Early surgical intervention for acute spinal cord injury: time is spine.

Acute traumatic spinal cord injury (tSCI) is a devastating occurrence that significantly contributes to global morbidity and mortality. Surgical decompression with stabilization is the most effective way to minimize the damaging sequelae that follow acute tSCI. In recent years, strong evidence has emerged that supports the rationale that early surgical intervention, within 24 h following the initial injury, is associated with a better prognosis and functional outcomes. In this review, we have summarized the evidence and elaborated on the nuances of this concept. Additionally, we have reviewed further concepts that stem from "time is spine," including earlier cutoffs less than 24 h and the challenging entity of central cord syndrome, as well as the emerging concept of adequate surgical decompression. Lastly, we identify barriers to early surgical care for acute tSCI, a key aspect of spine care that needs to be globally addressed via research and policy on an urgent basis.

Degenerative cervical myelopathy: Where have we been? Where are we now? Where are we going?

Degenerative cervical myelopathy (DCM), a recently coined term, encompasses a group of age-related and genetically associated pathologies that affect the cervical spine, including cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament (OPLL). Given the significant contribution of DCM to global disease and disability, there are worldwide efforts to promote research and innovation in this area. An AO Spine effort termed 'RECODE-DCM' was initiated to create an international multistakeholder consensus group, involving patients, caregivers, physicians and researchers, to focus on launching actionable discourse on DCM. In order to improve the management, treatment and results for DCM, the RECODE-DCM consensus group recently identified ten priority areas for translational research. The current article summarizes recent advancements in the field of DCM. We first discuss the comprehensive definition recently refined by the RECODE-DCM group, including steps taken to arrive at this definition and the supporting rationale. We then provide an overview of the recent advancements in our understanding of the pathophysiology of DCM and modalities to clinically assess and diagnose DCM. A focus will be set on advanced imaging techniques that may offer the opportunity to improve characterization and diagnosis of DCM. A summary of treatment modalities, including surgical and nonoperative options, is then provided along with future neuroprotective and neuroregenerative strategies. This review concludes with final remarks pertaining to the genetics involved in DCM and the opportunity to leverage this knowledge toward a personalized medicine approach.

Nervous system involvement in SARS-coronavirus infection: a review on lessons learned from the previous outbreaks, ongoing pandemic and what to expect in the future.

Viral infections have been associated with the deleterious damage to nervous system resulting in impairment of the central nervous system as late sequalae infections. Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), several studies have reported patients developing adverse neurological signs and symptoms. Like the outbreak of SARS in 2003, the recent outbreak has undermined the norm of the nervous system. This review will summarize the possible mechanism of neurological manifestations, the clinical presentations of patients with such symptoms secondary to SARS coronaviruses, and the prospective role of neurology and neurosurgery practice in managing these symptoms in the current climate.

Local failure after stereotactic radiosurgery (SRS) for intracranial metastasis: analysis from a cooperative, prospective national registry.

INTRODUCTION: Stereotactic radiosurgery (SRS) has been increasingly employed to treat patients with intracranial metastasis, both as a salvage treatment after failed whole brain radiation therapy (WBRT) and as an initial treatment. "Several studies have shown that SRS may be as effective as WBRT with the added benefit of preserving neuro-cognition". However, some patients may have local failure following SRS for intracranial metastasis, defined as increase in total lesion volume by 25% after at least 3 months of follow up. METHODS: The SRS registry, established by the Neuro point alliance (NPA) under the auspices of the American Association of Neurological Surgeons (AANS), was queried for patients with intracranial metastasis receiving SRS at the participating sites. Demographic, clinical symptoms, tumor, and treatment characteristics as well as follow up status were summarized for the cohort. A multivariable explanatory cox- regression was performed to evaluate the impact of each of the factors on time to local failure.at last follow-up. RESULTS: A total of 441 patients with 1255 intracranial metastatic lesions undergoing SRS were identified. The most common primary cancer histology was non-small cell lung cancer (43.8%, n = 193). More than half of the cohort had more than 1 metastatic lesion (2-3 lesions: 29.5%, n = 130; more than 3 lesions: 25.2% (n = 111). The average duration of follow-up for the cohort was found to be 8.4 months (SD = 7.61). The mean clinical treatment volume (CTV), after adding together the volume of each lesion for each patient was 5.39 cc (SD = 7.6) at baseline. A total of 20.2% (n = 89) had local failure (increase in volume by > 25%) with a mean time to progression of 7.719 months (SD = 6.09). The progression free survival (PFS) for the cohort at 3, 6 and 12 months were found to be 94.9%, 84.3%, and 69.4%, respectively. On multivariable cox regression analysis, factors associated with increased hazard of local failure included male gender (HR 1.65, 95% CI 1.03-2.66, p = 0.037), chemotherapy at or before SRS (HR = 2.39, 95% CI 1.41-4.05, p = 0.001), WBRT at or before SRS (HR = 2.21, 95% CI 1.16- 4.22, p = 0.017), while surgical resection (HR 0.45, 95% CI 0.21-0. 97, p = 0.04) and immunotherapy (0.34, 95% CI 0.16-0.50, p = 0.014) were associated with lower hazard of local failure. CONCLUSION: Factors found to be predictive of local failure included higher RPA score and those receiving chemotherapy, while patients undergoing surgical resection and those with occipital lobe lesions were less likely to experience local failure. Our analyses not only corroborate those previously reported but also demonstrate the utility of a multi-institutional registry to advance real-world SRS research for patients with intracranial metastatic lesions.

