Evidence-based consensus guidelines on patient selection and trial stimulation for spinal cord stimulation therapy for chronic non-cancer pain.

Spinal cord stimulation (SCS) has demonstrated effectiveness for neuropathic pain. Unfortunately, some patients report inadequate long-term pain relief. Patient selection is emphasized for this therapy; however, the prognostic capabilities and deployment strategies of existing selection techniques, including an SCS trial, have been questioned. After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, a steering committee was formed to develop evidence-based guidelines for patient selection and the role of an SCS trial. Representatives of professional organizations with clinical expertize were invited to participate as committee members. A comprehensive literature review was carried out by the steering committee, and the results organized into narrative reports, which were circulated to all the committee members. Individual statements and recommendations within each of seven sections were formulated by the steering committee and circulated to members for voting. We used a modified Delphi method wherein drafts were circulated to each member in a blinded fashion for voting. Comments were incorporated in the subsequent revisions, which were recirculated for voting to achieve consensus. Seven sections with a total of 39 recommendations were approved with 100% consensus from all the members. Sections included definitions and terminology of SCS trial; benefits of SCS trial; screening for psychosocial characteristics; patient perceptions on SCS therapy and the use of trial; other patient predictors of SCS therapy; conduct of SCS trials; and evaluation of SCS trials including minimum criteria for success. Recommendations included that SCS trial should be performed before a definitive SCS implant except in anginal pain (grade B). All patients must be screened with an objective validated instrument for psychosocial factors, and this must include depression (grade B). Despite some limitations, a trial helps patient selection and provides patients with an opportunity to experience the therapy. These recommendations are expected to guide practicing physicians and other stakeholders and should not be mistaken as practice standards. Physicians should continue to make their best judgment based on individual patient considerations and preferences.

A Novel Multi-Dimensional Clinical Response Index Dedicated to Improving Global Assessment of Pain in Patients with Persistent Spinal Pain Syndrome after Spinal Surgery, Based on a Real-Life Prospective Multicentric Study (PREDIBACK) and Machine Learning Techniques.

The multidimensionality of chronic pain forces us to look beyond isolated assessment such as pain intensity, which does not consider multiple key parameters, particularly in post-operative Persistent Spinal Pain Syndrome (PSPS-T2) patients. Our ambition was to produce a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and quantitative pain mapping, the objective being to achieve instantaneous assessment using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in the real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined, as exploratory factor analyses helped to create a single composite MCRI; using pairwise correlations between measurements, it appeared to more accurately represent all pain dimensions than any previous classical score. It represented the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by informing the physician's perception of patient condition on the basis of objective and holistic metrics, and also by providing new insights regarding therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

The Added Value of Subcutaneous Peripheral Nerve Field Stimulation Combined with SCS, as Salvage Therapy, for Refractory Low Back Pain Component in Persistent Spinal Pain Syndrome Implanted Patients: A Randomized Controlled Study (CUMPNS Study) Based on 3D-Mapping Composite Pain Assessment.

While Spinal Cord Stimulation (SCS) provides satisfaction to almost 2/3 of Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients implanted for refractory chronic back and/or leg pain, when not adequately addressed the back pain component, leaves patients in a therapeutic cul-de-sac. Peripheral Nerve field Stimulation (PNfS) has shown interesting results addressing back pain in the same population. Far from placing these two techniques in opposition, we suggest that these approaches could be combined to better treat PSPS-T2 patients. We designed a RCT (CUMPNS), with a 12-month follow-up, to assess the potential added value of PNfS, as a salvage therapy, in PSPS-T2 patients experiencing a "Failed SCS Syndrome" in the back pain component. Fourteen patients were included in this study and randomized into 2 groups ("SCS + PNfS" group/n = 6 vs. "SCS only" group/n = 8). The primary objective of the study was to compare the percentage of back pain surface decrease after 3 months, using a computerized interface to obtain quantitative pain mappings, combined with multi-dimensional SCS outcomes. Back pain surface decreased significantly greater for the "SCS + PNfS" group (80.2% ± 21.3%) compared to the "SCS only" group (13.2% ± 94.8%) (p = 0.012), highlighting the clinical interest of SCS + PNfS, in cases where SCS fails to address back pain.

Finite Mixture Models Based on Pain Intensity, Functional Disability and Psychological Distress Composite Assessment Allow Identification of Two Distinct Classes of Persistent Spinal Pain Syndrome after Surgery Patients Related to Their Quality of Life.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in "PREDIBACK", a multicenter observational prospective study including PSPS-T2 patients with one-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n = 136), and by pain perception for second class patients (n = 62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Machine Learning Algorithms Provide Greater Prediction of Response to SCS Than Lead Screening Trial: A Predictive AI-Based Multicenter Study.

Persistent pain after spinal surgery can be successfully addressed by spinal cord stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outco mes, with or without lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that machine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, regularized logistic regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient-boosted trees to test this hypothesis and to perform internal and external validations, the objective being to confront model predictions with lead trial results using a 1-year composite outcome from 103 patients. While almost all models have demonstrated superiority on lead trialing, the RLR model appears to represent the best compromise between complexity and interpretability in the prediction of SCS efficacy. These results underscore the need to use AI-based predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

Comparison of Spinal Cord Stimulation vs. Dorsal Root Ganglion Stimulation vs. Association of Both in Patients with Refractory Chronic Back and/or Lower Limb Neuropathic Pain: An International, Prospective, Randomized, Double-Blinded, Crossover Trial (BOOST-DRG Study).

