Analysis of intra-operative variables as predictors of 30-day readmission in patients undergoing glioma surgery at a single center.

PURPOSE: Reducing the time from surgery to adjuvant chemoradiation, by decreasing unnecessary readmissions, is paramount for patients undergoing glioma surgery. The effects of intraoperative risk factors on 30-day readmission rates for such patients is currently unclear. We utilized a predictive model-driven approach to assess the impact of intraoperative factors on 30-day readmission rates for the cranial glioma patient. METHODS: Retrospectively, the intraoperative records of 290 patients who underwent glioma surgery at a single institution by a single surgeon were assessed. Data on operative variables including anesthesia specific factors were analyzed via univariate and stepwise regression analysis for impact on 30-day readmission rates. A predictive model was built to assess the capability of these results to predict readmission and validated using leave-one-out cross-validation. RESULTS: In multivariate analysis, end case hypothermia (OR 0.28, 95% CI [0.09, 0.84]), hypertensive time > 15 min (OR 2.85, 95% CI [1.21, 6.75]), and pre-operative Karnofsky performance status (KPS) (OR 0.63, 95% CI [0.41, 0.98] were identified as being significantly associated with 30-day readmission rates (chi-squared statistic vs. constant model 25.2, p < 0.001). Cross validation of the model resulted in an overall accuracy of 89.7%, a specificity of 99.6%, and area under the receiver operator curve (AUC) of 0.763. CONCLUSION: Intraoperative risk factors may help risk-stratify patients with a high degree of accuracy and improve postoperative patient follow-up. Attention should be paid to duration of hypertension and end-case final temperature as these represent potentially modifiable factors that appear to be highly associated with 30-day readmission rates. Prospective validation of our model is needed to assess its potential for implementation as a screening tool to identify patients undergoing glioma surgery who are at a higher risk of post-operative readmission within 30 days.

Predictive modeling of brain tumor laser ablation dynamics.

INTRODUCTION: Laser interstitial thermal therapy (LITT) is a novel MR thermometry-guided thermoablative tool revolutionizing the clinical management of brain tumors. A limitation of LITT is our inability to estimate a priori how tissues will respond to thermal energy, which hinders treatment planning and delivery. The aim of this study was to determine whether brain tumor LITT ablation dynamics may be predicted by features of the preoperative MRI and the relevance of these data, if any, to the recurrence of metastases after LITT. METHODS: Intraoperative thermal damage estimate (TDE) map pixels representative of irreversible damage were retrospectively quantified relative to ablation onset for 101 LITT procedures. Raw TDE pixel counts and TDE pixel counts modelled with first order dynamics were related to eleven independent variables derived from the preoperative MRI, demographics, laser settings, and tumor pathology. Stepwise regression analysis generated predictive models of LITT dynamics, and leave-one-out cross validation evaluated the accuracy of these models at predicting TDE pixel counts solely from the independent variables. Using a deformable atlas, TDE maps were co-registered to the immediate post-ablation MRI, allowing comparison of predicted and actual ablation sizes. RESULTS: Brain tumor TDE pixel counts modelled with first order dynamics, but not raw pixel counts, are correlated with the independent variables. Independent variables showing strong relations to the TDE pixel measures include T1 gadolinium and T2 signal, perfusion, and laser power. Associations with tissue histopathology are minimal. Leave-one-out analysis demonstrates that predictive models using these independent variables account for 77% of the variance observed in TDE pixel counts. Analysis of metastases treated revealed a trend towards the over-estimation of LITT effects by TDE maps during rapid ablations, which was associated with tumor recurrence. CONCLUSIONS: Features of the preoperative MRI are predictive of LITT ablation dynamics and could eventually be used to improve the clinical efficacy with which LITT is delivered to brain tumors.

Alternative patterns of deep brain stimulation in neurologic and neuropsychiatric disorders.

