Michael Zhang
Affiliate, Dean's Office Operations - Dean Other
Resident in Neurosurgery
All Publications
-
Acquired dural arteriovenous fistula after subdural evacuation port system placement: A case report.
Surgical neurology international
2022; 13: 540
Abstract
The subdural evacuation port system (SEPS) is a rapid, bedside, and less invasive option for subdural hemorrhage management. Proper procedure planning and understanding of the relevant vascular anatomy is important for minimizing complications and future procedures.We describe a case where following placement of a SEPS, there was immediate development of a new dural arteriovenous fistula (dAVF) between the middle meningeal artery (MMA) and middle meningeal vein. Angiography confirmed site of shunting to be at the proximity of the twist drill hole placement. Subsequent MMA embolization was performed and follow-up MRI confirmed resolution of the dAVF.SEPS-associated dAVF is an underreported complication with potential long-term consequences. This case describes the complication and advocates avoiding SEPS anterior to the coronal suture.
View details for DOI 10.25259/SNI_671_2022
View details for PubMedID 36447876
View details for PubMedCentralID PMC9699867
-
5-Aminolevulinic Acid Imaging of Malignant Glioma.
Surgical oncology clinics of North America
2022; 31 (4): 581-593
Abstract
High-grade glioma is the most common malignant primary brain tumor in adults. Glioma infiltration renders it difficult to treat and likely to recur. Increasing the extent of resection has been associated with improving progression-free survival and overall survival by several months. The introduction of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery has allowed surgeons to better differentiate between neoplastic tissue and normal tissue, thus achieving greater extent of resection. The development of new intraoperative imaging modalities in combination with 5-ALA may provide additional benefits for glioma patients.
View details for DOI 10.1016/j.soc.2022.06.002
View details for PubMedID 36243495
-
Impact on neurosurgical management in a Level 1 trauma center post COVID-19 shelter-in-place restrictions.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
2022; 101: 131-136
Abstract
The stringent restrictions from shelter-in-place (SIP) policies placed on hospital operations during the COVID-19 pandemic led to a sharp decrease in planned surgical procedures. This study quantifies the surgical rebound experienced across a neurosurgical service post SIP restrictions in order to guide future hospital programs with resource management. We conducted a retrospective review of all neurosurgical procedures at a public Level 1 trauma center between February 15th to August 30th for the years spanning 2018-2020. We categorized patient procedures into four comparative one-month periods: pre-SIP; SIP; post-SIP; and late recovery. Patient procedures were designated as either cranial; spinal; and other; as well as Elective or Add-on (Urgent/Emergent). Categorical variables were analyzed using chi2 tests and Fisher's exact tests. A total of 347 cases were reviewed across the four comparative periods and three years studied; with 174 and 152 spinal and cranial procedures; respectively. There was a proportional increase; relative to historical controls; in total spinal procedures (p-value<0.001) and elective spinal procedures (p-value<0.001) in the 2020 SIP to Post-SIP. The doubling of elective spinal cases in the Post-SIP period returned to historical baseline levels in three months after SIP restrictions were lifted. Total cranial procedures were proportionally increased during the SIP period relative to historical controls (p-value=0.005). We provide a census on the post-pandemic neurosurgical operative demands at a major public Level 1 trauma hospital, which can potentially be applied for resource allocations in other disaster scenarios.
View details for DOI 10.1016/j.jocn.2022.04.033
View details for PubMedID 35597060
-
MRI Radiogenomics of Pediatric Medulloblastoma: A Multicenter Study.
Radiology
2022: 212137
Abstract
Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified. There were 1800 features extracted from T2- and contrast-enhanced T1-weighted preoperative MRI scans. A two-stage sequential classifier was designed-one that first identifies non-wingless (WNT) and non-sonic hedgehog (SHH) MB and then differentiates therapeutically relevant WNT from SHH. Further, a classifier that distinguishes high-risk group 3 from group 4 MB was developed. An independent, binary subgroup analysis was conducted to uncover radiomics features unique to infantile versus childhood SHH subgroups. The best-performing models from six candidate classifiers were selected, and performance was measured on holdout test sets. CIs were obtained by bootstrapping the test sets for 2000 random samples. Model accuracy score was compared with the no-information rate using the Wald test. Results The study cohort comprised 263 patients (mean age ± SD at diagnosis, 87 months ± 60; 166 boys). A two-stage classifier outperformed a single-stage multiclass classifier. The combined, sequential classifier achieved a microaveraged F1 score of 88% and a binary F1 score of 95% specifically for WNT. A group 3 versus group 4 classifier achieved an area under the receiver operating characteristic curve of 98%. Of the Image Biomarker Standardization Initiative features, texture and first-order intensity features were most contributory across the molecular subgroups. Conclusion An MRI-based machine learning decision path allowed identification of the four clinically relevant molecular pediatric medulloblastoma subgroups. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.
View details for DOI 10.1148/radiol.212137
View details for PubMedID 35438562
-
Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome.
NeuroImage. Clinical
2022: 103000
Abstract
Cerebellar mutism syndrome, characterised by mutism, emotional lability and cerebellar motor signs, occurs in up to 39% of children following resection of medulloblastoma, the most common malignant posterior fossa tumour of childhood. Its pathophysiology remains unclear, but prior studies have implicated damage to the superior cerebellar peduncles. In this study, the objective was to conduct high-resolution spatial profilometry of the cerebellar peduncles and identify anatomic biomarkers of cerebellar mutism syndrome. In this retrospective study, twenty-eight children with medulloblastoma (mean age 8.8±3.8years) underwent diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0±4.2years), scanned at a single timepoint, served as age- and sex-matched controls. Automated Fibre Quantification was used to segment cerebellar peduncles and compute fractional anisotropy (FA) at 30 nodes along each tract. Thirteen patients developed cerebellar mutism syndrome. FA was significantly lower in the distal third of the left superior cerebellar peduncle pre-operatively in all patients compared to controls (FA in proximal third 0.228, middle and distal thirds 0.270, p=0.01, Cohen's d=0.927). Pre-operative differences in FA did not predict cerebellar mutism syndrome. However, post-operative reductions in FA were highly specific to the distal left superior cerebellar peduncle, and were most pronounced in children with cerebellar mutism syndrome compared to those without at the 1-4month follow up (0.325 vs 0.512, p=0.042, d=1.36) and at the 1-year follow up (0.342, vs 0.484, p=0.038, d=1.12). High spatial resolution cerebellar profilometry indicated a site-specific alteration of the distal segment of the superior cerebellar peduncle seen in cerebellar mutism syndrome which may have important surgical implications in the treatment of these devastating tumours of childhood.
View details for DOI 10.1016/j.nicl.2022.103000
View details for PubMedID 35370121
-
Advances in Immunotherapies for Gliomas.
Current neurology and neuroscience reports
1800
Abstract
PURPOSE OF REVIEW: Immunotherapy-based treatment of glioblastoma has been challenging because of the tumor's limited neoantigen profile and weakly immunogenic composition. This article summarizes the current clinical trials underway by evaluating the leading immunotherapy paradigms, the encountered barriers, and the future directions needed to overcome such tumor evasion.RECENT FINDINGS: A limited number of phase III trials have been completed for checkpoint inhibitor, vaccine, as well as gene therapies, and have been unable to show improvement in survival outcomes. Nevertheless, these trials have also shown these strategies to be safe and promising with further adaptations. Further large-scale studies for chimeric antigen receptors T cell therapies and viral therapies are anticipated. Many current trials are broadening the number of antigens targeted and modulating the microtumor environment to abrogate early mechanisms of resistance. Future GBM treatment will also likely require synergistic effects by combination regimens.
View details for DOI 10.1007/s11910-022-01176-9
View details for PubMedID 35107784
-
An updated comparison between WHO grade 2 gemistocytic and diffuse astrocytoma survival and treatment patterns.
World neurosurgery
2021
Abstract
BACKGROUND: In 2016, the World Health Organization (WHO) revised its guidelines to retain only gemistocytic astrocytoma (GemA) as a distinct variant of diffuse astrocytoma (DA). In the past, grade 2 GemAs have been linked with a worse prognosis than DA. However, it is unclear how consistently the tumor subtype has been diagnosed over time. We used more recent data to compare outcomes between grade 2 GemA and DA.METHODS: WHO grade 2 DA and GemA patients were extracted from the SEER database between 1973-2016. Kaplan-Meier curves estimated survival differences across different eras, with a focus on patients diagnosed between 2000-2016, and propensity score matching (PSM) was used to balance baseline characteristics between DA and GemA cohorts RESULTS: Of 2,467 grade 2 astrocytoma patients between 2000-2016, 132 (5.35%) were diagnosed with GemA, and 2,335 (94.65%) were diagnosed with DA. At baseline, marked demographic and treatment differences were noted between tumor subtypes, including age of diagnosis and female sex. GemA patients did not have worse survival compared to DA patients at baseline (p=0.349) or after PSM (p=0.497). Multivariate Cox models found that surgical extent of resection was associated with a survival benefit for DA patients, and both DA and GemA patients aged >65 years had dramatically inferior survival.CONCLUSIONS: Our data suggest that the impact of GemA versus DA histopathology depends more upon the decade of queried data rather than patient-specific demographics. Using more recent longitudinal data, we found that grade 2 GemA and DA tumors did not have significant differences in survival. These data may prove useful for clinicians counseling patients diagnosed with grade 2 GemA.
View details for DOI 10.1016/j.wneu.2021.11.089
View details for PubMedID 34844008
-
Machine Learning Approach to Differentiation of Peripheral Schwannomas and Neurofibromas: A Multi-Center Study.
Neuro-oncology
2021
Abstract
BACKGROUND: Non-invasive differentiation between schwannomas and neurofibromas is important for appropriate management, preoperative counseling, and surgical planning, but has proven difficult using conventional imaging. The objective of this study was to develop and evaluate machine learning approaches for differentiating peripheral schwannomas from neurofibromas.METHODS: We assembled a cohort of schwannomas and neurofibromas from 3 independent institutions and extracted high-dimensional radiomic features from gadolinium-enhanced, T1-weighted MRI using the PyRadiomics package on Quantitative Imaging Feature Pipeline. Age, sex, neurogenetic syndrome, spontaneous pain, and motor deficit were recorded. We evaluated the performance of 6 radiomics-based classifier models with and without clinical features and compared model performance against human expert evaluators.RESULTS: 107 schwannomas and 59 neurofibroma were included. The primary models included both clinical and imaging data. The accuracy of the human evaluators (0.765) did not significantly exceed the no-information rate (NIR), whereas the Support Vector Machine (0.929), Logistic Regression (0.929), and Random Forest (0.905) classifiers exceeded the NIR. Using the method of DeLong, the AUC for the Logistic Regression (AUC=0.923) and K Nearest Neighbor (AUC=0.923) classifiers was significantly greater than the human evaluators (AUC=0.766; p = 0.041).CONCLUSIONS: The radiomics-based classifiers developed here proved to be more accurate and had a higher AUC on the ROC curve than expert human evaluators. This demonstrates that radiomics using routine MRI sequences and clinical features can aid in differentiation of peripheral schwannomas and neurofibromas.
View details for DOI 10.1093/neuonc/noab211
View details for PubMedID 34487172
-
Machine Assist for Pediatric Posterior Fossa Tumor Diagnosis: A Multinational Study.
