ABSTRACT
BACKGROUND: Abnormal synchronization of neuronal activity in dopaminergic circuits is related to motor impairment in Parkinson's disease (PD). Vibrotactile coordinated reset (vCR) fingertip stimulation aims to counteract excessive synchronization and induce sustained unlearning of pathologic synaptic connectivity and neuronal synchrony. Here, we report two clinical feasibility studies that examine the effect of regular and noisy vCR stimulation on PD motor symptoms. Additionally, in one clinical study (study 1), we examine cortical beta band power changes in the sensorimotor cortex. Lastly, we compare these clinical results in relation to our computational findings. METHODS: Study 1 examines six PD patients receiving noisy vCR stimulation and their cortical beta power changes after 3 months of daily therapy. Motor evaluations and at-rest electroencephalographic (EEG) recordings were assessed off medication pre- and post-noisy vCR. Study 2 follows three patients for 6+ months, two of whom received daily regular vCR and one patient from study 1 who received daily noisy vCR. Motor evaluations were taken at baseline, and follow-up visits were done approximately every 3 months. Computationally, in a network of leaky integrate-and-fire (LIF) neurons with spike timing-dependent plasticity, we study the differences between regular and noisy vCR by using a stimulus model that reproduces experimentally observed central neuronal phase locking. RESULTS: Clinically, in both studies, we observed significantly improved motor ability. EEG recordings observed from study 1 indicated a significant decrease in off-medication cortical sensorimotor high beta power (21-30 Hz) at rest after 3 months of daily noisy vCR therapy. Computationally, vCR and noisy vCR cause comparable parameter-robust long-lasting synaptic decoupling and neuronal desynchronization. CONCLUSION: In these feasibility studies of eight PD patients, regular vCR and noisy vCR were well tolerated, produced no side effects, and delivered sustained cumulative improvement of motor performance, which is congruent with our computational findings. In study 1, reduction of high beta band power over the sensorimotor cortex may suggest noisy vCR is effectively modulating the beta band at the cortical level, which may play a role in improved motor ability. These encouraging therapeutic results enable us to properly plan a proof-of-concept study.
ABSTRACT
BACKGROUND: Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options. METHODS: Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques. RESULTS: Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery. CONCLUSIONS: Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society.
