Reversible Conduction Block Research Articles

Detection of anti-ganglioside antibodies in Guillain-Barré syndrome.

Gangliosides are a class of glycosphingolipid molecules that are highly enriched in cellular membranes of the nervous system. The gangliosides associated with autoimmune diseases of the nervous system are mainly GM1, GD1a, GalNAc-GD1a, GM1b, GD3, CD1b, GT1a, and GQ1b. Multiple antibodies recognizing gangliosides are associated with some acute or chronic peripheral neuropathies, especially Guillain-Barré syndrome (GBS) and its clinical variants. Antibodies binding to gangliosides can activate complement system and recruit macrophages on the axolemma at the nodes of Ranvier of motor fibers, which are found in the course of GBS, causing axonal degeneration and reversible conduction block or conduction failure. Testing of anti-gangliosides autoantibodies is helpful for diagnosis of autoimmune peripheral neuropathies or support the diagnosis of the subtypes. These anti-gangliosides antibodies are usually detected by several qualitative or quantitative methods, particularly enzyme-linked immunosorbent assay (ELISA) and immunodot assays, which have been commercialized or established in-house worldwide. Herein, we introduce the methods and clinical applications of these assays in the diagnosis of autoimmune peripheral neuropathies. Anti-gangliosides antibodies are diagnostic markers of GBS subtypes. We use GBS as an example to explain the role of anti-gangliosides antibodies in the pathogenesis and diagnostic classification of neuropathies.

Soft, bioresorbable coolers for reversible conduction block of peripheral nerves.

Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.

Evaluation of Activated Carbon and Platinum Black as High-Capacitance Materials for Platinum Electrodes

The application of direct current (DC) produces a rapid and reversible nerve conduction block. However, prolonged injection of charge through a smooth platinum electrode has been found to cause damage to nervous tissue. This damage can be mitigated by incorporating high-capacitance materials (HCM) (e.g., activated carbon or platinum black) into electrode designs. HCMs increase the storage charge capacity (i.e., “Q value”) of capacitive devices. However, consecutive use of these HCM electrodes degrades their surface. This paper evaluates activated carbon and platinum black (PtB) electrode designs in vitro to determine the design parameters which improve surface stability of the HCMs. Electrode designs with activated carbon and PtB concentrations were stressed using soak, bend and vibration testing to simulate destructive in vivo environments. A Q value decrease represented the decreased stability of the electrode–HCM interface. Soak test results supported the long-term Q value stabilization (mean = 44.3 days) of HCM electrodes, and both HCMs displayed unique Q value changes in response to soaking. HCM material choices, Carbon Ink volume, and application of Nafion™ affected an electrode’s ability to resist Q value degradation. These results will contribute to future developments of HCM electrodes designed for extended DC application for in vivo nerve conduction block.

ID:16031 Noninvasive Thermal Nerve Block of Occipital Nerves in Patients With Occipital Neuralgia

Occipital neuralgia is a painful condition where the occipital nerves are injured or inflamed. There is no cure; thermal- and cryo-ablative techniques are often used to block axonal conduction through nerve destruction. Zhang et al. (1) demonstrated a thermal nerve block protocol that enables reversible nerve conduction block at a safe 15°C room temperature by first warming the nerve to 45°C. (1) This reversible nerve block has therapeutic potential for conditions modulated by peripheral nerves. We present promising results from 14 subjects who have intractable pain from occipital neuralgia.

