Closing the loop and raising the bar: Automated control systems in neuromodulation.

INTRODUCTION: Neuromodulation has emerged as a promising therapy for the management of chronic pain, movement disorders, and other neurological conditions. Spinal cord stimulation (SCS) is a widely used form of neuromodulation that involves the delivery of electrical impulses to the spinal cord to modulate the transmission of pain signals to the brain. In recent years, there has been increasing interest in the use of automation systems to improve the efficacy and safety of SCS. This narrative review summarizes the status of Food and Drug Administration-approved autonomous neuromodulation devices including closed loop, feedforward, and feedback systems. The review discusses the advantages and disadvantages of each system and focuses specifically on the use of these systems for SCS. It is important for clinicians to understand the expanding role of automation in neuromodulation in order to select appropriate therapies founded on automation systems to the specific needs of the patient and the underlying condition. CONCLUSION: The review also provides insights into the current state of the art in neuromodulation automation systems and discusses potential future directions for research in this field.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Occipital Nerve Stimulation for the Treatment of Patients With Medically Refractory Occipital Neuralgia: Update.

BACKGROUND: The Guidelines Task Force conducted a systematic review of the relevant literature on occipital nerve stimulation (ONS) for occipital neuralgia (ON) to update the original 2015 guidelines to ensure timeliness and accuracy for clinical practice. OBJECTIVE: To conduct a systematic review of the literature and update the evidence-based guidelines on ONS for ON. METHODS: The Guidelines Task Force conducted another systematic review of the relevant literature, using the same search terms and strategies used to search PubMed and Embase for relevant literature. The updated search included studies published between 1966 and January 2023. The same inclusion/exclusion criteria as the original guideline were also applied. Abstracts were reviewed, and relevant full text articles were retrieved and graded. Of 307 articles, 18 were retrieved for full-text review and analysis. Recommendations were updated according to new evidence yielded by this update . RESULTS: Nine studies were included in the original guideline, reporting the use of ONS as an effective treatment option for patients with medically refractory ON. An additional 6 studies were included in this update. All studies in the original guideline and this current update provide Class III evidence. CONCLUSION: Based on the availability of new literature, the current article is a minor update only that does not result in modification of the prior recommendations: Clinicians may use ONS as a treatment option for patients with medically refractory ON.

Closed-Loop Systems in Neuromodulation: Electrophysiology and Wearables.

Most currently available neuromodulation techniques for pain work through an open-loop system. The distance between the epidural space and the target of the stimulation in a dynamic body can change because of physiologic conditions. The closed-loop system in spinal cord neuromodulation consists of an integrated system that records real-time electrophysiological activity in the form of evoked compound action potentials and uses it in a feedback mechanism to adjust stimulus output. Wearables represent newly developed technologies that have gained traction in recent years. Their application in pain management is still developing but promising.

Neurophysiology during movement disorder surgery.

During stereotactic procedures for treating medically refractory movement disorders, intraoperative neurophysiology shifts its focus from simply monitoring the effects of surgery to an integral part of the surgical procedure. The small size, poor visualization, and physiologic nature of these deep brain targets compel the surgeon to rely on some form of physiologic for confirmation of proper anatomic targeting. Even given the newer reliance on imaging and asleep deep brain stimulator electrode placement, it is still a physiologic target and thus some form of intraoperative physiology is necessary. This chapter reviews the neurophysiologic monitoring method of microelectrode recording that is commonly employed during these neurosurgical procedures today.

Glossary of Neurostimulation Terminology: A Collaborative Neuromodulation Foundation, Institute of Neuromodulation, and International Neuromodulation Society Project.

