The Polyanalgesic Consensus Conference (PACC)®: Intrathecal Drug Delivery Guidance on Safety and Therapy Optimization When Treating Chronic Noncancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians and scientists based on expertise with international representation to establish evidence-based guidance on intrathecal drug delivery in treating chronic pain. This Polyanalgesic Consensus Conference (PACC)® project, created more than two decades ago, intends to provide evidence-based guidance for important safety and efficacy issues surrounding intrathecal drug delivery and its impact on the practice of neuromodulation. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when PACC® last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence is scant. RESULTS: The PACC® examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC® recommends best practices regarding intrathecal drug delivery to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

A Scoping Review of Focused Ultrasound Enhanced Drug Delivery for Across the Blood-Brain Barrier for Brain Tumors.

BACKGROUND AND OBJECTIVES: Previous mechanisms of opening the blood-brain barrier (BBB) created a hypertonic environment. Focused ultrasound (FUS) has recently been introduced as a means of controlled BBB opening. Here, we performed a scoping review to assess the advances in drug delivery across the BBB for treatment of brain tumors to identify advances and literature gaps. METHODS: A review of current literature was conducted through a MEDLINE search inclusive of articles on FUS, BBB, and brain tumor barrier, including human, modeling, and animal studies written in English. Using the Rayyan platform, 2 reviewers (J.P and C.Y) identified 967 publications. 224 were chosen to review after a title screen. Ultimately 98 were reviewed. The scoping review was designed to address the following questions: (1) What FUS technology improvements have been made to augment drug delivery for brain tumors? (2) What drug delivery improvements have occurred to ensure better uptake in the target tissue for brain tumors? RESULTS: Microbubbles (MB) with FUS are used for BBB opening (BBBO) through cavitation to increase its permeability. Drug delivery into the central nervous system can be combined with MB to enhance transport of therapeutic agents to target brain tissue resulting in suppression of tumor growth and prolonging survival rate, as well as reducing systemic toxicity and degradation rate. There is accumulating evidence demonstrating that drug delivery through BBBO with FUS-MB improves drug concentrations and provides a better impact on tumor growth and survival rates, compared with drug-only treatments. CONCLUSION: Here, we review the role of FUS in BBBO. Identified gaps in the literature include impact of tumor microenvironment and extracellular space, improved understanding and control of MB and drug delivery, further work on ideal pharmacologics for delivery, and clinical use.

The sex-dependent impact of adipose tissue and inflammation on chronic pain - A cross-sectional study from the all of us research program.

Emerging evidence suggests an association between chronic pain and elevated body fat. We sought to determine if individuals with higher body fat, measured by hip circumference (HC) and waist circumference (WC), are at risk for chronic pain when they demonstrate higher expression of inflammatory markers. We investigated the incidence and severity of pain in patients with varying WC/HC and inflammatory markers (C-Reactive Protein, IL-6, leptin) using the NIH-sponsored All of Us Database. For each inflammatory marker and sex, participants were divided into four groups based on combinations of normal/high marker levels and small/large WC/HC. We used statistical analysis to compare WC/HC and pain severity (mean NRS pain score) between groups of the same sex. In females, but not males, combinations of elevated CRP with large WC/HC exerted additive effects on the incidence of chronic pain (p < 0.01) and severe pain (p < 0.001), as well as on the severity of pain evaluated by the mean NRS pain score (p < 0.01). This relationship held true for females with high IL-6 or leptin and large WC or HC (p < 0.001 for chronic pain and severe pain incidence, and p < 0.05 for pain severity). Neither IL-6 nor leptin showed any significant impact on pain in males. Obesity status and CRP exert additive prognostic effects for chronic pain in females, but not in males. The concomitant evaluation of other inflammatory factors, such as IL-6 or leptin in females, may further augment the prediction of chronic pain. PERSPECTIVE: This article investigates the relationship between chronic pain, obesity, and inflammatory markers. It could help elucidating sex difference in pain mechanisms, as well as the risk factors for chronic pain, potentially improving patient diagnosis, follow-up and treatment.

