Failed back surgery syndrome (FBSS) is present in about 30% of the patients who have undergone surgery involving the discs of the lumbar spine.1 It is characterized by maintenance of a chronic painful state, wherein the original back pain source(s) was either not properly addressed by the surgery or an additional idiopathic source of pain existed that could not be treated by such a surgical intervention. FBSS may also describe patients who have acquired a new back pain condition after spinal surgery.
Various therapeutic approaches are currently used to treat refractory chronic back and leg pain after spinal surgery.1 Presently, spinal cord stimulation (SCS) is considered at a relatively late stage treatment for FBSS.1–6 This utilization late in the continuum of care is surprising as both Level 1 and Level 2 evidence exists indicating traditional SCS is a safe, clinically effective, and cost-effective treatment.7–9 Technological advancements such as novel waveforms, higher stimulation frequencies, and new anatomical targets have vastly expanded the field of SCS, resulting in greater effectiveness and broader applicability of this treatment. Additionally, these approaches may provide a rescue treatment for patients who have previously failed surgical and less invasive therapies, offering relief to a patient population among the most difficult to treat.
Although evidence supports its safety and efficacy, traditional low-frequency stimulation produces unpleasant paresthesias in 49% to 71% of the patients causing sudden surges and shocks that may become less tolerable over the time.2–9 Persistent paresthesias associated with low-frequency SCS and loss of efficacy from other unknown causes may result in attrition or “tolerance” in FBSS patients. However, such tolerance was not observed in at least one new study evaluating a high-frequency (HF) modality of SCS (10 kHz SCS).4,10
SCS for the treatment of chronic pain is becoming a fast advancing field of neuromodulation. Thus, it is difficult to predict how and where evidence will lead the field over the next 5 to 10 years when it comes to various stimulation frequencies and modalities of SCS treatments for FBSS. This text is intended to provide an overview of current evidence and to highlight recently published new waveform studies that are bringing so much excitement to the field of neuromodulation.
Data Sources and Search
A systematic literature review was performed using several bibliographic databases: EMBASE, Medline, and Cochrane. We searched databases up to July 2016. Prospective studies in adults using SCS for FBSS were included. Search terms included spinal cord stimulation, neurostimulation, failed back surgery syndrome, postlaminectomy syndrome, chronic pain, and prospective clinical trial.
Inclusion Criteria and Patient Selection
Studies were included in this review if they followed patients with pain persisting ≥ 3 months postspinal surgery that were then treated with SCS. All included clinical studies assessed pain outcomes in a prospective manner.
Data extracted included patient characteristics, treatment therapy and control, and outcomes.
Traditional Low-Frequency Spinal Cord Stimulation Studies for FBSS
One of the most studied indications for SCS is FBSS in the form of persistent radicular pain after any lumbar disc surgery. When it comes to use of traditional low-frequency SCS for FBSS, two randomized controlled trials and numerous retrospective studies have been published. Summarizing data collected over more than 25 years, traditional low-frequency SCS at any given time interval provides approximately 50% pain relief in about 50% of the patients. Outcomes remain unchanged from an early SCS era (before 1995;2,9) until now.10–12 While the proportion of patients reporting meaningful pain relief has remained stagnant yet remarkably consistent between studies, common complications have dropped drastically.4,10 Such improvements to implantation safety can likely be attributed to better implantation techniques, more effective anchoring, and advancements in reducing the size of implantable generators resulting in greater patient comfort and less invasive surgical techniques.
The two most cited, and the only randomized prospective trials on the use of traditional low-frequency SCS for FBSS, are those from North et al and Kumar et al.7–9 In addition, Kapural et al4,10 provided further evidence for both traditional and HF SCS in a comparative study with long-term outcomes. North et al7 enrolled 50 subjects in a crossover study, treating subjects with either SCS or spinal revision surgery, in a study known as PROCESS. Forty-five of those subjects were followed for up to 3 years. Nine of 19 subjects (47.4%) with SCS and 3 of 26 subjects (11.5%) who underwent repeated surgery had greater than 50% pain relief. The crossover rate was lower in the SCS group than in the group receiving additional surgery (5/24 vs. 14/26, respectively), indicating patient preference for SCS over repeated surgery.7
Dr. Kumar et al studied 100 patients who had predominant neuropathic leg pain after spinal surgery.8,9 Patients were randomized to either receive maximal conventional medical management (CMM), or maximal CMM plus SCS. At 6 months, 48% of the patients who had been treated with SCS had more than 50% pain relief, while only 9% in CMM group reported so. The crossover rate (at 6 mo) was much lower in the SCS group. Moreover, at 6 months, patients randomized to SCS achieved significantly greater improvement in functional capacity and quality of life (QOL) compared with CMM patients. Long-term follow-up of 12 months was reported in Kumar et al8 with the SCS group experiencing improved pain relief, QOL and functional capacity, as well as greater treatment satisfaction (P ≤ 0.05). At 24 months,9 37% of patients in SCS group continued to achieve at least 50% pain relief versus 2% of patients in the CMM group (P = 0.003).