Neurosurgery
2021
Abstract
BACKGROUND: Clinicians and machine classifiers reliably diagnose pilocytic astrocytoma (PA) on magnetic resonance imaging (MRI) but less accurately distinguish medulloblastoma (MB) from ependymoma (EP). One strategy is to first rule out the most identifiable diagnosis.OBJECTIVE: To hypothesize a sequential machine-learning classifier could improve diagnostic performance by mimicking a clinician's strategy of excluding PA before distinguishing MB from EP.METHODS: We extracted 1800 total Image Biomarker Standardization Initiative (IBSI)-based features from T2- and gadolinium-enhanced T1-weighted images in a multinational cohort of 274MB, 156 PA, and 97 EP. We designed a 2-step sequential classifier - first ruling out PA, and next distinguishing MB from EP. For each step, we selected the best performing model from 6-candidate classifier using a reduced feature set, and measured performance on a holdout test set with the microaveraged F1 score.RESULTS: Optimal diagnostic performance was achieved using 2 decision steps, each with its own distinct imaging features and classifier method. A 3-way logistic regression classifier first distinguished PA from non-PA, with T2 uniformity and T1 contrast as the most relevant IBSI features (F1 score 0.8809). A 2-way neural net classifier next distinguished MB from EP, with T2 sphericity and T1 flatness as most relevant (F1 score 0.9189). The combined, sequential classifier was with F1 score 0.9179.CONCLUSION: An MRI-based sequential machine-learning classifiers offer high-performance prediction of pediatric posterior fossa tumors across a large, multinational cohort. Optimization of this model with demographic, clinical, imaging, and molecular predictors could provide significant advantages for family counseling and surgical planning.
View details for DOI 10.1093/neuros/nyab311
View details for PubMedID 34392363
-
Machine-learning Approach to Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors: A Multicenter Study
AMER ASSOC NEUROLOGICAL SURGEONS. 2021
View details for Web of Science ID 000680654900137
-
Glioblastoma Multiforme (GBM): An overview of current therapies and mechanisms of resistance.
Pharmacological research
2021: 105780
Abstract
Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. Thus, durable GBM management will require the invention of innovative treatment strategies. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.
View details for DOI 10.1016/j.phrs.2021.105780
View details for PubMedID 34302977
-
Development and Validation of an Artificial Intelligence System to Optimize Clinician Review of Patient Records.
JAMA network open
2021; 4 (7): e2117391
Abstract
Importance: Physicians are required to work with rapidly growing amounts of medical data. Approximately 62% of time per patient is devoted to reviewing electronic health records (EHRs), with clinical data review being the most time-consuming portion.Objective: To determine whether an artificial intelligence (AI) system developed to organize and display new patient referral records would improve a clinician's ability to extract patient information compared with the current standard of care.Design, Setting, and Participants: In this prognostic study, an AI system was created to organize patient records and improve data retrieval. To evaluate the system on time and accuracy, a nonblinded, prospective study was conducted at a single academic medical center. Recruitment emails were sent to all physicians in the gastroenterology division, and 12 clinicians agreed to participate. Each of the clinicians participating in the study received 2 referral records: 1 AI-optimized patient record and 1 standard (non-AI-optimized) patient record. For each record, clinicians were asked 22 questions requiring them to search the assigned record for clinically relevant information. Clinicians reviewed records from June 1 to August 30, 2020.Main Outcomes and Measures: The time required to answer each question, along with accuracy, was measured for both records, with and without AI optimization. Participants were asked to assess overall satisfaction with the AI system, their preferred review method (AI-optimized vs standard), and other topics to assess clinical utility.Results: Twelve gastroenterology physicians/fellows completed the study. Compared with standard (non-AI-optimized) patient record review, the AI system saved first-time physician users 18% of the time used to answer the clinical questions (10.5 [95% CI, 8.5-12.6] vs 12.8 [95% CI, 9.4-16.2] minutes; P=.02). There was no significant decrease in accuracy when physicians retrieved important patient information (83.7% [95% CI, 79.3%-88.2%] with the AI-optimized vs 86.0% [95% CI, 81.8%-90.2%] without the AI-optimized record; P=.81). Survey responses from physicians were generally positive across all questions. Eleven of 12 physicians (92%) preferred the AI-optimized record review to standard review. Despite a learning curve pointed out by respondents, 11 of 12 physicians believed that the technology would save them time to assess new patient records and were interested in using this technology in their clinic.Conclusions and Relevance: In this prognostic study, an AI system helped physicians extract relevant patient information in a shorter time while maintaining high accuracy. This finding is particularly germane to the ever-increasing amounts of medical data and increased stressors on clinicians. Increased user familiarity with the AI system, along with further enhancements in the system itself, hold promise to further improve physician data extraction from large quantities of patient health records.
View details for DOI 10.1001/jamanetworkopen.2021.17391
View details for PubMedID 34297075
-
Machine-Learning Approach to Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors: A Multicenter Study.
Neurosurgery
2021
Abstract
BACKGROUND: Clinicoradiologic differentiation between benign and malignant peripheral nerve sheath tumors (PNSTs) has important management implications.OBJECTIVE: To develop and evaluate machine-learning approaches to differentiate benign from malignant PNSTs.METHODS: We identified PNSTs treated at 3 institutions and extracted high-dimensional radiomics features from gadolinium-enhanced, T1-weighted magnetic resonance imaging (MRI) sequences. Training and test sets were selected randomly in a 70:30 ratio. A total of 900 image features were automatically extracted using the PyRadiomics package from Quantitative Imaging Feature Pipeline. Clinical data including age, sex, neurogenetic syndrome presence, spontaneous pain, and motor deficit were also incorporated. Features were selected using sparse regression analysis and retained features were further refined by gradient boost modeling to optimize the area under the curve (AUC) for diagnosis. We evaluated the performance of radiomics-based classifiers with and without clinical features and compared performance against human readers.RESULTS: A total of 95 malignant and 171 benign PNSTs were included. The final classifier model included 21 imaging and clinical features. Sensitivity, specificity, and AUC of 0.676, 0.882, and 0.845, respectively, were achieved on the test set. Using imaging and clinical features, human experts collectively achieved sensitivity, specificity, and AUC of 0.786, 0.431, and 0.624, respectively. The AUC of the classifier was statistically better than expert humans (P=.002). Expert humans were not statistically better than the no-information rate, whereas the classifier was (P=.001).CONCLUSION: Radiomics-based machine learning using routine MRI sequences and clinical features can aid in evaluation of PNSTs. Further improvement may be achieved by incorporating additional imaging sequences and clinical variables into future models.
View details for DOI 10.1093/neuros/nyab212
View details for PubMedID 34131749
-
Impact on neurosurgical management in Level 1 trauma centers during COVID-19 shelter-in-place restrictions: The Santa Clara County experience.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
2021; 88: 128-134
Abstract
Early COVID-19-targeted legislations reduced public activity and elective surgery such that local neurosurgical care greatly focused on emergent needs. This study examines neurosurgical trauma patients' dispositions through two neighboring trauma centers to inform resource allocation. We conducted a retrospective review of the trauma registries for two Level 1 Trauma Centers in Santa Clara County, one academic and one community center, between February 1st and April 15th, 2018-2020. Events before a quarantine, implemented on March 16th, 2020, and events from 2018 to 19 were used for reference. Encounters were characterized by injuries, services, procedures, and disposition. Categorical variables were analyzed by the chi2 test, proportions of variables by z-score test, and non-parametric variables by Fisher's exact test. A total of 1,336 traumas were identified, with 31% from the academic center and 69% from the community center. During the post-policy period, relative to matching periods in years prior, there was a decrease in number of TBI and spinal fractures (24% versus 41%, p<0.001) and neurosurgical consults (27% versus 39%, p<0.003), but not in number of neurosurgical admissions or procedures. There were no changes in frequency of neurosurgery consults among total traumas, patients triaged to critical care services, or patients discharged to temporary rehabilitation services. Neurosurgical services were similarly rendered between the academic and community hospitals. This study describes neurosurgical trauma management in a suburban healthcare network immediately following restrictive quarantine during a moderate COVID-19 outbreak. Our data shows that neurosurgery remains a resource-intensive subspeciality, even during restrictive periods when overall trauma volume is decreased.
View details for DOI 10.1016/j.jocn.2021.03.017
View details for PubMedID 33992171
-
EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial.
Theranostics
2021; 11 (15): 7130-7143
Abstract
Rationale: First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG. Methods: Eleven patients with contrast-enhancing HGGs were systemically infused with panitumumab-IRDye800 at a low (50 mg) or high (100 mg) dose 1-5 days before surgery. Near-infrared fluorescence imaging was performed intraoperatively and ex vivo, to identify the optimal tumor-to-background ratio by comparing mean fluorescence intensities of tumor and histologically uninvolved tissue. Fluorescence was correlated with preoperative T1 contrast, tumor size, EGFR expression and other biomarkers. Results: No adverse events were attributed to panitumumab-IRDye800. Tumor fragments as small as 5 mg could be detected ex vivo and detection threshold was dose dependent. In tissue sections, panitumumab-IRDye800 was highly sensitive (95%) and specific (96%) for pathology confirmed tumor containing tissue. Cellular delivery of panitumumab-IRDye800 was correlated to EGFR overexpression and compromised blood-brain barrier in HGG, while normal brain tissue showed minimal fluorescence. Intraoperative fluorescence improved optical contrast in tumor tissue within and beyond the T1 contrast-enhancing margin, with contrast-to-noise ratios of 9.5 ± 2.1 and 3.6 ± 1.1, respectively. Conclusions: Panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. Smaller fragments of tumor could be detected at the 100 mg dose and thus more suitable for intraoperative imaging.
View details for DOI 10.7150/thno.60582
View details for PubMedID 34158840
View details for PubMedCentralID PMC8210618
-
Endoscopic Endonasal Resection of Rathke Cleft Cyst with Xanthogranulomatous Change: Two-Dimensional Operative Video
JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE
2021
View details for DOI 10.1055/s-0041-1727128
View details for Web of Science ID 000649537100001
-
Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases.
Journal of neuro-oncology
2021
Abstract
Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described.We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed.A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF.In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.
View details for DOI 10.1007/s11060-020-03686-3
View details for PubMedID 33415659
-
Retrograde Suction Decompression for Clipping of a Giant Ophthalmic Internal Carotid Artery Aneurysm: 2-Dimensional Operative Video.
Operative neurosurgery (Hagerstown, Md.)
2021
Abstract
Microsurgical clipping of large paraclinoid aneurysms is challenging because of the complex anatomy of the dural rings, lack of easy proximal control, and wide aneurysm necks. Proximal retrograde suction decompression, or the Dallas technique, can reduce aneurysm turgor and, with aspiration of the trapped cervical and supraclinoid internal carotid arteries (ICAs), can collapse the aneurysm to aid microsurgical clipping.1-5 A woman in her late 30s presented with decreased right-eye visual acuity. Informed written consent was obtained for microsurgical management and publication. Upon cervical exposure of the carotid bifurcation, we performed a standard pterional craniotomy, trans-sylvian exposure, and intradural anterior clinoidectomy. After burst suppression and cross-clamping of the carotid, we inserted an angiocatheter at the common carotid artery (CCA). Distal temporary clips were placed on the posterior communicating artery and C7 ICA. With the cervical ICA unclamped, retrograde suction was continuously applied to deflate the aneurysm. We applied 2 pairs of fenestrated-booster clips to the aneurysm dome and a fifth clip to the aneurysm neck. After restoration of flow, indocyanine green angiography and Doppler assessments were performed. The proximal clip was converted into a curved clip to optimize ICA flow. Postoperative angiography confirmed complete occlusion of the aneurysm. The patient was discharged on postoperative day 3, with stable visual acuity.6 This video demonstrates that retrograde suction decompression via the cervical CCA can be safely performed to facilitate clipping of complex paraclinoid ICA aneurysms. Comprehensive planning of temporary aneurysm trapping for suction decompression and permanent clip construct for aneurysm occlusion are needed for effective aneurysm repair.
