Overview

Epilepsy is a common neurological disorder affecting nearly 70 million people worldwide, often causing significant impairment to cognitive and memory function, leading to reduced quality of life.¹ Temporal lobe epilepsy is a form of epilepsy originating from the temporal lobe of the brain, affecting over 50 million people. 

Existing treatments termed anti-seizure medication (ASM) work to reduce the spread of the seizure activity through pharmacological intervention, but are refractory in about 30-40% of patients. The next solution would be surgery, to remove regions of the brain in which seizures originate; it is an irreversible procedure that carries significant risk.¹ 

Vagal nerve stimulation (VNS) is a potent antiepileptic therapy option that is minimally invasive and effective.² This article will explore VNS for temporal lobe epilepsy further, delving into the mechanism, clinical application, and potential side effects of this therapy. 

What is temporal lobe epilepsy

You might see the terms seizure and epilepsy referenced throughout this article, so to quickly clarify: 

• A seizure is a single event resulting from a burst of uncontrolled signals between neurons in the brain
• A convulsion is a rapid, uncontrolled muscle contraction that is common in epileptic seizures
• Epilepsy is a condition that involves multiple seizure events

Temporal lobe epilepsy is the most common form of seizure that originates from the temporal lobe region of the brain. It can be further subdivided into two categories:³

• Mesial Temporal Lobe Epilepsy (MTLE): This form is the most common type of temporal lobe seizures and involves regions of the temporal lobe that are at the innermost part of this structure, including the hippocampus, parahippocampal gyrus, and the amygdala. This form is often found in individuals who have also experienced hippocampal sclerosis (a loss of neurons in the hippocampus)
• Lateral Temporal Lobe Epilepsy (LTLE), a.k.a neocortical temporal lobe seizures: Very rare and are a result of genetic or acquired lesions within the temporal lobe of the brain

Seizures are thought to arise within the temporal lobe due to an imbalance of neurotransmitters, specifically, the overactivity of the stimulatory neurotransmitter glutamate and/or the underactivity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).¹ 

Notably, approximately 60% of all forms of epilepsy originate with a focal region (i.e., specific area within the brain where the effects are most prominent). Of this, a majority originate in the temporal lobe.⁴ 

The most common pathological finding in patients with temporal lobe epilepsy is hippocampal sclerosis. In this condition, neurons within the hippocampus, particularly in the region known as the hilus, undergo atrophy. This neuronal loss contributes to an imbalance of neurotransmitters, which may promote seizure activity.

What is vagus nerve stimulation?

The vagus nerve is often referred to as the ‘sixth sense’ and is a central component of interoception: sensing what is happening inside your body, including feelings of hunger, heart rate and how full one's bladder is.^1,2,5

The vagus nerve is also a major constituent of the autonomic nervous system. This nerve pathway has vital functions in regulating the balance of many bodily functions without conscious thought, such as metabolism, immune function, and heart rate. 

It is composed of two types of fibres: 

• Efferent: Making up 20% of the vagus nerve, these fibres send information from the brain to the body. E.g., to dampen the sensation of pain when you touch something hot
• Afferent: These ‘sensory’ fibres make up 80% of the vagus nerve. These carry information from the body to the brain. E.g., these nerves can detect nutrients in food and drinks to inform the brain of the body's requirements

Importantly, the vagus nerve acts as a key regulator of the parasympathetic nervous system, opposing the sympathetic nervous system. As part of the “rest and digest” response that promotes relaxation.⁵ 

Mechanism of action of vagus nerve stimulation

Neurostimulation mechanisms

As mentioned earlier, around 30-40% of people with seizures have refractory effects to ASM. Neuromodulation-based interventions are considered for these patients whose seizures are inadequately controlled. 

Additionally, compared to neurosurgical intervention, which removes the brain region at the focal point of the seizures, VNS offers a much reduced risk therapeutic option with much fewer complications for the person.⁵

The VNS is delivered through a neurocybernetic prosthesis, which is a surgically implanted device that has electrodes and is placed on the left cervical vagus nerve.⁶ And yes, with “cybernetic” in the name, having one technically makes you a cyborg (in a cool way, of course). This device provides intermittent stimulation of the vagus nerve. 

What are the seizure control settings of VNS?

Studies have shown that the anticonvulsant effects of VNS lasted at least four times the duration of the stimulation.¹ In these studies, the suggested maximum protection from seizures was achieved when stimuli were given periodically at 20-30 Hz. Most patients who currently have VNS are stimulated at 30Hz with a constant stimulation cycle of 30 seconds on and 5 minutes off. 

Indications and patient selection

Criteria for VNS therapy

The first generation of vagus nerve stimulators was developed by Dr Jacob Zabara and Terry Reese in 1987 via their company Cyberonics. The first VNS implanted, the Neurocybernetic prosthesis, was in 1988 by Dr. William Bell.⁷

Following their success, the United States Food and Drug Administration (FDA) approved VNS as an adjunctive therapy to adults and adolescents (12 years and older) who experienced partial-onset seizures and refraction to antiepileptic drugs. 

