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In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC).To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors.This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations.One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival.Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.

Chordomas are rare tumors of the embryologic spinal cord remnant. They are locally aggressive and typically managed with surgery and either adjuvant or neoadjuvant radiation therapy. However, there is great variability in practice patterns including radiation type and fractionation regimen, and limited high-level data to drive decision making. The purpose of this manuscript was to summarize the current literature specific to radiotherapy in the management of spine and sacral chordoma and to provide practice recommendations on behalf of the Spine Tumor Academy. A systematic review of the literature was performed using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) approach. Medline and Embase databases were utilized. The primary outcome measure was the rate of local control. A detailed review and interpretation of eligible studies is provided in the manuscript tables and text. Recommendations were defined as follows: (1) consensus: approved by >75% of experts; (2) predominant: approved by >50% of experts; (3) controversial: not approved by a majority of experts. Expert consensus supports dose escalation as critical in optimizing local control following radiation therapy for chordoma. In addition, comprehensive target volumes including sites of potential microscopic involvement improve local control compared with focal targets. Level I and high-quality multi-institutional data comparing treatment modalities, sequencing of radiation and surgery, and dose/fractionation schedules are needed to optimize patient outcomes in this locally aggressive malignancy.

Background and purpose The utility of preoperative embolization remains controversial within the literature. Here, we evaluate whether preoperative meningioma embolization is effective in reducing intraoperative blood loss, safe to perform, and cost-effective when compared with surgical resection without preoperative embolization. Methods Twenty-nine patients with meningiomas were matched by tumor size and location to 29 control patients with meningiomas at another institution where preoperative embolization was not practiced. The variables evaluated were pre- and post-operative hemoglobin and hematocrit levels as a measure of operative blood loss and postoperative morbidity. The additional cost of undergoing angiography and embolization was calculated from hospital charges obtained from the billing department. Results The mean decrease in perioperative hemoglobin and hematocrit was 0.9 and 2.7, respectively, in the embolization group and 2.8 and 10.0, respectively, in the control group for a significant decrease in operative blood loss as measured by change in hematocrit and hemoglobin levels after surgery. There was no significant difference in operative blood loss when subdividing patients based on tumor location. There were no angiogram-related complications. Twenty-two of 29 patients (76%) underwent embolization of a feeding artery, whereas 7 patients underwent only a diagnostic angiogram. The mean additional charge per patient in the embolization group was $88,767. Conclusions Preoperative embolization was safe and effective in reducing the overall perioperative blood loss in patients undergoing meningioma resection, as measured by the change in postoperative hemoglobin and hematocrit levels. However, the cost of embolization was significant.

Mechanistic target of rapamycin (mTOR), which functions via two multiprotein complexes termed mTORC1 and mTORC2, is positioned in the canonical phosphoinositide 3‑kinase‑related kinase (PI3K)/AKT (PI3K/AKT) pathways. These complexes exert their actions by regulating other important kinases, such as 40S ribosomal S6 kinases (S6K), eukaryotic translation initiation factor 4E (elF4E)‑binding protein 1 (4E‑BP1) and AKT, to control cell growth, proliferation, migration and survival in response to nutrients and growth factors. Glioblastoma (GB) is a devastating form of brain cancer, where the mTOR pathway is deregulated due to frequent upregulation of the Receptor Tyrosine Kinase/PI3K pathways and loss of the tumor suppressor phosphatase and tensin homologue (PTEN). Rapamycin and its analogs were less successful in clinical trials for patients with GB due to their incomplete inhibition of mTORC1 and the activation of mitogenic pathways via negative feedback loops. Here, the effects of selective ATP‑competitive dual inhibitors of mTORC1 and mTORC2, Torin1, Torin2 and XL388, are reported. Torin2 exhibited concentration‑dependent pharmacodynamic effects on inhibition of phosphorylation of the mTORC1 substrates S6KSer235/236 and 4E‑BP1Thr37/46 as well as the mTORC2 substrate AKTSer473 resulting in suppression of tumor cell migration, proliferation and S‑phase entry. Torin1 demonstrated similar effects, but only at higher doses. XL388 suppressed cell proliferation at a higher dose, but failed to inhibit cell migration. Treatment with Torin1 suppressed phosphorylation of proline rich AKT substrate of 40 kDa (PRAS40) at Threonine 246 (PRAS40Thr246) whereas Torin2 completely abolished it. XL388 treatment suppressed the phosphorylation of PRAS40Thr246 only at higher doses. Drug resistance analysis revealed that treatment of GB cells with XL388 rendered partial drug resistance, which was also seen to a lesser extent with rapamycin and Torin1 treatments. However, treatment with Torin2 completely eradicated the tumor cell population. These results strongly suggest that Torin2, compared to Torin1 or XL388, is more effective in suppressing mTORC1 and mTORC2, and therefore in the inhibition of the GB cell proliferation, dissemination and in overcoming resistance to therapy. These findings underscore the significance of Torin2 in the treatment of GB.

Spinal cord injury leads to a robust inflammatory response that is an unfavorable environment for stem cell implantation. In this study, we evaluated the effect of combined therapy of curcumin and mesenchymal stem cells (MSC) on behavioral recovery and tissue sparing, glial scar formation, axonal sprouting and inflammatory responses in a rat experimental model of spinal cord injury (SCI). Balloon-induced compression lesion was performed at thoracic (Th8-9) spinal level. Out of the four groups studied, two groups received curcumin on the surface of the spinal cord immediately after SCI and then once a week for 3 weeks together with an intraperitoneal daily curcumin injection for 28 days. The other two groups received saline. Seven days after SCI, human MSC were intrathecally implanted in one curcumin and one saline group. Both curcumin and curcumin combined with MSC treatment improved locomotor ability in comparison to the saline treated animals. The combined treatment group showed additional improvement in advanced locomotor performance. The combined therapy facilitated axonal sprouting, and modulated expression of pro-regenerative factors and inflammatory responses, when compared to saline and single treatments. These results demonstrate that preconditioning with curcumin, prior to the MSC implantation could have a synergic effect in the treatment of experimental SCI.

