Neurophysiological outcomes that sustained clinically significant improvements over 3 years of physiologic ECAP-controlled closed-loop spinal cord stimulation for the treatment of chronic pain.

INTRODUCTION: A novel, spinal cord stimulation (SCS) system with a physiologic closed-loop (CL) feedback mechanism controlled by evoked compound action potentials (ECAPs) enables the optimization of physiologic neural dose and the accuracy of the stimulation, not possible with any other commercially available SCS systems. The report of objective spinal cord measurements is essential to increase the transparency and reproducibility of SCS therapy. Here, we report a cohort of the EVOKE double-blind randomized controlled trial treated with CL-SCS for 36 months to evaluate the ECAP dose and accuracy that sustained the durability of clinical improvements. METHODS: 41 patients randomized to CL-SCS remained in their treatment allocation and were followed up through 36 months. Objective neurophysiological data, including measures of spinal cord activation, were analyzed. Pain relief was assessed by determining the proportion of patients with ≥50% and ≥80% reduction in overall back and leg pain. RESULTS: The performance of the feedback loop resulted in high-dose accuracy by keeping the elicited ECAP within 4µV of the target ECAP set on the system across all timepoints. Percent time stimulating above the ECAP threshold was >98%, and the ECAP dose was ≥19.3µV. Most patients obtained ≥50% reduction (83%) and ≥80% reduction (59%) in overall back and leg pain with a sustained response observed in the rates between 3-month and 36-month follow-up (p=0.083 and p=0.405, respectively). CONCLUSION: The results suggest that a physiological adherence to supra-ECAP threshold therapy that generates pain inhibition provided by ECAP-controlled CL-SCS leads to durable improvements in pain intensity with no evidence of loss of therapeutic effect through 36-month follow-up.

Impact of temperature on the magnitude and duration of relief after lumbar facets medial branch nerves radiofrequency ablation: a randomized double-blinded study.

INTRODUCTION: There are numerous studies appraising the variables that may influence the clinical outcomes after lumbar thermal radiofrequency ablation (RFA). Expanding the lesion size may increase the likelihood of capturing the target nerves in the lesion, thereby increasing the technical success rate of RFA. However, our literature search has failed to identify a consensus on the optimal target temperature. A retrospective study demonstrated that there seems to be significant functional improvement associated with the temperature of 90°C compared with 80°C. The authors prospectively studied the subject in a double-blinded randomized fashion. METHODS: Patients undergoing RFA for lumbar facetogenic pain were randomized in two cohorts (80°C and 90°C). Physicians and patients were blinded to the temperature used. The primary outcome was self-reported pain scores up to 12 months. Secondary outcomes included: self-reported functional improvement, duration of relief as measured by the time before repeat ablation of the same medial branches nerves, opioids' consumption, and patient satisfaction. RESULTS: Both groups reported pain improvement in all follow-up time points. Overall, both groups achieved statistically significant pain reduction (p<0.05). The median time to repeat RFA in the 80°C group was 112 (49-252) days, while it was 217 (198-348) days in the 90°C group (p<0.04). The univariate analysis emphasized that the RFA temperature is a statistically significant factor for pain improvement of more than 50%, OR 2.7 (1.1 to 6.6) p value=0.031. CONCLUSION: RFA has been demonstrated as an effective therapeutic modality for lumbar facetogenic back pain. Yet, the several factors involved in determining a favorable outcome of this procedure require further research and optimization. This prospective double-blinded randomized trial demonstrated that RFA at both temperatures (80°C, 90°C) provided significance at all the time periods examined. However, RFA at 90°C was superior to 80°C in regard to the duration of relief.

Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial.

INTRODUCTION: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. METHODS: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. RESULTS: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p<0.001 at all time points). CONCLUSION: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. TRIAL REGISTRATION NUMBER: NCT02924129.

Patient and physician radiation exposure during minimally invasive lumbar decompression: A prospective assessment of X-ray exposure risks.