A scoping review of mechanisms of auricular acupuncture for treatment of pain.

OBJECTIVES: Auricular acupuncture (AA) is becoming increasingly common in primary care clinics, emergency departments and peri-operatively for pain relief. Over the last decade, since the last comprehensive reviews were published, the literature has expanded. In this scoping review, we seek to document the efficacy of AA in treating both acute and chronic pain, describe the mechanism of action of AA in treating pain, and discuss how AA has been integrated into Western medicine to date. METHODS: The authors performed a MEDLINE search inclusive of articles from 1966 to June 2023 including articles written in English identifying literature. We included human studies when more than 3 patients were included. Three hundred and fourteen unique articles were identified and 152 were selected by title screen. After abstract review, 117 were chosen for full-text review. Following full-text review, 33 articles were excluded and 21 added from references, totaling 105 articles included in our scoping review. RESULTS: AA reduces pain severity in patients with both acute and chronic pain. The best studies in the acute settings have occurred in the peri-operative setting where sham AA is employed, multiple sessions of AA are given, and medication dosing is carefully monitored. In these cases, AA reduced pain and post-operative medications. In patients with chronic pain, multiple sessions of AA resulted not only in pain relief but also in improvements in function and disability. Literature suggests that AA works through multiple mechanisms with the most compelling data coupled to the autonomic nervous system and neuroendocrine system. Curriculums designed to teach AA and aid in implementation have been published. CONCLUSION: AA is an accessible, effective means of pain relief. AA is relatively straightforward to learn, and protocols and curriculums exist to teach healthcare professionals this valuable skill. Overcoming implementation barriers, including patient education, are essential next steps.

This review was written to analyze the current research on an increasingly popular pain relief treatment, auricular acupuncture. Auricular acupuncture has been an effective method of pain relief for patients with short-term pain. People who experienced pain after surgery and received auricular acupuncture experienced a decrease in pain and pain medications. Patients with chronic pain who underwent auricular acupuncture experienced pain relief and an increase in their functional abilities. Auricular acupuncture is thought to affect the body's autonomic nervous system and neuroendocrine system as it creates its source of pain relief for the body. Auricular acupuncture is increasingly popular in the education of healthcare workers and clinical practice. Research shows auricular acupuncture is an effective, easy, and less expensive method of pain relief, whose growth in pain management use may benefit from further education, especially for patients.

Gut dysbiosis in patients with chronic pain: a systematic review and meta-analysis.

Introduction: Recent evidence supports the contribution of gut microbiota dysbiosis to the pathophysiology of rheumatic diseases, neuropathic pain, and neurodegenerative disorders. The bidirectional gut-brain communication network and the occurrence of chronic pain both involve contributions of the autonomic nervous system and the hypothalamic pituitary adrenal axis. Nevertheless, the current understanding of the association between gut microbiota and chronic pain is still not clear. Therefore, the aim of this study is to systematically evaluate the existing knowledge about gut microbiota alterations in chronic pain conditions. Methods: Four databases were consulted for this systematic literature review: PubMed, Web of Science, Scopus, and Embase. The Newcastle-Ottawa Scale was used to assess the risk of bias. The study protocol was prospectively registered at the International prospective register of systematic reviews (PROSPERO, CRD42023430115). Alpha-diversity, ß-diversity, and relative abundance at different taxonomic levels were summarized qualitatively, and quantitatively if possible. Results: The initial database search identified a total of 3544 unique studies, of which 21 studies were eventually included in the systematic review and 11 in the meta-analysis. Decreases in alpha-diversity were revealed in chronic pain patients compared to controls for several metrics: observed species (SMD= -0.201, 95% CI from -0.04 to -0.36, p=0.01), Shannon index (SMD= -0.27, 95% CI from -0.11 to -0.43, p<0.001), and faith phylogenetic diversity (SMD -0.35, 95% CI from -0.08 to -0.61, p=0.01). Inconsistent results were revealed for beta-diversity. A decrease in the relative abundance of the Lachnospiraceae family, genus Faecalibacterium and Roseburia, and species of Faecalibacterium prausnitzii and Odoribacter splanchnicus, as well as an increase in Eggerthella spp., was revealed in chronic pain patients compared to controls. Discussion: Indications for gut microbiota dysbiosis were revealed in chronic pain patients, with non-specific disease alterations of microbes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023430115.