BACKGROUND CONTEXT Metastatic spine tumor surgery generally consists of palliative operations performed on frail patients with multiple medical comorbidities. Perioperative complications that may arise can mitigate any potential benefit in this vulnerable patient cohort. Enhanced recovery after surgery (ERAS) programs involve an evidence-based multidisciplinary approach to improve perioperative outcomes. While ERAS programs have been shown to be beneficial in other surgical fields, literature evaluating the feasibility, implementation, and outcomes of an ERAS program dedicated to metastatic spine tumor surgery is limited. PURPOSE We present the metastatic spine tumor ERAS pathway and describe the clinical outcomes of the program. STUDY DESIGN/SETTING The metastatic spine tumor ERAS program went into effect in April 2019. This protocol focused on multimodality analgesia, including preoperative gabapentinoid, NSAID, and acetaminophen administration in combination with local field blocks with liposomal bupivacaine, to minimize opioid consumption; intraoperative goal-directed fluid management, early advancement of diet, and early ambulation with physical therapy. PATIENT SAMPLE A total of 177 consecutive patients undergoing metastatic spine tumor surgery enrolled in the ERAS program were compared to 213 consecutive pre-ERAS patients. OUTCOME MEASURES Outcomes measured included: length of hospitalization stay, time to ambulation, urinary catheter duration, time to regular diet, total intraoperative fluid intake, estimated blood loss, intraoperative opioid use, and cumulative postop day 0-5 opioid use. Methods Single institution, retrospective review of prospectively collected data. Results While the case duration was similar in the ERAS vs pre-ERAS cohort (265 min vs 274 min, p = 0.22), the ERAS cohort had less estimated blood loss (157 mL vs 215 mL, p = 0.003), less postop day 0-5 cumulative opioid use (178 MME vs 396 MME, p Conclusions To date, this is the largest study focusing on outcomes of an ERAS program specifically for patients undergoing metastatic spine tumor surgery. The implementation of an evidence-based multidisciplinary ERAS program has led to a significant reduction in postoperative opioid consumption, improved clinical quality metrics, and shorter hospitalization. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Medulloblastoma (MB) is the most common primary pediatric malignant brain tumor. Current molecular analysis classifies MB into 4 groups, classic (WNT), sonic hedgehog (Shh), group 3, and group 4. Furthermore, atypical p53 signaling is associated with disease progression and confers poor prognosis. This study investigated the correlation of mutational status of p53 and iSO17q with disease progression and metastatic potential. In addition, we used small molecule inhibitors of PI3K (Buparlisib; BKM120) and HDAC (LBH-589) on a p53-mutant MB cell line to find novel therapeutic targets. Efficacy of these drugs were assessed using functional assays (cell proliferation, migration, cell cycle and drug resistance). MB tumors (n=53) were evaluated for GLI-1, GAB-1, NPR, KV1, YAP expression and mutant p53 via immunohistochemistry and correlated to patient outcomes. Results demonstrated that: 1) high expression of GAB-1 and YAP were found in the Shh group, while KV1 expression was present in all subtypes; 2) mutant p53 expression was present in various subsets of MB with no apparent correlation with metastasis or disease progression; 3) patients displaying iSO17q (determined by fluorescence in situ hybridization (FISH) technique) exhibited metastatic disease; 4) LBH-589 and BKM120 caused both time and dose-dependent inhibition of MB cell proliferation and migration; 5) combined treatment of BKM120 and LBH-589 had a synergistic effect; 6) MB cells demonstrated drug-resistance to BKM120. In conclusion, these findings underscore use of Buparlisib and LBH-589 in treatment of MB. Further, the role of mutant p53 in disease progression remains elusive, whereas presence of iSO17q defines metastatic potential.

Background Prior studies have shown that most patients with mild traumatic brain injury or negative computed tomography (CT) scans of the head rarely decline or require neurosurgical interventions. One common reason for a delayed decline is an intracranial hemorrhage that presents within 24–48 hours. This is typically seen in elderly patients and/or patients on antiplatelet or anticoagulation agents. We describe a case of a delayed subdural hemorrhage presenting in a young adult not on any antiplatelet or anticoagulation therapy. Case Description A 19-year-old male presented to the emergency department after being involved in a motor vehicle accident. He had a Glasgow Coma Scale of 15, and an initial CT was negative for any intracranial hemorrhage or pathology, so he was then admitted to the intensive care unit for further care. The patient received 1 dose of aspirin 325 mg the following day for treatment of blunt cerebrovascular injury. Six hours later he reported a severe headache and had an episode of emesis with a subsequent rapid neurologic decline. Repeat CT showed an acute right subdural hematoma, and he underwent an emergent right decompressive hemicraniectomy. Conclusions In rare cases, patients with negative initial head CT scans neurologically deteriorate as a result of a delayed acute subdural hematoma. We present an unusual case of a young patient on no medications with no CT findings of an intracranial injury who neurologically declined due to a delayed acute subdural hematoma.

A spontaneous spinal epidural hematoma is a collection of blood in the spinal epidural space that occurs in the absence of trauma. They most commonly present in the fourth to fifth decade in life with acute onset neck or back pain with delayed neurologic deficit. However, this presentation is often complicated in children because of the limitations in the pediatric neurologic exam. Magnetic resonance imaging is the imaging modality of choice for diagnosis. Here is a rare case of an infant spontaneous spinal epidural hematoma whose diagnosis was delayed because of a recent history of fever and viral pharyngitis before his development of neurologic deficits. Spontaneous spinal epidural hematomas are a rare phenomenon, which often present with nonspecific symptoms in the pediatric population. This diagnosis should be considered to initiate treatment in a timely manner. The treatment typically is emergent surgical decompression to minimize the risk of permanent neurologic deficit.

IntroductionA spinal dural arteriovenous fistula is a rare type of vascular malformation. If left untreated, these fistulas can result in significant neurological deficits secondary to spinal cord infarct or hemorrhage.Case presentationA 70-year-old female with a longstanding history of episodic progressive bilateral lower extremity weakness and sensory disturbances was previously misdiagnosed with multiple sclerosis. Imaging revealed a T2 signal change from T7 to the conus with associated signal change and she subsequently underwent a T10-L1 laminectomy for clip ligation of a spinal dural arteriovenous fistula. Here we present the clinical and radiographic progression of one patient with a spinal dural arteriovenous fistula.DiscussionSpinal dural arteriovenous fistulas are a rare but treatable cause of myelopathy, so it is important to understand its natural progression and radiologic findings as it is frequently misdiagnosed.