INTRODUCTION: Minimally invasive lumbar decompression (mild®) is becoming a popular procedure for treating lumbar spinal stenosis (LSS) secondary to hypertrophic ligamentum flavum (LF). The mild® procedure is commonly performed under live fluoroscopic guidance and carries a risk of radiation exposure to the patient and healthcare. METHODS: One physician performed mild® on 41 patients at the Cleveland Clinic Department of Pain Management from October 2019 to December 2021, while wearing a radiation exposure monitor (Mirion Technologies). Mean fluoroscopy time, mean exposure per case, and mean exposure per unilateral level decompressed were the primary outcomes measured. The secondary outcome was to provide a comparison of radiation exposure during similar fluoroscopically guided procedures. RESULTS: Mean patient fluoroscopy exposure time was 2.1 min ±0.9 (range: 1.1-5.6) fluoroscopy time per unilateral level decompressed. The mean patient radiation skin exposure from mild® was 1.1 ± 0.9 mGym2, and the mean total dose was 142.3 ± 108.6 mGy per procedure. On average, the physician was exposed to an average deep tissue exposure of 4.1 ± 3.2 mRem, 2.9 ± 2.2 mRem estimated eye exposure, and 14.7 ± 11.0 mRem shallow tissue exposure per unilateral level decompressed. An individual physician would exceed the annual exposure limit of 5 Rem after approximately 610 mild® procedures per year. CONCLUSIONS: This study is an attempt to quantify the radiation exposure to the physician and patient during the mild® procedure. Compared with other fluoroscopically guided pain management procedures, patient and physician radiation exposure during mild® was low.

The MOTION study: Two-year results of a real-world randomized controlled trial of the mild® procedure for treatment of lumbar spinal stenosis.

OBJECTIVE: The MOTION study is designed to measure the impact of percutaneous image-guided lumbar decompression as a first-line therapy on patients otherwise receiving real-world conventional medical management for lumbar spinal stenosis with neurogenic claudication secondary to hypertrophic ligamentum flavum. This prospective, multicenter randomized controlled trial uses objective and patient-reported outcome measures to compare the combination of the mild® percutaneous treatment and nonsurgical conventional medical management (CMM) to CMM-Alone. METHODS: Test group patients received the mild procedure after study enrollment. Test and control groups were allowed conventional conservative therapies and low-risk interventional therapies as recommended by their physicians. Subjective outcomes included the Oswestry Disability Index, Numeric Pain Rating Scale, and Zurich Claudication Questionnaire. Objective outcomes included a validated Walking Tolerance Test, the rate of subsequent lumbar spine interventions, and safety data. RESULTS: Two-year follow-up included 64 mild + CMM and 67 CMM-Alone patients. All outcome measures showed significant improvement from baseline for mild + CMM, whereas the majority of CMM-Alone patients had elected to receive mild treatment or other lumbar spine interventions by 2 years, precluding valid 2-year between-group comparisons. Neither group reported any device- or procedure-related adverse events. CONCLUSIONS: The durability of mild + CMM for this patient population was demonstrated for all efficacy outcomes through 2 years. Improvements in walking time from baseline to 2 years for patients treated with mild + CMM were significant and substantial. The lack of reported device or procedure-related adverse events reinforces the strong safety profile of the mild procedure. These results provide support for early interventional treatment of symptomatic LSS with the mild procedure.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

INTRODUCTION: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group. CONCLUSION: This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS. TRIAL REGISTRATION NUMBER: NCT02924129.

Pain Management Interventions for the Treatment of Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: Determine the relative effectiveness and safety profiles of percutaneous and minimally invasive interventions for chronic low back pain. METHODS: A systematic search was performed for randomized controlled trials published in the past 20 years reporting on radiofrequency ablation of the basivertebral, disk annulus and facet nerve structures, steroid injection of the disk, facet joint, and medial branch, biological therapies, and multifidus muscle stimulation. Outcomes evaluated included Visual Analog Scale (VAS) pain scores, Oswestry Disability Index (ODI) scores, quality of life (SF-36 and EQ-5D) scores, and serious adverse event (SAE) rates. Basivertebral nerve (BVN) ablation was chosen as the subject of comparison to all other therapies using a random-effects meta-analysis. RESULTS: Twenty-seven studies were included. BVN ablation was found to provide statistically significant improvements in VAS and ODI scores for 6-, 12- and 24-month follow-up ( P ≤0.05). Biological therapy and multifidus muscle stimulation were the only 2 treatments with both VAS and ODI outcomes not significantly different from BVN ablation at 6-, 12-, and 24-month follow-up. All outcomes found to be statistically significant represented inferior results to those of BVN ablation. Insufficient data precluded meaningful comparisons of SF-36 and EQ-5D scores. The SAE rates for all therapies and all reported time points were not significantly different from BVN ablation except for biological therapy and multifidus muscle stimulation at the 6-month follow-up. CONCLUSIONS: BVN ablation, biological therapy, and multifidus stimulation all provide significant, durable improvements in both pain and disability compared with other interventions, which provided only short-term pain relief. Studies on BVN ablation reported no SAEs, a significantly better result than for studies of biological therapy and multifidus stimulation.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis.

