Neurological Disorders In Children Research Articles

Metabolic and neurobehavioral disturbances induced by purine recycling deficiency in Drosophila.

Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are two structurally related enzymes involved in purine recycling in humans. Inherited mutations that suppress HGPRT activity are associated with Lesch-Nyhan disease (LND), a rare X-linked metabolic and neurological disorder in children, characterized by hyperuricemia, dystonia, and compulsive self-injury. To date, no treatment is available for these neurological defects and no animal model recapitulates all symptoms of LND patients. Here, we studied LND-related mechanisms in the fruit fly. By combining enzymatic assays and phylogenetic analysis, we confirm that no HGPRT activity is expressed in Drosophila melanogaster, making the APRT homolog (Aprt) the only purine-recycling enzyme in this organism. Whereas APRT deficiency does not trigger neurological defects in humans, we observed that Drosophila Aprt mutants show both metabolic and neurobehavioral disturbances, including increased uric acid levels, locomotor impairments, sleep alterations, seizure-like behavior, reduced lifespan, and reduction of adenosine signaling and content. Locomotor defects could be rescued by Aprt re-expression in neurons and reproduced by knocking down Aprt selectively in the protocerebral anterior medial (PAM) dopaminergic neurons, the mushroom bodies, or glia subsets. Ingestion of allopurinol rescued uric acid levels in Aprt-deficient mutants but not neurological defects, as is the case in LND patients, while feeding adenosine or N6-methyladenosine (m6A) during development fully rescued the epileptic behavior. Intriguingly, pan-neuronal expression of an LND-associated mutant form of human HGPRT (I42T), but not the wild-type enzyme, resulted in early locomotor defects and seizure in flies, similar to Aprt deficiency. Overall, our results suggest that Drosophila could be used in different ways to better understand LND and seek a cure for this dramatic disease.

Metabolic and neurobehavioral disturbances induced by purine recycling deficiency in Drosophila

Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are two structurally related enzymes involved in purine recycling in humans. Inherited mutations that suppress HGPRT activity are associated with Lesch–Nyhan disease (LND), a rare X-linked metabolic and neurological disorder in children, characterized by hyperuricemia, dystonia, and compulsive self-injury. To date, no treatment is available for these neurological defects and no animal model recapitulates all symptoms of LND patients. Here, we studied LND-related mechanisms in the fruit fly. By combining enzymatic assays and phylogenetic analysis, we confirm that no HGPRT activity is expressed in Drosophila melanogaster, making the APRT homolog (Aprt) the only purine-recycling enzyme in this organism. Whereas APRT deficiency does not trigger neurological defects in humans, we observed that Drosophila Aprt mutants show both metabolic and neurobehavioral disturbances, including increased uric acid levels, locomotor impairments, sleep alterations, seizure-like behavior, reduced lifespan, and reduction of adenosine signaling and content. Locomotor defects could be rescued by Aprt re-expression in neurons and reproduced by knocking down Aprt selectively in the protocerebral anterior medial (PAM) dopaminergic neurons, the mushroom bodies, or glia subsets. Ingestion of allopurinol rescued uric acid levels in Aprt-deficient mutants but not neurological defects, as is the case in LND patients, while feeding adenosine or N6-methyladenosine (m6A) during development fully rescued the epileptic behavior. Intriguingly, pan-neuronal expression of an LND-associated mutant form of human HGPRT (I42T), but not the wild-type enzyme, resulted in early locomotor defects and seizure in flies, similar to Aprt deficiency. Overall, our results suggest that Drosophila could be used in different ways to better understand LND and seek a cure for this dramatic disease.

Utility of next generation sequencing in paediatric neurological disorders: experience from South Africa.

