-
Neurology Apr 2024To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal...
BACKGROUND AND OBJECTIVES
To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal neurodevelopmental outcomes, focusing on social, emotional, behavioral, and adaptive domains of human function, and the frequency of neurodevelopmental and psychiatric disorders in ASM-exposed offspring.
METHODS
Electronic searches of MEDLINE, PsychINFO, and EMBASE were conducted and limited to studies published between 1990 and 2023 in English. Studies were eligible if they prospectively or retrospectively reported neurodevelopmental outcomes of ASM-exposed offspring. The Newcastle-Ottawa scale was used to conduct methodologic quality assessments of included studies, and a narrative synthesis integrated the review findings.
RESULTS
Forty-three studies were included. Valproate has been consistently associated with a 2- to 4-fold increased risk of autism spectrum disorder (ASD), 2- to 5-fold increased risk of intellectual disability (ID), and poor adaptive functioning. Growing evidence indicates that topiramate is associated with a 2-fold increased risk of ASD and 3- to 4-fold increased risk of ID. The risks of adverse neurodevelopmental outcomes for valproate and topiramate seem to be dose dependent. Phenobarbital has been suggested to be associated with deleterious neurodevelopmental effects, but data are limited. Levetiracetam has recently been linked with an increased risk of attention deficit hyperactivity disorder and anxiety disorders in a single study. Carbamazepine has been associated with variable neurodevelopmental outcomes. Lamotrigine seems to be "safe" in terms of postnatal neurodevelopment. Data for oxcarbazepine, phenytoin, and clonazepam are limited but seem to have little-to-no risk of adverse outcomes. Evidence for the remaining ASMs, including gabapentin, pregabalin, lacosamide, zonisamide, clobazam, perampanel, ethosuximide, or brivaracetam, is lacking. Several methodologic limitations impeded data synthesis, including heterogeneity in outcome measures and small samples of monotherapy exposures.
DISCUSSION
The findings of this review support the conclusion that valproate and topiramate use during pregnancy is associated with a significantly increased risk of neurodevelopmental effects on the fetus. Apart from lamotrigine, which seems to be free of adverse neurodevelopmental effects, data for the other ASMs are mixed or inadequate to draw definite conclusions. Further research into the neurodevelopmental effects of prenatal exposure to ASMs, including most newer agents, is much needed.
Topics: Pregnancy; Female; Humans; Valproic Acid; Lamotrigine; Topiramate; Autism Spectrum Disorder; Retrospective Studies; Anticonvulsants
PubMed: 38531021
DOI: 10.1212/WNL.0000000000209175 -
World Journal of Clinical Cases Mar 2024Sensory integration intervention is highly related to the child's effective interaction with the environment and the child's development. Currently, various sensory...
BACKGROUND
Sensory integration intervention is highly related to the child's effective interaction with the environment and the child's development. Currently, various sensory integration interventions are being applied, but research methodological problems are arising due to unsystematic protocols. This study aims to present the optimal intervention protocol by presenting scientific standards for sensory integration intervention through meta-analysis.
AIM
To prove the effectiveness of sensory integration therapy, examine the latest trend of sensory integration studies in Korea, and provide clinical evidence for sensory integration therapies.
METHODS
The database of Korean search engines, including RISS, KISS, and DBpia, was used to search for related literature published from 2001 to October 2020. The keywords, "Children", "Sensory integration", "Integrated sensory", "Sensory-motor", and "Sensory stimulation" were used in this search. Then, a meta-analysis was conducted on 24 selected studiesRISS, KISS, and DBpia, was used to search for related literature published from 2001 to October 2020. The keywords, "Children", "Sensory integration", "Integrated sensory", "Sensory-motor", and "Sensory stimulation" were used in this search. Then, a meta-analysis was conducted on 24 selected studies.
RESULTS
Sensory integration intervention has been proven effective in children with cerebral palsy, autism spectrum disorder, attention deficit/hyperactivity disorder, developmental disorder, and intellectual disability in relation to the diagnosis of children. Regarding sensory integration therapies, 1:1 individual treatment with a therapist or a therapy session lasting for 40 min was most effective. In terms of dependent variables, sensory integration therapy effectively promoted social skills, adaptive behavior, sensory processing, and gross motor and fine motor skills.
CONCLUSION
The results of this study may be used as therapeutic evidence for sensory integration intervention in the clinical field of occupational therapy for children, and can help to present standards for sensory integration intervention protocols.
