How Do I Know That Mr
Your medical team will conduct a complete assessment of your condition, conduct any needed addition tests, and then discuss if you are a candidate for this or other treatment options .
Generally, MR-guided focused ultrasound may be an option if:
- You have a confirmed diagnosis of essential tremor or tremor-dominant Parkinsons disease
- Have tremors that have not been relieved by medications
- Have tremors that limit your ability to perform daily activities
Focused Ultrasound Has Potential As A Non
Most people with Parkinsons will use medication to help control their symptoms, but for some, over time, medications alone may no longer be enough to control symptoms. This is when specialists may look towards surgical options. Currently deep brain stimulation offers the main surgical way to control movement symptoms of Parkinsons.
This type of surgery involves inserting fine wires into the brain to be controlled by a pulse generator that is placed under the skin around the chest or stomach area. When the pulse generator is switched on, the electrodes deliver high frequency stimulation to the targeted area. This stimulation changes the electrical signals in the brain that are causing some of the movement symptoms of Parkinsons.
Read more about the brief history of surgery for Parkinsons in a previous blog post.
But what if there was another way to target cells deep within the brain? This is where a technique called focused ultrasound comes in. It offers a way to change the way the brain works without the need for invasive brain surgery.
In this blog we find out exactly what focused ultrasound is and how it might help people with Parkinsons in the future.
To learn more, we spoke to Professor Wladyslaw Gedroyc, Consultant Radiologist at Imperial College Hospital, who has over 20 years experience investigating the potential of focused ultrasound.
Regulatory Approval & Reimbursement
The Exablate system manufactured by is approved in Europe and in the US for treating tremor-dominant Parkinson’s disease. Patients should talk with their physician if they are not sure if they have tremor-dominated Parkinsons disease. We recommend that they talk with the treatment site for questions about insurance coverage under Medicare, as some treatment sites are now being reimbursed by Medicare. Most commercial companies are not currently covering this procedure.
How Do I Know If I Am Eligible For Treatment
Your doctor is the best person to ask about this. He or she will be able to tell you if you are a suitable candidate. In general, people who cannot go into an MRI will not be able to go through the treatment – this includes patients with metallic implants, patients who are claustrophobic and patients who are allergic to contrast agents – a dye used during MR imaging, patients who are over 300 lbs and patients who are under 22 years of age.
- If you have any kind of metallic implants, such as pacemakers, neurostimulators, spine or bone fixation devices, total joints, metal clips, screws, etc., you may not be a candidate. Any metallic implants must be non-magnetic to prevent injury to the patient from the MRs strong magnetic field.
- If you are not generally healthy enough to withstand the treatment and lie still in the same position for approximately 3 hours, you may not be a suitable candidate for this treatment.
- If you have had a recent myocardial infarction or have congestive heart failure , unstable angina pectoris , or spinal conditions, are you should discuss these issues with your doctor.
- If you have extensive scarring on the scalp, you may not be a good candidate.
- If you have any tumors inside the skull, you may not be a good candidate.
- If you are on dialysis, you may not be a good candidate.
- If you have an active infection or severe hematological, neurological or other uncontrolled disease, you may not be a good candidate.
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.
Focused Ultrasound Shows Promise For Parkinsons Disease
Jeff Elias, MD, pioneered the use of focused ultrasound for the treatment of essential tremor and Parkinson’s disease.
A scalpel-free alternative to brain surgery has the potential to benefit people with Parkinsons disease symptoms that are much more severe on one side of the body, new research suggests.
More testing is needed, but the approach, which uses a technology called focused ultrasound, could offer a new option for patients whose symptoms are poorly controlled by medications and those who cannot or do not wish to undergo traditional brain surgery.
This small brain region, the subthalamic nucleus, had a very strong and potent effect on Parkinsonian symptoms when we targeted it with precise, focused ultrasound energy, said researcher Jeff Elias, MD, a neurosurgeon at UVA Health and a pioneer in the field of focused ultrasound. The key for the ultimate adoption of this new procedure will be further refinements of the technology to ensure reliability and safety.
