A total of 56 patients received VNS implantation in our institution during the study period. Nine patients were excluded from the outcome analyses: two patients who had to have their devices removed immediately postoperatively due to deep layer infection, six patients who were lost to follow-up within six months, and one patient who had additional resection surgery within six months after VNS insertion. Therefore, a total of 47 consecutive patients were included in the outcome analyses (Figure 1).
The demographic characteristics are shown in table 1. The mean age at seizure onset was 6.4 years (range, 0.2–15 years), and the mean age at VNS surgery was 14.7 years (range, 5–26 years). The mean interval of epilepsy from onset to surgery was 8.3 years (range, 2–16 years). Twenty-five patients were male (53%), and 22 patients were female (47%). The mean number of preoperative ASDs was 4.2 per day (range, 1–7). The mean follow-up duration was 58.5 months (range 12–156). The mean number of ASDs was kept steady, from 4.1 per day preoperatively to 4.2 per day at one postoperative year (p=0.371).
Normal MRI findings accounted for 22 patients (51%), whereas focal, multifocal and diffuse lesions accounted for six (13%), seven (15%), and 12 patients (26%), respectively. Thirty-six patients showed focal onset epilepsy on EEG. Regarding etiology, nine patients (19%) had structural lesions, five patients (11%) had genetic backgrounds such as SCN1A mutations or ATP1A3 mutations, nine patients had histories of central nervous system infections (19%), one patient (2%) had a lesion due to metabolic causes, and one patient had a lesion due to immune causes. The specific etiology was unknown in twenty-two patients.
At six months postoperatively, there were 22 patients who were responders (47%), whereas 25 patients (53%) were responders one year postoperatively (Figure 2). When the postoperative one-year responder was analyzed, the age at seizure onset was 6.9 years, the age at operation was 14.6 years, and the interval from epilepsy onset to surgery was 7.7 years. There was no statistically significant difference in the demographic characteristics between the responder and nonresponder. However, responders showed a tendency of later onset of seizure and a shorter interval from seizure onset to VNS implantation than nonresponders.
Concerning MRI findings, five out of six patients (83%) with a focal lesion became a responder one year postoperatively, whereas three out of seven patients with multifocal (43%) and five out of 12 patients with diffuse lesions (42%) became responders. When analyzed with EEG findings, 4 out of 7 (57%) generalized seizure patients and 19 out of 36 (53%) focal seizure patients showed a response. Six out of nine (67%) patients with a history of infection, and one out of four patients with a history of trauma had a response to VNS according to the etiology. Half of the patients with metabolic and genetic backgrounds were responders. Seven patients (15%) received resection or disconnection surgery prior to VNS implantation, and those were two temporal lobectomies, two total callosotomies, two focal cortical dysplasia removals, and one tumor (pleomorphic xanthoastrocytoma) removal. Three of five (60%) patients with a history of resection became responders. However, there was no statistically significant factor for better responses in terms of MRI, EEG, etiologies and resection history due to the small numbers of patients in each group.
The overall mean seizure frequency was reduced from 8.0 per week to 5.1 per weak (36%, p=0.006, Figure 2). The mean seizure frequency reduction rate was analyzed for the same variables used for analyses of ≥50% responders (Table 2). Of all variables, focal onset epilepsy on EEG and no prior resection surgery were statistically significant for seizure frequency reduction. Patients with focal onset epilepsy on EEG had 7.5 seizures per week preoperatively, which was reduced to 5.1 seizures per week (32%, p=0.009). Likewise, the seizure frequency reduction rate was 43% in patients who had not undergone previous resection (p=0.006).
Seven patients (9%) were able to reduce their ASDs by a mean of 1.4 ASD per patient. The characteristics and comparisons of ASD reduction and nonreduction groups are shown in table 3. The ASD reduction group demonstrated a shorter mean interval from epilepsy onset to operation than the nonreduction group. Four patients had normal MRI findings, and five patients had focal onset seizures on EEG. However, no statistical significance was obtained for the factors.
After VNS implantation, four (9%) patients complained of hoarseness and/or cough. Symptoms were managed by output current adjustment, and all were transient. Infection occurred in three patients (6%) when including the two patients initially excluded from the analyses because of early deep layer infection and VNS removal. The other patient could be managed by oral antibiotics without device removal.
The VNS battery was discharged in ten patients. The patients were consulted as to whether to maintain the VNS. Seven patients chose to keep their VNS treatment and underwent a battery change. One of the three patients who decided to discontinue VNS treatment remained in a seizure-free state for four years. The other two patients had minimal responses.