A peptide from the Japanese encephalitis virus failed to induce the production of anti-N-methyl-d-aspartate receptor antibodies via molecular mimicry in mice.

Background: The development of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis following viral encephalitis, such as Japanese encephalitis, has received increasing attention in recent years. However, the mechanism of anti-NMDAR antibody production following Japanese encephalitis has not been explored. Methods: A peptide from the Japanese encephalitis virus (JEV), which shares a similar amino acid sequence with GluN1, was identified by sequence comparison. We then explored whether active subcutaneous immunization with the JEV peptide could induce the production of anti-NMDAR antibodies and related pathophysiological and behavioral changes in mice. In addition, a published active immune model of anti-NMDAR encephalitis using a GluN1 peptide was used as the positive control. Results: A 6-amino-acid sequence with 83 % similarity between the envelope protein of the JEV (HGTVVI) and GluN1 (NGTHVI) was identified, and the sequence included the N368/G369 region. Active immunization with the JEV peptide induced a substantial and specific immune response in mice. However, anti-NMDAR antibodies were not detected in the serum of mice immunized with the JEV peptide by ELISA, CBA, and TBA. Moreover, mice immunized with the JEV peptide presented no abnormities related to anti-NMDAR antibodies according to western blotting, patch clamp, and a series of behavioral tests. In addition, active immunization with a recently reported GluN1 peptide failed to induce anti-NMDAR antibody production in mice. Conclusions: In this study, the attempt of active immunization with the JEV peptide to induce the production of anti-NMDAR antibodies via molecular mimicry failed. The pathogenesis of anti-NMDAR encephalitis following Japanese encephalitis remains to be elucidated.

Autophagy alleviates hippocampal neuroinflammation by inhibiting the NLRP3 inflammasome in a juvenile rat model exposed particulate matter.

Ambient fine particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological diseases, which typically involve neuroinflammation. We investigated the impact of PM exposure on neuroinflammation using both in vivo (in a juvenile rat model with PM exposure concentrations of 1, 2, and 10 mg/kg for 28 days) and in vitro (in BV-2 and HT-22 cell models with PM concentrations of 50-200 µg/ml for 24 h). We observed that PM exposure induced the activation of the NLRP3 inflammasome, leading to the production of IL-1ß and IL-18 in the rat hippocampus and BV-2 cells. Furthermore, inhibition of the NLRP3 inflammasome with MCC950 effectively reduced neuroinflammation and ameliorated hippocampal damage. In addition, autophagy activation was observed in the hippocampus of PM-exposed rats, and the promotion of autophagy by rapamycin (Rapa) effectively attenuated the NLRP3-mediated neuroinflammation induced by PM exposure. However, autophagic flow was blocked in BV-2 cells exposed to PM, and Rapa failed to ameliorate NLRP3 inflammasome activation. We found that autophagy was activated in HT-22 cells exposed to PM and that treatment with Rapa reduced the release of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as cell apoptosis. In a subsequent coculture model of BV-2 and HT-22 cells, we observed the activation of the NLRP3 inflammasome in BV-2 cells when the HT-22 cells were exposed to PM, and this activation was alleviated when PM-exposed HT-22 cells were pretreated with Rapa. Overall, our study revealed that PM exposure triggered hippocampal neuroinflammation by activating the NLRP3 inflammasome. Notably, autophagy mitigated NLRP3 inflammasome activation, potentially by reducing neuronal ROS and apoptosis. This research emphasized the importance of reducing PM exposure and provided valuable insight into its neurotoxicity.

PIGW-related glycosylphosphatidylinositol deficiency: A case report and literature review.