About Uvas Focused Ultrasound Research
UVA has been at the leading edge of research into focused ultrasounds potential to treat disease. For example, the federal Food and Drug Administration approved the technology for the treatment of essential tremor, a common movement disorder, based on Elias pioneering research. His work also paved the way for the FDA to authorize the technology to treat tremors caused by Parkinsons disease.
Other researchers at UVA are investigating the technologys potential to treat a wide variety of conditions, including epilepsy and breast cancer.
Is This A Cure For Parkinsons Disease
No.
This current research trial is investigating the safety of injecting an enzyme in conjunction with opening the BBB in the putamen, one of the key regions of the brain implicated in Parkinsons. The putamen is a key structure in controlling the brains motor circuitry.
The hope is that this technique may be a way to open temporary access ports into the brain and allow large molecules such as enzyme therapies to enter.
This Phase 1 clinical trial is a very early, but necessary step in this process.
What Other Exciting Opportunities Does This Technology Offer
There is ongoing research investigating whether this technology can reversibly open up the blood brain barrier to particular areas of the brain. This is extremely exciting because the blood brain barrier currently acts as an extra hurdle for drugs to reach the needed areas of the brain in neurological conditions, and therefore this could hold the opportunity to deliver more efficient and targeted treatment options in the future.
The technology is also being investigated for people with other neurological conditions such as obsessive compulsive disorders and epilepsy.
Huge thanks to Professor Wladyslaw Gedroyc, Consultant Radiologist at Imperial College Healthcare NHS Trust, London.
This blog is not meant as health advice. You should always consult a qualified health professional or specialist before making any changes to treatment or lifestyle.
About Dr Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Neurosurgery Associates.
A New Approach To Reach Tremors Root Cause
Patients with essential tremor have traditionally been presented with a variety of invasive treatment options, including surgical ablation and deep brain stimulationboth of which target tremor by disrupting abnormal signaling in the thalamus.
HIFU similarly targets the thalamus, but instead uses a noninvasive focused ultrasound beam that creates a lesion, eliminating the abnormal signaling at the root of tremor and thus normalizing the regions circuitry. Candidates for the procedure typically have tremor symptoms that interfere with their quality of lifepersisting despite conservative treatment. Requiring only a few hours to complete, HIFU is a safer, noninvasive treatment option with a much lower risk of complications and minimal recovery time.
The safe use of HIFU requires close partnership between neurosurgeons, neurologists, and neuroradiologists in order to visualize brain response during the procedure. The ability to regulate temperature as you precisely target the tremor-inducing misfiring neurons in the thalamus is vital to avoid brain injury, notes Alon Mogilner, MD, PhD, associate professor in the Departments of and Anesthesiology, Perioperative Care, and Pain Medicine and co-director of the Center for Neuromodulation. The combination of ultrasound with MRI thermography enables real-time visualization and temperature feedbackand makes HIFU both a safe and viable option for patients.
How Is The Blood
The patient is fitted with a specialized headframe, which directs ultrasound waves to precise targets in the brain. The patient is then placed in an MRI for the focused ultrasound treatment.
An ultrasound contrast agent, or microscopic bubbles, are injected intravenously and circulate in the bloodstream. These microbubbles are smaller than red blood cells; when low-intensity focused ultrasound energy is applied the circulating microbubbles vibrate, temporarily expanding the junctions between the cells of the BBB.
The small and temporary opening in the BBB created by focused ultrasound, allows the direct delivery of the enzyme replacement therapy. In this Phase 1 trial, the putamen is the region targeted for enzyme delivery because of its key functions in Parkinson disease and role in motor performance.
What Are The Benefits And Advantages Of Mr
Using this procedure:
- No holes are made in the skull
- No hardware/device are implanted
- No general anesthesia is used
- Theres no risk of infection or bleeding that would be present with incision-based procedures
- Physicians can determine if treatment is working in real time during the procedure as well as stop if adverse effects occur
How The Innovation Works
One advantage of ultrasound is that it does not damage the tissue it passes through, yet focusing multiple waves on a targeted area produces heat, which can destroy, or ablate, the tiny area of the brain causing the tremors.