Clinical characteristics and management differences for grade II and III spinal meningiomas.

PURPOSE: The majority of spinal meningiomas are grade I tumors, as defined by World Health Organization (WHO) classification making atypical (grade II) or anaplastic (grade III) tumors extremely rare lesions to encounter in clinical practice. Here, we present our institutional experience of management of grade II and III spinal meningiomas. METHODS: Following IRB approval, we queried all available institutional electronic medical records for patients undergoing surgical resection of pathology-proven spinal meningiomas, with further review of patients with grade II and III. Variables of interest included age, sex, histological type, tumor size, symptoms at baseline, treatment characteristics, symptom resolution at the last follow-up, recurrence, NF-2 status, concurrent intracranial meningioma, and mortality. Kaplan Meier curves were constructed to study time to progression/recurrence. RESULTS: A total of 188 patients undergoing surgical resection of spinal meningioma between 1988 and 2018 were identified. Among those, 172 (91.5%) patients had grade I meningioma and 16 (8.5%) patients had high grade meningiomas [grade II (15) and III (1)]. Over a median (IQR) follow-up of 8.0 years (5.1-13.0), mortality and recurrence rates were 18.8% (n = 3) and 47.1% (n = 8), respectively. In univariate analysis, adjuvant radiotherapy and thoracic segment involvement were associated with lower rates of recurrence while male sex was associated with a higher rate of recurrence. CONCLUSIONS: Results showed variations in clinical outcomes for patients with high grade spinal meningiomas, especially the recurrence. Adjuvant radiotherapy and thoracic segment involvement was associated with lower rates of recurrence while recurrence ocurred at a higher rate in males.

Early and sustained improvements in motor function in rats after infusion of allogeneic umbilical cord-derived mesenchymal stem cells following spinal cord injury.

STUDY DESIGN: Animal study. OBJECTIVES: Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have recently been shown to hold great therapeutic potential for spinal cord injury (SCI). However, majority of the studies have been done using human cells transplanted into the rat with immunosuppression; this may not represent the outcomes that occur in humans. Herein, we present the therapeutic effect of using rat UC-MSCs (rUC-MSC) without immunosuppression in a rat model of SCI. SETTING: Mayo Clinic, Rochester, MN, USA. METHODS: Twelve female rats were randomly divided into two groups, control, and rUC-MSC group, and then subjected to a T9 moderate contusion SCI. Next, 2 × 106 rUC-MSCs or ringer-lactate solution were injected through the tail vein at 7 days post injury. Rats were assessed for 14 weeks by an open-field Basso, Beattie, and Bresnahan (BBB) motor score as well as postmortem quantification of axonal sparing/regeneration, cavity volume, and glial scar. RESULTS: Animals treated with rUC-MSCs were found to have early and sustained motor improvement (BBB score of 14.6 ± 1.9 compared to 10.1 ± 1.7 in the control group) at 14 weeks post injury (mean difference: 4.55, 95% CI: 2.04 to 7.06; p value < 0.001). Total cavity volume in the injury epicenter was significantly reduced in the rUC-MSC group; control: 33.0% ± 2.1, rUC-MSC: 25.3% ± 3.8 (mean difference: -7.7% (95% CI: -12.3 to -2.98); p value < 0.05). In addition, spinal cords from rats treated with rUC-MSCs were found to have a significantly greater number of myelinated axons, decreased astrogliosis, and reduced glial scar formation compared to control rats. CONCLUSIONS: Our study indicates that intravenous injection of allogenic UC-MSCs without immunosuppression exert beneficial effects in subacute SCI and thus could be a useful therapy to improve the functional capacity among patients with SCI.

