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.

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.

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.

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.

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.

High-Frequency Stimulation of Dorsal Column Axons: Potential Underlying Mechanism of Paresthesia-Free Neuropathic Pain Relief.

OBJECTIVE: Spinal cord stimulation (SCS) treats neuropathic pain through retrograde stimulation of dorsal column axons and their inhibitory effects on wide dynamic range (WDR) neurons. Typical SCS uses frequencies from 50-100 Hz. Newer stimulation paradigms use high-frequency stimulation (HFS) up to 10 kHz and produce pain relief but without paresthesia. Our hypothesis is that HFS preferentially blocks larger diameter axons (12-15 µm) based on dynamics of ion channel gates and the electric potential gradient seen along the axon, resulting in inhibition of WDR cells without paresthesia. METHODS: We input field potential values from a finite element model of SCS into an active axon model with ion channel subcomponents for fiber diameters 1-20 µm and simulated dynamics on a 0.001 msec time scale. RESULTS: Assuming some degree of wave rectification seen at the axon, action potential (AP) blockade occurs as hypothesized, preferentially in larger over smaller diameters with blockade in most medium and large diameters occurring between 4.5 and 10 kHz. Simulations show both ion channel gate and virtual anode dynamics are necessary. CONCLUSION: At clinical HFS frequencies and pulse widths, HFS preferentially blocks larger-diameter fibers and concomitantly recruits medium and smaller fibers. These effects are a result of interaction between ion gate dynamics and the "activating function" (AF) deriving from current distribution over the axon. The larger fibers that cause paresthesia in low-frequency simulation are blocked, while medium and smaller fibers are recruited, leading to paresthesia-free neuropathic pain relief by inhibiting WDR cells.

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

BACKGROUND: Occipital neuralgia (ON) is a disorder characterized by sharp, electrical, paroxysmal pain, originating from the occiput and extending along the posterior scalp, in the distribution of the greater, lesser, and/or third occipital nerve. Occipital nerve stimulation (ONS) constitutes a promising therapy for medically refractory ON because it is reversible with minimal side effects and has shown continued efficacy with long-term follow-up. OBJECTIVE: To conduct a systematic literature review and provide treatment recommendations for the use of ONS for the treatment of patients with medically refractory ON. METHODS: A systematic literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and April 2014 using MeSH headings and keywords relevant to ONS as a means to treat ON. A second literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and June 2014 using MeSH headings and keywords relevant to interventions that predict response to ONS in ON. The strength of evidence of each article that underwent full text review and the resulting strength of recommendation were graded according to the guidelines development methodology of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Committee. RESULTS: Nine studies met the criteria for inclusion in this guideline. All articles provided Class III Level evidence. CONCLUSION: Based on the data derived from this systematic literature review, the following Level III recommendation can be made: the use of ONS is a treatment option for patients with medically refractory ON.

Primary Extradural Tumors of the Spine - Case Review with Evidence-guided Management.

BACKGROUND: Primary extradural tumors of the spine comprise only a small percentage of all spinal tumors. However, given their relative radioresistance and their typical malignant, invasive nature, surgery may be associated with fairly high morbidity and mortality rates. Furthermore, it may be especially difficult to achieve gross total resections with tumor-free margins. CASE DESCRIPTIONS: We present two cases and review the literature regarding the presentation, diagnosis, and evidence-based guidance/treatment of primary extradural spinal tumors. The first patient with an L1 chordoma presented with cauda equina syndrome. Following surgery, the second patient, with a giant cell tumor of the cervicothoracic junction, responded well to the novel drug denosumab, a monoclonal antibody to the RANK ligand. CONCLUSION: Primary extradural spine tumors pose significant challenges to surgeons as the aim is to achieve satisfactory surgical outcomes with clean tumor margins (e.g, thus avoid recurrence) while minimizing morbidity. Improvements in radiotherapy, chemotherapy, and novel molecular drugs may increase survival rates and improve overall outcomes.

Case series on variable presentation of ligamentum flavum stimulation following percutaneous cylindrical spinal cord stimulator lead implants.