INTRODUCTION: PIGW-related glycosylphosphatidylinositol deficiency is a rare disease that manifests heterogeneous clinical phenotypes. METHODS: We describe a patient with PIGW deficiency and summarize the clinical characteristics of the case. In addition, we conducted a literature review of previously reported patients with pathogenic variants of PIGW. RESULTS: A Chinese girl presented with refractory epilepsy, severe intellectual disability, recurrent respiratory infections, and hyperphosphatasia. Seizures worsened during fever and infections, making her more susceptible to epileptic status. She was found to carry a heterozygous variant of PIGW and a deletion of chromosome 17q12 containing PIGW. Only six patients with homozygous or compound heterozygous pathogenic variants of PIGW have been identified in the literature thus far. Epileptic seizures were reported in all patients, and the most common types of seizures were epileptic spasms. Distinctive facial and physical features and recurrent respiratory infections are common in these patients with developmental delays. Serum alkaline phosphatase (ALP) levels were elevated in four of the six patients. CONCLUSIONS: PIGW-related glycosylphosphatidylinositol deficiency is characterized by developmental delay, epilepsy, distinctive facial features, and multiple organ anomalies. Genetic testing is an important method for diagnosing this disease, and flow cytometry and serum ALP level detection are crucial complements for genetic testing.

Autoimmune encephalitis antibody profiles and clinical characteristics of children with suspected autoimmune encephalitis.

AIM: To identify the spectrum of autoimmune encephalitis antibody biomarkers (AE-Abs) in children with suspected autoimmune encephalitis and explore the clinical features indicating AE-Abs presence. METHOD: We included children with suspected autoimmune encephalitis who underwent AE-Abs tests at the Children's Hospital of Chongqing Medical University between June 2020 and June 2022. Clinical features suggestive of AE-Abs were analysed based on AE-Abs test results. RESULTS: A total of 392 children were tested for AE-Abs with suspected autoimmune encephalitis. Of these, 49.5% were male, with a median age of 7 years 11 months (6 months-17 years 11 months); 93.6% (367/392) of all patients had both serum and cerebrospinal fluid (CSF) tests performed. The antibody-positive rate in the cohort was 23.7% (93/392), the serum antibody-positive rate was 21.9% (84/384), and the CSF antibody-positive rate was 20.8% (78/375). Eleven different AE-Abs were detected. Serum analysis revealed that N-methyl-D-aspartate receptor immunoglobulin-G (NMDAR-IgG) (15.1%) was greater than myelin oligodendrocyte glycoprotein (MOG)-IgG (14.6%) and glial fibrillary acidic protein (GFAP)-IgG (3.3%). CSF analysis revealed that NMDAR-IgG (16.3%) was greater than MOG-IgG (13.8%) and GFAP-IgG (3.3%). Compared with antibody-negative patients, antibody-positive patients were more often female (odds ratio [OR] 1.86, p = 0.03), with memory impairment (OR 2.91, p = 0.01) and sleep disorders (OR 2.08, p = 0.02). INTERPRETATION: In children, the most frequent AE-Abs detected were NMDAR-IgG and MOG-IgG. Female sex, memory impairment, and sleep disorders predict a higher likelihood of AE-Abs.

ATP1A3-related phenotypes in Chinese children: AHC, CAPOS, and RECA.

