Disparities in Access to Deep Brain Stimulation and Responsive Neurostimulation Approaches to Drug-Resistant Epilepsy.

BACKGROUND: Epilepsy affects 1% to 2% of the global population, and those who are resistant to medical treatment may be candidates for neuromodulation. In select populations, brain stimulation approaches including deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used. Although studies have shown that patients from Black, Hispanic, lower income, and rural communities have less access to epilepsy care and have lower rates of epilepsy surgery, disparities in the use of brain stimulation for epilepsy treatment are currently not known. MATERIALS AND METHODS: We queried the US National Inpatient Sample data base from January 1, 2014 to December 31, 2019 for all patients discharged with an International Classification of Diseases (ICD) Ninth Revision or ICD Tenth Revision diagnosis of drug-resistant epilepsy. Among these patients discharged, the rates of brain stimulation treatment, including DBS and RNS, were reported in each subgroup of race, ethnicity, and insurance. To generate national estimates, all analyses were weighted. RESULTS: A total of 237,895 patients discharged with drug-resistant epilepsy were identified, of whom 4,925 (2.1%) received brain stimulation treatment for drug-resistant epilepsy. Black patients (n = 420, 0.9%, odds ratio [OR] = 0.51, 95% CI [0.40, 0.64]) were less likely to receive brain stimulation treatment than were White patients (n = 3300, 2.4%). There was no significant difference between Asian (n = 105, 2.3%, OR = 0.80, 95% CI [0.53, 1.33]) and Hispanic (n = 655, 2.6%, OR = 0.95, 95% CI [0.77, 1.17]) patients and White patients. No significant difference was observed between female (n = 2515, 2.1%, OR = 1.02, 95% CI [0.89, 1.17]) and male (n = 2410, 2.0%) patients either. Patients with Medicare (n = 1150, 1.2%, OR = 0.69, 95% CI [0.57, 0.84]) or Medicaid (n = 1150, 1.8%, OR = 0.52, 95% CI [0.44, 0.62]) were less likely to receive brain stimulation treatment than were those with private insurance as the primary payer (n = 2370, 3.9%). CONCLUSIONS: We discovered significant disparities in the use of brain stimulation treatments for drug-resistant epilepsy based on race and insurance status. More research will be required to determine the cause of these disparities.

Five-Year Longitudinal Follow-Up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction.

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology. MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data. RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed. CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women's Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

Maximal Analgesic Effect Attained by the Use of Objective Neurophysiological Measurements With Closed-Loop Spinal Cord Stimulation.

OBJECTIVES: Spinal cord stimulation (SCS) has been challenged by the lack of neurophysiologic data to guide therapy optimization. Current SCS programming by trial-and-error results in suboptimal and variable therapeutic effects. A novel system with a physiologic closed-loop feedback mechanism using evoked-compound action potentials enables the optimization of physiologic neural dose by consistently and accurately activating spinal cord fibers. We aimed to identify neurophysiologic dose metrics and their ranges that resulted in clinically meaningful treatment responses. MATERIALS AND METHODS: Subjects from 3 clinical studies (n = 180) with baseline back and leg pain ≥60 mm visual analog scale and physical function in the severe to crippled category were included. Maximal analgesic effect (MAE) was operationally defined as the greatest percent reduction in pain intensity or as the greatest cumulative responder score (minimal clinically important differences [MCIDs]) obtained within the first 3 months of SCS implant. The physiologic metrics that produced the MAE were analyzed. RESULTS: We showed that a neural dose regimen with a high neural dose accuracy of 2.8µV and dose ratio of 1.4 resulted in a profound clinical benefit to chronic pain patients (MAE of 79 ± 1% for pain reduction and 12.5 ± 0.4 MCIDs). No differences were observed for MAE or neurophysiological dose metrics between the trial phase and post-implant MAE visit. CONCLUSION: For the first time, an evidence-based neural dose regimen is available for a neurostimulation intervention as a starting point to enable optimization of clinical benefit, monitoring of adherence, and management of the therapy.