Next generation sequencing (NGS)-based tests have become routine first-line investigative modalities in paediatric neurology clinics in many high-income countries (HICs). Studies from these countries show that these tests are both cost-effective and reliable in diagnosing many complex childhood neurological diseases. However, NGS-based testing in low-and middle-income countries (LMICs) is limited due to affordability constraints. The primary objective of this study was to evaluate the diagnostic yield and impact of targeted gene panel sequencing in a selected paediatric cohort attending a tertiary paediatric neurology clinic in the Western Cape Province of South Africa. This retrospective study included 124 consecutive paediatric patients with neurological disease, aged 6 weeks to 17 years, referred for NGS-based multi-gene panel testing over a 41-month period. Twenty-four different disease group-specific panels were utilized. A caregiver experience questionnaire was administered when a pathogenic variant was identified. The overall study diagnostic yield (DY) was 45% (56/124 patients). The diagnostic yield in this study is similar to previously reported paediatric cohorts in HICs. The high yields for neuromuscular disorders (52%) and early epileptic encephalopathies (41%) suggest that NGS-based panels may be more cost-effective as first-line testing in well-defined phenotypes. The latter finding argues for early inclusion of all children with developmental epileptic encephalopathies (DEE), as early diagnosis leads to better treatment and avoidance of unnecessary investigations.

Expanding the Phenotype of the CACNA1C-Associated Neurological Disorders in Children: Systematic Literature Review and Description of a Novel Mutation

Expanding the Phenotype of the CACNA1C-Associated Neurological Disorders in Children: Systematic Literature Review and Description of a Novel Mutation

Integrated Intelligent Computing Models for Cognitive-Based Neurological Disease Interpretation in Children: A Survey

INTRODUCTION: This piece of work provides the description of integrated intelligent computing models for the interpretation of cognitive-based neurological diseases in children. These diseases can have a significant impact on children's cognitive and developmental functioning. 
 OBJECTIVES: The research work review the current diagnosis and treatment methods for cognitive based neurological diseases and discusses the potential of machine learning, deep learning, Natural language processing, speech recognition, brain imaging, and signal processing techniques in interpreting the diseases.
 METHODS: A survey of recent research on integrated intelligent computing models for cognitive-based neurological disease interpretation in children is presented, highlighting the benefits and limitations of these models.
 RESULTS: The significant of this work provide important implications for healthcare practice and policy, with strengthen diagnosis and treatment of cognitive-based neurological diseases in children.
 CONCLUSION: This research paper concludes with a discussion of the ethical and legal considerations surrounding the use of intelligent computing models in healthcare, as well as future research directions in this area.

Effectiveness of a Self-efficacy Enhanced Program Using Cartoon Animation for Self-care Behaviors Among Schoolchildren with Epilepsy: A Quasi-experimental Study

Epilepsy is one of the most common chronic neurological diseases in children and may cause repeated seizures and complications. Thus, self-care behavior is vital for effective seizure control. This quasi-experimental study examined the effectiveness of the Self-efficacy Enhanced Program Using Cartoon Animation for self-care behaviors among school children with epilepsy. The study was conducted at a pediatric neurological clinic in the outpatient department of a tertiary hospital in Bangkok, Thailand. There were 42 children with epilepsy, aged 10 to 12 years, who participated in the study: 21 in the experiment group and 21 in the control group. The experimental group received the program, which used two cartoon animation videos to enhance self-care behaviors for eight weeks, while the control group received regular care only. The data were collected using demographic and self-care behavior questionnaires and were analyzed using chi-square and t-tests.The results demonstrated that after program completion, the mean scores of total self-care behavior and subscale on medication taking, avoiding triggers seizures, and self-care of abnormal symptoms and seeking information in the experimental group were significantly higher than before receiving it and higher than those in the control group significantly. Nurses should use this program to increase self-care behaviors among children with epilepsy. However, testing the program in other settings with long-term follow-up is needed before it can be used widely.

Enterovirus-D68 – a reemerging non-polio enterovirus that causes severe respiratory and neurological disease in children

The past decade has seen the global reemergence and rapid spread of enterovirus D68 (EV-D68), a respiratory pathogen that causes severe respiratory illness and paralysis in children. EV-D68 was first isolated in 1962 from children with pneumonia. Sporadic cases and small outbreaks have been reported since then with a major respiratory disease outbreak in 2014 associated with an increased number of children diagnosed with polio-like paralysis. From 2014-2018, major outbreaks were reported every other year in a biennial pattern with > 90% of the cases occurring in children under the age of 16. With the outbreak of SARS-CoV-2 and the subsequent COVID-19 pandemic, there was a significant decrease in the prevalence EV-D68 cases along with other respiratory diseases. However, since the relaxation of pandemic social distancing protocols and masking mandates the number of EV-D68 cases have begun to rise again-culminating in another outbreak in 2022. Here we review the virology, pathogenesis, and the immune response to EV-D68, and discuss the epidemiology of EV-D68 infections and the divergence of contemporary strains from historical strains. Finally, we highlight some of the key challenges in the field that remain to be addressed.

