Long-term efficacy and predictors of vagus nerve stimulation in drug-resistant epilepsy: a multicenter cohort study

Vagus nerve stimulation (VNS) has been widely used in the treatment of drug-resistant epilepsy (DRE) in children. We aimed to explore the efficacy and safety of VNS, focusing on factors that can influence the efficacy of VNS, and construct a prediction model for the efficacy of VNS in the treatment of DRE children. Retrospectively analyzed 45 DRE children who underwent VNS at Qilu Hospital of Shandong University from June 2016 to November 2022. A ≥50% reduction in seizure frequency was defined as responder, logistic regression analyses were performed to analyze factors affecting the efficacy of VNS, and a predictive model was constructed. The predictive model was evaluated by receiver operating characteristic curve (ROC), calibration curves, and decision curve analyses (DCA). A total of 45 DRE children were included in this study, and the frequency of seizures was significantly reduced after VNS treatment, with 25 responders (55.6%), of whom 6 (13.3%) achieved seizure freedom. There was a significant improvement in the Quality of Life in Childhood Epilepsy Questionnaire (15.5%) and Seizure Severity Score (46.2%). 16 potential factors affecting the efficacy of VNS were included, and three statistically significant positive predictors were ultimately screened: shorter seizure duration, focal seizure, and absence of intellectual disability. We developed a nomogram for predicting the efficacy of VNS in the treatment of DRE children. The ROC curve confirmed that the predictive model has good diagnostic performance (AUC = 0.864, P < 0.05), and the nomogram can be further validated by bootstrapping for 1,000 repetitions, with a C-index of 0.837. Besides, this model showed good fitting and calibration and positive net benefits in decision curve analysis. VNS is a safe and effective treatment for DRE children. We developed a predictive nomogram for the efficacy of VNS, which provides a basis for more accurate selection of VNS patients.

The association between DTI-based thalamocortical structural connection and the efficacy of vagus nerve stimulation in patients with drug-resistant epilepsy.

To predict the vagus nerve stimulation (VNS) efficacy for pediatric drug-resistant epilepsy (DRE) patients, we aim to identify preimplantation biomarkers through clinical features and electroencephalogram (EEG) signals and thus establish a predictive model from a multi-modal feature set with high prediction accuracy. Sixty-five pediatric DRE patients implanted with VNS were included and followed up. We explored the topological network and entropy features of preimplantation EEG signals to identify the biomarkers for VNS efficacy. A Support Vector Machine (SVM) integrated these biomarkers to distinguish the efficacy groups. The proportion of VNS responders was 58.5% (38/65) at the last follow-up. In the analysis of parieto-occipital α band activity, higher synchronization level and nodal efficiency were found in responders. The central-frontal θ band activity showed significantly lower entropy in responders. The prediction model reached an accuracy of 81.5%, a precision of 80.1%, and an AUC (area under the receiver operating characteristic curve) of 0.838. Our results revealed that, compared to nonresponders, VNS responders had a more efficient α band brain network, especially in the parieto-occipital region, and less spectral complexity of θ brain activities in the central-frontal region. We established a predictive model integrating both preimplantation clinical and EEG features and exhibited great potential for discriminating the VNS responders. This study contributed to the understanding of the VNS mechanism and improved the performance of the current predictive model.

BackgroundUpper limb motor impairment is one of the main complications of stroke, affecting quality of life both for the patient and their family. The aim of this systematic review was to summarize the scientific evidence on the safety and efficacy of Vagus Nerve Stimulation (VNS) on upper limb motor recovery after stroke.MethodsA systematic review and meta-analysis of studies that have evaluated the efficacy or safety of VNS in stroke patients was performed. The primary outcome was upper limb motor recovery. A search of articles published on MEDLINE, CENTRAL, EBSCO and LILACS up to December 2021 was performed, and a meta-analysis was developed to calculate the overall effects.ResultsEight studies evaluating VNS effects on motor function in stroke patients were included, of which 4 used implanted and 4 transcutaneous VNS. It was demonstrated that VNS, together with physical rehabilitation, increased upper limb motor function on average 7.06 points (95%CI 4.96; 9.16) as assessed by the Fugl-Meyer scale. Likewise, this improvement was significantly greater when compared to a control intervention (mean difference 2.48, 95%CI 0.98; 3.98). No deaths or serious adverse events related to the intervention were reported. The most frequent adverse events were dysphonia, dysphagia, nausea, skin redness, dysgeusia and pain related to device implantation.ConclusionVNS, together with physical rehabilitation, improves upper limb motor function in stroke patients. Additionally, VNS is a safe intervention.

