High-dose Spinal Cord Stimulation Research Articles

ID:16364 Effectiveness of High Dose Spinal Cord Stimulation for Nonsurgical Intractable Lumbar Radiculopathy - HIDENS Study

Spinal cord stimulation (SCS) is increasingly being employed for non-surgical intractable neuropathic pain. This study was designed to evaluate the efficacy of High Dose (HD) sub-perception stimulation with higher frequency and pulse width in the surgery naïve population suffering from predominant low-back pain at 12 months’ post-implant.

Gradation of Clinical Holistic Response as New Composite Outcome to Evaluate Success in Spinal Cord Stimulation Studies for Pain

IntroductionThe most prominent outcome measurement in the field of neuromodulation is pain relief. Nevertheless, the number of studies that rely on composite outcomes has increased. The aims of this study are twofold: (1) to evaluate which measures are important to include in a composite outcome and (2) to develop this new composite outcome to evaluate the degree of being a clinical holistic responder with a corresponding minimal clinical important difference (MCID). Materials and MethodsData from patients with persistent spinal pain syndrome type 2 treated with High-Dose Spinal Cord Stimulation (HD-SCS) were used. Pain intensity for low back and leg pain, disability, health-related quality of life, medication use, and patient satisfaction were measured at baseline and after 12 months of HD-SCS. Exploratory and Confirmatory Factor Analyses were used to evaluate which measures should be included in the composite outcome. Anchor-based and distribution-based methods were applied to determine the MCID of the newly developed outcome measurement. ResultsA three-factor model was the most appropriate for this data set, in which leg pain intensity, EQ5D VAS, and disability had the largest loading on these factors. A clinical holistic outcome was created with a total score ranging from 0 (=better [no pain, no disability, and perfect health status]) to 300 (=worse [maximal pain, maximal disability, and worst health status]). The MCID value based on an absolute change score from baseline up to 12 months of HD-SCS was 87.97. When calculating with percentage changes, a MCID value of 48.4% was revealed. ConclusionsThis new composite outcome evaluating the degree of deviation from being a holistic responder is a step toward a meaningful, overall outcome assessment for patients who are treated with SCS. Further studies to evaluate the psychometric properties and the generalizability toward other patient populations still need to be performed.

The Influence of Missing Data on Disabilities in Patients Treated with High-Dose Spinal Cord Stimulation: A Tipping Point Sensitivity Analysis.

New waveforms have changed the field of Spinal Cord Stimulation (SCS) to optimize therapy outcomes, among which is High-Dose SCS (HD-SCS). Missing observations are often encountered when conducting clinical trials in this field. In this study, different approaches with varying assumptions were constructed to evaluate how conclusions may be influenced by these assumptions. The aim is to perform a tipping point sensitivity analysis to evaluate the influence of missing data on the overall conclusion regarding the effectiveness of HD-SCS on disability. Data from the Discover study were used, in which 185 patients with Failed Back Surgery Syndrome were included. Disability was evaluated before SCS and after 1, 3 and 12 months of HD-SCS. During the second, third and fourth visit, data from 130, 114 and 90 patients were available, respectively. HD-SCS resulted in a significant decrease in disability scores based on the analysis of observed data and with multiple imputations. The tipping point sensitivity analysis revealed that the shift parameter was 17. Thus, the conclusion concerning the time effect under a “missing at random” mechanism is robust when the shift parameter for the disability score is 17. From a clinical point of view, a shift of 17 points on disability is not very plausible. Therefore we tend to consider the conclusions drawn under “missing at random” as being robust.

