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Graphical Abstract

Models have been developed for predicting ideal contact and amplitude for subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Pulse-width is generally varied to modulate the size of the energy field produced. Effects of varying frequency in humans have not been systematically evaluated.

Deep brain stimulation (DBS) is a well‐accepted treatment of Parkinson's disease (PD). Motor phenotypes include tremor‐dominant (TD), akinesia‐rigidity (AR), and postural instability gait disorder (PIGD). The mechanism of action in how DBS modulates motor symptom relief remains unknown. Blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to determine whether the functional activity varies in response to DBS depending on PD phenotypes. Subjects underwent an fMRI scan with DBS cycling ON and OFF. The effects of DBS cycling on BOLD activation in each phenotype were documented through voxel‐wise analysis. For each region of interest, ANOVAs were performed using T‐values and covariate analyses were conducted. Further, a correlation analysis was performed comparing stimulation settings to T‐values. Lastly, T‐values of subjects with motor improvement were compared to those who worsened. As a group, BOLD activation with DBS‐ON resulted in activation in the motor thalamus (p< 0.01) and globus pallidus externa (p< 0.01). AR patients had more activation in the supplementary motor area (SMA) compared to PIGD (p< 0.01) and TD cohorts (p< 0.01). Further, the AR cohort had more activation in primary motor cortex (MI) compared to the TD cohort (p= 0.02). Implanted nuclei (p= 0.01) and phenotype (p= <0.01) affected activity in MI and phenotype alone affected SMA activity (p= <0.01). A positive correlation was seen between thalamic activation and pulse‐width (p= 0.03) and between caudate and total electrical energy delivered (p= 0.04). These data suggest that DBS modulates network activity differently based on patient motor phenotype. Improved understanding of these differences may further our knowledge about the mechanisms of DBS action on PD motor symptoms and to optimize treatment.

Newer generation deep brain stimulation (DBS) systems have recently become available in the United States. Data on real‐life experience are limited. We present our initial experience incorporating newer generation DBS with Parkinson's disease (PD) and essential tremor (ET) patients. Newer systems allow for smart energy delivery and more intuitive programming and hardware modifications including constant current and directional segmented contacts. We compared six‐month outcomes between 42 newer generation and legacy leads implanted in 28 patients. Two cohorts each included 7 PD patients with bilateral subthalamic nucleus (STN) stimulation and 7 ET patients with unilateral ventral intermediate nucleus (VIM) stimulation of the thalamus. All directional leads included 6172 Infinity 8‐Channel Directional leads and Infinity internal pulse generators (Abbott Neuromodulation, Plano, TX, USA) and nondirectional leads included lead 3389 with Activa SC for VIM and PC for STN (Medtronic, Minneapolis, MN, USA). Six‐month outcomes for medication reduction and motor score improvements between new and legacy DBS systems in PD and ET patients were similar. Directionality was employed in 1/3 of patients. Therapeutic window (difference between amplitude when initial symptom relief was obtained and when intolerable side effects appeared with the contact being used) was significantly greater in new DBS systems in both PD (p= 0.005) and ET (p= 0.035) patients. The windows for new and legacy systems were 3.60 V ± 0.42 and 2.00 V ± 0.32 for STN and 3.06 V ± 0.44 and 1.85 V ± 0.28 for VIM, respectively. The therapeutic window of newer systems, whether or not directionality was used, was significantly greater than that of the legacy system, which suggests increased benefit and programming options. Improvements in hardware and programming interfaces in the newer systems may also contribute to wider therapeutic windows. We expect that as we alter workflow associated with newer technology, more patients will use directionality, and amplitudes will become lower.

Pain is a prevalent and debilitating nonmotor symptom of Parkinson's disease (PD) that is often inadequately managed. Deep brain stimulation (DBS) has been shown to relieve pain in PD but an effective method of identifying which types of PD pain respond to DBS has not been established. We examine the effects of DBS on different types of PD pain using the King's Parkinson's disease pain scale (KPDPS), the only validated scale of PD pain. We prospectively followed 18 PD patients undergoing subthalamic nucleus (STN) or Globus pallidus interna (GPi) DBS. Subjects completed the KPDPS, low back disability index (LBDI), and McGill pain questionnaire (MPQ), preoperatively and at six months postoperatively. Subjects underwent the unified Parkinson's disease rating scale‐III (UPDRS‐III) with preoperative scores ON medication and postoperative scores ON medication/DBS stimulation. Of the 18 patients, a total of 12 subjects had STN DBS and 6 had GPi DBS. As a group, subjects showed improvement in total KPDPS score at six‐month postoperative follow‐up (p= 0.004). Fluctuation and nocturnal pain were most significantly improved (p= 0.006, 0.01, respectively). Significant improvements were found in fluctuation‐related pain domain following GPi DBS. In this pilot study, we are the first group to employ KPDPS to monitor pain relief following DBS in PD patients. We demonstrate that fluctuation‐related pain and nocturnal pain significantly improve with DBS. Use of the KPDPS in the future will allow better understanding of how STN and GPi DBS treat PD pain over time.

Accuracy of lead placement within the brain can affect the outcome of deep brain stimulation (DBS) surgery. Whether performing unilateral lead implantation, simultaneous bilateral lead implantation, or staged bilateral lead implantation affects accuracy has not yet been assessed. We compare lead placement errors to evaluate whether one approach affords greater lead accuracy. We retrospectively reviewed 205 leads placed in 125 DBS surgeries. The accuracy of lead placement, defined by differences in x, y, and z coordinates and error vector magnitudes, was compared between three surgery groups: unilateral leads, bilateral leads placed simultaneously, and bilateral leads placed in staged surgeries. We also compared accuracies between first and second leads within each bilateral cohort and between second leads of the bilateral cohorts. Finally, we examined the effect of target and age on accuracy. The accuracy of lead placement was comparable among unilateral, simultaneous bilateral, and staged bilateral leads. Timing of placement of the second lead in bilateral cases was not found to affect accuracy. The mean number of microelectrode trajectories was greater for first leads in simultaneous bilateral DBS (p= 0.032). No significant correlation between either age or target and accuracy was found. Although there may be other important reasons for performing DBS in a staged fashion, our study finds that neither laterality nor timing of second lead placement, patient age, or target site have significant impact on DBS lead accuracy, a finding that indicates with appropriate approach selection based on patient factors, accuracy does not have to be significantly compromised.

Graphical Abstract