[News] Non-invasive nerve stimulation treatment for epilepsy

[Endless]

I am loving this:

Nerve-Stimulation Treatment Proves Effective Against Drug-Resistant Epilepsy

Medications are the mainstay of treatment for epilepsy, but for a considerable number of patients estimated to be as many as 1 million in the U.S. drugs don't work. These patients suffer from a type of epilepsy known as refractory or drug-resistant epilepsy, in which drugs can't control their seizures.

But at an epilepsy conference last month, Dr. Christopher DeGiorgio, a UCLA professor of neurology, presented the results of a non-invasive, non-pharmaceutical treatment that shows promise in controlling seizures.

In his talk at the Antiepileptic Drug Trials XI Conference in Miami, Fla., DeGiorgio reported the results of a Phase 2 clinical trial of a new treatment called trigeminal nerve stimulation (TNS). He noted that 40 percent of the patients receiving TNS treatment experienced a significant improvement in seizure reduction.

The external stimulator, which is about the size of a large cell phone, attaches to a belt or can slip into a pocket. Wires from the stimulator are passed under the clothing and connected to conductive pads attached to the forehead. The electrodes, which can be covered by a cap or scarf, transmit a signal to the trigeminal nerve, which extends into the brain from the face and forehead and is known to play a role in seizure inhibition.

"TNS offers potential benefits it can be delivered bilaterally (to both sides of the brain) and at high frequencies," DeGiorgio said. "Since the electrical energy does not travel directly into the brain, TNS provides a safe method of brain modulation."

The clinical trial showed that at the end of the 18-week study, 40 percent of patients receiving TNS experienced a significant improvement in seizure reduction, which is defined as a 50 percent or greater decrease in the frequency of seizures.

"We showed that TNS works well, under stringent clinical-trial conditions. The fact that 40 percent showed a clinically-meaningful response is exciting," DeGiorgio said.

These results confirm and extend the findings of DeGiorgio's positive Phase 1 trial in epilepsy, reported in 2009 in the journal Neurology.

In addition, the researchers found that the TNS treatment also improved the mood of the participants. Since depression is a common problem in people with epilepsy, this finding could have significant impact on the quality of life of people who suffer from the disorder.

DeGiorgio, lead inventor of TNS, was the principal investigator for the Phase 2 study, which was conducted at Olive View UCLA Medical Center and the University of Southern California.

"I'm encouraged to see that our non-invasive and safe approach to neuromodulation compares favorably to pharmaceutical and surgically implanted device therapies of drug-resistant epilepsy," he said.

Source: University of California, Los Angeles (UCLA)

More Info:

WASHINGTON, Aug. 18, 2011 /PRNewswire-USNewswire/ -- The Epilepsy Therapy Project (ETP) and the Epilepsy Foundation (EF) announced today a New Therapy Grant to potentially help those with treatment resistant epilepsy. This grant was awarded to Alexander Rotenberg, M.D., Ph.D., Assistant Professor of Neurology, Children's Hospital Boston, and will support a clinical study to evaluate the repetitive transcranial magnetic stimulation (rTMS) H-Coil as a promising non-invasive method of inhibiting the abnormal electrical activity believed to underlie seizures in focal temporal lobe epilepsy (temporal lobe epilepsy). Seizures originating in this part of the brain are often difficult to treat and resistant to existing therapies.


"Temporal lobe epilepsy accounts for nearly 20 percent of all epilepsy and an estimated 70 percent of drug resistant focal epilepsy cases. rTMS is a new therapeutic intervention of immediate importance to patients with poor seizure control," said Dr. Rotenberg. "This award will speed the development of this approach to deep brain stimulation to treat temporal lobe epilepsy."


Dr. Rotenberg's program is based upon the premise that seizures may be managed by applying deep magnetic stimulation delivered around the head by the H-Coil technology to areas of the brain such as the temporal lobe, an area where many seizures start. The rTMS technology is approved for use in the treatment of major depression and other neuropsychiatric syndromes in Europe and Israel and marketed by Brainsway Ltd.


rTMS for Treatment of Temporal Lobe Epilepsy

Repetitive transcranial magnetic stimulation is a safe and painless method for focal brain stimulation, where small electrical currents inside the brain are induced by a powerful fluctuating magnetic field from outside the brain. Previous testing of low frequency rTMS did reduce brain excitability and suppressed seizures in some patients, but not in patients with temporal lobe epilepsy. However, the H-Coil's stronger effect penetrates into deeper brain regions.


