Publications by authors named "Marc Otten"

58 Publications

Deconvolution of cell type-specific drug responses in human tumor tissue with single-cell RNA-seq.

Genome Med 2021 May 11;13(1):82. Epub 2021 May 11.

Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA.

Background: Preclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity.

Methods: We combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to drug perturbations on slices derived from six glioblastoma (GBM) resections to identify conserved drug responses and to one additional GBM resection to identify patient-specific responses.

Results: We used scRNA-seq to demonstrate that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue and the feasibility of drug screening from an individual tumor. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients. Etoposide has a conserved impact on proliferating tumor cells, while panobinostat treatment affects both tumor and non-tumor populations, including unexpected effects on the immune microenvironment.

Conclusions: Acute slice cultures recapitulate the major cellular and molecular features of GBM at the single-cell level. In combination with scRNA-seq, this approach enables cell type-specific analysis of sensitivity to multiple drugs in individual tumors. We anticipate that this approach will facilitate pre-clinical studies that identify effective therapies for solid tumors.
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http://dx.doi.org/10.1186/s13073-021-00894-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114529PMC
May 2021

Gross Total Versus Subtotal Surgical Resection in the Management of Craniopharyngiomas.

Allergy Rhinol (Providence) 2020 Jan-Dec;11:2152656720964158. Epub 2020 Oct 29.

Department of Otolaryngology - Head and Neck Surgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, New York.

Craniopharyngiomas (CP) are suprasellar tumors that can grow into vital nearby structures and thus cause significant visual, endocrine, and hypothalamic dysfunction. Debate persists as to the optimal treatment strategy for these benign lesions, particularly with regards to the extent of surgical resection. The goals of tumor resection are to eliminate the compressive effect of the tumor on surrounding structures and minimize recurrence. It remains unclear whether a gross total resection (GTR) or subtotal resection (STR) with adjuvant therapy confers a better prognosis. Chemotherapy and radiation therapy (RT) have been explored as both neoadjuvant and adjuvant treatments to decrease tumor burden and prevent recurrence. The objective of this paper is to review the risks and benefits of GTR versus STR, specifically with regard to risk of recurrence and postoperative morbidity. Aggregated data suggest that STR monotherapy is associated with higher rates of recurrence relative to GTR (50.6% ± 22.1% vs 20.2% ± 13.5%), while STR combined with RT leads to recurrence rates similar to GTR. However, both GTR and RT are independently associated with higher rates of comorbidities including panhypopituitarism, diabetes insipidus, and visual deficits. The treatment strategy for CPs should ultimately be tailored to each patient's individual tumor characteristics, risk, symptoms, and therapeutic goals.
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http://dx.doi.org/10.1177/2152656720964158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675910PMC
October 2020

Endoscopic Petrous Apex Surgery: The Utilization of Frontal Sinus Instrumentation.

J Craniofac Surg 2020 Nov/Dec;31(8):2317-2319

Department of Otolaryngology-Head and Neck Surgery.

Background: The petrous apex is a complex anatomic region for which each surgical approach each has distinct limitations. The authors describe the use of frontal sinus instrumentation for the endonasal endoscopic approach to petrous apex lesions OBJECTIVE:: To demonstrate that the angled design of frontal sinus instrumentation has pronounced clinical utility for the transsphenoidal transclival approach to the petrous apex.

Methods: The authors present cases of expansile petrous apex lesions approached endoscopically via transsphenoid and transclival corridors, and highlight the technique of using curved frontal sinus instruments and angled endoscopes for posterolateral reach in the petrous apex dissection.

Results: As demonstrated in the accompanying video, dissection with frontal sinus instrumentation allows the surgeon to navigate around the internal carotid artery.

Conclusions: Significant technical and technological advances have been made in the field of expanded endoscopic endonasal skull base surgery in the past 3 decades. Increasing efforts are made to push the boundaries and access more laterally located lesions, such as those in the petrous apex. Surgical trajectory or vector is paramount to safely navigate around the internal carotid artery.
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http://dx.doi.org/10.1097/SCS.0000000000006716DOI Listing
April 2021

Gonadotroph tumours with a low SF-1 labelling index are more likely to recur and are associated with enrichment of the PI3K-AKT pathway.

Neuropathol Appl Neurobiol 2021 04 20;47(3):415-427. Epub 2020 Dec 20.

Department of Medicine, Columbia University Medical Center, New York, NY, USA.

Aims: The gonadotroph tumour (GT) is the most frequently resected pituitary neuroendocrine tumour. Although many symptomatic GT are successfully resected, some recur. We sought to identify histological biomarkers that may predict recurrence and explore biological mechanisms that explain this difference in behaviour.

Methods: SF-1 immunohistochemistry of 51 GT, a subset belonging to a longitudinal prospective cohort study (n = 25), was reviewed. Four groups were defined: Group 1-recently diagnosed GT (n = 20), Group 2-non-recurrent GT with long-term follow up (n = 11), Group 3-initial resections of GT that recur (n = 7) and Group 4-recurrent GT (n = 13). The percentage of SF-1 immunolabelling in the lowest staining fields (SF-1 labelling index (SLI)) was assessed and RNA sequencing was performed on 5 GT with SLI <80% and 5 GT with SLI >80%.

Results: Diffuse, strong SF-1 immunolabelling was the most frequent pattern in Groups 1/2, whereas patchy SF-1 staining predominated in Groups 3/4. There was a lower median SLI in Groups 3/4 than 1/2. Overall, GT with SLI <80% recurred earlier than GT with SLI >80%. Differential expression analysis identified 89 statistically significant differentially expressed genes (FDR <0.05) including over-expression of pituitary stem cell genes (SOX2, GFRA3) and various oncogenes (e.g. BCL2, ERRB4) in patchy SF-1 GT. Gene set enrichment analysis identified significant enrichment of genes involved in the PI3K-AKT pathway.

Conclusions: We speculate that patchy SF-1 labelling in GT reflects intratumoural heterogeneity and are less differentiated tumours than diffusely staining GT. SF-1 immunolabelling patterns may have prognostic significance in GT, but confirmatory studies are needed for further validation.
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http://dx.doi.org/10.1111/nan.12675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987644PMC
April 2021

Bilateral "Rescue Strip" Technique for Endoscopic Endonasal Approaches to the Clivus.

