MRI-guided focused ultrasound shows promise for subcortical epilepsy

WASHINGTON – MRI-guided focused ultrasound (FUS) is now being employed on an experimental basis to treat deep subcortical lesions, such as hypothalamic hamartoma, to control intractable epilepsy, according to an expert summary of a “hot topic” presented at the American Epilepsy Society annual meeting.

“If the risk of FUS is as low as we expect, it could change our paradigm,” reported Nathan B. Fountain, MD, director of the F.E. Dreifuss Comprehensive Epilepsy Program at the University of Virginia, Charlottesville.

Dr. Nathan B. Fountain

FUS has been used clinically for the treatment of uterine fibroids since 2004, according to an overview provided by Dr. Fountain. Clinical studies of MRI-guided FUS for lesions in the brain began in 2009. The approval of MRI-guided FUS thalamotomy for essential tumor in 2016 was based on a pivotal trial led by Jeffrey Elias, MD, a colleague of Dr. Fountain’s at the University of Virginia (N Engl J Med. 2016;375:730-9). Many of the principles for treating subcortical lesions causing epilepsy are the same as those for treating essential tremor.

Under MRI guidance, FUS is delivered via a helmet with 1,024 transducers. These focus sound waves to a highly targeted area of the brain, resulting in thermal ablation. The treatment is noninvasive in the sense that no craniotomy is involved. It can be delivered without anesthesia. When used to treat essential tremor in awake patients, MRI-guided FUS confirms the target when the tremor resolves.

“There is no injury to the brain as far as we can tell,” reported Dr. Fountain, referring to the tremor studies.

Because the thermal ablation is delivered by sound waves, this approach appears to be safer to structures surrounding the lesion than would be anticipated with energy delivered by radiation. For treatment of lesions in the hypothalamus, where surrounding tissue is responsible for important brain functions, the apparent low risk of collateral damage is a major potential advantage, according to Dr. Fountain.

Although Dr. Fountain conceded that the term “subcortical” is not commonly used to describe epilepsy lesions, he considers it appropriate to explain the role of MRI-guided FUS. Without technical advancements, this tool is not appropriate for the cortical lesions that are responsible for the majority of epileptic seizures. Rather, lesions must be positioned deep in the skull to be in the “envelope” where energy can be concentrated. Lesions in the temporal or hippocampal areas of the brain, for example, will not be suitable without technical advances.

Due to its position in the brain, “hypothalamic hamartoma is the prototype lesion,” Dr. Fountain reported. Importantly, these and other lesions within the envelope where energy can be targeted are the most difficult to treat with other options. Due to the need to transverse much of the brain to reach these areas, open surgery is often not practical. Even though Dr. Fountain acknowledged that MRI-guided stereotactic laser has been proposed for these types of lesions, the laser must also transverse vulnerable structures of the brain that can be avoided with MR-guided FUS.

Results on the first patient in a planned pediatric treatment series with MRI-guided FUS were presented at the AES annual meeting by Travis Tierney, MD, PhD, a neurosurgeon associated with Nicklaus Children’s Hospital in Miami. According to the data presented by Dr. Tierney, the 21-year-old patient was treated for a hypothalamic hamartoma. She was rendered seizure free and had no complications.

An adult series is now recruiting candidates, according to Dr. Fountain. He reported that adults of at least 18 years of age with intractable epilepsy due to subcortical lesions in the central envelope suitable for MRI-guided FUS are eligible if they have at least three seizures per month while taking at least two antiepileptic drugs. He encouraged referrals.

“The primary outcome will be just to demonstrate that a lesion can be created,” Dr. Fountain said. He reported that the planned enrollment of 15 subjects would not be sufficient to draw conclusions about efficacy “unless, of course, we eliminate everyone’s seizures – and that would be useful – but that is still a secondary outcome,”

There are a number of applications in neurology beyond treatment of tremors and epilepsy that are also being considered for MRI-guided FUS, Dr. Fountain reported. This could include, for example, clot lysis in stroke, but he indicated that there are a number of reasons to be particularly optimistic about its potential role in the treatment intractable epilepsy due to subcortical lesions. This strategy seems feasible in a condition with limited treatment options.