Device neuromodulation therapy is creating a new level of treatment personalization for patients with drug-resistant epilepsy who are not candidates for surgical resection.
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Specialists with the Epilepsy Center at Cleveland Clinic in Florida use vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) separately or in combination to offer seizure relief for patients with generalized seizures, multifocal seizures, or seizures originating near the eloquent cortex.
Approximately 30% of the 3.4 million people with epilepsy nationwide have intractable or drug-resistant epilepsy. These individuals have tried two or more appropriately selected and managed anti-epileptic drugs (AEDs) but failed to achieve seizure control.
“Many of these patients may be candidates for resective surgery, which is the most effective treatment for drug-resistant focal epilepsy and provides the best chance for achieving seizure freedom,” says Camilo Garcia,MD, a board-certified epileptologist with the Level IV epilepsy center based in Weston, Florida.
At Cleveland Clinic, about 60% of patients who undergo epilepsy surgery achieve long-term seizure freedom, while others obtain clinically meaningful quality-of-life gains.
“Over the past 25 years neuromodulation technology has been developed to provide relief for patients that cannot be successfully treated with medication or surgical resection,” explains Dr. Garcia. “In the last three years we’ve begun combining these innovative therapies to further help patients who continue to struggle with persistent seizures.”
VNS therapy received FDA approval in 1997 and is the oldest neuromodulation therapy for drug-resistant epilepsy. It is used for reducing the frequency of partial onset seizures that are refractory to AEDs. More than 125,000 patients have been implanted with the therapy worldwide.
The VNS system consists of an implantable pulse generator, which is placed subcutaneously in the chest, a lead that is cuffed around the vagus nerve at the neck, and an external programming system. It works by delivering continuous, intermittent electrical stimulation to the vagus nerve, with settings that can be customized for individual patients.
“About 40-50% of our patients with VNS have a seizure reduction of 50% or more, but less than 5% become seizure-free,” says Dr. Garcia. “When successful, VNS provides a quicker recovery from seizures than other stimulation therapies.”
RNS received FDA approval in 2013 and operates much like a heart pacemaker. The device is implanted in the skull and attached to one or two leads placed at seizure foci. The closed-loop system senses abnormal electrical activity which triggers modulating impulses in an attempt to stop a seizure or suspected seizure.
“We use RNS for patients with two epileptogenic foci, usually in the temporal lobes, hippocampi, or eloquent regions of the brain that control movement or speech,” explains Dr. Garcia. “Patients who respond to this therapy can experience a gradual improvement in seizure activity over the course of months and years.”
According to initial and long-term clinical studies, the median reduction in seizure frequency with RNS was 44% at 1 year and 53% at 2 years (Heck et al., 2014), increasing to 75% by year 9 (Nair and Morrell, 2018).
In addition to being a palliative procedure, Dr. Garcia notes that because the device records electrical activity, “We are able to quantify the number of seizures for each focal area. It can then become a bridge to resection surgery in select cases when one area is the dominant source of seizure activity,” he says.
Most recently, in 2018, the FDA approved the use of DBS therapy for focal epilepsy. In DBS, electrodes are typically placed in the anterior nucleus of the thalamus, an area of the brain that serves as a relay station for neural activity. They are attached to a pulse generator that is implanted underneath the skin below the collarbone.
“Like VNS, DBS uses continuous, intermittent electrical stimulation that is programmed to the individual patient,” says Dr. Garcia.
Long-term efficacy data from the SANTE trial found the median percent seizure reduction increased from 41% at 1 year to 69% at 5 years. “As with RNS, patients treated with DBS can experience long-term improvements, though very few achieve seizure freedom,” he says.
Despite the growing armamentarium for intractable epilepsy, seizure-freedom continues to elude a subset of patients. In recent years the epilepsy specialists at Cleveland Clinic in Florida have begun combining neuromodulation device therapies in select cases.
“We see patients who are actively treated with VNS but continue to experience life-impacting seizures,” says Dr. Garcia. “In some cases they may have dual pathologies that need to be addressed individually.”
Dr. Garcia points out that because the current neuromodulation devices use different mechanisms to alter abnormal brain activity, it is possible to combine them in a more tailored approach. “Today we have patients being treated with both VNS-RNS and VNS-DBS combo therapies,” he says.
Each surgical candidate at Cleveland Clinic is reviewed during a Patient Management Conference by a multidisciplinary team of specialists in radiology, nuclear medicine, neurosurgery and epileptology from across the Cleveland Clinic enterprise, including Florida and the main campus in Ohio.
“We use data gained from stereoelectroencephalography (SEEG), a minimally invasive surgical procedure, to help determine who is a surgical candidate and which type of procedure would work best,” says Dr. Garcia, noting the team uses a stereotactic robot to place the electrodes in the brain with great accuracy.
“Our Epilepsy Monitoring Unit captures data over the course of a week to localize the seizure source which is essential to choosing the right neuromodulation therapy,” he adds.
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