Peter Nakaji

The purpose of this ongoing study is to compare the safety and efficacy of microsurgical clipping and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to determine if one treatment is superior to the other by examining clinical and angiographic outcomes. The authors examined the null hypothesis that no difference exists between the 2 treatment modalities in the setting of subarachnoid hemorrhage (SAH). The current report is limited to the clinical results at 1 year after treatment.The authors screened 725 patients with SAH, resulting in 500 eligible patients who were enrolled prospectively in the study after giving their informed consent. Patients were assigned in an alternating fashion to surgical aneurysm clipping or endovascular coil therapy. Intake evaluations and outcome measurements were collected by nurse practitioners independent of the treating surgeons. Ultimately, 238 patients were assigned to aneurysm clipping and 233 to coil embolization. The 2 treatment groups were well matched. There were no anatomical exclusions. Crossing over was allowed, but primary outcome analysis was based on the initial treatment modality assignment. Posttreatment care was standardized for both groups. Patient outcomes at 1 year were independently assessed using the modified Rankin Scale (mRS). A poor outcome was defined as an mRS score > 2 at 1 year. The primary outcome was based on the assigned group; that is, by intent to treat.One year after treatment, 403 patients were available for evaluation. Of these, 358 patients had actually undergone treatment. The remainder either died before treatment or had no identifiable source of SAH. A poor outcome (mRS score > 2) was observed in 33.7% of the patients assigned to aneurysm clipping and in 23.2% of the patients assigned to coil embolization (OR 1.68, 95% CI 1.08-2.61; p = 0.02). Of treated patients assigned to the coil group, 124 (62.3%) of the 199 who were eligible for any treatment actually received endovascular coil embolization. Patients who crossed over from coil to clip treatment fared worse than patients assigned to coil embolization, but no worse than patients assigned to clip occlusion. No patient treated by coil embolization suffered a recurrent hemorrhage.One year after treatment, a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes than clip occlusion. Although most aneurysms assigned to the coil treatment group were treated by coil embolization, a substantial number crossed over to surgical clipping. Although a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes at 1 year, it remains important that high-quality surgical clipping be available as an alternative treatment modality.

Object. The authors prospectively compared a new technique of surgical microscope-based indocyanine green (ICG) videoangiography with intraoperative or postoperative digital subtraction (DS) angiography. Method. The technique was performed during 187 surgical procedures in which 124 aneurysms in 114 patients were clipped. Using a newly developed setup, the ICG technique has been integrated into an operating microscope (Carl Zeiss Co., Oberkochen, Germany). A microscope-integrated light source containing infrared excitation light illuminates the operating field. The dye is injected intravenously into the patient, and intravascular fluorescence from within the blood vessels is imaged using a video camera attached to the microscope. The patency of parent, branching, and perforating arteries and documentation of clip occlusion of the aneurysm as shown by ICG videoangiography were compared with intraoperative or postoperative findings on DS angiography. The results of ICG videoangiography corresponded with intra- or postoperative DS angiography in 90% of cases. The ICG technique missed mild but hemodynamically irrelevant stenosis that was evident on DS angiography in 7.3% of cases. The ICG technique missed angiographically relevant findings in three cases (one hemodynamically relevant stenosis and two residual aneurysm necks [2.7% of cases]). In two cases the missed findings were clinically and surgically inconsequential; in the third case, a 4-mm residual neck may require a second procedure. Indocyanine green videoangiography provided significant information for the surgeon in 9% of cases, most of which led to clip correction. Conclusions. Microscope-based ICG videoangiography is simple and provides real-time information about the patency of vessels of all sizes and about the aneurysm sac. This technique may be useful during routine aneurysm surgery as an independent form of angiography or as an adjunct to intra- or postoperative DS angiography.

Differentiating tumor growth from posttreatment radiation effect (PTRE) remains a common problem in neuro-oncology practice. To our knowledge, useful threshold relative cerebral blood volume (rCBV) values that accurately distinguish the 2 entities do not exist. Our prospective study uses image-guided neuronavigation during surgical resection of MR imaging lesions to correlate directly specimen histopathology with localized dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC) measurements and to establish accurate rCBV threshold values, which differentiate PTRE from tumor recurrence.Preoperative 3T gradient-echo DSC and contrast-enhanced stereotactic T1-weighted images were obtained in patients with high-grade glioma (HGG) previously treated with multimodality therapy. Intraoperative neuronavigation documented the stereotactic location of multiple tissue specimens taken randomly from the periphery of enhancing MR imaging lesions. Coregistration of DSC and stereotactic images enabled calculation of localized rCBV within the previously recorded specimen locations. All tissue specimens were histopathologically categorized as tumor or PTRE and were correlated with corresponding rCBV values. All rCBV values were T1-weighted leakage-corrected with preload contrast-bolus administration and T2/T2*-weighted leakage-corrected with baseline subtraction integration.Forty tissue specimens were collected from 13 subjects. The PTRE group (n = 16) rCBV values ranged from 0.21 to 0.71, tumor (n = 24) values ranged from 0.55 to 4.64, and 8.3% of tumor rCBV values fell within the PTRE group range. A threshold value of 0.71 optimized differentiation of the histopathologic groups with a sensitivity of 91.7% and a specificity of 100%.rCBV measurements obtained by using DSC and the protocol we have described can differentiate HGG recurrence from PTRE with a high degree of accuracy.

The authors report the 6-year results of the Barrow Ruptured Aneurysm Trial (BRAT). This ongoing randomized trial, with the final goal of a 10-year follow-up, compares the safety and efficacy of surgical clip occlusion and endovascular coil embolization in patients presenting with subarachnoid hemorrhage (SAH) from a ruptured aneurysm. The 1- and 3-year results of this trial have been previously reported.In total, 500 patients with an SAH met the entry criteria and were enrolled in the study. Of these patients, 471 were randomly assigned to the treatments: 238 to surgical clipping and 233 to endovascular coiling. Six patients who died before treatment and 57 patients with nonaneurysmal SAHs were excluded, leaving a total of 408 patients who underwent clipping (209 assigned) or coiling (199 assigned). Whether to treat patients within the assigned group or to cross over patients to the other group was at the discretion of the treating physician; 38% (75/199) of the patients assigned to coiling were crossed over to clipping and 1.9% (4/209) assigned to clipping were crossed over to coiling. The outcome data were collected by a dedicated nurse practitioner. The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. Six years after randomization, 336 (82%) of 408 patients who had been treated were available for examination.On the basis of an mRS score of > 2, and similar to the results at the 3-year follow-up, no significant difference in outcomes (p = 0.24) was detected between the 2 treatment groups. Complete aneurysm obliteration at 6 years was achieved in 96% (111/116) of the clipping group and in 48% (23/48) of the coiling group (p < 0.0001). In the period between the 3- and 6-year follow-ups, 3 additional patients assigned to coiling and none assigned to clipping received retreatment, for overall retreatment rates of 4.6% (13/280) for clipping and 16.4% (21/128) for coiling (p < 0.0001). When aneurysm location was considered, the 6-year results continued to match the previously reported results, with no difference in outcome for anterior circulation aneurysms at most time points. Of the anterior circulation aneurysms assigned to coiling treatment, 42% (70/168) were crossed over to clipping treatment. The outcomes for posterior circulation aneurysms continued to favor coiling. The randomization process was unexpectedly skewed, with 18 of 21 treated aneurysms of the posterior inferior cerebellar artery (PICA) being assigned to clipping, but even when PICA aneurysms were removed from the analysis, outcomes for the posterior circulation aneurysms still favored coiling.Although BRAT was statistically underpowered to detect small differences, these results suggest little difference in outcome between the 2 treatments for anterior circulation aneurysms. This was not the case for the posterior circulation aneurysms, where coil embolization appeared to provide a sustained advantage over clipping. Aneurysm obliteration rates in BRAT were significantly lower and retreatment rates significantly higher in the patients undergoing coiling than in those undergoing clipping. However, despite the fact that retreatment rates were higher after coiling, no recurrent hemorrhages were known to have occurred in patients undergoing coiling in BRAT who were followed up for 6 years. Sufficient questions remain about the relative benefits of the 2 treatment modalities to warrant further well-designed randomized trials.

Object The authors report the 3-year results of the Barrow Ruptured Aneurysm Trial (BRAT). The objective of this ongoing randomized trial is to compare the safety and efficacy of microsurgical clip occlusion and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to compare functional outcomes based on clinical and angiographic data. The 1-year results have been previously reported. Methods Two-hundred thirty-eight patients were assigned to clip occlusion and 233 to coil embolization. There were no anatomical exclusions. Crossovers were allowed based on the treating physician's determination, but primary outcome analysis was based on the initial assignment to treatment modality. Patient outcomes were assessed independently using the modified Rankin Scale (mRS). A poor outcome was defined as an mRS score &gt; 2. At 3 years' follow-up 349 patients who had actually undergone treatment were available for evaluation. Of the 170 patients who had been originally assigned to coiling, 64 (38%) crossed over to clipping, whereas 4 (2%) of 179 patients assigned to surgery crossed over to coiling. Results The risk of a poor outcome in patients assigned to clipping compared with those assigned to coiling (35.8% vs 30%) had decreased from that observed at 1 year and was no longer significant (OR 1.30, 95% CI 0.83–2.04, p = 0.25). In addition, the degree of aneurysm obliteration (p = 0.0001), rate of aneurysm recurrence (p = 0.01), and rate of retreatment (p = 0.01) were significantly better in the group treated with clipping compared with the group treated with coiling. When outcomes were analyzed based on aneurysm location (anterior circulation, n = 339; posterior circulation, n = 69), there was no significant difference in the outcomes of anterior circulation aneurysms between the 2 assigned groups across time points (at discharge, 6 months, 1 year, or 3 years after treatment). The outcomes of posterior circulation aneurysms were significantly better in the coil group than in the clip group after the 1st year of follow-up, and this difference persisted after 3 years of follow-up. However, while aneurysms in the anterior circulation were well matched in their anatomical location between the 2 treatment arms, this was not the case in the posterior circulation where, for example, 18 of 21 posterior inferior cerebellar artery aneurysms were in the clip group. Conclusions Based on mRS scores at 3 years, the outcomes of all patients assigned to coil embolization showed a favorable 5.8% absolute difference compared with outcomes of those assigned to clip occlusion, although this difference did not reach statistical significance (p = 0.25). Patients in the clip group had a significantly higher degree of aneurysm obliteration and a significantly lower rate of recurrence and retreatment. In post hoc analysis examining only anterior circulation aneurysms, no outcome difference between the 2 treatment cohorts was observed at any recorded time point. Clinical trial registration no.: NCT01593267 (ClinicalTrials.gov).

