Epilepsy is a common neurological disease that affects a wide range of people and seriously impairs patients' quality of life and social adaptability. Neuroinflammation plays an important role in the pathogenesis of epilepsy. Glial cells, particularly astrocytes and their differentiated forms, as well as their interactions with other cell types, are critical in the process of neuroinflammation. A better understanding of the inflammatory mechanisms of epilepsy might facilitate the development of new therapeutic strategies. Single-cell RNA sequencing has provided new insights into the inflammatory microenvironment of the nervous system in epilepsy by enabling high-resolution characterization of cell type-specific gene expression and signaling pathways. In this review, we summarized the differentiation, interactions, and transcriptional dynamics of microglia, astrocytes, and neurons in epilepsy using single-cell sequencing data from patients and animal models, providing a basis for the development of new strategies for epilepsy treatment.

BackgroundInfantile epileptic spasms syndrome (IESS) is a severe early-life epileptic encephalopathy with diverse etiologies, yet its precise pathogenesis remains unclear. The gut–brain axis has emerged as a key modulator of neurodevelopment and seizure susceptibility, and although gut microbiota dysbiosis has been implicated in various epilepsy syndromes, its role in IESS, particularly in relation to treatment response, remains unexplored. This preliminary study therefore investigated gut microbiota composition in pediatric IESS and its potential as a biomarker of response to adrenocorticotropic hormone (ACTH) therapy.MethodsEighteen patients with IESS were enrolled. Two age-matched control groups were established: a focal epilepsy (FE) group and a healthy (H) group. The 18 patients with IESS were subsequently categorized into two groups based on therapeutic response: ACTH-effective and ACTH-ineffective. Fecal samples were collected before and after ACTH treatment and subjected to 16S ribosomal DNA sequencing, followed by bioinformatics analyses.ResultsGut microbiota α-diversity was significantly lower in the IESS group than in the FE group, and β-diversity significantly differed among the IESS, FE, and H groups. Proteobacteria and Actinobacteria exhibited significantly higher relative abundances in the IESS group, while Ruminococcaceae was significantly lower than in the FE and H groups. The IESS group had significantly higher Veillonellaceae abundance but significantly lower Lachnospiraceae and Faecalibacterium abundances compared with the H group. Intestinal microbiota network structure was weaker in IESS than in the FE and H groups. Before ACTH treatment, the ACTH-ineffective subgroup exhibited significantly lower actinomycetes and bifidobacteria abundances, downregulated amino acid metabolism pathways, and weaker network aggregation than the effective subgroup. After treatment, the IESS group displayed enhanced network aggregation, significantly decreased Bacillus abundance, and downregulated retinol metabolism. Additionally, Corynebacteriales and Enterobacteriaceae were enriched before treatment, while Intestinibacter was enriched after treatment.ConclusionGut microbiota profiles in children with IESS suggested a potential association with response to ACTH therapy. These preliminary findings, while requiring validation in larger independent cohorts, highlight a potential role for the gut microbiota in the pathophysiology of IESS and underscore the need for further multi-omic investigations to elucidate underlying mechanisms.

Epilepsy affects around 70 million people worldwide, and roughly one-third of them respond poorly to standard antiepileptic drugs. Current treatments are directed almost entirely at neurons, leaving the contribution of non-neuronal cells largely unaddressed. Microglia, the resident immune cells of the central nervous system, both support neuronal survival and shape neural circuits by pruning synapses through “eat-me” and “don’t-eat-me” signals. In epilepsy, this pruning becomes dysregulated: microglia preferentially eliminate inhibitory synapses, producing excitatory/inhibitory (E/I) imbalance, synchronized network discharges, and a lowered seizure threshold. This review summarizes recent work on pathological synaptic pruning by microglia in epilepsy, focusing on the signaling pathways that drive the process and on whether they can be targeted therapeutically in drug-resistant epilepsy. The broader goal is to suggest new treatment directions beyond conventional, neuron-targeted pharmacology.

