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It has been suggested that asymmetric hypsarrhythmia is associated with structural etiology. We devised the Hypsarrhythmic Asymmetric Scoring Scheme (HASS) to quantify the degree of hypsarrhythmic asymmetry in a retrospective series of patients who underwent surgical treatment at our center. The present study aimed to investigate the role of HASS in predicting the postsurgical seizure outcomes.We retrospectively analyzed the records of 46 children with hypsarrhythmia who underwent resective epilepsy surgery between 2018 and 2020 and were followed up for at least 1 year after surgery. Hypsarrhythmia severity in each hemisphere was quantified and scored. The HASS score was calculated as the difference between the two hemispheres. Univariate results were submitted to logistic regression models to identify independent predictors for favorable surgical outcomes.Of the 46 patients who underwent resective surgery, Engel's class I-Ⅱ outcomes were achieved in 34 (73.9%). The Engel I-Ⅱ group had a significantly higher HASS score than the Engel Ⅲ-Ⅳ group (p0.001). Multivariate analysis showed that the HASS score was the only significant predictor of good outcomes (p = 0.011). Further receiver operating characteristic analysis showed that a threshold of 7 yielded a better seizure outcome with a sensitivity of 97.06% and specificity of 83.33%.As the first hypsarrhythmia scoring system specially designed for presurgical evaluation, the HASS score may contribute to predicting the postsurgical seizure outcome from the electroencephalography perspective.

We evaluated the efficacy and safety of vigabatrin in focal epilepsy associated with tuberous sclerosis complex by retrospectively reviewing patients with focal epilepsy and tuberous sclerosis complex treated with vigabatrin at a pediatric epilepsy center over an 8-year period. Of 85 patients, 20 (23.5%) were seizure-free for >12 months, 45 (52.9%) were responders (≥50% seizure reduction), and 20 (23.5%) were nonresponders. The median age (in months) at seizure onset in the seizure-free group (median, 15; interquartile range [IQR], 6-23.3) was higher than that of responders (median, 5; IQR, 3-14) and nonresponders (median, 6; IQR, 2-12). Fewer patients in the seizure-free group had calcification in their largest tubers, but the presence of tuber calcification did not differ among groups. Vigabatrin is more likely to result in seizure freedom in children with tuberous sclerosis complex who have later infantile onset of focal seizures and no calcification in their largest tuber.

PURPOSE To evaluate the retention rate, efficacy, and safety of ketogenic diet therapy for drug-resistant epilepsy in children and compare the results with those of a previous cohort at our institution. METHODS A total of 634 children with drug-resistant epilepsy were included in this retrospective study. Patients were categorized into two groups. The previous cohort was included as a control group and included 317 children assessed between 2004 and 2011, whereas the current group included 317 children assessed between 2015 and 2019. The control group was provided care as usual, and the current group additionally adopted the goal and long-term management strategy. Outcomes were measured with respect to retention rate, seizure reduction, and adverse reaction. RESULTS Patient demographics were consistent between both cohorts. Compared to the past ten years, the retention rate significantly increased over time (3 months: 62.8% vs. 82.0%, p

Tuberous sclerosis complex (TSC) is a multi-system genetic disorder. Most patients have germline mutations in TSC1 or TSC2 but, 10%-15% patients do not have TSC1/TSC2 mutations detected on routine clinical genetic testing. We investigated the contribution of low-level mosaic TSC1/TSC2 mutations in unsolved sporadic patients and families with TSC. Thirty-one sporadic TSC patients negative on routine testing and eight families with suspected parental mosaicism were sequenced using deep panel sequencing followed by droplet digital polymerase chain reaction. Pathogenic variants were found in 22/31 (71%) unsolved sporadic patients, 16 were mosaic (median variant allele fraction [VAF] 6.8% in blood) and 6 had missed germline mutations. Parental mosaicism was detected in 5/8 families (median VAF 1% in blood). Clinical testing laboratories typically only report pathogenic variants with allele fractions above 10%. Our findings highlight the critical need to change laboratory practice by implementing higher sensitivity assays to improve diagnostic yield, inform patient management and guide reproductive counseling.