While spinal cord stimulation (SCS) is a well-established therapy to address refractory persistent spinal pain syndrome after spinal surgery (PSPS-T2), its lack of spatial selectivity and reported discomfort due to positional effects can be considered as significant limitations. As alternatives, new waveforms, such as burst stimulation and different spatial neural targets, such as dorsal root ganglion stimulation (DRGS), have shown promising results. Comparisons between DRGS and standard SCS, or their combination, have never been studied on the same patients. "BOOST DRG" is the first prospective, randomized, double-blinded, crossover study to compare SCS vs. DRGS vs. SCS+DRGS. Sixty-six PSPS-T2 patients will be recruited internationally in three centers. Before crossing over, patients will receive each stimulation modality for 1 month, using tonic conventional stimulation. After 3 months, stimulation will consist in switching to burst for 1 month, and patients will choose which modality/waveform they receive and will then be reassessed at 6 and 12 months. In addition to our primary outcome based on pain rating, this study is designed to assess quality of life, functional disability, psychological distress, pain surface coverage, global impression of change, medication quantification, adverse events, brain functional imaging and electroencephalography, with the objective being to provide a multidimensional insight based on composite pain assessment.

A Randomized Controlled Trial of Subcutaneous Nerve Stimulation for Back Pain Due to Failed Back Surgery Syndrome: The SubQStim Study.

OBJECTIVES: To compare the effectiveness of peripheral nerve stimulation utilizing a subcutaneous lead implant technique-subcutaneous nerve stimulation (SQS) plus optimized medical management (SQS + OMM arm) vs. optimized medical management alone (OMM arm) in patients with back pain due to failed back surgery syndrome. PATIENTS AND METHODS: Patients were recruited from 21 centers, in Europe, Israel, and Australia. Eligible patients were randomized (1:1) to SQS + OMM or OMM arms. Those in the SQS arm were implanted with a neurostimulator and up to two subcutaneous percutaneous cylindrical leads in the area of pain. Patients were evaluated pre-randomization and at one, three, six, and nine months post-randomization. The primary endpoint was the proportion of subjects with a ≥50% reduction in back pain intensity ("responder") from baseline to nine months. Secondary outcomes included proportion of responders with a ≥50% reduction in back pain intensity at six months and ≥30% reduction at nine months, and the mean change from baseline in back pain intensity at six and nine months between the two arms. RESULTS: Due to the slow rate of recruitment, the study was terminated early with 116 subjects randomized. A total of 33.9% (19/56, missing: n = 20 [36%]) of subjects in the SQS + OMM arm and 1.7% (1/60, missing: n = 24 [40%]) in the OMM arm were responders at Month 9 (p < 0.0001). Secondary objectives showed a significant difference in favor of SQS + OMM arm. CONCLUSION: The results indicate that the addition of SQS to OMM is more effective than OMM alone in relieving low back pain at up to nine months.

Long-Term Relief of Painful Bladder Syndrome by High-Intensity, Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Right and Left Dorsolateral Prefrontal Cortices.

Aim: To show the value of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) to treat bladder pain syndrome (BPS), characterized by suprapubic pain, urgency and increased micturition frequency. Methods: A 68-year-old woman with BPS underwent 16 sessions of high-intensity, low-frequency (1 Hz) rTMS of the DLPFC, first on the right hemisphere (one daily session for 5 days, followed by one weekly session for 5 weeks), and then on the left hemisphere (one monthly session for 6 months). Results: At the end of the rTMS protocol, suprapubic pain completely vanished, micturition frequency dramatically decreased (by 60-80%), while fatigue and sleep quality improved (by 57-60%). The patient reported an overall satisfaction rate of 80% and her activities of daily living tending to normalize. Conclusion: This is the first report showing that high-intensity, low-frequency rTMS delivered on the DLPFC region of both hemispheres can relieve most symptoms of BPS (pain, urinary symptoms, and interference with physical functioning) in clinical practice.

Peripheral Nerve Stimulation of Brachial Plexus Nerve Roots and Supra-Scapular Nerve for Chronic Refractory Neuropathic Pain of the Upper Limb.

OBJECTIVES: We report the outcome of a consecutive series of 26 patients suffering from chronic medically-refractory neuropathic pain of the upper limb (including 16 patients with complex regional pain syndrome), topographically limited, treated by brachial plexus (BP) nerve roots or supra-scapular nerve (SSN) peripheral nerve stimulation (PNS). MATERIALS AND METHODS: The technique consisted in ultrasound-guided percutaneous implantation of a cylindrical lead (Pisces-Quad, Medtronic) close to the SSN or the cervical nerve roots within the BP, depending on the pain topography. All the patients underwent a positive trial stimulation before lead connection to a subcutaneous stimulator. Chronic bipolar stimulation mean parameters were: frequency 55.5 Hertz, voltage 1.17 Volts. The voltage was set below the threshold inducing muscle contractions or paresthesias. RESULTS: Two patients were lost immediately after surgery. At last follow-up (mean 27.5 months), the 20 patients still using the stimulation experienced a mean pain relief of 67.1%. Seventeen patients were improved ≥50%, including 12 improved ≥70%. In 11 patients with a follow-up >2 years, the mean pain relief was 68%. At last follow-up, respectively, six out of the nine (67%) patients treated by SSN stimulation and 10 out of 17 patients (59%) treated by BP stimulation were improved ≥50%. At last follow-up, 12 out of 20 patients still using the stimulation were very satisfied, six were satisfied, and two were poorly satisfied. Complications were: stimulation intolerance due to shock-like sensations (three cases), superficial infection (1), lead fractures (2), and migration (1). CONCLUSION: In this pilot study, SSN or BP roots PNS provided a relatively safe, durable and effective option to control upper limb neuropathic pain.