Characterization of the electrical properties of mammalian peripheral nerve laminae.

BACKGROUND AND OBJECTIVE: The intrinsic electrical material properties of the laminar components of the mammalian peripheral nerve bundle are important parameters necessary for the accurate simulation of the electrical interaction between nerve fibers and neural interfaces. Improvements in the accuracy of these parameters improve the realism of the simulation and enables realistic screening of novel devices used for extracellular recording and stimulation of mammalian peripheral nerves. This work aims to characterize these properties for mammalian peripheral nerves to build upon the resistive parameter set established by Weerasuriya et al. in 1984 for amphibian somatic peripheral nerves (frog sciatic nerve) that is currently used ubiquitously in the in-silico peripheral nerve modeling community. METHODS: A custom designed characterization chamber was implemented and used to measure the radial and longitudinal impedance between 10 mHz and 50 kHz of freshly excised canine vagus nerves using four-point impedance spectroscopy. The impedance spectra were parametrically fitted to an equivalent circuit model to decompose and estimate the components of the various laminae. Histological sections of the electrically characterized nerves were then made to quantify the geometry and laminae thicknesses of the perineurium and epineurium. These measured values were then used to calculate the estimated intrinsic electrical properties, resistivity and permittivity, from the decomposed resistances and reactances. Finally, the estimated intrinsic electrical properties were used in a finite element method (FEM) model of the nerve characterization setup to evaluate the realism of the model. RESULTS: The geometric measurements were as follows: nerve bundle (1.6 ± 0.6 mm), major nerve fascicle diameter (1.3 ± 0.23 mm), and perineurium thickness (13.8 ± 2.1 µm). The longitudinal resistivity of the endoneurium was estimated to be 0.97 ± 0.05 Ωm. The relative permittivity and resistivity of the perineurium were estimated to be 2018 ± 391 and 3.75 kΩm ± 981 Ωm, respectively. The relative permittivity and resistivity of the epineurium were found to be 9.4 × 106 ± 8.2 × 106 and 55.0 ± 24.4 Ωm, respectively. The root mean squared (RMS) error of the experimentally obtained values when used in the equivalent circuit model to determine goodness of fit against the measured impedance spectra was found to be 13.0 ± 10.7 Ω, 2.4° ± 1.3°. The corner frequency of the perineurium and epineurium were found to be 2.6 ± 1.0 kHz and 368.5 ± 761.9 Hz, respectively. A comparison between the FEM model in-silico impedance experiment against the ex-vivo methods had a RMS error of 159.0 ± 95.4 Ω, 20.7° ± 9.8°. CONCLUSION: Although the resistive values measured in the mammalian nerve are similar to those of the amphibian model, the relative permittivity of the laminae bring new information about the reactance and the corner frequency (frequency at peak reactance) of the peripheral nerve. The measured and estimated corner frequency are well within the range of most bioelectric signals, and are important to take into account when modeling the nerve and neural interfaces.

Durable scalable 3D SLA-printed cuff electrodes with high performance carbon + PEDOT:PSS-based contacts.