Tic disorders in children as polyethological nosology

Tic disorders (TR) occupies one of the leading places among neurological diseases of childhood. Recently, educators, medical psychologists, social workers and psychiatrists are increasingly faced with the problem of tic disorders in children, defining them as states of nervous development characterized by the presence of tics and related behavioral problems. Modern neurology, psychiatry and medical psychology need to update both the therapeutic and diagnostic aspects of tic disorders. This article presents an overview of the current literature on the problem of tic disorders in children, as well as methods of their correction. The analysis of the literature actualizes the polymodal approach, taking into account possible etiological predicates of the development of the disease.

Providing holistic care to children with cerebral palsy treated with transnasal neural stem cell transplantation.

Holistic care is a key element in nursing care. Aiming at the heterogeneous disease of cerebral palsy, researchers focused on children with cerebral palsy who received transnasal transplantation of neural stem cells as a specific group. Based on establishing a multidisciplinary team, comprehensive care is carried out for this type of patient during the perioperative period to improve the effectiveness and safety of clinical research and increase the comfort of children. Between January 2018 and June 2023, 22 children with cerebral palsy underwent three transnasal transplants of neural stem cells. No adverse reactions related to immune rejection were observed in the 22 children during hospitalization and follow-up. All children tolerated the treatment well, and the treatment was superior. One child developed nausea and vomiting after sedation; three had a small amount of bleeding of nasal mucosa after transplantation. Two children had a low fever (≤38.5°C), and one had a change in the type and frequency of complex partial seizures. Moreover, 3 children experienced patch shedding within 4 h of patch implantation into the nasal cavity. The project team adopted nasal stem cell transplantation technology. Based on the characteristics of transnasal transplantation of neural stem cells in the treatment of neurological diseases in children, a comprehensive and novel holistic care plan is proposed. It is of great significance to guide caregivers of children to complete proper care, further improve the safety and effectiveness of treatment, and reduce the occurrence of complications.

Long-term effects of levetiracetam and valproic acid on laboratory parameters in childhood epilepsy

Epilepsy is the most common neurological disorder in childhood which often requires long-term or sometimes lifelong treatment. In this study, we aimed to evaluate the change in hematological and biochemical laboratory parameters at the 24th month compared to the treatment baseline values in pediatric epilepsy patients receiving levetiracetam (LEV) and valproic acid (VPA) monotherapy. Complete blood count panel, biochemical and hormonal parameters were investigated retrospectively at baseline and at 24 months in patients diagnosed with epilepsy at the Balikesir University Medical Faculty pediatric neurology clinic, Türkiye, and started on LEV and VPA monotherapy between 01.08.2019 and 01.08.2022. Forty-nine patients were using LEV and 14 VPA. A statistically significant difference in terms of the complete blood count parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) was observed in the cases using LEV between baseline and the 24th month of treatment (p=0.006, p=0.004). Among the cases using VPA, significant differences between baseline and the 24th month of treatment were determined in the complete blood count parameters red blood cell (RBC), MCV, and monocyte (MON)% values (p=0.004, p=0.022, and p=0.01). In conclusion, epilepsy treatment is a lengthy process in pediatric patients, and patients need to be monitored using hematological and biochemical parameters at specific intervals in terms of potential seizure drug side effects.

Feasibility of mobile phone application “Epilepsy care” for self-management of children and adolescents with epilepsy in Phramongkutklao hospital: A randomized controlled trial

