PURPOSE:To characterise clinical features of Rasmussen encephalitis (RE) and identify factors associated with preoperative neurodevelopmental status in affected children. METHODS:This retrospective single-centre study included 51 paediatric patients diagnosed with RE who underwent surgical treatment. Demographic characteristics, seizure features, video-electroencephalography (VEEG) findings, magnetic resonance imaging (MRI) features, and neurodevelopmental assessments were systematically collected. Associations between full-scale developmental quotient/intelligence quotient (FSDQ/IQ) and clinical variables, including age at onset, disease duration, electroencephalography findings, MRI characteristics, and number of antiseizure medications (ASMs), were analysed. RESULTS:All patients underwent hemispherotomy or hemispherectomy and were seizure-free at the latest follow-up, although one experienced postoperative seizures from the contralateral hemisphere. Epilepsia partialis continua occurred in 54.9% of patients, and 52.9% had contralateral independent epileptiform discharges. Early MRI showed hemispheric or focal atrophy in 49%. Preoperative neurodevelopmental assessment was completed in 45 patients, with a mean FSDQ/IQ of 70.5. Overall, 55.6% demonstrated normal or borderline development, and 26.7% had mild developmental delay. Motor function was the most affected domain, whereas cognitive and non-motor domains were generally borderline. Patients with contralateral epileptiform discharges had lower FSDQ/IQ than those without (p = 0.001), and this association remained significant after adjustment for age at seizure onset, disease duration, and number of ASMs. CONCLUSION:Preoperative neurodevelopmental status in children with RE was heterogeneous, with overall scores in the borderline range. Contralateral independent epileptiform discharges were independently associated with lower FSDQ/IQ, although the underlying mechanisms and clinical significance of this association remain uncertain. These findings support close developmental monitoring and individualised preoperative assessment in RE.

IntroductionLinear scleroderma en coup de sabre (ECDS) is a rare disorder that often involves the central nervous system (CNS), requiring systemic immunotherapy. This study characterizes the clinical and neuroimaging features as well as the long-term treatment outcomes of pediatric ECDS.MethodsPatients with ECDS and CNS involvement were enrolled. Clinical manifestations, cranial imaging, pathology, and immunotherapy responses were documented.ResultsSeven patients (6 females and 1 male) were included, with onset ages ranging from 1.8 to 13.5 years. Rash preceded neurological symptoms in five patients; seizures were the initial manifestation in the remaining two. Seizures were the most common neurological symptom (5/7), followed by dizziness (3/7), movement disorder (2/7), blurred vision (1/7), and headache (1/7). All exhibited ipsilateral supratentorial MRI abnormalities, exclusively on the left side and predominantly frontal. White matter lesions were observed in all patients, and cyst-like lesions were identified in four. Brain biopsy performed in two patients indicated vasculitis. All received systemic corticosteroids, either alone (2 cases) or combined with other agents (methotrexate in 5, mycophenolate mofetil in 3, IVIg in 3, tocilizumab in 2, and rituximab in 1). Over 6 months to 15 years of follow-up, neurological symptoms resolved in five patients. Skin lesions progressed in three patients, stabilized in two, and improved in two.ConclusionLinear scleroderma en coup de sabre with CNS involvement predominantly affects females and typically involves the left cerebral hemisphere. Characteristic brain MRI findings include ipsilateral supratentorial white matter abnormalities and cyst-like lesions. Combination therapy with systemic corticosteroids and methotrexate is recommended as first-line treatment, while tocilizumab may be beneficial for refractory cases.