Same authors provided details on cost-effectiveness of SCS for FBSS.13,14 The above-discussed PROCESS study pointed to substantial cost savings for the treatment of chronic pain in the group that received SCS as opposed to the CMM group. Health-related QOL improved significantly after SCS treatment. When long-term cost-effectiveness of SCS therapy (over a period of 5 yrs) was compared with CMM treatment, higher costs over the first 30 months in the SCS group, primarily due to upfront implantation expense, are clearly offset by substantial savings postimplant. Additional benefits of traditional SCS include twice the improvement in QOL parameters and patient satisfaction scoring.13,14 Overall, clinical SCS usage is rapidly moving forward and beyond traditional paresthesia-based therapy. It is debatable if this traditional SCS approach will be replaced with more efficacious stimulation parameters like 10 kHz SCS, or other, complex programming parameters in the future.11,12
High-Frequency Spinal Cord Stimulation for FBSS
High-frequency spinal cord stimulation using 10 kHz frequency, called HF10 therapy or 10 kHz SCS (Nevro Corp, CA), is the first in the series of alternative frequency waveform therapies currently providing evidence of effective control of chronic back and leg pain.4,10 Pain control is achieved with anatomic placement of leads without the production of any paresthesias, negating the requirement of paresthesia mapping to the patient's painful areas for pain relief, as is necessary for traditional low-frequency SCS (Figure 1).
Initial, short-term clinical study on 10 kHz SCS documented significant improvement in back and leg pain scores, and provided evidence in favor of 10 kHz SCS over traditional low-frequency SCS with 88% (21/24) of patients preferring the former therapy over the latter, prompting further investigation.15 A much larger European study followed (83 patients), providing long-term data on 10 kHz SCS.16 During this two-center case series study, 10 kHz SCS provided significant analgesia (>50% of the pain relief) in >70% of the patients. Accuracy of lead placement is less rigorous than for conventional SCS, and thus less likely to be impacted by the electrode migration.16 The same group of researchers recently reported 2-year follow-up of the same study.17 HF stimulation resulted in significant and sustained back and leg pain relief, functional and sleep improvements, opioid use reduction, and matched patient satisfaction.
Finally, the SENZA-randomized controlled trial study, a multicenter, prospective, randomized, controlled clinical trial recently completed in the United States, provided Level 1 evidence evaluating the efficacy of 10 kHz SCS compared with traditional low-frequency SCS for subjects with both chronic back and leg pain.4,10 The study results led to US Food and Drug Administration approval of this therapy. A total of 198 subjects in 10 research centers with severe back and leg pain (that had a score of ≥5 cm on the visual analog csale [VAS] scale) were randomized in a 1:1 ratio to treatment groups of traditional SCS (Precision Plus System, Boston Scientific; Valencia, CA) and 10 kHz SCS (Senza SCS System, Nevro Corp; Menlo Park, CA).4 Out of 189 subjects who underwent trial stimulation, 171 passed a temporary trial with significant pain relief (≥40% pain relief) and were implanted with the assigned SCS system. The proportion of responding subjects with greater than 50% of back pain reduction with no stimulation-related significant adverse effects was assessed as the primary outcome in both groups. At 3 months, 84.5% of implanted 10 kHz SCS subjects were responders for back pain and 83.1% for leg pain, compared with 43.8% of traditional low-frequency SCS subjects who were responders for back pain and 55.5% for leg pain (P < 0.001 for both back and leg pain comparisons). The superiority of 10 kHz SCS over traditional low-frequency SCS for back and leg pain was sustained through 12 months (P < 0.001) and 24 months (P < 0.001). At 24 months, more subjects were responders to 10 kHz SCS than traditional low-frequency SCS (back pain: 76.5% vs. 49.3%; leg pain: 72.9% vs. 49.3% (P < 0.001 for noninferiority and P = 0.003 for superiority)) (Figure 2). None of the 10 kHz SCS subjects experienced paresthesias, while 46.5% of traditional low-frequency SCS subjects reported uncomfortable stimulation which ultimately resulted in reporting them as study-related adverse events from 11.3% of traditional low-frequency SCS subjects10 (Table 1).
There are only a few published studies evaluating therapeutic effect of other higher frequency SCS therapies. One of them is an animal study that compared the inhibitory effect on mechanical hypersensitivity from bipolar SCS of different intensities (20%, 40%, and 80% of the motor threshold), and frequencies (50 Hz, 1 kHz, and 10 kHz) in a rat model of neuropathic pain.18 The study provided evidence that analgesic effect of SCS in rats depends on both intensity and frequency of stimulation, and high-intensity, kilohertz-level SCS provided earlier inhibition of mechanical hypersensitivity than conventional 50-Hz SCS.