IntroductionEpilepsy is a common and serious brain disorder that often co-occurs with sleep disturbances. Sodium valproate, a conventional antiepileptic drug, alleviates sleep disorders in patients with epilepsy; however, the exact underlying mechanism remains unclear. The medial parabrachial nucleus is a crucial brain structure that regulates sleep-phase transitions. However, its role in pathogenesis of epilepsy remains uncertain. Therefore, we aimed to investigate whether medial parabrachial nucleus excitability is elevated during the chronic phase of temporal lobe epilepsy and whether sodium valproate could alleviate the pathological changes associated with temporal lobe epilepsy by modulating neuronal excitability in the medial parabrachial nucleus.MethodsWe used the whole-cell current clamp technique to investigate the excitability of the medial parabrachial nucleus in a mouse chronic epilepsy model. To validate our findings, we utilized immunofluorescence staining and Western blotting to detect changes in the expression of FosB, a marker of neuronal activity, and glial fibrillary acidic protein (GFAP), a marker of reactive astrocyte proliferation, in the medial parabrachial nucleus during the chronic phase of epilepsy. We conducted a 28-day continuous gastric lavage of sodium valproate for antiepileptic treatment and observed changes in the excitability of neurons in the medial parabrachial nucleus neurons and the expression of FosB protein and GFAP after drug treatment.ResultsWe observed that medial parabrachial nucleus neurons in slices from mice that received pilocarpine stimulation fired more action potentials than those in slices from control animals that received saline. However, after treatment with sodium valproate, the number of generated action potentials decreased significantly. Immunofluorescence staining and Western blotting data on FosB and GFAP expression confirmed the increased excitability of medial parabrachial nucleus neurons and enhanced astrocyte reactivity during the chronic epilepsy phase.ConclusionOur findings indicate an increase in the excitability of medial parabrachial nucleus neurons, along with increased reactivity of astrocytes in the chronic epilepsy model. Sodium valproate may improve the symptoms of temporal lobe epilepsy and reduce seizures by inhibiting medial parabrachial nucleus neuronal excitability. These results deepen our understanding of the pathogenesis of temporal lobe epilepsy and provide new perspectives and strategies for further research.

Nusinersen was the first approved disease modifying therapy (DMT) for spinal muscular atrophy (SMA). Intrathecal administration of nusinersen enables drug delivery directly to the central nervous system, where the motor neurons are located. Per the package insert, individuals with SMA receive 4 loading doses of nusinersen followed by maintenance doses every 4 months thereafter. The aim of this analysis was to investigate the administration practices of and adherence to nusinersen in Chinese children with SMA. Data were analyzed from a longitudinal, multicenter registry enrolling children with 5q-SMA in China. Information on nusinersen administration, including administration date, care setting, use of sedation and general anesthesia, method of administration, and use of imaging guidance before administration, was collected both retrospectively and prospectively. Adherence rate was calculated at dose and participant level. A dose was considered adherent if the inter-dose interval (for dose-level) and interval from the first dose (for participant-level) followed the standard dosing regimen, with a grace period of ± 7 days for Dose 2 to 4 and ± 28 days thereafter. A total of 385 participants receiving nusinersen with a total of 2,415 doses were included in the study. The median (interquartile range) number of doses administered per participant was 6 (5–7). Over 99

In the original publication [...].

Background Glucose transporter 1 deficiency syndrome(Glut1DS)was initially reported by De Vivo and colleagues in 1991.This disease arises from mutations in the SLC2A1 and presents with a broad clinical spectrum.It is a treatable neuro-metabolic condition,where prompt diagnosis and initiation of ketogenic dietary therapy can markedly enhance the prognosis.However,due to its rarity,Glut1DS is susceptible to misdiagnosis or missed diagnosis,which can lead to delayed treatment and irreversible dysfunction of the central nervous system.To promote diagnostic awareness and effective treatments,the recommendations for diagnosis and treatment have been developed. Methods The panel on Glut1DS included 28 participants from the members of the Ketogenic Diet Professional Commit-tee of the Chinese Epilepsy Association and Chinese experts with extensive experience in managing Glut1DS.All authors extensively reviewed the literature,and the survey results were discussed in detail over several online meetings.Following multiple deliberative sessions,all participants approved the final manuscript for submission. Results Early diagnosis and timely treatment of Glut1DS are crucial for improving prognosis.Physicians should be alert to suspiction of this disease if the following clinical manifestations appear:seizures,episodic or persistent movement disorders(often triggered by fasting,fatigue,or exercise),delayed motor and cognitive development.Characteristic clinical presenta-tions may include seizures combined with movement disorders,episodic eye-head movements,and paroxysmal exercise-induced dyskinesia(PED).In these cases,genetic testing should be promptly completed,and a lumbar puncture should be performed if necessary.The ketogenic diet is internationally recognized as the first-line treatment;the earlier it is started,the better the prognosis.It can effectively control seizures and improve motor disorders.Antiepileptic drug treatment is generally ineffective or provides limited symptom improvement before starting the ketogenic diet. Conclusion The recommendations provide clinicians with a relatively systematic guide for the rapid identification,diagnosis,and timely treatment of Glut1DS.

