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.

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.

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.

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.

The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for the Mitigation of Complications of Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise and international representation to establish evidence-based guidance on the mitigation of neuromodulation complications. This Neurostimulation Appropriateness Consensus Committee (NACC)® project intends to update evidence-based guidance and offer expert opinion that will improve efficacy and safety. 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 NACC last published guidelines) to October 2023. 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 was scant. RESULTS: The NACC 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 NACC recommends best practices regarding the mitigation of complications associated with neurostimulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

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.

Role of Integrative Health on Neuropathic Pain.

PURPOSE OF REVIEW: Patients diagnosed with neuropathic pain experience continuous or intermittent spontaneous pain throughout their lives. Pharmacological treatments often provide limited relief; therefore, a multidisciplinary approach should be utilized to manage neuropathic pain. This review examines the current literature on integrative health modalities (anti-inflammatory diets, functional movement, acupuncture, meditation, and transcutaneous therapy) for treating patients with neuropathic pain. RECENT FINDINGS: The use of an anti-inflammatory diet, functional movement, acupuncture, meditation, and transcutaneous therapy in treating neuropathic pain has been investigated in prior literature with positive outcomes. However, there remains a large void in evidence-based knowledge and clinical applicability for these interventions. Overall, integrative health offers a cost-efficient and harmless way of creating a multidisciplinary approach to managing neuropathic pain. There are many complementary approaches to treating neuropathic pain as part of an integrative medicine approach. Research is needed to explore other herbs and spices not yet reported in the peer-review literature. Additionally, follow-on research is needed to understand the clinical applicability of the proposed interventions as well as the dose and timing of the interventions to predict response and duration.

Establishing Minimal Clinically Important Difference in Sleep Outcomes after Spinal Cord Stimulation in Patients with Chronic Pain Disorders.

INTRODUCTION: As one of the most common medical conditions for which patients seek medical care, chronic pain can be debilitating. The relationship between chronic pain and sleep is thought to be bidirectional, suggesting that treatment of one can be beneficial to the other. There is mounting evidence that spinal cord stimulation (SCS) improves aspects of sleep. How meaningful that is to patients' lives has not been ascertained. OBJECTIVE: The aim of the current study was to further elucidate the effect of SCS on sleep by examining the relationship between pain outcome measures with the insomnia severity index (ISI) and to establish the minimally clinical important difference (MCID), which is defined as the smallest noticeable change that an individual perceives as clinically significant. MATERIALS AND METHODS: We prospectively collected ISI, Epworth sleepiness scale (ESS), Numerical Rating Scale, McGill Pain Questionnaire-Short Form, Oswestry Disability Index, Beck Depression Inventory, and Pain Catastrophizing Scale data both pre- and postoperatively for chronic pain patients who underwent SCS placement and had long-term outcomes. The ISI is a well-studied questionnaire used to assess an individual's level of insomnia. RESULTS: We correlated the ESS and ISI with pain outcome measures in sixty-four patients at a mean follow-up of 9.8 ± 2.9 months. The ISI showed correlations with disability as measured through the Oswestry Disability Index (p = 0.014) and depression as measured through the Beck Depression Inventory (p = 0.024). MCID values for the ISI were calculated using both anchor- and distribution-based methods. The minimal detectable change method resulted in an MCID of 2.4 points, standard error of measurement resulted in an MCID of 2.6 points, and the change difference resulted in an MCID of 2.45. The receiver operating characteristic method yielded an MCID of 0.5-point change with an area under the curve of 0.61. CONCLUSION: This study successfully established MCID ranges for the ISI outcome measure to help gauge improvement in insomnia after SCS. The ISI has ample evidence of its validity in assessment of insomnia, and MCID values of 2.4-2.6 correlate with improvement in disability and depression in our patients.

Artifacts Can Be Deceiving: The Actual Location of Deep Brain Stimulation Electrodes Differs from the Artifact Seen on Magnetic Resonance Images.

