The use of deep brain stimulation (DBS) to reduce tremor in Parkinson's patients was originally proposed in 1987 by Professor Louis Benabid. The first implantation area targeted was the ventral nucleus of the thalamus. Today, the targeted structures are the subthalamic nucleus and the internal globus pallidus.
This procedure consists of providing electrical stimulation to the target structures through the implantation of an electrode attached to a generator. The mechanisms that induce the beneficial effects of this technique are not yet fully understood.
Who can benefit from DBS ?
It is estimated that approximately 10-15% of patients are suitable for PCS.
This technique will be offered to people who experience disabling parkinsonian symptoms despite adequate treatment. It will also be proposed to people with major side effects related to dopaminergic treatment.
This technique is contraindicated in people over 70 years old because of its invasive nature. Dementia and psychological disorders also contraindicate this procedure.
How a DBS surgical operation is performed ?
The first step is to locate the site to be implanted. To do this, MRI images are taken after injection of a contrast product.
An electrophysiological exploration is then performed using microelectrodes. Several emission patterns allow the detection of structures of interest such as the subthalamic nucleus or the substantia nigra pars reticulata.
The implantation of the electrode is performed under local anesthesia. Some medical teams choose a general anesthesia to reduce the stress and pain related to the operation. However, this choice completely deprives them of intraoperative observation which can allow them to accurately estimate the correct positioning of the electrode. The effects of the stimulation on the symptoms can be directly tested during the operation.
Is this technique efficient ?
The benefit of this technique is demonstrated by a decrease in UPDRS II and UPDRS III scores after surgery, which is sustained over the long term. The UPDRS scale is recognized for measuring the progression of Parkinson's disease and assessing the effectiveness of treatments. Chapter II focuses on daily life and score III on the patient's motor abilities. This intervention reduces the effective dopaminergic treatment and consequently reduces its side effects such as motor fluctuations and dyskinesias. Overall, the patient's quality of life is improved compared to dopaminergic treatment alone.
What are the side effects and risks of deep brain stimulation ?
Side effects related to DBS can be related to three aspects:
The surgical procedure. The most common complication is bleeding, in the vast majority of cases, this complication does not affect the patient's health in the long term.
The implantation of the electrode. The side effects related to the implantation are variable, patients can encounter skin infection, skin erosion, cable rupture or generator dysfunction.
The stimulation itself. Side effects leading to neurological damage are rare. These side effects are often easily reversible by adjusting the stimulation parameters, such as frequency or intensity. Incorrect placement of the electrode may stimulate unwanted areas of the brain and cause side effects on speech or walking.
It is important to note that side effects related to this surgical technique are rare and that the benefit/risk balance of this procedure remains very favorable.
What are the future developments in deep brain stimulation ?
Today's DBS devices are open-loop, meaning that the stimulation sent is not regulated. The electrical pulse emitted is constant over time and can only be modified manually by the neurologist.
This technique tends to evolve towards closed loop solutions. The new devices will be equipped with a receiver probe, capable of analyzing the Beta waves in the implanted area. Depending on the brain activity, the stimulation can be regulated in two ways :
Reactive closed loop : a threshold of Beta wave power is defined. If this threshold is reached, the stimulation is triggered (ON state), otherwise, the stimulation is switched off (OFF state).
Adaptive closed loop : the stimulation power is modulated according to the measured Beta wave parameters
One of the main problems is to be able to analyze the brain waves while stimulating the patient. The electrical stimulation created by the electrode disturbs the possible analyses, making the detection of certain brain signals very complex.
Engineers have recently succeeded in creating an algorithm capable of identifying these parasite signals and filtering them, in order to obtain a clear signal, corresponding only to brain signals useful for DBS adaptation. This advance is an important step towards the development of adaptive DBS, able to stimulate and analyze in real time.
The stimulation emitted by these devices will be adapted to each patient and their symptom. This new approach will reduce the side effects caused by DBS and reduce the energy consumption of the devices.
Other techniques are being developed to provide non-invasive stimulation. Grossman's team has proposed a new technique based on the administration of an electric interference field. By applying two high-frequency fields to two specific points on the head, it is possible to obtain a resulting field that stimulates deep brain structures. The first studies on mice show promising results, which still need to be validated by studies on humans.
References
Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk H-J, et al. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16.
Benabid AL, Chabardes S, Mitrofanis J, Pollak P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. The Lancet Neurology. 2009 Jan 1;8(1):67–81.
Evan M. Dastin-van Rijn et al, Uncovering biomarkers during therapeutic neuromodulation with PARRM: Period-based Artifact Reconstruction and Removal Method, Cell Reports Methods (2021).