BackgroundKrabbe disease is a rare, rapidly progressive leukodystrophy with high early mortality. Hematopoietic stem cell transplantation (HSCT) is the main disease-modifying intervention used in clinical practice and may act through donor-derived myeloid and immune-cell replacement, enzymatic cross-correction, and immunomodulation. However, its benefits and immune-related toxicities remain incompletely quantified.MethodsWe conducted a systematic review and meta-analysis of studies reporting HSCT outcomes in genetically or enzymatically confirmed Krabbe disease. The primary outcome was overall survival (OS). Secondary outcomes included 5-year OS, transplant-related mortality (TRM), acute and chronic graft-versus-host disease (aGVHD and cGVHD), neurological stability, and MRI stability. For OS, publication bias or small-study effects were assessed using funnel-plot inspection and Egger’s regression test. Exploratory univariable meta-regression examined total study sample size, publication year, and Newcastle–Ottawa Scale (NOS) score, and robustness was assessed using leave-one-out sensitivity analysis.ResultsFifteen studies involving 141 patients were included. Pooled OS after HSCT was 84% (95% CI, 75%–93%), 5-year OS was 80% (69%–92%), and TRM was 7% (1%–13%). The pooled incidences of aGVHD and cGVHD were 53% (16%–90%) and 25% (0%–53%), respectively. Neurological stability was reported in only four studies including 15 patients (77%; 31%–100%), and MRI stability in four studies including 32 patients (49%; 7%–90%); both estimates showed substantial heterogeneity and wide confidence intervals. Subgroup analyses by disease-onset age, pre-transplant symptom status, and age at HSCT showed no statistically significant OS differences. Egger’s test detected no significant funnel-plot asymmetry (P = 0.569). Leave-one-out estimates ranged from 82% to 86%. Meta-regression showed inverse associations of reported OS with total study sample size and NOS score (both P < 0.001), whereas publication year was not significant (P = 0.118).ConclusionHSCT is associated with favorable survival and relatively low pooled TRM in selected patients with Krabbe disease. However, survival should not be interpreted as preservation of neurological function, because neurological, MRI, and GVHD outcomes were reported in few studies and patients and remained heterogeneous and imprecisely estimated. These findings require cautious interpretation but provide clinically useful benchmark data for counseling and comparison with emerging cellular and gene-based therapies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261285624.

BACKGROUND:This study aims to clarify the natural course of Alexander disease and explore genotype‒phenotype correlations and prognostic factors. METHODS:This single-center, bidirectional cohort study included patients genetically confirmed with Alexander disease, aged between 0 and 18 years. Survival curve analysis was conducted to evaluate the acquisition and loss of motor/cognitive skills to clarify the natural course of the disease. Statistical methods such as survival curve analysis and Cox regression analysis were used to analyze genotype‒phenotype correlations and prognostic factors. RESULTS:A total of 81 patients were included. A total of 27 types of gene variants were found among all the children, with 40.7% (11/27) in the 1A domain. At the last follow-up, 12.3% (10/81) of the patients had died. Survival curve analysis for the ability of "walking without support," "sitting down without support," "holding head upright," "understanding and following simple instructions," and "saying simple words" were lost at an average age of 15.2 ± 1.2 years, 17.3 ± 1.4 years, 17.2 ± 1.3 years, 18.8 ± 14.6 years, and 18.2 ± 1.3 years, respectively. Prognostic factor analysis via Cox single-factor and multifactor regression analysis found that patients with variants of R239 had a greater incidence of poor outcome than other variants did (hazard ratio: 2.597 [95% confidence interval: 1.052, 6.409], P = 0.038). CONCLUSIONS:The overall prognosis of Alexander disease is poor, with an average age at death of 18.6 ± 1.4 years and a high incidence of epilepsy (81.5%). Variants of R239 are potential prognostic factors for poor outcome.

