Mediating effects of sleep quality between clinical characteristics and quality of life in children with epilepsy: A cross-sectional study from Southwest China.

BACKGROUND: Although sleep quality (SQ) reportedly affects the health-related quality of life (QOL) of patients with epilepsy, little is known about the potential association between SQ and QOL, particularly in children with epilepsy (CWE). Our study aimed to investigate the mediating effect of SQ on the QOL of CWE to obtain more information for the prevention and treatment of epilepsy in children. METHODS: We collected general demographic and clinical data of 212 CWE and 79 controls (children who visited the Health Examination Department), and their guardians were instructed to answer the Children's Sleep Habits Questionnaire (CSHQ) and the optimized Quality of Life in Childhood Epilepsy Questionnaire-16 (QOLCE-16). The t-test, analysis of variance, chi-square test, and Fisher's exact test were used for between group comparisons. The Pearson correlation was used to analyze the correlation between variables. The direct, indirect, and total effects of predictors on the QOL of CWE were estimated based on an adjusted mediation model. RESULTS: CWE had significantly smaller long-term urban residence rates, less educated guardians, higher total CSHQ score, higher incidence of poor SQ, higher bedtime resistance, more sleep anxiety, worse sleep-disordered breathing, increased parasomnia, more daytime sleepiness, more frequent night waking, and greater sleep onset delay than controls (P < 0.05 for all). The univariable analysis showed significant differences in total CSHQ scores between CWE with different seizure frequency in the last month, whether or not drug-resistant epilepsy (DRE), and with different video electroencephalogram (VEEG) findings (P < 0.05 for all). Differences in QOLCE-16 scores between CWE with different guardian's employment status, age at diagnosis, number of anti-seizure medication (ASM) types, seizure frequency in the last month, DRE status, seizure type, VEEG findings, neuropsychological evaluation findings, magnetic resonance imaging (MRI) findings, and etiology were statistically significant (P < 0.05 for all). The correlation study indicated that the total CSHQ score was negatively correlated with the QOLCE-16 score (P < 0.05). The mediation analysis showed that DRE and VEEG abnormalities had a standardized direct effect on the QOL. Seizure frequency in the last month, DRE, and VEEG abnormalities had an indirect effect on the QOL through SQ, and their mediating effect values of SQ were 31.61 %, 13.45 %, and 14.35 %, respectively. CONCLUSION: Our findings uncovered the relationship of some clinical characteristics with SQ and QOL and characterized the nature of factors affecting the QOL of CWE. SQ could be a key factor in the prognosis of CWE experiencing epileptic seizures, and more attention should be paid on the management of SQ in interventions for epilepsy.

Clinical and electroencephalographic characteristics of 34 infant with onset of epileptic spasms before three months of age.

Epileptic spasms (ES) occur mostly between age 3 months and 24 months. ES beginning before 3 months of age were called early-onset ES in previous studies. The aim of this study was to identify clinical and electroencephalographic characteristics of patients with ES onset before 3 months of age. In total, 34 ES patients were retrospectively identified at Children's Hospital of Chongqing Medical University from January 1, 2020 to October 1, 2022. Our patients had diverse etiologies, including genetic (32.3 %), genetic-structural (11.8 %), structural-acquired (11.8 %), structural-congenital (8.8 %), and metabolic (5.9 %), with 29.4 % of patients having unknown etiology. Some patients experienced ES in clusters (either symmetrical or flexional) that occurred most often during awakening after sleep, and a minority of ES were characterized as isolated or asymmetrical, occurred during sleep, and could also manifest as relatively subtle. Approximately 35.3 % of patients also experienced other seizure types concurrently, including 10 focal seizures and 2 generalized seizures, and only half of the focal seizures had structural causes. The other seizure types occurred alone or sequentially with ES. Interictal electroencephalography revealed hypsarrhythmia or its variants, multifocal discharge, or burst suppression. 18 patients had no seizures lasting for more than 2 months, however, at the last follow-up visit, 5 of them had relapsed. All patients had different degrees of psychomotor retardation.

The prospective study of 54 children with electrical status epilepticus during sleep: How to simplify the electroencephalogram diagnosis and guide the treatment.

OBJECTIVE: To simplify the electroencephalogram (EEG) diagnosis and guide the treatment of electrical status epilepticus during sleep (ESES). METHODS: We recruited 54 children with ESES from December 2019 to December 2020 and compared various spike-wave index (SWI) calculation methods. Time-frequency analysis assessed the correlation between high-frequency oscillations energy and the SWI. We divided 42 children into responder and non-responder treatment groups based on the observations made during a 12-month follow-up period and evaluate different treatment and the independent risk factors of refractory ESES. RESULTS: The SWI of 5 min before the second sleep cycle of non-rapid eye movement (NREM; long method II) and that of all NREM sleep (total method) were not significantly different (p = .06). The average energy of γ (r = .288, p = .002) and ripple (r = .203, p = .04) oscillations were correlated with the SWI. Multivariable logistic regression analysis showed that encephalomalacia was an independent risk factor for refractory ESES (OR: 10.48, 95% CI: 1.62-67.63). The clinical seizure improvement rates of anti-seizure medications (ASMs), ASMs with benzodiazepines, and ASMs with benzodiazepines and steroids after 12 months were 9.3%, 42.8%, and 53.8%, EEG improvement rate were 5.5%, 30.9% and 37%, respectively. The intelligence of the children in the responder treatment group has improved during the 1-year follow-up. SIGNIFICANCE: These findings demonstrate EEG and clinical features of ESES and may provide basis for simplifying diagnosis and guiding the treatment of children with ESES.