Short-Term Health Care Costs of High-Frequency Spinal Cord Stimulation for the Treatment of Postsurgical Persistent Spinal Pain Syndrome.

OBJECTIVE: High-frequency spinal cord stimulation (HF-SCS) is a treatment option for postsurgical persistent spinal pain syndrome (type 2 PSPS). We aimed to determine the health care costs associated with this therapy in a nationwide cohort. MATERIALS AND METHODS: IBM Marketscan® Research Databases were used to identify patients who underwent HF-SCS implantation from 2016 to 2019. Inclusion criteria included prior spine surgery or diagnoses of PSPS or postlaminectomy pain syndrome any time within the two years before implantation. Inpatient and outpatient service costs, medication costs, and out-of-pocket costs were collected six months before implantation (baseline) and one, three, and six months after implantation. The six-month explant rate was calculated. Costs were compared between baseline and six months after implant via Wilcoxon sign rank test. RESULTS: In total, 332 patients were included. At baseline, patients incurred median total costs of $15,393 (Q1: $9,266, Q3: $26,216), whereas the postimplant median total costs excluding device acquisition were $727 (Q1: $309, Q3: $1,765) at one month, $2,840 (Q1: $1,170, Q3: $6,026) at three months, and $6,380 (Q1: $2,805, Q3: $12,637) at six months. The average total cost was reduced from $21,410 (SD $21,230) from baseline to $14,312 (SD $25,687) at six months after implant for an average reduction of $7,237 (95% CI = $3212-$10,777, p < 0.001). The median device acquisition costs were $42,937 (Q1: $30,102, Q3: $65,880). The explant rate within six months was 3.4% (8/234). CONCLUSIONS: HF-SCS for PSPS was associated with significant decreases in total health care costs and offsets acquisition costs within 2.4 years. With the rising incidence of PSPS, it will be critical to use clinically effective and cost-efficient therapies for treatment.

Health Care Resource Utilization of High-Frequency Spinal Cord Stimulation for Treatment of Chronic Refractory Low Back Pain.

INTRODUCTION: Chronic refractory low back pain (CRLBP) is a diagnosis characterized by chronic low back pain in patients who are poor candidates for surgery and fail conservative management. High-frequency spinal cord stimulation (HF-SCS) is a new advance in neuromodulation that may be effective in treating these patients. However, the cost burden of this therapy is yet undetermined. MATERIALS AND METHODS: IBM MarketScan® (IBM, Armonk, NY) data bases were used to retrospectively identify patients with HF-SCS implantation between 2016 and 2019 in the United States. Those with low back pain diagnosis without history of surgery were included in the cohort. Cost data, including inpatient and outpatient service, medication, and out-of-pocket costs, were collected at six months before HF-SCS implantation and one, three, and six months after implantation. The explant rate within six months was evaluated. RESULTS: A total of 119 patients met the inclusion criteria. Most patients were female (73.1%) and owned commercial insurance (83.2%). Common comorbidities included inflammatory arthritis (22.7%), depression (26.1%), hypertension (44.5%), and obesity (26.1%). In the six months before HF-SCS implantation, patients incurred median total costs of $15,766 (first quartile [Q1]: $8,847; third quartile [Q3]: $24,947), whereas the postimplant median total cost excluding device acquisition was $398 (Q1: $145, Q3: $1,272) at one month, $2,569 (Q1: $823, Q3: $5,266) at three months, and $5,840 (Q1: $2,160; Q3: $14,607) at six months. The average reduction in total cost was $6,914 (95% CI: $588, $12,458, p < 0.001). The median total acquisition cost was $43,586 (Q1: $29,506, Q3: $69,426), with most coming from outpatient services. Of 88 patients with six-month continuous enrollment, two (2.3%) had device explant. CONCLUSIONS: We present an analysis using large claims data bases of the cost of HF-SCS for treating CRLBP and show that it may be associated with a significant decrease in total health care costs, offsetting device acquisition costs in 27 months. As advances in neuromodulation expand therapy options for patients, it will be important to understand their financial implications.

