Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

Clinical analysis of developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep: A single tertiary care center experience in China.

PURPOSE: To analyze the electroclinical features of patients with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (DEE/EE-SWAS) and study the efficacy of different therapies on seizure control, electroencephalogram (EEG) improvements of electrical status epilepticus during sleep (ESES), and cognition outcomes. METHODS: Patients with DEE/EE-SWAS who underwent at least one follow-up EEG 3 months after therapy were retrospectively enrolled. The demographic and clinical characteristics of the patients were analyzed. Variables that influenced the outcomes were evaluated using logistic regression models. RESULTS: In total, 87 patients (47 males) were included. The median age at ESES recognition was 81.0 months (IQR 64.0, 96.0). Forty-six patients were diagnosed with self-limited focal epilepsies (SeLFEs) before ESES recognition, 24 with developmental and epileptic encephalopathies with spike-and-wave activation in sleep (DEE-SWAS), and 17 with other epilepsies. Steroids, benzodiazepines, and antiseizure medications (ASMs) were the initial treatment options for ESES. Patients with structural etiologies or slow EEG backgrounds at the time of ESES recognition were less likely to respond to treatment than other patients. However, only children with slow EEG backgrounds had lower odds of response in logistic regression models. Children with clinical or EEG response showed improvements in cognition. CONCLUSION: Steroids, benzodiazepines, and ASMs are effective treatments for patients with DEE/EE-SWAS. Children with structural etiologies or slow EEG backgrounds at the time of ESES recognition may have a poor long-term prognosis. The efficacy of seizure reduction and EEG improvement is associated with cognitive improvement.

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.

Etiologies and clinical characteristics of acute ataxia in a single national children's medical center.

OBJECTIVE: To analyze etiologic factors of pediatric acute ataxia and to identify the severity of its underlying causes for urgent medical intervention. METHODS: Clinical data of children diagnosed with acute ataxia between December 2015 and December 2021 from one national medical center were analyzed retrospectively. RESULTS: A total of 99 children (59 boys, 40 girls), median age at disease onset 55 (range: 12-168) months, were enrolled. The median follow period was 46 (range 6-78) months. Eighty-six (86.9 %) children were diagnosed with immune-associated acute ataxia, among which acute post-infectious cerebellar ataxia (APCA) was the most common diagnosis (50.5 %), followed by demyelinating diseases of the central nervous system (18.2 %) and Guillain-Barré syndrome (9.1 %). On cerebrospinal fluid (CSF) examination, 35/73 (47.9 %) patients had pleocytosis (>5 cells/mm3), and 18/73 (24.7 %) had elevated protein levels. Thirty-one patients (31.3 %) had an abnormal cerebral MRI. Children with other immune-associated acute cerebellar ataxia had more extracerebellar symptoms, intracranial MRI lesions, abnormal CSF results, longer hospital stay, higher recurrence rates and incidence of neurological sequelae than children with APCA. CONCLUSION: Immune-associated acute ataxia is the main cause of pediatric acute ataxia, among which APCA is the most common phenotype. However, some immune-associated diseases, especially autoantibody-mediated disease, which has a higher recurrence rate and neurological sequelae account for an increasing proportion of pediatric acute ataxia. When children present with extracerebellar symptoms, abnormal cranial MRI or CSF results, and without prodromal infection, prudent differential diagnosis is recommended.

Telemedicine during the COVID-19 epidemic improves outcomes in children with tuberous sclerosis complex: A 1206 visits retrospective cohort study.

