Evaluating Predictors of Successful Postoperative Day 1 Discharge Following Posterior Fossa Tumor Resection.

BACKGROUND: Current trends in surgical neuro-oncology show that early discharges are safe and feasible with shorter lengths of stay (LOS) and fewer thromboembolic complications, fewer hospital-acquired infections, reduced costs, and greater patient satisfaction. Traditionally, infratentorial tumor resections have been associated with longer LOS and limited data exist evaluating predictors of early discharge in these patients. The objective was to assess patients undergoing posterior fossa craniotomies for tumor resection and identify variables associated with postoperative day 1 (POD1) discharge. METHODS: A retrospective review of posterior fossa craniotomies for tumor resection at our institution was performed from 2011 to 2020. Laser ablations, nontumoral pathologies, and biopsies were excluded. Demographic, clinical, surgical, and postoperative data were collected. RESULTS: One hundred and seventy-three patients were identified and 25 (14.5%) were discharged on POD1. Median length of stay (LOS) was 6 days. The POD1 discharges had significantly better preoperative Karnofsky performance scores (P < 0.001) and modified Rankin scores (P = 0.002) and more frequently presented electively (P = 0.006) and without preoperative neurologic deficits (P = 0.021). No statistically significant difference in 30-day readmissions and rates of PE, UTI, and DVT was found. Univariate logistic regression identified better preoperative functional status, elective admission, and lack of preoperative hydrocephalus as predictors of POD1 discharge, however only the latter remained significant in the multivariable model (P = 0.001). CONCLUSIONS: Discharging patients on POD1 is feasible following posterior fossa tumor resection in a select group of patients. Although we found that the only independent predictor for a longer LOS was preoperative hydrocephalus, larger, prospective studies are needed to confirm these findings.

Safety of the utilization of telemedicine for brain tumor neurosurgery follow-up.

Background: There is a need to evaluate the outcomes of patients who underwent brain tumor surgery with subsequent telemedicine or in-person follow-up during the COVID-19 pandemic. Methods: We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). Results: Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine (TM) in 185 patients (58.17%), and in-person (IP) consults in 133 patients. We found that patients followed by TM lived significantly farther, with a median of 36.34 miles, compared to a median of 22.23 miles in the IP cohort (P = .0025). We found no statistical difference between the TM and the IP group, when comparing visits to the emergency department (ED) within 30 days after surgery (7.3% vs 6.01%, P = .72). Readmission rates, wound infections, and 30-day mortality were similar in both cohorts. These findings were also consistent after matching cohorts using a propensity score. The percentage of telemedicine follow-up consults was higher in the first semester (73.17%) of the COVID-19 pandemic, compared to the second (46.21%), and third semesters (47.86%). Conclusions: Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.

Using machine learning to evaluate large-scale brain networks in patients with brain tumors: Traditional and non-traditional eloquent areas.

Background: Large-scale brain networks and higher cognitive functions are frequently altered in neuro-oncology patients, but comprehensive non-invasive brain mapping is difficult to achieve in the clinical setting. The objective of our study is to evaluate traditional and non-traditional eloquent areas in brain tumor patients using a machine-learning platform. Methods: We retrospectively included patients who underwent surgery for brain tumor resection at our Institution. Preoperative MRI with T1-weighted and DTI sequences were uploaded into the Quicktome platform. We categorized the integrity of nine large-scale brain networks: language, sensorimotor, visual, ventral attention, central executive, default mode, dorsal attention, salience and limbic. Network integrity was correlated with preoperative clinical data. Results: One-hundred patients were included in the study. The most affected network was the central executive network (49%), followed by the default mode network (43%) and dorsal attention network (32%). Patients with preoperative deficits showed a significantly higher number of altered networks before the surgery (3.42 vs 2.19, P < .001), compared to patients without deficits. Furthermore, we found that patients without neurologic deficits had an average 2.19 networks affected and 1.51 networks at-risk, with most of them being related to non-traditional eloquent areas (P < .001). Conclusion: Our results show that large-scale brain networks are frequently affected in patients with brain tumors, even when presenting without evident neurologic deficits. In our study, the most commonly affected brain networks were related to non-traditional eloquent areas. Integrating non-invasive brain mapping machine-learning techniques into the clinical setting may help elucidate how to preserve higher-order cognitive functions associated with those networks.

A single institution experience with proximal junctional kyphosis in the context of existing classification schemes - Systematic review.

