Corey T. Walker

Genetic Alterations in intervertebral Disc Disease

Background Intervertebral disc degeneration (IVDD) is considered a multifactorial disease that is influenced by both environmental and genetic factors. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single-nucleotide polymorphisms (SNPs) that are associated with IVDD. Aim This review presents comprehensive and updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD. An organized collection of information is provided regarding genetic polymorphisms that have been identified to influence the risk of developing IVDD. Understanding the proteins and signaling systems involved in IVDD can lead to improved understanding and targeting of therapeutics. Materials and methods An electronic literature search was performed using the National Library of Medicine for publications using the keywords genetics of IVDD, lumbar disc degeneration, degenerative disc disease, polymorphisms, SNPs, and disc disease. The articles were then screened based on inclusion criteria that included topics that covered the correlation of SNPs with developing IVDD. Sixty-five articles were identified as containing relevant information. Articles were excluded if they investigated lower back pain or just disc herniation without an analysis of disc degeneration. This study focuses on the chronic degeneration of IVDs. Results Various genes were identified to contain SNPs that influenced the risk of developing IVDD. Among these are genes contributing to structural proteins, such as COL1A1, COL9A3, COL9A3, COL11A1, and COL11A2, ACAN, and CHST3. Furthermore, various SNPs found in the vitamin-D receptor gene are also associated with IVDD. SNPs related to inflammatory cytokine imbalance are associated with IVDD, although some effects are limited by sex and certain populations. SNPs in genes that code for extracellular matrix-degrading enzymes, such as MMP-1, MMP-2, MMP-3, MMP-9, MMP-14, ADAMTS-4, and ADAMTS-5 are also associated with IVDD. Apoptosis-mediating genes, such as caspase 9 gene (CASP9), TRAIL, and death receptor 4 (DR4), as well as those for growth factors, such as growth differentiation factor 5 and VEGF, are identified to have polymorphisms that influence the risk of developing IVDD. Conclusion Within the last 10u2009years, countless new SNPs have been identified in genes previously unknown to be associated with IVDD. Furthermore, the last decade has also revealed new SNPs identified in genes already known to be involved with increased risk of developing IVDD. Improved understanding of the numerous genetic variants behind various pathophysiological elements of IVDD could help advance personalized care and pharmacotherapeutic strategies for patients suffering from IVDD in the future.

Genetics Underlying an Individualized Approach to Adult Spinal Disorders

Adult spinal disorders are a significant cause of morbidity across the world and carry significant health and economic burdens. Genetic predispositions are increasingly considered for these conditions and are becoming understood. Advances in molecular technologies since the mid-1990s have made possible genetic characterizations of these diseases in many populations, and recent findings have provided insight into the underlying pathophysiologic mechanisms. These studies have made clear the genetic heterogeneity producing clinical phenotypes and suggest that individualized treatments are possible in the future. We review the genetics and heritability of cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament and perform a systematic review of the genetics of adult lumbar degenerative scoliotic deformity, highlighting recent discoveries and the potential for personalized future therapeutics for these patients.

Human Amniotic Membrane for the Prevention of Intradural Spinal Cord Adhesions: Retrospective Review of its Novel Use in a Case Series of 14 Patients

BACKGROUNDnTethering after spinal surgery is caused by adhesions that arise from intradural tissue manipulation. Microsurgical detethering is the only treatment for symptomatic patients, but retethering occurs commonly and no treatment is widely available to prevent this complication.nnnOBJECTIVEnTo apply human amniotic membrane (HAM) grafts, which are immune-privileged and known to possess antifibrogenic properties, in patients requiring microsurgical detethering. For this first-in-human use, we evaluated the safety and potential efficacy of these grafts for preventing retethering.nnnMETHODSnWe retrospectively reviewed the medical records of all patients who required detethering surgery and received an HAM graft between 2013 and 2016 at our institution after various previous intradural spinal surgeries. In all 14 cases, intradural lysis of adhesions was achieved, an HAM graft was sewn in place intradurally, and a dural patch was closed in a watertight fashion over the graft.nnnRESULTSnFourteen patients had received HAM grafts to prevent retethering. All patients had at least 6 mo of follow-up (mean follow-up, 14 mo). Retethering was noted in only 1 patient. Surgical re-exploration showed that the retethering occurred caudal to the edge of the HAM graft, with no tethering underneath the original graft. No complications were attributed specifically to the HAM graft placement.nnnCONCLUSIONnThis first-in-human series provides evidence that HAM grafts are a safe and potentially efficacious method for preventing retethering after microsurgical intradural lysis of adhesions. These results lay the groundwork for further prospective controlled trials in patients with this difficult-to-treat pathology.

