Positive transfer of secondary focus (PTS) refers to new epileptogenesis outside the primary focus and is minimally controlled by existing treatments. Low-frequency stimulation (LFS) has benefits on the onset of epilepsy and epileptogenesis. However, it's unclear whether LFS can retard the PTS in epilepsy. Here we found that PTS at both contralateral amygdala and ipsilateral hippocampus were promoted after the primary focus was fully kindled in rat kindling model. The promotion of PTS at the mirror focus started when the primary kindling acquisition reached focal seizures. LFS retarded the promotion of PTS when it was applied at the primary focus during its kindling acquisition, while it only slightly retarded the promotion of PTS when applied after generalized seizures. Meanwhile, we found the expression of potassium chloride cotransporter 2 (KCC2) decreased during PTS, and LFS reversed this. Further, the decreased expression of KCC2 was verified in patients with PTS. These findings suggest that LFS may be a potential therapeutic approach for PTS in epilepsy.
Objective
To evaluate the efficacy and safety of domestic vagus nerve stimulator for the treatment of pharmaco-resistant epilepsy (PRE) through a prospective, multicenter, randomized, double-blind, parallel controlled trial.
Methods
A total of 72 patients with PRE in 5 hospitals were enrolled from August 2014 to December 2014. A domestic vagus nerve stimulator was used to conduct vagus nerve stimulation (VNS). All patients with PRE were divided into either a test group (n=35) or a control group (n=37) according to the principle of central randomization. Two weeks after procedure, the vagus nerve stimulator of the test group was turned on really. The parameters (electric current, pulse width, frequency, duration of stimulation, and time interval) of the stimulus set were optimized; whereas that of the control group was turned on simulatedly. At 4 months after operation, the stimulator was turned on and unblinded. According to the Mchugh classification and the modified Engel classification standards, the effectiveness and safety of using the stimulator to treat PRE were evaluated at 4 and 8 months after procedure in both groups.
Results
At 4 months after procedure, there were 16, 8, 8, 0, and 3 patients, respectively in the McHugh classification grade Ⅰ, Ⅱ, Ⅲ , Ⅳ and Ⅴ test groups, and 9, 3, 16, 0, and 9 patients in the control group, respectively. There were 8, 4, 12, and 11 patients, respectively in the modified Engel classification grade Ⅰ, Ⅱ, Ⅲ , Ⅳ and Ⅴ test groups, and there were 4, 5, 3, and 25 in the control group, respectively. At 4 months after procedure, the seizures in the test groups were improved obviously compared with before procedure. The improvement of the test groups were significantly better than the control group (the improvement rates of seizures were -63.0% and -34.0%, respectively; P=0.006). The symptoms were improved gradually after turning on the stimulator in the control group. At 8 months after procedure, there were 15, 10, 7, 2, and 1 patient, respectively in the Mchugh classification grade Ⅰ, Ⅱ, Ⅲ , Ⅳ, and Ⅴ test groups, and there were 9, 9, 19, 0, and 0 patients in control group, respectively. There were 7, 2, 19, and 9 patients respectively in the modified Engel classification grade Ⅰ, Ⅱ, Ⅲ and Ⅳ test groups, respectively, and there were 4, 2, 12, and 19 patients in the control group, respectively. The efficacy of the control group was gradually similar to the test groups. Compared with the baseline, the efficacy was improved significantly (P<0.001). At 8 months after procedure, the seizure frequency of 33.3% of patients reduced more than 80%, and that of 59.7% of patients reduced more than 50%.
Conclusions
Using domestic vagus nerve stimulators can significantly reduce the seizure frequency in patients with PRE. It has higher effectiveness and safety. It is suitable for the treatment of patients with PRE.