Epilepsy is a common neurological disorder in children. Mobile applications have shown potential in improving self-management for patients with chronic illnesses. To address language barriers, we developed the first Thai version of the “Epilepsy care” mobile application for children and adolescents with epilepsy in Thailand. A prospective, randomized controlled trial with 220 children and adolescents living with epilepsy who had a smartphone and were treated at the pediatric neurology clinic was conducted, with one group using the mobile application and the other receiving standard epilepsy guidance. The primary outcome assessed epilepsy self-management using the Pediatric Epilepsy Self-Management Questionnaire (PEMSQ) in the Thai version, which comprised 27 questions. These questions aimed to determine knowledge, adherence to medications, beliefs about medication efficacy, and barriers to medication adherence. The secondary outcome evaluated seizure frequency at baseline, 3, and 6 months after initiation of an application. Eighty-five participants who were randomized to a mobile application achieved significantly higher PEMSQ scores in the domain of barriers to medication adherence (p < 0.05) at 6 months follow-up. Other domains of PEMSQ showed no statistically significant difference. Baseline median seizure frequencies per month were 7 in the control group and 5.5 in the intervention group. At 3 and 6 months, these decreased significantly to 1.5 and 1 for the control group and 2.5 and 1 for the intervention group (p < 0.001). In addition, the study revealed that 94.9 % of the participants in a mobile application group were highly satisfied with using application. These findings suggest that the mobile application “Epilepsy care” may serve as an effective adjunctive therapy to enhance self-management and seizure control in children and adolescents with epilepsy.

Differential diagnosis and treatment of idiopathic occipital epilepsy and visual seizures in an adolescent case: Is “hallucination” always “hallucination”?

Epilepsy is the most common childhood neurological disorder that affects 0.5 to 1.0 % of children younger than 16 years of age. Cognitive and behavioral impairments as well as various psychiatric and neurodevelopmental disorders can accompany this condition. Among children and adolescents, occipital epilepsy can be easily overlooked because it can mimic other epileptic syndromes and symptoms may be subtle. The initial complaint of a patient suffering from occipital epilepsy could be visual hallucinations. Child and adolescent psychiatrists must be aware of the difference between these neurological-originated hallucinations and others denoting psychopathologies.

Clinical characteristics and prognostic analysis of acute necrotizing encephalopathy of childhood: a retrospective study at a single center in China over 3 years.

Acute Necrotizing Encephalopathy of Childhood (ANEC) is a rare, fulminant neurological disease in children with unknown mechanisms and etiology. This study summarized the clinical characteristics, treatment, and prognosis of ANEC through a retrospective analysis, providing insights into the ANEC early diagnosis and prognosis assessment. Clinical data of children diagnosed with ANEC at the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from July 1, 2020, to June 30, 2023, were retrospectively analyzed. There were 25 cases, 14 males and 11 females, with a median age of 3 years. Hospital admissions were mainly in the winter (14/25, 56%) and spring (9/25, 36%). All patients presented with varying degrees of fever and altered consciousness, with 92% (23/25) experiencing high body temperatures (>39.1°C) and 88% (22/25) having a Glasgow coma scale (GCS) score of ≤8. Seizures were observed in 88% (22/25) of patients. Laboratory findings indicated 100% B lymphocyte activation (14/14), and 78% (14/18) of patients showed cytokine storm (interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-α). Neuroimaging showed symmetrical thalamus involvement, commonly involving basal ganglia and brainstem regions. Viral infection (23/24, 96%) was the predominant etiological finding, with 42% (10/24) of cases due to SARS-CoV-2 infection and 42% (10/24) to influenza A virus infection. Multi-organ dysfunction occurred in 68% (17/25) of patients, and 52% (13/25) died. Correlation analysis revealed the death group exhibited higher proportion of male, lower GCS scores, higher IL-6 level and a greater likelihood of associated brainstem impairment (p < 0.05). ANEC is more prevalent in the winter and spring, and its etiology may be associated with B lymphocyte activation and cytokine storm following viral infections. Clinical manifestations lack specific features, with fever, consciousness disturbances, and seizures being the main presentations, particularly in cases of high fever and hyperpyrexia. ANEC progresses rapidly and has a high mortality rate. The child's gender, GCS score, IL-6 levels, and the presence of brainstem involvement can serve as important risk factors for assessing the risk of mortality.