OBJECTIVE: Spinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. MATERIALS AND METHODS: The EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. RESULTS: The mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved "good sleep quality" scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. "Normative" sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. CONCLUSIONS: ECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. CLINICAL TRAIL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02924129.

The MOTION Study: A Randomized Controlled Trial with Objective Real-World Outcomes for Lumbar Spinal Stenosis Patients Treated with the mild® Procedure: One-Year Results.

OBJECTIVE: The purpose of this study is to provide Level-1 objective, real-world outcome data for patients with lumbar spinal stenosis suffering from neurogenic claudication secondary to hypertrophic ligamentum flavum. DESIGN: The MOTION Study is a prospective, multicenter, randomized controlled trial comparing the mild® Procedure (minimally invasive lumbar decompression; Vertos Medical, Aliso Viejo, CA, USA) as a first-line therapy in combination with nonsurgical conventional medical management (CMM) vs CMM alone as the active control. METHODS: Patients in the test group received the mild Procedure at baseline. Both the mild+CMM group and the control group were allowed unrestricted access to conventional real-world therapies. Patient-reported outcomes included the Oswestry Disability Index, the Zurich Claudication Questionnaire, and the Numeric Pain Rating Scale. A validated Walking Tolerance Test, the incidence of subsequent lumbar spine interventions, and the occurrence of adverse events were used to measure objective outcomes. RESULTS: Sixty-nine patients in each group were analyzed at 1-year follow-up. No device- or procedure-related adverse events were reported in either group. Results from all primary and secondary outcome measures showed statistical significance in favor of mild+CMM. CONCLUSIONS: One-year results of this Level-1 study demonstrated superiority of mild+CMM over CMM alone for patients with lumbar spinal stenosis who were suffering from neurogenic claudication secondary to hypertrophic ligamentum flavum. Use of the validated Walking Tolerance Test to objectively measure increased ability to walk without severe symptoms provided evidence of statistically significantly better outcomes for mild+CMM than for CMM alone. With no reported device or procedure-related adverse events, the long-standing safety profile of the mild Procedure was reaffirmed. mild is a safe, durable, minimally invasive procedure that has been shown to be effective as an early interventional therapy for patients suffering from symptomatic lumbar spinal stenosis.

Durability of Clinical and Quality-of-Life Outcomes of Closed-Loop Spinal Cord Stimulation for Chronic Back and Leg Pain: A Secondary Analysis of the Evoke Randomized Clinical Trial.

