Highlights • Safety of rTMS was assessed ex and in-vivo in a patient with implanted subdural cortical electrodes. • There were no serious adverse effects after the rTMS protocol. • rTMS may be a safe ...therapeutic tool in patients with implanted subdural cortical electrodes.
ABSTRACT
Background
A hallmark of Parkinson's disease (PD) is progressive loss of dopamine terminals in the basal ganglia, with clinical symptoms including motor and non‐motor manifestations such as ...bradykinesia, rigidity, and cognitive impairment. Dopamine transporter single‐photon emission computed tomography (DaT‐SPECT) can be used to assess dopaminergic denervation by detecting loss of striatal dopamine transporters (DaT).
Objective
We examined DaT binding scores’ (DaTbs) association with motor outcomes in PD and explored its usefulness as a predictor of disease progression. Faster dopaminergic denervation in the basal ganglia was hypothesized to have stronger correlation and predictive value for poor motor outcomes.
Methods
Data was analyzed from the Parkinson's Progression Markers Initiative. DaTbs in the putamen and caudate nucleus were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) scores for walking and balance difficulties, gait difficulties, and presence of dyskinesias. A predictive model using baseline speed of drop in DaT binding score was performed for each motor outcome.
Results
All motor outcomes had mild, significantly negative correlation with DaTbs in the putamen and caudate nucleus, with similar degree of correlation per region. Speed of drop was predictive of only substantial gait difficulties when evaluated in the putamen but not the caudate.
Conclusions
These findings suggest that analyzing speed of drop in DaTbs, which occurs early in the motor phase of the disease, may be helpful for predicting clinical outcomes in PD. Longer observation of this cohort may provide further data to investigate DaTbs as a prognostic marker in PD.
Levodopa-induced dyskinesias (LID) are amongst the most disabling side-effects of levodopa therapy for Parkinson's disease (PD). It has been suggested that that N-Methyl-D-Aspartate (NMDA)-receptor ...antagonist may reduce peak-dose dyskinesia in PD patients and may lead to motor improvement. In this study, we compared the efficacy of NMDA receptor antagonists versus placebo in the treatment of LID in PD through a meta-analysis of controlled trials.
Electronic search of Pubmed (1990 - 2010), Medline (1966-2010), EMBASE (1974-2010) and other databases for relevant studies were performed. Controlled clinical trials of the effects of NMDA antagonists on LID that fulfill the study protocol were selected. Pooled data from included studies was then used to perform random and fixed effect models meta-analysis.
The search resulted in 11 randomized, placebo controlled clinical trials that involved a total of 253 PD patients with peak-dose LID. The outcome measures were various dyskinesia rating scales and the Unified Parkinson Disease Rating Scale (UPDRS) subscales III and IV. The analysis showed significant reduction in Standard Mean Difference (SMD) for UPDRS IV (SMD -1.45; 95%CI -2.28 to -0.63) and UPDRS III (SMD -0.41; 95%CI -0.69 to -0.12) after treatment with amantadine. Other included drugs did not show significant change in the outcomes measured.
This meta-analysis provides an update on the clinical trials and confirms the short-term benefits of amantadine therapy in the treatment of dyskinesia. The effects of other NMDA receptor antagonists need to be evaluated further in clinical trials.
Objective
Internal globus pallidus (GPi) deep brain stimulation (DBS) relieves symptoms in dystonia patients. However, the physiological effects produced by GPi DBS are not fully understood. In ...particular, how a single‐pulse GPi DBS changes cortical circuits has never been investigated. We studied the modulation of motor cortical excitability and plasticity with single‐pulse GPi DBS in dystonia patients with bilateral implantation of GPi DBS.
Methods
The cortical evoked potentials from DBS were recorded with electroencephalography. Transcranial magnetic stimulation with a conditioning test paired‐pulse paradigm was used to investigate the effect of GPi DBS on the primary motor cortex. How GPi DBS might modulate the motor cortical plasticity was tested using a paired associative stimulation paradigm with repetitive pairs of GPi DBS and motor cortical stimulation at specific time intervals.
Results
GPi stimulation produced 2 peaks of cortical evoked potentials with latencies of ∼10 and ∼25 milliseconds in the motor cortical area. Cortical facilitation was observed at ∼10 milliseconds after single‐pulse GPi DBS, and cortical inhibition was observed after a ∼25‐millisecond interval. Repetitive pairs of GPi stimulation with cortical stimulation at these 2 time intervals produced long‐term potentiation‐like effects in the motor cortex.
Interpretation
Single‐pulse DBS modulates cortical excitability and plasticity at specific time intervals. These effects may be related to the mechanism of action of DBS. Combination of DBS with cortical stimulation with appropriate timing has therapeutic potential and could be explored in the future as a method to enhance the effects of neuromodulation for neurological and psychiatric diseases. Ann Neurol 2018;83:352–362
Background Electrode implantation for deep brain stimulation (DBS) can be performed in numerous ways, but the current “gold standard” is the use of frame-based systems for accuracy. Robotic ...stereotactic procedures, however, have gained increased interest because of their ease of use and reliability, but there could be concern about their safety in the United States as the result of recent lawsuits (e.g., the da Vinci Surgical System). We report the first DBS implantation performed using a robot (ROSA robotic device) approved by Food and Drug Administration for use in North America. Case Description A 56-year-old, right-handed woman with a 12-year history of Parkinson disease is described. She was offered bilateral subthalamic nucleus DBS placement to address motor fluctuations and dyskinesias. DBS electrode implantation was implemented successfully with ROSA robotic stereotactic assistance. Using preoperative magnetic resonance imaging scan acquisitions, we targeted the patient's subthalamic nucleus bilaterally. Bone fiducials were placed and intraoperative computed tomography (CT) imaging was obtained. The magnetic resonance imaging and CT were fused, and the patient was registered to the ROSA software. Trajectories were obtained and a microdrive device was fixed to the robotic arm to advance the electrode to the correct location. Electrodes were then placed bilaterally. Intraoperative CT showed good placement with no complications encountered. Conclusions The advantages of robotic assistance in stereotactic procedures are as follows: 1) improved accuracy, 2) “arc-less” approach, and 3) minor adjustments can be made in multiple planes to the entry point without adjustment of a frame. The case demonstrates robotic stereotactic assistance viability as an alternative to traditional frame-based or frameless systems in U.S. hospitals.
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