Paraspinal Sarcopenia and Lower Hounsfield Units are Independent Predictors of Increased Risk for Proximal Junctional Complications Following Thoracolumbar Fusions Terminating in the Upper Thoracic Spine.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The impact of paraspinal sarcopenia following fusions that extend to the upper thoracic spine remain unknown. The purpose of the present study was to assess the impact of sarcopenia on the development of PJK and PJF following spine fusion surgery from the upper thoracic spine to the pelvis. METHODS: We performed a retrospective review of patients who underwent spine fusion surgery that extended caudally to the pelvis and terminated cranially between T1-6. The cohort was divided into 2 groups: (1) patients without PJK or PJF and (2) patients with PJK and/or PJF. Univariate and multivariate analyses were performed to determine risk factors for the development of proximal junctional complications. RESULTS: We identified 81 patients for inclusion in this study. Mean HU at the UIV was 186.1 ± 47.5 in the cohort of patients without PJK or PJF, which was substantially higher than values recorded in the PJK/PJF subgroup (142.4 ± 40.2) (P < 0.001). Severe multifidus sarcopenia was identified at a higher rate in the subgroup of patients who developed proximal junction pathology (66.7%) than in the subgroup of patients who developed neither PJK nor PJF (7.4%; P < 0.001). Multivariate analysis demonstrated both low HU at the UIV and moderate-severe multifidus sarcopenia to be risk factors for the development of PJK and PJF. CONCLUSIONS: Severe paraspinal sarcopenia and diminished bone density at the UIV impart an increased risk of developing PJK and PJF in following thoracolumbar fusions from the upper thoracic spine to the pelvis.

Transforming Outcomes of Spine Surgery-Exploring the Power of Enhanced Recovery After Surgery Protocol: A Systematic Review and Meta-Analyses of 15 198 Patients.

BACKGROUND AND OBJECTIVES: Enhanced recovery after surgery (ERAS) protocols aim to optimize patient outcomes by reducing the surgical stress response, expediting recovery, and reducing care costs. We aimed to evaluate the impact of implementing ERAS protocols on the perioperative surgical outcomes and financial implications associated with spine surgeries. METHODS: A systematic review and meta-analysis of peer-reviewed studies directly comparing outcome differences between spine surgeries performed with and without utilization of ERAS pathways was conducted along Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of 676 unique articles identified, 59 with 15 198 aggregate patients (7748 ERAS; 7450 non-ERAS) were included. ERAS-treated patients had shorter operative times (mean difference [MD]: 10.2 mins; P < .01), shorter hospitalizations (MD: 1.41 days, P < .01), fewer perioperative complications (relative risk [RR] = 0.64, P < .01), lower postoperative opioid use (MD of morphine equivalent dose: 164.36 mg; P < .01), and more rapid mobilization/time to first out-of-bed ambulation (MD: 0.92 days; P < .01). Spine surgeries employing ERAS were also associated with lower total costs (MD: $1140.26/patient; P < .01), especially in the United States (MD: $2869.11/patient, P < .01) and lower postoperative visual analog pain scores (MD = 0.56, P < .01), without any change in odds of 30-day readmission (RR: 0.80, P = .13) or reoperation (RR: 0.88, P = .60). Subanalyses based on the region of spine showed significantly lower length of stay in both cervical and lumbar surgeries implementing ERAS. Type of procedure showed a significantly lesser time-to-initiate mobilization in fusion surgeries using ERAS protocols compared with decompression. CONCLUSION: The present meta-analysis indicates that current literature supports ERAS implementation as a means of reducing care costs and safely accelerating hospital discharge for patients undergoing spine surgery.

Spine Image Guidance and Robotics: Exposure, Education, Training, and the Learning Curve.

The use of intraoperative robotics and imaging for spine surgery has been shown to be safe, efficacious, and beneficial to patients, offering accurate placement of instrumentation, decreased operative time and blood loss, and improved postoperative outcomes. Despite these proven benefits, it has yet to be uniformly adopted. One of the major barriers for universal adoption of intraoperative robotics is the learning curve for this complex technology, in conjunction with a lack of formalized training. These same obstacles for universal adoption were faced in the introduction of surgical technology in other disciplines, and the use of this technology has become the standard of care in some of those specialties. Part of the success and widespread implementation of prior novel technology was the introduction of formalized training systems, which are currently lacking in advanced spine surgical technology. Therefore, the future success of intraoperative robotics and imaging for spine surgery depends on the creation of a formalized training system. We detail the best techniques for surgical pedagogy, as well as propose a comprehensive curriculum.

