Clinical features of unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy and seizure outcome with different treatment options.

OBJECTIVE: To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). METHODS: We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long-term outcomes after surgical or nonsurgical (anti-seizure medications, ASMs) treatment. RESULTS: A total of 70 patients (49 surgical, 21 non-surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0-4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow-up (median 14.1 years), the rates of seizure-freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure-freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. SIGNIFICANCE: In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. PLAIN LANGUAGE SUMMARY: We aim to summarize clinical characteristics and compare the long-term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

Long-term seizure and developmental outcomes of epilepsy surgery in children under 3 years old: A single-center study of 113 patients.

AIMS: To investigate the clinical characteristics, surgical strategy, developmental and seizure outcomes, and predictors of surgical outcome in children with drug-resistant epilepsy (DRE) under 3 years old. METHODS: One hundred thirteen consecutive children younger than 3 years of age with DRE underwent curative surgical treatment after multidisciplinary preoperative evaluation using the strategy developed in the pediatric epilepsy center of Peking University First Hospital (PKFHPEC) between 2014 and 2018. These patients were selected for retrospective study. The relevant clinical data were collected and analyzed. The surgical prognoses were classified using the Engel classification, and the developmental assessment results were collected. Statistical analysis of the clinical data was performed to analyze the predictors of seizure outcomes and their correlation with developmental outcomes. RESULTS: All the patients were followed up for more than 3 years, and 98 (86.7%) patients had no seizure recurrence. One year after surgery, the seizure-free rate was 86.7%, which was as high as that at the last follow-up. Cortical dysplasia was the most frequent etiology of DRE in this cohort, accounting for 77.0%. According to the Engel classification, acute postoperative seizure (APOS; p < 0.001) was a predictor of seizure recurrence. No deaths occurred. No unpredicted long-term severe complications occurred except for one ventricular peritoneal shunt. The patients' neurodevelopmental statuses were improved after successful surgery, while the scores of the pre- and postoperative developmental assessments were closely correlated. CONCLUSIONS: For children who are younger than 3 years old and have DRE and structural abnormalities, early curative treatment can lead to long-term good seizure outcomes and a low complication rate. The development of appropriate strategies for both presurgical evaluation and resection is crucial for the success of surgery.

Novel STAMBP mutations in a Chinese girl with rare symptoms of microcephaly-capillary malformation syndrome and Mowat-Wilson syndrome.

Microcephaly-capillary malformation syndrome (MIC-CAP) and Mowat-Wilson syndrome (MWS) are both rare hereditary diseases with several overlapping symptoms. We here report a Chinese patient simultaneously affected by MIC-CAP and MWS, presenting with moderate anaemia because of repeated, unilateral refractory epistaxis. The girl was initially diagnosed with MWS after discovery of a pathogenic nonsense mutation in ZEB2. Starting from the age of 3 years old, the child experienced repeated epistaxis on the right side without obvious incentive or trauma. The bleeding was quite difficult to stop and her hemoglobin dropped from 124 g/L to 64 g/L in three months. Both coagulation disorders and allergic rhinitis were excluded by extensive workup and experimental therapeutics. Retrospective genetic analysis revealed that she carried two novel compound heterozygous mutations in STAMBP (c.610T > C: p.Ser204Pro and c.945C > G: p.Asn315Lys). This case report demonstrates a rare presentation of MIC-CAP in the pediatric population and enriches the variant spectrum of STAMBP.

Brain functional connectivity-based prediction of vagus nerve stimulation efficacy in pediatric pharmacoresistant epilepsy.

OBJECTIVE: Although vagus nerve stimulation (VNS) is a common and widely used therapy for pharmacoresistant epilepsy, the reported efficacy of VNS in pediatric patients varies, so it is unclear which children will respond to VNS therapy. This study aimed to identify functional brain network features associated with VNS action to distinguish VNS responders from nonresponders using scalp electroencephalogram (EEG) data. METHODS: Twenty-three children were included in this study, 16 in the discovery cohort and 7 in the test cohort. Using partial correlation value as a measure of whole-brain functional connectivity, we identified the differential edges between responders and nonresponders. Results derived from this were used as input to generate a support vector machine-learning classifier to predict VNS outcomes. RESULTS: The postcentral gyrus in the left and right parietal lobe regions was identified as the most significant differential brain region between VNS responders and nonresponders (p < 0.001). The resultant classifier demonstrated a mean AUC value of 0.88, a mean sensitivity rate of 91.4%, and a mean specificity rate of 84.3% on fivefold cross-validation in the discovery cohort. In the testing cohort, our study demonstrated an AUC value of 0.91, a sensitivity rate of 86.6%, and a specificity rate of 79.3%. Furthermore, for prediction accuracy, our model can achieve 81.4% accuracy at the epoch level and 100% accuracy at the patient level. SIGNIFICANCE: This study provides the first treatment response prediction model for VNS using scalp EEG data with ictal recordings and offers new insights into its mechanism of action. Our results suggest that brain functional connectivity features can help predict therapeutic response to VNS therapy. With further validation, our model could facilitate the selection of targeted pediatric patients and help avoid risky and costly procedures for patients who are unlikely to benefit from VNS therapy.

