Preoperative Counseling in Spinal Cord Stimulation: A Designated Driver in Implantable Pulse Generator-Related Inconveniences?

BACKGROUND: Spinal cord stimulation (SCS) has been reported to cause substantial pain relief and improved quality of life (QoL) in patients with persistent spinal pain syndrome (PSPS). Despite implantable pulse generator (IPG)-related inconveniences such as pain, shame, and discomfort affecting QoL and patient satisfaction, these are often neglected. Hence, the current study aims to determine the associations between patient satisfaction, IPG-related inconveniences, and preoperative counseling in a homogeneous group of patients with PSPS receiving SCS with IPG implantation in the gluteal or abdominal area. MATERIALS AND METHODS: Retrospective data on sample characteristics were gathered from the EPIC (electronic health record software) digital patient data base. Prospective data on patient satisfaction were obtained with a questionnaire that covered various topics such as shame, pain, disturbances in daily/intense activities, night rest and/or sleep, discomfort caused by clothing, and preoperative counseling. The exact location of the IPG and its scar were determined with photo analysis. Thereafter, the site of IPG placement was classified into separate quadrants within the gluteal and abdominal area. Patient satisfaction was defined as accepting the current location of the IPG without having the wish to undergo revision surgery. RESULTS: In total, 81 participants (50.9 ± 10 years) were included in this analysis, with patient satisfaction observed in 61 patients (75.3%). Among satisfied patients, more extensive preoperative counseling concerning IPG pain and discomfort was reported compared with patients who were not satisfied (p < 0.001). When comparing the two groups, significant differences were found in shame (8/81, 9.9%), IPG site pain (21/81, 25.9%), disturbance of activities (42/81, 51.9%), and clothing-related discomfort (42/81, 51.9%). CONCLUSIONS: On the basis of the current results, shared decision-making and comprehensive preoperative provision of information are recommended to optimize patient satisfaction regarding IPG pain, discomfort, and inconveniences. Although many patients experience these disadvantages despite successful SCS for pain related to PSPS, most of them accept this if they have received adequate preoperative information about expectations.

Four Decades of Occipital Nerve Stimulation for Headache Disorders: A Systematic Review.

PURPOSE OF REVIEW: Chronic headaches are a significant source of disability worldwide. Despite the development of conventional strategies, a subset of patients remain refractory and/or experience side effects following these treatments. Hence, occipital nerve stimulation (ONS) should be considered as an alternative strategy for intractable chronic headaches. This review aims to provide a comprehensive overview of the effectiveness, safety, mechanisms and practical application of ONS for the treatment of headache disorders. RECENT FINDINGS: Overall response rate of ONS is 35.7-100%, 17-100%, and 63-100% in patients with cluster headache, chronic migraine and occipital neuralgia respectively. Regarding the long-term effectivity in all groups, 41.6-88.0% of patients remain responders after ≥ 18.3 months. The most frequently reported adverse events include lead migration/fracture (13%) and local pain (7.3%). Based on our results, ONS can be considered a safe and effective treatment for chronic intractable headache disorders. To support more widespread application of ONS, additional research with larger sample sizes should be conducted.

Cingulotomy: the last man standing in the battle against medically refractory poststroke pain.

Introduction: Central poststroke pain (CPSP) places a huge burden on patient lives because patients are often refractory to conventional strategies and have little chance for spontaneous recovery. A subset of patients is even given approval for euthanasia and is without any perspective. Because the anterior cingulate cortex historically seems to be a promising target for patients with both mental and chronic pain disorders, lesioning of this central "hub" with cingulotomy may be a useful strategy for medically refractory CPSP. However, limited research is available on cingulotomy for central pain. Hence, we represent a rare case in which cingulotomy is performed on a patient with CPSP. Objectives: To describe the potential of cingulotomy in a case with CPSP. Methods: The case presented in this study concerns a 60-year-old woman who experienced CPSP, caused by a hemorrhagic stroke in the basal ganglia and thalamus. The patient visited several centers and tried multiple off-label treatments; however, she was told nothing else could be done and was even given approval for euthanasia. Hence, anterior cingulotomy was performed. Results: After surgery, no transient adverse events occurred, except for vocabulary disturbances post stroke, which disappeared after several weeks. After 14 weeks, changes in pain behavior were observed, followed by a decreased pain intensity. At a later follow-up, the pain had completely disappeared. Conclusion: Anterior cingulotomy seems to be a suitable "last-resort" option for patients with CPSP. Future research, including homogenous groups, to define the best location for lesioning is required to allow the revival of this "old" technique in the current era.

