Key Points
- Dr. Jeanmonod was one of the first physicians to translate modern focused ultrasound to human patients with neuropathic pain and movement disorders.
- Learn about his role in discovering the brain mechanism behind these disorders and how he translated that knowledge into effective treatments.
Do you know who provided the evidence for the unified mechanism behind neuropathic pain and movement disorders? It happens to be one of the first physicians to translate modern focused ultrasound to human patients: Daniel Jeanmonod, MD.
Professor Jeanmonod recently retired and closed SoniModul, his focused ultrasound clinic in Switzerland. This pioneer in functional neurosurgery changed the way that patients are treated when he worked with legendary neuroscientist Professor Rodolfo Llinás to discover and document thalamocortical dysrhythmia, the neuronal hyperactivity that causes Parkinson’s disease and is the source of neuropathic pain.
“Daniel Jeanmonod is the quintessential pioneer in focused ultrasound,” says Foundation Chairman Neal F. Kassell, MD. “His seminal work on making lesions deep in the brain – in and around the thalamus – is what triggered the rapid growth of the field of focused ultrasound. Not only were his studies important for treating neuropathic pain, but they served as the predicate for using focused ultrasound to treat essential tremor, Parkinson’s, and many other disorders in the brain and the rest of the body.”
We interviewed Prof. Jeanmonod to learn more about his incredible career as a functional neurosurgeon and how he plans to spend his retirement sharing what he learned about the psycho-emotional management of complex pain syndromes and the integration of spiritual health into medicine.
What is your background in medicine?
I obtained the Swiss medical degree in 1978 and specialized as a neurosurgeon in Switzerland, England, and France to earn the title of Swiss neurosurgeon and began using stereotactic radiofrequency technology for lesioning in 1989. I was head of the Department of Functional Neurosurgery at Zürich University Hospital between 1989 and 2009. I held a Professorship of Functional Neurosurgery at the University of Zürich between 2001 and 2019 and one in Physiology and Neuroscience at New York University between 1998 and 2018. I founded the SoniModul Center for Ultrasound Functional Neurosurgery in Solothurn, Switzerland, in 2010. As a functional neurosurgeon, I treated people with brain diseases that produce symptoms from neuronal overactivity in the brain. I had a particular interest in treating patients with neurogenic (or neuropathic) pain and movement disorders, including Parkinson’s disease and essential tremor.
In 1998, what research were you doing when you won the Foundation Pfizer Research Prize?
I was studying the mechanisms behind abnormal movements and neuropathic pain. To perform stereotactic radiofrequency operations, we had to penetrate the brain with an electrode and then apply the radiofrequency current to make small therapeutic lesions. Before that, we used microelectrodes to record electrical brain activity; these were single-unit, cell-by-cell recordings.
This work allowed us to first guarantee precision, but it also led us to discover how neurons behave in the thalamus of the brain. The thalamus is a structure in the middle of each hemisphere that is in close connection with the entire cortical domain. Based on our studies, we proposed that the thalamus and cortex, which together represent the largest brain mass in our heads, are reciprocally interconnected by feedback loops, and this type of organization exists for all brain areas: areas addressing movement, cognition, emotion, and the different senses. These areas are all organized in the same way and overlap with one another. During interventions, we found that the same special neuronal activity was responsible for the symptoms found in movement disorders, pain, tinnitus, epilepsy, and neuropsychiatry. In 1996, we published these findings in Brain and then learned about similar thalamic research being conducted by Professor Rodolfo Llinás.
So, in 1998, we joined energies to work together with Dr. Llinás and his team on thalamocortical dynamics. Together we proposed the term thalamocortical dysrhythmia, which means improper or inadequate rhythmicity, that is too much activity in the brain. If an area of the brain is a motor area and is affected by this mechanism, we get abnormal movements. If it is the pain domain, we have neuropathic pain. It was all a great endeavor, and great work to do together. The results, “Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography,” were published in the Proceedings of the National Academy of Science (PNAS) in 1999.
How did your thalamocortical dysrhythmia work inform your approach for using focused ultrasound?