Despite improvements in the medical and surgical management of patients with glioblastoma, tumor recurrence remains inevitable. For recurrent glioblastoma, however, the clinical value of a second resection remains uncertain. Specifically, what proportion of contrast-enhancing recurrent glioblastoma tissue must be removed to improve overall survival and what is the neurological cost of incremental resection beyond this threshold?The authors identified 170 consecutive patients with recurrent supratentorial glioblastomas treated at the Barrow Neurological Institute from 2001 to 2011. All patients previously had a de novo glioblastoma and following their initial resection received standard temozolomide and fractionated radiotherapy.The mean clinical follow-up was 22.6 months and no patient was lost to follow-up. At the time of recurrence, the median preoperative tumor volume was 26.1 cm(3). Following re-resection, median postoperative tumor volume was 3.1 cm(3), equating to an 87.4% extent of resection (EOR). The median overall survival was 19.0 months, with a median progression-free survival following re-resection of 5.2 months. Using Cox proportional hazards analysis, the variables of age, Karnofsky Performance Scale (KPS) score, and EOR were predictive of survival following repeat resection (p = 0.0001). Interestingly, a significant survival advantage was noted with as little as 80% EOR. Recursive partitioning analysis validated these findings and provided additional risk stratification at the highest levels of EOR. Overall, at 7 days after surgery, a deterioration in the NIH stroke scale score by 1 point or more was observed in 39.1% of patients with EOR ≥ 80% as compared with 16.7% for those with EOR < 80% (p = 0.0049). This disparity in neurological morbidity, however, did not endure beyond 30 days postoperatively (p = 0.1279).For recurrent glioblastomas, an improvement in overall survival can be attained beyond an 80% EOR. This survival benefit must be balanced against the risk of neurological morbidity, which does increase with more aggressive cytoreduction, but only in the early postoperative period. Interestingly, this putative EOR threshold closely approximates that reported for newly diagnosed glioblastomas, suggesting that for a subset of patients, the survival benefit of microsurgical resection does not diminish despite biological progression.

INTRODUCTION: Contrast-enhanced MRI (CE-MRI) represents the current mainstay for monitoring treatment response in glioblastoma multiforme (GBM), based on the premise that enlarging lesions reflect increasing tumor burden, treatment failure, and poor prognosis. Unfortunately, irradiating such tumors can induce changes in CE-MRI that mimic tumor recurrence, so called post treatment radiation effect (PTRE), and in fact, both PTRE and tumor re-growth can occur together. Because PTRE represents treatment success, the relative histologic fraction of tumor growth versus PTRE affects survival. Studies suggest that Perfusion MRI (pMRI)–based measures of relative cerebral blood volume (rCBV) can noninvasively estimate histologic tumor fraction to predict clinical outcome. There are several proposed pMRI-based analytic methods, although none have been correlated with overall survival (OS). This study compares how well histologic tumor fraction and OS correlate with several pMRI-based metrics. METHODS: We recruited previously treated patients with GBM undergoing surgical re-resection for suspected tumor recurrence and calculated preoperative pMRI-based metrics within CE-MRI enhancing lesions: rCBV mean, mode, maximum, width, and a new thresholding metric called pMRI–fractional tumor burden (pMRI-FTB). We correlated all pMRI-based metrics with histologic tumor fraction and OS. RESULTS: Among 25 recurrent patients with GBM, histologic tumor fraction correlated most strongly with pMRI-FTB (r = 0.82; P < .0001), which was the only imaging metric that correlated with OS (P<.02). CONCLUSION: The pMRI-FTB metric reliably estimates histologic tumor fraction (i.e., tumor burden) and correlates with OS in the context of recurrent GBM. This technique may offer a promising biomarker of tumor progression and clinical outcome for future clinical trials.

Glioblastoma (GBM) exhibits profound intratumoral genetic heterogeneity. Each tumor comprises multiple genetically distinct clonal populations with different therapeutic sensitivities. This has implications for targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI and conventional sampling techniques have failed to resolve this heterogeneity, particularly for nonenhancing tumor populations. This study explores the feasibility of using multiparametric MRI and texture analysis to characterize regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor segments.We collected multiple image-guided biopsies from primary GBM patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number variants for core GBM driver genes reported by The Cancer Genome Atlas. We co-registered biopsy locations with MRI and texture maps to correlate regional genetic status with spatially matched imaging measurements. We also built multivariate predictive decision-tree models for each GBM driver gene and validated accuracies using leave-one-out-cross-validation (LOOCV).We collected 48 biopsies (13 tumors) and identified significant imaging correlations (univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest. Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%), and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4 driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples (n = 16) compared with those from ENH segments (n = 32).MRI and texture analysis can help characterize regional genetic heterogeneity, which offers potential diagnostic value under the paradigm of individualized oncology.

Background and Purpose— Intracerebral hemorrhage (ICH) is a devastating disease without a proven therapy to improve long-term outcome. Considerable controversy about the role of surgery remains. Minimally invasive endoscopic surgery for ICH offers the potential of improved neurological outcome. Methods— We tested the hypothesis that intraoperative computerized tomographic image–guided endoscopic surgery is safe and effectively removes the majority of the hematoma rapidly. A prospective randomized controlled study was performed on 20 subjects (14 surgical and 4 medical) with primary ICH of &gt;20 mL volume within 48 hours of ICH onset. We prospectively used a contemporaneous medical control cohort (n=36) from the MISTIE trial (Minimally Invasive Surgery and r-tPA for ICH Evacuation). We evaluated surgical safety and neurological outcomes at 6 months and 1 year. Results— The intraoperative computerized tomographic image–guided endoscopic surgery procedure resulted in immediate reduction of hemorrhagic volume by 68±21.6% (interquartile range 59–84.5) within 29 hours of hemorrhage onset. Surgery was successfully completed in all cases, with a mean operative time of 1.9 hours (interquartile range 1.5–2.2 hours). One surgically related bleed occurred peri-operatively, but no patient met surgical safety stopping threshold end points for intraoperative hemorrhage, infection, or death. The surgical intervention group had a greater percentage of patients with good neurological outcome (modified Rankin scale score 0–3) at 180 and 365 days as compared with medical control subjects (42.9% versus 23.7%; P =0.19). Conclusions— Early computerized tomographic image–guided endoscopic surgery is a safe and effective method to remove acute intracerebral hematomas, with a potential to enhance neurological recovery. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00224770.

OBJECTIVE The authors present the 10-year results of the Barrow Ruptured Aneurysm Trial (BRAT) for saccular aneurysms. The 1-, 3-, and 6-year results of the trial have been previously reported, as have the 6-year results with respect to saccular aneurysms. This final report comparing the safety and efficacy of clipping versus coiling is limited to an analysis of those patients presenting with subarachnoid hemorrhage (SAH) from a ruptured saccular aneurysm. METHODS In the study, 362 patients had saccular aneurysms and were randomized equally to the clipping and the coiling cohorts (181 each). The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score &gt; 2 and was independently adjudicated. The extent of aneurysm obliteration was adjudicated by a nontreating neuroradiologist. RESULTS There was no statistically significant difference in poor outcome (mRS score &gt; 2) or deaths between these 2 treatment arms during the 10 years of follow-up. Of 178 clip-assigned patients with saccular aneurysms, 1 (&lt; 1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. After the initial hospitalization, 2 of 241 (0.8%) clipped saccular aneurysms and 23 of 115 (20%) coiled saccular aneurysms required retreatment (p &lt; 0.001). At the 10-year follow-up, 93% (50/54) of the clipped aneurysms were completely obliterated, compared with only 22% (5/23) of the coiled aneurysms (p &lt; 0.001). Two patients had documented rebleeding, both died, and both were in the assigned and treated coiled cohort (2/83); no patient in the clipped cohort (0/175) died (p = 0.04). In 1 of these 2 patients, the hemorrhage was not from the target aneurysm but from an incidental basilar artery aneurysm, which was coiled at the same time. CONCLUSIONS There was no significant difference in clinical outcomes between the 2 assigned treatment groups as measured by mRS outcomes or deaths. Clinical outcomes in the patients with posterior circulation aneurysms were better in the coiling group at 1 year, but after 1 year this difference was no longer statistically significant. Rates of complete aneurysm obliteration and rates of retreatment favored patients who actually underwent clipping compared with those who underwent coiling. Clinical trial registration no.: NCT01593267 (clinicaltrials.gov)

Microscope-integrated indocyanine green (ICG) fluorescence angiography is a novel technique in vascular neurosurgery with potential utility in treating arteriovenous malformations (AVMs).We analyzed the application of intraoperative ICG in 10 consecutive AVM surgeries for which surgical video was available. The ability to distinguish AVM vessels (draining veins, feeding and nidal arteries) from each other and from normal vessel was evaluated, and ICG angiographic findings were correlated with intra- and postoperative findings on digital subtraction angiography (DSA).ICG angiography was found to be useful by the surgeon in 9 of 10 patients. In 8 patients, it helped to distinguish AVM vessels. In 3 of 4 patients undergoing a postresection injection, it demonstrated that there was no residual arteriovenous shunting. In 1 patient, it helped to identify a small AVM nidus that was otherwise inapparent within a hematoma. Intraoperative DSA showed residual AVM in 2 of 10 patients requiring further resection of AVM not visualized during surgery.Microscope-integrated ICG angiography is a useful tool in AVM surgery. It can be used to distinguish AVM vessels from normal vessels and arteries from veins based on the timing of fluorescence with the dye. Our experience suggests that it is less useful with deep-seated lesions or when AVM vessels are not on the surface. ICG angiography complements rather than replaces DSA.

