Camilla Kilbane, Adolfo Ramirez-Zamora, Elena Ryapolova-Webb, Salman Qasim, Graham A. Glass, Philip A. Starr, and Jill L. Ostrem
Holmes tremor (HT) is characterized by irregular, low-frequency (< 4.5 Hz) tremor occurring at rest, with posture, and with certain actions, often affecting proximal muscles. Previous reports have tended to highlight the use of thalamic deep brain stimulation (DBS) in cases of medication-refractory HT. In this study, the authors report the clinical outcome and analysis of single-unit recordings in patients with medication-refractory HT treated with globus pallidus internus (GPi) DBS.
The authors retrospectively reviewed the medical charts of 4 patients treated with pallidal DBS for medication-refractory HT at the University of California, San Francisco, and San Francisco Veterans Affairs Medical Center. Clinical outcomes were measured at baseline and after surgery using an abbreviated motor-severity Fahn-Tolosa-Marin (FTM) tremor rating scale. Intraoperative microelectrode recordings were performed with patients in the awake state. The neurophysiological characteristics identified in HT were then also compared with characteristics previously described in Parkinson's disease (PD) studied at the authors' institution.
The mean percentage improvement in tremor motor severity was 78.87% (range 59.9%–94.4%) as measured using the FTM tremor rating scale, with an average length of follow-up of 33.75 months (range 18–52 months). Twenty-eight GPi neurons were recorded intraoperatively in the resting state and 13 of these were also recorded during contralateral voluntary arm movement. The mean firing rate at rest in HT was 56.2 ± 28.5 Hz, and 63.5 ± 19.4 Hz with action, much lower than the GPi recordings in PD. GPi unit oscillations of 2–8 Hz were prominent in both patients with HT and those with PD, but in HT, unlike PD, these oscillations were not suppressed by voluntary movement.
The efficacy of GPi DBS exceeded that reported in prior studies of ventrolateral thalamus DBS and suggest GPi may be a better target for treating HT. These clinical and neurophysiological findings help illuminate evolving models of HT and highlight the importance of cerebellar–basal ganglia interactions.
Takashi Tsuboi, Janine Lemos Melo Lobo Jofili Lopes, Kathryn Moore, Bhavana Patel, Joseph Legacy, Adrianna M. Ratajska, Dawn Bowers, Robert S. Eisinger, Leonardo Almeida, Kelly D. Foote, Michael S. Okun, and Adolfo Ramirez-Zamora
Few studies have reported long-term outcomes of globus pallidus internus (GPi) deep brain stimulation (DBS) in Parkinson’s disease (PD). The authors aimed to investigate long-term outcomes of bilateral GPi DBS for 5 years and beyond for PD patients.
The authors retrospectively analyzed the clinical outcomes in 65 PD patients treated with bilateral GPi DBS at a single center. The outcome measures of motor symptoms and health-related quality of life (HRQoL) included the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Parkinson’s Disease Questionnaire (PDQ-39). Scores at baseline were compared with those at 1, 3, 5, and 6–8 years after implantation using Wilcoxon signed-rank tests with α correction.
GPi DBS significantly improved the off-medication UPDRS III total scores, UPDRS IV, and dyskinesia score at 1 year when compared with baseline (all p < 0.001). The off- and on-medication tremor scores, UPDRS IV, and dyskinesia scores showed moderate and sustained improvement (the ranges of the mean percentage improvement at each time point were 61%–75%, 30%–80%, 29%–40%, and 40%–65%, respectively) despite lacking statistical significance at long-term follow-up with diminishing sample sizes. The off-medication UPDRS III total scores did not show significant improvement at 5 years or later, primarily because of worsening in rigidity, akinesia, speech, gait, and postural stability scores. The on-medication UPDRS III total scores also worsened over time, with a significant worsening at 6–8 years when compared with baseline (p = 0.008). The HRQoL analyses based on the PDQ-39 revealed significant improvement in the activities of daily living and discomfort domains at 1 year (p = 0.003 and 0.006, respectively); however, all the domains showed gradual worsening at the later time points without reaching statistical significance. At 3 years, the communication domain showed significant worsening compared with baseline scores (p = 0.002).
GPi DBS in PD patients in this single-center cohort was associated with sustained long-term benefits in the off- and on-medication tremor score and motor complications. HRQoL and the cardinal motor symptoms other than tremor may worsen gradually in the long term. When counseling patients, it is important to recognize that benefits in tremor and dyskinesia are expected to be most persistent following bilateral GPi DBS implantation.
Abigail Belasen, Khizer Rizvi, Lucy E. Gee, Philip Yeung, Julia Prusik, Adolfo Ramirez-Zamora, Era Hanspal, Priscilla Paiva, Jennifer Durphy, Charles E. Argoff, and Julie G. Pilitsis
Chronic pain is a major distressing symptom of Parkinson's disease (PD) that is often undertreated. Subthalamic nucleus (STN) deep brain stimulation (DBS) delivers high-frequency stimulation (HFS) to patients with PD and has been effective in pain relief in a subset of these patients. However, up to 74% of patients develop new pain concerns while receiving STN DBS. Here the authors explore whether altering the frequency of STN DBS changes pain perception as measured through quantitative sensory testing (QST).
Using QST, the authors measured thermal and mechanical detection and pain thresholds in 19 patients undergoing DBS via HFS, low-frequency stimulation (LFS), and off conditions in a randomized order. Testing was performed in the region of the body with the most pain and in the lower back in patients without chronic pain.
In the patients with chronic pain, LFS significantly reduced heat detection thresholds as compared with thresholds following HFS (p = 0.029) and in the off state (p = 0.010). Moreover, LFS resulted in increased detection thresholds for mechanical pressure (p = 0.020) and vibration (p = 0.040) compared with these thresholds following HFS. Neither LFS nor HFS led to changes in other mechanical thresholds. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick compared with thresholds following HFS (p = 0.032).
Recent literature has suggested that STN LFS can be useful in treating nonmotor symptoms of PD. Here the authors demonstrated that LFS modulates thermal and mechanical detection to a greater extent than HFS. Low-frequency stimulation is an innovative means of modulating chronic pain in PD patients receiving STN DBS. The authors suggest that STN LFS may be a future option to consider when treating Parkinson's patients in whom pain remains the predominant complaint.
Takashi Morishita, Yoshio Tsuboi, Masa-aki Higuchi, and Tooru Inoue