An open-label, single-arm trial of cryoneurolysis for improvements in pain, activities of daily living and quality of life in patients with symptomatic ankle osteoarthritis

ObjectiveCryoneurolysis, cold-induced reversible conduction block of peripheral nerves, is an effective treatment for reducing knee osteoarthritis (OA) symptoms and opioid use following knee arthroplasty. There are however, limited data concerning its use for ankle OA. Our aim was to assess clinically significant long-term symptomatic relief of ankle OA with cryoneurolysis. MethodThis single-center, open-label trial included participants aged >18 years with radiographic tibiotalar OA, unilateral ankle pain ≥5/10 on Numerical Rating Scale (NRS), and with no ankle surgery within 6-months of screening. Following ultrasound-guided cryoneurolysis of nerves in the participant's pain distribution (sural, saphenous, superficial and/or deep fibular nerves), outcomes were assessed at clinic visits (6, 12 and 24-weeks) and by telephone interview (3, 9, 18-weeks). The primary endpoint was change in Foot and Ankle Outcome Score (FAOS) (pain subscale) at 12-weeks. Change in quality of life (FAOS-QoL), activities of daily living (FAOS-ADL), NRS-pain, and physical performance measures were also assessed. Longitudinal mixed models were constructed to evaluate changes from baseline at 6, 12- and 24-weeks post-treatment. ResultsForty participants enrolled (50% female, mean ​± ​SD age 63.0 ​± ​12.8 years). At 12-weeks post treatment, FAOS-pain (20.8, p ​< ​0.0001), ADL (18.1, p ​= ​0.0003), QoL (19.9, p ​= ​0.0003) and NRS-pain (−2.6, p ​< ​0.0001) were significantly improved from baseline. No difference in 40-m fast-paced walking test was detected at 12-weeks post-treatment (−1.2sec, p ​= ​0.59). For all outcomes, similar findings were observed at 6- and 24-week visits. ConclusionCryoneurolysis resulted in statistically significant improvements in ankle pain, physical function and QoL for up to 24-weeks in participants with unilateral, symptomatic ankle OA.

B-AB03-01 DOSE-DEPENDENT TRANSIENT AV NODAL CONDUCTION BLOCK USING REVERSIBLE ELECTROPORATION

Membrane pores created with pulsed electrical fields (PF) can be reversible if delivered sub-threshold allowing for purposeful reversible electroporation (RE) of tissue. To evaluate the response of AV node to RE pulses in a preclinical model. Under general anesthesia, percutaneous femoral venous access was obtained in two swine. Abbreviated pulses were delivered to the AV node area using a 9mm lattice-tip catheter with varying PF waveforms using a custom mapping system and PF generator (Sphere-9, Prism-1, HexaPulse; Affera Inc, MA). RE pulses were delivered at either low-dose or high-dose. AV conduction was monitored following delivery. In sinus rhythm, a His potential was successfully recorded. A total of 9 low-dose and 7 high-dose RE pulses were delivered. Immediately following low-dose applications, PR prolongation (median 104 ms, IQR 10, 232ms) was observed in 7 of 9 applications (no change in 2 of 9); there was complete recovery to baseline in 6 of 7 within 4.7±3.7sec (the last 1 of 7 recovered to 10ms of baseline after 64 sec of observation). With high-dose RE, complete AV block occurred in 6 of 7 (PR prolongation in the remaining 1 of 7); there was complete recovery to baseline in 5 of 7 in 152±84 sec (the last 2 of 7 both recovered to within 30ms of baseline after 56 and 710 sec of observation, respectively). Pulsed electrical fields can be employed in a manner as to cause reversible conduction block of AV conduction in a dose-dependent manner. If reproduced clinically in other myocardial tissues, this introduces a potentially novel approach to interrogating arrhythmias.

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

BackgroundThis 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).MethodsTwo 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.ResultsLFAC 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.ConclusionThese novel findings suggest that LFAC is a potential alternative or complementary method to other electrical blocking techniques in clinical applications.

Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications.

