Epigenetics and pediatric neurological disorders

Neurological disorders are among the major causes of physical disability in children. The aim of this study was to investigate the prevalence and pattern of Paediatric Neurological Disorders (PNDs) managed in outpatient Physiotherapy clinics in Kano. The 10-year retrospective descriptive study collected relevant data on PNDs from case files of the children who have been managed in Physiotherapy clinics of the 5 major referral hospitals in Kano using a data capture form. The population of children in Kano State based on the 2006 Census and the projected population for 2017 was obtained from the National Population Commission, Kano State office. The data obtained was analysed with descriptive statistics of mean, standard deviation, frequency and percentage. Dataanalysis was done using Microsoft excel and SPSS version 20. Results showed that 1927paediatric cases were analysed out of which PNDs accounted for 1618 (83.96%). The mean age of the children at the time of their first treatment visit was 3.13 years ± 3.04years (range =33days-12years). Most of the children with PNDs are males 1101(57.1%), with male to female ratio of 1.3:1. The Prevalence of PNDs in Kano was 0.257/1000 (i.e.25.7/100,000). The most common PND that was managed by physiotherapists in KanoState was cerebral palsy which has a prevalence of 0.106/1000 (i.e.10.6/100,000),(proportion = 41.16%). It was concluded that PNDs are the most common paediatric cases managed by physiotherapists in Kano State with cerebral palsy having higherprevalence

Due to the broad application of next-generation sequencing, the molecular diagnosis of genetic disorders in pediatric neurology is no longer an unachievable goal. However, treatments for neurological genetic disorders in children remain primarily symptomatic. On the other hand, with the continuous evolution of therapeutic viral vectors, gene therapy is becoming a clinical reality. From this perspective, we wrote this reviewto illustrate the current state regarding viral-mediated gene therapy in childhood neurological disorders. We searched databases, including PubMed and Google Scholar, using the keywords "adenovirus vector," "lentivirus vector," and "AAV" for gene therapy, and "immunoreaction induced by gene therapy vectors," "administration routes of gene therapy vectors," and "gene therapy" with "NCL," "SMA," "DMD," "congenital myopathy," "MPS" "leukodystrophy," or "pediatric metabolic disorders". We also screened the database of ClinicalTrials.gov using the keywords "gene therapy for children" and then filtered the results with the ones aimed at neurological disorders. The time range of the search procedure was from the inception of the databases to the present. We presented the characteristics of commonly used viral vectors for gene therapy for pediatric neurological disorders and summarized their merits and drawbacks, the administration routes of each vector, the research progress, and the clinical application status of viral-mediated gene therapy on pediatric neurological disorders. Viral-mediated gene therapy is on the brink of broad clinical application. Viral-mediated gene therapy will dramatically change the treatment pattern of childhood neurological disorders, and many children with incurable diseases will meet the dawn of a cure. Nevertheless, the vectors must be optimized for better safety and efficacy.

It is no doubt for the health effect of the radiation from the nuclear detonation from the destroyed nuclear power plant. Due to the present crisis in Japan, the public health concern on this issue should be raised. In pediatric neurology, there are some interesting reports on pediatric neurological disorder and its relationship to leaked radiation. In this specific brief article, the author hereby discusses on the nuclear detonation and pediatric neurological disorder. Although there are some reports on the increased incidence of some pediatric neurological malignancies and congenital neurological anomalies there is no confirmed evidence. Effect on cognitive function is still controversial. The induction of abnormal electroencephalography is also mentioned. The observation on the effect of present crisis in pediatric neurology can provide more information and help better understand this topic.

Objective: Therapeutic plasma exchange (TPE) is performed in various neurological, hematological, renal and autoimmune diseases. This study was conducted to determine the indications, efficacy, safety and complications of TPE in pediatric autoimmune neurological diseases. Methods: In this study, patients who were hospitalized in the pediatric intensive care unit of a tertiary university hospital between January 2017 and December 2021 and underwent TPE due to neurological diseases were evaluated retrospectively. Results: A total of 20 patients were included in the study. Their ages ranged from 6 to 237 months, with a mean age of 63.16±183.12 months. Neurological TPE indications of the patients were autoimmune encephalitis (50%, n=10), Guillain-Barre Syndrome (45%, n=9) and Acute Demyelinating Encephalomyelitis (6.7%, n=1), respectively. Catheter occlusion was observed in 2 (10%) patients, allergic reaction in 1 (5%) patient, and hypotension in 1 (5%) patient as complications of TPE. Muscle strength of patients with GBS was evaluated according to the Medical Research Council scale before transfer to the service. It was determined that the score increased from 0 to 1 in two patients, from 0 to 3 in three patients, and from 1 to 5 in four patients. In 9 of the patients diagnosed with encephalitis, regression of acute phase reactants and improvement in neurological evaluation were observed. Conclusion: When TPE is applied with appropriate indications and by an experienced team in pediatric neurological diseases, treatment results can are satisfactory, its effectiveness increases and the complication rate decreases.