Assessment of Health Care Costs and Total Baclofen Use Associated With Targeted Drug Delivery for Spasticity.

BACKGROUND: Chronic spasticity causes significant impairment and financial burden. Oral baclofen, the first-line therapy, can have intolerable, dose-dependent side effects. Targeted drug delivery (TDD) through intrathecal baclofen delivers smaller amounts of baclofen into the thecal sac via an implanted infusion system. However, the health care resource utilization of patients with spasticity receiving TDD has not been studied extensively. MATERIALS AND METHODS: Adult patients who received TDD for spasticity between 2009 and 2017 were identified using the IBM MarketScan® data bases. Patients' use of oral baclofen and health care costs were examined at baseline (one year before implantation) and three years after implantation. A multivariable regression model using the generalized estimating equations method and a log link function was used to compare postimplantation costs with those at baseline. RESULTS: The study identified 771 patients with TDD for medication analysis and 576 for cost analysis. At baseline, the median costs were $39,326 (interquartile range [IQR]: $19,526-$80,679), which increased to $75,728 (IQR: $44,199-$122,676) in year 1, decreased to $27,160 (IQR: $11,896-$62,427) in year 2, and increased slightly to $28,008 (IQR: $11,771-$61,885) in year 3. In multivariable analysis, the cost was 47% higher than at baseline (cost ratio [CR] 1.47, 95% CI: 1.32-1.63) in year 1 but was 25% lower (CR 0.75, 95% CI: 0.66-0.86) in year 2 and 32% lower (CR 0.68, 95% CI: 0.59-0.79) in year 3. Before implant, 58% of patients took oral baclofen, which decreased to 24% by year 3. The median daily baclofen dose decreased from 61.8 mg (IQR: 40-86.4) before TDD to 32.8 mg (IQR: 30-65.7) three years later. CONCLUSIONS: Our findings indicate that patients who undergo TDD use less oral baclofen, potentially reducing the risk of side effects. Although total health care costs increased immediately after TDD, most likely owing to device and implantation costs, they decreased below baseline after one year. The costs of TDD reach cost neutrality approximately three years after implant, indicating its potential for long-term cost savings.

Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial.

BACKGROUND: Impaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward. OBJECTIVE: This study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Open-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation. RESULTS: At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. CONCLUSIONS: At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The study is registered on clinicaltrials.gov with identifier NCT02577354.

Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction.

BACKGROUND: Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability. OBJECTIVE: Evaluation of three-year effectiveness and safety in patients with refractory, disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Prospective, observational follow-up of the 204 implanted trial participants. Low back pain visual analog scale (VAS), Oswestry Disability Index (ODI), EuroQol quality of life survey, and opioid intake were assessed at baseline, six months, and one, two, and three years after activation. The mixed-effects model repeated measures approach was used to provide implicit imputations of missing data for continuous outcomes and multiple imputation for proportion estimates. RESULTS: Data were collected from 133 participants, and 16 patients missed their three-year follow-up because of coronavirus disease restrictions but remain available for future follow-up. A total of 62% of participants had a ≥ 70% VAS reduction, and 67% reported CLBP resolution (VAS ≤ 2.5cm); 63% had a reduction in ODI of ≥ 20 points; 83% had improvements of ≥ 50% in VAS and/or ≥ 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 71% (36/51) participants on opioids at baseline had voluntarily discontinued (49%) or reduced (22%) opioid intake. The attenuation of effectiveness in the imputed (N = 204) analyses was relatively small and did not affect the statistical significance and clinical relevance of these results. The safety profile remains favorable, and no lead migrations have been observed to date. CONCLUSION: At three years, 83% of participants experienced clinically substantial improvements in pain, disability, or both. The results confirm the long-term effectiveness, durability, and safety of restorative neurostimulation in patients with disabling CLBP associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354.

Construct validity of the Surgical Autonomy Program for the training of neurosurgical residents.