INTRODUCTION: Deep brain stimulation (DBS) is a common treatment for a variety of neurological and psychiatric disorders. Recent studies have highlighted the role of neuroimaging in localizing the position of electrode contacts relative to target brain areas in order to optimize DBS programming. Among different imaging methods, postoperative magnetic resonance imaging (MRI) has been widely used for DBS electrode localization; however, the geometrical distortion induced by the lead limits its accuracy. In this work, we investigated to what degree the difference between the actual location of the lead's tip and the location of the tip estimated from the MRI artifact varies depending on the MRI sequence parameters such as acquisition plane and phase encoding direction, as well as the lead's extracranial configuration. Accordingly, an imaging technique to increase the accuracy of lead localization was devised and discussed. METHODS: We designed and constructed an anthropomorphic phantom with an implanted DBS system following 18 clinically relevant configurations. The phantom was scanned at a Siemens 1.5 Tesla Aera scanner using a T1MPRAGE sequence optimized for clinical use and a T1TSE sequence optimized for research purposes. We varied slice acquisition plane and phase encoding direction and calculated the distance between the caudal tip of the DBS lead MRI artifact and the actual tip of the lead, as estimated from MRI reference markers. RESULTS: Imaging parameters and lead configuration substantially altered the difference in the depth of the lead within its MRI artifact on the scale of several millimeters - with a difference as large as 4.99 mm. The actual tip of the DBS lead was found to be consistently more rostral than the tip estimated from the MR image artifact. The smallest difference between the tip of the DBS lead and the tip of the MRI artifact using the clinically relevant sequence (i.e., T1MPRAGE) was found with the sagittal acquisition plane and anterior-posterior phase encoding direction. DISCUSSION/CONCLUSION: The actual tip of an implanted DBS lead is located up to several millimeters rostral to the tip of the lead's artifact on postoperative MR images. This distance depends on the MRI sequence parameters and the DBS system's extracranial trajectory. MRI parameters may be altered to improve this localization.

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.

Clinical Longevity of 106,462 Rechargeable and Primary Cell Spinal Cord Stimulators: Real World Study in the Medicare Population.

INTRODUCTION: Spinal cord stimulators (SCS) are available with either primary cell (PC) or rechargeable cell (RC) batteries. Although RC systems are proposed to have a battery longevity upward of nine years, in comparison with four years for PC systems, there are few studies of longevity of SCS in the real world. MATERIALS AND METHODS: This was an observational, nonrandomized, retrospective study of Medicare beneficiaries who received neurostimulator implants in the outpatient hospital. This study used Medicare fee-for-service claims data from 2013 to 2020. The clinical longevity of the implantable pulse generator (IPG), defined as the duration from implant until removal for any reason, was compared between PC and RC devices. Life distribution analysis was used to approximate device lifespan. The secondary analysis separated removals into explant or replacements. The statistics were adjusted for relevant clinical covariates. RESULTS: A total of 25,856 PC and 79,606 RC systems were included in the study. At seven years after implant, 53.8% of PC IPGs and 55.0% of RC IPGs remained in use. The life distribution modeling analysis projected a median lifespan of 8.2 years for PC and 9.0 years for RC devices. The rate of explant was lower for PC devices (19.2%) than for RC devices (22.0%, hazard ratio (HR) = 0.96, p = 0.082), whereas the rate of replacements was higher for PC devices (33.7%) than for RC devices (29.5%, HR = 1.31, p < 0.001). An analysis of the battery type used in device replacements showed an increasing adoption of PC devices over time. CONCLUSIONS: This large, retrospective, real-world analysis of Medicare claims data demonstrated that the clinical longevity of neurostimulator devices is similar for PC and RC batteries. In the past, clinicians may have defaulted to RC devices based on the assumption that they provided extended battery life. Considering this longevity data, clinicians should now consider the choice between PC and RC devices based on other individual factors pertinent to the patient experience and not on purported longevity claims.

Holistic Treatment Response: An International Expert Panel Definition and Criteria for a New Paradigm in the Assessment of Clinical Outcomes of Spinal Cord Stimulation.

BACKGROUND: Treatment response to spinal cord stimulation (SCS) is focused on the magnitude of effects on pain intensity. However, chronic pain is a multidimensional condition that may affect individuals in different ways and as such it seems reductionist to evaluate treatment response based solely on a unidimensional measure such as pain intensity. AIM: The aim of this article is to add to a framework started by IMMPACT for assessing the wider health impact of treatment with SCS for people with chronic pain, a "holistic treatment response". DISCUSSION: Several aspects need consideration in the assessment of a holistic treatment response. SCS device data and how it relates to patient outcomes, is essential to improve the understanding of the different types of SCS, improve patient selection, long-term clinical outcomes, and reproducibility of findings. The outcomes to include in the evaluation of a holistic treatment response need to consider clinical relevance for patients and clinicians. Assessment of the holistic response combines two key concepts of patient assessment: (1) patients level of baseline (pre-treatment) unmet need across a range of health domains; (2) demonstration of patient-relevant improvements in these health domains with treatment. The minimal clinical important difference (MCID) is an established approach to reflect changes after a clinical intervention that are meaningful for the patient and can be used to identify treatment response to each individual domain. A holistic treatment response needs to account for MCIDs in all domains of importance for which the patient presents dysfunctional scores pre-treatment. The number of domains included in a holistic treatment response may vary and should be considered on an individual basis. Physiologic confirmation of therapy delivery and utilisation should be included as part of the evaluation of a holistic treatment response and is essential to advance the field of SCS and increase transparency and reproducibility of the findings.