Using Lower Amplitudes to Maintain Effective High Dose Spinal Cord Stimulation Therapy (SCS Dosing Pilot Study)

ObjectiveSpinal cord stimulation is an effective therapy for chronic back and/or leg pain. Amplitude dose–response studies are lacking; therefore, little guidance exists regarding the minimum amplitude requirements with specific high dose parameters. This study characterized the minimum amplitude level that maintained SCS therapy satisfaction and pain relief when stimulating at 1000 Hz and 90 μsec. Materials and MethodsQualified patients had back and leg pain, an implanted neurostimulator programmed to 1000 Hz and 90 μsec, and were very or somewhat satisfied with the therapy, and an average overall VAS pain score ≤ 4 from a daily diary. Patients received four blinded amplitudes (titrated from 80%, 60%, 40%, and 20% of baseline perception threshold), approximately two weeks each, with 1000 Hz and 90 μsec and position-adaptive stimulation enabled. Patients’ satisfaction and overall VAS pain scores were collected for each period. All patients continued through the study, even after reporting lack of therapy satisfaction or pain relief. ResultsThe minimum amplitude, which maintained therapy satisfaction, was 80% of perception threshold for two patients, 60% for one patient, and 20% for 21 patients. Additionally, six patients lost satisfaction changing from their baseline amplitude to 80% perception threshold. The minimum amplitude level, which maintained overall pain relief, was 80% perception threshold for three patients, 60% perception threshold for one patient, 40% perception threshold for two patients, and 20% perception threshold for 19 patients. Five patients required the setting they were programmed to during the baseline period. ConclusionThe qualified study patients defined an implanted population reporting good pain relief and satisfaction using HD SCS therapy at baseline. The majority of these patients were able to maintain therapy satisfaction and pain relief (70% and 63.3%, respectively) with 20% perception threshold amplitude. Amplitudes below perception threshold could potentially maintain effective SCS therapy with HD stimulation in a subset of patients.

The Long-Term Response to High-Dose Spinal Cord Stimulation in Patients With Failed Back Surgery Syndrome After Conversion From Standard Spinal Cord Stimulation: An Effectiveness and Prediction Study

Spinal cord stimulation (SCS) is nowadays available with several stimulation paradigms. New paradigms, such as high dose (HD-)SCS, have shown the possibility to salvage patients who lost their initial pain relief. The first aim of this study is to evaluate the effectiveness of HD-SCS after conversion from standard SCS. The second aim is to develop a model for prediction of long-term response of HD-SCS after unsatisfactory standard SCS. Seventy-eight patients with failed back surgery syndrome (FBSS) who are treated with standard SCS were enrolled in the study. Self-reporting questionnaires and outcomes were assessed before conversion and at 1, 3, and 12 months of HD-SCS. Longitudinal mixed models were used to determine the effectiveness of HD-SCS. Logistic regression and classification and decision tree analyses were performed to predict responders (NRS decrease ≥2/10) after 12 months of HD-SCS. Significant time effects were found for both low back and leg pain responders, suggesting the effectiveness of HD-SCS after conversion. Logistic regression models revealed the importance of pain intensity scores, medication use, paresthesia coverage (for back pain) and EQ5D (for leg pain) as predictors for being a responder after 12 months of HD-SCS. Converting patients with unsatisfactory responses from standard SCS to HD-SCS may be an effective strategy to obtain and maintain pain relief in a challenging subgroup of patients with FBSS refractory to standard SCS. The prediction models may guide clinicians in their decision making when considering conversion to HD-SCS in patients with FBSS experiencing inadequate response to standard SCS.

High-Dose Spinal Cord Stimulation Reduces Long-Term Pain Medication Use in Patients With Failed Back Surgery Syndrome Who Obtained at Least 50% Pain Intensity and Medication Reduction During a Trial Period: A Registry-Based Cohort Study