Circumferential dural resection technique and reconstruction for the removal of giant calcified transdural herniated thoracic discs

OBJECTIVE The authors report a novel paradigm for resection of the disc or dural complex to treat giant calcified transdural herniated thoracic discs, and they describe a technique for the repair of dural defects. These herniated thoracic discs are uncommon, complicated lesions that often require a multidisciplinary team for effective treatment. The intradural component must be removed to effectively decompress the spinal cord. The opening of the friable dura mater, which frequently adheres to the extradural component of the disc, can result in large defects and difficult-to-manage CSF leaks. METHODS The authors performed a retrospective study of the technique and outcomes in patients with a transdural herniated disc treated at St. Josephs Hospital and Medical Center within a 4-year period between 2012 and 2015. RESULTS During the study period, 7 patients (mean age 56.1 years) presented to the department of neurosurgery with clinical symptoms consistent with myeloradiculopathy. In all cases, 2-level corpectomies of the involved levels were combined with circumferential resection of the dura and complete decompression of the spinal cord. The dural defect was repaired with an onlay dural patch, and a large piece of AlloDerm (LifeCell Corp) graft was sewn to close the pleural defect. Every patient had a perioperative lumbar drain placed for CSF diversion. No patient suffered neurological decline related to the surgery, and 3 patients experienced clinically significant improvement in function. Two patients developed an early postoperative CSF leak that required operative revision to oversew the defects. CONCLUSIONS This novel technique for decompression of the spinal cord by dural resection for the removal of giant calcified transdural herniated thoracic discs is safe and results in excellent decompression of the spinal cord. The technique becomes necessary when primary repair of the dura is not possible, and it can be used in cases in which the resection of pathology includes the dura.

Deep Brain Stimulation of the Hypothalamus Leads to Increased Metabolic Rate in Refractory Obesity

OBJECTIVEnObesity has become a worldwide epidemic, with very few long-term successful treatment options for refractory disease. Deep brain stimulation (DBS) of the bilateral lateral hypothalamus (LH) in refractory obesity has been performed safely. However, questions remain regarding the optimal settings and its effects on metabolic rate. The goals of our experiment were to determine the optimal DBS settings and the actual effect of optimal stimulation on energy expenditure.nnnMETHODSnAfter bilateral LH DBS implantation, 2 subjects with treatment refractory obesity underwent 4 days of metabolic testing. The subjects slept overnight in a respiratory chamber to measure their baseline sleep energy expenditure, followed by 4 consecutive days of resting metabolic rate (RMR) testing at different stimulation settings. On day 4, the optimized DBS settings were used, and sleep energy expenditure was measured again overnight in the room calorimeter.nnnRESULTSnDuring daily testing, the RMR fluctuated acutely with changes in stimulation settings and returned to baseline immediately after turning off the stimulation. Optimal stimulation settings selected for participants showed a 20% and 16% increase in RMR for the 2 participants. Overnight sleep energy expenditure measurements at these optimized settings on day 4 yielded a 10.4% and 4.8% increase over the baseline measurements for the 2 participants.nnnCONCLUSIONSnThese findings have demonstrated the efficacy of optimized DBS of the LH on increasing the RMR acutely and maintaining this increase during overnight sleep. These promising preliminary findings have laid the groundwork for the possible treatment of refractory obesity with DBS.

Combined lateral transpsoas anterior column realignment with pedicle subtraction osteotomy to treat severe sagittal plane deformity: Cadaveric feasibility study and early clinical experience

BACKGROUNDnTraditional open approaches to correct lumbar spine deformities include 3-column osteotomies, such as a pedicle subtraction osteotomy (PSO). Minimally invasive surgical (MIS) techniques have been developed for lateral transpsoas anterior column realignment (ACR). These 2 techniques have not previously been combined. Our objective was to investigate the cadaveric feasibility of a combined hybrid MIS ACR-PSO technique for deformity correction and to review early clinical experience.nnnMETHODSnThe feasibility of the combined ACR-PSO technique was evaluated in 4 fresh cadaveric specimens. The operative experience, complications, and early clinical outcomes in patients treated with the combined approach to correct global sagittal imbalance were reviewed.nnnRESULTSnIn the cadaveric study, the combined ACR-PSO resulted in a mean 46.0° increase in lordosis (P < 0.001). Nine patients treated with ACR-PSO were evaluated (mean age, 65.2 years; 33.3% female). Most patients (6/9; 66.7%) underwent ACR at L1/2 or L3/4; 8 (88.8%) had PSO at L3 or L4. On average, 10.6 ± 3.8 levels were fused. Significant decreases in mean pelvic tilt (Pxa0= 0.01), spinopelvic mismatch (P < 0.001), and T1 spinopelvic inclination (Pxa0=xa00.03) were observed postoperatively; mean lumbar lordosis (Pxa0= 0.007), intradiscal angle (Pxa0= 0.001), and thoracic kyphosis (Pxa0= 0.04) significantly increased. The overall complication rate was 55.6% (5/9).nnnCONCLUSIONSnOur early experience suggests that a combined ACR-PSO with posterior fixation allows for significant correction of segmental lordosis and global imbalance. This combined approach may maximize results attainable with hybrid MIS-open surgical techniques and represents a complementary option to PSO and other posterior approaches.