Clinical characteristics and surgical outcomes in children with mild malformation of cortical development and oligodendroglial hyperplasia in epilepsy.

OBJECTIVE: Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a new and rare histopathological entity of cortical developmental malformations. The clinical characteristics of MOGHE remain challenging. METHODS: Children with histologically confirmed MOGHE were retrospectively studied. The clinical findings, electroclinical and imaging features, and postoperative outcomes were analyzed, and previously published studies were reviewed up to June 2022. RESULTS: Thirty-seven children were included in our cohort. Clinical characteristics included early onset in infancy (94.6% before 3 years), multiple seizure types, and moderate or severe delay. Epileptic spasm is the most common seizure type and initial manifestation. The lesions were mainly multilobar (59.5% multiple lobes and 8.1% hemispheres), and predominance in the frontal lobe was observed. The interictal EEG pattern was circumscribed or widespread. The prominent MRI characteristics were cortical thickening, cortical/subcortical hyperintense T2/FLAIR signal, and blurring at the GM and WM transition. Among the 21 children followed up for more than 1 year after surgery, 76.2% were seizure-free. Preoperative interictal circumscribed discharges and larger resections were significantly associated with a good postoperative outcome. The clinical features of 113 patients in the reviewed studies were similar to those we reported, but the lesions were mainly unilobar (73.5%) and Engel I was achieved in only 54.2% after surgery. SIGNIFICANCE: Distinct clinical characteristics in MOGHE, especially age at onset, epileptic spasm, and age-related MRI characteristics, can help in early diagnosis. Preoperative interictal discharge and surgical strategy may be predictors of postoperative outcomes.

Pediatric epilepsy surgery in patients with Lennox-Gastaut syndrome after viral encephalitis.

Objective: To analyse the surgical outcomes of pediatric patients with Lennox-Gastaut syndrome (LGS) secondary to viral encephalitis. Methods: We retrospectively analyzed the data of four patients with LGS secondary to viral encephalitis who underwent surgery at the pediatric epilepsy center of Peking University First Hospital from January 2014 to December 2019. Preoperative evaluations included a detailed history, long-term video electroencephalography (VEEG), brain magnetic resonance imaging (MRI), positron emission tomography (PET) and a neuropsychological test. All patients were followed up at 1, 3, and 6 months and then yearly. The surgical outcome was evaluated according to the Engel classification. Results: Among the four children, the surgeries were right temporo-parieto-occipital disconnection (case 1), corpus callosotomy (case 2), left temporo-parieto-occipital disconnection (case 3), and left temporal lobectomy (case 4). The pathology was gliosis secondary to viral encephalitis. The median follow-up time was 4 years (3-5 years). At the last follow-up, one case had Engel I, two cases had Engel III, and one case had Engel IV. Conclusions: Preliminary observations shows that surgical treatment may be challenging for patients with LGS secondary to viral encephalitis. However, suitable surgical candidacy and approaches have a significant impact on the prognosis of the patients.

Identification of gene mutations in six Chinese patients with maple syrup urine disease.

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD. Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)-Sanger sequencing technology. Bioinformatics software analyzed the variants' pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins. Result: A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C>T(p.A220V), c.818C>T(p.T273I), c.1134C>G(p.D378E), and c.1006G>A(p.G336S); two non-sense mutations: c.1291C>T(p.R431*) and c.331C>T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing's results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation. Conclusion: This study identified nine pathogenic variants in the BCKDHA, BCKDHB, and DBT genes in six MSUD families, including two novel pathogenic variants in the BCKDHB gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD's differential diagnosis, early treatment, and prenatal diagnosis.

