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The main clinical phenotypes, imaging features and genetic test results of a child with Joubert syndrome treated in Shenzhen Children′s Hospital in July 2020 were analyzed retrospectively, and the literature on Joubert syndrome was summarized.The main manifestations of the protester during infancy were respiratory abnormalities and developmental retardation.The brain magnetic resonance imaging (MRI) showed a " molar sign" , which was consistent with the diagnosis of Joubert syndrome.Genetic testing suggested that the protestor carried complex heterozygous variations of KIAA0586 gene.Two variants were not reported previously, one of which was synonymous mutation.The child is the first case of Joubert syndrome caused by KIAA0586 gene in China.Joubert syndrome is a rare congenital brain development malformation characterized by high clinical heterogeneity and MRI molar signs.It may involve multiple systems.Early identification and intervention can improve outcomes.
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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.
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Humans , Drug Resistant Epilepsy , Electroencephalography , Prospective Studies , Scalp , Treatment Outcome , Vagus Nerve StimulationABSTRACT
Objective To investigate the effects of ketogenic diet ( KD) treatment on helper T cell subsets in children with intractable epilepsy( IP) . Methods Thirty-five children with IP and eighteen age-matched healthy subjects were enrolled in this study.The percentages of CD3+CD8-IFN-γ+( Th1 ) cells, CD3+CD8-IL-17A+(Th17) cells and CD4+CD25+Foxp3+(Treg) cells were analyzed by flow cytometry.Re-al-time PCR assay was performed to evaluate the expression of T-bet, ROR-γ, IFN-γ, IL-17A and peroxi-some proliferator activated receptorγ( PPAR-γ) at mRNA level in CD4+CD25-T cells and the transcription-al levels of Foxp3, GITR, CTLA-4 and PPAR-γin CD4+CD25+T cells.The concentrations of cyclooxygen-ases-2 (COX-2) and prostaglandin F2a (PGF2α) in plasma samples were measured by enzyme-linked im-munosorbent assay.The expression of IL-17A and IFN-γin plasma samples were detected by using cytomet-ricbeadarray(CBA).Results (1)ThepercentagesofTregcellsinperipheralbloodsamplesfrompa-tients with IP were lower than those in healthy subjects (P<0.05), which were significantly increased with the treatment of KD (P<0.05).The percentages of Th17 and Th1 cells in patients with IP were significantly higher than those in healthy children (P<0.05), but were remarkably decreased with the treatment of KD (P<0.05).Patients with IP showed decreased transcriptional levels of Foxp3, GITR and CTLA-4 in CD4+CD25+T cells as compared with healthy controls, but were up-regulated with the treatment of KD.The ex-pression of transcription factors including T-bet, ROR-γ, IFN-γand IL-17A in CD4+CD25-T cells in pa-tients with IP were higher than those in healthy subjects and were down-regulated after the treatment of KD (P<0.05).(2) The expression of PPAR-γat mRNA level in CD4+CD25-T and CD4+CD25+T cells were decreased in patients with IP as compared with those in heathy controls, but were increased after the treat-ment of KD (P<0.05).Correlation analysis showed that Treg cells had a positive correlation with PPAR-γ(r=0.61, P<0.05).However, the Th1 and Th17 cells were negatively correlated with PPAR-γ[Th1 (r=-0.54, P<0.05), Th17 (r=-0.64, P<0.05) ].(3) The levels of IL-17A and IFN-γin patients with IP were higher than those in healthy controls, but were decreased with KD treatment (P<0.05).The levels of COX-2 and PGF2αin plasma samples from patients with IP were higher than those in healthy controls ( P<0.05).A negative correlation was observed between COX-2 and PPAR-γ(r=-0.571, P<0.05). Moreover, PGF2αand PPAR-γhad a negative correlation as well (r=-0.586, P<0.05).Conclusion The treatment of KD might enhance the expression of PPAR-γthrough inhibiting the products of oxidative stress such as COX-2 and PGF2α, resulting in the rebalance of Th cell subsets and reduced expression of in-flammatory cytokines.
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Objective To explore the efficacy of ketogenic diet( KD) in the treatment of status epi-lepticus( SE) and whether KD could protect the brain,and propose a new thought on SE patients′reasonably individualized treatment, brain protection and prognosis improvement. Methods From Sep 2013 to Jan 2015,all the patients diagnosed as SE were advised to apply KD treatment; the patients who refused KD treatment were included in the control group,while the patients who accepted KD treatment were included in the treatment group. Based on the SE treatment principles,the control group applied traditional anti-convulsive therapy,while the treatment group applied traditional therapy combined with KD treatment. Before the treat-ment and after the epilepsy control,the patients′ serum was collected to test neuron specific enolase( NSE) and S100βlevels,and the duration of epilepsy control was recorded. Results The treatment group included a total of 10 patients; 3 patients had a good efficacy and obtained seizure-free after the treatment; clinical seizures declined significantly in 6 patients. The treatment group′s overall response rate was 9/10,which was higher than that of the control group(5/8)(P<0. 01). The treatment group′s duration to gain efficacy was shorter than that of the control group[(5. 2 ± 2. 9) d vs. (9. 8 ± 1. 5) d,P<0. 01]. After the treatment,the patients′NSE and S100β in both groups were significantly decreased than those before the treatment ( P<0. 001 or P<0. 05). After the treatment,the serum NSE and S100β of the patients in the treatment group were lower than those in the control group,with statistically significant difference(P<0. 05). Conclusion Frequent epileptic seizures and SE would impair the patient′s brain. Controlling the epileptic seizures actively could lower the severity of brain injury. KD could effectively control the epileptic seizure and had neuropro-tective effects.
