Deep Brain Stimulation (DBS) is a widely used treatment for advanced Parkinson’s disease (PD), essential tremor, and dystonia, and its clinical applications for other debilitating neurological disorders are continuously being explored. Severe cases of Tourette’s syndrome, obsessive-compulsive disorder and epilepsy that are refractory to traditional therapies are now being treated with DBS. In addition to the extension of clinical applications of DBS over the last three decades there has been a tremendous growth in DBS technology. The advent of competition in the DBS hardware industry led to a surge of innovative technologies. Currently, we have multiple DBS systems with different leads, extension and batteries that are approved by the European and US regulatory agencies. Although some changes in the new systems have shown improvement in clinical outcomes, the true impact of most modifications has not been determined. Nevertheless, these new developments in DBS technology are encouraging to the patient community and to us as health care providers. We will now be asked by our patients and colleagues about the importance of considering certain features or the cost and reliability of particular technologies in each particular case. In this blog, we invite Drs. Foote, Reddy, and Fasano who have expertise in this field to discuss novel DBS technologies and their potential impact for improving global DBS outcomes.
How important is the technology for improvement of clinical outcomes of DBS?
Dr. Fasano
DBS is one of the best examples of how biotechnology has widened our horizons in the treatment of neurological diseases. Technological advances are tightly connected with the history of DBS development and its future. There is an evolving crosstalk between DBS technology and clinical practice. New devices may address our unmet clinical needs and may lead the way to new targets and indications as well as a better understanding of CNS physiology.
Dr. Reddy
The efficacy and utility of DBS for improving clinical outcomes for disorders such as PD, essential tremor, and dystonia is well established. However, the variables that impact DBS, such as the frequency, voltage, and current of stimulation are innumerable, and the impact of these variables on the nervous system are not well understood. The continuous expansion of knowledge in neuroscience refines our understanding of neuroanatomic targets, the underlying physiology, and the means by which DBS can modulate these circuits. Advancing DBS technology affords us an essential tool to investigate these mechanisms and optimize clinical outcome.
Lead design in DBS – Is this a true leading edge for the field?
Dr. Fasano
Traditionally DBS current is delivered through a 4-contact lead with cylindrical electrodes stacked one above the other. More recent lead designs include an 8-contact electrode to deliver current over larger regions and multiple targets. This new system with multiple independent current sources offers increased flexibility in current distribution and allows delivery of constant-current in controlled proportions. Smaller electrodes in the segmented lead enable some directional steering of therapeutic current that could diminish adverse effects and enhance therapeutic benefit. Although lead design is a true leading edge for our field from a technological standpoint, we still need more studies analyzing whether the new leads are superior to the conventional ones. Novel leads will also have to be connected to an implantable pulse generator (IPG) capable of supporting the new lead features. In addition, the challenge is to effectively and rapidly program these devices. In other words, we are dealing with a revolution of DBS at multiple levels, focusing on one aspect does not give justice to the enormous opportunities that we may be able to offer to our patients.
Dr. Foote
Lead design is, of course, an important area for improvement in DBS delivery, and some of the recent innovations in this domain hold the potential to improve DBS outcomes for at least a subset of DBS patients. By contrast to larger cylindrical electrodes, segmented leads offer the possibility of recording local field potentials (LFPs) with higher spatial resolution. Some new systems are capable of continuously sensing and recording LFPs, and can be programmed (in theory) to identify neurophysiologic features of pathological states for optimal delivery of therapeutic stimulation automatically. This technique of adaptive or “closed-loop” stimulation promises several advantages: stimulation delivery to match the patient’s fluctuations for optimal clinical benefit, reduced adverse effects, extended battery life, and elimination of manual programming. It needs to be understood, however, that none of these has been achieved at this time.
As we move into the next generation of brain circuitry modulation, DBS leads and systems that enable more accurate, precise and flexible delivery of current to therapeutic targets in the brain will be critically important. These technological advances may also allow us to improve our understanding of functional (and malfunctioning) neurocircuitry.
Are directional current leads capable of truly steering the DBS field?
