Pediatric Disorders Research Articles

Evaluating Family Coping Mechanisms in Pediatric Seizure Disorders: From Emergency Room to Long-Term Follow-Up.

Pediatric seizure disorders profoundly impact family dynamics, often escalating stress and impairing coping mechanisms. This study aimed to longitudinally assess the impact of pediatric seizures on family stress and coping, evaluating the efficacy of multidisciplinary follow-up care in enhancing psychological resilience and adaptation. A longitudinal study design was implemented, enrolling children aged 1-18 who presented with a first seizure and received a neurologist's diagnosis at the Emergency Clinical Hospital for Children "Louis Turcanu," Timisoara, Romania. Validated questionnaires, including the Parenting Stress Index (PSI), Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS-10), and Parental Concerns Questionnaire (PCQ), were employed at baseline, 6, and 12 months. Statistical analysis utilized ANOVA and t-tests to evaluate changes in stress and coping outcomes. The study involved 68 families, with significant reductions in stress and anxiety reported over the follow-up period. Initial PSI scores showed high stress levels across various domains: Emotional Stress (59.47) decreased to 50.63 at one year; Parent-Child Communication Difficulties started at 66.03 ± 20.15 and reduced to 56.92 ± 18.74; and Total Family Stress decreased from 65.55 to 55.97. The HADS scores indicated initial anxiety and depression at 8.2 ± 3.1 and 7.1 ± 2.8, respectively, with reductions to 6.8 and 5.9 by the end of the year. The overall HADS score showed a decrease from 15.4 to 12.8. PCQ results mirrored these findings, with Total Score dropping from 9.7 to 7.7. PSS-10 scores declined from 13.5 to 11.3, with a significant reduction in the positive sub-score. The proactive, multidisciplinary care approach significantly reduced stress and enhanced coping mechanisms in families dealing with pediatric seizures. The decreases in stress, anxiety, and depression scores highlight the potential for integrated care models to improve long-term outcomes in these families. These findings support the continued development of targeted interventions to aid in the management of chronic pediatric conditions.

Effects of COVID-19-targeted non-pharmaceutical interventions on pediatric emergency department use: a quasi-experimental study interrupted time-series analysis in North Italian hospitals, 2017 to 2022.

The use of Non-Pharmaceutical Interventions (NPIs) during the COVID-19 pandemic is debated. Understanding the consequences these measures may have on vulnerable populations including children and adolescents is important. This is a multicenter, quasi-experimental before-after study involving 12 hospitals of the North Italian Emilia-Romagna Region, with NPI implementation as the intervention event. The 3 years preceding NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (SC) and a subsequent mitigation measures phase (MM) with milder restrictions. Interrupted Time Series (ITS) regression analysis was used to calculate PED Standardized Incidence Rate Ratios (SIRR) on the diagnostic categories exhibiting the greatest frequency and/or variation. In the 60 months of the study there were 765,215 PED visits. Compared to the pre-pandemic rate, overall PED presentations dropped by 58 and 39% during SC and MM, respectively. "Symptoms, signs and Ill-defined conditions," "Injury and poisoning" and "Diseases of the Respiratory System" accounted for 74% of the reduction. A different pattern was instead seen for "Mental Disorders," which exhibited the smallest decrease during SC, and is the only category which rose already at the end of SC. ITS analysis confirmed the strong decrease during SC (level change, IRR 0.17, 95%CI 0.12-0.27) and a significant increase in MM (slope change, IRR 1.23, 95%CI 1.13-1.33), with the sharpest decline (-94%) and rise (+36%) observed in the "Diseases of the Respiratory System" category. Mental Disorders showed a significant increasing trend of 1% monthly over the whole study period exceeding pre-pandemic levels at the end of MM. Females and adolescents showed higher increasing rates both in SC and MM. NPIs appear to have influenced PED attendance in different ways according to diagnostic categories, mirroring different mechanisms of action. These effects are beneficial in some cases and harmful in others, and establishing a clear balance between pros and cons is a difficult task for public health decision makers. The role of NPIs on PED use appropriateness deserves investigation. The rise in pediatric mental disorders independent of the pandemic makes interventions addressing these issues urgent.