OBJECTIVE: There is no standard way in which physicians teach or evaluate surgical residents intraoperatively, and residents are proving to not be fully competent at core surgical procedures upon graduating. The Surgical Autonomy Program (SAP) is a novel educational model that combines a modified version of the Zwisch scale with Vygotsky's social learning theory. The objective of this study was to establish preliminary validity evidence that SAP is a reliable measure of autonomy and a useful tool for tracking competency over time. METHODS: The SAP breaks each surgical case into 4 parts, or zones of proximal development (ZPDs). Residents are evaluated on a 4-tier autonomy scale (TAGS scale) for each ZPD in every surgical case. Attendings were provided with a teaching session about SAP and identified appropriate ZPDs for surgical cases under their area of expertise. All neurosurgery residents at Duke University Hospital from July 2017 to July 2021 participated in this study. Chi-square tests and ordinal logistic regression were used for the analyses. RESULTS: Between 2017 and 2021, there were 4885 cases logged by 27 residents. There were 30 attendings who evaluated residents using SAP. Faculty completed evaluations on 91% of cases. The ZPD of focus directly correlated with year of residency (postgraduate year) (χ2 = 1221.1, df = 15, p < 0.001). The autonomy level increased with year of residency (χ2 = 3553.5, df = 15, p < 0.001). An ordinal regression analysis showed that for every year increase in postgraduate year, the odds of operating at a higher level of independence was 2.16 times greater (95% CI 2.11-2.21, p < 0.001). The odds of residents performing with greater autonomy was lowest for the most complex portion of the case (ZPD3) (OR 0.18, 95% CI 0.17-0.20, p < 0.001). Residents have less autonomy with increased case complexity (χ2 = 160.28, df = 6, p < 0.001). Compared with average cases, residents were more likely to operate with greater autonomy on easy cases (OR 1.44, 95% CI 1.29-1.61, p < 0.001) and less likely to do so on difficult cases (OR 0.72, 95% CI 0.67-0.77, p < 0.001). CONCLUSIONS: This study demonstrates preliminary evidence supporting the construct validity of the SAP. This tool successfully tracks resident autonomy and progress over time. The authors' smartphone application was widely used among surgical faculty and residents, supporting integration into the perioperative workflow. Wide implementation of SAP across multiple surgical centers will aid in the movement toward a competency-based residency education system.

Palliative Care Consultations in Patients with Severe Traumatic Brain Injury: Who Receives Palliative Care Consultations and What Does that Mean for Utilization?

BACKGROUND: Palliative care has the potential to improve goal-concordant care in severe traumatic brain injury (sTBI). Our primary objective was to illuminate the demographic profiles of patients with sTBI who receive palliative care encounters (PCEs), with an emphasis on the role of race. Secondary objectives were to analyze PCE usage over time and compare health care resource utilization between patients with or without PCEs. METHODS: The National Inpatient Sample database was queried for patients age ≥ 18 who had a diagnosis of sTBI, defined by using International Classification of Diseases, 9th Revision codes. PCEs were defined by using International Classification of Diseases, 9th Revision code V66.7 and trended from 2001 to 2015. To assess factors associated with PCE in patients with sTBI, we performed unweighted generalized estimating equations regression. PCE association with decision making was modeled via its effect on rate of percutaneous endoscopic gastrostomy (PEG) tube placement. To quantify differences in PCE-related decisions by race, race was modeled as an effect modifier. RESULTS: From 2001 to 2015, the proportion of palliative care usage in patients with sTBI increased from 1.5 to 36.3%, with 41.6% White, 22.3% Black, and 25% Hispanic patients with sTBI having a palliative care consultation in 2015, respectively. From 2008 to 2015, we identified 17,673 sTBI admissions. White and affluent patients were more likely to have a PCE than Black, Hispanic, and low socioeconomic status patients. Across all races, patients receiving a PCE resulted in a lower rate of PEG tube placement; however, White patients exhibited a larger reduction of PEG tube placement than Black patients. Patients using palliative care had lower total hospital costs (median $16,368 vs. $26,442, respectively). CONCLUSIONS: Palliative care usage for sTBI has increased dramatically this century and it reduces resource utilization. This is true across races, however, its usage rate and associated effect on decision making are race-dependent, with White patients receiving more PCE and being more likely to decline the use of a PEG tube if they have had a PCE.