Streptococcus pneumoniae is a Gram-positive, human-specific commensal infectious pathogen that can lead to death worldwide, especially in children under five. A deeper understanding of the immune response in pneumococcal meningitis (PM) has high scientific importance. In this study, we performed single-cell RNA sequencing of peripheral blood mononuclear cells from PM patients and healthy individuals. Both platelets and neutrophils were found with higher proportions in the PM group compared to the control group. Of the differentially expressed genes (DEGs), the genes involved in the immune functions of neutrophils were up-regulated in many immune cells, including platelets, myeloid cells and B cells, suggesting excessive neutrophil activation; while the genes involved in antigen processing and presentation in myeloid cells and B cells were down-regulated in the PM group, which indicated adaptive immune deficiency in the PM patients. Consistently, the proportions of plasmacytoid dendritic cells and T cells were decreased. Furthermore, genes involved in cytotoxity were down-regulated in both NK cells and T cells, and T cell activation was deficient. Many DEGs were also enriched in some signaling pathways that mediate interactions between S. pneumoniae and immune cells, including the Toll-like receptor pathway, the Nucleotide oligomerization domain-like signaling pathway, and the tumor necrosis factor signaling pathway. In conclusion, our study provided a global characterization of S. pneumoniae-induced systemic immune responses, which may have implications for identification of potential targets to improve the immune response in PM.

Myelin oligodendrocyte glycoprotein (MOG) antibodies mediate inflammatory demyelinating diseases of the central nervous system. This study aimed to understand the clinical characteristics of MOG antibody-associated aseptic meningitis (MOGAM).Here, we report the cases of two children with MOGAM. A systematic literature review was conducted and included patients who had MOGAM only, without neurological parenchymal lesions. The clinical characteristics that may have affected the outcome were statistically analyzed.We reviewed 12 cases of MOGAM; male: female = 9: 3. Prolonged fever lasting over 7 days (11/12) was the most frequent symptom, followed by headache (10/12), vomiting (5/12), and seizures (4/12). None of the patients had focal neurological manifestations or parenchymal lesions on imaging. Cerebrospinal fluid (CSF) leukocytosis was observed in all patients (12/12), and blood leukocytosis and elevated CSF pressure was observed in all patients who had corresponding results (9/9 and 4/4, respectively). Seizures occurrence was lower than that of MOG antibody-associated cortical encephalitis. Seven cases progressed to other MOG antibody-associated diseases (MOGADs) in the later phase of MOGAM. Patients who did not progress to other MOGADs had a shorter disease duration from onset to the initiation of intravenous methylprednisolone than those who did. All the patients achieved full recovery after steroid treatment. One patient had relapses.MOGAM without inflammatory demyelination is a rare but distinct phenotype of MOGAD, with fewer clinical manifestations mimicking bacterial or viral meningitis/encephalomeningitis. Delayed diagnosis and treatment may induce the progression to other severe MOGADs. Early recognition of this unique autoimmune aseptic meningitis may contribute to early diagnosis, treatment, and better outcomes.

Electroencephalogram (EEG) has been an important tool for scientists to study epilepsy and evaluate the treatment of epilepsy for half a century, since epilepsy seizures are caused by the diffusion of excessive discharge of brain neurons. This paper reviews the clinical application of scalp EEG in the treatment of intractable epilepsy with vagus nerve stimulation (VNS) in the past 30 years. It mainly introduces the prediction of the therapeutic effect of VNS on intractable epilepsy based on EEG characteristics and the effect of VNS on EEG of patients with intractable epilepsy, and expounds some therapeutic mechanisms of VNS. For predicting the efficacy of VNS based on EEG characteristics, EEG characteristics such as epileptiform discharge, polarity of slow cortical potential changes, changes of EEG symmetry level and changes of EEG power spectrum are described. In view of the influence of VNS treatment on patients' EEG characteristics, the change of epileptiform discharge, power spectrum, synchrony, brain network and amplitude of event-related potential P300 are described. Although no representative EEG markers have been identified for clinical promotion, this review paves the way for prospective studies of larger patient populations in the future to better apply EEG to the clinical treatment of VNS, and provides ideas for predicting VNS efficacy, assessing VNS efficacy, and understanding VNS treatment mechanisms, with broad medical and scientific implications.癫痫发作是由于大脑神经元过度放电的扩散而引起的，因此半个世纪以来脑电图（EEG）一直是科学家研究癫痫以及评估癫痫治疗的重要工具。本文综述了近 30 年头皮 EEG 在迷走神经电刺激（VNS）治疗难治性癫痫的临床研究中的应用，重点从基于 EEG 特征预测 VNS 对药物难治性癫痫的疗效和 VNS 治疗对药物难治性癫痫患者的 EEG 影响两方面展开介绍，并阐述相关 VNS 治疗机制。其中，针对基于 EEG 特征预测 VNS 疗效方面，介绍了痫样放电变化、慢皮质电位变化极性、脑电对称性以及脑电功率谱变化等特征指标与疗效的关系；针对 VNS 治疗对患者 EEG 特征的影响方面，介绍了 VNS 治疗后痫样放电、功率谱、同步性、脑网络以及事件相关电位 P300 振幅的变化等影响。尽管目前的研究尚未确定具有代表性的、可用于临床推广的 EEG 标志物，本综述可为大宗案例的前瞻性研究奠定基础，有利于指导 EEG 应用于 VNS 的临床治疗，为预测、评估 VNS 疗效以及理解 VNS 治疗机制提供思路，具有重要的临床价值和科学意义。.