In situ photo-crosslinking silk fibroin based hydrogel accelerates diabetic wound healing through antibacterial and antioxidant.

Bacterial infection and excessive reactive oxygen species (ROS) in diabetic wounds lead to a prolonged inflammatory phase, and injuries are highly susceptible to developing into chronic wounds. Improving the poor microenvironment is vital to achieving effective diabetic wound healing. In this work, methacrylated silk fibroin (SFMA) was combined with ε-polylysine (EPL) and manganese dioxide nanoparticles (BMNPs) to form an SF@(EPL-BM) hydrogel with in situ forming, antibacterial and antioxidant properties. EPL imparted high antibacterial activity (>96 %) to the hydrogel. BMNPs and EPL showed good scavenging activity against a variety of free radicals. SF@(EPL-BM) hydrogel had low cytotoxicity and could alleviate H2O2-induced oxidative stress in L929 cells. In diabetic wounds infected with Staphylococcus aureus (S. aureus), the SF@(EPL-BM) hydrogel exhibited better antibacterial properties and reduced wound ROS levels more significantly than that of the control in vivo. In this process, the pro-inflammatory factor TNF-α was down-regulated, and the vascularization marker CD31 was up-regulated. H&E and Masson staining showed a rapid transition from the inflammatory to the proliferative phase of the wounds, with significant new tissue and collagen deposition. These results confirm that this multifunctional hydrogel dressing holds well potential for chronic wound healing.

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.

Clinical and electroencephalography characteristics of 41 children with epileptic spasms onset after 1 year of age.

The incidence of epileptic spasms (ES) that begin after the first year of life is much lower than that before 1 year of age. The aim of this study was to identify clinical and electroencephalography (EEG) characteristics, etiologies, treatments, and prognoses in pediatric patients with ES onset after 1 year of age. Forty-one children were retrospectively identified in Children's Hospital of Chongqing Medical University between January 1, 2020 and December 1, 2021. ES onset after 1 year of age have diverse presentations. Although most occur in clusters, are symmetrical and flexional, and occur frequently during awakening, some are characterized as isolated and asymmetrical, have a tonic component, and can also occur during sleep. The hypsarrhythmia variants and focal or multifocal discharges occur alternately in the interictal period, and the focal spikes and slow waves predominated in the unilateral temporal or frontotemporal areas. These patients had diverse etiologies, including structural (51.2 % of patients) and genetic (22.0 %) ones, and 11 patients (26.8 %) had an unknown etiology. No patients in our study had an infectious or immune-mediated etiology. Forty-eight percent of patients responded to hydrocortisone and/or adrenocorticotropic hormone. The efficacy of antiepileptic drug therapy was lower in patients who did not receive concurrent steroid therapy. However, ES onset after 1 year of age caused by a tumor, brain malformation, or other focal lesions, may be cured by focal cortical resection despite a lack of clearly localized EEG surface anomalies. Delays in motor, language, and cognitive development, or behavioral problems were observed in all but three patients.

A retrospective study of 92 children with new-onset refractory status epilepticus.

Little is known of the etiology, course, and treatment of new-onset refractory status epilepticus (NORSE) in children. Here we identified etiologies, electroencephalography (EEG) characteristics, and neuroimaging findings among pediatric patients with NORSE and among two patient subgroups, febrile infection-related epilepsy syndrome (FIRES) group and non-FIRES group. We also examined treatments and risk factors related to poor prognosis. Ninety-two children with NORSE were identified in Children's Hospital of Chongqing Medical University between January 1, 2010 and September 1, 2020. The end date was chosen to guarantee at least a 6-month follow-up. Our results indicated that patients with FIRES account for 90% of pediatric patients with NORSE. The clinical, EEG, and neuroimaging results and prognosis were not significantly different between the FIRES group and non-FIRES group of individuals. 68.5% of our patients had unknown etiology, and viral etiology was the most common identified cause (26.1%). Electroencephalography might have a certain diagnostic value for NORSE. A gradual increase in seizure burden was obvious from the onset of disease, and continuous or recurrent ictal discharge lasting ≥ 30 min was quite common in our study. The mortality was 22.8% in our study. Among the 71 surviving patients, the outcome at discharge was poor but improved during follow-up, and 68.5% had good or fair outcomes at their last follow-up. A poor outcome was observed in 39 of 92 cases (42%), with 43.9% and 30% of individuals in the FIRES group and non-FIRES group, respectively, having a poor outcome. The presence of super refractory status epilepticus (SRSE), electrographic seizures and nonconvulsive status epilepticus (NCSE), and diffuse cortical edema and multifocal abnormality may be related to a poor prognosis. Our analysis did not indicate that prognosis was directly related to etiology or treatment. Management of NORSE is challenging, and the role of immunotherapy warrants further investigation.

