Multi-dimensional influence of pediatric epilepsy on children and their families: A cross-sectional study.

OBJECTIVE: In this study, we aimed to evaluate the effects of pediatric epilepsy on family burden, parental anxiety, depression states, and quality of life of both parents and children. METHODS: The study was undertaken between March and December 2021 using an online questionnaire that included the Family Burden Scale of Disease, the 7-item Generalized Anxiety Disorder scale, the 9-item Patient Health Questionnaire, the WHO Quality of Life Scale (WHOQOL-BREF), and the PedsQL 4.0 Generic Core Scales (parent-proxy report). RESULTS: A total of 288 parents of children aged 2-18 years were included. Overall, 94.8% of the participating families experienced high levels of disease burden, 67.0% of parents suffered from anxiety states, 57.0% suffered from depression states, and 56.2% of children with epilepsy suffered from comorbid neuropsychiatric symptoms. The mean WHOQOL-BREF score for parental quality of life was 53.7 ± 12.8, while the median PedsQL score for children's quality of life was 65.4 (49.6-81.7). Parental depression states contributed the most to family burden and parental quality of life, whereas comorbidities of epilepsy contributed the most to children's quality of life. Seizure frequency significantly influenced parental anxiety states, and family burden was the most significant predictor of parental depression states. CONCLUSION: Heavy disease burden, anxiety states, and depression states are prevalent in families with children suffering from epilepsy, and most have a poor quality of life. There is a need for greater focus on the quality of life of this patient population and their caregivers, as well as increased resources to help combat anxiety, depression, and poor quality of life.

A case-control evaluation of Spasm control and Tolerability of the Modified Atkins diet versus classic ketogenic diet in Chinese Children with infantile epileptic spasms syndrome.

OBJECTIVE: This study was conducted to compare the efficacy, tolerability and safety of the modified Atkins diet (MAD) and the classic ketogenic diet (KD) in Chinese children with infantile epileptic spasms syndrome. METHODS: We retrospectively recruited and analyzed 56 children with infantile epileptic spasms syndrome started on the MAD (n = 21) and classic KD (n = 35) at our institution from June 2016 to July 2022. RESULTS: The MAD group had exhibited comparable rates of spasm reduction (>50%) as the classic KD group at the time point of 3 months (66.7% for MAD, 75% for KD; p = 0.510), 6 months (75% for MAD, 82.6% for KD; p = 0.694), and 12 months (84.6% for MAD, 90.9% for KD; p = 1.000). The probability of patients remaining on the MAD was higher (p = 0.048) than those consuming the classic KD. By analyzing discontinuation reasons, we found that the MAD patients had a lower rate of poor compliance than the classic KD patients (p = 0.014). Response to the diet at 1 month and fewer anti-seizure medicines (ASMs) had tried before KD initiation were possible factors in regard to likelihood of spasm-free response to the diet therapy at 3 months (p = 0.001 and p = 0.014, respectively). CONCLUSIONS: The efficacy of spasm control was similar in the MAD, with better tolerability and higher compliance compared to the classic KD. Therefore, MAD could be the primary treatment for children in China with- infantile epileptic spasms syndrome. Additionally, an earlier beginning of the diet treatment may have significant advantages.

Diagnosis of Neurological Infections in Pediatric Patients from Cell-Free DNA Specimens by Using Metagenomic Next-Generation Sequencing.

Central nervous system (CNS) infections can cause significant morbidity and mortality, especially in children. Rapid and accurate pathogenic detection in suspected CNS infections is essential for disease control at the early stage of infection. To evaluate the performance of metagenomic next-generation sequencing (mNGS) of cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) in pediatric patients, we retrospectively analyzed the efficiency of cfDNA mNGS in children with CNS infections (n = 257) or noninfectious neurological disorders (n = 81). The CSF samples of 124 random subjects were used to evaluate the accuracy between mNGS of cfDNA and whole-cell DNA (wcDNA). In total, cfDNA mNGS detected a wide range of microbes with a detection rate of 71.0%, and the sensitivity and total coincidence rate with clinical diagnosis reached 68.9% and 67.5%, respectively. Compared with wcDNA mNGS, cfDNA mNGS had a higher efficacy in detecting viruses (66 versus 13) and Mycobacterium (7 versus 1), with significantly higher reads per million. The dominant causative pathogens were bacteria and viruses in CNS infections, but these presented with different pathogen spectra in different age categories. The best timing for the mNGS test ranged from 1 to 6 days after the start of anti-infection therapy, and the earlier mNGS started, the better was identification of bacterial CNS infections. This study emphasized that cfDNA mNGS had overall superiority to conventional methods on causative pathogen detection in pediatric CNS infections, and it was even better than wcDNA mNGS. Furthermore, research needs to be better validated in large-scale clinical trials to improve the clinical applications of cfDNA mNGS. IMPORTANCE Our study emphasized that cfDNA mNGS had overall superiority to conventional methods on causative pathogen detection in CNS-infected children, and it was even better than wcDNA mNGS. cfDNA mNGS detected a wide range of pathogens with a high total coincidence rate (67.5%) against clinical diagnosis. The best timing for cfDNA mNGS detection ranged from 1 to 6 days, rather than 0 days, after the start of empirical anti-infection therapy. The earlier mNGS started, the better the identifications of bacterial CNS infections. To the best of our knowledge, this research is the first report evaluating the clinical utility of mNGS with different methods (cfDNA versus wcDNA) of extracting DNA from CSF specimens in diagnosing pediatric CNS infections. Meanwhile, this is the largest cohort study that has evaluated the performance of mNGS using cfDNA from CSF specimens in pediatric patients with CNS infections.