Key words:
Vagus nerve stimulation; Multicenter study; Randomized controlled trial; Clinical trial; Pharmaco-resistant epilepsy
To evaluate the therapeutic effect of methylprednisolone for electrical status epilepticus during sleep (ESES) in children.The clinical and EEG data of 82 epilepsy patients with ESES, which included benign childhood epilepsy with centro temporal spikes (BECT) variants, epilepsy with continuous spikes and waves during slow sleep (CSWS) , Landau-Kleffner syndrome (LKS) collected from department of pediatrics, Peking University First Hospital were analyzed from July 2007 to September 2012. During ESES period, all patients received methylprednisolone treatment for three courses, which included methylprednisolone intravenous infusion for three days, followed by oral prednisone for four days every time. After three courses, prednisone [1-2 mg/(kg × d)] were taken by all patients for 6 months. The ESES phenomenon and seizures were observed before and after treatment. The efficacy of corticosteroid on ESES suppression, seizure control of three epilepsy syndrome were analyzed.Thirty-nine cases were male and 43 cases were female. The epilepsy syndromes included 49 patients diagnosed as benign childhood epilepsy with centrotemporal spike (BECT) variants, 27 patients diagnosed as epilepsy with continuous spikes and waves during slow sleep (CSWS), and 6 patients diagnosed as LKS. Age of onset ranged from 1 year and 4 months to 11 years. The age of ESES newly monitored was from 2 years to 10 years and 8 months. The total effective rate of corticosteroid was 83% (68/82) for ESES, BECT variants was 82% (40/49), CSWS was 81% (22/27), LKS was 100% (6/6). There was no statistically significant difference in effective rates between the front two (χ² = 0.09, P > 0.05). The seizures were improved in the first month after methylprednisolone treatment in 3 epilepsy syndromes. The recurrence rate of BECT variants was 47% (23/49) , CSWS was 59% (16/27) , LKS was 50% (3/6) after 1 year follow up. There was no association between disease parameters, including age at seizure onset, duration of ESES and the treatment effect of ESES examined by Kruskal-Wallis method (χ² = 3.585, 0.932, P > 0.05).Methylprednisolone was effective for improving ESES and seizures in 3 epilepsy syndromes combined with ESES. There was no significant correlation between age at seizure onset, duration of ESES and treatment effect of ESES.
Growing evidence shows the bidirectional interactions between sleep, circadian rhythm and epilepsy. Comprehending how these interact with each other may help to advance our understanding of the pathophysiology of epilepsy and develop new treatment strategies to improve seizure control by reducing the medication side- effects and the risks associated with seizures. In this review, we present the overview of different temporal patterns of interictal epileptiform discharges and epileptic seizures over a period of 24 consecutive hours. Furthermore, we discuss the underlying mechanism of the core clock gene in periodic seizure occurrences. Finally, we outline the role of circadian patterns of seizures on seizure forecasting models and its implication for chronotherapy in epilepsy.
This study first aimed to establish the prevalence and predictors of subclinical seizures in patients with epilepsy undergoing video electroencephalographic monitoring, then to evaluate the relationship of sleep/wake and circadian pattern with subclinical seizures.We retrospectively reviewed the charts of 742 consecutive patients admitted to our epilepsy center between July 2012 and October 2014. Demographic, electro-clinical data and neuroimage were collected.A total of 148 subclinical seizures were detected in 39 patients (5.3%) during video electroencephalographic monitoring. The mean duration of subclinical seizures was 47.18 s (range, 5-311). Pharmacoresistant epilepsy, abnormal MRI and the presence of interictal epileptiform discharges were independently associated with subclinical seizures in multivariate logistic regression analysis. Subclinical seizures helped localizing the presumed epileptogenic zone in 24 (61.5%) patients, and suggested multifocal epilepsy in five (12.8%). In addition, subclinical seizures occurred more frequently in sleep and night than wakefulness and daytime, respectively, and they were more likely seen between 21:00-03:00 h, and less likely seen between 09:00-12:00 h. Thirty patients (76.9%) had their first subclinical seizures within the first 24 h of monitoring while only 7.7% of patients had their first subclinical seizures detected within 20 min.Subclinical seizures are not uncommon in patients with epilepsy, particularly in those with pharmacoresistant epilepsy, abnormal MRI or interictal epileptiform discharges. Subclinical seizures occur in specific circadian patterns and in specific sleep/wake distributions. A 20-min VEEG monitoring might not be long enough to allow for their detection.
