Vagal nerve stimulation (VNS), delivered by the NCP System (Cyberonics, Houston, TX, USA) for treatment of drug-resistant epilepsy is approved as an add-on therapy in adults and children for partial and generalized epileptic seizures. New, noninvasive stimulation devices are under development [
1,
2]. The VNS efficacy has been established, showing a 50% reduction in epileptic seizure rate in approximately 30% of patients after one year with an increase to approximately 50-70% after three years, with relatively few patients (less than 10%) becoming seizure free [
3‐
5]. Despite more than 20 years of VNS accessibility, the discussion of its safety and efficacy is ongoing. The evidence-based guidelines from the American Academy of Neurology in 2013 [
6] emphasized the need for further safety information.
The adverse events (AE) of VNS are of two types: implantation procedure-related and stimulation-related. Surgery-related AE have been reported in 3-22% of VNS implantations. The most often reported surgery-related AE are hardware failure in 3.7-16.8%, lead fracture or disconnection in 3.7-13.7%, wound infections in 1.7-7.1%, wound hematoma in 0.7-1.9%, transient asystole/bradycardia up to 1%, left vocal cord palsy, mostly transient, in 1.4-5.1%, and lower facial weakness in 0.2-1.2% [
7‐
14]. Stimulation-related AE in different studies have been reported to occur in up to 68% of patients, with 97.8% of the AE reported as mild to moderate. The AE usually appeared immediately after VNS adjustments and disappeared spontaneously over some time or after the adjustment of the stimulation current to the previous level of stimulation [
7,
15‐
17]. Most often reported stimulation-related AE were voice alterations (6-66%), hoarseness (1.4-64%), cough (7-45%), dyspnea (2-25%), throat pain (4.7-22%), neck pain and/or tingling and twitching in the neck muscles (0.5–22%), dysphagia (13-17.9%), headache (7-30%) and chest pain (up to 13%). Cases with some pain were reported in 6-30% of implantations [
7,
18‐
23]. In addition to the VNS side effects reported in population studies, there are rare cases or case series reports of unusual or late-onset stimulation-related AE such as parkinsonism [
24], late-onset bradyarrhythmia/asystole [
25‐
28], sleep apnea [
29,
30], psychosis or mania [
31], glossopharyngeal tonsillar pain [
32] and pharyngeal dysesthesia [
33]. Cases of late-onset trigeminal pain associated with VNS, considering the large number of VNS implantations performed worldwide, are an extremely rare and unexpected event [
34,
35] (Table
1).
Table 1
Characteristics of late-onset trigeminal pain under VNS in reported patients
| Epilepsy-Tuberous sclerosis | 9 months | 2 months | 1.25a
| Left cheek, mentally retarded child with unprecise description of the pain |
Carius and Schulze-Bonhage [ 34] | Cryptogenic epilepsy, focal seizures | 5 months | few days | 1.5a
| The lower jaw, left |
Epilepsy-right frontotemporal | 2 months | 1 month | 0.5a
| The lower jaw and occipital headache, left |
Epilepsy- bitemporal | 11 months | 2 weeks | 1.75a
| The lower jaw and throat, left |