Indications investigated
History and mode of action of focused ultrasound
A technical revolution or old wine in new bottles? Even before the invention of deep brain stimulation and even before the development of drug treatment for Parkinson’s disease, it was known that tremor on the opposite side of the body could be treated very effectively by targeted destruction of tissue in the “tremor nucleus” of the thalamus. In the past, this so-called ablation (tissue destruction) of an approx. 3x4mm area in the brain was carried out by inserting a probe and heating the tip for a few seconds.
The disadvantage of this procedure compared to deep brain stimulation is that there is no possibility of reversing the tissue destruction if the ablation is performed incorrectly or if side effects occur. As these side effects occurred frequently, the procedure was largely abandoned in the 1990s. Today, thanks to focused ultrasound, the technical possibilities have developed further and ablation for the treatment of tremor and increasingly also other diseases and symptoms is being rediscovered.
The main further developments are the possibility of treatment without a skin incision and without opening the skull surgically, as well as the possibility of monitoring the procedure in real time using MRI. In this respect, the risks that arose at that time from the finality of the destruction of brain tissue must be reassessed. Today, experts in movement disorders worldwide agree that treatment with focused ultrasound is a valuable addition to established methods.
For treatment with focused ultrasound, the energy from up to 1024 ultrasound sources is bundled in a single central point in the brain, where it leads to targeted heating of the tissue. The procedure is highly precise and the small target area can be heated with millimeter accuracy. In addition, the entire treatment is carried out under real-time monitoring with magnetic resonance imaging, so that it is possible to recognize how many °C the tissue is heated to. This is done step by step:
Initially, the temperature in the tissue is only slightly increased (to approx. 50°C), which already has an inhibitory effect on the cells, but does not yet destroy the tissue after a short exposure. This allows a neurological examination to assess whether a good improvement in tremor can be achieved at the heated target point and whether side effects occur. If the result is satisfactory, the target is heated further to 55 to 60°C and a small area of 3 to 4 mm in size is finally destroyed. The effect is immediate. The aim of the treatment is to permanently reduce the tremor by 50 to 75%, not to completely normalize it. In severely affected patients, the second side of the body can also be treated after an interval of nine months and after thorough interdisciplinary consideration and careful risk assessment, provided there are no lasting relevant side effects from the first treatment.
As a rule, deep brain stimulation is preferred for patients who have a pronounced bilateral tremor. This also applies in particular if structures in the middle of the body are affected, i.e. if there is a tremor in the head or voice. On the other hand, focused ultrasound is particularly suitable if the tremor is more pronounced on one side, without accompanying head or voice tremor. Furthermore, focused ultrasound is particularly suitable for patients with a higher risk of surgery and delirium. These are mainly older people with many other illnesses, as well as people who do not have easy access to a specialized center. This is the case, for example, if a move to another country with less dense medical care is planned.
Preliminary and follow-up examinations
What are the risks?
Although the skin and skull are not opened for treatment with focused ultrasound, permanent damage to brain tissue is caused with high energy. This can lead to rare but potentially serious complications.
On the one hand, there are surgical risks: The vibrations generated by the ultrasound can theoretically cause fine blood vessels to rupture. A cerebral hemorrhage can cause permanent neurological disorders or even be fatal. The risk is extremely low and
cannot yet be quantified with certainty. However, it is certainly less than 0.5%. If the device malfunctions, the target region could theoretically be missed and damage could be caused elsewhere in the brain. This would also lead to neurological disorders. However, as the therapy is carried out with real-time monitoring, this risk is extremely low.
In addition, there are side effects that arise when neighboring structures of the core area are disturbed in their function. These correspond to those that can also occur with deep brain stimulation. As explained above, these side effects arise both from the actual lesion and from the temporary swelling that surrounds it. The swelling is dynamic and disappears over time – the lesion itself, however, is permanent. For this reason, there are more side effects in the early phase after treatment. Over time, many of them disappear or gradually improve.
