VNS Therapy™ in Drug-Resistant Epilepsy
Disclosure
Disclaimer
This interactive case study was organised and funded by LivaNova.
This case presents data from a real patient. Individual patient journeys and results may vary.
Neurology
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These interactive case studies were developed with support from LivaNova.
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This is a real patient case but may not be reflective of clinical studies or all real-life circumstances. Approved indications for VNS Therapy™ vary based on geographic location. Please consult your local labelling and prescribing information, available here.
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10 months old
3 years old
6 years old
Patient History Click to learn more >>
At 10 months, the patient presented with febrile seizures.
At 6 years old, he is diagnosed with drug-resistant epilepsy (DRE). Three prior antiseizure medications (ASM) prior to initiation of VNS Therapy™.
At 3 years of age, he had his first unprovoked seizure. Seizure type: Focal tonic-clonic with impaired awareness. Frequency: Approximately 2–3 times a month, each lasting approximately 3–4 minutes. Two incidents of shoulder dislocation.
Did you know? Persons with epilepsy are believed to be at higher risk of incurring accidental injury, such as contusions, wounds, abrasions, fractures, and concussions.1
Beghi E. Accidents and injuries in patients with epilepsy. Expert Rev Neurother. 2009;9(2):291–8.
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ASM Treatment Regimen
At 6 years old, he is diagnosed with drug-resistant epilepsy (DRE). Three prior antiseizure medications (ASM) prior to initiation of vagus nerve stimulation (VNS) Therapy™.
At 3 years of age, he had his first unprovoked seizure. Seizure type: Focal tonic-clonic with impaired awareness. Frequency: Approximately 2/3 times a month, each lasting approximately 3/4 minutes. Two incidents of shoulder dislocation.
Beghi E. Accidents and injuries in patients with epilepsy. Expert Rev Neurother. 2009;9(2):291–8
Prior to initiation of VNS Therapy™, the patient’s ASM treatment regimen included:
His development was normal, meeting all milestones on time, with good academic performance. He reports mild anxiety.
Addition of levetiracetam: Seizure frequency decreased to once every 8 months. Side effects included development of aggression, behavioural outbursts, and mood swings.
Oxcarbazepine: Seizure frequency reduced to once every 4–6 months.
Addition of brivaracetam: Seizure frequency reduced to once every 8–9 months.
4/18
What’s your experience? Do your paediatric patients frequently experience behavioural side effects with ASM therapy?
A
B
C
Yes
No
I'm not sure
Did you know? ASM therapy is often associated with behavioural side effects, including agitation, aggression, hyperactivity, and restlessness.1 Children appear to be especially vulnerable to behavioural side effects. Guilfoyle et al.2 reported that children 2–11 years of age receiving ASM therapy for new onset epilepsy had higher scores of the Perceptual Evaluation of Speech Quality (PESQ) than adolescents 12 years of age receiving ASM therapy.2 Thigpen J et al. Behavioral side effects of antiepileptic drugs. US Pharm. 2013;38(11):HS15-20. Guilfoyle SM et al. Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy. Epilepsia. 2018;59(1):146-154.
Did you know? The risks of ongoing, poorly controlled seizures could lead to cognitive impairment, mental health issues, and reduced independence and future employment opportunities.1-3 Fisher RS et al. The impact of epilepsy from the patient’s perspective I. Descriptions and subjective perceptions. Epilepsy Res. 2000;41(1):39-51. Gilliam F. Optimizing health outcomes in active epilepsy. Neurology. 2002;58 (8 Suppl 5):S9-20. Wheless JW. Intractable epilepsy: a survey of patients and caregivers. Epilepsy Behav. 2006;8(4):756-64.
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EEG, MRI, and Seizure Localisation Studies Were Carried Out Click on each diagnostic method to learn more >>
Abnormal EEG due to the presence of slightly low occipital dominant rhythm for age; suggests a diffuse disturbance in cerebral function1 Presence of a superimposed right occipital intermittent focal slowing; suggests a focal disturbance in cerebral function in that region1 Correlation with imaging is recommended1
EEG
MRI
Localisation
Normal MRI
Did not localise seizures into one area
Did you know? The International League Against Epilepsy (ILAE) expert consensus recommends surgical evaluation as soon as drug-resistant epilepsy is established in patients up to 70 years of age, with referral also considered for older patients without surgical contraindications, and seizure-free patients with a brain lesion in non-eloquent cortex. Referral should not be offered to patients with active substance abuse who are non-cooperative with management.1
1. Tatum WO et al. American Clinical Neurophysiology Society guideline 7: guidelines for EEG reporting. J Clin Neurophysiol. 2016;33(4):328-32.