Relative cerebral blood volume (rCBV) accuracy can vary substantially depending on the dynamic susceptibility-weighted contrast-enhanced (DSC) acquisition and postprocessing methods, due to blood-brain barrier disruption and resulting T1-weighted leakage and T2- and/or T2*-weighted imaging (T2/T2*WI) residual effects. We set out to determine optimal DSC conditions that address these errors and maximize rCBV accuracy in differentiating posttreatment radiation effect (PTRE) and tumor.We recruited patients with previously treated high-grade gliomas undergoing image-guided re-resection of recurrent contrast-enhancing MR imaging lesions. Thirty-six surgical tissue samples were collected from 11 subjects. Preoperative 3T DSC used 6 sequential evenly timed acquisitions, each by using a 0.05-mmol/kg gadodiamide bolus. Preload dosing (PLD) and baseline subtraction (BLS) techniques corrected T1-weighted leakage and T2/T2*WI residual effects, respectively. PLD amount and incubation time increased with each sequential acquisition. Corresponding tissue specimen stereotactic locations were coregistered to DSC to measure localized rCBV under varying PLD amounts, incubation times, and the presence of BLS. rCBV thresholds were determined to maximize test accuracy (average of sensitivity and specificity) in distinguishing tumor (n = 21) and PTRE (n = 15) samples under the varying conditions. Receiver operator characteristic (ROC) areas under the curve (AUCs) were statistically compared.The protocol that combined PLD (0.1-mmol/kg amount, 6-minute incubation time) and BLS correction methods maximized test AUC (0.99) and accuracy (95.2%) compared with uncorrected rCBV AUC (0.85) and accuracy (81.0%) measured without PLD and BLS (P = .01).Combining PLD and BLS correction methods for T1-weighted and T2/T2*WI errors, respectively, enables highly accurate differentiation of PTRE and tumor growth.

Patients with atypical meningioma often undergo gross-total resection (GTR) at initial presentation, but the role of adjuvant radiation therapy remains unclear. The increasing prevalence of stereotactic radiosurgery (SRS) in the modern neurosurgical era has led to the use of routine postoperative radiation therapy in the absence of evidence-based guidelines. This study sought to define the long-term recurrence rate of atypical meningiomas and identify the value of SRS in affecting outcome.The authors identified 228 patients with microsurgically treated atypical meningiomas who underwent a total of 257 resections at the Barrow Neurological Institute over the last 20 years. Atypical meningiomas were diagnosed according to current WHO criteria. Clinical and radiographic data were collected retrospectively.Median clinical and radiographic follow-up was 52 months. Gross-total resection, defined as Simpson Grade I or II resection, was achieved in 149 patients (58%). The median proliferative index was 6.9% (range 0.4%-20.6%). Overall 51 patients (22%) demonstrated tumor recurrence at a median of 20.2 months postoperatively. Seventy-one patients (31%) underwent adjuvant radiation postoperatively, with 32 patients (14%) receiving adjuvant SRS and 39 patients (17%) receiving adjuvant intensity modulated radiation therapy (IMRT). The recurrence rate for patients receiving SRS was 25% (8/32) and for IMRT was 18% (7/39), which was not significantly different from the overall group. Gross-total resection was predictive of progression-free survival (PFS; relative risk 0.255, p < 0.0001), but postoperative SRS was not associated with improved PFS in all patients or in only those with subtotal resections.Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection. This analysis of the largest patient series to date suggests that close observation remains reasonable in the setting of aggressive microsurgical resection. Although postoperative adjuvant SRS did not significantly affect tumor recurrence rates in this experience, a larger cohort study with longer follow-up may reveal a therapeutic benefit in the future.

Quantifying MVA rather than MVD provides better correlation with survival in HGG. This is attributed to a specific "glomeruloid" vascular pattern, which is better characterized by vessel area than number. Despite its prognostic value, MVA quantification is laborious and clinically impractical. The DSC-MR imaging measure of rCBV offers the advantages of speed and convenience to overcome these limitations; however, clinical use of this technique depends on establishing accurate correlations between rCBV, MVA, and MVD, particularly in the setting of heterogeneous vascular size inherent to human HGG.We obtained preoperative 3T DSC-MR imaging in patients with HGG before stereotactic surgery. We histologically quantified MVA, MVD, and vascular size heterogeneity from CD34-stained 10-μm sections of stereotactic biopsies, and we coregistered biopsy locations with localized rCBV measurements. We statistically correlated rCBV, MVA, and MVD under conditions of high and low vascular-size heterogeneity and among tumor grades. We correlated all parameters with OS by using Cox regression.We analyzed 38 biopsies from 24 subjects. rCBV correlated strongly with MVA (r = 0.83, P < .0001) but weakly with MVD (r = 0.32, P = .05), due to microvessel size heterogeneity. Among samples with more homogeneous vessel size, rCBV correlation with MVD improved (r = 0.56, P = .01). OS correlated with both rCBV (P = .02) and MVA (P = .01) but not with MVD (P = .17).rCBV provides a reliable estimation of tumor MVA as a biomarker of glioma outcome. rCBV poorly estimates MVD in the presence of vessel size heterogeneity inherent to human HGG.

Neurosurgery simulator development is growing as practitioners recognize the need for improved instructional and rehearsal platforms to improve procedural skills and patient care. In addition, changes in practice patterns have decreased the volume of specific cases, such as aneurysm clippings, which reduces the opportunity for operating room experience.The authors developed a hands-on, dimensionally accurate model for aneurysm clipping using patient-derived anatomic data and three-dimensional (3D) printing. Design of the model focused on reproducibility as well as adaptability to new patient geometry.A modular, reproducible, and patient-derived medical simulacrum was developed for medical learners to practice aneurysmal clipping procedures. Various forms of 3D printing were used to develop a geometrically accurate cranium and vascular tree featuring 9 patient-derived aneurysms. 3D printing in conjunction with elastomeric casting was leveraged to achieve a patient-derived brain model with tactile properties not yet available from commercial 3D printing technology. An educational pilot study was performed to gauge simulation efficacy.Through the novel manufacturing process, a patient-derived simulacrum was developed for neurovascular surgical simulation. A follow-up qualitative study suggests potential to enhance current educational programs; assessments support the efficacy of the simulacrum.The proposed aneurysm clipping simulator has the potential to improve learning experiences in surgical environment. 3D printing and elastomeric casting can produce patient-derived models for a dynamic learning environment that add value to surgical training and preparation.

Although the Fisher scale is commonly used to grade vasospasm risk in aneurysmal subarachnoid hemorrhage (aSAH) patients, it fails to account for increasing subarachnoid hemorrhage (SAH) thickness.We developed a simple quantitative scale based on maximal SAH thickness and compared its reproducibility and ability to predict symptomatic vasospasm against the Fisher scale.The incidence of radiographic and symptomatic vasospasm among 250 aSAH patients treated at our institution was investigated. Admission head computed tomography scans were graded according to the Fisher scale and the proposed scale, which assigns a score from 1 to 5 based on a single measurement of maximum SAH thickness. We calculated vasospasm risk per grade for the Fisher scale and the proposed scale, and compared inter- and intraobserver variability for both scales.Forty-five patients (20.6%) developed symptomatic vasospasm. On the proposed scale, grade 5 patients were at highest risk, with an odds ratio for symptomatic vasospasm of 11 (95% confidence interval [CI] 2.27-53.37). Odds ratios for proposed grades 4 and 3 were 4.63 (95% CI 1.10-19.59) and 3.04 (95% CI 0.85-10.90), respectively. The odds ratio for Fisher grade 3 was 3.3 (0.96-11.30). Mean inter- and intraobserver agreement was greater for the proposed scale in comparison with the Fisher scale (κ0.65 and κ0.81 vs κ0.51 and κ0.35, respectively).The new scale accounted for increasing SAH thickness and was superior to the Fisher scale in inter- and intraobserver agreement and in predicting symptomatic vasospasm, particularly among the highest-risk patients.

Background Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM. Methods We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei) for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set. Results We collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients). The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients). Conclusion Multi-parametric MRI and texture analysis can help characterize and visualize GBM's spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.