The aim of this research is to study the phenotype, genotype, treatment strategies, and short-term prognosis of Chinese children with ATP1A3 (Na+/K+-ATPase alpha 3 gene)-related disorders in Southwest China. Patients with pathogenic ATP1A3 variants identified using next-generation sequencing were registered at the Children's Hospital of Chongqing Medical University from December 2015 to May 2019. We followed them as a cohort and analyzed their clinical data. Eleven patients were identified with de novo pathogenic ATP1A3 heterozygous variants. One (c.2542 + 1G > T, splicing) has not been reported. Eight patients with alternating hemiplegia of childhood (AHC), one with cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS), and two with relapsing encephalopathy with cerebellar ataxia (RECA) were included. The initial manifestations of AHC included hemiplegia, oculomotor abnormalities, and seizures, and the most common trigger was an upper respiratory tract infection without fever. All patients had paroxysmal hemiplegic attacks during their disease course. The brain MRI showed no abnormalities. Six out of eight AHC cases reached a stable disease state after treatment. The initial symptom of the patient with CAPOS was ataxia followed by developmental regression, seizures, deafness, visual impairment, and dysarthria, and the brain MRI indicated mild cerebellar atrophy. No fluctuation was noted after using Acetazolamide. The initial manifestations of the two RECA cases were dystonia and encephalopathy, respectively. One manifested a rapid-onset course of dystonia triggered by a fever followed by dysarthria and action tremors, and independent walking was impossible. The brain MRI image was normal. The other one presented with disturbance of consciousness, seizures, sleep disturbance, tremor, and dyskinesias. The EEG revealed a slow background (δ activity), and the brain MRI result was normal. No response to Flunarizine was noted for them, and it took 61 and 60 months for them to reach a stable disease state, respectively. CONCLUSION: Pathogenic ATP1A3 variants play an essential role in the pathogenesis of Sodium-Potassium pump disorders, and AHC is the most common phenotype. The treatment strategies and prognosis depend on the phenotype categories caused by different variation sites and types. The correlation between the genotype and phenotype requires further exploration. WHAT IS KNOWN: • Pathogenic heterozygous ATP1A3 variants cause a spectrum of neurological phenotypes, and ATP1A3-disorders are viewed as a phenotypic continuum presenting with atypical and overlapping features. • The genotype-phenotype correlation of ATP1A3-disorders remains unclear. WHAT IS NEW: • In this study, the genotypes and phenotypes of ATP1A3-related disorders from Southwest of China were described. The splice-site variation c.2542+1G>T was detected for the first time in ATP1A3-related disorders. • The prognosis of twins with AHC p. Gly947Arg was more serious than AHC cases with other variants, which was inconsistent with previous reports. The phenomenon indicated the diversity of the correlation between the genotype and phenotype.

Role of SERPINI1 pathogenic variants in familial encephalopathy with neuroserpin inclusion bodies: A case report and literature review.

BACKGROUND: Familial encephalopathy with neuroserpin inclusion bodies (FENIB), a rare neurogenetic disease, is characterized by progressive cognitive decline and myoclonus and caused by pathogenic variants of the SERPINI1 gene that lead to the formation of neuroserpin inclusion bodies. METHODS: We described the case of an Asian patient with FENIB associated with a pathogenic variant of SERPINI1 and summarized and analyzed the clinical characteristics of the case. In addition, we conducted a literature review of previously reported patients with this disease. RESULTS: The patient, a 16-year-old Chinese girl, presented with progressive cognitive decline and myoclonus that had started at the age of 11 years. The girl was found to carry a de novo heterozygous c.1175G>A (p.G392E) variant of the SERPINI1 gene, which is a pathogenic variant according to the guidelines of the American College of Medical Genetics and Genomics. She had responded poorly to antiseizure medications (ASMs). At the last follow-up, her myoclonus was still out of control, and her self-care ability was poor. Our literature review revealed that 13 similar cases (including 9 cases in male patients) have been reported so far, in which six pathogenetic variations in SERPINI1, including G392E, were responsible for FENIB. All the patients presented with myoclonus, and 12 patients had experienced at least one other type of seizure. Further, as observed in our case, 9 out of 12 patients did not respond to ASMs. Progressive cognitive decline was observed in all the patients, and 10 out of 13 patients had dyskinesia. The median age of disease onset was 21 years, and the median age at the time of death was 33 years. Further, 9 out of 13 patients showed signs of cerebral and/or cerebellar atrophy. Finally, neuroserpin inclusion bodies were identified in six patients who underwent brain biopsy or autopsy. CONCLUSIONS: Pathogenic variants of SERPINI1 should be suspected in children with progressive cognitive decline and myoclonus, especially in those with progressive myoclonus epilepsy. Further, gene detection and brain biopsy are important means for the diagnosis of FENIB.

Severe epilepsy phenotype with SCN1A missense variants located outside the sodium channel core region: Relationship between functional results and clinical phenotype.