Biallelic null variants in PNPLA8 cause microcephaly by reducing the number of basal radial glia.

Patatin-like phospholipase domain-containing lipase 8 (PNPLA8), one of the calcium-independent phospholipase A2 enzymes, is involved in various physiological processes through the maintenance of membrane phospholipids. Biallelic variants in PNPLA8 have been associated with a range of paediatric neurodegenerative disorders. However, the phenotypic spectrum, genotype-phenotype correlations and the underlying mechanisms are poorly understood. Here, we newly identified 14 individuals from 12 unrelated families with biallelic ultra-rare variants in PNPLA8 presenting with a wide phenotypic spectrum of clinical features. Analysis of the clinical features of current and previously reported individuals (25 affected individuals across 20 families) showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. We found that complete loss of PNPLA8 was associated with the more profound end of the spectrum, with congenital microcephaly. Using cerebral organoids generated from human induced pluripotent stem cells, we found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Spatial transcriptomics revealed that loss of PNPLA8 altered the fate specification of apical radial glial cells, as reflected by the enrichment of gene sets related to the cell cycle, basal radial glial cells and neural differentiation. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. The reduced number of basal radial glial cells in patient-derived cerebral organoids was rescued, in part, by the addition of lysophosphatidic acid. Our data suggest that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.

Brain MRI findings in paediatric genetic disorders associated with white matter abnormalities.

To describe the specific brain magnetic resonance imaging (MRI) patterns of the paediatric genetic disorders associated with white matter abnormalities in Northern Finland. In this retrospective population-based longitudinal study, brain MRI scans accumulated from 1990 to 2019 at Oulu University Hospital, Finland, were assessed. Inclusion criteria were defined as leukodystrophies or genetic diseases with significant white matter abnormalities that did not meet the criteria for leukodystrophy, at least one brain MRI, and age under 18 years at diagnosis. A total of 83 patients (48 males, 35 females) were found with 52 different diseases. The median age at the time of the brain MRI was 22 months (interquartile range [IQR] = 46 months). In 72 (87%) of the children, brain MRIs revealed abnormal findings, including cerebral white matter abnormalities (n = 49, 59%), brainstem signal abnormalities (n = 28, 34%), thinning of the corpus callosum (n = 30, 36%), delayed myelination (n = 11, 13%), and permanent hypomyelination (n = 9, 11%). Symmetrical and bilateral white matter signal patterns of the brain MRI should raise suspicion of genetic disorders when the clinical symptoms are compatible. This study illustrates brain imaging patterns of childhood-onset genetic disorders in a population in Northern Finland and improves the diagnostic accuracy of rare genetic disorders.

From Zero to Overwhelm: PANS and PANDAS as Culprits Behind Sudden OCD in Pediatrics

