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Because the presence of pain impedes motor recovery in individuals with spinal cord injury (SCI), it is necessary to understand their supraspinal substrates in translational animal models. Using functional magnetic resonance imaging (fMRI) in a rat model of hemicontusion cervical SCI, supraspinal changes were mapped and correlated with sensorimotor behavioral outcomes. Female adult rats underwent sham or SCI using a 2.5 mm impactor and 150 kdyn force. SCI permanently impaired motor activity in only the ipsilesional forelimb along with thermal hyperalgesia at 5 and 6 weeks. Spinal MRI at 8 weeks after SCI showed ipsilateral T1 and T2 lesions with no discernable lesions across shams. fMRI mapping during electrical forepaw stimulation indicated SCI-induced sensorimotor reorganization with an expansion of the contralesional forelimb representation. Resting state fMRI-based functional connectivity density (FCD), a marker of regional neuronal hubs, increased or decreased across brain regions involved in nociception. FCD increases after SCI were in the primary and secondary somatosensory cortices (S1 and S2), anterior cingulate cortex (ACC), insula, and the pre-frontal cortex (PFC), and decreases were across the hippocampus, thalamus, hypothalamus, and amygdala in SCI. Resting state functional connectivity (RSFC) assessments from the FCD altered regions of interest indicated cortico-cortical RSFC increases and cortico-insular, cortico-thalamic, and cortico-hypothalamic RSFC decreases after SCI. Hippocampus, amygdala, and thalamus showed decreased RSFC with most cortical regions and between themselves except the hippocampus–amygdala network, which showed increased RSFC after SCI. Whereas select nociceptive region's intrinsic activity associated strongly with evoked pain behaviors after SCI (e.g., PFC, ACC, hippocampus, thalamus, hypothalamus, M1, and S1(BF)) other nociceptive regions had weaker associations (e.g., amygdala, insula, auditory cortex, S1(FL), S1(HL), S2, and M2), but differed significantly in their intrinsic activities between sham and SCI. The weaker associated nociceptive regions may possibly encode both the evoked and affective components of pain.

OBJECTIVE In a 2014 analysis of orthopedic and neurological surgical case logs published by the Accreditation Council for Graduate Medical Education (ACGME), it was reported that graduating neurosurgery residents performed more than twice the number of spinal procedures in their training compared with graduating orthopedic residents. There has, however, been no follow-up assessment of this trend. Moreover, whether this gap in case volume equates to a similar gap in procedural hours has remained unstudied. Given the association between surgical volume and outcomes, evaluating the status of this disparity has value. Here, the authors assess trends in case volume and procedural hours in adult spine surgery for graduating orthopedic and neurological surgery residents from 2014 to 2019. METHODS A retrospective analysis of ACGME case logs from 2014 to 2019 for graduating orthopedic and neurological surgery residents was conducted for adult spine surgeries. Case volume was converted to operative hours by using periprocedural times from the 2019 Medicare/Medicaid Physician Fee Schedule. Graduating residents’ spinal cases and hours, averaged over the study period, were compared between the two specialties by using 2-tailed Welch’s unequal variances t-tests (α = 0.05). Longitudinal trends in each metric were assessed by linear regression followed by cross-specialty comparisons via tests for equality of slopes. RESULTS From 2014 to 2019, graduating neurosurgical residents logged 6.8 times as many spinal cases as their orthopedic counterparts, accruing 431.6 (95% CI 406.49–456.61) and 63.8 (95% CI 57.08–70.56) cases (p < 0.001), respectively. Accordingly, graduating neurosurgical residents logged 6.1 times as many spinal procedural hours as orthopedic surgery residents, accruing 1020.7 (95% CI 964.70–1076.64) and 166.6 (95% CI 147.76–185.35) hours (p < 0.001), respectively. Over these 5 years, both fields saw a linear increase in graduating residents’ adult spinal case volumes and procedural hours, and these growth rates were higher for neurosurgery (+16.2 cases/year vs +4.4 cases/year, p < 0.001; +36.4 hours/year vs +12.4 hours/year, p < 0.001). CONCLUSIONS Graduating neurosurgical residents accumulated substantially greater adult spinal case volumes and procedural hours than their orthopedic counterparts from 2014 to 2019. This disparity has been widened by a higher rate of growth in adult spinal cases among neurosurgery residents. Accordingly, targeted efforts to increase spinal exposure for orthopedic surgery residents—such as using cross-specialty collaboration—should be explored.

Study design This was a survey of the surgeon members of the Lumbar Spine Research Society (LSRS). Objective The purpose of this study was to assess trends in surgical practice and patient management involving elective and emergency surgery in the early months of the coronavirus pandemic. Summary of background data The novel coronavirus has radically disrupted medical care in the first half of 2020. Little data exists regarding the exact nature of its effect on spine care. Methods A 53-question survey was sent to the surgeon members of the LSRS. Respondents were contacted via email 3 times over a 2-week period in late April. Questions concentrated on surgical and clinical practice patterns before and after the pandemic. Other data included elective surgical schedules and volumes, as well as which emergency cases were being performed. Surgeons were asked about the status of coronavirus disease 2019 (COVID-19) virus testing. Circumstances for performing surgical intervention on patients with and without testing as well as patients testing positive were explored. Results A total of 43 completed surveys were returned of 174 sent to active surgeons in the LSRS (25%). Elective lumbar spine procedures decreased by 90% in the first 2 months of the pandemic, but emergency procedures did not change. Patients with "stable" lumbar disease had surgeries deferred indefinitely, even beyond 8 weeks if necessary. In-person outpatient visits became increasingly rare events, as telemedicine consultations accounted for 67% of all outpatient spine appointments. In total, 91% surgeons were under some type of confinement. Only 11% of surgeons tested for the coronavirus on all surgical patients. Conclusions Elective lumbar surgery was significantly decreased in the first few months of the coronavirus pandemic, and much of outpatient spine surgery was practiced via telemedicine. Despite these constraints, spine surgeons performed emergency surgery when indicated, even when the COVID-19 status of patients was unknown. Level of evidence Level IV.

