Introduction
In the past three decades the resurgence of invasive surgical procedures to produce local lesions or apply DBS (Deep brain stimulation) have radically improved the quality of life of many patients with Parkinson’s disease, tremor and other movement disorders. Recently, MRI-guided focused ultrasound (FUS), which employs ultrasound waves to create a lesion in the brain without surgery has emerged as a new treatment for drug-irresponsive tremor and Parkinson’s disease.
This “non-invasive” approach has significant advantages over DBS regarding adverse effects and technical complications such as those caused by the batteries of implantable stimulators. However, this new treatment may also have inherent risks related to the type of brain lesion, and limitations with regard to different brain targets.
We have invited three experts in this field to discuss the use of FUS for the treatment of movement disorders.
What is MRI-guided focused ultrasound (FUS), and how was it developed to treat a movement disorder?
Prof. Taira
FUS is a new less-invasive technology to make a thermal lesion in the brain without making scalp incision nor skull hole. More than 1000 beams of ultrasound over the head focus to a certain point in the brain to create a thermal lesion. In the past, scattering and refraction, which are natural properties of ultrasound, prevented the clinical use of this technology. Such problems were eliminated by incorporating sonic and anatomical information of the skull with very sophisticated computer algorithms. With these progress, ultrasound can be used clinically to produce a small lesion in the intended target of the brain.
Dr. Obeso
The use of focal ultrasound has a long history since the Fry brothers experiments in the early 50´s, and the idea of performing precise lesions without opening the skull is old but had been impossible until recently. With the development of new FUS devices, the wish of carrying out incision-less lesions in deep brain structures becomes true.
FUS devices consist in 1024 transducers each one of those generates an ultrasound beam that will get through the skull focusing into a precise target such as the basal ganglia creating a thermal lesion. During most of the procedure, the patient is awake and 3T MRI thermography sequences are acquired so that clinical and neuroimaging feedback are available throughout the whole treatment.
So far, we know that abnormal neuron activity in terms of firing frequency, pattern, synchrony, etc. within brain networks causes /mediates the classic movement disorders. Thus, abolition or inhibition of this abnormal firing patterns leads to the improvement of parkinsonian motor features, ameliorates dystonia and stops tremor of many causes. Considering this, a device that allows ablating deep brain nuclei has an important role in the treatment of movement disorders.
Can FUS be applied extensively for the treatment of movement disorders that are currently treated with DBS?
Prof. Taira
I do not think so. Every treatment has its own pros and cons. FUS still has limitations in patients with bone-marrow rich thick skull which prevents penetration of ultrasound. FUS is less technically efficient to make a lesion located more distant from the center of the brain. There is a large debate on pros and cons about DBS versus lesioning, and there is no unanimous conclusion. The advantages of DBS are adjustability and reversibility. This also is useful for blinded/controlled studies. However, DBS does not provide a permanent (curative) treatment, and device related complications of DBS are not rare if patients are followed-up for long period. Patients have to avoid using some electric devices and device dysfunction is a matter of concern to many patients.. Conversely, the effect of lesioning is irreversible, which means it can be potentially curative in some disorders, such as focal hand dystonia and pure writing tremor. Surgical lesion is more difficult because it requires more accurate targeting and intraoperative assessment of the symptoms. If we can resolve the current issues of FUS application, particularly the, problem of skull density, or cavitation, this will be an ideal lesioning procedure except for its cost.
Dr. Lozano
MRgFUS delivers acoustic energy to a focal point within the skull. This creates a lesion whose thermal characteristics can be measured in near-real time using MRI thermography to pinpoint the precise location and size of the lesion. So far, patients have to have their hair shaved and cold water circulates over their scalp to serve as a sound conducting medium and to provide cooling for the heating that occurs with the absorption of ultrasound by the skull.
Movement disorders treated with lesioning procedures or DBS could at least in theory also be treated with MRgFUS. So far FUS has been used in the motor thalamus, the globus pallidus and the subthalamic nucleus to treat Parkinson’s disease, various forms of tremor, chorea and dystonia. FUS may not be appropriate in movement disorders where DBS is used to drive neural activity for example, PPN DBS.
