Unique microenvironmental responses to PDGF stimulation in brain and spinal cord gliomas determine tumor phenotype.

Injection of a PDGF-B expressing retrovirus into the subcortical white matter of adult rats induces the rapid formation of brain tumors that have the histological features of glioblastoma. In contrast, when the same retrovirus is injected into the spinal cord of adult rats the resulting tumors are more indolent and display a unique histology characterized by nests of tumor cells separated by a dense vascular network without areas of necrosis. To study whether these differences are determined by the tumor cell of origin or due to microenvironmental influences, we conducted a series of transplantation experiments. Cells were independently isolated from PDGF-induced brain and cord tumors then subsequently transplanted into naive rat forebrains and spinal cords. The resulting tumors were characterized by histological analysis, marker expression profiling, PDGFR subtyping, and latency to tumor-induced morbidity. Tumor phenotypes were found to be consistently predicted by the tissue into which they were transplanted rather than by the tissue of origin. These results suggest that tumor microenvironment rather than the tumor cell of origin may be the primary determinant of glioma phenotype in the model presented.

Medulloblasoma: challenges for effective immunotherapy.

For medulloblastoma patients, the current therapeutic paradigm of surgery followed by radiation and chemotherapy can lead to long-term remission. However, the sequelae of treatment can be very debilitating, particularly in young children. Immunotherapy is an attractive treatment approach to optimize the targeting of tumor cells while sparing the vulnerable surrounding brain that is still developing in children. Understanding the relationship between medulloblastoma and the immune system is critical to develop effective immunologic-based treatment strategies for these patients. This review focuses on current knowledge of tumor immunology and the factors that contribute to the lack of immune system recognition of these tumors. The specificity of tumor antigens present in medulloblastoma is also discussed along with a summary of early clinical immunotherapy results.

Platelet-derived growth factor receptor (PDGFR) expression in primary spinal cord gliomas.

Abnormal signaling through the platelet-derived growth factor receptor (PDGFR) has been proposed as a possible mechanism of spinal cord glioma initiation and progression. However, the extent of PDGFR expression in human spinal cord gliomas remains unknown. In this study we perform immunohistochemical analysis of PDGFRα expression in a series of 33 primary intramedullary spinal cord gliomas of different types and grades. PDGFRα was seen to be expressed in a significant subset of these tumors across all major glioma types including ependymoma, oligodendroglioma, pilocytic astrocytoma, astrocytoma, and glioblastoma. These results support the hypothesis that growth factor signaling through the PDGFR may be important for the development of at least a subset of human spinal cord gliomas. Further studies investigating the prognostic significance of PDGFR expression as well as the role of PDGF signaling on the development of intramedullary spinal cord gliomas are warranted.

Enhanced Recovery After Surgery Protocol in Minimally Invasive Lumbar Fusion Surgery Reduces Length of Hospital Stay and Inpatient Narcotic Use.

Background: The application of enhanced recovery after surgery (ERAS) has the potential to improve outcomes, hasten patient recovery, and reduce costs. ERAS has been applied to spine surgery for several years, but data are limited around the impact of ERAS on minimally invasive spine surgery, specifically. The authors report their experience implementing a multimodal ERAS protocol for patients receiving minimally invasive transforaminal lumbar interbody fusion. Methods: The ERAS protocol was implemented at The Valley Hospital Hospital in Ridgewood, New Jersey in January 2020. Following implementation, all patients receiving minimally invasive transforaminal lumbar interbody fusion by a single surgeon were studied. The authors analyze the impact of the protocol on length of stay (LOS), disposition post discharge, and opioid consumption postoperatively in the inpatient and outpatient settings. Results: Sixteen patients were enrolled in the protocol and compared with 17 historical controls. LOS was significantly shorter in the ERAS cohort (1.6 vs. 2.4 days, P = 0.022). There was no significant difference between the groups with respect to disposition; the majority of patients were discharged to home without need for in-home medical services. Patients in the ERAS cohort consumed significantly fewer opioid analgesics postoperatively in the inpatient setting (51 mg morphine milligram equivalents vs. 320 mg morphine milligram equivalents, P = 0.00016). On average, patients in the ERAS cohort were prescribed fewer opioids analgesics post discharge. Conclusions: ERAS application to minimally invasive transforaminal lumbar interbody fusion was safe and effective, significantly reducing LOS and inpatient opioid consumption. These data reflect the importance of uniformly applying a multimodal ERAS protocol to accelerate recovery and reduce narcotic use.