Highlights • Astroglial TLRs mediate host-defense and pathogen dissemination in CNS infections. • Astroglial TLRs help clearance of protein aggregates in neurodegenerative diseases. • Astroglial TLR signaling contributes to inflammation in CNS injury and disease. • Signaling through TLRs promotes beneficial and detrimental functions of astrocytes. • TLRs in astrocytes could be therapeutic targets in CNS disease and injury., Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes and microglia are the principal cells that mediate innate immunity in the CNS. Pattern recognition receptors (PRRs), expressed by astrocytes and microglia, sense pathogen-derived or endogenous ligands released by damaged cells and initiate the innate immune response. Toll-like receptors (TLRs) are a well-characterized family of PRRs. The contribution of microglial TLR signaling to CNS pathology has been extensively investigated. Even though astrocytes assume a wide variety of key functions, information about the role of astroglial TLRs in CNS disease and injuries is limited. Because astrocytes display heterogeneity and exhibit phenotypic plasticity depending on the effectors present in the local milieu, they can exert both detrimental and beneficial effects. TLRs are modulators of these paradoxical astroglial properties. The goal of the current review is to highlight the essential roles played by astroglial TLRs in CNS infections, injuries and diseases. We discuss the contribution of astroglial TLRs to host defense as well as the dissemination of viral and bacterial infections in the CNS. We examine the link between astroglial TLRs and the pathogenesis of neurodegenerative diseases and present evidence showing the pivotal influence of astroglial TLR signaling on sterile inflammation in CNS injury. Finally, we define the research questions and areas that warrant further investigations in the context of astrocytes, TLRs, and CNS dysfunction.

Contract negotiation is a reality in the career of any neurosurgeon. However, little formal training exists for physicians - including neurosurgeons - on potential techniques and strategies for conducting meaningful contract negotiation. Increasing numbers of neurosurgeons seek hospital employment for which an employment contract will be provided. During contract negotiation, it is likely that a young neurosurgeon will be in discussion with an experienced negotiator acting on behalf of a hospital, practice, or department. Understanding and adapting to this imbalance in experience and using basic negotiating techniques as a means of approaching and resolving key contract issues is critical for the neurosurgeon to maximize his or her value in the course of contract negotiation. Even without formal training in negotiation in residency, negotiation skills can be taught, practiced, and improved. In affiliation with the Medical Director's Ad-Hoc Representational Section of Council of State Neurosurgical Societies (CSNS) this article is intended to serve as a practical guide for contract negotiation. Contract basics, negotiation terms, strategies, unique neurosurgical issues, and value creation are explored.

Study Design: Secondary analysis of data from the multicenter, randomized, parallel-controlled Food and Drug Administration (FDA) investigational device exemption study. Objective: Studies on outcomes following anterior cervical discectomy and fusion (ACDF) in individuals with diabetes are scarce. We compared 24-month radiological and clinical outcomes in individuals with and without diabetes undergoing single-level ACDF with either i-FACTOR or local autologous bone. Methods: Between 2006 and 2013, 319 individuals with single-level degenerative disc disease (DDD) and no previous fusion at the index level underwent ACDF. The presence of diabetes determined the 2 cohorts. Data collected included radiological fusion evaluation, neurological outcomes, Neck Disability Index (NDI), Visual Analog Scale (VAS) scores, and the 36-Item Short Form Survey Version 2 (SF-36v2) Physical and Mental component summary scores. Results: There were 35 individuals with diabetes (11.1%; average body mass index [BMI] = 32.99 kg/m2; SD = 5.72) and 284 without (average BMI = 28.32 kg/m2; SD = 5.67). The number of nondiabetic smokers was significantly higher than diabetic smokers: 73 (25.70%) and 3 (8.57%), respectively. Preoperative scores of NDI, VAS arm pain, and SF-36v2 were similar between the diabetic and nondiabetic participants at baseline; however, VAS neck pain differed significantly between the cohorts at baseline ( P = .0089). Maximum improvement for NDI, VAS neck and arm pain, and SF-36v2 PCS and MCS scores was seen at 6 months in both cohorts and remained stable until 24 months. Conclusions: ACDF is effective for cervical radiculopathy in patients with diabetes. Diabetes is not a contraindication for patients requiring single-level surgery for cervical DDD.