The differential diagnosis for trigeminal neuralgia like-symptoms includes cerebellopontine angle lesions causing regional mass effect upon the trigeminal nerve (Fig. 1). Here we present an operative video manuscript of a patient experiencing trigeminal neuralgia, secondary to an epidermoid cyst, in which a retrosigmoid craniectomy was performed to resect the epidermoid and decompress the trigeminal nerve (Fig. 2). This video highlights the operative nuances to achieving a successful surgery, including appropriate patient positioning, dural exposure to the transverse-sigmoid sinus junction, arachnoid dissection, and decompression of cranial nerves. A gross total resection was achieved; the patient reported immediate relief of facial pain postoperatively and has been pain free at the ten month follow-up.The link to the video can be found at: https://youtu.be/Ja2eE0uGk4E.

OBJECT Multiple myeloma is the most common primary tumor of the spine and is the most common primary malignant tumor of bone. Although spinal myeloma is classically a radiosensitive lesion, clinical or radiographic signs of instability merit surgical intervention. The authors present the epidemiology, surgical indications, and outcome data of a series of consecutive cases involving 31 surgically treated patients with diagnoses of multiple myeloma and plasmacytoma of the spine (the largest such series reported to date). METHODS Surgical instability was the criterion for operative intervention in this patient cohort. The Spinal Instability Neoplastic Score (SINS) was used to make this assessment of instability. The cases were analyzed using location of the lesion, spinal levels involved, Frankel score, adjuvant therapy, functional outcome, and patient survival. RESULTS All patients undergoing surgical intervention were determined to have indeterminate or gross spinal column instability according to SINS criteria. The median survival was 78.9 months. No significant difference in survival was seen for patients with higher SINS scores or for older patients (> 55 years). There was a statistically significant difference in survival benefit observed for patients receiving chemotherapy and radiation versus radiation alone as an adjuvant to surgery (p = 0.02). CONCLUSIONS In this 10-year analysis, the authors report outcomes of surgical intervention for patients with indeterminate or gross spinal instability due to multiple myeloma and plasmacytoma of the spine with improved neurological function following surgery and low rates of instrumentation failure.

Stents and flow diverters have revolutionized the treatment of cerebrovascular disease. Guglielmi coils, flexible microcatheters, and first-generation intracranial stents, such as Neuroform (Stryker Neurovascular) and Enterprise stents (Codman/DePuy-Synthes), have paved the way for the development of the Pipeline Embolization Device (PED) (ev3/Covidien/Medtronic) and other endovascular approaches. This review discusses the historical development of flow diverter technologies from the PED to similar devices, such as the Surpass stent (Stryker Neurovascular), the Flow-Redirection Endoluminal Device (FRED; MicroVention, Inc.), the SILK stent (Balt Extrusion), and the p64 Flow Modulation Device (Phenox). In addition, the potential use of drug-eluting stents and various bioresorbable scaffolds (e.g., poly-l-lactic acid, magnesium), new developments in stent material (e.g., thin-film nitinol), design (e.g., biocompatible polymers, embedded microcircuitry, flow models), and potential applications for flow diverters will be considered. Endovascular treatment of cerebrovascular disease is rapidly advancing via continued development of new technology.

Spinal cord injury (SCI) is a debilitating condition which is characterized by an extended secondary injury due to the presence of inflammatory local milieu. Epigallocatechin gallate (EGCG) appears to possess strong neuroprotective properties. Here, we evaluated the beneficial effect of EGCG on recovery from SCI. Male Wistar rats were given either EGCG or saline directly to the injured spinal cord and thereafter a daily IP injection. Behavior recovery was monitored by BBB, plantar, rotarod and flat-beam tests. The levels of inflammatory cytokines were determined on days 1, 3, 7, 10 and 14 after SCI. Additionally, NF-κB pathway activity was evaluated. The results demonstrated that EGCG-treated rats displayed a superior behavioral performance in a flat beam test, higher axonal sprouting and positive remodelation of glial scar. Cytokine analysis revealed a reduction in IL-6, IL2, MIP1α and RANTES levels on days 1 and 3, and an upregulation of IL-4, IL-12p70 and TNFα 1 day following SCI in EGCG-treated rats. Treatment with EGCG was effective in decreasing the nuclear translocation of subunit p65 (RelA) of the NF-κB dimer, and therefore canonical NF-κB pathway attenuation. A significant increase in the gene expression of growth factors (FGF2 and VEGF), was noted in the spinal cord of EGCG-treated rats. Further, EGCG influenced expression of M1 and M2 macrophage markers. Our results have demonstrated a therapeutic value of EGCG in SCI, as observed by better behavioral performance measured by flat beam test, modulation of inflammatory cytokines and induction of higher axonal sprouting.

Object A number of imaging techniques have been introduced to minimize the risk of pedicle screw placement. Intraoperative CT has been recently introduced to assist in spinal instrumentation. The aim of this study was to study the effectiveness of intraoperative CT in enhancing the safety and accuracy of pedicle screw placement. Methods The authors included all cases from December 2009 through July 2012 in which intraoperative CT scanning was used to confirm pedicle screw placement. Results A total of 203 patients met the inclusion criteria. Of 1148 screws, 103 screws (8.97%) were revised intraoperatively in 72 patients (35.5%): 14 (18.42%) were revised in the cervical spine (C-2 or C-7), 25 (7.25%) in the thoracic spine, and 64 (8.80%) in the lumbar spine. Compared with screws in the thoracic and lumbar regions, pedicle screws placed in the cervical region were statistically more likely to be revised (p = 0.0061). Two patients (0.99%) required reoperations due to undetected misplacement of pedicle screws. Conclusions The authors describe one of the first North American experiences using intraoperative CT scanning to confirm the placement of pedicle screws. Compared with a similar cohort of patients from their institution who had pedicle screws inserted via the free-hand technique with postoperative CT, the authors found that the intraoperative CT lowers the threshold for pedicle screw revision, resulting in a statistically higher rate of screw revision in the thoracic and lumbar spine (p < 0.0001). During their 2.5-year experience with the intraoperative CT, the authors did not find a reduction in rates of reoperation for misplaced pedicle screws.