Efficacy of vagus nerve stimulation in 95 children of drug-resistant epilepsy with structural etiology.

Vagus nerve stimulation (VNS) is one of the treatment options for drug-resistant epilepsy (DRE). To analyze the efficacy of VNS in children of DRE with structural etiology, we conducted a cohort study including 95 patients of DRE with structural etiology who underwent VNS treatment. Patients were followed up every 3 months at the outpatient department or via a remote programming platform. The median follow-up period was 2.6 years (range 1.0-4.6 years). The respective responder rates at 6, 12, 18, and 24 months of follow-up were 40.0% (38/95), 52.6% (50/95), 56.0% (47/84), and 59.7% (37/62). The respective seizure-free rates at 12, 18, and 24 months of follow-up were 8.4% (8/95), 9.5% (8/84), and 9.7% (6/62). The patients were divided into four groups based on etiologies: malformations of cortical development (n = 26), post-encephalitic lesions (n = 36), perinatal brain injury lesions (n = 31), and hippocampal sclerosis (n = 2). The respective responder rates at 12 months of follow-up in these groups were 53.8% (14/26), 52.8% (19/36), 51.6% (16/31), and 50.0% (1/2). There were no significant differences in gender, age at onset, age at stimulator implantation, epilepsy duration prior to VNS implantation, number of anti-seizure medications ever tried before VNS treatment, pulse amplitude of VNS, specific structural etiologies, lobe distribution or hemispheric side of structural lesions between responders and non-responders. Of the 95 patients, 8 (8.4%) underwent lesion surgery or hemispherectomy before VNS implantation, and 6/8 (75%) of these patients had a >50% reduction in seizure frequency. One patient who had a corpus callosotomy before VNS implantation had no response to VNS treatment. In conclusion, VNS is an effective treatment in children of DRE with structural etiology. There was no significant difference in VNS efficacy in patients with different structural etiologies. Vagus nerve stimulation treatment may also control seizures well in some patients with poor outcomes after lesion resection or hemispherectomy before VNS implantation.

Safety and efficacy of rapid withdrawal of antiseizure medications during long-term video-electroencephalogram monitoring in children with drug-resistant epilepsy: A retrospective study.

OBJECTIVE: Performing long-term video-electroencephalographic monitoring (LTVEM) to obtain the ictal electroencephalogram (EEG) is important for presurgical evaluation. This study aimed at investigating the safety and efficacy of our protocol developed at Peking University First Hospital (PUFH) for rapid withdrawal of antiseizure medications (ASMs) during LTVEM to induce seizures in children with drug-resistant epilepsy (DRE) exhibiting nondaily seizures. METHODS: Children with DRE who followed the PUFH protocol for rapid withdrawal of ASMs during LTVEM between 2018 and 2021 were enrolled. The occurrence of seizures, number of ASMs withdrawn, seizure onset time after ASM tapering initiation, changes in interictal epileptiform discharge (IED), and adverse events were evaluated during LTVEM. RESULTS: Among 80 children evaluated in this study, seizures were induced successfully in 72 (90%) children. Furthermore, no change in IED sites was observed in these 72 children following the initiation of ASM tapering while 2 children exhibited secondary bilateral tonic-clonic seizures. The median time from ASM tapering initiation to the onset of the first seizure was found to be 3 days (2-4), while the median number of ASMs withdrawn was 2 (1-2). Finally, 66 children (91.7%) had habitual seizures while 6 children had nonhabitual seizure semiology. SIGNIFICANCE: The PUFH protocol can be used for the rapid withdrawal of ASMs during LTVEM in children with DRE. Using this protocol, ictal EEG patterns can be obtained in a relatively short time for most patients with fewer adverse effects during LTVEM, which may provide meaningful electro-clinical information for presurgical evaluation.

Identification of GJC2 gene mutations in Chinese patients with Pelizaeus-Merzbacher-like disease.