BACKGROUND: The stimulation and recording performance of implanted neural interfaces are functions of the physical and electrical characteristics of the neural interface, its electrode material and structure. Therefore, rapid optimization of such characteristics is becoming critical in most clinical and research studies. This paper describes the development of an upgraded 3D printed cuff electrode shell design containing a novel intrinsically conductive polymer (ICP) for stimulation and recording of peripheral nerve fibers. METHODS: A 3D stereolithography (SLA) printer was used to print a scalable, custom designed, C-cuff electrode and I-beam closure for accurate, rapid implementation. A novel contact consisting of a percolated carbon graphite base electrodeposited with an intrinsically conductive polymer (ICP), poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) produced a PEDOT:PSS + carbon black (CB) matrix that was used to form the electrochemical interface on the structure. Prototype device performance was tested both in-vitro and in-vivo for electrical chemical capacity, electrochemical interfacial impedance, surgical handling, and implantability. The in-vivo work was performed on the sciatic nerve of 25 anesthetized Sprague Dawley rats to demonstrate recording and stimulating ability. RESULTS: Prototypes of different spatial geometries and number of contacts (bipolar, tripolar, and tetrapolar) were designed. The design was successfully printed with inner diameters down to 500 µm. Standard bipolar and tripolar cuffs, with a 1.3 mm inner diameter (ID), 0.5 mm contact width, 1.0 mm pitch, and a 1.5 mm end distance were used for the functional tests. This geometry was appropriate for placement on the rat sciatic nerve and enabled in-vivo testing in anesthetized rats. The contacts on the standard bipolar electrode had an area of 2.1 × 10-2  cm2 . Cyclic voltammetry on ICP coated and uncoated graphite contacts showed that the ICP increased the average charge storage capacity (CSC) by a factor of 30. The corresponding impedance at 1 Hz was slightly above 1 kΩ, a 99.99% decrease from 100 kΩ in the uncoated state. The statistical comparison of the pre- versus post-stimulation impedance measurements were not significantly different (p-value > 0.05). CONCLUSIONS: The new cuff electrode enables rapid development of cost-effective functional stimulation devices targeting nerve bundles less than 1.0 mm in diameter. This allows for recording and modulation of a low-frequency current targeted within the peripheral nervous system.

In vivo peripheral nerve activation using sinusoidal low-frequency alternating currents.

BACKGROUND: The sinusoidal low-frequency alternating current (LFAC) waveform was explored recently as a novel means to evoke nerve conduction block. In the present work, we explored whether increasing the amplitude of the LFAC waveform results in nerve fiber activation in autonomic nerves. In-silico methods and preliminary work in somatic nerves indicated a potential frequency dependency on the threshold of activation. The Hering-Breuer (HB) reflex was used as a biomarker to detect cervical vagus nerve activation. METHODS: Experiments were conducted in isoflurane-anesthetized swine (n = 5). Two stimulating bipolar cuff electrodes and a tripolar recording cuff electrode were implanted on the left vagus nerve. To ensure the electrical stimulation affects only the afferent pathways, the nerve was crushed caudal to the electrodes to eliminate cardiac effects. (1) Standard pulse stimulation (Vstim) using a monophasic train of pulses was applied through the caudal electrode to elicit HB reflex and to identify the activated nerve fiber type. (2) Continuous sinusoidal LFAC waveform with a frequency ranging from 5 through 20 Hz was applied to the rostral electrode without Vstim to explore the activation thresholds at each LFAC frequency. In both cases, the activation of nerve fibers was detected by a HB reflex-induced reduction in the breathing rate. RESULTS: LFAC was found to be capable of eliciting an HB response. The LFAC activation thresholds were found to be frequency-dependent. The HB threshold was 1.02 ± 0.3 mAp at 5 Hz, 0.66 ± 0.3 mAp at 10 Hz, and 0.44 ± 0.2 mAp at 20 Hz. In comparison, it was 0.7 ± 0.47 mA for a 100 µs pulse. The LFAC amplitude was within the linear limits of the electrode interface. Damage to the cuff electrodes or the nerve tissues was not observed. Analysis of Vstim-based compound nerve action potentials (CNAP) indicated that the decrease in breathing rate was found to be correlated with the activation of slower components of the CNAP suggesting that LFAC reached and elicited responses from these slower fibers associated with afferents projecting to the HB response. CONCLUSIONS: These results suggest the feasibility of the LFAC waveform at 5, 10, and 20 Hz to activate autonomic nerve fibers and potentially provide a new modality to the neurorehabilitation field.

High Aspect Ratio Structuring of Glass with Ultrafast Bessel Beams.

