Epilepsy Talk

Treating Seizures — 7 Amazing New Breakthroughs | March 11, 2022

What if you could predict an oncoming seizure in time for you stop it? Or even prevent it?

That day may be coming sooner than you think, thanks to these seven new technologies.

You’ll learn what they are, how they work and how far along they are.

There’s a lot of new and exciting research going on — all over the world — about predicting and preventing seizures. 

The latest research combines scientists who excel in engineering, math, physics and technology in a dedicated collaborative effort.

And even though most the actual technology isn’t here yet, the future holds promise for us all.

Deep Brain Stimulation

One seizure-interrupting device, called a responsive neurostimulator system, is for patients with temporal lobe epilepsy, bi-temporal epilepsy, and neocortical epilepsy.

This therapy uses a pacemaker-like device, implanted in the brain to deliver a small amount of electricity when it detects the onset of a seizure.

Approximately 30,000 people worldwide are currently using deep brain stimulation (DBS) to treat neurological or psychological conditions.

And DBS is only the beginning.

Aryeh Taub of Tel Aviv University’s School of Psychological Sciences believes that, in the future, an interface with the ability to restore behavioral or motor function, lost due to tissue damage is achievable — especially with the help of their new electrode coating.

“We duplicate the function of brain tissue onto a silicon chip and transfer it back to the brain,” Taub says, explaining that the electrodes will pick up brain waves and transfer these directly to the chip.

“The chip then does the computation that would have been done in the damaged tissue, and feeds the information back into the brain — prompting functions that would have otherwise gotten lost.”

The theory is that direct electrical stimulation of the brain can prevent or decrease seizure activity.

However, several fundamental questions remain to be resolved. They include where in the brain the stimulus should be delivered and what type of stimulation would be most effective.

One goal of this research is to combine the beneficial aspects of electrical stimulation with seizure detection technology, in an implantable responsive stimulator.

The device would detect the onset of a seizure and deliver an electrical stimulus that would safely block seizure activity, without interfering with normal brain function.

The device works by combing three components:

A lead, composed of a thin wire with electrode contacts on it, is implanted surgically into the brain. (Sometimes only one side of the brain is treated, and other times two brain leads are implanted, one on the right side and one on the left.)

A pacemaker-like generator, which is placed under the skin in the chest region, and is programmed to deliver the electrical stimulation to the brain lead.

A connecting cable, tunneled under the scalp and neck, which links the brain lead to the generator.

A programming computer, which allows the doctor to adjust the stimulation intensity and rate, along with other settings from outside the body. Settings are adjusted to maximize benefit and minimize any side-effects related to the stimulation.

Overall, researchers say more than half of those treated experienced a reduction in epileptic seizures of at least 50 per cent.

However, even though the effectiveness of this new treatment focuses on those with drug-resistant epilepsy, the treatment will not be suitable for all patients with epilepsy.

Brain Sensors

The Responsive Neurostimulator System (RNS) has been shown to treat “untreatable” seizures. Especially for those people with epilepsy that have seizures that begin at one focal point in the brain, but aren’t appropriate for epilepsy surgery.

It uses a pacemaker-like device implanted in the brain to deliver a small amount of electricity when it detects the onset of a seizure.

The Responsive Neurostimulation System consists of a miniaturized, implanted computer. (One that’s flat and about the size of a half-dollar.) It can detect seizures from electrodes implanted into or on the surface of the brain and then delivers an electrical pulse to stop them.

Unlike the Vagus Nerve Stimulator (VNS), Responsive Neurostimulation (RNS) is designed to detect abnormal electrical activity in the brain and respond by delivering electrical stimulation to normalize brain activity before the patient experiences seizure symptoms.

While other devices stimulate the nervous system continuously or in a predetermined pattern, the Neurostimulator implant is unique in that it monitors the brain, delivering jolts of electricity only when it detects the abnormal electrical activity that signals the onset of a seizure.

“It’s like dousing a spark before it becomes a flame,” said Martha Morrell, Neuropace’s chief medical officer.

Gene Therapy

The discovery of gene mutations that cause specific epilepsy syndromes, has led to the possibility of using gene therapy to counter the effects of these mutations.

In gene therapy, researchers typically introduce new genes into brain cells.

Viruses can also be used to introduce genes for proteins such as GABA into non-neuronal cells. These cells are then transplanted into the brain to act as “factories” to produce potentially therapeutic proteins.

One advantage of gene therapy is that it can alter the cells in just one part of the brain.

Researchers can control the activity of the introduced genes by using a genetic “switch” that responds to antibiotics or other chemicals.

This allows doctors to turn the gene therapy off if it causes intolerable side-effects or other problems.

Theoretically, this type of therapy should last longer and cause fewer side-effects than medication. 

Also, researchers are working to identify more gene variations and to understand how they influence individual responses to treatment.

