Abstract & Commentary
Therapeutic Target for DBS for Dystonia
By Alexander Shtilbans, MD, PhD
Assistant Professor of Neurology, Weil Cornell Medical College
Dr. Shtilbans reports no financial relationships relevant to this field of study.
Synopsis: The authors of the current study created a volume-of-tissue-activation model in order to identify the area within the globus pallidus that provides the most effective target for deep brain stimulation for dystonia.
Source: Cheung T, et al. Defining a therapeutic target for pallidal deep brain stimulation for dystonia. Ann Neurol 2014;76:22-30.
Dystonia is a movement disorder characterized by abnormal muscle contraction and abnormal postures. The pharmacological treatment consists mostly of anticholinergic and antispasticity agents that have systemic side effects. Focal dystonia can be effectively treated with botulinum toxin injections. Severe generalized dystonia, refractory to medications, can be effectively treated surgically with deep brain stimulation (DBS) of the globus pallidus pars interna (GPi). DBS is also used for treatment of Parkinson disease and essential tremor, although different anatomical targets are used. Although the exact mechanism of action of DBS is unknown, it is believed to inhibit electrochemical conduction through myelinated nerve fibers of the motor control regions, alleviating the dystonic symptoms. The outcome of this surgical treatment varies depending on the position of the electrodes in the GPi and the stimulation parameters used. Furthermore, the effect of the stimulation on dystonia might be delayed by 3 to 5 months after the surgery, for unclear reasons. Therefore, it is vitally important to ensure proper placement of the electrodes within GPi to maximize the effect. For this reason, models studying volume-of-tissue-activation (VTA), which can predict effective regions of stimulation, have been developed previously for Parkinson disease.
The objective of this study by Cheung et al was to identify and characterize the region of the brain that was targeted in clinically successful pallidal stimulation for dystonia, utilizing VTA models. The authors retrospectively studied a cohort of 21 primary DYT1 dystonia patients, treated for at least 1 year with bilateral DBS in GPi. Upon placement of the electrodes, the 12-month stimulation parameters were entered into the model to calculate individualized VTA. Clinically, changes in disease severity were measured in patients using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The authors associated each VTA with its corresponding BFMDRS score. The authors constructed target volume using clinical improvement and activation thresholds of 75%. As a result, the mean improvement in the 12-month period was calculated to be 83%. The mean individual VTA volume was 501 mm3. The authors then created a dystonia stimulation atlas (DSA) for the studied cohort of patients using stereotactic mapping. The analysis revealed that 32 of the 42 electrodes evaluated met the 75% improvement threshold. Using this threshold, the volume of the calculated target within GPi was 152.7 mm3.
The authors concluded that the resulting maps provided quantified localization of the regions that underwent direct activation after 12 months of follow-up. Considering the stimulation areas that were in common, there was a relatively small area located in the middle of GPi representing the best potential target for therapeutic DBS for dystonia. Therefore, the atlas might be a useful tool for physicians implanting and programming the stimulation devices. The authors further suggested that increasing total electrical energy delivered to the tissue to achieve better clinical improvement may not provide the desired effect, whereas simulation of the correct regions within GPi should provide a better outcome.
The authors of the current study created a model to identify the area within GPi that might provide the most effective target for DBS, resulting in the best possible clinical improvement of dystonia symptoms. The authors correctly acknowledged limitations of this study, which included individual patient variability and limitations of MRI resolution, possibly affecting the accuracy of anatomic mapping. In addition, this cohort of patients showed better outcomes in comparison to previously reported groups of patients with dystonia treated with DBS. The clinical evaluations were performed in an open-label fashion, which potentially could have played a role in the better-than-average outcomes.
The study examines only patients with DYT1 dystonia, and it would be interesting to see if the proposed model also applies to other types of generalized dystonia. Furthermore, since the onset of the clinical improvement after DBS for dystonia can be delayed up to several months, it would be useful to know if the onset of improvement correlates with the location of the electrodes within GPi according to the described model in this study.
The authors rightfully argue that the region they identified represents a potential target and can help with surgical planning. Current research in DBS technology involves programmable selection of lateral directional stimulation to achieve better clinical results. The described model could potentially help guide a clinician in choosing the appropriate direction for stimulation. Therefore, these targets are important and warrant further investigation through validation studies in larger and more diverse groups of patients with dystonia.