Background: Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and epileptic seizures, primarily caused by dysfunction of the maternal UBE3A gene in the 15q11.2 region. The genetic etiology is heterogeneous, including maternal 15q11-q13 deletions, paternal uniparental disomy (UPD) of chromosome 15, maternal pathogenic UBE3A variants, or imprinting defects. This diversity necessitates comprehensive diagnostic approaches, posing challenges for precise diagnosis and genetic counseling. Methods: Clinically suspected AS patients were recruited, and their clinical and genetic data were analyzed. Multiple genetic testing methods were employed, including methylation-specific MLPA (MS-MLPA), trio-based whole-exome sequencing (WES), whole-genome sequencing (WGS), SNP-array and copy number variation sequencing (CNV-seq). Long-range PCR (LR-PCR), PacBio Sequel series Single Molecule Real-Time (SMRT) sequencing technology and Blocker displacement amplification (BDA) were used to determine parental allele origin and detect low-level mosaicism. Results: Thirteen patients were included. All exhibited moderate to severe developmental delay, six had epilepsy with characteristic EEG findings. Ataxia, frequent smiling and laughter, microcephaly and dysmorphism were observed in 5, 4, 2, and 2 cases, respectively. Brain MRI findings were either normal or showed nonspecific abnormalities. Genetic analysis identified UBE3A heterozygous variants (8 cases), 15q11-q13 deletions (4 cases) and paternal UPD (1 case). Three novel variants in UBE3A (c.409T > G p. (Cys137Gly), c.2038_2042del p. (Ser680fs), c.2510C > T p. (Ser837Phe)) have not been reported before. Notably, two siblings harbored the same UBE3A variant (c.409T > C p. (Cys137Arg)) undetectable in parental blood; PacBio sequencing confirmed parental allele origin. Negative BDA result suggests the mosaic mother either does not harbor this variant or this variant exists in the assessed somatic samples but at a level lower than 5‰. Conclusions: This study summarizes characteristics of 13 Chinese patients with AS, expanding the clinical and genetic spectrum of AS. It reveals the genetic heterogeneity of AS, emphasizing the necessity of multimodal testing for accurate diagnosis. Long-read sequencing enhances parental origin determination, and germline mosaicism underscores the need for prenatal counseling.

The SSPOP gene, currently classified as a pseudogene in the human genome, encodes the SCO-spondin protein, which plays an important role in human neurodevelopment, although its function remains poorly understood. In this study, we used trio-based whole exome sequencing to identify compound heterozygous SSPOP variants in four children from three unrelated families, including one pair of dizygotic twins. These children exhibited variable phenotypes, including variation in age of onset, seizure semiology, and response to antiseizure medications, along with neurodevelopmental disorders. We demonstrated that SSPOP is a functional gene by confirming its expression at both the transcriptional and protein levels. We analysed 10 brain tissue samples from seven paediatric patients and brain organoids derived from human induced pluripotent stem cells to confirm its expression via qRT-PCR, immunofluorescence and western blotting, supporting its biological function during both pre- and post-natal stages of brain development. In addition, CRISPR-mediated sspo knockout zebrafish demonstrated abnormal neurodevelopment and epileptic discharges in vivo. Together, these findings suggest that SSPOP is a functional gene and a potential contributor to neurodevelopmental disorders and epilepsy.

Febrile infection-related epilepsy syndrome (FIRES) is a rare and severe epileptic encephalopathy characterized by refractory seizures following a febrile infection. FIRES is a subtype of new-onset refractory status epilepticus with an unknown etiology. Tocilizumab is an interleukin-6 receptor antagonist which has been recommended as an anti-inflammatory treatment for the acute phase of FIRES. However, the efficacy of tocilizumab for the chronic phase of FIRES remains unclear. This study aimed to analyze the efficacy and safety of tocilizumab in the treatment of pediatric patients with FIRES during the chronic phase. We conducted a retrospective cohort study in pediatric patients with FIRES during the chronic phase who received tocilizumab treatment. The primary outcome was the response rate at 16 weeks after tocilizumab initiation, defined as the proportion of pediatric patients who achieved a 50