PubMed: 38524513
DOI: 10.12998/wjcc.v12.i7.1260 -
BMC Pediatrics Mar 2024Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for Rett syndrome, there is a dire need for effective interventions.
OBJECTIVE
To evaluate the safety and efficacy of trofinetide in Randomized Controlled Trials (RCTs) that report on Rett syndrome patients.
METHODS
We identified 109 articles from four databases (Scopus, PubMed, Web of Science, and Cochrane CENTRAL). After removing the duplicates, we narrowed them down to 59 articles for further assessment. We included RCTs that evaluated the efficacy and safety of trofinetide in patients with Rett syndrome. Three studies were eligible for inclusion. Two independent reviewers evaluated the identified studies' titles, abstracts, and full texts, extracting pertinent data. We assessed the quality of the studies using the Cochrane Risk of Bias (RoB) 2.0 tool. We then conducted a meta-analysis using the fixed effects model in the case of insignificant heterogeneity; otherwise, we used the random effects model. Based on the nature of the outcome, we analyzed the mean difference or the odds ratio. Analysis was conducted using RevMan version 5.3.
RESULTS
Among the analyzed outcomes in 181 patients in the trofinetide group and 134 patients in the placebo group, significant improvement in Rett Syndrome Behavior Questionnaire (RSBQ) scores was observed at 200 mg dosage (overall mean difference: -3.53, p = 0.001). Clinical Global Impression-Improvement (CGI-I) scores improved considerably at 200 mg dosage (overall mean difference: -0.34, p < 0.0001). No substantial changes were observed in Motor Behavioral Assessment (MBA) or Top 3 Caregiver Concerns. We evaluated Treatment Emergent Adverse Events (TEAEs) across the various dosages and noted significant associations with diarrhea (200 mg), vomiting (200 mg), and irritability (200 mg). However, we did not find a significant association between any of the dosages and the incidence of decreased appetite.
CONCLUSION
Trofinetide demonstrated potential in improving RSBQ and CGI-I scores at 200 mg dosage. Although no substantial changes were found in MBA and top 3 caregiver concerns. Adverse events were linked to specific dosages.
Topics: Female; Humans; Rett Syndrome; Randomized Controlled Trials as Topic; Glutamates; Diarrhea
PubMed: 38521908
DOI: 10.1186/s12887-024-04526-3 -
European Child & Adolescent Psychiatry Mar 2024While youths with intellectual disability (ID) have increased vulnerability for depressive disorders, cognitive problems and combined functional barriers make them less... (Review)
Review
While youths with intellectual disability (ID) have increased vulnerability for depressive disorders, cognitive problems and combined functional barriers make them less prone to receive adequate treatments. A systematic review of the literature was conducted (PROSPERO Registration number: CRD42022347703) based on several databases from 1980 to 2022 to examine the quality of tools for measuring depression in children and adolescents with ID. The COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) checklist was used to assess several psychometric domains. Twelve studies evaluated the properties of six tools for measuring depression in youths with ID. The Center for Epidemiologic Studies Depression Scale-Intellectual Disability (CESD-ID) was the only scale with at least five domains of psychometric properties assessed to have strong or moderate evidence. Based on the reviewed findings, tools specifically developed for populations with developmental disabilities should be considered first in order to screen depression in youths with ID. Much work is required to confirm their validity in clinical samples with patients with a complex form of developmental disabilities. As a complement to self- and caregivers-report questionnaires, clinician rating scales were considered useful to catch the full picture of depression in youths with ID, in particular associated behavioral expressions. Their validity received little scrutiny and certainly deserve more attention to improve care practice of youths with ID.
PubMed: 38509427
DOI: 10.1007/s00787-024-02405-x -
Immunity, Inflammation and Disease Mar 2024Down syndrome (DS) is associated with multiple comorbid conditions and chronic immune dysfunction. Persons with DS who contract COVID-19 are at high risk for... (Review)
Review
INTRODUCTION
Down syndrome (DS) is associated with multiple comorbid conditions and chronic immune dysfunction. Persons with DS who contract COVID-19 are at high risk for complications and have a poor prognosis. We aimed to study the clinical symptoms, laboratory and biochemical profiles, radiologic findings, treatment, and outcomes of patients with DS and COVID-19.
