Emerging Targets for Stimulation-Refractory Movement Disorders

Abstract

Deep brain stimulation has proven an effective addition to the optimized medical management of some primary movement disorders. Sustained symptomatic improvement has been demonstrated for Parkinson's disease, forms of dystonia, and essential tremor. However, despite dramatic improvements in the tremor, rigidity, bradykinesia, and dyskinesias of Parkinson's disease, DBS of the STN and GPi have provided inconsistent relief of gate abnormalities and freezing. Similarly, DBS of the Vim has proven effective for distal tremors resulting from a variety of etiologies, but has limited efficacy for tremors with proximal spread. Accumulating clinical, neurophysiologic, and neuroanatomic evidence supports the pedunculopontine nucleus as a modulator of postural control and gait initiation. Further, both historical and contemporary preclinical and clinical data support the zona incerta and prelemniscal radiations as targets within the greater subthalamic area for tremor containing proximal spread. On the basis of these observations, there is considerable interest in PPN DBS for control of gate abnormalities in PD, and in ZI and PRL DBS as a means for modulation of pronounced tremor with axial involvement. The clinical evidence for consideration of the PPN and ZI/PRL as alternate stimulation targets for treatment of refractory movement disorder manifestations is reviewed.