Clinical features and long-term outcomes of seizures associated with autoimmune encephalitis: A follow-up study in East China.

PURPOSE: To evaluate the clinical characteristics, treatment outcomes, prognosis and potential risk factors of patients in East China with seizure secondary to autoimmune encephalitis. METHODS: From February 2014 to June 2016, 113 patients diagnosed with autoimmune encephalitis in Huashan Hospital, Fudan University, were enrolled in our study. After at least two years of follow-up, we retrospectively analyzed the patients' clinical details, electroencephalograph performance, brain MRI findings, and the therapeutic outcome. Patients underwent clinical evaluation every 3 months. We compared the clinical characteristics and epileptic prognosis of autoimmune encephalitis per antibody type. The association of the epileptic prognosis and EEG abnormalities was evaluated. GTE (Grand Total EEG) Score was used to evaluate EEG abnormalities. Statistic methods included ANOVA, Bonferroni correction test. RESULTS: Treatment outcomes were assessabled in 103 patients (10 patients died or withdrew), including anti-GABABR encephalitis (11), anti-LGI1 encephalitis (16), anti-NMDAR encephalitis (73), Caspr2 antibody encephalitis (3). 83 patients had seizures, who underwent both immunotherapy and anti-epileptic drugs therapy. In terms of seizure type, 57 (68.7%) patients exhibited focal to bilateral tonic-clonic seizure (FBTCS), 51 (61.4%) patients exhibited focal-impaired awareness seizure (FIAS) or focal aware seizure (FAS). 18 (21.7%) patients developed to status epilepticus. 30 (36%) patients had multiple types of seizures. 39 (47%) patients had daily seizures. 80.7% (67/83) of patients with epilepsy had seizure remission. During the 24 months of follow-up, 11 (11%) patients had clinical relapses. GTE scores were significantly different between the group with seizure reduction < 75% and the group with seizure remission (p = 0.009). Imaging abnormalities existed in 53% of the patients in our cohort, but lacked specificity during the acute phase. CONCLUSION: Autoimmune encephalitis (AE) presents with large seizure burden with differing seizure semiology among different antibody types. Except for anti-GABAb receptor encephalitis, it may not be necessary for other AE types to apply long-term use of anti-epileptic drugs (AEDs). The GTE Score can be used to evaluate the EEG abnormalities and may be a predictor of seizure outcomes. MRI findings during the acute phase are non-specific. Long-term follow-up MRIs may be much more meaningful in evaluating prognosis.

Standardized medication strategy for new diagnosed epilepsy / 中华神经科杂志

Objective To formulate and detect the efficacy and safety of standardized medication strategy of epilepsy. Methods The normalized medication strategy was worked out in 278 new diagnosed patients, whose effect, retention rate and safety were evaluated after 24 months of treatment. Results Of all the 278 patients, 235 patients were taken mono-therapy while other 43 patients used therapeutic alliance.Most patients took CBZ or VPA as mono-therapy drugs. At the time after 24 months, almost 76. 3%(212/278) patients got seizure free, and the effectiveness was 22. 7% (63/278). The retention rate of those mono-therapy drugs were investigated respectively. CBZ presented 69. 8%, VPA presented 76. 2%,OXC was 68.0%, TPM was 69. 6%, LTG was 83. 3%, LEV presented 85.7%, and 100% for PHT.Conclusions All epileptic patients were well-controlled after taking standardized medication. The standardized medication strategy of epilepsy possesses valuable importance in clinical practice, which deserves further popularization.

Effect of Tenidap on expression of inwardly rectifying potassium channel 2.3 in hippocampi of chronic temporal lobe epileptic rats / 中华神经科杂志