Mitochondria is the cell’s powerhouse. Mitochondrial disease refers to a group of clinically heterogeneous disorders caused by dysfunction in the mitochondrial respiratory chain, often due to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) that encodes mitochondrial proteins. This dysfunction can lead to a variety of clinical phenotypes, particularly affecting organs with high energy demands, such as the brain and muscles. Epilepsy is a prevalent neurological disorder in children and is also a frequent manifestation of mitochondrial disease. The exact mechanisms underlying epilepsy in mitochondrial disease remain unclear and are thought to involve multiple contributing factors. This review explores common mitochondrial diseases associated with epilepsy, focusing on their prevalence, seizure types, EEG features, therapeutic strategies, and outcomes. It also summarizes the relationship between the molecular genetics of mitochondrial respiratory chain components and the development of epilepsy.

BackgroundRiboflavin (vitamin B2), a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is essential for mitochondrial function, redox balance, and neuronal viability. Impairments in riboflavin transport and metabolism contribute to a growing spectrum of neurological diseases.ObjectiveThis review provides a comprehensive update on the therapeutic applications, metabolic mechanisms, and gene-based strategies involving riboflavin in neurological disorders.MethodsWe systematically analyzed clinical and experimental studies published between 2012 and 2025, focusing on riboflavin-responsive conditions and molecular mechanisms relevant to neurological pathology.ResultsRiboflavin supplementation—particularly in high doses—has demonstrated substantial efficacy in conditions such as riboflavin transporter deficiency (RTD), multiple acyl-CoA dehydrogenase deficiency (MADD), and migraine. Emerging data suggest potential benefit in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and acute brain injury. Mechanistically, riboflavin supports mitochondrial bioenergetics, antioxidant systems, and epigenetic regulation. Recent advances in gene therapy and pharmacological chaperones targeting riboflavin-dependent pathways offer promising therapeutic directions.ConclusionRiboflavin is evolving from a conventional micronutrient into a multifaceted therapeutic agent in neurology. Integration of gene-based approaches, targeted delivery systems, and biomarker-guided interventions may establish riboflavin as a key component of precision medicine strategies for neurological disorders.

This review summarizes the clinical and electromyography (EMG) characteristics and peripheral myelin protein 22 (PMP22) gene-related diseases of hereditary neuropathy with liability to pressure palsies (HNPP). Clinical, EMG, and laboratory data of patients diagnosed with HNPP at our institution from 2022 to 2023 were retrospectively reviewed. Relevant literature from January 2003 to June 2024 was retrieved from PubMed using the keywords “hereditary neuropathy with liability to pressure palsies” and “HNPP.” Clinical manifestations, EMG characteristics, and gene detection results of HNPP were summarized. All patients exhibited transient neurological symptoms and tested positive for the PMP22 deletion. EMG revealed multiple peripheral nerve abnormalities. Sixty-eight studies meeting the inclusion and exclusion criteria were included, comprising 124 HNPP cases (including six from our study), with 67 males and 57 females. The mean age of onset and diagnosis for the 124 cases were 26.5 ± 18 years and 32.7 ± 18.9 years, respectively, with a maximum onset-to-diagnosis interval of 40 years. Typical weakness and numbness in vulnerable areas were observed in 63.7