There have been two main parts to my career: First, understanding the problem and second, treating the problem. Focused ultrasound came in the second part. Before focused ultrasound, we had to penetrate the brain with electrodes, with risks to the brain (e.g., bleeding, infection). Any displacement of the brain could also reduce precision of all the techniques that we might use. Focused ultrasound offered the possibility to continue to do the same treatments that were based on our discoveries, but to do them more precisely and less invasively. And the results have shown that that was indeed the case: Of more than 500 interventions performed on over 600 targets, we did not have a single case of bleeding or infection, and the precision was inside half a millimeter. So, technologically, thanks to focused ultrasound, we had the chance to optimize precision and safety.
When did you first learn about focused ultrasound?
It must have been about 2004 when I received a phone call from my colleague, Ernst Martin, MD, a radiologist who told me about focused ultrasound. He knew that I was making tiny, millimeter-sized therapeutic lesions in the middle of the brain and suggested that focused ultrasound could be an ideal technology to explore for these procedures. He was quite right, indeed! We then joined together and developed our own research program and performed our first clinical trial, where we used focused ultrasound to treat patients with neuropathic pain.
The first team using focused ultrasound to address the brain was our colleagues in Boston, at Brigham and Women’s Hospital. They were working on brain tumors. So, they were really the pioneers. We had a field that was very handy thanks to small therapeutic work performed in the middle of the brain on histologically normal tissue.
Throughout your long career, what did you learn about how to best target the thalamus with focused ultrasound?
We had to take the techniques that we had developed over the years using electrodes and transfer it to the different situations with focused ultrasound. The target stayed the same, but how to reach it, how to cover it as completely and as safely as possible was the goal of our development. The way to apply heat was another consideration (i.e., radiofrequency uses an electrode, but the heat is applied differently than with focused ultrasound). Optimally, we needed complete target coverage to get the best possible results.
What gave you the courage to try new treatments that others had not yet tried in humans?
I was encouraged, as I mentioned before, by my colleagues in Boston at Brigham and Women’s Hospital. They were the ones who had the idea to do treatments in the brain. They had a much more difficult context, because they were treating brain tumors that are more difficult to reach and that can bleed. But I was encouraged by the fact that there was another entire team that was solidly considering the possibility of focused ultrasound. I also considered the way the Insightec system had been developed, and it all made a lot of sense to me. Having a small target in the center of the brain offered an amazing possibility to optimize safety and efficacy. It completely made sense. Having contact with Insightec, the company that produced the system, also helped greatly. I was impressed by the solidity and serious safety measures implemented in all parts of the system (as much as a doctor can judge, as I am not a technologist!). I had long discussions with these people, particularly Eyal Zadicario and Kobi Vortman, and I was impressed by the quality of their engineering. In fact, it was confirmed when we started the project: our last step toward human application was relatively easy, because the machine already contained all the elements that we needed to demonstrate that it would work.
You were the first in the world to use transcranial focused ultrasound to treat patients with neuropathic pain. Tell us about that first clinical trial.
Between 2005 and 2009, at the University Children’s Hospital of Zürich, Dr. Martin and I tested everything needed to move focused ultrasound into human brain treatments. For example, we conducted cadaver research and tested many facets of the technology. We chose neuropathic pain as the indication, targeted the central lateral thalamus, and set the goals of the first trial to determine safety, feasibility, and reproducibility of the technique for 9 patients. These results were published in 2009 in the Annals of Neurology. The first therapeutic results (one-year follow-up) of using focused ultrasound central lateral thalamotomy to treat pain were published in 2012 in Neurosurgical Focus. The whole work was supported by the University of Zürich, the Swiss Federal Institute of Technology Zürich, the University Children’s Hospital Zürich, the Swiss National Center of Competence in Research (NCCR) “Computer Aided and Image Guided Medical Interventions,” the Focused Ultrasound Foundation (Charlottesville, VA), the Gönnerverein des Kinderspitals Zürich, and the Sanitas Hospital in Kirchberg. Technical support was provided by Insightec, Ltd. (Tirat Carmel, Israel).
What were the reactions from the participants in the clinical trial?
Pain relief is always very appreciated in patients with chronic, therapy-resistant, long-lasting, and severe pain conditions.
When did you open SoniModul, the Center of Ultrasound Functional Neurosurgery, in Solothurn, Switzerland? What were some of the first cases you treated at your practice?
