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The director of the Epilepsy Center at Cleveland Clinic spoke about the use of deep brain stimulation for the treatment of refractory epilepsy, and who the ideal candidate is for implantation.
Imad Najm, MD
Recently, neuromodulation has taken a step in the field of epilepsy. In May 2018, Medtronic’s deep brain stimulation (DBS) therapy was approved by the FDA for the adjunctive treatment for patients with focal epilepsy who fail multiple antiepileptic medications, adding to the options physicians have for addressing refractory patients.
Although, now the question of candidacy for these devices has become a discussion in some circles. To provide additional insight into the process that leads to the selection of candidacy for DBS, NeurologyLive sat with Imad Najm, MD, the director of the Epilepsy Center at Cleveland Clinic, at the American Epilepsy Society’s annual meeting in New Orleans, Louisiana.
Najm explained that there is a protocol in place for deciding on who is a proper candidate for DBS, and provided some insight into the other options for neuromodulation and what some of the clinical trial data have shown.
Imad Najm, MD: This technique, or this method, of simulating a small area of the brain has been shown in clinical trials to decrease the frequency of seizures over time, and then in some other situations, to get our patients to be seizure-free. Now, the big question that comes up is: Who would be a very good, or a good, candidate for the placement of deep brain simulation electrodes? There is a protocol that we are all following that includes a process that would lead to the selection of these patients.
DBS has been approved in epilepsy as an adjunctive treatment for these patients who fail multiple antiepileptic medications. That is the first criteria in the selection of these patients for candidacy for DBS. Second, these patients who may be candidate for DBS should show that they have focal epilepsy—epilepsy coming from a particular area of the brain or multiple areas on the brain—and these patients should have undergone an extensive evaluation that would include an MRI to look for a possible lesion or lesions that would explain why this patient may have had or may be having these seizures. We may also do other studies that will include a PET scan looking for hypometabolic areas, an area of dysfunction within the brain, and in some situations, they undergo an ictal SPECT, looking for the pathways or the networks that are activated during a seizure. And, if available a MEG, or magnetic encephalography, test that will help us localize this 3-dimensional space where the epileptic area is.
Based on these results, a discussion should be held, what we call a multi-disciplinary patient management confidence—including the neurologists, the neurosurgeons, the radiologist, nuclear medicine specialists, MEG specialists, psychologists, psychiatrists, and social workers—to discuss all of the data in the context of the patient's history of epilepsy. Based on this discussion, there may be various outcomes. The first, that the patient should undergo, or is clear to undergo, resective surgery—taking or ablating one part of the brain that is suspected to be the pacemaker of the seizures. Or, that could be that the patient needs further evaluation and then the situation, intracranial electrodes will be placed.
The most commonly used one in the world is what you call SEEG, or stereotactically implanted EEG depth electrodes. The goal from this is to find out if we can further pinpoint the area of epileptic activity, and to assess how safe it is for us to take it out. If the results of this evaluation show a distinct seizure-onset area, and we show that it is relatively safe to take that particular region, a surgery or resective surgery will be done.
If the patient is deemed to be not a resective surgery candidate, we start to consider other treatment modalities. One of them would be vagus nerve stimulation—it's been available since the late 1990s in this country, with mixed results. Our second one would be responsive neurostimulation, which consists of placing an electrode on the area suspected to be in the epileptic focus or the pacemaker of the seizures, linking it to a smart recording system that’s connected to a live analysis of the EEG patterns. Then, when the seizure is detected, it will blast electricity to try to shut down the seizure activity.
The newest treatment modality that is approved as an adjunctive treatment in patients with medically intractable epilepsy is the DBS of a structure that is called the anterior nucleus of the thalamus. It’s deep inside the brain. The thalamus is like the Grand Central Station of the brain—it gets information from everywhere in the body and then sends it everywhere in the brain, and vice versa. Therefore, this is a strategic location for the placement of electrodes—2 electrodes—1 on the left and 1 on the right, to connect from one single area to the rest of the brain and to deliver a repetitive stimulation that will somehow modulate and change the behavior of neurons in the rest of the brain to be better, and therefore, to make these neurons in the brain less excitable and less prone to fire an uncontrolled manner. That's basically the principle of DBS.
We should expect some decrease in seizure frequency, and a small number of these patients may become seizure-free, which is basically our Holy Grail. This is our major goal, to shut down the seizures. This is based on the clinical trials, but obviously, we don't have after-market experience in DBS because it just got approved. Who are the candidates for this? Patients who failed antiepileptic medication, patients who underwent a presurgical evaluation, who are not deemed to be a resective surgical candidate, and who are not candidates for responsive neurostimulation.
Now, an interesting fact about what we learned from the data that was acquired during clinical trials and after the clinical trials continued to follow these patients is that something seemed to be happening here with these patients. With time, their seizures were getting under better control, which is the opposite of what we would see with medication. With time, patients with on the deep brain stimulator seem to be getting better. How long is that going be the case? We don't know. Is it going to be a continuous process over 5, 10, or 15 years? We don't know.
But this will give us hope in patients in whom we implant these this device and, early on, don’t have very encouraging results. There is hope that, in the future things will get better, and we will have a neuromodulatory effect that is building up in the brain, leading to less excitation and less firing in the brain and, therefore, fewer seizures coming from the epileptic focus area.
Transcript edited for clarity.