Relative Contribution of Magnetic Resonance Imaging, Microelectrode Recordings, and Awake Test Stimulation in Final Lead Placement during Deep Brain Stimulation Surgery of the Subthalamic Nucleus in Parkinson's Disease

Introduction: For deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN) in Parkinson's disease (PD), many centers employ visualization of the nucleus on magnetic resonance imaging (MRI), intraoperative microelectrode recordings (MER), and test stimulation in awake patients. The value of these steps is a subject for ongoing debate. In the current study, we determined the relative contribution of MRI targeting, multitrack MER, and awake test stimulation in final lead placement during STN DBS surgery for PD. Methods: Data on PD patients undergoing MRI-targeted STN DBS surgery with three-channel MER and awake test stimulation between February 2010 and January 2014 were analyzed to determine in which MER trajectory final leads were implanted and why this tract was chosen. Results: Seventy-six patients underwent implantation of 146 DBS leads. In 92% of the STN, the final leads were implanted in one of the three planned channels. In 6%, additional channels were needed. In 2%, surgery was aborted before final lead implantation due to anxiety or fatigue. The final leads were implanted in the channels with the longest STN MER signal trajectory in 60% of the STN (38% of the bilaterally implanted patients). This was the central channel containing the MRI target in 39% of the STN (18% bilaterally). The most frequently noted reasons why another channel than the central channel was chosen for final lead placement were (1) a lower threshold for side effects (54%) and (2) no or a too short trajectory of the STN MER signal (40%) in the central channel. The latter reason correlated with larger 2D (x and y) errors in our stereotactic method. Conclusions: STN DBS leads were often not implanted in the MRI-planned trajectory or in the trajectory with the longest STN MER signal. Thresholds for side effects during awake test stimulation were decisive for final target selection in the majority of patients

Levodopa Response in Patients with Early Parkinson Disease: Further Observations of the LEAP Study

Background and Objectives: The Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease. Methods: The LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations. Results: A total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early-and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was-0.33 for bradykinesia,-0.29 for rigidity, and-0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively,-0.49,-0.36, and-0.44 (small to medium effect); and from baseline to week 40, respectively,-0.32,-0.19, and-0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01). Discussion: In patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier. Classification of Evidence: This study provides Class II evidence that the effect of levodopa on bradykinesia, rigidity, and tremor is larger after 22 weeks compared with 4 weeks of treatment. Trial Registration Information: ISRCTN30518857, EudraCT number 2011-000678-72