ObjectivesHigh-dose spinal cord stimulation (HD-SCS) revealed positive results for obtaining pain relief in patients with failed back surgery syndrome (FBSS). However, it is less clear whether HD-SCS also is able to reduce pain medication use. The aim of this registry-based cohort study is to explore the impact of HD-SCS on pain medication use in FBSS patients. Materials and MethodsData from the Discover registry was used in which the effectiveness of HD-SCS was explored in neurostimulation-naïve FBSS patients as well as in rescue patients. All neurostimulation-naïve FBSS patients positively responded to a four-week SCS trial period in which at least 50% pain relief and 50% medication reduction were obtained. Medication use was measured with the Medication Quantification Scale III (MQS) in 259 patients at baseline and at 1, 3, and 12 months of HD-SCS. Additionally, defined daily doses (DDD) and morphine milligram equivalents (MME) were calculated as well. ResultsOne hundred thirty patients reached the visit at 12 months. In neurostimulation-naïve patients, a statistically significant decrease in MQS (χ2 = 62.92, p < 0.001), DDD (χ2 = 11.47, p = 0.009), and MME (χ2 = 21.55, p < 0.001) was found. In rescue patients, no statistically significant improvements were found. In both patient groups, statistically significant reductions in the proportion of patients on high-risk MME doses ≥90 were found over time. At the intraindividual level, positive correlations were found between MSQ scores and pain intensity for back (r = 0.56, r = 0.31, p < 0.001) and leg pain (r = 0.61, r = 0.22, p < 0.001) in neurostimulation-naïve and rescue patients, respectively. ConclusionsRegistry data on HD-SCS in FBSS patients revealed a statistically significant and sustained decrease in pain medication use, not only on opioids, but also on anti-neuropathic agents in neurostimulation-naïve patients, who positively responded to an SCS trial period with at least 50% pain relief and 50% pain medication decrease, but not in rescue patients.

Long-term quality of life and work status after high-dose spinal cord stimulation in patients with failed back surgery syndrome: a secondary analysis of real-world data.

In recent years, the use of high-dose spinal cord stimulation (HD-SCS) as a treatment option for patients with failed back surgery syndrome (FBSS) has drastically increased. However, to the authors' knowledge a thorough evaluation of health-related quality of life (HRQOL) and work status in these patients has not yet been performed. Moreover, it is unclear whether patients who are treated with HD-SCS can regain the same levels of HRQOL as the general population. Therefore, the aims of this study were to compare the HRQOL of patients who receive HD-SCS to HRQOL values in an age- and sex-adjusted population without FBSS and to evaluate work status in patients who are receiving HD-SCS. HRQOL, measured with the 3-level EQ-5D (EQ-5D-3L), and work status were evaluated in 185 FBSS patients at baseline (i.e., before SCS) and at 1, 3, and 12 months of treatment with HD-SCS. Difference scores in utility values between patients and an age- and sex-adjusted normal population were calculated. One-sample Wilcoxon tests were used to assess the EQ-5D-3L difference scores. Mixed models were used to evaluate the evolution over time in EQ-5D-3L utility scores and EQ-5D visual analog scale (VAS) scores in patients and matched controls. Quality-adjusted life-years (QALYs) were calculated using the area under the curve method. An overall significant increase in EQ-5D-3L utility scores and EQ-5D VAS scores was found over time in the patient group. Wilcoxon tests indicated that the difference scores in utility values between patients and the normal population were significantly different from zero at all time points. The median incremental QALY after 12 months of HD-SCS was 0.228 (Q1-Q3: 0.005-0.487) in comparison to continued conservative treatment. At 12 months, 13.75% of patients resumed work. HD-SCS may lead to significantly increased HRQOL at 12 months in patients with FBSS. Despite the increase, reaching the HRQOL level of matched controls was not achieved. Only a limited number of patients were able to return to work. This finding indicates that specialized programs to enhance return to work may be beneficial for patients undergoing SCS.

Determining the Minimal Clinical Important Difference for Medication Quantification Scale III and Morphine Milligram Equivalents in Patients with Failed Back Surgery Syndrome.

The Medication Quantification Scale III (MQS) is a tool to represent the negative impact of medication. A reduction in medication can serve as an indicator to evaluate treatment success. However, no cut-off value has yet been determined to evaluate whether a decrease in medication is clinically relevant. Therefore, the objective is to estimate the thresholds for the MQS and morphine milligram equivalents (MMEs) that best identify a clinically relevant important improvement for patients. Data from the Discover registry, in which patients with failed back surgery syndrome were treated with high-dose spinal cord stimulation, were used. Patient satisfaction was utilized to evaluate a clinically important outcome 12 months after stimulation. Anchor-based and distribution-based methods were applied to determine the minimal clinical important difference (MCID). Distribution-based methods revealed a value of 4.28 for the MQS and 33.61 for the MME as MCID. Anchor-based methods indicated a percentage change score of 41.2% for the MQS and 28.2% for the MME or an absolute change score of 4.72 for the MQS and 22.65 for the MME. For assessing a treatment outcome, we recommend using the percentage change score, which better reflects a clinically important outcome and is not severely influenced by high medication intake at baseline.