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Objective To explore the impact of ketogenic diet (KD) on follicular helper T cells(TFH) in children with intractable epilepsy.Methods Thirty-three cases with intractable epilepsy were selected between Jul.2013 and Jan.2014 in Shenzhen Children's Hospital,19 boys and 14 girls; average age was 39.6 months,and seventeen age-matched healthy children who took a physical examination in the same hospital were assigned as the healthy control group.Blood samples were collected from the children with refractory epilepsy before and after 1 week of KD treatment.The proportions of the various stages of B cells and TFH cells were detected by flow cytometry.The plasma concentration of interleukin-21 (IL-21) was determined by enzyme-linked immunosorbent assay(ELISA),and realtime quantitative PCR(RT-PCR) was performed to detect the levels of peroxisome proliferator-activated receptor gamma (PPAR-γ),B-lymphocyte-induced maturation protein-1 (Blimp-1),B-cell lymphoma 6 (Bcl6) and IL-21 mRNA expression in CD4 + T cells.Results (1) The number of TFH cells in children with intractable epilepsy [(3.57 ± 0.58) ％] was remarkably decreased after KD treatment(P ＜ 0.01),while there were no difference between after KD treatment and healthy control group[(4.93 ±0.70)％ vs (5.03 ±0.63)％,P ＞0.05].(2) The levels of transcription factor Bcl6 expression after treatment were significantly decreased,while inhibitory factor Blimp-1 expression increased (P ＜ 0.05).(3)The plasma concentration of IL-21 had a trend to decrease (P ＞ 0.05),while there were no difference before and after KD treatment,and levels of IL-21 mRNA expressions in CD4 +T cells were significantly decreased after the treatment (8.28 × 10-3 ± 1.19 × 10-3 vs 1.72 × 10-2 ± 0.81 × 10-2,t =3.08,P ＜ 0.05).(4) There was no significant difference in CD27-IgD + B cells before and after KD treatment (P ＞ 0.05),CD27 + IgD + B cell and CD27-IgD-B cells had a trend to decrease after KD treatment(P ＞0.05),and CD27 + IgD-B cells and CD27 + IgD-CD38 high plasma cells were significantly decreased after KD treatment (P ＜ 0.05).(5) The number of TFH cells were correlated positively with the number of CD27 + IgD-B cells and CD27 + IgD-CD3g high plasma cells (r =0.785,0.745,P ＜ 0.05).(6) The levels of PPAR-γmRNA in CD4 + T cells expression were significantly up-regulated after KD treatment (3.49 × 10-3 ± 1.10 × 10-3 vs 2.28 ± 10-3 ± 1.30 × 10-3,t =3.41,P ＜0.05),and the number of TFH cells and PPAR-γgene expression was correlated negatively (r =-0.619,P ＜ 0.05).Conclusions KD might down regulate TFH cell number and function through inducing PPAR-γexpression and could inhibit B cell differentiation,which might be one of the factors for hypogammaglobuinemia by KD treatment.
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Objective To investigate the possible mechanism of hypogammaglobuinemia caused by ketongenic diet (KD).Methods Thirty-six children with intractable epilepsy (IP) and seventeen age-matched healthy children were recruited in this study.The percentages of B cells at various stages of devel-opment and follicular helper T ( Tfh) cells were detected by flow cytometry.The plasma concentrations of IL-21 were determined by ELISA.Real-time quantitative PCR was performed to detect the expression of mam-malian target of rapamycin ( mTOR) , Blimp-1, Bcl-6 and IL-21 at mRNA level in CD4+T cells.Results mTOR at mRNA level was significantly down-regulated after KD treatment (P<0.05).The numbers of Tfh cells were positively correlated with the transcriptional level of mTOR (r=-0.691, P<0.05).Conclusion KD treatment might down-regulate Tfh and B cells through suppressing the expression of mTOR at mRNA level, suggesting a possible mechanism of hypogammaglobuinemia induced by KD treatment.
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Objectives To investigate the clinical features of Guillain-Barré syndrome (GBS) in children from Shen-zhen. Methods The clinical manifestations, results of electrophysiological tests and prognosis of 28 GBS patients from July 2002 to July 2012 were retrospectively analysed. Results Of 28 children, 16(57.1%) had preceding acute upper respiratory infection for 3-14 days but no patient had acute gastroenteritis. One had received HBV vaccination in 2 weeks before the onset of GBS. The peak season for GBS is spring. According to the clinical presentations and the neurophysiological results 17 patients had demyelinating neuropathy, 5 acute motor axonal neuropathy, 2 acute motor sensory axonal neuropathy, 3 Miller-fisher syndrome, and 1 polyneuritis cranialis. 14 (50.0%) patients suffered from pain in limbs which is the most nota-ble symptom in the early stage. Intravenous immune globulin (IVIG) and steroids were given during the acute phases in the majority of the patients, and assisted ventilation was performed in 2 patients due to respiratory muscle paralysis. No diffe-rence was found in Hughes scores, average hospitalization durations, and the prognosis between patients with GBS variants patients and patients with classic GBS. Conclusions Children with GBS in Shenzhen area have different clinical features.