Literature Review: Mechanism, Indications, and Clinical Efficacy of Peripheral Nerve Stimulators in Lower Extremity Pain.

PURPOSE OF REVIEW: Lower extremity pain is deemed by Center for Disease Control and Prevention (CDC) to be a significant source of chronic pain in adults. If not appropriately managed, patients are subjected to risks of prolonged musculoskeletal dysfunction, disruption to quality of life, and elevated healthcare expenditures. Peripheral nerve stimulation (PNS) has shown great potential in recent years demonstrating efficacy in multiple diagnoses ranging from acute post-surgical pain to complex regional pain syndrome (CRPS). This study seeks to delineate efficacy of peripheral neuromodulation in the context of chronic lower extremity pain. RECENT FINDINGS: Prevailing clinical studies demonstrate evidence levels ranging from II to V (Oxford Centre of Level of Evidence) in lower limb PNS, attaining positive outcomes in pain scores, opioid use, and quality of life measures. Nerves most frequently targeted are the sciatic and femoral nerves with post-amputation pain and CRPS most commonly investigated for efficacy. PNS is a promising therapeutic modality demonstrated to be effective for a variety of nociceptive and neuropathic pain conditions in the lower extremity. PNS offers chronic pain physicians a powerful tool in the multi-modal management of lower limb chronic pain.

The Untold Story of Occipital Nerve Stimulation in Patients With Cluster Headache: Surgical Technique in Relation to Clinical Efficacy.

OBJECTIVES: Approximately one in every 1000 adults experiences cluster headache (CH). Although occipital nerve stimulation (ONS) appears encouraging in treatment for most patients with refractory CH, some patients do not reach adequate pain relief with ONS. A reason for failure of ONS might be anatomical variations and different surgical approaches. Therefore, an extensive literature analysis was performed, and cadaveric experimentation was combined with our clinical experience to provide a standardized proposal for ONS and obtain optimal management of patients with refractory CH. MATERIALS AND METHODS: Data from 36 articles published between 1998 and 2023 were analyzed to retrieve information on the anatomical landmarks and surgical technique of ONS. For the cadaveric experimentation (N = 1), two electrodes were inserted from the region over the foramen magnum and projected toward the lower third of the mastoid process. RESULTS: The existence of multiple approaches of ONS has been confirmed by the present analysis. Discrepancies have been found in the anatomical locations and corresponding landmarks of the greater and lesser occipital nerve. The surgical approaches differed in patient positioning, electrode placement, and imaging techniques, with an overall efficacy range of 35.7% to 90%. CONCLUSIONS: Reports on the surgical approach of ONS remain contradictory, hence emphasizing the need for standardization. Only if all implanting physicians perform the ONS surgery using a standardized protocol, can future data be combined and outcomes compared and analyzed.

Does spinal cord stimulation improve gait in Parkinson's disease: A comprehensive review.

INTRODUCTION: Axial disability, including gait disturbances, is common in Parkinson's disease (PD), especially in advanced stages. Epidural spinal cord stimulation (SCS) has been investigated as a treatment option for gait disorders in PD. Here, we review the literature on SCS in PD and evaluate its efficacy, optimal stimulation parameters, optimal electrode locations, possible effects of concurrent deep brain stimulation, and possible working mechanisms on gait. METHODS: Databases were searched for human studies involving PD patients who received an epidural SCS intervention and who had at least one gait-related outcome measure. The included reports were reviewed with respect to design and outcomes. Additionally, the possible mechanisms of action underlying SCS were reviewed. RESULTS: Out of 433 records identified, 25 unique studies with in total 103 participants were included. Most studies included only a few participants. The gait disorders of most PD patients with concurrent pain complaints, mostly low back pain, improved with SCS in almost all cases, regardless of stimulation parameters or electrode location. Higher-frequency stimulation (>200 Hz) seemed to be more effective in pain-free PD patients, but the results were inconsistent. Heterogeneity in outcome measures and follow-up times hindered comparability. CONCLUSIONS: SCS may improve gait in PD patients with neuropathic pain, but its efficacy in pain-free patients remains uncertain due to a lack of thorough double-blind studies. Apart from a well-powered, controlled, double-blind study design, future studies could further explore the initial hints that higher-frequency stimulation (>200 Hz) might be the best approach to improve gait outcomes in pain-free patients.