View details for DOI 10.1093/ons/opab349
View details for PubMedID 34624887
-
EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial
Theranostics
2021; 11 (15): 7130-7143
View details for DOI 10.7150/thno.60582
-
Radiomic Signatures of Posterior Fossa Ependymoma: Molecular Subgroups and Risk Profiles.
Neuro-oncology
2021
Abstract
The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB.We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers.For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (p < 0.0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (p = 0.002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86.We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.
View details for DOI 10.1093/neuonc/noab272
View details for PubMedID 34850171
-
High-quality neurosurgeon communication and visualization during telemedicine encounters improves patient satisfaction
Journal of Clinical Neuroscience
2021; 94: 18-23
View details for DOI 10.1016/j.jocn.2021.09.013
-
Focused ultrasound: growth potential and future directions in neurosurgery.
Journal of neuro-oncology
2021
Abstract
Over the past two decades, vast improvements in focused ultrasound (FUS) technology have made the therapy an exciting addition to the neurosurgical armamentarium. In this time period, FUS has gained US Food and Drug Administration (FDA) approval for the treatment of two neurological disorders, and ongoing efforts seek to expand the lesion profile that is amenable to ultrasonic intervention. In the following review, we highlight future applications for FUS therapy and compare its potential role against established technologies, including deep brain stimulation and stereotactic radiosurgery. Particular attention is paid to tissue ablation, blood-brain-barrier opening, and gene therapy. We also address technical and infrastructural challenges involved with FUS use and summarize the hurdles that must be overcome before FUS becomes widely accepted in the neurosurgical community.
View details for DOI 10.1007/s11060-021-03820-9
View details for PubMedID 34410576
-
In Vivo Evaluation of Near-Infrared Fluorescent Probe for TIM3 Targeting in Mouse Glioma.
Molecular imaging and biology
2021
Abstract
Current checkpoint inhibitor immunotherapy strategies in glioblastoma are challenged by mechanisms of resistance including an immunosuppressive tumor microenvironment. T cell immunoglobulin domain and mucin domain 3 (TIM3) is a late-phase checkpoint receptor traditionally associated with T cell exhaustion. We apply fluorescent imaging techniques to explore feasibility of in vivo visualization of the immune state in a glioblastoma mouse model.TIM3 monoclonal antibody was conjugated to a near-infrared fluorescent dye, IRDye-800CW (800CW). The TIM3 experimental conjugate and isotype control were assessed for specificity with immunofluorescent staining and flow cytometry in murine cell lines (GL261 glioma and RAW264.7 macrophages). C57BL/6 mice with orthotopically implanted GL261 cells were imaged in vivo over 4 days after intravenous TIM3-800CW injection to assess tumor-specific uptake. Cell-specific uptake was then assessed on histologic sections.The experimental TIM3-800CW, but not its isotype control, bound to RAW264.7 macrophages in vitro. Specificity to RAW264.7 macrophages and not GL261 tumor cells was quantitatively confirmed with the corresponding clone of TIM3 on flow cytometry. In vivo fluorescence imaging of the 800CW signal was localized to the intracranial tumor and significantly higher for the TIM3-800CW cohort, relative to non-targeting isotype control, immediately after tail vein injection and for up to 48 h after injection. Resected organs of tumor bearing mice showed significantly higher uptake in the liver and spleen. TIM3-800CW was seen to co-stain with CD3 (13%), CD11b (29%), and CD206 (26%).We propose fluorescent imaging of immune cell imaging as a potential strategy for monitoring and localizing immunologically relevant foci in the setting of brain tumors. Alternative markers and target validation will further clarify the temporal relationship of immunosuppressive effector cells throughout glioma resistance.
View details for DOI 10.1007/s11307-021-01667-0
View details for PubMedID 34846678
-
Acetazolamide-Challenged Arterial Spin Labeling Detects Augmented Cerebrovascular Reserve After Surgery for Moyamoya
Stroke
2021
View details for DOI 10.1161/STROKEAHA.121.036616
-
Status epilepticus after intracranial neurosurgery: incidence and risk stratification by perioperative clinical features.
Journal of neurosurgery
2021: 1–13
Abstract
Status epilepticus (SE) is associated with significant mortality, cost, and risk of future seizures. In one of the first studies of SE after neurosurgery, the authors assess the incidence, risk factors, and outcome of postneurosurgical SE (PNSE).Neurosurgical admissions from the MarketScan Claims and Encounters database (2007 through 2015) were assessed in a longitudinal cross-sectional sample of privately insured patients who underwent qualifying cranial procedures in the US and were older than 18 years of age. The incidence of early (in-hospital) and late (postdischarge readmission) SE and associated mortality was assessed. Procedural, pathological, demographic, and anatomical covariates parameterized multivariable logistic regression and Cox models. Multivariable logistic regression and Cox proportional hazards models were used to study the incidence of early and late PNSE. A risk-stratification simulation was performed, combining individual predictors into singular risk estimates.A total of 197,218 admissions (218,217 procedures) were identified. Early PNSE occurred during 637 (0.32%) of 197,218 admissions for cranial neurosurgical procedures. A total of 1045 (0.56%) cases of late PNSE were identified after 187,771 procedure admissions with nonhospice postdischarge follow-up. After correction for comorbidities, craniotomy for trauma, hematoma, or elevated intracranial pressure was associated with increased risk of early PNSE (adjusted OR [aOR] 1.538, 95% CI 1.183-1.999). Craniotomy for meningioma resection was associated with an increased risk of early PNSE compared with resection of metastases and parenchymal primary brain tumors (aOR 2.701, 95% CI 1.388-5.255). Craniotomies for infection or abscess (aHR 1.447, 95% CI 1.016-2.061) and CSF diversion (aHR 1.307, 95% CI 1.076-1.587) were associated with highest risk of late PNSE. Use of continuous electroencephalography in patients with early (p < 0.005) and late (p < 0.001) PNSE rose significantly over the study time period. The simulation regression model predicted that patients at high risk for early PNSE experienced a 1.10% event rate compared with those at low risk (0.07%). Similarly, patients predicted to be at highest risk for late PNSE were significantly more likely to eventually develop late PNSE than those at lowest risk (HR 54.16, 95% CI 24.99-104.80).Occurrence of early and late PNSE was associated with discrete neurosurgical pathologies and increased mortality. These data provide a framework for prospective validation of clinical and perioperative risk factors and indicate patients for heightened diagnostic suspicion of PNSE.
View details for DOI 10.3171/2020.10.JNS202895
View details for PubMedID 33990087
-
Commentary: Predicting Postoperative Outcomes in Brain Tumor Patients With a 5-Factor Modified Frailty Index.
Neurosurgery
2020
View details for DOI 10.1093/neuros/nyaa407
View details for PubMedID 32888308
-
Extraforaminal Vertebral Artery Anomalies and their Associated Surgical Implications: an epidemiological and anatomic report on 1000 patients.
World neurosurgery
2020
Abstract
OBJECTIVE: Extraforaminal vertebral anomalies involve entry at cervical transverse foramina other than at C6 and can appear with other anatomical variations along the V2 segment. Such unexpected vessel courses can have implications on surgical planning. We sought to evaluate the incidence of anomalous V2 segment entries, as well as their associations with vessel dominance, medialization, and C7 pedicle width.METHODS: We conducted a retrospective study on 1000 consecutive computed tomography angiograms, documenting level and laterality of vessel of entry, as well as vertebral dominance patterns. Patients with rostral C4 anomalies were assessed for medialization. The pedicle widths ipsilateral to caudal C7 anomalies were compared to those of contralateral and matched controls.RESULTS: A total of 157 patients were identified with extraforaminal entries, with 25 having bilateral findings. The most common alternative entry was at C5 (70.3%), followed by C4 (17.6%) and C7 (11.5%). Among patients with unilateral anomalies, there was an increased representation of contralateral vertebral dominance, relative to ipsilateral dominance (79.6% vs 20.4%, p < 0.0001). Among anomalous C4 entries, vertebral medialization was seen along the right (35%) and left sides (23.1%) spanning C6-T1. Among C7 anomalous entries there was no statistical difference in pedicle width.CONCLUSIONS: Extraforaminal anomalies may be more frequent than previously reported and are important considerations during subaxial cervical spine surgery planning. Particular attention should be paid towards the contralateral dominance pattern within this subgroup. In patients with anomalous V2 segment entries, adherence to the standard, anatomical landmarks remains desirable.
View details for DOI 10.1016/j.wneu.2020.06.110
View details for PubMedID 32585381
-
Boda Bodas and Road Traffic Injuries in Uganda: An Overview of Traffic Safety Trends from 2009 to 2017.
International journal of environmental research and public health
2020; 17 (6)
Abstract
INTRODUCTION: Road traffic injuries (RTIs) are an important contributor to the morbidity and mortality of developing countries. In Uganda, motorcycle taxis, known as boda bodas, are responsible for a growing proportion of RTIs. This study seeks to evaluate and comment on traffic safety trends from the past decade.METHODS: Traffic reports from the Ugandan police force (2009 to 2017) were analyzed for RTI characteristics. Furthermore, one month of casualty ward data in 2015 and 2018 was collected from the Mulago National Referral Hospital and reviewed for casualty demographics and trauma type.RESULTS: RTI motorcycle contribution rose steadily from 2009 to 2017 (24.5% to 33.9%). While the total number of crashes dropped from 22,461 to 13,244 between 2010 and 2017, the proportion of fatal RTIs increased from 14.7% to 22.2%. In the casualty ward, RTIs accounted for a greater proportion of patients and traumas in 2018 compared to 2015 (10%/41% and 36%/64%, respectively).CONCLUSIONS: Although RTIs have seen a gross reduction in Uganda, they have become more deadly, with greater motorcycle involvement. Hospital data demonstrate a rising need for trauma and neurosurgical care to manage greater RTI patient burden. Combining RTI prevention and care pathway improvements may mitigate current RTI trends.
View details for DOI 10.3390/ijerph17062110
View details for PubMedID 32235768
-
Treatment patterns and outcomes for cerebellar glioblastoma in the concomitant chemoradiation era: A National Cancer database study.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
2020; 82 (Pt A): 122–27
Abstract
Cerebellar glioblastoma (GB) is much rarer than its supratentorial counterpart, and potentially of different molecular origin. Prior database studies are of limited size and reported on patients who preceded the validation of temozolomide. Thus, we provide an updated population-based analysis of the treatment trends and outcomes since the standardization of GB adjuvant chemoradiation. Patients diagnosed with primary cerebellar and supratentorial GB were identified from the National Cancer Database spanning 2005-2015. Patients were characterized by demographics, extent of resection, and adjuvant chemotherapy or radiation status. Cohorts were primarily and secondarily assessed for overall survival by tumor site and treatment history, respectively. A total of 655 patients with cerebellar GB were identified (0.6%). Cerebellar GB patients, compared to supratentorial GB were more likely to undergo a biopsy or subtotal resection (13.4% vs 9.3% and 16.0% vs 13.4%, p-value < 0.001), and less likely to pursue adjuvant therapy (48.4% vs 52.7%, p-value < 0.001). Overall median survivals were 9.3 and 9.4 months, respectively. On multivariable analysis, gross total resection, radiation, and chemotherapy were found to be predictors of improved overall survival (HR 0.77, p = 0.038; HR 0.67, p < 0.001; and HR = 0.77, p = 0.030, respectively). While many management principles are currently shared between cerebellar and supratentorial GB, aggressive regimens appear less frequently prescribed. Survival continues to match supratentorial outcomes and may benefit from future, systemic guidance by distinguishing molecular features.