To evaluate the correlation between vagus nerve stimulation (VNS) efficacy and partial seizures originating from different brain regions. The authors retrospectively analyzed the data of 46 subjects with medically intractable epilepsy who had insertion of VNS between April 1999 and July 2005. The clinical outcome was assessed with Engel classification. Subjects were divided into group A (Engel I, II, and III) and group B (Engel IV) for statistical analysis. Group A was referred as a satisfactory outcome. The statistical analysis of the data was assessed whether these parameters such as age, type of seizure, age at insertion of VNS, and lengths of follow-up affect the outcome. Nineteen patients (41.3%) had a satisfactory outcome (Engel II, III). The analysis of VNS efficacy demonstrated that 65% of the patients with frontal lobe epilepsy and only 15% of the patients with temporal lobe epilepsy (TLE) had a satisfactory outcome. There was a statistically significant difference between these types of epilepsyand VNS outcomes (Fisher exact test, P = 0.004). VNS is more effective in frontal lobe epilepsy than in temporal lobe epilepsy. Further studies are warranted to verify our findings and the correlation between types of epilepsy and VNS outcome.

Long-Term Vagus Nerve Stimulation for Severe Refractory Depression: A Case Study With a Six-Year Follow-Up

Efficacy of vagus nerve stimulation for drug-resistant epilepsy in children age six and younger

Purpose: Since 1993, we have studied the efficacy and safety of vagus nerve stimulation (VNS) with a Neurocyberhetic Prosthesis (NCP) (Cyberonics, U.S.A.) against medically intractable epilepsy first in Japan. We summarize the intermediate results so far acquired in this report. Methods: Patients with intractable partial seizures were selected as candidates for implantation of the NCP. This type of therapy has been tested in individuals whose seizure activity has not been effectively controlled by pharmacotherapy. The result was a reduction in the rate of seizures in each period compared with the average number of seizures before implantation of the NCP. To avoid nerve fatigue, the upper limits of the parameters were set as follows: frequency, 30 Hz; pulse width, 1,000 μ; on time, 60 s; output current, 3.0 mA. After informed consent, the leads of the NCP were connected under general anesthesia to the cervical portion of the left vagus nerve. Those leads were connected through a subcutaneous tunnel with the NCP implanted subcutaneously on the breast. Thirty‐four patients have been implanted with the NCP, and 31 patients have started stimulation as of September, 1997. We have analyzed the data from 16 male and 15 female patients who were followed up for &gt;6 months with a mean follow‐up period of 20.0 months; their ages ranged from 19 to 52 years with a mean age of 31.2 years. Their types of seizures included 28 complex partial seizures (CPSs), 12 simple partial seizures (SPSs) and 11 secondarily generalized seizures (SGSs). The number of seizures during a month was counted for 3 consecutive months before implantation of NCP. These values were compared with average number of seizures that occurred during the 4–6 months after VNS. We also calculated the patients with a 50% reduction in seizure frequency compared with the baseline. Results: the mean seizure‐changing rates during the 4–6 months after stimulation were −26.4 2 13.2% (mean ± SEM) in total seizure numbers, −41.9 ± 13.0% in seizure with disturbance of consciousness, −37.0 ± 19.9% in SGSs, −70.4 ± 17.6% in CPSs, and −15.5 ± 16.2% in SPSs. The 50% reduction rates were 48.4% for all seizure types, 63.3% in seizures with disturbance of consciousness, 58.6% in CPSs, 63.6% in SGSs, and 47.1% in SPSs during the 4 4 months after stimulation. Conclusions: Our early results demonstrated the efficacy and safety of VNS with the NCP in medically intractable epilepsy. We adpated the VNS for intractable epilepsy, and our results demonstrated its efficacy. The reduction of seizures was observed more strongly in the latest 3 months than during the 4–6 months after starting the VNS. This result may be due to the characteristics of VNS or the period when we needed to adjust the parameters of the NCP. The efficacy of VNS during the latest 3 months is better than that of recent antiepileptic agents. However, we have not yet achieved any seizure‐free patients, although their seizure rates have been reduced. We need more experiences with VNS to determine the appropriate parameters and find out how to select the most suitable cases.

We examined the efficacy of vagal nerve stimulation (VNS) for patients suffering from medically intractable epilepsy. Four randomized controlled trials (RCTs - 3 adult RCTs and 1 pediatric RCT) were identified in our comprehensive literature search. Across the 4 studies, high frequency VNS stimulation (frequency >20Hz) consistently achieved a greater seizure frequency reduction (23.4-33.1%) relative to low frequency VNS stimulation (1Hz, .6-15.2%). We identified 2 RCTs examining whether the parameters of stimulation influenced seizure control. These studies reported that VNS achieved seizure control comparable to those reported by the first 4 RCTs (22-43% seizure frequency reduction), irrespective of the parameters utilized for VNS stimulation. In terms of VNS associated morbidity, these morbidities were consistently higher in adults who underwent high frequency VNS stimulation (eg dysphonia 37-66%, dyspnea 6-25.3%). However, no such differences were observed in the pediatric population. Moreover, <2% of patients withdrew from the RCTs/prospective studies due to intolerable symptoms. To provide an assessment of how the risks and benefits of VNS impact the patient experience, 1 study assessed the well-being of enrolled patients (as a secondary end point) and found VNS was associated with an overall improvement in well-being. Consistent with this observation, we identified a prospective, non-randomized study that demonstrated improved quality of life for epilepsy patients managed with VNS and best medical practice relative to best medical practice alone. In aggregate, these RCT studies support the efficacy and benefit of VNS as a neuro-modulatory platform in the management of a subset of medically refractory epilepsy patients.

