Utility of GPI+VIM dual-lead deep brain stimulation for Parkinson’s disease patients with significant residual tremor on medication

OBJECTIVE Randomized controlled trials have demonstrated that deep brain stimulation (DBS) of both the globus pallidus internus (GPI) and subthalamic nucleus (STN) for Parkinson’s disease (PD) is superior to the best medical therapy. Tremor is particularly responsive to DBS, with reports of 70%–80% improvement. However, a small number of patients do not obtain the expected response with both STN and GPI targets. Indeed, the authors’ patient population had a similar 81.2% tremor reduction with a 9.6% failure rate. In an analysis of these failures, they identified patients with preoperative on-medication tremor who subsequently received a GPI lead as a subpopulation at higher risk for inadequate tremor control. Thereafter, STN DBS was recommended for patients with on-medication tremor. However, for the patients with symptoms and comorbidities that favored GPI as the target, dual GPI and ventral intermediate nucleus of the thalamus (VIM) leads were proposed. This report details outcomes for those patients. METHODS This is a retrospective review of patients with PD who met the criteria for and underwent simultaneous GPI+VIM DBS surgery from 2015 to 2020 and had available follow-up data. The preoperative Unified Parkinson’s Disease Rating Scale scores were obtained with the study participants on and off their medication. Postoperatively, the GPI lead was kept on at baseline and scores were obtained with and without VIM stimulation. RESULTS Thirteen PD patients with significant residual preoperative tremor on medication underwent simultaneous GPI+VIM DBS surgery (11 unilateral, 2 bilateral). A mean 90.6% (SD 15.0%) reduction in tremor scores was achieved with dual GPI+VIM stimulation compared to a 21.8% (SD 71.9%) reduction with GPI stimulation alone and a 30.9% (SD 37.8%) reduction with medication. Although rigidity and bradykinesia reductions were accomplished with just GPI stimulation, 13 of the 15 hemispheres required VIM stimulation to achieve excellent tremor control. CONCLUSIONS GPI+VIM stimulation was required to adequately control tremor in all but 2 patients in this series, substantiating the authors’ hypothesis that, in their population, medication-resistant tremor does not completely respond to GPI stimulation. Dual stimulation of the GPI and VIM proved to be an effective option for the patients who had symptoms and comorbidities that favored GPI as a target and had medication-resistant tremor.

Constructing Adult Zebrafish Einthoven’s Triangle to Define Electrical Heart Axes

Zebrafish is a popular high-throughput vertebrate model to study human cardiac electrophysiology, arrhythmias, and myopathies. One reason for this popularity is the purported striking similarities between zebrafish and human electrocardiograms (ECGs). However, zebrafish electrical heart axes were unknown. It is impossible to define heart axis based on single-lead ECG because determination of an electrical heart axis in the frontal plane requires the use of the hexaxial reference system (or Cabrera system) derived from Einthoven’s triangle. Construction of Einthoven’s triangle requires simultaneous ECG recording from at least two Einthoven bipolar leads. Therefore, we systematically constructed the first zebrafish Einthoven’s triangle by simultaneous bipolar dual-lead ECG recording to determine for the first time the three frontal electrical heart axes using the Cabrera system. Comparing zebrafish with human Einthoven’s triangle reveals that their normal frontal electrical axes were reflections of each other across 0° in the Cabrera system. The responsible mechanisms involve zebrafish vs. human cardiac activation propagating in the same direction along the heart horizontal axis but in opposite directions along the heart longitudinal axis. The same observations are true for zebrafish vs. human cardiac repolarization. This study marks a technical breakthrough in the first bipolar dual-lead ECG recording in live adult zebrafish to construct for the first time zebrafish Einthoven’s triangle. This first systematic analysis of the actual differences and similarities between normal adult zebrafish and human Einthoven’s triangles unmasked differences and similarities in the underlying cardiac axis mechanisms. Insights of the live adult zebrafish main heart axis and its three frontal electrical heart axes provide critical contextual framework to interpret the clinical relevance of the adult zebrafish heart as model for human cardiac electrophysiology.