METHOD
We systematically searched PubMed, MEDLINE, Web of Science, Scopus, and the Cochrane Library using the keywords COVID-19 or coronavirus or SARS-CoV-2 and DS or trisomy 21. Seventeen articles were identified: eight case reports and nine case series published from December 2019 through March 2022, with a total of 55 cases.
RESULTS
Patients averaged 24.8 years (26 days to 60 years); 29 of the patients were male. The most common symptoms were fever, dyspnea, and cough. Gastrointestinal and upper respiratory tract symptoms were commonly reported for pediatric patients. The most common comorbidities present in patients with DS were obesity (49.0%), hypothyroidism (21.6%) and obstructive sleep apnea (15.6%). The patients were hospitalized for a mean of 14.8 days. When the patients were compared with the general COVID-19 population, the mean number of hospitalized days was higher. Most patients had leukopenia, lymphopenia, and elevated inflammatory markers (d-dimer and C-reactive protein). Bilateral infiltrations and bilateral ground-glass opacifications were frequently seen in chest radiographs and chest computed tomographic imaging. Most of the patients were treated with methylprednisolone, macrolides, and hydroxychloroquine. Of the 55 patients, 22 died. The mean age of the patients who died was 42.8 years. Mortality rate was higher in individuals with DS over 40 years of age.
CONCLUSION
More studies are needed to better understand COVID-19 infections among persons with DS. In addition, the study was limited by a lack of statistical analyses and a specific comparison group.
Topics: Adult; Child; Female; Humans; Male; Middle Aged; Cough; COVID-19; Down Syndrome; Lymphopenia; SARS-CoV-2; Infant, Newborn; Infant; Child, Preschool; Adolescent; Young Adult
PubMed: 38501534
DOI: 10.1002/iid3.1219 -
Seizure Apr 2024Adequate pre-pregnancy counselling and education planning are essential to improve outcomes for offspring of women with epilepsy (OWWE). The current systematic review... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Adequate pre-pregnancy counselling and education planning are essential to improve outcomes for offspring of women with epilepsy (OWWE). The current systematic review and meta-analysis aimed to compare outcomes for OWWE and offspring of women without epilepsy (OWWoE).
METHODS
We conducted a systematic review and meta-analysis. We searched MEDLINE, EMBASE, CINAHL, PsycINFO (database inception-1 January 2023), OpenGrey, GoogleScholar, and hand-searched journals and reference lists of included studies to identify eligible studies. We placed no language restrictions and included observational studies concerning OWWE and OWWoE. We followed the PRIMSA checklist for abstracting data. The Newcastle-Ottawa Scale for risk of bias assessment was conducted independently by two authors with mediation by a third. We report pooled unadjusted odds ratios (OR) or mean differences (MD) with 95% confidence intervals (95CI) from random (I>50%) or fixed (I<50%) effects meta-analyses. Outcomes of interest included offspring autism, attention deficit/hyperactive disorder, intellectual disability, epilepsy, developmental disorder, intelligence, educational, and adulthood socioeconomic outcomes.
RESULTS
Of 10,928 articles identified, we included 21 in meta-analyses. OWWE had increased odds of autism (2 articles, 4,502,098 offspring) OR [95CI] 1·67 [1·54, 1·82], attention-deficit/hyperactivity disorder (3 articles, 957,581 offspring) 1·59 [1·44, 1·76], intellectual disability (2 articles, 4,501,786 children) 2·37 [2·13, 2·65], having special educational needs (3 articles, 1,308,919 children) 2·60 [1·07, 6·34]. OWWE had worse mean scores for full-scale intelligence (5 articles, 989 children) -6·05 [-10·31, -1·79]. No studies were identified that investigated adulthood socioeconomic outcomes.
CONCLUSIONS
Increased odds of poor outcomes are higher with greater anti-seizure medication burden including neurodevelopmental and educational outcomes. In fact, these two outcomes seem to be worse in OWWE compared to OWWoE, even if there was no ASM exposure during pregnancy, but further work is needed to take into account potential confounding factors.
Topics: Humans; Epilepsy; Female; Pregnancy; Adult; Pregnancy Complications; Neurodevelopmental Disorders; Educational Status; Socioeconomic Factors; Developmental Disabilities
PubMed: 38484631
DOI: 10.1016/j.seizure.2024.02.014 -
Frontiers in Endocrinology 2024Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations...
BACKGROUND
Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.
METHODS
We systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.
RESULTS
Our study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.
CONCLUSION
Based on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.