Fluorescence-guided surgery is one of the rapidly emerging methods of surgical "theranostics." In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies.Review of the literature.A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

Object Infiltrative tumor resection is based on regional (macroscopic) imaging identification of tumorous tissue and the attempt to delineate invasive tumor margins in macroscopically normal-appearing tissue, while preserving normal brain tissue. The authors tested miniaturized confocal fiberoptic endomicroscopy by using a near-infrared (NIR) imaging system with indocyanine green (ICG) as an in vivo tool to identify infiltrating glioblastoma cells and tumor margins. Methods Thirty mice underwent craniectomy and imaging in vivo 14 days after implantation with GL261-luc cells. A 0.4 mg/kg injection of ICG was administered intravenously. The NIR images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope probe. Histological samples were acquired from matching imaged areas for correlation of tissue images. Results In vivo NIR wavelength confocal endomicroscopy with ICG detects fluorescence of tumor cells. The NIR and ICG macroscopic imaging performed using a surgical microscope correlated generally to tumor and peritumor regions, but NIR confocal endomicroscopy performed using ICG revealed individual tumor cells and satellites within peritumoral tissue; a definitive tumor border; and striking fluorescent microvascular, cellular, and subcellular structures (for example, mitoses, nuclei) in various tumor regions correlating with standard clinical histological features and known tissue architecture. Conclusions Macroscopic fluorescence was effective for gross tumor detection, but NIR confocal endomicroscopy performed using ICG enhanced sensitivity of tumor detection, providing real-time true microscopic histological information precisely related to the site of imaging. This first-time use of such NIR technology to detect cancer suggests that combined macroscopic and microscopic in vivo ICG imaging could allow interactive identification of microscopic tumor cell infiltration into the brain, substantially improving intraoperative decisions.

OBJECTIVE This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors. METHODS CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging–matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard. RESULTS CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3–73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas. CONCLUSIONS CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.

Given advances in endovascular technique, the indications for revascularization in aneurysm surgery have declined.We sought to define indications, outline technical strategies, and evaluate the outcomes of patients treated with bypass in the endovascular era.We retrospectively reviewed all aneurysms treated between September 2006 and February 2013.We identified 54 consecutive patients (16 males and 39 females) with 56 aneurysms. Aneurysms were located along the cervical internal carotid artery (ICA) (n = 1), petrous/cavernous ICA (n = 1), cavernous ICA (n = 16), supraclinoid ICA (n = 7), posterior communicating artery (n = 2), anterior cerebral artery (n = 4), middle cerebral artery (MCA) (n = 13), posterior cerebral artery (PCA) (n = 3), posterior inferior cerebellar artery (n = 4), and vertebrobasilar arteries (n = 5). Revascularization was performed with superficial temporal artery (STA) to MCA bypass (n = 25), STA to superior cerebellar artery (SCA) (n = 3), STA to PCA (n = 1), STA-SCA/STA-PCA (n = 1), occipital artery (OA) to PCA (n = 2), external carotid artery/ICA to MCA (n = 15), OA to MCA (n = 1), OA to posterior inferior cerebellar artery (n = 1), and in situ bypasses (n = 8). At a mean clinical follow-up of 18.5 months, 45 patients (81.8%) had a good outcome (Glasgow Outcome Scale 4 or 5). There were 7 cases of mortality (12.7%) and an additional 9 cases of morbidity (15.8%). At a mean angiographic follow-up of 17.8 months, 14 bypasses were occluded. Excluding the 7 cases of mortality, the majority of aneurysms (n = 42) were obliterated. We identified 7 cases of residual aneurysm and recurrence in 6 patients at follow-up.Given current limitations with existing treatments, cerebral revascularization remains an essential technique for aneurysm surgery.

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by hydrocephalus in 6.5%–67% of cases. Some patients with aSAH develop shunt dependency, which is often managed by ventriculoperitoneal shunt placement. The objectives of this study were to review published risk factors for shunt dependency in patients with aSAH, determine the level of evidence for each factor, and calculate the magnitude of each risk factor to better guide patient management. METHODS The authors searched PubMed and MEDLINE databases for Level A and Level B articles published through December 31, 2014, that describe factors affecting shunt dependency after aSAH and performed a systematic review and meta-analysis, stratifying the existing data according to level of evidence. RESULTS On the basis of the results of the meta-analysis, risk factors for shunt dependency included high Fisher grade (OR 7.74, 95% CI 4.47–13.41), acute hydrocephalus (OR 5.67, 95% CI 3.96–8.12), in-hospital complications (OR 4.91, 95% CI 2.79–8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80–5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51–4.21), rehemorrhage (OR 2.21, 95% CI 1.24–3.95), posterior circulation location of the aneurysm (OR 1.85, 95% CI 1.35–2.53), and age ≥ 60 years (OR 1.81, 95% CI 1.50–2.19). The only risk factor included in the meta-analysis that did not reach statistical significance was female sex (OR 1.13, 95% CI 0.77–1.65). CONCLUSIONS The authors identified several risk factors for shunt dependency in aSAH patients that help predict which patients are likely to require a permanent shunt. Although some of these risk factors are not independent of each other, this information assists clinicians in identifying at-risk patients and managing their treatment.

Parasellar and sellar meningiomas are challenging tumors owing in part to their proximity to important neurovascular and endocrine structures. Complete resection can be associated with significant morbidity, and incomplete resections are common. In this study, the authors evaluated the outcomes of parasellar and sellar meningiomas managed with Gamma Knife radiosurgery (GKRS) both as an adjunct to microsurgical removal or conventional radiation therapy and as a primary treatment modality.A multicenter study of patients with benign sellar and parasellar meningiomas was conducted through the North American Gamma Knife Consortium. For the period spanning 1988 to 2011 at 10 centers, the authors identified all patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were also required to have a minimum of 6 months of imaging and clinical follow-up after GKRS. Factors predictive of new neurological deficits following GKRS were assessed via univariate and multivariate analyses. Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.The authors identified 763 patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were assessed clinically and with neuroimaging at routine intervals following GKRS. There were 567 females (74.3%) and 196 males (25.7%) with a median age of 56 years (range 8-90 years). Three hundred fifty-five patients (50.7%) had undergone at least one resection before GKRS, and 3.8% had undergone prior radiation therapy. The median follow-up after GKRS was 66.7 months (range 6-216 months). At the last follow-up, tumor volumes remained stable or decreased in 90.2% of patients. Actuarial progression-free survival rates at 3, 5, 8, and 10 years were 98%, 95%, 88%, and 82%, respectively. More than one prior surgery, prior radiation therapy, or a tumor margin dose < 13 Gy significantly increased the likelihood of tumor progression after GKRS. At the last clinical follow-up, 86.2% of patients demonstrated no change or improvement in their neurological condition, whereas 13.8% of patients experienced symptom progression. New or worsening cranial nerve deficits were seen in 9.6% of patients, with cranial nerve (CN) V being the most adversely affected nerve. Functional improvements in CNs, especially in CNs V and VI, were observed in 34% of patients with preexisting deficits. New or worsened endocrinopathies were demonstrated in 1.6% of patients; hypothyroidism was the most frequent deficiency. Unfavorable outcome with tumor growth and accompanying neurological decline was statistically more likely in patients with larger tumor volumes (p = 0.022) and more than 1 prior surgery (p = 0.021).Gamma Knife radiosurgery provides a high rate of tumor control for patients with parasellar or sellar meningiomas, and tumor control is accompanied by neurological preservation or improvement in most patients.

Abstract Glioblastoma (GBM) is a heterogeneous and lethal brain cancer. These tumors are followed using magnetic resonance imaging (MRI), which is unable to precisely identify tumor cell invasion, impairing effective surgery and radiation planning. We present a novel hybrid model, based on multiparametric intensities, which combines machine learning (ML) with a mechanistic model of tumor growth to provide spatially resolved tumor cell density predictions. The ML component is an imaging data-driven graph-based semi-supervised learning model and we use the Proliferation-Invasion (PI) mechanistic tumor growth model. We thus refer to the hybrid model as the ML-PI model. The hybrid model was trained using 82 image-localized biopsies from 18 primary GBM patients with pre-operative MRI using a leave-one-patient-out cross validation framework. A Relief algorithm was developed to quantify relative contributions from the data sources. The ML-PI model statistically significantly outperformed (p &lt; 0.001) both individual models, ML and PI, achieving a mean absolute predicted error (MAPE) of 0.106 ± 0.125 versus 0.199 ± 0.186 (ML) and 0.227 ± 0.215 (PI), respectively. Associated Pearson correlation coefficients for ML-PI, ML, and PI were 0.838, 0.518, and 0.437, respectively. The Relief algorithm showed the PI model had the greatest contribution to the result, emphasizing the importance of the hybrid model in achieving the high accuracy.

Background and Purpose- The CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) demonstrated equivalent composite outcomes between carotid endarterectomy (CEA) and carotid artery stenting (CAS) for treating carotid stenosis. We investigated nationwide trends in these procedures and associated periprocedural stroke, myocardial infarction, death, cost, and readmission rates since CREST outcomes were published. Methods- We queried the Nationwide Readmissions Database to identify patients undergoing CEA and CAS for asymptomatic and symptomatic carotid stenosis from 2010 to 2015. Patients were matched based on demographics, comorbidities, and severity of illness. Results- In total, 378 354 CEA and 57 273 CAS patients were treated during this 6-year period. CEA volume decreased by an average of 2669 procedures annually (P=0.001) with stable CAS volume (P=0.225). After matching, CEA patients had a higher rate of periprocedural stroke than CAS patients, driven by increased stroke risk in symptomatic CEA patients (8.1% versus 5.6%; odds ratio, 1.47 [CI, 1.29-1.68]; P<0.001) but a lower rate of overall inpatient mortality (0.8% versus 1.4%; odds ratio, 0.57 [CI, 0.48-0.68]; P<0.001). CEA patients were less likely to be readmitted within 30 days (7.2% versus 8.0%; odds ratio, 0.90 [CI, 0.84-0.96]; P=0.018) and 90 days (12.3% versus 14.1%; odds ratio, 0.86 [CI, 0.81-0.90]; P<0.001), and mean hospital costs were lower for CEA compared with CAS ($14 433 versus $19 172; P<0.001). Conclusions- The procedural treatment of carotid stenosis has changed dramatically in the post-CREST era. When matched for characteristics and illness severity, patients undergoing CEA had a higher rate of perioperative stroke than patients undergoing CAS, primarily among symptomatic patients. These findings are in contrast to the findings of CREST, which showed nearly twice the risk of stroke in CAS patients compared with CEA patients. CEA was associated with lower procedure cost and readmission rate.