Pediatric autoimmune neuropsychiatric disorders (PANDAS) and patient neuropsychiatric syndrome (PANS) are psychiatric illnesses characterized by a rapid onset of symptoms, including obsessive-compulsive disorder (OCD), behavioral symptoms and poor motor functions in children. The rapid onset and severity of OCD symptoms prompted investigations to provide an evidence-based intervention. This case series investigates the causes, diagnosis and treatment of the disease among children presenting with neuropsychiatric symptoms and acute-onset OCD. The diagnostic procedures provided grounds for the indication of medication. Methods: Bacterial infections, autoimmune cases and viral infections among 12 children with PANDAS and PANS were retrospectively studied. Pre- and post-treatment symptomatology were examined to monitor the effectiveness of interventions, following laboratory diagnostic approaches, including the Cunningham panel, serology, stool sample analysis, polymerase chain reaction (PCR), and bacterial cultures to determine the cause of the disorder. Diagnostic results informed treatments like non-steroidal anti-inflammatory drugs (NSAIDs), intravenous immunoglobulin (IVIG), fluid therapy, antibiotics, antivirals, steroids, and selective serotonin reuptake inhibitors (SSRIs) in each child. Post-treatment diagnostic results revealed remarkably improved symptoms of PANDAS and PANS, like inflammation and viral or bacterial infection. A combined therapy of antibiotics and NSAIDs or steroids was used to clear bacterial infections and manage inflammation. SSRIs and antiviral or fluid therapy were indicated for OCD and viral infections, respectively. Conclusions: OCD is a common comorbid disorder among children with PANS and PANDAS. Despite the severity and prevalence, OCD in children raises health concerns. The case series demonstrated the effectiveness of antibiotic therapy, RRIs, cognitive behavioral therapy, IVIG, steroids and NSAIDs in managing OCD in PANDAS and PANS, with a unique rationale of indication to every child. Keywords: PANS, PANDAS, Sudden Onset OCD, Pediatric OCD, Autoimmune Neuropsychiatric Disorders

Influencing factors for pediatric eye disorders and health related quality of life: a cross-sectional study in Shanghai, China.

Myopia, strabismus, and ptosis are common pediatric eye diseases, which have a negative impact on children and adolescents in terms of visual function, mental health, and health-related quality of life (HRQoL). Therefore, this study focused on those pediatric eye diseases by analyzing their risk factors and HRQoL for the comprehensive management of myopia, strabismus, and ptosis. A total of 363 participants (2-18 years old) were included in this study for risk factors analysis of myopia, strabismus, and ptosis. We collected demographic characteristics, lifestyle habits and eye care habits of these children and analyzed them by using univariable and multivariable logistic regression. In addition, we applied the Chinese version of Pediatric Quality of Life Inventory-Version 4.0 (PedsQL 4.0) to assess HRQoL in 256 children with strabismus and ptosis. Univariable and multivariable linear regression models were applied to evaluate potential influencing factors of HRQoL. Of all the participants, 140 had myopia, 127 had strabismus, and 145 had ptosis. Based on the multivariable logistic regression analysis model, we found that the history of parental myopia and daily average near-distance eye usage time were risk factors for myopia, and increased body mass index (BMI) was identified as a risk factor for strabismus and ptosis. Individuals with ptosis possessed decreased HRQoL. The multivariable linear regression model suggested that daily average near-distance eye usage time, light intensity during visual tasks, and daily average sleep duration had potential influences on HRQoL. This is the first study to assess the risk factors and HRQoL of myopia, strabismus, and ptosis together. We identified risk factors for these common pediatric eye diseases to help doctors, parents, and teachers better manage them. Our study discovered that children with eye disorders exhibit a notably diminished HRQoL. Consequently, it emphasizes the necessity for increased social attention and mental health assistance for these children.

IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency

Metabolic dysregulation is one of the most common causes of pediatric neurodegenerative disorders. However, how the disruption of ubiquitous and essential metabolic pathways predominantly affect neural tissue remains unclear. Here we use mouse models of a childhood neurodegenerative disorder caused by AMPD2 deficiency to study cellular and molecular mechanisms that lead to selective neuronal vulnerability to purine metabolism imbalance. We show that mouse models of AMPD2 deficiency exhibit predominant degeneration of the hippocampal dentate gyrus, despite a general reduction of brain GTP levels. Neurodegeneration-resistant regions accumulate micron-sized filaments of IMPDH2, the rate limiting enzyme in GTP synthesis, while these filaments are barely detectable in the hippocampal dentate gyrus. Furthermore, we show that IMPDH2 filament disassembly reduces GTP levels and impairs growth of neural progenitor cells derived from individuals with human AMPD2 deficiency. Together, our findings suggest that IMPDH2 polymerization prevents detrimental GTP deprivation, opening the possibility of exploring the induction of IMPDH2 assembly as a therapy for neurodegeneration.