Age as an Independent Predictor of Adult Spinal Cord Stimulation Pain Outcomes.

INTRODUCTION: Spinal cord stimulation (SCS) is an efficacious chronic pain treatment most commonly used in middle-aged patients. Results from previous studies that investigated SCS' effects in older patient populations have been equivocal. We examine whether SCS outcomes correlate with age. METHODS: We retrospectively examined prospectively collected outcomes from 189 patients who underwent SCS at Albany Medical Center between 2012 and 2020. The patients completed the Numerical Rating Scale (NRS), McGill Pain Questionnaire (MPQ), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), and Pain Catastrophizing Scale (PCS) preoperatively and 1 year postoperatively. The mean percent change in each outcome was determined and compared via a regression analysis to determine relationships between patient age and each respective outcome metrics. Demographics were compared between patients aged under 65 versus those aged 65 and older via χ2 tests. RESULTS: All subjects demonstrated the expected improvement on NRS, BDI, PCS, and MPQ from baseline to 1-year follow-up, with several demonstrating statistically significant changes: NRS-worst pain (18.66%, p < 0.001), NRS-least pain (26.9%, p < 0.001), NRS-average pain (26.9%, p < 0.01), NRS-current pain (26.4%, p < 0.001), ODI (19.6%, p < 0.001), PCS (29.8%, p < 0.001), and MPQ (29.4%, p < 0.001). There was no significant difference between patients aged under 65 versus those aged 65 and older based on lead type (p = 0.454). Six patients (3.1%) had lead migration, one of whom was 65 or older. Regression analysis revealed improvements in MPQ-sensory and MPQ-affective scores as age increased (p < 0.001, R2 = 0.09; p = 0.046, R2 = 0.05, respectively). Age did not correlate with NRS, ODI, BDI, or PCS. Diagnosis, spinal level of SCS, and lead type were not found to influence any respective outcome measure based on covariate analysis. CONCLUSION: This study represents the largest study where age was correlated to specific pain, depression, and disability outcomes following SCS. We provide evidence that SCS outcomes are equivalent, or better, in older patients following SCS. Based on these findings, SCS is a viable option for treatment of chronic pain in elderly patient populations.

Botulinum Toxin as an Effective Treatment for Trigeminal Neuralgia in Surgical Practices.

BACKGROUND: Trigeminal neuralgia (TN) is a common cause of craniofacial pain with many medical and surgical therapies, all of which are imperfect. We examine the use of botulinum toxin type-A (BTX-A) as an intermediary approach in surgical practices. METHODS: We retrospectively identified TN patients seen by both pain neurology and neurosurgery at our center. Demographics were collected. Pain intensity was assessed using the numerical rating scale (NRS) and compared from baseline to after BTX-A treatment via paired t test. Responder status was assessed, and success of BTX-A was determined for each cohort. Doses of common medications were compared between baseline visit and the most recent BTX-A administration visit. RESULTS: Thirty-one patients underwent BTX-A therapy for TN, 24 (77%) female and 7 (23%) male. Mean age was 62.5 ± 3.1 years and 29 (94%) identified as white. When divided into cohorts according to indication, 11 (35%) failed prior TN surgery, 9 (29%) either declined surgery or were poor surgical candidates, 4 (13%) had multiple sclerosis, 4 (13%) had trigeminal neuropathic pain, and 3 (10%) had atypical TN with pain in additional dermatomes outside the trigeminal distribution. Significant reductions in NRS from baseline to following initial BTX-A treatment were seen in the declined/high risk for surgery (p = 0.004) and those who failed prior TN surgery (p = 0.035) groups. No significant variation in demographics was found between any two groups (p > 0.05 for all). Finally, there was no significant reduction in total daily dose of gabapentin, carbamazepine, oxcarbazepine, baclofen, or lamotrigine in BTX-A responders (p > 0.05 for all). DISCUSSION: Indication is an important predictor for BTX-A, with classical TN patients exhibiting the highest response rates. This research highlights the viability of BTX-A as an important tool in the arsenal of providers seeking to treat TN in a minimally invasive manner.

