Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Psychogenic non-epileptic seizures are accompanied by motor,behavioral,sensory,and/or cognitive changes,with the clinical manifestations similar to epileptic seizures.This disease is easy to be misdiagnosed and neglected in clinical work.At present,most intervention measures still depend on the experience of clinicians.This article reviews the comorbidities of psychogenic non-epileptic seizures,including mental and cognitive disorders,somatic syndrome,sleep disorders,and epilepsy.This review aims to strengthen the precision of clinical treatment and management of patients with psychogenic non-epileptic seizures and provide more efficient individualized diagnosis and treatment programs for patients.
Humans ; Seizures/diagnosis* ; Comorbidity ; Epilepsy ; Sleep Wake Disorders ; Mental Disorders ; Psychophysiologic Disorders ; Cognition Disorders

The occurrence of seizures after hemorrhagic stroke is a significant contributor to mortality in patients with hemorrhagic stroke. Compared with ischemic stroke， hemorrhagic stroke is more frequently to cause seizures， with high disability and high mortality. If not detected early and treated in time， seizures may aggravate patient’s conditions in the acute stage， and cause accidental injuries in the recovery stage， increasing the burden on patient’s family. Early prediction and timely treatment of seizures can improve the survival rate and quality of life of patients. With science and technology advances， domestic and international researchers have established prediction models for seizures after hemorrhagic stroke， which use machine learning methods to process and identify relevant data， improving the accuracy of prediction for the disease. This review aims to summarize risk factors for post-hemorrhagic stroke seizures and related prediction models， so as to provide guidance for clinical diagnosis and treatment.
Seizures

BACKGROUND AND OBJECTIVE

Benign convulsions with mild gastroenteritis (CwG) is common but not readily recognizable to primary care physicians and pediatricians. Most literature comes from East Asia and Western countries. Studies among the Filipino population are lacking. This study aimed to determine the clinical presentation, management, and outcomes, and provide knowledge for accurate diagnosis and appropriate management.

This is a retrospective cohort study on pediatric patients diagnosed with CwG admitted at a tertiary hospital in the Philippines from January 2020 to December 2023. The study included patients 1-72 months old presenting with seizures accompanied by symptoms of gastroenteritis, without clinical signs of dehydration, electrolyte derangement, and fever (body temperatureRESULTS

Twenty patients met the criteria for CwG, aged 7-60 months, with a male:female ratio of 1:1. Most seizures were brief, generalized tonic-clonic occurring in clusters, with an average frequency of 3 per day. Laboratory findings, electroencephalogram, and neuroimaging results were mostly normal. Anti-seizure medications (ASMs) were prescribed in 65% (n=13), with levetiracetam being the most common. Most seizure clusters did not persist, and none needed additional ASM. Follow-up showed normal neurodevelopmental profiles.

This study highlights that CwG is also encountered among Filipino children. The clinical characteristics align with the known presentation of CwG. Most patients had normal test results and a benign course. Given this selflimiting nature, extensive testing and unnecessary therapy are not recommended, and instead provision of adequate counseling to the caregivers is advocated.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Neuropsychiatric SLE (NPSLE) comprises the neurologic and psychiatric syndromes observed in patients with SLE after exclusion of other causes. The diagnosis of NPSLE is challenging due to diverse clinical manifestations and absence of laboratory or radiologic biomarkers.

We present the case of a patient with SLE with a chronic isolated seizure and was successfully managed with antiepileptic medication and high-dose corticosteroids.

Seizures may occur as an isolated manifestation of an SLE flare. Ischemic and inflammatory causes of seizure may coexist in active lupus and both should be considered in managing patients. A prompt and holistic workup to rule out metabolic, infectious, and structural neural causes and lupus disease activity of seizures is prudent for patients with SLE.

Neuropsychiatric SLE (NPSLE) comprises the neurologic and psychiatric syndromes observed in patients with SLE after exclusion of other causes. The diagnosis of NPSLE is challenging due to diverse clinical manifestations and absence of laboratory or radiologic biomarkers.

We present the case of a patient with SLE with a chronic isolated seizure and was successfully managed with antiepileptic medication and high-dose corticosteroids.

Seizures may occur as an isolated manifestation of an SLE flare. Ischemic and inflammatory causes of seizure may coexist in active lupus and both should be considered in managing patients. A prompt and holistic workup to rule out metabolic, infectious, and structural neural causes and lupus disease activity of seizures is prudent for patients with SLE.

OBJECTIVE: To explore the genetic etiology of a child with Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS). METHODS: A child who was admitted to the Children's Hospital Affiliated to Nanjing Medical University in April 2022 for motor developmental delay, intellectual disability, and hypertonia was selected as the study subject. Relevant clinical data were retrospectively analyzed. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were searched in the Single Nucleotide Polymorphism Database (dbSNP) and Online Mendelian Inheritance in Man (OMIM) database. Pathogenicity of the variants was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Using key words such as "HACE1 gene" "Spastic paraplegia and psychomotor retardation with or without seizures" and "SPPRS", previous reports on SPPRS patients due to HACE1 gene variants were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, CQVIP, and PubMed databases, with the time set from January 1, 2000 to April 7, 2024. A mutation map for the HACE1 protein in the patients was created. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Nanjing Medical University (Ethics No. 202404008-1). RESULTS: The clinical manifestations of the child had included motor developmental delay, intellectual disability and hypertonia. Magnetic resonance imaging revealed hypoplasia of posterior corpus callosum and splenium, with slight enlargement of lateral ventricles. WES revealed that the child has harbored compound heterozygous variants of the HACE1 gene, namely c.535(exon7)_c.538(exon7)delACAG (p.T179fs*5) and c.1678+2(IVS15)T>C, which were respectively inherited from his parents. Based on the guidelines from the ACMG, the variants were respectively rated as likely pathogenic (PVS1 + PM2_Supporting) and pathogenic (PVS1 + PM2_Supporting + PM3). Literature search has identified 8 papers, which reported 23 SPPRS cases due to HACE1 gene variants. All patients exhibited psychomotor developmental delay, among whom 18 HACE1 gene variants were identified. CONCLUSION The c.535(exon7)_c.538(exon7)delACAG (p.T179fs*5) and c.1678+2(IVS15)T>C compound heterozygous variants of the HACE1 gene probably underlay the pathogenesis of SPPRS in this child. Above discovery has enriched the mutational and phenotypic spectrum of the HACE1 gene and provided a reference for clinical diagnosis and genetic counseling.
Humans ; Male ; Seizures/genetics* ; Ubiquitin-Protein Ligases/genetics* ; Heterozygote ; Mutation ; Child ; Child, Preschool ; Paraplegia/genetics* ; Intellectual Disability/genetics* ; Polymorphism, Single Nucleotide ; Exome Sequencing ; Psychomotor Disorders/genetics*

OBJECTIVE: To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS). METHODS: A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital of Zhengzhou University (Ethics No. 2024-KY-1103-001). RESULTS: The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c.1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. CONCLUSION The hemizygous c.1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.
Humans ; Male ; Infant ; Microcephaly/genetics* ; Spasms, Infantile/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing ; Intellectual Disability/genetics* ; Genetic Diseases, X-Linked/genetics* ; Mutation ; Seizures/genetics* ; Ataxia ; Epilepsy ; Ocular Motility Disorders