Minimally Invasive Transforaminal Interbody Fusion With Robotically Assisted Bilateral Pedicle Screw Fixation: 2-Dimensional Operative Video

Minimally invasive surgery (MIS) techniques may enable faster patient recovery and reduce the incidence of postoperative infections. Image-guided approaches to spinal instrumentation and interbody fusion have gained popularity in MIS, reducing radiation exposure and improving screw placement accuracy. Use of a novel computed tomography (CT) navigation-based robotic arm provides for live image-guided surgery, with the potential for augmenting existing MIS approaches and improving the accuracy of instrumentation placement. We report on the surgical technique of MIS transforaminal lumbar interbody fusion (TLIF) performed with the assistance of a new robotic device (ExcelsiusGPS, Globus Medical Inc, Audubon, Pennsylvania) and intraoperative CT guidance in a patient with single-level lumbar spondylolisthesis. The patient gave written informed consent before treatment. Institutional review board approval was deemed unnecessary. The patient was positioned prone on the operating room table, and an intraoperative CT was obtained with stereotactic arrays placed bilaterally in the posterior superior iliac spine. Screw trajectories were planned using the ExcelsiusGPS software and placed percutaneously with the robotic arm without using a Kirschner wire. Interbody placement was performed via an expandable retractor after muscle dilation. Screw placement accuracy was determined with postoperative CT, which demonstrated good screw positioning without breach. The patient recovered well and was discharged home without complications. The combined use of the new robotic device and intraoperative CT enables accurate and safe fixation for the treatment of symptomatic lumbar spondylolisthesis. The operative video demonstrates the technical nuances of positioning, stereotactic marker placement, work flow, and screw placement. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Minimally Invasive Single-Position Lateral Interbody Fusion With Robotic Bilateral Percutaneous Pedicle Screw Fixation: 2-Dimensional Operative Video.

Lateral interbody fusion has distinct advantages over traditional posterior approaches. When adjunctive percutaneous pedicle screw fixation is required, placement from the lateral decubitus position theoretically increases safety and improves operative efficiency by obviating the need for repositioning. However, safe cannulation of the contralateral, down-side pedicles remains technically challenging and often prohibitive. In this video, we present the case of a 59-yr-old man with refractory back pain and bilateral lower extremity radiculopathy that was worse on the left than right side. The patient provided written informed consent before undergoing treatment. We performed minimally invasive single-position lateral interbody fusion with robotic (ExcelsiusGPS, Globus Medical Inc, Audubon, Pennsylvania) bilateral percutaneous pedicle screw fixation for the treatment of asymmetric disc degeneration, dynamic instability, and left paracentral disc herniation with corresponding stenosis at the L3-4 level. A left-sided minimally invasive transpsoas lateral interbody graft was placed with fluoroscopic guidance. Without changing the position of the patient or breaking the sterile field, an intraoperative cone-beam computed tomography image was obtained for navigational screw placement with stereotactic trackers in the iliac spine. Screw trajectories were planned using the robotic navigation software and were placed percutaneously in the bilateral L3 and L4 pedicles using the robotic arm. Concomitant lateral fluoroscopy may be used if desired to ensure the fidelity of the robotic guidance. The patient recovered well postoperatively and was discharged home within 36 h, without complication. Single-position lateral interbody fusion and percutaneous pedicle screw fixation can be accomplished using robotic-assisted navigation and pedicle screw placement. Used with permission from Barrow Neurological Institute.

Minimally Invasive Spine Surgery

In contrast to traditional open spine procedures, minimally invasive spine (MIS) surgery reduces approach-related soft tissue disruption through retraction of local musculature and soft tissue. Aiding the development of MIS surgery have been the development of the intraoperative binocular microscope, muscular distraction systems such as tubular dilation, and percutaneous instrumentation, all of which have facilitated its application to a broad range of conditions (e.g., laminectomy, decompression, discectomy, interbody spacer placement, spinal deformity correction).