Toward Generalizable Trajectory Planning for Human Intracerebral Trials and Therapy.

INTRODUCTION: Stereotactic neurosurgical techniques are increasingly used to deliver biologics, such as cells and viruses, although standardized procedures are necessary to ensure consistency and reproducibility. OBJECTIVE: We provide an instructional guide to help plan for complex image-guided trajectories; this may be of particular benefit to surgeons new to biologic trials and companies planning such trials. METHODS: We show how nuclei can be segmented and multiple trajectories with multiple injection points can be created through a single or multiple burr hole(s) based on preoperative images. Screenshots similar to those shown in this article can be used for planning purposes and for quality control in clinical trials. RESULTS: This method enables the precise definition of 3-D target structures, such as the putamen, and efficient planning trajectories for biologic injections. The technique is generalizable and largely independent of procedural format, and thus can be integrated with frame-based or frameless platforms to streamline reproducible therapeutic delivery. CONCLUSIONS: We describe an easy-to-use and generalizable protocol for intracerebral trajectory planning for stereotactic delivery of biologics. Although we highlight intracerebral stem cell delivery to the putamen using a frame-based stereotactic delivery system, similar strategies may be employed for different brain nuclei using different platforms. We anticipate this will inform future advanced and fully automated neurosurgical procedures to help unify the field and decrease inherent variability seen with manual trajectory planning.

Revision and Replacement of Spinal Cord Stimulator Paddle Leads.

OBJECTIVES: Paddle leads for spinal cord stimulation (SCS) offer more efficient energy delivery and advantages in some patients. However, there is concern for how safely SCS paddles can be replaced once previously implanted because of scar tissue and the relative vulnerability of the thoracic cord. In this study, we share our experience on SCS paddle replacement. MATERIALS AND METHODS: Participants who underwent SCS replacement at Albany Medical Center between 2011 and 2020 were identified. The medical records were reviewed for demographic data and information regarding initial complications, reason for removal or revision, subsequent complications of replacement surgery and its timing, and whether the implant was ultimately removed. Percutaneous lead replacement cases performed over the same period were used as a comparison group. RESULTS: A total of 1265 patients were identified to have had an SCS-related procedure based on billing codes. Of these, 73 involved replacement of epidural leads (51 paddles, 22 percutaneous). Most paddles (48/51) were replaced at the time of removal. A total of 30 of the 51 paddle replacements required additional lamina removal. Re-operations that occurred more than one year after initial implant were significantly more likely to require additional bone removal (p < 0.001). Paddle re-operations lasted in general 1.7 ± 0.2 hours and had 35 ± 5 mL of blood loss, whereas percutaneous operations lasted 1.3 ± 0.2 hours and had 12.5 ± 2 mL of blood loss. Despite the invasive nature of paddle replacement, there was no difference in complications (p = 0.23) compared with that in percutaneous leads. CONCLUSIONS: This study characterizes the safety profile of SCS paddle replacement surgeries. Here, we demonstrate that the replacement of paddle leads at the time of removal, with additional lamina removal if needed because of scar, is associated with low rates of complications. This validates the feasibility and low-risk profile of replacing paddle leads when clinically indicated for experienced surgeons with specialization in SCS.

Association of Outcomes of Spinal Cord Stimulation for Chronic Low Back Pain and Psoas Measurements Based on Size of Iliopsoas Muscles.

INTRODUCTION: Patients experience variable long-term improvement in chronic back pain despite successful spinal cord stimulation (SCS) trials. Iliopsoas (IP) size has been shown to differ between patients with low back pain and healthy controls. In this study, we examine whether the IP muscle cross-sectional area (CSA) is associated with SCS outcomes. MATERIALS AND METHODS: We examined patients for whom we had lumbar MRIs 6.3 years prior to SCS and baseline and one-year outcome data. Percent change from baseline to one year was calculated for Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), Pain Catastrophizing Scale (PCS), and McGill Pain Questionnaire (MPQ). Correlations between IP muscle CSA, ratio of iliopsoas muscle size to the vertebral body area (P/VBA), and the ratio of iliopsoas muscle size to BMI (P/BMI) were examined. Sex differences were considered. RESULTS: A total of 73 subjects were included in this study, including 30 females and 43 males. Males had significantly larger IP (males 15.70 ± 0.58, females 9.72 ± 0.43; p < 0.001), P/VBA (males 1.00 ± 0.04, females 0.76 ± 0.03; p < 0.001), and P/BMI ratio (males 0.51 ± 0.02, females 0.32 ± 0.01; p < 0.001) than females. In females, P/VBA predicted NRS worst pain scores (ß = 0.82, p = 0.004, r2 = 0.55) and BDI (ß = 0.59, p = 0.02, r2 = 0.24). In males, P/BMI was a significant predictor of BDI outcome scores (ß = 0.45, p = 0.03, r2 = 0.16). Males who had more muscle mass measured by iliopsoas size had more depression as measured using BDI (p = 0.03, r = 0.61). Females with less muscle mass measured by P/VBA also experienced more depression (p = 0.02, r = 0.74). CONCLUSIONS: Our study showed that psoas measurements correlated with various pain outcomes specifically. P/VBA was most predictive in females and P/BMI in males. Depression correlated with P/BMI, reinforcing the complex relationship between depression and constant chronic pain. Tertile analyses further showed a relationship between iliopsoas CSA and depression in males and females. We provide preliminary data of sex-specific psoas measurements as a risk factor for worse SCS outcomes.