We opened the SoniModul Center in 2010 and conducted a large, official, company-sponsored clinical trial supported by Insightec from 2011 to 2012, treating patients with neuropathic pain, Parkinson’s, and essential tremor. SoniModul then proceeded independently until its closure.
In 2023, you published a follow-up analysis of 55 consecutive patients with chronic and therapy-resistant neuropathic pain who were treated with focused ultrasound central lateral thalamotomy. What were those results?
This study was published in the Journal of Neurosurgery. With a long mean follow-up time of 55 months (4.5 years), good outcomes (50% pain relief or better) were found in 54% of patients at 3 months, 49% at 1 year, and 51% at the last follow-up. So, more than 50% of the patients had more than 50% pain relief. On the visual analog scale, continuous pain and pain attacks were reduced 40% to 50% at the last follow-up. The mean frequency of pain attacks was reduced by 92%, and allodynia (oversensitivity where light touch or light pressure produces pain) was reduced or suppressed in 68% of patients and never appeared de novo after MR-guided focused ultrasound central lateral thalamotomy. In the entire series, there was only one complication, which was a reduction of sensitivity on a small area of the face. It is important to mention that this procedure, the central lateral thalamotomy, is one of the oldest functional neurosurgical interventions ever performed, as it was already being performed in the late 1940s and early 1950s.
What are your research contributions to essential tremor, Parkinson’s disease, and other indications?
From our work at SoniModul, we published about 10 peer-reviewed papers on essential tremor, Parkinson’s, and chronic pain. I am happy to leave it to the attention and development of other colleagues in the field to further pursue focused ultrasound treatments for epilepsy, psychiatry, and tinnitus.
Who were your mentors?
Professor Henrik van der Loos, a Dutch neuroanatomist who was at the University of Lausanne, Switzerland at the time, was my mentor for my doctoral thesis. I am lucky that he introduced me to the arcana of science, and that I could do my thesis on brain plasticity. Professor Rodolfo Llinás, a renowned neurophysiologist, was my mentor, and he became a dear friend of mine; it was great to develop the thalamocortical dysrhythmia concept together. I owe a lot to him and to all the very fruitful discussions we have had for many years now. Professor Gazi Yarşargil, the renowned neurosurgeon and chief of the neurosurgical clinic in Zürich in which my department of functional neurosurgery was inserted, has never stopped supporting us and stimulating us. Prof. Yarşargil’s successor, Professor Yasuhiro Yonekawa, gave us the same, much appreciated support.
When you retired earlier this year, you closed your SoniModul clinic. How do you reflect on your legacy?
It was a miraculous, amazing 14-year period. We developed a small center with a staff of less than 10, administered by a small, family-based company. We endeavored to keep the standards of academic medicine by publishing 10 peer-reviewed papers in the field. I am proud that we integrated the very important domain of emotions and feelings into treating our patients. It simply has been an amazing adventure. I am delighted and grateful to have had the chance to do it all with a dear and dedicated team.
What are your greatest achievements?
On the scientific level, my greatest achievement is co-discovering the thalamocortical dysrhythmia. Clinically, it has been opening the SoniModul clinic and working there for 14 years.
What patient stories stand out to you?
I often think about my patients with neuropathic pain. One patient had a discal hernia operation in the lumbar sacral area. The hernia could be repaired, but the compression on the nerve root produced a typical neuropathic pain situation that could not be controlled by other interventions or medications. During the procedure for the neuropathic pain, the patient cried out. The procedure was being done under local anesthesia, and the patient was having a surprising reaction. We stopped everything. When I talked to him, he told me, “It’s incredible…I can feel my leg again!” What we discovered from this simple outcry was that, indeed, together with pain production, the thalamocortical system can produce a block of somatosensory perception. Starting to work on the target was allowing him to feel his leg again. We could thus uncover a component of the thalamocortical dysrhythmia syndrome: it can produce pain AND a deficit, over- AND underactivity. That was an incredible moment.