BACKGROUND: Proximal junctional kyphosis is a kyphotic deformity following spine instrumentation, predominantly seen in scoliosis patients. There have been previous attempts to develop classification schema of PJK. We analyzed the factors contributing to PJK based upon our own clinical experience with the goal of developing a clinical guidance tool which took into account both etiology and mechanism of failure. METHODS: We performed a retrospective analysis of all re-operation thoracolumbar surgeries at a single institution over a 14-year period. Patients with PJK were identified and categorized based upon the etiology, mechanism of failure, and an indication of revision. Next, we conducted a systematic review on articles emphasizing a classification system for PJK. RESULTS: Fourteen PJK patients were identified out of 121 patients who required revision spine surgery. The average age was 64.9 ± 10.2 years, with 10 males (71%) and 4 females (29%). Three primary etiologies were identified: 6/14 (47%) overcorrection, 6/14 (47%) osteopenia, and 2/14 (14%) ligamentous disruption. The mechanism of failure was likewise divided into three categories: 9/14 (64%) compression fracture, 1/14 (7%) hardware failure, and 4/14 (29%) disc degeneration. The relationship between osteopenia and the development of a compression fracture leading to PJK was statistically significant (p = 0.031). CONCLUSION: There are multiple current classification systems for PJK. Our study findings were in line with previously published literature and suggest the need for a future classification system combining both etiology, mechanism of failure, and severity of disease.

Treatment strategies for patients with concurrent blunt cerebrovascular and traumatic brain injury.

Patients who present with traumatic brain injury (TBI) combined with blunt cerebrovascular injuries (BCVI) are difficult to manage, in part because treatment for each entity may exacerbate the other. It is necessary to develop a treatment paradigm that ensures maximum benefit while mitigating the opposing risks. A cohort of 150 patients from 2015 to present, with either internal carotid artery (ICA) and/or vertebral artery (VA) dissections or pseudoaneurysms, was cross-referenced with those who had sustained TBI. Of the 38 patients identified with both TBI and BCVI, 25 suffered ICA injuries, 10 had VA injuries and 3 had combined ICA/VA injuries. Unilateral BCVI occurred in 30 patients, while 8 had bilateral BCVI. Two patients required surgical intervention for TBI, and 5 patients required endovascular intervention for BCVI. Positive emboli detection studies (EDS) on transcranial dopplers (TCD) were demonstrated in 19 patients, with 9 patients having radiographic evidence of stroke. Anti-platelet therapy was initiated in 32 patients, and anti-coagulation in 10 patients, without new or worsening intracranial hemorrhages (ICH). Overall, 76% of patients were able to be discharged home or to rehabilitation, with good recovery demonstrated in 73% of the patients who had appropriate follow-up. In the setting of concurrent TBI and BCVI, use of anti-platelet/coagulation to prevent stroke can be safe if monitored closely. Here we describe a treatment paradigm which weighs the risk and benefits of therapies based on severity of ICH and stroke prevention, which tended to result in good disposition and recovery.

The Effects of Lockdown During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on Neurotrauma-Related Hospital Admissions.

BACKGROUND: The response to the global severe acute respiratory syndrome coronavirus 2 pandemic culminated in mandatory isolation throughout the world, with nationwide confinement orders issued to decrease viral spread. These drastic measures were successful in "flattening the curve" and maintaining the previous rate of coronavirus disease 2019 infections and deaths. To date, the effects of the coronavirus disease 2019 pandemic on neurotrauma has not been reported. METHODS: We retrospectively analyzed hospital admissions from Ryder Trauma Center at Jackson Memorial Hospital, during the months of March and April from 2016 to 2020. Specifically, we identified all patients who had cranial neurotrauma consisting of traumatic brain injury and/or skull fractures, as well as spinal neurotrauma consisting of vertebral fractures and/or spinal cord injury. We then performed chart review to determine mechanism of injury and if emergent surgical intervention was required. RESULTS: Compared with previous years, we saw a significant decline in the number of neurotraumas during the pandemic, with a 62% decline after the lockdown began. The number of emergent neurotrauma surgical cases also significantly decreased by 84% in the month of April. Interestingly, although the number of vehicular traumas decreased by 77%, there was a significant 100% increase in the number of gunshot wounds. CONCLUSIONS: Population seclusion had a direct effect on the frequency of neurotrauma, whereas the change in relative proportion of certain mechanisms may be associated with the psychosocial effects of social distancing and quarantine.