BACKGROUND: Stimulation-evoked discomfort secondary to ligamentum flavum stimulation (LFS) is a technological limitation of percutaneous spinal cord stimulator (SCS) lead implants. There is a paucity of literature describing the clinical presentation and time periods at which this side effect may present following insertion of cylindrical lead(s). OBJECTIVE: To describe a series of 5 patients who presented at varying time periods after SCS lead placement with LFS. STUDY DESIGN: Retrospective case series. METHODS: We performed a chart review of online medical records of patients with symptoms consistent with LFS at an academic interventional pain clinic identified over 7 consecutive years (2006 - 2013). RESULTS: LFS most frequently presented within months of implantation of cylindrical leads. One patient complained of LFS during the temporary trial while another developed LFS after lead revision. All patients were successfully treated when paddle electrodes replaced percutaneous cylindrical leads. CONCLUSION: LFS may present as a barrier to successful SCS treatment. Clinicians placing percutaneous SCS leads should be aware of the variable time course of LFS presentation. Paddle style electrodes seem to offer an enduring solution to LFS so that patients may continue to benefit from SCS therapy.

Mechanism of dorsal column stimulation to treat neuropathic but not nociceptive pain: analysis with a computational model.

OBJECTIVE: Stimulation of axons within the dorsal columns of the human spinal cord has become a widely used therapy to treat refractory neuropathic pain. The mechanisms have yet to be fully elucidated and may even be contrary to standard "gate control theory." Our hypothesis is that a computational model provides a plausible description of the mechanism by which dorsal column stimulation (DCS) inhibits wide dynamic range (WDR) cell output in a neuropathic model but not in a nociceptive pain model. MATERIALS AND METHODS: We created a computational model of the human spinal cord involving approximately 360,000 individual neurons and dendritic processing of some 60 million synapses--the most elaborate dynamic computational model of the human spinal cord to date. Neuropathic and nociceptive "pain" signals were created by activating topographically isolated regions of excitatory interneurons and high-threshold nociceptive fiber inputs, driving analogous regions of WDR neurons. Dorsal column fiber activity was then added at clinically relevant levels (e.g., Aß firing rate between 0 and 110 Hz by using a 210-µsec pulse width, 50-150 Hz frequency, at 1-3 V amplitude). RESULTS: Analysis of the nociceptive pain, neuropathic pain, and modulated circuits shows that, in contradiction to gate control theory, 1) nociceptive and neuropathic pain signaling must be distinct, and 2) DCS neuromodulation predominantly affects the neuropathic signal only, inhibiting centrally sensitized pathological neuron groups and ultimately the WDR pain transmission cells. CONCLUSION: We offer a different set of necessary premises than gate control theory to explain neuropathic pain inhibition and the relative lack of nociceptive pain inhibition by using retrograde DCS. Hypotheses regarding not only the pain relief mechanisms of DCS were made but also regarding the circuitry of pain itself, both nociceptive and neuropathic. These hypotheses and further use of the model may lead to novel stimulation paradigms.

Modeling effects of scar on patterns of dorsal column stimulation.

OBJECTIVE: The purpose of this study was to examine how scar formation may affect electrical current distribution in the spinal cord when using paddle leads placed in the epidural space during treatment with spinal cord stimulation. MATERIALS AND METHODS: A finite element model of the spinal cord was used to examine changes in stimulation using a guarded cathode configuration with and without scar. Additionally, two potential "compensatory" programming patterns were examined in order to understand how the three-dimensional electrical field may be affected by scar. Direct comparisons with prior studies in the literature and use of known anatomy of dorsal column fiber distributions also enabled a computational estimate of the number of fibers likely reaching threshold with each stimulus pattern. RESULTS: Notable potential and current distribution changes were found related to the modeled scar. Compensatory stimulation patterns (both in spatial and in amplitude dimensions) affect the fiber activation patterns in complex ways that may not be easily predetermined by a programming specialist. CONCLUSIONS: This study is one of the first to examine the effects of scar tissue on dorsal column stimulation and the only one using a detailed computational approach toward that end. It appears that different thickness and location of scar between electrode contacts and the dura may likely lead to a significant number and location of complex changes in the activated fibers. It is likely that a more complete assessment of scarring and its effect on the electrical environment of any given paddle lead would allow more accurate and predictable reprogramming of patients with commercially available systems in place.

Localized stimulation and recording in the spinal cord with microelectrode arrays.

The use of microelectrodes for both recording and stimulation of cortical tissue is a well-established technique in neuroscience. We demonstrate that the use of existing microelectrode arrays and instrumentation can be extended to studying the spinal cord. We show that microelectrode arrays can be used to perform stimulation and recording in the corticospinal tract of an animal model commonly used in spinal cord injury (SCI) research. This technique could not only provide fundamental insights into the structure and function of the spinal cord, but also ultimately serve as the basis of a therapeutic treatment for severe spinal cord injuries.