N-methyl-D-aspartate receptors (NMDARs) play a pivotal role in neurodevelopment. While pathogenic variants in GRIN genes cause a broad spectrum of epileptic and developmental disorders, the precise molecular determinants that drive specific neurodevelopmental courses remain poorly understood. This study aims to utilize high-resolution structural modeling to identify associations between localized conformational alterations in NMDARs and distinct clinical phenotypes. We retrospectively evaluated a cohort of 31 Chinese pediatric patients with GRIN-related epilepsy (GRIN1, n = 3; GRIN2A, n = 14; GRIN2B, n = 11; GRIN2D, n = 3) using detailed electroclinical and neurodevelopmental phenotyping. Concurrently, three-dimensional structural models for 23 missense variants were generated using AlphaFold2. Domain-specific root-mean-square deviation (RMSD) and Euclidean displacements of transmembrane helices were quantified. Patients in this cohort predominantly presented with early-onset epilepsy, multiple seizure types, and significant pharmaco-resistance, with 41.9

Dravet syndrome (DS) is a developmental and epileptic encephalopathy caused mainly by SCN1A variants, several other genes have been implicated in DS-like phenotype. DS and DS-like patients were collected from February 2005 to December 2023. Clinical data and genetic results were collected and analyzed. 1215 patients were enrolled. SCN1A variants were identified in 1061 patients (87.3

Objective To observe the improvement of upper limb motor function in children with hemiplegic spastic cerebral palsy(HSCP)by different time serial modes of"brain-limb coordination".Methods Clinical data of 60 children with HSCP admitted to Department of Children's Rehabilitation,Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from June 2023 to August 2024 were retrospectively analyzed.All patients were randomly divided into the observation group(n=30)and control group(n=30).Patients in two groups were treated with routine rehabilitation,combined with repeated transcranial magnetic stimulation and massage,respectively.In addition,synchronous mode of"brain-limb coordination"was adopted in the observation group,while asynchronous mode of"brain-limb coordination"in the control group for consecutive 12 weeks.The muscle tension of biceps brachii and flexor carpi in hemiplegic upper limbs was evaluated by Modified Ashworth Scale(MAS).The grasping ability and visual-motor comprehensive ability were assessed by Peabody Developmental Motor Scale-Fine Motor(PDMS-FM)and Fine Motor Quotient(FMQ),respectively.The upper limb function was evaluated by Carroll Upper Extremity Function Test(UEFT).The changes of upper limb muscle tension grade were observed before and after treatment.The upper limb motor function,hand fine motor quotient,upper limb grasping function and hand coordination score were statistically compared between two groups.Independent sample t test was used for comparison between two groups,and paired t test was used for intra-group comparison before and after interventions.Results After 12 weeks of treatment,children in the two groups obtained lower MAS scores of biceps brachii(t=-7.259,-3.924;both P＜0.05)and flexor carpi(t=-10.818,-6.233;both P＜0.05)compared with those before treatment.The muscle tension MAS scores of biceps brachii and flexor carpi in the observation group were lower than those in the control group(t=-2.195,-2.322;both P＜0.05).The PDMS-FM scores(t=14.035,12.269;both P＜0.05)and FMQ scores(t=11.987,7.773;both P＜0.05)in two groups were higher than those before treatment.In addition,the PDMS-FM and FMQ scores in the observation group were higher than those in the control group(t=2.784,3.448;both P＜0.05).The UEFT scores of grasping(t=5.277,2.755;both P＜0.05),UEFT score of coordination(t=5.115,8.428;both P＜0.05)and the total UEFT score(t=5.960,3.467;both P＜0.05)in two groups were higher than those before treatment.Moreover,the UEFT score of grasping and total UEFT score in the observation group were higher than those in the control group(t=2.437,2.269;both P＜0.05),whereas no significant difference was noted in the UEFT score of bilateral hand coordination between two groups(t=0.679;P>0.05).Conclusion Synchronous mode of"brain-limb coordination"can effectively improve muscle tension and motor function of the upper limbs in children with HSCP,which yields better rehabilitation efficacy compared with asynchronous mode.