Medical Malpractice and Trigeminal Neuralgia: An Analysis of 49 Cases.

PURPOSE: Our study fills the vacancy of litigation research related to trigeminal neuralgia management, giving health care providers the information needed to understand the potential litigious outcomes that follow treatment methods. METHODS: We queried the Westlaw database to identify litigation cases related to trigeminal neuralgia management. Key variables extracted included medical complaints, trial outcomes, and demographics. Continuous variables were compared between cases in favor of defendant and cases in favor of plaintiff using t-test or Wilcoxon rank sum test. Categorial variables were compared using χ2 or Fisher exact test. RESULTS: About 49 cases met the inclusion criteria-for those cases surgical complications (42.9%) were cited as the most common reasons for malpractice claims. Cranial nerve deficits (34.7%) were the most frequent postoperative complaints. Verdicts ruled in favor of the plaintiff in 26.5% of cases with a mean payout of $1,982,428.46. Dentists were included in the most cases, 63.3%, and the average payout was $415,908, whereas neurosurgeons were involved in 20.4% of cases with an average payout of $618,775. Cases with verdicts in favor of the plaintiff were more likely to be older than cases with verdicts in favor of the defendant (P = .03). CONCLUSIONS: Over one-half of cases resulted in verdicts in favor of the defendant with surgical complications cited as the most common reason for litigation. Dentistry was the most common individual clinical specialty for defendants, whereas neurosurgery contributed to the largest average payout based on specialty (for n > 1). Cranial nerve deficits were the most common plaintiff postoperative complaints. These analyses may help doctor teams involved in management of trigeminal neuralgia to have a more informed discussion with the patient at every visit so that such litigations may be avoided.

Improved 3-year survival rates for glioblastoma multiforme are associated with trends in treatment: analysis of the national cancer database from 2004 to 2013.

PURPOSE: Glioblastoma multiforme (GBM) is a common and aggressive malignancy associated with poor prognosis. Characteristics and treatment of long-term survivors are of particular interest in efforts to improve outcomes. Therefore, the objective of this study was to examine trends and prognostic factors for 3-year survival from a national database. METHODS: The National Cancer Database (NCDB) was queried for patients diagnosed with cranial GBM from 2004 to 2013 and with 3-year follow-up. Trends in 3-year and overall survival, patient characteristics, tumor properties, and treatment modalities were examined. Multivariable logistic regression was utilized to investigate the association of these factors with 3-year survival. Predictor importance analysis was conducted using a metric defined as Wald χ2 penalized by degrees of freedom. RESULTS: A total of 88,919 GBM patients with 3-year follow-up were identified. Overall, 8757 (9.8%) patients survived ≥ 3 years. Three-year survival significantly improved from 8.0 to 10.5% (p < 0.001) from 2004 to 2013. Trimodal treatment administration also significantly increased from 38.7 to 55.9% (p < 0.001). During this span, patients increasingly presented as older (p = 0.040), without private insurance (p < 0.001), and with a higher comorbidity index (p < 0.001). On multivariable regression, factors such as trimodal treatment (p < 0.001), younger age (p < 0.001), and MGMT methylation (p < 0.001) were significantly associated with increased odds of 3-year survival. Predictor importance analysis indicated that MGMT methylation, age, and treatment modality were the most significant relative determinants of 3-year survival. CONCLUSION: These findings illustrate an improved 3-year survival rate for GBM patients from 2004 to 2013 with a concurrent increase in trimodal treatment administration despite more adverse patient presenting characteristics.

The role of radiation and chemotherapy in adult patients with high-grade brainstem gliomas: results from the National Cancer Database.