Dual-Lead 55 mm Impedance Pneumography

In recent years, respiratory monitoring has gained attention due to the high prevalence and severe consequences of sleep apnea, post-anesthesia respiratory instability and respiratory diseases. Nevertheless, respiratory monitoring oftentimes relies on obtrusive masks and belts, which are unsuitable for wearable, long-term monitoring. Impedance pneumography (IP) is a bioimpedance method aiming to assess respiratory parameters unobtrusively. However, most IP configurations require far-spaced electrodes. Based on our recent work on wearable IP, we propose a dual-lead, wearable IP setup with 55 mm electrode spacing to estimate respiratory flow and rate (RR). Using our recently presented multimodal patch stethoscope as well as commercial systems, we conducted a study including 10 healthy subjects which were recorded in the supine, lateral and prone position. Using time-delay neural networks, we achieved RR estimation errors below 0.6 breaths per minute and flow correlations of 0.88 with relative errors of 25 % to a pneumotachometer reference. We conclude that dual-lead IP increases the performance of respiratory signal estimation compared to a single lead and recommend research in the area of subject position dependency and movement artefacts.

Medication-Refractory Parkinsonian Tremor Requiring Dual Lead Implantation for Tremor Control

A 52-year-old man with Parkinson disease (PD) of 9 years’ duration was referred to the DBS clinic for medication-refractory severe unilateral rest and re-emergent tremor and frequent motor fluctuations. He was approved for DBS, with debate over the optimal target to treat severe tremor and fluctuations (subthalamic nucleus [STN] plus/minus the ventral intermediate [Vim] thalamus) and unilateral versus bilateral implantation. The committee decided to perform unilateral STN lead placement first, to provide benefit for both motor fluctuation and tremor, with the option of adding Vim concurrently if required. Intraoperatively, there was incomplete tremor capture, so a second lead was placed in Vim with success. Subsequent DBS programming achieved marked improvement of tremor and fluctuations at low stimulation, although side effects necessitated bipolar configurations in both leads. The patient reported excellent sustained tremor suppression at 2-year follow-up, although motor fluctuations recurred. This case illustrates that for intraoperative stimulation-refractory PD tremor, consideration can be given to adding a second Vim DBS target (dual DBS targets).

A Novel Approach for Multi-Lead ECG Classification Using DL-CCANet and TL-CCANet

Cardiovascular disease (CVD) has become one of the most serious diseases that threaten human health. Over the past decades, over 150 million humans have died of CVDs. Hence, timely prediction of CVDs is especially important. Currently, deep learning algorithm-based CVD diagnosis methods are extensively employed, however, most such algorithms can only utilize one-lead ECGs. Hence, the potential information in other-lead ECGs was not utilized. To address this issue, we have developed novel methods for diagnosing arrhythmia. In this work, DL-CCANet and TL-CCANet are proposed to extract abstract discriminating features from dual-lead and three-lead ECGs, respectively. Then, the linear support vector machine specializing in high-dimensional features is used as the classifier model. On the MIT-BIH database, a 95.2% overall accuracy is obtained by detecting 15 types of heartbeats using DL-CCANet. On the INCART database, overall accuracies of 94.01% (II and V1 leads), 93.90% (V1 and V5 leads) and 94.07% (II and V5 leads) are achieved by detecting seven types of heartbeat using DL-CCANet, while TL-CCANet yields a higher overall accuracy of 95.52% using the above three leads. In addition, all of the above experiments are implemented using noisy ECG data. The proposed methods have potential to be applied in the clinic and mobile devices.

Grid Generation for CFD Analysis and Design of a Variety of Twin Screw Machines

A detailed study of the fluid flow and thermodynamic processes in positive displacement machines requires 3D CFD modeling in order to capture their real geometry, including leakage gaps. However, limitations in the conventional computational grids, used in commercial software packages, exclude their use for classical twin screw machines. The screw compressor rotor grid generator (SCORG) is a customized grid generation tool developed to overcome these limitations. This paper shows how it can be further extended to include non-conventional rotor designs, such as those with variable lead or profile variation and even internally geared machines with conical rotors. Other arrangements possible with this improvement include multiple gate rotors to increase volumetric displacement or dual lead, high wrap angle rotors for very high-pressure differences and vacuum applications. A case study of a water-injected twin screw compressor is included to demonstrate its use for both detailed flow analysis and design.