OBJECTIVE:KCNT1 encodes a sodium-activated potassium channel, and its variant can lead to refractory epilepsy. The resistance to antiseizure medication in KCNT1 variant-related epilepsy suggests the presence of complex gene regulation. Our goal is to clarify the pathogenicity of a KCNT1 variant associated with epilepsy. METHODS:Here, we intended to characterize the pathogenicity of the Kcnt1-269 variant (c.805 G > A, c.807 G > C, p.G269S; corresponding to c.862 G > A, p.G288S in human) in vitro and in vivo, and to analyze the transcriptome of the rat cerebral cortex through RNA sequencing. RESULTS:Our study revealed that homozygous Kcnt1-269 variant rats showed excessive neuroexcitability in CA1 pyramidal neurons, including enhanced neuronal action potential amplitudes, decreased action potential thresholds, and increased neuronal firing numbers. Homozygous and heterozygous Kcnt1-269 variant rats had high frequency of evoked action potential under different step currents. The cumulative dose of pentetrazol required to induce epileptic seizures in homozygous Kcnt1-269 variant rats was significantly lower compared with wild-type rats. Transcriptome analysis of the cerebral cortex identified 190 upregulated and 149 downregulated genes in heterozygous Kcnt1-269 variant rats compared with wild-type rats. Functional enrichment analysis revealed that "nucleolus," "neuropeptide signaling pathway," "dendrite," and "protein binding" were the most prominent Gene Ontology terms, while "neuroactive ligand-receptor interaction" was one of the most significant Kyoto Encyclopedia of Genes and Genomes terms. CONCLUSION:Our findings elucidate the epileptogenicity of the Kcnt1-269 variant in rats and may provide new insights into the pathways associated with Kcnt1 variant-related epilepsy through transcriptome analysis.

AIM:To explore the phenotypic spectrum and refine the genotype-phenotype correlation of YWHAG-related epilepsy. METHOD:This study used a retrospective cohort design to evaluate the clinical data of 15 patients with epilepsy and YWHAG variants in our Chinese cohort (nine males, six females; median age: 6 years 4 months; range: 1 year 6 months-12 years 8 months) and 40 patients with epilepsy with YWHAG variants from published studies (21 males, 19 females; median age: 10 years; range: 3 years-67 years). RESULTS:In our cohort, seven variants were de novo and five were new. Seizure onset for 14 of 15 patients occurred within the first 2 years of life. Nine of 15 patients had a history of febrile seizures. Seizure types included generalized tonic-clonic seizures (GTCS) and myoclonic seizures. Developmental delay was present in 11 of 15 patients. Three patients were diagnosed with febrile seizures plus, one was diagnosed with myoclonic epilepsy in infancy, one had infantile epileptic spasm syndrome, and 10 had developmental and epileptic encephalopathy that could not be further classified into a specific epilepsy syndrome. Seizures were controlled in 7 of 15 patients; most were treated with valproate and levetiracetam. Collectively, in our cohort and from published studies, most variants (38 of 55, 69.1%) were located in the highly conserved triad (HCT) domain of Arg132-Arg57-Tyr133. Mild phenotypes were more frequently observed in patients with variants located outside the HCT domain, with a significant difference of 70.6% versus 27.0% (p < 0.01). INTERPRETATION:Most patients with YWHAG variants were diagnosed during infancy. The most common seizure types were GTCS and myoclonic seizures. The phenotypic spectrum of epilepsy ranged from mild febrile seizures to severe developmental delay and epileptic encephalopathy. Most variants were localized in the HCT domain; variants residing outside the HCT domain were correlated with milder phenotypes.

AIMS:Alexander disease (AxD) is a leukodystrophy caused by mutations in the astrocytic filament gene GFAP. There are currently no effective treatments for AxD. Previous studies have rarely established AxD models with the patient's original GFAP mutations. In this study, we aimed to explore the morphological and transcriptomic characteristics of GFAP-mutant astrocytes via induced pluripotent stem cell (iPSC) models of AxD. METHODS:Fibroblasts from three AxD children were reprogrammed into iPSCs. Wild-type (WT) and AxD-iPSCs were differentiated into astrocytes. We compared the morphological and transcriptomic differences between WT- and AxD iPSC-derived astrocytes. RESULTS:Astrocytes induced from AxD-derived iPSCs exhibited the Rosenthal fibers (RFs), the main pathological phenotype of AxD. Compared with WT astrocytes, AxD astrocytes had shorter processes, more branches, and larger cell bodies. Transcriptomic analysis revealed that extracellular matrix (ECM) components, particularly chondroitin sulfate proteoglycans (CSPGs), were upregulated, and ECM-degrading enzymes were generally downregulated. These changes may lead to abnormalities in neurons and myelination. CONCLUSIONS:We explored the morphological characteristics of AxD astrocytes via iPSC models and revealed the ECM, previously unexplored for AxD, may be an important new pathogenic mechanism of this disease.