Application of High-Frequency Oscillations on Scalp EEG in Infant Spasm: A Prospective Controlled Study.

OBJECTIVE: We quantitatively analyzed high-frequency oscillations (HFOs) using scalp electroencephalography (EEG) in patients with infantile spasms (IS). METHODS: We enrolled 60 children with IS hospitalized from January 2019 to August 2020. Sixty healthy age-matched children comprised the control group. Time-frequency analysis was used to quantify γ, ripple, and fast ripple (FR) oscillation energy changes. RESULTS: γ, ripple, and FR oscillations dominated in the temporal and frontal lobes. The average HFO energy of the sleep stage is lower than that of the wake stage in the same frequency bands in both the normal control (NC) and IS groups (P < 0.05). The average HFO energy of the IS group was significantly higher than that of the NC group in γ band during sleep stage (P < 0.01). The average HFO energy of S and Post-S stage were higher than that of sleep stage in γ band (P < 0.05). In the ripple band, the average HFO energy of Pre-S, S, and Post-S stage was higher than that of sleep stage (P < 0.05). Before treatment, there was no significant difference in BASED score between the effective and ineffective groups. The interaction of curative efficacy × frequency and the interaction of curative efficacy × state are statistically significant. The average HFO energy of the effective group was lower than that of the ineffective group in the sleep stage (P < 0.05). For the 16 children deemed "effective" in the IS group, the average HFO energy of three frequency bands was not significantly different before compared with after treatment. SIGNIFICANCE: Scalp EEG can record HFOs. The energy of HFOs can distinguish physiological HFOs from pathological ones more accurately than frequency. On scalp EEG, γ oscillations can better detect susceptibility to epilepsy than ripple and FR oscillations. HFOs can trigger spasms. The analysis of average HFO energy can be used as a predictor of the effectiveness of epilepsy treatment.

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.

Early diagnosis improving the outcome of an infant with epileptic encephalopathy with cytoplasmic FMRP interacting protein 2 mutation: Case report and literature review.

RATIONALE: Early infantile epileptic encephalopathy (EIEE) 65 was recently shown to be caused by the cytoplasmic FMRP interacting protein 2 (CYFIP2) mutation. To date, only 5 cases have been reported in two articles, and all the outcomes in all cases were poor. PATIENT CONCERNS: In this study, we reported an 8-month-old girl with a 1 month-long history of seizures and developmental delay. Over 1 month later, she developed epileptic spasms in clusters with hypsarrhythmia on electroencephalography. DIAGNOSIS: The patient was diagnosed with EIEE 65 and trio-based whole-exome sequencing revealed a causative de novo CYFIP2 mutation c.260G >T (p.Arg87Leu). INTERVENTIONS: The proband was successively treated with multiple antiepileptic drugs, including levetiracetam, phenobarbital, VitB6, topiramate, methylprednisolone, prednisone, valproic acid and vigabatrin. OUTCOMES: After resistance to multiple anti-epileptic drugs over 2 months of treatment, she finally achieved seizure-free several days after vigabatrin administration and her developmental delay steadily improved. LESSONS: OUR: case confirmed that CYFIP2 was the pathogenic gene of EIEE 65. We also first demonstrated vigabatrin might be effective for control of seizures and helpful for the improved outcomes of these patients.

Early­onset epilepsy and microcephaly­capillary malformation syndrome caused by a novel STAMBP mutation in a Chinese boy.

To the best of our knowledge, the present study reported the case of the first Chinese patient with microcephaly­capillary malformation (MIC­CAP) syndrome caused by a novel compound heterozygous mutation in the STAMBP gene, which encodes STAM binding protein. The present study also provides a review of relevant previously published studies. A boy with MIC­CAP syndrome with developmental delay, intractable epilepsy and prominent dyskinesia was examined. A pathogenic mutation was identified by whole­exome sequencing, and the protein structure and function affected by this mutation were predicted using bioinformatics analysis. Finally, the clinical features of 16 other cases reported in previous studies were reviewed and compared. A novel compound heterozygous mutation of the STAMBP (c.1119­1G>T, c.968A>G) was identified in the present study and epilepsy was refractory, consistent with previously reported cases. The present study also highlighted the fact that STAMBP mutation­associated MIC­CAP often presents as intractable early­life epilepsy, which may lead to mortality.