View details for DOI 10.1016/j.jocn.2020.10.049
View details for PubMedID 33317719
-
Commentary: The Effects of Postoperative Neurological Deficits on Survival in Patients With Single Brain Metastasis.
Operative neurosurgery (Hagerstown, Md.)
2020
View details for DOI 10.1093/ons/opaa267
View details for PubMedID 32860056
-
Rathke's cleft cyst with xanthogranulomatous change: A case report and review of the literature.
Surgical neurology international
2020; 11: 246
Abstract
Rathke's cleft cysts (RCCs) are benign, typically asymptomatic sellar lesions found incidentally in adults, with a dramatically lower incidence in pediatric patients (<18 years). We present a case of RCC with xanthogranulomatous change (XGC) - an even less common subtype of RCC - treated by endoscopic endonasal surgical resection. This is the second reported instance of an RCC with XGC occurring in a pediatric patient.The patient is a 17-year-old male with delayed puberty who presented with bitemporal hemianopsia and was found to have a 2.6 cm lesion, initially thought to be a craniopharyngioma. He subsequently underwent uncomplicated transsphenoidal endoscopic endonasal resection. Histology confirmed the diagnosis of RCC and demonstrated marked degenerative XGCs with squamous metaplasia. The patient tolerated the procedure well with improvement in visual symptoms.RCC with XGC is a very rare pathology, particularly in the pediatric population. These lesions, while benign, can manifest clinically with significant symptoms. While treatment paradigms are not fully established with a small cohort of cases, endoscopic endonasal approaches have made surgical resection of these lesions a safe and effective treatment strategy, even in the pediatric population.
View details for DOI 10.25259/SNI_277_2020
View details for PubMedID 32905293
View details for PubMedCentralID PMC7468188
-
Elevated risk of venous thromboembolism among post-traumatic brain injury patients requiring pharmaceutical immobilization.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
2020
Abstract
Traumatic brain injury (TBI) patients are known to have a high rate of venous thromboembolism (VTE), and additional neuromuscular blockade or barbiturate coma therapy has the theoretical risk of exacerbating baseline hemostasis and elevating the incidence of thromboembolic events. We conducted a single-institution retrospective review of patients surviving severe TBI, as determined by need for intracranial pressure (ICP) monitoring, who further required paralytics or barbiturate therapy to maintain ICP control. Patients were administered VTE prophylaxis as clinically appropriate. Predictors for VTE were subsequently determined with univariate and logistic multivariate regression analyses. The main cohort includes 144 patients, 34 of whom received pharmaceutical immobilization for ICP control. Mean ISS and GCS at intake were 31.9 and 5.2, respectively. Among those receiving vs not-receiving paralytics and/or barbiturate therapy, there was a statistical difference of 12/34 (35.3%) vs 18/110 (16.4%, p = 0.0280) in VTE events, at a mean time greater than two weeks from the time of trauma. Multivariate logistics regression indicated 3.2 times increased odds of developing a VTE (log odds = 1.17, p = 0.023). No pediatric patients were positive for an event (0/12 vs 7/22, p = 0.0356), and infections were only documented among those with VTE (0/22 vs 4/12, p = 0.0107). Overall, paralytics and barbiturate therapy were correlated with a higher incidence of VTE among TBI patients. Although the need for ICP control will outweigh an increase in thromboembolic risk, there is value for increased surveillance and screening during the prolonged inpatient stay of these patients.
View details for DOI 10.1016/j.jocn.2020.03.028
View details for PubMedID 32245600
-
Costs and Complications Associated with Resection of Supratentorial Tumors with and without the Operative Microscope in the United States.
World neurosurgery
2020
Abstract
The operative microscope, a commonly used tool in neurosurgery, is critical in many supratentorial tumor cases. However, use of operating microscope for supratentorial tumor varies by surgeon.To assess complication rates, readmissions, and costs associated with operative microscope use in supratentorial resections.A retrospective analysis was conducted using a national administrative database to identify patients with glioma or brain metastases who underwent supratentorial resection between 2007 and 2016. Univariate and multivariate analyses were used to assess 30-day complications, readmissions and costs between patients who underwent resection with and without use of microscope.The cohort included 12058 glioma patients and 5433 metastasis patients. Rates of microscope use varied by state from 19.0% to 68.6%. Microscope use was associated with $5228.9 in additional costs of index hospitalization among glioma patients (p < 0.001), and $2824.0 among metastasis patients (p < 0.001). Rates of intraoperative cerebral edema were lower among the microscope cohort than among the non-microscope cohort (p < 0.027). Microscope use was associated with a slight reduction in 30-day rates of neurological complications (14.7% vs. 16.7%, p = 0.048), specifically in nonspecific cerebrovascular complications. There were no differences in rates of other complications, readmissions, or 30-day postoperative costs.Use of operative microscope for supratentorial resections varies by state and is associated with higher cost of surgery. Microscope use may be associated with lower rates of intraoperative cerebral edema and some cerebrovascular complications, but is not associated with significant differences in other complications, readmissions, or 30-day costs.
View details for DOI 10.1016/j.wneu.2020.03.021
View details for PubMedID 32171932
-
Intracranial Tumor Control Following Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma.
World neurosurgery
2020
Abstract
Immunotherapy for melanoma patients with brain metastasis has significantly improved outcomes; however, they have also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports suggest these reactions can precede improved treatment responses. We sought to identify if such association exists for intracranial disease control.We conducted a retrospective chart review of melanoma patients who underwent immunotherapy treatment following diagnosis of brain metastasis. The study cohort was then stratified into two groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analysis were used to evaluate survival and predictors of outcomes.Fifty-two patients met inclusion criteria, seventeen of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 vs 10.5 months (p = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival, mean (33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (p = 0.013, HR = 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (p = 0.015, HR = 10.73) CONCLUSION: Immune related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to demonstrate promising outcomes as a first-line agent for melanoma with brain metastasis.
View details for DOI 10.1016/j.wneu.2020.08.124
View details for PubMedID 32853767
-
Contralateral acute vascular occlusion following revascularization surgery for moyamoya disease
JOURNAL OF NEUROSURGERY
2019; 131 (6): 1702–8
Abstract
OBJECTIVERevascularization surgery is a safe and effective surgical treatment for symptomatic moyamoya disease (MMD) and has been shown to reduce the frequency of future ischemic events and improve quality of life in affected patients. The authors sought to investigate the occurrence of acute perioperative occlusion of the contralateral internal carotid artery (ICA) with contralateral stroke following revascularization surgery, a rare complication that has not been previously reported.METHODSThis study is a retrospective review of a prospective database of a single surgeon's series of revascularization operations in patients with MMD. From 1991 to 2016, 1446 bypasses were performed in 905 patients, 89.6% of which involved direct anastomosis of the superficial temporal artery (STA) to a distal branch of the middle cerebral artery (MCA). Demographic, surgical, and radiographic data were collected prospectively in all treated patients.RESULTSSymptomatic contralateral hemispheric infarcts occurred during the postoperative period in 34 cases (2.4%). Digital subtraction angiography (DSA) was performed in each of these patients. In 8 cases (0.6%), DSA during the immediate postoperative period revealed associated new occlusion of the contralateral ICA. In each of these cases, revascularization surgery involved direct anastomosis of the STA to an M4 branch of the MCA. Preoperative DSA revealed moderate (n = 1) or severe (n = 3) stenosis or occlusion (n = 4) of the ipsilateral ICA and mild (n = 2), moderate (n = 4), or severe (n = 2) stenosis of the contralateral ICA. The baseline Suzuki stage was 4 (n = 7) or 5 (n = 1). The collateral supply originated exclusively from the intracranial circulation in 4/8 patients (50%), and from both the intracranial and extracranial circulation in the remaining 50% of patients. Seven (88%) of 8 patients improved symptomatically during the acute postoperative period with induced hypertension. The modified Rankin Scale (mRS) score at discharge was worse than baseline in 7/8 patients (88%), whereas 1 patient had only minor deficits that did not affect the mRS score. At the 3-year follow-up, 3/8 patients (38%) were at their baseline mRS score or better, 1 patient had significant disability compared with preoperatively, 2 patients had died, and 1 patient was lost to follow-up. Three-year follow-up is not yet available in 1 patient.CONCLUSIONSAcute occlusion of the ICA on the contralateral side from an STA-MCA bypass is a rare, but potentially serious, complication of revascularization surgery for MMD. It highlights the importance of the hemodynamic interrelationships that exist between the two hemispheres, a concept that has been previously underappreciated. Induced hypertension during the acute period may provide adequate cerebral blood flow via developing collateral vessels, and good outcomes may be achieved with aggressive supportive management and expedited contralateral revascularization.
View details for DOI 10.3171/2018.8.JNS18951
View details for Web of Science ID 000500253800003
View details for PubMedID 30554188
-
Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
2019
Abstract
We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomide and MRT (n = 9), AGuIX and MRT (n = 7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n = 9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1 h after intravenous injection, reaching a mean of 227.9 ± 60 muM. This was compared to concentrations of 10.5 ± 9.2 muM and 62.9 ± 24.7 muM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p < 0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46 days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation.
View details for DOI 10.1016/j.jocn.2019.05.065
View details for PubMedID 31281087
-
Microglia are effector cells of CD47-SIRP alpha antiphagocytic axis disruption against glioblastoma
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2019; 116 (3): 997–1006
View details for DOI 10.1073/pnas.1721434116
View details for Web of Science ID 000455610300043
-
Microglia are effector cells of CD47-SIRPalpha antiphagocytic axis disruption against glioblastoma.
Proceedings of the National Academy of Sciences of the United States of America
2019
Abstract
Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the tumor microenvironment. Hence, modulation and reeducation of tumor-associated macrophages and microglia in GBM is considered a promising antitumor strategy. Resident microglia and invading macrophages have been shown to have distinct origin and function. Whereas yolk sac-derived microglia reside in the brain, blood-derived monocytes invade the central nervous system only under pathological conditions like tumor formation. We recently showed that disruption of the SIRPalpha-CD47 signaling axis is efficacious against various brain tumors including GBM primarily by inducing tumor phagocytosis. However, most effects are attributed to macrophages recruited from the periphery but the role of the brain resident microglia is unknown. Here, we sought to utilize a model to distinguish resident microglia and peripheral macrophages within the GBM-TAM pool, using orthotopically xenografted, immunodeficient, and syngeneic mouse models with genetically color-coded macrophages (Ccr2 RFP) and microglia (Cx3cr1 GFP). We show that even in the absence of phagocytizing macrophages (Ccr2 RFP/RFP), microglia are effector cells of tumor cell phagocytosis in response to anti-CD47 blockade. Additionally, macrophages and microglia show distinct morphological and transcriptional changes. Importantly, the transcriptional profile of microglia shows less of an inflammatory response which makes them a promising target for clinical applications.