Insulin receptor substrate 1 (IRS-1) is a key mediator of insulin signaling linked to focal cortical dysplasia. While previous studies have primarily focused on IRS-1 in peripheral tissues, its function in the central nervous system has remained largely unexplored. This study aimed to investigate the spatiotemporal expression patterns of IRS-1 protein in mouse cerebral cortex and human brain organoids, along with its role in neural development. In mice, Irs-1 expression was consistent throughout brain development, with notable localization in the ventricular/subventricular zone during early gestation and later in the outer cerebral cortex. In human brain organoids, IRS-1 was primarily found in rosette structures initially, shifting to the outer cortical layer as they matured. Knockdown of Irs-1 at embryonic day 14.5 via in-utero electroporation impaired neuronal migration, resulting in more neurons remaining in the intermediate zone compared to controls. Moreover, SH-SY5Y cells treated with isotretinoin exhibited a significant decrease in IRS-1 protein expression during maturation. RNA sequencing indicates an upregulation of neurodevelopment-related genes alongside a downregulation of the IRS-1. These findings underscore the significance of IRS-1 in brain development, particularly regarding neuronal migration and differentiation.

Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a new histopathological entity identified in the surgically resected brain tissue of patients with drug-resistant epilepsy. Somatic variants in SLC35A2 have been increasingly identified in MOGHE brain resections. SLC35A2 protein transports uridine 5'-diphosphogalactose (UDP-Gal) into the Golgi lumen, playing a crucial role in the process of N-glycosylation. Currently, research on the pathogenic mechanism of SLC35A2 variants in MOGHE is limited. Here we conducted genetic testing on brain samples and paired blood samples from 28 pediatric patients pathologically diagnosed with MOGHE. We performed an in-depth functional analysis of somatic variants identified in SLC35A2, integrating glycan labeling and intact glycopeptide profiling to assess N-glycosylation defects. With whole-exome sequencing and validation with ultra-deep amplicon sequencing, we identified 101 potentially pathogenic somatic variants (PPSVs) across 87 genes. Nine PPSVs in SLC35A2 were found in 10 samples. The 9 identified variants of SLC35A2, characterized by various mutation types (4 frameshift, 3 missense and 2 nonsense variants), were all confirmed to be loss-of-function via altered glycan chains. Intact glycopeptide analysis at the cellular level indicated an increase in truncated N-glycan glycoforms. Analysis of brain tissue revealed N-glycosylated proteins and glycosites modified with agalactosylated glycoforms, and glycoproteins bearing agalactosylated N-glycans were significantly enriched in cell adhesion and axon guidance-related pathways. Additionally, chemoenzymatic glycan labeling in lesions demonstrated N-glycan damage of heterotopic neurons, suggesting a potential diagnostic approach for MOGHE. Our findings provide a comprehensive somatic landscape of MOGHE and a rich resource of somatic SLC35A2 variant-related glycoform and glycoprotein abnormalities, thereby unveiling valuable insights into compromised N-glycosylation and MOGHE formation.

