Infantile spasms (IS) is a specific type of epileptic encephalopathy associated with severe developmental disabilities. Genetic factors are strongly implicated in IS, however, the exact genetic defects remain unknown in the majority of cases. Rare mutations in a single gene or in copy number variants (CNVs) have been implicated in IS of children in Western countries. The objective of this study was to dissect the role of copy number variations in Chinese children with infantile spasms.

Objective: Tuberous sclerosis complex (TSC) is a rare disease with a high risk of epilepsy and cognitive impairment in children. Ketogenic diet (KD) therapy has been consistently reported to be beneficial to TSC patients. In this study, we aimed to investigate the efficacy and safety of KD in the treatment of drug-resistant epilepsy and cognitive impairment in children with TSC. Methods: In this multicenter study, 53 children (33 males and 20 females) with drug-resistant epilepsy or cognitive impairment caused by TSC were retrospectively recruited from 10 hospitals from January 1, 2010, to December 31, 2020. Intention-to-treat analysis was used to evaluate seizure reduction and cognition improvement as outcomes after KD therapy. Results: Of the 53 TSC patients included, 51 failed to be seizure-free with an average of 5.0 (range, 4–6) different anti-seizure medications (ASMs), before KD therapy. Although the other two patients achieved seizure freedom before KD, they still showed psychomotor development delay and electroencephalogram (EEG) abnormalities. At 1, 3, 6, and 12 months after the KD therapy, 51 (100%), 46 (90.2%), 35 (68.6%), and 16 patients (31.4%) remained on the diet therapy, respectively. At these time points, there were 26 (51.0%), 24 (47.1%), 22 (43.1%) and 13 patients (25.5%) having ≥50% reductions in seizure, including 11 (21.6%), 12 (23.5%), 9 (17.6%) and 3 patients (5.9%) achieving seizure freedom. In addition, of 51 patients with psychomotor retardation, 36 (36 of 51, 70.6%) showed cognitive and behavioral improvements. During the KD therapy, no serious side effects occurred in any patient. The most common side effects were gastrointestinal disturbance (20 of 53, 37.7%) and hyperlipidemia (6 of 53, 11.3%). The side effects were gradually relieved after adjustment of the ketogenic ratio and symptomatic treatment. Conclusion: KD is an effective and safe treatment for TSC-related drug-resistant epilepsy and cognitive impairment in children. KD can reduce seizure frequency and may potentially improve cognition and behavior.

Angelman syndrome (AS) is a neurodevelopmental genetic disorder, but there has been limited analysis of a large cohort of Chinese children with Angelman syndrome. This study aims to assess the phenotype and genotype of Chinese children with Angelman syndrome. We retrospectively analyzed data through a detailed online survey combined with an on-site study. Furthermore, phenotype analysis stratified by deletion and non-deletion groups was carried out. The responses of family members of 695 individuals with AS revealed that 577 patients (83.02%) had maternal deletions, 65 patients (9.35%) carried UBE3A mutations, 31 (4.46%) patients had UPD15pat (one patient with UPD15pat constituted by a mosaic), 10 patients (1.44%) had imprinting defects and 12 (1.58%) patients only showed abnormal methylation without further detection. We identified 50 different pathogenic variants in this cohort, although 18 of these variants were unreported. Recurrent variant c.2507_2510del (p.K836Rfs*4) was found in 7 patients. In the deletion group, patients were diagnosed at an earlier age, had a more severe clinical phenotype, a higher rate of epilepsy with more multiple seizure types, and more frequently combined medication. Strabismus and sleep disturbances were both common in deletion and non-deletion groups. The top three resources invested in caring for AS children are: daily involvement in patient care, rehabilitation cost, and anti-epileptic treatment. Our study showed the genetic composition of Chinese children with 83.02% of maternal deletions, and the mutation spectrum for UBE3A variants was expanded. Developmental outcomes are associated with genotype, and this was confirmed by deletion patients having a worse clinical phenotype and complex epilepsy.

Objective: To summarize the clinical, electrophysiological, neuroimaging, and immunological characteristics of seven cases of Bickerstaff brainstem encephalitis (BBE) in China and to determine whether certain clinical features suggestive of BBE can facilitate diagnosis and treatment. Patients and Methods: The clinical data of seven BBE patients treated at the Children's Hospital of Fudan University between 2016 and 2019 were retrospectively analyzed. The clinical and laboratory characteristics of the BBE patients were studied. Results: The seven patients in this study included four females and three males, and the median age at diagnosis was 5.3 years (interquartile range: 3.0–7.1 years). All seven patients had an acute onset with a preinfection history. Seven cases of acute extraocular paralysis, ataxia, and an impaired level of consciousness, two cases of tendon hyperreflexia, one case of positive pathology, and five cases of cranial nerve involvement (the facial nerve and oculomotor nerve) were noted. Cerebrospinal fluid (CSF) examination of five patients showed albuminocytologic dissociation. Electromyography (EMG) was used to examine seven patients; the results were normal in four patients, showed axonal involvement in two patients, and showed demyelination in one patient. The head magnetic resonance imaging (MRI) results of all seven patients were normal. Electroencephalogram (EEG) background activity in the five monitored patients was slowed down. Seven patients underwent serum antibody testing, three of whom were positive for anti-GQ1b antibody, while one was positive for anti-GM1 antibody. Three patients received glucocorticoid combined with intravenous immunoglobulin (IVIG) therapy, and four received only IVIG therapy. One patient required a nasal catheter for oxygen during the disease course, and left upper limb muscle dysfunction (grade III muscle strength of the left upper limb) was observed during the 6-month follow-up. The other six patients had a good prognosis and no dysfunction. Conclusion: Our study identified clinical, imaging, and treatment characteristics that may have prognostic value for pediatric BBE. The positive rate of head MRI was low, the positive rate of serum anti-GQ1b ganglioside antibody was low, and the therapeutic effect of IVIG therapy was good.