Dr. Rotenberg and his research team hypothesize that rTMS with the H-Coil, designed to generate sufficient magnetic field strength, can safely and effectively stimulate deeper brain structures and may inhibit the electrical and neurotransmitter activity that underlies seizures in temporal lobe epilepsy. Their hypothesis is based in part on the encouraging antiepileptic effect of conventional rTMS in other types of epilepsy, and on their animal studies which showed that deeper brain stimulation by rTMS can suppress seizures in rats. The New Therapy Grant will support a clinical study of the H-Coil in children and adults with intractable temporal lobe epilepsy.


If this study shows the expected effect in seizure control, the H-Coil could rapidly move to commercialization for temporal lobe epilepsy treatment because a different version of the H-Coil that targets other deep brain areas is already marketed for treatment of major depression and other neuropsychiatric syndromes.


The New Therapy Grants Program is a unique joint venture between two non-profit epilepsy organizations, The Epilepsy Therapy Project and the Epilepsy Foundation. Grants are awarded to support programs that demonstrate promise as new treatments through critical early clinical milestones and readiness for further investment and development. Applications are evaluated by scientific and business advisory board members including experienced clinicians, scientists, investors and pharmaceutical and device industry executives. Awards are given based on the potential to provide substantial benefit in a timeframe relevant to those living with epilepsy today. To date, more than 45 grants have been awarded for the advancement of new therapeutics and devices that have demonstrated a more rapid path to benefitting patients and future commercialization.


"We regard the New Therapy Grants Program as an engine to accelerate the development of the most promising new epilepsy therapies, especially approaches with near-term promise to improve the lives of those with epilepsy," said Warren Lammert, chairman of the Epilepsy Therapy Project. "We believe the H-Coil, with proven safety and efficacy in other medical conditions, may have direct applicability to epilepsy. We are pleased to provide critical clinical support that may advance this device towards proof of concept and late-stage evaluation."


"This innovative cutting edge study underscores the missions of our two organizations," said Rich Denness, president & CEO of the Epilepsy Foundation. "This kind of translational research transforms scientific concepts into real treatments for real people and can help eliminate seizures and improve the quality of life for people living with epilepsy."

http://news.yahoo.com/non-invasive-m...132208698.html

http://news.yahoo.com/non-invasive-m...132208698.html

[Birdbomb]

Beam me up Scotty!

BTW, their test results are BETTER than Cyberonic$' VNS !
AWESOME!!!

[survivor]

So now we have both the CN V and CN X being stimulated. Is there any work being done which suggests that whether vagus or trigeminal nerve stimulation gives better results or both have the same efficacy?

[Endless]

From the articles below it looks like the rTMS significantly reduced seizures in 40% of people. The VNS significantly reduces seizures in 33% of people. "significantly reduced" means reducing seizures by 50% or more. So on that one measure, rTMS is more effective than VNS.

I don't think the below articles give much other info how much the seizures are reduced in the people where it worked. But check my work - read the whole things through and maybe look for more. The journal articles would probably say more, if they are published yet.

[AM2012]

The TNS sounds very interesting. I've never heard of it before. Hopefully, it'll be released ASAP.

EDIT: Here's some more recent updates on the development of this I just found:

NeuroSigma Receives Notice of Award from NIH for an STTR Grant for its Trigeminal Nerve Stimulation Therapy for Epilepsy

LOS ANGELES, Sept. 6, 2011 /PRNewswire/ -- NeuroSigma, Inc., a Los Angeles-based medical device company, today announced it has received a notice of award for an NIH Small Business Technology Transfer (STTR) Phase I grant from the National Institute of Neurological Disorders and Stroke (NINDS). This will support further development of external trigeminal nerve stimulation (eTNS™) therapy for the treatment of drug-resistant epilepsy, for which NeuroSigma is the exclusive worldwide licensee of intellectual property developed by the University of California, Los Angeles (UCLA). The STTR program requires that the small business collaborates with a non-profit research institution, which must perform at least 30% of the work. UCLA's role as a subcontractor in this project is primarily focused on conducting the human clinical studies.

