New Targets for Deep Brain Stimulation Treatment of Parkinson's Disease

Anna Castrioto; Elena Moro


Expert Rev Neurother. 2013;13(12):1319-1328. 

In This Article

Controversy on Classical Targets for DBS

GPi versus STN

There is still some debate on whether the STN or the GPi should be the preferred target in PD patients. In the 1990s, the initial clinical data mainly favored STN stimulation because of a greater reduction of dopaminergic medication and more stable results over time.[80,81] Recently, the US Veteran Affairs study, a large randomized double-blind trial with a follow-up up to 36 months, has shown that the two targets were equally effective, and with less cognitive side effects in the GPi group.[82,83] However, the global motor improvement achieved with stimulation in this study was less consistent and remarkable than expected.[84]

Some concerns have been raised about possible detrimental cognitive and behavioral effects induced directly by STN stimulation,[85] thus suggesting the GPi as a preferable target in the presence of preoperative neuropsychiatric symptoms.

Behavioral issues are frequent non-motor symptoms in PD. They can be devised in hypodopaminergic symptoms, when deriving from a deficit of dopamine state (such as depression, apathy and anxiety), and hyperdopaminergic symptoms, when caused by an overdose of dopaminergic medication (including dopamine dysregulation syndrome, impulsive behaviors and punding).[71,86] The effect of STN DBS on hyperdopaminergic syndromes has been controversial.[87,88] While in the acute postoperative phase, STN DBS might induce hypomania or frank mania, in the long-term the chronic and marked reduction of dopaminergic medication allows the control of the hyperdopaminergic syndrome. Indeed, a recent prospective study has showed that hyperdopaminergic syndrome completely disappears after STN surgery with a chronic drastic dopaminergic medication reduction.[71]

More recently, a larger randomized trial comparing STN and GPi stimulation specifically designed to investigate the superiority of GPi on mood, cognition and behavior, has failed in finding any differences in cognitive and behavioral outcomes, while showing a superiority of motor effects with STN stimulation.[89] However, the choice of the target remains a complex issue, involving also the specific surgical center experience with the two targets The GPi indeed is a larger nucleus, ideally easier to target and not requiring a substantial modification of medical treatment and a meticulous programming of stimulation parameters.

Bilateral versus Unilateral STN DBS

Since PD becomes always a bilateral disease within its course, bilateral STN DBS has preferentially been performed. However, some studies have highlighted that unilateral STN DBS can be an effective alternative therapeutic approach, being associated not only with contralateral but also ipsilateral improvement, although to a less extent (see [90] for a review). Moreover, the concept of a dominant STN has been recently suggested, coming from the observation that in some patient the stimulation of one STN can be as effective as the stimulation of both STN together.[91] To date, it seems reasonable to propose unilateral STN DBS to patients with a very asymmetrical disease.[92]