Right-sided vagus nerve stimulation [Neurosurgery Wiki]

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====== Right-sided vagus nerve stimulation ======

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**Right-Sided Vagus Nerve Stimulation in Drug-Resistant Epilepsy: A Niche but Necessary Alternative**

Vagus nerve stimulation (VNS) is an established adjunct therapy for patients with drug-resistant epilepsy (DRE). Over the past three decades, this therapy has demonstrated effectiveness in reducing seizure frequency and, in some cases, improving patient quality of life. Conventionally, VNS leads are implanted along the left vagus nerve to minimize the potential for cardiac side effects, given the right vagus nerve’s predominant cardiac innervation. However, in certain clinical situations—such as anatomical constraints, infection of the left-sided implant site, or left VNS lead deficiency—right-sided VNS (R-VNS) may be the only viable option.

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### Limited but Growing Evidence for R-VNS

**Systematic Review Evidence**

A recent systematic review identified a scant number of cases in which R-VNS was employed for DRE, underscoring the rarity of this procedure and the paucity of supporting data \[1\]. After screening 2,333 initial records, only four studies with a total of seven patients met the inclusion criteria. Six of the seven patients showed a 25% to 100% seizure frequency reduction with R-VNS, while in one case the VNS effect was unclear. One patient experienced nocturnal asymptomatic bradycardia, and another had to discontinue stimulation due to exercise-induced airway disease exacerbation. Interestingly, one case documented that R-VNS was more effective than left-sided VNS (69% vs 50%), whereas in another case, it was less effective (50% vs 95%).

This review highlights two crucial points: (1) R-VNS, while rarely employed, can be effective for seizure control; and (2) clinical outcomes appear heterogeneous, possibly reflecting differences in patient-specific anatomical considerations and comorbidities.

**Questionnaire-Based Multicenter Case Series**

Further insight comes from a large questionnaire-based series capturing 38 R-VNS patients from specialized epilepsy surgery centers worldwide \[2\]. Among these, 55% were responders, with a mean seizure frequency reduction of approximately 56%. Importantly, 84% of the patients underwent a preoperative cardiac assessment—an essential safeguard given the theoretical risk of R-VNS–induced cardiac dysrhythmias. Although three patients experienced postoperative cardiac side effects and three discontinued R-VNS for other reasons (e.g., infection, dyspnea, sleep apnea), the majority of patients tolerated the therapy well. When comparing seizure outcomes, 20 patients reported similar effectiveness between left- and right-sided VNS, 1 experienced lesser, and 2 reported greater effectiveness with right-sided placement.

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### Mechanistic Insights and Physiological Considerations

The rationale behind prioritizing left-sided implantation is largely to limit cardiac involvement via the right vagus nerve’s innervation of the sinoatrial and atrioventricular nodes. Nonetheless, controlled experimental studies suggest right-sided stimulation also has a robust effect on neuromodulatory pathways. A single-blind randomized crossover study showed that acute right-sided transcutaneous auricular VNS enhanced stomach-brain coupling and modulated activity in the nucleus of the solitary tract (NTS) and midbrain \[3\]. These findings demonstrate that vagal afferents—right or left—can significantly influence central autonomic and reward-related networks. In epilepsy management, this may translate into seizure control benefits as part of a broader, systemic modulation of excitatory-inhibitory balance.

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### Case Reports: Safety and Efficacy in Individualized Contexts

Multiple case reports spanning adult and pediatric populations describe modest to marked seizure frequency reduction with R-VNS \[4–6\]. Overall, none of these patients experienced severe or life-threatening cardiac events, though respiratory effects such as dyspnea or sleep apnea were noted in some. Collectively, these reports illustrate two principles:  
1. **R-VNS is generally well tolerated** but may require closer cardiopulmonary monitoring, especially in patients with preexisting respiratory disease.  
2. **Response to R-VNS can vary**: some patients match or exceed prior left-sided VNS efficacy, whereas others show diminished benefit.  

