ObjectiveTo investigate key differentially expressed genes (DEGs) in peripheral blood of idiopathic epilepsy patients, as well as their biological functions, cellular localization, involved signaling pathways, through bioinformatics analysis. So to provide new insights for the pathogenesis and prevention of idiopathic epilepsy.MethodsFirstly, we screened and downloaded microarray data including 6 peripheral blood samples of drug-naive patients with idiopathic epilepsy, 8 peripheral blood samples of responders of idiopathic epilepsy treated with Valproate (VPA), and 10 peripheral blood samples of non-responders of idiopathic epilepsy treated with VPA from Gene Expression Omnibus (GEO) data series GSE143272, which Public in January 2020. Secondly, we identified DEGs via the limma package and others in R software. Then we had gotten 74 DEGs, and subsequently conducted gene ontology and pathway enrichment analysis, PPI network analysis and hub gene analysis, using multiple methods containing DAVID, STRING, and Cytohubba in Cytoscape.ResultsWe had identified significant hub DEGs, including TREML3P, KCNJ15, ORM1, RNA28S5, ELANE, RETN, ARG1, LCN2, SLPI, HP, PGLYRP1, BPI, DEFA4, TCN1, MPO, MMP9, CTSG, CXCL8, RNASE3, RNASE2, S100A12, DEFA1B, DEFA1, DEFA3, CEACAM8, MS4A3, PTGS2, PI3, CCL3. The biological processes involved in these DEGs include immune response, inflammatory response, chemotaxis, etc. While, the molecular function is focused on peroxidase activity, chemokine activity, etc. Moreover, KEGG pathway enrichment analysis shows that DEGs were mainly involved in cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway and so on.ConclusionThese important key DEGs may be involved in the onset and development of idiopathic epilepsy through a variety of signaling pathways and complex mechanisms.
ObjectiveTo explore the molecular characteristics of partial epilepsy with febrile seizures plus(PEFS+). MethodsWe systematically reviewed all SCN1A mutation-related publications that published between Jan.2000 and Dec.2014 on Pubmed and established a database of SCN1A mutations (http://www.gzneurosci.com/SCN1Adatabase/). The characteristics of mutations that cause PEFS+ were analyzed and compared with that of severe myoclonic epilepsy in infancy (SMEI). ResultsThe database included 1, 257 SCN1A mutations, which identified from 1, 727 unrelated cases. In which there were 30 mutations, from 32 unrelated cases, were associated with PEFS+. 76.7% (23/30) mutations were missense, of which 47.8% (11/23) were located on pore region. Significant difference in the percentage of truncation mutation was observed between PEFS+ and SMEI (P < 0.05). There was no significant difference in the percentage of missense mutation that located on the pore region between PEFS+ and SMEI; but the differ significantly in D-value of the missense mutations, which quantified the alteration of amino acid(P=0.042, rank sum test). ConclusionsPEFS+, which distinguishes from GEFS+ and SMEI in clinical and molecular characteristics, is a special phenotype of epilepsy that is associated with SCN1A mutations.
Objective The purpose of this study was to explore the expressions of EPO-R, JAK2 and STAT-5 in the human brain with refractory epilepsy and the role in neural apotosis. Methods Collecting the brain tissue of 24 patients with intractable epilepsy (as experimental group) who were hospitalized and underwent surgery in the Epilepsy Center of the First Hospital Jilin University between March 2010 to July 2011 and 6 cases of accidental or unnatural death immediately following autopsy (as control group) as required by law during the same term. Immunohistochemical was performed to observe the expression of EPO-R, JAK2 and STAT-5 in brain tissue and statistical analysis was performed. Results ① EPO-R, JAK2 and STAT-5 were expressed in both experimental and control groups. In experimental group, the positive-cell number were 41.05±2.40, 50.21±2.50 and 60.18±2.84 under light microscope (400×). While in control group, the positive-cell number were 23.00±0.49, 27.00±0.88 and 25.93±0.33. There were significant differences between the 2 groups (P<0.001). ② There were the pathologic and ultrastructural changes in the human brain with refractory epilepsy. Under the optical microscope, we can observe that the distribution of neurons was uneven and immature neurons were visible. We can see that the nuclei were vacuolar, less cytoplasm, dark staining, hyalomitome acidophilic body, and the neurons became triangular due to degeneration. The proliferation and hyperemia appeared in small vascular and glial cells. Under the transmission electron microscope we observed degeneration and necrosis of the nerve cells, nuclear karyopyknosis, nucleolis dyssymmetry and karyolemma breakage and even dissolution. The mitochondria and astrocytes were swelling. We also saw that part of the mitochondrial cristae was abnormal. Conclusion ① We found neuronal apotosis in the human brain with refractory epilepsy. ② The expression of EPO-R, JAK2 and STAT-5 in intractable epilepsy was significantly increased in neurons and glial cells compared with the control group. The high expression of EPO-R, JAK2 and STAT-5 is unrelated with course and frequency of epileptic seizures. ③ The pathway of EPO-R/JAK2/STAT-5 may be involved in the pathophysiological processes of neural protective effect of endogenous EPO against brain injury induced by epileptic seizures.