The Added Value of High Dose Spinal Cord Stimulation in Patients with Failed Back Surgery Syndrome after Conversion from Standard Spinal Cord Stimulation.

Patients with Failed Back Surgery Syndrome (FBSS) report a considerably lower health- related quality of life (HRQoL), compared to the general population. Spinal cord stimulation (SCS) is an effective treatment to offer pain relief in those patients. Despite initial treatment success of SCS, its effect sometimes wears off over time. This study investigates the added value of high dose SCS (HD-SCS) in patients with unsatisfactory conventional SCS, from a quality of life perspective. Seventy-eight FBSS patients who were treated with conventional SCS that failed to provide pain relief, were recruited in 15 centers. HRQoL was assessed before converting to HD-SCS (baseline) and three times after converting to HD-SCS using the EuroQol-5D-3L. Quality adjusted life years (QALY) were calculated and compared with conventional SCS. An overall significant increase over time was seen in utility values of the EQ5D-3L, as the mean value at baseline 0.283 (±0.21) increased to 0.452 (±0.29) at 12 months of HD-SCS. This average increase in utility coincides with an average increase of 0.153 (±0.24) QALY’s in comparison to continued conventional SCS. Besides the potential of HD-SCS to salvage patients with failed responses to conventional SCS, this treatment seems to be a more efficient treatment than conventional SCS.

High-dose spinal cord stimulation for patients with failed back surgery syndrome: a multicenter effectiveness and prediction study

The use of high-dose spinal cord stimulation (HD-SCS) has increased drastically during the past few years, with positive results. However, there remains a deficit of real-world data of the effectiveness of HD-SCS. Therefore, the primary aim was to evaluate the effectiveness of HD-SCS in patients with failed back surgery syndrome (FBSS). The second aim was to develop a prediction model for a holistic responder. One hundred ninety-four patients were recruited to a multicenter real-world registry. Self-reporting outcome variables were evaluated at baseline (before SCS) and at 1, 3, and 12 months of HD-SCS implant. Outcome measures were the mean pain intensity over time, sleep quality, disability, health-related quality of life, and medication use. Besides the effectiveness, logistic regression and decision tree analysis were performed to define a holistic responder (pain intensity reduction, medication reduction, Oswestry disability index reduction, and EQ5D improvement) after 12 months of HD-SCS. Of 185 FBSS patients who underwent a baseline visit, 75.13% had a successful HD trial. At 12 months, 92 patients were still receiving HD-SCS. Both low back and leg pain significantly decreased at 12 months. All outcome measures revealed a significant time-dependent effect from baseline to 12 months. Holistic responders could be predicted with a sensitivity and specificity of 90%. Clinically significant and sustained pain relief over a period of 12 months was achieved with HD-SCS in patients with FBSS. In addition, HD-SCS also achieved an improvement in sleep quality, functionality, and a decrease in pain medication.

Options: A Prospective, Open-Label Study of HighDose Spinal Cord Stimulation in Patients with Chronic Back and Leg Pain