Importance: Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system. Objective: To determine whether ECAP-controlled, closed-loop SCS is associated with better outcomes compared with fixed-output, open-loop SCS at 24 months following implant. Design, Setting, and Participants: The Evoke study was a double-blind, randomized, controlled, parallel arm clinical trial with 36 months of follow-up. Participants were enrolled from February 2017 to 2018, and the study was conducted at 13 US investigation sites. SCS candidates with chronic, intractable back and leg pain refractory to conservative therapy, who consented, were screened. Key eligibility criteria included overall, back, and leg pain visual analog scale score of 60 mm or more; Oswestry Disability Index score of 41 to 80; stable pain medications; and no previous SCS. Analysis took place from October 2020 to April 2021. Interventions: ECAP-controlled, closed-loop SCS was compared with fixed-output, open-loop SCS. Main Outcomes and Measures: Reported here are the 24-month outcomes of the trial, which include all randomized patients in the primary and safety analyses. The primary outcome was a reduction of 50% or more in overall back and leg pain assessed at 3 and 12 months (previously published). Results: Of 134 randomized patients, 65 (48.5%) were female and the mean (SD) age was 55.2 (10.6) years. At 24 months, significantly more closed-loop than open-loop patients were responders (≥50% reduction) in overall pain (53 of 67 [79.1%] in the closed-loop group; 36 of 67 [53.7%] in the open-loop group; difference, 25.4% [95% CI, 10.0%-40.8%]; P = .001). There was no difference in safety profiles between groups (difference in rate of study-related adverse events: 6.0 [95% CI, -7.8 to 19.7]). Improvements were also observed in health-related quality of life, physical and emotional functioning, and sleep, in parallel with opioid reduction or elimination. Objective neurophysiological measurements substantiated the clinical outcomes and provided evidence of activation of inhibitory pain mechanisms. Conclusions and Relevance: ECAP-controlled, closed-loop SCS, which elicited a more consistent neural response, was associated with sustained superior pain relief at 24 months, consistent with the 3- and 12-month outcomes.

Impact of biological sex on the outcomes of spinal cord stimulation in patients with chronic pain.

BACKGROUND: Spinal cord stimulation (SCS) continues to gain increasing popularity in the pain management field for the treatment of different painful conditions; however, to-date, the correlation between the SCS effectiveness and biological sex has not been fully established. We aimed to investigate the correlation between the biological sex and SCS outcomes. METHODS: Following Institutional Review Board approval, a retrospective cohort study was performed by collecting data for patients treated with SCS at a tertiary academic center between the years 2002 and 2019. Data was assessed with multivariable linear regression to investigate the association between biological sex and pain scores at baseline, 6-, and 12- months following SCS implantation. Propensity score matching (PSM) was performed based on a set of covariates including age, duration of pain, time since implant, BMI, opioid medications use, smoking, depression and history of alcohol, or substance abuse. RESULTS: Of the patients treated with SCS implants, 418 patients fit the inclusion and exclusion criteria, out of which the majority were females (272, 65%). The pre-matching data reported a significant difference in history of diabetes and depression and was also significant for greater opioid use in male patients at baseline, 6-, and 12-months post-SCS implant. Propensity score matching (PSM) was performed based on the above mentioned covariant. After matching, no statistical difference was found among the variables, in both groups. Furthermore, after matching no significant differences in the pain scores at baseline, 6-, and 12-months post-SCS implant were observed. CONCLUSION: No biological sex-based differences in the analgesic response to SCS therapy was detected at 6- and 12-months post-SCS implant between groups with similar demographics, biomedical, and psychological values.

The durability of minimally invasive lumbar decompression procedure in patients with symptomatic lumbar spinal stenosis: Long-term follow-up.

BACKGROUND: Minimally invasive lumbar decompression (mild® ) has been shown to be safe and effective for the treatment of lumbar spinal stenosis patients with hypertrophic ligamentum flavum as a contributing factor. This study examines the long-term durability of the mild procedure through 5-year follow-up. Pain relief and opioid medications utilization during 12-month follow-up were also assessed. METHODS: All patients diagnosed with lumbar spinal stenosis secondary to ligamentum flavum hypertrophy who underwent mild from 2010 through 2015 at the Cleveland Clinic Department of Pain Management were included in this retrospective longitudinal observational cohort study. The primary outcome measure was the incidence of open lumbar decompression surgery at the same level(s) as the mild intervention during 5-year follow-up. Secondary outcome measures were the change in pain levels using the Numeric Rating Scale and opioid medications utilization using Morphine Milligram Equivalent dose per day from baseline to 3, 6, and 12 months post-mild procedure. Postprocedural complications (minor or major) were also collected. RESULTS: Seventy-five patients received mild during the protocol-defined time period and were included in the study. Only 9 out of 75 patients required lumbar surgical decompression during the 5-year follow-up period. Subjects experienced statistically significant pain relief and reduction of opioid medications utilization at 3, 6, and 12 months compared to baseline. CONCLUSION: Based on our analysis, the mild procedure is durable over 5 years and may allow elderly patients with symptomatic lumbar spinal stenosis to avoid lumbar decompression surgery while providing significant symptomatic relief.