Dr. Obeso
At this point, FUS in the field of movement disorders is expanding and even though FUS treatments now are unilateral, the field is moving fast and bilateral studies surely will come soon. Indeed, studies with bilateral FUS thalamotomy are already ongoing. In essential tremor, patients are often elderly and most would be ruled out for DBS surgery, but FUS thalamotomy, even if only unilateral, allows them the chance of a huge improvement in daily living activities and quality of life. With Parkinson´s disease (PD) the debate becomes more complex. To date, we have treated with FUS patients with very asymmetric PD. Anyway, the experience with STN radiofrequency lesions leads to think that unilateral or bilateral staging subthalamotomy at mid-stage disease would potentially avoid many patients from developing severe drug-related complications thanks to motor improvement achieved with the lesion. Those patients may never develop severe bilateral motor manifestations and the accompanying motor complications that lead to DBS treatment. Nevertheless, we must be cautious, DBS has a long history of success along the last three decades, and FUS is not here to replace it but rather become a less-invasive alternative for patients whether they were candidates for DBS or not.
What are the advantages and disadvantages of FUS in comparison with DBS?
Prof. Taira
Obviously, there are no device-related complications with FUS as opposed to DBS. This is very important, because patients with DBS must carry mental and social stress for life. They may fear about dysfunction of the device, and this feeling is stressful to function in society and in many aspects of daily living. The disadvantages of FUS are the need of completely shaving the head hair, and the difficulty of targeting more laterally located regions such as the globus pallidus.
Dr. Lozano
FUS has no skin incision, no risk of infection, no implants, no need for programming and has the potential to become an outpatient procedure. The costs of FUS are likely significantly lower and the need for clinic visits is reduced compared to DBS. The main disadvantages of FUS is that it makes a lesion, that the effects are irreversible and that at least for now, there are significant concerns in its use in bilateral treatments due to the high risks of speech and gait disturbances with bilateral lesions.
Dr. Obeso
The main advantage is obvious, there is no surgery in classic terms, with everything it implies: no infection or air within brain as well as the shortening of the hospital stay. The follow-up is far more bearable to the patient and less time-consuming to the institution because of the lack of the DBS post-operative management needs. Also, there is no need of carrying a battery or having electrodes and cables within patient´s body and no risk of device-related complications such are infections, and no need of battery replacement. The main disadvantage of FUS compared to DBS is the irreversibility of the effect, thus, permanent side effects related to lesion although rare, could happen.
What is your opinion about the future of FUS versus DBS for the therapy of movement disorders?
Prof. Taira
We need not only FUS and DBS, but also radiofrequency and gamma-knife lesioning. These four procedures are basically indispensable in management of movement disorders. However, other surgical approaches may be necessary in selected movement disorders, like intrathecal baclofen and peripheral denervation. Movement disorder specialists should understand the pros and cons of these treatment modalities without historical/commercial bias. Neurosurgeons should be able to choose any of such procedures with confidence. We have to solve the skull penetration issue of FUS, as well as the long-term device related problems of DBS.
Dr. Lozano
While DBS for movement disorders has been available for 30-40 years, FUS is in its infancy and much remains to be learned. Over time, we may be able to use FUS to stimulate and map brain function, something that will make the procedure more effective and safer. I see that both techniques will be used in the future with the choice depending of the indication, the technical availability and expertise of the technology and treatment team and ever importantly, the relative costs. A major factor will also be patient preference for one procedure over the other.
Dr. Obeso
It is in human nature to compare and compete but to be honest, and as I said before, this is not about FUS OR DBS but more about FUS AND DBS. Not in any given patient where we should choose the best choice individually, but for the whole landscape of the movement disorders there will be a place for both techniques. FUS is growing up fast and some key aspects as avoiding head shaving and improving intra-procedure imaging will arrive soon and make things easier both for patients and doctors. There is still room for innovation in DBS like the recent development of directional leads and, therefore, the future of both FUS and DBS looks promising.