OBJECTIVE We retrospectively reviewed our experience treating third ventricular colloid cysts to compare the efficacy of endoscopic and transcallosal approaches. METHODS Between September 1994 and March 2004, 55 patients underwent third ventricular colloid cyst resection. The transcallosal approach was used in 27 patients; the endoscopic approach was used in 28 patients. Age, sex, cyst diameter, and presence of hydrocephalus were similar between the two groups. RESULTS The operating time and hospital stay were significantly longer in the transcallosal craniotomy group compared with the endoscopic group. Both approaches led to reoperations in three patients. The endoscopic group had two subsequent craniotomies for residual cysts and one repeat endoscopic procedure because of equipment malfunction. The transcallosal craniotomy group had two reoperations for fractured drainage catheters and one operation for epidural hematoma evacuation. The transcallosal craniotomy group had a higher rate of patients requiring a ventriculoperitoneal shunt (five versus two) and a higher infection rate (five versus none). Intermediate follow-up demonstrated more small residual cysts in the endoscopic group than in the transcallosal craniotomy group (seven versus one). Overall neurological outcomes, however, were similar in the two groups. CONCLUSION Compared with transcallosal craniotomy, neuroendoscopy is a safe and effective approach for removal of colloid cysts in the third ventricle. The endoscope can be considered a first-line treatment for these lesions, with the understanding that a small number of these patients may need an open craniotomy to remove residual cysts.

Object Nonconvulsive status epilepticus (NCSE) is an underrecognized and poorly understood complication of aneurysmal subarachnoid hemorrhage (SAH). The authors evaluated the risk factors, electroencephalographic (EEG) characteristics, hospital course, and clinical outcomes associated with NCSE in a population with SAH treated at a single institution. Methods The hospitalization and outcome data were reviewed in 11 patients who had received a diagnosis of NCSE and SAH. The study included individuals from a cohort of 389 consecutive patients with SAH who were treated between March 2003 and June 2005, and who were analyzed retrospectively. The patients' medical history, neurological grade, events of hospitalization, EEG morphological patterns, and disposition were analyzed. Advanced age, female sex, need for ventriculostomy, poor neurological grade (Hunt and Hess Grade III, IV, or V), thick cisternal blood clots, and structural lesions (intracerebral hemorrhage and stroke) were common in the population with NCSE. Patients with normal results on angiograms, good neurological grade (Hunt and Hess Grade I or II), and minimal SAH (Fisher Grade 1 or 2) were at lower risk. The most common ictal patterns were intermittent, and consisted of generalized periodic epileptiform discharges. Medical complications were also frequent, and the outcome of these patients was poor despite aggressive treatment regimens. Conclusions Nonconvulsive status epilepticus is a devastating complication of SAH with a high rate of associated morbidity. Based on these findings it appears that the patients at highest risk for NCSE can be identified, and this should provide a basis for further studies designed to determine the clinical significance of various EEG patterns and to develop preventative strategies.

Frozen-section analysis is the current standard for the intraoperative diagnosis of brain tumors. Intraoperative confocal microscopy is an emerging technology with the potential to visualize tumor histopathological features and cell morphology in real time. The authors report their findings using this new intraoperative technology in vivo with sodium fluorescein contrast during the course of 50 microsurgical tumor resections.Eighty-eight regions were visualized with confocal microscopy, and corresponding biopsy samples were examined with routine neuropathological analysis. The tumors studied included meningiomas, schwannomas, gliomas of various grades, and a hemangioblastoma. The confocal microscopic features of each tumor and of various artifacts inherent to the technology were documented. A pathologist working in a blinded fashion reviewed a subset of the images in a further evaluation of the usefulness of the device as a diagnostic tool.Overall, intraoperative confocal imaging correlated surprisingly well with corresponding traditional histological findings, including the identification of many pathognomonic cytoarchitectural features of various brain tumors. In the blinded study, 26 (92.9%) of 28 lesions were diagnosed correctly.Further study will be necessary for better definition of the role of intraoperative confocal microscopy as a routine adjunct for intraoperative brain tumor diagnosis.

Giant aneurysms of the vertebral and basilar arteries are formidable lesions to treat.To evaluate the long-term outcomes of patients with vertebrobasilar aneurysms treated with extracranial-intracranial bypass and flow reduction.We retrospectively reviewed a prospective database of aneurysms cases treated between December 1993 and August 2011.Eleven patients (8 male, 3 female) with 12 aneurysms were treated. There were 3 basilar apex aneurysms, 2 aneurysms of the basilar trunk, and 7 vertebrobasilar junction aneurysms. There were 5 saccular and 7 fusiform aneurysms. All patients underwent extracranial-intracranial bypass and vessel occlusion. Flow was reversed or reduced by complete (n = 6) or partial occlusion of the basilar artery (n = 3) or by occlusion of the vertebral arteries distal to the posterior inferior cerebellar artery (n = 3). Postoperatively (mean follow-up, 71.6 months; range, 4-228; median, 49 months), the bypass patency rate was 92.3% (12/13). The perioperative mortality rate for the initial treatment was 18.2% (2/11). In 4 cases, the aneurysms continued to grow and required further treatment; after re-treatment, 3 of these patients died. Of the initial 11 patients, 6 were treated successfully and 5 died. The mean preoperative modified Rankin Scale score was 2.1 (range, 1-3; median, 2). At last follow-up for all patients, the mean modified Rankin Scale score was 3.45 (range, 1-6; median, 3) and 2.5 (range, 1-4; median, 2.5) for the 6 long-term survivors.Vertebrobasilar aneurysms are challenging lesions with limited microsurgical or endovascular options. Despite aggressive surgical treatment, the long-term outcome remains poor for most patients.

Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management.A PubMed search was performed using the key words "genetic," "molecular," "brain," "cerebral," "arteriovenous," "malformation," "rupture," "management," "embolization," and "radiosurgery." Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed.Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed.Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

The ability to diagnose brain tumors intraoperatively and identify tumor margins during resection could maximize resection and minimize morbidity. Advances in optical imaging enabled production of a handheld intraoperative confocal microscope.To present a feasibility analysis of the intraoperative confocal microscope for brain tumor resection.Thirty-three patients with brain tumor treated at Barrow Neurological Institute were examined. All patients received an intravenous bolus of sodium fluorescein before confocal imaging with the Optiscan FIVE 1 system probe. Optical biopsies were obtained within each tumor and along the tumor-brain interfaces. Corresponding pathologic specimens were then excised and processed. These data was compared by a neuropathologist to identify the concordance for tumor histology, grade, and margins.Thirty-one of 33 lesions were tumors (93.9%) and 2 cases were identified as radiation necrosis (6.1%). Of the former, 25 (80.6%) were intra-axial and 6 (19.4%) were extra-axial. Intra-axial tumors were most commonly gliomas and metastases, while all extra-axial tumors were meningiomas. Among high-grade gliomas, vascular neoproliferation, as well as tumor margins, were identifiable using confocal imaging. Meningothelial and fibrous meningiomas were distinct on confocal microscopy--the latter featured spindle-shaped cells distinguishable from adjacent parenchyma. Other tumor histologies correlated well with standard neuropathology tissue preparations.Intraoperative confocal microscopy is a practicable technology for the resection of human brain tumors. Preliminary analysis demonstrates reliability for a variety of lesions in identifying tumor cells and the tumor-brain interface. Further refinement of this technology depends upon the approval of tumor-specific fluorescent contrast agents for human use.

OBJECT Posterior fossa meningiomas represent a common yet challenging clinical entity. They are often associated with neurovascular structures and adjacent to the brainstem. Resection can be undertaken for posterior fossa meningiomas, but residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been used to treat meningiomas, and this study evaluates the outcome of this approach for those located in the posterior fossa. METHODS At 7 medical centers participating in the North American Gamma Knife Consortium, 675 patients undergoing SRS for a posterior fossa meningioma were identified, and clinical and radiological data were obtained for these cases. Females outnumbered males at a ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12–89 years). Prior resection was performed in 43.3% of the patient sample. The mean tumor volume was 6.5 cm 3 , and a median margin dose of 13.6 Gy (range 8–40 Gy) was delivered to the tumor. RESULTS At a mean follow-up of 60.1 months, tumor control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and 81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI 1.30–4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69–15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01–1.08, p = 0.005). Clinical stability or improvement was achieved in 92.3% of patients. Increasing tumor volume (odds ratio [OR] 1.06, 95% CI 1.01–1.10, p = 0.009) and clival, petrous, or cerebellopontine angle location as compared with petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05–3.65, p = 0.036) were predictive of neurological decline after radiosurgery. After radiosurgery, ventriculoperitoneal shunt placement, resection, and radiation therapy were performed in 1.6%, 3.6%, and 1.5%, respectively. CONCLUSIONS Stereotactic radiosurgery affords a high rate of tumor control and neurological preservation for patients with posterior fossa meningiomas. Those with a smaller tumor volume and no prior radiation therapy were more likely to have a favorable response after radiosurgery. Rarely, additional procedures may be required for hydrocephalus or tumor progression.