Clinical outcomes after microendoscopic discectomy for recurrent lumbar disc herniation.

STUDY DESIGN: Retrospective review of consecutive case series. OBJECTIVE: To assess the safety and efficacy of the microendoscopic approach for treatment of recurrent lumbar disc herniation. SUMMARY OF BACKGROUND DATA: The standard surgical approach for the treatment of recurrent disc herniation uses an open technique with a wide exposure. Many would consider a minimally invasive approach such as microendoscopic discectomy (MED) to be contraindicated in the setting of recurrent disc herniation. METHODS: Sixteen consecutive patients with recurrent lumbar disc herniation who failed conservative management underwent MED. Before surgery and at follow-up, patients completed the Oswestry Disability Index, SF-36, and assessment of leg pain using the Visual Analog Scale. Outcome was also assessed using modified McNab criteria. RESULTS: No case required conversion to an open procedure. Mean operative time was 108 minutes, and mean estimated blood loss was 32 mL. The only surgical complications were 2 durotomies that were treated with dural sealant without sequelae. Mean hospital stay was 23 hours, and mean follow-up was 14.7 months. Approximately 80% of patients had good or excellent outcomes based on modified McNab criteria. The remaining 3 patients had fair outcomes, and no patient had a poor outcome. All standardized measures improved significantly, including mean Visual Analog Scale for leg pain (8.2 to 2.2, P<0.001), mean Oswestry Disability Index (59.3 to 26.7, P<0.001), SF-36 Physical Component Summary score (28.3 to 42.4, P<0.001), and SF-36 Mental Component Summary score (38.2 to 48.3, P<0.001). As of last follow-up no patient has showed recurrence of herniation or evidence of delayed instability. CONCLUSIONS: MED is a safe and effective surgical approach for the treatment of recurrent lumbar disc herniation. Standardized measures of outcome show that MED for recurrent herniation produces improvement in pain, disability, and functional health that is at least comparable with outcomes reported for conventional open microdiscectomy.

Cadaveric evaluation of minimally invasive posterolateral thoracic corpectomy: a comparison of 3 approaches.

STUDY DESIGN: A cadaver study comparing 3 different minimally invasive approaches to the anterior thoracic spine. OBJECTIVE: To assess the feasibility of minimally invasive thoracic corpectomy from a posterolateral approach and to compare surgical results from 3 approaches. SUMMARY OF BACKGROUND DATA: Traditional posterolateral approaches to the thoracic spine are effective but are associated with a high rate of operative morbidity. METHODS: Thoracic corpectomies were performed using a modified tubular retractor starting at 3, 6, and 9 cm off of midline. Postoperative computed tomography scans were performed and analyzed to assess the extent of corpectomy and ventral decompression. RESULTS: From 3 to 6 to 9 cm, a significant difference in extent of corpectomy (65.8%, 81.5%, and 82.6%, P=0.02) and ventral decompression (83.6%, 90.4%, 94.6%, P=0.05) was noted between 3 cm and the more lateral approaches. The 9 cm approach required more rib resection and average working distances of 8.4 to 11.3 cm, which made the procedure more difficult technically and less suited to the length of standard instruments. CONCLUSIONS: Minimally invasive thoracic corpectomy is feasible and a 6 cm approach off of midline appears optimal.

Minimally invasive posterior thoracic fusion.