Laser Ablation for Cerebral Metastases.

Laser interstitial thermal therapy is a minimally invasive surgical alternative to craniotomy that uses laser light through a fiber optic probe placed within a target lesion to create thermal tissue damage, resulting in cellular death. It is used in neuro-oncology to treat inaccessible lesions and obviate morbidity in high-risk patients. Overall complication rates and outcome measures are comparable with those seen in radiation and/or craniotomy. Laser interstitial thermal therapy can be an effective option for recurrent brain metastases. Prospective, randomized trials must be performed to evaluate the efficacy of laser interstitial thermal therapy as a primary treatment for brain metastases.

Expression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes.

BACKGROUND: Glioma is a family of primary brain malignancies with limited treatment options and in need of novel therapies. We previously demonstrated that the adhesion G protein-coupled receptor GPR133 (ADGRD1) is necessary for tumor growth in adult glioblastoma, the most advanced malignancy within the glioma family. However, the expression pattern of GPR133 in other types of adult glioma is unknown. METHODS: We used immunohistochemistry in tumor specimens and non-neoplastic cadaveric brain tissue to profile GPR133 expression in adult gliomas. RESULTS: We show that GPR133 expression increases as a function of WHO grade and peaks in glioblastoma, where all tumors ubiquitously express it. Importantly, GPR133 is expressed within the tumor bulk, as well as in the brain-infiltrating tumor margin. Furthermore, GPR133 is expressed in both isocitrate dehydrogenase (IDH) wild-type and mutant gliomas, albeit at higher levels in IDH wild-type tumors. CONCLUSION: The fact that GPR133 is absent from non-neoplastic brain tissue but de novo expressed in glioma suggests that it may be exploited therapeutically.

The posterior nasoseptal flap: A novel technique for closure after endoscopic transsphenoidal resection of pituitary adenomas.

BACKGROUND: While effective for the repair of large skull base defects, the Hadad-Bassagasteguy nasoseptal flap increases operative time and can result in a several-week period of postoperative crusting during re-mucosalization of the denuded nasal septum. Endoscopic transsphenoidal surgery for pituitary adenoma resection is generally not associated with large dural defects and high-flow cerebrospinal fluid (CSF) leaks requiring extensive reconstruction. Here, we present the posterior nasoseptal flap as a novel technique for closure of skull defects following endoscopic resection of pituitary adenomas. This flap is raised in all surgeries during the transnasal exposure using septal mucoperiosteum that would otherwise be discarded during the posterior septectomy performed in binostril approaches. METHODS: We present a retrospective, consecutive case series of 43 patients undergoing endoscopic transsphenoidal resection of a pituitary adenoma followed by posterior nasoseptal flap placement and closure. Main outcome measures were extent of resection and postoperative CSF leak. RESULTS: The mean extent of resection was 97.16 ± 1.03%. Radiographic measurement showed flap length to be adequate. While a defect in the diaphragma sellae and CSF leak were identified in 21 patients during surgery, postoperative CSF leak occurred in only one patient. CONCLUSIONS: The posterior nasoseptal flap provides adequate coverage of the surgical defect and is nearly always successful in preventing postoperative CSF leak following endoscopic transsphenoidal resection of pituitary adenomas. The flap is raised from mucoperiosteum lining the posterior nasal septum, which is otherwise resected during posterior septectomy. Because the anterior septal cartilage is not denuded, raising such flaps avoids the postoperative morbidity associated with the larger Hadad-Bassagasteguy nasoseptal flap.

Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2.

Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis.

Traumatic brain injury and subsequent glioblastoma development: Review of the literature and case reports.

BACKGROUND: Previous reports have proposed an association between traumatic brain injury (TBI) and subsequent glioblastoma (GBM) formation. METHODS: We used literature searches and radiographic evidence from two patients to assess the possibility of a link between TBI and GBM. RESULTS: Epidemiological studies are equivocal on a possible link between brain trauma and increased risk of malignant glioma formation. We present two case reports of patients with GBM arising at the site of prior brain injury. CONCLUSION: The hypothesis that TBI may predispose to gliomagenesis is disputed by several large-scale epidemiological studies, but supported by some. Radiographic evidence from two cases presented here suggest that GBM formed at the site of brain injury. We propose a putative pathogenesis model that connects post-traumatic inflammation, stem and progenitor cell transformation, and gliomagenesis.