Feasibility study of a novel digital health platform for patients undergoing transcatheter aortic valve replacement.

INTRODUCTION: Despite abundant evidence indicating that digital health solutions improve outcomes in chronic medical conditions, there are few validated solutions for acute surgical episodes. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to open surgery that is becoming more prevalent. We assessed the feasibility of ManageMySurgery (MMS), a smartphone application that combines patient education and outcomes tracking for patients undergoing TAVR procedures. METHODS: MMS was offered to patients receiving TAVR at an academic health center. Pre- and postoperatively, patients completed app-based tasks and reported clinical results using validated NYHA and KCCQ-12 surveys. Additionally, users reported levels of satisfaction with the digital platform. RESULTS: Sixty-nine patients were invited to use MMS, of which 43 (62%) downloaded and used the platform. The median age of patients was 77 years and 66.7% were male. The platform was accessed at an average of 2.6 times per user, with 79.1% of patients logging in one to three times. On average, 5.2 frequently asked questions were viewed. Of the 37 patients who completed the feedback survey (86%), 73.0% said it was helpful in preparation for surgery and 86.5% would recommend MMS to others. DISCUSSION: It is possible to utilize a digital health platform to guide patients undergoing TAVR through their interventional journey. Additional research is warranted to assess whether digital patient navigation tools provide an added benefit over traditional perioperative care alone, in terms of long-term patient engagement and outcomes.

A high-resolution interactive atlas of the human brainstem using magnetic resonance imaging.

Conventional atlases of the human brainstem are limited by the inflexible, sparsely-sampled, two-dimensional nature of histology, or the low spatial resolution of conventional magnetic resonance imaging (MRI). Postmortem high-resolution MRI circumvents the challenges associated with both modalities. A single human brainstem specimen extending from the rostral diencephalon through the caudal medulla was prepared for imaging after the brain was removed from a 65-year-old male within 24 h of death. The specimen was formalin-fixed for two weeks, then rehydrated and placed in a custom-made MRI compatible tube and immersed in liquid fluorocarbon. MRI was performed in a 7-Tesla scanner with 120 unique diffusion directions. Acquisition time for anatomic and diffusion images were 14 h and 208 h, respectively. Segmentation was performed manually. Deterministic fiber tractography was done using strategically chosen regions of interest and avoidance, with manual editing using expert knowledge of human neuroanatomy. Anatomic and diffusion images were rendered with isotropic resolutions of 50 µm and 200 µm, respectively. Ninety different structures were segmented and labeled, and 11 different fiber bundles were rendered with tractography. The complete atlas is available online for interactive use at https://www.civmvoxport.vm.duke.edu/voxbase/login.php?return_url=%2Fvoxbase%2F. This atlas presents multiple contrasting datasets and selected tract reconstruction with unprecedented resolution for MR imaging of the human brainstem. There are immediate applications in neuroanatomical education, with the potential to serve future applications for neuroanatomical research and enhanced neurosurgical planning through "safe" zones of entry into the human brainstem.