Chronic pain is one of the leading causes of disability and disease burden worldwide, accounting for a prevalence between 6.9% and 10% in the general population. Pharmacotherapy alone results ineffective in about 70-60% of patients in terms of a satisfactory degree of pain relief. Focused ultrasound is a promising tool for chronic pain management, being approved for thalamotomy in chronic neuropathic pain and for bone metastases-related pain treatment. FUS is a noninvasive technique for neuromodulation and for tissue ablation that can be applied to several tissues. Transcranial FUS (tFUS) can lead to opposite biological effects, depending on stimulation parameters: from reversible neural activity facilitation or suppression (low-intensity, low-frequency ultrasound, LILFUS) to irreversible tissue ablation (high-intensity focused ultrasounds, HIFU). HIFU is approved for thalamotomy in neuropathic pain at the central nervous system level and for the treatment of facet joint osteoarthritis at the peripheral level. Potential applications include HIFU at the spinal cord level for selected cases of refractory chronic neuropathic pain, knee osteoarthritis, sacroiliac joint disease, intervertebral disc nucleolysis, phantom limb, and ablation of peripheral nerves. FUS at nonablative dosage, LILFUS, has potential reversible and tissue-selective effects. FUS applications at nonablative doses currently are at a research stage. The main potential applications include targeted drug and gene delivery through the Blood-Brain Barrier, assessment of pain thresholds and study of pain, and reversible peripheral nerve conduction block. The aim of the present review is to describe the approved and potential applications of the focused ultrasound technology in the field of chronic pain management.

Blocking peripheral drive from colorectal afferents by subkilohertz dorsal root ganglion stimulation.

Clinical evidence indicates dorsal root ganglion (DRG) stimulation effectively reduces pain without the need to evoke paresthesia. This paresthesia-free anesthesia by DRG stimulation can be promising to treat pain from the viscera, where paresthesia usually cannot be produced. Here, we explored the mechanisms and parameters for DRG stimulation using an ex vivo preparation with mouse distal colon and rectum (colorectum), pelvic nerve, L6 DRG, and dorsal root in continuity. We conducted single-fiber recordings from split dorsal root filaments and assessed the effect of DRG stimulation on afferent neural transmission. We determined the optimal stimulus pulse width by measuring the chronaxies of DRG stimulation to be below 216 µs, indicating spike initiation likely at attached axons rather than somata. Subkilohertz DRG stimulation significantly attenuates colorectal afferent transmission (10, 50, 100, 500, and 1000 Hz), of which 50 and 100 Hz show superior blocking effects. Synchronized spinal nerve and DRG stimulation reveals a progressive increase in conduction delay by DRG stimulation, suggesting activity-dependent slowing in blocked fibers. Afferents blocked by DRG stimulation show a greater increase in conduction delay than the unblocked counterparts. Midrange frequencies (50-500 Hz) are more efficient at blocking transmission than lower or higher frequencies. In addition, DRG stimulation at 50 and 100 Hz significantly attenuates in vivo visceromotor responses to noxious colorectal balloon distension. This reversible conduction block in C-type and Aδ-type afferents by subkilohertz DRG stimulation likely underlies the paresthesia-free anesthesia by DRG stimulation, thereby offering a promising new approach for managing chronic visceral pain.

High-Frequency Alternating Current Block Using Macro-Sieve Electrodes: A Pilot Study.

Background and objectiveHigh-frequency alternating current (HFAC) can yield a rapid-acting and reversible nerve conduction block. The present study aimed to demonstrate the successful implementation of HFAC block delivery via regenerative macro-sieve electrodes (MSEs).MethodsDual-electrode assemblies in two configurations [dual macro-sieve electrode-1 (DMSE-I), DMSE-II] were fabricated from pairs of MSEs and implanted in the transected and subsequently repaired sciatic nerves of two male Lewis rats. After four months of postoperative nerve regeneration through the MSEs' transit zones, the efficacy of acute HFAC block was tested for both configurations. Frequencies ranging from 10 kHz to 42 kHz, and stimulus amplitudes with peak-to-peak voltages ranging from 2 V to 20 V were tested. Evoked muscle force measurement was used to quantify the nerve conduction block.ResultsHFAC stimulation delivered via DMSE assemblies obtained a complete block at frequencies of 14 to 26 kHz and stimulus amplitudes of 12 to 20 V p-p. The threshold voltage for the complete block showed an approximately linear dependence on frequency. The threshold voltage for the partial conduction block was also approximately linear. For those frequencies that displayed both partial and complete block, the partial block thresholds were consistently lower.ConclusionThis study provides a proof of concept that regenerative MSEs can achieve complete and reversible conduction block via HFAC stimulation of regenerated nerve tissue. A chronically interfaced DMSE assembly may thereby facilitate the inactivation of targeted nerves in cases wherein pathologic neuronal hyperactivity is involved.

Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance

Reversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers that are blocked. Previous in vivo studies reported non-monotonic relationships between block signal frequency and block threshold, suggesting the potential for fiber-selective block. However, the mechanisms of non-monotonic block thresholds were unclear, and these findings were not replicated in a subsequent in vivo study. We used high-fidelity computational models and in vivo experiments in anesthetized rats to show that non-monotonic threshold-frequency relationships do occur, that they result from amplitude- and frequency-dependent charge imbalances that cause a shift between kilohertz frequency and direct current block regimes, and that these relationships can differ across fiber diameters such that smaller fibers can be blocked at lower thresholds than larger fibers. These results reconcile previous contradictory studies, clarify the mechanisms of interaction between kilohertz frequency and direct current block, and demonstrate the potential for selective block of small fiber diameters.

Sacral nerve stimulation for refractory OAB and idiopathic urinary retention: Can phenotyping improve the outcome for patients: ICI-RS 2019?

Sacral nerve stimulation (SNS) is widely used to treat refractory idiopathic overactive bladder (OAB) and idiopathic urinary retention. However, clinical outcomes are variable and understanding predictive factors for success or side-effects would enable personalization of therapy and optimization of outcomes. At the International Consultation on Incontinence-Research Society meeting 2019, a Think Tank was convened to discuss how advances in the basic science study of SNS may be translatable into clinical practice to improve outcomes of patients undergoing SNS treatment. We conducted a literature review and expert consensus meeting focusing on current methods of phenotyping patients and specifically, how advances in basic science research of the mechanism of action of SNS can be translated into clinical practice to improve patient selection for therapy. The terms "Idiopathic OAB" and "idiopathic urinary retention" encompass several underlying pathophysiological phenotypes. Commonly, phenotyping is based on clinical and urodynamic factors. Animal studies have demonstrated that high-frequency stimulation can produce rapid onset, reversible conduction block in peripheral nerves. Altering stimulation parameters may potentially enable personalization of therapy depending upon the clinical indication in the future. Similarly, advances in conditional and closed-loop stimulation may offer greater efficacy for certain patients. Phenotyping based on psychological comorbidity requires further study to potentially optimize patient selection for therapy. Idiopathic OAB and idiopathic urinary retention are heterogenous conditions with multiple potential underlying phenotypes. Tailoring stimulation parameters to the needs of each individual according to phenotype could optimize outcomes. Assessing psychological comorbidity may improve patient selection. Areas for further research are proposed.

Kilohertz waveforms optimized to produce closed-state Na+channel inactivation eliminate onset response in nerve conduction block.

The delivery of kilohertz frequency alternating current (KHFAC) generates rapid, controlled, and reversible conduction block in motor, sensory, and autonomic nerves, but causes transient activation of action potentials at the onset of the blocking current. We implemented a novel engineering optimization approach to design blocking waveforms that eliminated the onset response by moving voltage-gated Na+ channels (VGSCs) to closed-state inactivation (CSI) without first opening. We used computational models and particle swarm optimization (PSO) to design a charge-balanced 10 kHz biphasic current waveform that produced conduction block without onset firing in peripheral axons at specific locations and with specific diameters. The results indicate that it is possible to achieve onset-free KHFAC nerve block by causing CSI of VGSCs. Our novel approach for designing blocking waveforms and the resulting waveform may have utility in clinical applications of conduction block of peripheral nerve hyperactivity, for example in pain and spasticity.