Untreated, moyamoya angiopathy is a progressive vaso-occlusive process that can lead to ischemic or hemorrhagic stroke.To review 1 institution's surgical experience with both direct and indirect bypass (encephaloduroarteriosynangiosis) in adult and pediatric groups.A retrospective review was conducted of a consecutive series of patients treated for moyamoya angiopathy between 1995 and 2009.Thirty-nine adult patients underwent indirect bypass as their initial therapy; 29 adult patients underwent direct bypass. Twenty-four pediatric patients included 20 indirect bypasses and 4 direct bypasses. Overall, 140 hemispheres were treated; 48 patients received revascularization of both hemispheres. There were 14 additional revascularization procedures (10% per hemisphere) performed over a site of continued hypoperfusion postoperatively. Fourteen postoperative ischemic strokes occurred during the entire follow-up (10% per hemisphere), and the Kaplan-Meier analysis was not significantly different between groups (P = .59). Four grafts (9.09%) had failed at radiographic follow-up of the 44 direct bypasses performed. Before the initial surgery, the modified Rankin Scale score was 1.58 ± 0.93, 1.48 ± 0.74, and 1.8 ± 1.1 in the pediatric, adult direct, and adult indirect groups (P = .39). At last follow-up, it was 1.29 ± 1.31, 1.09 ± 0.90, and 1.94 ± 1.51 (P = .04) in the pediatric, adult direct, and adult indirect groups.This series demonstrates that both direct and indirect bypasses can be equally effective in preventing stroke. However, in adult patients, direct bypass patients had significantly greater improvement in symptoms, as seen in modified Rankin Scale scores. Pediatric patients, despite undergoing predominantly indirect bypasses, fared roughly the same as the adults in the direct bypass group.

Spinal arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs) are rare, complex spinal vascular lesions that are challenging to manage. Recently, understanding of these lesions has increased thanks to neuroimaging technology. Published reports of surgical results and clinical outcome are limited to small series. The authors present a large contemporary series of patients with spinal AVFs and AVMs who were treated at Barrow Neurological Institute in Phoenix, Arizona.Retrospective detailed review of a prospective vascular database was performed for all patients with spinal AVFs and AVMs treated between 2000 and 2013. Patient demographic data, AVF and AVM characteristics, surgical results, clinical outcomes, complications, and long-term follow-up were reviewed.Between 2000 and 2013, 110 patients (57 male and 53 female) underwent obliteration of spinal AVFs and AVMs. The mean age at presentation was 42.3 years (range 18 months-81 years). There were 44 patients with AVFs and 66 with AVMs. The AVM group included 27 intramedullary, 21 conus medullaris, 12 metameric, and 6 extradural. The most common location was thoracic spine (61%), followed by cervical (22.7%), lumbar (14.5%), and sacral (1.8%). The most common presenting signs and symptoms included paresis/paralysis (75.5%), paresthesias (60%), pain (51.8%), bowel/bladder dysfunction (41.8%), and myelopathy (36.4%). Evidence of rupture was seen in 26.4% of patients. Perioperative embolization was performed in 42% of patients. Resection was performed in 95 patients (86.4%). Embolization alone was the only treatment in 14 patients (12.7%). One patient was treated with radiosurgery alone. Angiographically verified AVF and AVM obliteration was achieved in 92 patients (83.6%). At a mean follow-up duration of 30.5 months (range 1-205 months), 43 patients (97.7%) with AVFs and 57 (86.4%) with AVMs remained functionally independent (McCormick Scale scores ≤ 2). Perioperative complications were seen in 8 patients (7%). No deaths occurred. Temporary neurological deficits were observed in 27 patients (24.5%). These temporary deficits recovered 6-8 weeks after treatment. Recurrence was identified in 6 patients (13.6%) with AVFs and 10 (15.2%) with AVMs.Spinal AVFs and AVMs are complex lesions that should be considered for surgical obliteration. Over the last several decades the authors have changed surgical strategies and management to achieve better clinical outcomes. Transient neurological deficit postoperatively is a risk associated with intervention; however, clinical outcomes appear to exceed the natural history based on patients' ability to recover during the follow-up period. Due to the recurrence rate associated with these lesions, long-term follow-up is required.

Object Cerebral vasospasm following subarachnoid hemorrhage (SAH) causes significant morbidity in a delayed fashion. The authors recently published a new scale that grades the maximum thickness of SAH on axial CT and is predictive of vasospasm incidence. In this study, the authors further investigate whether different aneurysm locations result in different SAH clot burdens and whether any concurrent differences in ruptured aneurysm location and maximum SAH clot burden affect vasospasm incidence. Methods Two hundred fifty patients who were part of a prospective randomized controlled trial were reviewed. Most outcome and demographic variables were included as part of the prospective randomized controlled trial. Additional variables were also collected at a later time, including vasospasm data and maximum clot thickness. Results Aneurysms were categorized into 1 of 6 groups: intradural internal carotid artery aneurysms, vertebral artery (VA) aneurysms (including the posterior inferior cerebellar artery), basilar trunk or basilar apex aneurysms, middle cerebral artery aneurysms, pericallosal aneurysms, and anterior communicating artery aneurysms. Twenty-nine patients with nonaneurysmal SAH were excluded. Patients with pericallosal aneurysms had the least average maximum clot burden (5.3 mm), compared with 6.4 mm for the group overall, but had the highest rate of symptomatic vasospasm (56% vs 22% overall, OR 4.9, RR 2.7, p = 0.026). Symptomatic vasospasm occurrence was tallied in patients with clinical deterioration attributable to delayed cerebral ischemia. There were no significant differences in maximum clot thickness between aneurysm sites. Middle cerebral artery aneurysms resulted in the thickest mean maximum clot (7.1 mm) but rates of symptomatic and radiographic vasospasm in this group were statistically no different compared with the overall group. Vertebral artery aneurysms had the worst 1-year modified Rankin scale (mRS) scores (3.0 vs 1.9 overall, respectively; p = 0.0249). A 1-year mRS score of 0–2 (good outcome) was found in 72% of patients overall, but in only 50% of those with pericallosal and VA aneurysms, and in 56% of those with basilar artery aneurysms (p = 0.0044). Patients with stroke from vasospasm had higher mean clot thickness (9.71 vs 6.15 mm, p = 0.004). Conclusions The location of a ruptured aneurysm minimally affects the maximum thickness of the SAH clot but is predictive of symptomatic vasospasm or clinical deterioration from delayed cerebral ischemia in pericallosal aneurysms. The worst 1-year mRS outcomes in this cohort of patients were noted in those with posterior circulation aneurysms or pericallosal artery aneurysms. Patients experiencing stroke had higher mean clot burden.

Educational simulators provide a means for students and experts to learn and refine surgical skills. Educators can leverage the strengths of medical simulators to effectively teach complex and high-risk surgical procedures, such as placement of an external ventricular drain.Our objective was to develop a cost-effective, patient-derived medical simulacrum for cerebral lateral ventriculostomy.A cost-effective, patient-derived medical simulacrum was developed for placement of an external lateral ventriculostomy. Elastomeric and gel casting techniques were used to achieve realistic brain geometry and material properties. 3D printing technology was leveraged to develop accurate cranial properties and dimensions. An economical, gravity-driven pump was developed to provide normal and abnormal ventricular pressures. A small pilot study was performed to gauge simulation efficacy using a technology acceptance model.An accurate geometric representation of the brain was developed with independent lateral cerebral ventricular chambers. A gravity-driven pump pressurized the ventricular cavities to physiologic values. A qualitative study illustrated that the simulation has potential as an educational tool to train medical professionals in the ventriculostomy procedure.The ventricular simulacrum can improve learning in a medical education environment. Rapid prototyping and multi-material casting techniques can produce patient-derived models for cost-effective and realistic surgical training scenarios.

Acute hydrocephalus is a well-known sequela of aneurysmal subarachnoid hemorrhage (SAH). Controversy exists about whether open microsurgical methods serve to reduce shunt dependency compared with endovascular techniques.To determine predictors of shunt-dependent hydrocephalus and functional outcomes after aneurysmal SAH.A total of 471 patients who were part of a prospective, randomized, controlled trial from 2003 to 2007 were retrospectively reviewed. All variables including demographic data, medical history, treatment, imaging, and functional outcomes were included as part of the trial. No additional variables were retrospectively collected.Ultimately, 147 patients (31.2%) required a ventriculoperitoneal shunt (VPS) in our series. Age, dissecting aneurysm type, ruptured vertebrobasilar aneurysm, Fisher grade, Hunt and Hess grade, admission intraventricular hemorrhage, admission intraparenchymal hemorrhage, blood in the fourth ventricle on admission, perioperative ventriculostomy, and hemicraniectomy were significant risk factors (P < .05) associated with shunt-dependent hydrocephalus on univariate analysis. On multivariate analysis, intraventricular hemorrhage and intraparenchymal hemorrhage were independent risk factors for shunt dependency (P < .05). Clipping vs coiling treatment was not statistically associated with VPS after SAH on both univariate and multivariate analyses. Patients who did not receive a VPS at discharge had higher Glasgow Outcome Scale and Barthel Index scores and were more likely to be functionally independent and to return to work 72 months after surgery (P < .05).There is no difference in shunt dependency after SAH among patients treated by endovascular or microsurgical means. Patients in whom shunt-dependent hydrocephalus does not develop after SAH tend to have improved long-term functional outcomes.

Object The authors sought to assess the feasibility of a handheld visible-wavelength confocal endomicroscope imaging system (Optiscan 5.1, Optiscan Pty., Ltd.) using a variety of rapid-acting fluorophores to provide histological information on gliomas, tumor margins, and normal brain in animal models. Methods Mice (n = 25) implanted with GL261 cells were used to image fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA), acridine orange (AO), acriflavine (AF), and cresyl violet (CV). A U251 glioma xenograft model in rats (n = 5) was used to image sulforhodamine 101 (SR101). A swine (n = 3) model with AO was used to identify confocal features of normal brain. Images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope. Histological samples were acquired through biopsies from matched imaging areas. Samples were visualized with a benchtop confocal microscope. Histopathological features in corresponding confocal images and photomicrographs of H &amp; E–stained tissues were reviewed. Results Fluorescence induced by FNa, 5-ALA, AO, AF, CV, and SR101 and detected with the confocal endomicroscope allowed interpretation of histological features. Confocal endomicroscopy revealed satellite tumor cells within peritumoral tissue, a definitive tumor border, and striking fluorescent cellular and subcellular structures. Fluorescence in various tumor regions correlated with standard histology and known tissue architecture. Characteristic features of different areas of normal brain were identified as well. Conclusions Confocal endomicroscopy provided rapid histological information precisely related to the site of microscopic imaging with imaging characteristics of cells related to the unique labeling features of the fluorophores. Although experimental with further clinical trial validation required, these data suggest that intraoperative confocal imaging can help to distinguish normal brain from tumor and tumor margin and may have application in improving intraoperative decisions during resection of brain tumors.