OBJECTIVEThe long-term efficacy of posterior foraminotomy compared with anterior cervical decompression and fusion (ACDF) for the treatment of degenerative disc disease with radiculopathy has not been previously investigated in a population-based cohort.METHODSAll patients in the national Swedish Spine Register (Swespine) from January 1, 2006, until November 15, 2017, with cervical degenerative disc disease and radiculopathy were assessed. Using propensity score matching, patients treated with posterior foraminotomy were compared with those undergoing ACDF. The primary outcome measure was the Neck Disability Index (NDI), a patient-reported outcome score ranging from 0% to 100%, with higher scores indicating greater disability. A minimal clinically important difference was defined as > 15%. Secondary outcomes were assessed with additional patient-reported outcome measures (PROMs).RESULTSA total of 4368 patients (2136/2232 women/men) met the inclusion criteria. Posterior foraminotomy was performed in 647 patients, and 3721 patients underwent ACDF. After meticulous propensity score matching, 570 patients with a mean age of 54 years remained in each group. Both groups had substantial decreases in their NDI scores; however, after 5 years, the difference was not significant (2.3%, 95% CI −4.1% to 8.4%; p = 0.48) between the groups. There were no significant differences between the groups in EQ-5D or visual analog scale (VAS) for neck and arm scores. The secondary surgeries on the index level due to restenosis were more frequent in the foraminotomy group (6/100 patients vs 1/100), but on the adjacent segments there was no difference between groups (2/100).CONCLUSIONSIn patients with cervical degenerative disc disease and radiculopathy, both groups demonstrated clinical improvements at the 5-year follow-up that were comparable and did not achieve a clinically important difference from one another, even though the reoperation rate favored the ACDF group. This study design obtains population-based results, which are generalizable.

Background The recruitment of immune system cells into the central nervous system (CNS) has a profound effect on the outcomes of injury and disease. Glia-derived chemoattractants, including chemokines, play a pivotal role in this process. In addition, cytokines and chemokines influence the phenotype of infiltrating immune cells. Depending on the stimuli present in the local milieu, infiltrating macrophages acquire the classically activated M1 or alternatively activated M2 phenotypes. The polarization of macrophages into detrimental M1 versus beneficial M2 phenotypes significantly influences CNS pathophysiology. Earlier studies indicated that a toll-like receptor 9 (TLR9) antagonist modulates astrocyte-derived cytokine and chemokine release. However, it is not known whether these molecular changes affect astrocyte-induced chemotaxis and polarization of macrophages. The present studies were undertaken to address these issues. Methods The chemotaxis and polarization of mouse peritoneal macrophages by spinal cord astrocytes were evaluated in a Transwell co-culture system. Arrays and ELISA were utilized to quantify chemokines in the conditioned medium (CM) of pure astrocyte cultures. Immunostaining for M1- and M2-specific markers characterized the macrophage phenotype. The percentage of M2 macrophages at the glial scar was determined by stereological approaches in mice sustaining a mid-thoracic spinal cord contusion injury (SCI) and intrathecally treated with oligodeoxynucleotide 2088 (ODN 2088), the TLR9 antagonist. Statistical analyses used two-tailed independent-sample t-test and one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test. A p value Results ODN 2088-treated astrocytes significantly increased the chemotaxis of peritoneal macrophages via release of chemokine (C-C motif) ligand 1 (CCL1). Vehicle-treated astrocytes polarized macrophages into the M2 phenotype and ODN 2088-treated astrocytes promoted further M2 polarization. Reduced CCL2 and CCL9 release by astrocytes in response to ODN 2088 facilitated the acquisition of the M2 phenotype, suggesting that CCL2 and CCL9 are negative regulators of M2 polarization. The percentage of M2 macrophages at the glial scar was higher in mice sustaining a SCI and receiving ODN 2088 treatment as compared to vehicle-treated injured controls. Conclusions TLR9 antagonism could create a favorable environment during SCI by supporting M2 macrophage polarization and chemotaxis via modulation of astrocyte-to-macrophage signals.

Purpose To compare patient-reported 5-year clinical outcomes between laminectomy alone versus laminectomy with instrumented fusion in patients with degenerative cervical myelopathy in a population-based cohort. Methods All patients in the national Swedish Spine Register (Swespine) from January 2006 until March 2019, with degenerative cervical myelopathy, were assessed. Multiple imputation and propensity score matching based on clinicodemographic and radiographic parameters were used to compare patients treated with laminectomy alone with patients treated with laminectomy plus posterior-lateral instrumented fusion. The primary outcome measure was the European Myelopathy Score, a validated patient-reported outcome measure. The scale ranges from 5 to 18, with lower scores reflecting more severe myelopathy. Results Among 967 eligible patients, 717 (74%) patients were included. Laminectomy alone was performed on 412 patients (mean age 68 years; 149 women [36%]), whereas instrumented fusion was added for 305 patients (mean age 68 years; 119 women [39%]). After imputation, the propensity for smoking, worse myelopathy scores, spondylolisthesis, and kyphosis was slightly higher in the fusion group. After imputation and propensity score matching, there were on average 212 pairs patients with a 5-year follow-up in each group. There were no important differences in patient-reported clinical outcomes between the methods after 5 years. Due to longer hospitalization times and implant-related costs, the mean cost increase per instrumented patient was approximately $4700 US. Conclusions Instrumented fusions generated higher costs and were not associated with superior long-term clinical outcomes. These findings are based on a national cohort and can thus be regarded as generalizable.

Electrical stimulation is used to elicit muscle contraction and can be utilized for neurorehabilitation following spinal cord injury when paired with voluntary motor training. This technology is now an important therapeutic intervention that results in improvement in motor function in patients with spinal cord injuries. The purpose of this review is to summarize the various forms of electrical stimulation technology that exist and their applications. Furthermore, this paper addresses the potential future of the technology.