Finding a way to get ultrasound to penetrate the dense tissue of the skull and accommodate individual variability took years of development. INSIGHTEC, which was founded in 1999 and has dual headquarters in Haifa, Israel, and Miami, developed hardware that produced ultrasound powerful enough to penetrate the skull, and software that corrects for skull shape and thickness.
The technology often can use a facility’s existing MRI, Ferr says, which enables the neurosurgeon to guide the high-energy focused ultrasound waves. The procedure is known as MRgFUS and the treatment is an incisionless thalamotomy.
Patients are awake during the process and wear a special helmet that delivers the ultrasound treatment from inside the MRI machine. They typically start the session unable to drink water from a glass or write legibly because of tremors. Before the ablation occurs, the medical team does preliminary testing to ensure the proper brain location is pinpointed.
Focused Ultrasound Vs Deep Brain Stimulation
Focused ultrasound and deep brain stimulation are both surgical procedures for Parkinsons. Both are FDA-approved to treat tremor that does not benefit from medication. DBS also is approved for Parkinsons movement symptoms and dyskinesia, and clinical trials are evaluating FUS for these same indications.
Focused ultrasound and DBS work in the same brain areas but in different ways. FUS destroys cells, and DBS delivers small electrical pulses to those same cells to interrupt abnormal signaling. FUS is permanent and irreversible, while DBS may be reversed by removing the system or turning it off. Focused ultrasound is non-invasive there are no incisions and no hardware is placed in the body. For DBS surgery, doctors make incisions in the skull to insert wires in the brain and in the chest to place a battery below the collarbone. FUS is a one-time procedure that does not require adjustment. DBS needs programming to find the right electrical stimulation settings to maximize benefit and limit side effects.
Focused ultrasound may be an option in people who can’t or don’t want to pursue deep brain stimulation. Some are unable to undergo invasive surgery because of heart or bleeding problems. Others aren’t DBS candidates because of memory and thinking problems. Still others don’t want to manage the logistics of DBS programming and future battery replacements. Focused ultrasound expands the available treatment choices for patients and doctors.
Am I A Candidate For Mrgfus
MRgFUS is FDA approved for the treatment of patients with essential tremor and tremor-dominant Parkinson disease. It can only be used to treat one side of the brain even if tremor is present on both sides. MRgFUS is not yet FDA approved to treat both sides. If first line medications fail to adequately control your tremor, your doctor may consider recommending either MRgFUS, deep brain stimulation, or radiosurgical thalamotomy. Compared to other surgical treatments for essential tremor, no device implant is needed, no incision is required, and the treatment works immediately. To read more about What to Expect During Consultation for Essential Tremor, .
Why Is This Relevant To People With Parkinsons
As I said, so far most of the work has been done in people with essential tremor but these techniques are now being applied to Parkinsons.
Parkinsons can affect people in different ways. Those people that have what is known as tremor dominant Parkinsons, can be treated in a similar way to those undergoing focused ultrasound treatment for essential tremor by interrupting the tissue pathways that contribute to the cause of tremor in the nucleus ventralis intermedius .
We have treated a few patients with tremor dominant Parkinsons, currently about five, and we see similar improvements to those with essential tremor. But there have been much fewer research studies investigating focused ultrasound for Parkinsons so more research is needed before this technique can be recommended and available on the NHS for people with Parkinsons.
We want to carry out a randomised clinical trial to see if focused ultrasound is beneficial to people with tremor dominant Parkinsons. This is something that is currently under discussion.
There is also ongoing research looking at focused ultrasound for people with other types of Parkinsons, for instance bradykinetic Parkinsons. Bradykinesia means slowness of movement and can be responsible for symptoms such as freezing. The results from this trial can hopefully be expected soon.
How Does This Technique Compare To Dbs
DBS works in a different way to focused ultrasound, DBS overwhelms the faulty circuits whereas focused ultrasound destroys the circuits, to help with movement symptoms.