Intraoperative angiography in cerebrovascular neurosurgery can drive the repositioning or addition of aneurysm clips. Our institution has switched from a strategy of intraoperative digital subtraction angiography (DSA) universally, to a strategy of indocyanine green (ICG) videoangiography with DSA on an as-needed basis. We retrospectively evaluated whether the rates of perioperative stroke, unexpected postoperative aneurysm residual, or parent vessel stenosis differed in 100 patients from each era (2002, “DSA era”; 2007, “ICG era”). The clip repositioning rate for neck residual or parent vessel stenosis did not differ significantly between the two eras. There were no differences in the rate of perioperative stroke or rate of false-negative studies. The per-patient cost of intraoperative imaging within the DSA era was significantly higher than in the ICG era. The replacement of routine intraoperative DSA with ICG videoangiography and selective intraoperative DSA in cerebrovascular aneurysm surgery is safe and effective.

Abstract BACKGROUND Hypothalamic hamartomas (HH) are rare lesions associated with treatment-resistant epilepsy. Open surgery results in modest seizure control (about 50%) but has a significant associated morbidity. Radiosurgery is limited to a subset of patients due to latent therapeutic effects. Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) offers a novel minimally invasive option. OBJECTIVE To evaluate a single center's outcomes for the LITT treatment of HH. METHODS We retrospectively reviewed our experience with LITT for the treatment of HH using our institution's prospectively maintained patient database. RESULTS Eighteen patients (mean age, 21.1 yr; median age, 11 yr) underwent 21 total LITT treatments for HH. Mean follow-up was 17.4 mo. The length of stay was 1 night for 16 (89%) patients. At the end of follow-up, 11 of 18 patients (61%) had full disconnection of the HH, and 12 of 15 (80%) patients with gelastic seizures and 5 (56%) of 9 patients with nongelastic seizures were seizure free (International League Against Epilepsy Class 1). Immediate complications included a 39% (7/18) incidence of neurological deficits, including 1 case of hemiparesis. At the end of follow-up, 22% of patients (4/18) had persistent deficits. The hypothyroidism that occurred was delayed in 11% of patients (2/18), as was short-term memory loss (22%, 4/18) and weight gain (22%, 4/18). CONCLUSION LITT therapy for HH can achieve excellent rates of seizure control with low morbidity and a short postoperative stay in a majority of patients. Additional research is needed to assess the durability of results and the full spectrum of cognitive outcomes.

OBJECT Hemorrhagic origin is unidentifiable in 10%–20% of patients presenting with spontaneous subarachnoid hemorrhage (SAH). While the patients in such cases do well clinically, there is a lack of long-term angiographic followup. The authors of the present study evaluated the long-term clinical and angiographic follow-up of a patient cohort with SAH of unknown origin that had been enrolled in the Barrow Ruptured Aneurysm Trial (BRAT). METHODS The BRAT database was searched for patients with SAH of unknown origin despite having undergone two or more angiographic studies as well as MRI of the brain and cervical spine. Follow-up was available at 6 months and 1 and 3 years after treatment. Analysis included demographic details, clinical outcome (Glasgow Outcome Scale, modified Rankin Scale [mRS]), and repeat vascular imaging. RESULTS Subarachnoid hemorrhage of unknown etiology was identified in 57 (11.9%) of the 472 patients enrolled in the BRAT study between March 2003 and January 2007. The mean age for this group was 51 years, and 40 members (70%) of the group were female. Sixteen of 56 patients (28.6%) required placement of an external ventricular drain for hydrocephalus, and 4 of these subsequently required a ventriculoperitoneal shunt. Delayed cerebral ischemia occurred in 4 patients (7%), leading to stroke in one of them. There were no rebleeding events. Eleven patients were lost to followup, and one patient died of unrelated causes. At the 3-year follow-up, 4 (9.1%) of 44 patients had a poor outcome (mRS &gt; 2), and neurovascular imaging, which was available in 33 patients, was negative. CONCLUSIONS Hydrocephalus and delayed cerebral ischemia, while infrequent, do occur in SAH of unknown origin. Long-term neurological outcomes are generally good. A thorough evaluation to rule out an etiology of hemorrhage is necessary; however, imaging beyond 6 weeks from ictus has little utility, and rebleeding is unexpected.

Surgical revascularization for adults with moyamoya disease (MD) includes direct, indirect, or combination bypasses. It is unclear which provides the best outcomes. We sought to determine the best surgical management for adults with MD by comparing perioperative complications and long-term outcomes among 3 bypass types. Literature databases were searched for articles reporting revascularization bypass outcomes for adults with MD. A pooled analysis of all qualified studies and meta-analysis using only studies reporting direct comparisons of 2 bypass types were performed. Overall odds ratios (ORs) comparing 2 bypass types were computed and publication bias was assessed. Rates of perioperative and long-term hemorrhage and ischemia and favorable outcomes were compared. Forty-seven studies were analyzed; 8 had level 1 or 2 evidence. Pooled analyses showed that perioperative hemorrhage rates were significantly (P = 0.02) lower with indirect compared with direct (OR, 0.03; 95% confidence interval [CI], 0.002–0.55) or combined (OR, 0.03; 95% CI, 0.002–0.53) bypasses. Meta-analysis showed that direct bypass was better at preventing long-term hemorrhage than was indirect bypass (OR, 0.26; 95% CI, 0.09–0.79; P = 0.02). Pooled analyses showed that direct is significantly better (P < 0.01) than indirect (OR, 0.51; 95% CI, 0.33–0.77) and combined (OR, 0.47; 95% CI, 0.31–0.72) bypasses in preventing long-term ischemia. Meta-analysis showed that direct was better than indirect bypass in producing long-term favorable outcomes (OR, 2.62; 95% CI, 1.19–5.79; P = 0.02), and the pooled analysis showed that combined bypass was better than indirect bypass in producing long-term favorable outcomes (OR, 1.26; 95% CI, 1.03–1.54; P = 0.02). Overall, our analyses suggest that direct bypass with or without indirect augmentation provides the best outcomes for adults with MD.

OBJECTIVE The Barrow Ruptured Aneurysm Trial (BRAT) is a prospective, randomized trial in which treatment with clipping was compared to treatment with coil embolization. Patients were randomized to treatment on presentation with any nontraumatic subarachnoid hemorrhage (SAH). Because all other randomized trials comparing these 2 types of treatments have been limited to saccular aneurysms, the authors analyzed the current BRAT data for this subgroup of lesions. METHODS The primary BRAT analysis included all sources of SAH: nonaneurysmal lesions; saccular, blister, fusiform, and dissecting aneurysms; and SAHs from an aneurysm associated with either an arteriovenous malformation or a fistula. In this post hoc review, the outcomes for the subgroup of patients with saccular aneurysms were further analyzed by type of treatment. The extent of aneurysm obliteration was adjudicated by an independent neuroradiologist not involved in treatment. RESULTS Of the 471 patients enrolled in the BRAT, 362 (77%) had an SAH from a saccular aneurysm. Patients with saccular aneurysms were assigned equally to the clipping and the coiling cohorts (181 each). In each cohort, 3 patients died before treatment and 178 were treated. Of the 178 clip-assigned patients with saccular aneurysms, 1 (1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. There was no statistically significant difference in poor outcome (modified Rankin Scale score > 2) between these 2 treatment arms at any recorded time point during 6 years of follow-up. After the initial hospitalization, 1 of 241 (0.4%) clipped saccular aneurysms and 21 of 115 (18%) coiled saccular aneurysms required retreatment (p < 0.001). At the 6-year follow-up, 95% (95/100) of the clipped aneurysms were completely obliterated, compared with 40% (16/40) of the coiled aneurysms (p < 0.001). There was no difference in morbidity between the 2 treatment groups (p = 0.10). CONCLUSIONS In the subgroup of patients with saccular aneurysms enrolled in the BRAT, there was no significant difference between modified Rankin Scale outcomes at any follow-up time in patients with saccular aneurysms assigned to clipping compared with those assigned to coiling (intent-to-treat analysis). At the 6-year follow-up evaluation, rates of retreatment and complete aneurysm obliteration significantly favored patients who underwent clipping compared with those who underwent coiling. Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).

The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed.A COMPREHENSIVE LITERATURE SEARCH WAS PERFORMED UTILIZING PUBMED AND KEY WORDS: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics.Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications.In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery.