INTRODUCTION: Surgical resection of high-grade brainstem gliomas is challenging and treatment mostly involves radiation and chemotherapy. In this study, we utilized registry data to determine prognostic features and impact of chemotherapy and radiation on overall survival. METHODS: The National Cancer Database was queried from 2006 to 2015 for adult cases with histologically confirmed high-grade brainstem glioma. Covariates including patient demographics, comorbidities, tumor characteristics and treatment parameters were captured. Multivariable Cox proportional hazards regression was performed to identify predictors of survival. RESULTS: A total of 422 patients were analyzed. Most patients (66.6%) underwent postoperative radiation with chemotherapy, 9.2% underwent radiation alone, while the remaining had no postoperative treatment (24.2%). Overall median survival was 9.8 months (95% CI 8.8-12). Survival was longer (p < 0.001) in the radiation + chemotherapy group (median: 14.2 months, 95% CI 11.7-17.1) compared to radiation alone (median: 5.7 months, 95% CI 3.7-12) and no postoperative treatment (median: 1.8 months, 95% CI 1.4-4) groups. In multivariable analysis, increasing age was associated with worse survival (HR: 1.87, 95% CI 1.47-2.37, p < 0.001), whereas radiation + chemotherapy was associated with lower mortality compared to radiation alone (HR: 0.67, 95% CI 0.46-0.98, p = 0.038). In subgroup analysis, postoperative chemotherapy with radiation was associated with significant survival benefit compared to radiation alone for grade IV (HR: 0.46, 95% CI 0.28-0.76, p = 0.003), but not for grade III tumors (HR: 0.87, 95% CI 0.48-1.58, p = 0.65). CONCLUSION: Analysis from a national registry illustrated the effectiveness of radiation with chemotherapy for adult patients with high-grade brainstem gliomas, particularly grade IV. Further research should identify specific patient profiles and molecular subgroups that are more likely to benefit from multimodality therapy.

Adjuvant radiation for WHO grade II and III intracranial meningiomas: insights on survival and practice patterns from a National Cancer Registry.

INTRODUCTION: WHO grades II (atypical) and III (malignant) meningiomas are associated with significant morbidity and mortality. The role of adjuvant radiotherapy (RT) in management remains controversial. The goal of this study was to evaluate the impact of adjuvant RT on 5-year survival in patients with atypical and malignant meningiomas. We secondarily aimed to assess contemporary practice patterns and the impact of sociodemographic factors on outcome. METHODS: We queried the National Cancer Database for patients ≥ 18 years of age with cranial atypical or malignant meningiomas from 2010 through 2015 who underwent surgical resection with or without adjuvant radiotherapy. Subjects with unknown WHO grade or radiation status and those not receiving any surgical procedure were excluded from analysis. RESULTS: The study includes 7486 patients, 6788 with atypical and 698 with malignant meningiomas. Overall 5-year survival was 76.9% (95% CI 75.5-78.3%) and 43.3% (95% CI 38.8-48.2%) among patients with WHO grades II and III meningiomas, respectively. Adjuvant RT correlated with improved survival in a multivariable model in patients with grade II tumors (HR 0.78; p = 0.029) regardless of the extent of resection. Age (HR 2.33; p < 0.001), male sex (HR 1.27; p < 0.001), Black race (HR 1.27; p = 0.011) and Charlson-Deyo Score ≥ 2 (1.35; p = 0.001) correlated with poorer survival whereas private insurance (HR 0.71; p < 0.001) correlated with improved survival. Adjuvant RT was also associated with improved 5-year survival among those with grade III tumors on univariate analysis (log-rank p = 0.006) but was underpowered for multivariable modeling. Utilization of adjuvant radiotherapy was only 28.4% and correlated with private insurance status. Academic institutions (25.3%) and comprehensive community cancer programs (21.4%) had lower radiotherapy utilization rates compared with integrated network cancer programs (30.5%) and community cancer programs (29.7%). CONCLUSIONS: Adjuvant RT may correlate with improved overall survival in patients with grades II and III intracranial meningiomas regardless of the extent of resection. There is poor utilization of adjuvant RT for patients with grades II and III meningiomas likely due to a paucity of quality data on the subject. These findings will be strengthened with prospective data evaluating the role of adjuvant RT.

Comparison of narcotic pain control between stereotactic electrocorticography and subdural grid implantation.