Oper Neurosurg (Hagerstown) 2021 01;20(2):E112-E115

Division of Rhinology and Anterior Skull Base Surgery, Department of Otolaryngology - Head and Neck Surgery, New York-Presbyterian Hospital, New York, New York.

Background: The vascularized nasoseptal flap (NSF) is a pillar of contemporary endoscopic skull base reconstruction. The pedicle for the NSF is supplied by the posterior septal branch of the sphenopalatine artery, which courses along the arch of the choana and sphenoid rostrum before entering the nasal septum. Resection or mobilization of this region is necessary for surgical access to the clivus.

Objective: To describe a technique for preserving bilateral NSF pedicles during endoscopic endonasal resection of the clivus, thereby safeguarding availability of the flaps for future skull base repair needs.

Methods: Report of operative technique with video demonstration.

Results: This technique for NSF preservation allows for wide access to the clivus while saving the future option for vascularized flap repairs of skull base defects. The patient in whom we demonstrate this technique underwent complete resection of her clivus without cerebrospinal fluid leak and with preservation of both NSF pedicles.

Conclusion: The "rescue strip" technique for endonasal endoscopic clival surgery preserves the bilateral NSF pedicles for future use without compromising surgical access to the clivus.
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http://dx.doi.org/10.1093/ons/opaa304DOI Listing
January 2021

Treatment Strategies and Outcomes of Pediatric Esthesioneuroblastoma: A Systematic Review.

Front Oncol 2020 24;10:1247. Epub 2020 Jul 24.

Department of Otolaryngology - Head and Neck Surgery, New York-Presbyterian Hospital - Columbia University Irving Medical Center, New York, NY, United States.

Esthesioneuroblastoma, also known as olfactory neuroblastoma, is a small round blue cell tumor of nasal neuroepithelium first described in 1924. Though this tumor is especially rare in the pediatric population with an incidence of <0.1 per 100,000, it is the most common pediatric nasal cavity neoplasm. The purpose of this systematic review is to examine the treatment modalities utilized for pediatric esthesioneuroblastoma and overall survival. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pubmed, EMBASE, and Ovid MEDLINE databases were queried for studies pertinent to treatment modalities for pediatric esthesioneuroblatoma and survival outcomes. Two hundred and seventy-sixth articles were identified, with seven meeting inclusion criteria. Ninety-four patients with an age range of 0.9-21 years old with esthesioneuroblastoma were included. Nearly 90% of patients were of stage Kadish B or C at time of presentation, while 20% presented with cervical lymphadenopathy. Only about 10% of patients underwent single modality therapy. Overall, 5-year survival ranged from 44 to 91% with a median follow-up of 3-13 years. Children with esthesioneuroblastoma usually present at an advanced stage and undergo multi-modality therapy at a higher rate than adult patients. There is a wide range of documented overall survival though this lack of precision could be due to a paucity of patients.
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http://dx.doi.org/10.3389/fonc.2020.01247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393231PMC
July 2020

Pediatric sinonasal and skull base lesions.

World J Otorhinolaryngol Head Neck Surg 2020 Jun 8;6(2):118-124. Epub 2020 Apr 8.

Department of Otolaryngology, Head and Neck Surgery, New York Presbyterian Hospital - Columbia University Medical Center, New York, NY, USA.

Pediatric skull base lesions are complex and challenging disorders. Safe and comprehensive management of this diverse group of disorders requires the expertise of an experienced multidisciplinary skull base team. Adult endoscopic skull base surgery has evolved due to technologic and surgical advancements, multidisciplinary team approaches, and continued innovation. Similar principles continue to advance the care delivered to the pediatric population. The approach and management of these lesions varies considerably based on tumor anatomy, pathology, and surgical goals. An understanding of the nuances of skull base reconstruction unique to the pediatric population is critical for successful outcomes.
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http://dx.doi.org/10.1016/j.wjorl.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296510PMC
June 2020

Frontal osteoplastic flap without frontal sinus obliteration for orbital roof decompression.

Orbit 2021 Apr 27;40(2):145-149. Epub 2020 Apr 27.

Division of Rhinology and Anterior Skull Base Surgery, Department of Otolaryngology - Head and Neck Surgery, Columbia University Irving Medical Center , New York, New York, USA.

: We describe a novel surgical approach for bilateral orbital roof decompression using a frontal osteoplastic flap without frontal sinus obliteration. This technique utilizes a combined external and endonasal endoscopic approach for wide exposure to the orbital roof bilaterally. We demonstrate this technique for the resection of a massive frontal fibrous dysplasia lesion in a healthy male with bilateral orbital roof involvement. The endonasal endoscopic portion of the technique includes a Draf III frontal sinusotomy (endoscopic modified Lothrop procedure) which precludes the need for frontal sinus obliteration, restores normal frontal sinus function, and allows for postoperative endoscopic surveillance. : Report of novel surgical technique with video demonstration. : This technique for orbital roof decompression allows for removal of a frontal lesion, wide decompression of the bilateral orbital roof, and post-operative endonasal endoscopic surveillance of the cavity. The patient in whom we demonstrate this technique had complete resolution of his orbital symptoms and minimal residual fibrous dysplasia postoperatively. : Bilateral orbital roof decompression for frontal lesions can be performed safely and effectively with a frontal osteoplastic flap without frontal sinus obliteration, restoring normal orbital and sinus function.
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http://dx.doi.org/10.1080/01676830.2020.1757126DOI Listing
April 2021

Presenting Features in 269 Patients With Clinically Nonfunctioning Pituitary Adenomas Enrolled in a Prospective Study.

J Endocr Soc 2020 Apr 18;4(4):bvaa021. Epub 2020 Feb 18.

Departments of Neurosurgery, Mount Sinai School of Medicine, New York, New York.