PURPOSE: Most SCN1A missense variants located outside the sodium channel core region show a mild phenotype. However, there are exceptions, because of which it is challenging to determine the correlation between genotype and phenotype. In this study, we aimed to determine whether functional study could be used to determine disease severity in cases with such variants, and elucidate possible genotype-phenotype relationships. METHODS: Forty-seven patients with SCN1A missense variants were recruited, and one with a Dravet syndrome phenotype with an SCN1A missense variant (c.3811T>C/ p.W1271R) located outside the core region was screened with electrophysiological tests. We also reviewed functional SCN1A studies on patients with inconsistent phenotypes and genotypes, and studied the relationship between electrophysiological measurements and clinical phenotype. RESULTS: Patch clamp experiments showed that the W1271R variant caused significantly reduced sodium current, decreased channel voltage sensitivity, loss of channel availability, and prolonged recovery time from inactivation compared with wild type (WT), which ultimately caused a change in loss of function (LOF). Twelve cases of severe SCN1A-related epilepsy with missense variants located outside the channel core region were also included from the functional studies. Nine patients with missense SCN1A variants showed complete (3/9) or partial (6/9) physiological LOF. Two missense SCN1A variants caused physiological gain-and-loss of function (G-LOF), and one caused decreased excitability (DE). CONCLUSIONS: Not all missense variants located outside the core region cause a mild phenotype. Although current functional studies in heterologous expression systems do not accurately reflect disease severity caused by SCN1A missense variants, they could be an effective model for generation of data to study the initial effects of SCN1A missense variants.

External Assessment of the Anti-N-Methyl-D-Aspartate Receptor Encephalitis One-Year Functional Status Score in Chinese Pediatric Patients.

Objective: to assess the performance of the Anti-N-Methyl-D-Aspartate Receptor encephalitis (NMDAR) One-Year Functional Status (NEOS) score in predicting one-year functional outcome in Chinese children with anti-NMDAR encephalitis. Methods: children with anti-NMDAR encephalitis at the Children's Hospital of Chongqing Medical University were retrospectively enrolled from January 2014 to December 2020. Patients were categorized into two groups based on the modified Rankin Scale (mRS) at one-year follow-up. Discrimination of the NEOS score was assessed by the area under curve (AUC) of the receiver operating characteristic curve. Calibration of the NEOS score was assessed by comparing predicted probabilities with observed probabilities using a calibration curve and the Hosmer-Lemeshow test. The clinical practicability of the NEOS score was evaluated by performing a decision curve analysis. Results: one hundred seventy-five children (101 females and 74 males) with anti-NMDAR encephalitis and a median age of 7.7 years were enrolled. Of those, 149 (85.1%) had a good outcome at 1 year (mRS ≤ 2), and the remaining 26 (14.9%) had a poor outcome (mRS > 2). Patients with a higher NEOS score had a significantly higher mRS at one-year follow-up [Spearman r = 0.3878, 95% confidence interval (CI): 0.2500-0.5103, P < 0.001]. The AUC of the NEOS score was 0.870 (95% CI: 0.801-0.938, P < 0.001). The observed probability and predicted probability showed moderate consistency in the calibration curve and the Hosmer-Lemeshow test (P = 0.912). The decision curve analysis showed that using the NEOS score to predict one-year outcomes could provide additional net benefit during clinical practice. Conclusions: the NEOS score is a potentially reliable model to predict the one-year functional outcome in Chinese children with anti-NMDAR encephalitis.

The Role and Mechanism of AMIGO3 in the Formation of Aberrant Neural Circuits After Status Convulsion in Immature Mice.