Eventually, it may become possible to test for these genetic variations and, to use the information to prescribe more effective treatments.

Researchers also may be able to develop ways of overcoming genetic resistance to treatment.

“What effect a compound is going to have partly depends on where in the seizure circuit that new compound or gene is being placed. You could put the same chemical in two places and get two different results,” said Dr. Edward Bertram III, a professor of neurology at the University of Virginia.

“That is going to be the issue as they try to develop this: Where should we be putting this to have the best effect?

“On the promising side, they put (the gene) in a restricted area and had an effect. That is a great first step.”

Cell Transplantation

Another emerging approach for treating epilepsy is cell transplantation.

Researchers can transplant either your own mature cells or stem cells derived from fetal tissue.

Cells used for transplant are sometimes genetically engineered to produce substances to reduce seizures, or protect neurons from damage.

Cell transplantation therapies for epilepsy are still in preliminary stages of development.

However, the encouraging results of animal studies suggest that this type of therapy may eventually be used to treat drug-resistant human epilepsy.

In about 50 percent to 70 percent of epilepsy cases, an underlying cause of seizures cannot be determined.

But in recent years, advances in genetics, biochemistry and functional imaging have helped researchers identify the biological basis of some forms of the disease.

The lab team of Scott C. Baraban, PhD, a key scientist at the UCSF is working with mice that possess the same genetic, biochemical and anatomical defects that are seen in specific types of human epilepsy.

“The cells actually make new synapses,” says Baraban. “That’s the key feature. By making a new synapse with host cells, a transplanted cell acts more like a native cell. We’re basically rewiring the brain.”

It takes about a month for transplanted cells to spread out from the site of transplantation, settle down at their new neural addresses, grow up and connect with their neighbors.

Baraban and his colleagues have also begun working with human stem cells in a project funded by the California Institute for Regenerative Medicine.

The aim is to develop a treatment, based on using cell transplantation, to boost inhibitory circuits in the brain.

While the strategy appears quite promising so far, there is plenty of additional pre-clinical work to do before any human clinical trials begin.

Focal Cooling

Previous clinical and experimental observations have demonstrated that gentle cooling of the brain to 20 degrees celsius is capable of markedly reducing subsequent seizure frequency and intensity in focal seizures. And even terminate them.

Researchers at University of Chicago’s Argonne National Laboratory have developed the first automated system that can both reliably predict epileptic seizures in advance of clinical onset, and induce local hypothermia to the affected brain region quickly enough to suppress the seizures.

This ground-breaking technology consists of miniature brain implants for automatic prediction and control of seizures in humans, with a small external unit for monitoring both patient and system.

The detection device is a surface acoustic wave probe implant, which measures local changes in the brain temperature as a predictor of epileptic neuron activity.

The cooling component consists of an array of probes, implanted in the brain as a means of rapidly cooling the epileptic zone to suppress seizures.

The cooling device and sensor electronics are mounted on the head; a small telemetry system worn around the waist measures the sensor readings and triggers the cooling device.

The Argonne-developed system has the potential to revolutionize the treatment of epilepsy and improve the quality of life for thousands of epilepsy patients who, thus far, have been debilitated by seizures.

Vaccines

In recent years, researchers have begun to develop immune-modulating therapies, or vaccines, to treat neurological disorders.

This type of therapy employs the immune system to disable proteins contributing to disease.

Investigators are now beginning to test immune therapies specifically for epilepsy.

Forexample, in one study of an experimental vaccine for epilepsy, researchers used an AAV (adeno-associated virus) vaccine to generate antibodies that blocked a sub-unit of the NMDA receptor.

NMDA receptors are one kind of receptor for the excitatory neurotransmitter glutamate; previous studies have shown that they contribute to the neuronal injury associated with epilepsy.

The vaccine in this study helped to prevent seizures in a rat model of temporal lobe epilepsy.

And researchers at Jefferson Medical College have developed an oral vaccine that protects rats’ brains from stroke and prevents seizures.

Eventually, such a vaccine may be used for epilepsy.

The oral vaccine causes the body to develop antibodies that recognize a protein in the brain.

“Because of the brain’s blood-brain barrier, the vaccine causes no impairment of a rats animals’ behavior,” says, Matthew During, MD, professor of neurosurgery at Jefferson, who led the work.

“It protects them significantly from subsequent insults such as an epileptic seizure or a stroke for at least five months after a single oral dose.”

“It’s been difficult to develop good drugs because when they get across the blood-brain barrier, they don’t function very well and don’t have much selectivity,” Dr. During says.

“A major problem in treating many neurological diseases is not so much the target, but those drugs which cross the blood-brain barrier tend to affect and alter the function of all the brain, not just the area where the problem lies.”

“Here with our vaccine approach, the antibodies don’t get across the barrier efficiently,” he says. “However, with epilepsy, the increased brain activity allows the antibodies to cross the barrier more readily.”