INTRODUCTION: The choice of subdural grid (SDG) or stereoelectroencephalography (sEEG) for patients with epilepsy can be complex and in some cases overlap. Comparing postoperative pain and narcotics consumption with SDG or sEEG can help develop an intracranial monitoring strategy. MATERIALS AND METHODS: A retrospective study was performed for adult patients undergoing SDG or sEEG monitoring. Numeric Rating Scale (NRS) was used for pain assessment. Types and dosage of the opioids were calculated by converting into milligram morphine equivalents (MME). Narcotic consumption was analyzed at the following three time periods: I. the first 24 h of implantation; II. from the second postimplantation day to the day of explantation; and III. the days following electrode removal to discharge. RESULTS: Forty-two patients who underwent SDG and 31 patients who underwent sEEG implantation were analyzed. After implantation, average NRS was 3.7 for SDG and 2.2 for sEEG (P < .001). After explantation, the NRS was 3.5 for SDG and 1.4 in sEEG (P < .001). Sixty percent of SDG patients and 13% of sEEG patients used more than one opioid in period III (P < .001). The SDG group had a significantly higher MME throughout the three periods compared with the sEEG group: period I: 448 (SDG) vs. 205 (sEEG) mg, P = .002; period II: 377 (SDG) vs. 102 (sEEG) mg, P < .001; and period III: 328 (SDG) vs. 75 (sEEG) mg; P = .002. Patients with the larger SDG implantation had the higher NRS (P = .03) and the higher MME at period I (P = .019). There was no correlation between the number of depth electrodes and pain control in patients with sEEG. CONCLUSIONS: Patients undergoing sEEG had significantly less pain and required fewer opiates compared with patients with SDG. These differences in perioperative pain may be a consideration when choosing between these two invasive monitoring options.

Medical malpractice and meningiomas: an analysis of 47 cases.

OBJECTIVE: Among medical practices, surgical fields, including neurosurgery, are at a high risk for medical malpractice litigation. With meningiomas contributing to 10% of the total neurosurgery litigation cases, the aim of this study was to identify demographic characteristics, reasons for litigation, and surgical complications commonly reported in these cases. This analysis serves to increase neurosurgeons' awareness of factors associated with medical malpractice litigation. METHODS: The online legal database Westlaw was utilized to query public litigation cases related to the medical management of meningiomas between December 1985 and May 2020. Variables extracted included the following: plaintiff and defendant demographics, litigation category, plaintiff medical complaints, and trial outcomes. The authors compared these characteristics between cases with decisions in favor of the defendant and those with decisions in favor of the plaintiff. RESULTS: A total of 47 cases met the inclusion criteria. Failure to diagnose (68.1%) was the most common type of malpractice claim, and surgical complications (19.1%), motor weakness (33%), and financial loss (33%) were cited as the most common postoperative complaints. Individual specialties that most often required defense due to malpractice claims were radiology (21.7%) and neurosurgery (19.6%). The jury verdict was in favor of the defense in 51.1% of cases and in favor of the plaintiff in 27.7% of cases. A settlement was reached in 19.1% of cases. The mean payout for a verdict in favor of the plaintiff was $3,409,650.22, while the mean payout for settlements was $867,555.56. The greatest average payout for specialties was in neurosurgery at $3,414,400, followed by radiology at $3,192,960. Cases with a verdict in favor of the plaintiff were more likely to involve an internal medicine physician as a defendant (p = 0.007). CONCLUSIONS: Over one-half of the cases resulted in a defendant's verdict with failure to diagnose cited as the most common reason for litigation. Radiology and neurosurgery were the most common specialties for legal cases and also had some of the largest average payouts based on specialty. Motor weakness and financial loss were the most common plaintiff postoperative complaints. These findings may inform surgeons on active measures to take, such as increasing focus on diagnostic accuracy and reducing specific postoperative complaints, such as motor weakness, through risk management and prophylactic measures, to reduce unfavorable legal outcomes.

Quality Outcomes Database Spine Care Project 2012-2020: milestones achieved in a collaborative North American outcomes registry to advance value-based spine care and evolution to the American Spine Registry.

The Quality Outcomes Database (QOD), formerly known as the National Neurosurgery Quality Outcomes Database (N2QOD), was established by the NeuroPoint Alliance (NPA) in collaboration with relevant national stakeholders and experts. The overarching goal of this project was to develop a centralized, nationally coordinated effort to allow individual surgeons and practice groups to collect, measure, and analyze practice patterns and neurosurgical outcomes. Specific objectives of this registry program were as follows: "1) to establish risk-adjusted national benchmarks for both the safety and effectiveness of neurosurgical procedures, 2) to allow practice groups and hospitals to analyze their individual morbidity and clinical outcomes in real time, 3) to generate both quality and efficiency data to support claims made to public and private payers and objectively demonstrate the value of care to other stakeholders, 4) to demonstrate the comparative effectiveness of neurosurgical and spine procedures, 5) to develop sophisticated 'risk models' to determine which subpopulations of patients are most likely to benefit from specific surgical interventions, and 6) to facilitate essential multicenter trials and other cooperative clinical studies." The NPA has launched several neurosurgical specialty modules in the QOD program in the 7 years since its inception including lumbar spine, cervical spine, and spinal deformity and cerebrovascular and intracranial tumor. The QOD Spine modules, which are the primary subject of this paper, have evolved into the largest North American spine registries yet created and have resulted in unprecedented cooperative activities within our specialty and among affiliated spine care practitioners. Herein, the authors discuss the experience of QOD Spine programs to date, with a brief description of their inception, some of the key achievements and milestones, as well as the recent transition of the spine modules to the American Spine Registry (ASR), a collaboration between the American Association of Neurological Surgeons and the American Academy of Orthopaedic Surgeons (AAOS).

