Focused Ultrasound for Parkinson’s disease

Although elective procedures are currently being postponed in hospitals across the country because of the necessary focus on COVID-19, eventually our hospitals will return to normal and non-emergent procedures will be performed again. This will include elective procedures for the treatment of Parkinson’s disease (PD).

Two brain procedures that are approved for use in PD are deep brain stimulation (DBS) and high intensity focused ultrasound (FUS). I encourage you to read more about DBS and view our webinar which outlines the newest features of this procedure.

What is high intensity focused ultrasound (FUS)?

The newer of these two treatments for PD is FUS in which beams of ultrasound waves are focused on a designated target in the body, thereby concentrating enough energy to create a small lesion. Individual ultrasound waves do not contain enough energy to do damage as they pass through the body’s tissue. It is not until multiple waves are all focused on a particular spot that a lesion is formed, which can be therapeutic in certain clinical situations. Previously FUS had been approved by the Food and Drug Administration (FDA) to treat bone metastases, uterine fibroids, enlarged prostate cancer and essential tremor.

FUS Approved by FDA for Treatment of Parkinson’s Tremor

In 2018, tremor-predominant PD was added as an FDA-approved indication for the use of FUS.  When an FUS-induced lesion is created in specific locations in the brain, it can disrupt abnormal PD circuitry. In this procedure, MRI is used to precisely direct the ultrasound waves to the ventral intermediate (VIM) nucleus of the thalamus, a structure that acts as a relay station for many of the brain’s functions. Abnormalities of thalamic circuitry are known to play a role in tremor and lesioning this area of the thalamus decreases tremor.

Clinical Trials Currently Underway

FUS treatments of other brain regions are under investigation for other PD symptoms. A clinical trial is currently underway to test whether FUS of the globus pallidus will improve medically-refractory dyskinesias or motor fluctuations in advanced PD. Another study is investigating whether FUS of the subthalamic nucleus can help motor symptoms of PD such as slowness and stiffness.

It is interesting to note, that prior to the advent of DBS as a surgical option for PD, lesioning surgery of the thalamus and other brain areas was used to treat the symptoms of PD. In these surgeries, the skull was opened in order to enter the brain and brain tissue had to be disturbed in order to access the deep structures of the brain. FUS can perform approximately the same role as lesioning surgery in a much less invasive way.

DBS vs. FUS

Currently, FUS is only approved for tremor in PD, but when additional clinical trial data is available, it is anticipated that FUS will be used to treat the same set of symptoms as DBS including wearing off, motor fluctuations and dyskinesias. With the additional option of FUS to treat PD symptoms, many are wondering which treatment is better to pursue? This requires an in-depth discussion with your neurosurgeon, but I will give an overview of the pros of each procedure.

Pros of focused ultrasound

• FUS does not require any incisions or holes in the skull. No hardware is left in the body. DBS does require both an incision and a hole in the skull and hardware is permanently placed in the brain and body. This makes DBS more invasive, with an increased risk of bleeding and infection as compared to FUS.
• In FUS, the individual ultrasound waves that penetrate the brain are too weak to cause damage until the waves converge on the designated deep brain structure. DBS on the other hand, requires an electrode to be passed through healthy brain on its route to the deep brain structures. Although any damage to healthy brain that DBS may cause is minimal, this is even less of an issue with FUS.
• FUS is a single procedure. DBS requires one procedure to place the electrode in the brain and another to implant the implantable pulse generator (IPG). There are also subsequent visits to program the IPG and adjust settings. The battery also needs periodic replacement.

Pros of deep brain stimulation

• DBS is done routinely on both sides of the brain. FUS is currently done on only one side as the full side effects of having FUS done on both sides of the brain is not yet fully understood. This may change in the future as more is understood about FUS.
• DBS has been an FDA-approved procedure for decades. Because of this, neurosurgeons will have much more experience with it than with FUS.
• Although symptoms of PD progress with time and may therefore lead to an overall worsening of a person’s condition, the effects of DBS itself do not wane. The longevity of improvements from FUS is not yet fully known.
• DBS is programmable. As PD symptoms progress and change, adjustments can be made to improve the efficacy of DBS. FUS is a procedure that is performed once and can’t be adjusted.
• The DBS hardware is removable if necessary, which makes the procedure reversible. FUS is not reversible. Once the lesion is created, it is permanently in the brain.

Low intensity focused ultrasound to help deliver therapies

While high intensity FUS is a treatment for PD as described above, low intensity FUS can be used in an entirely different way to help treat PD. This type of FUS may allow for disruption of the blood brain barrier. The blood brain barrier refers to the cells that line the blood vessels within the brain which keep foreign substances, such as toxins and microbes, in the bloodstream and out of the brain.

Normally, this mechanism is advantageous and protects the brain. However, the blood brain barrier may also keep out molecules that could help to treat brain diseases. Therefore, disrupting the blood brain barrier could allow for penetration of these molecules into particular areas of the brain. A whole variety of different molecules such as antibodies, nerve growth factors and gene therapy may be able to take advantage of this approach. Further research is necessary to determine if this will be a useful method for drug delivery into the brain.

Tips and takeaways

• Deep brain stimulation and focused ultrasound are two brain procedures that may be used to help PD symptoms in certain patients.
• Currently, focused ultrasound is only approved for tremor in PD, but clinical trials for other PD symptoms are underway.
• Pros and cons of deep brain stimulation and focused ultrasound are complicated and must be reviewed with the treating neurosurgeon.
• Focused ultrasound may also one day be used to enhance drug delivery into the brain.
• Not all procedures make sense for every person with PD, so it is important to talk to your doctor about your options and carefully discuss the risks and benefits of any new treatment or procedure.