High-Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Nonsurgical Refractory Back Pain: Design of a Pragmatic, Multicenter, Randomized Controlled Trial.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to provide pain relief for chronic back and leg pain due to failed back surgery syndrome. But many patients with chronic back pain have not had major back surgery or are not good candidates for surgery, and conventional medical management (CMM) provides limited relief. We have termed this condition nonsurgical refractory back pain (NSRBP). Level 1 evidence does not yet exist showing the therapeutic benefit of SCS for NSRBP. OBJECTIVE: To compare 10-kHz SCS plus CMM (10-kHz SCS + CMM) to CMM alone for treatment of NSRBP in terms of clinical and cost effectiveness. STUDY DESIGN: Multicenter, randomized controlled trial (RCT), with subjects randomized 1:1 to either 10-kHz SCS + CMM or CMM alone. Optional crossover occurs at 6 months if treatment does not achieve ≥50% pain relief. METHODS: Patients with NSRBP as defined above may be enrolled if they are ineligible for surgery based on surgical consultation. Subjects randomized to 10-kHz SCS + CMM will receive a permanent implant if sufficient pain relief is achieved in a temporary trial. Both groups will receive CMM per standard of care and will undergo assessments at baseline and at follow-ups to 12 months. Self-report outcomes include pain, disability, sleep, mental health, satisfaction, healthcare utilization, and quality of life. RESULTS: Enrollment was initiated on September 10, 2018. Prespecified independent interim analysis at 40% of the enrollment target indicated the sample size was sufficient to show superiority of treatment at the primary endpoint; therefore, enrollment was stopped at 211. CONCLUSIONS: This large multicenter RCT will provide valuable evidence to guide clinical decisions in NSRBP.

Impact of Neurapheresis System on Intrathecal Cerebrospinal Fluid Dynamics: A Computational Fluid Dynamics Study.

It has been hypothesized that early and rapid filtration of blood from cerebrospinal fluid (CSF) in postsubarachnoid hemorrhage patients may reduce hospital stay and related adverse events. In this study, we formulated a subject-specific computational fluid dynamics (CFD) model to parametrically investigate the impact of a novel dual-lumen catheter-based CSF filtration system, the Neurapheresis™ system (Minnetronix Neuro, Inc., St. Paul, MN), on intrathecal CSF dynamics. The operating principle of this system is to remove CSF from one location along the spine (aspiration port), externally filter the CSF routing the retentate to a waste bag, and return permeate (uncontaminated CSF) to another location along the spine (return port). The CFD model allowed parametric simulation of how the Neurapheresis system impacts intrathecal CSF velocities and steady-steady streaming under various Neurapheresis flow settings ranging from 0.5 to 2.0 ml/min and with a constant retentate removal rate of 0.2 ml/min simulation of the Neurapheresis system were compared to a lumbar drain simulation with a typical CSF removal rate setting of 0.2 ml/min. Results showed that the Neurapheresis system at a maximum flow of 2.0 ml/min increased average steady streaming CSF velocity 2× in comparison to lumbar drain (0.190 ± 0.133 versus 0.093 ± 0.107 mm/s, respectively). This affect was localized to the region within the Neurapheresis flow loop. The mean velocities introduced by the flow loop were relatively small in comparison to normal cardiac-induced CSF velocities.

Structural mapping with fiber tractography of the human cuneate fasciculus at microscopic resolution in cervical region.

Human spinal white matter tract anatomy has been mapped using post mortem histological information with the help of molecular tracing studies in animal models. This study used 7 Tesla diffusion MR tractography on a human cadaver that was harvested 24 hours post mortem to evaluate cuneate fasciculus anatomy in cervical spinal cord. Based on this method, for the first time much more nuanced tractographic anatomy was used to investigate possible new routes for cuneate fasciculus in the posterior and lateral funiculus. Additionally, current molecular tracing studies were reviewed, and confirmatory data was presented along with our radiological results. Both studies confirm that upon entry to the spinal cord, upper cervical level tracts (C1-2-3) travel inside lateral funiculus and lower level tracts travel medially inside the posterior funiculus after entry at posterolateral sulcus which is different than traditional knowledge of having cuneate fasciculus tracts concentrated in the lateral part of posterior funiculus.

Spinal Cord Stimulation for Restless Legs Syndrome: Case Series and Mechanistic Hypothesis.

