A woman began walking with a more fluid gait, while another patient could suddenly eat using utensils. Both patients, in advanced stages of Parkinson’s disease, experienced immediate relief from severe tremor on one side of their body.
What’s behind these dramatic patient outcomes? A high-intensity focused ultrasound (HIFU) procedure that targets two tracts of the brain only a few millimeters – six to nine, to be precise – apart.
The two recent treatments were performed by the Advanced Therapies in Movement Disorders (ATMD) Program at CU Anschutz. They were the first dual-target procedures using HIFU in the Rocky Mountain region.
The team leading the procedure included Drew Kern, MD, MS, associate professor of neurology, and Daniel Kramer, MD, associate professor of neurosurgery, both at the CU Anschutz School of Medicine. While the treatments provided immediate motor performance symptom relief for the two patients, further study is needed to determine HIFU’s durability, potential cognitive effects and the merits of a bilateral treatment approach.
“We did it one week, and it worked great,” Kern said of the dual-target procedure performed on the woman. “Then we thought about it for another patient – a man who had dementia. And sure enough, afterward he had zero rigidity and very little slowness of movement, plus no tremor. His wife said that was the best night of sleep they’ve had in years because he wasn’t having a tremor. And, for the first time, he actually ate breakfast without any difficulty.”
Dyskinesia, or involuntary movement, and bradykinesia, or slowness of movement, are among the motor complications affecting people with advanced Parkinson’s disease. More than 1.2 million Americans have Parkinson’s, a progressive neurological disorder with no cure.
Deep brain stimulation (DBS), where surgeons implant electrodes in a targeted area of the brain, has been used to treat motor problems of Parkinson’s disease for decades. In recent years another therapeutic option, incisionless HIFU, has become available for patients with advanced Parkinson’s who haven’t found symptom relief from medications and aren’t candidates for DBS, due to infection risk and other reasons.
First, the U.S. Food and Drug Administration (FDA) approved HIFU to treat tremor-dominant Parkinson’s, which affects approximately 10-20% of the Parkinson’s population. This procedure delivers ultrasound waves to the dentatorubral thalamic tract (DRTT) of the brain, which plays a critical role in regulating tremor movements. More recently, the FDA approved HIFU for the pallidothalamic tract (PTT), which is an area of the brain that, when compromised, causes stiffness, slowness of movement and involuntary movement.
The ATMD team has treated over 100 patients with the DRTT target, Kern said, with patients showing significant tremor improvement. “The outcomes support sustained benefit for at least five years as this treatment has only become more widely used over that period,” he said. “As time goes on, we will be able to evaluate even longer outcomes.”
Targeting the PTT could make focused ultrasound an option for patients with Parkinson’s symptoms beyond tremor, including rigidity and bradykinesia. “The PTT area was thought of as a possible target because of the circuitry involved that might improve the cardinal symptoms of advanced Parkinson’s disease – that being potentially the rest tremor, but also bradykinesia, which is the slowness of movement and stiffness.”
Kern called the PTT procedure results on the female patient’s left side of her body, where her motor complications were most pronounced, “a remarkable improvement.”
Both target areas – DRTT and PTT – were performed in the same outpatient procedure, which took about 90 minutes. During the DRTT, the woman experienced about 60-70% improvement of her rest tremor, with little improvement in stiffness and slowness of movement. After the PTT procedure, however, “she got the full benefit and had zero tremor. In addition, she had, I would estimate at least 70% improvement of stiffness and about the same with the speed of her movements.
“The beneficial results were immediate on the MRI table, so that’s how we know that we’re in a good place,” Kern added.
DBS wasn’t a viable option for either the male or female HIFU patient, “so for any individual who isn’t really a great candidate for DBS, this might give them another option, another hope.”
The patients will return for follow-up visits in a couple months, according to Kern. Longer-term outcomes with PTT continue to be studied, including possible cognitive effects. HIFU is an ablative-focused procedure, interrupting the circuitry that causes the motor performance symptoms.
Research continues on the longer-term outcomes of the dual-target treatment.
Studies are also examining the potential motor performance benefits of focused ultrasound, staged bilateral PTT, which was approved by the FDA last year, after encouraging outcomes in a clinical trial. So far, the ATMD has performed only unilateral (one side of the brain) HIFU. The FDA requires that patients who have undergone HIFU on one side must wait at least six months before the second side procedure.
“We need more studies to convince us that doing a bilateral PTT HIFU is in a patient’s best interest,” Kern said. “It’s something we certainly would have to discuss as a team.”
Key points:
- CU Anschutz physicians performed the first dual-target focused ultrasound procedures for Parkinson’s disease in the Rocky Mountain region.
- The procedure targets both the DRTT and PTT, with the goal of addressing tremor as well as other motor symptoms.
- The two patients experienced immediate improvements in symptoms, according to the treating physicians.
- Focused ultrasound may offer an alternative to some patients with advanced Parkinson’s disease who are not candidates for deep brain stimulation.
- Longer-term effectiveness and safety, including potential cognitive effects and bilateral treatment, continue to be studied.