BackgroundNeuropathic pain is often observed in individuals with multiple sclerosis (MS) and spinal cord injury (SCI) and is not adequately alleviated by current pharmacotherapies. A better understanding of underlying mechanisms could facilitate the discovery of novel targets for therapeutic interventions. We previously reported that decreased plasma membrane calcium ATPase 2 (PMCA2) expression in the dorsal horn (DH) of healthy PMCA2+/−mice is paralleled by increased sensitivity to evoked nociceptive pain. These studies suggested that PMCA2, a calcium extrusion pump expressed in spinal cord neurons, plays a role in pain mechanisms. However, the contribution of PMCA2 to neuropathic pain processing remains undefined. The present studies investigated the role of PMCA2 in neuropathic pain processing in the DH of wild-type mice affected by experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and following SCI.MethodsEAE was induced in female and male C57Bl/6N mice via inoculation with myelin oligodendrocyte glycoprotein fragment 35–55 (MOG35–55) emulsified in Complete Freund’s Adjuvant (CFA). CFA-inoculated mice were used as controls. A severe SC contusion injury was induced at thoracic (T8) level in female C57Bl/6N mice. Pain was evaluated by the Hargreaves and von Frey filament tests. PMCA2 levels in the lumbar DH were analyzed by Western blotting. The effectors that decrease PMCA2 expression were identified in SC neuronal cultures.ResultsIncreased pain in EAE and SCI was paralleled by a significant decrease in PMCA2 levels in the DH. In contrast, PMCA2 levels remained unaltered in the DH of mice with EAE that manifested motor deficits but not increased pain. Interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and IL-6 expression were robustly increased in the DH of mice with EAE manifesting pain, whereas these cytokines showed a modest increase or no change in mice with EAE in the absence of pain. Only IL-1β decreased PMCA2 levels in pure SC neuronal cultures through direct actions.ConclusionsPMCA2 is a contributor to neuropathic pain mechanisms in the DH. A decrease in PMCA2 in DH neurons is paralleled by increased pain sensitivity, most likely through perturbations in calcium signaling. Interleukin-1β is one of the effectors that downregulates PMCA2 by acting directly on neurons.

Increasing evidence indicates that innate immune receptors play important, yet controversial, roles in traumatic central nervous system (CNS) injury. Despite many advances, the contributions of toll-like receptors (TLRs) to spinal cord injury (SCI) remain inadequately defined. We previously reported that a toll-like receptor 9 (TLR9) antagonist, oligodeoxynucleotide 2088 (ODN 2088), administered intrathecally, improves the functional and histopathological outcomes of SCI. However, the molecular and cellular changes that occur at the injury epicenter following ODN 2088 treatment are not completely understood. Following traumatic SCI, a glial scar, consisting primarily of proliferating reactive astrocytes, forms at the injury epicenter and assumes both beneficial and detrimental roles. Increased production of chondroitin sulfate proteoglycans (CSPGs) by reactive astrocytes inhibits the regeneration of injured axons. Astrocytes express TLR9, which can be activated by endogenous ligands released by damaged cells. It is not yet known how TLR9 antagonism modifies astrocyte function at the glial scar and how this affects axonal preservation or re-growth following SCI. The present studies were undertaken to address these issues. We report that in female mice sustaining a severe mid-thoracic (T8) contusion injury, the number of proliferating astrocytes in regions rostral and caudal to the lesion border increased significantly by 30- and 24-fold, respectively, compared to uninjured controls. Intrathecal ODN 2088 treatment significantly reduced the number of proliferating astrocytes by 60% in both regions. This effect appeared to be, at least partly, mediated through the direct actions of ODN 2088 on astrocytes, since the antagonist decreased proliferation in pure SC astrocyte cultures by preventing the activation of the Erk/MAPK signaling pathway. In addition, CSPG immunoreactivity at the lesion border was more pronounced in vehicle-treated injured mice compared to uninjured controls and was significantly reduced following administration of ODN 2088 to injured mice. Moreover, ODN 2088 significantly decreased astrocyte migration in an in vitro scratch-wound assay. Anterograde tracing and quantification of corticospinal tract (CST) axons in injured mice, indicated that ODN 2088 preserves proximal axons. Taken together, these findings suggest that ODN 2088 modifies the glial scar and creates a milieu that fosters axonal protection at the injury site.

Klippel-Feil syndrome (KFS) occurs due to failure of vertebral segmentation during development. Minimal research has been done to understand the prevalence of associated symptoms. Here, we report one of the largest collections of KFS patient data. Data were obtained from the CoRDS registry. Participants with cervical fusions were categorized into Type I, II, or III based on the Samartzis criteria. Symptoms and comorbidities were assessed against type and location of fusion. Seventy-five patients (60F/14M/1 unknown) were identified and classified as: Type I, n = 21(28%); Type II, n = 15(20%); Type III, n = 39(52%). Cervical fusion by level were: OC–C1, n = 17(22.7%), C1–C2, n = 24(32%); C2–C3, n = 42(56%); C3–C4, n = 30(40%); C4–C5, n = 42(56%); C5–C6, n = 32(42.7%); C6–C7, n = 25(33.3%); C7–T1, n = 13(17.3%). 94.6% of patients reported current symptoms and the average age when symptoms began and worsened were 17.5 (± 13.4) and 27.6 (± 15.3), respectively. Patients reported to have a high number of comorbidities including spinal, neurological and others, a high frequency of general symptoms (e.g., fatigue, dizziness) and chronic symptoms (limited range of neck motion [LROM], neck/spine muscles soreness). Sprengel deformity was reported in 26.7%. Most patients reported having received medication and invasive/non-invasive procedures. Multilevel fusions (Samartzis II/III) were significantly associated with dizziness (p = 0.040), the presence of LROM (p = 0.022), and Sprengel deformity (p = 0.036). KFS is associated with a number of musculoskeletal and neurological symptoms. Fusions are more prevalent toward the center of the cervical region, and less common at the occipital/thoracic junction. Associated comorbidities including Sprengel deformity may be more common in KFS patients with multilevel cervical fusions. These slides can be retrieved under Electronic Supplementary Material.

