Globus Pallidus Internus (GPi) Deep Brain Stimulation for Parkinson's Disease: Expert Review and Commentary

Abstract

Introduction: The globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients.

Methods: The literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping.

Results: There are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD.

Conclusion: GPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages.

Keywords: DBS; Deep brain stimulation; GPi; Globus pallidus internus; Neuromodulation; Outcomes; Parkinson’s disease; STN; Subthalamic nucleus; Targeting.

Fig. 1

Timeline of the development of pallidal deep brain stimulation (DBS). FDA US Food and Drug Administration, ET essential tremor, PD Parkinson’s disease, STN subthalamic nucleus

Fig. 2

Dissection of white matter of the internal globus pallidus (GPi). a Lateral to medial dissections, b anterior to posterior dissections, c medial to lateral dissections, d inferior to superior dissections showing relationship of GPi to the optic tract, e inferior to superior dissections showing relationship of GPi to external globus pallidus (GPe), putamen and internal capsule (Int. Caps.), f deep brain stimulation of the GPi lead trajectory dissections until the GPi is reached. Accumb Accumbens, Ant. anterior, Comm. commissure, Caud. caudate, CN III third cranial nerve, Cor. Rad. corona radiata, Gl. gland, Innom. innominata, Nucl. nucleus, Olf. olfactory, Post. posterior, Subst. substantia, Tr. tract

Fig. 3

Functional regions of the GPi

Fig. 4

Somatotopic organization of the GPi. IC Internal capsule, OT optic tract, Th thalamus, Pt Putamen

Fig. 5

The GPi and surrounding structures