ANALYSIS OF MORBIDITY AMONG EXTREMELY PREMATURE CHILDREN AT EARLY AGE

Introduction. The state of health of prematurely born children is an important medical and social concern. Today, the number of premature babies is increasing all over the world. According to the World Health Organization, about 15 million children are born prematurely every year. About 80% of children are born with a particular pathology. Premature infants are a special group of pediatric patients, who necessitate prompt diagnosis and intervention.&#x0D; The purpose of this study was to investigate the morbidity rates among patients in the intensive care unit born with very low and extremely low body weight.&#x0D; Materials and methods. The results of the clinical observation of 178 premature newborns, who were born with a body weight less than 1500 g, are presented. Somatic diseases and disabling pathology experienced by the child during the first three years of life were examined.&#x0D; Results. The data we received show that almost 50% of babies are discharged from obstetric hospitals with anemia, in the next six months the number of children with anemia reached approximately 60%. We found that iron deficiency in the post-neonatal period correlates with the formation of remote neurological disorders in children born with a body weight less than 1500 g. Diseases of the nervous system play a predominant role in the spectrum of health issues affecting premature infants. This emphasizes the need for ongoing enhancements in diagnostic methods and timely interventions to improve the prognosis for their future development.&#x0D; Conclusions. The emergence of neurological complications in the long-term for very-low-birth-weight infants is closely tied to critical conditions during the perinatal and neonatal periods. This underscores the importance of considering these factors in the planning and implementation of preventive and therapeutic measures. The efficacy of follow-up observations for this cohort of children is heightened through the application of early intervention methods. Early intervention ensures the prompt identification and correction of adverse consequences stemming from premature birth in accordance with contemporary standards.

Febrile seizures cause a decrease in calcium-permeable AMPA receptors at synapses of rat cortical and hippocampal pyramidal neurons

Febrile seizures (FS) are a prevalent childhood neurological disorder that can result in lasting functional alterations in neural networks, contributing to the onset of epilepsy and cognitive impairment [1]. Higher levels of calcium-permeable AMPA receptors (CP-AMPARs), which lack the GluA2 subunit, are detected in the hippocampus and cortex at an early age. CP-AMPARs are involved in various plastic changes within the central nervous system (CNS), including regular physiological processes (synaptic plasticity) and various pathological conditions. Such changes occur when these receptors are included in the neurons’ membrane, where they are not typically expressed. CP-AMPARs were demonstrated to incorporate into synapses during seizures [2]. The effect of FSs on CP-AMPAR expression is uncertain, and the resultant alterations in neuronal network function are unclear. The aim of this study was to determine whether the proportion of CP-AMPARs at synapses of pyramidal neurons in the rat entorhinal cortex and hippocampus alters immediately (at 15 min) and 48 h post FS. Ten-day-old rats were exposed to a stream of warm air (46 °C) for 30 minutes to induce hyperthermia, resulting in the development of FS. Only animals with FS that lasted for a minimum of 15 minutes were included in the study. The control group was comprised of littermates removed from the dam for an equivalent period but kept at room temperature. Isolated pyramidal neurons were used to determine the proportion of CP-AMPARs in the hippocampus. AMPAR-mediated currents were induced by application of 100 μM kainate. Excitatory postsynaptic currents (EPSCs) were evoked by extracellular stimulation in the entorhinal cortex. The antagonist IEM-1460 was used to selectively block CP-AMPARs. The rectification index of AMPA-mediated EPSCs was calculated to better assess the contribution of CP-AMPARs. Neurons expressing CP-AMPARs were visualized using the kainate-induced cobalt uptake method. Brain slices were stimulated with kainate while AR-5 and TTX were present. The DNQX blocker was used for the determination that the influx of Co2+ was mediated by AMPARs. Basal synaptic transmission was assessed by recording field postsynaptic responses in the hippocampus stimulated by Shaffer collaterals at different current strengths. FS induced a rapid decrease in the levels of CP-AMPARs on the membranes of pyramidal neurons in the hippocampus. As a result, 15 min after FS, IEM-1460 caused significantly less blockade of kainate-evoked current in neurons isolated from rat hippocampus compared to control (22% vs. 14%, p 0.05). A similar finding was observed for EPSCs evoked extracellularly in the entorhinal cortex, with a frequency of 10% in the FS group compared to 3% in the control group (p 0.05). Furthermore, the FS group’s neurons exhibited a significantly greater rectification index of EPSCs compared to the control group’s neurons. However, two days post-FS, no significant differences existed between the two groups. This observation may be attributed to the rapid decrease in the proportion of CP-AMPARs in pyramidal neurons at this stage. The cobalt uptake method supported electrophysiological findings, revealing higher staining levels in the CA1 field of the hippocampus and entorhinal cortex of control rats compared to FS rats. The observed effect surfaced 15 minutes after FS, and no divergences emerged between the groups after two days. Although the proportion of CP-AMPARs was reduced, basal neurotransmission levels in brain slices obtained from rats that underwent FS did not differ from control values. In summary, the expression of CP-AMPARs in entorhinal cortex and hippocampal pyramidal neurons in young rats decreases significantly with FS. These alterations do not impact the characteristics of basal synaptic transmission in the hippocampus.