Diagnosis of Sacroiliac Joint Pain: Predictive Value of Three Diagnostic Clinical Tests.

INTRODUCTION: To date, there have been no acceptable and accurate diagnostic criteria or standards of care for the management of sacroiliac joint (SIJ) pain. Several studies have yielded different contributions of clinical presentation, history, and physical examination in the diagnosis of SIJ pain. Our goal in this study was to assess the sensitivity and specificity of the diagnostic clinical tests and their predictive value in accurately diagnosing SIJ pain. METHODOLOGY: Upon enrolling 200 eligible patients with SIJ pain as their primary diagnosis, they were re-evaluated and their verbal rating scale (VRS) pain scores and demographic data were obtained. Thereafter, three SIJ diagnostic tests were performed: the thigh thrust test, the Patrick test, and a modified version of the Gaenslen test that is referred to as the Mekhail test. Subsequently, the patients were taken to the procedure room to undergo SIJ injection, for which a confirmative result was ≥50% pain relief. The physicians performing the procedure were blinded of the results of the 3 tests performed. Results from the 3 tests were incorporated with the procedure results, from which we drew statistical and medical conclusions determining their predictive value and degree of aid to physicians in diagnosing SIJ pain. RESULTS: We found that the cumulative effect of adding simultaneous tests increased the sensitivity of the testing but decreased the specificity, which generates a powerful screening tool. The combination of the Patrick and Mekhail tests demonstrated the best accuracy, with 94% sensitivity, 17% specificity, 81% positive predictive value, and 44% negative predictive value. The Patrick test was better than other tests for differentiating patients with SIJ pain from those with non-SIJ pain. No combination yielded both significant sensitivity and specificity. Generally, the overall predictive value of any of the tests on their own or their combination did not vary significantly from the predictive value of baseline demographics, including pre-injection pain score and pain referral diagram. CONCLUSION: In conclusion, our study results were similar to those of previous investigators who found that physical examination plays a limited role in diagnosing SIJ pain. Specifically, we found that the clinical tests and/or their combinations added no significant predictive capacity compared to patients' baseline characteristics in predicting the response to diagnostic SIJ injection, albeit the combination of the Mekhail and Patrick tests yielded high sensitivity (94%), making them viable for consecutive screening, possibly reducing the unnecessary costs of diagnostic SIJ injection procedures.

The Impact of Age on the Outcomes of Minimally Invasive Lumbar Decompression for Lumbar Spinal Stenosis.

BACKGROUND AND PURPOSE: Minimally invasive lumbar decompression (mild ®) is an effective long-term therapy for patients with symptomatic lumbar spinal stenosis (LSS) resulting primarily from hypertrophic ligamentum flavum (HLF). Most subjects in clinical studies of the mild procedure have been older adults (age≥65). While the incidence of LSS increases with age, a substantial number of adults (age<65) also suffer from neurogenic claudication secondary to HLF. In this report, outcomes of mild were compared between adults and older adults. PATIENTS AND METHODS: All prospective studies of the mild procedure with a 1-year follow-up completed since the beginning of 2012 that allowed the inclusion of adult patients of all ages were reviewed. Outcomes of visual analog scale (VAS), Oswestry Disability Index (ODI), Pain Disability Index (PDI), Roland Morris Low Back Pain and Disability Questionnaire (RMQ), standing time and walking distance were compared for adults and older adults. RESULTS: Four studies met the inclusion criteria, resulting in an analysis of 49 adults and 160 older adults. Patients in both age groups experienced significant mean improvements in all but one outcome measure at 6- and 12-month follow-up. Differences between the two age groups in all scores at 6 and 12 months were not statistically significant. CONCLUSION: Analysis of the four studies indicated that symptom improvements for adults and older adults were significant from baseline, and no statistically significant difference was observed between the two age groups. These results illustrate that mild can be an effective treatment for LSS due primarily to HLF, regardless of the adult patient age.

Longevity and Utilization Cost of Rechargeable and Non-Rechargeable Spinal Cord Stimulation Implants: A Comparative Study.