Objective: The etiology and outcome of status epilepticus with continuous epileptic spasms have not been fully understood; and only rare cases have been reported in the literature. Here, we described 11 children, who manifested continuous epileptic spasms with various etiologies and different outcomes. Methods: This is a case series study designed to systematically review the charts, video-electroencephalography (video-EEG), magnetic resonance images, and longitudinal follow-up of patients who presented continuous epileptic spasms lasting more than 30 min. Results: Median age at onset was 2 years old, ranging from 2 months to 5.6 years. The etiology of continuous epileptic spasms for these 11 cases consisted of not only some known electro-clinical epilepsy syndromes like West Syndrome and Ohtahara Syndrome, but also secondary symptomatic continuous epileptic spasms, caused by acute encephalitis or encephalopathy, which extends the etiological spectrum of continuous epileptic spasms. The most characteristic feature of these 11 cases was prolonged epileptic spasms, lasting for a median of 13.00 days (95% CI: 7.26-128.22 days). The interictal EEG findings typically manifested as hypsarrhythmia or its variants, including burst suppression. Hospital stays were much longer in acute symptomatic cases than in primary epileptic syndromic cases (59.67 ± 50.82 vs. 15.00 ± 1.41 days). However, the long-term outcomes were extremely poor in the patients with defined electro-clinical epilepsy syndromes, including severe motor and intellectual developmental deficits (follow-up of 4.94 ± 1.56 years), despite early diagnosis and treatment. Continuous epileptic spasms were refractory to corticosteroids, immuno-modulation or immunosuppressive therapies, and ketogenic diet. Conclusion: Continuous epileptic spasms were associated with severe brain impairments in patients with electro-clinical syndromes; and required long hospital stays in patients with acute symptomatic causes. We suggest to include continuous epileptic spasms in the international classification of status epilepticus, as a special form. Further investigations are required to better recognize this condition, better understand the etiology, as well as to explore more effective treatments to improve outcomes.