BACKGROUND: Spinal cord stimulation (SCS) is a well-established therapy for chronic pain syndromes, with growing applicability to other conditions. Restless legs syndrome (RLS) is a widespread, chronic movement disorder managed primarily and incompletely by medication, and its etiology can be classified as idiopathic or secondary. METHODS: Three patients underwent SCS implantation for chronic back and/or leg pain with concomitant targeting of RLS: (1) a 34-year-old man with sporadic RLS symptoms that strongly intensified after military-related spinal fractures, (2) a 54-year-old man with RLS likely secondary to meralgia paresthetica, and (3) a 42-year-old man with low back and right lower extremity pain after a military motor vehicle accident. RESULTS: Continuing through 40-month, 2-month, and 28-month follow-ups, respectively, the patients experienced exemplary relief of their RLS symptoms. Notably in the case of patient 1, this benefit appears separate from his pain relief, as during the 5-month period directly after surgery but before adjusted targeting, he only experienced pain alleviation. CONCLUSIONS: To our knowledge, this is the first reported case of using SCS as a potentially long-lasting, safe, and highly effective therapy for RLS of mixed etiology. Additionally, 2 patients with RLS possibly secondary to chronic pain also benefited from the therapy. This success may be due to increased inhibition from hypothalamic cells controlling dopaminergic input to the spine.

Prevalence and Cost Analysis of Chronic Pain After Hernia Repair: A Potential Alternative Approach With Neurostimulation.

OBJECTIVES: Chronic pain (CP) affects a significant number of patients following hernia repair, ranging from 11 to 54% in the literature. The aim of this study was to assess the prevalence, overall costs, and health care utilization associated with CP after hernia repair. MATERIALS AND METHODS: A retrospective longitudinal study was performed using the Truven MarketScan® data base to identify patients who develop chronic neuropathic posthernia repair pain from 2001 to 2012. Patients were grouped into CP and No Chronic Pain (No CP) cohorts. Patients were excluded if they 1) were under 18 years of age; 2) had a previous pain diagnosis; 3) had CP diagnosed <90 days after the index hernia repair; 4) had less than one year of follow-up; or 5) had less than one-year baseline record before hernia repair. Patients were grouped into the CP cohort if their CP diagnosis was made within the two years following index hernia repair. Total, outpatient, and pain prescription costs were collected in the period of five years prehernia to nine years posthernia repair. A longitudinal multivariate analysis was used to model the effects of chronic neuropathic posthernia repair pain on total inpatient/outpatient and pain prescription costs. RESULTS: We identified 76,173 patients who underwent hernia repair and met inclusion criteria (CP: n = 14,919, No CP: n = 61,254). There was a trend for increased total inpatient/outpatient and pain prescription costs one-year posthernia repair, when compared to baseline costs for both cohorts. In both cohorts, total inpatient/outpatient costs remained elevated from baseline through nine years posthernia repair, with the CP cohort experiencing significantly higher cumulative median costs (CP: $51,334, No CP: $37,388). The CP diagnosis year was associated with a 1.75-fold increase (p < 0.001) in total inpatient/outpatient costs and a 2.26-fold increase (p < 0.001) in pain prescription costs versus all other years. In the longitudinal analysis, the CP cohort had a 1.14-fold increase (p < 0.001) in total inpatient/outpatient costs and 2.00-fold increase (p < 0.001) in pain prescription costs. CONCLUSIONS: Our study demonstrates the prevalence of CP after hernia surgery to be nearly 20%, with significantly increased costs and healthcare resource utilization. While current treatment paradigms are effective for many, there remains a large number of patients that could benefit from an overall approach that includes nonopioid treatments, such as potentially incorporating neurostimulation, for CP that presents posthernia repair.

Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy.

Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal meningitis worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite a significant improvement in survival compared with uniform mortality without treatment, this drug paradigm has not led to a consistent cure. Neurapheresis therapy, extracorporeal filtration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro filtration of CSF through this platform yielded a 5-log reduction in concentration of the yeast and a 1-log reduction in its polysaccharide antigen over 24 hours. Additionally, an analogous closed-loop system achieved 97% clearance of yeasts from the subarachnoid space in a rabbit model over 4-6 hours. This is the first publication demonstrating the direct ability to rapidly clear, both in vitro and in vivo, the otherwise slowly removed fungal pathogen that directly contributes to the morbidity and mortality seen in CM.

Prevalence and Cost Analysis of Complex Regional Pain Syndrome (CRPS): A Role for Neuromodulation.