ObjectiveTo investigate the efficacy and safety of the phase Ⅰ corpus callosotomy in the treatment of adult refractory epilepsy. MethodsWe conducted a retrospective analysis of 56 adults with intractable epilepsy in Tangdu Hospital from January 2011 to July 2016.All patients were treated for the phase Ⅰ total corpus callosotomy, followed up 1~5 years after surgery. Results14 cases (25.0%) patients achieved complete seizure free after surgery, 19 cases (33.9%) whose seizures reduced more than 90%, 10 cases (17.9%) reduced between 50%~90%, 7 cases (12.5%) between 30%~50%, 6 cases (10.7%) decreased below 30%; Drop attacks of 47 cases (83.9%) patients disappeared. Postoperative complications occurred in 13 cases(23.2%), and most of them recovered well. 5 cases(8.9%) had long-term sensory disassociation, no serious complications and death. The percentage of patients reporting improvement in quality of life was 67.9%. ConclusionsFor patients with intractable epilepsy who can not undergo focal resection, Ⅰ phase total corpus callosotomy has a certain effect on reducing seizure frequency, eliminating drop attacks, and improving the quality of life.
ObjectiveTo analyze the effect of magnetic resonance-guided laser interstitial thermal therapy (Magnetic resonance-guided laser interstitial thermal therapy , MRgLITT) for drug resistant epilepsy (DRE). MethodsThe present study analyzed the clinical information of DRE patients treated by MRgLITT in Beijing Tiantan Hospital from August 2020 to February 2021, including the type of disease, postoperative complications, and prognosis (Engel classification) in the one year after surgery. ResultsA total of 55 patients were enrolled. There were 27 males and 28 females, with an average of (21.7±14.1) years, all of whom successfully completed the operation and were followed up for the 1 year after surgery. The diagnosis included intracranial tumors, hypothalamic hamartoma (HH), focal cortical dysplasia (FCD), cavernous malformations (CM), mesial temporal lobe epilepsy (mTLE), and idiopathic generalized epilepsy (underwent corpus callosotomy). The patients with seizure freedom accounted for 59.6% (31/52), and the average remission rate of palliative surgery was 68.6%. The short-term postoperative complications included bleeding in neurological deficit in 6 cases (10.9%), 4 cases (7.3%), and noninfectious fever in 2 cases (3.6%). No serious, long-term complications occurred. The average postoperative hospital stay was (4.7±1.6) days. ConclusionsMRgLITT is gradually mature and has a wide range of indications. This technology provides a safe and effective therapy for DRE patients.
It is very important for epilepsy treatment to distinguish epileptic seizure and non-seizure. In this study, an automatic seizure detection algorithm based on dual density dual tree complex wavelet transform (DD-DT CWT) for intracranial electroencephalogram (iEEG) was proposed. The experimental data were collected from 15 719 competition data set up by the National Institutes of Health (NINDS) in Kaggle. The processed database consisted of 55 023 seizure epochs and 501 990 non-seizure epochs. Each epoch was 1 second long and contained 174 sampling points. Firstly, the signal was resampled. Then, DD-DT CWT was used for EEG signal processing. Four kinds of features include wavelet entropy, variance, energy and mean value were extracted from the signal. Finally, these features were sent to least squares-support vector machine (LS-SVM) for learning and classification. The appropriate decomposition level was selected by comparing the experimental results under different wavelet decomposition levels. The experimental results showed that the features selected in this paper were different between seizure and non-seizure. Among the eight patients, the average accuracy of three-level decomposition classification was 91.98%, the sensitivity was 90.15%, and the specificity was 93.81%. The work of this paper shows that our algorithm has excellent performance in the two classification of EEG signals of epileptic patients, and can detect the seizure period automatically and efficiently.