Stabilization of Weakly Unstable Fixed Points as a Common Dynamical Mechanism of High-Frequency Electrical Stimulation

While high-frequency electrical stimulation often used to treat various biological diseases, it is generally difficult to understand its dynamical mechanisms of action. In this work, high-frequency electrical stimulation is considered in the context of neurological and cardiological systems. Despite inherent differences between these systems, results from both theory and computational modeling suggest identical dynamical mechanisms responsible for desirable qualitative changes in behavior in response to high-frequency stimuli. Specifically, desynchronization observed in a population of periodically firing neurons and reversible conduction block that occurs in cardiomyocytes both result from bifurcations engendered by stimulation that modifies the stability of unstable fixed points. Using a reduced order phase-amplitude modeling framework, this phenomenon is described in detail from a theoretical perspective. Results are consistent with and provide additional insight for previously published experimental observations. Also, it is found that sinusoidal input is energy-optimal for modifying the stability of weakly unstable fixed points using periodic stimulation.

High-Frequency Peripheral Nerve Stimulation for Craniofacial Pain.

Since the first successful use of high-frequency electrical stimulation of trigeminal branches for treatment of facial pain in 1962, neuromodulation techniques become well established but remain greatly underutilised. Most subsequent implantation techniques and commercial devices for peripheral nerve stimulation, available until the last decade, utilised frequencies in the range 1-100 Hz. With the commercial introduction of 10-kHz spinal cord stimulation, there has been renewed interest in peripheral applications of kHz frequency neuromodulation. High-frequency biphasic stimulation causes rapid onset, reversible conduction block in mammalian nerves which might be useful in human peripheral neuromodulation applications, but the conduction block induced at kilohertz frequencies may not be the only mechanism contributing to analgesia. We discuss likely mechanisms of action of high-frequency peripheral nerve stimulation and present several clinical examples of successful use of this modality in various facial pain conditions. A change to sub-threshold higher frequencies in the 10 kHz range adds a number of distinct advantages. The lack of paresthesias is welcomed by patients. The ability to place the stimulating electrode approximately 1 cm away from the targeted nerve has an anatomical and surgical advantage.

S43. Single vs serial nerve conduction study in Guillain Barré syndrome

Nerve conduction study (NCS) is the important diagnostic tool in Guillain Barré syndrome (GBS). Many electrodiagnostic criteria sets have been proposed to distinguish demyelinating from axonal pathology. Misclassification often occurs in early course of the disease. Moreover, timing and selection of the nerves are crucial. Repeated NCS may provide more definite diagnosis. Therefore, the aim of this study is to describe NCS results and their serial changes in specific nerves and related parameters. Retrospective and prospective review of medical records of GBS patients, who were 15 years of age or older, visited to Thammasat University Hospital and Bangkok Hospital Medical Center in Thailand between 1st January 2009 and 31st October 2017. Every patient had at least one nerve conduction study at the time of diagnosis and confirmed by the neuromuscular specialist or treating neurologist. Forty-four patients were recruited, 23 (52.3%) of these were female. The mean age at presentation was 49.2 years old. Most patients are Asian (59.1%) or European (15.9%). Antecedent infection mainly were upper respiratory tract and GI infection. The most common clinical diagnostic subtype was AIDP (63%). Other subtypes were AMAN (15.9%), MFS (11%), pharyngeal-cervical-brachial weakness (9%) and AMSAN (2%). Comparing the difference of demyelinating criteria sets revealed that Albers criteria showed the highest sensitivity (98%) to defined demyelinating pattern, whereas Cornblath criteria was the lowest (53%). On the other hand, Ho (94%) and Hadden (91%) criteria sets demonstrated indifferent diagnostic results. Initial NCS was abnormal in 34 of 44 patients (78%). Demyelinating pattern was found in 28 patients (64%), mixed axonal and demyelinating pattern in 6 patients (14%) and the rest was equivocal. Second NCS was performed in 20 patients and the classification was changed in 2 of 20 patients (10%), shifting from demyelinating to axonal subtypes in final NCS. This might reflect reversible conduction block in early axonal GBS. Demyelinating pattern was more prevalent in lower limbs (tibial and peroneal nerves) which were most defined by slow conduction velocity and conduction block. While in upper limb, median nerve was the most commonly affected, based on the conduction velocity, distal latency and temporal dispersion. Sural sparing pattern was common and it was present in 44 studies (80%) in AIDP according to Albers criteria. AIDP is the most common subtype of GBS in Thai tertiary care centers. Albers criteria is the most sensitive criteria, whereas Cornblath criteria is the lowest. Initial NCS reveals abnormality in 78% of patients while serial NCS demonstrates subtype change from demyelinating to axonal pattern in 10% of patients. Tibial and peroneal nerves are most frequently affected. Appropriate selection of the studied nerves and classification criteria, combined with serial NCS are important to identify accurate GBS subtypes.