Context: Clinically nonfunctioning pituitary adenomas (CNFPAs) typically remain undetected until mass effect symptoms develop. However, currently, head imaging is performed commonly for many other indications, which may increase incidental discovery of CNFPAs. Since current presentation and outcome data are based on older, retrospective series, a prospective characterization of a contemporary CNFPA cohort was needed.

Objective: To determine the prevalence of incidental presentation and hypopituitarism and its predictors in a CNFPA cohort that spanned 6 to 9 mm micro- to macroadenoma included observational and surgical therapy.

Methods: At enrollment in a prospective, observational study, 269 patients with CNFPAs were studied by history, examination, blood sampling, and pituitary imaging analysis and categorized into incidental or symptoms presentation groups that were compared.

Results: Presentation was incidental in 48.7% of patients and due to tumor symptoms in 51.3%. In the symptoms and incidental groups, 58.7% and 27.4% of patients had hypopituitarism, respectively, and 25% of patients with microadenomas had hypopituitarism. Many had unappreciated signs and symptoms of pituitary disease. Most tumors were macroadenomas (87%) and were larger in the symptoms than incidental and hypopituitary groups than in the eupituitary groups. The patients in the incidental group were older, and males were older and had larger tumors in both the incidental and symptoms groups.

Conclusions: Patients with CNFPAs commonly present incidentally and with previously unrecognized hypopituitarism and symptoms that could have prompted earlier diagnosis. Our data support screening all large micro and macro-CNFPAs for hypopituitarism. Most patients with CNFPAs still have mass effect signs at presentation, suggesting the need for more awareness of pituitary disease. Our ongoing, prospective observation of this cohort will assess outcomes of these CNFPA groups.
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http://dx.doi.org/10.1210/jendso/bvaa021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101088PMC
April 2020

Primary Episcleral Melanoma Consistent with Uveal Melanoma Mutations Treated by Excision and Gamma Knife Stereotactic Radiosurgery.

Ocul Oncol Pathol 2020 Mar 18;6(2):93-98. Epub 2019 Sep 18.

Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, New York, USA.

Ocular melanocytosis has traditionally been associated with increased risk of developing uveal melanoma; however, rarely primary episcleral melanoma has been reported in the literature. Herein, we present the third case of primary episcleral melanoma treated by complete excision and cryotherapy. In contrast to previous cases, we obtained molecular genetic testing which revealed a GNA-11 mutation, and gene expression profiling resulted in a Class 2 PRAME positive tumor diagnosis. These two tests which have never been performed on previous cases, support lineage similar to uveal melanoma. In addition, we are the first case to report treatment of the surgical bed and surrounding orbital tissue with Gamma Knife stereotactic radiotherapy to both treat residual tissue and decrease risk of recurrence.
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http://dx.doi.org/10.1159/000502309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109391PMC
March 2020

Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks.

Nat Med 2020 01 6;26(1):52-58. Epub 2020 Jan 6.

Department of Neurological Surgery, Columbia University, New York, NY, USA.

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce. In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH), a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20-30 min). In a multicenter, prospective clinical trial (n = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory.
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http://dx.doi.org/10.1038/s41591-019-0715-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960329PMC
January 2020

Transoral Finger-Retraction for Endonasal Endoscopic Resection of Masseteric and Buccal Space Lesions.

J Craniofac Surg 2019 May/Jun;30(3):800-802

Department of Otolaryngology - Head and Neck Surgery.

Lesions involving the masseteric and buccal spaces have traditionally required transoral or transcervical approaches. Herein, the authors describe the successful endonasal endoscopic resection of a juvenile nasopharyngeal angiofibroma (JNA) with significant extension into the masseteric and buccal spaces facilitated by transoral finger retraction. Juvenile nasopharyngeal angiofibromas are hypervascular tumors originating in the pterygopalatine fossa (PPF) with complex relationships to skull base and orbital structures. Endoscopic approaches have allowed for resection of JNAs with excellent visualization and without traditional transfacial approaches, decreasing morbidity and reducing incidence of facial deformity with similar outcomes as open approaches. While the endonasal endoscopic approach to the masseteric and buccal spaces is unconventional, encapsulated tumors in these regions can be delivered into the nasal cavity through the maxilla and PPF with the use of transoral finger-retraction. The authors present a case of a 10-year-old male referred to their tertiary care center with left-sided epistaxis, nasal obstruction, and facial swelling. Imaging demonstrated a vascular lesion in the PPF involving the left nasal cavity and paranasal sinuses, with extension into left middle cranial fossa, infratemporal fossa, orbit, and deep spaces of the neck including the masticator, masseteric, and buccal spaces. The patient underwent preoperative embolization and endoscopic endonasal surgical resection with transoral finger-retraction without complication. Transoral finger-retraction represents a supplemental technique that allows for encapsulated lesions involving the masseteric and buccal spaces to be delivered into the nasal cavity for endoscopic resection in a safe and effective fashion, preventing the need for transfacial incisions.
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http://dx.doi.org/10.1097/SCS.0000000000004931DOI Listing
July 2019

Plasma Agouti-Related Protein and Cortisol Levels in Cushing Disease: Evidence for the Regulation of Agouti-Related Protein by Glucocorticoids in Humans.

J Clin Endocrinol Metab 2019 03;104(3):961-969

Columbia University Vagelos College of Physicians and Surgeons, New York, New York.

Context: Glucocorticoids regulate energy balance, in part by stimulating the orexigenic neuropeptide agouti-related protein (AgRP). AgRP neurons express glucocorticoid receptors, and glucocorticoids have been shown to stimulate AgRP gene expression in rodents.

Objective: We sought to determine whether there is a relationship between plasma AgRP and hypothalamic AgRP in rats and to evaluate the relationship between cortisol and plasma AgRP in humans.

Methods: We retrospectively evaluated plasma AgRP levels prior to transsphenoidal surgery in 31 patients with Cushing disease (CD) vs 31 sex- and body mass index-matched controls from a separate study. We then prospectively measured plasma AgRP, before and 6 to 12 months after surgery, in a subgroup of 13 patients with CD. Plasma and hypothalamic AgRP were measured in adrenalectomized rats with and without corticosterone replacement.

