An Overview of Neuromodulation Devices for Migraine Treatment With Dr Stewart Tepper

In Part 1 of this podcast, Neurology Learning Network Section Editor Dr Stewart Tepper, MD, Professor of Neurology, Geisel School of Medicine, Director, Dartmouth Headache Center, gives an overview of the 5 types of neuromodulation devices approved by the FDA and describes their use in treating migraines. 

Heather Flint: Hello Neurology Learning Network. I'm your senior digital managing editor, Heather Flint. And I am joined today by Dr. Stewart Tepper. And we're going to discuss migraine treatments and neuromodulation devices. Dr. Tepper, if you can introduce yourself, please.

Dr Stewart Tepper: Hello, I'm Stewart Tepper. I'm a professor of neurology at Dartmouth and I'm director of the Dartmouth Headache Center in New Hampshire.

Heather Flint: Thank you so much for being here today. I wanted to just have you, if you could briefly describe for us what a noninvasive neuromodulation device is and how it can be used in treatment of migraines.

Dr Stewart Tepper: These are portable devices that change the way the brain perceives pain in primary headache disorders. They are cleared by the FDA for various indications, which we'll talk about, and they activate inhibitory pathways within the brain from different access points outside the skull. Some of them are electrical, some of them are magnetic, and most of them have a designation or are in the process of obtaining a designation from the FDA as nonsignificant risk devices, and patients apply them and activate them for varying periods of time, either daily or on an as needed basis for either the prevention of headache disorders or the acute termination of a particular headache.

Heather Flint: Excellent. And now I guess the practical issues around these devices seem to be that you said they were nonsignificant. So I guess there's no medication being put through, so they're not altering any sort of state. You can conduct your daily activities with this, and it's a portable device. So it doesn't kind of hinder or inhibit your daily activities, is that correct?

Dr Stewart Tepper: Some of them are more convenient than others. For example, the noninvasive vagal nerve stimulator is a device, which is placed on the neck and the patient has to apply gel to 2 electrodes. And when the device is activated, it's turned on for 2 minutes at a time during which time the lateral aspect of the lip may be twitching. It's probably not something you're going to do in the middle of a meeting at work, although it could certainly be done discretely in a bathroom or in a private room. Other devices, such as the remote electrical neuromodulation device, are placed on the arm, activated with a smartphone, and this can be done under a shirt and could actually be activated during a meeting. So, it really depends on the device and on the nature, what somebody is doing, but yes, people in general can go about their business while these devices are activated.

Heather Flint: Oh, excellent. And when we're talking about the devices, there seem to be 5 typical devices used. I think, you just talked about 2 specifically. What are the other devices, the other ways that they work?

Dr Stewart Tepper: Well, why don't I just go through them in the order at which the FDA cleared them. The first device is the external trigeminal neurostimulator is called the Cefaly device, and it's placed on the forehead and it snaps onto an electrode, which is placed on the forehead. And this device is FDA cleared for prevention of migraine and for acute treatment of migraine. The second cleared device was a single pulse transcranial magnetic stimulator, which is marketed as sTMS mini. And that's a device about the size of a small shoebox, and it's a magnet that's placed at the back of the head and then pulsed, it pulses very quickly. And it is also FDA cleared for both preventive and acute treatment of migraine.

That third device is what I alluded to, which is the noninvasive vagal nerve stimulator, which is called gammaCore. And the gammaCore is FDA cleared for prevention of migraine and acute treatment of migraine. It's also FDA cleared for the acute treatment of episodic cluster headache for the adjunctive treatment to prevent all kinds of cluster headache. And it's also cleared for the treatment of 2  trigeminal autonomic cephalalgias hemicrania continua, and paroxysmal hemicrania. The fourth device is the remote electrical neuromodulation device that I talked about, which is called Nerivio. That's the one that goes on the arm. That's FDA cleared at this time, only for the acute treatment of migraine. And then the final device, which is being rolled out gradually this year is a combine trigeminal and occipital neuro stimulator or neuromodulation device that's FDA cleared for the acute treatment of migraine. And that has the brand name Relivion.

Heather Flint: So, Dr. Tepper, can you give us an overview of the mechanism of action for each of these devices?

Dr Stewart Tepper: We don't know 100%, but one way to think about this as a neurologist is that you're inhibiting central pain pathways through peripheral access. And each one of these has slightly different peripheral access. The external trigeminal neurostimulator inhibits pathways coming in on the super orbital and supratrochlear nerves, which are branches of the first division of the trigeminal nerve, the ophthalmic division. Patients will feel paresthesias on the forehead as this device is activated. My thought about this is that coming in on the ophthalmic division in an inhibitory way, we know what's going to happen. We know that signal's going to go in through the trigeminal ganglia, it's going to come into central pathways, it's going to go down to the trigeminal cervical complex. And my thought is that it's through that system that the inhibition of pain occurs, especially in migraine, in the trigeminal cervical complex. The second one, the single pulse transcranial magnetic stimulator pulses a magnet and this magnet—magnetic wave—terminates cortical spreading depolarization, which is the mechanism for aura.

And in fact, it was originally studied in only in migraine with aura, but it also has an inhibitory effect on the thalamus and that inhibitory effect on the switching center for all sensory processes appears to be the way that it gradually down regulates the frequency of primary headache disorders, especially migraine. And the actual wave does not go any further forward than the thalamus or below the neck. And so the National Health Service in the UK actually gave it an okay for use in pregnancy because it has such a limited area of stimulation. The noninvasive vagal nerve stimulator, the one on the neck, also has thalamic inhibitory effect, and it ascends on afferent fibers of the vagus to the thalamus and turns down the thalamus—the thalamic pain pathways—it modulates them. It also interrupts cortical spreading depolarization. So in some ways, even though it's coming in a completely different way with a completely different energy modality, it's doing very similar things to the single pulse transcranial magnetic stimulator.

The remote electrical neuromodulation device is very interesting. It uses something called the condition pain modulation reflex, which is a nociceptive reflex, even though it doesn't hurt, it's a nociceptive reflex that goes up to the brain stem and then inhibits descending pain pathways, maybe as high up as the periaqueductal gray and as low as the rostral ventral medulla. But this condition pain modulation reflex, which was also called diffuse nociceptive inhibitory control or DNIC was specifically sought for this device in which nociceptive afferents in location A will inhibit pain in location B. Very, very clever design.

And then finally the last device, the combined occipital and trigeminal neurostimulator, that one works exactly the same as the external trigeminal neuro stimulator, but which goes in on the ophthalmic division, but also inhibits through the greater occipital nerves, which are cervical derived. And remember both of those afferent pathways end up in the trigeminal cervical complex. Though you can see how each of these actually gets in and works at areas of pain control. And remember neuromodulation is not always neuro termination. So these gradually modulate central pain pathways, peripheral access, and then central benefit.

Heather Flint: Excellent. Well, thank you. It's great to get a really just like I said, a giant comprehensive overview of how everything works and the best ways to implement them with patient care is very important. And I know this was a big topic of discussion at the recent migraine summit, and there were some presentations on these devices and how beneficial they can be. So I appreciate the follow up here and kind of giving a broader scope to the audience on that.

Stewart Tepper, MD, is a professor of Neurology at the Geisel School of Medicine at Dartmouth, Director of the Dartmouth Headache Center, and a board member at large of the American Headache Society.