Jehi L et al. Timing of referral to evaluate for epilepsy surgery: expert consensus recommendations from the Surgical Therapies Commission of the International League Against Epilepsy. Epilepsia. 2022;63(10):2491-506.
6/18
Alternative Therapies Were Discussed with the Patient’s Parents
What drove recommendation to explore alternative therapies?
What did the conversation with the patient/family entail?
DRE with persistence of seizures Need to more effectively control seizure activity to avoidpotential long-term consequences on development and quality of life (QoL) Risk of sudden unexpected death in epilepsy (SUDEP)
Epilepsy surgery could be an option, but low probability of seizure freedom. Non-lesional nature and >1 seizure semiology Seizure localisation studies did not localise seizures to one area Therapy without systemic side effects is desirable.
Initial discussion Family is not interested in nonpharmacological options because the patient has normal development, very little limitations/impact on QoL, and low frequency of seizures Difficulty in understanding that the patient has DRE Discussed negative impact of seizures on QoL, long-term consequences (e.g., driving, independent living, and social life) Family concerned about risk of sudden unexpected death in epilepsy SUDEP
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Follow-Up: 2 Months Later
Follow-up 2 months later: non-pharmacological discussion Seizures are still happening, albeit not at a high frequency Family’s goals: optimise QoL, decrease risk of SUDEP, potentially reduce ASM Family does not want to go through non-lesional epilepsy surgery Low likelihood of seizure freedom, risk of loss of function VNS Therapy™ surgical procedure and outcomes discussed with family Reviewed surgical procedure, risk of infection, and potential cosmetic impact Reviewed the data on reductions in seizure frequency, severity, and duration, and common side effects from stimulation
Did you know? Paediatric patients who did not achieve seizure freedom for 5 continuous years were at a 5.2x greater risk of SUDEP (95% CI: 1.4–18.5).1 Silanpaa M et al. Long-term mortality in childhood-onset epilepsy. NEJM. 2010;363(26):2522-9
Benbadis SR et al. Putting it all together: options for intractable epilepsy: an updated algorithm on the use of epilepsy surgery and neurostimulation. Epilepsy Behav. 2018;88S:33-8.
VNS Therapy™ has been used across a range of focal epilepsy types, including well-defined, non-localisable, and multifocal focal epilepsies.1 VNS Therapy™ indications for use vary by geographic location. Please consult your local labelling.
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When can a patient be deemed to be drug-resistant?
After failure of one appropriately chosen and tolerated ASM
When the patient exhibits severe seizures
After the failure of two appropriately chosen and tolerated ASMs
D
After the failure of two ASMs which exhibited adverse events
Did you know? According to the ILAE, drug-resistant epilepsy may be defined as a failure of adequate trials of two tolerated and appropriately chosen and used ASM schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom.1 Approximately 30–40% of children with epilepsy develop DRE.1-3 Kwan P et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069-77. Boonluksiri P et al. Clinical prediction rule of drug resistant epilepsy in children. J Epilepsy Res. 2015;5(2):84-8. Aaberg KM et al. Short-term seizure outcomes in childhood epilepsy. Pediatrics. 2018;141(6):e20174016.
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VNS Therapy™ Works Through Monoaminergic Modulation of Limbic and Thalamocortical Circuitry
The Vagal Afferent Network1,2 Vagal afferents primarily project to the nucleus tractus solitarius (NTS), which then sends fibres to other brainstem nuclei that modulate subcortical and cortical activity1,2 This vagal afferent network is likely the neural substrate of the antiseizure effects of VNS Therapy™1
The following information is based primarily on animal research and provides an overview of how VNS Therapy™ is believed to have anti-seizure effects on the brain.
References
Hachem LD et al. The vagus afferent network: emerging role in translational connectomics. Neurosurg Focus. 2018;45(3):E2. Carron R et al. Latest views on the mechanisms of action of surgically implanted cervical vagal nerve stimulation in epilepsy. Neuromodulation. 2023;26(3):498-506.