View details for PubMedID 30602457
-
Outcomes and costs following Ommaya placement with thrombocytopenia among US cancer patients.
World neurosurgery
2019
Abstract
Placement of Ommaya reservoirs for administration of intrathecal chemotherapy may be complicated by comorbid thrombocytopenia among patients with hematologic or leptomeningeal disease. Aggregated data on risks of Ommaya placement among thrombocytopenic patients is lacking. This study assesses complications, revision rates, and costs associated with Ommaya placement among patients with thrombocytopenia in a large population sample.Using a national administrative database, this retrospective study identifies a cohort of adult cancer patients who underwent Ommaya placement between 2007 and 2016. Preoperative thrombocytopenia was defined as diagnosis of secondary thrombocytopenia, bleeding event, procedure to control bleeding, or platelet transfusion, within 30 days prior to index admission. Univariate and multivariate analyses were performed to assess costs, 30-day complications, readmissions, and revisions among patients with and without preoperative thrombocytopenia.The analytic cohort included 1652 patients, of whom 29.3% met criteria for preoperative thrombocytopenia. In-hospital mortality rates were 7.7% among thrombocytopenic patients vs. 1.2% among non-thrombocytopenic patients (p < 0.001). Preoperative thrombocytopenia was associated with 14.5 times greater hazard of intracranial hemorrhage within 30 days following Ommaya placement, occurring in 25.6% vs. 2.0% of thrombocytopenic and non-thrombocytopenic patients, respectively (p < 0.014). Revision rates did not differ significantly between thrombocytopenic and non-thrombocytopenic patients. Thrombocytopenia was associated with longer length of stay (7.4 vs 13.9 days, p < 0.001) and additional $10,000 per patient in costs of index hospitalization (p < 0.001).This is the largest study to date documenting costs and complication rates of Ommaya placement in patients with and without thrombocytopenia.
View details for DOI 10.1016/j.wneu.2019.12.063
View details for PubMedID 31866457
-
Milestones in stereotactic radiosurgery for the central nervous system
JOURNAL OF CLINICAL NEUROSCIENCE
2019; 59: 12–19
View details for DOI 10.1016/j.jocn.2018.09.029
View details for Web of Science ID 000457660200003
-
Non-Contrast T2-Weighted MR Sequences for Long Term Monitoring of Asymptomatic Convexity Meningiomas.
World neurosurgery
2019
Abstract
Gadolinium based contrast agents (GBCA) used to enhance MRs have been linked to tissue deposition, including in the brain. The management of indolent tumors such as meningiomas requires frequent MRs to monitor for interval growth. Given concern regarding GBCA deposition, we sought to determine if non-contrast MRs in patients with asymptomatic meningiomas were equivalent to GBCA-enhanced MRs in surveillance monitoring.This IRB-approved retrospective chart review included 106 MR sequences from 18 patients. Inclusion criteria were adult patients with asymptomatic meningiomas who received baseline contrast-enhanced and non-contrast axial MR imaging of the brain. Exclusion criteria included: 1) baseline or follow-up axial images were not available for review 2) baseline scan was obtained without contrast 3) diagnosis of meningioma was uncertain. Percent tumor growth was measured by comparing cross-sectional area at maximum tumor diameter from the earliest and most recent scans. For each patient, change in tumor size over time was compared using T1+contrast, T2, and T2 FLAIR sequences. These were compared to a qualitative consensus reading by a neurosurgeon and a neuroradiologist.Measured change of greater than 10% was taken to represent tumor growth. In 17 out of 18 patients, measurement of non-contrast studies (T2 and T2 FLAIR) matched consensus. For one patient, imaging on T2 suggested 11% growth while T2 FLAIR and overall consensus was stability.Our study provides evidence that non-contrasted MR images are equivalent to contrast-weighted MRs to follow change in tumor size over time in asymptomatic meningiomas.
View details for DOI 10.1016/j.wneu.2019.11.051
View details for PubMedID 31734418
-
Milestones in stereotactic radiosurgery for the central nervous system.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
2019; 59: 12–19
Abstract
INTRODUCTION: Since Lars Leksell developed the first stereotactic radiosurgery (SRS) device in 1951, there has been growth in the technologies available and clinical indications for SRS. This expansion has been reflected in the medical literature, which is built upon key articles and institutions that have significantly impacted SRS applications. Our aim was to identify these prominent works and provide an educational tool for training and further inquiry.METHOD: A list of search phrases relating to central nervous system applications of stereotactic radiosurgery was compiled. A topic search was performed using PubMed and Scopus databases. The journal, year of publication, authors, treatment technology, clinical subject, study design and level of evidence for each article were documented. Influence was proposed by citation count and rate.RESULTS: Our search identified a total of 10,211 articles with the top 10 publications overall on the study of SRS spanning 443-1313 total citations. Four articles reported on randomized controlled trials, all of which evaluated intracranial metastases. The most prominent subtopics included SRS for arteriovenous malformation, glioblastoma, and acoustic neuroma. Greatest representation by treatment modality included Gamma Knife, LINAC, and TomoTherapy.CONCLUSIONS: This systematic reporting of the influential literature on SRS for intracranial and spinal pathologies underscores the technology's rapid and wide reaching clinical applications. Moreover the findings provide an academic guide to future health practitioners and engineers in their study of SRS for neurosurgery.
View details for PubMedID 30595165
-
Lumbar Puncture for the Injection of Intrathecal Fluorescein: Should It Be Avoided in a Subset of Patients Undergoing Endoscopic Endonasal Resection of Sellar and Parasellar Lesions?
Journal of neurological surgery. Part B, Skull base
2018; 79 (6): 554–58
Abstract
Objectives The use of intrathecal fluorescein (ITF) has become an increasingly adopted practice for the identification of cerebrospinal fluid (CSF) leaks during endoscopic skull base surgery for pituitary adenomas. Administration through lumbar puncture can result in postoperative positional headaches, increasing morbidity, cost, and length of stay. We sought to identify the incidence of and variables associated with postoperative headaches to determine if there was a subgroup of patients in whom this procedure should be avoided. Methods We conducted a retrospective single-institution review of 148 patients who underwent endoscopic resection with ITF for pituitary adenoma between December 2003 and February 2016. We excluded patients who had lumbar drains and with intraoperative CSF leak, as these patients may have other headache etiologies. Patient demographics, comorbidities, tumor features, surgical approach, surgical closure, and histology were recorded. Primary outcomes included the presence of postoperative and positional headaches. Results We identified 62 patients with postoperative headaches (41.9%) and 10 with positional headaches (6.8%), of whom 6 underwent blood patch with complete resolution. Following univariate analysis, there was a significant positive association with prolactin-secreting tumors ( p =0.008). There was a negative association with a history of hypertension ( p =0.0001) and age ( p =0.01). Following multivariate modeling, the significance for hypertension ( p =0.01) was preserved. Conclusions Positional headaches in patients who receive ITF are uncommon and should not limit its use in the preparations for endoscopic resection of pituitary adenomas. Avoiding ITF in younger patients without hypertension with prolactinomas might decrease the risk of post-ITF positional headaches.
View details for DOI 10.1055/s-0038-1635257
View details for PubMedID 30456024
-
Long-Term Effectiveness of Gross-Total Resection for Symptomatic Spinal Cord Cavernous Malformations
NEUROSURGERY
2018; 83 (6): 1201–8
View details for DOI 10.1093/neuros/nyx610
View details for Web of Science ID 000454360000027
-
Radiographic Rate and Clinical Impact of Pseudarthrosis in Spine Radiosurgery for Metastatic Spinal Disease.
Cureus
2018; 10 (11): e3631
Abstract
Purpose Pseudarthrosis within the spine tumor population is increased from perioperative radiation and complex stabilization for invasive and recurrent pathology. We report the radiographic and clinical rates of pseudarthrosis following multiple courses of instrumented fusion and perioperative stereotactic radiosurgery (SRS). Methods We performed a single institution review of 418 patients treated with non-isocentric SRS for spine between October 2002 and January 2013, identifying those with spinal instrumentation and greater than six months of follow-up. Surgical history, radiation planning, and radiographic outcomes were documented. Results Eleven patients whomet criteria for inclusion underwent 21 sessions of spinal SRS and 16 instrumented operations. Radiographic follow-up was 48.9 months; 3/11 (27%) were with radiographic hardware failure, and one (9%) separate case ultimately warranted externalization due to tumor recurrence. SRS was administered to treat progression of disease in 12/21 (57%) procedures, and residual lesions in 7/11 (64%) procedures. Following first and second SRS, 8/11 (73%) and 2/7 (29%) patients were with symptomatic improvement, respectively. Conclusion Risk of pseudarthrosis following SRS for patients with oncologic spinal lesions will become increasingly apparent with the optimized management of and survival from spinal pathologies. We highlight how the need for local control outpaces the risk of instrumentation failure.
View details for PubMedID 30705790
-
Radiographic Rate and Clinical Impact of Pseudarthrosis in Spine Radiosurgery for Metastatic Spinal Disease
CUREUS
2018; 10 (11)
View details for DOI 10.7759/cureus.3631
View details for Web of Science ID 000458695500098
-
How Intraoperative Tools and Techniques Have Changed the Approach to Brain Tumor Surgery
CURRENT ONCOLOGY REPORTS
2018; 20 (11)
View details for DOI 10.1007/s11912-018-0723-9
View details for Web of Science ID 000445745000002
-
How Intraoperative Tools and Techniques Have Changed the Approach to Brain Tumor Surgery.
Current oncology reports
2018; 20 (11): 89
Abstract
PURPOSE OF REVIEW: Surgical treatment of brain tumors remains an integral part of a comprehensive treatment plan. Here, we review technological advances that have enhanced what surgeons are capable of doing within and outside the traditional operating room.RECENT FINDINGS: Extent of surgical resection has improved with the use of MRI and fluorescent dyes intraoperatively. Neurological injury during brain tumor surgery has decreased with appropriate use of neurophysiological monitoring. New operative scopes have enhanced ability of surgeons to visualize tissues during dissection. Laser interstitial therapy and radiation treatment have made possible the treatment of previously considered non-operable brain tumors in addition to replacing or serving as adjunct to surgical treatment of brain tumors. Surgery remains an important pillar in treatment of most brain tumors. Ongoing technological advances have augmented extent of what is possible in this realm.
View details for PubMedID 30259202
-
Brainstem Dose Constraints in Nonisometric Radiosurgical Treatment Planning of Trigeminal Neuralgia: A Single-Institution Experience
WORLD NEUROSURGERY
2018; 113: E399–E407
Abstract
CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) administers nonisometric, conformational high-dose radiation to the trigeminal nerve with risk of subsequent hypoesthesia.We performed a retrospective, single-institution review of 66 patients with TGN treated with CyberKnife SRS to compare outcomes from 2 distinct treatment periods: standard dosing (n = 38) and reduced dosing (n = 28). Standard and reduced dosing permitted a maximum brainstem dose of 45 Gy and 25 Gy, respectively, each with a prescription dose of 60 Gy. Primary and secondary outcomes were Barrow Neurologic Institute pain and numbness scores. Maximum brainstem dose, prepontine nerve length, and treatment history were recorded for their predictive contributions by logistic regression.After matching, patients in the standard dosing and reduced dosing groups were followed for a median of 25 months and 19.5 months, respectively. Mean trigeminal nerve length was 8.55 mm in the standard dosing group and 9.46 mm in the reduced dosing group. Baseline rates of poorly controlled pain were 97% and 88%, respectively, which improved to 23.4% and 8.3%, respectively (P < 0.001 for both). The baseline rates of bothersome numbness were null in both groups, and increased to 25% in the standard group (P = 0.006) and to 21% in the reduced group (P = 0.07). Regression analyses suggested that reduced brainstem exposure (P = 0.01), as well as a longer trigeminal nerve (P = 0.01), were predictive of durable pain control.These outcomes demonstrate that a lower maximum brainstem dose can provide excellent pain control without affecting facial numbness. Longer nerves may achieve better long-term outcomes and help optimize individual plans.