One study examined the efficacy of 5 kHz SCS in patients already implanted with a commercially available system that was modified to deliver therapeutic stimulation and failed to show any benefit over placebo. Using a randomized controlled trial design, Perruchoud et al19 studied 40 patients with implanted SCS systems for low back and leg pain. This study used 5 kHz SCS (monophasic pulses with 60 μs pulse width) delivered at intensities set below perception. Patient global impressions of change (main outcome), pain intensity (VAS), and QOL (measured by EQ-5D) were not observed to be different for 5 kHz SCS compared with sham (no stimulation). Multiple factors could explain these different clinical results. Most importantly, in the Perruchoud et al study,19 all patients had prior successful experience with traditional SCS at frequencies producing paresthesia, which neither the sham group nor the 5 kHz SCS group experienced. It is generally accepted that paresthesias are required for efficacy when conventional frequencies of stimulation are used for SCS, and all patients in the Perruchoud et al study were most probably conditioned to this coupling of paresthesia with success of therapy. Other factors that might explain these differing clinical results include (A) the possibility that 10 kHz SCS is efficacious but 5 kHz SCS is not; (B) that study design flaws (study bias) existed in one or both of the investigations; (C) that there are differing amounts of electrical energy delivered to the spinal cord by each system; and (D) that the leads in each study were placed in different areas of the spinal cord.
The two clinical studies of 10 kHz SCS provided consistent set of data, and much better clinical efficacy4,10 than traditional SCS setting a new efficacy standard that emerging waveform modalities of SCS should match or exceed (Figures 2 and 3). Based on the current status of clinical evidence, paresthesias during SCS are not essential for pain relief. It has thus far proven to be uncomfortable, limiting acceptable time interval and amplitude of stimulation.
Burst Stimulation for FBSS
Burst stimulation utilizes complex programming to deliver a 40 Hz burst mode, each burst consisting of five spikes at 500 Hz per spike delivered in a constant current mode.20 Using this methodology, paresthesia-free stimulation can be achieved in > 80% of the patients.21,22 It was suggested that burst stimulation may specifically activate lateral perceptive pathway and the medial pathway by activating the dorsal anterior cingulate and the right dorsolateral prefrontal cortex, and that was modulating affective component of pain.20–22 There is no direct evidence on such a differential effect of burst stimulation. As of writing of this text, results of the largest randomized prospective study on burst stimulation (SUNBURST Study) were not published yet. Based on initially reported data for the same study, burst stimulation may provide better pain relief when compared with traditional SCS.23
Adverse Events: Safety of SCS
SCS has been under peer and public scrutiny because of possibility of severe complications related to nerve damage, bleeding, or infection. The occurrence of the most common complications of SCS for FBSS like uncomfortable paresthesia, pain at the implantation site, and lead migration, has drastically decreased over the last 5 years (Table 1). Using more portable systems, better anchors and anchoring techniques, better practice guidelines may influence the rate of complications.
Infection, either superficial, deep, or epidural abscess, is the most concerning complication of SCS system implantation. Wound dehiscence and/or device erosion, and presence of seroma may relate to surgical technique and patient's comorbidities. Neuroaxial hematoma is rare, but dreadful complication of SCS implantation. Currently, proper guidelines exist for the management of a patient on anticoagulation medications. Nerve damage including quadriparesis has been described in the literature. Dural puncture and headache are common complications of typically large, 14G, needle placement in epidural space erroneously advancing intrathecally producing a so-called wet tap. Other complications are less frequent and include immunologic reactions, epidural fibrosis, renal failure, nausea, or even diarrhea.24,25
Patient Selection; Psychological Evaluation for Implantable Devices
Psychosocial evaluation for implantable devices requires detailed testing inventories, but should also explore patient expectations, presence of psychological disease, and barriers to proposed treatment.26 It is clear nowadays that such an evaluation improves long-term outcomes of SCS. Long et al27 reported a 33% success rate of SCS trialing in psychologically “unscreened” patients and a 70% rate in “screened” patients. North et al28 suggested that certain psychological variables are associated with pain relief during the trial, after implant, but not at longer, 3 months follow-up. Proper assessment of pain relief, improvement in function, and patient satisfaction during the trial together may improve its predictive value.29 Mood disorders such as depression and anxiety are most common psychological comorbidities associated with disabling medical conditions and may not be obvious because of individual's adaptive coping. Therefore, in addition to regular assessments, psychological interventions may need to be implemented before trialing, or postimplantation of the system. Patients with somatization disorders or emotional reactivity may be more likely to have positive trial followed by ineffective SCS therapy.28 Intolerance to paresthesias, when traditional low-frequency SCS is used, is more likely in those with somatic preoccupation, hysteria, obsessive-compulsive tendencies, and anxiety upon psychological testing.29
DISCUSSION AND CONCLUSION
SCS is an effective treatment option for neuropathic pain of FBSS. Recent scientific and technical advancement of SCS systems, new waveforms, and paradigms has led to improvement in patient outcomes, particularly long-term decrease in pain scores and increase in functional capacity (Figures 2 and 3). Careful preoperative patient selection is still most important for the long-term success of the SCS therapy.
- SCS is an effective treatment option for neuropathic pain of FBSS.
- Recent scientific and technical advancement of SCS systems, new waveforms, and paradigms has led to improvement in patient outcomes, particularly long-term decrease in pain scores and increase in functional capacity.
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