An Adaptable Phase-Tracking System for Parkinsonian Rest Tremor: Design and In-Clinic Feasibility

Identifying and troubleshooting low-frequency artifacts mimicking atrial flutter caused by deep brain stimulator

The effects of subthalamic nucleus deep brain stimulation on parkinsonian tremor

Do patient's get angrier following STN, GPi, and thalamic deep brain stimulation

Parkinson's disease is a neurodegenerative disorder that manifests clinically with variable degrees of tremor, muscle rigidity, bradykinesia and postural instability. Tremor-predominant Parkinson's disease is characterised by prominent tremor of one or more limbs with a relative lack of significant rigidity and bradykinesia. Despite the lack of other disabling motor symptoms, the tremor of tremor-predominant Parkinson's disease can be very disabling, especially if a postural and kinetic component exists. A wide variety of treatments for Parkinson's disease tremor are currently available and include use of oral medications, injections with botulinum toxin and neurosurgical procedures. Some of the first line medications (levodopa, dopamine agonists, anticholinergics) are very effective in controlling tremor. However, some patients with Parkinson's disease tremors are unresponsive to first line drugs and treatment with second line medications (clozapine, amantadine, clonazepam, propranolol, neurontin) should be attempted. In the small number of patients with disabling tremor that is refractory to all medications, neurosurgical intervention should be considered. Both thermocoagulation and deep brain stimulation at several different neuroanatomical sites (thalamus, globus pallidus, subthalamic nucleus) offer good to excellent tremor control with relatively low risk to the patient.

Functional magnetic resonance imaging studies suggest that different subcortico-cortical circuits control different aspects of Parkinsonian rest tremor. The basal ganglia were proposed to drive tremor onset, and the cerebellum was suggested to be responsible for tremor maintenance (“dimmer-switch” hypothesis). Although several electrophysiological correlates of tremor have been described, it is currently unclear whether any of these is specific to tremor onset or maintenance. In this study, we present data from a single patient measured repeatedly within 2 years after implantation of a deep brain stimulation (DBS) system capable of recording brain activity from the target. Local field potentials (LFPs) from the subthalamic nucleus and the scalp electroencephalogram were recorded 1 week, 3 months, 6 months, 1 year, and 2 years after surgery. Importantly, the patient suffered from severe rest tremor of the lower limbs, which could be interrupted voluntarily by repositioning the feet. This provided the unique opportunity to record many tremor onsets in succession. We found that tremor onset and tremor maintenance were characterized by distinct modulations of subthalamic oscillations. Alpha/low-beta power increased transiently immediately after tremor onset. In contrast, beta power was continuously suppressed during tremor maintenance. Tremor maintenance was additionally associated with subthalamic and cortical power increases around individual tremor frequency. To our knowledge, this is the first evidence of distinct subthalamic LFP modulations in tremor onset and tremor maintenance. Our observations suggest the existence of an acceleration signal for Parkinsonian rest tremor in the basal ganglia, in line with the “dimmer-switch” hypothesis.

Parkinson's Disease (PD) is the second most common neurodegenerative disease, characterized by progressive motor (such as resting tremor, hypokinesia, postural instability) and non-motor symptoms (such as neuropsychiatric decline and autonomic dysfunction). Since its introduction in the late 1980s, deep brain stimulation (DBS) has revolutionized the treatment of PD. Initially used in patients' with advanced PD with either medically refractory motor symptoms or medication intolerance, DBS typically provides excellent improvement in motor symptoms. Indications for DBS have continued to expand, with demonstrated efficacy in early PD and essential tremor, and promising preliminary results in the treatment of epilepsy, psychiatric disease, and depression. Advancements in DBS hardware, programming, neuroimaging, and surgical techniques have led to progressive improvement in efficacy and safety profiles. Thanks to ongoing research into remote programming, adaptive DBS, new targets, and alternative interventions, such as transcranial magnetic stimulation, the opportunities for further improvements in DBS and neuromodulation are bright.