ObjectiveThe purpose of this study was to find a new method for the treatment of drug-resistant epilepsy, and to study the efficacy and safety of Bacteroidesfragilis (BF839) in the adjunctive treatment of refractory epilepsy, as well as the improvement of comorbidity.MethodsA prospective, single-arm, open pilot clinical study was designed for the additive treatment of drug-resistant epilepsy using BacteroidesFragilis 839 (BF839). 47 patients with refractory epilepsy, who were admitted to the epilepsy outpatient clinic of the Second Affiliated Hospital of Guangzhou Medical University from April 2019 to October 2019, were enrolled and treated with BF839 adjunct treatment. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week treatment period. Other efficacy analysis included response rate(proportion of patients with ≥ 50% seizure reduction) in the 16 weeks period, the proportion of patients seizure free and the retention rate after12 months intervention, and the observance of the side effects and comorbidities.ResultsThe median reduction percent of all seizure types was −53.5% (P=0.002). The response rate was 61.1% (22/36). 8.5% (4/47) patients seizure free at 12 months. The retention rate at 12 months was 57.4% (27/47). The side effects were diarrhea 4.3% (2/47) and constipation 4.3% (2/47). 48.9% (23/47) of the patients reported improvement in comorbidities, with cognitive improvement of 21.2% (10/47).ConclusionBF839 can be used as an effective additive therapy to treat drug-resistant epilepsy. It is safe and beneficial to the improvement of comorbidities. This is the first time in the world that a single intestinal strain has been reported to be effective in treating drug-resistant epilepsy. This research has important implications.
Objective To study the clinical efficacy of topiramate combined with carbamazepine combined with phenytoin in elderly seizures. Methods A total of 105 elderly patients with epilepsy were enrolled in this study from August 2014 to July 2016 in Fuzhou Chinese and Western Medicine Hospital. The patients were aged 61 to 80 years. There were 42 males and 63 females with epilepsy. The course were 1 to 5 years; 55 cases were partial onset, 50 cases were systemic attack. According to the different treatment methods, the patients were divided into A, B, C three groups, each group were 35 patients. Group A was daily treated with 4 to 8 mg/kg topiramate; Group B was treated with 0.3 g carbamazepine combined with 250 to 300 mg phenytoin per day. Group C was daily treated with 4 to 8 mg/kg topiramate and 0.3 g carbamazepine combined with 250 to 300 mg phenytoin. The total effective rate, the incidence of adverse reactions, the number of seizures before and after treatment were compared among the three groups. Results The total effective rate of group C was higher than that of group A and B, and the difference was statistically significant (P<0.05). There were no significant differences in the number of epileptic seizures between the three groups before treatment (P>0.05). The number of seizures in group C was significantly lower than that in group A and B (P<0.05). Conclusions The treatment of topical epilepsy patients with topiramate and carbamazepine combined with phenytoin can significantly improve the total effective rate of treatment, protect the safety of medication, reduce the number of patients with epilepsy, so that patients can quickly return to normal life. It would be worthy for clinical promotion and use.
ObjectiveTo compare the efficacy and compliance of children children with refractory epilepsy receiving ketogenic diet (KD) in outpatient department with children receiving KD treatment in inpatient department. MethodsA retrospective study of 44 children with intractable epilepsy receiving the modified classical ketogenic diets in outpatient department from June 2014 to December 2015, who were followed-up during the third, sixth and twelfth month. Records of epileptic seizures and adverse reactions were used to evaluate the efficacy and retention rate of inpatient department KD treatment in children with refractory epilepsy, and compared with 104 children receiving KD treatment in inpatient department at the same period. ResultsThirty-four of the forty-four children comleted observation after 12-month follow-up, 15 cases had been seizure freedom, 22 cases had more than 50% reduction in seizure frequency, 12 patients had less than 50% reduction in seizure frequency.The total effective rate of the KD therapy in outpatient department was 64.7%, and the retention rate was 71%. 18 of of the 104 children with KD treatment in inpatient department at the same period comleted observation after 12-month follow-up, 3 cases had been seizure freedom, 5 cases had more than 50% reduction in seizure frequency, 13 cases had less than 50% reduction in seizure frequency.The total effective rate of the KD therapy in inpatient department was 27.8%, and the retention rate was 17.3%. ConclusionThe KD therapy in outpatient department is effective to children with intractable epilepsy, and there is a highly efficacy and compliance of children receiving KD in outpatient department comparing with children receiving KD in inpatient department. Therefore, it's optional to children with refractory epilepsy who can't received KD by inpatient department because of insufficient number of beds.
In order to investigate the effect of deep brain stimulation on diseases such as epilepsy, we developed a closed-loop electrical stimulation system using LabVIEW virtual instrument environment and NI data acquisition card. The system was used to detect electrical signals of epileptic seizures automatically and to generate electrical stimuli. We designed a novel automatic detection algorithm of epileptic seizures by combining three features of field potentials: the amplitude, slope and coastline index. Experimental results of rat epileptic model in the hippocampal region showed that the system was able to detect epileptic seizures with an accuracy rate 91.3% and false rate 8.0%. Furthermore, the on-line high frequency electrical stimuli showed a suppression effect on seizures. In addition, the system was adaptive and flexible with multiple work modes, such as automatic and manual modes. Moreover, the simple time-domain algorithm of seizure detection guaranteed the real-time feature of the system and provided an easy-to-use equipment for the experiment researches of epilepsy control by electrical stimulation.