Topics: Humans; Hedgehog Proteins; Pituitary Diseases; Pituitary Gland; Hypopituitarism; Mutation; Syndrome
PubMed: 38464967
DOI: 10.3389/fendo.2024.1338781 -
Epilepsia May 2024Fully elucidating the burden that Lennox-Gastaut syndrome (LGS) places on individuals with the disease and their caregivers is critical to improving outcomes and quality... (Review)
Review
Fully elucidating the burden that Lennox-Gastaut syndrome (LGS) places on individuals with the disease and their caregivers is critical to improving outcomes and quality of life (QoL). This systematic literature review evaluated the global burden of illness of LGS, including clinical symptom burden, care requirements, QoL, comorbidities, caregiver burden, economic burden, and treatment burden (PROSPERO ID: CRD42022317413). MEDLINE, Embase, and the Cochrane Library were searched for articles that met predetermined criteria. After screening 1442 deduplicated articles and supplementary manual searches, 113 articles were included for review. A high clinical symptom burden of LGS was identified, with high seizure frequency and nonseizure symptoms (including developmental delay and intellectual disability) leading to low QoL and substantial care requirements for individuals with LGS, with the latter including daily function assistance for mobility, eating, and toileting. Multiple comorbidities were identified, with intellectual disorders having the highest prevalence. Although based on few studies, a high caregiver burden was also identified, which was associated with physical problems (including fatigue and sleep disturbances), social isolation, poor mental health, and financial difficulties. Most economic analyses focused on the high direct costs of LGS, which arose predominantly from medically treated seizure events, inpatient costs, and medication requirements. Pharmacoresistance was common, and many individuals required polytherapy and treatment changes over time. Few studies focused on the humanistic burden. Quality concerns were noted for sample representativeness, disease and outcome measures, and reporting clarity. In summary, a high burden of LGS on individuals, caregivers, and health care systems was identified, which may be alleviated by reducing the clinical symptom burden. These findings highlight the need for a greater understanding of and better definitions for the broad spectrum of LGS symptoms and development of treatments to alleviate nonseizure symptoms.
Topics: Humans; Lennox Gastaut Syndrome; Cost of Illness; Caregivers; Quality of Life; Intellectual Disability; Caregiver Burden
PubMed: 38456647
DOI: 10.1111/epi.17932 -
Molecular Genetics & Genomic Medicine Mar 2024Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual... (Review)
Review
BACKGROUND
Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities.
METHODS
We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.
RESULTS
We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.
CONCLUSION
We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.
Topics: Adult; Female; Humans; Asian People; Databases, Factual; Genotype; Intellectual Disability; Phenotype
PubMed: 38444259
DOI: 10.1002/mgg3.2398 -
Evidence-based Dentistry Mar 2024A systematic review. (Meta-Analysis)
Meta-Analysis
DESIGN
A systematic review.
AIM
Assess the effectiveness of manual toothbrushes (MTB) and powered toothbrushes (PTB) for people with physical or intellectual disabilities.
DATA SOURCES AND STUDY SELECTION
The following data sources (MEDLINE-PubMed, Cochrane-CENTRAL and EMBASE) were searched from the date of creation to February 2022 for papers which met the inclusion criteria. There were no language limitations set. The included studies were then hand-searched for relevant studies to be included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers screened the studies from the searches using Rayyan web application (Artificial-Intelligence search engine). Studies which met the inclusion criteria were selected. The studies were independently screened for the inclusion/exclusion criteria. Disagreement was resolved by discussion and consensus, or by a third party. Studies were then classified as low/moderate/high risk of bias. Analysis was performed on four subgroups; individual performing the brushing - (1) caregiver or (2) participant, main disability of the participant - (3) physical or (4) intellectual disability. Due to insufficient numerical data, a descriptive analysis was completed in place of the planned meta-analysis.
RESULTS
In total, 16 publications were included within the results. There was no significant difference between manual or powered toothbrushing in both disability groups for the removal of plaque or gingival health. This applied to both self-brushing and caregiver brushing.
CONCLUSIONS
There is no significant difference between powered and manual toothbrushes for effective oral hygiene maintence for people with physical or intellectual disabilities.
Topics: Humans; Toothbrushing; Gingivitis; Intellectual Disability; Oral Hygiene; Gingiva; Equipment Design
PubMed: 38443442
DOI: 10.1038/s41432-024-00981-0