Spinal Cord Stimulation for Failed Back Surgery Syndrome: to Trial or Not to Trial?

Spinal cord stimulation (SCS) is a recommended therapy to treat failed back surgery syndrome (FBSS). A trial period is practiced to enhance patient selection. However, its fundamental evidence is limited, especially concerning long-term benefit and therapy safety. We compared the long-term (5.3 ± 4.0 years) clinical outcome and therapy safety of a trialed and nontrialed implantation strategy, including multidimensional variables and pain intensity fluctuations over time. A multicenter cohort analysis was performed in 2 comparable groups of FBSS patients. Regarding eligibility, patients had to be treated with SCS for at least 3 months. While the Trial group comprised patients who underwent an SCS implantation after a successful trial, the No-Trial group encompassed patients who underwent complete implantation within 1 session. The primary outcome measures were pain intensity scores and complications. The Trial and No-Trial groups consisted of 194 and 376 patients (N = 570), respectively. A statistically but not clinically significant difference in pain intensity (P = .003; effect = 0.506 (.172-.839)) was found in favor of the Trial group. No interaction between a time dependency effect and pain intensity was noted. Whereas trialed SCS patients were more likely to cease opioid usage (P = .003; OR = .509 (.326-.792)), patients in the No-Trial group endured fewer infections (P = .006; proportion difference = .43 (.007-.083)). Although the clinical relevance of our findings should be proven in future studies, this long-term real-world data study indicates that patient-centered assessments on whether an SCS trial should be performed have to be investigated. According to the current ambiguous evidence, SCS trials should be considered on a case-by-case basis. PERSPECTIVE: The currently available comparative evidence, together with our results, remains ambiguous on which SCS implantation strategy might be deemed superior. An SCS trial should be considered on a case-by-case basis, for which further investigation of its clinical utility in certain patient populations or character traits is warranted.

Spinal cord stimulation in patients suffering from chronic pain after surgery for spinal intradural tumors: A case report and literature summary.

BACKGROUND: The prevalence of pain after treatment of a spinal intradural tumor is remarkably high, approximately up to 40% of the patients suffer from central neuropathic pain. Publications on spinal cord stimulation (SCS) and its effect on pain caused by intradural spinal tumors are rare. We discuss the case of a patient suffering from chronic pain after removal of a Th7 level meningioma who was successfully treated with SCS and give an overview of the literature. METHODS: MEDLINE database was searched for neuropathic pain and intradural tumors. RESULTS: The initial search identified 35 articles, including hand-searched manuscripts. Six articles were included for analysis. CASE REPORT: A 57-year-old female suffers from neuropathic pain in both legs after surgical removal of a Th7 level intradural meningioma. Postoperative magnetic resonance imaging shows no gross abnormalities, although she developed chronic pain in both legs. Pain in combination with side effects of analgesic intake are too disabling to have decent quality of life. A successful implantation of SCS is achieved at Th5 level as a treatment for the central neuropathic pain, and, at 36 months follow-up, there is significant pain relief and almost complete discontinuation of analgesics. DISCUSSION: Central pain from spinal intradural tumors may have a different mechanism of origin than pain seen after an acute spinal cord injury (SCI). However, the basic principles of neuromodulation are the same in both etiologies, as for successful stimulation intact pathways in the spinal cord are necessary. The efficacy of SCS as treatment in intradural spinal tumors is rarely described as only a handful of case reports are published. Interestingly, the case reports show that stimulation both above and below the lesion can be effective. In patients with incomplete SCI or intradural tumor resection stimulation below the lesion could be considered and tried in a trial setting before definitive implantation.