Correlation of return to work with patient satisfaction after surgery for lumbar spondylolisthesis: an analysis of the Quality Outcomes Database.

OBJECTIVE: Return to work (RTW) and satisfaction are important outcome measures after surgery for degenerative spine disease. The authors queried the prospective Quality Outcomes Database (QOD) to determine if RTW correlated with patient satisfaction. METHODS: The QOD was queried for patients undergoing surgery for degenerative lumbar spondylolisthesis. The primary outcome of interest was correlation between RTW and patient satisfaction, as measured by the North American Spine Society patient satisfaction index (NASS). Secondarily, data on satisfied patients were analyzed to see what patient factors correlated with RTW. RESULTS: Of 608 total patients in the QOD spondylolisthesis data set, there were 292 patients for whom data were available on both satisfaction and RTW status. Of these, 249 (85.3%) were satisfied with surgery (NASS score 1-2), and 224 (76.7%) did RTW after surgery. Of the 68 patients who did not RTW after surgery, 49 (72.1%) were still satisfied with surgery. Of the 224 patients who did RTW, 24 (10.7%) were unsatisfied with surgery (NASS score 3-4). There were significantly more people who had an NASS score of 1 in the RTW group than in the non-RTW group (71.4% vs 42.6%, p < 0.05). Failure to RTW was associated with lower level of education, worse baseline back pain (measured with a numeric rating scale), and worse baseline disability (measured with the Oswestry Disability Index [ODI]). CONCLUSIONS: There are a substantial number of patients who are satisfied with surgery even though they did not RTW. Patients who were satisfied with surgery and did not RTW typically had worse preoperative back pain and ODI and typically did not have a college education. While RTW remains an important measure after surgery, physicians should be mindful that patients who do not RTW may still be satisfied with their outcome.

Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation.

Primary high-grade infiltrating gliomas of the spinal cord are rare, with prior series including limited numbers of cases and reporting poor outcomes. Additionally, the molecular profile of high-grade infiltrating gliomas of the spinal cord has not been well characterized. We identified 13 adult patients whose surgery had been performed at our institution over a 26-year-period. Radiologically, nine cases harbored regions of post-contrast enhancement. Existing slides were reviewed, and when sufficient tissue was available, immunohistochemical stains (IDH1-R132H, H3-K27M, H3K27-me3, ATRX, p53 and BRAF-V600E), and a targeted 150-gene neuro-oncology next-generation sequencing panel were performed. The 13 patients included 11 men and 2 women with a median age of 38 years (range = 18-69). Histologically, all were consistent with an infiltrating astrocytoma corresponding to 2016 WHO grades III (n = 5) and IV (n = 8). By immunohistochemistry, six cases were positive for H3K27M, all showing concomitant loss of H3K27-me3. Next-generation sequencing was successfully performed in ten cases. Next-generation sequencing studies were successfully performed in four of the cases positive for H3K27M by immunohistochemistry, and all were confirmed as H3F3A K27M-mutant. Additional recurrent mutations identified included those of TERT promoter (n = 3), TP53 (n = 5), PPM1D (n = 3), NF1 (n = 3), ATRX (n = 2), and PIK3CA (n = 2). No HIST1H3B, HIST1H3C, IDH1, IDH2, or BRAF mutations were detected. Ten patients have died since first surgery, with a median survival of 13 months and 1 year of 46%. Median survival was 48.5 months for H3K27M-positive cases, compared to 1 month for those with TERT promoter mutation and 77 months for those harboring neither (p = 0.019). Median survival for cases with TP53 mutations was 11.5 months and for those with PPM1D mutations was 84 months. Our findings suggest that high-grade infiltrating gliomas of the spinal cord in adults represent a heterogeneous group of tumors, with variable outcomes possibly related to their molecular profiles.

Clinical presentation, natural history and outcomes of intramedullary spinal cord cavernous malformations.