Importance Cervical spondylotic myelopathy is the most common cause of spinal cord dysfunction worldwide. It remains unknown whether a ventral or dorsal surgical approach provides the best results. Objective To determine whether a ventral surgical approach compared with a dorsal surgical approach for treatment of cervical spondylotic myelopathy improves patient-reported physical functioning at 1 year. Design, Setting, and Participants Randomized clinical trial of patients aged 45 to 80 years with multilevel cervical spondylotic myelopathy enrolled at 15 large North American hospitals from April 1, 2014, to March 30, 2018; final follow-up was April 15, 2020. Interventions Patients were randomized to undergo ventral surgery (n = 63) or dorsal surgery (n = 100). Ventral surgery involved anterior cervical disk removal and instrumented fusion. Dorsal surgery involved laminectomy with instrumented fusion or open-door laminoplasty. Type of dorsal surgery (fusion or laminoplasty) was at surgeon’s discretion. Main Outcomes and Measures The primary outcome was 1-year change in the Short Form 36 physical component summary (SF-36 PCS) score (range, 0 [worst] to 100 [best]; minimum clinically important difference = 5). Secondary outcomes included 1-year change in modified Japanese Orthopaedic Association scale score, complications, work status, sagittal vertical axis, health resource utilization, and 1- and 2-year changes in the Neck Disability Index and the EuroQol 5 Dimensions score. Results Among 163 patients who were randomized (mean age, 62 years; 80 [49%] women), 155 (95%) completed the trial at 1 year (80% at 2 years). All patients had surgery, but 5 patients did not receive their allocated surgery (ventral: n = 1; dorsal: n = 4). One-year SF-36 PCS mean improvement was not significantly different between ventral surgery (5.9 points) and dorsal surgery (6.2 points) (estimated mean difference, 0.3; 95% CI, −2.6 to 3.1;P = .86). Of 7 prespecified secondary outcomes, 6 showed no significant difference. Rates of complications in the ventral and dorsal surgery groups, respectively, were 48% vs 24% (difference, 24%; 95% CI, 8.7%-38.5%;P = .002) and included dysphagia (41% vs 0%), new neurological deficit (2% vs 9%), reoperations (6% vs 4%), and readmissions within 30 days (0% vs 7%). Conclusions and Relevance Among patients with cervical spondylotic myelopathy undergoing cervical spinal surgery, a ventral surgical approach did not significantly improve patient-reported physical functioning at 1 year compared with outcomes after a dorsal surgical approach. Trial Registration ClinicalTrials.gov Identifier:NCT02076113

Aim: Structural connectivity in the reorganizing spinal cord after injury dictates functional connectivity and hence the neurological outcome. As magnetic resonance imaging (MRI)-based structural parameters are mostly accessible across spinal cord injury (SCI) patients, we studied MRI-based spinal morphological changes and their relationship to neurological outcome in the rat model of cervical SCI. Introduction: Functional connectivity assessments on patients with SCI rely heavily on MRI-based approaches to investigate the complete neural axis (both spinal cord and brain). Hence, underlying MRI-based structural and morphometric changes in the reorganizing spinal cord and their relationship to neurological outcomes is crucial for meaningful interpretation of functional connectivity changes across the neural axis. Methods: Young adult rats, aged 1.5 months, underwent a precise mechanical impact hemicontusion incomplete cervical SCI at the C4/C5 level, after which sensorimotor behavioral assessments were tracked during the reorganization period of 1–6 weeks, followed by MRI of the cervical spinal cord at 8 weeks after SCI. Results: A significant ipsilesional forelimb motor debilitation was observed from 1 to 6 weeks after injury. Heat sensitivity testing (Hargreaves) showed ipsilesional forelimb hypersensitivity at 5 and 6 weeks after SCI. MRI of the cervical spine showed ipsilateral T1- and T2-weighted lesions across all SCI rats compared with no significant lesions in sham rats. Morphometric assessments of the lesional and nonlesional changes showed the diverse nature of their interindividual variability in the SCI receiving rats. While the various T1 and T2 MRI lesional volumes associated weakly or moderately with neurological outcome, the nonlesional spinal morphometric changes associated much more strongly. The results have important implications for interpreting functional MRI-based functional connectivity after SCI by providing vital underlying structural changes and their relative neurological impact. IMPACT STATEMENT: Functional connectivity assessments on patients with SCI relies heavily upon MRI based approaches. Hence, underlying MRI based structural and morphometric changes in the reorganizing spinal cord and its relationship to neurological outcomes is vital for meaningful interpretation of functional connectivity changes across the complete neural axis (both spinal cord and the brain).