Spinal Cord Stimulation in Failed Back Surgery Syndrome: An Integrative Review of Quantitative and Qualitative Studies.

BACKGROUND: Spinal cord stimulation (SCS) is an established therapy of failed back surgery syndrome (FBSS), although the effects on daily functioning, quality of life (QoL), and patients' expectations, experiences, and satisfaction remain elusive. The current integrative review aimed to summarize the overall effects of SCS in patients with FBSS on pain relief, health-related QoL, and daily activities. MATERIALS AND METHODS: PubMed, CINAHL, Embase, ClinicalTrials.gov, gray literature, and reference lists of relevant articles were searched for additional papers. All included studies were assessed for risk of bias using the Mixed Methods Appraisal Tool. Following the methods of Whittemore and Knafl, an integrative review and a meta-analysis were performed. RESULTS: In total, 16 articles were included; 11 articles presented quantitative outcomes, and five articles presented qualitative data. Lower back pain, leg pain, overall pain, Oswestry Disability Index, EuroQol Five Dimensions Health Questionnaire three-level/five-level, and the physical component score of Short Form Health Survey (SF-36) significantly improved during all follow-up moments. Only the mental component score of the SF-36 did not significantly improve, compared with baseline. Heterogeneity was diversely present among the studies. Patients' expectations and goals were disparate, although patients seemed to desire a return to their pre-FBSS state. Experiences with regard to the outcomes showed that patients largely recuperated after SCS, although limitations were still present. Patients also expressed inconvenience with regard to the trial period, implantation location, and recharging of the implantable pulse generator. CONCLUSIONS: SCS showed beneficial effects on different domains of life in patients with FBSS. The quantitative analyses suggest an overall improvement in most domains, although patients' experiences show that limitations in daily life and living with the SCS system persist. Multiple extensive preoperative counseling sessions and discussions with patients are deemed necessary to improve patient satisfaction and meet their expectations. Shared decision-making and provision of complete information are key factors for success.

Rare central nervous system tumors in adults: a population-based study of ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors.

Background: Ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors occur relative frequently in children, but are rare central nervous system (CNS) tumors in adults. In this population-based survey, we established incidence, treatment, and survival patterns for these tumors diagnosed in adult patients (≥18 years) over a 30-year period (1989-2018). Methods: Data on 1384 ependymomas, 454 pilocytic astrocytomas, 205 medulloblastomas, and 112 intracranial germ cell tumors were obtained from the Netherlands Cancer Registry (NCR) on the basis of a histopathological diagnosis. For each tumor type, age-standardized incidence rates and estimated annual percentage change were calculated. Trends in incidence and main treatment modalities were reported per 5-year periods. Overall survival was calculated using the Kaplan-Meier method, and relative survival rates were estimated using the Pohar-Perme estimator. Results: Incidence and survival rates remained generally stable for pilocytic astrocytomas, medulloblastomas, and germ cell tumors. Increasing incidence was observed for spinal ependymomas, mostly for myxopapillary ependymomas, and survival improved over time for grade II ependymomas (P < .01). Treatment patterns varied over time with shifting roles for surgery in ependymomas and for chemotherapy and radiation in medulloblastomas and germinomas. Conclusions: The study provides baseline information for highly needed national and international standard treatment protocols, and thus for further improving patient outcomes in these rare CNS tumors.

Dutch Consensus Paper: A Consensus View on the Place of Neurostimulation Within the Treatment Arsenal of Five Reimbursed Indications for Neurostimulation in The Netherlands.

