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NEWS FROM THE AMERICAN EPILEPSY SOCIETY ANNUAL MEETING
Early Reports Show Promise in Laser Surgery for Intractable Focal Epilepsy

The use of lasers to make a precise cut below the cortical surface may one day be an alternative to traditional brain surgery for patients with intractable focal epilepsy, according to three independent reports presented at the American Epilepsy Society annual meeting last month.

Investigators at Miami Children's Hospital are now testing the benefits of thermal ablation of soft tissue using a system called Visualase that has been approved for use in neurosurgery since 2007. It has been used primarily for the treatment of brain and spinal cord tumors. The hope is that it can be used effectively to heat the tissue that triggers seizures and ablate it, all without performing a craniotomy.

Ian Miller, MD, and his colleagues brought the Visualase system into their neurosurgical suite in May 2011. Since then, almost a dozen children with intractable epilepsy have been treated with the system, which they say has many “theoretical advantages over conventional neurosurgical resection, including smaller exposure, shorter recovery, and less pain.”

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REPORT ON FIVE CASES

They are now testing their theory and report on the first five cases. The patients ranged in age from 11 to 18, with a mean age of epilepsy onset at 7.6 years. The procedure is done under MRI guidance.

Three of the five cases were done successfully. One child required conventional resection during the procedure following a complication with the placement of the device. Another patient required a second Visualase ablation. The average length of stay was 1.6 days and there were no complications from infection, bleeding, or unintended neurological injury.

Two of the five patients are now seizure-free after Visualase surgery, including the one who had a second Visualase ablation, said Dr. Miller. In the remainder, one patient had a reduction in seizures and another showed no benefit. The patient who had a conventional resection following a failed Visualase ablation is also now seizure-free.

The benefits, said Dr. Miller, are that it is safe and effective. “The biggest factor determining success was precise placement of the laser fiber, and complete destruction of the epileptogenic zone,” he said. He added that this device may be particularly useful in treating small, deep lesions, such as those seen in patients with tuberous sclerosis. They now have data on 10 patients.

USE IN NON-MESIAL TEMPORAL FOCAL EPILEPSY

In another study, Michael Chez, MD, director of pediatric neurology at the Sutter Neuroscience Medical Group in Sacramento, CA, and his colleagues reported on their experience using laser ablation in four children — two boys, ages eight and 11, and two girls, ages 14 and 19 — with intractable non-mesial temporal focal epilepsy. They used surface EEG, MEG, and fMRI combined with Brainlab Localization to guide the ablation.

Three of the four patients are on the autism spectrum or have cognitive disability that made standard intracranial grid mapping and craniotomy less desirable. They also used the Visualase system.

The investigators reported that the patients were ambulatory within six to eight hours post-ablation and were eating and exhibited no outward signs of pain. The first patient remained seizure free at the six-month follow-up and has been off medications and showed improvements in memory and language abilities. Another went from four seizures a day to two or three a week and over a course of months tapered off to one seizure a week. The others remained seizure free and are already tapering off medications with normal EEG.

The investigators said that more studies are needed to show long-term efficacy and reduction in the use of anti-seizure medicines. Dr. Chez said that his team has now done laser surgery in an additional four children, and are in planning stages with another six children.

All of the children were not candidates for craniotomy, he noted. Several children were autistic and “this is a much more tolerable procedure” than resection, said Dr. Chez. He said that the success rate is about 70 percent.

SHORT OPTICAL PULSES: FOCAL SEIZURES

In another study, Chris B. Schaffer, PhD, an associate professor in the department of biomedical engineering at Cornell University, and his colleagues are testing the use of femtosecond-duration laser pulses — a laser that emits ultrashort optical pulses in the domain of femtoseconds — to treat focal seizures. Dr. Schaffer said that this light scalpel could be used to create precise incisions around the epileptic focus and reduce or stop seizure propagation. This would be a less invasive way to get deep into the brain to disrupt the neural connections seizures propagate along.

He is using his understanding of the way the brain is wired to devise a way to deliver infrared energy to cut only some neural connections in the brain and reduce the propagation across the area. Focal seizures start in one neighborhood and move out horizontally along the surface of the cortex, he said. Normal brain functions, on the other hand, rely more on vertical connections in the cortex.

These studies are being done in collaboration with neurosurgeon Theodore Schwartz, MD, at Weill Cornell Medical College. The idea is to cut the horizontal connections at the seizure focus to block the seizure's propensity to propagate. The horizontal connections are several millimeters below the surface of the brain and traveling down through the layers of tissue opens up risk for stroke within the blood vessels.

Dr. Schaffer and his colleagues have been testing the effectiveness of short infrared laser pulses. The wavelength is infrared so that the tissue is normally transparent. But the use of femtosecond-duration pulses and tight focusing of the laser allows the laser to ablate the tissue and cut the desired connections. Critically the technique cuts the site of the seizure activity without harming any tissue along its journey.

So far, they've done the work in rodents. Dr. Schaffer explained that femtosecond laser pulses are tightly focused into the brain to produce multiple 750 by 750 μm box cuts at depths ranging from 200 μm to 800 μm below the brain surface. Through a glass micropipette, they inject a toxin inside the box of cuts to induce seizures and they record local field potential (LFP), while another distant electrode is implanted outside the box to record LFP. “If the laser cuts are effective,” he said, “we expect seizure activity to be contained to the focal region within the cuts and not propagate outwards to the distant electrode.”

The precision of the laser ablation technique is so exact that they can cut dendrites off a single neuron in a living animal, he said, although the cuts used to block seizures are more extensive. “The propagation is completely blocked half the time and the rest of the time there is a significant delay in the propagation of the seizure and it is much smaller in amplitude,” he added. Preliminary evidence also suggests that these cuts do not disrupt normal neural functionality.

They have just studied the efficacy of the procedure over a few hours. They are now extending this period to see how long it blocks the propagation of the seizure. “We know it works right away but we don't know how long it will work,” he said.

PROMISING RESULTS

Gregory K. Bergey, MD, professor of neurology and vice chair for research in the department of neurology at Johns Hopkins University School of Medicine and director of John Hopkins Epilepsy Center, said that lasers are an attractive alternative to traditional resection.

“There are a number of promising results [for laser ablation] but it is still preliminary,” said Dr. Bergey. “It is well tolerated and it may be quite effective at reducing seizures,” but he added, “we need to perform larger laser trials and compare them to traditional surgery. Even if the side effect profile was the same and the efficacy was the same, surgeons can use scans to see what they are taking out. I am quite excited by the findings.”