NeuroSigma's grant award from NINDS extends over a period of approximately two years and will provide total funding of approximately $750,000, with the second year of funding subject to the availability of funds and satisfactory progress during the first year. The NINDS STTR program may provide up to an additional $3 million of follow-on Phase II funding for additional clinical studies. The major focus of the project is clinical testing of a new proprietary eTNS™ pulse generator and animal and human testing of a new generation of electrodes designed to mitigate minor skin irritation, which was the primary side-effect reported by subjects in the Phase I and recently completed Phase II clinical trials.

NeuroSigma's eTNS™ system utilizes a self-adhesive conductive pad applied to the forehead to stimulate branches of the trigeminal nerve, which are located very close to the surface of the skin of the forehead. The trigeminal nerve is the largest cranial nerve, offering a high-bandwidth pathway for signals to enter the brain.

Drs. Christopher DeGiorgio and Ian Cook, UCLA faculty in the Departments of Neurology and Psychiatry, are the principal investigators of this project. Together they have pioneered TNS for epilepsy, depression, post-traumatic stress disorder and other indications.

"We have already seen the safety and efficacy of our non-invasive eTNS™ therapy in prior clinical trials and look forward to the opportunity to further validate our therapy through the valuable funding provided by NINDS," said Dr. DeGiorgio. "We are also very pleased to receive this grant knowing that NIH's highly regarded peer review process includes a rigorous review by leading medical experts."

CAUTION: The eTNS™ system is an investigational device and at this time is limited by United States law for investigational use only.

About NeuroSigma, Inc.

NeuroSigma is a Los Angeles-based medical technology company established to develop early stage technologies with the potential to transform medical practice. Currently, NeuroSigma is focused on a number of neuromodulation therapies and through our majority-owned subsidiary, NSVascular, on Thin-Film Nitinol covered stents for endovascular applications. NeuroSigma employs two neuromodulation therapy platforms: Trigeminal Nerve Stimulation (TNS) and Deep Brain Stimulation (DBS). NeuroSigma has amassed significant intellectual property that is based on technology licensed on an exclusive basis from the University of California, Los Angeles (UCLA), including potential therapies for epilepsy, depression and post-traumatic stress disorder (PTSD) via TNS and for PTSD, obesity and cachexia via DBS.
SOURCE NeuroSigma

New Device Reduces Seizures, No Surgery Required
Christopher DeGiorgio, UCLA neurologist and inventor of the device.

A experimental device that delivers electrical pulses to the forehead can help control epileptic seizures, say scientists at the University of California, Los Angeles.

The device works by stimulating the trigeminal nerve, which runs just beneath the skin covering the eyebrows. Electrical signals follow that nerve to areas in the brain where seizures often begin, researchers say.

The approach, which is not yet approved by the FDA, could offer an alternative or enhancement to treatment with drugs, says Christopher DeGiorgio, the neurologist at UCLA who invented the new approach.

”Medications can cause mood problems, fatigue, or problems with thinking for some people. I see this as an alternative because it doesn’t cause those side effects.” – Christopher DeGiorgio, UCLA neurologist and inventor of the device
About 3 million Americans have epilepsy, and for about one-third of them, drugs alone do not control their seizures. A study of 50 people with drug-resistant epilepsy found that the trigeminal nerve stimulator was able to greatly reduce seizures for about 40 percent of them.

“For me it’s extremely effective,” says Jennifer Rees, 49, who lives in the Los Angeles area and has been using the nerve stimulator for six years.

Rees says that before using the stimulator, she was having up to eight seizures a month. The device alone reduced that to about one seizure a year. And she hasn’t had any seizures since she added low doses of a medication more than 18 months ago.

The device is appealing because it doesn’t require surgery, doesn’t have side effects and is very easy to use, Rees says. She wears her device while she sleeps.

“For me, all it involved was putting two gel pads above my eyebrows, one on each eyebrow,” she says. The device causes “a slight tingling sensation” on her skin, she says.

Researchers believe electrical pulses can act like a sort of pacemaker in the brain, heading off the chaotic “electrical storms” that cause epileptic seizures. And the trigeminal nerve stimulator is not the first time researchers have used electrical pulses to prevent seizures.