Object The rib head is an important landmark in the anterolateral approach to the thoracic spine. Resection of the rib head is typically the first step in gaining access to the underlying pedicle and ultimately the spinal canal. The goal of this work is to quantify the relationship of the rib head to the spinal canal and adjacent aorta at each thoracic level using CT-based morphometric measurements. Methods One hundred thoracic spine CT scans (obtained in 50 male and 50 female subjects) were evaluated in this study. The width and depth of each vertebra body were measured from T-1 to T-12. In addition, the distance of each rib head to the spinal canal was determined by drawing a line connecting the rib heads bilaterally and measuring the distance to this line from the most ventral aspect of the spinal canal. Finally, the distance of the left rib head to the thoracic aorta was measured at each thoracic level below the aortic arch. Results The vertebral body depth progressively increased in a rostral to caudal direction. The vertebral body width was at its minimum at T-4 and progressively increased to T-12. The rib head extended beyond the spinal canal maximally at T-1. This distance incrementally decreased toward the caudal levels, with the tip of the rib head lying approximately even with the ventral canal at T-11 and T-12. The distance between the aorta and the left rib head increased in a rostral to caudal direction as well. Conclusions The rib head is an important landmark in the anterolateral approach to the thoracic spine. At more cephalad levels, a larger portion of rib head requires resection to gain access to the spinal canal. At more caudad levels, there is a safer working distance between the rib head and aorta.

Activation of PI3K/Akt/mTOR (mechanistic target of rapamycin) signaling cascade has been shown in tumorigenesis of numerous malignancies including glioblastoma (GB). This signaling cascade is frequently upregulated due to loss of the tumor suppressor PTEN, a phosphatase that functions antagonistically to PI3K. mTOR regulates cell growth, motility, and metabolism by forming two multiprotein complexes, mTORC1 and mTORC2, which are composed of special binding partners. These complexes are sensitive to distinct stimuli. mTORC1 is sensitive to nutrients and mTORC2 is regulated via PI3K and growth factor signaling. mTORC1 regulates protein synthesis and cell growth through downstream molecules: 4E-BP1 (also called EIF4E-BP1) and S6K. Also, mTORC2 is responsive to growth factor signaling by phosphorylating the C-terminal hydrophobic motif of some AGC kinases like Akt and SGK. mTORC2 plays a crucial role in maintenance of normal and cancer cells through its association with ribosomes, and is involved in cellular metabolic regulation. Both complexes control each other as Akt regulates PRAS40 phosphorylation, which disinhibits mTORC1 activity, while S6K regulates Sin1 to modulate mTORC2 activity. Another significant component of mTORC2 is Sin1, which is crucial for mTORC2 complex formation and function. Allosteric inhibitors of mTOR, rapamycin and rapalogs, have essentially been ineffective in clinical trials of patients with GB due to their incomplete inhibition of mTORC1 or unexpected activation of mTOR via the loss of negative feedback loops. Novel ATP binding inhibitors of mTORC1 and mTORC2 suppress mTORC1 activity completely by total dephosphorylation of its downstream substrate pS6KSer235/236, while effectively suppressing mTORC2 activity, as demonstrated by complete dephosphorylation of pAKTSer473. Furthermore, proliferation and self-renewal of GB cancer stem cells are effectively targetable by these novel mTORC1 and mTORC2 inhibitors. Therefore, the effectiveness of inhibitors of mTOR complexes can be estimated by their ability to suppress both mTORC1 and 2 and their ability to impede both cell proliferation and migration.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Signal transducers and activators of transcription 3 (STAT3) is a transcription factor that translocates to the nucleus to modulate the expression of a variety of genes associated with cell survival, differentiation, proliferation, angiogenesis, and immune function. Several cancers induce constitutive STAT3 activation. Most studies have reported that STAT3 inhibition has antineoplastic activity; however, emerging evidence suggests that the role of STAT3 activity in GBM may be more nuanced than initially appreciated. The authors review the roles of STAT3 in GBM and discuss potential strategies for targeting STAT3.

Thromboembolic events and anticoagulation-associated bleeding events represent frequent complications following cardiac mechanical valve replacement. Management guidelines regarding the timing for resuming anticoagulation therapy following a surgically treated subdural hematoma (SDH) in patients with mechanical valves remains to be determined.To determine optimal anticoagulation management in patients with mechanical heart valves following treatment of SDH.Outcomes were retrospectively reviewed for 12 patients on anticoagulation therapy for thromboembolic prophylaxis for mechanical cardiac valves who underwent surgical intervention for a SDH at the Johns Hopkins Hospital between 1995 and 2010.The mean age at admission was 71 years. All patients had St. Jude's mechanical heart valves and were receiving anticoagulation therapy. All patients had their anticoagulation reversed with vitamin K and fresh frozen plasma and underwent surgical evacuation. Anticoagulation was withheld for a mean of 14 days upon admission and a mean of 9 days postoperatively. The average length of stay was 19 days. No deaths or thromboembolic events occurred during the hospitalization. Average follow-up time was 50 months, during which two patients had a recurrent SDH. No other associated morbidities occurred during follow-up.Interruptions in anticoagulation therapy for up to 3 weeks pose minimal thromboembolic risk in patients with mechanical heart valves. Close follow-up after discharge is highly recommended, as recurrent hemorrhages can occur several weeks after the resumption of anticoagulation.

The clinical presentation of dural arteriovenous fistulas (DAVFs), in particular the associated risk of intracranial hemorrhage, shows a strong correlation with their pattern of venous drainage. The two most commonly used and clinically accepted DAVF classifications are the Merland-Cognard classification and the Borden classification, both based on the morphology of the venous drainage. A revised classification that grades DAVFs through a combination of angiographic and clinical features has also been proposed. This article offers a review of these various classification schemes, and discusses their application to treatment decision making.