Controlling the formation of high aspect ratio void channels inside glass is important for applications like the high-speed dicing of glass. Here, we investigate void formation using ultrafast Bessel beams in the single shot illumination regime. We characterize the morphology of the damages as a function of pulse energy, pulse duration, and position of the beam inside fused silica, Corning Eagle XG, and Corning Gorilla glass. While a large set of parameters allow for void formation inside fused silica, the operating window is much more restricted for Eagle XG and Gorilla glass. The transient formation of a molten layer around voids enables us interpreting the evolution of the morphology with pulse energy and duration.

Postoperative Pain Is Driven by Preoperative Pain, Not by Endometriosis.

(1) Background: The aim of this study was to evaluate the impact of endometriosis on postoperative pain following laparoscopic hysterectomy; (2) Methods: A total of 214 women who underwent a laparoscopic hysterectomy between January 2013 and October 2017 were divided into four subgroups as follows: (1) endometriosis with chronic pain before the surgery (n = 57); (2) pain-free endometriosis (n = 50); (3) pain before the surgery without endometriosis (n = 40); (4) absence of both preoperative pain and endometriosis (n = 67). Postoperative pain was compared by using Visual Analog Scale (VAS) scores and by tracking the use of painkillers during the day of surgery and the first two postoperative days; (3) Results: Women with chronic pain before the surgery reported higher VAS scores during the first postoperative days, while the use of analgesics was similar across the groups. There was no difference in the postoperative pain when comparing endometriosis patients to non-endometriosis patients; (4) Conclusions: Women with chronic pelvic pain demonstrated increased postoperative pain after laparoscopic hysterectomy, which was independent of the presence or severity of endometriosis. The increased VAS scores did not, however, translate into equally greater use of painkillers, possibly due to the standardised protocols of analgesia in the immediate postoperative period. These findings support the need for careful postsurgical pain management in patients with pain identified as an indication for hysterectomy, independent of the extent of the surgery or underlying diagnosis.

In-vivo application of low frequency alternating currents on porcine cervical vagus nerve evokes reversible nerve conduction block.

BACKGROUND: This paper describes a method to reversibly block nerve conduction through direct application of a 1 Hz sinusoidal current waveform delivered through a bipolar nerve cuff electrode. This low frequency alternating current (LFAC) waveform was previously shown to reversibly block the effects of vagal pulse stimulation evoked bradycardia in-vivo in the anaesthetised rat model (Mintch et al. 2019). The present work measured the effectiveness of LFAC block on larger caliber myelinated vagal afferent fibers in human sized nerve bundles projecting to changes in breathing rate mediated by the Hering-Breuer (HB) reflex in anaesthetized domestic swine (n=5). METHODS: Two bipolar cuff electrodes were implanted unilaterally to the left cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar recording cuff electrode was placed rostral to the bipolar stimulating electrodes on the same nerve to measure changes in the compound nerve action potentials (CNAP) elicited by the vagal pulse stimulation and conditioned by the LFAC waveform. Standard pulse stimulation was applied at a sufficient level to induce a reduction in breathing rate through the HB reflex. If unblocked, the HB reflex would cause breathing to slow down and potentially halt completely. Block was quantified by the ability of LFAC to reduce the effect of the HB reflex by monitoring the respiration rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone. RESULTS: LFAC achieved 87.2 ±8.8% block (n=5) at current levels of 1.1 ±0.3 mAp (current to peak), which was well within the water window of the working electrode. CNAP showed changes that directly correlated to the effectiveness of LFAC block, which manifested itself as the slowing and amplitude reduction of components of the CNAP. CONCLUSION: These novel findings suggest that LFAC is a potential alternative or complementary method to other electrical blocking techniques in clinical applications.

Does the Number of Levels Fused Affect Spinopelvic Parameters and Clinical Outcomes Following Posterolateral Lumbar Fusion for Low-Grade Spondylolisthesis?

