Target sites for brain stimulation in Parkinson's disease
There are two main target sites for deep brain stimulation as a symptomatic treatment for Parkinson's: the subthalamic nucleus (STN) and a nucleus called the internal globus pallidus (GPI).
DBS surgeries for these two nuclei have existed since the last century with significant success rates, but there is a "debate" as to whether one is preferable to the other in terms of effectiveness and in terms of side effects. Many studies have been done that examined the issue, but there was no uniformity among them in terms of research methods, which caused considerable difficulty in making a decision.
For the most part, the studies dealt with only one type of GPI or STN target site, in different studies patients were selected with different symptoms of Parkinson's ("predominant tremor" type Parkinson's versus "rigidity-slowness" type Parkinson's). Studies were done that compared patients with and without surgery at all compared to studies that only examined patients who underwent DBS implantation and followed them, patients who were implanted with one electrode / two electrodes. The follow-up period after surgery varied between the studies, there were differences in the number of subjects included in each study, etc. Some studies tried to give a more accurate answer by purposefully comparing patients who are candidates for DBS surgery and were randomly selected to receive brain electrodes to STN or GPI, but even when such a comparison was made, different results were obtained regarding the superiority of one target site over the other.
The basis for the existence of the debate lies in several fundamental differences between deep stimulation of the STN versus GPI, and mostly in reference to bilateral stimulation (most of the patients in deep brain stimulation are currently implanted with electrodes on both sides of the brain). When deep brain stimulation to the STN is treated, a parallel process of lowering the levodopa dose occurs, but stimulation of the GPI often does not result in a significant decrease in the levodopa dose. One of the reasons for this is that GPI stimulation causes an anti-dyskinesia effect and allows continued treatment with levodopa without significant change, while in order to reduce dyskinesia in STN stimulation, it is necessary to lower the dose of levodopa. On the other hand, stimulation of STN improves the OFF symptoms so that the dose of levodopa can be lowered without symptomatic aggravation. Regarding possible side effects of mood changes and cognitive changes - no significant differences were found between GPI and STN, but speech disorder is apparently more common after STN DBS.
There were studies that tested stimulation of other sites such as PPI for freezing in walking, but did not show unequivocal results of improvement in walking and are therefore currently considered experimental only.
In recent years, researchers have been trying to focus on subpopulations with a certain symptom profile and examine the effect of DBS on them so that the treatment can be directed in a more personalized way for each patient.
For example: a preliminary study (PILOT STUDY) that tested deep brain stimulation to the STN on one side of the brain and GPI on the other side in 8 relatively elderly patients who had clear asymmetry between the sides of the body or those who had significant mid-body line symptoms (talking, standing, walking, balance ). Distraction of the STN was done on the severe side in terms of motor symptoms and GPI on the other side. In cases where there were severe go symptoms, GPI was chosen for the right brain and STN for the left brain. When they were followed for a year, an improvement was demonstrated in quality of life indicators and motor test during OFF and ON times. Other studies tested the implantation of one electrode that simultaneously stimulates two brain sites: one target site VIM (anterior motor nucleus of the thalamus) where a technique of burning or deep brain stimulation is used for primary tremor (ET) and a second target site which is the STN. The researchers found that there is good control of tremors and Parkinsonian indices in the transplanted patients, and in addition that the procedure is safe, even though from a surgical point of view it is done in a slightly different way than STN transplantation alone. Another option being tested is simultaneous stimulation of GPI and STN on the same side of the brain.
In conclusion, the two main sites used for deep brain stimulation in Parkinson's have a similar although probably not identical efficacy and safety profile. There is reason to consider the implantation of electrodes aimed at different sites in the same patient and it is possible that in certain populations of patients there will be a preference for "diversity" in implantation sites compared to bilateral implantation to the same brain site. I will qualify what has been said by saying that most of the studies on which they were based until today were not done with multi-directional electrodes and without recording beta waves from the transplant site after the surgery. It is hoped that future studies will add information regarding the effectiveness and safety of implanting electrodes to the above sites for the treatment of Parkinson's disease symptoms.
Sources:
Globus Pallidus Internus (GPi) Deep Brain Stimulation for Parkinson's Disease: Expert Review and Commentary. Ka Loong Kelvin Au. Joshua K. Wong. Takashi Tsuboi Robert S. Eisinger. Kathryn Moore. Janine Lemos Melo Lobo Jofili Lopes. Marshall T. Holland. Vanessa M. Holanda. Zhongxing Peng-Chen .Addie Patterson . Kelly D. Foote. Adolfo Ramirez-Zamora. Michael S. Okun. Leonardo Almeida. Neurol Ther https://doi.org/10.1007/s40120-020-00220-5.
Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomized controlled trial. Vincent JJ Odekerken, Teus van Laar, Michiel J Staal, Arne Mosch, Carel FE Hoffmann, Peter CG Nijssen, Guus N Beute, Jeroen PP van Vugt, Mathieu WPM Lenders, M Fiorella Contarino, Marieke SJ Mink, Lo J Bour, Pepijn van den Munckhof, Ben A Schmand, Rob J de Haan, P Richard Schuurman, Rob MA de Bie. Lancet Neurol. http://dx.doi.org/10.1016/S1474-4422(12)70264-8.
Combined Unilateral Subthalamic Nucleus and Contralateral Globus Pallidus Interna Deep Brain Stimulation for Treatment of Parkinson's Disease: A Pilot Study of Symptom-Tailored Stimulation. Chencheng Zhang, LinbinWang, Wei Hu, TaoWang, Yijie Zhao, Yixin Pa , Leonardo Almeida, Adolfo Ramirez-Zamora, Bomin Sun, Dianyou Li. NeurosurgeryDOI:10.1093/neuros/nyaa201.