A Retrospective Study of Rare Listeria Meningoencephalitis in Immunocompetent Children in China.

Objectives: Listeria meningoencephalitis (LMM) is very rare in healthy children. We aimed to assess the clinical features, differential diagnosis, treatment options, and outcomes of LMM in immunocompetent children through a retrospective study. Methods: The clinical symptoms, laboratory findings, imaging features, antibiotic use, and metagenomic next-generation sequencing (mNGS) results of the cerebrospinal fluid (CSF) were obtained from immunocompetent children who were diagnosed with LMM and admitted to the Xi'an Children's Hospital from May 2018 to July 2020. Results: The data from 8 immunocompetent children were retrospectively analyzed in this study. The cohort included data from 5 males and 3 females who were aged from 1 year and 7 months to 16 years and 6 months. A total of 4 patients had chilled food before onset. The complications included hyponatremia (3/8), hydrocephalus (2/8), and hemophagocytic syndrome (1/8). In total, 8 patients were diagnosed with Listeria monocytogenes by positive CSF culture or mNGS results. The positive rate of CSF culture was 62.5% (5/8). A total of 5 patients conducted CSF mNGS, and the results of the mNGS were positive in 4 patients (80%, 4/5) and suspected in 1 patient. A total of 7 patients changed their therapeutic regimen to combined antibacterial therapies that included linezolid and meropenem (5/8), or ampicillin and meropenem (2/8). A total of 5 patients had favorable outcomes (Glasgow Outcome Scale, GOSE = 5) while two patients had unfavorable outcomes (GOSE = 1) and were complicated with hyponatremia and hydrocephalus. Conclusions: Listeria meningoencephalitis (LMM) can occur in children with normal immune function and is commonly mistaken for other central nervous system infections. L. monocytogenes can be quickly and accurately detected by mNGS. Hyponatremia and hydrocephalus may indicate unfavorable outcomes.

The clinical features, treatment and outcomes of 33 children from Northwestern China with Anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVES: We analyzed the clinical features and outcomes of children with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in Northwestern China. METHODS: We retrospectively recruited 33 pediatric patients with anti-NMDAR encephalitis in Northwestern China from December 2013 to April 2020. The demographics, clinical features, treatments, and outcomes were reviewed. RESULTS: 33 patients with anti-NMDAR encephalitis were enrolled in this study (a median age of 6.8 years, 20 females and 13 males). The initial symptoms included seizures (42.4%), psychiatric symptoms (39.4%), speech dysfunction (12.1%), and paralysis (6.1%). During the course of the disease, 31 patients (93.9%) presented with psychiatric symptoms, 29 patients (87.9%) presented with speech dysfunction, 25 patients (75.8%) presented with movement disorders and 24 patients (72.7%) presented with sleep disorders followed by seizures, consciousness disturbance, autonomic nervous dysfunction, paralysis, and hypoventilation. 12 patients (36.4%) had abnormal cerebrospinal fluid (CSF) findings, 10 patients (30.3%) exhibited abnormal brain magnetic resonance imaging (MRI) results, and 29 patients (87.9%) showed abnormal Electroencephalography (EEG) findings. None of the patients had tumors. All patients received first-line immunotherapy and 8 patients both received first and second-line immunotherapy. 30 of the 33 patients achieved good outcomes (score on the modified Rankin Scale [mRS] of 0-2), whilst the other 3 patients had poor outcomes (mRS score of 3-6). CONCLUSIONS: Patients with higher CSF anti-NMDAR body titer were more likely to develop sleep disorders, consciousness disturbances and more severe disease states.