STUDY DESIGN: Retrospective cohort. OBJECTIVES: To determine how the number of fused intervertebral levels affects radiographic parameters and clinical outcomes in patients undergoing open posterolateral lumbar fusion (PLF) for low-grade degenerative spondylolisthesis. METHODS: This was a retrospective cohort study on patients who underwent open PLF for low-grade spondylolisthesis at a single institution from 2011 to 2018. Patients were divided into groups based on number of levels fused during their procedure (1, 2, or 3 or more). Preoperative and postoperative spinopelvic radiographic parameters, patient-reported outcomes (Visual Analog Scale [VAS]-back, VAS-leg, Oswestry Disability Index [ODI]), and postoperative complications were compared. RESULTS: Of the 316 patients eligible (203 one-level, 95 two-level, 18 three or more levels), change in initial postoperative to final pelvic incidence-lumbar lordosis was greatest in 2-level fusions (P = .039), while 3 or more level fusions had worse final pelvic tilt measures (P = .021). In addition, multilevel fusions had worse final VAS-back scores (2-level: P = .015; 3 or more levels: P = .011), higher rates of dural tears (2-level: P = .001), reoperation (2-level: P = .039), and discharge to facility (3 or more levels: P = .047) when compared with 1-level fusions. CONCLUSIONS: Patients in multilevel fusions experienced less improvement in back pain, had more complications, and were more commonly discharged to a facility compared with single-level PLF patients. These findings are important for operative planning, for setting appropriate preoperative expectations, and for risk stratification in patients undergoing posterior lumbar fusion for low-grade spondylolisthesis.

Does increasing age impact clinical and radiographic outcomes following lumbar spinal fusion?

BACKGROUND CONTEXT: Despite the growing senior population within the United States, there is a lack of consensus regarding the safety and efficacy of performing lumbar spinal fusion for this population. PURPOSE: To evaluate the clinical and radiographic outcomes in different age cohorts following lumbar spinal fusion. STUDY DESIGN: Retrospective cohort analysis. PATIENT SAMPLE: Analysis of 1,184 patients who underwent posterolateral lumbar fusion from 2011 to 2018. Surgery was indicated after failure of conservative treatment to address radiculopathy and/or neurogenic claudication. Patients were excluded if they were under 18 years of age at the time of surgery, had a lumbar fracture, tumor, or infection, or had fusions involving the thoracic spine, high-grade spondylolisthesis, or concomitant deformity. Of the 1,184 patients, 850 patients were included. Patients were divided into three roughly equal groups for analysis: young (18-54 years), middle-aged (55-69 years), and senior (≥70 years). OUTCOME MEASURES: Visual Analog Scale Back/Leg pain, and Oswestry Disability Index (ODI) were collected, and achievement of minimal clinically important difference was evaluated. Lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), and PI-LL difference were measured on radiographs. Rates of postoperative complications were analyzed. METHODS: Several radiographic parameters were measured using plain radiographs obtained at preoperative, immediately postoperative (standing radiographs performed on postoperative day 1), and most recent follow-up visits. Preoperative and final patient-reported outcomes, along with demographic information, were obtained all patients. Binary outcome variables were compared between groups with multivariate logistic regression, and continuous outcome variables were compared using multivariate linear regression, with age 18 to 54 years used as the reference. Multivariate regressions were used to compare outcomes between cohorts while controlling baseline characteristics. RESULTS: A total of 850 patients were included; 330 young (38.80%), 317 middle-aged (37.30%), and 203 senior (23.90%). Seniors had higher postoperative length of stay compared to younger patients (p<.001). Younger patients had worse final ODI scores compared to middle-aged patients (p=.002). Seniors had higher rates of proximal ASD (p=.002) compared to young patients. There was no difference in achievement of minimal clinically important differences (MCID) between all three groups. CONCLUSIONS: Senior patients have significant improvement in patient-reported clinical outcomes, despite having greater comorbidities, and longer length of stay. However, given a general lack of achievement of MCID across all cohorts, these findings suggest the need for a critical re-evaluation of the role of lumbar spinal fusion in the management of patients with refractory radiculopathic and/or neurogenic claudication symptoms.

A case report of several intraoperative convulsions while using the Narcotrend monitor: Significance and predictive use.