OBJECTIVE: Consistent terminology is necessary to facilitate communication, but limited efforts have addressed this need in the neurostimulation community. We set out to provide a useful and updated glossary for our colleagues and prospective patients. MATERIALS AND METHODS: This collaborative effort of the Neuromodulation Foundation (NF), the Institute of Neuromodulation (IoN), and the International Neuromodulation Society (INS) expands a glossary first published in 2007 for spinal cord stimulation. Peripheral nerve, dorsal root ganglion, deep brain, and motor cortex stimulation have been added to our scope. Volunteers from the collaborating entities used a nominal group process, consensus development panels, and the Delphi technique to reach consensus on inclusion and definition of terms. We created a glossary suitable for print and for expansion on the websites of the collaborating entities, which will offer the possibility of explaining definitions for a general audience. We excluded proprietary and brand names but included terms that have attracted proprietary interest without becoming brands or trademarks. We made an effort to be inclusive while also being concise and economical with space. RESULTS: We identified and defined 91 terms for this print edition and created an accompanying list of acronyms. As appropriate, we provided figures to illustrate the definitions. CONCLUSIONS: Although we refer to the glossary presented herein as the print edition, it can of course be viewed and searched electronically. NF, IoN, and INS will continue to collaborate on expanded web editions that can include hyperlinks for internal and external navigation. We believe this glossary will benefit our growing field by facilitating communication and mitigating inappropriate use of neurostimulation terms.

Neurophysiologic Intraoperative Monitoring for Spine Surgery: A Practical Guide From Past to Present.

Intraoperative neuromonitoring was introduced in the second half of the 20th century with the goal of preventing patient morbidity for patients undergoing complex operations of the central and peripheral nervous system. Since its early use for scoliosis surgery, the growth and utilization of IOM techniques expanded dramatically over the past 50 years to include spinal tumor resection and evaluation of cerebral ischemia. The importance of IOM has been broadly acknowledged, and in 1989, the American Academy of Neurology (AAN) released a statement that the use of SSEPs should be standard-of-care during spine surgery. In 2012, both the AAN and the American Clinical Neurophysiology Society (ACNS) recommended that: "Intraoperative monitoring (IOM) using SSEPs and transcranial MEPs be established as an effective means of predicting an increased risk of adverse outcomes, such as paraparesis, paraplegia, and quadriplegia, in spinal surgery." With a multimodal approach that combines SSEPs, MEPs, and sEMG with tEMG and D waves, as appropriate, sensitivity and specificity can be maximized for the diagnosis of reversible insults to the spinal cord, nerve roots, and peripheral nerves. As with most patient safety efforts in the operating room, IOM requires contributions from and communication between a number of different teams. This comprehensive review of neuromonitoring techniques for surgery on the central and peripheral nervous system will highlight the technical, surgical and anesthesia factors required to optimize outcomes. In addition, this review will discuss important trouble shooting measures to be considered when managing ION changes concerning for potential injury.

Thirty-Day Outcomes From Standalone Minimally Invasive Surgery-Transforaminal Lumbar Interbody Fusion Patients in an Ambulatory Surgery Center vs. Hospital Setting.

Objectives We sought to evaluate differences in perioperative baseline characteristics, operative efficiency, and 30-day safety events for patients undergoing standalone minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF) in a hospital versus an ambulatory surgery center (ASC). Methods Patients were retrospectively identified and sequentially enrolled from the office records of a single, community neurosurgeon. Records for the first 50 qualifying patients in the hospital and ASC cohorts were retrieved. Variables collected included: baseline demographic and health status, operative safety (intra-op complications) and efficiency (operative time, fluoroscopy time, etc.), and 30-day post-operative safety (emergency room visits, re-admission, and re-operation). Results At baseline, hospital and ASC patients were equivalent in gender distribution, BMI, and pre-operative narcotic use. Statistically significant differences were found in age and comorbidity burden (ASA status and Charleson Comorbidity Index); p < 0.0001, p = 0.0039, and p < 0.001 respectively. The only significant difference in construct type between hospital and ASC patients was the proportion of one- versus two-level fusions; all two-level fusions were performed in the hospital group. There were no differences in operative time, need for transfusions, or iatrogenic complications. There were also no differences between the groups in 30-day events of ER visits, re-admission, re-operation, or post-operative narcotic refill use. The length of stay was significantly different between the ASC and hospital settings (p < 0.0001). Conclusions As expected, ASC patients were younger and relatively healthier compared to their hospital counterparts. Thirty-day safety events of ER visits, re-admission, re-operation, and narcotic refill utilization were representative of population norms. Patients with standalone, expandable MIS-TLIF underwent efficient operative procedures and experienced minimal 30-day complications independent of their operative status. ASC patients had the added benefit of significantly reduced length of stay over their hospital counterparts. Given the equivalency of the 30-day post-operative course for both patient cohorts, a substantial reduction in economic burden is likely for the ASC patients.