To summarize the clinical features of those Duchenne and Becker muscular dystrophy (DMD and BMD) patients who are complicated with epilepsy, and try to analyze the genotype- phenotype correlation.By a retrospective analysis of 307 patients with DMD and BMD who attended Peking University First Hospital from February 2006 to September 2014,7 patients complicated with epilepsy were identified and their clinical data were collected. The possible mechanism of epilepsy in DMD and BMD patients was proposed after analyzing the genotype-phenotype correlation.(1) Among 307 DMD and BMD patients, 7 cases had epilepsy, the prevalence was 2. 28%. (2) The age of onset of epilepsy ranged from 8 months to 11 years. Focal seizure was the most common seizure type (6 cases) , while other seizure types were also involved, such as generalized tonic-clonic seizure. As to epilepsy syndromes, 1 boy was diagnosed as benign childhood epilepsy with centrotemporal spikes (BECT). Six patients were treated with 1 or 2 types of antiepileptic drugs and seizures were controlled well. On follow-up, 6 of the 7 children had normal mental development, while the remaining 1 patient was diagnosed as mild mental retardation. (3) DMD gene mutations of all 7 patients were analyzed. Exons deletions were found in 6 cases while point mutation was found in 1 case.The prevalence of epilepsy in DMD and BMD patients was higher than the prevalence in normal population. The age of onset of epilepsy varies, and focal seizure may be the most common seizure type. Some patients may also present as some kind of epilepsy syndrome, such as BECT. In most patients, seizures can be controlled well by 1 or 2 types of antiepiletic drugs. No clear correlation was found between genotype and phenotype in DMD and BMD patients who were complicated with epilepsy, probably due to limited number of cases.
Generalized seizures were often thought to be contraindications for hemispherectomy. However, few studies had investigated this issue comprehensively, as well as the predictors for generalized seizures in hemispheric lesion. We studied the predictors of generalized seizures and their potential link to seizure outcomes in a cohort of children who underwent hemispherectomy.A cohort of 76 children with hemispherectomy were reviewed and dichotomized into two groups with and without generalized seizures confirmed by vEEG presurgically. All preoperative evaluation data correlated to generalized seizures and postoperative prognosis were collected and analysed.Of 76 patients, 11 (14.5%) cases were documented with various generalized seizures, including atypical absence (54.5%, 6/11), myoclonic (45.5%, 5/11), atonic (36.4%, 4/11), myoclonic-atonic (18.2%, 2/11), myoclonic-absence (9.1%, 1/11) and spasms (9.1%). Electrical status epilepticus during sleep (ESES) was recorded in 3 patients (27.3%, 3/11). At last follow-up, 72.7% (8/11) patients remained seizure-free. ESES was a predictor of generalized seizures (χ2 = 4.69, P = 0.043). No correlation was found between generalized seizures and unfavourable postoperative seizure outcome (P = 0.153). For different seizure types, focal to bilateral tonic-clonic seizures (P = 0.020) and myoclonic-atonic seizures (P = 0.002) might correlate with unfavourable outcomes.Generalized seizures were not an absolute contraindication for hemispherectomy. Those patients with ESES might experience generalized seizures presurgically. Focal to bilateral tonic-clonic seizures and myoclonic-atonic seizures pre-surgery may indicate unfavourable post-operative seizure outcomes.
Abstract Aims Epilepsy, frequently comorbid with depression, easily develops drug resistance. Here, we investigated how dorsal raphe (DR) and its 5‐HTergic neurons are implicated in epilepsy. Methods In mouse hippocampal kindling model, using immunochemistry, calcium fiber photometry, and optogenetics, we investigated the causal role of DR 5‐HTergic neurons in seizure of temporal lobe epilepsy (TLE). Further, deep brain stimulation (DBS) of the DR with different frequencies was applied to test its effect on hippocampal seizure and depressive‐like behavior. Results Number of c‐fos + neurons in the DR and calcium activities of DR 5‐HTergic neurons were both increased during kindling‐induced hippocampal seizures. Optogenetic inhibition, but not activation, of DR 5‐HTergic neurons conspicuously retarded seizure acquisition specially during the late period. For clinical translation, 1‐Hz‐specific, but not 20‐Hz or 100‐Hz, DBS of the DR retarded the acquisition of hippocampal seizure. This therapeutic effect may be mediated by the inhibition of DR 5‐HTergic neurons, as optogenetic activation of DR 5‐HTergic neurons reversed the anti‐seizure effects of 1‐Hz DR DBS. However, DBS treatment had no effect on depressive‐like behavior. Conclusion Inhibition of hyperactivity of DR 5‐HTergic neuron may present promising anti‐seizure effect and the DR may be a potential DBS target for the therapy of TLE.
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