BACKGROUND: Pedicle screws are used to stabilize all 3 columns of the spine, but can be technically demanding to place. Although intraoperative fluoroscopy and stereotactic-guided techniques slightly increase placement accuracy, they are also associated with increased radiation exposure to patient and surgeon as well as increased operative time. OBJECTIVE: To describe and critically evaluate our 7-year institutional experience with placement of pedicle screws in the thoracic and lumbar spine using a free-hand technique. METHODS: We retrospectively reviewed records of all patients undergoing free-hand pedicle screw placement without fluoroscopy in the thoracic or lumbar spine between June 2002 and June 2009. Incidence and extent of cortical breach by misplaced pedicle screw was determined by review of postoperative computed tomography scans. We defined breach as more than 25% of the screw diameter residing outside of the pedicle or vertebral body cortex. RESULTS: A total of 964 patients received 6816 free-hand placed pedicle screws in the thoracic or lumbar spine. Indications for hardware placement were degenerative/deformity disease (51.2%), spondylolisthesis (23.7%), tumor (22.7%), trauma (11.3%), infection (7.6%), and congenital (0.9%). A total of 115 screws (1.7%) were identified as breaching the pedicle in 87 patients (9.0%). Breach occurred more frequently in the thoracic than the lumbar spine (2.5% and 0.9%, respectively; P < .0001) and was more often lateral (61.3%) than medial (32.8%) or superior (2.5%). T4 (4.1%) and T6 (4.0%) experienced the highest breach rate, whereas L5 and 51 had the lowest breach rate. Eight patients (0.8%) underwent revision surgery to correct malpositioned screws. CONCLUSION: Free-hand pedicle screw placement based on external anatomy alone can be performed with acceptable safety and accuracy and allows avoidance of radiation exposure encountered in fluoroscopic techniques. Image-guided assistance may be most valuable when placing screws between T4 and T6, where breach rates are highest.

Comprehensive studies of the medulloblastoma (MB) genome, epigenome and transcriptome have placed MB in four molecular subgroups: WNT, SHH, and two non-WNT/non-SHH: Group 3 and Group 4. Furthermore, studies suggest that p53-mutated SHH MBs frequently harbor genetic anomalies involving MYCN and GLI2 amplifications, which confer poor prognosis and resistance to treatments. The phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) intracellular signaling pathway that regulates cell growth, survival and invasion, is commonly deregulated in MB. Therefore, the PI3K/Akt/mTOR pathway may be a suitable target for therapeutic intervention. Moreover, Histone deacetylases (HDAC) regulate cancer initiation and progression, and studies have shown that small molecule inhibitors of HDAC can effectively limit MB proliferation. We aim to determine the status of tumor suppressor gene p53 in defining metastatic potential in SHH-MB and to establish the therapeutic efficacy of targeting these pathways in p53-driven MB cells with a dual agent or individual agents. Immunohistochemistry and FISH were used to determine the status of mutant p53 and MYC amplification or iso-p53, respectively, in MB tumors (n=41). p53-mutant MB cell line was used to investigate the signaling pathway that regulates proliferation, migration, and drug resistance using inhibitors of HDAC (LBH-589) and PI3K/mTOR (BKM-120/rapamycin) or CUDC-907 (dual inhibitor of HDACs and the PI3K/AKT). Results demonstrated that: 1) GAB-1 was highly expressed in the Shh group (82%) and KV1 expression was evenly distributed in all subtypes; 2) loss of p53 and overexpression of MYC varied in each subtype, but did not correlate with metastasis; 3) combined treatment with LBH-589 and BKM-120 or single treatment with CUDC-907 reduced cell proliferation, migration and S-phase entry; 4) MB cells were resistant to BKM -120, while LBH-589 or CUDC-907 caused apoptosis; 5) tumor formation was suppressed by BKM-120 given with mTOR inhibitors; 6) AKT and 4E-BP1 dephosphorylated following treatments with BKM-120 or CUDC-907. In conclusion, despite current clinical limitations, dual HDAC and PI3K inhibitors may benefit the understanding of aberrant signaling pathways in genetically driven MB, and may provide basis for future targeted therapies. Citation Format: Jennifer S. Ronecker, Julia Pazniokas, Anubhav G. Amin, Raphael Salles Scortegagna de Medeiros, Sidnei Epelman, Chirag Ghandi, Nelci Zanon, Meic H. Schmidt, Meena Jhanwar-Uniyal. Dual inhibition of HDAC and PI3 kinase signaling pathways with CUDC-907 in treatment of p53-driven medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3982.

Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining) and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

The relation of the pelvis to the spine has previously been overlooked as a contributor to sagittal balance. However, it is now recognized that spinopelvic alignment is important to maintain an energy-efficient posture in normal and disease states. The pelvis is characterized by an important anatomic landmark, the pelvic incidence (PI). The PI does not change after adolescence, and it directly influences pelvic alignment, including the parameters of pelvic tilt (PT) and sacral slope (SS) (PI = PT 1 SS), overall sagittal spinal balance, and lumbar lordosis. In the setting of an elevated PI, the spineadapts with increased lumbar lordosis. To prevent or limit sagittal imbalance, the spine may also compensate with increased PT or pelvic retroversion to attempt to maintain anupright posture. Abnormal spinopelvic parameters contribute to multiple spinal conditions including isthmic spondylolysis, degenerative spondylolisthesis, deformity, and impact outcome after spinal fusion. Sagittal balance, pelvic incidence, and all spinopelvic parameters are easily and reliably measured on standing, full-spine (lateral) radiographs, and it is essential to accurately assess and measure these sagittal values to understand their potential role in the disease process, and to promote spinopelvic balance at surgery. In this article, we provide a comprehensive review of the literature regarding the implications of abnormal spinopelvic parameters and discuss surgical strategies for correction of sagittal balance. Additionally, the authors rate and critique the quality of the literature cited in a systematic review approach to give the reader an estimate of the veracity of the conclusions reached from these reports.