Fiber Threshold Accommodation as a Mechanism of Burst and High-Frequency Spinal Cord Stimulation.

OBJECTIVES: Burst and high-frequency spinal cord stimulation (SCS), in contrast to low-frequency stimulation (LFS, < 200 Hz), reduce neuropathic pain without the side effect of paresthesia, yet it is unknown whether these methods' mechanisms of action (MoA) overlap. We used empirically based computational models of fiber threshold accommodation to examine the three MoA. MATERIALS AND METHODS: Waveforms used in SCS are composed of cathodic, anodic, and rest phases. Empirical studies of human peripheral sensory nerve fibers show different accommodation effects occurring in each phase. Notably, larger diameter fibers accommodate more than smaller fibers. We augmented our computational axon model to replicate fiber threshold accommodation behavior for diameters from 5 to 15 µm in each phase. We used the model to predict threshold change in variations of burst, high frequency, and LFS. RESULTS: The accommodation model showed that 1) inversion of larger and smaller diameter fiber thresholds produce a therapeutic window in which smaller fibers fire while larger ones do not and 2) the anodic pulses increase accommodation and perpetuate threshold inversion from burst to burst and between cathodic pulses in burst, high frequency, and variations, resulting in an amplitude "window" in which larger fibers are inactivated while smaller fibers fire. No threshold inversion was found for traditional LFS. CONCLUSIONS: The model, based on empirical data, predicts that, at clinical amplitudes, burst and high-frequency SCS do not activate large-diameter fibers that produce paresthesia while driving medium-diameter fibers, likely different from LFS, which produce analgesia via different populations of dorsal horn neural circuits.

Safety and Efficacy of the VariLift-C® Cervical Standalone Interbody Fusion Device with Emphasis on Multiple-level and Prior Fusion Cases.

Introduction The VariLift-C® is a stand-alone, expandable, cervical interbody fusion device, not requiring the addition of anterior plating. Because of the access and placement technique, as well as not needing a plate, the device could potentially be used preferentially for patients with prior anterior fusions or for multiple, non-contiguous vertebral segments. Methods A retrospective chart review was conducted and all cases of anterior cervical discectomy and fusion (ACDF) using VariLift-C® implants by a single surgeon were included. Patient baseline and operative characteristics were collected, and their follow-up notes were searched for outcomes. Descriptive statistics are provided. Results Seventy-one patients were included in this study, 14 of which had had a prior fusion, and 32 underwent a multilevel ACDF. A total of 108 cervical levels were fused. Mean age (± SD) at surgery was 50.3 ± 11.4 years and mean (± SD) follow-up was 6.5 ± 10.7 months. There were 39 single-level, 27 two-level and five three-level fusions. Four cases (5.6%) underwent multilevel re-operations. Thirty-three patients (80.3%) reported substantial improvement in their symptoms on follow-up, 19 of whom (26.8%) had no residual symptoms. Only two patients (2.8%) reported a worsened condition after surgery. There were 10 cases (12.8%) of postoperative neurologic deficit, one case of dysphagia and three cases of vocal cord paresis. Conclusions These results display the use of VariLift-C® for symptomatic cervical degenerative disorders, with a focus on fusion extension or multiple-segment ACDF procedures. Our experience with favorable self-reported outcomes and low complication rates showcases the safety and efficacy of the VariLift-C® device for ACDF.

Factors influencing the presence of hemiparesis in chronic subdural hematoma.