INTRODUCTION: After an interpretation trajectory, the Dutch Quality of Healthcare Institute recommended that for five indications, spinal cord stimulation, dorsal root ganglion stimulation, or occipital nerve stimulation, together referred to as neurostimulation, can be considered effective and be reimbursed in the Netherlands. These five indications are the well and largely studied, accepted neurostimulation indications in scientific literature. As an extension of this, all the scientific societies involved in the Netherlands were required to reach a consensus about the diagnosis and treatment of these five formulated indications to describe the place of neurostimulation within the treatment algorithm. This article describes the development process and content of the consensus paper. MATERIALS AND METHODS: A scientific committee, consisting of three anesthesiologists/pain physicians (one of whom acted as the working group's chair), a neurosurgeon, a neurologist, a rehabilitation physician, and three nurse practitioners, participated. A quality advisor of the Knowledge Institute of the Dutch Federation of Medical Specialists supported the committee. The committee participated on behalf of their various scientific and professional societies. Three sessions were organized during which the place of neurostimulation in the treatment algorithm of the five relevant indications was discussed extensively. A narrative literature review and experts' opinions formed the basis of decision-making in the process. RESULTS: For all five diagnoses, general and diagnosis-specific treatment requirements, conservative treatments, and minimally invasive treatments are listed. These treatments should be considered in the chronic pain management algorithm before eventually proceeding to neurostimulation. DISCUSSION/CONCLUSION: The content of this consensus view was discussed and compared with other literature on cost-effectiveness and the place in the algorithm of treating chronic pain. This Dutch consensus paper could ultimately contribute to the maintenance or expansion of neurostimulation and the reimbursement.

Surgical Paddle Electrode Implantation as a Rescue Therapy to Failed Percutaneous Leads in Failed Back Surgery Syndrome Patients.

INTRODUCTION: Spinal cord stimulation (SCS) to treat failed back surgery syndrome (FBSS) can be provided with either percutaneously or surgically implanted electrodes. Percutaneous electrodes are considered the first choice in many pain practices, but surgical paddle electrodes can also be indicated if a percutaneous electrode fails to retain sufficient pain relief or if percutaneous implantation is considered unachievable. Although the current efficacy of surgical paddle electrodes has been based mainly upon pain intensity scores, the evidence on surgical paddle electrodes as a rescue to failed percutaneous electrodes remains even more scarce. OBJECTIVE: This study aimed to evaluate the safety and clinical effectiveness of rescue surgical paddle electrodes in FBSS patients, multidimensionally. MATERIALS AND METHODS: The occurrence of complications, pain intensity scores, psychosocial-related questionnaires, and medication intake were collected. Subsequently, a Quality-of-Life Index (QLI) was calculated. A clinically relevant effect was obtained if the minimal clinically important difference regarding pain intensity was reached. RESULTS: A total of 25 patients were included in the study. The pain intensity scores were significantly reduced (p < 0.001), and clinically relevant reductions occurred during short-term (0-6 months), mid-term (1-3 years), and long-term follow-up (≥4 years). The structural morphine usage and QLI were significantly decreased at short-term follow-up (p = 0.038 and p = 0.036, respectively). Six complications occurred in five patients, of which, four concerned hardware-related problems and two were of biological origin. CONCLUSION: SCS utilizing a surgical paddle electrode as a salvage treatment to failed conventional percutaneous cylindrical lead SCS can be practiced safely and effectively to treat FBSS. Because of potentially improved clinical effectiveness and cost-effectiveness resulting from fewer reoperations, a SCS treatment algorithm may benefit from expediting surgical paddle electrodes.

Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial.

BACKGROUND: Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS could serve as an effective treatment for patients with MICCH. METHODS: The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks' baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and near-discomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25-48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21-24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631). FINDINGS: Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15·75; IQR 9·44 to 24·75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7·38 (2·50 to 18·50; p<0·0001) in weeks 21-24, a median change of -5·21 (-11·18 to -0·19; p<0·0001) attacks per week. In the 100% ONS stimulation group, mean attack frequency decreased from 17·58 (9·83 to 29·33) at baseline to 9·50 (3·00 to 21·25) at 21-24 weeks (median change from baseline -4·08, -11·92 to -0·25), and for the 30% ONS stimulation group, mean attack frequency decreased from 15·00 (9·25 to 22·33) to 6·75 (1·50 to 16·50; -6·50, -10·83 to -0·08). The difference in median weekly mean attack frequency between groups at the end of the masked phase in weeks 21-24 was -2·42 (95% CI -5·17 to 3·33). In the masked study phase, 129 adverse events occurred with 100% ONS and 95 occurred with 30% ONS. None of the adverse events was unexpected but 17 with 100% ONS and eight with 30% ONS were labelled as serious, given they required brief hospital admission for minor hardware-related issues. The most common adverse events were local pain, impaired wound healing, neck stiffness, and hardware damage. INTERPRETATION: In patients with MICCH, both 100% ONS intensity and 30% ONS intensity substantially reduced attack frequency and were safe and well tolerated. Future research should focus on optimising stimulation protocols and disentangling the underlying mechanism of action. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

Experiences From the Patient Perspective on Spinal Cord Stimulation for Failed Back Surgery Syndrome: A Qualitatively Driven Mixed Method Analysis.