Another story: a young lady had a brain infarct in her thalamus, which was caused by a malformation. Because she was a young person, she recovered well from the motor losses, but kept a neuropathic pain syndrome in the whole hemibody contralateral to the thalamus (as is always the case). She had allodynia as part of her syndrome, which is an extremely painful sensation to light touch on the skin. The allodynia was on her arm, and she was unable to wear a blouse or anything because any touch was very painful, like electricity discharges or pins and needles. When we began to work on the target, again under local anesthesia, the patient began caressing her arm without a sign of pain. We were all extremely delighted, of course, so I let her do that for a moment to allow her to integrate the new situation. I then asked her, “Do you feel any change now?” And she thought two seconds and said, “No, it’s exactly the same.” The next day, I sat with her to try to understand what was happening. She revealed that having the brain infarct had been a nightmare that she could not accept. She had completely rejected the reality of her condition, and her non-acceptance was stronger than the effect of surgery. This discovery is important for anyone who is treating pain, because we cannot see the symptom, so we have to trust what the patient says, and integrate the essential role of emotions.
With neuropathic pain treatments, one cannot expect 100% pain relief because of the psycho-emotional factors that are present. In 2011, we published the postoperative results of patients who had a pain thalamocortical dysrhythmia. Two-thirds of them had good pain relief, and one-third were below 50%. In the group of patients who had good relief, their EEG activity was normalized over the course of the year of follow-up. The group with insufficient relief kept the overactivity. The same operation, within the millimeter, can give 0% to 100% pain relief. Additionally, we found a solid correlation between paralimbic overactivity (inside the emotional areas of the brain) and a scale of frustration. In pain management, non-acceptance and frustration are an issue (as in the case of the patient with the infarct). Frustration (and also anxiety) must therefore be considered every time pain surgery is considered.
Do patients who go on to work with a psychologist have reduced pain?
Yes, absolutely. In another case, an American patient who had had a herniated disc developed neuropathic pain. The presurgical EEG showed overactivity where we expected it, in the pain-related areas of the brain. After surgery, she only had diffuse overactivity in her emotional brain; it was weaker but still present, and she had insufficient pain relief at the time. She was a very religious person, so I advised her to find an environment where she could have psychotherapy that was compatible with her religious feelings. She found that, and when she returned a year later, her EEG had normalized. When asked about such a great evolution, she said that thanks to her psychotherapy, she had realized the following: “If God is perfect, he can have only perfect children,” therefore, she could not be as bad as she thought. It was a deep insight into the strong emotional factor of self-hate and frustration.
Psycho-emotional elements can indeed be addressed with psychotherapy. Patients who undergo psychotherapy can improve further after surgery if they can then reduce their frustration levels or their anxiety. One can well estimate that a large percentage of the patients who do not have enough pain relief would need psychotherapy.
When did you first hear about the Focused Ultrasound Foundation? Has the Foundation played a role in your work?
It must have been at the beginning of the Zürich clinical trial – I would suppose 2005 or 2006. I have always had amazing contacts within the Foundation, and we had its financial support for our work. The Foundation has a detailed and updated website describing studies and experiences worldwide, with the locations of the centers that perform focused ultrasound. The website was fundamentally important for us, because many patients that consulted the Foundation’s website found their way to us. We had many constructive contacts with many collaborators at the Foundation. Tim Meakem, among others, has been incredibly supportive.
What advice do you have for young neurosurgeons who are using focused ultrasound for functional neurosurgery?
In this field, it is important to understand the different dimensions of anatomy and physiology of the brain, and the technology of the machine one wants to use. The decision to treat a patient should always be based on the underlying mechanism of the disease. These days, empiricism is somewhat dominant. In my opinion, there is often not enough interest in the underlying mechanism of a disorder. “What’s the mechanism?” dictates the flow of the work. And always in medicine, but in this field particularly, the psycho-emotional and psychosocial dimensions must be included. Importantly, our small group was able to offer to patients a high-tech, scientific dimension together with a family-like and holistic environment, so that our patients could feel understood and supported including at the emotional level.
What is next for you? How will you spend your retirement?
I would like to write a book or two. One topic will be the role of emotions. It is highly relevant to insist on the deep integration of ideas and emotions in medicine. This is something I had to discover over the years of my career – to work toward my better integration of these dimensions. It allowed me to understand things I could not before. Another topic is the spiritual dimension. As human beings, we are often wondering whether we deserve what happens to us. The answer may depend on one’s spiritual or materialistic insights. These dimensions need so much to be considered and integrated into the practice of medicine.
Listen to the Curing with Sound Podcast that Features Dr. Jeanmonod.
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