Evaluation of the seizure control and the tolerability of ketogenic diet in Chinese children with structural drug-resistant epilepsy.

OBJECTIVES: In this study, we aimed to evaluate the efficacy and tolerability of ketogenic diet (KD) in Chinese children with drug-resistant epilepsy (DRE) due to structural etiology. METHODS: We retrospectively analyzed data from 23 pediatric patients with DRE due to structural etiology who were treated with KD at Department of Neurology, between May 2014 and December 2020. Based on etiological classifications, the patients were divided into a neonatal brain injury (Group 1), an intracranial infection group (Group2) and a group that showed malformations of cortical development (MCDs) (Group 3). RESULTS: The 23 patients remained on the KD for a mean duration of 15.3 ± 9.7 months. The response rates for the control of seizures were 60.9% (14/23), 52.2 % (12/23), 47.8% (11/23) at 3, 6 and 12 months, respectively. Subjective improvements in cognition were observed in 87.0% (20/23) of the children during follow-up. Reductions in the frequency of seizures of > 50% were more commonly achieved by patients in group 1 (75.0%, 9/12) compared to the patients in groups 2 (60.0%, 3/5) and 3 (33.4%, 2/6). Further analysis of the patients in Group 1 showed that children with a history of hypoxic ischemic encephalopathy (HIE) (100.0%, 6/6) had the highest rate of > 50% seizure reduction. The main reasons for the discontinuation of the KD were due to lack of efficacy and poor compliance. Most of the side effects associated with the KD diet were minor and easily corrected by appropriately adjusting the diet. Only 1 patient discontinued the diet due to severe refusal to eat. CONCLUSIONS: KD is an effective and safe treatment for Chinese children with DRE due to structural etiology. Better efficacy of seizure control was observed in patients with a history of neonatal brain injury. Patients with DRE secondary to HIE may be particularly responsive to the KD therapy, and so KD should be considered earlier in those patients.

Efficacy and Safety of Rituximab in Chinese Children With Refractory Anti-NMDAR Encephalitis.

Purpose: To assess the efficacy and safety of rituximab treatment as second-line immunotherapy in pediatric cases of anti-NMDA receptor (NMDAR) encephalitis. Methods: We retrospectively recruited 8 patients with anti-NMDAR encephalitis who were treated with rituximab as second-line immunotherapy. We evaluated the clinical features, laboratory examination results and treatment protocols of the Chinese children and defined good outcomes based on the modified Rankin scale (mRS) score (0-2) at the last follow-up. Results: A total of eight pediatric patients (median age 6.7 years; four female) with refractory anti-NMDAR encephalitis were recruited to the study. Rituximab was given after a median duration of disease of 57 days (range 50.5-113.75 days). The use of rituximab led to a significant reduction in the mRS and CD19+ B-cells compared to before rituximab infusion (P < 0.05). Five patients (62.5%) had a good outcome (mRS ≤ 2) including four patients (50%) who showed complete recovery (mRS = 0) at the last follow-up. Transient infusion adverse events were recorded in 2 patients (25%). Two patients (25%) had severe infectious adverse events (AEs) and two patients with grade 5 (death). None of the patients developed progressive multifocal leukoencephalopathy (PML). Conclusion: Our study provides evidence that rituximab can efficiently improve the clinical symptoms of anti-NMDAR encephalitis in children. However, due to the risk of adverse infections, rituximab should be restricted in pediatric patients with high rates of mortality and disability.

Role of endothelin­1 and its receptors in cerebral vasospasm following subarachnoid hemorrhage.

Cerebral vasospasm (CVS) is a severe complication of subarachnoid hemorrhage (SAH), and endothelin­1 (ET­1) may be involved in its pathogenesis. The present study aimed to investigate the expression of ET­1 in cerebrospinal fluid (CSF) in patients with SAH and to analyze rat arterial contractility and the expression levels of ET­1 receptors in vitro. CSF samples were collected from 28 patients and the expression levels of ET­1 were measured. Rat cerebral basilar arteries were isolated and incubated with hemorrhagic or clear CSF. Contractility, as well as ETA and ETB mRNA expression were measured. ET­1 levels in CSF increased and reached a peak within the initial 5 days after SAH onset and then gradually subsided. After 12 or 24 h, the contraction of arteries incubated in hemorrhagic CSF was substantially stronger than those in clear CSF. The mRNA expression levels of endothelin receptor type A and B in arteries incubated in hemorrhagic CSF were significantly higher than those in clear CSF. ET­1 and its receptors may be involved in the pathogenic mechanism of CVS following SAH. ET­1 expression in CSF may be used as a marker in CVS and its receptors may provide novel therapeutic targets in CVS.