Deep brain stimulation (DBS) is a widely used clinical therapy that modulates neuronal firing in subcortical structures, eliciting downstream network effects. Its effectiveness is determined by electrode geometry and location as well as adjustable stimulation parameters including pulse width, interstimulus interval, frequency, and amplitude. These parameters are often determined empirically during clinical or intraoperative programming and can be altered to an almost unlimited number of combinations. Conventional high-frequency stimulation uses a continuous high-frequency square-wave pulse (typically 130-160 Hz), but other stimulation patterns may prove efficacious, such as continuous or bursting theta-frequencies, variable frequencies, and coordinated reset stimulation. Here we summarize the current landscape and potential clinical applications for novel stimulation patterns.

Endoscopic Endonasal Resection of Rathke Cleft Cyst with Xanthogranulomatous Change: Two-Dimensional Operative Video.

Objective Sellar xanthogranulomas (XGAs) are a rare pathological subtype of hypophysitis reflecting a degenerative process of Rathke's cleft cyst with predilection in young adults. While the histological features have been described, there is limited discussion on the technical expectations in surgical management. We present the clinical, radiographic, and surgical features of the third literature-reported XGA in the pediatric population. Setting The patient was a 17-year-old boy who first identified by ophthalmologically confirmed peripheral vision loss. Subsequent endocrine workup identified delayed-onset puberty and hypopituitarism. Magnetic resonance imaging (MRI) showed a nonenhancing 2.6-cm T1 and T2 sellar-based hyperintense mass with suprasellar extension and mass effect on the optic chiasm. A small T1 hypointense encased nodule was also seen ( Fig. 1 ). Consent for resection was obtained. Results Intraoperatively the tumor was firm and adherent, requiring piecemeal removal. Radiofrequency ablation enabled ergonomic debulking and minimize thermal injury ( Fig. 2 ). 1 We used initial settings of 25 W, equivalent to 55 W. A cystic component with motor oil-like fluid was encountered and decompressed. The tumor was notably very adherent to the optic nerve and infiltrated the stalk, requiring its truncation. Closure was achieved by fat graft dead space plugging, fascia lata underlay, Medpor gasket seal, and nasoseptal flap. Conclusion Pathology confirmed dense fibrous tissue with features of chronic inflammation, cholesterol clefts, hemosiderin pigment, multinucleate giant cells, and foamy macrophages. Additional cyst wall sampling identified squamous and ciliated epithelial lining, collectively consistent with Rathke's cleft cyst and xanthogranulomatous reaction. These lesions can undergo surgical cure with resection, most commonly by transsphenoidal approach. The link to the video can be found at: https://youtu.be/S2n5iQ3aFgc .

Targeting Microglial Polarization to Improve TBI Outcomes.

Traumatic Brain Injury (TBI) is still the worldwide leading cause of mortality and morbidity in young adults. Improved safety measures and advances in critical care have increased chances of surviving a TBI, however, numerous secondary mechanisms contribute to the injury in the weeks and months that follow TBI. The past 4 decades of research have addressed many of the metabolic impairments sufficient to mitigate mortality, however, an enduring secondary mechanism, i.e. neuroinflammation, has been intractable to current therapy. Neuroinflammation is particularly difficult to target with pharmacological agents due to lack of specificity, the blood brain barrier, and an incomplete understanding of the protective and pathologic influences of inflammation in TBI. Recent insights into TBI pathophysiology have established microglial activation as a hallmark of all types of TBI. The inflammatory response to injury is necessary and beneficial while the death of activated microglial is not. This review presents new insights on the therapeutic and maladaptive features of the immune response after TBI with an emphasis on microglial polarization, followed by a discussion of potential targets for pharmacologic and non-pharmacologic treatments. In aggregate, this review presents a rationale for guiding TBI inflammation towards neural repair and regeneration rather than secondary injury and degeneration, which we posit could improve outcomes and reduce lifelong disease burden in TBI survivors.

Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas.

Glioblastoma multiforme (GBM) represents one of the most challenging malignancies due to many factors including invasiveness, heterogeneity, and an immunosuppressive microenvironment. Current treatment modalities have resulted in only modest effect on outcomes. The development of viral vectors for oncolytic immunovirotherapy and targeted drug delivery represents a promising therapeutic prospect for GBM and other brain tumors. A host of genetically engineered viruses, herpes simplex virus, poliovirus, measles, and others, have been described and are at various stages of clinical development. Herein we provide a review of the advances and current state of oncolytic virotherapy for the targeted treatment of GBM and malignant gliomas.

