Neuromodulation for Epilepsy: What Are the Options and Where Are We Going?

Electrical stimulation is used to modulate brain activity in patients with epilepsy. Specific stimulation parameters in targeted locations have been successful in interfering with pathological activity and in retraining abnormal brain networks over time.

Although widely known for its use in movement disorders, neurostimulation (also called neuromodulation) has an established role in treating refractory epilepsy (drug-resistant to two or more anti-seizure medications). Penn Medicine epilepsy specialists have mastered recent advances in neurostimulation devices to open the door to treatment and hope for even more patients.

The Penn epilepsy team provides the full range of neurostimulatory device options to help reduce seizure frequency and intensity and improve quality of life with epilepsy. With a surgical therapy for almost every patient, Penn providers have much more to offer when anti-seizure medications do not work and surgery to remove or ablate brain tissue is not possible.

Who Can Benefit From a Neurostimulation Device?

Refractory epilepsy occurs in one-third of patients with epilepsy. Once an individual has tried two anti-seizure medications unsuccessfully, Penn specialists consider other treatment options, as the chances of any subsequent medication working becomes vanishingly low.

“At this point, patients should get referred to our epileptologists at Penn for a comprehensive evaluation, and then come to neurosurgery as needed,” says H. Isaac Chen, MD, surgical director of the Penn Epilepsy Center and an assistant professor of neurosurgery.

Neurostimulation for epilepsy may optimally benefit drug-resistant patients who:

  • Are not candidates for resective surgery or laser ablation, for reasons such as involvement of eloquent brain tissue or patient preference
  • Continue to experience seizures after resective surgery or laser ablation
  • Have multiple seizure foci
  • Have generalized epilepsy

Neurostimulation for Epilepsy at Penn

“Here at Penn, we provide the entire breadth of therapeutic epilepsy surgeries available,” says Dr. Chen. He adds that Penn offers every make and model of neurostimulation device, which allows the team to match specific device features with the specific needs of a patient for personalized therapy.

Penn epilepsy specialists have developed a vibrant collaboration with community healthcare centers to provide advanced surgical care to more people. This includes the implantation of the following neurostimulation devices:

“Although we don’t cure seizures with neurostimulation, patients can experience a significant decrease in their seizure frequency,” says Dr. Chen. “That decrease makes a huge difference in terms of their quality of life.”

Vagus Nerve Stimulation (VNS) for Seizure Control

Approved by the Food and Drug Administration (FDA) in 1997, VNS is the oldest neurostimulation approach for epilepsy. The VNS lead wraps around and stimulates the vagus nerve in the neck, powered by a pulse generator implanted in the chest.

VNS projections to the brain work to inhibit seizure activity. Patients can hold a special magnet over the device in their chest if they sense the onset of a seizure to temporarily increase stimulation.

Penn neurosurgeons choose from VNS devices that deliver regular electrical pulses, and from newer models that vary stimulation. The latest option monitors patient vital signs and sends stronger stimulation when it detects increased heart rate, a physiological response associated with the majority of seizure onsets. They also allow Penn neurologists to customize stimulation strength to vary throughout the day based on a patient’s seizure patterns.

“About half of patients will benefit from VNS, with an average decrease in seizure frequency of 50 percent,” says Dr. Chen. “We consider VNS when we want a very minimally invasive, low-burden type of therapy.” The neurosurgery team finds that VNS stimulation best suits patients with generalized seizures and severe neurological deficits.

Responsive Neurostimulation (RNS) with EEG Insights

RNS received FDA approval in 2013 to treat focal epilepsy with one or two seizure foci. With RNS, neurosurgeons implant up to four intracranial leads (only two can be active at a time) in or over areas where seizures originate. Neurosurgeons implant the pulse generator inside the skull and secure it to the bone.

The device stimulates brain tissue only when it senses seizure activity. It simultaneously records electroencephalography (EEG) data. Whenever possible, patients swipe a magnet over the device at the time of a seizure to help the device contextualize EEG recordings.

Each day, patients sync the RNS device with an online portal to remotely upload the data to their epilepsy care team. Highly skilled in interpreting EEG, Penn neurologists adjust stimulation patterns to personalize stimulation to a patient’s unique brain activity. The team can also switch between implanted leads for bipolar or monopolar stimulation or change out which leads are currently active.

“The RNS device was initially thought to be more like a cardiac defibrillator, where it would sense a seizure and then shock the brain to stop seizure activity,” says Dr. Chen. “It may still do that in some instances, but it’s more likely that the stimulation over the long term retrains the brain network.”

The longer the RNS system is in place, the more likely it is to help patients and decrease seizure frequency. In a study, patients experience an average 82 percent reduction in seizures after three or more years.

Deep Brain Stimulation (DBS) for Epilepsy

DBS is the newest neurostimulation technique for epilepsy, FDA-approved in 2018. Two intracranial leads deliver bilateral stimulation to different nuclei of the thalamus, a deep part of the brain that is widely connected to other brain regions. The pulse generator sits in the chest, as with VNS.

“With DBS, we are trying to alter seizures by targeting an area of the brain that is involved in the broader seizure network,” notes Dr. Chen. “This approach is particularly helpful when multiple areas of the brain are involved in initiating seizures.”

Researchers think that the anterior nucleus of the thalamus is involved in the spread of focal seizures. By targeting this region, stimulation has the potential to interfere with and retrain the larger seizure network as a whole. Patients see a 68 percent median decrease in seizures after five years.

Intraoperative MRI Guidance for Intracranial Neurostimulation

Dr. Chen and his colleagues have the option of using intraoperative 3T MRI guidance to optimize electrode placement in RNS and DBS. With this technique, the scanner detects the trajectory of electrode placement as the team performs the procedure.

“The really nice thing about this approach is that we get updated images throughout the procedure to confirm that the electrode is where it’s supposed to be,” says Dr. Chen. “Without it, you have to rely on the assumption that the preoperative image is still representative of the brain during surgery.”

Intraoperative MRI guidance helps adjust for electrode placement through the ventricle during DBS surgery due to inaccuracies from brain shift. At times, the Penn team also uses the Robotic Surgical Assistant (ROSA robot) for precise electrode placement.

What’s Next in Neurostimulation for Epilepsy?

As Penn providers implant neurostimulation devices, they aim to further their use for neuromodulation for epilepsy and better understand their clinical utility. The team’s current research investigates the use of:

  • Approved devices in different patient populations, for generalized epilepsy
  • DBS targeting the centromedian nucleus of the thalamus to treat generalized seizures
  • Transcranial magnetic stimulation (TMS) for focal-onset epilepsy as a side-effect sparing therapy with seizure reduction comparable to an additional anti-epileptic drug.

Explore Resources at Penn Epilepsy Center

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