INTRODUCTION: When neither pharmacological therapies nor alternative interventions provide sufficient pain relief, spinal cord stimulation (SCS) can be used to treat Failed Back Surgery Syndrome (FBSS). Although it seems reasonable that quality of life (QoL)- and psychosocial-related factors contribute to the outcome of SCS since pain is a multidimensional experience, few qualitative studies have explored the expectations of SCS and experiences on SCS to treat FBSS from the patient perspective. OBJECTIVES: The aim of this study was to qualitatively and quantitatively map the FBSS patients' experiences with SCS and the effects of SCS on low back pain caused by FBSS. MATERIALS AND METHODS: A qualitative study with in-depth semi-structured interviews, assisted by the Brief Pain Inventory (BPI)-questionnaire. RESULTS: Seven themes regarding patients' experiences, subdivided into 15 categories, were identified, including an understudied theme within this field of research, Spiritual Well-Being. "Acceptance" and "coping" emerged as pre-eminent motifs throughout these themes. Moreover, the realization of patients' expectations were variable throughout the presented themes. According to the BPI Questionnaire, four out of 13 patients (31%) had significant pain relief (≥50%). Seven out of 13 (54%) reported a ≥50% increase regarding enjoyment of life. CONCLUSION: Multiple QoL- and psychosocial-related themes are related to SCS-outcomes. In order to improve SCS-outcomes for both short- and long-term, these themes should be implemented as a multidimensional approach, both prior to implantation as during follow-up.

Motor cortex stimulation in chronic neuropathic orofacial pain syndromes: a systematic review and meta-analysis.

Invasive motor Cortex Stimulation (iMCS) was introduced in the 1990's for the treatment of chronic neuropathic orofacial pain (CNOP), although its effectiveness remains doubtful. However, CNOP is known to be a heterogeneous group of orofacial pain disorders, which can lead to different responses to iMCS. Therefore, this paper investigated (1) whether the effectiveness of iMCS is significantly different among different CNOP disorders and (2) whether other confounding factors can be impacting iMCS results in CNOP. A systematic review and meta-analysis using a linear mixed-model was performed. Twenty-three papers were included, totaling 140 CNOP patients. Heterogeneity of the studies showed to be 55.8%. A visual analogue scale (VAS) measured median pain relief of 66.5% (ranging from 0-100%) was found. Linear mixed-model analysis showed that patients suffering from trigeminal neuralgia responded significantly more favorable to iMCS than patients suffering from dysfunctional pain syndromes (p = 0.030). Also, patients suffering from CNOP caused by (supra)nuclear lesions responded marginally significantly better to iMCS than patients suffering from CNOP due to trigeminal nerve lesions (p = 0.049). No other confounding factors were elucidated. This meta-analysis showed that patients suffering from trigeminal neuralgia and patients suffering from (supra)nuclear lesions causing CNOP responded significantly more favorable than others on iMCS. No other confounding factors were found relevant.

Invasive Motor Cortex Stimulation Influences Intracerebral Structures in Patients With Neuropathic Pain: An Activation Likelihood Estimation Meta-Analysis of Imaging Data.