Therapeutic approaches to spinal cord stimulation (SCS) continue to evolve and improve patient outcomes in patients receiving SCS therapy secondary to failed back surgery syndrome. The aim of this study was to evaluate pain relief and other patient outcomes of SCS using selected high-dose programming parameters. This was a prospective cohort study. This study took place at 11 centers in North America. Forty-four SCS-naive patients underwent trialing, starting with 1,000 Hz frequency, 90 µs pulse width followed by 300 Hz frequency, 800 µs pulse width, if pain relief was inadequate. Patients with 50% or greater pain relief were eligible for permanent implantation. Patient's pain rating, global impression of change, health-related quality of life, functional disability, satisfaction/recommendation, stimulation perception, device programming, and adverse events were assessed at 3 months postimplant. There were significant improvements from baseline in mean Numeric Rating Scale (NRS-11) pain scores for overall pain (7.5 to 3.8; P < 0.01), back pain (7.2 to 3.4; P < 0.01), leg pain (7.2 to 3.1; P < 0.01), Oswestry Disability Index (ODI) score (51.5 to 32.1; P < 0.01), and European Quality of Life-Five Dimensions, version 5L score (EQ-5D-5L) (0.58 to 0.74; P < 0.01). Twenty-eight of 32 patients (88%) had significant, favorable improvement in Patient Global Impression of Change (PGIC). Eighty-four percent of patients were "satisfied," and 78.1% would "definitely" recommend SCS. Eighteen patients (56%) used 1,000 Hz frequency and 90 µs pulse width exclusively; these patients experienced mean NRS-11 overall pain score improvement of 4.7 points. Device-, therapy-, or procedure-related adverse events were experienced in 19 patients (40%, 19 of 48), and all events resolved without reoperation and were similar to those observed with traditional SCS systems. There was no active or sham comparator group, and therefore the reported effects may not be solely attributable to therapy effects and may be related to other, nonspecific effects of SCS. Improvements in pain relief, PGIC, EQ-5D-5L, ODI, and patient satisfaction were all clinically relevant and statistically significant. Future studies are needed to understand how these high-dose parameters perform versus a standard comparator. Spinal cord stimulation, high-frequency electrical stimulation, failed back surgery syndrome, neurostimulation, prospective, nonrandomized study.

Cortical Mapping in Conventional and High Dose Spinal Cord Stimulation: An Exploratory Power Spectrum and Functional Connectivity Analysis With Electroencephalography

Spinal cord stimulation (SCS) is considered an effective pain-relieving treatment for patients with Failed Back Surgery Syndrome (FBSS). Despite the clinical effectiveness, it is unknown whether the altered functional connectivity in such patients, as compared to healthy persons, can be influenced by SCS. Therefore, the goal of this study is to evaluate whether brain connectivity assessed by EEG differs between baseline and SCS in patients with FBSS. Eight patients with FBSS underwent a resting-state EEG protocol before SCS, 1.5 months and 2.5 months after receiving SCS. At each frequency band, power spectrums were compared for no SCS, conventional (CON) SCS and High Dose (HD) SCS. Functional connectivity, with the aid of eConnectome was also calculated. Significant differences in the average power density spectrum over the whole scalp were observed between no SCS, CON SCS and HD SCS in delta, theta and beta frequency bands (p < 0.01). The average power spectrum for CON SCS was significantly lower than the average power spectrum for HD SCS. Marked increases in strength of the information flow between electrode pair FC3-TP9 in the beta frequency band (p = 0.006) were found in favor of HD SCS. The differences in power spectrum and connectivity between the three conditions lead to the hypothesis that HD SCS differs from CON SCS on average power spectrum, suggesting that HD SCS may have a higher contribution on the excitatory bottom-up pathway.

The association between pain intensity and disability in patients with failed back surgery syndrome, treated with spinal cord stimulation

Objective Pain researchers demonstrated that pain intensity is not the most reliable measure of the success of chronic-pain treatment. Several research groups have proposed “core outcome domains”, such as measurements of disability, to assess the effect of an intervention in pain patients. Up till now, studies investigating the relation between pain intensity and disability in patients treated with spinal cord stimulation (SCS) are lacking. Therefore, the current objective is to examine which pain-reporting strategy, routinely used in pain research, associates best with the degree of disability in these patients. Methods Eighty-one failed back surgery syndrome patients (37 males and 44 females, mean age 54.6 years), treated with high-dose spinal cord stimulation (HD-SCS) are recruited. Pain intensity was scored on an 11-point numerical rating scale (NRS) for leg and back pain, while disability was assessed with the Oswestry disability index (ODI). The association between both variables was investigated with Spearman’s correlation and Cramér’s V. Results Significant correlations (p < 0.001) are found between the absolute and relative differences of the ODI and NRS. Significant associations were found between reported cut-offs in literature (≤3, ≤5, and 50% pain relief) and the degree of disability. Finally, a significant association (p < 0.001) was found between the minimal clinical important difference. Conclusions In this study, we showed that the degree of disability was strongly associated with the pain intensity as measured using different methods. The standard method for reporting pain intensity reduction (50%) seems to associate the strongest with the degree of disability. However, a low degree of disability does not always reflect a low pain intensity. Implications for rehabilitation The degree of disability reveals a good association with the reporting methods of pain intensity from the literature. The Oswestry disability index could serve as a valid tool to measure the effect of spinal cord stimulation on pain. Disability measures offer a better insight in the clinical profile of chronic pain patients than a pain intensity score.