Appointment Blitz: Optimizing Patient-Therapist Rehab Scheduling.

Taiwan has a well-structured healthcare insurance system that offers accessible medical resources to the public through nominal health insurance fees. Consequently, individuals in need of care willingly pay nominal charges for medical services, including rehabilitation treatment. This study delves into the rehabilitation department of a medical center in southern Taiwan. Despite offering comprehensive traditional rehabilitation services covering neurological, musculoskeletal, pediatric, cardiopulmonary, communication, and swallow disorders, the demand for appointments significantly surpasses the number of available therapists. Therefore, this paper proposes an efficiently method to optimize patient-therapist appointment. With a Complex Conditional Logic that we have designed in this paper, we aim to simplify the scheduling processing for patient seeking appointment either online or via phone calls. More than 50,000 cases have been treated since the system's launch within a year, facilitates hospital resource allocation and enhancing patient medical experiences.

Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality.

Primary mitochondrial diseases (PMDs) are associated with pediatric neurological disorders and are traditionally related to oxidative phosphorylation system (OXPHOS) defects in neurons. Interestingly, both PMD mouse models and patients with PMD show gliosis, and pharmacological depletion of microglia, the innate immune cells of the brain, ameliorates multiple symptoms in a mouse model. Given that microglia activation correlates with the expression of OXPHOS genes, we studied whether OXPHOS deficits in microglia may contribute to PMDs. We first observed that the metabolic rewiring associated with microglia stimulation in vitro (via IL-33 or TAU treatment) was partially changed by complex I (CI) inhibition (via rotenone treatment). In vivo, we generated a mouse model deficient for CI activity in microglia (MGcCI). MGcCI microglia showed metabolic rewiring and gradual transcriptional activation, which led to hypertrophy and dysfunction in juvenile (1-month-old) and adult (3-month-old) stages, respectively. MGcCI mice presented widespread reactive astrocytes, a decrease of synaptic markers accompanied by an increased number of parvalbumin neurons, a behavioral deficit characterized by prolonged periods of immobility, loss of weight and premature death that was partially rescued by pharmacologic depletion of microglia. Our data demonstrate that microglia development depends on mitochondrial CI and suggest a direct microglial contribution to PMDs.

Simultaneous presentation and differential reinforcement to increase consumption

AbstractMany autistic children display feeding difficulties and consume a limited food variety. These feeding difficulties could be conceptualized as change‐resistant behavior because children often exhibit rigid mealtime routines, avoid novel foods, and only consume foods according to specific types, textures, or under specific mealtime conditions. Currently, behavior‐analytic treatments for pediatric feeding disorders have the most empirical support and many studies have demonstrated the effectiveness of extinction‐based treatments. However, there is less research on alternative treatments for increasing consumption of novel or non‐preferred foods among children with autism spectrum disorder (ASD). In the current study, we evaluated simultaneous presentation and differential reinforcement to increase consumption of novel, target foods for two participants with ASD and change‐resistant feeding behavior.

Sustained Treatment Gains in Intensive Virtual and In-Person CBT for Pediatric Anxiety Disorders and OCD

Sustained Treatment Gains in Intensive Virtual and In-Person CBT for Pediatric Anxiety Disorders and OCD

Implementing nursing interventions based on stress system theory alongside painting therapy for pediatric post-traumatic stress disorder following accidental injury

