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The Use of New Surgical Technologies for Deep Brain Stimulation
Introduction
Deep brain stimulation (DBS) is an established treatment for movement disorders with distinct advantages over best medical therapy and lesioning procedures ( ). In Parkinson disease (PD), for example, in addition to improving motor symptoms, DBS improves the overall quality of life ( ) and is more cost effective than medical therapy alone in younger patients ( ). While the efficacy of lesioning (thalamotomy) may eventually fade, the benefits of DBS can be sustained for several years in refractory essential tremor (ET) ( ). Both subthalamic nucleus (STN) ( ) and globus pallidus interna (GPi) ( ) are equally efficacious, and the choice of one over the other may be tailored to patient-specific indications (e.g., GPi may be more suited for patients with PD with significant axial symptoms and dyskinesias). DBS also appears to be more efficacious than medical therapy in patients with PD with early motor complications ( ). Finally, the safety profile of DBS has been excellent with only 1%–2% the risk of serious complications after surgery ( ).
Despite this proven track record, only 10%–15% of eligible patients eventually undergo DBS; for example, with 10 million patients with ET ( ) and 1 million patients with PD ( ) living in the United States, only 5000 DBS procedures are performed annually ( ). Patient perceptions against invasive surgery and conservative approach of referring providers may be important drivers for this low utilization rate. It is also important to recognize that DBS has inherent limitations for the treatment of complex and progressive neurodegenerative disorders; despite an excellent motor efficacy, bilateral STN stimulation does not prevent falls and may be associated with adverse effects like dysarthria, paresthesias, and fatigue ( ). Loss of DBS efficacy in ET maybe a concern with one study reporting waning benefits in 73% of the patients after 18 months ( ). Although efficacy is satisfactory for primary generalized primary dystonia and DYT1 mutation, the results are less satisfactory in patients with secondary generalized dystonia ( ). Finally, DBS use for psychiatric applications has met with less-than-expected outcomes. Despite an established role of subgenual cingulate in the pathogenesis of major depressive disorder (MDD) ( ) and a promising pilot study, the pivotal multicenter trial was negative based on a predetermined improvement in primary outcome variable. Another large trial of DBS for depression was halted after a futility analysis ( ).
With increasing understanding of neural substrates of efficacious stimulation and the recognition of DBS-mediated modulation of brain networks, novel techniques and technologies are being used to address some of these challenges. We classify these advances in two major categories: those directed toward precise identification of stereotactic targets and those aimed at improving the stimulation paradigms. We also discuss a road map for the integration of these advances in future efforts to address the major challenges in this field.
Precise Identification of Targets and Improved Stereotactic Targeting
Indirect Targeting
The major interest in the past 10 years has been concentrated on improving the accuracy of targeting since it is crucial for achieving good clinical outcomes ( ). For better target identification, several human brain atlases, both printed and electronic, were introduced ( ). These atlases were based on anatomy of few postmortem brains and therefore the content was difficult to map on the patient brain. More recently, deformable computerized brain atlases have been developed ( ). This has improved registration, but there are some limitations in regions with high spatial complexity (e.g., the gyral anatomy of the cortex) ( ). Nonlinear registration methods are still under investigation and have yet to be used for clinical application. Overall, though, the accuracy of atlas-based stereotactic targeting is limited by the intrinsic variability in the location of deep targets that are not distinctly visible on structural imaging ( ). compared the atlas-based VIM target with the location of the dentorubrothalamic tract (as determined by deterministic tractography) and concluded that the “optimal” implantation coordinates were more lateral than the planned atlas-based coordinates. Similarly, correlated the lead location in STN and GPi relative to MCP with the motor outcome in 96 patients with PD. The MCP-based lead location did not correlate with postoperative Unified Parkinson’s Disease Rating Scale (UPDRS) score variation. The authors concluded that the MCP-based coordinate could not capture the variability in individual anatomy and connectivity. Because microelectrode recording and testing represent the gold standard for intraoperative target confirmation ( ), creating probabilistic maps with physiologic and functional information appears to be the most comprehensive approach for developing targeting atlases ( ). For improving the targeting accuracy, intraoperative guidance with two-dimensional radiographs is most commonly used ( ). Additional emerging methods include O-Arm (Medtronic, Inc.) ( ) and intraoperative computed tomography ( ).
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