Objective To observe the change of expression of inwardly rectifying K+(Kir)2.3 mRNA and protein of Kir in the hippocampus of rats with chronic temporal lobe epilepsy(TLE)in different time points and the effect of Tenidap a Kir2.3 channel opener on its expression,investigate the relationship between Kir2.3 and the pathogenesis of TLE and to explore the potential of Kir agonists as anti-epileptic drugs.Methods The pilocarpine TLE rat model was used.Animals were randomly assigned to the control or the status epilepticus(SE)groups,which were further divided into four time point subgroups consisting of 0.6,72 hours,and 2 weeks post-SE termination.Another subgroup was given Tenidap,a Kir2.3 channel opener,and tested 2 weeks post-SE.Hippoeampi were removed and the expression of Kir2.3 mRNA and protein at different time points was measured by reverse transcription polymerase chain reaction(RT-PCR)and western blotting.Results The ratios of Kir2.3 mRNA and β-actin in normal control and 0,6,72hours and 2 weeks after SE termination were 0.080±0.030,0.103±0.045,0.164±0.026,0.132±0.024.0.011±0.008,respectively(F=23.684,P<0.01).The ratios of Kir2.3 protein and GAPDH in propotional groups were0.305±0.030,0.263±0.028,0.767±0.167,0.498±0.077,0.176±0.026(F=44.183.P<0.05).The expression of Kir2.3 channel in the epileptic rats was bimodal,increasing immediately after SE,relative to controls,and declining in the chronically epileptic period.Tenidap administration upregulated both the mRNA(0.021±0.006)and protein expression(0.636±0.140) of Kir2.3(F=25.216 and 47.355,P<0.05 and 0.01).Condusion These findings suggest that the pathogenesis of TLE is accompanied by a decrease in Kit2.3 expression,which may be ameliorated by the administration of tenidap.

Dynamic changes of Kir2.3 mRNA in the hippocampus of rats with chronic temporal lobe epilepsy / 复旦学报（医学版）

Objective To observe dynamic changes of Kir2. 3 mRNA in the hippocampus of rats with chronic temporal lobe epilepsy, and to discuss the relationship between Kir2. 3 expression and the pathogenesis of chronic temporal lobe epilepsy. Methods We used pilocarpine to induce status epilepticus (SE) in rats,which became chronic temporal lobe epileptic rats in 2 weeks. The expression of Kir2.3 mRNA was measured by reverse transcription polymerase chain reaction (RT-PCR) at the time points of 0, 6, 72 hours and 2 weeks after SE. Results The ratios of Kir2. 3 mRNA to β-actin of normal control and 0, 6, 72 hours, 2 weeks after SE were 0. 080 ± 0. 030, 0. 103 ± 0. 045, 0. 164 ± 0. 026, 0. 132 ± 0. 024, and 0. 011 ± 0. 008, respectively. The ratio was significantly higher 6 and 72 hours after SE and significantly lower 2 weeks after SE than that of the normal control. Conclusions Two weeks after SE, when the rats had spontaneous recurrent seizures, the expression rate of Kir2.3 reached a turning point, which possibly became the basis of epileptogenesis.

Correlative genes in intractable temporal lobe epilepsy / 中华神经科杂志

Objective To survey gene expression profiles in nonlesional refractory temporal lobe epilepsy(TLE)and to further verify the difference of gene expression.thus to evaluate the possible molecular pathogenesis of this kind of epilepsy that can help to supply a new way for the diagnosis and treatment.Methods The TLE samples and control cases were studied by means of cDNA microarray consisting of 1 8 000 genes.Reverse transcription polymerase chain reaction(RT-PCR)Was performed to measure the expression alterations of SH3GL2.BTNN2A2 and KCNJ4 mRNA in temporal cortex samples from patients who had undergone temporal lobectomy surgery for intractable epilepsy.Tissue from 10 subjects who did not have epilepsy served as controls.Results The known genes differently expressed in those TLE samples involved immunity correlation factor genes,signal conduction genes,ion channel transportation genes;mitochondria function genes and SO on were identified.Among which.the expression of SH3GL2 mRNA Was significantly increased in epileptic brain(1.022±0.547)compared with the controls(0.446±0.171,t=-3.181).In TLE group(0.481±0.196),the expression of BTN2A2 mRNA was also significantly higher than that of control subjects(0.243±0.111,t=3.351).Compared with control group(O.795±0.112),the expression of KCNJ4 mRNA Was significantly decreased in TLE patients(0.438±0.178).Conclusions cDNA microarray is an efficient and high.throughout method to survey gene expression profiles in intractable temporal lobe epilepsy.The variation of those gene expressions might be a potential etiological agent for TLE that may offer a novel target for anticonvulsant therapy.

Spectrum analysis of the EEG in patients with brain death / 临床神经病学杂志

Objective To quantify the EEG data in patients with brain death, expecting to obtain a criteria with high sensitivity and specificity for the diagnosis of brain death. Methods Analyzed the EEG data obtained from 17 brain dead cases and 5 clinical brain dead cases with spectrum analysis and made comparison with that from 13 non-brain dead cases. Results The EEG electric power of the brain dead group was significantly lower than that of non-brain dead group (P