AIMS: To evaluate the benefits of telemedicine in children with tuberous sclerosis complex during the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted, comparing telemedicine and in-person visits within the timeframe spanning from June 1, 2021, to June 1, 2022. Disparities in demographics, emergency visits, hospitalizations, adverse effects (AEs) associated with sirolimus, and the incidence of drug-refractory epilepsy (DRE) between telehealth and in-person care were assessed. Additionally, distinctions between audio and video telehealth, as well as varying frequencies of telehealth encounters, were investigated and reported as odds ratios (ORs). RESULTS: A total of 378 patients with 1206 visits were included, of which 137 were telemedicine patients and 241 were in-person patients. The median age was 5.0 years (IQR 2.8-10.0 years). There were 197 males (52.12%), 691 in-person visits (57.30%), and 515 telemedicine visits (42.70%). Children under 12 years old, those farther away from the center, mothers with more than 12 years of education, and children treated with sirolimus were more likely to visit via telemedicine. Telehealth was associated with significantly fewer emergency visits, hospitalizations, AEs of sirolimus, and DRE. With 10 or more visits, the incidence of emergency visits, hospitalization, and DRE was significantly reduced. CONCLUSION: Telemedicine visits are almost as close in number as in-person visits. Younger patients, patients in remote areas, and mothers with higher education levels are more willing to complete telemedicine visits. Telemedicine visits were associated with a significantly lower number of emergency visits, hospitalizations, and AEs of sirolimus. Patients with more than 10 visits per year seemed to have better clinical outcomes.

[Clinical and genetic analysis of a child with Cerebral creatine deficiency syndrome due to variant of SLC6A8 gene].

OBJECTIVE: To explore the clinical features and genetic variant in a child with Cerebral creatine deficiency syndrome (CCDS). METHODS: A child who had presented at the Affiliated Children's Hospital of Fudan University on March 5, 2021 was selected as the study subject. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing. The level of creatine in the brain was determined by magnetic resonance spectroscopy. RESULTS: The patient, a 1-year-and-10-month male, had presented with developmental delay and epilepsy. Both his mother and grandmother had a history of convulsions. MRS showed reduced cerebral creatine in bilateral basal ganglia and thalamus. The child was found to harbor a hemizygous splicing variant of the SLC6A8 gene, namely c.1767+1_1767+2insA, which may lead to protein truncation. The variant was not found in the public databases. Both his mother and grandmother were heterozygous carriers for the same variant. CONCLUSION: The hemizygous c.1767+1_1767+2insA variant of the SLC6A8 gene probably underlay the CCDS in this child. Discovery of the novel variant has also expanded the mutational spectrum of the SLC6A8 gene.

Long-term efficacy and safety of tacrolimus in young children with myasthenia gravis.

OBJECTIVE: This study was performed to evaluate the efficacy and long-term safety of tacrolimus for young children with myasthenia gravis (MG). METHODS: Children with corticosteroids (CSs)-ineffective, CSs-dependent or CSs-intolerable MG treated with tacrolimus for at least one year were recruited. The Myasthenia Gravis Foundation of America (MGFA) clinical classification and MGFA post-intervention status (MGFA-PIS) were used to evaluate before tacrolimus administration and at the last visit, respectively. MG Activities of Daily Living (MG-ADL) score and the dose of prednisone were recorded. Patients were divided into responders and poor responders based on changes in MG-ADL score to investigate the factors that affected tacrolimus efficacy. Unfavorable events were recorded. RESULTS: Twenty-one patients with MG were enrolled. The median age of starting tacrolimus was 8.7 (range 2.2-15.1) years old. At the last visit, 15 patients (71.4%) achieved minimal manifestation (MM) or better status. The symptoms evaluated by MG-ADL improved significantly one month after initiating tacrolimus (p＜0.05) and the dose of prednisone decreased significantly three months later (p＜0.05), and it continued to improve throughout the study. Thirteen patients (61.9%) were ultimately weaned off prednisone. Compared with 16 responders, 5 poor responders had lower MG-ADL scores. MG-ADL score was the only clinical factor of tacrolimus efficacy. Intraocular pressure and transient urine microprotein were present in one patient. CONCLUSION: A course of tacrolimus of more than one year was effective and well-tolerated in young children with MG, and tacrolimus improved MG symptoms and reduced the dose and adverse events of oral prednisone.

Long-term effectiveness and seizure recurrence risk factors of ketogenic diet for pediatric refractory epilepsy: Experience from a tertiary care center in China.