Evolution of Deep Brain Stimulation Techniques for Complication Mitigation.

Complication mitigation in deep brain stimulation has been a topic matter of much discussion in the literature. In this article, we examine how neurosurgeons as individuals and as a field generated and adapted techniques to prevent infection, lead fracture/lead migration, and suboptimal outcomes in both the acute period and longitudinally. The authors performed a MEDLINE search inclusive of articles from 1987 to June 2023 including human studies written in English. Using the Rayyan platform, two reviewers (J.P. and R.M.) performed a title screen. Of the 776 articles, 252 were selected by title screen and 172 from abstract review for full-text evaluation. Ultimately, 124 publications were evaluated. We describe the initial complications and inefficiencies at the advent of deep brain stimulation and detail changes instituted by surgeons that reduced them. Furthermore, we discuss the trend in both undesired short-term and long-term outcomes with emphasis on how surgeons recognized and modified their practice to provide safer and better procedures. This scoping review adds to the literature as a guide to both new neurosurgeons and seasoned neurosurgeons alike to understand better what innovations have been trialed over time as we embark on novel targets and neuromodulatory technologies.

Improved Selectivity in Eliciting Evoked Electromyography Responses With High-Resolution Spinal Cord Stimulation.

BACKGROUND AND OBJECTIVES: As spinal cord stimulation (SCS) offers a therapy for increasing numbers of patients with chronic pain and spinal cord injury, it becomes increasingly important to better understand its somatotopy. In this prospective study, we investigate whether high-resolution SCS (HR-SCS) offers improved selectivity assessed through elicitation of evoked electromyography (EMG) responses as compared with commercial paddle leads. METHODS: Vertical tripole configurations were used to elicit EMG responses in both types of paddles placed for standard-of-care indications between T6 and T10. In HR-SCS, evoked EMG responses in lower extremity/abdominal muscle groups were monitored at 6 to 8 mediolateral sites. All commercial paddle columns were tested. Percentage change in the maximum root mean square value was calculated at a group level. Heat maps were generated to identify responders for each muscle group. Responders were considered patients who had a >50% change in root mean square over baseline. RESULTS: We demonstrated significantly greater motor responses across medial and lateral contacts and greater responder rates consistently at the T6 and T9 levels with HR-SCS as compared with commercial paddles in 18 patients. Distal muscle groups (gastrocnemius and tibialis anterior) and proximal muscle groups (biceps femoris and quadriceps) were selectively activated at both levels. CONCLUSION: We demonstrate that HR-SCS has greater selectivity in eliciting evoked EMG responses in an intraoperative setting. HR-SCS offers recruitment of muscle groups at lateral contacts concurrently with medial contacts. We provide data that HR-SCS may provide higher spatial resolution, which has the potential to allow for personalization of care and treatment of pain syndromes/symptoms which to date have not been effectively treated.

Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III).

BACKGROUND: Recruitment of participants is the greatest risk to completion of most clinical trials, with 20-40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke. We report on the experience using a novel hybrid recruitment approach of a patient-facing portal to self-identify and perform an initial screen for general trial eligibility (tier 1), followed by phone screening and medical records review (tier 2) prior to a final in-person visit to confirm eligibility and consent. METHODS: Two tiers of screening were established: an initial screen of general eligibility using a patient-facing web portal (tier 1), followed by a more detailed screen that included phone survey and medical record review (tier 2). If potential participants passed the tier 2 screen, they were referred directly to visit 1 at a study site, where final in-person screening and consent were performed. Rates of screening were tracked during the period of trial recruitment and sources of referrals were noted. RESULTS: The approach to screening and recruitment resulted in 6125 tier 1 screens, leading to 1121 referrals to tier 2. The tier 2 screening resulted in 224 medical record requests and identification of 86 qualifying participants for referral to sites. The study attained a viable recruitment rate of 6 enrolled per month prior to being disrupted by COVID 19. CONCLUSIONS: A tiered approach to eligibility screening using a hybrid of web-based portals to self-identify and screen for general eligibility followed by a more detailed phone and medical record review allowed the study to use fewer sites and reduce cost. Despite the difficult and narrow population of patients suffering moderate chronic disability from stroke, this strategy produced a viable recruitment rate for this invasive study of intracranially injected neural stem cells. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03629275.