Thoracic spine fusion may be indicated in the surgical treatment of a wide range of pathologies, including trauma, deformity, tumor, and infection. Conventional open procedures for surgical treatment of thoracic spine disease can be associated with significant approach-related morbidity, which has motivated the development of minimally invasive approaches. Thoracoscopy and, later, video-assisted thoracoscopic surgery were developed to address diseases of the thoracic cavity and subsequently adapted for thoracic spine surgery. Although video-assisted thoracoscopic surgery has been used to treat a variety of thoracic spine diseases, its relatively steep learning curve and high rate of pulmonary complications have limited its widespread use. These limitations have motivated the development of minimally invasive posterior approaches to address thoracic spine pathology without the added risk of morbidity involved in surgically entering the chest. Many of these advances are ongoing and represent the forefront of minimally invasive spine surgery. As these techniques are developed and applied, it will be important to assess their equivalence or superiority in comparison with standard open techniques using prospective trials. In this paper the authors focus on minimally invasive posterior thoracic procedures that include fusion, and provide a review of the current literature, a discussion of future pathways for development, and case examples. The topic is divided by pathology into sections including trauma, deformity, spinal column tumors, and osteomyelitis.

Anterior approach to cervical intramedullary pilocytic astrocytoma. Case report.

Although there has been considerable experience with anterior approaches to ventral intradural, extramedullary, and pial-based spinal lesions, there is no information in the literature regarding the safety and feasibility of the resection of an intramedullary tumor via an anterior approach. The authors report on the gross-total resection of an intramedullary cervical pilocytic astrocytoma via a C-7 corpectomy and anterior myelotomy. The surgery proceeded without complication, and postoperatively the patient maintained the preoperative deficit of mild unilateral hand weakness but had no sensory deficits. Follow-up MR imaging at 6 months showed gross-total macroscopic resection. Selected intramedullary tumors can be safely removed via an anterior approach. This approach avoids the typical sensory dysfunction associated with posterior midline myelotomy.

Intramedullary inclusion cysts of the cervicothoracic junction. Report of two cases in adults and review of the literature.

Intramedullary inclusion cysts are extremely rare within the rostral spinal cord. In this case report the authors outline the clinical features and surgical treatment of one dermoid cyst and one epidermoid cyst of the cervicothoracic junction. The authors also include a relevant literature discussion regarding the treatment and the embryological origin of these lesions.

Assessment of Paraspinal Muscle Cross-sectional Area After Lumbar Decompression: Minimally Invasive Versus Open Approaches.

STUDY DESIGN: A retrospective, blinded analysis of imaging studies. SUMMARY OF BACKGROUND DATA: To evaluate changes in paraspinal muscle cross-sectional area (CSA) after surgical treatment for lumbar stenosis and to compare these changes between minimally invasive and standard open approaches. The open approach to lumbar stenosis is effective, but it involves retraction and resection of muscle from the spinous process, which can result in ischemia and denervation of paraspinal musculature and may lead to muscle atrophy and pain. OBJECTIVE: It is hypothesized that the microendoscopic decompression of stenosis (MEDS) technique will better preserve the paraspinal muscles compared with the open procedure. MATERIALS AND METHODS: A total of 18 patients underwent a 1-level posterior decompression for lumbar stenosis, (9 open, 9 MEDS). Lumbar magnetic resonance imaging was obtained before surgery and after surgery (open approach average 16.3 mo; MEDS average 16.6 mo). CSA of paraspinal muscles were averaged over the distance of the surgical site. RESULTS: The mean age of patients treated with the open and MEDS approaches were 55.2 and 66.4 years, respectively (P=0.07). Paraspinal muscle CSA decreased by an average of 5.4% (SD=10.6%; range, -24.5% to +7.7%) in patients treated with the open approach and increased by an average of 9.9% (SD=14.4%; range, -9.8% to +33.1%) in patients treated with MEDS (P=0.02). For the open approach, changes in CSA did not differ significantly between the left and right sides for erector spinae (P=0.35) or multifidus muscles (P=0.90). After the MEDS approach there were no significant differences between the dilated and contralateral sides with regard to change in CSA for erector spinae (P=0.85) or multifidus muscles (P=0.95). CONCLUSIONS: Compared with the open approach for lumbar stenosis, MEDS had significantly less negative impact on the paraspinal muscle CSA. Previous reports have documented negative effects of paraspinal muscle injury, including weakness, disability, and pain. Collectively, these data suggest that the MEDS approach for lumbar decompression is less destructive to the paraspinous muscles than the open approach and may facilitate better clinical outcomes.