Leucine rich repeat and immunoglobulin-like domain-containing protein 1 (Lingo-1) has gained considerable interest as a potential therapy for demyelinating diseases since it inhibits axonal regeneration and myelin production. However, the results of clinical trials targeted at Lingo-1 have been unsatisfactory. Amphoterin-induced gene and open reading frame-3 (AMIGO3), which is an analog of Lingo-1, might be an alternative therapeutic target for brain damage. In the present study, we investigated the effects of AMIGO3 on neural circuits in immature mice after status convulsion (SC) induced by kainic acid. The expression of both AMIGO3 and Lingo-1 was significantly increased after SC, with levels maintained to 20 days after SC. Following SC, transmission electron microscopy revealed the impaired microstructure of myelin sheaths and Western blot analysis showed a decrease in myelin basic protein expression, and this damage was alleviated by downregulation of AMIGO3 expression. The ROCK/RhoA signaling pathway was inhibited at 20 days after SC by downregulating AMIGO3 expression. These results indicate that AMIGO3 plays important roles in seizure-induced damage of myelin sheaths as well as axon growth and synaptic plasticity via the ROCK/RhoA signaling pathway.

Clinical and genetic characteristics of epilepsy of infancy with migrating focal seizures in Chinese children.

OBJECTIVE: Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare and severe developmental epileptic encephalopathy. The aim of this study was to improve our understanding of EIMFS by using phenotype-genotype correlation. METHODS: We recruited, performed clinical genetic testing, and summarized the clinical features and genetic characteristics in five patients with EIMFS in China. RESULTS: The five recruited patients included 2 males and 3 females. The median age of seizure onset was 2 months (range, day 3 to 3 months). All patients exhibited the characteristics of clinically migrating focal motor (tonic or clonic) seizures. Typical migrating ictal electrical patterns were found in 1 patient; the remaining four patients presented with overlapping seizures with different areas of ictal onset in differing hemispheres. All the patients had the associated variants, including KCNT1, SCN1A, SCN2A, TBC1D24 and ALG1. All patients received two or more antiseizure medications, and 1 patient became seizure-free, 1 reported >75 % seizure reduction, 2 reported >50 % seizure reduction, and 1 patient showed no improvement. Varying degrees of psychomotor developmental delays were observed in all patients. CONCLUSIONS: The course of EIMFS could be related to the type of gene variant present, and different genes may have specific clinical features. Larger cohorts are required to elucidate such potential phenotype-genotype correlations.

Characteristics and outcomes of children with dissociative (conversion) disorders in western China: a retrospective study.

BACKGROUND: Dissociative (conversion) disorder in children is a complex biopsychosocial disorder with high rates of medical and psychiatric comorbidities. We sought to identify the characteristics and outcomes of children with dissociative (conversion) disorders in western China. METHODS: We conducted a retrospective cohort study of 66 children admitted with dissociative (conversion) disorders from January 2017 to July 2019, and analyzed their clinical characteristics, socio-cultural environmental variables, and personality and psychiatric/psychological characteristics. Binary logistic regression was used to analyze the variables associated with clinical efficacy. RESULTS: Of these 66 patients, 38 (57.6%) were male and 28 (42.4%) were female, 46 (69.7%) had an antecedent stressor, 30 (45.5%) were left-behind adolescents, and 16 (24.2%) were from single-parent families. In addition, 30 patients (45.5%) were not close to their parents, 38 patients (59.4%) had an introverted personality, and 34 (53.1%) had unstable emotions. Thirteen families (19.7%) were uncooperative with the treatment. Patients who had cormorbid anxiety or depression exhibited significantly lower cognitive ability (P < 0.01). Logistic regression found that better treatment outcomes were positively associated with having a close relationship with parents, parental cooperation with treatment, and having a father with a lower level of education (i.e., less than junior college or higher). CONCLUSIONS: The characteristics and outcomes of children with dissociative (conversion) disorders are related to socio-cultural environmental variables and psychiatric/psychological factors. Timely recognition and effective treatment of dissociative (conversion) disorders are important.

Case Report: Novel SLC9A6 Splicing Variant in a Chinese Boy With Christianson Syndrome With Electrical Status Epilepticus During Sleep.

