Landmark Progress in Noninvasive Treatment of Brain Disorders


functional neurosurgery feasibility study shows potential for treating brain disorders with MR-guided focused ultrasound

Eben Alexander III, M.D., and Rolf Taylor

A groundbreaking new study has paved the way for clinical studies on the noninvasive treatment of a broad spectrum of brain disorders including Parkinson’s disease, epilepsy, stroke, and brain tumors.

A team at the University of Zürich, in Switzerland, has completed a pilot study using MR-guided focused ultrasound to treat 10 patients with neuropathic pain. The origin of pain in these patients included post-amputation phantom limb syndrome, nerve injury, stroke, trigeminal neuralgia, and post-herpetic neuralgia from shingles.  The findings will be published in a forthcoming issue of Annals of Neurology.

The study was partially funded by the Focused Ultrasound Surgery Foundation, which funds translational and clinical research into new therapeutic applications of MR-guided focused ultrasound (MRgFUS).

The preliminary results in these patients are comparable to those obtained with conventional therapy – radiofrequency ablation – an invasive procedure that involves making an incision in the scalp, drilling a hole in the skull, inserting an electrode through normal brain tissue into the thalamus, and using radiofrequency electromagnetic waves to create the lesion.

Functional neurosurgery involves alteration of the brain’s circuitry to treat various neurological conditions such as pain, movement, and behavioral disorders. It is a growing discipline that has developed over more than 60 years.  In general, treatment involves creating  lesions (destruction) in a neural circuit using radiofrequency ablation, or placing an electronic deep brain stimulator (DBS) to modulate the activity of a circuit.  Ablation has the advantage of treating the patient with a single procedure; however, it involves the risk of long-term neurological complications if the location of the lesion is suboptimal.

Use of DBS has the advantage of reversibility in the event of improper location, but is far more expensive in terms of monetary cost and the time spent by specialists programming and maintaining the stimulator and its power supply. In addition, both ablative lesions (commonly performed by inserting a radiofrequency electrode) and DBS involve electrode passage through the brain itself, with a significant risk of hemorrhage or infection. The latter is especially problematic in DBS placement for patients with Parkinson’s Disease, whose state of health and poor self-care result in four to seven times the risk of infection, compared to general neurosurgical patients.

Stereotactic radiosurgery (using the Gamma Knife or Linear Accelerator) has demonstrated a somewhat limited applicability as a noninvasive method in certain functional neurosurgical disorders, especially trigeminal neuralgia (a common type of facial pain). However, its use of high levels of ionizing radiation may lead to significant complications.

Focused ultrasound is the first truly noninvasive treatment approach to emerge as an alternative to surgery and radiation. By focusing thousands of ultrasound beams on a single point, the medical team can achieve the same therapeutic effect as radio frequency ablation and radiosurgery, but without the risks and complications associated with traditional surgery or ionizing radiation.

“This study showed that we can perform successful operations in the depths of the brain without opening the cranium or physically penetrating the brain with medical tools, something that appeared to be unimaginable only a few years ago,” says Daniel Jeanmonod M.D., a neurosurgeon at the University of Zürich and the study’s co-principal investigator.

“By eliminating any physical penetration into the brain, we hope to duplicate the therapeutic effects of invasive deep brain ablation without the side effects, and for a wider group of patients. The research funding from the Focused Ultrasound Surgery Foundation allowed us to conduct the study rapidly and with scientific rigor,” adds Dr Jeanmonod. “We are an academic institution and this type of award is essential to our research process.”

According to Neal Kassell, M.D., a neurosurgeon at the University of Virginia and chairman of the Focused Ultrasound Surgery Foundation, the key advantage of focused ultrasound is that it is noninvasive. This, in principle, makes it safer than conventional surgery by avoiding the associated risks of infection, hemorrhage, and damage to the brain.

“This research demonstrates that MR-guided focused ultrasound can be used noninvasively to produce small thermal ablations with extreme precision and accuracy deep in the brain,” explains Dr Kassell. “This lays the foundation for revolutionizing the treatment of a variety of brain disorders that traditionally required surgery, including Parkinson’s disease and essential tremor, epilepsy, brain tumors, and stroke.”

“We are pleased to have been able to provide funding for this groundbreaking research,” adds Eben Alexander, M.D., director of the Brain Development Program at the Focused Ultrasound Surgery Foundation. “Dr. Jeanmonod’s work may help open the door to enable the noninvasive treatment of some of these most prevalent brain disorders.”

Other research sites are expected to initiate clinical studies on the use of MR-guided focused ultrasound for treating brain disorders within the next year.