Subependymomas Are Low-Grade Heterogeneous Glial Neoplasms Defined by Subventricular Zone Lineage Markers.

OBJECTIVE: Subependymomas are infrequent, low-grade gliomas associated with the ventricular system and the spinal cord. Little is known about the origin and natural history of these slow-growing lesions. METHODS: We identified all patients with pathologically proven subependymomas presenting to our institution between 1998 and 2016. We retrospectively reviewed clinical, radiographic, histologic, and surgical outcomes data in all patients who underwent surgical resection. Immunohistochemical analyses for cell lineage markers were performed. RESULTS: A total of 31 patients with pathologically proven subependymomas were identified. Of these, 7 asymptomatic lesions were discovered at autopsy and 24 symptomatic cases were treated surgically. There were 15 (48%) lateral ventricle tumors, 11 (35%) fourth ventricular tumors, and 5 (17%) spinal tumors. Symptomatic intracranial lesions most commonly presented with headaches and balance and gait abnormalities. Subependymomas had no distinguishing radiographic features that provided definitive preoperative diagnosis. At last follow-up, no patient treated surgically experienced recurrence. Immunohistochemical analyses demonstrated a diffusely GFAP-positive glial neoplasm with mixed populations of cells that were variably positive for Olig2, NHERF1, Sox2, and CD44. The Ki67 proliferation index was generally low (<1% in many of the tumors). CONCLUSIONS: Subependymomas demonstrate mixed populations of cells expressing glial lineage markers as well as putative stem cell markers, suggesting these tumors may arise from multipotent glial progenitors that reside in the subventricular zone. Definitive diagnosis requires surgical sampling. Although the clinical course of subependymomas appears benign, the inability to radiographically diagnose these lesions, and the possibility of an alternative malignant lesion support a low threshold for early and safe maximal resection.

Single-stage debridement and instrumentation for pyogenic spinal infections.

Surgical intervention is indicated for pyogenic vertebral discitis and osteomyelitis in patients in whom medical therapy has failed, and in those with neurological compromise, mechanical instability, epidural abscess, or intractable pain. Surgical management has evolved to include single-stage operations for debridement and stabilization as well as more aggressive reconstruction strategies with respect to instrumentation. A review of the literature demonstrates excellent outcomes with single-stage operations and placement of hardware wherever it is required. Using this method, the authors have treated 16 patients without a single incidence of recurrent infection or hardware failure after almost 2 years of follow up.

Primary dural repair in minimally invasive spine surgery.

We describe an effective surgical technique in primary repair of the spinal dura during minimally invasive spine surgery (MISS). Objective. Minimally invasive spine surgery includes the treatment of intradural lesions, and proper closure of the dura is necessary. However, primary dural closure can be difficult due to the restricted space of MIS retractors and the availability of appropriate surgical instrumentation. Methods. We describe the use of a needle already used in the pediatric neurosurgical arena that can facilitate easier and safer closure of spinal dura through MISS retractors in two illustrative intradural cases. Results and Discussion. The primary dural closure technique is described and patient demographics are included. The instruments specifically used for the intradural closure through MIS retractor systems include (1) 4-0 Surgilon braided nylon (Covidien, Dublin, Ireland) with a CV-20 taper 1/2 circle, 10 mm diameter needle; (2) Scanlan (Saint Paul, MN, USA) dura closure set. Conclusion. Successful primary dural repair can be performed on primary and incidental durotomies during minimally invasive spinal surgery. We describe the novel use of a 10 mm diameter needle to help surgeons safely and efficiently close the dura with more ease than previously described.

Minimally invasive thoracic microendoscopic diskectomy: surgical technique and case series.