BACKGROUND AND OBJECTIVE:To understand the prevalence and risk factors of acute symptomatic seizures (ASSs) and epilepsy in children with central nervous system inflammatory demyelinating diseases (CIDDs). METHODS:The cohort of children with CIDDs in pediatric department of Peking University First Hospital between January 2013 and June 2024 were followed up. We evaluated and compared the incidence of ASSs among patients with different CIDDs. The correlation between clinical information and the occurrence of ASS was further analyzed. The incidence of epilepsy was analyzed in patients with disease course longer than 1 year. RESULTS:Of 204 patients with CIDDs, 97 were female (47.5 %), and the age at onset was 6.75 (IQR: 4.50, 9.73) years, with a total of 598 attacks. Of 204 patients, 75 (36.8 %) experienced ASSs, and the incidence of ASSs were significantly higher in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) (39/94, 41.5 %) and seronegative CIDDs (31/72, 43.1 %). Among 598 attacks, 143 (23.9 %) were accompanied by ASSs. ASSs were more likely to occur in attacks manifested as acute disseminated encephalomyelitis (ADEM) and cerebral cortical encephalitis (CCE) phenotypes. Fever (OR=0.453) and cortical involvement on brain MRI (OR=0.191) were independent risk factors for ASSs. Prevalence of epilepsy was 9.9 % (19/192). Patients with multiple demyelinating attacks were more likely to develop epilepsy. CONCLUSION:The incidence of ASS in children with CIDDs was 36.8 %, which was more common in children with MOGAD or seronegative CIDDs. ASSs were more likely to occur in attacks presented with ADEM and CCE. Prevalence of epilepsy was 9.9 %.

BackgroundEvidence regarding the efficacy of vagus nerve stimulation (VNS) in treating developmental and epileptic encephalopathy/ epileptic encephalopathy with spike-and-wave activation in sleep (DEE/EE-SWAS), particularly its impact on the SWAS remains limited. We present a boy with EE-SWAS who was treated with VNS at 4.8 years of age.Case presentationA male patient developed seizures at 2.3 years of age. At 2.8 years of age, electroencephalography (EEG) showed SWAS, leading to regression in cognitive, motor, and language functions. Administration of multiple anti-seizure medications (ASMs) achieved poor efficacy, and repeated corticosteroids resulted in only transient improvement. He was treated with VNS at 4.8 years of age. Seizure freedom was achieved at 1.3 years postoperatively. The SWAS pattern was not observed on follow-up EEG 2 years after implantation. Concurrently, his neurodevelopment improved. No new ASMs or corticosteroids were added during this period. VNS was interrupted due to pulse generator battery depletion at 5.6 years after implantation. Increased SWI was showed on the EEG 6 months after the interruption of stimulation.ConclusionEarly VNS intervention should be considered in addition to conventional medication for young children with SWAS who have greater distance from the self-limited age.

Hypomyelinating leukodystrophies (HLDs) are genetic disorders characterized by deficient myelination. While TMEM63A variants are associated with HLD19, the specific lipid alterations in affected brain regions remain to be fully characterized. This study aimed to investigate the spatial distribution of lipid changes in a Tmem63a mutant rat model of hypomyelination. A homozygous Tmem63a c.500G > A p.(G167E) knock-in rat model (Tmem63aG167E/G167E) was established. Brain sections from Tmem63aG167E/G167E and Tmem63aWT rats (n = 3/group) were analyzed using MALDI-MSI for lipid profiling across nine distinct brain regions. Myelin structure was characterized by transmission electron microscopy (TEM) and g-ratio quantification. Statistical analyses included Mann-Whitney U tests for g-ratio distributions and ROC analysis for feature screening. Out of 702 analyzed features, 124 were differentially expressed. Lipids constituted the most altered class (43 features), including 22 glycerophospholipid, 9 fatty acid, 5 sphingolipid, 5 sterol lipid, and 2 prenol lipid species. These alterations were predominantly observed in white matter-rich regions and gray-white matter junctions. TEM revealed thinner and less dense myelin sheaths in Tmem63aG167E/G167E rats, with a reduced proportion of optimal g-ratios. This study provides a comprehensive spatial lipidomic characterization in a Tmem63a mutant rat model, revealing significant lipid alterations associated with hypomyelination. These findings offer new insights into the pathology of hypomyelination and highlight specific lipid species for future investigation.