Ventriculostomy supply cart decreases time-to-external ventricular drain placement in the emergency department.

BACKGROUND: Minimizing time-to-external ventricular drain (EVD) placement in the emergency department (ED) is critical. We sought to understand factors affecting time-to-EVD placement through a quality improvement initiative. METHODS: The use of process mapping, root cause analyses, and interviews with staff revealed decentralized supply storage as a major contributor to delays in EVD placement. We developed an EVD "crash cart" as a potential solution to this problem. Time-to-EVD placement was tracked prospectively using time stamps in the electronic medical record (EMR); precart control patients were reviewed retrospectively. RESULTS: The final cohorts consisted of 33 precart and 18 postcart cases. The mean time-to-EVD in the precart group was 99.09 min compared to 71.88 min in the postcart group (two-tailed t-test, P = 0.023). Median time-to-EVD was 92 min in the precart group compared to 64 min in the postcart group (rank sum test, P = 0.0165). Postcart patients trended toward improved outcomes with lower modified Rankin score scores at 1 year, but this did not reach statistical significance (two-tailed t-test, P = 0.177). CONCLUSION: An EVD "crash cart" is a simple intervention that can significantly reduce time-to-EVD placement and may improve outcomes in patients requiring an EVD.

Supratentorial intraventricular rosette-forming glioneuronal tumors - Case report and review of treatment paradigms.

BACKGROUND: Rosette-forming glioneuronal tumors (RGNT) are slow-growing WHO Grade I tumors that are characterized by mixed histology and rosette formation. Although typically located in the posterior fossa, these tumors can rarely originate elsewhere. Here, we describe the fourth case in literature where an RGNT was localized to the lateral ventricles and detail the treatment approach. CASE DESCRIPTION: A 41-year-old male presented with a 10 day history of gradually worsening headaches and mild gait difficulty. Computed tomography and magnetic resonance imaging (MRI) identified a heterogeneously enhancing 6.0 cm left lateral ventricular cystic mass with hydrocephalus. An interhemispheric transcallosal approach was performed for tumor debulking. The mass was emanating from the roof of the left lateral ventricle. Sub-total resection (STR) was achieved. Pathology showed a glioneuronal neoplasm with vague neurocytic rosettes and loose perivascular pseudorosettes. Tumor vessels were thickly hyalinized and contained eosinophilic granular bodies and Rosenthal fibers. Tumor stained positive for GFAP, S-100, OLIG2, and SOX10, and patchy positive for epithelial membrane antigen (EMA), D2-40, CD99, and p16. Neurocytic rosettes and perivascular structures stained positive for synaptophysin. The patient was discharged home uneventfully and remained intact at his 6-month follow-up visit. Long-term care included MRI surveillance with repeat surgery being considered in case of progression. CONCLUSION: In this report, we describe the fourth case of an RGNT being isolated to the lateral ventricles and the first where it stained positive for EMA and D2-40. Our patient's uneventful recovery after STR indicates that surgery alone continues to be a viable initial treatment option.

Prolonged tracheal extubation time after glioma surgery was associated with lack of familiarity between the anesthesia provider and the operating neurosurgeon. A retrospective, observational study.

STUDY OBJECTIVE: We consider the effect of the number of previous interactions between the anesthesia provider and a single neurosurgeon during neurosurgical procedures ("familiarity") and occurrence of an interval ≥15 min from the end of surgery (i.e., dressings applied) to tracheal extubation ("prolonged extubation") during subsequent glioma procedures by that neurosurgeon. The value of 15min is a threshold at which post-case activity by non-anesthesia personnel in the operating room ends. DESIGN: Historical observational study. SETTING: Neurosurgical operating room suite in an academic teaching hospital. PATIENTS: 294 patients undergoing elective supratentorial glioma surgery between 2012 and 2017 by a single neurosurgeon. MEASUREMENTS: 1) Time from end of surgery ("dressings applied") to extubation; 2) number of previous cases where the anesthesia provider had been present at the end of a neurosurgical procedure performed by the neurosurgeon; 3) case duration. MAIN RESULTS: Anesthesia providers (nurse anesthetists or anesthesia residents) were considered "unfamiliar" with the neurosurgeon if they had been present at the time of extubation for <5 previous neurosurgical cases (including glioma and non-glioma surgery) performed by the neurosurgeon during the study interval. For approximately half the cases the anesthesia provider was unfamiliar with the neurosurgeon. There was an association between the provider's number of historical cases with the neurosurgeon and prolonged extubation (P = 0.0048); the adjusted odds ratio (by unadjusted logistic regression) for unfamiliarity was 2.10 (95% CI 1.28 to 3.44, P = 0.025). Consistent with previously shown associations between case duration and prolonged extubation, analyses were valid based on a near-linear relationship between the logit (prevalence of prolonged extubation) and the case duration quintile. CONCLUSIONS: Lack of familiarity between the anesthesia provider and neurosurgeon during previous anesthetics is associated with prolonged tracheal extubation following intracranial glioblastoma surgery.