OBJECTIVE: Invasive motor cortex stimulation (iMCS) has been proposed as a treatment for intractable neuropathic pain syndromes. Although the mechanisms underlying the analgesic effect of iMCS remain largely elusive, several studies found iMCS-related changes in regional cerebral blood flow (rCBF) in neuropathic pain patients. The aim of this study was to meta-analyze the findings of neuroimaging studies on rCBF changes to iMCS. METHODS: PubMed, Embase, MEDLINE, Google Scholar, and the Cochrane Library were systematically searched for retrieval of relevant scientific papers. After initial assessment of relevancy by screening title and abstract by two investigators, independently, predefined inclusion and exclusion criteria were used for final inclusion of papers. Descriptive results were statistically assessed, whereas coordinates were pooled and meta-analyzed in accordance with the activation likelihood estimation (ALE) methodology. RESULTS: Six studies were included in the systematic narrative analysis, suggesting rCBF increases in the cingulate gyrus, thalamus, insula, and putamen after switching the MCS device "ON" as compared to the "OFF" situation. Decreases in rCBF were found in for example the precentral gyrus and different occipital regions. Two studies did not report stereotactic coordinates and were excluded from further analysis. ALE meta-analysis showed that, after switching the iMCS electrode "ON," increased rCBF occurred in the (1) anterior cingulate gyrus; (2) putamen; (3) cerebral peduncle; (4) precentral gyrus; (5) superior frontal gyrus; (6) red nucleus; (7) internal part of the globus pallidus; (8) ventral lateral nucleus of the thalamus; (9) medial frontal gyrus; (10) inferior frontal gyrus; and (11) claustrum, as compared to the "OFF" situation. Reductions in rCBF were found in the posterior cingulate gyrus when the iMCS electrode was turned "OFF." CONCLUSIONS: These findings suggested that iMCS induces changes in principal components of the default mode-, the salience-, and sensorimotor network.

A systematic review of the proposed mechanisms underpinning pain relief by primary motor cortex stimulation in animals.

Experimental treatments for treating neuropathic pain include transcranial magnetic stimulation (TMS) and invasive electric motor cortex stimulation (iMCS) of the primary motor cortex (M1). Mechanisms of action of both methods, however, remain largely elusive. Within this paper, we focus on animal-based experiments in order to investigate the biological mechanisms that are involved in alleviating pain by use of TMS and/or iMCS. Therefore, this paper systematically reviewed the animal-based evidence on these mechanisms. Multiple online databases were systematically searched and retrieved articles were assessed using predefined inclusion and exclusion criteria. Twenty-three suitable articles were included; six on TMS and seventeen on iMCS. In general, iMCS and TMS were found to impact the primary motor cortex structure and function in animals. Furthermore, structural and functional changes within the thalamus, striatum, periaqueductal grey, rostral ventromedial medulla and dorsal horn were reported to occur. Although widespread, all areas in which structural and functional changes occurred after TMS and iMCS have been found to be interconnected anatomically. This could provide a rationale for future investigations of treating neuropathic pain by use of neuromodulation.

Post-mortem 11.7 Tesla Magnetic Resonance Imaging vs. Polarized Light Imaging Microscopy to Measure the Angle and Orientation of Dorsal Root Afferents in the Human Cervical Dorsal Root Entry Zone.

Background: Destruction of the afferents by dorsal root entry zone (DREZ) surgery may be an effective treatment of intractable neuropathic pain, though it remains a high-risk surgical intervention. Potential complications due to the lesioning of structures within the cervical spinal cord other than the DREZ can be minimized by accurate knowledge of the optimal insertion angle [i.e., the angle between the DREZ and the posterior median sulcus (PMS)]. The employed insertion angle was based on measurements between the DREZ and the PMS on post-mortem transverse slices. However, new, more sophisticated imaging techniques are currently available and are thought to yield higher spatial resolution and more accurate images. Obejctive: This article measures the angle between the DREZ and the PMS on 11.7T post-mortem magnetic resonance images and compares these findings with polarized light imaging (PLI) microscopy images of the same specimens in order to quantify fiber orientation within the DREZ. Methods: To visualize the anatomy of the cervical DREZ, magnetic resonance imaging (MRI), diffusion-weighted MRI (dMRI), probabilistic tractography, and PLI were performed on three post-mortem human cervical spinal cords at level C5-C6. The MR data was used to measure the angle between the DREZ and the PMS. MR images were complemented by probabilistic tractography results. Then, the orientation of fibers within the DREZ was quantified by use of PLI microscopy. Results: Median angle between the DREZ and the PMS, as measured on MR-images, was found to be 40.1° (ranging from 34.2° to 49.1°) and 39.8° (ranging from 31.1° to 47.8°) in the left and right hemicord, respectively. Median fiber orientation within the DREZ, as quantified by PLI, was 28.5° (ranging from 12.0° to 44.3°) and 27.7° (ranging from 8.5° to 38.1°) in the left and right hemicord, respectively. Conclusion: Our study, which provides an improved understanding of the anatomy of the DREZ, the angle between the DREZ and the PMS and the median fiber orientation within the DREZ, could contribute to safer DREZ-lesioning surgery to treat chronic neuropathic pain in the future.

