| Objective: To explore the efficacy of Vagus Nerve Stimulation（VNS）in the treatment of drug-resistant epilepsy（DRE）in children,and analyze the factors that may affect the efficacy of Vagus Nerve Stimulation.Methods: Data of 81 children who received left vagus nerve stimulation device implantation in the Department of Neurosurgery,Children’s Hospital Affiliated to the Capital Pediatric Institute from August 2016 to December 2019 were collected and summarized.According to the inclusion and exclusion criteria,58 children with DRE met the criteria of this study.The general clinical data of the children were obtained through the electronic medical record system,including the type of seizures,the degree of seizures,and the use of anti-epilepsy drugs（AEDs）.The cause of epilepsy in children was determined by combining 24-hour video electroencephalograph（VEEG）data,cranialmagnetic resonance imaging（MRI）,blood and urine metabolism tests,and epilepsy genetic tests.Stimulation parameters were adjusted 2 weeks after the implantation of the left vagus nerve stimulation device,and increased or decreased the stimulation current according to the control plan according to regulation plan and the patient’s seizure status provided by the guardian.Follow-up records of children and their guardians at 6,12,18,and 24 months after surgery were collected.The content of the follow-up included: the general condition of the child,the condition of epileptic seizures,the use of AEDs after the operation,whether other treatment methods were added,and the postoperative adverse reactions.The effect of epilepsy control is evaluated according to Mc Hugh rating standard.Mc Hugh I（seizure frequency reduction> 80%）and Mc Hugh II（seizure frequency reduction> 50%）are defined as effective treatment,Mc Hugh Ⅲ（seizure frequency reduction ≤ 50%）,Ⅳ（seizure frequency reduction ≤ 50%） Frequency reduction ≤ 25%),Mc Hugh V（no change in seizure frequency）is defined as treatment ineffective.The mean epileptic seizure remission rate at each follow-up time point after surgery was also calculated.The surgical efficacy of VNS was evaluated according to these two indexes.The differences in baseline clinical characteristics of children with different outcomes were analyzed for statistical significance.Continuous variables（age,epilepsy duration,preoperative seizure frequency）were included in the receiver operating characteristic curve（ROC）analysis,and the children were divided into groups after the cutoff value was determined.Pearson’s chi-square test and Mann-Whitney test were used to perform univariate analysis of each factor.The statistically significant variables in the univariate analysis were included in the multivariate logistic regression analysis to test the differences in the efficacy of VNS among different groups of children with gender,age,course of disease and follow-up time.The difference is considered statistically significant when the P value is less than 0.05.Results: A total of 58 children（22 females,48 males）were included in this study.The median age at the time of implantation was 4.8（1.7,7.0）years,the median epilepsy course was 30 months,the median seizure frequency was 60（12,236）times per month.The etiology of the 58 children could be divided into four categories: genetic factors（12 cases）,structural factors（19 cases）,infectious factors（10 cases）and unknown causes（17 cases）.The Mc Huch classification of 58 children at 6 months after surgery: 10 cases of grade I（17.2%）,5 cases of grade II（8.6%）,15 cases of grade III（25.9%）,27 cases of grade IV（46.6%）,Ⅴ Grade 1 case（1.7%）,the effective rate was 25.8%（15/58）,the median seizure frequency was 26（3,150）times/month,and the seizure remission rate was 56.7%.The difference was statistically significant compared with that before surgery（Z=-2.116,P=0.034）.The Mc Huch classification at 12 months after surgery: 15 cases of grade I（25.9%）,12 cases of grade II（20.7%）,12 cases of grade III（20.7%）,18 cases of grade IV（31.0%）,and 1 case of grade V（1.7%）,the effective rate was 46.6%（27/58）,the median seizure frequency was 17（1,93）times/month,the seizure remission rate was 71.7%,and the difference was statistically significant compared with that before surgery（Z =-2.898,P=0.004）.The cut-off value of age determined by ROC curve analysis was 4.4 years,the cut-off value of epilepsy course was 42 months,and the cut-off value of seizure frequency was 12 times per month.Univariate analysis showed that there were significant differences in the efficacy of VNS treatment in children with different etiologies and with different seizure frequencies at 12 months（P1=0.008,P2=0.036）.There were statistically significant differences in the Mc Hugh classification of VNS treatment at 12 months in children of different ages（P=0.027）.Multivariate Logistic regression analysis showed that there was a statistically significant difference in the efficacy of VNS between patients with disease course > 42 months and patients with disease course ≤42 months.[OR value=0.122（95%CI 0.020~0.724）] There was also a statistically significant difference in VNS efficacy between children with genetic factors and children with unknown etiology.[OR value=7.399（95%CI 1.138~48.106）] 41 of the 58 children underwent VNS treatment for more than 24 months.The effective rate of VNS 6 months after operation was 31.7%（13/41）,the median seizure frequency was 30（4,135）times/month,and the difference was statistically significant compared with that before operation（Z=-2.483,P=0.013）.The seizure remission rate was 60.0%.12 months after the operation,the effective rate was 48.8%（20/41）,the median seizure frequency was 24（3,75）times/month,and the seizure remission rate was 68.0%.18 months after operation,the effective rate was 48.8%（20/41）,the median seizure frequency was 23（3,68）times/month,and the seizure remission rate was 69.3%.The response rate was 65.6%（27/41）,the median seizure frequency was 10（0.75,55）times/month,and the seizure remission rate was 86.7%.Minor adverse reactions occurred in 10 children（14.2%）after surgery,and all of them gradually relieved and disappeared within 3 days after surgery.During the regulation period of VNS parameters,a small number of parents also reported adverse reactions in their children,but all of them recovered spontaneously within a relatively short time.No adverse reactions were observed during regular visits to the hospital.Conclusion: VNS is a safe and effective treatment for children with DRE,and can significantly reduce the frequency of seizures.The effective rate of VNS treatment increased with the prolongation of the stimulation period within two years.The preoperative analysis of the clinical characteristics of children with DRE will help to screen the most suitable children for VNS surgery.Children with epileptic course less than 42 months and hereditary epilepsy may be more responsive to VNS treatment.It is recommended to consider VNS treatment in the early course of epilepsy.Considering VNS treatment early in the course of epilepsy may help improve the prognosis of such children.The conclusions of this study and the long-term efficacy of VNS need to be further studied with a larger sample size and longer follow-up observation period. |
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