Results: Plasma AgRP was stimulated by corticosterone in rats and correlated with hypothalamic AgRP expression. Plasma AgRP levels were higher in patients with CD than in controls (139 ± 12.3 vs 54.2 ± 3.1 pg/mL; P < 0.0001). Among patients with CD, mean 24-hour urine free cortisol (UFC) levels were 257 ± 39 μg/24 hours. Strong positive correlations were observed between plasma AgRP and UFC (r = 0.76; P < 0.0001). In 11 of 13 patients demonstrating surgical cure, AgRP decreased from 126 ± 20.6 to 62.5 ± 8.0 pg/mL (P < 0.05) postoperatively, in parallel with a decline in UFC.

Conclusions: Plasma AgRP levels are elevated in CD, are tightly correlated with cortisol concentrations, and decline with surgical cure. These data support the regulation of AgRP by glucocorticoids in humans. AgRP's role as a potential biomarker and as a mediator of the adverse metabolic consequences of CD deserves further study.
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http://dx.doi.org/10.1210/jc.2018-01909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364508PMC
March 2019

Extent of BOLD Vascular Dysregulation Is Greater in Diffuse Gliomas without Isocitrate Dehydrogenase 1 R132H Mutation.

Radiology 2018 06 24;287(3):965-972. Epub 2018 Jan 24.

From the Department of Neurological Surgery (Z.K.E., M.L.O., J.N.B.), Gabriele Bartoli Brain Tumor Research Laboratory (Z.K.E., J.N.B., P.C.), Department of Pathology and Cell Biology (P.C.), and Department of Radiology (A.L., J.G.), Columbia University Medical Center, 710 W 168th St, Room B404, New York, NY 10032; Department of Radiology, Northwell Health, Manhasset, NY (C.I.H.); Department of Neurological Surgery, Oregon Health and Science University, Portland, OR (S.G.B.); and Department of Radiology, University of California-Irvine, Irvine, Calif (D.S.C.).

Purpose To determine the effect that R132H mutation status of diffuse glioma has on extent of vascular dysregulation and extent of residual blood oxygen level-dependent (BOLD) abnormality after surgical resection. Materials and Methods This study was an institutional review board-approved retrospective analysis of an institutional database of patients, and informed consent was waived. From 2010 to 2017, 39 treatment-naïve patients with diffuse glioma underwent preoperative echo-planar imaging and BOLD functional magnetic resonance imaging. BOLD vascular dysregulation maps were made by identifying voxels with time series similar to tumor and dissimilar to healthy brain. The spatial overlap between tumor and vascular dysregulation was characterized by using the Dice coefficient, and areas of BOLD abnormality outside the tumor margins were quantified as BOLD-only fraction (BOF). Linear regression was used to assess effects of R132H status on the Dice coefficient, BOF, and residual BOLD abnormality after surgical resection. Results When compared with R132H wild-type (R132H-) gliomas, R132H-mutated (R132H+) gliomas showed greater spatial overlap between BOLD abnormality and tumor (mean Dice coefficient, 0.659 ± 0.02 [standard error] for R132H+ and 0.327 ± 0.04 for R132H-; P < .001), less BOLD abnormality beyond the tumor margin (mean BOF, 0.255 ± 0.03 for R132H+ and 0.728 ± 0.04 for R132H-; P < .001), and less postoperative BOLD abnormality (residual fraction, 0.046 ± 0.0047 for R132H+ and 0.397 ± 0.045 for R132H-; P < .001). Receiver operating characteristic curve analysis showed high sensitivity and specificity in the discrimination of R132H+ tumors from R132H- tumors with calculation of both Dice coefficient and BOF (area under the receiver operating characteristic curve, 0.967 and 0.977, respectively). Conclusion R132H mutation status is an important variable affecting the extent of tumor-associated vascular dysregulation and the residual vascular dysregulation after surgical resection. RSNA, 2018 Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2017170790DOI Listing
June 2018

Natural history of spinal cavernous malformations.

Handb Clin Neurol 2017 ;143:233-239

Department of Neurological Surgery, Columbia University Medical Center, Neurological Institute of New York, New York, NY, USA. Electronic address:

Spinal cavernous malformations are intramedullary vascular lesions. They have low pressure and flow, so they may take many years to present with clinical symptoms. Because of their relatively benign nature, surgical intervention is not always indicated. An understanding of the natural history of cavernous malformations helps make decisions about when and if to intervene. In patients who do not have surgery, 88.7% have stable or improved neurologic function, whereas 89.3% have these outcomes in the surgical group. Of note, 51.5% of patients were found to improve in the surgical group, compared to 30.2% in the nonsurgical group. Characteristics that correlated with better neurologic outcome were: resection within 3 months of the onset of symptoms, gross total resection, presentation with motor symptoms, and an acute course. Sensory symptoms correlated with worse outcome. Given the natural history of spinal cavernous malformations, surgery may be considered for symptomatic patients, when general medical health and lesion location permit safe resection. The severity of symptoms must also be considered, as the natural history of the disease can be benign.
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http://dx.doi.org/10.1016/B978-0-444-63640-9.00022-9DOI Listing
March 2018

Minimizing Septectomy for Endoscopic Transsphenoidal Approaches to the Sellar and Suprasellar Regions: A Cadaveric Morphometric Study.

J Neurol Surg B Skull Base 2016 Dec 9;77(6):479-484. Epub 2016 May 9.

Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States; Department of Otolaryngology, Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, United States.