Systematic Review and Neural Network Analysis to Define Predictive Variables in Implantable Motor Cortex Stimulation to Treat Chronic Intractable Pain.

Implantable motor cortex stimulation (iMCS) has been performed for >25 years to treat various intractable pain syndromes. Its effectiveness is highly variable and, although various studies revealed predictive variables, none of these were found repeatedly. This study uses neural network analysis (NNA) to identify predictive factors of iMCS treatment for intractable pain. A systematic review provided a database of patient data on an individual level of patients who underwent iMCS to treat refractory pain between 1991 and 2017. Responders were defined as patients with a pain relief of >40% as measured by a numerical rating scale (NRS) score. NNA was carried out to predict the outcome of iMCS and to identify predictive factors that impacted the outcome of iMCS. The outcome prediction value of the NNA was expressed as the mean accuracy, sensitivity, and specificity. The NNA furthermore provided the mean weight of predictive variables, which shows the impact of the predictive variable on the prediction. The mean weight was converted into the mean relative influence (M), a value that varies between 0 and 100%. A total of 358 patients were included (202 males [56.4%]; mean age, 54.2 ±13.3 years), 201 of whom were responders to iMCS. NNA had a mean accuracy of 66.3% and a sensitivity and specificity of 69.8% and 69.4%, respectively. NNA further identified 6 predictive variables that had a relatively high M: 1) the sex of the patient (M = 19.7%); 2) the origin of the lesion (M = 15.1%); 3) the preoperative numerical rating scale score (M = 9.2%); 4) preoperative use of repetitive transcranial magnetic stimulation (M = 7.3%); 5) preoperative intake of opioids (M = 7.1%); and 6) the follow-up period (M = 13.1%). The results from the present study show that these 6 predictive variables influence the outcome of iMCS and that, based on these variables, a fair prediction model can be built to predict outcome after iMCS surgery. PERSPECTIVE: The presented NNA analyzed the functioning of computational models and modeled nonlinear statistical data. Based on this NNA, 6 predictive variables were identified that are suggested to be of importance in the improvement of future iMCS to treat chronic pain.

Ex vivo visualization of the trigeminal pathways in the human brainstem using 11.7T diffusion MRI combined with microscopy polarized light imaging.

Classic anatomical atlases depict a contralateral hemispheral representation of each side of the face. Recently, however, a bilateral projection of each hemiface was hypothesized, based on animal studies that showed the coexistence of an additional trigeminothalamic tract sprouting from the trigeminal principal sensory nucleus that ascends ipsilaterally. This study aims to provide an anatomical substrate for the hypothesized bilateral projection. Three post-mortem human brainstems were scanned for anatomical and diffusion magnetic resonance imaging at 11.7T. The trigeminal tracts were delineated in each brainstem using track density imaging (TDI) and tractography. To evaluate the reconstructed tracts, the same brainstems were sectioned for polarized light imaging (PLI). Anatomical 11.7T MRI shows a dispersion of the trigeminal tract (tt) into a ventral and dorsal portion. This bifurcation was also seen on the TDI maps, tractography results and PLI images of all three specimens. Referring to a similar anatomic feature in primate brains, the dorsal and ventral tracts were named the dorsal and ventral trigeminothalamic tract (dtt and vtt), respectively. This study shows that both the dtt and vtt are present in humans, indicating that each hemiface has a bilateral projection, although the functional relevance of these tracts cannot be determined by the present anatomical study. If both tracts convey noxious stimuli, this could open up new insights into and treatments for orofacial pain in patients.