Efficacy of vagus nerve stimulation for children with drug-resistant epilepsy: Retrospective study

Vagus nerve stimulation versus “best drug therapy” in epilepsy patients who have failed best drug therapy

Objective To explore the efficacy of vagus nerve stimulation (VNS) for the treatment of drug resistant epilepsy. Methods The clinical data of 110 patients with drug resistant epilepsy who underwent VNS at Department of Neurosurgery, Provincial Hospital Affiliated to Anhui Medical University (the First Affiliated Hospital of University of Science and Technology of China) from February 2014 to March 2018 were analyzed retrospectively. The frequency and severity of seizures were followed up by outpatient review, and the efficacy was analyzed according to the McHugh seizure outcome classifications. Results The results of McHugh grade of 110 patients were as follows: grade ⅠA in 10 cases, grade ⅠB in 6, grade ⅡA in 25, grade ⅡB in 7, grade ⅢA in 30, grade ⅢB in 8, grade Ⅳ in 1 and grade Ⅴ in 20, and 3 patients were lost to follow-up. There was significant difference in seizure frequency between preoperative and postoperative conditions (P 0.05). In terms of seizure types, there were significant difference in the distribution of the McHugh classifications between patients with seizures of unclassified onset, focal onset and generalized onset (all P<0.05). The frequency of seizures decreased gradually with prolonged VNS stimulation time(P<0.05). Conclusions VNS could significantly reduce the frequency of seizure. VNS has a better effect on seizures with focal onset and generalized onset, while it has a poor effect on seizure types that cannot be classified. With the increase of stimulation time, the therapeutic effect of VNS is gradually improved. However, the age, sex or duration of disease is not related to the effect of VNS. Key words: Epilepsy; Vagus nerve stimulation; Treatment outcome; McHugh seizure outcome classifications

To study the efficacy of vagus nerve stimulation (VNS) therapy in a highly drug-resistant childhood epilepsy patient group and to investigate the effect of age at implantation on efficacy. The efficacy of VNS treatment was analysed in a cohort of 70 patients with drug-resistant epilepsy. Both children with focal (n=16) and generalized epilepsies (n=54) were included. Age at implantation varied between 19 months and 25 years. Overall, responder rate was 54% with 5.7% children becoming seizure-free. The only factor in our analysis that could predict good outcome was age at implantation. In the youngest group (<5 years), the responder rate was 77% and this group also included three of the four seizure-free children. These three seizure-free children were known to have tuberous sclerosis. There were no outcome differences between generalized and focal epilepsies. Our single centre study confirms previous studies on the efficacy of VNS in children. A larger study using multivariate analysis to disentangle the contribution of different factors (such as age at implantation, aetiology, and epilepsy duration) is necessary to confirm our preliminary finding that younger age at VNS implantation might result in a better outcome.

Background This study is the first to assess the safety and therapeutic efficacy of vagus nerve stimulation (VNS) as an adjunctive treatment for Chinese patients suffering from treatment-resistant depression (TRD). Methods A total of seven patients with TRD underwent surgical implantation of a VNS device were followed over a 9-month period. The 24-item Hamilton Rating Scale for Depression (HAMD-24) and the 14-item Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms, respectively. Neurocognitive function was measured with the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale (WMS). Results After 3 months of treatment with VNS, the antidepressant response and remission rates were 42.9% and 28.6%, respectively. After 9 months of treatment with VNS, the response and remission rates increased to 85.7% and 57.1%, respectively. Significant time main effects were identified for HAMD-24 scores, HAMA scores, the WMS memory quotient, and the full intelligence quotients measured with the WAIS (all ps < 0.05). The most frequent adverse effects of VNS treatment were voice alteration (100%) and cough frequency increase (71.4%). Conclusion This preliminary study indicated that adjunctive VNS was effective and safe in treating Chinese patients who were suffering from TRD, and its efficacy increased with time. Key points There is positive evidence to support the role of VNS as an adjunctive treatment in Chinese patients with TRD. The antidepressant efficacy of adjunctive VNS for Chinese patients with TRD increased with time. The most frequent adverse effects of VNS treatment were voice alteration and cough frequency increase.

An analysis of quality of life (QOL) in patients with epilepsy and comorbid psychogenic nonepileptic seizures (PNES) after vagus nerve stimulation (VNS).