The following side effects in particular are possible for treatment in the “tremor core”:
- Sensory disturbances such as a feeling of numbness or tingling over certain areas of the body
- Taste disorders such as a metallic taste in the mouth or altered perception of food
- Gait disturbances: Unsteady gait “as if drunk”, twisting to one side, risk of falling
- Speech disorders or slurred speech
- Swallowing disorder
- Coordination disorders such as unsteady grasping of objects
Gait disturbance plays a particularly important role. It occurs temporarily after treatment in around three quarters of patients and can persist for months. In the vast majority of patients, this side effect is only mild. This means that it is noticeable but does not restrict everyday life. However, around a quarter of patients still complain of a temporary gait disorder that is significant in everyday life. For this reason, patients with a pre-existing gait disorder may only be treated after very careful risk assessment. It also makes sense to plan outpatient physiotherapy in advance. Over time – with regular training and the disappearance of the swelling around the ultrasound lesion – the gait disorder usually improves significantly. Thus, in our own series of 52 treated patients, 5 to 10% still had a gait disorder after six months that interfered with everyday life. This was the most frequent, relevant, “permanent” side effect. A sensory disturbance was recorded in around 10% of people. But it hardly ever interfered with everyday life. The same applied to the coordination disorder (reaching), which was also observed in around 10% of patients. This often does not play a major role either, because the tremor, which has a much greater impact on coordination, is improved. Overall, the risk of side effects increases with the degree of tremor improvement. This means that patients with good or very good control of tremors are more likely to have a side effect. Those with less successful tremor therapy usually have no side effects.
What are the chances that I will be “satisfied” with the treatment after six months?
We asked the 52 patients after six months whether, based on their experience, they would undergo the treatment again if they could turn back time. 87% answered “yes” and 13% “no”. As explained above, this is often a trade-off between the positive effect on tremors and possible side effects, which in rare cases can be permanent. It has been shown that the majority of those treated attach greater importance to inadequate tremor control than any side effects. Or to put it another way: mild side effects are more likely to be accepted because the gain in quality of life due to the tremor improvement clearly outweighs the side effects.
Because the tremors came back mainly in people with Parkinson’s, they also had the greatest risk of being dissatisfied with the result after six months.
Is focused ultrasound "less invasive" than deep brain stimulation?
Many patients have the idea that focused ultrasound is completely harmless due to the non-invasive nature of sound waves. This also has to do with the fact that ultrasound is considered a safe medical instrument: Ultrasound is also used for regular examinations during pregnancy. On the other hand, deep brain stimulation is invasive because a hole has to be drilled into the skull and the associated effort is greater: longer hospital stay, possibly rehabilitation, adjustment process lasting several weeks. But this idea is misleading.
Focused ultrasound is less invasive in terms of the surgical technique: not a drop of blood flows, the skull remains intact and anesthesia is not required at any time. On the other hand, focused ultrasound is even more invasive than deep brain stimulation because a piece of brain tissue is deliberately and irreversibly destroyed. As a result, any side effects that occur may be permanent. From the neuromedical point of view, this piece of brain tissue is actually “more valuable” than the piece of bone that is pierced during deep brain stimulation.
The procedure for focused ultrasound treatment in the "tremor core" and the difference to deep brain stimulation at the same location
The preparation and clarification phase before the procedure corresponds to that before deep brain stimulation in the “tremor core”. This also includes an alcohol test. The only additional examination required is a computer tomography (CT) of the skull. This is used to examine the thickness of the skull. In some people, the skull is structured in such a way that treatment with focused ultrasound is not possible. In this case, deep brain stimulation or radiofrequency ablation remain as alternatives. Many patients want an open-ended assessment for escalation therapy. If a focused ultrasound is an option, we perform a CT scan. During the clarifications, there are many opportunities to discuss the alternative procedures and to choose the instrument that best suits your needs.
is suitable for the patient. As with deep brain stimulation, the patient enters the day before the treatment. Since no anesthesia or opening of the skull is performed during the procedure, patients can
return directly to their room. On the following day, follow-up examinations are carried out in the motor skills laboratory to document the success of the treatment and to check for side effects. In addition, another MRI scan of the head is performed to check the size and position of the ablation created. Patients are allowed to get up and walk around immediately, but with particular caution in the first few days, as the main side effect of the treatment is gait disturbance with the risk of falling. The irritation of the tissue around the ablation increases in the first few days after treatment, which usually leads to surprisingly good tremor control, but also to a temporary increase in side effects. If the gait disorder is only mild or non-existent, patients can go home the day after treatment. If necessary, they will remain in hospital for a few days for intensive physiotherapy. Only a few patients require inpatient rehabilitation due to the gait disorder.