In 2005, the FDA approved a device that stimulates another nerve that leads to the brain — the vagus nerve. But stimulating the vagus nerve requires surgery to implant a device near the collarbone.

The trigeminal nerve stimulator, in contrast, never penetrates the skin and is powered by an external device about the size of a large cell phone, DeGiorgio says.

And DeGiorgio says he’s found an interesting benefit to trigeminal nerve stimulation. It tends to relieve depression, which is common among people with epilepsy.

Source: NPR

NeuroSigma Responds to Substantial Interest Generated by NPR Story on Promising Epilepsy Clinical Trial

LOS ANGELES, Aug. 4, 2011 /PRNewswire/ — NeuroSigma, Inc., a Los Angeles-based medical device company, today provided an update in response to substantial interest and inquiries generated by a National Public Radio (NPR) news story which aired July 27, 2011 on the use of non-invasive Trigeminal Nerve Stimulation (TNS) for the treatment of drug-resistant epilepsy.


Dr. Christopher DeGiorgio, a neurologist at the University of California, Los Angeles (UCLA) and scientific advisor to NeuroSigma, who was interviewed in the NPR story, pioneered the development of TNS for epilepsy. NeuroSigma is the exclusive licensee of UCLA‘s TNS intellectual property


NeuroSigma is now planning a Phase III pivotal trial for its external TNS (eTNS™) system. Earlier this year, Dr. DeGiorgio delivered results of the 50-subject Phase II double-blind clinical trial to the Antiepileptic Drug Trials XI Conference in Miami, Florida. The results compared favorably with those of pharmaceuticals and surgically-implanted devices.

The study found that subjects receiving NeuroSigma’s active eTNS™ treatment experienced a significant improvement in seizure reduction, while those randomized to receive the control condition (“sham” or “placebo”) did not. Subjects receiving active treatment showed a 40% responder rate after 18 weeks of daily stimulation compared to a 15% responder rate in the placebo group. A responder is defined as someone who experiences a greater than 50% reduction in seizures. In addition to reducing seizures, eTNS™ also improved mood. These results confirm and extend the findings of DeGiorgio’s positive feasibility trial in epilepsy, reported in 2009 in the journal, Neurology.


At the same conference, DeGiorgio also revealed a potential mechanism of action for the eTNS™ treatment of epilepsy. Using Positron Emission Tomography (PET), significant decreases in regional cerebral blood flow were detected in several regions of the cerebral cortex, which is where seizures originate.


NeuroSigma is currently developing its next generation eTNS™ system and in 2012 anticipates filing a CE Mark application for approval to commence marketing its new eTNS™ system for the treatment of epilepsy in Europe.


In addition, in 2012, the company anticipates filing an IDE for an upcoming multi-center Phase III pivotal trial in the United States. Neither NeuroSigma nor UCLA are currently enrolling subjects for eTNS™ epilepsy trials.

Future updates regarding clinical trials, including potential enrollment details, and study results will be posted on NeuroSigma’s website

Couple questions if anyone can find anything more about this:
Would you have to wear this 24/7 to get the benefit? EDIT: I just found that Neurosigma is developing 2 different types of TNS devices known as "eTNS" and "sTNS" (subcutaneous) with the implantable version being given to those that respond well to "eTNS". Guess that partially answers it. Although I'm still wondering if the benefits continue to last after the external electrodes are removed...? Ok, I was just able to find the information myself. The trial participants wore the device 8 hours every night so it looks like that's the standard.

How would the location of the electical spikes in the brain effect the outcome for this kind of therapy? With it being reliant on stimulating the trigeminal nerve, it seems it wouldn't be possible to move the placement of the electrode so I'm kind of wondering how the parameters would be customized by individual?





rTMS:
It's interesting to see the technology mentioned in the press release is the same external based deep rTMS ("H-coil") that was developed in Israel years ago. I see there's a number of videos on youtube that show this in use (some of which seem to be posted through the company "Brainsway" including an animation of the device in action). Brainsway's website also gives more info. about the technology as well as the list of conditions apparently currently being treated with it. As this technology has gained use for all sorts of disorders abroad, hopefully it'll be available in the states soon as well.

Does anyone know how the H-coil differs for epilepsy treatment compared to that used for other disorders?