Notably, a few case reports raise the question of whether R-VNS should be considered even in patients who have “failed” left VNS if there is a suspicion that differential innervation patterns may yield different antiseizure responses \[6\]. However, the evidence remains anecdotal, highlighting the need for systematic research.

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### The Way Forward

Though R-VNS is far less common than left-sided VNS, it represents a critical alternative for selected patients. Both the systematic review and the largest multicenter case series to date underscore that R-VNS can achieve meaningful seizure reduction in a majority of patients, with a relatively low complication rate \[1,2\]. The primary concern—potential cardiac side effects—appears manageable, especially when proper cardiac evaluations and vigilant postoperative follow-ups are in place.

Nonetheless, the available data are limited, relying primarily on case reports, retrospective reviews, and a single multicenter questionnaire-based series. Prospective trials with standardized protocols, robust cardiac and respiratory monitoring, and well-defined efficacy metrics will be essential. Comparative effectiveness studies—ideally randomized—would provide definitive evidence on whether R-VNS can rival or, in some scenarios, surpass left-sided VNS in seizure control and patient quality of life.

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### Conclusion

Right-sided VNS remains a niche but necessary alternative for treating drug-resistant epilepsy. Preliminary evidence suggests that its safety and effectiveness are broadly comparable to conventional left-sided implantation, though vigilance for respiratory side effects seems warranted. Ultimately, for patients who cannot undergo left-sided placement, R-VNS should be considered a viable recourse rather than a last resort. Ongoing research will help refine patient selection criteria, optimize stimulation parameters, and further elucidate the physiological underpinnings of this promising therapy.

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**References**  
1. Hamza M, Carron R, Dibué M, et al. *Right-sided vagus nerve stimulation for drug-resistant epilepsy: A systematic review of the literature and perspectives.* Seizure. 2024;117:298-304.  
2. Zanello M, Voges B, Chelvarajah R, et al. *Right-sided vagus nerve stimulation: Worldwide collection and perspectives.* Ann Clin Transl Neurol. 2025. doi: 10.1002/acn3.52312.  
3. Müller SJ, Teckentrup V, Rebollo I, et al. *Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway.* Brain Stimul. 2022;15(5):1279-1289.  
4. Navas M, Navarrete EG, Pascual JM, et al. *Treatment of refractory epilepsy in adult patients with right-sided vagus nerve stimulation.* Epilepsy Res. 2010;90(1-2):1-7.  
5. Spuck S, Nowak G, Renneberg A, et al. *Right-sided vagus nerve stimulation in humans: an effective therapy?* Epilepsy Res. 2008;82(2-3):232-234.  
6. McGregor A, Wheless J, Baumgartner J, et al. *Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans.* Epilepsia. 2005;46(1):91-96.
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[[Vagus nerve stimulation]] (VNS) is an established therapy for [[drug-resistant epilepsy]] (DRE) and is indicated for [[implantation]] on the left [[vagus nerve]] only. In rare cases, right-sided [[VNS]] may be the only option. 

===== Systematic reviews =====


A [[systematic review]] following [[PRISMA]] [[guideline]]s was conducted: [[Pubmed]]/[[MEDLINE]], The [[Cochrane Library]], [[Scopus]], [[Embase]] and [[Web of science]] databases were searched from inception to August 13th,2023. [[Gray literature]] was searched in two libraries. Eligible studies included all studies reporting, at least, one single case of RS-VNS in patients for the treatment of drug-resistant epilepsy.

Results: Out of 2333 initial results, 415 studies were screened by abstract. Only four were included in the final analysis comprising seven patients with RS-VNS for a drug-resistant epilepsy. One patient experienced nocturnal asymptomatic bradycardia whereas the other six patients did not display any cardiac symptom. RS-VNS was discontinued in one case due to exercise-induced airway disease exacerbation. Decrease of epileptic seizure frequency after RS-VNS ranged from 25 % to 100 % in six cases. In the remaining case, VNS effectiveness was unclear. In one case, RS-VNS was more efficient than left-sided VNS (69 % vs 50 %, respectively) whereas in another case, RS-VNS was less efficient (50 % vs 95 %, respectively).

