The most common movement disorder, essential tremor often doesn’t respond to meds and depresses quality of life. As neurosurgeon Doris Wang, MD, PhD, explains in this short, information-packed presentation, focused ultrasound can bring immediate and lasting relief to many. She describes the procedure; benefits and potential complications; outcomes data; and how techniques developed at UCSF improve target visualization, enhancing accuracy and effectiveness.
mm hmm, mm hmm. Hello. My name is Doris wang. I am a functional neurosurgeon and assistant professor in the department of neurological surgery here at University of California san Francisco. Today I'd like to discuss a novel technology focused ultrasound for the treatment of essential tremor. This is an outline of my talk today. First I will give an overview of the central tremor discusses prevalence characteristics of the symptoms as well as main treatment options. Next I will give an in depth review of focused ultrasound, what the technology is, how it works as well as the clinical results. Finally, I will talk about getting focused ultrasound treatment at UCSF, our evaluation process and the treatment day. Essential tremor is a neurological condition characterized by involuntary shaking usually involving the upper extremities and the tremors worsened with movement and activity and usually is calm at rest. The central tremor is the most common movement disorder in the world, affecting 1- 2% of the population. Its incidence increases with age too, affecting about 4-5% of the population over the age of 65. The tremors can start at any age with average onset between 40 and 50 years. Tremor can start as early as childhood and follows a bimodal distribution With peak onset in the 2nd and 6th decade of life in terms of what the tremor looks like. These tremors are characterized by again increasing shaking with certain movements in certain with certain actions and with certain postures. It usually involves rhythmic again involuntary tremors of the upper extremities but can't actually involve any part of the body including the head, the voice or the lower extremities. While essential tremor is a movement disorder, there are other non motor symptoms that are involved as well. Recent studies have shown that many patients with essential tremor have co morbid non motor symptoms, including mild cognitive changes, depression and anxiety. In both the motor and non motor symptoms of this disease can make activities of daily living very challenging and has a huge negative impact on a patient's quality of life. The path of physiology of essential tremor is not well known. So it is thought to involve rhythmic oscillations generated by the cerebellum that oscillate throughout the cerebral cortex, the ponds and the thalamus. So the origin of these oscillations is not well known at this point. So when a patient is diagnosed with essential tremor and the tremors are affecting daily activities. Usually the first line of treatment is with medication. There are many types of medication that can be used to treat a central tremor. The most common are per panel which is a beta blocker and printed um which is an anticonvulsant. Unfortunately about 30-50% of patients may not respond to medical therapy. And plus medical therapy can cause side effects including slow heart rate, low blood pressure, dizziness and sedative effects. Another treatment for a central tremor include botulinum toxin injection and has been shown to be somewhat effective for tremors involving the head and the voice. The Botox injection is not as effective for hand trimmer. The other negative side effect of Botox injection included the transient nature of the therapy, therefore requiring multiple injections to see a long lasting effect. Surgical intervention has been shown to be a very effective treatment for a central tremor. So bring surgeries such as deep brain stimulation. Surgery or DBS involves implantation of a battery powered device that supplies electricity to leads that are implanted to the brain that can modulate the brain circuits that control movement. It is highly effective but does require device maintenance implantation of devices as well as maintenance post post op. Finally, another type of surgery that can be used to treat essential tremor are a blade of surgeries, also known as the Kalamata me, where these are non reversible surgeries that target application of heat to oblate or lesion tissue that drives the ET symptoms. And focused ultrasound is a type of a blade of surgery. So focused ultrasound is a type of Kalamata me where we lesion a specific region of the brain. It was approved by the FDA in 2016 to treat essential tremor and in 2019 focused ultrasound was approved to treat tremor Dominant Parkinson's disease. The technology uses up to 1020 for sound waves from a helmet shaped device that can precisely deliver and safely through the skull. With no incisions. These sound waves converge to raise the temperature inside the brain and the temperature will raise to such a degree that it can cause permanent lesion of the brain