Faculty Bibliography

BACKGROUND: Up to 20% of meningiomas are aggressive tumors with high recurrence rates and poor prognosis. Biomarkers predicting the risk of an unfavorable clinical course are lacking although aberrations in NF2, increased copy number variations and a hypomethylated phenotype have been associated with more aggressive behavior. Mutational signatures (MS) are characteristic patterns of somatic mutations seen in cancer genomes associated with aging, exposure to certain mutagens, or defective DNA repair. We aimed to identify MS patterns in clinically aggressive meningiomas.
METHOD(S): We performed whole exome sequencing of 18 de novo meningiomas (locally invasive and recurrent WHO I, n=6; atypical WHO II, n=4; anaplastic WHO III, n=8). Median PFS was 18.9 months. Copy numbers and DNA methylation phenotype were assessed by DNA methylation array analysis. Mutational signatures were identified using published signature algorithms (COSMIC).
RESULT(S): MS1 and MS5 (aging) were found in 18 (100%) cases. MS associated with defective DNA MMR were highly prevalent: MS20 and MS26 were detected in 18 (100%) and MS6 in 2 (12%) cases. MS12 (unknown etiology) was present in 14 (82%) cases. Despite the association with defective DNA MMR, none (0%) of the MS6 cases harbored somatic mutations associated with DNA MMR while MS12 tumors were enriched for mutations in DNA MMR (43%), chromatin remodeling (36%) and other cancer-associated genes (7%). MS6 tumors had significantly lower indels compared to non-MS6 tumors (p=0.01). Tumors with mutations in chromatin remodeling genes had a significantly higher rate of single nucleotide variants (SNVs) compared to cases without such mutations (p=0.02).
CONCLUSION(S): MS associated with defective DNA MMR were highly prevalent in this set of aggressive meningiomas. However, despite the association with DNA MMR, MS6 meningiomas harbored no somatic mutations associated with DNA MMR while MS12 tumors were enriched for mutations in DNA MMR, chromatin remodeling and cancerassociated genes

OBJECTIVECerebral venous sinus thrombosis (CVST) is a known complication of surgeries near the major dural venous sinuses. While the majority of CVSTs are asymptomatic, severe sinus thromboses can have devastating consequences. The objective of this study was to prospectively evaluate the true incidence and risk factors associated with postoperative CVST and comment on management strategies.METHODSA prospective study of 74 patients who underwent a retrosigmoid, translabyrinthine, or suboccipital approach for posterior fossa tumors, or a supratentorial craniotomy for parasagittal/falcine tumors, was performed. All patients underwent pre- and postoperative imaging to evaluate sinus patency. Demographic, clinical, and operative data were collected. Statistical analysis was performed to identify incidence and risk factors.RESULTSTwenty-four (32.4%) of 74 patients had postoperative MR venograms confirming CVST, and all were asymptomatic. No risk factors, including age (p = 0.352), BMI (p = 0.454), sex (p = 0.955), surgical approach (p = 0.909), length of surgery (p = 0.785), fluid balance (p = 0.943), mannitol use (p = 0.136), tumor type (p = 0.46, p = 0.321), or extent of resection (p = 0.253), were statistically correlated with thrombosis. All patients were treated conservatively, with only 1 patient receiving intravenous fluids. There were no instances of venous infarctions, hemorrhages, or neurological deficits. The rate of CSF leakage was significantly higher in the thrombosis group than in the nonthrombosis group (p = 0.01).CONCLUSIONSThis prospective study shows that the radiographic incidence of postoperative CVST is higher than that previously reported in retrospective studies. In the absence of symptoms, these thromboses can be treated conservatively. While no risk factors were identified, there may be an association between postoperative CVST and CSF leak.

OBJECTIVE The objective of this study was to determine the effects of a quality improvement initiative in which daily antibiotics and daily sampling of cerebrospinal fluid (CSF) were discontinued for patients with lumbar drains. METHODS The frequency of surgical site infections (SSIs), antibiotic-related complications (development of Clostridium difficile infection [CDI] and growth of resistant bacteria), and cost for patients with lumbar drains were compared during 3 periods: 1) prolonged prophylactic systemic antibiotics (PPSA) until the time of drain removal and daily CSF sampling (September 2013-2014), 2) PPSA and CSF sampling once after placement then as needed (January 2015-2016), and 3) antibiotics only during placement of the lumbar drain and CSF sampling once after placement then as needed (April 2016-2017). RESULTS Thirty-nine patients were identified in period 1, 53 patients in period 2, and 39 patients in period 3. There was no change in the frequency of SSI after discontinuation of routine CSF testing or PPSA (0% in period 1, 2% in period 2, and 0% in period 3). In periods 1 and 2, 3 patients developed infections due to resistant organisms and 2 patients had CDI. In period 3, 1 patient had an infection due to a resistant organism. The median cost of CSF tests per patient was $100.68 (interquartile range [IQR] $100.68-$134.24) for patients in period 1 and $33.56 (IQR $33.56-$33.56) in periods 2 and 3 (p < 0.001). The median cost of antibiotics per patient was $26.32 (IQR $26.32-$30.65) in periods 1 and 2 and $3.29 ($3.29-$3.29) in period 3 (p < 0.001). The cost associated with growth of resistant bacteria and CDI was $91,291 in periods 1 and 2 and $25,573 in period 3. CONCLUSIONS After discontinuing daily antibiotics and daily CSF sampling for patients with lumbar drains, the frequency of SSI was unchanged and the frequency of antibiotic-related complications decreased.