Background: Vagal nerve stimulation (VNS) may control seizures of pediatric intractable epilepsy (PIE) as a clinically adjunctive therapy. However, high-evidence level data for younger children are needed. Methods: In this multicenter, double-blind, randomized controlled trial (VNS-PIE), we recruited children aged 3-6 years with PIE from eleven hospitals specialized in epilepsy in China. Enrolled children underwent computer-generated randomization at 1:1 ratio. Within first 12-week double-blind period, children in stimulation group received active electrical stimulation while others in control group received sham treatment. Children, their parents and investigators assessing outcomes were masked to random allocation; unmasked investigators were responsible for stimulation parameter programming. After unblinding, all children received active electrical stimulation for the subsequent 12 weeks. The primary outcome was the reduction percentage of seizure frequency between two groups at the end of the double-blind period. Findings: Between Sep 29, 2017, and May 29, 2018, 93 children were enrolled and randomly assigned to 47(51%) in stimulation group and 46(49%) in control group (Dropout: one (2%) in stimulation group). At the end of the double-blind period, the median reduction in seizure from baseline was 40·0%(IQR:[0, 71·7%]) in stimulation group, compared to 21·2%(IQR:[-15·9, 68·0%]) in control group (Adjusted median difference(AMD), 12·6%; 95% CI, 10·3% to 34·7%; p=0·23; n=93, FAS); Between-group difference of seizure decrease significantly favored electrical stimulation with respect to subgroup analysis without surgery honeymoon effect (AMD: 21·6 %; 95% CI, -4·2% to 43·3%; p=0·043; n=78, PPS). There was no significant difference in the efficacy of mental development on Gesell scale. Incision infection was common in 9 severe adverse events and cough was most frequent in 41 adverse events. Interpretation: The results from this trial of VNS supported its clinical use for younger children with PIE. Trial Registration: This trial was registered with ClinicalTrials.gov, number NCT03062514. Funding: Pins Medical Ltd; NKRDPC; NSFC; SICRP. Declaration of Interests: ZY, JD, XYQ, TYC, XF, YY and ZYW reports grants from The National Key Research and Development Program of China, grants from National Natural Science Foundation of China, grants from Shenzhen International Cooperative Research Project during the conduct of the study. TYJ, QZL, JXL, FY, YHC, LPZ, BML, YXG, XMS, SPH, FG, JML, SFL, JP, SWS, JW, CC, WXS, MQT, LY, YH, YPH, YW, HX, LXC and YWJ reports institution remunerated for recruitment of patients from Pins Medical during the conduct of the study. HWH reports grants from The National Key Research and Development Program of China, grants from National Natural Science Foundation of China, grants from Shenzhen International Cooperative Research Project during the conduct of the study; grants for advisory broad outside the submitted work. LML reports grants from The National Key Research and Development Program of China, grants from National Natural Science Foundation of China, grants from Shenzhen International Cooperative Research Project during the conduct of the study; grants for neuromodulation research outside the submitted work. Ethics Approval Statement: The trial was approved by each ethical committee of participating hospitals (Trial protocol number: G112L31101; version date: 7/31/2017) and was performed in accordance with the principles of the Declaration of Helsinki.

The ketogenic diet (KD) is an effective treatment for intractable epilepsy (IE), however the therapeutic mechanism is still unclear. This study was designed to investigate T helper type 17/regulatory T cell (Th17/Treg) levels in children with IE and age-matched healthy controls following KD.Circulating levels of Th17/Treg cells were analyzed by flow cytometry. Plasma concentration of interleukin (IL)-17 was measured by cytometric bead array assay. Real-time PCR was performed to measure mRNA levels of mTOR, HIF1α and Th17/Treg associated factors in purified CD4(+)CD25(+) T and CD4(+)CD25(-) T cells.By one-way ANOVA, the proportion of circulating Th17 cells and expression of IL-17A and RORγt were significantly higher (P.05), while the proportion of circulating Tregs and expression of Foxp3, GITR, CTLA-4 were significantly lower (P.05) in IE patients than healthy subjects. However, these alternations were reversed following KD (P.05). In CD4(+)CD25(+) T and CD4(+)CD25(-) T cells mTOR and HIF1α expression were significantly higher in IE patients (P.05), however KD reduced mTOR and HIF1α expression (P.05). The plasma IL-17A concentrations were higher in IE patients than controls (P.05). KD partially reduced IL-17A levels (P.05).Our results suggest that Th17/Treg imbalance is characteristic of childhood IE, and may contribute to IE pathogenesis. KD treatment is able to correct this imbalance, probably via inhabiting the mTOR/HIF-1α signaling pathway.

Background Recent clinical observations have reported the potential benefit of vagus nerve stimulation (VNS) as an adjunctive therapy for pediatric epilepsy. Preliminary evidence suggests that VNS treatment is effective for seizure reduction and mental development in young participants between 3 and 6 years of age who suffer from intractable epilepsy. However, robust clinical evidence for quantifying the difference of the efficacy and safety of VNS treatment in this specific patient population has yet to be reported. Methods/design A two-armed, multicenter, randomized, double-blind, prospective trial will be carried out to evaluate whether VNS is beneficial and safe for pediatric epilepsy. Pediatric participants aged between 3 to 6 years old with intractable epilepsy will be recruited and randomly assigned to experimental and control groups with a 1:1 allocation using a computer-generating randomization schedule. Before enrollment, informed consent will be signed by the parents of the participants and the study researchers. Participants in the experimental group will receive electrical stimulation over 24 weeks under standard stimulation parameters. Participants in the control group will not receive any stimulation during the 12 weeks of the double-blind period. The guardians of the participants are required to keep a detailed diary to record seizure activity. Outcome assessments including seizure frequency, Gesell Mental Developmental Scale scores, use of antiepileptic drugs and dosages, and adverse events will be collected at baseline, 6, 12, 18 and/or 24 weeks after electrical stimulation is initiated. The effects of treatment will be analyzed with time and treatment group comparisons. Discussion This trial will evaluate quantitative differences in efficacy and safety with/without VNS treatment for pediatric participants aged between 3 to 6 years with intractable epilepsy and will explore whether the current age range of VNS therapy can be expanded. Trial registration ClinicalTrials.gov, ID: NCT03062514, Registered on 23 February 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3087-4) contains supplementary material, which is available to authorized users.

AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota (GM), and how ketogenic diet (KD) alters GM. METHODS A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16S rDNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR, and inter-group comparison was conducted by R software. RESULTS After being on KD treatment for a week, 64% of epileptic infants showed an obvious improvement, with a 50% decrease in seizure frequency. GM structure in epileptic infants (P1 group) differed dramatically from that in healthy infants (Health group). Proteobacteria, which had accumulated significantly in the P1 group, decreased dramatically after KD treatment (P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group, in which Prevotella and Bifidobacterium also grew in numbers and kept increasing. CONCLUSION GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.

Background: Bacterial meningitis is still a common disease in China, and has long hospital stay of about one month and high incidence of fatality and sequelae. We assumed that ketogenic diet (KD) could increase the low glucose in the cerebral spinal fluid, provide energy to brain, shorten the hospital stay and decrease the incidence of its fatality and sequelae, because of its action of anti-microorganisms, inflammation, antiseizure and neuroprotection. Method: Reviewing the patient’s charts. This is a retrospective case study of two consecutive early infant cases with bacterial meningitis. Results: After consulted to an infant who was with meningococcal bacterial meningitis and had left severe occipital encephalomalacia, came the infant girl with bacterial meningitis, because of three days fever and a 30 minutes seizure. Blood culture got pneumonia streptococcus and cerebral spinal fluid (CSF) smear gram stain positive bacteria. The glucose was 0.02 mmol/L and cell count was 326*10^6/L in her CSF, even if the blood glucose was 3.8 mmol/L. She was treated with routine treatment: antibiotics and dexamethasone. On day 2, her frequent focal seizures originated from the left side brain because of the magnetic resonance scan demonstrated subdural emission were deterioratedlasted 11 days, PICU stay 2 days. Informed consent was gotten and medical ethnic permission was approved. On day three of admission KD was initiated by fasting for 29 hours, then her blood betahydroxybutyric acid level reached 2.3 mmol/L, and then with 2:1 Qitong (Zeneca, China) liquid ketogenic diet. 3 days later the ratio of KD increased to 3:1. On day 7, three days after ketosis the glucose in cerebral spinial fluid increased quickly from 0.02 mmol/L to 1.98 mmol/L and white cell counts and protein decreased significantly within one week as well. The blood glucose level was 3.94 ± 0.51 mmol/L (n=30), range 2.8-5.3 mmol/L, median 3.9 mmol/L, 95% CI 3.75-4.13 mmol/L. The blood ketone body (beta-hydroxybutyric acid) level was 1.5 ± 0.82 mmol/L (n=21), range 0.5-3, median 1.2 and 95% CI 1.13-1.88 mmol/L. On day 9 and day 10 of admission the blood betahydroxytutyric acid level was 2.28 ± 0.58 (n=8, range and median, 1.4-3.0,2.4) mmol/L, blood glucose level was 4.13 ± 0.32 (n=8, range and median, 3.7-4.8, 4.10). From day 11, frequent monitoring of blood glucose and ketone body was discontinued. 29 days later she was discharged from hospital. The KD was discontinued after 3 months. The blood sugar and ketone bodies was monitored about every 6 h in hospital, then ketone bodies were monitored two times weekly. After 5.5 months the MRI scan showed mild atrophy of the left brain. Follow-up was performed 1, 3, 6, 12 and 24 months. No symptomatic hypoglycemia and other significant complications happened. No more seizures happened. Her physical and neuropsychological development is similar to that of her same age children at last follow-up. Conclusion: KD might be a safe and effective adjunctive therapy for bacterial meningitis, increasing the glucose in cerebral spinal fluid quickly and inhibiting the inflammation process. It might reduce the complications and sequalae of bacterial meningitis. Further investigations including clinical trial with more cases need to be performed.