tissue. And the target we're trying to find is the V. I. M. Or the ventral intermediate nucleus of the thalamus, which is a target commonly used for deep brain stimulation surgery, as well as other types of surgical Kalamata me. The ventral intermediate nucleus or the V. I. M. Is a very small region in the center of the brain. It's measures about three x 5 mm and it's located in the thalamus of the brain. As you can see, it's a very tiny region and identifying it accurately is critical for the success and the safety of the surgery. So this is an animation of how the focused ultrasound works, a patient is placed inside an MRI scanner with this helmet shaped device around his or her head. Hundreds of ultrasound beams are aimed at the thalamus part of the brain that's causing the tremor. While each beam is harmless but just like focusing light with a magnifying glass where all the beams meet the temperature rises to the point of destroying that tissue. And this can be done in a very precise way. So these Kalamata me has been around for many decades. So what sets focused ultrasound Kalamata me apart from other types of Kalamata me procedures. First of all focused ultrasound Kalamata me is incision lys. It does not require a craniotomy or burr hole to pass a probe into the target tissue to heat it up. Also the ultrasound waves can accurately oblate the target tissue with extreme precision. And now with the event of M. R. I. Guided thermography where we can accurately and in real time monitor the brain tissue temperature. As we're performing the procedure, we have a chance to really monitor the amount of tissue or lesion ng in real time, ensuring safety and efficacy. Also, we can perform the procedure with the patient awake where physicians can perform real time assessment to see tremor improvement and also potential side effects before we commit patient to a permanent lesion. And again with these 1,024 sound wave sources, we can precisely alter and change the shape of our lesion before we commit to a permanent lesion. So what are the clinical results? These videos demonstrate a patient with severe each central tremor in his right hand. Before and after the procedure. In the video on the left, you can see that was holding his hands in an extended posture. The right tremor is very disabling and severe. And after his treatment with focused ultrasound, you can see significant improvement in his right hand tremor. So in the landmark study published a New England Journal of Medicine 2016 76 patients with moderate severe essential tremor were randomized to either focus ultrasounds Kalamata Me vs a sham procedure for treatment of their tremor primary outcome was tremor rating skill before and after the procedure in between the two patient groups in the graph here, shown on the right, you can see that for those who receive focused ultrasound, Kalamata me showing blue here, there is immediate and sustained tremor decrease compared with the sham group. The secondary outcome included significant improvements in disability and quality of life metrics, as shown by these bar graphs. Again, those receiving focused ultrasound Kalamata me had significant improvement in disability score compared with those who received sham treatment. So while this study shows significant and immediate benefit of focused ultrasound are the effects durable. Recently, there has been several articles and studies published on the durability of focused ultrasound. Kalamata me in each central tremor. In this one study, which was prospective study Four years after focused ultrasound, Kalamata me, there was an average of 56% improvement in hand tremor, 70% improvement in postural tremor, 63% improvement in action tremor as well as disability compared with baseline. So this and other studies have all shown that there's significant sustained improvement in tremor score over the study period after Kalamata me. As with any surgical intervention, focused ultrasound has its associated adverse effects immediately after treatment. The most common adverse events include imbalance gait disturbances About numbness and tingling. In about 1/3 of the study subjects, headache and head ping in about half of the study subjects, But of all these adverse events, about half of them resolved within 30 days and additional button. Common side effects include dizziness, taste disturbances, slurred speech fatigue and vomiting. So out of the side effects which ones are persistent. So in the study um again from the same group of patients who underwent the perspectively randomized control trial after three years, persistent adverse events included imbalance on steadiness, gait disturbances as well as musculoskeletal weakness and numbness and tingling. But as you can see all these side effects are very rare. And to summarize there are many advantages of focused ultrasound kalamata. Me, first of all, you see an immediate and durable tremor improvement in the patient's there is significant improvement in quality of life. It is an outpatient procedure where patients can go home the same day. It has little to no risk