Effects of the coronavirus disease outbreak on the development of neurological disorders in children: A comparison of the incidence of febrile seizure and epilepsy using an interrupted time-series approach

BackgroundWith the outbreak of COVID-19, school closures and quarantines following social distancing have brought significant changes to children's lifestyles. Therefore, we aimed to compare the population-adjusted incidence of febrile seizures(FS) and epilepsy before and after the COVID-19 outbreak in Korea and to assess the effects of the COVID-19 outbreak on the incidence by region and age group. MethodsA retrospective cohort study was conducted using nationwide claims data and covid data from January 2019 to December 2020. The incidence of diseases and difference in incidence before (Jan 20 to Dec 30, 2019) and after (Jan 20 to Dec 30, 2020) the COVID-19 outbreak was measured using rate ratio. An Interrupted time series analysis was used to identify the effect of COVID-19 on trends of FS and epilepsy. Subgroup analysis by age, sex, insurance, and risk of coronavirus by area were conducted. ResultsFollowing the onset of the pandemic, the number of newly diagnosed FS cases decreased sharply by 69 % (24,182 to 7238), whereas the incidence of epilepsy, increased to 1.02 times (30,286−29,312), when adjusted in proportion to the population. Notably, a greater decrease in the incidence of FS were found in the regions with high-risk of coronavirus. A result of segmented regression analysis proved the decrease was significant and made immediately after the pandemic started(p < 0.001). In contrast to the incidence of FS, that of epilepsy did not exhibit a significant month-to-month change during the baseline period, immediately after the pandemic started, and during the pandemic. ConclusionsThe COVID-19 outbreak and resulting social distancing measures reduced the incidence of febrile seizure immediately rather than gradually. Unlike in the case of acute febrile seizure, the COVID-19 pandemic had no effect on the incidence of chronic epilepsy.

Association between SCN1A polymorphism and risk of epilepsy in children: A systematic review and meta-analysis.

Epilepsy is a common neurological disorder in children. Numerous studies have demonstrated the association between SCN1A polymorphisms and risk of epilepsy in adults, but their role in epilepsy in children has just gained traction and results have remained inconsistent. In this work, we performed a systematic review and meta-analysis to assess the association between SCN1A polymorphisms and risk for epilepsy in children. A systematic literature search was performed in PubMed, Scopus, Web of Science, China National Knowledge Internet, Wanfang and VIP databases to identify eligible studies up to June 2023. Quantitative data synthesis was then performed under five genetic models: dominant, recessive, homozygous, heterozygous, and allele. Five studies involving 1380 subjects were included in the meta-analysis. Among many SCN1A polymorphisms reported, only rs2298771 was repeatedly studied in these reports. Pooled analysis demonstrated that there was no significant association between the polymorphism and risk of epilepsy in children (P>0.05). In conclusion, SCN1A rs2298771 polymorphism was not significantly associated with the risk of epilepsy in children.

Characterization of a monoclonal antibody specific to California serogroup orthobunyaviruses and development as a chimeric immunoglobulin M-positive control in human diagnostics.