OBJECTIVEThe Neurosurgery Research & Education Foundation (NREF), previously known as the Research Foundation of the American Association of Neurological Surgeons (AANS), was established in 1980 to encourage and facilitate innovation through financial support to young neurosurgeons in the process of honing their competencies in neurosciences and neurological surgery. This article provides a historical overview of NREF, its mission, and charitable contributions and the ever-expanding avenues for neurosurgeons, neurosurgical residents and fellows, and medical students to supplement clinical training and to further neurosurgical research advances.METHODSData were collected from the historical archives of the AANS and NREF website. Available data included tabulated revenue, geographic and institutional records of funding, changes in funding for fellowships and awards, advertising methods, and sources of funding.RESULTSSince 1984, NREF has invested more than $23 million into the future of neurosurgery. To date, NREF has provided more than 500 fellowship opportunities which have funded neurosurgeons’ education and research efforts at all stages of training and practice.CONCLUSIONSNREF is designed to serve as the vehicle through which the neurosurgical community fosters the continued excellence in the care of patients with neurosurgical diseases.

Earlier studies on genetically modified mice indicated that plasma membrane calcium ATPase 2 (PMCA2), a calcium extrusion pump, plays a novel and sex-dependent role in mechanical pain responses: female, but not male, PMCA2+/− mice manifest increased mechanical pain compared to female PMCA2+/+ mice. The goal of the present studies was to determine the contribution of ovarian steroids to the genotype- and sex-dependent manifestation of mechanical pain in PMCA2+/+ versus PMCA2+/− mice. Ovariectomy increased mechanical pain sensitivity and 17β-estradiol (E2) replacement restored it to basal levels in PMCA2+/+ mice, but not in PMCA2+/− littermates. Intrathecal administration of an estrogen receptor alpha (ERα) agonist induced ERα signaling in the dorsal horn (DH) of female PMCA2+/+ mice, but was ineffective in PMCA2+/− mice. In male PMCA2+/+ and PMCA2+/− mice, E2 treatment following orchidectomy did not recapitulate the genotype-dependent differential pain responses observed in females and the agonist did not elicit ERα signaling. These findings establish a novel, female-specific link between PMCA2, ERα and mechanical pain. It is postulated that PMCA2 is essential for adequate ERα signaling in the female DH and that impaired ERα signaling in the female PMCA2+/− mice hinders the analgesic effects of E2 leading to increased sensitivity to mechanical stimuli.

CONTEXT: Cervical myelopathy occurs as a result of compression of the cervical spinal cord. Symptomatology includes, but is not limited to, pain, weakness, paresthesias, or gait/balance difficulties. OBJECTIVE: To present a two-decade experience with the management of cervical myelopathy. METHODS: Literature was reviewed to provide current guidelines for management as well as accompanying clinical presentations. RESULTS: Surgical decompression, if necessary, may be achieved from either an anterior, a posterior, or a combined anterior-posterior (AP) approach. The indications for each approach, as well as the surgical techniques, are described. CONCLUSION: Several etiologies may lead to cord compression and cervical myelopathy. The best vector of approach with regard to anterior versus posterior surgical intervention is still under investigation. Regardless, management via surgical decompression has been demonstrated repeatedly to improve the CSM patients’ quality of life.

Anterior lumbar interbody fusion (ALIF) is a widely performed surgical treatment for various lumbar spine pathologies. The authors present the first reports of virtually identical cases of complications with integrated screws in stand-alone interbody cages. Two patients presented with the onset of S-1 radiculopathy due to screw misplacements following an ALIF procedure. In both cases, an integrated screw from the cage penetrated the dorsal aspect of the S-1 cortical margin of the vertebra, extended into the neural foramen, and injured the traversing left S-1 nerve roots. Advanced neuroimaging findings indicated nerve root impingement by the protruding screw tip. After substantial delays, radiculopathic symptoms were treated with removal of the offending instrumentation, aggressive posterior decompression of the bony and ligamentous structures, and posterolateral fusion surgery with pedicle screw fixation. Postoperative radiographic findings demonstrated decompression of the symptomatic nerve roots via removal of the extruded screw tips from the neural foramina.

OBJECTIVEPedicle screw fixation is a technique widely used to treat conditions ranging from spine deformity to fracture stabilization. Pedicle screws have been used traditionally in the lumbar spine; however, they are now being used with increasing frequency in the thoracic spine as a more favorable alternative to hooks, wires, or cables. Although safety concerns, such as the incidence of adjacent-segment disease (ASD) after cervical and lumbar fusions, have been reported, such issues in the thoracic spine have yet to be addressed thoroughly. Here, the authors review the literature on ASD after thoracic pedicle screw fixation and report their own experience specifically involving the use of pedicle screws in the thoracic spine.METHODSSelect references from online databases, such as PubMed (provided by the US National Library of Medicine at the National Institutes of Health), were used to survey the literature concerning ASD after thoracic pedicle screw fixation. To include the authors’ experience at Rutgers New Jersey Medical School, a retrospective review of a prospectively maintained database was performed to determine the incidence of complications over a 13-year period in 123 consecutive adult patients who underwent thoracic pedicle screw fixation. Children, pregnant or lactating women, and prisoners were excluded from the review. By comparing preoperative and postoperative radiographic images, the occurrence of thoracic ASD and disease within the surgical construct was determined.RESULTSDefinitive radiographic fusion was detected in 115 (93.5%) patients. Seven incidences of instrumentation failure and 8 lucencies surrounding the screws were observed. One patient was observed to have ASD of the thoracic spine. The mean follow-up duration was 50 months.CONCLUSIONSThis long-term radiographic evaluation revealed the use of pedicle screws for thoracic fixation to be an effective stabilization modality. In particular, ASD seems to be less of a problem in the relatively immobile thoracic spine than in the more mobile cervical and lumbar spines.