INTRODUCTION: Intraoperative seizures under general anesthesia are rare and our observation is the first to demonstrate a distinct electroencephalogram (EEG) pattern on the Narcotrend monitor. PATIENT CONCERNS: We present the case of a 30-year-old man undergoing craniotomy for glioblastoma resection under general anesthesia who suffered tonic-clonic seizures captured in a specific pattern by the intraoperative EEG. DIAGNOSES: Our depth of anesthesia monitor recorded, before the seizure, a widening of the beta-wave performance in a distinct "triangular-shaped" pattern. This pattern was repeated before the second seizure. The patient had no previous history of seizures and following surgery no further seizures were recorded. INTERVENTIONS: A spectrogram analysis showed a distinct increase in mean absolute beta power immediately prior to the first seizure. The EEG immediately prior to the second seizure was characterized by broadband noise. Both seizures were characterized by increased mean absolute delta, theta, and beta power. OUTCOMES: The increase in EEG beta activity seen before the tonic-clonic movements may represent cortical irritability secondary to surgical manipulation, induced by electrical stimulation, reflecting progressive brain over-arousal. The attentive analysis of the relative beta power may have helped forecast the occurrence of the second seizure. LESSONS: We report the use of a simple, inexpensive, and portable EEG-based monitoring device to assist seizure detection and decision making.

Implementation and Evaluation of a Web-Based Distribution System For Anesthesia Department Guidelines and Standard Operating Procedures: Qualitative Study and Content Analysis.

BACKGROUND: Digitization is spreading exponentially in medical care, with improved availability of electronic devices. Guidelines and standard operating procedures (SOPs) form an important part of daily clinical routine, and adherence is associated with improved outcomes. OBJECTIVE: This study aimed to evaluate a digital solution for the maintenance and distribution of SOPs and guidelines in 2 different anesthesiology departments in Switzerland. METHODS: A content management system (CMS), WordPress, was set up in 2 tertiary-level hospitals within 1 year: the Department of Anesthesiology and Pain Medicine at the Kantonsspital Lucerne in Lucerne, Switzerland, as an open-access system, followed by a similar system for internal usage in the Department of Anaesthesiology and Pain Medicine of the Inselspital, Bern University Hospital, in Bern, Switzerland. We analyzed the requirements and implementation processes needed to successfully set up these systems, and we evaluated the systems' impact by analyzing content and usage. RESULTS: The systems' generated exportable metadata, such as traffic and content. Analysis of the exported metadata showed that the Lucerne website had 269 pages managed by 44 users, with 88,124 visits per month (worldwide access possible), and the Bern website had 341 pages managed by 35 users, with 1765 visits per month (access only possible from within the institution). Creation of an open-access system resulted in third-party interest in the published guidelines and SOPs. The implementation process can be performed over the course of 1 year and setup and maintenance costs are low. CONCLUSIONS: A CMS, such as WordPress, is a suitable solution for distributing and managing guidelines and SOPs. Content is easily accessible and is accessed frequently. Metadata from the system allow live monitoring of usage and suggest that the system be accepted and appreciated by the users. In the future, Web-based solutions could be an important tool to handle guidelines and SOPs, but further studies are needed to assess the effect of these systems.

Real and virtual propagation dynamics of angular accelerating white light beams.

Accelerating waves have received significant attention of late, first in the optical domain and later in the form of electron matter waves, and have found numerous applications in non-linear optics, material processing, microscopy, particle manipulation and laser plasma interactions. Here we create angular accelerating light beams with a potentially unlimited acceleration rate. By employing wavelength independent digital holograms for the creation and propagation of white light beams, we are able to study the resulting propagation in real and virtual space. We find that dephasing occurs for real propagation and that this can be compensated for in a virtual propagation scheme when single plane dynamics are important. Our work offers new insights into the propagation dynamics of such beams and provides a versatile tool for further investigations into propagating structured light fields.

Generalized radially self-accelerating helicon beams.