ObjectivesRest tremor is a cardinal symptom of Parkinson’s disease (PD), and is readily suppressed by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The therapeutic effect of the latter on bradykinesia and rigidity has been associated with the suppression of exaggerated beta (13–30 Hz) band synchronization in the vicinity of the stimulating electrode, but there is no correlation between beta suppression and tremor amplitude. In the present study, we investigate whether tremor suppression is related to suppression of activities at other frequencies.Materials and MethodsWe recorded hand tremor and contralateral local field potential (LFP) activity from DBS electrodes during stimulation of the STN in 15 hemispheres in 11 patients with PD. DBS was applied with increasing voltages starting at 0.5 V until tremor suppression was achieved or until 4.5 V was reached.ResultsTremor was reduced to 48.9% ± 10.9% of that without DBS once stimulation reached 2.5–3 V (t14 = −4.667, p < 0.001). There was a parallel suppression of low gamma (31–45 Hz) power to 92.5% ± 3% (t14 = −2.348, p = 0.034). This was not seen over a band containing tremor frequencies and their harmonic (4–12 Hz), or over the beta band. Moreover, low gamma power correlated with tremor severity (mean r = 0.43 ± 0.14, p = 0.008) within subjects. This was not the case for LFP power in the other two bands.ConclusionsOur findings support a relationship between low gamma oscillations and PD tremor, and reinforce the principle that the subthalamic LFP is a rich signal that may contain information about the severity of multiple different Parkinsonian features.

Rest tremor is a most common symptom of Parkinson’s Disease (PD), with diagnosis and severity estimation often being hindered by subjectivity and limitations of existing methods. Additionally, treatment strategies for PD face challenges in monitoring symptom fluctuations with clinical methods, like the MDS-UPDRS and motor diaries, suffering from subjectivity, limited sensitivity, and infrequent sampling, potentially impacting treatment effectiveness. Hence, methods that can yield explainable biomarkers that accurately describe properties of PD rest tremor, while accounting for the presence of ongoing treatments, such as Deep Brain Stimulation (DBS) and medication, are important for integration in accurate AI-powered wearable systems. To that end, a Higher Order Spectrum (HOS)-based analysis to extract features from index finger velocity recordings of 16 PD patients is proposed. Two different scenarios are implemented for characterizing and classifying treatment (medication/DBS) effectiveness and tremor severity (Low-/High-Amplitude (LAT/HAT)), by means of statistical tests and a leave-one-subject-out cross-validation classification scheme, respectively. The proposed analysis resulted in area under the Receiver Operating Characteristics curve (AUC) score of 0.94 for the Medication treatment classification, 0.71 for the DBS treatment and 0.83 for LAT/HAT prediction. Our results demonstrate that the proposed approach can effectively assess the influence of medication and DBS and recognize rest tremor severity. Finally, our HOS-based methodology enables the establishment of new rest tremor classes, based on its nonlinearity and allows for new insights about the dynamic nature of the resting tremor production system.

Rest tremor correlates with reduced contralateral striatal dopamine transporter binding in Parkinson's disease

Deep brain stimulation (DBS) is well recognized as an effective treatment for symptoms of movement disorders such as Parkinson's disease (PD), Essential Tremor, and dystonia. The selection of the appropriate contact on the DBS lead for optimal clinical efficacy can be challenging, particularly when considering directional leads. Electroencephalograms (EEG) and electrocorticography has been utilized to better understand the pathophysiology of PD but a methodology to provide an objective biomarker of effective stimulation has yet to be developed. Using machine learning techniques for feature extraction and classification, we contrast high resolution EEG captured during DBS against its resting state counterpart with the DBS off. We demonstrate, using 16 patients under DBS treatment for movement disorders, EEG's informative capacity to detect both effective DBS and the region undergoing stimulation.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely performed for medically refractory Parkinson’s disease (PD). Several western studies have examined the long-term outcomes of STN DBS. However, the long-term outcomes in Japanese patients have not been reported. Methods: We studied the long-term outcomes of STN DBS in Japanese patients with PD. Fifty-five consecutive patients treated with bilateral STN DBS were followed for 5 years after surgery. Each patient underwent Unified Parkinson’s Disease Rating Scale assessments preoperatively and 1 and 5 years after surgery. Results: Twelve patients (22%) were lost to follow up within 5 years. Among them, 7 died and 5 became bed ridden because of PD deterioration. In the 43 patients followed for 5 years, STN DBS significantly improved motor function. The cardinal motor symptoms of tremor, rigidity, and bradykinesia in medication-on periods were significantly better than baseline 5 years after DBS. However, axial motor symptoms of speech, gait and postural stability gradually deteriorated and significantly worsened 5 years after DBS. Motor complications, including dyskinesia and motor fluctuations, significantly improved after DBS with a marked reduction in dopaminergic medication. These effects were maintained 5 years after DBS. Frequently, persisting adverse effects included apraxia of eyelid opening and dysarthria. Conclusions: STN DBS significantly improved motor symptoms in patients with advanced PD. These effects were maintained over 5 years in most patients. However, some showed rapid PD progression even after STN DBS. Other treatments for the axial symptoms and disease progression are needed in long-term PD treatment.