OBJECTIVE:This study aimed to evaluate the efficiency of an RF-TC Target Planning Software in enhancing outcomes of SEEG-guided RF-TC for pediatric drug-resistant epilepsy. METHODS:A retrospective analysis of 68 cases at Peking University First Hospital from May 2018 and November 2023 was conducted. Of these, software-assisted planning and manual planning were utilized in 27 and 41 patients, respectively. Surgical parameters, primarily the number of contact pairs, planning time, and postoperative results were analyzed. Statistical analysis compared seizure-free rates and other key metrics across the two planning groups. RESULTS:A larger group with software-assisted planning was associated with a significantly higher number of contact pairs for RF-TC and lower planning time. The software-assisted group's seizure-free rate was 77.78 % after 23 months, compared to 29.41 % over 57.97 months for the manual planning group. Transient contralateral limb weakness was observed in 11.11 % of software-assisted cases, but full recovery was eventually noted for all patients. INTERPRETATION:The RF-TC Target Planning Software enhances the effectiveness and efficiency of SEEG-guided RF-TC by improving electrode contact pair choice, reducing planning time, and increasing postoperative seizure-free rates. In complex situations, such as hypothalamic hamartomas, the software displays its value by reducing the risk of missed electrode pairings. Notwithstanding its advantages, the software-assisted approach may raise transient postoperative neurological deficits slightly. Additional studies with expanded cohorts and extended follow-ups are necessary for a comprehensive assessment of this technique's long-term effectiveness.

OBJECTIVE:To compare the efficacy and safety of vagus nerve stimulation using different modes in patients with drug-resistant epilepsy (DRE). METHODS:Children with DRE who underwent vagus nerve stimulator implantation between March 2019 and December 2022 were prospectively enrolled at the Peking University First Hospital. Ninety-four children were randomly divided into the high pulse amplitude [pulse amplitude was gradually increased to maximum tolerance value (≤2.8 mA) and duty cycle was maintained at 10%] and high duty cycle groups [pulse amplitude was maintained at 1.5 mA and duty cycle was subsequently increased to maximum tolerance value (≤37%)]. At the 55-week follow-up, the responder rate, seizure-free rate, and adverse effects were compared between the two groups. RESULTS:Ninety-four children with DRE were included (47 patients each in the high pulse amplitude group and the high duty cycle group). For epileptic seizures, the responder rate of the high pulse amplitude group was 53.2% (25/47), while that of the high duty cycle group was 38.3% (18/47). High pulse amplitude had a higher responder rate of focal seizures (60.7% in the high pulse amplitude group vs. 29.2% in the high duty cycle group; chi-squared test, p = 0.023). Among children with a ≥ 75% reduction in epileptic spasms, the high duty cycle group had a higher responder rate than the high pulse amplitude group (54.5% vs. 16.7%; Fisher's exact test, p = 0.022). In addition, in the high duty cycle group, the responder rate in children with epileptic spasms was higher than that in children without epileptic spasms (59.1% vs. 20.0%; chi-square test, p = 0.011). Among children with implantation age <6 years, the responder rate of the high pulse amplitude group was higher (chi-square test, p = 0.024). The incidence of adverse effects in the two groups was not statistically different. SIGNIFICANCE:The overall responder rates in the two modes were similar. The high pulse amplitude mode may be more effective for focal seizures, whereas the high duty cycle mode may be more effective for epileptic spasms. Patients aged <6 years with DRE and VNS implantation may require a higher pulse amplitude to achieve better efficacy. PLAIN LANGUAGE SUMMARY:This study compared the anti-seizure efficacy of two different vagus nerve stimulation (VNS) treatments. We found that the overall efficacy of the two treatments was similar. The high pulse amplitude mode may be more effective for focal seizures, whereas the high duty cycle mode may be more effective for epileptic spasms. Patients aged <6 years with drug-resistant epilepsy (DRE) and VNS treatment may require a higher pulse amplitude to achieve better efficacy.