INTRODUCTION: Despite major advancements in features and capabilities of the implantable pulse generator (IPG), real-life longevity and cost-effectiveness studies to guide pain specialists to make the appropriate choice between rechargeable and non-rechargeable IPG are limited. Our study aimed to compare the longevity and cost effectiveness of rechargeable vs. non-rechargeable IPG and SCS systems. METHODS: Data were collected for all SCS implantations performed between 1994 and 2018. The primary goal was to determine IPG longevity, defined as the time interval between IPG implantation and elective replacement due to IPG end of life (EOL). On the other hand, SCS system longevity was defined as the time between SCS implantation and its removal or revision for any reason other than IPG EOL. Kaplan-Meier and log-rank tests were used to assess IPG and SCS system longevities. Cost analysis was performed for cost effectiveness. RESULTS: The median IPG longevity was significantly higher for rechargeable SCS devices than for non-rechargeable SCS devices (7.20 years and 3.68 years, respectively). The median cost per day was similar for both IPGs, $13.90 and $13.81 for non-rechargeable and rechargeable, respectively. The median cost for SCS systems was higher for the rechargeable group ($60.70) compared with the non-rechargeable group ($31.38). CONCLUSIONS: Rechargeable IPG had increased longevity compared to their non-rechargeable counterparts, yet there was no significant difference in the actual longevity due to premature revisions or explantations between both SCS systems. Furthermore, non-rechargeable SCS systems were found to be the more cost-effective option when compared with rechargeable SCS systems.

Choice of spinal cord stimulation versus targeted drug delivery in the management of chronic pain: a predictive formula for outcomes.

Contemporary nonmalignant pain treatment algorithms commence with conservative non-invasive strategies, later progressing from minimally invasive interventions to invasive techniques or implantable devices. The most commonly used implantable devices are spinal cord stimulation (SCS) systems or targeted drug delivery (TDD) devices. Historically, SCS had been considered in advance of TDD, positioning TDD behind SCS failures. Following Institutional Review Board approval, data were extracted from electronic medical records of patients who underwent SCS trial in the Department of Pain Management at Cleveland Clinic from 1994 to 2013. The sample size was analyzed in two cohorts: those who succeeded with SCS and those who failed SCS and consequently proceeded to TDD. Univariate and multivariate analyses were performed and a predictive formula for successful outcomes was created. 945 patients were included in the cohort of which 119 (12.6%) subjects achieved adequate pain relief with TDD after failure of SCS. Gender, age, depression and primary pain diagnosis were significantly different in this subgroup. Males were 52% less likely to experience pain relief with SCS. The odds of SCS success decreased as age increased by 6% per year. Patients with comorbid depression, interestingly, were 63% more likely to succeed with SCS. A logistic model was created to predict SCS success which was used to create a predictive formula. Older male patients diagnosed with spine-related pain were more likely to benefit from TDD than SCS. This observation potentially identifies a subgroup in whom consideration for TDD in advance of SCS failure could prove more efficient and cost effective. These retrospective findings warrant prospective comparative studies to validate this derived predictive formula.

Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial.