We investigated the existence and potential pathogenicity of a SLC9A6 splicing variant in a Chinese boy with Christianson Syndrome (CS), which was reported for the first time in China. Trio whole-exome sequencing (WES) was performed in the proband and his parents. Multiple computer prediction tools were used to evaluate the pathogenicity of the variant, and reverse transcription-polymerase chain reaction (RT-PCR) analysis and cDNA sequencing were performed to verify the RNA splicing results. The patient presented with characteristic features of CS: global developmental delay, seizures, absent speech, truncal ataxia, microcephaly, ophthalmoplegia, smiling face and hyperkinesis with electrical status epilepticus during sleep (ESES) detected in an electroencephalogram (EEG). A SLC9A6 splicing variant was identified by WES and complete skipping of exon 10 was confirmed by RT-PCR. This resulted in altered gene function and was predicted to be pathogenic. ESES observed early in the disease course is considered to be a significant feature of CS with the SLC9A6 variant. Combined genetic analysis at both the DNA and RNA levels is necessary to confirm the pathogenicity of this variant and its role in the clinical diagnosis of CS.

Prolactin levels as a criterion to differentiate between psychogenic non-epileptic seizures and epileptic seizures: A systematic review.

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are conversion disorders with functional neurological symptoms that can resemble epileptic seizures (ES). We conducted a systematic review to obtain an overview of the value of prolactin (PRL) levels in the differential diagnosis between PNES and ES. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases for studies published up to June 4th, 2020. Published studies were included if they fulfilled the following criteria: original research on PRL changes after ES and PNES. By applying Bayes' theorem, we calculated the predicted values of PRL with pretest probabilities of 90 % and 75 % in ES. RESULTS: Sixteen studies were included in this review. All the studies showed that PRL levels increase after ES, especially 10-20 min after ES, when the elevation was most obvious. In studies where capillary PRL level measurements were included, the median sensitivity in the diagnosis of ES (all epileptic seizure types), generalized tonic clonic seizures (GTCS), focal impaired awareness seizures (FIAS), and focal aware seizures (FAS) was 67.3 %, 66.7 %, 33.9 %, and 11.1 %, respectively. The median specificity in the diagnosis of ES was 99.1 %. By using Bayes' theorem, when we used the median specificity and sensitivity for predictive value calculation, assuming a pretest probability of 90 %, a positive PRL measure was highly predictive (99 %) of all types of ES, and negative predictive values were all below 30 %. When we used the lowest specificity and sensitivity for predictive value calculation, assuming a pretest probability of 75 %, ES and GTCS had positive predictive values of 77.2 % and 81.0 %, respectively; the negative predictive values of PRL in ES and GTCS were 26.2 % and 29.6 %, respectively. CONCLUSIONS: The use of PRL could be a useful adjunct to differentiate GTCS from PNES. However, PRL levels are of limited use for differentiating FIAS or FAS from PNES, and a negative PRL measure is not predictive of PNES.

Efficacy of the ketogenic diet in patients with Dravet syndrome: A meta-analysis.

PURPOSE: Dravet syndrome is an infantile epilepsy syndrome with drug resistant seizures and cognitive impairment. The aim of this meta-analysis was to summarize the findings of relevant published studies to identify the efficacy of a ketogenic diet in patients with Dravet syndrome and their compliance thereof, and to provide useful information for clinical practice. METHODS: The PubMed, Embase, Wanfang, and CNKI databases were searched for relevant studies published up to September 25, 2019; the included studies were reviewed. Meta-analyses were performed using R software to determine the combined efficacy rates and retention rate for the ketogenic diet in patients with Dravet syndrome. RESULTS: Seven studies involving 167 patients met the inclusion criteria: four were retrospective studies, and three were prospective studies. The meta-analysis revealed that 63 %, 60 %, and 47 % of responder patients achieved ≥50 % seizure reduction at month 3, 6, and 12, respectively. The pooled retention rate of the ketogenic diet at month 6 and month 12 was 78 % and 49 %, respectively. CONCLUSIONS: Our meta-analysis indicates that the ketogenic diet is a treatment option for patients with Dravet syndrome. The ketogenic diet is safe and its adverse effects are mostly acceptable. However, further investigations, especially high-quality controlled trials with large samples, are required.