View details for PubMedID 29454124
-
Long-Term Effectiveness of Gross-Total Resection for Symptomatic Spinal Cord Cavernous Malformations.
Neurosurgery
2018
Abstract
Intramedullary spinal cord cavernous malformations (CMs) account for 5% of all CMs in the central nervous system and 5% to 12% of all spinal cord vascular lesions, yet their optimal management is controversial.To identify factors associated with the clinical progression of spinal cord CMs and quantify the range of surgical outcomes.Retrospective observational cohort study of 32 patients who underwent open surgical resection for spinal CMs, the majority of which presented to a dorsal or lateral pial surface, from 1996 to 2017 at a single institution. We evaluated outcomes as clinically improved, worsened, or unchanged against preoperative baseline; Frankel and Aminoff-Logue disability grades were also calculated.Mean age at presentation was 44.2 (range, 0.5-77 yr). Symptoms included sensory deficits (n = 26, 81%), loss of strength/coordination (n = 16, 50%), pain (n = 16, 50%), and bladder/bowel dysfunction (n = 6, 19%). Thoracic (n = 16, 50%) and cervical CMs (n = 16, 50%) were equally common, with overall mean size of 7.1 mm (range, 1-20 mm). Functional outcomes at last follow-up, compared to preoperative status for patients with >6 mo of follow-up, were improved in 6 (23%), unchanged in 19 (73%), and worsened in 1 (4%) patients. Preoperative Frankel grade and improved Frankel grade immediately following resection were strongly associated with improvement from baseline at long-term followup (P < .01).Gross total resection of symptomatic spinal cord CMs can prevent further neurological decline. Our experience suggests excellent long-term outcomes and minimal surgical morbidity following resection.
View details for PubMedID 29425323
-
Implications of Antiangiogenic Therapy on Radiographic Assessment of Brain Tumors
WORLD NEUROSURGERY
2017; 108: 380–82
View details for DOI 10.1016/j.wneu.2017.09.035
View details for Web of Science ID 000415874900050
-
Management of Arteriovenous Malformations Associated with Developmental Venous Anomalies: A Literature Review and Report of 2 Cases
WORLD NEUROSURGERY
2017; 106: 563–69
Abstract
Classification of cerebrovascular malformations has revealed intermediary lesions that warrant further review owing to their unusual presentation and management. We present 2 cases of arteriovenous malformation (AVM) associated with a developmental venous anomaly (DVA), and discuss the efficacy of previously published management strategies.Two cases of AVMs associated with DVA were identified, and a literature search for published cases between 1980 and 2016 was conducted. Patient demographic data and clinical features were documented.In case 1, a 29-year-old female presenting with parenchymal hemorrhage and left homonymous hemianopia was found to have a right parieto-occipital AVM fed from the anterior cerebral, middle cerebral, and posterior cerebral arteries, with major venous drainage to the superior sagittal sinus. In case 2, imaging in a 34-year-old female evaluated for night tremors and incontinence revealed a left parietal AVM with venous drainage to the superior sagittal sinus. Including our 2 cases, 22 cases of coexisting AVMs and DVAs have been reported in the literature. At presentation, 68% had radiographic evidence of hemorrhage. Stereotactic radiosurgery was performed in 7 cases, embolization in 6 cases, surgical resection in 4 cases, and multimodal therapy in 5 cases. Radiography at follow-up demonstrated successful AVM obliteration in 67% of cases (12 of 18).Patients with coexisting AVMs and DVAs tend to have a hemorrhagic presentation. Contrary to traditional AVM management, in these cases it is important to preserve the draining vein via the DVA to ensure a safe, sustained circulatory outflow of the associated brain parenchyma while achieving safe AVM obliteration.
View details for PubMedID 28735125
-
Surgeon Procedure Volume and Complication Rates in Anterior Cervical Discectomy and Fusions: Analysis of a National Longitudinal Database.
Clinical spine surgery
2017; 30 (5): E633-E639
Abstract
Retrospective study using the MarketScan longitudinal database (2006-2010).Compare complication rates between groups of patients undergoing anterior cervical discectomy and fusion (ACDF) procedures performed by surgeons with high versus low mean annual ACDF volume.Over the past decade the volume of ACDFs performed has increased, concurrent with greater appreciation of potential for associated complications. The effect of surgeon procedure volume on adverse events occurrence in the postoperative period has not been described.We evaluated the relationship between surgeon procedure volume and postoperative incidence of any complication using a multivariate logistic regression model. A total of 24,461 patients undergoing single and multiple level ACDFs were identified in the MarketScan database by Current Procedural Terminology coding. Annual surgeon volume was determined by tracking of anonymized surgeon identification numbers, with high-volume surgeons defined as those performing an average of at least 30 ACDF procedures annually.Over 50% of unique surgeon identifiers reported <9 ACDF operations per year, whereas the highest decile reported a range of 44-101. High surgeon volume was protective for any complication [odds ratio (OR), 72; 95% confidence interval, 0.65-0.81; P<0.0001], with an adjusted number needed to harm of 44. Patients treated by high-volume physicians specifically had lower odds of dysphagia (2.22% vs. 3.08%; OR, 0.71; P<0.0013), neurological complications (0.33% vs. 0.64%; OR, 0.52; P<0.0107), new diagnosis of chronic pain (0.48% vs. 0.82%; OR, 0.58; P<0.0119), pulmonary complications (1.10% vs. 1.58%; OR, 0.69; P<0.0138), and other wound complications (0.06% vs. 0.22%; OR, 0.28; P<0.0242).We demonstrate a possible association between higher surgeon procedure volume and decreased postoperative complications after ACDF. There was no difference observed in need for revision surgery or readmission rates.
View details for DOI 10.1097/BSD.0000000000000238
View details for PubMedID 28525490
-
Surgeon Adherence to Medical Ethics as Contingent on Their Leadership in the Changing Economics of Health Care.
World neurosurgery
2017
View details for DOI 10.1016/j.wneu.2017.04.115
View details for PubMedID 28456737
-
Disrupting the CD47-SIRP alpha anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors
SCIENCE TRANSLATIONAL MEDICINE
2017; 9 (381)
Abstract
Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic agent for managing multiple pediatric central nervous system malignancies.
View details for DOI 10.1126/scitranslmed.aaf2968
View details for PubMedID 28298418
-
Clinical and Arterial Spin Labeling Brain MRI Features of Transitional Venous Anomalies.
Journal of neuroimaging : official journal of the American Society of Neuroimaging
2017
Abstract
Transitional venous anomalies (TVAs) are rare cerebrovascular lesions that resemble developmental venous anomalies (DVAs), but demonstrate early arteriovenous shunting on digital subtraction angiography (DSA) without the parenchymal nidus of arteriovenous malformations (AVMs). We investigate whether arterial spin labeling (ASL) magnetic resonance imaging (MRI) can distinguish brain TVAs from DVAs and guide their clinical management.We conducted a single-center retrospective review of patients with brain parenchymal DVA-like lesions with increased ASL signal on MRI. Clinical histories and follow-up information were obtained. Two readers assessed ASL signal location relative to the vascular lesion on MRI and, if available, the presence of arteriovenous shunting on DSA.Thirty patients with DVA-like lesions with increased ASL signal were identified. Clinical symptoms prompted MRI evaluation in 83%. Symptoms did not localize to the venous anomaly in 90%. Ten percent presented with acute symptoms, only one of whom presented with hemorrhage. ASL signal in relation to the venous anomaly was identified in: 50% in the adjacent parenchyma, 33% in the lesion, 7% in a distal draining vein/sinus, and 10% in at least two of these sites. Follow-up DSA confirmed arteriovenous shunting in 71% of ASL-positive venous anomalies. Interrater agreement was very good (κ = .81-1.0, P < .001).A DVA-like lesion with increased ASL signal likely represents a TVA with arteriovenous shunting. Our study indicates that these lesions are usually incidentally detected and have a lower risk of hemorrhage than AVMs. ASL-MRI may be a useful tool to identify TVAs and guide further management of patients with TVAs.
View details for PubMedID 29205641
-
Implications of Antiangiogenic Therapy on Radiographic Assessment of Brain Tumors.
World neurosurgery
2017; 108: 380–82
View details for PubMedID 28919561
-
CyberKnife stereotactic radiosurgery for the treatment of symptomatic vertebral hemangiomas: a single-institution experience
NEUROSURGICAL FOCUS
2017; 42 (1)
Abstract
OBJECTIVE Symptomatic vertebral hemangiomas (SVHs) are a very rare pathology that can present with persistent pain or neurological deficits that warrant surgical intervention. Given the relative rarity and difficulty in assessment, the authors sought to present a dedicated series of SVHs treated using stereotactic radiosurgery (SRS) to provide insight into clinical decision making. METHODS A retrospective review of a single institution's experience with hypofractionated radiosurgery for SVH from 2004 to 2011 was conducted to determine the clinical and radiographic outcomes following SRS treatment. The authors report and analyze the treatment course of 5 patients with 7 lesions, 2 of which were treated primarily by SRS. RESULTS Of the 5 patients studied, 4 presented with a chief complaint of pain refractory to conservative measures. Three patients reported dysesthesias, and 2 reported upper-extremity weakness. Following radiosurgery, 4 of 5 patients exhibited improvement in their primary symptoms (3 for pain and 1 for weakness), achieving a clinical response after a mean period of 1 year. In 2 cases there was 20%-40% reduction in lesion size in the most responsive dimension as noted on images. All treatments were well tolerated. CONCLUSIONS SRS for SVH is a safe and feasible treatment strategy, comparable to prior radiotherapy studies, and in select cases may successfully confer delayed decompressive effects. Additional investigation will determine future patient selection and how conformal SRS treatment can best be administered.
View details for DOI 10.3171/2016.9.FOCUS16372
View details for Web of Science ID 000392113200013
View details for PubMedID 28041316
-
Outcomes of cervical laminoplasty-Population-level analysis of a national longitudinal database.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
2017
Abstract
Cervical laminoplasty is an important alternative to laminectomy in decompressing of the cervical spine. Further evidence to assess the utility of laminoplasty is required. We examine outcomes of cervical laminoplasty via a population level analysis in the United States.We performed a population-level analysis using the national MarketScan longitudinal database to analyze outcomes and costs of cervical laminoplasty between 2007 and 2014. Outcomes included postoperative complications, revision rates, and functional outcomes.Using a national administrative database, we identified 2613 patients (65.6% male, mean 58.5 years) who underwent cervical laminoplasty. Mean length of stay was 3.1 ± 2.8 days and mean follow-up was 795.5 ± 670.6 days. The overall complication rate was 22.5% (N = 587), 30-day readmission rate was 7.5% (N = 195), and mortality rate was 0.08% (N = 2, elderly patients only). The complication rate was significantly increased in elderly patients (age >65 years) compared to non-elderly patients (OR 0.751, p < .01). The use of intraoperative neuromonitoring (IONM) during the cervical laminoplasty procedure did not significantly impact outcomes. The overall re-operation rate after the initial procedure was 10.9%. Total costs of cervical laminoplasty were mainly driven by hospital charges with physician-related payments comprising a small amount.Our national analysis of cervical laminoplasty found the procedure to be clinically effective with low complication rates and postoperative symptomatic improvement.