Currently, the FDA has expanded these criteria and allowed patients 4 years and older to be fitted with VNS. In 2012, 20 years following its original approval, more than 100,000 people had been implanted with VNS.² 

Contraindications and cautions

There are several conditions that may exclude a person's suitability for VNS. These include:⁸

• Active cancer or recent cancer remission: The vagus nerve regulates the immune system and dampens it. Therefore, stimulation of the immune system in a person with cancer or who has recently achieved cancer remission would reduce the immune system's capacity to contain cancer and reduce its spread/return
• Low blood pressure: The vagus nerve, part of the parasympathetic nervous system, reduces blood pressure through adrenergic receptors. VNS stimulation could result in lower-than-normal blood pressure, leading to side effects such as dizziness and fainting 

Clinical efficacy of VNS for epilepsy treatment

In general, VNS is well tolerated by people with temporal lobe epilepsy and has been shown to have optimal effects around 6 months of treatment:⁵

• The frequency at which seizures occur is reduced by 50-100% in ~45-65% of patients
• One study found on average a 55.6% reduction in seizures after 1 year, with 4 of the patients being seizure-free.⁶ The effectiveness of stimulation-driven seizure treatment increased to 63.2% after 3 years, with 5 patients reporting seizure-free states 
• This study found that the efficiency of VNS increased over time following implantation of the neurocybernetic prosthesis, with early exposure improving prognosis 

Comparison with other treatment options

Anti-epileptic drugs (AEDs)

Following the diagnosis of temporal lobe epilepsy, a person would initially be treated with pharmacological intervention in the form of AEDs. These include:⁴ 

• Phenytoin
• Valproate 
• Lamotrigine
• Levetiracetam 

Though some of the mechanisms by which AEDs work remain elusive, they tend to be grouped into principal modes of action. 

Surgical intervention 

In drug-resistant epilepsy, a temporal lobectomy or temporal lobe resection is undertaken. This neurosurgical procedure removes the front part of the temporal lobe of the brain. This form of treatment is for individuals who have tried several anti-seizure medications but experience seizures that interfere with daily life. Temporal lobe resection is recommended for individuals who experience focal seizures that originate in the temporal lobe.⁹

Procedure and implementation

The VNS device is made up of a wire and three helical contacts, and a one-pin battery.⁷ The stimulator is implanted on the left side of the chest to avoid the cardiac (heart) side. This procedure is known as anterior cervical discectomy.⁹ Following the procedure, VNS is usually started 2 weeks after.¹⁰

Post-implantation care and adjustments

Follow-up care after VNS installation includes:⁹

• Keeping the incision site clean and dry to prevent infections from occurring
• Avoiding overly strenuous activity and heavy lifting for several weeks post-operation
• Ensuring to follow doctors/healthcare professionals' advice and report any swelling, pus discharge or signs of infection immediately 

Side effects and complications

As mentioned earlier, 80% of the vagus nerve fibres are afferent and carry information to the brain rather than the body. However, the VNS device stimulates the left mid-cervical vagus nerve, which may result in:^3,10

• Voice alterations
• Cough 
• Dyspnea (shortness of breath)
• Dysphagia (difficulty swallowing)
• Neck pain or paresthesias (abnormal tickling sensation described as ‘pins and needles’)

Managing side effects

The reported side effects of VNS are mostly stimulation-related and are experienced for a very short intermittent time. 

Future directions and research

Through many successful applications of VNS, its clinical potential has gained greater appreciation. Though its initial development was for the treatment of AED-resistant epilepsy, it has expanded and gained approval/clearance in the treatment of medication-refractory epilepsy, treatment-resistant depression, obesity, and post-stroke motor rehabilitation.^11,12

FAQs

Can vagus nerve stimulation treat epilepsy?

Yes, it has shown to be an effective treatment with a majority of patients showing 50-100% reduction in seizure events.

What are the VNS settings for epilepsy?

The maximum level of protection from seizures was achieved when stimuli were delivered periodically at 20-30Hz. Most patients receive VNS at 30Hz in a cycle of 30 seconds on and 5 minutes off. 

Is VNS funded by the NHS?

Yes. You can read more about this in their epilepsy treatment policy report. 

Summary

Vagus nerve stimulation, a neuromodulation therapy, offers a minimally invasive, highly effective and manageable form of treatment for individuals experiencing drug treatment-resistant temporal lobe epilepsy. Through the implantation of a neurocybernetic prosthesis, a stimulation is provided to the efferent fibres of the vagus nerve, resulting in the dampening of seizure activity in the brain. This form of treatment for temporal lobe epilepsy has been shown to reduce seizures by 50% to even complete absence. Due to this success, VNS is being explored in clinical trials to treat other major neurological conditions such as treatment-resistant depression and post-stroke rehabilitation.