KCNQ2 related early-onset epileptic encephalopathies in Chinese children.

OBJECTIVE: To study the phenotype, genotype, treatment strategies, and short-term prognosis of Chinese children with KCNQ2 (potassium voltage-gated channel subfamily Q member 2) related early-onset epileptic encephalopathies (KCNQ2-EOEEs) in Southwest China. METHODS: We used targeted next-generation sequencing (NGS) to identify KCNQ2 variants in Chinese patients with EOEEs. And patients with KCNQ2-EOEEs were confirmed after clinical and genetic analyses. We followed them in our cohort and analyzed their clinical data. RESULTS: 122 patients with EOEEs were registered from August 2015 to October 2017, and 78 underwent targeted NGS. Seven among them were confirmed to be caused by pathogenic KCNQ2 variants, 6 of that were de novo and 1 was inherited. The median seizure onset age of the 7 patients was 5 days. Tonic-clonic and tonic seizures were the major seizure types; the electroencephalograms of all patients showed multifocal sharp waves initially. When new seizure types appeared in infancy, the most common type was epileptic spasm. At the last follow-up, seizures persisted in only one patient, and another patient had seizure recurrence. The identified pathogenic KCNQ2 variants introduced amino acid missense changes, or in one instance, frameshift variant, four of which have not been reported. Valproic acid (VPA) was effective as concomitant treatment in three patients, and all patients had intellectual/developmental disabilities (IDDs). CONCLUSIONS: The KCNQ2 missense variant plays an important role in EOEE pathogenesis, and patients with KCNQ2-EOEEs mainly present with intractable seizures and IDDs. Moreover, VPA has potential as an effective therapeutic strategy.

Genetic and phenotypic characteristics of SCN1A-related epilepsy in Chinese children.

SCN1A gene mutations are associated with epilepsy and neurodevelopmental disorders. This study aimed to explore the genotype and phenotype spectrum of SCN1A gene related epilepsy. Epileptic patients who were treated in the Children's Hospital of Chongqing Medical University from January 2015 to July 2018 and identified as having SCN1A mutations by targeted next-generation sequencing were included. Clinical manifestations of all patients were analyzed retrospectively. A total of 24 patients with SCN1A mutations were identified. The age of epilepsy onset ranged from 2 months to 2 years and 9 months. Multiple seizure types were observed. A total of 13 (54.2%) patients had three or more types of seizures. Overall, 16 (66.7%) patients had status epilepticus, 11 (45.8%) patients had fever sensitivity, and nine (37.5%) patients had seizures after vaccination. Moreover, 15 (62.5%) patients showed varying degrees of cognitive and motor development retardation. In addition, two patients had mutations inherited from one of their parents and 22 (91.7%) patients had de novo mutations. The following SCN1A mutation types were identified: missense (16 patients, 66.7%), nonsense (four patients, 16.7%), splice site (one patient), frameshift (one patient), and large deletions (two patients). Overall, 23 of the patients received antiepileptic therapy, of which eight (33.3%) patients had no decrease in seizures and 11 (45.8%) patients had more than 50% decrease in seizure frequency. Three patients had poor response to antiepileptic drug therapy before attempting ketogenic diet, after which seizure frequency decreased by 50%. A total of 10 (41.7%) patients had used sodium channel blockers before accurate diagnosis, all of whom showed ineffective or even aggravated seizure response. SCN1A mutations are associated with a spectrum of seizure-related disorders, ranging from a relatively mild form of febrile seizures to a more severe epileptic encephalopathy known as Dravet syndrome. Early diagnosis of SCN1A mutation-associated epilepsy can aid in appropriate choice of antiepileptic drugs for treatment and reducing adverse sequelae.