Background i-Factor™ Bone Graft (Cerapedics Inc, Westminster, Colorado) is a composite bone substitute material consisting of P-15 synthetic collagen fragment adsorbed onto anorganic bone mineral suspended in an inert biocompatible hydrogel carrier. A pivotal, noninferiority, US FDA Investigational Device Exemption study demonstrated the benefits of i-Factor™ compared to local autograft bone in single-level anterior cervical discectomy and fusion at 1-yr postoperative. Objective To report 2-yr follow-up. Methods Subjects randomly received either autograft (n = 154) or i-Factor™ (n = 165) in a cortical ring allograft and followed using radiological, clinical, and patient-reported outcomes. Results At 2 yr, the fusion rate was 97.30% and 94.44% in i-Factor™ and autograft subjects, respectively (P = .2513), and neurological success rate was 94.87% (i-Factor™) and 93.79% (autograft; P = .7869). Neck Disability Index improved 28.30 (i-Factor™) and 26.95 (autograft; P = .1448); Visual Analog Scale arm pain improved 5.43 (i-Factor™) and 4.97 (autograft) (p = .2763); Visual Analog Scale neck pain improved 4.78 (i-Factor™) and 4.41 (autograft; P = .1652), Short Form-36 (SF-36v2) Physical Component Score improved 10.23 (i-Factor™) and 10.18 (autograft; P = .4507), and SF36v2 Mental Component Score improved 7.88 (i-FactorTM) and 7.53 (autograft; P = .9872). The composite endpoint of overall success (fusion, Neck Disability Index improvement >15, neurological success, and absence of re-operations) was greater in i-Factor™ subjects compared to autograft subjects (69.83% and 56.35%, respectively, P = .0302). Twelve (7.45%) i-Factor™ subjects and 16 (10.53%) autograft subjects underwent re-operation (P = .3411). There were no allergic reactions associated with i-Factor™. Conclusion Use of i-Factor™ in anterior cervical discectomy and fusion is effective and safe, and results in similar outcomes compared to local autograft bone at 2 yr following surgery.

Background: The modulus of elasticity of an assortment of materials used in spinal surgery, as well as cortical and cancellous bones, is determined by direct measurements and plotting of the appropriate curves. When utilized in spine surgery, the stiffness of a surgical implant can affect its material characteristics. The modulus of elasticity, or Young’s modulus, measures the stiffness of a material by calculating the slope of the material’s stress-strain curve. While many papers and presentations refer to the modulus of elasticity as a reason for the choice of a particular spinal implant, no peer-reviewed surgical journal article has previously been published where the Young’s modulus values of interbody implants have been measured. Methods: Materials were tested under pure compression at the rate of 2 mm/min. A maximum of 45 kilonewtons (kN) compressive force was applied. Stress-strain characteristics under compressive force were plotted and this plot was used to calculate the elastic modulus. Results: The elastic modulus calculated for metals was more than 50 Gigapascals (GPa) and had significantly higher modulus values compared to poly-ether-ether-ketone (PEEK) materials and allograft bone. Conclusions: The data generated in this paper may facilitate surgeons to make informed decisions on their choices of interbody implants with specific attention to the stiffness of the implant chosen.

Background The political action committee (PAC) of the American Association of Neurological Surgeons, known as NeurosurgeryPAC, was formed in August 2005 to strengthen neurosurgical advocacy efforts. Since its establishment, NeurosurgeryPAC has made nonpartisan, direct campaign contributions to hundreds of candidates for the U.S. Senate and U.S. House of Representatives. Methods Historical contribution data for 2005–2018 was obtained from NeurosurgeryPAC. Data analyzed by year, and a 2-year election cycle included total amount raised, number of contributors, average donation, and percent participation. NeurosurgeryPAC contribution amounts for election cycles were also compared with those of other physician PACs. Results NeurosurgeryPAC has raised $2,953,870 since its inception in 2005, for an average of $210,991 per year. For this fundraising, the average annual donation amount is $796 per donor. The number of unique contributors per cycle has varied from 316–504, with an average of 389 individuals per annum and a participation rate of 7.8%. To date, the total amount raised in election years ($1,605,940) is 16.1% higher than that raised in nonelection years ($1,347,930). Among 28 physician PACs, NeurosurgeryPAC has ranked as high as 13 and as low as 17 in total hard money contributions. The orthopedic, neurology and general surgery PACs have consistently ranked higher than NeurosurgeryPAC, whereas the otolaryngology, spine, and plastic surgery PACs have ranked lower. Conclusions Since its creation, NeurosurgeryPAC has collected a steady stream of donations to support political candidates. These donations have helped lawmakers who are supportive of policy issues important to neurosurgery, particularly physician reimbursement, medical liability reform, and graduate medical education. However, there remains a significant opportunity to increase the neurosurgeon participation rate in this vital organization. It is truly through advocacy that we will be able to positively affect the future of neurologic surgery in the United States.

Traumatic spinal fractures are a leading cause of morbidity in the trauma population. They must be assessed and managed differently than other spinal pathology including degenerative, neoplastic or infectious. Establishing stability, restoring alignment and decompression of neural elements are critical to the successful management of traumatic spinal injury. In this chapter, we will review the relevant anatomy, biomechanics of injury and principles of management to avoid complications in the treatment of traumatic spinal fractures.