Medulloblastoma (MB) is the most common primary pediatric malignant brain tumor. Genetic classification and distinct histologic subtypes defines MB into 4 groups: classic (WNT), sonic hedgehog (Shh), group 3 and group 4. In addition, recent studies have provided evidence that p53 abnormalities is seen in various sub-groups of MB and that p53-mutated SHH MBs commonly harbor genetic anomalies including MYCN and GLI2 amplifications, which confers drug resistance. Here, we test the hypothesis that specific immunohistological markers, their correlation with the amplification of the oncogene MYC, and abnormalities in tumor suppressor gene p53, may define their metastatic potential. Materials and Methods: Immunohistological analysis of MB tumors (n=41) was evaluated for the expression of glioma transcription factor 1 (GLI-1), Grb2-associated binding protein 1 (GAB-1), natriuretic peptide receptor (NPR), voltage-gated potassium channel (KV1) and mutant p53. FISH analysis was performed to determine MYC amplification or iso- P53. p53-mutant MB cell line was used to investigate the signaling pathway leading to proliferation, migration, and drug resistance using HDAC (LBH-589) and PI3K/mTOR (BKM-120/rapamycin) inhibitors. Results: we showed that: 1) GAB-1 was highly expressed in the Shh group (82%) and KV1 expression was evenly distributed in all subtypes; 2) No obvious correlation with expression of GLI-1, GAB-1, NPR, or KV1 with metastasis was seen; 3) Analysis of loss of p53 and overexpression of MYC varied in each subtype; 4) Combined Treatment with LBH-589 and BKM-120 reduced cell proliferation, migration and S-phase entry, however, MB cells were resistant to BKM -120 treatments, while LBH-589 caused massive apoptosis; 5) Tumor formation was suppressed by BKM-120 given with mTOR inhibitors. Conclusion: the result of this study suggests that expression of GLI-1, GAB-1, NPR, KV1 and p53 was important in defining the subgroups of MB, although their metastatic potential remains to be understood. MB cells shows reduced cell proliferation, cell cycle and migration, when treated with HDAC inhibitor LBH-589, however these cells display complete drug resistance to PI3K inhibitors. Citation Format: Samuel Gelnick, Anubhav G. Amin, Molly Gordon, Raphael Salles Scortegagna de Medeiros, Nelci Zanon, Raj Murali, Meena Jhanwar-Uniyal. Histological subtypes correlate with distinct genetic abnormalities in defining therapeutic targets in medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3118. doi:10.1158/1538-7445.AM2017-3118

Glioblastoma (GB) is the most common malignant primary brain tumor, which is characterized by marked intra-tumor genetic heterogeneity in receptor tyrosine kinases (RTK) genes. Aberrations in the RTK/PI3K/Akt pathways in GB leads to an abnormal signaling pathway of mechanistic target of Rapamycin (mTOR). mTOR exists in two distinct complexes, namely, mTORC1 and mTORC2, which are involved in regulation of cell survival, growth, and motility. In this investigation, we test the hypothesis that the genetic heterogeneity of GBM cells and its stem cells with respect to the expression of EGFR and/or PDGFRα may define the treatment efficacy of RTK inhibitors with or without PI3K/ mTOR inhibitors. We demonstrated that GB tumors over-expressed PDGFRα and EGFR at range of 80% and 30%, respectively, with varying degree of overlap. Combined treatment with the inhibitors of PDGFRα (AC 710) or EGFR (gefitinib), with or without inhibitors of mTORC1 (rapamycin) or mTORC1/2 (Torin1 and Torin 2), led to suppression of cell proliferation, cell cycle, cell migration and drug resistance in GB cells to varying degrees that correlated with EGFR or PDGFRα expression. Downstream signaling pathway substrates of mTORC 1 and 2, namely pS6k and pAkt, respectively, were suppressed by combined treatments of RTK and mTORC1/2 inhibitors. Furthermore, GB stem cell self-renewal and growth was also suppressed with combined treatments. The combination of AC710 plus mTORC1/2 inhibitor, Torin2, was the most effective. These findings underscore the usefulness of determining PDGFRα and EGFR status when considering viable PI3K/mTOR inhibitors for targeted treatment of GB. Citation Format: Anubhav G. Amin, Arthur Wang, Alex Braun, Michael Tobias, Raj Murali, Meena Jhanwar-Uniyal. Therapeutic implications of mTORC1 and mTORC2 inhibitors in genetically heterogeneous glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3125. doi:10.1158/1538-7445.AM2017-3125

Object The most common neurosurgical condition observed in preterm infants is intraventricular hemorrhage (IVH), which often results in posthemorrhagic hydrocephalus (PHH). These conditions portend an unfavorable prognosis; therefore, the potential for poor neurodevelopmental outcomes necessitates a better understanding of the comparative effectiveness of 2 temporary devices commonly used before the permanent insertion of a ventriculoperitoneal (VP) shunt: the ventricular reservoir and the ventriculosubgaleal shunt (VSGS). Methods The authors analyzed retrospectively collected information for 90 patients with IVH and PHH who were treated with insertion of a ventricular reservoir (n = 44) or VSGS (n = 46) at their institution over a 14-year period. Results The mean gestational age and weight at device insertion were lower for VSGS patients (30.1 ± 1.9 weeks, 1.12 ± 0.31 kg) than for reservoir patients (31.8 ± 2.9 weeks, 1.33 ± 0.37 kg; p = 0.002 and p = 0.004, respectively). Ventricular reservoir insertion was predictive of more CSF taps prior to VP shunt placement compared with VSGS placement (10 ± 8.7 taps vs 1.6 ± 1.7 taps, p < 0.001). VSGS patients experienced a longer time interval prior to VP shunt placement than reservoir patients (80.8 ± 67.5 days vs 48.8 ± 26.4 days, p = 0.012), which corresponded to VSGS patients gaining more weight by the time of shunt placement than reservoir patients (3.31 ± 2.0 kg vs 2.42 ± 0.63 kg, p = 0.016). Reservoir patients demonstrated a trend toward more positive CSF cultures compared with VSGS patients (n = 9 [20.5%] vs n = 5 [10.9%], p = 0.21). There were no significant differences in the rates of overt device infection requiring removal (reservoir, 6.8%; VSGS, 6.5%), VP shunt insertion (reservoir, 77.3%; VSGS, 76.1%), or early VP shunt infection (reservoir, 11.4%; VSGS, 13.0%) between the 2 cohorts. Conclusions Although the rates of VP shunt requirement and device infection were similar between patients treated with the reservoir versus the VSGS, VSGS patients were significantly older and had achieved greater weights at the time of VP shunt insertion. The authors' results suggest that the VSGS requires less labor-intensive management by ventricular tapping; the VSGS patients also attained higher weights and more optimal surgical candidacy at the time of VP shunt insertion. The potential differences in long-term developmental and neurological outcomes between VSGS and reservoir placement warrant further study.