of infection. There are no implants, probes or ionizing radiation required for treatment and oftentimes there's no anesthesia that's needed for the treatment. So now I would like to take this opportunity to talk about focused ultrasound treatment at UCSF and some of the advances that we are doing here. So if you have a patient who is interested in receiving the therapy, the evaluation process consists of evaluation by a neurosurgeon as well as some movement disorder neurologist. So patients should have a confirmed diagnosis of medically refractory essential tremor or tremor dominant Parkinson's disease. They should have failed to. First line medications must be an adult And can tolerate the procedure by lying still in the M. R. I. for about 2-3 hours. Patients should be able to communicate um sensations and also improvements during the procedure that they can activate the stops on occasion button if needed to stop the procedure. So contra indications for receiving focused ultrasound include the standard country indications for obtaining an M. R. I. Including having a non M. R. I. Compatible implant in the body. Also for patients with scold density ratio of less than 0.5. As calculated from a screening CT is not suitable for the procedure. So during screening a CT scan is performed to determine the thickness and density of the skull and whether it's suitable for the procedure. During treatment the patient's hair is shaved to ensure nothing will interfere with the ultrasound waves. Patients hair will grow back naturally. After local numbing medication is applied. A frame will be secured to the patient's head to ensure there is no movement. During the treatment an elastic cap will be placed to seal the helmet to ensure water will circulate around the patient's head. During treatment. During treatment the patient will be laying down in the treatment bed inside the M. R. I. Scanner the medical team will be in the control room. A patient will be able to communicate with the team. The patient's head will be placed in the focused ultrasound helmet which will be filled with water and the patient will be given a stops on occassion button If at any point the patient needs to stop the treatment. M. R. I. Images will be taken to plan the treatment. The physician will first apply light doses of ultra sound energy to identify the correct location in the brain for the treatment like a testes. Then full intensity focused ultrasound energy will be applied. The treatment bed will be moved in and out of the M. R. I. Machine and after each treatment, the patient will be tested for clinical improvement in trimmer and assess for any potential side effects. Improvements in tremor should be seen immediately at the end of the treatment. An M. R. I. Scan will be taken to evaluate the size of the lesion. The frame will be removed and the patient will spend an hour in the recovery room and go home the same day. So critical to the success of the focused ultrasound procedure is ability to accurately identify the V. I. M. Region of the thalamus. As I mentioned before, it is a very small region in the middle of the brain and the V. I. M. Also receives cerebellum inputs and as part of the dentist, oh, rubio thalamic tract with the D. R. T. So identifying the V. I. M. Can be challenging sometimes because it cannot be visualized on traditional M. Ri sequences on the right image here is the standard T. Two weighted image. It's motion degraded and one cannot really visualize where the V. I. M. Is located. So most often times, physicians rely on consensus coordinates for targeting with awake inter operative testing for confirmation here at UCSF we have developed novel ways to visualize the V. I. M better using M. R. I. Technology. So in the right here you see an M. R. I. Image is called a proton density scan which looks for water content within each Vauxhall and the V. I. M. Can be readily visualized these darker areas within the M. R. I scan. So these images compare a traditional T. Two weighted image on the left here and a proton density scan on the right in the same patient, again showing the regions of the I. M. Using the proton density scan. And as I mentioned before, the V. I. M received inputs from the cerebellum and using track ta graffiti. We can map out this fiber track the dentist, adorable thalamic track and really lesion at the intersection of the V. I. M. And the fiber track. This will not only improve accuracy and efficacy of treatment but can potentially avoid side effects. In conclusion, focused ultrasound is a safe effective treatment for essential tremor. It uses ultrasound waves to precisely lesion part of the brain that's involved with tremor generation. And here at UCSF we use advanced imaging techniques to improve targeting accuracy and efficacy. If you are interested in pursuing this treatment or have a patient who may be interested you can email us at bring high food at UCSF dot e d u. This is also our website for our treatment page for focused ultrasound here at UCSF. And lastly, please feel free to reach out for any questions. Mm hmm, mm hmm. Yeah.