The Medial Orbitofrontal Cortex-Basolateral Amygdala Circuit Regulates the Influence of Reward Cues on Adaptive Behavior and Choice.

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are largely distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC-BLA connections in reward-directed behavior. We found evidence that the mOFC→BLA pathway mediates the use of environmental cues to understand which specific reward is predicted, information needed to infer which action to choose, and how desirable that reward is to ensure adaptive responses to the cue. By contrast, the BLA→mOFC pathway is not needed to use the identity of an expected reward to guide choice but does mediate adaptive responses to cues based on the current desirability of the reward they predict. These functions differ from those we previously identified for the lOFC-BLA circuit. Collectively, the data reveal the mOFC-BLA circuit as critical for the cue-dependent reward outcome expectations that influence adaptive behavior and decision making.SIGNIFICANCE STATEMENT To make good decisions we evaluate how advantageous a particular course of action would be. This requires understanding what rewarding outcomes can be expected and how desirable they currently are. Such prospective considerations are critical for adaptive decision making but disrupted in many psychiatric diseases. Here, we reveal that direct connections between the medial orbitofrontal cortex and basolateral amygdala mediate these functions. These findings are especially important in light of evidence of dysfunction in this circuit in substance use disorder and mental illnesses marked by poor decision making.

Prediction Models in Degenerative Spine Surgery: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: To review the existing literature of prediction models in degenerative spinal surgery. METHODS: Review of PubMed/Medline and Embase databases was conducted to identify articles between January 1, 2000 and March 1, 2020 that reported prediction model performance for outcomes following elective degenerative spine surgery. RESULTS: Thirty-one articles were included. Twenty studies were of thoracolumbar, 5 were of cervical, and 6 included all spine patients. Five studies were externally validated. Prediction models were developed using machine learning (42%) and logistic regression (42%) as well as other techniques. Web-based calculators were included in 45% of published articles. Various outcomes were investigated, including complications, infection, length of stay, discharge disposition, reoperation, readmission, disability score, back pain, leg pain, return to work, and opioid dependence. CONCLUSIONS: Significant heterogeneity exists in methods used to develop prediction models of postoperative outcomes after degenerative spine surgery. Most internally validate their scores, but a few have been externally validated. Areas under the curve for most models range from 0.6 to 0.9. Techniques for development are becoming increasingly sophisticated with different machine learning tools. With further external validation, these models can be deployed online for patient, physician, and administrative use, and have the potential to optimize outcomes and maximize value in spine surgery.

A Basomedial Amygdala to Intercalated Cells Microcircuit Expressing PACAP and Its Receptor PAC1 Regulates Contextual Fear.

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state.SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.

The effect of renin-angiotensin system blockers on spinal cord dysfunction and imaging features of spinal cord compression in patients with symptomatic cervical spondylosis.

