated cases that indicate such a relationship. These reports on adverse effects following immunization (AEFI) reduce social confidence in vaccination; however, their background may be rare genetic defects. The aim of the presented study was to examine if neurological AEFI in children may be associated with variants in genes related to neurodevelopment. To identify such possible associations, a descriptive study of the Polish case series was conducted. We performed next-generation sequencing in patients who, up to 4 weeks of injection of any vaccine, manifested neurological AEFI. We included 23 previously normally developing children with first seizures that occurred after vaccination. We identified pathogenic/likely pathogenic variants in genes engaged in neurodevelopment in nine patients and variants of uncertain significance in another nine patients. The mutated genes belonged to the group of genes related to epilepsy syndromes/epileptic encephalopathy. We showed that AEFI might have a genetic background. We hypothesized that in some AEFI patients, the vaccine might only trigger neurological symptoms that would have been manifested anyway as a result of a pathogenic variant in a gene engaged in neurodevelopment.

Anti-NMDA receptor encephalitis - the narrative review of literature with particular regard to pediatric population. / Zapalenie mózgu z obecnoscia przeciwcial przeciwko receptorom NMDA ­ narracyjny przeglad literatury przedmiotu ze szczególnym uwzglednieniem populacji pediatrycznej.

In recent years, the frequency of diagnosing autoimmune encephalitis has increased significantly, both in the population of adults and children and adolescents. This fact is undoubtedly related to the dynamic development of new diagnostic methods, as well as the progress of medical knowledge. A particular type of this condition is anti-NMDA receptor encephalitis. Due to the presence of psychiatric symptoms in this disease, psychiatrists are often the first specialists who treat a patient with the above diagnosis. Differential diagnosis is extremely difficult and primarily based on the history and presence of typical clinical symptoms. Therefore, based on a narrative review of the literature on the subject searched by the PubMed, EMBASE, and Cochrane library databases from 2007-2021 with the keywords "anti-NMDAR encephalitis", "children", and "adolescents", the author described the characteristic course of the disease, diagnostic methods used to confirm the diagnosis, and presents current treatment guidelines. Due to high prevalence, anti-NMDA receptor encephalitis is a diagnosis that should be considered in the differential diagnosis in everyday psychiatric practice.

Mania induced by antidepressants - characteristics and specific phenomena in children and adolescents. / Mania indukowana lekami przeciwdepresyjnymi ­ charakterystyka zjawiska u dzieci i mlodziezy.

The phenomenon of drug-induced mania, i.e., a manic episode associated with the use of pharmacotherapy (in particular antidepressants) is well defined and described in groups of adult patients. The negative effect on the course of bipolar disorder has been confirmed. In the group of children and adolescents, this subject is still poorly known and rarely described because of controversies in diagnosing early-onset bipolar disorder. The authors present an overview of current research on this problem starting from case reports, through open studies to randomized trials. Because the results of studies are ambiguous, the main problems that hinder the formulation of objective conclusions and the most important directions for further research are also discussed. The authors also present current hypotheses on the phenomenon of drug-induced mania in children and adolescents to systematize knowledge on the subject and provide diagnostic help in everyday clinical work. In agroup of children and adolescents, there is aneed to differentiate the phenomenon of drug-induced mania depending on the basic disorder, because similarly to studies that concern adult patients this problem seems to occur more frequently in patients with bipolar disorder than in other psychiatric disorders. It seems that the diagnosis of drug-induced mania is possible in children and adolescents at the present stage of knowledge, however, the assessment of the prevalence of this phenomenon requires careful evaluation in further studies.