Salvage craniotomy for treatment-refractory symptomatic cerebral radiation necrosis.

BACKGROUND: The incidence of symptomatic radiation necrosis (RN) has risen as radiotherapy is increasingly used to control brain tumor progression. Traditionally managed with steroids, symptomatic RN can remain refractory to medical treatment, requiring surgical intervention for control. The purpose of our study was to assess a single institution's experience with craniotomy for steroid-refractory pure RN. METHODS: The medical records of all tumor patients who underwent craniotomies at our institution from 2011 to 2016 were retrospectively reviewed for a history of preoperative radiotherapy or radiosurgery. RN was confirmed histopathologically and patients with active tumor were excluded. Preoperative, intraoperative, and outcome information was collected. Primary outcomes measured were postoperative KPS and time to steroid freedom. RESULTS: Twenty-four patients with symptomatic RN were identified. Gross total resection was achieved for all patients. Patients with metastases experienced an increase in KPS (80 vs 100, P < .001) and required a shortened course of dexamethasone vs patients with high-grade gliomas (3.4 vs 22.2 weeks, P = .003). RN control and neurological improvement at 13.3 months' follow-up were 100% and 66.7%, respectively. Adrenal insufficiency after rapidly tapering dexamethasone was the only morbidity (n = 1). Overall survival was 93.3% (14/15) at 1 year. CONCLUSION: In cases of treatment-refractory symptomatic RN, resection can lead to an overall improvement in postoperative health status and neurological outcomes with minimal RN recurrence. Craniotomy for surgically accessible RN can safely manage symptomatic patients, and future studies assessing the efficacy of resection vs bevacizumab may be warranted.

Central Neurocytoma Treatment Modalities: A Systematic Review Assessing the Outcomes of Combined Maximal Safe Resection and Radiotherapy with Gross Total Resection.

BACKGROUND: Central neurocytomas (CNCs) are rare intraventricular lesions comprising <1% of primary brain tumors. Their surgical and adjuvant management is unclear. OBJECTIVE: Our goal was to update Rades et al.'s 2006 systematic review to assess the outcome differences among 3 fundamental therapies for CNC: gross total resection with and without radiation therapy (RT) versus maximal safe resection with adjuvant RT. METHODS: Articles indexed on PubMed and Google Scholar and published between January 1, 2006 and December 31, 2019 were selected using the PRISMA criteria. Studies were excluded if they had fewer than 3 cases, did not categorize extent of resection, or were duplicate studies, technical reports, case reports, or studies without follow-up. Complication rates, recurrence rates, overall survival and progression-free survival were extracted where possible. χ2 proportionality tests were used for comparison (P values >0.05 suggested significance). RESULTS: On aggregation, 615 patients from 13 studies including ours were assessed. Although overall survival was not significantly different (χ2 = 1.56; P = 0.46), the recurrence rate differed significantly between GTR + RT (6.9%, 92.11 months), GTR-RT (23.9%, 96.8 months), and MSR + RT (16.8%, 85 months) (χ2 = 10.94; P = 0.004). Pooled complication rates for GTR and MSR + RT were 31.2% and 24% (P = 0.049), respectively. CONCLUSIONS: RT remains an important adjuvant treatment that can improve patient survival in the presence of MSR to levels comparable to those of GTR or GTR + RT. Where total resection carries too much risk, MSR + RT can be considered as the next best alternative for tumor control.