Incidence and Prevalence of Pain Medication Prescriptions in Pathologies with a Potential for Chronic Pain.

BACKGROUND: Heightened risks of dependence, addiction, anxiolytic effects, or prescription overdose death due to long-term use of pain medication have increased awareness about extended pain medication use in chronic pain populations. The goal of this study was to evaluate the incidence and prevalence of pain medication prescriptions from 2012 to 2022 in common pathologies with a potential for chronic pain. METHODS: A retrospective cohort study was conducted using electronic health records from TriNetX (Cambridge, Massachusetts) Global Collaborative Network. For 10 distinct cohorts (total n = 9,357,584 patients), pain medication prescriptions were extracted for five classes, namely nonsteroidal anti-inflammatory drug (NSAIDs) and acetaminophen, opioids, gabapentinoids, neuropathic mood agents, and muscle relaxants. Annual incidence and prevalence of each class of medication were evaluated for the past 11 yr. RESULTS: From 2012 to 2022, there was a significant increase in prescriptions of NSAIDs, except for patients with fibromyalgia, and persistent spinal pain syndrome (PSPS) type 2. Interestingly, over time, prescriptions of opioids in patients with complex regional pain syndrome, endometriosis, osteoarthritis, and PSPS type 2 increased, as did prescriptions of muscle relaxants for all cohorts except those with fibromyalgia. Incidence of prescriptions of neuropathic mood agents is high for patients with complex regional pain syndrome (both types) and PSPS type 2. Only for benzodiazepines did there seem to be a decline over the years, with a significantly decreased time trend in patients with complex regional pain syndrome type 1, fibromyalgia, and PSPS type 2. CONCLUSIONS: During the last 11 yr, an increase in incidence of NSAIDs and acetaminophen, opioids, neuropathic agents, and muscle relaxants was observed. Only prescriptions of benzodiazepines significantly decreased over time in specific cohorts. Overall, patients with PSPS type 2 and complex regional pain syndrome (both types) consume a broad variety of pain medication classes.

The Evolution of Surgical Technique in Spinal Cord Stimulation: A Scoping Review.

Since the advent of spinal cord stimulation (SCS), its operative technique has consistently advanced. We performed a scoping review of the literature regarding SCS operative techniques to highlight key advancements. To review, summarize, and highlight key changes in SCS implantation techniques since their inception. The authors performed a MEDLINE search inclusive of articles from 1967 to June 2023 including human and modeling studies written in English examining the role of trialing, intraoperative neuromonitoring, and surgical adaptations. Using the Rayyan platform, two reviewers performed a blinded title screen. Of the 960 articles, 197 were included in the title screen, 107 were included in the abstract review, and ultimately 69 articles met inclusion criteria. We examined the utility of trialing and found that historical controls showed significant efficacy, whereas recent results are more equivocal. We discuss the significant improvement in outcomes with intraoperative neuromonitoring for asleep SCS placement. We highlight technique improvements that led to significant reductions in infection, lead migration, and inadequate pain relief. Physicians implanting SCS systems for chronic pain management must continually refine their surgical techniques to keep up with this rapidly evolving therapy. In addition, through collaborative efforts of neuromodulators and industry, SCS is safer and more effective for patients suffering from chronic pain.

Predictors of Skip Laminotomy for Placement of Paddle Leads for Spinal Cord Stimulation.

