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Objectives: Spinal cord stimulation (SCS) is a surgical treatment for severe, chronic, neuropathic pain. It is based on one to two lead(s) implanted in the epidural space, stimulating the dorsal column. It has long been assumed that when deactivating SCS, there is a variable interval before the patient perceives the return of the pain, a phenomenon often termed echo or carryover effect. Although the carryover effect has been problematized as a source of error in crossover studies, no experimental investigation of the effect has been published. This open, prospective, international multicenter study aimed to systematically document, quantify, and investigate the carryover effect in SCS., Materials and Methods: Eligible patients with a beneficial effect from their SCS treatment were instructed to deactivate their SCS device in a home setting and to reactivate it when their pain returned. The primary outcome was duration of carryover time defined as the time interval from deactivation to reactivation. Central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) were registered and correlated with carryover time using nonparametric tests (Mann-Whitney/Kruskal-Wallis) for categorical data and linear regression for continuous data., Results: In total, 158 patients were included in the analyses. A median carryover time of five hours was found (interquartile range 2.5;21 hours). Back pain as primary indication for SCS, high-frequency stimulation, and higher pain score at the time of deactivation were correlated with longer carryover time., Conclusions: This study confirms the existence of the carryover effect and indicates a remarkably high degree of interindividual variation. The results suggest that the magnitude of carryover may be correlated to the nature of the pain condition and possibly stimulation paradigms., Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT03386058., Competing Interests: Conflict of Interest Bart Billet serves as a consultant for Abbott, Saluda, Bioelectronics, and Medtronic. Helga Angela Gulisano has received lecture fees from Medtronic. Jens Christian Hedemann Sørensen has received consulting fees from Novo Nordic and has a patent application for wireless brain-computer interface and stock options with Cenexum ApS and Neurizon ApS. Kaare Meier has received speaker’s fees from Abbott and has coownership of data base company Neurizon. Kliment Gatzinsky has received honoraria from Boston Scientific for lectures and serves on the advisory boards for Medtronic and Boston Scientific. Thomas Ruland reports consulting fees from Abbott. The remaining authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To support rational decision-making on spinal cord stimulation (SCS), a European expert panel developed an educational e-health tool using the RAND/University of California at Los Angeles Appropriateness Method. This retrospective study aimed to determine the applicability and validity of the tool using data from patients for whom SCS had been considered., Materials and Methods: A total of 12 European implant centers retrieved data from 25 to 50 consecutive patients for whom SCS was considered in 2018-2019. For each patient, data were captured on the clinical and psychosocial variables included in the e-health tool, center decisions on SCS, and patient outcomes. Patient outcomes included global perception of effect by the patient and observer, and pain reduction (numeric pain rating scale) at six-month follow-up., Results: In total, 483 patients were included, of whom 133 received a direct implant, 258 received an implant after a positive trial, 32 had a negative trial, and 60 did not receive SCS for reasons other than a negative trial. The most frequent indication was persistent spinal pain syndrome type 1 and type 2 (74%), followed by neuropathic pain syndromes (13%), complex regional pain syndrome (12%), and ischemic pain syndromes (0.8%). Data on the clinical and psychosocial variables were complete for 95% and 93% of patients, respectively, and missing data did not have a significant impact on the study outcomes. In patients who had received SCS, panel recommendations were significantly associated with patient outcomes (p < 0.001 for all measures). Substantial improvement ranged from 25% if the e-health tool outcome was "not recommended" to 83% if SCS was "strongly recommended". In patients who underwent a trial (N = 290), there was 3% of trial failure when SCS was "strongly recommended" vs 46% when SCS was "not recommended"., Conclusions: Retrospective application of the e-health tool on patient data showed a strong relationship between the panel recommendations and both SCS trial results and treatment outcomes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on the use of neurostimulation in the cervical region to improve outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for an often-overlooked area of neurostimulation practice., Materials and Methods: Authors were chosen based upon their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to the present. Identified studies were graded using the US Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant., Results: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process., Conclusions: The NACC recommends best practices regarding the use of cervical neuromodulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be utilized as a guide to assist decision making when clinically appropriate., (Copyright © 2021 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Introduction: The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications., Methods: The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar., Results: Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated., Conclusions: Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation., (© 2014 International Neuromodulation Society.)

Apoptosis-related mechanisms are important in the pathophysiology of hypoxic-ischemic injury in the neonatal brain. Caspases are the major executioners of apoptosis, but there are a number of upstream players that influence the cell death pathways. The Bcl-2 family proteins are important modulators of mitochondrial permeability, working either to promote or prevent apoptosis. In this study we focused on the anti-apoptotic Bcl-2 protein after neonatal cerebral hypoxia-ischemia (HI) in 8-day-old rats. Bcl-2 translocated to nuclei and accumulated there over the first 24h of reperfusion after HI, as judged by immunohistochemistry and immuno-electron microscopy. We also found that the total level of Bcl-2 decreased after HI in vivo and after ionophore challenge in cultured human neuroblastoma (IMR-32) cells in vitro. Furthermore, the Bcl-2 reduction was calpain-dependent, because it could be prevented by the calpain inhibitor CX295 both in vivo and in vitro, suggesting cross-talk between excitotoxic and apoptotic mechanisms., (Copyright 2009 Elsevier Inc. All rights reserved.)