OBJECTIVE: To present operative details and clinical follow-up of a series of patients with thoracic disk herniation treated with the minimally invasive technique of thoracic microendoscopic diskectomy (TMED). METHODS: TMED was performed in 16 consecutive patients (age range, 18-79 years old) with 18 thoracic disk herniations. One patient with a calcified herniation in a direct ventral location was not included in this series. Patients were positioned prone, and a tubular retractor system was placed through a muscle dilating approach. The procedure was performed with endoscopic visualization. Outcomes were assessed using modified McNab criteria. RESULTS: There were no complications, and no case required conversion to an open procedure. The mean operative time was 153 minutes per level, and mean blood loss was 69 mL per level. Mean hospital stay was 21 hours. At a mean follow-up of 24 months (median, 22 months), 13 patients (81%) had excellent or good outcomes, 1 patient (6%) had a fair outcome, and 2 patients (13%) had poor outcomes. The two patients with poor outcomes had neurologic diagnoses (multiple sclerosis and multiple systems atrophy) that were ultimately found to be responsible for their symptoms and deficits. CONCLUSIONS: TMED is a safe and effective minimally invasive posterolateral approach for the treatment of thoracic disk herniations that lacks the morbidity associated with traditional approaches.

Retroviral delivery of platelet-derived growth factor to spinal cord progenitor cells drives the formation of intramedullary gliomas.

BACKGROUND: High-grade gliomas of the spinal cord are poorly understood tumors that are very commonly associated with bad outcomes. The transforming effects of platelet-derived growth factor (PDGF) on spinal cord glial progenitor cells may play an important role in the development of these tumors. OBJECTIVE: To investigate the possible tumor-initiating effects of PDGF overexpression in the spinal cord, we delivered a PDGF retrovirus directly into the substance of the spinal cord. METHODS: The spinal cords of wild-type adult rats were surgically exposed and injected with 106 colony-forming units of a green fluorescent protein-tagged, PDGF-expressing retrovirus. A control virus was injected to assess the cell types that become infected during retroviral delivery to the spinal cord. RESULTS: It was observed that PDGF overexpression in the spinal cord causes morbidity from high-grade intramedullary glioma formation between 27 and 49 days after PDGF retrovirus injection. Retroviral transduction was highly efficient with 100% of injected animals displaying the tumor phenotype. The tumors produced were highly proliferative, were locally invasive, and displayed the immunophenotype of virus-targeted glial progenitor cells (Olig2+PDGFR+NG2+GFAP-). CONCLUSION: PDGF is capable of driving glial progenitor cells within the adult spinal cord to form high-grade gliomas. Further investigation of PDGF signaling in the spinal cord is needed to better understand and treat these devastating tumors.

Spinal cord bypass surgery with intercostal and spinal accessory nerves: an anatomical feasibility study in human cadavers.

OBJECT: Despite extensive study, no meaningful progress has been made in encouraging healing and recovery across the site of spinal cord injury (SCI) in humans. Spinal cord bypass surgery is an unconventional strategy in which intact peripheral nerves rostral to the level of injury are transferred into the spinal cord below the injury. This report details the feasibility of using spinal accessory nerves to bypass cervical SCI and intercostal nerves to bypass thoracolumbar SCI in human cadavers. METHODS: Twenty-three human cadavers underwent cervical and/or lumbar laminectomy and dural opening to expose the cervical cord and/or conus medullaris. Spinal accessory nerves were harvested from the Erb point to the origin of the nerve's first major branch into the trapezius. Intercostal nerves from the T6-12 levels were dissected from the lateral border of paraspinal muscles to the posterior axillary line. The distal ends of dissected nerves were then transferred medially and sequentially inserted 4 mm deep into the ipsilateral cervical cord (spinal accessory nerve) or conus medullaris (intercostals). The length of each transferred nerve was measured, and representative distal and proximal cross-sections were preserved for axonal counting. RESULTS: Spinal accessory nerves were consistently of sufficient length to be transferred to caudal cervical spinal cord levels (C4-8). Similarly, intercostal nerves (from T-7 to T-12) were of sufficient length to be transferred in a tension-free manner to the conus medullaris. Spinal accessory data revealed an average harvested nerve length of 15.85 cm with the average length needed to reach C4-8 of 4.7, 5.9, 6.5, 7.1, and 7.8 cm. The average length of available intercostal nerve from each thoracic level compared with the average length required to reach the conus medullaris in a tension-free manner was determined to be as follows (available, required in cm): T-7 (18.0, 14.5), T-8 (18.7, 11.7), T-9 (18.8, 9.0), T-10 (19.6, 7.0), T-11 (18.8, 4.6), and T-12 (15.8, 1.5). The number of myelinated axons present on cross-sectional analysis predictably decreased along both spinal accessory and intercostal nerves as they coursed distally. CONCLUSIONS: Both spinal accessory and intercostal nerves, accessible from a posterior approach in the prone position, can be successfully harvested and transferred to their respective targets in the cervical spinal cord and conus medullaris. As expected, the number of axons available to grow into the spinal cord diminishes distally along each nerve. To maximize axon "bandwidth" in nerve bypass procedures, the most proximal section of the nerve that can be transferred in a tension-free manner to a spinal level caudal to the level of injury should be implanted. This study supports the feasibility of SAN and intercostal nerve transfer as a means of treating SCI and may assist in the preoperative selection of candidates for future human clinical trials of cervical and thoracolumbar SCI bypass surgery.