OBJECTIVES: Placement of a standard paddle lead for spinal cord stimulation (SCS) requires a laminotomy for positioning of the lead within the epidural space. During initial placement, an additional laminotomy or laminectomy, termed a "skip" laminotomy, may be necessary at a higher level to pass the lead to the appropriate midline position. Patient and radiographic factors that predict the need for a skip laminotomy have yet to be identified. MATERIALS AND METHODS: Participants who underwent SCS paddle placement at Albany Medical Center between 2016 and 2017 were identified. Operative reports were reviewed to identify the paddle type, level of initial laminotomy, target level, and skip laminotomy level. Preoperative thoracic magnetic resonance images (MRIs) were reviewed, and spinal canal diameter, interpedicular distance, and dorsal cerebral spinal fluid thickness were measured for each participant when available. RESULTS: A total of 106 participants underwent thoracic SCS placement. Of these, 97 had thoracic MRIs available for review. Thirty-eight participants required a skip laminotomy for placement of the paddle compared with 68 participants who did not. There was no significant difference in demographic features including age, sex, body mass index, and surgical history. Univariate analyses that suggested trends were selected for further analysis using binary logistic regression. Level of initial laminotomy (odds ratio [OR] = 1.51, p = 0.028), spinal canal diameter (OR = 0.71, p = 0.015), and dorsal cerebrospinal fluid thickness (OR = 0.61, p = 0.011) were correlated with skip laminotomy. Target level (OR = 1.27, p = 0.138) and time from trial (1.01, p = 0.117) suggested potential association. The multivariate regression was statistically significant, X2(10) = 28.02, p = 0.002. The model explained 38.3% of the variance (Nagelkerke R2) and predicted skip laminectomy correctly in 73.3% of cases. However, for the multivariate regression, only a decrease in spinal canal diameter (OR = 0.59, p = 0.041) was associated with a greater odds of skip laminotomy. CONCLUSIONS: This study aims to characterize the patient and radiographic factors that may predict the need to perform a skip laminotomy during the initial placement of SCS paddles. Here, we show that radiographic and anatomic variables, primarily spinal canal diameter, play an important role in predicting the need for a skip laminotomy. Furthermore, we suggest that target level for placement and level of initial laminotomy also may contribute. Further investigation of the predictive factors for performing a skip laminotomy would help optimize surgical planning and preoperative patient selection and counseling.

Sacral Tarlov perineurial cysts: a systematic review of treatment options.

Tarlov perineurial spinal cysts (TCs) are an underrecognized cause of spinal neuropathic symptoms. TCs form within the sensory nerve root sleeves, where CSF extends distally and can accumulate pathologically. Typically, they develop at the sacral dermatomes where the nerve roots are under the highest hydrostatic pressure and lack enclosing vertebral foramina. In total, 90% of patients are women, and genetic disorders that weaken connective tissues, e.g., Ehlers-Danlos syndrome, convey considerable risk. Most small TCs are asymptomatic and do not require treatment, but even incidental visualizations should be documented in case symptoms develop later. Symptomatic TCs most commonly cause sacropelvic dermatomal neuropathic pain, as well as bladder, bowel, and sexual dysfunction. Large cysts routinely cause muscle atrophy and weakness by compressing the ventral motor roots, and multiple cysts or multiroot compression by one large cyst can cause even greater cauda equina syndromes. Rarely, giant cysts erode the sacrum or extend as intrapelvic masses. Disabling TCs require consideration for surgical intervention. The authors' systematic review of treatment analyzed 31 case series of interventional percutaneous procedures and open surgical procedures. The surgical series were smaller and reported somewhat better outcomes with longer term follow-up but slightly higher risks. When data were lacking, authorial expertise and case reports informed details of the specific interventional and surgical techniques, as well as medical, physical, and psychological management. Cyst-wrapping surgery appeared to offer the best long-term outcomes by permanently reducing cyst size and reconstructing the nerve root sleeves. This curtails ongoing injury to the axons and neuronal death, and may also promote axonal regeneration to improve somatic and autonomic sacral nerve function.