OBJECTIVE: Chronic subdural hematoma (CSDH) has a variety of clinical presentations, including hemiparesis. Hemiparesis is of the utmost importance because it is one of the major indications for surgical intervention and influences outcome. In the current study, the authors intended to identify factors influencing the presence of hemiparesis in CSDH patients and to determine the threshold value of hematoma thickness and midline shift for development of hemiparesis. METHODS: The authors retrospectively reviewed 325 patients (266 with unilateral and 59 with bilateral hematomas) with CSDH who underwent surgical evacuation, regardless of presence or absence of hemiparesis. RESULTS: In univariate analysis, hematoma loculation, age, hematoma maximal thickness, and midline shift were significantly associated with hemiparesis. Moreover, patients with unilateral hematomas had a higher rate of hemiparesis than patients with bilateral hematomas. Sex, trauma history, anticoagulant and antiplatelet drug use, presence of comorbidities, Glasgow Coma Scale score, hematoma density characteristics on CT scan, and hematoma signal intensity on T1- and T2-weighted MRI were not associated with hemiparesis. In multivariate analysis, the presence of loculation and hematoma laterality (unilateral vs bilateral) influenced hemiparesis. For unilateral hematomas, maximal hematoma thickness of 19.8 mm and midline shift of 6.4 mm were associated with a 50% probability of hemiparesis. For bilateral hematomas, 29.0 mm of maximal hematoma thickness and 6.8 mm of shift were associated with a 50% probability of hemiparesis. CONCLUSIONS: Presence of loculations, unilateral hematomas, older patient age, hematoma maximal thickness, and midline shift were associated with a higher rate of hemiparesis in CSDH patients. Moreover, 19.8 mm of hematoma thickness and 6.4 mm of midline shift were associated with a 50% probability of hemiparesis in patients with unilateral hematomas.

Factors Predicting the Need for Surgery of the Opposite Side After Unilateral Evacuation of Bilateral Chronic Subdural Hematomas.

BACKGROUND: Patients with bilateral chronic subdural hematoma (bCSDH) undergo unilateral evacuation for the large or symptomatic side because the contralateral hematoma is either small or asymptomatic. However, the contralateral hematoma may subsequently grow and require evacuation. OBJECTIVE: To characterize factors that predict contralateral hematoma growth and need for evacuation. METHODS: A retrospective study on 128 surgically treated bCSDHs. RESULTS: Fifty-one and 77 were bilaterally and unilaterally evacuated, respectively. Glasgow Coma Scale was lower and midline shift was higher in those evacuated unilaterally compared to those evacuated bilaterally. Hematoma size was a significant determinant of decision for unilateral vs bilateral evacuation. The contralateral side needed evacuation at a later stage in 7 cases (9.1%). There was no significant difference in terms of reoperation rate between those evacuated unilaterally and bilaterally. Greater contralateral hematoma thickness on the first postoperative day computed tomography (CT) and more postoperative midline shift reversal had higher rates of operation in the opposite side. There was no difference between the daily pace of hematoma decrease in the operated and nonoperated sides (0.7% decrease per day vs 0.9% for the operated and nonoperated sides, respectively). CONCLUSION: Results of this study show that most bCSDHs evacuated unilaterally do not experience growth in the nonoperated side and unilateral evacuation results in hematoma resolution for both sides in most cases. Hematoma thickness on the opposite side on the first postoperative day CT and amount of midline shift reversal after surgery are the most important factors predicting the need for surgery on the opposite side.

Dynamic Computational Model of the Human Spinal Cord Connectome.

Connectomes abound, but few for the human spinal cord. Using anatomical data in the literature, we constructed a draft connectivity map of the human spinal cord connectome, providing a template for the many calibrations of specialized behavior to be overlaid on it and the basis for an initial computational model. A thorough literature review gleaned cell types, connectivity, and connection strength indications. Where human data were not available, we selected species that have been studied. Cadaveric spinal cord measurements, cross-sectional histology images, and cytoarchitectural data regarding cell size and density served as the starting point for estimating numbers of neurons. Simulations were run using neural circuitry simulation software. The model contains the neural circuitry in all ten Rexed laminae with intralaminar, interlaminar, and intersegmental connections, as well as ascending and descending brain connections and estimated neuron counts for various cell types in every lamina of all 31 segments. We noted the presence of highly interconnected complex networks exhibiting several orders of recurrence. The model was used to perform a detailed study of spinal cord stimulation for analgesia. This model is a starting point for workers to develop and test hypotheses across an array of biomedical applications focused on the spinal cord. Each such model requires additional calibrations to constrain its output to verifiable predictions. Future work will include simulating additional segments and expanding the research uses of the model.

Neuromonitoring for Spinal Cord Stimulation Lead Placement Under General Anesthesia.

Spinal cord stimulation (SCS) is a common therapeutic technique for treating medically refractory neuropathic back and other limb pain syndromes. SCS has historically been performed using a sedative anesthetic technique where the patient is awakened at various times during a surgical procedure to evaluate the location of the stimulator lead. This technique has potential complications, and thus other methods that allow the use of a general anesthetic have been developed. There are two primary methods for placing leads under general anesthesia, based on 1) compound muscle action potentials and 2) collisions between somatosensory evoked potentials. Both techniques are discussed, and the literature on SCS lead placement under general anesthesia using intraoperative neurophysiological mapping is comprehensively reviewed.