OBJECTIVE: This study aimed to assess the long-term effectiveness and seizure recurrence risk in children with drug-resistant epilepsy who achieved seizure freedom on a ketogenic diet (KD). Predictors associated with seizure recurrence were also evaluated. METHODS: Patients with drug-resistant epilepsy who received KD therapy for at least 3 months between May 2011 and April 2020 were included. The clinical efficacy of the KD was evaluated. Patients who achieved seizure freedom for at least 3 months on the KD were focused. Multivariate Cox regression models were used to explore the risk factors of seizure relapse in patients who achieved seizure freedom. RESULTS: This study included 288 patients (163 males, 125 females). The seizure-free rates of the KD at 3, 6, 12, and 24 months were 9.7%, 16.7%, 14.2%, and 9.0%, respectively. Additionally, the seizure reduction rates between 50% and 99% were 46.5%, 39.9%, 30.2%, and 20.5%, respectively. Patients with Angelman syndrome (AS) showed the highest efficacy rate, followed by those with Dravet syndrome (DS). 51 patients achieved at least 3 months of seizure freedom on the KD. Seizures recurred in 24 (47.1%) patients. None of the patients with AS relapsed, while those with DS had the highest recurrence rate. The etiology of epilepsy, KD maintenance treatment period, and electroencephalography (EEG) abnormalities during follow-up differed significantly between patients with and without recurrence. However, multivariate Cox regression analysis indicated that a KD maintenance treatment period of less than 12 months and the presence of EEG abnormalities during follow-up were significantly correlated with a higher risk of relapse. Epilepsy control was restored in 3 of the 24 (12.5%) patients who experienced relapse. SIGNIFICANCE: KD appears to be effective in children with various types of drug-resistant epilepsy. A short KD maintenance treatment period and EEG abnormalities during follow-up were associated with an increased risk of seizure recurrence.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Identification of a novel splicing variant in the phosphatidylinositol glycan class S (PIGS) gene that is associated with early onset epilepsy, severe developmental delay, and ventricular septal defect: a case report.

Background: Glycosylphosphatidylinositols (GPI) are glycolipids that act as membrane anchors of many cell surface proteins. The phosphatidylinositol glycan class S (PIGS) gene encodes an essential component of the multi-subunit, membrane-bound, GPI transamidase that comprises 4 other proteins including PIGK, GPAA1, PIGT, and PIGU. To date, 13 patients with PIGS variants have been identified with developmental delay, seizures, and hypotonia, and only one canonical splicing variant has been reported. Case Description: This case study describes a boy with very early onset refractory seizures, developmental delay, hypotonia, ventricular septal defect, nystagmus, and some facial dysmorphism. His seizures were responsive to vitamin B6 administration. Compound heterozygous variants (c.1141_1164dup and c.935-6C>G) in PIGS were identified in the proband by trio whole exome sequencing (WES). The c.1141_1164dup has been previously reported in two unrelated patients with PIGS variants. The skipping of exon 10 was observed in the proband by RNA analysis, and the pathogenicity of the splicing variant c. 935-6C>G was confirmed. Conclusions: Our identification of the c. 935-6C>G variant enlarges the variant spectrum in the PIGS gene. It is a novel splicing variant which leads to the skipping of exon 10 in the PIGS gene. Furthermore, the phenotypic spectrum of PIGS variants has also been expanded, with ventricular septal defect in heart being reported in patients with PIGS variants for the first time.

Further delineation of EBF3-related syndromic neurodevelopmental disorder in twelve Chinese patients.

Neurodevelopmental disorders (NDDs) have heterogeneity in both clinical characteristics and genetic factors. EBF3 is a recently discovered gene associated with a syndromic form of NDDs characterized by hypotonia, ataxia and facial features. In this study, we report twelve unrelated individuals with EBF3 variants using next-generation sequencing. Five missense variants (four novel variants and one known variant) and seven copy number variations (CNVs) of EBF3 gene were identified. All of these patients exhibited developmental delay/intellectual disability. Ataxia was observed in 33% (6/9) of the patients, and abnormal muscle tone was observed in 55% (6/11) of the patients. Aberrant MRI reports were noted in 64% (7/11) of the patients. Four novel missense variants were all located in the DNA-binding domain. The pathogenicity of these variants was validated by in vitro experiments. We found that the subcellular protein localization of the R152C and F211L mutants was changed, and the distribution pattern of the R163G mutant was changed from even to granular. Luciferase assay results showed that the four EBF3 mutants' transcriptional activities were all significantly decreased (p < 0.01). Our study further expanded the gene mutation spectrum of EBF3-related NDD.