R-Baclofen Reverses a Social Behavior Deficit and Elevated Protein Synthesis in a Mouse Model of Fragile X Syndrome.

BACKGROUND: Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability and the single genomic cause of autism spectrum disorders. It is caused by the absence of a fragile X mental retardation gene (Fmr1) product, FMRP, an RNA-binding translation suppressor. Elevated rates of protein synthesis in the brain and an imbalance between synaptic signaling via glutamate and γ-aminobutyric acid (GABA) are both considered important in the pathogenesis of FXS. In a mouse model of FXS (Fmr1 knockout [KO]), treatment with R-baclofen reversed some behavioral and biochemical phenotypes. A remaining crucial question is whether R-baclofen is also able to reverse increased brain protein synthesis rates. METHODS: To answer this question, we measured regional rates of cerebral protein synthesis in vivo with the L-[1-(14)C]leucine method in vehicle- and R-baclofen-treated wildtype and Fmr1 KO mice. We further probed signaling pathways involved in the regulation of protein synthesis. RESULTS: Acute R-baclofen administration corrected elevated protein synthesis and reduced deficits on a test of social behavior in adult Fmr1 KO mice. It also suppressed activity of the mammalian target of rapamycin pathway, particularly in synaptosome-enriched fractions, but it had no effect on extracellular-regulated kinase 1/2 activity. Ninety min after R-baclofen treatment, we observed an increase in metabotropic glutamate receptor 5 expression in the frontal cortex, a finding that may shed light on the tolerance observed in human studies with this drug. CONCLUSIONS: Our results suggest that treatment via activation of the GABA (GABA receptor subtype B) system warrants further study in patients with FXS.

Cerebral protein synthesis in a knockin mouse model of the fragile X premutation.

The (CGG)n-repeat in the 5'-untranslated region of the fragile X mental retardation gene (FMR1) gene is polymorphic and may become unstable on transmission to the next generation. In fragile X syndrome, CGG repeat lengths exceed 200, resulting in silencing of FMR1 and absence of its protein product, fragile X mental retardation protein (FMRP). CGG repeat lengths between 55 and 200 occur in fragile X premutation (FXPM) carriers and have a high risk of expansion to a full mutation on maternal transmission. FXPM carriers have an increased risk for developing progressive neurodegenerative syndromes and neuropsychological symptoms. FMR1 mRNA levels are elevated in FXPM, and it is thought that clinical symptoms might be caused by a toxic gain of function due to elevated FMR1 mRNA. Paradoxically, FMRP levels decrease moderately with increasing CGG repeat length in FXPM. Lowered FMRP levels may also contribute to the appearance of clinical problems. We previously reported increases in regional rates of cerebral protein synthesis (rCPS) in the absence of FMRP in an Fmr1 knockout mouse model and in a FXPM knockin (KI) mouse model with 120 to 140 CGG repeats in which FMRP levels are profoundly reduced (80%-90%). To explore whether the concentration of FMRP contributes to the rCPS changes, we measured rCPS in another FXPM KI model with a similar CGG repeat length and a 50% reduction in FMRP. In all 24 brain regions examined, rCPS were unaffected. These results suggest that even with 50% reductions in FMRP, normal protein synthesis rates are maintained.

Risk of contrast-induced nephropathy in hospitalized patients with cirrhosis.

AIM: To evaluate the incidence of contrast-induced nephropathy (CIN) in cirrhotic patients and to identify risk factors for the development of CIN. METHODS: We performed a retrospective review of 216 consecutive patients with cirrhosis who underwent computed tomography (CT) with intravenous contrast at the University of Rochester between the years 2000-2005. We retrospectively examined factors associated with a high risk for CIN, defined as a decrease in creatinine clearance of 25% or greater within one week after receiving contrast. RESULTS: Twenty-five percent of our patients developed CIN, and 74% of these patients had ascites seen on CT. Of the 75% of patients who did not develop CIN, only 46% had ascites. The presence of ascites was a significant risk factor for the development of CIN (P = 0.0009, OR 3.38, 95% CI 1.55-7.34) in multivariate analysis. Patient age, serum sodium, Model for End-stage Liver Disease score, diuretic use, and the presence of diabetes were not found to be significant risk factors for the development of CIN. Of the patients who developed CIN, 11% developed chronic renal insufficiency, defined as a creatinine clearance less than baseline for 6 wk. CONCLUSION: Our results suggest that in hospitalized cirrhotic patients, especially those with ascites, the risk of CIN is substantial.