The purpose of this study was to evaluate the effect of posterior septectomy size on surgical exposure and surgical freedom during the endoscopic transsphenoidal approach to the sella and parasellar region. Dissections were performed on 10 embalmed cadaver heads. Dissections started with wide bilateral sphenoidotomies, lateralization of middle turbinates, and a 5-mm posterior septectomy. The posterior septectomy was increased in 5-mm increments to a maximum of 35 mm, followed by bilateral middle turbinectomies. Surgical exposure was defined as the distance between the ipsilateral and contralateral limit of exposure as allowed by the posterior septum along a midsphenoid horizontal meridian. Surgical freedom was defined as the angle between the ipsilateral and contralateral limit. The mean baseline width of the posterior sphenoid sinus was 29.4 ± 3.7 mm. With a 5-mm septectomy, the mean width of surgical exposure was 21.1 ± 2.8 mm. The surgical exposure increased significantly with progressively larger posterior septectomy until a 20-mm posterior septectomy, after which no further increase in surgical exposure or freedom was obtained. Bilateral lateral opticocarotid recesses were accessible with a 15-mm posterior septectomy. The addition of bilateral middle turbinectomies did not significantly increase lateral exposure within the sphenoid sinus compared with middle turbinate lateralization.
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http://dx.doi.org/10.1055/s-0036-1584077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112168PMC
December 2016

Perforation of a nasoseptal flap does not increase the rate of postoperative cerebrospinal fluid leak.

Int Forum Allergy Rhinol 2015 Apr 26;5(4):353-5. Epub 2015 Jan 26.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Philadelphia, PA.

Background: The nasoseptal flap (NSF) has been shown to be a valuable addition to the reconstructive armamentarium of the endoscopic skull-base surgeon. We aimed to evaluate the rate of postoperative cerebrospinal fluid (CSF) leak after use of a NSF that had a small tear during harvest.

Methods: After Institutional Review Board (IRB) approval, we analyzed our database of patients undergoing skull-base resection. We included all patients who had a NSF reconstruction, septoplasty, and/or spur on preoperative computed tomography (CT) imaging. We then evaluated video of each procedure to determine if a tear occurred in the NSF during harvest. Patient records were reviewed to determine if a postoperative CSF leak occurred.

Results: We evaluated video of 21 patients who underwent a skull-base resection, were reconstructed with a NSF, and had either a septoplasty or evidence of a septal spur on CT imaging. Of these 21 cases, 11 small tears occurred during harvest of the NSF flap and none of the patients with a torn NSF had a postoperative CSF leak.

Conclusion: Our series shows a 0% postoperative CSF leak rate in patients undergoing skull-base reconstruction with a NSF that was torn during harvest. Small tears in the NSF do not seem to affect postoperative CSF leak rates.
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http://dx.doi.org/10.1002/alr.21480DOI Listing
April 2015

Direct, intraoperative observation of ~0.1 Hz hemodynamic oscillations in awake human cortex: implications for fMRI.

Neuroimage 2014 Feb 1;87:323-31. Epub 2013 Nov 1.

Laboratory for Functional Optical Imaging, Department of Biomedical Engineering, Columbia University, USA; Department of Radiology, Columbia University, USA. Electronic address:

An almost sinusoidal, large amplitude ~0.1 Hz oscillation in cortical hemodynamics has been repeatedly observed in species ranging from mice to humans. However, the occurrence of 'slow sinusoidal hemodynamic oscillations' (SSHOs) in human functional magnetic resonance imaging (fMRI) studies is rarely noted or considered. As a result, little investigation into the cause of SSHOs has been undertaken, and their potential to confound fMRI analysis, as well as their possible value as a functional biomarker has been largely overlooked. Here, we report direct observation of large-amplitude, sinusoidal ~0.1 Hz hemodynamic oscillations in the cortex of an awake human undergoing surgical resection of a brain tumor. Intraoperative multispectral optical intrinsic signal imaging (MS-OISI) revealed that SSHOs were spatially localized to distinct regions of the cortex, exhibited wave-like propagation, and involved oscillations in the diameter of specific pial arterioles, indicating that the effect was not the result of systemic blood pressure oscillations. fMRI data collected from the same subject 4 days prior to surgery demonstrates that ~0.1 Hz oscillations in the BOLD signal can be detected around the same region. Intraoperative optical imaging data from a patient undergoing epilepsy surgery, in whom sinusoidal oscillations were not observed, is shown for comparison. This direct observation of the '0.1 Hz wave' in the awake human brain, using both intraoperative imaging and pre-operative fMRI, confirms that SSHOs occur in the human brain, and can be detected by fMRI. We discuss the possible physiological basis of this oscillation and its potential link to brain pathologies, highlighting its relevance to resting-state fMRI and its potential as a novel target for functional diagnosis and delineation of neurological disease.
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http://dx.doi.org/10.1016/j.neuroimage.2013.10.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961585PMC
February 2014

Complement inhibition promotes endogenous neurogenesis and sustained anti-inflammatory neuroprotection following reperfused stroke.

PLoS One 2012 26;7(6):e38664. Epub 2012 Jun 26.

Department of Neurological Surgery, Columbia University, New York, New York, United States of America.

Background And Purpose: The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points.

Methods: To evaluate the effect of C3a-receptor antagonism on post-ischemic neurogenesis and neurological outcome in the subacute period of stroke, transient focal cerebral ischemia was induced in adult male C57BL/6 mice treated with multiple regimens of a C3a receptor antagonist (C3aRA).

Results: Low-dose C3aRA administration during the acute phase of stroke promotes neuroblast proliferation in the subventricular zone at 7 days. Additionally, the C3a receptor is expressed on T-lymphocytes within the ischemic territory at 7 days, and this cellular infiltrate is abrogated by C3aRA administration. Finally, C3aRA treatment confers robust histologic and functional neuroprotection at this delayed time-point.

Conclusions: Targeted complement inhibition through low-dose antagonism of the C3a receptor promotes post-ischemic neuroblast proliferation in the SVZ. Furthermore, C3aRA administration suppresses T-lymphocyte infiltration and improves delayed functional and histologic outcome following reperfused stroke. Post-ischemic complement activation may be pharmacologically manipulated to yield an effective therapy for stroke.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038664PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383680PMC
March 2013

Motor deficits correlate with resting state motor network connectivity in patients with brain tumours.

Brain 2012 Apr 8;135(Pt 4):1017-26. Epub 2012 Mar 8.

Department of Neurosurgery, Columbia University, 710 West 168th Street, Suite 4-404, New York, NY 10032, USA.

While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery.
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http://dx.doi.org/10.1093/brain/aws041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326259PMC
April 2012

Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke.