ObjectiveThe aim of this study is to examine the impact of a nursing intervention based on stress system theory, coupled with painting therapy, on children experiencing post-traumatic stress disorder (PTSD) subsequent to an accidental injury.MethodsThe clinical data of 100 children diagnosed with PTSD following accidental injuries were retrospectively analyzed for the period spanning April 2021 to May 2023. There were 48 children who received standard nursing care between April 2021 and April 2022 in the control group, and 52 children who received nursing intervention based on stress system theory combined with painting therapy between May 2022 and May 2023 in the observation group. Scores of PTSD Self-evaluation Scale (PTSD-SS), post-traumatic growth, coping style, quality of life, and family satisfaction were compared between the two groups.ResultsPrior to nursing care, the scores of each dimension in the PTSD-SS, post-traumatic growth, coping style, and quality of life were similar between the two groups (P > 0.05). Following nursing intervention, the observation group exhibited lower scores in each dimension of the PTSD-SS compared to the control group. Moreover, the scores in each dimension of the children’s version of the Post-Traumatic Growth Inventory (PTGI) were higher in the observation group than in the control group. Additionally, the Confrontation scores in the Medical Coping Modes Questionnaire (MCMQ) were higher in the observation group than in the control group, while the scores of Avoidance and Resignation were lower in the observation group than in the control group. The scores of each dimension in the Pediatric Quality of Life Inventory Measurement Models (PedsQL4.0) were higher than those in the control group (P < 0.05), and the family satisfaction in the observation group (96.15%) was higher than that in the control group (81.25%), with P < 0.05.ConclusionThe implementation of nursing intervention based on stress system theory combined with painting therapy in children with PTSD following an accidental injury can alleviate stress, help them actively cope with the condition, promote post-traumatic growth, and improve the quality of life and family satisfaction.

Reliability and validity of a newly developed PANDAS/PANS questionnaire

ObjectiveThis study aimed to examine the reliability and validity of a newly developed questionnaire for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). The aim was to contribute to future standardisation of screening methods for symptoms and comorbidity, as well as the measurement of symptom severity, daily life impairment, and treatment effectiveness in individuals diagnosed with PANDAS/PANS. Methods27 items from the PANDAS/PANS questionnaire concerning symptoms and comorbidities associated with PANDAS/PANS were divided into ten domains. To assess the external validity, 119 PANDAS/PANS questionnaires from a cohort of 65 children with PANDAS/PANS were correlated with three well-known validated questionnaires: the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS), and the Strengths and Difficulties Questionnaire (SDQ). The internal validity of the PANDAS/PANS questionnaire was assessed by correlating the PANDAS/PANS items with the domains. ResultsInternal consistency of the PANDAS/PANS questionnaire was high, measuring moderate to very strong correlations. The external correlations for the PANDAS/PANS questionnaire showed a higher correlation with the ADHD-RS and CY-BOCS (rs ≥ 0.60) than with the SDQ (rs < 0.40). ConclusionThe validity and clinical feasibility of the PANDAS/PANS questionnaire were confirmed as an effective tool for screening symptoms, assessing symptom severity, and evaluating comorbidity and daily life impairment in individuals with PANDAS/PANS. These findings can potentially enhance the management of PANDAS/PANS patients in both clinical and research settings.

The Klotho protein and FGF23 as well-known players in the aging process but underestimated in the process of individual development and selected diseases of childhood and adolescence – a systematic review

Introduction and objective: The FGF23–Klotho endocrine axis plays a pivotal role not only in processes associated with aging but also in metabolic pathways, with implications for paediatric disorders. The aim of this study was to systematically review the existing literature on Klotho and FGF23 in the paediatric population. Materials and methods: Based on the PubMed and Web of Science databases, we conducted a PRISMA-guided search using (klotho) AND (children); (FGF23) AND (children), adhering strictly to the PRISMA guidelines, and assessed evidence quality. Results: The systematic review included 66 studies. Altered Klotho and FGF23 serum levels were observed in paediatric metabolic conditions (chronic kidney disease, diabetes), cardiovascular, and growth and musculoskeletal disorders. In some of them, Klotho and FGF23 serum levels changed with disorder treatment. Elevated FGF23 and Klotho deficiency in renal failure adversely impacted the cardiovascular system. Lower Klotho levels were found in preterm neonates, especially with bronchopulmonary dysplasia. Early Klotho supplementation in a bronchopulmonary dysplasia model mitigated lung tissue changes and improved the cardiac function. Children with lower Klotho levels undergoing cardiac surgeries faced a higher risk of postoperative complications, especially acute kidney injury. In X-linked hypophosphataemia, excess FGF23 led to musculoskeletal consequences. FGF23 serum levels aided the diagnosis of hypophosphataemic rickets, and anti-FGF23 antibody emerged as a common X-linked hypophosphataemia treatment. Conclusions: Klotho and FGF23 serve as promising early markers for paediatric metabolic disorders, offering a valuable tool for assessing complication risks. Klotho supplementation holds promise as a treatment method for specific paediatric disorders, while anti-FGF23 antibody is already established in X-linked hypophosphataemia treatment.