A case of acute motor sensory axonal neuropathy presenting reversible conduction block

A case of acute motor sensory axonal neuropathy presenting reversible conduction block

Reversible conduction block in peripheral nerve using electrical waveforms.

Electrical nerve block uses electrical waveforms to block action potential propagation. Two key features that distinguish electrical nerve block from other nonelectrical means of nerve block: block occurs instantly, typically within 1 s; and block is fully and rapidly reversible (within seconds). Approaches for achieving electrical nerve block are reviewed, including kilohertz frequency alternating current and charge-balanced polarizing current. We conclude with a discussion of the future directions of electrical nerve block. Electrical nerve block is an emerging technique that has many significant advantages over other methods of nerve block. This field is still in its infancy, but a significant expansion in the clinical application of this technique is expected in the coming years.

AB097. Conduction block of mammalian myelinated nerve by local cooling to 15–30 °C after a brief heating

BackgroundThis study aimed at understanding thermal effects on nerve conduction and developing new methods to produce a reversible thermal block of axonal conduction in mammalian myelinated nerves.MethodsIn 13 cats, conduction block of pudendal nerves by cooling (5–30 °C) or heating (42–54 °C) a small segment of the nerve was monitored by the urethral striated muscle contractions and increases in intraurethral pressure induced by intermittent electrical stimulation of the nerve.ResultsCold block was observed at 5–15 °C while heat block occurred at 50–54 °C. Cold block was fully reversible, but only brief complete heat block was reversible. A brief reversible complete heat block at 50–54 °C significantly increased the cold block temperature to 15–30 °C.ConclusionsThis study discovered a novel method to block mammalian myelinated nerves at 15–30 °C, providing the possibility to develop an implantable device to block axonal conduction and treat many chronic diseases.

Kilohertz Electrical Stimulation Nerve Conduction Block: Effects of Electrode Surface Area.

Kilohertz electrical stimulation (KES) induces repeatable and reversible conduction block of nerve activity and is a potential therapeutic option for various diseases and disorders resulting from pathological or undesired neurological activity. However, successful translation of KES nerve block to clinical applications is stymied by many unknowns, such as the relevance of the onset response, acceptable levels of waveform contamination, and optimal electrode characteristics. We investigated the role of electrode geometric surface area on the KES nerve block threshold using 20- and 40-kHz current-controlled sinusoidal KES. Electrodes were electrochemically characterized and used to characterize typical KES waveforms and electrode charge characteristics. KES nerve block amplitudes, onset duration, and recovery of normal conduction after delivery of the KES were evaluated along with power requirements for effective KES nerve block. Results from this investigation demonstrate that increasing electrode geometric surface area provides for a more power-efficient KES nerve block. Reductions in block threshold by increased electrode surface area were found to be KES-frequency-dependent, with block thresholds and average power consumption reduced by greater than two times with 20-kHz KES waveforms and greater than three times for 40-kHz KES waveforms.