J Neurosci 2011 Jun;31(24):8894-904

Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

Despite extensive research to develop an effective neuroprotective strategy for the treatment of ischemic stroke, therapeutic options remain limited. Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. Using an unbiased caspase-trapping technique in vivo, we isolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). Caspase-9 inhibition provided neurofunctional protection and established caspase-6 as its downstream target. The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke.
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http://dx.doi.org/10.1523/JNEUROSCI.0698-11.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143191PMC
June 2011

Systemic expression of matrix metalloproteinase-9 in patients with cerebral arteriovenous malformations.

Neurosurgery 2010 Feb;66(2):343-8; discussion 348

Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA.

Objective: Increased expression angiogenic factors, such as matrix metalloproteinases (MMPs), are associated with the formation of cerebral arteriovenous malformations (AVMs). The objective of this study was to determine plasma levels of MMP-9 of patients with AVMs.

Methods: Blood samples were drawn from 15 patients with AVMs before treatment, 24 hours postembolization, 24 hours postresection, and 30 days postresection. Blood samples were also obtained from 30 healthy controls. Plasma MMP-9 concentrations were measured via enzyme-linked immunosorbent assay.

Results: The mean plasma MMP-9 level in AVM patients at baseline was significantly higher than in control patients: 108.04 +/- 16.11 versus 41.44 +/- 2.44 ng/mL, respectively. The mean plasma MMP-9 level 1 day after embolization increased to 172.35 +/- 53.76 ng/mL, which was not significantly elevated over pretreatment levels. One day after resection, plasma MMP-9 levels increased significantly over pretreatment levels to 230.97 +/- 51.00 ng/mL. Mean plasma MMP-9 concentrations 30 days after resection decreased to 92.8 +/- 18.7 ng/mL, which was not different from pretreatment levels but was still significantly elevated over control levels. MMP-9 levels did not correlate with patient sex, age, presentation, or AVM size.

Conclusion: Plasma MMP-9 levels are significantly elevated over controls at baseline, increase significantly immediately after surgery, and decrease to pretreatment levels during follow-up.
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http://dx.doi.org/10.1227/01.NEU.0000363599.72318.BADOI Listing
February 2010

Treatment guidelines for cerebral arteriovenous malformation microsurgery.

Br J Neurosurg 2009 Aug;23(4):376-86

Department of Neurosurgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

The goal of cerebral arteriovenous malformation (AVM) treatment is to eliminate intracerebral hemorrhage risk and to preserve or maximize neurological functions of the patient. Interventional planning must determine the modality or combination of modalities with the greatest success rate according to patient characteristics, AVM architecture, and the capabilities of the treatment option to fulfill the goals of treatment. Although there is a lack of data from randomized trials to guide AVM management, microsurgery is a mainstay of therapy in patients receiving definitive intervention. In this paper, we review current guidelines for surgical planning, risk-benefit analysis, and prediction of outcome in AVM patients.
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http://dx.doi.org/10.1080/02688690902977662DOI Listing
August 2009

Elevated troponin levels are predictive of mortality in surgical intracerebral hemorrhage patients.

Neurocrit Care 2010 Apr 21;12(2):199-203. Epub 2009 Jul 21.

Department of Neurosurgery, Columbia University, Room 431, 710 West 168th Street, New York, NY 10032, USA.

Objective: Elevated troponin levels are a common occurrence after ischemic stroke and subarachnoid hemorrhage (SAH), and have been described as a neurogenic form of myocardial injury. The prognostic significance of this event is controversial with numerous studies citing conflicting results. The importance of cardiac stress is of particular relevance in the operative management of intracerebral hemorrhage (ICH). To this end, we investigated whether troponin levels were an independent predictor of in-hospital mortality from all causes in surgically treated ICH patients.

Methods: We performed a retrospective analysis of 110 patients admitted to Columbia Presbyterian hospital between 1999 and 2007 for ICH and subsequent clot evacuation. Those with angina or recent myocardial infarction were excluded. CT scans were reviewed to determine hematoma size, location, presence of intraventricular hemorrhage (IVH) or SAH, hydrocephalus, and midline shift. Hospital records were examined for known demographic and clinical predictors of mortality. Univariate analysis was used to screen for predictive factors (P
Results: Of 110 patients, 10 were excluded due to insufficient records or pre-existing cardiovascular disease. Ninety-five patients had at least one troponin level and 83 had multiple levels. Univariate analysis revealed nine factors that predicted in-hospital mortality (P < 0.20): smoking, volume of hemorrhage, midline shift, IVH, neurological status on admission, admission troponin, post-surgical troponin, warfarin use, and international normalized ratio. Only two factors were significant in the final multi-variate model: admission troponin and volume of hemorrhage. Admission troponin levels were a significant risk factor for in-hospital mortality even after controlling for hemorrhage volume, gender, and age.

Conclusions: Elevated cardiac troponin levels are predictive of mortality in surgically treated ICH patients and should be considered in management decisions. Implementation of cardio-protective strategies may improve outcomes in this patient population.
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http://dx.doi.org/10.1007/s12028-009-9245-5DOI Listing
April 2010

The complement cascade: new avenues in stroke therapy.

Curr Vasc Pharmacol 2009 Jul;7(3):287-92

Department of Neurological Surgery, Columbia University, New York, NY 10011, USA.

Recent evidence has shown that after the initial occlusion, a large portion of stroke patients achieve some degree of reperfusion either through collateral circulation or clot dissolution. However, it appears that this reperfusion may lead to increased inflammation-induced damage. Even though the exact mechanism of this secondary injury is unclear, several experimental studies have indicated an intimate connection between complement and this secondary form of damage. We review the available literature and attempt to identify promising clinical therapeutic targets.
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http://dx.doi.org/10.2174/157016109788340677DOI Listing
July 2009

Adjuvant embolization with N-butyl cyanoacrylate in the treatment of cerebral arteriovenous malformations: outcomes, complications, and predictors of neurologic deficits.

Stroke 2009 Aug 28;40(8):2783-90. Epub 2009 May 28.

Department of Neurosurgery, Columbia University, 710 West 168th Street, Room 428, Neurological Institute, New York, NY 10032, USA.

