Laura Rocchi, Patricia Carlson-Kuhta, Lorenzo Chiari, Kim J. Burchiel, Penelope Hogarth and Fay B. Horak
Difficulty with step initiation, called “start hesitation,” is related to gait bradykinesia and is an early hallmark of gait freezing in Parkinson disease (PD). Authors of this study investigated the effects of deep brain stimulation (DBS) and levodopa on step initiation before and 6 months after DBS surgery in 29 patients with PD who were randomized to either the bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) as the DBS site.
The authors measured the amplitude and duration of anticipatory postural adjustments (APAs), the feed-forward postural preparation that precedes the onset of voluntary step initiation, based on center-of-pressure displacements on a force plate. They also measured the length and velocity of the first step using a motion analysis system to study kinematics. Some of the patients (22) were from a large, multicenter, double-blind clinical trial, and all patients in the study (29, PD-DBS group) were randomized to DBS in either the bilateral STN (15 patients) or bilateral GPi (14 patients). Differences in step initiation were investigated in 2 conditions before surgery (off/on levodopa) and in 4 conditions after surgery (off/on levodopa combined with off/on DBS). Twenty-eight elderly healthy control volunteers (CTRL group) were also tested, and 9 control volunteers with PD who met the criteria for DBS (PD-C group) were tested at baseline and 6 months later.
Patients in the PD-DBS group had smaller amplitudes and longer durations of APAs compared with those in the 28 healthy control volunteers in all conditions. Before surgery, APAs improved with levodopa. After surgery, the APAs were significantly worse than in the best-treatment state before surgery (DOPA condition), and responsiveness to levodopa decreased. No differences in APAs were detected between the STN and GPi groups. A comparison with PD control volunteers who did not undergo DBS surgery confirmed that a deterioration in step preparation was not related to disease progression.
Step length and velocity were smaller in the PD-DBS group than in controls in all conditions. Before surgery, levodopa improved the length and velocity of the first step. Both step length and velocity were unchanged in the best-treatment state before surgery (DOPA condition) as compared with after surgery (DBS+DOPA), with only step velocity in the STN group getting worse after surgery.
Six months of DBS in the STN or GPi impaired anticipatory postural preparation for step initiation, the opposite effect as with levodopa. Deep brain stimulation disrupted postural preparation more than step execution, suggesting independent motor pathways for preparation and execution of gait. Although turning the stimulators on after surgery combined with levodopa benefited the postural preparation to step, a comparison of pre- and postsurgery conditions suggests that either the surgery itself or 6 months of continuous stimulation may lead to an alteration of circuits or plastic changes that impair step initiation.
Rebecca J. St George, Patricia Carlson-Kuhta, Kim J. Burchiel, Penelope Hogarth, Nicholas Frank and Fay B. Horak
The effect of deep brain stimulation (DBS) for Parkinson disease (PD) on balance is unclear. The goal of this study was to investigate how automatic postural responses (APRs) were affected in patients randomized to either subthalamic nucleus (STN) or globus pallidus internus (GPi) surgery.
The authors tested 24 patients with PD who underwent bilateral DBS, 9 control patients with PD who did not undergo DBS, and 17 age-matched control volunteers. The electrode placement site was randomized and blinded to the patients and to the experimenters. Kinematic, kinetic, and electromyographic recordings of postural responses to backward disequilibrium via forward translations of the standing surface were recorded in the week prior to surgery while the patients were off (OFF) and on (ON) antiparkinsonian medication (levodopa), and then 6 months after surgery in 4 conditions: 1) off medication with DBS switched off (OFF/OFF); 2) off medication with DBS on (DBS); 3) on medication with DBS off (DOPA); and 4) with both medication and DBS on (DBS+DOPA). Stability of the automatic postural response (APR) was measured as the difference between the displacement of the center of pressure and the projected location of the center of body mass.
Patients with PD had worse APR stability than controls. Turning the DBS on at either site improved APR stability compared with the postoperative OFF condition by lengthening the tibialis response, whereas medication did not show an appreciable effect. The STN group had worse APR stability in their best functional state (DBS+DOPA) 6 months after the DBS procedure compared with their best functional state (ON levodopa) before the DBS procedure. In contrast, the GPi group and the PD control group showed no change over 6 months. The APR stability impairment in the STN group was associated with smaller tibialis response amplitudes, but there was no change in response latency or coactivation with gastrocnemius.
Turning the DBS current on improved APR stability for both STN and GPi sites. However, there was a detrimental DBS procedural effect for the STN group, and this effect was greater than the benefit of the stimulating current, making overall APR stability functionally worse after surgery for the STN group.
Lee T. Robertson, Rebecca J. St George, Patricia Carlson-Kuhta, Penelope Hogarth, Kim J. Burchiel and Fay B. Horak
While deep brain stimulation (DBS) has proven to be an effective treatment for many symptoms of Parkinson disease (PD), a deterioration of axial symptoms frequently occurs, particularly for speech and swallowing. These unfavorable effects of DBS may depend on the site of stimulation. The authors made quantitative measures of jaw velocity to compare the relative effectiveness of DBS in the globus pallidus internus (GPi) or the subthalamic nucleus (STN). This was a randomized, double-blind, and longitudinal study, with matched healthy controls.
The peak velocities of self-scaled and externally scaled jaw movements were studied in 27 patients with PD before and after 6 months of bilateral DBS in the GPi or the STN. A mixed-effects model was used to identify differences in jaw velocity before DBS surgery (baseline) while off and on levodopa therapy, and after 6 months of DBS (postoperative) during 4 treatment conditions (off- and on-levodopa states with and without DBS).
Self-scaled jaw velocity was impaired by the DBS procedure in the STN; velocity was significantly decreased across all postoperative conditions compared with either the off- or on-levodopa baseline conditions. In contrast, the postoperative velocity in the GPi group was generally faster than the baseline off-levodopa state. Turning the DBS off and on had no effect on jaw velocity in either group. Unlike baseline, levodopa therapy postoperatively no longer increased jaw velocity in either group, and this lack of effect was not related to postoperative changes in dose. The externally scaled jaw velocity was little affected by PD, but DBS still slightly affected performance, with the STN group significantly slower than the GPi group for most conditions.
The authors' results suggest that either the electrode implant in STN or the subsequent period of continuous STN stimulation negatively affected voluntary jaw velocity, including the loss of the preoperative levodopa-induced improvement. While the GPi group showed some improvement in voluntary jaw velocity postoperatively, their performance during the combination of DBS and levodopa was not different from their best medical management presurgery. The results have implications for DBS target selection, particularly for those patients with oromotor dysfunctions.