Incidence of Infections, Explantations, and Displacements/Mechanical Complications of Spinal Cord Stimulation During the Past Eight Years.

OBJECTIVES: The overall awareness and potential of real-world data have drastically increased in the medical field, with potential implications for postmarket medical device surveillance. The goal of this study was to evaluate real-world data on incidence of infections, explantations, and displacements/mechanical complications of spinal cord stimulation (SCS) during the past eight years and to forecast point estimates for the upcoming three years on the basis of the identified patterns. MATERIALS AND METHODS: Based on electronic health records from 80 healthcare organizations within the TriNetX data base in the USA, data of 11,934 patients who received SCS as treatment for persistent spinal pain syndrome type 2 (PSPS T2) were extracted. Events of interest were explantations and displacements/mechanical complications of both the lead and implanted pulse generator (IPG), in addition to infection rates from 2015 to 2022. Mann-Kendall tests were performed to detect monotonic trends in the time series. Forecasts were conducted for the upcoming three years for every event of interest. RESULTS: Statistically significant increasing time trends were revealed for the annual incidence of IPG and lead displacements/mechanical complications in patients with PSPS T2 over the past eight years. These time trends were visible in both male and female patients and in smokers and nonsmokers. For annual incidence of explantations and infections, no significant time effect was observed. In 2025, the incidence of displacements/mechanical complications of the lead (3.07%) is predicted to be the highest, followed by explantations of the IPG (2.67%) and lead (2.02%). CONCLUSIONS: Based on real world data, device explantation was the most frequent event of interest, with negative peaks in the time series in 2016 and 2020, presumably due to the introduction of rechargeable pulse generators and to the COVID-19 pandemic, respectively.

Investigation of the intraoperative cortical responses to spinal motor mapping in a patient with chronic pain.

Intraoperative neurophysiological monitoring (IONM) in spinal cord stimulation (SCS) surgery for chronic pain is shown to provide effective guidance during device placement. Electromyography (EMG) is used to determine the laterality of the paddle. In some SCS cases, laterality cannot be obtained via EMG due to patient physiology. Electroencephalography (EEG) is already used in IONM to monitor cortical responses. Here, we show proof-of-concept of assessing the responses of epidurally evoked EMGs simultaneously with EEGs to determine laterality during IONM using a high-resolution (HR) SCS paddle. An 8-column HR-SCS paddle was acutely placed at T9-T10 interspace in patients with failed back surgery syndrome. EMG signals from 18 muscle groups were recorded simultaneously with 60-channel EEG signals at various stimulation amplitudes (0-10 mA). Particular attention was paid to regions associated with pain including the somatosensory cortex (S1), prefrontal cortex (PFC), and motor cortex (M1). When left and right lateral contacts were stimulated at low amplitudes (1-2 mA), significant changes were seen in θ, α, and ß powers in the contralateral PFC but not in M1 or S1. There was a significant correlation between M1 and contralateral contacts in α power. At higher currents (7-8 mA), right-sided contacts resulted in α power change. We found significant differences in α, θ, and ß powers in PFC for contralateral stimulation of the lateral SCS contacts at low amplitudes and in α power at higher amplitudes. The changes in PFC suggest the potential of EEG for understanding a cortical mechanism of action of SCS and provide insight into the pathophysiology of chronic pain.NEW & NOTEWORTHY Here, we present proof of concept of assessing the responses of epidurally evoked electromyography simultaneously with scalp electroencephalography to determine whether both laterality and insights into pain mechanisms can be elucidated. With stimulation, significant changes were seen in θ, α, and ß band power in the contralateral prefrontal cortex and in α power in the motor cortex. We provide insight into the mechanism of action of SCS in preventing pain in this patient.

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.

An assessment of the long-term impacts of the coronavirus disease 2019 pandemic on academic neurosurgery.