BACKGROUND: Clinical and genetic features were analyzed in five pedigrees with Pelizaeus-Merzbacher-like disease (PMLD) to provide bases for genetic counseling and prenatal diagnosis. CONCLUSIONS: Six patients from five pedigrees were diagnosed with PMLD based on their clinical data. Six GJC2 novel mutations were found in this study, expanding the spectrum of GJC2 mutations. This is the second group of GJC2 mutations reported from six Chinese patients with PMLD. METHODS: Clinical data including medical history, physical signs, and auxiliary examinations were collected from six patients and their family numbers in five pedigrees with PMLD. Polymerase chain reaction and sequence analysis were used to amplify GJC2 and PLP1 alterations, while multiplex ligation-dependent probe amplification (MLPA) was performed to detect PLP1 dosage changes. The gene mutations were diagnosed for further analysis of the genetic features. RESULTS: A total of seven GJC2 mutations were identified in these patients, including two novel missense mutations (c.217C>T, p.Pro73Ser; c.1199C>A, p.Ala400Glu), one nonsense mutation (c.735C>A, p.Cys245X), three novel frameshift mutations (c.579delC, p.Gly193fsX17 and c.1296_1297insG, p.Gly433fsX59; c.689delG, p.Gly230AlafsX241), and one known missense mutation (c.814T>G, p.Tyr272Asp). Compound heterozygotes were found for P1-3, while homozygotes were found for P4-6 that were inherited from their parents with normal phenotypes except for P5 and P6, respectively. The c.814T>G (p.Tyr272Asp) mutation in P5 was de novo. A c.1199C>A (p.Ala400Glu) homozygous mutation in GJC2 was identified in P6. A heterozygous variation was found in his father and the wild type was seen in his mother.

Efficient and generalizable cross-patient epileptic seizure detection through a spiking neural network.

Introduction: Epilepsy is a global chronic disease that brings pain and inconvenience to patients, and an electroencephalogram (EEG) is the main analytical tool. For clinical aid that can be applied to any patient, an automatic cross-patient epilepsy seizure detection algorithm is of great significance. Spiking neural networks (SNNs) are modeled on biological neurons and are energy-efficient on neuromorphic hardware, which can be expected to better handle brain signals and benefit real-world, low-power applications. However, automatic epilepsy seizure detection rarely considers SNNs. Methods: In this article, we have explored SNNs for cross-patient seizure detection and discovered that SNNs can achieve comparable state-of-the-art performance or a performance that is even better than artificial neural networks (ANNs). We propose an EEG-based spiking neural network (EESNN) with a recurrent spiking convolution structure, which may better take advantage of temporal and biological characteristics in EEG signals. Results: We extensively evaluate the performance of different SNN structures, training methods, and time settings, which builds a solid basis for understanding and evaluation of SNNs in seizure detection. Moreover, we show that our EESNN model can achieve energy reduction by several orders of magnitude compared with ANNs according to the theoretical estimation. Discussion: These results show the potential for building high-performance, low-power neuromorphic systems for seizure detection and also broaden real-world application scenarios of SNNs.

An Explainable Statistical Method for Seizure Prediction Using Brain Functional Connectivity from EEG.

Background: Epilepsy is a group of chronic neurological disorders characterized by recurrent and abrupt seizures. The accurate prediction of seizures can reduce the burdens of this disorder. Now, existing studies use brain network features to classify patients' preictal or interictal states, enabling seizure prediction. However, most predicting methods are based on deep learning techniques, which have weak interpretability and high computational complexity. To address these issues, in this study, we proposed a novel two-stage statistical method that is interpretable and easy to compute. Methods: We used two datasets to evaluate the performance of the proposed method, including the well-known public dataset CHB-MIT. In the first stage, we estimated the dynamic brain functional connectivity network for each epoch. Then, in the second stage, we used the derived network predictor for seizure prediction. Results: We illustrated the results of our method in seizure prediction in two datasets separately. For the FH-PKU dataset, our approach achieved an AUC value of 0.963, a prediction sensitivity of 93.1%, and a false discovery rate of 7.7%. For the CHB-MIT dataset, our approach achieved an AUC value of 0.940, a prediction sensitivity of 93.0%, and a false discovery rate of 11.1%, outperforming existing state-of-the-art methods. Significance. This study proposed an explainable statistical method, which can estimate the brain network using the scalp EEG method and use the net-work predictor to predict epileptic seizures. Availability and Implementation. R Source code is available at https://github.com/HaoChen1994/Seizure-Prediction.

Vagus nerve stimulation in children with drug-resistant epilepsy of monogenic etiology.