After discharge, follow-up checks are usually carried out after one and three months. After 6 months there is a more detailed examination in our motor skills laboratory. At this point, we repeat the clarifications from before the procedure. We can offer patients with a long journey the check-ups after one and after three months as a digital consultation. However, the 6-month check-up is mandatory and takes place in our motor skills laboratory.
When can the lasting effect of focused ultrasound treatment be assessed?
It is important to understand that focused ultrasound treatment starts a dynamic process in the brain. On the day of treatment, a small lesion (a “hole”) is “burned” into the tremor core from the outside. The brain reacts to this deliberate tissue destruction with an inflammatory reaction. This leads to swelling around the lesion – similar to when you hit your ankle and the ankle swells as a result.
This swelling or “edema” can have two effects. On the one hand, it can make a positive contribution to reducing tremors. For this reason, tremors are typically best controlled shortly after treatment. On the other hand, swelling can cause side effects if it also affects neighboring structures. To minimize this risk, patients are given a cortisone preparation for the duration of their hospital stay. This should prevent the swelling from developing.
In the early days after treatment, it is possible that the swelling will initially increase again: The bruised ankle is also often at its thickest a few days after the accident. If this is the case, new side effects may occur that were not present during the hospital stay. In this case, those affected can contact us at any time. We then clarify whether the swelling can be contained with a cortisone preparation or whether it is necessary to return to hospital.
In the subsequent phase, the swelling around the lesion decreases again and eventually disappears. This sometimes takes several months. Side effects caused by the swelling may then improve or disappear completely. At the same time, however, the tremor can get worse again.
The extent to which any side effects improve and the tremor returns depends on the role played by the swelling, which disappears over time, and the role played by the actual lesion, which remains permanent. The final condition can be assessed after about six months. Now the positive effects of the improvement in tremor and the negative effects of the side effects of ultrasound treatment can only be explained by the actual lesion.
However, the following restrictions should be noted:
- The six months mentioned by us are an approximate period. There are patients in whom the swelling disappears sooner or later. For this reason, side effects that are still present six months after treatment may disappear in individual cases.
- Not every change after treatment is due to the reduction in swelling. The brain is also plastic and changes – above all by constantly learning. This is where physiotherapy comes into play in the event of a gait disorder.
- We must not forget that the disease is not cured and that it is progressive. In this respect, a worsening of tremor can also be due to an increase in tremor sickness.
What are the chances of improving tremors and quality of life?
Our own experience and the available studies show that tremor in essential tremor, Parkinson’s tremor and dystonic tremor is improved by an average of around 60 to 70% six months after focused ultrasound treatment. This figure is an average value. This means that some patients have a permanent 90% improvement in tremor, while there are also patients in whom the tremor returns to the same extent after some time. Fortunately, the latter is very rare.
In our own series of 52 patients treated at the University Hospital Zurich, we found this phenomenon in four patients. All four of those affected suffered from Parkinson’s disease. In those with essential tremor, no one lost the treatment effect over time. It therefore appears that the presence of Parkinson’s disease increases the risk of an earlier loss of efficacy of the treatment. In contrast, 40% of patients still had an excellent tremor response after six months (>75% improvement), 30% a good response (>50% improvement) and 15% a moderate response (25-50% improvement). The remaining 15% had little or no lasting therapeutic success (<25% improvement).
It should also be noted that these percentages of tremor improvement are based on certain scales and do not necessarily reflect the gain in quality of life. For example, there are patients for whom we note "only" a 50% response on the basis of a tremor scale, but who are finally able to write, eat or drink independently again. This may suddenly massively improve the subjective quality of life. Someone else may be disappointed by the same result because they had hoped to be able to do very difficult fine motor work again, which they need for their job, for example. This difference has to do with our own expectations and the demands of everyday life.
In this context, it should be emphasized once again that focused ultrasound only treats tremors on one side of the body. Trembling in the center of the body (head, voice, chin) or on the opposite side is not improved. Many patients describe that the tremor on the opposite side even subjectively increases, which often contradicts the fact that we cannot measure any increase. The reason for this is that this side is now increasingly being noticed and is coming to the fore in everyday life. The same applies to patients who do not have essential tremor, but also have other symptoms, such as Parkinson's disease or dystonic tremor. Here, too, other complaints may come to the fore after successful tremor improvement and reduce the quality of life.