BACKGROUND: Spinal cord stimulation has been an established treatment for chronic back and leg pain for more than 50 years; however, outcomes are variable and unpredictable, and objective evidence of the mechanism of action is needed. A novel spinal cord stimulation system provides the first in vivo, real-time, continuous objective measure of spinal cord activation in response to therapy via recorded evoked compound action potentials (ECAPs) in patients during daily use. These ECAPs are also used to optimise programming and deliver closed-loop spinal cord stimulation by adjusting the stimulation current to maintain activation within patients' therapeutic window. We aimed to examine pain relief and the extent of spinal cord activation with ECAP-controlled closed-loop versus fixed-output, open-loop spinal cord stimulation for the treatment of chronic back and leg pain. METHODS: This multicentre, double-blind, parallel-arm, randomised controlled trial was done at 13 specialist clinics, academic centres, and hospitals in the USA. Patients with chronic, intractable pain of the back and legs (Visual Analog Scale [VAS] pain score ≥60 mm; Oswestry Disability Index [ODI] score 41-80) who were refractory to conservative therapy, on stable pain medications, had no previous experience with spinal cord stimulation, and were appropriate candidates for a spinal cord stimulation trial were screened. Eligible patients were randomly assigned (1:1) to receive ECAP-controlled closed-loop spinal cord stimulation (investigational group) or fixed-output, open-loop spinal cord stimulation (control group). The randomisation sequence was computer generated with permuted blocks of size 4 and 6 and stratified by site. Patients, investigators, and site staff were masked to the treatment assignment. The primary outcome was the proportion of patients with a reduction of 50% or more in overall back and leg pain with no increase in pain medications. Non-inferiority (δ=10%) followed by superiority were tested in the intention-to-treat population at 3 months (primary analysis) and 12 months (additional prespecified analysis) after the permanent implant. This study is registered with ClinicalTrials.gov, NCT02924129, and is ongoing. FINDINGS: Between Feb 21, 2017, and Feb 20, 2018, 134 patients were enrolled and randomly assigned (67 to each treatment group). The intention-to-treat analysis comprised 125 patients at 3 months (62 in the closed-loop group and 63 in the open-loop group) and 118 patients at 12 months (59 in the closed-loop group and 59 in the open-loop group). The primary outcome was achieved in a greater proportion of patients in the closed-loop group than in the open-loop group at 3 months (51 [82·3%] of 62 patients vs 38 [60·3%] of 63 patients; difference 21·9%, 95% CI 6·6-37·3; p=0·0052) and at 12 months (49 [83·1%] of 59 patients vs 36 [61·0%] of 59 patients; difference 22·0%, 6·3-37·7; p=0·0060). We observed no differences in safety profiles between the two groups. The most frequently reported study-related adverse events in both groups were lead migration (nine [7%] patients), implantable pulse generator pocket pain (five [4%]), and muscle spasm or cramp (three [2%]). INTERPRETATION: ECAP-controlled closed-loop stimulation provided significantly greater and more clinically meaningful pain relief up to 12 months than open-loop spinal cord stimulation. Greater spinal cord activation seen in the closed-loop group suggests a mechanistic explanation for the superior results, which aligns with the putative mechanism of action for spinal cord stimulation and warrants further investigation. FUNDING: Saluda Medical.

The Impact of Tobacco Smoking on Spinal Cord Stimulation Effectiveness in Complex Regional Pain Syndrome Patients.

OBJECTIVES: We aim to investigate the correlation of smoking and spinal cord stimulation (SCS) effectiveness for pain relief in complex regional pain syndrome (CRPS) patients while controlling for possible confounding factors including opioid intake. MATERIALS AND METHODS: Following Institutional Review Board approval, a retrospective cohort study was performed by collecting data for all CRPS patients treated with SCS at Cleveland Clinic between 1998 and 2013. We divided patients into three groups based on their smoking status at the time of SCS device implant: Current smokers, former smokers, or nonsmokers. We used a linear mixed modeling to assess the association between smoking status and pain score at baseline and at 3, 6, and 12 months. We then used pairwise t-tests for post hoc comparisons of pain scores. RESULTS: Of the 420 CRPS patients treated with SCS implants, the reduction in pain score was highest among nonsmokers. Nonsmokers demonstrated a consistent and steady decrease in pain scores over time, whereas the current and former smoker cohorts showed an initial reduction in pain at three months compared to baseline which was not sustained to the 12-months benchmark. Nonetheless, former smokers continued to report slightly lower pain scores than current smokers, although not statistically significant. The baseline opioid consumption was least among nonsmokers (30 [0, 62] oral mg morphine sulfate equivalent). We also found a statistically significant association between time postimplant and reported pain score (χ2 = 508.88, p < 0.001). The overall mean pain score for all three cohorts was highest at baseline (7.6 ± 1.7) and showed a decrease at the 3, 6, and 12 months postimplant time points with mean score of 5.7 ± 2.0, 5.6 ± 2.3, and 5.4 ± 2.5, respectively. CONCLUSION: Tobacco cigarette smoking was associated with reduced SCS effectiveness for pain relief.

The impact of obesity on the effectiveness of spinal cord stimulation in chronic spine-related pain patients.