Literature on the present topic is limited. In six out of seven patients, RS-VNS for drug-resistant epilepsy displayed reasonable effectiveness with a low complication rate. Further research, including prospective studies, is necessary to assess safety and effectiveness of RS-VNS for drug-resistant epilepsy patients
((Hamza M, Carron R, Dibué M, Moiraghi A, Barrit S, Filipescu C, Landré E, Gavaret M, Domenech P, Pallud J, Zanello M. Right-sided vagus nerve stimulation for drug-resistant epilepsy: A systematic review of the literature and perspectives. Seizure. 2024 Apr;117:298-304. doi: 10.1016/j.seizure.2024.02.011. Epub 2024 Feb 19. PMID: 38615369.)).

===== Questionnaires =====


An anonymous 38-item [[questionnaire]] was sent to expert surgeons implanting VNS for DRE. The questions covered demographics and clinical characteristics, the reason for right-sided implantation, and both neurological and surgical outcomes of right-sided VNS.

The [[survey]] captured 38 cases of right-sided VNS (18 females, mean age at surgery of 28.0 ± 16.3 years). Right-sided VNS was performed because of VNS lead deficiency (n = 20), anatomical constraints (n = 8), infection of a left-sided VNS site (n = 9), and the presence of a left ventricular shunt (n = 1). Thirty-two patients (84%) had a preoperative cardiac assessment. Three patients presented postoperative cardiac side effects. Right-sided VNS was stopped at the last follow-up in three patients: due to deep infection (n = 1), due to dyspnea (n = 1), and due to sleep apnea syndrome (n = 1). Twenty-one patients (55%) were responders to right-sided VNS and the mean reduction of seizure frequency under right-sided VNS was 56.2 ± 18.8%. Focusing on seizure frequency reduction between right-sided VNS and left-sided VNS: 20 patients experienced similar effectiveness, 1 experienced lesser effectiveness, and 2 patients experienced greater effectiveness with right-sided VNS.

This multicenter case series significantly augments the available literature on right-sided VNS. This suggests comparable effectiveness to left-sided VNS but potentially lower tolerability. Further studies are warranted to better evaluate the safety and efficacy of right-sided VNS
((Zanello M, Voges B, Chelvarajah R, Sen A, Petelin Gadže Ž, Penchet G, De Benedictis A, Fornaro R, Iwasaki M, Iijima K, Jiltsova E, Mrak G, Barrit S, Moiraghi A, Landi A, Neale M, Magdum S, Caire F, Godet B, Domenech P, Gaillard R, Guenot M, Labuschagne J, Rainha Campos A, Rooijakkers H, El Tahry R, Von Hertwig Fernandes De Oliveira T, Alvarez-Sala A, Torres CV, Vale F, Pallud J, Carron R. Right-sided vagus nerve stimulation: Worldwide collection and perspectives. Ann Clin Transl Neurol. 2025 Feb 3. doi: 10.1002/acn3.52312. Epub ahead of print. PMID: 39901698.))

===== Controlled experimental studies =====

Using a single-blind randomized crossover design, Müller et al. investigated the effect of acute right-sided transcutaneous auricular vagus nerve stimulation (taVNS) versus [[sham]] stimulation on stomach-brain coupling.

In line with preclinical research, taVNS increased stomach-brain coupling in the nucleus of the solitary tract (NTS) and the midbrain while boosting coupling across the brain. Crucially, in the cortex, taVNS-induced changes in coupling occurred primarily in transmodal regions and were associated with changes in hunger ratings as indicators of the subjective metabolic state.

taVNS increases stomach-brain coupling via an NTS-midbrain pathway that signals gut-induced reward, indicating that communication between the brain and the body is effectively modulated by vago-vagal signaling. Such insights may help us better understand the role of vagal afferents in orchestrating the recruitment of the gastric network which could pave the way for novel neuromodulatory treatments
((Müller SJ, Teckentrup V, Rebollo I, Hallschmid M, Kroemer NB. Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway. Brain Stimul. 2022 Sep-Oct;15(5):1279-1289. doi: 10.1016/j.brs.2022.08.019. Epub 2022 Sep 5. PMID: 36067977.)).

