Clinical Topics & News

Neuromodulation Strategies for Seizure Control

Vijay Thadani, MD
Dr. Thadani is Professor of Neurology at Geisel School of Medicine at Dartmouth, at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire.


 

References

A number of different neuromodulation strategies have been used to try to control epileptic seizures. The fundamental idea is that since epileptic seizures are an electrical phenomenon in the brain, by changing the electricity of the brain one should, in principle, be able to prevent or abort seizures. This has been attempted in a number of ways.

The first modern attempt goes back to the late 1960s and early 1970s. Working on the principle that the output of the cerebellum is principally inhibitory in character, eminent neurosurgeon Irving Cooper theorized that stimulating the cerebellum, and thus presumably increasing its output, would have an inhibitory effect on the rest of the brain and thus reduce seizures. He implanted a number of people with cerebellar stimulators that delivered chronic stimulation to the cerebellum. It is possible that some of those patients did show some improvement in seizure control, but by and large that approach has not really caught on or been shown to be particularly effective.

Going on from there, a number of other approaches have been tried. In more modern times one very important idea has been the vagal nerve stimulator. This device is commercially available. It is implanted under the patient’s clavicle and the left vagus nerve is stimulated on a chronic intermittent basis. Through the vagus nerve one influences the brain stem and the nucleus of the tractus solitarius, from where there are projections diffusely, particularly to the frontal lobes. The idea is that intermittent stimulation of the vagus nerve will gradually dampen abnormal electrical activity in the brain and reduce the likelihood of seizures. This has been shown to be a safe and effective device. This is indirect stimulation of the brain done on a regular intermittent basis, unrelated to the patient’s seizure activity.

There are also approaches for direct brain stimulation. A major trial involving chronic stimulation of the thalamus was carried out recently. The goal was altering thalamic cortical connections and down-regulating seizure activity. This large trial, using a Medtronic stimulator, showed moderate effectiveness but was not felt to be effective enough to warrant FDA approval. It is, however, approved as a seizure-control device in Europe.

Both the vagus nerve stimulator and the thalamic stimulator are devices that deliver current to the brain on a regular schedule with the goal of altering the electrical milieu. By analogy with the heart, they are akin to pace-maker devices. A different approach would be, again by analogy with the heart, a defibrillator approach that would both detect a seizure and then deliver a counter-shock to stop it. That is also being done now.

The NeuroPace device essentially works like a defibrillator. It is implanted in the skull and wires are run to the site of the seizure focus. The device detects the onset of the seizure and then delivers a counter-shock to abort it. This has shown enough promise in clinical trials that it is now an approved treatment in the United States. Interestingly, it is not yet approved in Europe.

So depending on which side of the Atlantic you are on, you can get your brain stimulated either regularly or on an as-needed basis. That’s where we stand with regard to approved devices at the moment.

Stimulation with the devices discussed above involves alternating current. The cerebellar stimulators of Irving Cooper, the vagus nerve stimulator, the thalamic stimulator, and the NeuroPace cortical stimulator all deliver alternating current at fairly high frequencies.

There are tests being done using very low amplitude direct current stimulator devices, which would deliver small amounts of current directly in the way that a battery does. Research has been done trying to stimulate the trigeminal nerve with electrodes applied over the eyebrows. This approach delivers low-amperage direct current on a chronic basis, again with the idea of down-regulating electrical activity in the brain. These devices have the advantage being noninvasive. Superficial electrodes are applied to the skin, and then low-amperage currents are run through them using direct current generators. There is no approved device, but pilot trials have shown modest improvements in seizure control.

Not all stimulation is electrical. There are devices being tested using transcranial magnetic stimulation to stimulate the brain. A magnetic stimulus with a rapidly shifting magnetic field delivered to the brain will generate an electrical current in the brain. Using rapidly altering magnetic fields that are transmitted through the skull using a magnetic stimulator, one can stimulate the brain electrically. Several pilot projects have been attempted where magnetic stimulation is given for a few minutes every day or a few hours every week. Again, the goal is to alter the electrical milieu of the brain. Results of these trials have been less promising than direct electrical stimulation of the brain but some improvements in seizure control have been reported. One such device claims to abort migraine headaches.

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