A number of imaging techniques have been introduced to minimize the risk of pedicle screw placement. Intraoperative CT has been recently introduced to assist in spinal instrumentation. The aim of this study was to study the effectiveness of intraoperative CT in enhancing the safety and accuracy of pedicle screw placement.The authors included all cases from December 2009 through July 2012 in which intraoperative CT scanning was used to confirm pedicle screw placement.A total of 203 patients met the inclusion criteria. Of 1148 screws, 103 screws (8.97%) were revised intraoperatively in 72 patients (35.5%): 14 (18.42%) were revised in the cervical spine (C-2 or C-7), 25 (7.25%) in the thoracic spine, and 64 (8.80%) in the lumbar spine. Compared with screws in the thoracic and lumbar regions, pedicle screws placed in the cervical region were statistically more likely to be revised (p = 0.0061). Two patients (0.99%) required reoperations due to undetected misplacement of pedicle screws.The authors describe one of the first North American experiences using intraoperative CT scanning to confirm the placement of pedicle screws. Compared with a similar cohort of patients from their institution who had pedicle screws inserted via the free-hand technique with postoperative CT, the authors found that the intraoperative CT lowers the threshold for pedicle screw revision, resulting in a statistically higher rate of screw revision in the thoracic and lumbar spine (p0.0001). During their 2.5-year experience with the intraoperative CT, the authors did not find a reduction in rates of reoperation for misplaced pedicle screws.

Study design Laboratory cadaveric study. Objective To delineate the pertinent surgical anatomy of the diaphragm during access to the anterolateral thoracolumbar junction. Summary of background data The general anatomy of the thoracic diaphragm is well described. The specific surgical anatomy as it pertains to the lateral and thoracoabdominal approaches to the thoracolumbar junction is not well described. Methods Dissections were performed on adult fresh cadaveric specimens. Special attention was paid to the diaphragmatic attachments to the lower rib cage and to the spinal thoracolumbar junction. Results The pertinent diaphragmatic attachments to the rib cage are at the 11th and 12th ribs. Whether the diaphragm is incised or mobilized ventrally, the pertinent spinal attachments are the lateral and medial arcuate ligaments. Identifying and sectioning these structures allows for direct access to the thoracolumbar junction, particularly the L1 vertebral body. Conclusions An understanding of the diaphragmatic-costal and diaphragmatic-spinal attachments is key for the safe and effective implementation of diaphragm mobilization during the lateral and thoracoabdominal approaches to the spine.

Retrospective case series.Evaluate the incidence and clinical significance of vascular encroachment resulting from freehand placement of pedicle screws in the thoracic and lumbosacral spine.Pedicle screws are routinely used to effectively stabilize all 3 columns of the spine but can be technically demanding to place in the setting of variable anatomy. There is a paucity of data regarding iatrogenic major vascular injuries during posterior instrumentation procedures.We retrospectively reviewed the records of all patients undergoing freehand pedicle screw placement without image guidance in the thoracic or lumbar spine during a 7-year period. The incidence and extent of vascular encroachment by a pedicle screw was determined by review of routine postoperative computed tomographic scans obtained within 24 hours of all surgical procedures. Vascular encroachment was defined as a pedicle screw that was touching or deforming the wall of a major vessel.A total of 964 patients received 6816 freehand-placed pedicle screws in the thoracolumbar spine. Fifteen (0.22%) screws that encroached a major vascular structure were identified. Ten (0.29%) thoracic pedicle screws encroached on the aorta, 4 (0.14%) lumbar screws on the common iliac vein, and 1 S1 screw (0.19%) on the internal iliac vein. In consultation with vascular surgery, it was determined whether revision surgery and the technique/approach for the revision procedure should be recommended. Two (0.21%) patients required revision surgery to remove the encroaching pedicle screw (T5 and T8) due to concern for vascular injury. Both patients were asymptomatic and recovered without further complications after revision surgery.Vascular encroachment of major vessels occurs rarely in the setting of freehand pedicle screw placement in the thoracolumbar spine. Although rare, delayed vascular injury from errant pedicle screw placement has been reported in the literature. The aorta seems to be the vessel at the highest risk of injury. Routine intraoperative or postoperative computed tomographic scanning allows for early identification of pedicle screws encroaching on vascular structures thereby facilitating early revision surgery.4.

The rib head is an important landmark in the anterolateral approach to the thoracic spine. Resection of the rib head is typically the first step in gaining access to the underlying pedicle and ultimately the spinal canal. The goal of this work is to quantify the relationship of the rib head to the spinal canal and adjacent aorta at each thoracic level using CT-based morphometric measurements.One hundred thoracic spine CT scans (obtained in 50 male and 50 female subjects) were evaluated in this study. The width and depth of each vertebra body were measured from T-1 to T-12. In addition, the distance of each rib head to the spinal canal was determined by drawing a line connecting the rib heads bilaterally and measuring the distance to this line from the most ventral aspect of the spinal canal. Finally, the distance of the left rib head to the thoracic aorta was measured at each thoracic level below the aortic arch.The vertebral body depth progressively increased in a rostral to caudal direction. The vertebral body width was at its minimum at T-4 and progressively increased to T-12. The rib head extended beyond the spinal canal maximally at T-1. This distance incrementally decreased toward the caudal levels, with the tip of the rib head lying approximately even with the ventral canal at T-11 and T-12. The distance between the aorta and the left rib head increased in a rostral to caudal direction as well.The rib head is an important landmark in the anterolateral approach to the thoracic spine. At more cephalad levels, a larger portion of rib head requires resection to gain access to the spinal canal. At more caudad levels, there is a safer working distance between the rib head and aorta.

