Vagus nerve stimulation

Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. 

It is used as an add-on treatment for certain types of intractable epilepsy and treatment-resistant depression.

VNS is approved as adjunctive therapy for those 4 years of age or older with refractory focal onset seizures. 

VNS is only use following an adequate trial of at least 2 appropriately chosen anti-seizure medications and that the patient is ineligible for epilepsy surgery.

Patients who have poor adherence or tolerance of anti-seizure medications may be good candidates for VNS.

Patients with comorbid depression have mood improvements with VNS therapy.

VNS may provide benefit for particular epilepsy syndromes and seizure types such as Lennox-Gastaut syndrome, tuberous sclerosis complex related epilepsy, refractory absence seizures and atonic seizures.

There are also reports of VNS being successfully utilized in patients with refractory and super-refractory status epilepticus.

A meta-analysis of 74 clinical studies with 3321 patients found that VNS produced an average 51% reduction in seizures after 1 year of therapy.

Response to VNS increases over time:  following 74 patients for 10-17 years found a seizure frequency reduction of 50-90% in 38.4%, 51.4%, 63.6% and 77.8% of patients at 1-, 2-, 10- and 17-years following implantation, respectively.

Approximately, 8% of patients treated with VNS have total resolution of seizures.

VNS reduce rates of sudden unexpected death in epilepsy and to improves quality of life.

Factors that predict a favorable clinical response have been identified including epilepsy onset > 12 years of age, generalized epilepsy type, non-lesional epilepsy, posttraumatic epilepsy and those who have less than a 10 year history of seizures.

VNS for treatment resistant major depression  is approved, effective and well-tolerated long-term therapy.

The vagus nerve is the tenth cranial nerve and arises from a series of rootlets in the medulla; it carries both afferent (80%) and efferent (20%) fibers. 

It has the longest and widest distribution of all the cranial nerves and functions as a bidirectional link between the brain and peripheral organs. 

Afferents from the vagus nerve project to the nucleus tractus solitarii which subsequently communicates with other regions of the brain including the dorsal raphe nucleus, locus coeruleus, amygdala other areas.

VNS results in cortical desynchronization in epilepsy patients who had a favorable clinical response relative to those who did not.

Evidence suggests that inflammation plays a significant role in epilepsy as well as associated neurobehavioral comorbidities such as depression, autism spectrum disorder and cognitive impairment, and VNS has an anti-inflammatory effect through both peripheral and central mechanisms.

VNS can change the activity of several neurotransmitter systems involving serotonin, norepinephrine and GABA, which are involved in both epilepsy and other neuropsychiatric conditions such as depression and anxiety.

VNS may alter the functional connectivity in several brain regions and enhance synaptic plasticity to reduce excitatory activity involved in seizures.

It has also been shown to change the functional connectivity of the default mode network in depressed patients.

Adverse events associated with VNS: (1) those related to the surgical procedure and (2) those related to stimulation. 

Old study surgical complication rate of 8.6%.

The common adverse events included infection in 2.6%, hematoma at the surgical site in 1.9% and vocal cord palsy in 1.4%.

The most common stimulation related side effect at 1 year following implantation are hoarseness in 28% and paraesthesias in the throat-chin region in 12%.

At the third year the rate of stimulation related adverse effects decreased substantially with shortness of breath being the most common and occurring in 3.2%.

VNS is well tolerated and side effects diminish over time. 

There is evidence that VNS can induce sleep apnea in as many as 28% of adult patients.

The device’s generator the size of a matchbox that is implanted under the skin below the person’s collarbone. 

Lead wires from the generator are tunnelled up to the patient’s neck and wrapped around the left vagus nerve at the carotid sheath, where it delivers electrical impulses to the nerve.

Implantation of the VNS device is usually done as an out-patient procedure. 

Once successfully implanted, the generator sends electric impulses to the vagus nerve at regular intervals. 

The left vagus nerve is stimulated rather than the right because the right plays a role in cardiac function such that stimulating it could have negative cardiac effects.

Adjustments include current, frequency, pulse width, and duty cycle.

Wearable devices involve transcutaneous stimulation do not require surgery. 

Electrical impulses are targeted at the auricle of the ear at points where branches of the vagus nerve are close to the surface.

It is non-invasive and based on the rationale that there is vagus nerve distribution on the surface of the ear.

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