A Preliminary Assessment to Determine the Starting Point for Treatment of Pediatric Feeding Disorders

A Preliminary Assessment to Determine the Starting Point for Treatment of Pediatric Feeding Disorders

Health Related Quality of Life of Children with Pediatric Mental Disorders and Their Caregivers

Abstract Background Studies have shown that the presence of pediatric mental disorders causes great impairment in academic, social, and professional activities as well as in the quality of life (QoL) of the patients as well as their caregivers. Aim of the Work Compare the health related quality of life (HRQoL) scores of children with pediatric mental disorders and their caregivers to those of apparently healthy children of comparable sex and age. Patients and Methods This was an observational study that included seventy-five (75) children with various pediatric mental disorders of different diagnoses (25 cases ASD, 25 cases nocturnal enuresis, 25 cases ADHD) represented the patient group (1). They were 25 females and 50 males. Their ages ranged between 4–15 years with mean ± SD of 9.32 ± 4.72 years. Another 25 healthy children matched in age and sex with the patients’ group (1) were selected as a control group (2). Results Caregivers of children with ASD, nocturnal enuresis and ADHD had an elevated risk of experiencing mental health problems. Children with ASD, enuresis and ADHD have a higher risk for additional behavioral problems tested by Pediatric Symptom Checklist, Child Behavior Checklist and DSM-V. Female cases, in all subgroups, had lower scores than male cases in the three subgroups regarding PSC and CBCL of attention, internalizing and externalizing subscales; however, results didn’t reach level of significance Conclusion Children with ASD, enuresis and ADHD and their caregivers have a higher risk for additional behavioral problems than children without mental disorders.

Quality of Life in Pediatric Iritable Bowel Syndrome among a Sample of Egyptian Children at Ain Shams University Hospitals

Abstract Background Iritable bowel syndrome (IBS) is one of the pediatric functional gastrointestinal disorder with upper and lower gastrointestinal symptoms.IBS afects the child’s daily activities and quality of life (QoL) negatively, and can often persist into adulthood. Objectives To measure the dimensions of QoL of children with IBS among a sample of Egyptian pediatric patients at Ain Shams University Hospitals. Methods A cross-sectional study was conducted on 80 children aged 5-15 years old, who were diagnosed as IBS, according to Rome IV criteria Pediatric quality of life Inventory Generic Core (PedsQL generic core scale was used to measure QoL of the patients,where 100 is the maximum quality score. Results A total of 80 children participated in the study ; 48 (60%) males and 32 (40%) females with mean age 10.6 (SD2.7) years. Physical functioningscorewascalculatedtobe96.04(SD5.5), socialfunctioning score was 99.37 (SD3.95), emotional functioning score was 90.37 (SD8.85), and school functioning score was 73.25 (SD27.34).The school functioning scale was higher among male participants (P-value0.31), also the emotional scale was higher among male participants with no statistical significant diference (P-value0.70). Conclusion IBS afects the school functioning dimension of OoL among the pediatric age group rather than other dimensions.

Pathogenic variants associated with speech/cognitive delay and seizures affect genes with expression biases in excitatory neurons and microglia in developing human cortex.

