A Fully Implantable Miniaturized Liquid Crystal Polymer (LCP)-Based Spinal Cord Stimulator for Pain Control

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.

Profibrillatory Structural and Functional Properties of the Atrial-Pulmonary Junction in the Absence of Remodeling

Background: Sole pulmonary vein (PV) isolation by ablation therapy prevents atrial fibrillation (AF) in patients with short episodes of AF and without comorbidities. Since incomplete PV isolation can be curative, we tested the hypothesis that the PV in the absence of remodeling and comorbidities contains structural and functional properties that are proarrhythmic for AF initiation by reentry.Methods: We performed percutaneous transvenous in vivo endocardial electrophysiological studies and quantitative histological analysis of PV from healthy sheep.Results: The proximal PV contained more myocytes than the distal PV and a higher percentage of collagen and fat tissue relative to myocytes than the left atrium. Local fractionated electrograms occurred in both the distal and proximal PVs, but a large local activation (>0.75 mV) was more often present in the proximal PV than in the distal PV (86 vs. 50% of electrograms, respectively, p = 0.017). Atrial arrhythmias (run of premature atrial complexes) occurred more often following the premature stimulation in the proximal PV than in the distal PV (p = 0.004). The diastolic stimulation threshold was higher in the proximal PV than in the distal PV (0.7 [0.3] vs. 0.4 [0.2] mA, (median [interquartile range]), p = 0.004). The refractory period was shorter in the proximal PV than in the distal PV (170 [50] vs. 248 [52] ms, p < 0.001). A linear relation existed between the gradient in refractoriness (distal-proximal) and atrial arrhythmia inducibility in the proximal PV.Conclusion: The structural and functional properties of the native atrial-PV junction differ from those of the distal PV. Atrial arrhythmias in the absence of arrhythmia-induced remodeling are caused by reentry in the atrial-PV junction. Ablative treatment of early paroxysmal AF, rather than complete isolation of focal arrhythmia, may be limited to inhibition of reentry.

Localized Pulmonary Vein Scar Promotes Atrial Fibrillation in High Left Atrial Pressure

BackgroundPulmonary vein (PV) ablation is unsuccessful in atrial fibrillation (AF) patients with high left atrial (LA) pressure. Increased atrial stretch by increased pressure is proarrhythmic for AF, and myocardial scar alters wall deformation. We hypothesized that localized PV scar is proarrhythmic for AF in high LA pressure.MethodsRadiofrequency energy was delivered locally in the right PV of healthy sheep. The sheep recovered for 4 months. Explanted hearts (n = 9 PV scar, n = 9 controls) were perfused with 1:4 blood:Tyrode’s solution in a four-chamber working heart setup. Programmed PV stimulation was performed during low (∼12 mmHg) and high (∼25 mmHg) LA pressure. An AF inducibility index was calculated based on the number of induction attempts and the number of attempts causing AF (run of ≥ 20 premature atrial complexes).ResultsIn high LA pressure, the presence of PV scar increased the AF inducibility index compared with control hearts (0.83 ± 0.20 vs. 0.38 ± 0.40 arb. unit, respectively, p = 0.014). The diastolic stimulation threshold in high LA pressure was higher (108 ± 23 vs. 77 ± 16 mA, respectively, p = 0.006), and its heterogeneity was increased in hearts with PV scar compared with controls. In high LA pressure, the refractory period was shorter in PV scar than in control hearts (178 ± 39 vs. 235 ± 48 ms, p = 0.011).ConclusionLocalized PV scar only in combination with increased LA pressure facilitated the inducibility of AF. This was associated with changes in tissue excitability remote from the PV scar. Localized PV ablation is potentially proarrhythmic in patients with increased LA pressure.

Retrospective Study of Nerve Injury and Pedicle Screw Breach after Pedicle Screw Fixation with Intraoperative Triggered Electromyography Monitoring

Objective: To evaluate the incidence of nerve injury and pedicle breach after pedicle screw fixation (PSF) with intraoperative triggered electromyography (tEMG) monitoring.Material and Methods: All patients who underwent PSF with intraoperative tEMG at Vajira Hospital between October 2018 and March 2020 were included. Patients with dysmorphic pedicle features, preoperative infection, or incomplete follow-up data were excluded. PSF was done with intraoperative tEMG. The stimulation threshold was recorded. Stimulation threshold <7 mA was not allowed to proceed with the procedure and required reposition of pedicle screw immediately. Post-operative nerve injury was evaluated by physical examination and computer tomography of the spine was done to detect any pedicle breaches. The sensitivity and specificity of intraoperative tEMG to detect pedicle breach were calculated. The risk factors associated with pedicle breach were analyzed.Results: The records of thirty-six patients with 278 pedicle screws were analyzed. No post-operative nerve injuries were found. The incidence of pedicle breach was 2.2%. The sensitivity and specificity were 83.0% and 91.0%, respectively. The risk factors associated with pedicle breach were degenerative disease and tumor(s) (odds ratio (OR) 3.05, 95% confidence interval (CI) 1.11-8.41, p-value=0.030) and stimulation threshold 7-10 mA (OR 0.02, 95% CI 0.00-0.19, p-value< 0.001). Conclusion: PSF with intraoperative tEMG was safe for neural integrity. Intraoperative tEMG had the ability to detect pedicle breaches with fair sensitivity and high specificity. Patients with degenerative disease, tumors, or stimulation threshold less than 11 mA had a higher risk of pedicle breach.

The Relationship Between Stimulation Current and Functional Site Localization During Brain Mapping

BACKGROUND Gliomas are often in close proximity to functional regions of the brain; therefore, electrocortical stimulation (ECS) mapping is a common technique utilized during glioma resection to identify functional areas. Stimulation-induced seizure (SIS) remains the most common reason for aborted procedures. Few studies have focused on oncological factors impacting cortical stimulation thresholds. OBJECTIVE To examine oncological factors thought to impact stimulation threshold in order to understand whether a linear relationship exists between stimulation current and number of functional cortical sites identified. METHODS We retrospectively reviewed single-institution prospectively collected brain mapping data of patients with dominant hemisphere gliomas. Comparisons of stimulation threshold were made using t-tests and ANOVAs. Associations between oncologic factors and stimulation threshold were made using multivariate regressions. The association between stimulation current and number of positive sites was made using a Poisson model. RESULTS Of the 586 patients included in the study, SIS occurred in 3.92% and the rate of SIS events differed by cortical location (frontal 8.5%, insular 1.6%, parietal 1.3%, and temporal 2.8%; P = .009). Stimulation current was lower when mapping frontal cortex (P = .002). Stimulation current was not associated with tumor plus peritumor edema volume, world health organization) (WHO grade, histology, or isocitrate dehydrogenase (IDH) mutation status but was associated with tumor volume within the frontal lobe (P = .018). Stimulation current was not associated with number of positive sites identified during ECS mapping (P = .118). CONCLUSION SISs are rare but serious events during ECS mapping. SISs are most common when mapping the frontal lobe. Greater stimulation current is not associated with the identification of more cortical functional sites during glioma surgery.