OBJECTIVE: The diagnosis and treatment of complex regional pain syndrome (CRPS) is challenging and there is a paucity of data describing its overall cost burden and quantifying its impact on the US healthcare system. The aim of this study was to assess the prevalence and healthcare utilization costs associated with CRPS. MATERIALS AND METHODS: A retrospective longitudinal study was performed using the Truven MarketScan® database to identify patients with a new indexed diagnosis of CRPS (Type I, II, or both) from 2001 to 2012. We collected total, outpatient, and pain prescription costs three years prior to CRPS diagnosis (baseline), at year of CRPS diagnosis, and eight-year post-CRPS diagnosis. A longitudinal multivariate analysis was used to model the estimated total and pain prescription cost ratios comparing patients diagnosed before and after CRPS. RESULTS: We included 35,316 patients with a newly indexed diagnosis of CRPS (Type I: n = 18,703, Type II: n = 14,599, Unspecified: n = 2014). Baseline characteristics were similar between the CRPS cohorts. Compared to two- and three-year baseline costs, one-year prior to diagnosis for all CRPS patients yielded the highest interquartile median [IQR] costs: total costs $7904[$3469, $16,084]; outpatient costs $6706[$3119, $12,715]; and pain prescription costs $1862[$147, $7649]. At the year of CRPS diagnosis, the median [IQR] costs were significantly higher than baseline costs: total costs $8508[$3943, $16,666]; outpatient costs $7251[$3527, $13,568]; and pain prescription costs $2077[$140, $8856]. Over the eight-year period after CRPS diagnosis, costs between all the years were similar, ranging from the highest (one-year) to lowest (seven-years), $4845 to $3888. The median total cumulative cost 8-years after CRPS diagnosis was $43,026 and $12,037 for pain prescription costs. [Correction added on 06 November 2017 after first online publication: the preceding sentence has been updated to demonstrate the median cumulative cost in replacement of the additive cumulative mean costs.]. During the CRPS diagnosis period, patients are expected to have a total cost 2.17-fold and prescription cost 2.56-fold of their baseline cost annually. CONCLUSIONS: Our study demonstrates that there is a significant increase in cost and healthcare resource utilization one-year prior to and around the time of CRPS diagnosis. Furthermore, there is an increased annual cost post-diagnosis compared to baseline costs prior to CRPS diagnosis.

Drivers and Risk Factors of Unplanned 30-Day Readmission Following Spinal Cord Stimulator Implantation.

OBJECTIVES: Unplanned 30-day readmission rates contribute significantly to growing national healthcare expenditures. Drivers of unplanned 30-day readmission after spinal cord stimulator (SCS) implantation are relatively unknown. The aim of this study was to determine drivers of 30-day unplanned readmission following SCS implantation. METHODS: The National Readmission Database was queried to identify all patients who underwent SCS implantation for the 2013 calendar year. Patients were grouped by readmission status, "No Readmission" and "Unplanned 30-day Readmission." Patient demographics and comorbidities were collected for each patient. The primary outcome of interest was the rate of unplanned 30-day readmissions and associated driving factors. A multivariate analysis was used to determine independent predictors of unplanned 30-day readmission after SCS implantation. RESULTS: We identified 1521 patients who underwent SCS implantation, with 113 (7.4%) experiencing an unplanned readmission within 30 days. Baseline patient demographics, comorbidities, and hospital characteristics were similar between both cohorts. The three main drivers for 30-day readmission after SCS implantation include: 1) infection (not related to SCS device), 2) infection due to device (limited to only hardware infection), and 3) mechanical complication of SCS device. Furthermore, obesity was found to be an independent predictor of 30-day readmission (OR: 1.86, p = 0.008). CONCLUSION: Our study suggests that infectious and mechanical complications are the primary drivers of unplanned 30-day readmission after SCS implantation, with obesity as an independent predictor of unplanned readmission. Given the technological advancements in SCS, repeated studies are necessary to identify factors associated with unplanned 30-day readmission rates after SCS implantation to improve patient outcomes and reduce associated costs.