Should the Globus Pallidus Targeting Be Refined in Dystonia?

Abstract

Background and study aims:  Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective therapy for primary generalized and focal dystonias, but therapeutic success is compromised by a nonresponder rate of up to 20%. Variability in electrode placement and in tissue stimulated inside the GPi may explain in part different outcomes among patients. Refinement of the target within the pallidal area could be helpful for surgery planning and clinical outcomes. The objective of this study was to discuss current and potential methodological (somatotopy, neuroimaging, and neurophysiology) aspects that might assist neurosurgical targeting of the GPi, aiming to treat generalized or focal dystonia.

Methods:  We selected published studies by searching electronic databases and scanning the reference lists for articles that examined the anatomical and electrophysiologic aspects of the GPi in patients with idiopathic/inherited dystonia who underwent functional neurosurgical procedures.

Results:  The sensorimotor sector of the GPi was the best target to treat dystonic symptoms, and was localized at its lateral posteroventral portion. The effective volume of tissue activated (VTA) to treat dystonia had a mean volume of 153 mm³ in the posterior GPi area. Initial tractography studies evaluated the close relation between the electrode localization and pallidothalamic tract to control dystonic symptoms.Regarding the somatotopy, the more ventral, lateral, and posterior areas of the GPi are associated with orofacial and cervical representation. In contrast, the more dorsal, medial, and anterior areas are associated with the lower limbs; between those areas, there is the representation of the upper limb. Excessive pallidal synchronization has a peak at the theta band of 3 to 8 Hz, which might be responsible for generating dystonic symptoms.

Conclusions:  Somatotopy assessment of posteroventral GPi contributes to target-specific GPi sectors related to segmental body symptoms. Tractography delineates GPi output pathways that might guide electrode implants, and electrophysiology might assist in pointing out areas of excessive theta synchronization. Finally, the identification of oscillatory electrophysiologic features that correlate with symptoms might enable closed-loop approaches in the future.