The influence of High Dose Spinal Cord Stimulation on the descending pain modulatory system in patients with failed back surgery syndrome.

The descending pain modulatory system (DPMS) comprises a network of cortical and subcortical brain and brainstem regions that can inhibit nociceptive afferent brain input (Ossipov et al., 2010; Tracey, 2010; Zhuo and Gebhart, 1997). These pathways seem to be altered in several chronic pain syndromes such as knee osteoarthritis, fibromyalgia, painful diabetic neuropathy and low back pain (Brietzke et al., 2019; da Graca-Tarrago et al., 2019; Kong et al., 2018; Segerdahl et al., 2018). The DPMS network comprises the bilateral anterior insulae (AI), the anterior cingulate cortex (ACC), bilateral middle frontal gyri (mFG), both amygdalae (AMY), the rostral ventromedial medulla (RVM) and the periaqueductal gray (PAG) (Goksan et al., 2018; Schweinhardt and Bushnell, 2010). In the past, it has been suggested that traditional, paresthesia-generating Spinal Cord Stimulation (SCS) induces several changes in modulation circuits located in the cerebrum and brainstem. An inhibitory effect of traditional SCS on somatosensory evoked potentials, and potential mediators like the thalamus and the anterior cingulate cortex (ACC), could play a role in the mechanism of action (MOA) of SCS as well (Bentley et al., 2016; De Ridder and Vanneste, 2016; Moens et al., 2013, 2012). Several studies have provided evidence of the impact of SCS on the DPMS resulting in this inhibitory supraspinal effect (Sankarasubramanian et al., 2018; Schuh-Hofer et al., 2018). More recently, researchers have hypothesized similar influences on the DPMS by other paradigms of SCS such as high frequency SCS at 10 kHz and Burst SCS, as well as by other forms of neurostimulation e.g. occipital nerve field stimulation (Ahmed et al., 2018a, 2018c). Tonic SCS at sub-sensory threshold and at 500 Hz and pulse width 500μsec, so called high density or high dose SCS (HD-SCS), is a SCS form based on the impact of electrical charge delivery to the spinal cord (Chen et al., 2018; Linderoth and Foreman, 2017; Miller et al., 2016; Sweet et al., 2016; Wille et al., 2017). After some initial case series studies, researchers are still exploring the clinical effect and impact on chronic pain of HD-SCS (De Jaeger et al., 2017; Provenzano et al., 2017; Wille et al., 2017). In the past, several researchers have investigated the supraspinal effects of SCS by examining human cerebral circuits via different neuroimaging techniques (e.g. MR Spectroscopy (MRS), single photon emission computerized tomography (SPECT), positron emission tomography (PET), electroencephalography (EEG) and, functional magnetic resonance imaging (fMRI)) to capture alterations in modulation circuits (De Ridder and Vanneste, 2016; Kishima et al., 2010; Moens et al., 2013, 2012; Nagamachi et al., 2006). fMRI is especially interesting due to the robustness and test-retest reliability of the functional connectivity (FC) method in clinical applications (Apkarian, 2015; Shehzad et al., 2009). Additionally, the introduction of MRI-conditioned SCS devices enables further exploration of MOA of SCS, not only during trial period but also on long-term implanted devices. Based on this knowledge, we hypothesized, in this study, that HD-SCS may alter the DPMS and indirectly, might generate an inhibitory supraspinal effect. This hypothesis-driven pilot study aimed to investigate the influence of HD-SCS on FC within the DPMS, measured by resting state fMRI.