California serogroup viruses (CSGVs) of medical importance in the United States include La Crosse virus, Jamestown Canyon virus (JCV), California encephalitis virus, and snowshoe hare virus. Current diagnosis of CSGVs relies heavily on serologic techniques for detecting immunoglobulin M (IgM), an indication of a recent CSGV infection. However, human-positive control sera reactive to viruses in the serogroup are scarce because detection of recent infections is rare. Here, we describe the development of new murine monoclonal antibodies (MAbs) reactive to CSGVs and the engineering of a human-murine chimeric antibody by combining the variable regions of the broadly CSGV cross-reactive murine MAb, 3-3B6/2-3B2 and the constant region of the human IgM. MAb 3-3B6/2-3B2 recognizes a tertiary epitope on the Gn/Gc heterodimer, and epitopes important in JCV neutralization were mapped to the Gc glycoprotein. This engineered human IgM constitutively expressed in a HEK-293 stable cell line can replace human-positive control sera in diagnostic serological techniques such as IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Compared to the parent murine MAbs, the human-chimeric IgM antibody had identical serological activity to CSGVs in ELISA and demonstrated equivalent reactivity compared to human immune sera in the MAC-ELISA.IMPORTANCEOrthobunyaviruses in the California serogroup cause severe neurological disease in children and adults. While these viruses are known to circulate widely in North America, their occurrence is rare. Serological testing for CSGVs is hindered by the limited availability and volumes of human-positive specimens needed as controls in serologic assays. Here, we described the development of a murine monoclonal antibody cross-reactive to CSGVs engineered to contain the variable regions of the murine antibody on the backbone of human IgM. The chimeric IgM produced from the stably expressing HEK293 cell line was evaluated for use as a surrogate human-positive control in a serologic diagnostic test.

Neurofilament light chain: serum reference intervals in Danish children aged 0-17 years

Elevated levels of neurofilament light chain (NfL) in the blood is an unspecific biomarker for damage to neuronal axons. The measurement of NfL levels in the blood can provide useful information for monitoring and prognostication of various neurological disorders in children, but a reference interval (RI) is needed before the clinical implementation of the biomarker. We aimed to establish a RI for children aged 0–17 years. Serum samples from 292 healthy reference subjects aged 0.4–17.9 years were analysed by a single-molecule array (Simoa®) established for routine clinical use. Non-parametric quantile regression was used to model a continuous RI, and a traditional age-partitioned non-parametric RI was established according to Clinical and Laboratory Standard Institute (CLSI) guideline C28-A3. Furthermore, we investigated the effect of hemolysis on assay performance. The traditional age-partitioned non-parametric RI for the age group <3 years was 3.5–16.6 ng/L and 2.1–13.9 ng/L in the age group ≥3 years, respectively. The continuous RI showed an age-dependent decrease in median NfL levels in the first three years of life which was also evident in the age-partitioning of the traditional RI. We found no difference between sexes and no impact of hemolysis on the NfL test results. This study establishes a pediatric RI for serum NfL and lays the groundwork for its future use in clinical practice.

Clinical and Demographic Characteristics of Families Attending the Epilepsy, Neuromuscular, and Child Wellbeing Clinics.

Background Neurological diseases entail a broad spectrum of disorders. Among such ailments are epilepsy and neuromuscular disorders which impose a substantial burden on children and their families. Ensuring adequate access to outpatient services is crucial for these children regardless of the subclinical specialty, and clinicians can better comprehend the caregivers' perspectives by being aware of their backgrounds which can be aided using epidemiological studies. Methods In June 2023, a cross-sectional study was carried out in pediatric neurology clinics at a tertiary care center. The study included all families with a child or more (14 years and younger) diagnosed with neurological disorders. The study adopted a three-section survey delivered to participants recruited using a non-probability sampling technique to achieve a 95% confidence interval with a 5% margin of error. Results A total of 821 families participated in this study. The mean age of respondents was 40.46±8.72 years. Of the affected children, there were 600 (73.08%) children following up with the general neurology and epilepsy clinics, 164 (19.98%) were following up with the neuromuscular disorders clinics, and 57 (6.94%) were following up with the neurogenetic clinics. Familial status had no association with the type of clinic the patient was following up with p=0.0054. Single respondents had a significantly higher prevalence of children with epilepsy (p<0.0001). Parents with a high school level of education or lower had a significantly greater prevalence of epilepsy clinic follow-ups (p=0.0048). Conclusion The findings of this study contribute to the assessment of prevalent neurological disorders in children and shed light on the family dynamics surrounding these conditions. Through statistical analysis, the study establishes connections between certain demographic and clinical traits and specific neurological disorders among pediatric patients and their families. The study emphasizes the importance of socio-economic and socio-clinical support in promoting child health in such cases. Similar research would offer a more accurate portrayal of the challenges faced by families in these circumstances.