Focused Ultrasound for the Treatment of Parkinson’s Disease

Post by Natalia Ladyka-Wojcik

A primer on motor symptoms in Parkinson’s disease

Parkinson’s disease (PD) is a complex neurodegenerative disorder that affects over 10 million people globally, typically in individuals aged 60 years or older. PD affects a central brain area called the basal ganglia, leading to a range of motor, cognitive, and sleep changes. A particularly affected region of the basal ganglia is a crescent-shaped cell mass in the brain stem called the substantia nigra. The neurons in this tiny region produce the neurotransmitter dopamine and play a big role in planning and controlling body movement. In PD, these neurons begin to die off and hallmark motor symptoms of PD such as tremor, rigidity, and slowness of movement tend to emerge when about 80% of dopamine is lost.

Dopamine is critical for stimulating receptors in one of the basal ganglia called the striatum, which works with the substantia nigra to send signals between the spinal cord and the brain. If striatum receptors aren’t sufficiently stimulated, other portions of the basal ganglia may also be over- or under-stimulated: the hallmark tremors associated with PD result from overstimulation whereas rigidity and slowness of movement result from understimulation. Perhaps unsurprisingly, patients with PD report that the severity and frequency of these symptoms significantly decrease their quality of life, highlighting the importance of targeted treatment for these symptoms.

Current challenges in treating Parkinson’s disease symptoms

Traditionally, PD treatments have largely relied on medications, which aim to either preserve dopamine in the brain by preventing its breakdown, increase dopamine release, or mimic dopamine altogether. Although clinical research has made great strides in developing effective medications for PD, these medications tend to work better in the early stages of the disease. Moreover, some of these medications can cause unwanted side effects, including hallucinations, nausea, depression, and even obsessive behavior. Given these considerations, research has turned to exciting new avenues for treating PD by leveraging advanced therapeutic technologies. Here, we’ll survey two major technologies to better understand the future of PD treatment: (1) deep brain stimulation, and (2) focused ultrasound.

Deep brain stimulation for Parkinson’s disease

Deep brain stimulation (DBS) is a surgical therapy that addresses the movement symptoms of PD but can also help improve other non-motor symptoms including changes in sleep. In the U.S., it is approved by the Food and Drug Administration and is especially effective in individuals with severe tremors. In DBS surgery, electrodes are inserted into the basal ganglia and then a pacemaker-like implant is placed either under the collarbone or in the abdomen. This implant delivers electrical neurostimulation to the basal ganglia which the patient controls with a remote. On average, DBS patients with optimal drug therapy require lower medication doses compared to a control group receiving only optimal drug therapy. Importantly, DBS patients also show slowed progression of tremor symptoms. The future of DBS as a therapy for PD holds much promise, with larger randomized control studies to investigate DBS efficacy underway by the Food and Drug Administration.

Focused ultrasound: A cutting-edge therapy for Parkinson’s tremors

When imagining what neurosurgery is like, you might visualize the surgical incisions needed for neurosurgeons to access the brain. However, focused ultrasound therapy is a new noninvasive approach: beams of ultrasonic energy are used to precisely and accurately target deep brain structures with thermal lesions without damaging surrounding healthy tissue. This technique massively reduces risks of infection or brain bleeding compared to traditional surgery and does not require any external implants to be placed in the patient’s body. Neurosurgeons typically use magnetic resonance imaging (MRI) to guide the ultrasound beams to the desired location in the patient’s brain, ensuring that thermal lesions are done accurately. On average, patients show marked improvements in motor symptoms of PD, especially tremor, although some negative side effects have been reported. In the future, some scientists hope that focused ultrasound technology can even be used to disrupt the blood-brain barrier, a selective semi-permeable membrane that defends the brain from external substances and can sometimes prevent medication from successfully reaching the brain. This means that in addition to directly manipulating dysfunctional brain signaling, focused ultrasound may also help PD medications be even more effective.

What’s the bottom line?

Every year 90,000 people are diagnosed with PD in the United States alone, and it is the second-most common neurodegenerative disease after Alzheimer’s dementia. PD is associated with progressive symptoms, especially related to motor skills, which are managed by available medications only to a certain degree of efficacy. New technologies, including DBS and focused ultrasound, provide exciting new avenues for the treatment of PD.

References +

Hacker, M. L., Turchan, M., Heusinkveld, L. E., Currie, A. D., Millan, S. H., Molinari, A. L., Konrad, P. E., Davis, T. L., Phibbs, F. T., Hedera, P., Cannard, K. R., Wang, L., & Charles, D. (2020). Deep brain stimulation in early-stage Parkinson disease. Neurology, 95(4), e393–e401.

Moosa, S., Martínez‐Fernández, R., Elias, W. J., Del Alamo, M., Eisenberg, H. M., & Fishman, P. S. (2019). The role of high‐intensity focused ultrasound as a symptomatic treatment for Parkinson's disease. Movement Disorders, 34(9), 1243-1251.

Rahman, S., Griffin, H. J., Quinn, N. P., & Jahanshahi, M. (2008). Quality of life in Parkinson’s disease: The relative importance of the symptoms. Movement Disorders, 23(10), 1428–1434.

Whitney, C. M. (2007). Medications for Parkinsonʼs Disease. The Neurologist, 13(6), 387–388.