Background And Purpose: The purpose of this study was to assess the frequency, severity, and predictors of neurological deficits after adjuvant embolization for cerebral arteriovenous malformations.

Methods: From 1997 to 2006, 202 of 275 patients with arteriovenous malformation received embolization before microsurgery (n=176) or radiosurgery (n=26). Patients were examined before and after endovascular embolization and at clinical follow-up (mean, 43.4+/-34.6 months). Outcome was classified according to the modified Rankin Scale. New neurological deficits after embolization were defined as minimal (no change in overall modified Rankin Scale), moderate (modified Rankin Scale < or =2), or significant (modified Rankin Scale >2).

Results: Two hundred two patients were treated in 377 embolization procedures. There were a total of 29 new clinical deficits after embolization (8% of procedures; 14% of patients), of which 19 were moderate or significant. Postembolization deficits resolved in a significant number of patients over time (P<0.0001). Five patients had persistent neurological deficits due to embolization (1.3% of procedures; 2.5% of patients). In multivariate analysis, the following variables significantly predicted new neurological deficit after embolization: complex arteriovenous malformation with treatment plan specifying more than one embolization procedure (OR, 2.7; 95% CI, 1.4 to 8.6), diameter <3 cm (OR, 3.2; 95% CI, 1.2 to 9.1), diameter >6 cm (OR, 6.2; 95% CI, 1.0 to 57.0), deep venous drainage (OR, 2.7; 95% CI, 1.1 to 6.9), or eloquent location (OR, 2.4; 95% CI, 1.0 to 5.7). These variables were weighted and used to compute an arteriovenous malformation Embolization Prognostic Risk Score for each patient. A score of 0 predicted no new deficits, a score of 1 predicted a new deficit rate of 6%, a score of 2 predicted a new deficit rate of 15%, a score of 3 predicted a new deficit rate of 21%, and a score of 4 predicted a new deficit rate of 50% (P<0.0001).

Conclusions: Small and large size, eloquent location, deep venous drainage, and complex vascular anatomy requiring multiple embolization procedures are risk factors for the development of immediate postembolization neurological deficits. Nevertheless, a significant number of patients with treatment-related neurological deficits improve over time. The low incidence of permanent neurological deficits underscores the usefulness of this technique in carefully selected patients.
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http://dx.doi.org/10.1161/STROKEAHA.108.539775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745321PMC
August 2009

Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage.

Brain Res 2009 Nov 4;1298:171-7. Epub 2009 May 4.

Department of Neurological Surgery, Columbia University, 710 West 168th Street, New York, NY 10032, USA.

Background: Intracerebral hemorrhage (ICH) is associated with neurological injury that may be ameliorated by a neuroprotective strategy targeting the complement cascade. We investigated the role of C5a-receptor antagonist (C5aRA) solely and in combination with C3a-receptor antagonist (C3aRA) following ICH in mice.

Methods: Adult male C57BL/6J mice were randomized to receive vehicle, C5aRA alone or C3aRA and C5aRA 6 and 12 h after ICH, and every 12 h thereafter. A double injection technique was used to infuse 30 microL of autologous whole blood into the right striatum. A final group of mice received a sham procedure consisting only of needle insertion followed by vehicle injections. Brain water content and flow cytometry analysis for leukocyte and microglia infiltration and activation in both hemispheres were measured on day 3 post ICH. Neurological dysfunction was assessed using a Morris water-maze (MWM), a 28-point scale, and a corner test at 6, 12, 24, 48 and 72 h after ICH induction.

Results: Neurological deficits were present and comparable in all three cohorts 6 h after ICH. Animals treated with C5aRA and animals treated with combined C3aRA/C5aRA demonstrated significant improvements in neurological function assessed by both the corner turn test and a 28-point neurological scale at 24, 48 and 72 h relative to vehicle-treated animals. Similarly, C5aRA and C3aRA/C5aRA-treated mice demonstrated better spatial memory retention in the Morris water-maze test compared with vehicle-treated animals (C3aRA/C5aRA: 23.4+/-2.0 s p< or =0.0001 versus vehicle: 10.0+/-1.7 s). Relative to vehicle-treated mice, the brain water content in C3aRA/C5aRA-treated mice was significantly decreased in the ipsilateral cortex and ipsilateral striatum (ipsilateral cortex: C3aRA/C5aRA: 0.755403+/-0.008 versus 0.773327+/-0.003 p=0.01 striatum: 0.752273+/-0.007 versus 0.771163+/-0.0036 p=0.02). C5aRA-treated mice and C3aRA/C5aRA-treated mice had a decreased ratio of granulocytes (CD45(+)/CD11b(+)/Ly-6G(+)) in the hemorrhagic versus non-hemorrhagic hemispheres relative to vehicle-treated animals (C5aRA: 1.78+/-0.36 p=0.02 C3aRA/C5aRA: 1.59+/-0.22 p=0.005 versus vehicle: 3.01).

Conclusions: While administration of C5aRA alone provided neuroprotection, combined C3aRA/C5aRA therapy led to synergistic improvements in neurofunctional outcome while reducing inflammatory cell infiltration and brain edema. The results of this study indicate that simultaneous blockade of the C3a and C5a receptors represents a promising neuroprotective strategy in hemorrhagic stroke.
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http://dx.doi.org/10.1016/j.brainres.2009.04.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760685PMC
November 2009

Evaluation of a revised Glasgow Coma Score scale in predicting long-term outcome of poor grade aneurysmal subarachnoid hemorrhage patients.

J Clin Neurosci 2009 Jul 16;16(7):894-9. Epub 2009 Apr 16.

Department of Neurology and Neurosurgery, Columbia University, 710 West 168th Street, New York, New York 10032, USA.