===== Case reports =====

Two adult patients who underwent R-VNS. One of the patients improved dramatically after L-VNS, but the device had to be removed because of mechanical malfunction. This patient was thought to be at high risk for nerve injury if L-VNS reimplantation was done, thus R-VNS was chosen. In the other patient, L-VNS was first attempted, but the operation had to be stopped due to significant bleeding caused by the accidental tearing of an ectopic vein. Both patients had a marked reduction in their seizure activity and none of them had cardiac side effects from therapeutic R-VNS. We conclude that R-VNS therapy is an alternative, promising therapy for reducing seizure activity in those patients who cannot undergo L-VNS implantation. Close follow-up and frequent ECG monitoring are required to detect cardiac side effects
((Navas M, Navarrete EG, Pascual JM, Carrasco R, Núñez JA, Shakur SF, Pastor J, Sola RG. Treatment of refractory epilepsy in adult patients with right-sided vagus nerve stimulation. Epilepsy Res. 2010 Jun;90(1-2):1-7. doi: 10.1016/j.eplepsyres.2010.04.007. Epub 2010 May 21. PMID: 20488666.)).
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In a 16-year-old boy suffering from medically refractory psychomotor seizures with secondary generalization, L-VNS reduced the frequency of generalized seizures. A deep wound infection required the removal of the system eight weeks later. Cicatrisation did not allow the preparation of the left vagus nerve. Therefore, we implanted R-VNS with sufficient seizure suppression. However, compared to L-VNS, the effect occurred months later, and cardiac symptoms were induced by stimulation of the right vagus nerve. R-VNS seems to be an effective and alternative therapy in selected patients responding to L-VNS where left-sided reimplantation is not possible. Placement and adjustment of the device should be performed under ECG control. Further studies are necessary to compare the efficacy of L-VNS and R-VNS
((Spuck S, Nowak G, Renneberg A, Tronnier V, Sperner J. Right-sided vagus nerve stimulation in humans: an effective therapy? Epilepsy Res. 2008 Dec;82(2-3):232-4. doi: 10.1016/j.eplepsyres.2008.08.003. Epub 2008 Sep 18. PMID: 18801642.))
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Three patients with R-VNS for the treatment of intractable seizures. All three patients improved dramatically with left-sided vagus nerve stimulation (L-VNS), but the devices had to be removed because of infection. The patients were thought to be at high risk for nerve injury if they were reapproached for L-VNSs; therefore R-VNSs were implanted.

All three patients with an R-VNS had a reduction in seizures. Our first patient has had an R-VNS for 5 years; he has been seizure-free for >2 years on R-VNS monotherapy. The second patient had an R-VNS for 8 months. His seizure control improved slightly, but not as dramatically as with L-VNS. The third child has had an R-VNS for >7 months and has cessation of his most disabling seizure type (generalized tonic-clonic seizures). None of the patients had cardiac side effects from therapeutic R-VNS. However, two of the three patients had respiratory events with R-VNS.

Conclusions: VNS is known to be an effective treatment in pharmacoresistant epilepsy. R-VNS should be considered if a patient has significant benefit from L-VNS but cannot continue with L-VNS. R-VNS appears also to have antiepilepsy effects. Additionally, our case report suggests that in some patients, a differential response is found regarding seizure control with R-VNS or L-VNS, raising the question of whether L-VNS failures should pursue a trial of R-VNS. Patients should be cautioned and monitored for reactive airway disease if they undergo R-VNS. More research is needed to compare the effects of right- and left-sided VNS on cardiac and pulmonary function in humans and to determine which has the best antiseizure effect
((McGregor A, Wheless J, Baumgartner J, Bettis D. Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans. Epilepsia. 2005 Jan;46(1):91-6. doi: 10.1111/j.0013-9580.2005.16404.x. PMID: 15660773.)).