BACKGROUND CONTEXT: Cervical spondylosis may lead to spinal cord compression, poor vascular perfusion, and ultimately, cervical myelopathy. Studies suggest a neuroprotective effect of renin-angiotensin system (RAS) inhibitors in the brain, but limited data exist regarding their impact on the spinal cord. PURPOSE: To investigate whether RAS blockers and other antihypertensive drugs are correlated with preoperative functional status and imaging markers of cord compression in patients with symptomatic cervical spondylosis. STUDY DESIGN: Retrospective observational study. PATIENT SAMPLE: Individuals with symptomatic degenerative cervical stenosis who underwent surgery. OUTCOME MEASURES: Imaging features of spinal cord compression and functional status (modified Japanese Orthopedic Association [mJOA] and Nurick grading scales). METHODS: Two hundred sixty-six operative patients with symptomatic degenerative cervical stenosis were included. Demographic data, comorbidities, antihypertensive medications, and functional status (including mJOA and Nurick grading scales) were collected. We evaluated canal compromise, cord compromise, surface area of T2 signal cord change, and pixel intensity of signal cord change compared with normal cord on T2-weighted magnetic resonance imaging sequences. RESULTS: Of 266 patients, 41.7% were women, 58.3% were men; median age was 57.2 years; 20.6% smoked tobacco; 24.7% had diabetes mellitus. One hundred forty-nine patients (55.8%) had hypertension, 142 (95.3%) of these were taking antihypertensive medications (37 angiotensin-II receptor blockers [ARBs], 44 angiotensin-converting enzyme inhibitors, and 61 other medications). Patients treated with ARBs displayed a higher signal intensity ratio (ie, less signal intensity change in the compressed cord area) compared with untreated patients without hypertension (p=.004). Patients with hypertension had worse preoperative mJOA and Nurick scores than those without (p<.001). In the multivariate analysis, ARBs remained an independent beneficial factor for lower signal intensity change (p=.04), whereas hypertension remained a risk factor for worse preoperative neurological status (p<.01). CONCLUSIONS: In our study, patients with hypertension who were treated with RAS inhibitors had decreased T2-weighted signal intensity change than untreated patients without hypertension. Patients with hypertension also had worse preoperative functional status. Prospective case-control studies may deepen understanding of RAS modulators in the imaging and functional status of chronic spinal cord compression.

Assessment of a Triage Protocol for Emergent Neurosurgical Cases at a Single Institution.

BACKGROUND: Level I trauma centers use patient triaging systems to deploy neurosurgical resources and pursue good outcomes; however, data describing the effectiveness these triage systems are lacking. We reviewed the leveling protocol (cases designated urgent and emergent) of a regional Level I trauma center to obtain epidemiologic data about the efficiency of that system and identify areas for improvement. METHODS: We retrospectively reviewed leveled neurosurgical cases from January 2015 to October 2017, assessing surgery date, neurosurgical procedure, posted surgical urgency level (levels 1-3, with 1 being most urgent), and post-to-room (PTR) time (i.e., the time between initial leveling and admission of the patient to the operating room). Mean PTR times were compared between case types using one-way analysis of variance with post hoc Tukey honestly significant difference analysis. RESULTS: Of 1469 cases, 577 (39.3%) were shunt placement or revision, 231 (15.7%) were craniectomy or craniotomy for hematoma, 147 (10.0%) were craniectomy or craniotomy for tumor, and 514 (35.0%) were for other indications. Among level 1 cases, PTR time was lowest for craniotomies to evacuate intracranial hematoma (mean 16.2 minutes) and highest for spinal decompression procedures and wound washouts (mean 36.2 and 42.4 minutes, respectively). CONCLUSIONS: To our knowledge, this is the first study of variability in PTR timing as a function of surgical urgency or indication. The most common leveled cases were craniectomies or craniotomies to relieve increased intracranial pressure, which were also the most common level 1 cases. Significant variability occurred within each leveling category; thus, further investigation is required.

Horner Syndrome After Anterior Cervical Discectomy and Fusion: Case Series and Systematic Review.

BACKGROUND: Horner syndrome is an infrequently seen complication of anterior cervical discectomy and fusion (ACDF). Multicenter studies have reported a very low incidence, less than 0.1%. OBJECTIVE: To identify the incidence in, characteristics of, and postoperative course in patients in whom postoperative Horner syndrome developed after ACDF. METHODS: We performed a retrospective review of all patients who experienced Horner syndrome after ACDF for cervical degenerative disease at a single tertiary care institution between 2017 and 2018. A systematic review was then performed to identify studies investigating prevalence, diagnosis, and treatment of postoperative Horner syndrome after ACDF. RESULTS: Of 1116 patients at our institution who underwent ACDF, the incidence of Horner syndrome was 0.45%. C4/5 and C5/6 were the 2 most common surgical levels. The complication was noted to occur immediately after surgery, and at least partial improvement was identified in all patients an average 3.5 months after surgery (range, 10 days to 6 months). These findings were consistent with our systematic review of 21 studies that showed an incidence of 0.6% (range, 0.02% to 4.0%), the most common surgical level C5/6 (64%), and 82% of patients experiencing at least partial resolution of symptoms within 1 year (60.7% complete, 21.4% partial resolution). CONCLUSION: Horner syndrome occurs in 0.6% of patients undergoing ACDF. Careful postoperative examination should reveal this complication, which may be underdiagnosed or underreported in larger multicenter case series. The majority of patients experience complete resolution of symptoms within 6 months to 1 year and can be treated conservatively and expectantly.