Congenital brain malformations and neurodevelopmental disorders (NDDs) are common pediatric neurological disorders and result in chronic disability. With the expansion of genetic testing, new etiologies for NDDs are continually uncovered, with as many as one third attributable to single-gene pathogenic variants. While our ability to identify pathogenic variants has continually improved, we have little understanding of the underlying cellular pathophysiology in the nervous system that results from these variants. We therefore integrated phenotypic information from subjects with monogenic diagnoses with two large, single-nucleus RNA-sequencing (snRNAseq) datasets from human cortex across developmental stages in order to investigate cell-specific biases in gene expression associated with distinct neurodevelopmental phenotypes. Phenotypic data was gathered from 1) a single-institution cohort of 84 neonates with pathogenic single-gene variants referred to Duke Pediatric Genetics, and 2) a cohort of 4,238 patients with neurodevelopmental disorders and pathogenic single-gene variants enrolled in the Deciphering Developmental Disorders (DDD) study. Pathogenic variants were grouped into genesets by neurodevelopmental phenotype and geneset expression across cortical cell subtypes was compared within snRNAseq datasets from 86 human cortex samples spanning the 2nd trimester of gestation to adulthood. We find that pathogenic variants associated with speech/cognitive delay or seizures involve genes that are more highly expressed in cortical excitatory neurons than variants in genes not associated with these phenotypes (Speech/cognitive: p=2.25×10-7; Seizures: p=7.97×10-12). A separate set of primarily rare variants associated with speech/cognitive delay or seizures, distinct from those with excitatory neuron expression biases, demonstrated expression biases in microglia. We also found that variants associated with speech/cognitive delay and an excitatory neuron expression bias could be further parsed by the presence or absence of comorbid seizures. Variants associated with speech/cognitive delay without seizures tended to involve calcium regulatory pathways and showed greater expression in extratelencephalic neurons, while those associated with speech/cognitive delay with seizures tended to involve synaptic regulatory machinery and an intratelencephalic neuron expression bias (ANOVA by geneset p<2×10-16). By combining extensive phenotype datasets from subjects with neurodevelopmental disorders with massive human cortical snRNAseq datasets across developmental stages, we identified cell-specific expression biases for genes in which pathogenic variants are associated with speech/cognitive delay and seizures. The involvement of genes with enriched expression in excitatory neurons or microglia highlights the unique role both cell types play in proper sculpting of the developing brain. Moreover, this information begins to shed light on distinct cortical cell types that are more likely to be impacted by pathogenic variants and that may mediate the symptomatology of resulting neurodevelopmental disorders.

Role of trichoscopy in diagnosis of different hair and scalp disorders in pediatrics

Role of trichoscopy in diagnosis of different hair and scalp disorders in pediatrics

Pediatric Treatment-Resistant Obsessive Compulsive Disorder: Treatment Options and Challenges.

Pediatric obsessive-compulsive disorder (OCD) is a chronic, potentially debilitating psychiatric condition. Although effective treatments exist, at least 10% of youth do not achieve remission despite receiving first-line treatments. This article reviews the extant, albeit limited, evidence supporting treatment approaches for youth with treatment-resistant OCD. A literature search for articles addressing pediatric treatment-resistant OCD was conducted through April 11, 2024. These results were augmented by searching for treatment-resistant OCD in adults; treatment strategies discovered for the adult population were then searched in the context of children and adolescents. In general, intensive treatment programs and antipsychotic augmentation of an antidepressant had the most substantial and consistent evidence base for treatment-resistant youth with OCD, although studies were limited and of relatively poor methodological quality (i.e., open trials, naturalistic studies). Several pharmacological approaches (clomipramine, antipsychotics [e.g., aripiprazole, risperidone], riluzole, ketamine, D-cycloserine, memantine, topiramate, N-acetylcysteine, ondansetron), largely based on supporting data among adults, have received varying levels of investigation and support. There is nascent support for how to treat pediatric treatment-resistant OCD. Future treatment studies need to consider how to manage the significant minority of youth who fail to benefit from first-line treatment approaches.