The Role of Laser Interstitial Thermal Therapy in Surgical Neuro-Oncology: Series of 100 Consecutive Patients.

BACKGROUND: Laser interstitial thermal therapy (LITT) is an adjuvant treatment for intracranial lesions that are treatment refractory or in deep or eloquent brain. Initial studies of LITT in surgical neuro-oncology are limited in size and follow-up. OBJECTIVE: To present our series of LITT in surgical neuro-oncology to better evaluate procedural safety and outcomes. METHODS: An exploratory cohort study of all patients receiving LITT for brain tumors by a single senior neurosurgeon at a single center between 2013 and 2018. Primary outcomes included extent of ablation (EOA), time to recurrence (TTR), local control at 1-yr follow-up, and overall survival (OS). Secondary outcomes included complication rate. Outcomes were compared by tumor subtype. Predictors of outcomes were identified. RESULTS: A total of 91 patients underwent 100 LITT procedures; 61% remain alive with 72% local control at median 7.2 mo follow-up. Median TTR and OS were 31.9 and 16.9 mo, respectively. For lesion subtypes, median TTR (months, not applicable [N/A] if <50% rate observed), local control rates at 1-yr follow-up, and median OS (months) were the following: dural-based lesions (n = 4, N/A, 75%, 20.7), metastases (n = 45, 55.9, 77.4%, 16.9), newly diagnosed glioblastoma (n = 11, 31.9, 83.3%, 32.3), recurrent glioblastoma (n = 14, 5.6, 24.3%, 7.3), radiation necrosis (n = 20, N/A, 67.2%, 16.4), and other lesions (n = 6, 12.3, 80%, 24.4). TTR differed by tumor subtype (P = .02, log-rank analysis). EOA predicted local control (P = .009, multivariate proportional hazards regression); EOA > 85% predicted longer TTR (P = .006, log-rank analysis). Complication rate was 4%. CONCLUSION: Our series of LITT in surgical neuro-oncology, 1 of the largest to date, further evidences its safety and outcomes profile.

Enduring Neuroprotective Effect of Subacute Neural Stem Cell Transplantation After Penetrating TBI.

Traumatic brain injury (TBI) is the largest cause of death and disability of persons under 45 years old, worldwide. Independent of the distribution, outcomes such as disability are associated with huge societal costs. The heterogeneity of TBI and its complicated biological response have helped clarify the limitations of current pharmacological approaches to TBI management. Five decades of effort have made some strides in reducing TBI mortality but little progress has been made to mitigate TBI-induced disability. Lessons learned from the failure of numerous randomized clinical trials and the inability to scale up results from single center clinical trials with neuroprotective agents led to the formation of organizations such as the Neurological Emergencies Treatment Trials (NETT) Network, and international collaborative comparative effectiveness research (CER) to re-orient TBI clinical research. With initiatives such as TRACK-TBI, generating rich and comprehensive human datasets with demographic, clinical, genomic, proteomic, imaging, and detailed outcome data across multiple time points has become the focus of the field in the United States (US). In addition, government institutions such as the US Department of Defense are investing in groups such as Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug-screening consortium to address the barriers in translation. The consensus from such efforts including "The Lancet Neurology Commission" and current literature is that unmitigated cell death processes, incomplete debris clearance, aberrant neurotoxic immune, and glia cell response induce progressive tissue loss and spatiotemporal magnification of primary TBI. Our analysis suggests that the focus of neuroprotection research needs to shift from protecting dying and injured neurons at acute time points to modulating the aberrant glial response in sub-acute and chronic time points. One unexpected agent with neuroprotective properties that shows promise is transplantation of neural stem cells. In this review we present (i) a short survey of TBI epidemiology and summary of current care, (ii) findings of past neuroprotective clinical trials and possible reasons for failure based upon insights from human and preclinical TBI pathophysiology studies, including our group's inflammation-centered approach, (iii) the unmet need of TBI and unproven treatments and lastly, (iv) present evidence to support the rationale for sub-acute neural stem cell therapy to mediate enduring neuroprotection.