Pediatric neurological disorders are frequently devastating and present unmet needs for effective medicine. The successful treatment of spinal muscular atrophy with splice-switching antisense oligonucleotides (SSO) indicates a feasible path to targeting neurological disorders by redirecting pre-mRNA splicing. One direct outcome is the development of SSOs to treat haploinsufficient disorders by targeting naturally occurring non-productive splice isoforms. The development of personalized SSO treatment further inspired the therapeutic exploration of rare diseases. This review will discuss the recent advances that utilize SSOs to treat pediatric neurological disorders.

Pediatric neurological disorders are a diverse group of conditions affecting the nervous system in children, often challenging to diagnose due to their nonspecific and overlapping clinical features. Advances in molecular diagnostics, particularly whole exome sequencing (WES), have significantly improved the identification of genetic causes, enabling precise diagnoses and personalized treatments. This study explores the application of WES in diagnosing pediatric neurological disorders within Moroccan childrens with undiagnosed or challenging pediatric neurological conditions to uncover genetic causes of complex pediatric neurological conditions unresolvable by traditional diagnostic methods. The study included 188 pediatric patients with complex neurological conditions from theChildren'sHospital of Rabat who underwent exome sequencing to investigate suspected genetic causes. WES revealed a diagnostic yield of 45%, identifying conditions such as intellectual disabilities, hereditary metabolic disorders and epilepsies. It also uncovered neurodevelopmental and neurodegenerative disorders, neuromuscular diseases, and genetic syndromes. A total of 157 variants were detected: 34% were classified as pathogenic, 28.5% as likely pathogenic, and 37.5% as variants of uncertain significance (VUS). These findings underscore the utility of WES as a robust diagnostic tool, providing insights into genetic causes and enabling tailored treatment strategies. They also highlight the importance of expanding genetic research to improve diagnostic accuracy and clinical management of pediatric neurological disorders.

Oriental herbal medicine (OHM) has been widely used in pediatric neurological disorders and has attracted attention as a safe and effective treatment. We aim to summarize and evaluate the evidence for OHM in pediatric neurological disorders for evidence-based decision-making. Without language restrictions, up-to-date research data were obtained from nine electronic databases. Systematic reviews (SRs) assessing the efficacy of OHM for pediatric neurological disorders were included. The methodological quality of each review was assessed using the AMSTAR instrument. The quality of evidence for the main findings was evaluated using the GRADE approach. Sixteen SRs comprising 169 randomized controlled trials with 19,542 participants were included. In epilepsy (six SRs, ), OHM as an adjunctive or alternative therapy to antiepileptic drugs showed higher clinical symptom improvements than did antiepileptic drugs alone. The Activities of Daily Living scale score was significantly higher in children with cerebral palsy (one SR, ) when OHM was added to rehabilitation. There were inconsistent results for tic disorder (four SRs, ) and enuresis (two SRs, ) and unclear results for attention deficit hyperactivity disorder (two SRs, ) and autism spectrum disorder (one SR, ). Eleven SRs reported adverse events, but no fatal adverse reaction was reported. The methodological quality of the included reviews was medium-to-high. The overall quality of evidence ranged from "very low" to "moderate." In conclusion, the efficacy of OHM is promising for some pediatric neurological disorders such as epilepsy and cerebral palsy. However, more high-quality evidence is needed to make clinical recommendations on OHM use.

Background: A marriage is said to be consanguineous, where the marriages are solemnized among persons descending from the same stock or common ancestor with close biological relations. The aim of the study was to role of consanguinity in paediatric neurological disorders. Methods: The cases of the present study were selected from various units of paediatric ward in Velammal medical college hospital, Madurai, Tamilnadu, India, over a period of 2 years between Nov-2013 to oct-2015. This is a prospective observational study of 152 children, out of which 83 children were products of non-consanguineous with neurological disorders and 69 children were products of consanguineous marriage with neurological disorders, confirmed by history and clinical examination and correlated with appropriate investigations. Results: It was found that out of 152 neurological cases admitted, during the study period, 69 (45.3%) of patients were products of consanguineous marriage and 83 (54.6%) were products of non-consanguineous marriage. Out of 69 cases that were product of consanguineous marriage, 27 cases (39.1%) born of second degree consanguinity and 42 cases (60.8%) were products of third degree consanguinity. Out of the 69 cases, 7 (10.1 %) of them had siblings with similar neurological problems. The prevalence of seizure disorder was 27 (17.7%), developmental delay 13 (8.5%), isolated speech delay 2 (1.3%), hearing impairment 5 (3.2%), mental retardation 11 (7.2%), visual impairment 2 (1.3%), ataxia telangiectasia 2 (1.3%) among the products of consanguineous marriage. The above stated prevalence of neurological disorders being slightly higher than that of the products of non-consanguineous marriage. Conclusions: It is important to prevent hereditary diseases that are associated with consanguineous marriage through public education.