Low Intensity Focused Ultrasound Increases Duration of Anti-Nociceptive Responses in Female Common Peroneal Nerve Injury Rats.

OBJECTIVE: Chronic pain affects 7%-10% of Americans, occurs more frequently and severely in females, and available treatments have been shown to have less efficacy in female patients. Preclinical models addressing sex-specific treatment differences in the treatment of chronic pain have been limited. Here we examine the sex-specific effects of low intensity focused ultrasound (liFUS) in a modified sciatic nerve injury (SNI) model. MATERIALS AND METHODS: A modified SNI performed by ligating the common peroneal nerve (CPN) was used to measure sensory, behavioral pain responses, and nerve conduction studies in female and male rats, following liFUS of the L5 dorsal root ganglion. RESULTS: Using the same dose of liFUS in females and males of the same weight, CPN latency immediately after treatment was increased for 50 min in females compared to 25 min in males (p < 0.001). Improvements in mechanical pain thresholds after liFUS lasted significantly longer in females (seven days; p < 0.05) compared to males (three days; p < 0.05). In females, there was a significant improvement in depression-like behavior as a result of liFUS (N = 5; p < 0.01); however, because males never developed depression-like behavior there was no change after liFUS treatment. CONCLUSIONS: Neuromodulation with liFUS has a greater effect in female rats on CPN latency, mechanical allodynia duration, and depression-like behavior. In order to customize neuromodulatory techniques for different patient phenotypes, it is essential to understand how they may alter sex-specific pathophysiologies.

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized, Double-Blind Primary Endpoint.

OBJECTIVE: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease. MATERIALS AND METHODS: Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life. RESULTS: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period. CONCLUSION: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.

Predicting ablation zones with multislice volumetric 2-D magnetic resonance thermal imaging.

BACKGROUND: High-intensity focused ultrasound (HIFU) serves as a noninvasive stereotactic system for the ablation of brain metastases; however, treatments are limited to simple geometries and energy delivery is limited by the high acoustic attenuation of the calvarium. Minimally-invasive magnetic resonance-guided robotically-assisted (MRgRA) needle-based therapeutic ultrasound (NBTU) using multislice volumetric 2-D magnetic resonance thermal imaging (MRTI) overcomes these limitations and has potential to produce less collateral tissue damage than current methods. OBJECTIVE: To correlate multislice volumetric 2-D MRTI volumes with histologically confirmed regions of tissue damage in MRgRA NBTU. METHODS: Seven swine underwent a total of 8 frontal MRgRA NBTU lesions. MRTI ablation volumes were compared to histologic tissue damage on brain sections stained with 2,3,5-triphenyltetrazolium chloride (TTC). Bland-Altman analyses and correlation trends were used to compare MRTI and TTC ablation volumes. RESULTS: Data from the initial and third swine's ablations were excluded due to sub-optimal tissue staining. For the remaining ablations (n = 6), the limits of agreement between the MRTI and histologic volumes ranged from -0.149 cm3 to 0.252 cm3 with a mean difference of 0.052 ± 0.042 cm3 (11.1%). There was a high correlation between the MRTI and histology volumes (r2 = 0.831) with a strong linear relationship (r = 0.868). CONCLUSION: We used a volumetric MRTI technique to accurately track thermal changes during MRgRA NBTU in preparation for human trials. Improved volumetric coverage with MRTI enhanced our delivery of therapy and has far-reaching implications for focused ultrasound in the broader clinical setting.