OBJECTIVE: There is a paucity of literature investigating the clinical course of patients with spinal intramedullary cavernous malformations (ISCMs). We present a large case series of ISCMs to describe clinical presentation, natural history and outcomes of both surgical and conservative management. METHODS: We retrospectively reviewed the clinical course of patients diagnosed with ISCMs at our institution between 1995 and 2016. Haemorrhage was defined as clinical worsening in tandem with imaging changes visualised on follow-up MRI. Outcomes assessed included neurological status and annual haemorrhage rates. RESULTS: A total of 107 patients met inclusion criteria. Follow-up data were available for 85 patients. While 21 (24.7%) patients underwent immediate surgical resection, 64 (75.3%) were initially managed conservatively. Among this latter group, 16 (25.0%) suffered a haemorrhage during follow-up and 11 (17.2%) required surgical resection due to interval bleeding or neurological worsening. The overall annual risk of haemorrhage was 5.5% per person year. The rate among patients who were symptomatic and asymptomatic on presentation was 9.5% and 0.8%, respectively. Median time to haemorrhage was 2.3 years (0.1-12.3). Univariate analysis identified higher ISCM size (p=0.024), history of prior haemorrhage (p=0.013) and presence of symptoms (p=0.003) as risk factors for subsequent haemorrhage. Multivariable proportional hazards analysis revealed presence of symptoms to be independently associated with haemorrhage during follow-up (HR 9.39, CI 1.86 to 170.8, p=0.013). CONCLUSION: Large, symptomatic ISCMs appear to be at increased risk for subsequent haemorrhage. Surgery may be considered in such lesions to prevent rebleeding and subsequent neurological worsening.

Outcomes following surgical versus endovascular treatment of spinal dural arteriovenous fistula: a systematic review and meta-analysis.

Although surgical resection is associated with a complete cure in most cases of spinal dural arteriovenous fistulas (SDAVF), there has been an increasing trend towards embolisation. We performed a systematic review and meta-analysis comparing surgical resection with endovascular treatment in terms of success of treatment, rate of recurrence and complications. A literature search was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Strength of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation Working Group system. Surgical outcomes such as initial treatment failure, late recurrence, neurological improvement and complications were compared between the two approaches. We included 57 studies with 2029 patients, of which 32 studies with 1341 patients directly compared surgery (n=590) and embolisation (n=751). Surgery was found to be associated with significantly lower odds of initial treatment failure (OR: 0.15, 95% CI 0.09 to 0.24, I2 0%, p<0.001) and late recurrence (OR 0.18, 95% CI 0.09 to 0.39, I2 0%, p<0.001). The odds of neurological improvement following surgery were also significantly higher compared with embolisation alone (OR: 2.73, CI:1.67 to 4.48, I2 :49.5%, p<0.001). No difference in complication rates was observed between the two approaches (OR 1.78, 95% CI 0.97 to 3.26, I2 0%, p=0.063). Onyx was associated with significantly higher odds of initial failure/late recurrence as compared with n-butyl 2-cyanoacrylate (OR: 3.87, CI: 1.73 to 8.68, I2 :0%, p<0.001). Surgery may be associated with superior outcomes for SDAVFs in comparison to endovascular occlusion. Newer embolisation agents like Onyx have not conferred a significant improvement in occlusion rate.

Intramedullary spinal cord metastases: an institutional review of survival and outcomes.

INTRODUCTION: Intramedullary spinal cord metastases (ISCMs) are rare lesions affecting the spinal cord in patients with disseminated malignancy. Today, due to increased survival, these lesions are more frequently diagnosed. Literature on survival and neurologic outcomes is sparse. Herein, we describe a single institutional case series on ISCMs reported to date in the English literature. METHODS: We retrospectively analyzed the medical records of patients diagnosed with intramedullary metastatic lesions at our institution between 1997 and 2016. We analyzed different approaches to management and factors influencing survival and neurologic outcomes. RESULTS: A total of 70 patients (86 lesions) were analyzed. Most lesions were found in thoracic spinal cord (50%) followed by cervical (34%) and conus medullaris (14%). Mean age at diagnosis was 55.6 ± 10.6 years with 60% (n = 42) being females. Median survival was 104.5 days (range 1-888 days). Twenty-three patients (33%) received conservative management, 39 (56%) received palliative radiotherapy, whereas 8 (11%) underwent surgery with one patient receiving only a biopsy. Age, sex, presence of concomitant brain and other systemic metastasis didn't influence survival. Patients with solitary metastases had longer survival compared to multiple lesions (3.6 vs. 2.2 months, p = 0.01). In patients with solitary lesions without brain metastasis, surgical resection was associated with significantly longer survival (6 months vs. 3 months, p = 0.02). CONCLUSION: The overall survival in patients with intramedullary metastasis remains poor. Surgical management may contribute to improved survival and neurologic outcomes in selected patients. Intramedullary metastasis may have a greater role on overall survival compared to systemic metastatic burden.