Minimally invasive resection of intramedullary ependymoma: case report.

OBJECTIVE: This report illustrates the adequacy of minimally invasive exposure for the resection of an intramedullary ependymoma. CLINICAL PRESENTATION: The patient presented with a history of upper back pain, but a lesion was found during a workup for increased back pain after a motor vehicle accident. INTERVENTION: The intramedullary ependymoma was approached using a muscle-splitting retractor and extended hemilaminar exposure. The tumor was removed using conventional techniques. CONCLUSION: This minimally invasive exposure is adequate for selected intramedullary lesions and may be especially useful in patients with a high risk of postlaminectomy deformity.

A biomechanical evaluation of graded posterior element removal for treatment of lumbar stenosis: comparison of a minimally invasive approach with two standard laminectomy techniques.

STUDY DESIGN: A validated finite element model of the intact lumbar spine (L1-S1) was modified to study the biomechanical changes as a result of surgical alteration for treatment of stenosis at L3-L4 and L4-L5 using 2 established techniques and 1 new minimally invasive technique. OBJECTIVE: To investigate the impact of graded posterior element removal associated with new surgical techniques on postoperative segmental motion and loading in the annulus. SUMMARY OF BACKGROUND DATA: Several studies have shown that laminectomy increases and produces segmental instability unless fusion is performed. However, no data exist comparing the biomechanical impact of completely preserving the contralateral anatomy and what effect this has compared to traditional approaches. METHODS: The effect of graded removal of posterior elements because of iatrogenic change associated with the 3 approaches was investigated using an 800 N compressive preload using the follower load technique and application of 8 Nm flexion, 6 Nm extension, 4 Nm torsion, and 6 Nm lateral bending moments. RESULTS: This study shows that removal of posterior elements for treatment of stenosis at L3-L4 and L4-L5 results in increased flexion-extension and axial rotation at the surgical site. This study also shows that the segmental motion following a traditional laminectomy is greater than the minimally invasive approach in flexion, extension, left and right axial rotation. Moderate preservation of the posterior elements which occurs in the intralaminar approach generates greater segmental motion that the minimally invasive approach in extension, left and right axial rotation. CONCLUSION: Minimization of bone and ligament removal associated with minimally invasive procedures results in greater preservation of the normal motion of the lumbar spine after surgery. This study suggests that preservation of the posterior spinal elements associated with minimally invasive surgery could minimize the risk of developing de novo postoperative changes in spinal alignment and/or acceleration of facet and disc degeneration.

Operative management of spinal hemangioblastoma.

Hemangioblastomas occur in 2% to 15% of reported series of intramedullary spinal cord tumors. They are benign, highly vascular tumors that can be cured with surgical resection. Complete removal of these tumors with low morbidity is possible with current microneurosurgical techniques and a thorough understanding of the typical relationship of the tumor to adjacent neural structures. We describe our experience with 16 intramedullary and 2 lumbosacral nerve root hemangioblastomas and review the relevant published literature. A detailed discussion of the operative technique is provided along with an operative video. Three illustrative cases are used to demonstrate clinical considerations that can arise with these tumors, including surgery during pregnancy, symptoms related to syrinx or syringomyelia, and postoperative consequences of neurological deficits.