View details for PubMedID 29153782
-
The Outcome of Hypofractionated Stereotactic Radiosurgery for Large Vestibular Schwannomas.
World neurosurgery
2016; 93: 398-409
Abstract
Stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS) remains controversial. We studied the tumor local control and toxicity rates after hypofractionated SRS for VS > 3 cm.A total of 587 patients with VS treated with SRS between 1998 and 2014 were reviewed retrospectively, and 30 Koos grade IV VSs were identified. There were 6 patients with neurofibromatosis 2 (NF2), 8 with cystic tumors, 22 with solid tumors, 19 who underwent primary CyberKnife (CK), and 11 with >3 cm after previous resection. Patients were treated by a median of 3 fractions at 18 Gy.After a median 97 months, the 3- and 10-year Kaplan-Meier estimates of local control were 85% and 80%, respectively, with 20% requiring salvage treatment. For patients who had previous tumor resection rather than primary CK, the estimates were 46% and 5%, respectively, with progression, and 3-year control rates of 71% and 94% (P = 0.008). Tumor control was also lower among NF2 versus non-NF2 patients (40% vs. 95%; P = 0.0014). Among patients with good clinical baselines before CK, 88% were functionally independent (modified Rankin Scale score, 0-2), 88% had good facial function (House-Brackmann grade I-II), and 38% had serviceable hearing (Gardner-Robertson grade I-II) at last follow-up. Hearing worsening was more likely among patients treated with primary CK (33% vs. 90%; P = 0.04).Overall, 80% of large VSs were adequately controlled by CK with 97 months of median follow-up. Patients with previous surgery and NF2 also appeared to have higher rates of tumor progression, and less favorable functional outcomes.
View details for DOI 10.1016/j.wneu.2016.06.080
View details for PubMedID 27368508
-
Required Reading: The Most Impactful Articles in Endoscopic Endonasal Skull Base Surgery.
World neurosurgery
2016; 92: 499-512 e2
Abstract
Endoscopic endonasal skull base surgery has become a widely accepted field in neurosurgery and otolaryngology over the last 15 years. However, there has yet to be a formal curation of the most impactful articles for an introductory curriculum to its technical evolution.The Science Citation Index Expanded was used to generate a citation rank list (October 2015) on articles relevant to endoscopic skull base surgery. The top 35 cited articles overall, as well as the top 15 since 2009, were identified. Journal, year, author, study population, article format, and level of evidence were compiled. Additional surgeon-experts were polled and made recommendations for significant contributions to the literature.The top 35 publications ranged from 98 to 467 citations and were published in 10 different journals. Four articles had over 250 citations. A period of frequent contribution occurred between 2005-2009, when 21/35 reports were published. 18/35 articles were case series, and 13/35 were technical reports. There were 11/35 articles focused primarily on pituitary surgery, and 10/35 on extra-sellar lesions. The top 15 articles since 2009 had 8/15 articles focus on extra-sellar lesions. Polled surgeons consistently identified the most prominently cited articles, and their recommendations drew attention to CSF-leak as well as extra-sellar management.Identification of the most cited works within endoscopic endonasal skull base surgery demonstrates greater anatomical access and safety over the last two decades. These articles can serve as an educational tool for novices or mid-level practitioners wishing to obtain a greater understanding of the field.
View details for DOI 10.1016/j.wneu.2016.06.016
View details for PubMedID 27312387
-
CyberKnife Stereotactic Radiosurgery for Atypical and Malignant Meningiomas.
World neurosurgery
2016; 91: 574-581 e1
Abstract
Recurrent World Health Organization (WHO) grade II and III meningiomas have traditionally been treated by surgery alone, but early literature suggests that adjuvant stereotactic radiosurgery may greatly improve outcomes. We present the long-term tumor control and safety of a hypofractionated stereotactic radiosurgery regimen.Prospectively collected data of 44 WHO grade II and 9 WHO grade III meningiomas treated by CyberKnife for adjuvant or salvage therapy were reviewed. Patient demographics, treatment parameters, local control, regional control, locoregional control, overall survival, radiation history, and complications were documented.For WHO grade II patients, recurrence occurred in 41%, with local, regional, and locoregional failure at 60 months recorded as 49%, 58%, and 36%. For WHO grade III patients, recurrence occurred in 66%, with local, regional, and locoregional failure at 12 months recorded as 57%, 100%, and 43%. The 60-month locoregional control rates for radiation naïve and experienced patients were 48% and 0% (P = 0.14). Overall, 7 of 44 grade II patients and 8 of 9 grade III patients had died at last follow-up. The 60-month and 12-month overall survival rates for grade II and III meningiomas were 87% and 50%, respectively. Serious complications occurred in 7.5% of patients.Stereotactic radiosurgery for adjuvant and salvage treatment of WHO grade II meningioma using a hypofractionated plan is a viable treatment strategy with acceptable long-term tumor control, overall survival, and complication rates. Future studies should focus on radiation-naïve patients and local management of malignant meningioma.
View details for DOI 10.1016/j.wneu.2016.04.019
View details for PubMedID 27108030
-
Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo
PLOS ONE
2016; 11 (4)
Abstract
Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo.
View details for DOI 10.1371/journal.pone.0153550
View details for Web of Science ID 000374541200027
View details for PubMedID 27092773
View details for PubMedCentralID PMC4836698
-
Intracranial Dislocation of the Mandibular Condyle: A Case Report and Literature Review
WORLD NEUROSURGERY
2016; 86
View details for DOI 10.1016/j.wneu.2015.09.007
View details for PubMedID 26365884
-
Neural Placode Tissue Derived From Myelomeningocele Repair Serves as a Viable Source of Oligodendrocyte Progenitor Cells.
Neurosurgery
2015; 77 (5): 794-802
Abstract
The presence, characteristics, and potential clinical relevance of neural progenitor populations within the neural placodes of myelomeningocele patients remain to be studied. Neural stem cells are known to reside adjacent to ependyma-lined surfaces along the central nervous system axis.Given such neuroanatomic correlation and regenerative capacity in fetal development, we assessed myelomeningocele-derived neural placode tissue as a potentially novel source of neural stem and progenitor cells.Nonfunctional neural placode tissue was harvested from infants during the surgical repair of myelomeningocele and subsequently further analyzed by in vitro studies, flow cytometry, and immunofluorescence. To assess lineage potential, neural placode-derived neurospheres were subjected to differential media conditions. Through assessment of platelet-derived growth factor receptor α (PDGFRα) and CD15 cell marker expression, Sox2+Olig2+ putative oligodendrocyte progenitor cells were successfully isolated.PDGFRαCD15 cell populations demonstrated the highest rate of self-renewal capacity and multipotency of cell progeny. Immunofluorescence of neural placode-derived neurospheres demonstrated preferential expression of the oligodendrocyte progenitor marker, CNPase, whereas differentiation to neurons and astrocytes was also noted, albeit to a limited degree.Neural placode tissue contains multipotent progenitors that are preferentially biased toward oligodendrocyte progenitor cell differentiation and presents a novel source of such cells for use in the treatment of a variety of pediatric and adult neurological disease, including spinal cord injury, multiple sclerosis, and metabolic leukoencephalopathies.
View details for DOI 10.1227/NEU.0000000000000918
View details for PubMedID 26225855
-
Retrosigmoid Versus Translabyrinthine Approach for Acoustic Neuroma Resection: An Assessment of Complications and Payments in a Longitudinal Administrative Database
CUREUS
2015; 7 (10)
View details for DOI 10.7759/cureus.369
View details for Web of Science ID 000453606600030
-
Anterior Versus Posterior Approach for Multilevel Degenerative Cervical Disease A Retrospective Propensity Score-Matched Study of the MarketScan Database
SPINE
2015; 40 (13): 1033-1038
Abstract
Retrospective 2:1 propensity score-matched analysis on a national longitudinal database between 2006 and 2010.To compare rates of adverse events, revisions procedure rates, and payment differences in anterior cervical fusion procedures compared with posterior laminectomy and fusion procedures with at least 3 levels of instrumentation.The comparative benefits of anterior versus posterior approach to multilevel degenerative cervical disease remain controversial. Recent systematic reviews have reached conflicting conclusions. We demonstrate the comparative economic and clinical outcomes of anterior and posterior approaches for multilevel cervical degenerative disk disease.We identified 13,662 patients in a national billing claims database who underwent anterior or posterior cervical fusion procedures with 3 or more levels of instrumentation. Cohorts were balanced using 2:1 propensity score matching and outcomes were compared using bivariate analysis.With the exception of dysphagia (6.4% in anterior and 1.4% in posterior), overall 30-day complication rates were lower in the anterior approach group. The rate of any complication excluding dysphagia with anterior approaches was 12.3%, significantly lower (P < 0.0001) than that of posterior approaches, 17.8%. Anterior approaches resulted in lower hospital ($18,346 vs. $23,638) and total payments ($28,963 vs. $33,526). Patients receiving an anterior surgical approach demonstrated significantly lower rate of 30-day readmission (5.1% vs. 9.9%, P < 0.0001), were less likely to require revision surgery (12.8% vs. 18.1%, P < 0.0001), and had a shorter length of stay by 1.5 nights (P < 0.0001).Anterior approaches in the surgical management of multilevel degenerative cervical disease provide clinical advantages over posterior approaches, including lower overall complication rates, revision procedure rates, and decreased length of stay. Anterior approach procedures are also associated with decreased overall payments. These findings must be interpreted in light of limitations inherent to retrospective longitudinal studies including absence of subjective and radiographical outcomes.3.
View details for DOI 10.1097/BRS.0000000000000872
View details for Web of Science ID 000357946000009
-
Anterior Versus Posterior Approach for Multilevel Degenerative Cervical Disease: A Retrospective Propensity Score-Matched Study of the MarketScan Database.
Spine
2015; 40 (13): 1033-1038
Abstract
Retrospective 2:1 propensity score-matched analysis on a national longitudinal database between 2006 and 2010.To compare rates of adverse events, revisions procedure rates, and payment differences in anterior cervical fusion procedures compared with posterior laminectomy and fusion procedures with at least 3 levels of instrumentation.The comparative benefits of anterior versus posterior approach to multilevel degenerative cervical disease remain controversial. Recent systematic reviews have reached conflicting conclusions. We demonstrate the comparative economic and clinical outcomes of anterior and posterior approaches for multilevel cervical degenerative disk disease.We identified 13,662 patients in a national billing claims database who underwent anterior or posterior cervical fusion procedures with 3 or more levels of instrumentation. Cohorts were balanced using 2:1 propensity score matching and outcomes were compared using bivariate analysis.With the exception of dysphagia (6.4% in anterior and 1.4% in posterior), overall 30-day complication rates were lower in the anterior approach group. The rate of any complication excluding dysphagia with anterior approaches was 12.3%, significantly lower (P < 0.0001) than that of posterior approaches, 17.8%. Anterior approaches resulted in lower hospital ($18,346 vs. $23,638) and total payments ($28,963 vs. $33,526). Patients receiving an anterior surgical approach demonstrated significantly lower rate of 30-day readmission (5.1% vs. 9.9%, P < 0.0001), were less likely to require revision surgery (12.8% vs. 18.1%, P < 0.0001), and had a shorter length of stay by 1.5 nights (P < 0.0001).Anterior approaches in the surgical management of multilevel degenerative cervical disease provide clinical advantages over posterior approaches, including lower overall complication rates, revision procedure rates, and decreased length of stay. Anterior approach procedures are also associated with decreased overall payments. These findings must be interpreted in light of limitations inherent to retrospective longitudinal studies including absence of subjective and radiographical outcomes.3.
