NeuroVoices: Cornelia Drees, MD, on Understanding the Different Advantages of Microburst Vagus Nerve Stimulation

Cornelia Drees, MD

This is a 2-part interview. Click here for part 1.

Vagus nerve stimulation (VNS) is an FDA-approved treatment approach for patients with focal or partial seizures that do not respond to antiseizure medications (ASMs). The therapy typically consists of a device that is implanted under the skin in the left chest area, with an electrode or wire attached to the generator around the vagus nerve in the neck. The device is programmed in the outpatient clinic to deliver pulses or stimulation at regular intervals, and has become increasingly popular as an option for drug-resistant epilepsy for years.

A newer approach, microburst stimulation VNS, uses high-frequency bursts that are believed to be more tolerable and efficacious than standard VNS therapy. In a recently published prospective, unblinded study of 32 individuals with either refractory focal or generalized epilepsy with tonic-clonic convulsions, treatment with the therapy resulted in significant seizure reduction and improvements in quality of life. At 12 months, overall seizure severity decreased in 70% of all individuals (21 of 30), and median ASM drug load decreased by 10%.

Lead investigator Cornelia Drees, MD, sat down to discuss the findings, as well as the potential therapeutic benefit of microburst VNS. Drees, a senior associate consultant in the Department of Neurology at Mayo Clinic, provided perspective on the flexibility of this approach, how it differs from traditional VNS, and whether traditional guidelines can be used to treat patients.

NeurologyLive®: How does microburst VNS differ from traditional VNS?

Cornelia Drees, MD: It’s the same looking device, the same container, but the stimulation that is provided with a standard vagus nerve stimulator is in the range of 1-30 Hz. With microburst stimulation, the stimulation frequency is between 100-300 Hz, and it's delivered in short bursts, 2-7 pulses that are interrupted or alternating with stimulation-free periods. It's basically a repetitive firing of bursts, followed by quietness and repetitive firing, and then an off time, whereas standard VNS stimulate for the whole on time, and then it's followed by an off time.

That is in terms of the treatment. One of the novelties of the study assessing the feasibility of this kind of treatment was that the treatment effect was measured in a functional MRI. The concern that people usually have is that you cannot even stimulate within an MRI. This time, a functional MRI was monitoring the treatment effect, the stimulation effect. The stimulation effect, especially the blood flow changes within the thalamus, were used to find or determine the stimulation settings.

Are there complexities with understanding the rate of bursts a patient should receive?

Why is it used at all? Because it has shown more effect on seizure frequency and seizure occurrence in animals, including rodents as well as monkeys. That was basically the impetus to try to look at that effect in humans. The ability to change the microbursts settings are very similar to what is done with standard VNS settings.

In the study, which did not include a control group, we got into a bit of a bind. If you use functional MRI to determine the optimal settings, by looking at whether the functional MRI showed peak activation of blood flow in the thalamus, then why would you change afterwards? How could you possibly improve on something that you try to determine with an imaging correlate, functional MRI?

In the study, we ended up having adjusting patients based on their current, not usually in terms of the microburst frequency that was used or determined during the functional MRI. That was done if the person continued to have seizures, whereas people who didn't have seizures often didn't have any changes to their stimulation settings. But it would also be possible [to change these settings]. It would be possible to change current frequency stimulation on and off times with any standard VNS. That would be the same in terms of the options.

Are there consensus guidelines you and your colleagues follow?

Typically, you start with default settings that come with VNS: 30 seconds ON, 5 minutes OFF, 30 hz frequency stimulation for 30 seconds with a pulse width of 500 microseconds and that you can alter depending on the level of discomfort that the patient has. In terms of a therapeutic effect, you increase the settings to maybe between 1.5 and 2.0 milliamps and you may change the duty cycle to more ON time and less OFF time. There are patterns for following steps if patients continue to have seizures or continue to have discomfort. It's not guidelines. It's just suggestions that are commonly used.

Transcript edited for clarity.