This study investigates the influence of N-methyl-D-aspartate receptor (NMDAR) antagonists on the mismatch negativity (MMN) components of event-related potentials (ERPs) in healthy subjects and explores whether NMDAR antagonists have different effects on MMN components under different types of antagonists, drug dosages, and deviant stimuli. We conducted a comprehensive literature search of PubMed, EMBASE, and the Cochrane Library from inception to August 1, 2023 for studies comparing the MMN components between the NMDAR antagonist intervention group and the control group (or baseline). All statistical analyses were performed using Stata version 12.0 software. Sixteen articles were included in the systematic review: 13 articles were included in the meta-analysis of MMN amplitudes, and seven articles were included in the meta-analysis of MMN latencies. The pooled analysis showed that NMDAR antagonists reduced MMN amplitudes [SMD (95% CI) = 0.32 (0.16, 0.47), P < 0.01, I-2 = 47.3%, p < 0.01] and prolonged MMN latencies [SMD (95% CI) = 0.31 (0.13, 0.49), P = 0.16, I-2 = 28.3%, p < 0.01]. The type of antagonist drug regulates the effect of NMDAR antagonists on MMN amplitudes. Different antagonists, doses of antagonists, and types of deviant stimuli can also have different effects on MMN. These findings indicate a correlation between NMDAR and MMN, which may provide a foundation for the application of ERP-MMN in the early identification of NMDAR encephalitis.

OBJECTIVE:To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients. METHODS:Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results. RESULTS:As of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4-5.4) and 4.1 (2.8-5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7-3.1) and 2.3 (1.2-3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5-5.3) and 4.3 (2.6-6.0) in HFMSE, and 2.1 (1.2-3.0) and 1.5 (0.0-3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae. CONCLUSIONS:These data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance.

Purpose: This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type Methods: Thirty NT1 patients and thirty-five healthy controls were enrolled and evaluated using the Epworth sleepiness scale (ESS), latency test, and brain function state monitoring. Statistical analyses were performed using SPSS Statistics for Windows, version 23.0. Benjamini-Hochberg correction was performed to control the false discovery rate. Results: Apart from typical clinical manifestations, patients with NT1 are prone to comorbidities such as nocturnal sleep disorders, anxiety, depression, and fatigue. Compared with the control group, patients with NT1 exhibited abnormal sleep structure, including increased total sleep time (P-adj=0.007), decreased sleep efficiency (P-adj=0.002), shortening of sleep onset latency (P-adj<0.001), elevated wake after sleep onset (P-adj=0.002), increased N1% (Padj=0.006), and reduced N2%, N3%, and REM% (P-adj=0.007, P-adj <0.001, P-adj=0.013). Thirty-seven percent of patients had moderate to severe obstructive sleep apnea-hypopnea syndrome. And sixty percent of patients were complicated with REM sleep without atonia. Patients with NT1 displayed increased anxiety propensity (P-adj<0.001), and increased brain fatigue (P-adj=0.020) in brain function state monitoring. FSS scores were positively correlated with brain fatigue (P-adj<0.001) and mean sleep latency was inversely correlated with FSS scores and brain fatigue (P-adj =0.013, P-adj=0.029). Additionally, ESS scores and brain fatigue decreased after 3 months of therapy (P=0.012, P=0.030). Conclusion: NT1 patients had abnormal nocturnal sleep structures, who showed increased anxiety, depression, and fatigue. Excessive daytime sleepiness and fatigue improved after 3 months of treatment with methylphenidate hydrochloride prolonged-release tablets in combination with venlafaxine.

Spinal muscular atrophy (SMA) is a rare, autosomal recessive, neuromuscular disease that leads to progressive muscular weakness and atrophy. Nusinersen, an antisense oligonucleotide, was approved for SMA in China in February 2019. We report interim results from a post-marketing surveillance phase 4 study, PANDA (NCT04419233), that collects data on the safety, efficacy, and pharmacokinetics of nusinersen in children with SMA in routine clinical practice in China. Participants enrolled in PANDA will be observed for 2 years following nusinersen treatment initiation. The primary endpoint is the incidence of adverse events (AEs)/serious AEs (SAEs) during the treatment period. Efficacy assessments include World Health Organization (WHO) Motor Milestones assessment, the Hammersmith Infant Neurological Examination (HINE), and ventilation support. Plasma and cerebrospinal fluid (CSF) concentrations of nusinersen are measured at each dose visit. Fifty participants were enrolled as of the January 4, 2023, data cutoff: 10 with infantile-onset (≤ 6 months) and 40 with later-onset (> 6 months) SMA. All 50 participants have received at least one dose of nusinersen; 6 have completed the study. AEs were experienced by 45 (90