The advantage of DBS is once the electrodes are in the correct position in the brain you can turn it on and off, dial it up and down depending on the severity of the symptoms. Whereas, focused ultrasound is a permanent non-invasive procedure.
One of the current limitations of focused ultrasound is that it is currently only carried out to one side of the brain, since studies using treatment to both sides are only in their infancy at the moment. For most people with Parkinsons their movement symptoms impact both sides of their body. For this reason DBS still offers an excellent way to manage Parkinsons as it can control tremor on both sides.
We are starting to look at using focused ultrasound bilaterally, on both sides of the brain. But we need to be cautious, as in the past a technique called leisioning that targeted regions of the brain on both sides resulted in a high number of people developing speech problems. That being said, this previous technique was much less accurate than focused ultrasound and early results treating both sides are very promising.
What Is Focused Ultrasound
Focused ultrasound is a non-invasive, image-guided surgical technology that harnesses the power of ultrasound energy. Using a specially designed helmet, ultrasound is delivered across the skull to deep brain targets without requiring scalpels or incisions. At Sunnybrook focused ultrasound is delivered in an MRI so real time image guidance can be used.
What Neurologic Conditions Can Be Treated With Mr
The U.S. Food and Drug Administration has approved focused ultrasound for the following conditions:
- Essential tremor. MR-guided focused ultrasound is approved for the treatment of essential tremor that cannot be controlled with medication. Approval is for treatment of one side of the brain only. Patients must be at least 22 years of age.
- Tremor-dominant Parkinsons disease. MR-guided focused ultrasound is approved to treat patients with Parkinsons disease whose main symptom is tremor. Patients must be at least 30 years of age.
Use of MR-guided focused ultrasound is being explored for other neurologic conditions including the tremors associated with multiple sclerosis, epileptic seizures that cannot be controlled by other treatment approaches, other movement disorders, , brain tumors and neuropathic pain. Treating these other conditions is considered experimental at this time.
What Are Potential Benefits Of Fus Therapy For Parkinsons Related Tremor
Dr. Shah: Since were using the FUS energy to create a thermal lesions its really a one-time procedure. Its a single treatment and that in and of itself is attractive to a lot of patients.
Tremor ends up often being this particularly outlying symptom that can be more difficult in a certain subset of Parkinsons patients to get control of. Our thought is that we have the tremor pathway that is fairly well defined, not only in essential tremor but also has an analogue in Parkinsons disease. We can potentially use the same target the VIM nucleus of the thalamusin the essential tremor trial and use that for these tremor dominant, medication- refractory Parkinsons patients, knowing that the other features of the Parkinsons either arent very prominent or are adequately being treated with the medications they are on to begin with.
What Is The Evidence For Fus Therapy For Tremor
Dr. Shah: The majority of the reports that we have are smaller series. At UVA we have the largest series, which is 15 patients, all of whom have completed a year of follow up and some of whom have gotten past two years. The main outcome weve looked at is safety first of alland thats typically the case with any new treatment paradigmIs this safe?and then secondly, Is this effective? And certainly when were talking about lesions in the brain thats a paramount concern.
The safety profile has been favorable. There have been some patients out of those 15 who had immediate side effects, such as instability or the feeling of some numbness or tingling particularly around the mouth or in the hand thats being treated for tremor. But the vast majority had improved within a couple of weeks. What was left at one year was a single patient out of those 15 who was left with a bit of tingling along the aspect of their forefinger in the treated hand.
In terms of efficacy, we found quite a significant reduction in 14 of the 15 patients where there was over a 50 percent reduction in the rating scales, as we measured them using the clinical rating scale in tremor. Some of the patients had almost near resolution of tremor thats been persistent for a year to two years.
Patient Story: Focused Ultrasound And Parkinsons Disease
It all started with a tiny tingle and I worried it was a sign of something bigger.
I was at a chili taste-testing contest when I reached to pick up a glass of hot apple cider and my baby finger tingled.
In that moment, I was concerned it was Parkinsons disease.
I had a feeling because my dad had had Parkinsons.
