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

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.

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

Purpose: 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. Methods: Report of novel surgical technique with video demonstration. Results: 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. Conclusion: 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.

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

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.

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

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.

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

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.

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

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.

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

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.

A 53-year-old woman with a rapidly progressive, non-enhancing left frontotemporal lesion.

Fifty-three-year-old woman presented with chronic, episodic headache.

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

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.

A Standardized Approach to Treatment Over Objection in Patients Lacking Decision-Making Capacity Secondary to Neurologic Disease.

Neurologic diseases, ranging from Alzheimer dementia to mass lesions in the frontal lobe, may impair decision making. When patients with neurologic disease lack decision-making capacity, but refuse treatment, should they be treated over their objection? To address this type of ethical dilemma in medical illness, Rubin and Prager developed a standardized 7-question approach: (1) How imminent is harm without intervention? (2) What is the likely severity of harm without intervention? (3) What are the risks of intervention? (4) What are the logistics of treating over objection? (5) What is the efficacy of the proposed intervention? (6) What is the likely emotional effect of a coerced intervention? (7) What is the patient's reason for refusal? We describe the application of the standardized Rubin/Prager approach as a checklist to the case of a 50-year-old woman with a large frontal lobe meningioma, who lacked capacity as a result of the meningioma, but refused surgery. This approach may be applied to similar ethical dilemmas of treatment over objection in patients lacking capacity as a result of neurologic disease.

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

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.

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

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.

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

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

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

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.

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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

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

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.

Pediatric sinonasal and skull base lesions.

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.

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

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.

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

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery1. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive2,3. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce4. In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH)5-7, 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)2. 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.

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

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.