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Nucleus tractus solitarius1,2*† Region of the brain that is first activated by VNS Therapy™1,2
Bottom-Up Modulation of Seizure-Propagating Circuitry: Brainstem The Brainstem: Click to Explore >>
1
2
Locus coeruleus1,3,4*† Main production site for noradrenaline1,3 Lesioning LC blocks the antiseizure effects of VNS Therapy™4
Dorsal raphe nuclei1,4* Main production site of serotonin1,4
3
*Activated through chronic stimulation; ranges from 2 weeks to 3 months. †Activated through acute stimulation; ranges from 1 minute to 3 days. Carron R et al. Latest views on the mechanisms of action of surgically implanted cervical vagal nerve stimulation in epilepsy. Neuromodulation. 2023;26(3):498-506. Nosaka S. Solitary nucleus neurons transmitting vagal visceral inputs to the forebrain via a direct pathway in rats. Exp Neurol. 1984;85(3):493-505. Henry TR. Therapeutic mechanisms of vagus nerve stimulation. Neurology. 2002;24:59(6 suppl 4):S3-14. Jobe PC, Browning RA. The serotonergic and noradrenergic effects of antidepressant drugs are anticonvulsant, not proconvulsant. Epilepsy Behav. 2005;7(4):602-19.
Footnotes
11/18
Hippocampus1 Key role in aberrant circuitry that may drive seizures Local modulation allows neurogenesis and plasticity2
Bottom-Up Modulation of Seizure-Propagating Circuitry: Limbic System The Limbic System Click to Explore >>
Amygdala1,3,4 Key role in hyperexcitation Elevates seizure threshold1,3 Reduces excitability1,4
Thalamus5 Key role in seizure spread Improves thalamic metabolism5 Improves seizure responses5
Hachem LD et al. The vagus afferent network: emerging role in translational connectomics. Neurosurg Focus. 2018;45(3):E2. Marrosu F et al. Increase in 20-50 Hz (gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation. Clin Neurophysiol. 2005;116(9):2026-36. Alexander GM et al. Vagus nerve stimulation elevates seizure threshold in the kindling model. Epilepsia. 2012;53(11):2043-52. Wassum KM et al. The basolateral amygdala in reward learning and addiction. Neurosci Biobehav Rev. 2015;57:271-83. Liu W-C et al. Bold fMRI activation induced by vagus nerve stimulation in seizure patients. J Neurol Neurosurg Psychiatry. 2003;74:811-13.
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Cortex1,2 Increases cortical receptor density of GABAA receptors1 Much of the connectivity with subcortical structures is reciprocal2
Bottom-Up Modulation of Seizure-Propagating Circuitry: Cortex The Cortex: Click to Explore >>
Marrosu F et al. Increase in 20-50 Hz (gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation. Clin Neurophysiol. 2005;116(9):2026-36. Fuster JM. The prefrontal cortex – an update: time is of the essence. Neuron. 2001;30(2):319-33.
13/18
What is the likely neural substrate for antiseizure effects demonstrated by VNS Therapy™?
The hippocampus
The vagal afferent network
The sympathetic autonomic nervous system
Cortical motor neurons
The following information is based primarily on animal research and provides an overview of how VNS Therapy™ is believed to have anti-seizure effects on the brain. 1. Hachem LD et al. The vagus afferent network: emerging role in translational connectomics. Neurosurg Focus. 2018;45(3):E2.
The vagal afferent network1
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Laxer KD et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav. 2014;37:59-70. Edwards JC et al. Marginal decision-making in the treatment of refractory epilepsy. J Med Econ. 2018;21(5):438-42.
Did you know? The Scheduled Programming option in SenTiva™ (LivaNova, London, UK) enables patients to follow a programmed titration schedule towards a target dose range and can decrease the number of required in-person programming visits.¹ LivaNova USA Inc. VNS Therapy™ Product Manuals. 2020. Available at: https://www.livanova.com/epilepsy-vnstherapy/en-us/hcp/product-manuals. Last accessed: 26 March 2026.
Clarify expectations of the treatment team Develop and utilise a treatment algorithm for identifying and treating DRE Educate patients
Clarify roles for all members of the treatment team Identify key office staff to: Document patient eligibility Coordinate with the multidisciplinary team Adjust VNS Therapy™ dose and programming Field patient calls
Set clear family expectations related to: Clinical outcomes Dose adjustments and response optimisation Postoperative complications Stimulation-related side effects Medication use and/or dose QoL
Implementing VNS Therapy™ in Your Practice
Therapy to address DRE should be considered early to reduce patient exposure to risks and morbidity.1,2
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It is critical that patients/families understand the procedure, its risks, the course of therapy, and potential side effects/benefits, including:
In children treated with VNS Therapy™, some experienced fewer, shorter, and less intense seizures, as well as improved post-ictal recovery.1,2 The benefits of VNS Therapy™ are not always seen right away. In fact, seizure activity may improve slowly over the first 2 years of treatment.3
Infection is the most common complication of the surgical procedure. Overall, there were 525 events of infection reported to the FDA over approximately 7 years (1 July 1997–8 October 2004) in 32,065 device implants with 80,144 device-years of implant experience (incidence rate of infection per device-years of implant experience=0.66).4
Children (<12 years of age) may have a greater risk for infection when compared to adolescent and adult patients (≥12 years of age). Careful monitoring for site infection, as well as the avoidance of manipulation of the surgical site post-implant in children should be stressed.4
Adjustments to stimulation parameters will be needed to optimise the response.4
The most common side effects of VNS Therapy™ stimulation include: Voice alteration/hoarseness Increased coughing Sore throat The most common side effects of VNS Therapy™ typically occur only during stimulation and generally become less noticeable over time for most patients. Infection is the most common complication of the surgical procedure.