Vagus nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy (DRE). The present study evaluated the efficacy of VNS in pediatric patients with DRE of monogenic etiology. A total of 20 patients who received VNS treatment at our center were followed up every 3 months through outpatient visits or a remote programming platform. The median follow-up time was 1.4 years (range: 1.0-2.9). The rate of response to VNS at 12 months of follow-up was 55.0% (11/20) and the seizure-free rate was 10.0% (2/20). We found that 75.0% (3/4) of patients with an SCN1A variant had a >50% reduction in seizure frequency. Patients with pathogenic mutations in the SLC35A2, CIC, DNM1, MBD5, TUBGCP6, EEF1A2, and CHD2 genes or duplication of X q28 (MECP2 gene) had a >50% reduction in seizure frequency. Compared with the preoperative electroencephalography (EEG), at 6, 12, 18, and 24 months after stimulator implantation, the percentage of the patients whose background frequency increased >1.5 Hz was respectively, 15.0% (3/20), 50.0% (10/20), 58.3% (7/12) and 62.5% (5/8); the percentage of the patients whose interictal EEG showed a >50% decrease in spike number was respectively 10% (2/20), 40.0% (8/20), 41.6% (5/12) and 50.0% (4/8). In the 9 patients with no response to VNS treatment, there was no difference in terms of spike number and background frequency between preoperative and postoperative EEG. Five of the 20 children (25.0%) reached new developmental milestones or acquired new skills after VNS compared to the preoperative evaluation. The efficacy of VNS in pediatric patients with DRE of monogenic etiology is consistent with that in the overall population of pediatric DRE patients. Patients with Dravet syndrome (DS), tuberous sclerosis complex (TSC), or Rett syndrome/MECP2 duplication syndrome may have a satisfactory response to VNS, but it is unclear whether patients with rare variants of epilepsy-related genes can benefit from the treatment.

Lesional Intractable Epileptic Spasms in Children: Electroclinical Localization and Postoperative Outcomes.

To analyze the influence of seizure semiology, electroencephalography (EEG) features and magnetic resonance imaging (MRI) change on epileptogenic zone localization and surgical prognosis in children with epileptic spasm (ES) were assessed. Data from 127 patients with medically intractable epilepsy with ES who underwent surgical treatment were retrospectively analyzed. ES semiology was classified as non-lateralized, bilateral asymmetric, and focal. Interictal epileptiform discharges were divided into diffusive or multifocal, unilateral, and focal. MRI results showed visible local lesions for all patients, while the anatomo-electrical-clinical value of localization of the epileptogenic zone was dependent on the surgical outcome. During preoperative video EEG monitoring, among all 127 cases, 53 cases (41.7%) had ES only, 46 (36.2%) had ES and focal seizures, 17 (13.4%) had ES and generalized seizures, and 11 (8.7%) had ES with focal and generalized seizures. Notably, 35 (27.6%) and 92 cases (72.4%) showed simple and complex ES, respectively. Interictal EEG showed that 22 cases (17.3%) had bilateral multifocal discharges or hypsarrhythmia, 25 (19.7%) had unilateral dominant discharges, and 80 (63.0%) had definite focal or regional discharges. Ictal discharges were generalized/bilateral in 71 cases (55.9%) and definite/lateralized in 56 cases (44.1%). Surgically resected lesions were in the hemisphere (28.3%), frontal lobe (24.4%), temporal lobe (16.5%), temporo-parieto-occipital region (14.2%), and posterior cortex region (8.7%). Seizure-free rates at 1 and 4 years postoperatively were 81.8 and 72.7%, respectively. There was no significant difference between electroclinical characteristics of ES and seizure-free rate. Surgical treatment showed good outcomes in most patients in this cohort. Semiology and ictal EEG change of ES had no effect on localization, while focal or lateralized epileptiform discharges of interictal EEG may affect lateralization and localization. Complete resection of epileptogenic lesions identified via MRI was the only factor associated with a positive surgical outcome.

Subtotal hemispherotomy for intractable lesional hemispheric epilepsy without hemiparesis in children.