Background The Open Payments Database (OPD) was launched by the Centers for Medicare & Medicaid Services in 2014. Through this online searchable database, the public can explore physician-industry interactions. To date, there is no published literature on the accuracy of the database for neurosurgeons or any physician specialty. Objective To study the accuracy of published records and scope of industry-neurosurgeon relationships between neurosurgeons and industry within the OPD. Methods We searched 4.3 million records in 2013 and 11.41 million records in 2014 in the OPD for board-certified neurosurgeons verified by the American Board of Neurological Surgery. Delimit software was used to condense these data, Microsoft Access for database queries, and STATA to perform descriptive analyses. Results Of the 3240 neurosurgeons in the OPD in 2013, 2020 were identified correctly as neurosurgeons within the database (62%). Of the 3593 neurosurgeons in the OPD in 2014, 2433 were identified correctly as neurosurgeons (68%). Within the OPD in 2013, there were 72 066 attributed records for neurosurgeons; within the 2014 OPD, there were 160 563 attributed records for neurosurgeons. Total payments to neurosurgeons in 2013 (for the 9 months published in OPD): $61 802 659.37; in 2014: $117 127 824.00. Conclusion The OPD details physician interactions with industry and has multiple inaccuracies. Publicly availing inaccurate information through a searchable governmental website that can be accessed by patients and journalists alike has the potential to tarnish individual neurosurgeons and undermine professional credibility. Abbreviations CMS, Centers for Medicare & Medicaid ServicesOPD, Open Payments Database.

STUDY DESIGN A prospective, randomized, controlled, parallel, single-blinded noninferiority multicenter pivotal FDA IDE trial. OBJECTIVE The objective of this study was to investigate efficacy and safety of i-Factor Bone Graft (i-Factor) compared with local autograft in single-level anterior cervical discectomy and fusion (ACDF) for cervical radiculopathy. SUMMARY OF BACKGROUND DATA i-Factor is a composite bone substitute material consisting of the P-15 synthetic collagen fragment adsorbed onto anorganic bone mineral and suspended in an inert biocompatible hydrogel carrier. P-15 has demonstrated bone healing efficacy in dental, orthopedic, and nonhuman applications. METHODS Patients randomly received either autograft (N = 154) or i-Factor (N = 165) in a cortical ring allograft. Study success was defined as noninferiority in fusion, Neck Disability Index (NDI), and Neurological Success endpoints, and similar adverse events profile at 12 months. RESULTS At 12 months (follow-up rate 87%), both i-Factor and autograft subjects demonstrated a high fusion rate (88.97% and 85.82%, respectively, noninferiority P = 0.0004), significant improvements in NDI (28.75 and 27.40, respectively, noninferiority P

OBJECT Recent studies have examined the impact of perceived medicolegal risk and compared how this perception impacts defensive practices within the US. To date, there have been no published data on the practice of defensive medicine among neurosurgeons in Canada. METHODS An online survey containing 44 questions was sent to 170 Canadian neurosurgeons and used to measure Canadian neurosurgeons’ perception of liability risk and their practice of defensive medicine. The survey included questions on the following domains: surgeon demographics, patient characteristics, type of physician practice, surgeon liability profile, policy coverage, defensive behaviors, and perception of the liability environment. Survey responses were analyzed and summarized using counts and percentages. RESULTS A total of 75 neurosurgeons completed the survey, achieving an overall response rate of 44.1%. Over one-third (36.5%) of Canadian neurosurgeons paid less than $5000 for insurance annually. The majority (87%) of Canadian neurosurgeons felt confident with their insurance coverage, and 60% reported that they rarely felt the need to practice defensive medicine. The majority of the respondents reported that the perceived medicolegal risk environment has no bearing on their preferred practice location. Only 1 in 5 respondent Canadian neurosurgeons (21.8%) reported viewing patients as a potential lawsuit. Only 4.9% of respondents would have selected a different career based on current medicolegal risk factors, and only 4.1% view the cost of annual malpractice insurance as a major burden. CONCLUSIONS Canadian neurosurgeons perceive their medicolegal risk environment as more favorable and their patients as less likely to sue than their counterparts in the US do. Overall, Canadian neurosurgeons engage in fewer defensive medical behaviors than previously reported in the US.

Background While recent data has demonstrated the utility of lumbar pedicle screws for the treatment of vertebral osteomyelitis, the data are limited for thoracic pedicle screws. Objective To investigate the effectiveness of thoracic pedicle screws for the surgical treatment of vertebral osteomyelitis. Methods A retrospective review of all operations performed by 2 spinal neurosurgeons from 1999 to 2012 yielded 30 cases of vertebral osteomyelitis that were treated with thoracic pedicle screws. Sixteen (53%) of which underwent combined anterior and posterior fusion and 14 patients (47%) underwent standalone posterior fusion. Postoperative records were analyzed for pertinent clinical, laboratory, and radiographic data. Results Of the 30 patients, 21 were males (70%), 8 were females (27%), and 1 was transsexual (3%). The mean age was 47 yr (range 18-69). The most common organism cultured was Staphylococcus aureus in 12 cases (50%). The mean patient stay in the hospital was 12.4 d after surgery (range 5-38 d). The mean antibiotic duration after discharge was 8 wk (range 1-24 wk). Of the 25 patients with long-term follow-up (mean, 49 mo), 92% had improved back pain (6/25 marked improvement, 17/25 complete resolution), 83% had improved muscle weakness (8/18 marked improvement, 7/18 complete resolution), and 100% had improved urinary incontinence (3/8 marked improvement, 5/8 complete resolution). Two patients (7%) required additional surgical revision due to instrumentation failure or wound infection. Conclusion This study demonstrates the efficacy of utilizing thoracic pedicle screws as a primary intervention to treat vertebral osteomyelitis.