Theoretical Effect of DBS on Axonal Fibers of Passage: Firing Rates, Entropy, and Information Content.

BACKGROUND: Deep brain stimulation (DBS) has effects on axons that originate and terminate outside the DBS target area. OBJECTIVE: We hypothesized that DBS generates action potentials (APs) in both directions in "axons of passage," altering their information content and that of all downstream cells and circuits, and sought to quantify the change in fiber information content. METHODS: We incorporated DBS parameters (fiber firing frequency and refractory time, and AP initiation location along the fiber and propagation velocity) in a filtering function determining the AP frequency reaching the postsynaptic cell. Using neural circuitry simulation software, we investigated the ability of the filtering function to predict the firing frequency of APs reaching neurons targeted by axons of passage. We calculated their entropy with and without DBS, and with the electrode applied at various distances from the cell body. RESULTS: The predictability of the filtering function exceeded 98%. Entropy calculations showed that the entropy ratio "without DBS" to "with DBS" was always >1.0, thus DBS reduces fiber entropy. CONCLUSIONS: (1) The results imply that DBS effects are due to entropy reduction within fibers, i.e., a reduction in their information. (2) Where fibers of passage do not terminate in target regions, DBS may have side effects on nontargeted circuitry.

Lumbar disk herniation during pregnancy: a review on general management and timing of surgery.

STUDY DESIGN: Narrative review with case illustration. OBJECTIVE: Provide an overview of existing management strategies to suggest a guideline for surgical management of lumbar disk herniation in pregnant women based on time of presentation. METHODS: We performed a narrative review on the topic using the PubMed database. A total of 63 relevant articles published after 1992 were identified, of which 17 fulfilled selection criteria. RESULTS: A total of 22 published cases of spine surgery for disk herniation during pregnancy were found in 17 studies on the topic. Prone positioning was reported in the majority of cases during the first and early second trimester. C-sections were performed prior to spine surgery in the prone position for the majority of patients operated during the third trimester. The left lateral position with continued pregnancy was preferred during the latter half of the second trimester when delivery of the fetus cannot yet be performed but surgery is indicated. CONCLUSION: Spine surgery during pregnancy is a rare scenario but can be performed safely when needed if providers adhere to general guidelines. Surgical approaches and overall management are influenced by the stage of pregnancy.

Factors predicting reoperation of chronic subdural hematoma following primary surgical evacuation.

OBJECTIVEChronic subdural hematoma (CSDH) is commonly encountered in neurosurgical practice. However, surgical evacuation remains complicated by a high rate of reoperation. The optimal surgical approach to reduce the reoperation rate has not been determined. In the current study, the authors evaluated the prognostic value of clinical and radiographic factors to predict reoperation in the context of CSDH.METHODSA retrospective review of 325 CSDH patients admitted to an academic medical center in the United States, between 2006 and 2016, was performed. Clinical and radiographic factors predictive of the need for CSDH reoperation were identified on univariable and multivariable analyses.RESULTSUnivariable analysis showed that warfarin use, clopidogrel use, mixed hypo- and isointensity on T1-weighted MRI, greater preoperative midline shift, larger hematoma/fluid residual on first postoperative day CT, lesser decrease in hematoma size after surgery, use of monitored anesthesia care (MAC), and lack of intraoperative irrigation correlated with a significantly higher rate of reoperation. Multivariable analysis, however, showed that only the presence of loculation, clopidogrel or warfarin use, and percent of hematoma change after surgery significantly predicted the need for reoperation. Our results showed that 0% (no reduction), 50%, and 100% hematoma maximum thickness change (complete resolution of hematoma after surgery) were associated with a 41%, 6%, and < 1% rate of reoperation, respectively. The use of drains, either large diameter or small caliber, did not have any effect on the likelihood of reoperation.CONCLUSIONSAmong many factors, clopidogrel or warfarin use, hematoma loculation on preoperative CT, and the amount of hematoma evacuation on the first postoperative CT were the strongest predictors of reoperation.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Bleeding and Coagulation Management in Neurostimulation Devices.