PURPOSE: We analyzed the surgical indications, outcomes, and prognostic factors of subtotal hemispherotomy for intractable lesional hemispheric epilepsy in children with almost normal motor function and summarized its surgical strategies. METHODS: We retrospectively analyzed 20 children who underwent subtotal hemispherotomy (hemispheric disconnection sparing sensorimotor cortex) between March 2015 and May 2021. The children were divided into seizure-free group and residual seizures group according to their surgical outcomes. The surgical outcome was based on International League Against Epilepsy (ILAE) classification (class 1-6). All presurgical evaluation data were collected and analyzed. RESULTS: Among the 20 children, the mean age at the time of seizure onset, mean age at the time of surgery, and mean follow-up time was 3.2 ± 2.8, 7.5 ± 4.4, and 3.5 ± 2.1 years, respectively. All children had hemispheric lesion on MRI. At the last follow-up evaluation, 75% (15/20) of children remained seizure-free. Univariate analyses revealed that the electrocorticogram finding of epileptiform discharges in the central cortex after disconnection were poor prognostic factors for seizure outcomes (P < 0.05). Disconnection of the central operculum and insula was a poor prognostic factor for motor function after surgery (P < 0.05). CONCLUSIONS: For intractable lesional hemispheric epilepsy with no hemiparesis, subtotal hemispherotomy can be performed with favorable seizure outcome. Disconnection of the central operculum and insula may increase the possibility of motor function injury.

A prediction model integrating synchronization biomarkers and clinical features to identify responders to vagus nerve stimulation among pediatric patients with drug-resistant epilepsy.

AIMS: Vagus nerve stimulation (VNS) is a neuromodulation therapy for children with drug-resistant epilepsy (DRE). The efficacy of VNS is heterogeneous. A prediction model is needed to predict the efficacy before implantation. METHODS: We collected data from children with DRE who underwent VNS implantation and received regular programming for at least 1 year. Preoperative clinical information and scalp video electroencephalography (EEG) were available in 88 children. Synchronization features, including phase lag index (PLI), weighted phase lag index (wPLI), and phase-locking value (PLV), were compared between responders and non-responders. We further adapted a support vector machine (SVM) classifier selected from 25 clinical and 18 synchronization features to build a prediction model for efficacy in a discovery cohort (n = 70) and was tested in an independent validation cohort (n = 18). RESULTS: In the discovery cohort, the average interictal awake PLI in the high beta band was significantly higher in responders than non-responders (p < 0.05). The SVM classifier generated from integrating both clinical and synchronization features had the best prediction efficacy, demonstrating an accuracy of 75.7%, precision of 80.8% and area under the receiver operating characteristic (AUC) of 0.766 on 10-fold cross-validation. In the validation cohort, the prediction model demonstrated an accuracy of 61.1%. CONCLUSION: This study established the first prediction model integrating clinical and baseline synchronization features for preoperative VNS responder screening among children with DRE. With further optimization of the model, we hope to provide an effective and convenient method for identifying responders before VNS implantation.

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study.

Vagus nerve stimulation (VNS) is a safe and effective therapy for pediatric patients with drug-resistant epilepsy (DRE). However, in children with DRE, the effects of VNS on autistic behaviors remain controversial. We retrospectively collected data from 10 children with DRE who underwent VNS implantation and regular parameter regulation in three pediatric epilepsy centers, and completed the behavioral assessments, including the autistic behavior checklist and the child behavior checklist, at follow-ups 1 (mean 2.16 years) and 2 (mean 2.98 years). The 10 children maintained stable seizure control between the two follow-ups. Their autistic behaviors, especially in language, social and self-help, were reduced at follow-up 2 compared to follow-up 1 (p = 0.01, p = 0.01, respectively). Moreover, these improvements were not associated with their seizure control, whether it was positive or negative. These results suggested that the VNS had a positive effect on autistic behaviors, which provided a preliminary clinical basis that VNS may benefit to younger children with DRE comorbidity autism spectrum disorder (ASD).

Postoperative seizure and developmental outcomes of children with hemimegalencephaly and drug-resistant epilepsy.

OBJECTIVE: To evaluate seizure and developmental outcomes in the short and long term in children with hemimegalencephaly (HMEG) after surgery. METHODS: This is a cohort study of 36 children who underwent surgery for HMEG were followed up for at least 1 year postoperatively. The Griffiths Mental Development Scales, Ages and Stages Questionnaire version 3, and Peabody Developmental Motor Scales were used to assess development. RESULTS: The median postoperative follow-up duration was 2.7 (1.0-5.0) years, and median age at surgery was 1.9 years (5.8 months-5.9 years). At the last follow-up, 83% of children were seizure-free. the predicted probability of being seizure-free three years after surgery was 79%. The proportion of patients who were moderate to severe delay declined from 97% preoperatively to 76% at least 1 year after surgery. Catch-up, stabilization, and regression of developmental quotient (DQ) was observed in 41%, 35%, and 24% of children 3 months after surgery, respectively. The corresponding proportions during long-term follow-up were 40%, 33%, and 27%, respectively. Change of DQ shortly after surgery was negatively correlated with age at seizure onset and age at surgery. The long-term DQ was positively correlated with the preoperative DQ. Long-term change of DQ was positively correlated with change of DQ shortly after surgery. CONCLUSIONS: Most of patients with HMEG could achieve seizure free after surgery. After surgery, the proportion of catch-up, stabilization, and regression in both short- and long-term DQ was approximately 40%, 35%, and 25%, respectively. The change of DQ shortly after surgery may be a predictor for long-term developmental change.