BACKGROUND CONTEXT: Chronic pain and obesity are both on the rise. Spinal cord stimulation has gained increasing popularity in the pain management field for the treatment of spine-related chronic pain, however to-date, the correlation between the spinal cord stimulator effectiveness and increasing body mass index (BMI) has not been fully established. PURPOSE: We aimed to investigate the correlation between patients' BMI and the percentage of pain relief as well as opioid utilization in chronic spine-related pain patients treated with spinal cord stimulation. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Patients with chronic spine-related pain who were treated with a spinal cord stimulator. OUTCOME MEASURES: Eleven-point numeric rating scale for pain and opioid utilization. METHODS: Following Institutional Review Board approval, data from all eligible subjects who had undergone successful spinal cord stimulation (SCS)-trial defined as ≥50% decrease in pain followed by SCS implant were collected and statistically analyzed. Patients were divided into four groups according to BMI. Self-reported pain scores on the 11-point numerical rating scale were collected at baseline, 6 months and 12 months post SCS-implant visits. Opioid utilization, if any, was collected at baseline and 12 months post-SCS implant. RESULTS: In all, 181 patients were included. Thirty-three were under and/or normal weight (≤24.9 kg/m2), 72 overweight (25.0-29.9 kg/m2), 63 obese (30.0-39.9 kg/m2), and 13 morbidly obese (≥40.0 kg/m2). The estimated coefficients from multivariable linear regression analysis were -1.91% (95% CI: -2.82% to -0.991%) and -1.48% (95% CI: -2.30% to -0.660%) reduction in pain improvement per unit increase of BMI for 6 months and 12 months scores, respectively. The estimated coefficient of disability status was -15.3% (95% CI: -22.1% to -8.48%). The estimated coefficient for 12 month opioid equivalence was -0.08% (95% CI: -0.14 to -0.021), per` 1 mg unit increase of morphine opioid equivalency. The data showed a statistically significant negative association between increasing BMI and SCS effectiveness at 6 and 12 months post-SCS therapy with a 2% reduction in efficacy for every unit increase of BMI after adjusting for confounding factors and a 20% better response in underweight and/or normal patients over the morbidly obese individuals which was not related to baseline pain score level. The significant difference in pain scores at 6 months (p = .0003) and 12 months (p = .04) post-SCS implant between obese and nonobese patients was not attributable to differences in baseline pain scores. There was no significant change in opioid utilization between baseline and 12 months post-SCS therapy. CONCLUSION: A negative association between SCS effectiveness and increasing BMI was found, whereas, no significant difference was noted amongst the various BMI cohorts and the daily opioid consumption.

The Impact of Tobacco Cigarette Smoking on Spinal Cord Stimulation Effectiveness in Chronic Spine-Related Pain Patients.

BACKGROUND AND OBJECTIVES: Despite the observation that select nicotine receptor agonists have analgesic effects, smokers report higher pain scores and more functional impairments than lifelong nonsmokers, attributable to exaggerated stress responses, receptor desensitization, and altered pharmacokinetics compounded by accelerated structural damage resulting from impaired bone healing, osteoporosis, and advancement of disk disease. We hypothesized that smoking diminishes the analgesic response to spinal cord stimulation (SCS) in patients with chronic spine-related pain conditions. METHODS: A retrospective cohort study was performed at Cleveland Clinic by collecting and assessing data of 213 patients who had been implanted with SCS for spine-pain indications. History of tobacco smoking was subcategorized into 3 categories: past (former smoker), present (current smoker), or those who had never previously smoked (lifelong nonsmokers), and a multivariable linear regression was run to measure the correlation, if any, between smoking status and numerical rating scale pain score. In addition, opioid consumption at baseline and 12-month follow-up, expressed in milligram oral morphine equivalents, was collected and compared. RESULTS: Adjusted for differences, at 1-year follow-up, current smokers (n = 62) reported numerical rating scale pain score of 7.0, which is 1.93 (P < 0.001) and 1.32 (P = 0.001) points higher than those of lifelong nonsmokers (n = 77) and former smokers (n = 74), respectively. Opioid intake was 2.4 times higher (P = 0.004) in smokers than in lifelong nonsmokers. CONCLUSIONS: Among our SCS-implanted sample, a positive correlation was observed between tobacco use and degree of pain reduction as early as 12 months postimplant; this was evident by the reported higher pain scores and opioid use in current smokers in comparison with former smokers and lifelong nonsmokers.