Spinal muscular atrophy with hypoplasia of the corpus callosum: a case report.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Hypoplasia of the corpus callosum is underdevelopment or thinness of the corpus callosum. SMA and callosal hypoplasia are relatively rare, and there is limited information sharing the diagnosis and treatment for SMA patients with callosal hypoplasia. CASE DESCRIPTION: A boy with callosal hypoplasia, small penis, and small testes had been perceived with motor regression at 5 months. He was referred to the rehabilitation department and neurology department at 7 months. Physical examination showed absent deep tendon reflexes, proximal weakness and significant hypotonia. He was recommended to perform trio whole-exome sequencing (WES) and array comparative genomic hybridization (aCGH) for his complicated conditions. The subsequent nerve conduction study revealed some characteristics of motor neuron diseases. We identified a homozygous deletion in exon 7 of the SMN1 gene by multiplex ligation-dependent probe amplification and failed to find further pathogenic variations responsible for multiple malformations by trio WES and aCGH. He was diagnosed as SMA. Despite some concerns, he received the therapy of nusinersen for nearly 2 years. He gained the milestone of sitting without support, which he had never accomplished, after the seventh injection, and he continued to improve. During follow-up, there were no adverse events reported and no signs of hydrocephalus. CONCLUSIONS: Some extra features which could not belong to neuromuscular manifestation made the diagnosis and treatment of SMA more complicated.

Unrelated umbilical cord blood transplantation for children with hereditary leukodystrophy: A retrospective study.

Objective: To analyze the efficiency of unrelated umbilical cord blood transplantation (UCBT) in the treatment of hereditary leukodystrophy following busulfan- and cyclophosphamide-based myeloablative chemotherapy. Methods: A retrospective study was performed in patients with hereditary leukodystrophy who underwent UCBT after myeloablative chemotherapy between April 2015 and March 2020. Results: The study cohort included 12 pediatric patients (ten males), nine with cerebral adrenoleukodystrophy (ALD) and three with juvenile globoid cell leukodystrophy (GLD). All received HLA-matched or partially mismatched unrelated UCBT. There were no cases of graft rejection. Median neutrophil engraftment time was 20 days [12-33 days] and median platelet engraftment time was 29 days [14-65 days]. Median follow-up was 36 months [1-86 months], and the overall survival rate for patients with cerebral ALD and juvenile GLD after UCBT was 77.8% (7/9) and 100% (3/3), respectively. In patients with ALD, although lipid profiles (serum very-long-chain fatty acid) were improved post-UCBT, six patients demonstrated worse neurologic function score and performance status post-UCBT, and six patients had higher Loes scores at last follow-up compared with baseline. In patients with juvenile GLD, all patients showed stable neurologic function score and performance status despite the Loes score of one patient increased slightly after transplantation. Conclusion: In patients with cerebral ALD, patients with no or mild neurological symptoms can benefit from UCBT, while UCBT cannot reverse advanced disease. In patients with juvenile GLD, UCBT is safe and contributes to stabilize neurological function.

Astrocytic GABA transporter 1 deficit in novel SLC6A1 variants mediated epilepsy: Connected from protein destabilization to seizures in mice and humans.

OBJECTIVE: Mutations in γ-aminobutyric acid (GABA) transporter 1 (GAT-1)-encoding SLC6A1 have been associated with myoclonic atonic epilepsy and other phenotypes. We determined the patho-mechanisms of the mutant GAT-1, in order to identify treatment targets. METHODS: We conducted whole-exome sequencing of patients with myoclonic atonic epilepsy (MAE) and characterized the seizure phenotypes and EEG patterns. We studied the protein stability and structural changes with homology modeling and machine learning tools. We characterized the function and trafficking of the mutant GAT-1 with 3H radioactive GABA uptake assay and confocal microscopy. We utilized different models including a knockin mouse and human astrocytes derived from induced pluripotent stem cells (iPSCs). We focused on astrocytes because of their direct impact of astrocytic GAT-1 in seizures. RESULTS: We identified four novel SLC6A1 variants associated with MAE and 2 to 4 Hz spike-wave discharges as a common EEG feature. Machine learning tools predicted that the variant proteins are destabilized. The variant protein had reduced expression and reduced GABA uptake due to endoplasmic reticular retention. The consistent observation was made in cortical and thalamic astrocytes from variant-knockin mice and human iPSC-derived astrocytes. The Slc6a+/A288V mouse, representative of MAE, had increased 5-7 Hz spike-wave discharges and absence seizures. INTERPRETATION: SLC6A1 variants in various locations of the protein peptides can cause MAE with similar seizure phenotypes and EEG features. Reduced GABA uptake is due to decreased functional GAT-1, which, in thalamic astrocytes, could result in increased extracellular GABA accumulation and enhanced tonic inhibition, leading to seizures and abnormal EEGs.