Background/UNASSIGNED:Numerous medical society guidelines recommend discontinuation of antibiotics at a maximum of 24 hours after noninstrumented spinal surgery, even when a drain is left in place. As a result of these recommendations, our institution's Neurosurgery Quality Improvement Committee decided to stop administering prolonged prophylactic systemic antibiotics (PPSAs) to patients with drains after noninstrumented spinal surgery. Methods/UNASSIGNED:We retrospectively reviewed data for patients who had noninstrumented spinal surgery performed by a neurosurgeon at our institution between December 2012 and July 2014 (PPSA period) and December 2014 and July 2016 (non-PPSA period) and had a drain left in place postoperatively. In the PPSA period, patients received antibiotics until drain removal. In the non-PPSA period, patients received antibiotics for a maximum of 24 hours. Results/UNASSIGNED:= .24). Conclusion/UNASSIGNED:After discontinuing PPSAs for patients with noninstrumented spinal procedures, as is recommended for quality improvement, we saw a nonsignificant increase in our rate of SSIs. Further monitoring of this population is warranted.

INTRODUCTION: Postoperative antibiotics (PA) are often administered to patients after instrumented spinal surgery until all drains are removed to prevent surgical site infections (SSI). This practice is discouraged by numerous medical society guidelines, so our institutional Neurosurgery Quality Improvement Committee decided to discontinue use of PA for this population. METHODS: We retrospectively reviewed data for patients who had instrumented spinal surgery at our institution for seven months before and after this policy change and compared the frequency of SSI and development of antibiotic related complications in patients who received PA to those who did not (non-PA). RESULTS: We identified 188 PA patients and 158 non-PA patients. Discontinuation of PA did not result in an increase in frequency of SSI (2% of PA patients vs. 0.6% of non-PA patients, p = .4). Growth of resistant bacteria was not significantly reduced in the non-PA period in comparison to the PA period (2% in the PA period and 1% in the non-PA period). The cost of antibiotics for PA patients was $5,499.62, whereas the cost of antibiotics for the non-PA patients was $0. On a per patient basis, the cost associated with antibiotics and resistant infections was significantly greater for patients who received PA than for those who did not (median of $26.32 with IQR $9.87-$46.06 vs. median of $0 with IQR $0-$0; p < .0001). CONCLUSION: After discontinuing PA for patients who had instrumented spinal procedures, we did not observe an increase in the frequency of SSI. We did, however, note that there was a non-significant decrease in the frequency of growth of resistant organisms. These findings suggest that patients in this population do not need PA, and complications can be reduced if PA are withheld.

Background: Assessment of preoperative imaging is important for operative planning of meningioma resection. A hyperintense rim on T2-weighted (T2W) MRI is frequently thought to represent a CSF cleft between the tumor and the brain, suggesting a clean arachnoid plane. However, brain invasion (loss of arachnoid plane) is often encountered instead. We sought to further characterize this radiographic finding and identify correlates with intraoperative brain invasion and pathology in patients undergoing meningioma resection. Methods: Retrospective review of 42 patients (mean age: 54.2 years, SD: 13.0, 76% female) who underwent meningioma resection between 2013 and 2016 at a single institution. Demographic variables and pathology results were recorded. Radiographic variables on preoperative MRI included presence and size of a hyperintense rim on T2W MRI, a contrast-enhancing rim on fluid-attenuated inversion recovery (FLAIR), and adjacent edema. Operative reports were reviewed for identification of loss of arachnoid plane (brain invasion) noted during surgery. Radiographic findings were then correlated with brain invasion using nonparametric statistics. Results: Of 42 meningiomas resected, there were 29 (69%) WHO Grade I, 12 (29%) WHO Grade II, and 1 (2%) WHO Grade III. Twenty-three tumors (55%) were located at the skull base. On preoperative T2WI, 36 (86%) of meningiomas demonstrated a hyperintense cleft with a mean width of 2.86 mm (SD: 1.66) and 16 had adjacent edema. Twenty-six meningiomas demonstrated a contrast-enhancing rim on FLAIR with a mean width of 2.85 mm (SD: 1.06) and 28 meningiomas exhibited a rim that was both T2 hyperintense and enhancing on FLAIR. Intraoperatively, 24 (57%) of meningiomas were found to have partial or complete loss of an arachnoid plane between the tumor and adjacent brain parenchyma. Both a hyperintense T2 cleft and enhancing FLAIR rim were associated with loss of arachnoid plane (p=0.004 for T2, <0.001 for FLAIR, <0.001 for combined). Conclusion: Preoperative MRI of meningiomas often identifies a T2 hyperintense rim frequently thought to represent a CSF cleft. A correlation with enhancement on FLAIR and intraoperative loss of arachnoid plane suggests this may be a useful marker of brain invasion and could aid in operative planning and risk assessment