Subependymomas are rare, indolent neoplasms that have been described in the brain and the spinal cord. The purpose of this study is to report the clinical and radiolographic features, and surgical outcomes of this entity.Twenty-six patients with pathologically-verified subependymomas were treated from 1990 through 2009, with a mean follow-up of 39 months. The clinical and radiological records were reviewed and outcomes analyzed.There were 15 fourth ventricle tumors, 6 lateral ventricle tumors, and 5 spinal tumors. For the intracranial tumors, headaches, changes in vision, and difficulties with balance were the most common symptoms. Most tumors were heterogeneously enhancing and hypointense or isointense to gray matter on T1-imaging and hyperintense on T2-imaging. All patients with tumors in the fourth ventricle underwent a suboccipital craniotomy and seven patients received an additional C1 laminectomy. Patients with lateral ventricular tumors underwent craniotomy with primarily a transcallosal resection. Patients with spinal tumors underwent laminectomy with intramedullary tumor resection. All tumors were resected employing microsurgical techniques. Overall, six patients had a sub-total resection. No recurrence of tumor or symptoms was noted at last follow-up for any patient, suggesting that maximal safe resection is often sufficient to provide symptomatic relief. Three patients had long-term complications from surgery. Tumor location was not associated with age at presentation, resection achieved, or development of complications.Subependymomas are indolent tumors that when symptomatic can present with cerebrospinal fluid (CSF) obstructive symptoms in the brain and myelopathy in the spinal cord. There is no one symptom diagnostic for subependymomas. Surgical treatment can provide long term tumor control.

Object Pedicle screws provide efficient stabilization along all 3 columns of the spine, but they can be technically demanding to place, with malposition rates ranging from 5% to 10%. Intraoperative electromyographic (EMG) monitoring has the capacity to objectively identify a screw breaching the medial pedicle cortex that is in proximity to a nerve root. The purpose of this study is to describe and evaluate the authors' 7-year institutional experience with intraoperative EMG monitoring during placement of lumbar pedicle screws and to determine the clinical utility of intraoperative EMG monitoring. Methods The authors retrospectively studied 2450 consecutive lumbar pedicle screws placed in 418 patients from June 2002 through June 2009. All screws were inserted using a free-hand technique and anatomical landmarks, stimulated at 10.0 mA, and evaluated with CT scanning within 48 hours postoperatively. Medial pedicle screw breach was defined as having greater than 25% of the screw diameter extend outside of the pedicle, as confirmed on CT scanning or intraoperatively by a positive EMG response indicating a medial breach. The sensitivity and specificity of intraoperative EMG monitoring in detecting the presence of a medial screw breach was evaluated based on the following definitions: 1) true positive (a positive response to EMG stimulation confirmed as a breach intraoperatively or on postoperative CT scans); 2) false positive (positive response to EMG stimulation confirmed as a correctly positioned screw on postoperative CT scans); 3) true negative (no response to EMG stimulation confirmed as a correctly positioned screw on postoperative CT scans); or 4) false negative (no response to EMG stimulation but confirmed as a breach on postoperative CT scans). Results One hundred fifteen pedicle screws (4.7%) showed positive stimulation during intraoperative EMG monitoring. At stimulation thresholds less than 5.0, 5.0–8.0, and > 8.0 mA, the specificity of a positive response was 99.9%, 97.9%, and 95.9%, respectively. The sensitivity of a positive response at these thresholds was only 43.4%, 69.6%, and 69.6%, respectively. At a threshold less than 5.0 mA, 91% of screws with a positive EMG response were confirmed as true medial breaches. However, at thresholds of 5.0–8.0 mA or greater than 8.0 mA, a positive EMG response was associated with 89% and 100% false positives (no breaches), respectively. Conclusions When using intraoperative EMG monitoring, a positive response at screw stimulation thresholds less than 5.0 mA was highly specific for a medial pedicle screw breach but was poorly sensitive. A positive response to stimulation thresholds greater 5.0 mA was associated with a very high rate of false positives. The authors' experience suggests that pedicle screws showing positive stimulation below 5.0 mA warrants intraoperative investigation for malpositioning while responses at higher thresholds are less reliable at accurately representing a medial breach.

Introduction Multiple myeloma is the most common primary tumor of the spine. Spinal multiple myeloma is classically a radiosensitive lesion; however, clinical or radiographic signs of instability merit surgical intervention. The authors present the epidemiology, surgical indications, and outcome data of the largest single series of 31 consecutive surgically treated patients with diagnoses of multiple myeloma and plasmacytoma of the spine. Methods The Spinal Instability Neoplastic Score (SINS) was utilized to make an assessment of surgical instability as the criteria for operative intervention. Patients were analyzed using lesion location, Frankel score, adjuvant therapy, outcome, and survival. Results All patients undergoing surgical intervention had either indeterminate or gross spinal column instability according to SINS criteria. Median survival was 78.9 months. No significant difference in survival was seen for patients with higher SINS scores or for older patients (> 55 years). There was a statistically significant difference in survival benefit observed in patients receiving chemotherapy and radiation versus radiation alone as an adjuvant to surgery ( p = 0.02). Conclusion The report demonstrates outcomes for patients with indeterminate stability and gross spinal instability because of multiple myeloma and plasmacytoma of the spine who underwent surgical intervention with improved neurological function following surgery and low rates of instrumentation failure.

Purpose The role of distal traction in the form of a tethered spinal cord in exacerbating anatomical findings or symptoms of Chiari II malformation (CIIM) has been debated for decades. Despite the association of Chiari II malformation with myelomeningocele, the impact of tethered cord release on CIIM symptoms in patients has not been explored. Methods A retrospective review of 59 patients born with a myelomeningocele was performed. A total of 92 untethering procedures were performed in which symptoms of CIIM were present in 29 cases. In 57 out of 92 cases, the patients did not have symptoms of CIIM prior to untethering. Six cases were excluded because cervicomedullary decompression was performed prior to untethering. The response of CIIM symptoms, syrinx size, and cerebellar tonsil position were examined before and after spinal cord untethering. Results Forty-four characteristic signs and symptoms of CIIM were present prior to 29 untetherings. Thirty-three of 44 (75%) symptoms improved following spinal cord untethering, though no symptom resolved completely. Syrinx size and cerebellar tonsil position were unchanged following untethering. Conclusion The authors conclude that mild to moderate symptoms of CIIM may respond positively to spinal cord untethering, potentially by normalization cerebrospinal fluid flow dynamics. Symptom improvement occurs despite the lack of radiographic evidence of CIIM resolution.