A Hybrid Expert System for Individualized Quantification of Electrical Status Epilepticus During Sleep Using Biogeography-Based Optimization.

Electrical status epilepticus during sleep (ESES) is an epileptic encephalopathy in children with complex clinical manifestations. It is accompanied by specific electroencephalography (EEG) patterns of continuous spike and slow-waves. Quantifying such EEG patterns is critical to the diagnosis of ESES. While most of the existing automatic ESES quantification systems ignore the morphological variations of the signal as well as the individual variability among subjects. To address these issues, this paper presents a hybrid expert system that dedicates to mimicking the decision-making process of clinicians in ESES quantification by taking the morphological variations, individual variability, and medical knowledge into consideration. The proposed hybrid system not only offers a general scheme that could propel a semi-auto morphology analysis-based expert decision model to a fully automated ESES quantification with biogeography-based optimization (BBO), but also proposes a more precise individualized quantification system to involve the personalized characteristics by adopting an individualized parameters-selection framework. The feasibility and reliability of the proposed method are evaluated on a clinical dataset collected from twenty subjects at Children's Hospital of Fudan University, Shanghai, China. The estimation error for the individualized quantitative descriptor ESES is 0-4.32% and the average estimation error is 0.95% for all subjects. Experimental results show the presented system outperforms existing works and the individualized system significantly improves the performance of ESES quantification. The favorable results indicate that the proposed hybrid expert system for automatic ESES quantification is promising to support the diagnosis of ESES.

Prenatal diagnosis and intervention improve developmental outcomes and epilepsy prognosis in children with tuberous sclerosis complex.

AIM: To assess whether prenatal diagnosis and early intervention are beneficial for developmental outcomes and epilepsy prognosis in individuals with tuberous sclerosis complex (TSC). METHOD: This retrospective study originated from a single-centre TSC-specific cohort. We enrolled 273 individuals (138 males, 145 females; 2 years-7 years 6 months, mean 4 years 5 months, SD 1 year 6 months) with definitive TSC who completed TSC1/TSC2 genetic testing and were followed up to 2 years of age. The benefits of early attention and intervention were assessed by comparing epilepsy and developmental outcomes between groups with or without a prenatal diagnosis and with or without presymptomatic preventive intervention. RESULTS: The epilepsy occurrence rate was significantly lower in individuals diagnosed prenatally than in individuals diagnosed postnatally (p = 0.027). In individuals diagnosed prenatally, the epilepsy rate in the preventive intervention subgroup was significantly lower than that in the subgroup without preventive intervention (p = 0.008). Significant improvements in cognitive, language, and motor development were observed in individuals diagnosed prenatally compared to individuals diagnosed postnatally and in the preventive intervention subgroup compared to the subgroup without preventive intervention (p < 0.05). INTERPRETATION: Based on this study, we cautiously speculate that early postpartum intervention may reduce the incidence of epilepsy and intractable epilepsy and improve developmental outcomes. Prophylactic intervention with sirolimus and vigabatrin may reduce the incidence of epilepsy. Larger prospective randomized controlled studies are required to support these findings. WHAT THIS PAPER ADDS: Prenatal diagnosis and early intervention may improve developmental outcomes in children with tuberous sclerosis complex (TSC). Prophylactic intervention with sirolimus and vigabatrin may reduce the incidence of epilepsy. Cardiac and/or intracranial lesions combined with genetic testing can be used to diagnose TSC prenatally.