Opioid overprescription is a problem in orthopaedic surgery. Arthroscopic surgery, given its minimally invasive nature, represents an opportunity to minimize opioid prescription and consumption by using effective pain management adjuncts. Thus, the primary question posed in this study was which noninvasive pain management modalities can effectively manage pain and reduce opioid intake after arthroscopic surgery. The databases PubMed, MEDLINE, EMBASE, Scopus, and Web of Science were searched on August 10, 2022. Randomized controlled trials (RCTs) evaluating noninvasive pain management strategies in arthroscopy patients were evaluated. Eligible studies were selected through a systematic screening process. Meta-analysis was performed for pain scores and opioid consumption at time points which had sufficient data available. Twenty-one RCTs were included, with a total of 2,148 patients undergoing shoulder, knee, and hip arthroscopy. Meta-analysis comparing nonopioid, oral analgesic regimens, with or without patient education components, with the standard of care or placebo demonstrated no difference in pain scores at 24 hours, 4 to 7 days, or 14 days postoperatively. Nonopioid regimens also resulted in significantly lower opioid consumption in the first 24 hours postoperatively (mean difference, -37.02 mg oral morphine equivalents, 95% confidence interval, -74.01 to -0.03). Transcutaneous electrical nerve stimulation (TENS), cryotherapy, and zolpidem were also found to effectively manage pain and reduce opioid use in a limited number of studies. A range of noninvasive pain management strategies exist to manage pain and reduce opioid use after arthroscopic procedures. The strongest evidence base supports the use of multimodal nonopioid oral analgesics, with some studies incorporating patient education components. Some evidence supports the efficacy of TENS, cryotherapy, and nonbenzodiazepine sleeping aids. Direction from governing bodies is an important next step to incorporate these adjuncts into routine clinical practice to manage pain and reduce the amount of opioids prescribed and consumed after arthroscopic surgery. Level II, systematic review and meta-analysis of RCTs. See Instructions for Authors for a complete description of the levels of evidence.

BackgroundResting tremor is common in Parkinson’s disease (PD), but up to 47% of PD patients have action tremor, which is sometimes resistant to medications. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus or subthalamic nucleus (STN) is effective for medication-refractory tremor in PD, though it remains unclear whether STN DBS is as effective as VIM DBS for postural/action tremor related to PD.MethodsWe carried out a single-center retrospective review of patients with medication-refractory resting, postural, and action PD tremor, treated with either VIM or STN DBS between August 2004 and March 2014. We assessed the degree of improvement using items 20 and 21 of the Unified Parkinson’s Disease Rating Scale (UPDRS) motor scale and examined the proportion of patients achieving tremor arrest.ResultsA total of 18 patients were analyzed, 10 treated with STN and eight treated with VIM, with similar off-medication motor UPDRS scores. There was no significant difference in improvement in tremor scores or in the proportion of patients experiencing tremor arrest between the two stimulation sites. Overall, 56% and 72% of patients experienced complete absence of postural/action tremor and resting tremor, respectively, at last follow-up.DiscussionThis study demonstrated excellent outcomes on both resting and postural/action tremor after either VIM or STN DBS. Resting tremor improved to a greater degree than postural/action tremor in both groups. These results suggest that a large randomized controlled trial is needed to show a superior effect of one target on PD tremor.

Objectives: To evaluate the safety and efficacy of a new dual channel stimulator (Kinetra) in patients with severe Parkinson's disease (PD) or essential tremor (ET). Methods: 111 patients with PD...

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD) and other movement disorders. The ventral intermediate nucleus of the thalamus is considered as the target of choice for tremor disorders, including tremor-dominant PD not suitable for DBS in the subthalamic nucleus (STN). In the last decade, several studies have shown promising results on tremor from DBS in the posterior subthalamic area (PSA), including the caudal zona incerta (cZi) located posteromedial to the STN. The aim of this study was to evaluate the long-term effect of unilateral cZi/PSA-DBS in patients with tremor-dominant PD. Methods: Thirteen patients with PD with medically refractory tremor were included. The patients were evaluated using the motor part of the Unified Parkinson Disease Rating Scale (UPDRS) off/on medication before surgery and off/on medication and stimulation 1–2 years (short-term) after surgery and at a minimum of 3 years after surgery (long-term). Results: At short-term follow-up, DBS improved contralateral tremor by 88% in the off-medication state. This improvement persisted after a mean of 62 months. Contralateral bradykinesia was improved by 40% at short-term and 20% at long-term follow-up, and the total UPDRS-III by 33% at short-term and by 22% at long-term follow-up with stimulation alone. Conclusions: Unilateral cZi/PSA-DBS seems to remain an effective treatment for patients with severe Parkinsonian tremor several years after surgery. There was also a modest improvement on bradykinesia.