Deep brain stimulation for Parkinson’s disease
Introduction
Deep brain stimulation (DBS) is a technique used in functional neurosurgery, which consists of delivering a neural brain structure continuous electrical stimulation through chronically implanted electrodes connected to an internalized neuropacemaker or stimulator, usually programmable in amplitude, pulse width and frequency. The electrodes are inserted using stereotactic methods (including radiological methods to localize the targets and electrophysiological exploration of the target area) and then connected to the chronically implanted stimulator. The tuning of this stimulator can be done at intervals depending on the patient’s needs, and allows adaptation of the therapy to the evolution of the symptoms. The most common utilisation has been to treat pain, by stimulating, usually at classical physiological frequencies (30 to 60 pulses per second, or Hertz) considered as excitatory, various neural structures such as nuclei or fiber tracts. The discovery we made in 1987 that frequencies at 100 Hz and above were, on the contrary, inhibitory, has provided a new and powerful method to achieve similar effects to lesions at the same site, in a titratable and reversible, and therefore safer, manner than the former destructive (or ablative) stereotactic methods (mainly thalamotomies and pallidotomies). Besides the reversibility of its effects, high frequency stimulation has proven to be well tolerated in a large variety of deep brain structures, and its effects can be adapted to the specific patient’s needs by adjusting the parameters of stimulation (current intensity, pulse width, frequency). During surgery, the reversibility of the effects provides a powerful tool for exploring the patient and their functional targets, and for optimizing the placement of the electrode. This provides a powerful method applicable to a large variety of pathological situations, which are far from being fully explored at the present time. Since 1987, high frequency stimulation (HFS) in the basal ganglia has been proven to produce the same effects as lesioning, which previously was used as a treatment for movement disorders. This has been quickly extended from the thalamus to the pallidum and finally to the subthalamic nucleus (STN) to treat Parkinson’s disease (PD). The literature on the subject has quickly grown, providing additional confirmation of the efficiency of HFS as well as opening debates on the various topics related to this method, including the methodology and moreover the mechanisms, which are still yet not completely understood. This has triggered a vast amount of research, both clinical and basic, and more recently, new applications outside of the movement disorders field have been initiated, such as those for epilepsy (in the anterior nuclei of the thalamus, the subthalamus and the centrum medianum-parafascicularis complex [CM-Pf]), psychosurgery (in the anterior limb of the internal capsule, the nucleus accumbens, and the subthalamic nucleus), and cluster headaches (posterior hypothalamus), or they have been experimentally investigated, such as those for obesity (in the anterior hypothalamus, ventromedial and lateral). The concept of manipulation of brain structures by HFS has been introduced, raising questions and hypotheses about the effects of chronic HFS on membranes, cells, axons, networks, biochemistry and gene expression. This also leads us to revisit the data and concepts of the organization of the basal ganglia (BG) that is involved in the control of movement. Here, I discuss mainly the application of HFS DBS to movement disorders, and in particular to Parkinson’s Disease. I review the current indications and the average rates of improvement, highlighting the technical aspects that are specific to these applications. I then review current opinion on the mechanisms involved in the observed effect of HFS and highlight the various hypotheses that are currently being debated.
Section snippets
Surgical consensus for deep brain stimulation
Financial, social, regulatory, technical and profit oriented considerations are different around the globe, making it difficult to reach an international surgical consensus. The goal is to agree upon a general surgical concept meant to achieve the best clinical results with minimal complications. The worldwide interest in the method has opened discussions about all kinds of features that could optimize the surgical process. Everyone agrees that clinical improvement depends on the accuracy of
Which target?
Although comparative studies have not been performed for all targets, the general trend that appears is that treating the STN improves all symptoms, directly (akinesia and rigidity) or indirectly (dyskinesias), making it the best target for DBS. Treating Vim solely improves tremor 11., 12., but only as efficiently as treating the STN. Stimulation of the CM-Pf might be involved in the suppression of tremor as well as suppression of levodopa induced dyskinesias [13], treatment of GPi [14]
Motor symptoms
STN deep brain stimulation improves the motor symptoms of the disease in the ‘off’ drug condition (when the patient is not under the effect of their medication, as opposed to the ‘on’ situation, when the patient has taken and experiences the effects of the drugs) as well as activities of daily living as assessed by either part II of the Unified Parkinson’s Disease Rating Scale (UPDRS) or the Schwab and England scale. Moreover, levodopa induced dyskinesias are improved in the ‘on’ drug
Mechanism of action of deep brain stimulation
Knowing the mechanism of action of DBS might help to improve the type, parameters and tools for stimulation, to provide an even better clinical effect.
Moreover, basic neuroscience issues are involved: is HFS doing anything different to low frequency stimulation, which is namely exciting neural structures? The observed effect then relates to the specific wiring of the network, the excitation of one of its components leading to the final interruption of the network and the ‘functional end
Positive aspects
The reversibility of DBS is a unique surgical feature, and it matches one of the major advantages of pharmacological approaches: it allows us to explore putative targets, and to cease all activity in case of unacceptable side effects. It leaves our options open in case a better treatment is found in the future. The adaptability through adjustable parameters is another similarity with pharmacological treatment. However, the strict spatial localization of DBS effects is an advantage over
Conclusions
In patients with advanced PD and severe ‘off’ period disability, the quality of life after DBS improves to the level of a large population of patients with mild PD. A decrease in the social isolation of the patients is the real success of STN stimulation. It is worth taking the relatively small risk and operating on patients before their quality of life has reached a too low level. A better social life is the result of improvement in ‘off’ drug motor symptoms and dyskinesias, as they interfere
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
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of special interest
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of outstanding interest
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