EMD-WOG-2DCNN based EEG signal processing for Rolandic seizure classification.

Objective Approximately 65 million people have epilepsy around the world. Recognition of epilepsy types is the basis to determine the treatment method and predict the prognosis in epilepsy patients. Childhood benign epilepsy with centrotemporal spikes (BECTS) or benign Rolandic epilepsy is the most common focal epilepsy in children, accounting for 15-20% of childhood epilepsies. These EEG patterns of individuals usually predict good treatment responses and prognosis. Until now, the interpretation of EEG still depends entirely on experienced neurologists, which may be a lengthy and tedious task. Method In this article, we proposed a novel machine learning model that efficiently distinguished Rolandic seizures from normal EEG signals. The proposed machine learning model processes the identification procedure in the following order (1) creating preliminary EEG features using signal empirical mode decomposition, (2) applying weighted overlook graph (WOG) to represent the decomposed EMD of IMF, and (3) classifying the results through a two Dimensional Convolutional Neural Network (2DCNN). The performance of our classification model is compared with other representative machine learning models. Results The model offered in this article gains an accuracy performance exceeding 97.6% in the Rolandic dataset, which is higher than other classification models. The effect of the model on the Bonn public dataset is also comparable to existing methods and even performs better in some subsets. Conclusion The purpose of this study is to introduce the most common childhood benign epilepsy type and propose a model that meets the real clinical needs to distinguish this Rolandic EEG pattern from normal signals accurately. Significance Future research will optimize the model to categorize other types of epilepsies beyond BECTS and finally implement them in the hospital system.

Comprehensive profile and natural history of pediatric patients with spinal muscular atrophy: A large retrospective study from China.

Background: There is a large population of people with spinal muscular atrophy (SMA) in China, and new disease-modifying therapies have become available recently. However, comprehensive data on the management and profile of treatment-naive SMA patients in China are still lacking. Methods: As a retrospective study, a large cohort of treatment-naive patients with clinical and genetic diagnoses of 5q SMA were enrolled, ranging from neonatal to 18 years old, from the Neurology Department of Children's Hospital of Fudan University between January 2013 and December 2020. The data regarding their clinical presentations, genetic defects, motor function assessment results, and follow ups were reviewed. Results: We enrolled 392 SMA patients (male: female = 189: 203): 1a = 46, 1b = 44, 1c = 31, 2a = 119, 2b = 56, 3a = 52, 3b = 14, from 27 of the 34 administrative districts in China, and 389 patients harbored homozygous deletion of exon 7 in the SMN1 gene (99.2%). The median age of onset was 0.08 (range: 0-0.30), 0.25 (0.06-0.60), 0.42 (0.08-1.50), 0.67 (0.07-5.08), 1.0 (0.40-1.83), 1.5 (1.00-3.00), and 4.04 (1.80-12.00) years old for SMA 1a, 1b, 1c, 2a, 2b, 3a, and 3b patients, while the median age of first assessment was 0.25 (0.08-2.60), 0.42 (0.17-1.90), 0.80 (0.17-4.5), 2.50 (0.5-15.83), 2.92 (1.08-13.42), 4.25 (1.58-17.33), and 7.34 (3.67-14.00) years old, respectively. Patients were followed up with for up to 15.8 years. The median event-free survival time was 7 months, 15 months, and indeterminate in SMA 1a, 1b, and 1c patients (p < 0.0001), with a better survival situation for higher SMN2 copies (p = 0.0171). The median age of sitting loss was 5.75 years and 13.5 years in SMA 2a and 2b (p = 0.0214) and that of ambulation loss was 9.0 years and undefined in SMA 3a and 3b (p = 0.0072). Cox regression analysis showed that higher SMN2 copies indicated better remaining ambulation in SMA 3. The median time to develop orthopedic deformities was 4.5, 5.2, and 10.1 years in SMAs 1c, 2, and 3, respectively (p < 0.0001), with a possible trend of better preservation of joint function for patients under regular rehabilitation (p = 0.8668). Conclusion: Our study elucidated insight into the comprehensive management and profile of different types of SMA patients in China, providing a clinical basis for assessing the efficacy of new therapies.