Surgical treatment of children with drug-resistant epilepsy involving the Rolandic area.

We retrospectively analysed the clinical features and prognostic factors of surgery in children with drug-resistant epilepsy involving the Rolandic area, and the relationship between the stable compound muscle action potentials (CMAPs) of intraoperative neurophysiological monitoring (IONM) and good motor function outcomes postoperatively. A study was conducted on the clinical data of 91 patients with epilepsy who underwent epilepsy surgery involving the Rolandic area and IONM from November 2015 to February 2019. In total, 91 patients were included in this study. The median age at seizure onset was 1.3 years old. The median age at surgery was 4.4 years old. Twenty-seven patients (29.7%), with age at onset below three years old, had epileptic spasms. The central operculum was the most common surgical region in 52 patients (57.1%). The most common pathology was focal cortical dysplasia (FCD) in 67 patients. At the last follow-up visit, 69 patients (75.8%) were seizure-free. Interictal epileptiform discharges in the Rolandic area were associated with good seizure outcome (p=0.016). Out of 91 patients, successful IONM was performed in 88 patients (96.7%). Stable CMAP was seen in 79 of 88 patients (89.8%), and irreversible disappearance of CMAP was seen in nine patients (10.2%). New permanent motor deficit was observed in 13 of 88 patients (14.8%). There was a significant correlation between stable CMAP and good motor function outcome (p<0.001). This is the largest reported cohort of children with drug-resistant epilepsy involving the Rolandic area who received surgery from a single centre. Epileptic spasms were only observed in young children with age at onset below three years old. The major aetiology was FCD. The rate of seizure freedom was 75.8%. Epileptiform discharges in the Rolandic area were the main prognostic factor affecting surgical outcome. Stable CMAP can predict good motor function outcome postoperatively.

ATP1A1 de novo Mutation-Related Disorders: Clinical and Genetic Features.

Background: ATP1A1 encodes an α1 isoform of Na+/K+-ATPase, which is expressed abundantly in kidneys and central nervous system. ATP1A1 variants may cause Na+/K+-ATPase loss of function and lead to a wide spectrum of phenotypes. This study aims to summarize the clinical and genetic features of ATP1A1 de novo mutation-related disorders and explore the potential correlations between phenotypes and genotypes. Methods: We analyzed two new cases harboring novel de novo ATP1A1 variants and reviewed all reported cases. Results: Both our probands had developmental delay, patient 1 accompanied with sleep disorders, irritability, and patient 2 with refractory seizures. They each had a novel de novo heterozygous missense variant, c.2797G>A[p.Asp933Asn] (NM_000701) and c.2590G>A[p.Gly864Arg] (NM_000701) respectively. Four patients with de novo ATP1A1 variants have been reported in two previous papers. Among them, three patients had refractory seizures and one patient had complex hereditary spastic paraplegia (HSP). Therefore, all six patients had developmental delay, and four of them had epilepsy. All variants located in the transmembrane regions M3, M4, M7, and M8 of ATP1A1 protein. Four patients with mutations in M3 and M7 had more severe phenotypes, including developmental delay and epileptic encephalopathy, three of them with hypomagnesemia, whereas two patients with mutations in M4 and M8 had milder phenotypes, only with mild developmental delay, without seizures or hypomagnesemia. Correcting hypomagnesemia had not controlled those seizures. Conclusions: Two novel de novo ATP1A1 variants identified in two patients here enriched the genotypic and phenotypic spectrum of ATP1A1 mutation-related disorder. Our findings suggest that hypomagnesemia in this disorder might relate to more severe phenotype and indicate more severe Na+/K+-ATPase dysfunction. Variations in M3 and M7 transmembrane regions were related to more severe phenotype than those in M4 and M8, which suggested that variations in M3 and M7 might cause more severe ATP1A1 functional defect.