For patients with drug-resistant epilepsy, focused ultrasound (FUS) is a safe, noninvasive treatment option that takes 10 minutes to perform, early research suggests. However, one expert cautions the results are “highly preliminary.”

In a phase 1 trial that involved six participants, no radiologic changes resulted from FUS treatment. Although two patients experienced treatment-related adverse events (AEs), the AEs completely resolved with time.

“Navigation-system-guided, low-intensity FUS could be used safely in patients with focal epilepsy in terms of neuromodulation,” co-investigator Hsiang-Yu Yu, MD, chief of the epilepsy section, Taipei Veterans General Hospital, and associate professor at National Yang Ming Chiao Tung University, Taipei, Taiwan, told Medscape Medical News.

The findings were published online November 2 in Epilepsia.

Alternative to Surgery?

The estimated prevalence of drug-resistant epilepsy may be as high as 36%. Although surgical interventions provide seizure freedom for many of these patients, not all are good surgical candidates.

Neuromodulation is an alternative to surgery but often requires the implantation of electrodes or other devices. FUS, on the other hand, is noninvasive, and in a recent animal study, it provided neuromodulation.

The current proof-of-concept study was an open-label, uncontrolled trial that assessed the safety of FUS in humans. The study included six patients (67% men; median age, 31.5 years; median epilepsy duration, 12 years) with drug-resistant epilepsy who underwent implantation with stereo electroencephalography (SEEG) for surgical evaluation. SEEG and scalp EEG were recorded simultaneously for all patients.

The FUS system used in the study provided transcranial treatment that was guided by a neuronavigation tracking system. The researchers targeted for treatment the brain regions that showed the earliest changes in SEEG during seizures.

The maximum treatment intensity was <2.8 W/cm², pulse repetition frequency was 100 Hz, burst length/focus exposure was 3 ms, and duty cycle was 30%. Total exposure time was 10 min. Patients were awake throughout treatment, and SEEG was recorded simultaneously.

No Radiologic Changes

MRI conducted immediately after FUS showed no radiologic changes. The investigators observed normal cortical lamination and no focal edema.

In the 72 hours after FUS treatment, seizures occurred in three participants. Seizure frequency was decreased in two of the patients. Although one patient experienced increased seizure frequency, these new seizures were subclinical.

Following FUS, the number of interictal epileptiform discharges decreased in four patients and increased in two.

One of the two reported AEs was uncomfortable scalp heating, which prompted treatment interruption. Treatment resumed an hour later without complications.

The other AE, in another participant, was impairment in naming and memory, which occurred between days 4 and 11 after FUS. This patient’s neuroimaging and scalp EEG were normal. The symptoms did not affect daily life and resolved completely within 3 weeks.

Current neuromodulation treatments for epilepsy are based mainly on electrical or magnetic mechanisms, the investigators note.

“FUS modulates neural activity through mechanical effects, which is different from vagus nerve stimulation [VNS], deep brain stimulation, transcranial magnetic stimulation, or transcranial direct current stimulation,” said Yu.

“The observation period was not long enough to demonstrate clinical efficacy in this phase 1 study,” Yu noted, although the intracranial EEG recording did show a “power spectrum change after focused ultrasound treatment without lesioning effect, which was later proved by MRI,” she said.

The investigators are now conducting a phase 2 trial with a longer observation period and short-duration, repetitive treatment. “We are hoping to see the clinical efficacy by these new methods,” Yu said.

“Highly Preliminary”

Commenting on the study for Medscape Medical News, Samuel Wiebe, MD, professor of neurology at the University of Calgary, in Calgary, Canada, urged caution when interpreting the findings.

“We should all be very aware that these are highly preliminary results,” said Wiebe, who was not involved in the research.

The study provides no evidence of damage or permanent structural changes to the brain tissue when using low-frequency FUS for neuromodulation, he added.

The neuromodulation effect of FUS has been demonstrated in animals, and the researchers claim that their study provides initial evidence of neuromodulation in humans, Wiebe noted.

“I would see the contribution of this paper as one more block in the edifice of safety,” he said. “It tells us absolutely nothing yet about its ability to change ictogenesis or epileptogensis in humans at this stage.”

VNS provides nonspecific stimulation to the CNS via the vagus nerve, whereas FUS targets a specific brain area. “I don’t think we know exactly how either of the techniques works,” said Wiebe. “It is thought to be a mechanical alteration of the membrane and the ion channels, perhaps, but the mechanism is not totally clear.”

Many conditions associated with epilepsy cannot be addressed without standard surgical procedures, Wiebe noted. FUS opens the possibility of offering minimally invasive or noninvasive treatment as an initial step to appropriate patients with discrete epileptic foci. If the patient does not respond, then other techniques can be considered, he said.

“This would open up a window of enormous potential. The opportunities are really, in my view, very significant. These technologies could be game changers,” Wiebe said.

For the immediate future, collaborative research will be necessary, he added.

“Getting the numbers of patients and getting to share data and collaborate is going to be really important in moving this field forward,” said Wiebe.

The study was funded by NaviFUS Corporation, the Taiwan Ministry of Science and Technology, and the National Health Research Institutes. Yu and Wiebe have disclosed no relevant financial relationships.

Epilepsia. Published online November 2, 2021. Full article

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