Until now, there were two main techniques for treating the most common type of stroke – the ischemic kind, in which a clot blocks one or several major blood vessels of the brain and prevents blood from reaching the vital tissue, causing the nerve cells to die. The widely used therapies for acute stroke open blocked arteries by dissolving or removing a clot, but they have to be performed quickly and are not effective on all patients.
Now, neurologists at the University of California at Los Angeles (UCLA) and at 73 medical centers around the world, including Jerusalem’s Shaare Zedek Medical Center, have shown that stimulation of the nerves can provide a new treatment option for ischemic stroke.
The new Israeli-developed approach applies electrical stimulation to nerve cells behind the nose, increasing blood flow in the brain by dilating undamaged arteries and bypassing the blockage to treat the threatened region of the brain. It can increase blood flow and improve the blood flow in patients up to 24 hours after the stroke occurs. The treatment uses a small neurostimulator electrode that is temporarily implanted using local anesthesia through the roof of the mouth. During the study, the electrode actively stimulated the nerve cell cluster four hours a day for five consecutive days.
A study of 1,000 patients, just published in the prestigious journal The Lancet, found evidence that the minimally invasive technique – active nerve cell cluster or sphenopalatine ganglion stimulation – reduced the patients’ degree of disability three months after they suffered an acute cortical ischemic stroke, which affects the surface of the brain. It included patients (men aged 40 to 80 years and women aged 40 to 85 years) with anterior-circulation acute ischemic stroke.
Dr. Jeffrey Saver, director of the UCLA Comprehensive Stroke Center, was the co-principal investigator of the study. “We believe this represents the advent of an entirely new treatment for patients with acute ischemic stroke,” said Saver, who also is senior associate vice chair for clinical research in neurology at the David Geffen School of Medicine at UCLA.
The medical device company – BrainsGate – that makes the system used in the technique is Israeli. Established in 2000, BrainsGate is committed to developing innovative therapies for patients suffering from central nervous system diseases.
“Stroke continues to be a major cause of death and disability in the US and around the world, making it imperative that we develop new, effective treatments to complement existing therapies, including in the extended treatment window,” said Saver, who along with Prof. Natan Bornstein, head of Shaare Zedek’s neurological division and a neurology professor at Tel Aviv University were the study’s co-first authors.
BrainsGate’s platform technology involves electrical stimulation of the Spheno-Palatine Ganglion (SPG), a nervous center known to increase cerebral blood flow. “We should be proud that it is Israeli,” said Bornstein.
In previous studies to understand the mechanism by which the treatment would work, scientists found that the nerve cell cluster stimulation not only increases blood flow, but also preserves the blood-brain barrier, which prevents brain swelling. It also improved neurons’ ability to compensate for injury and form new connections.
In a study subset of 520 people who had major deficits and confirmed injury to the cerebral cortex, 40% of those who did not have the stimulation had favorable outcomes, versus 50% of those who did have the stimulation. Although those results fell just short of statistical significance, when the data is combined with similar findings from an earlier trial, the cumulative statistics indicate that the therapy is effective when administered eight to 24 hours after the onset of a cortical acute ischemic stroke.
The first treatment for ischemic stroke, the clot-dissolving drug alteplase (tissue plasminogen activator), was approved by the US Food and Drug Administration in 1996. When administered soon after onset, the drug (which is also called tPA) can sometimes clear a blocked artery, restore blood flow and avert stroke damage. But its effectiveness is reduced if treatment is delayed beyond three hours after the stroke. In addition, it doesn’t work for all patients, and some people have conditions that preclude its use.
More recently, the FDA has approved clot-retrieval devices that are threaded through arteries to capture and remove blockages. Used alone or in conjunction with tPA, those devices have extended treatment time to 24 hours after the onset of stroke in some patients, but earlier treatment is more effective and the devices require expertise that may be unavailable outside major medical centers.
The UCLA-directed study found that the new stimulation treatment can be safe and effective for people who cannot undergo clot-dissolving medication, Saver said. Future studies will determine the effectiveness of the new therapy when it is used with clot-dissolving medications and clot-retrieving devices.