View details for DOI 10.1097/BRS.0000000000000872
View details for PubMedID 25768690
-
NOTCH1 PROMOTES MYC MEDULLOBLASTOMA METASTASIS, INITIATION AND MAINTENANCE
OXFORD UNIV PRESS INC. 2015: 19–20
View details for Web of Science ID 000361304800078
-
Deep Brain Stimulation for Obesity.
Cureus
2015; 7 (3)
Abstract
Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer's disease, and depression and obsessive-compulsive disorder have demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain.
View details for DOI 10.7759/cureus.259
View details for PubMedID 26180683
-
Deep Brain Stimulation for Obesity
CUREUS
2015; 7 (3)
View details for DOI 10.7759/cureus.259
View details for Web of Science ID 000453602300008
-
Macrophages eat cancer cells using their own calreticulin as a guide: Roles of TLR and Btk.
Proceedings of the National Academy of Sciences of the United States of America
2015; 112 (7): 2145-2150
Abstract
Macrophage-mediated programmed cell removal (PrCR) is an important mechanism of eliminating diseased and damaged cells before programmed cell death. The induction of PrCR by eat-me signals on tumor cells is countered by don't-eat-me signals such as CD47, which binds macrophage signal-regulatory protein α to inhibit phagocytosis. Blockade of CD47 on tumor cells leads to phagocytosis by macrophages. Here we demonstrate that the activation of Toll-like receptor (TLR) signaling pathways in macrophages synergizes with blocking CD47 on tumor cells to enhance PrCR. Bruton's tyrosine kinase (Btk) mediates TLR signaling in macrophages. Calreticulin, previously shown to be an eat-me signal on cancer cells, is activated in macrophages for secretion and cell-surface exposure by TLR and Btk to target cancer cells for phagocytosis, even if the cancer cells themselves do not express calreticulin.
View details for DOI 10.1073/pnas.1424907112
View details for PubMedID 25646432
-
Retrosigmoid Versus Translabyrinthine Approach for Acoustic Neuroma Resection: An Assessment of Complications and Payments in a Longitudinal Administrative Database.
Cure¯us
2015; 7 (10)
Abstract
Object Retrosigmoid (RS) and translabyrinthine (TL) surgery remain essential treatment approaches for symptomatic or enlarging acoustic neuromas (ANs). We compared nationwide complication rates and payments, independent of tumor characteristics, for these two strategies. Methods We identified 346 and 130 patients who underwent RS and TL approaches, respectively, for AN resection in the 2010-2012 MarketScan database, which characterizes primarily privately-insured patients from multiple institutions nationwide. Results Although we found no difference in 30-day general neurological or neurosurgical complication rates, in TL procedures there was a decreased risk for postoperative cranial nerve (CN) VII injury (20.2% vs 10.0%, CI 0.23-0.82), dysphagia (10.4% vs 3.1%, CI 0.10-0.78), and dysrhythmia (8.4% vs 2.3%, CI 0.08-0.86). Overall, there was no difference in surgical repair rates of CSF leak; however, intraoperative fat grafting was significantly higher in TL approaches (19.8% vs 60.2%, CI 3.95-9.43). In patients receiving grafts, there was a trend towards a higher repair rate after RS approach, while in those without grafts, there was a trend towards a higher repair rate after TL approach. Median total payments were $16,856 higher after RS approaches ($67,774 vs $50,918, p < 0.0001), without differences in physician or 90-day postoperative payments. Conclusions Using a nationwide longitudinal database, we observed that the TL, compared to RS, approach for AN resection experienced lower risks of CN VII injury, dysphagia, and dysrhythmia. There was no significant difference in CSF leak repair rates. The payments for RS procedures exceed payments for TL procedures by approximately $17,000. Data from additional years and non-private sources will further clarify these trends.
View details for DOI 10.7759/cureus.369
View details for PubMedID 26623224
View details for PubMedCentralID PMC4659577
-
Galvanizing medical students in the administration of influenza vaccines: the Stanford Flu Crew.
Advances in medical education and practice
2015; 6: 471-477
Abstract
Many national organizations call for medical students to receive more public health education in medical school. Nonetheless, limited evidence exists about successful servicelearning programs that administer preventive health services in nonclinical settings. The Flu Crew program, started in 2001 at the Stanford University School of Medicine, provides preclinical medical students with opportunities to administer influenza immunizations in the local community. Medical students consider Flu Crew to be an important part of their medical education that cannot be learned in the classroom. Through delivering vaccines to where people live, eat, work, and pray, Flu Crew teaches medical students about patient care, preventive medicine, and population health needs. Additionally, Flu Crew allows students to work with several partners in the community in order to understand how various stakeholders improve the delivery of population health services. Flu Crew teaches students how to address common vaccination myths and provides insights into implementing public health interventions. This article describes the Stanford Flu Crew curriculum, outlines the planning needed to organize immunization events, shares findings from medical students' attitudes about population health, highlights the program's outcomes, and summarizes the lessons learned. This article suggests that Flu Crew is an example of one viable service-learning modality that supports influenza vaccinations in nonclinical settings while simultaneously benefiting future clinicians.
View details for DOI 10.2147/AMEP.S70294
View details for PubMedID 26170731
View details for PubMedCentralID PMC4492543
-
Intraoperative Neuromonitoring in Single-Level Spinal Procedures A Retrospective Propensity Score-Matched Analysis in a National Longitudinal Database
SPINE
2014; 39 (23): 1950-1959
Abstract
Study Design. Retrospective propensity score-matched analysis on a national database (MarketScan) between 2006 and 2010.Objective. To compare rates of neurological deficits after elective single level spinal procedures with and without intraoperative neuromonitoring, as well as associated payment differences and geographic variance.Summary of Background Data. Intraoperative neurophysiologic monitoring is a technique that may contribute to avoiding permanent neurological injury during some spine surgery procedures. However, it is unclear if all patients undergoing spine surgery benefit from neuromonitoring.Methods. An identified 85,640 patients underwent single level spinal procedures including anterior cervical discectomy and fusion (ACDF), lumbar fusion, lumbar laminectomy, or lumbar discectomy. Neuromonitoring was identified with appropriate Current Procedural Terminology (CPT) codes. Cohorts were balanced on baseline comorbidities and procedure characteristics using propensity score matching. Trauma and spinal tumors cases were excluded.Results. 12.66% patients received neuromonitoring intraoperatively. Lumbar laminectomies had reduced 30-day neurological complication rate with neuromonitoring (0.0% vs 1.18%, p = 0.002). Neuromonitoring did not correlate with reduced intraoperative neurological complications in ACDFs (0.09% vs 0.13%), lumbar fusions (0.32% vs 0.58%), or lumbar discectomy (1.24% vs. 0.91%). With the addition of neuromonitoring, payments for ACDFs increased 16.24% ($3,842), lumbar fusions 7.84% ($3,540), lumbar laminectomies 24.33% ($3,704), and lumbar discectomies 22.54% ($2.859). Significant geographic variation was evident. Some states had no recorded single-level spinal cases with concurrent neuromonitoring. Rates for ACDFs and lumbar fusions, laminectomies, and discectomies ranged as high as 61%, 58%, 22%, and 21%, respectively.Conclusions. With intraoperative neurological monitoring in single level procedures, neurological complications were only decreased among lumbar laminectomies. No difference was observed in ACDFs, lumbar fusions, or lumbar discectomies. There was a significant increase in total payments associated with the index procedure and hospitalization. We demonstrate significant geographic variation in neuromonitoring.
View details for DOI 10.1097/BRS.0000000000000593
View details for Web of Science ID 000344606100014
-
Intraoperative neuromonitoring in single-level spinal procedures: a retrospective propensity score-matched analysis in a national longitudinal database.
Spine
2014; 39 (23): 1950-1959
Abstract
Study Design. Retrospective propensity score-matched analysis on a national database (MarketScan) between 2006 and 2010.Objective. To compare rates of neurological deficits after elective single level spinal procedures with and without intraoperative neuromonitoring, as well as associated payment differences and geographic variance.Summary of Background Data. Intraoperative neurophysiologic monitoring is a technique that may contribute to avoiding permanent neurological injury during some spine surgery procedures. However, it is unclear if all patients undergoing spine surgery benefit from neuromonitoring.Methods. An identified 85,640 patients underwent single level spinal procedures including anterior cervical discectomy and fusion (ACDF), lumbar fusion, lumbar laminectomy, or lumbar discectomy. Neuromonitoring was identified with appropriate Current Procedural Terminology (CPT) codes. Cohorts were balanced on baseline comorbidities and procedure characteristics using propensity score matching. Trauma and spinal tumors cases were excluded.Results. 12.66% patients received neuromonitoring intraoperatively. Lumbar laminectomies had reduced 30-day neurological complication rate with neuromonitoring (0.0% vs 1.18%, p = 0.002). Neuromonitoring did not correlate with reduced intraoperative neurological complications in ACDFs (0.09% vs 0.13%), lumbar fusions (0.32% vs 0.58%), or lumbar discectomy (1.24% vs. 0.91%). With the addition of neuromonitoring, payments for ACDFs increased 16.24% ($3,842), lumbar fusions 7.84% ($3,540), lumbar laminectomies 24.33% ($3,704), and lumbar discectomies 22.54% ($2.859). Significant geographic variation was evident. Some states had no recorded single-level spinal cases with concurrent neuromonitoring. Rates for ACDFs and lumbar fusions, laminectomies, and discectomies ranged as high as 61%, 58%, 22%, and 21%, respectively.Conclusions. With intraoperative neurological monitoring in single level procedures, neurological complications were only decreased among lumbar laminectomies. No difference was observed in ACDFs, lumbar fusions, or lumbar discectomies. There was a significant increase in total payments associated with the index procedure and hospitalization. We demonstrate significant geographic variation in neuromonitoring.
View details for DOI 10.1097/BRS.0000000000000593
View details for PubMedID 25202940
-
Involvement of Notch1 signaling pathway in medulloblastoma metastasis
AMER ASSOC CANCER RESEARCH. 2014
View details for DOI 10.1158/1538-7445.AM2014-4041
View details for Web of Science ID 000349910202024
-
Outcomes following malignant degeneration of benign vestibular schwannomas after stereotactic radiosurgery.
World neurosurgery
2014; 82 (3-4): 346-349
View details for DOI 10.1016/j.wneu.2014.03.005
View details for PubMedID 24613663
-
OVERCOMING IMMUNE EVASION IN PEDIATRIC BRAIN TUMORS: A PRE-CLINICAL DEVELOPMENT STUDY USING A HUMANIZED ANTI-CD47 ANTIBODY
OXFORD UNIV PRESS INC. 2014: 138
View details for Web of Science ID 000337924200531