Background NARS2 as a member of aminoacyl-tRNA synthetases was necessary to covalently join a specific tRNA to its cognate amino acid. Biallelic variants in NARS2 were reported with disorders such as Leigh syndrome, deafness, epilepsy, and severe myopathy. Case presentation Detailed clinical phenotypes were collected and the NARS2 variants were discovered by whole exome sequencing and verified by Sanger sequencing. Additionally, 3D protein structure visualization was performed by UCSF Chimera. The proband in our study had early-onset status epilepticus with abnormal EEG and MRI results. She also performed global developmental delay (GDD) and myocardial dysfunction. Next-generation sequencing (NGS) and Sanger sequencing revealed compound heterozygous missense variants [NM_024678.6:exon14: c.1352G > A(p.Arg451His); c.707T > C(p.Phe236Ser)] of the NARS2 gene. The proband develops refractory epilepsy with GDD and hyperlactatemia. Unfortunately, she finally died for status seizures two months later. Conclusion We discovered two novel missense variants of NARS2 in a patient with early-onset status epilepticus and myocardial dysfunction. The NGS enables the patient to be clearly diagnosed as combined oxidative phosphorylation deficiency 24 (COXPD24, OMIM:616,239), and our findings expands the spectrum of gene variants in COXPD24.

[This corrects the article DOI: 10.3389/fneur.2020.584446.].

The authors regret that they divided the blots from the same groups of samples into two images (Fig. 4 C and 4D) in consideration of layout neatness but used the same beta -actin. Although Fig. 4 C and D were both from the same group of samples, it is not properly to use the same beta -actin in Fig. 4 C and 4D. Similar blot division and usage of the same beta -actin could also be found in Fig 5B and 5C. The authors would like to merge figure Fig. 4C and D into one image, and merge figure Fig.5B and 5C into one image. Thus, they make this corrigendum.

Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.

ObjectiveThe objective of this study was to better understand the clinical features of photosensitive epilepsy (PSE) in Chinese children. MethodsThirty-one children with PSE were screened out of 398 children with epilepsy who were consecutively diagnosed by the video-electroencephalogram (VEEG) monitoring method and by using an intermittent photic stimulation (IPS) test. Their EEGs and clinical features were retrospectively analyzed, and their treatment outcomes were followed up. ResultsPSE accounted for 7.79% (31/398) of children with epilepsy during the observation period in our single epilepsy center. The male to female ratio of PSE was 1:3.43, and the average seizure onset age was 7.8 +/- 3.28 years. The highest range of frequency sensitivity of the IPS test for the induction of EEG epileptic discharge or electroclinical seizures was within 10-20 Hz. Electroclinical seizures were induced in 41.94% (13/31) of PSE patients by using the IPS test, while EEG discharge without clinical seizures was induced in 58.06% (18/31) of PSE patients. Among all PSE patients, an IPS-positive reaction in the eye-closure state was induced in 83.87% of patients, and this rate was significantly higher than that in the eye-opened state (41.94%) or eye-closed state (35.48%). (Eye-closure IPS stimulation means: make the subjects close their eyes at the beginning of each stimulation, open their eyes at the end of the stimulation, and close their eyes again at the beginning of the next stimulation, and so on. While Eye-closed IPS stimulation means the stimulation is started after 5 s of eye closure, and the subjects are kept closed throughout the whole process.) The common and effective drugs used for single or combined therapy in PSE children were valproic acid and levetiracetam. ConclusionThis study provides some useful information about electroclinical characteristics in a cohort of 31 PSE children. It may be beneficial for pediatric neurologists in terms of paying more attention to PSE and correctly dealing with it.