VNS Therapy™ may help to reduce the dosage of ASMs. Some studies have also shown the number of ASMs may decrease in some patients. VNS Therapy™ can improve quality of life for some patients, including an improved feeling of well-being, improved mood, and improved alertness, memory, and thinking skills.
Prickling or tingling of the skin Shortness of breath
Kawai K et al. Outcome of vagus nerve stimulation for drug-resistant epilepsy: the first three years of a prospective Japanese registry. Epileptic Disord. 2018;19:327-38. Orosz I et al. Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children. Epilepsia. 2014;55(1):1576-84. LivaNova USA Inc. VNS Therapy™ Patient's guide for epilepsy. 2025. Available at: https://www.emjreviews.com/wp-content/uploads/2026/09/Epilepsy-Patient-Guide-US.pdf. Last accessed: 10 September 2026. LivaNova USA Inc. VNS Therapy™ Product Manuals. 2020. Available at: https://www.livanova.com/epilepsy-vnstherapy/en-us/hcp/product-manuals. Last accessed: 26 March 2026.
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VNS Therapy™ Implantation and Follow-up
Placement and optimisation of VNS Therapy™ parameters
Clinical follow-up post VNS Therapy™ implantation
VNS Therapy™ was implanted and adjusted to achieve optimal benefit. Current parameter adjustment settings:
Family was eager to decrease seizure medication Patient weaned off brivaracetam 6 months post-implantation Remained seizure-free for 11 months post-implantation before having a breakthrough seizure At 10 years of age, 2 years post-implantation On oxcarbazepine monotherapy Has been seizure-free for the past 11 months Seizure worry has decreased
Did you know? Optimising VNS Therapy™ parameters is critical to achieving the best patient outcomes.1,2 Target output current range is 1.50–2.25 mA.1 Continue to optimise dose to target dose range or tolerability and give the patient time to adapt to parameter changes.1 Livanova. VNS Therapy System Epilepsy Physician's Manual. 2025. Available at: https://dynamic.livanova.com/. Last accessed: 13 May 2026 Tzadok M et al. Rapid titration of VNS therapy reduces time-to-response in epilepsy. Epilepsy Behav. 2022;134:108861.
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What outcomes may patients experience after the implantation of VNS Therapy™? (Select all which apply)
Reduction in seizure frequency
Bell shaped curve result between VNS total charge delivered and increased response rate
Increased need for ASMs
Potential post-implantation infection
Did you know? In paediatric patients, VNS Therapy™ can result in meaningful reductions in seizure frequency that may improve over time.1 In children treated with VNS Therapy™, some children experienced fewer seizures, shorter seizures, and improved recovery after seizures.2 Englot DJ et al. Efficacy of vagus nerve stimulation for epilepsy by patient age, epilepsy duration, and seizure type. Neurosurg Clin N Am. 2011;22(4):443-v. Orosz I et al. Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children. Epilepsia. 2014;55(1):1576-84.
SUBMIT
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Review the patient’s therapeutic journey to date and educate them on the successes and failures Discuss clinical practice recommendations for the treatment of DRE Discuss the implications of inadequately treated seizures Educate parents and their caregivers about the treatment options that could benefit them
Key Takeaways
When considering VNS Therapy™ for the treatment of DRE…
Implement a therapeutic rationale that acknowledges the unique set of treatment challenges posed by paediatric patients.
Establish an open dialogue with the patient and their family
Educate patients and their families/caregivers about the VNS Therapy™ option
Clearly define the roles of the healthcare team in the support process.
Review the surgical procedure, including risks and long-term outcomes Establish realistic expectations for clinical outcomes and the potential for side effects Ensure that patients and caregivers understand that stimulation dose adjustments will be needed to optimise response to VNS Therapy™
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