“If the antibodies get across the barrier, bind to and antagonize the receptor specifically in the injured brain region, animals will behave perfectly normal and you’ve protected against the epileptic seizure.”

Neuroengineering

The relatively young field of neuroengineering uses engineering technology, to investigate and treat neurological diseases.

Using the electrochemical properties of neurons as a foundation, neuroengineers seek to monitor and modulate abnormal brain function, using several novel — and often nonpharmacological — methods.

These new implantable antiepileptic devices, currently under development and in pivotal clinical trials, hold great promise for improving the quality of life for millions of people with epileptic seizures in the future.

A broad range of strategies is currently being investigated, using various modes of control and intervention in an attempt to stop seizures.

The initial results are exciting, but considerable development and controlled clinical trials will be required before these treatments become accepted for clinical care.

For example, investigators are also working to develop a high-quality, complete archive of intracranial EEG data, symptoms, brain images, and other information to help researchers understand how to predict and interrupt seizures.

They are developing improved batteries, electrode arrays, and brain-computer interfaces.

NeuroVista has developed an implantable device system that continuously collects and analyzes EEG data to detect impending seizures.

The system uses an external patient-carried device with a very simple interface — three colored lights — to indicate the risk of an impending seizure. It’s currently undergoing study human clinical trials in Australia.

The hope is to use this technology to guide the administration of fast-acting drugs to prevent seizures.

Other research adds hope that people with epilepsy could one day wear tiny brain sensors that detect an impending seizure and, release medicine from implanted pumps in time to avert an attack.

And Danish scientists have found a physiological way to predict a seizure.

By measuring the heart rate variability of patients with epilepsy, they have constructed a wireless epilepsy alarm, which is easier and less dangerous to implant in patients.

“It’s much less complicated to construct a wireless sensor which can be attached to a patient’s heart than constructing a sensor for the brain,” says Jesper Jeppesen, leader of the project.

The researchers estimate that a wireless epilepsy alarm will be developed in approximately 5-10 years, since the method has to be tested over a longer period of time on patients with different types of epilepsy.

The field of seizure prediction, in which engineering technologies are used to decode brain signals and search for precursors of impending epileptic seizures, holds great promise to elucidate the dynamical mechanisms underlying the disorder, as well as to enable implantable devices to intervene in time to treat epilepsy.

Much of this research uses computational neuroscience, which involves both measuring and extracting quantitative features from neurophysiological data, in order to localize, decode and predict the behavior of a system.

By using mathematical models of neural function, investigators can test diagnostic and therapeutic technologies robustly before implementation in humans.

Such computer models are particularly powerful because they can simulate neurological function on multiple scales simultaneously, ranging from individual ion channels and single cell function, through local networks of neurons,to complete systems.

The evolution of engineering technology as applied to epilepsy presents renewed promise to potentially identify periods of time when the probability of seizure onset is increased, and to deliver responsive therapy to prevent epileptic events from occurring.

Many investigators feel that it is likely that seizure detection and prediction methods will be improved if they are tuned to each individual patient.

It is also likely that as the network dynamics and high-frequency data are further understood, new methods of seizure prediction will be discovered.

It’s a brave new world out there. And although these detecting devices are just at the testing stage, in time, perhaps this new technology will be used to predict, interrupt or even prevent a seizure.

Individually, they present so many possibilities.

And together, they represent hope for all of us in the future.

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Resources:

Deep Brain Stimulation

https://www.epilepsysociety.org.uk/deep-brain-stimulation#.V3LEDLgrLAs

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941772/

http://www.webmd.com/epilepsy/news/20100317/deep-brain-stimulation-stops-seizures

Brain Sensors

http://abcnews.go.com/Health/story?id=117686&page=1#.UCKztE1lQ3g

https://www.epilepsy.org.uk/news/news/new-sensor-could-monitor-effectiveness-brain-treatments-72624

https://medicalxpress.com/news/2018-08-brain-implant-epilepsy-seizures.html

Gene Therapy

http://www.sciencedaily.com/releases/2010/08/100825093541.htm

https://www.nature.com/articles/d41586-018-07644-y

https://ghr.nlm.nih.gov/primer/therapy/genetherapy

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1176330/

Cell Transplantation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200730/

https://www.sciencedaily.com/releases/2018/12/181220130219.htm

https://www.epilepsy.com/article/2016/6/use-stem-cell-therapy-epilepsy

Focal Cooling

http://www.ncbi.nlm.nih.gov/pubmed/14636319

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084201/

https://www.sciencedaily.com/releases/2017/10/171005141831.htm

Vaccines

http://www.sciencedaily.com/releases/2000/02/000225080601.htm

Neuroengineering

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904395/

https://pubmed.ncbi.nlm.nih.gov/18301414/

https://www.nature.com/articles/ncpneuro0750

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