Although many scales attempt to predict outcome following aneurysmal subarachnoid hemorrhage (aSAH), none have achieved universal acceptance, and most scales in common use are not statistically derived. We propose a statistically validated scale for poor grade aSAH patients that combines the Hunt and Hess grades and the Glasgow Coma Scale (GCS) scores; we refer to this as the Poor Grade GCS (PGS). The GCS scores of 160 poor grade aSAH patients (Hunt and Hess Grades 4 and 5) were recorded throughout their hospital stay. Outcomes were assessed by the modified Rankin scale (mRS). Analysis of variance and the Chi-square test were used to guide an analysis of GCS breakpoints according to outcomes. Multivariable logistic regression analysis was used to assess the ability of the Hunt and Hess, GCS, World Federation of Neurological Surgeons Grading Scale, and the PGS to predict long-term outcome. Outcome analysis revealed significant breakpoints in admission GCS scores: PGS-A (GCS 10-12); PGS-B (GCS 8-9); PGS-C (GCS 5-7); PGS-D (GCS 3-4) (p<0.001). In surgical patients, 95.2% of PGS-A, 58.1% of PGS-B, 35.4% of PGS-C, and 28.6% of PGS-D had a favorable one-year outcome. When controlling for age, sex, and operation status, PGS was the only scale predictive of long-term outcome. The odds ratios (OR) for unfavorable outcome according to PGS admission scores (with PGS-A as the reference) were: PGS-B, OR=14.2 (95% CI 1.5-140.5); PGS-C, OR=38.5 (95% CI 4.2-340.0); and PGS-D, OR=63.4 (95% CI 5.6-707.1). In addition to PGS admission scores, an age of 70 or greater was a significant predictor of poor outcome with an OR of 7.5 (95% CI 1.8-30.7). No patients with a PGS-C or PGS-D over the age of 70 had a favorable long-term outcome. Therefore, elements of the Hunt and Hess and GCS can be combined into the PGS to predict long-term outcome in poor grade aSAH patients. However, patients with PGS-C and PGS-D over the age of 70 should be assessed carefully prior to definitive treatment.
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http://dx.doi.org/10.1016/j.jocn.2008.10.010DOI Listing
July 2009

Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease. Clinical article.

J Neurosurg 2009 Nov;111(5):936-42

Department of Neurological Surgery, Columbia University, New York, New York 10032, USA.

Object: The object of this study was to report the clinical features, surgical treatment, and long-term outcomes in adults with moyamoya phenomenon treated at a single institution in the US.

Methods: Forty-three adult patients with moyamoya disease (mean age 40 +/- 11 years [SD], range 18-69 years) were treated with encephaloduroarteriosynangiosis (EDAS). Neurologists examined patients pre- and postoperatively. Follow-up was obtained in person or by structured telephone interview (median 41 months, range 4-126 months). The following outcomes were collected: transient ischemic attack (TIA), infarction, graft collateralization, change in cerebral perfusion, and functional level according to the modified Rankin scale (mRS). Kaplan-Meier estimates of infarction risk were calculated for comparison of surgically treated and contralateral hemispheres.

Results: The majority of patients were women (65%), were Caucasian (65%), presented with ischemic symptoms (98%), and had bilateral disease (86%). Nineteen patients underwent unilateral and 24 patients bilateral EDAS (67 treated hemispheres). Collateral vessels developed in 50 (98%) of 52 hemispheres for which imaging was available and there was evidence of increased perfusion on SPECT scans in 41 (82%) of the 50 hemispheres evaluated. Periprocedural infarction (< 48 hours) occurred in 3% of the hemispheres treated. In the follow-up period patients experienced 10 TIAs, 6 infarctions, and 1 intracranial hemorrhage. Although the hemisphere selected for surgery was based upon patients' symptoms and severity of pathology, the 5-year infarction-free survival rate was 94% in the surgically treated hemispheres versus < 36% in the untreated hemispheres (p = 0.007). After controlling for age and sex, infarction was 89% less likely to occur in the surgically treated hemispheres than in the contralateral hemispheres (hazard ratio 0.11, 95% CI 0.02-0.56). Thirty-eight (88%) of 43 patients had preserved or improved mRS scores, relative to baseline status.

Conclusions: In this mixed-race population of North American patients, indirect bypass promoted adequate pial collateral development and increased perfusion in the majority of adult patients with moyamoya disease. Patients had low rates of postoperative TIAs, infarction, and hemorrhage, and the majority of patients had preserved or improved functional status.
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http://dx.doi.org/10.3171/2009.3.JNS08837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783413PMC
November 2009

Predictors of seizure onset after intracerebral hemorrhage and the role of long-term antiepileptic therapy.

J Crit Care 2009 Sep 13;24(3):335-9. Epub 2009 Feb 13.

Department of Neurosurgery, Columbia University, New York, NY 10032, USA.

Objective: Seizures are a common complication after hemorrhagic stroke that may slow recovery and decrease quality of life. Recent evidence suggests that early- and late-onset seizures have distinct etiologies, rendering the role of prophylactic long-term antiepileptic drugs controversial. We investigated predictors of early- and late-onset seizures after evacuation of intracerebral hemorrhage (ICH) in an attempt to guide antiepileptic drug management in this patient population.

Methods: We performed a retrospective analysis of 110 patients admitted to Columbia University Medical Center between 1999 and 2007 for ICH and subsequent clot evacuation. Patients were included if they had a head computed tomography indicating ICH, an operative note confirming surgical evacuation, and sufficient medical records to determine seizure status. Demographic, clinical, and radiographic findings were recorded. Univariate and multivariate logistic regression analyses were used to determine factors associated with early- and late-onset electrographic and clinical seizures.

Results: Seizures occurred in 41.8% of patients, 29.6% of which had clinical manifestations and 16.3% of which were recorded on continuous electroencephalogram (EEG). After controlling for demographic factors, multivariate analysis identified 3 factors that were predictive of early-onset seizures (volume of hemorrhage, presence of subarachnoid hemorrhage, and subdural hemorrhage) and 2 factors that were predictive of late onset seizures (subdural hemorrhage and increased admission international normalized ratio (INR)).

Conclusions: The presence of subdural hematoma and increased INR is predictive of late-onset seizures in patients undergoing clot evacuation after ICH. The use of long-term antiepileptic therapy should be further studied in patients with these radiographic and clinical characteristics.
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http://dx.doi.org/10.1016/j.jcrc.2008.10.015DOI Listing
September 2009
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