Astrocyte Form and Function in the Developing Central Nervous System

Diffusion MRI abnormalities in pediatric neurological disorders

Crucial time is often lost while waiting for approval of therapies for pediatric neurological disorders, many of which have aggressive manifestations with devastating effects. There are logistical, ethical, and financial impediments that face the studies needed to determine efficacy and safety of therapies in children. In this article, the authors present the Food and Drug Administration's programs aimed at facilitating the development of pediatric drugs, focusing on their application to pediatric neurological disorders. They also provide examples of drugs that received, or are currently enrolled in, these programs. Reflecting upon the commonalities of drugs receiving these designations, the authors highlight underlying ethical issues related to pediatric drug development and emphasize the need for structured incentives to stimulate approval and production of drug therapies for pediatric neurology patients. By consolidating information that applies to drug approval of pediatric neurological disorders, stakeholders in drug development can enhance treatment development for these disorders.

Population-based registries using multidisciplinary reporters: A method for the study of pediatric neurologic disorders

Background: Pediatric neurological disorders such as craniosynostosis demand timely and accurate diagnosis to prevent complications like developmental delays and increased intracranial pressure. Among available imaging modalities, computed tomography (CT) remains the gold standard due to its superior ability to visualize cranial sutures and detect premature fusion, which is central to diagnosing craniosynostosis and planning appropriate intervention. Objective: To evaluate the diagnostic role of CT scans in pediatric neurological disorders with a focus on craniosynostosis and to assess their association with clinical outcomes including developmental delay, increased intracranial pressure (ICP), and surgical necessity. Methods: This cross-sectional study was conducted at Tehsil Head Quarter Hospital, Arif Wala, Punjab, Pakistan, involving 80 pediatric patients aged 1–12 years who presented with suspected neurological disorders. Non-contrast CT brain scans were performed using a standardized pediatric protocol, including multiplanar reconstructions and 3D volume rendering to assess cranial sutures. Inclusion criteria were newly suspected cases, and patients with prior diagnoses or non-diagnostic imaging were excluded. Ethical approval was obtained, and informed consent was secured from guardians. Data were collected using structured questionnaires and analyzed using SPSS Version 25. Results: Out of 80 children (mean age: 5.83 ± 3.16 years; 56.3% female), CT scans confirmed craniosynostosis in 69 cases (86.3%). Developmental delay was noted in 63 patients (78.8%), while increased ICP was seen in 36 (45%). Surgical intervention was deemed necessary in 23 patients (28.8%). Common cranial deformities included positional molding (25%) and scaphocephaly (18.8%). CT attenuation was low in 38 patients (47.5%) and high in 34 (42.5%). Conclusion: CT scans demonstrated high diagnostic accuracy for craniosynostosis and proved essential for identifying cranial abnormalities, planning surgeries, and predicting clinical outcomes in pediatric patients. Their precision makes CT an indispensable tool in early diagnosis and management of craniosynostosis.

To investigate the diagnostic yield and treatment impact of whole-genome sequencing (WGS) in patients with paediatric neurological disorders. From January 2016 to December 2019, paediatric patients who had suspected genetic neurological disorders were assessed using WGS. The phenotypes of eligible patients were divided into four groups: patients with neurodevelopmental disorders; patients with epilepsy; patients with neuromuscular disorders; and patients with movement disorders. A total of 214 consecutive patients (128 males, 86 females) underwent WGS. The mean (SD) age of disease onset was 13.8 (27.6) months (range 1d-15y 5mo). The mean (SD) age at which WGS was performed was 71.7 (58.9) months (range 8d-18y). A molecular diagnosis was reported in 43.9% of patients. The highest diagnostic rate was achieved in 62.5% of patients with neuromuscular disorders, 47.5% of patients with epilepsy, 41.1% of patients with neurodevelopment disorders, and 15.4% of patients with movement disorders. All 94 patients with a WGS diagnosis were given access to genetic counselling and 23.4% of patients had immediate changes in treatment strategies after undergoing WGS. WGS allows paediatric neurologists to integrate genomic data into their diagnosis and adjust management strategies for a range of clinical and genetically heterogeneous disease entities to improve the clinical outcomes of patients. In our cohort, the diagnosis of a significant proportion of patients was reached through WGS (43.9%). Clinicians could use these results to directly guide the management of their patients and improve their clinical outcomes (23.4%). What this paper adds For selected children in our cohort, the diagnostic yield of whole-genome sequencing (WGS) was 43.9%. WGS can be used to expand our knowledge of phenotype-genotype variations.

Deep brain stimulation (DBS) has emerged as an important therapeutic intervention, effectively addressing a spectrum of drug-resistant neurological and psychiatric disorders. Although its efficacy has been validated in adult populations, the current literature reveals a significant gap concerning its application in pediatric patients. Specifically, pediatric populations afflicted with severe conditions such as dystonia, drug-resistant epilepsy, Tourette syndrome, and some other neuropsychiatric conditions demonstrate an urgent need for alternative therapeutic options. This review systematically examined the existing literature on the application of DBS in pediatric neurological disorders, focusing on the aforementioned conditions. Preliminary findings indicate that while DBS shows potential for a specific subset of pediatric patients, the current data is limited and lacks statistical power. Reported cases exhibit varying degrees of therapeutic success. Although adverse effects associated with DBS in pediatric populations are rare, further investigation is essential to define safety profiles accurately. Future research should focus on conducting large-scale, randomized controlled trials to validate outcomes and determine optimal patient selection criteria, thereby broadening its clinical application within the pediatric population.