Multidisciplinary surgical planning for en bloc resection of malignant primary cervical spine tumors involving 3D-printed models and neoadjuvant therapies: report of 2 cases.

Effective en bloc resection of primary spinal tumors necessitates careful consideration of adjacent anatomical structures in order to achieve negative margins and reduce surgical morbidity. This can be particularly challenging in the cervical spine, where vital neurovascular and connective tissues are present in the region. Early multidisciplinary surgical planning that includes clinicians and engineers can both optimize surgical planning and enable a more feasible resection with oncological margins. The aim of the current work was to demonstrate two cases that involved multidisciplinary surgical planning for en bloc resection of primary cervical spine tumors, successfully utilizing 3D-printed patient models and neoadjuvant therapies.

Epstein-Barr virus-associated smooth muscle tumor involving the spine of an HIV-infected patient: Case report and review of the literature.

Within the last two decades, there have been multiple reports of Epstein-Barr virus (EBV)-associated smooth muscle tumors in immunocompromised patients. This includes HIV-infected patients, post-transplant patients, and patients with congenital defects of their immune systems. Here we report the case of a 24-year-old African American female with congenital HIV presenting with progressive lower extremity weakness, constipation, aching pain in her shoulders, and subcostal anesthesia. Magnetic resonance imaging (MRI) revealed a large circumferential lesion extending from T1-T3 and a smaller left paraspinal lesion at C6-C7. The T1-T3 mass was excised via a right-sided costotransversectomy with laminectomy and fusion from T1-T3. Highly active antiretroviral therapy (HAART) was started postoperatively, and adjuvant radiotherapy was initiated but patient was lost to follow-up. Surgical pathology demonstrated a smooth muscle tumor diffuse nuclear positivity for EBV-encoded small RNA 1 by in situ hybridization. Although eight studies have reported HIV patients with EBV-associated smooth muscle tumors of the spine, to the author's knowledge, this is the first review comprised solely of patients with spinal involvement with the addition of our patient case.

Risk factors for wound-related reoperations in patients with metastatic spine tumor.

OBJECTIVE Resection of metastatic spine tumors can improve patients' quality of life by addressing pain or neurological compromise. However, resections are often complicated by wound dehiscence, infection, instrumentation failures, and the need for reoperation. Moreover, when reoperations are needed, the most common indication is surgical site infection and wound breakdown. In turn, wound reoperations increase morbidity as well as the length and cost of hospitalization. The aim of this study was to examine perioperative risk factors associated with increased rate of wound reoperations after metastatic spine tumor resection. METHODS A retrospective study of patients at a single institution who underwent metastatic spine tumor resection between 2003 and 2013 was conducted. Factors with a p value < 0.200 in a univariate analysis were included in the multivariate model. RESULTS A total of 159 patients were included in this study. Karnofsky Performance Scale score > 70, smoking status, hypertension, thromboembolic events, hyperlipidemia, increasing number of vertebral levels, and posterior approach were included in the multivariate analysis. Thromboembolic events (95% CI 1.19-48.5, p = 0.032) and number of levels involved were independently associated with increased wound reoperation rates in the multivariate model. For each additional spinal level involved, the risk for wound reoperations increased by 21% (95% CI 1.03-1.43, p = 0.018). CONCLUSIONS Although wound complications and subsequent reoperations are potential risks for all patients with metastatic spine tumor, due to adjuvant radiotherapy and other medical comorbidities, this study identified patients with thromboembolic events or those requiring a larger incision as being at the highest risk. Measures intended to decrease the occurrence of perioperative venous thromboembolism and to improve wound care, especially for long incisions, may decrease wound-related revision surgeries in this vulnerable group of patients.