OBJECTIVE: The goal of this study was to survey residents, fellows, and residency program leadership to assess the long-term impacts of the coronavirus disease 2019 (COVID-19) on residency training by using a structured survey methodology. METHODS: A survey was distributed to US neurosurgical residents and fellows (n = 2085) as well as program directors (PDs) and chairs (n = 216) in early 2022. Bivariate analysis was performed to identify factors associated with a decreased likelihood of pursuing a career in academic neurosurgery because of the pandemic, a perception that surgical skills preparation was negatively impacted, personal financial concerns, and a preference for remote education. Significant differences in the bivariate analysis underwent further multivariate logistic regression analysis to evaluate for predictors of these outcomes. RESULTS: An analysis of complete surveys from 264 residents and fellows (12.7%) and 38 PDs and chairs (17.6%) was performed. Over half of the residents and fellows (50.8%) believed that their surgical skills preparation was negatively impacted by the pandemic, and a notable proportion believed that they were less likely to go into academics because of the pandemic's impact on their professional (20.8%) and personal (28.8%) life. Those less likely to pursue academics were more likely to report that work-life balance did not improve (p = 0.049), personal financial concerns increased (p = 0.01), and comradery among residents (p = 0.002) and with faculty (p = 0.001) did not improve. Residents who indicated they were less likely to go into academics were also more likely to have been redeployed (p = 0.038). A large majority of PDs and chairs indicated that the pandemic resulted in financial setbacks for their departments (71.1%) and institutions (84.2%), with 52.6% reporting reduced faculty compensation. Financial setbacks at the institutional level were associated with a worsened opinion of hospital leadership (p = 0.019) and reports of a reduced quality of care for non-COVID-19 patients (p = 0.005) but not from faculty member losses (p = 0.515). A plurality of trainees (45.5%) reported a preference for a remote format for educational conferences compared to 37.1% who disagreed. CONCLUSIONS: This study provides a cross-section of the pandemic's impact on academic neurosurgery, highlighting the importance of continued efforts to assess and address the long-term consequences of the COVID-19 pandemic for US academic neurosurgery.

Machine Learning in Spinal Cord Stimulation for Chronic Pain.

Spinal cord stimulation (SCS) is an effective treatment for chronic neuropathic pain. The success of SCS is dependent on candidate selection, response to trialing, and programming optimization. Owing to the subjective nature of these variables, machine learning (ML) offers a powerful tool to augment these processes. Here we explore what work has been done using data analytics and applications of ML in SCS. In addition, we discuss aspects of SCS which have narrowly been influenced by ML and propose the need for further exploration. ML has demonstrated a potential to complement SCS to an extent ranging from assistance with candidate selection to replacing invasive and costly aspects of the surgery. The clinical application of ML in SCS shows promise for improving patient outcomes, reducing costs of treatment, limiting invasiveness, and resulting in a better quality of life for the patient.

Assessing the Location, Relative Expression and Subclass of Dopamine Receptors in the Cerebellum of Hemi-Parkinsonian Rats.

Parkinson's Disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons in the nigrostriatal pathway resulting in basal ganglia (BG) dysfunction. This is largely why much of the preclinical and clinical research has focused on pathophysiological changes in these brain areas in PD. The cerebellum is another motor area of the brain. Yet, if and how this brain area responds to PD therapy and contributes to maintaining motor function fidelity in the face of diminished BG function remains largely unanswered. Limited research suggests that dopaminergic signaling exists in the cerebellum with functional dopamine receptors, tyrosine hydroxylase (TH) and dopamine transporters (DATs); however, much of this information is largely derived from healthy animals and humans. Here, we identified the location and relative expression of dopamine 1 receptors (D1R) and dopamine 2 receptors (D2R) in the cerebellum of a hemi-parkinsonian male rat model of PD. D1R expression was higher in PD animals compared to sham animals in both hemispheres in the purkinje cell layer (PCL) and granule cell layer (GCL) of the cerebellar cortex. Interestingly, D2R expression was higher in PD animals than sham animals mostly in the posterior lobe of the PCL, but no discernible pattern of D2R expression was seen in the GCL between PD and sham animals. To our knowledge, we are the first to report these findings, which may lay the foundation for further interrogation of the role of the cerebellum in PD therapy and/or pathophysiology.