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.

Neurovascular and Neurometabolic Couplings in Dynamic Calibrated fMRI: Transient Oxidative Neuroenergetics for Block-Design and Event-Related Paradigms.

Functional magnetic resonance imaging (fMRI) with blood-oxygenation level dependent (BOLD) contrast is an important tool for mapping brain activity. Interest in quantitative fMRI has renewed awareness in importance of oxidative neuroenergetics, as reflected by cerebral metabolic rate of oxygen consumption(CMRO2), for supporting brain function. Relationships between BOLD signal and the underlying neurophysiological parameters have been elucidated to allow determination of dynamic changes inCMRO2 by "calibrated fMRI," which require multi-modal measurements of BOLD signal along with cerebral blood flow (CBF) and volume (CBV). But how doCMRO2 changes, steady-state or transient, derived from calibrated fMRI compare with neural activity recordings of local field potential (LFP) and/or multi-unit activity (MUA)? Here we discuss recent findings primarily from animal studies which allow high magnetic fields studies for superior BOLD sensitivity as well as multi-modal CBV and CBF measurements in conjunction with LFP and MUA recordings from activated sites. A key observation is that while relationships between neural activity and sensory stimulus features range from linear to non-linear, associations between hyperemic components (BOLD, CBF, CBV) and neural activity (LFP, MUA) are almost always linear. More importantly, the results demonstrate good agreement between the changes inCMRO2 and independent measures of LFP or MUA. The tight neurovascular and neurometabolic couplings, observed from steady-state conditions to events separated by <200 ms, suggest rapid oxygen equilibration between blood and tissue pools and thus calibrated fMRI at high magnetic fields can provide high spatiotemporal mapping ofCMRO2 changes.

Energetics of neuronal signaling and fMRI activity.

Energetics of resting and evoked fMRI signals were related to localized ensemble firing rates (nu) measured by electrophysiology in rats. Two different unstimulated, or baseline, states were established by anesthesia. Halothane and alpha-chloralose established baseline states of high and low energy, respectively, in which forepaw stimulation excited the contralateral primary somatosensory cortex (S1). With alpha-chloralose, forepaw stimulation induced strong and reproducible fMRI activations in the contralateral S1, where the ensemble firing was dominated by slow signaling neurons (SSN; nu range of 1-13 Hz). Under halothane, weaker and less reproducible fMRI activations were observed in the contralateral S1 and elsewhere in the cortex, but ensemble activity in S1 was dominated by rapid signaling neurons (RSN; nu range of 13-40 Hz). For both baseline states, the RSN activity (i.e., higher frequencies, including the gamma band) did not vary upon stimulation, whereas the SSN activity (i.e., alpha band and lower frequencies) did change. In the high energy baseline state, a large majority of total oxidative energy [cerebral metabolic rate of oxygen consumption (CMR(O2))] was devoted to RSN activity, whereas in the low energy baseline state, it was roughly divided between SSN and RSN activities. We hypothesize that in the high energy baseline state, the evoked changes in fMRI activation in areas beyond S1 are supported by rich intracortical interactions represented by RSN. We discuss implications for interpreting fMRI data where stimulus-specific DeltaCMR(O2) is generally small compared with baseline CMR(O2).