INTRODUCTION: The Neurostimulation Appropriateness Consensus Committee (NACC) was formed by the International Neuromodulation Society (INS) in 2012 to evaluate the evidence to reduce the risk of complications and improve the efficacy of neurostimulation. The first series of papers, published in 2014, focused on the general principles of appropriate practice in the surgical implantation of neurostimulation devices. The NACC was reconvened in 2014 to address specific patient care issues, including bleeding and coagulation. METHODS: The INS strives to improve patient care in an evidence-based fashion. The NACC members were appointed or recruited by the INS leadership for diverse expertise, including international clinical expertise in many areas of neurostimulation, evidence evaluation, and publication. The group developed best practices based on peer-reviewed evidence and, in the absence of specific evidence, on expert opinion. Recommendations were based on international evidence in accordance with guideline creation. CONCLUSIONS: The NACC has recommended specific measures to reduce the risk of bleeding and neurological injury secondary to impairment of coagulation in the setting of implantable neurostimulation devices in the spine, brain, and periphery.

The Neurostimulation Appropriateness Consensus Committee (NACC) Safety Guidelines for the Reduction of Severe Neurological Injury.

INTRODUCTION: Neurostimulation involves the implantation of devices to stimulate the brain, spinal cord, or peripheral or cranial nerves for the purpose of modulating the neural activity of the targeted structures to achieve specific therapeutic effects. Surgical placement of neurostimulation devices is associated with risks of neurologic injury, as well as possible sequelae from the local or systemic effects of the intervention. The goal of the Neurostimulation Appropriateness Consensus Committee (NACC) is to improve the safety of neurostimulation. METHODS: The International Neuromodulation Society (INS) is dedicated to improving neurostimulation efficacy and patient safety. Over the past two decades the INS has established a process to use best evidence to improve care. This article updates work published by the NACC in 2014. NACC authors were chosen based on nomination to the INS executive board and were selected based on publications, academic acumen, international impact, and diversity. In areas in which evidence was lacking, the NACC used expert opinion to reach consensus. RESULTS: The INS has developed recommendations that when properly utilized should improve patient safety and reduce the risk of injury and associated complications with implantable devices. CONCLUSIONS: On behalf of INS, the NACC has published recommendations intended to reduce the risk of neurological injuries and complications while implanting stimulators.

Investigation of mechanisms of vagus nerve stimulation for seizure using finite element modeling.

OBJECTIVE: While the efficacy of vagus nerve stimulation (VNS) to reduce seizures in pharmaco-resistant patients is clinically proven, its efficacy and side effects mechanisms are not fully understood. Our goals were 1) to use a finite element model (FEM) and axon models to examine different fiber activation and blocking thresholds and 2) examine fiber activation and blocking in three fiber groups likely to be responsible for efficacy and side effects. METHODS: Using FEM, we examined the field potential along axons within a vagus nerve model with fascicles. These data were input to a computational fiber model to estimate numbers of axons activated across all diameters. We estimated numbers of activated and blocked fibers by diameter. RESULTS: 1) At the low end of VNS amplitudes, little efficacy for seizure control is appreciated while large Aß fibers associated with the recurrent laryngeal nerve are recruited. As amplitudes are increased, Aß fibers can produce hoarseness, and next recruited are fast B fibers associated with the aortic fascicle. We hypothesize these B fibers are the source of efficacy in treating seizure. As amplitudes are further increased, coughing may occur, possibly due to recruitment of smaller and deeper pulmonary fibers. 2) Clinical parameters are in a range that could cause inadvertent blocking at the cathode and activation at the anode. Conversely, innovative approaches to field shape and charge-balancing can allow controlled fiber activation at the cathode for maximum activation of the fibers responsible for efficacy, and possibly blocking at the anode to minimize side effects and expand therapeutic range. In design and operation, the cathode and anode can each be approached as a band pass filter. SIGNIFICANCE: The B fiber group is necessary and possibly sufficient to produce VNS efficacy in epilepsy. This group may emanate from aortic baroreceptors that, via synapses in the solitary tract nucleus, stimulate the locus coeruleus, hypothalamus and other influential targets such as the hippocampus. Responder rates may be increased with a lead that fully encircles the nerve. With better identification of the fiber groups involved in VNS, efficacy, side effects, therapeutic range and responder rates can be optimized.