We report, in theory and experiment, on a new class of optical beams that are radially self-accelerating and nondiffracting. These beams continuously evolve on spiraling trajectories while maintaining their amplitude and phase distribution in their rotating rest frame. We provide a detailed insight into the theoretical origin and characteristics of radial self-acceleration and prove our findings experimentally. As radially self-accelerating beams are nonparaxial and a solution to the full scalar Helmholtz equation, they can be implemented in many linear wave systems beyond optics, from acoustic and elastic waves to surface waves in fluids and soft matter. Our work generalized the study of classical helicon beams to a complete set of solutions for rotating complex fields.

Impact of arrhythmias on health-related quality of life in adults with congenital cardiac disease.

BACKGROUND: Health-related quality of life in adults with congenital cardiac disease appears to be impaired, but the determinants of this alteration remain largely unknown. The aim of our study was to examine the impact of arrhythmias on quality of life in patients late after the atrial redirection operation for transposition, or after complete correction of tetralogy of Fallot. PATIENTS AND METHODS: We enrolled 32 patients with transposition, and 35 patients with tetralogy of Fallot, in a prospective study. Quality of life was assessed using RAND-36 questionnaires. Quality of life data were compared with those of an age-matched control population. Patients underwent 24-hour and 7-day electrocardiographic recordings, echocardiography, and exercise testing. RESULTS: Patients without arrhythmias had quality of life comparable to that of the general population. All 8 domains in the questionnaire showed scores 22 to 51 percent lower in 12 patients with atrial tachyarrhythmias, and/or sinus nodal dysfunction, requiring insertion of a pacemaker in comparison with 55 patients without arrhythmias. In patients with transposition, low scores were not only associated with arrhythmias, but also correlated with impaired exercise capacity. CONCLUSIONS: Atrial tachyarrhythmias, and sinus nodal dysfunction, requiring insertion of a pacemaker, were associated with impaired quality of life in adults late after atrial surgical correction of transposition or correction of tetralogy of Fallot.

Effect of mild endurance exercise training and pravastatin on peripheral vasodilatation of forearm resistance vessels in patients with coronary artery disease.

BACKGROUND: Improved endothelial function may contribute to the beneficial effects of cholesterol lowering therapy in patients with coronary artery disease (CAD), but results of the effect of statin therapy on endothelial function are disparate in these patients. Exercise training has been reported to improve endothelial function of patients at risk of or with established CAD. The goal of the study was to compare the effect of mild exercise training or statin therapy on forearm endothelial function in CAD patients with average cholesterol levels. DESIGN AND METHODS: Twenty-eight sedentary male patients with angiographically documented CAD and average pretreatment total plasma cholesterol levels (5.1+/-0.9 mmol/l) aged 42-75 years were included. They were randomly assigned in a 2 : 1 order to either statin therapy (pravastatin, 40 mg daily) or exercise training therapy (mild endurance exercise three or more times a week). The effects of 10 weeks of either treatment on endothelium-dependent and independent vasodilation of forearm resistance vessels was assessed by plethysmography. Cardiopulmonary exercise testing was performed at baseline and after 10 weeks. RESULTS: Ten weeks of pravastatin therapy significantly reduced low-density lipoprotein cholesterol (from 3.8+/-0.6 to 3.1+/-0.6 mmol/l at study end, P=0.04) and the ratio of total to high-density lipoprotein cholesterol (from 4.9+/-0.8 to 3.7+/-0.7 mmol/l, P=0.002). Exercise training did not significantly modify the lipid profile. Peak oxygen consumption, maximal achieved workload and exercise duration tended to improve in the exercise training group but remained unchanged in the pravastatin-treated group. Neither 10 weeks of pravastatin nor mild endurance exercise training improved endothelium-dependent or independent vasomotor function in forearm resistance vessels. CONCLUSIONS: In patients with CAD and average cholesterol levels, 10 weeks of treatment with mild endurance exercise training or with pravastatin failed to improve endothelium-dependent or independent vasomotor function in forearm resistance vessels.