Dr. Reddy
Depending on the configuration of stimulation, the 4-contact ring electrode creates a spherical or cylindrical electrical field along the lead axis which may have drawbacks in certain circumstances. For example, if the lead in the subthalamic nucleus is placed slightly lateral to the optimal position, it is likely that a spherical volume of tissue activation will result in the spread of current into the internal capsule, producing adverse effects. Spherical stimulation also fails to account for the variable shapes of targeted brain structures. With segmented electrodes it is possible to control the shape of the electrical field and steer it away from structures that produce unwanted side effects. This technique has been dubbed “directional current steering”. A more appropriate name for this concept might be “directional current shaping.” At least four studies that have investigated the benefits of directional current steering in the subthalamic nucleus have found an expansion of the therapeutically usable current ranges. window mostly related to higher current requirements to induce adverse effects. However, the true outcome of these new directional strategies remains to be seen, pending analysis of long-term follow-up data. While the capability to place more contacts or shaped (partial circumference) contacts (for directional leads) indeed warrants cautious optimism, recent developments in the field of spinal cord stimulation have shown that more contacts are not necessarily better.
Dr. Fasano
A directional current lead is capable of steering the DBS field even though I see five issues: 1) Programming is getting longer, although one can argue that moving forward the programmer’s task will get easier as patients may need fewer visits to tackle side effects. 2) Patients’ expectations are increasing as advertisement of the concept of current steering and treatment personalization can give the false impression that we can fix any PD-related problem. 3) Steering the electrical field can make the difference only when the electrode is slightly misplaced: neurosurgeons will still need to do their best during the targeting process. 4) Directional leads can perform best when powered by independent sources for each contact, as the impedance may differ from contact to contact. 5) The currently available directional leads can only steer electricity at two of the four contact levels because in the segmented electrode rings two contacts still feature the classic ring design distributing the current radially.
All points considered, what are the future directions to develop an ideal DBS system?
Dr. Fasano
An ideal DBS system should feature an electrode with multiple smaller contacts allowing directional stimulation at any level. The IPG should be able to record LFPs from each contact and automatically send power towards the areas where pathologic signals are captured according to an adaptive (or closed-loop) approach. The latter feature will have three main advantages: 1) no need (in theory) to have IPGs with several independent power sources; 2) automated programming; and 3) reduced battery consumption. Finally, the use of smaller devices, possibly implanted in the skull will speed up surgery time as there will be no need for general anesthesia.
Dr. Foote
An ideal DBS system will deliver electrical current to modulate malfunctioning neural circuitry with great spatial and temporal precision, as well as excellent accuracy. In each patient with a given circuitry disorder and a given set of symptoms, an appropriate neuroanatomic target for stimulation will be identified and precisely localized in the patient’s brain (indirect targeting is obsolete and is now, in my opinion, below the standard of care for DBS targeting). I believe that an ideal DBS system will include “smart” targeting software that can process high quality brain imaging and automatically perform a nonlinear deformation of a normalized brain atlas to produce an accurately conforming, patient-specific, three-dimensional atlas overlay that includes pertinent targeted structures. The predicted optimal volume of tissue activation to produce maximal therapeutic benefit for a given symptom, or to minimize the risk of adverse effects (based on large cohorts of outcomes data correlated with stimulation sites) will be automatically identified in each patient’s brain and depicted as a three dimensional target. Enhanced targeting systems using intra-operative imaging and neurophysiologic recording data will enable more accurate implantation of a high density electrode array in the desired target. Because brain circuitry is dynamic and the patient’s condition fluctuates over time, the optimal stimulation for a given patient may vary over time. An ideal DBS system will, therefore, continuously record the electrical activity in a pathological neural network, monitor physiological features of pathologic or healthy states, and automatically adjust the stimulation (intensity, pattern, or spatial distribution) to continuously optimize therapeutic benefit and minimize adverse effects. This will not only result in more consistent optimal DBS outcomes, but it will obviate the need for repetitive, lengthy DBS programming sessions and extend the battery life of the DBS pulse generator.