Variation in management of spinal gliobastoma multiforme: results from a national cancer registry.

PURPOSE: Primary glioblastoma of the spinal cord (spinal GBM) is a rare central nervous system tumor, relative to its cranial counterpart (cranial GBM). Our current knowledge of spinal GBM epidemiology, tumor characteristics and treatment are insufficient and mostly based on single-institution case series. METHODS: All patients diagnosed with grade-4 GBM from 2004 to 2014 were queried from the National Cancer Database. Chi square analysis was used to compare presenting characteristics while Kaplan-Meier and Cox regression analyses were employed for survival analyses. RESULTS: Total 103,496 patients with cranial GBM and 190 patients with spinal GBM were analyzed. Median survival for spinal GBM was found to be higher compared to cranial GBM (p = 0.07). Spinal GBM patients had significant better survival in 18 to 65 years age group than < 18 years and > 65 years age group (p = 0.003). Overall survival time for 95 spinal GBM patients with available treatment data was not statistically different among the four treatment modalities (radiation with or without chemotherapy, surgery alone, surgery with adjuvant therapy, and palliative therapy; p = 0.28).On multivariable analysis, < 18 years age group was associated with improved survival (HR 0.50, 95% CI 0.23-1.00, p = 0.046), while tumor extension was associated with poor survival (HR 2.71, 95% CI 1.04-6.22, p = 0.041). Interestingly surgery with adjuvant therapy was unable to show increase survival compared to other treatment modalities. CONCLUSIONS: Our study adds to the growing literature on spinal GBM with a focus on comparative trends with cranial GBM and outcomes with different treatment modalities.

Trends in the utilization of radiotherapy for spinal meningiomas: insights from the 2004-2015 National Cancer Database.

OBJECTIVERecent studies have reported on the utility of radiosurgery for local control and symptom relief in spinal meningioma. The authors sought to evaluate national utilization trends in radiotherapy (including radiosurgery), investigate possible factors associated with its use in patients with spinal meningioma, and its impact on survival for atypical tumors.METHODSUsing the ICD-O-3 topographical codes C70.1, C72.0, and C72.1 and histological codes 9530-9535 and 9537-9539, the authors queried the National Cancer Database for patients in whom spinal meningioma had been diagnosed between 2004 and 2015. Patients who had undergone radiation in addition to surgery and those who had received radiation as the only treatment were analyzed for factors associated with each treatment.RESULTSFrom among 10,458 patients with spinal meningioma in the database, the authors found a total of 268 patients who had received any type of radiation. The patients were divided into two main groups for the analysis of radiation alone (137 [51.1%]) and radiation plus surgery (131 [48.9%]). An age > 69 years (p < 0.001), male sex (p = 0.03), and tumor size 5 to < 6 cm (p < 0.001) were found to be associated with significantly higher odds of receiving radiation alone, whereas a Charlson-Deyo Comorbidity Index ≥ 2 (p = 0.01) was associated with significantly lower odds of receiving radiation alone. Moreover, a larger tumor size (2 to < 3 cm, p = 0.01; 3 to < 4 cm, p < 0.001; 4 to < 5 cm, p < 0.001; 5 to < 6 cm, p < 0.001; and ≥ 6 cm, p < 0.001; reference = 1 to < 2 cm), as well as borderline (p < 0.001) and malignant (p < 0.001) tumors were found to be associated with increased odds of undergoing radiation in addition to surgery. Receiving adjuvant radiation conferred a significant reduction in overall mortality among patients with borderline or malignant spinal meningiomas (HR 2.12, 95% CI 1.02-4.1, p = 0.02).CONCLUSIONSThe current analysis of cases from a national cancer database revealed a small increase in the use of radiation for the management of spinal meningioma without a significant increase in overall survival. Larger tumor size and borderline or malignant behavior were found to be associated with increased radiation use. Data in the present analysis failed to show an overall survival benefit in utilizing adjuvant radiation for atypical tumors.