Over time I began noticing changes. My hand and arms started to tremor and my handwriting got progressively worse.
When my neurologist first gave me my diagnosis, I didnt want to believe it was Parkinsons. I wanted to fight it and beat it.
I still do.
Right now, there is no cure for Parkinsons disease. Its a progressive disease and its symptoms such as stiffness and tremor worsen over time. Each person with Parkinsons disease, experiences it differently.
For me, living with Parkinsons is a challenge. My main symptom is dyskinesia, which can include fidgeting or body swaying. My body isnt always doing exactly what I want it to do. Each day is different and depends on how my body is reacting to the medication that Im taking to help ease my symptoms.
I ended up retiring early from my job as a private school secretary. Day-to-day tasks take a bit longer to do, but I want to do things myself and I just take breaks when I need to.
The first participant of a world-first clinical trial
While some parts of my life are different, what hasnt changed for me is how determined I am to help in the search for a treatment or cure for Parkinsons disease.
Study Design And Patients
This was a prospective, single-arm, non-randomized, proof-of-concept, safety, and feasibility phase I trial of focal BBB disruption in patients with PDD. Power calculations were not performed to determine the number of patients as this was a pilot investigation. Since this was an exploratory study, the results are presented in a purely descriptive manner. All patients demonstrated neuroimaging abnormalities in the targeted area, and the right parieto-occipito-temporal cortex BBB opening sessions were separated by 23 weeks based on the patients availability. This study was approved by the Research Ethics Board at HM Hospitales and the Spanish Agency of Medicines and Medical Products number 627/17/EC, and registered at ClinicalTrial.gov number NCT03608553. The study design and conduct complied with all relevant regulations regarding the use of human study participants and was conducted in accordance to the Declaration of Helsinki.
How Does Focused Ultrasound Work
Ultrasound is typically used to diagnose problems, but in this case, it’s used as a therapy.
During the procedure, sound waves are directed from all different angles towards the target, the ventral intermediate nucleus of the thalamus. When these sound waves come together in the target, they generate sufficient heat to make a tiny lesion in your brain, resulting in a therapeutic effect.
You will be inside of an MRI scanner during the entire procedure. This enables your doctor to easily plan, guide and target the treatment area, and monitor temperature throughout the procedure to ensure that the tissue is treated correctly and thoroughly.
About Focused Ultrasound At Uva
UVA has been at the leading edge of research into the technologys potential to treat disease. For example, the federal Food and Drug Administration approved focused ultrasound for the treatment of essential tremor, a common movement disorder, based on Elias pioneering research. His work also paved the way for the FDA to authorize the technology to treat tremors caused by Parkinsons disease.
Other researchers at UVA are investigating the technologys potential to treat a wide variety of conditions, including epilepsy and breast cancer.
Focused Ultrasound And Parkinsons Disease
Parkinsons Disease is a neurodegenerative brain disease that is progressively debilitating and leads to motor dysfunction and cognitive decline. PD affects more than 10 million people worldwide and nearly 1 million in the US. Healthcare costs in the US alone related to PD are estimated at $52 billion per year.
PD is caused by degeneration of dopamine neurons that reside predominantly in a location of the midbrain called the substantia nigra. These neurons project to other areas within the brain and normally work to promote smooth, effective motor function. With the loss of dopamine neurons caused by PD, these pathways are disrupted, leading to a slowing of voluntary movements and increased involuntary movements .
Another hallmark of PD is an abnormal accumulation of a protein called alpha-synuclein, which can become misfolded and aggregate into clumps within the brain. It is thought that these abnormal deposits of alpha-synuclein play a role in the pathophysiology of PD, but the exact mechanism is unknown.
Clinical Trial Update: Treating Parkinson’s with Focused Ultrasound
In all of these clinical trials, patients were shown to have improvements in their global rating scores for motor disability while experiencing no serious adverse events. As with any brain treatment, there were some side effects, but most of these were transient and resolved over time.
Preclinical Research Update
Antibody Delivery through the BBB Opening in an Alpha-Synuclein ModelColumbia University