Background: High-grade glioma (HGG) is associated with a dismal prognosis despite significant advances in adjuvant therapies, including chemotherapy, immunotherapy, and radiotherapy. Extent of resection continues to be the most important independent prognosticator of survival. This underlines the significance of increasing gross total resection (GTR) rates by using adjunctive intraoperative modalities to maximize resection with minimal neurological morbidity. 5-aminolevulinic acid (5-ALA) is the only US Food and Drug Administration-approved intraoperative optical agent used for fluorescence-guided surgical resection of gliomas. Despite several studies on the impact of intra-operative 5-ALA use on the extent of HGG resection, a clear picture of how such usage affects patient survival is still unavailable. Methods: A systematic review was conducted of all relevant studies assessing the GTR rate and survival outcomes [overall survival (OS) and progression-free survival (PFS)] in HGG. A meta-analysis of eligible studies was performed to assess the influence of 5-ALA-guided resection on improving GTR, OS, and PFS. GTR was defined as >95% resection. Results: Of 23 eligible studies, 19 reporting GTR rates were included in the meta-analysis. The pooled cohort had 998 patients with HGG, including 796 with newly diagnosed cases. The pooled GTR rate among patients with 5-ALA-guided resection was 76.8% (95% confidence interval, 69.1-82.9%). A comparative subgroup analysis of 5-ALA-guided vs. conventional surgery (controlling for within-study covariates) showed a 26% higher GTR rate in the 5-ALA subgroup (odds ratio, 3.8; P < 0.001). There were 11 studies eligible for survival outcome analysis, 4 of which reported PFS. The pooled mean difference in OS and PFS was 3 and 1 months, respectively, favoring 5-ALA vs. control (P < 0.001). Conclusions: This meta-analysis shows a significant increase in GTR rate with 5-ALA-guided surgical resection, with a higher weighted GTR rate (~76%) than the pivotal phase III study (~65%). Pooled analysis showed a small yet significant increase in survival measures associated with the use of 5-ALA. Despite the statistically significant results, the low level of evidence and heterogeneity across these studies make it difficult to conclusively report an independent association between 5-ALA use and survival outcomes in HGG. Additional randomized control studies are required to delineate the role of 5-ALA in survival outcomes in HGG.

Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.

Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient's overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment.

Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14+ monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort. Initially, hematoma myeloid cells expressed a robust anabolic proinflammatory profile characterized by activation of hypoxia-inducible factors (HIFs) and expression of genes encoding immune factors and glycolysis. Subsequently, inflammatory gene expression decreased over time, whereas anti-inflammatory circuits were maintained and phagocytic and antioxidative pathways up-regulated. During this transition to immune resolution, glycolysis gene expression and levels of the potent proresolution lipid mediator prostaglandin E2 remained elevated in the hematoma, and unexpectedly, these elevations correlated with positive patient outcomes. Ex vivo activation of human macrophages by ICH-associated stimuli highlighted an important role for HIFs in production of both inflammatory and anti-inflammatory factors, including PGE2, which, in turn, augmented VEGF production. Our findings define the time course of myeloid activation in the human brain after ICH, revealing a conserved progression of immune responses from proinflammatory to proresolution states in humans after brain injury and identifying transcriptional programs associated with neurological recovery.

We examined the surgical approaches used at a single institution to treat petroclival meningioma and evaluated changes in method utilization over time.Craniotomies performed to treat petroclival meningioma between September of 1994 and July of 2005 were examined retrospectively. We reviewed 46 patients (mean follow-up, 3.6 yr). Techniques included combined petrosal or transcochlear approaches (15% of patients), retrosigmoid craniotomies with or without some degree of petrosectomy (59% of patients), orbitozygomatic craniotomies (7% of patients), and combined orbitozygomatic-retrosigmoid approaches (19% of patients). In 18 patients, the tumor extended supratentorially. Overall, the rate of gross total resection was 43%. Seven patients demonstrated progression over a mean of 5.9 years. No patients died. At 36 months, the progression-free survival rate for patients treated without petrosal approaches was 96%. Of 14 patients treated with stereotactic radiosurgery, none developed progression.Over the study period, a diminishing proportion of patients with petroclival meningioma were treated using petrosal approaches. Utilization of the orbitozygomatic and retrosigmoid approaches alone or in combination provided a viable alternative to petrosal approaches for treatment of petroclival meningioma. Regardless of approach, progression-free survival rates were excellent over short-term follow-up period.

BACKGROUND: Brainstem cavernous malformations (BSCMs) are believed to compose 9% to 35% of all cerebral cavernous malformations, but these lesions have been reported in children in very limited numbers. OBJECTIVE: To review surgical outcomes of pediatric patients with BSCMs treated at 1 institution. METHODS: We retrospectively analyzed the course of 40 pediatric patients (19 males, 21 females; age range, 10 months to 18.9 years; mean, 12.3 years) who underwent surgery between 1984 and 2009. Age, sex, presenting symptoms, location of lesion, surgical approach, new postoperative deficits, Glasgow Outcome Scale score, recurrences, and resolution of baseline symptoms were recorded. RESULTS: Thirty-nine patients experienced hemorrhage before surgery. Lesion locations included the pons (n = 22), midbrain (n = 4), midbrain and thalamus (n = 4), pontomesencephalic junction (n = 3), medulla (n = 3), pontomedullary junction (n = 3), and cervicomedullary junction (n = 1). Mean lesion size was 2.3 cm. Mean length of hospital stay was 10.7 days. The average clinical follow-up was 31.9 months in 36 patients with follow-up after discharge. At last follow-up, 5 patients had experienced symptoms and/or imaging consistent with rehemorrhage, either from a residual that enlarged or true recurrence (5.25% annual rebleed risk per patient after surgery); 2 required reoperation for further resection of cavernoma. Mean Glasgow Outcome Scale score was 4.2 on admission, 4.05 at discharge, and 4.5 at latest follow-up. Preoperative symptoms and deficits improved in 16 patients (40%). New neurological deficits developed in 19 patients (48%) and resolved in 9, leaving 10 patients (25%) with new permanent deficit. CONCLUSION: Compared with adults, pediatric patients with BCSMs tend to have larger lesions and higher rates of recurrence (regrowth of residual lesion). Given the greater life expectancy of children, surgical treatment seems warranted in those with surgically accessible lesions that have bled. Outcomes were similar to those in our adult series of patients with BSCMs.

Postsurgical pneumocephalus is an unavoidable sequela of craniotomy. Sufficiently large volumes of intracranial air can cause headaches, lethargy, and neurological deficits. Supplemental O(2) to increase the rate of absorption of intracranial air is a common but unsubstantiated neurosurgical practice. To the authors' knowledge, this is the first prospective study to examine the efficacy of this therapy and its effect on the rate of pneumocephalus absorption.Thirteen patients with postoperative pneumocephalus that was estimated to be > or = 30 ml were alternately assigned to breathe 100% O(2) using a nonrebreather mask (treatment group) or to breathe room air (control group) for 24 hours. Head computed tomography (CT) scans without contrast enhancement were obtained at the beginning and end of treatment or control therapy. A neuroradiologist blinded to the type of treatment used software to calculate the 3D volume of the pneumocephalus from the CT scans. The percentage of pneumocephalus absorption was calculated for each study participant.There was no statistically significant difference between the treatment and control groups regarding the mean initial pneumocephalus volume or time interval between CT scans. There was a significant difference (p = 0.009) between the mean rate of pneumocephalus volume reduction in the treatment (65%) and control groups (31%) per 24 hours. No patient suffered adverse effects related to treatment.Administration of postsurgical supplemental O(2) through a nonrebreather mask significantly increases the absorption rate of postcraniotomy pneumocephalus as compared with breathing room air.

Abstract OBJECTIVE: To compare anatomically the surgical exposure provided by pterional (PT), orbitozygomatic (OZ), and minisupraorbital (SO) craniotomies. @@METHODS:@@ Seven sides of six fixed cadaver heads injected with silicone were used. The mini-SO craniotomy followed by the PT and OZ approaches were performed sequentially. The bony flaps were attached with miniplates and screws, allowing easy conversion between the approaches. A frameless stereotactic device was used to calculate an area of surgical exposure and the angles of approach for six different anatomic targets. An image guidance system was used to demonstrate the limits of the surgical exposure for each technique. RESULTS: No significant differences were observed in the total area of surgical exposure when comparing the mini-SO (A = 1831.2 ± 415.3 mm2), PT (A = 1860.0 ± 617.2 mm2), and OZ approaches (A = 1843.3 ± 358.1 mm2; P &amp;gt; 0.05). Angular exposure was greater for the OZ and PT approaches than for the mini-SO approach, either in the vertical and horizontal axes, considering all of the six targets studied (P&amp;lt; 0.05). Except for the distal segment of the ipsilateral sylvian fissure, no practical differences in the limits of the exposure were detected. CONCLUSION: The mini-SO approach may offer a similar surgical working area compared with that provided by standard craniotomies and constitutes an excellent alternative to the OZ and PT craniotomies in selected patients. Selection should not be based primarily on the area to be exposed, but rather on the working angles that are anticipated to be required. The key point is to use the most adequate technique for a particular patient, rather than using a one-size-fits-all approach for all patients.

Bambakidis, Nicholas C. M.D.; Kakarla, U. Kumar M.D.; Kim, Louis J. M.D.; Nakaji, Peter M.D.; Porter, Randall W. M.D.; Daspit, C. Phillip M.D.; Spetzler, Robert F. M.D.

OBJECTIVE The evaluation of patients with subarachnoid hemorrhage (SAH) with negative initial catheter-based angiography is a diagnostic challenge. Better diagnostic strategies based on hemorrhage patterns are needed. METHODS We retrospectively investigated the yield of focused history taking, magnetic resonance imaging of the brain and cervical spine, follow-up vascular imaging, laboratory investigations, and craniotomy for vessel exploration in 100 patients with SAH and negative initial catheter-based angiography. RESULTS The most common distribution of hemorrhage was in a “classic” aneurysmal pattern filling the basal cisterns or posterior fossa (44 patients). A cause was determined in 13 patients (13%), the most common of which was aneurysm (7 patients). Repeat angiography was the most useful diagnostic modality, detecting seven lesions. The yield of the second angiogram was best in patients with a classic hemorrhage pattern (10%) and worse in patients with a negative computed tomographic scan and positive lumbar puncture (0%). The most common reason that a lesion was not detected on initial angiography was aneurysmal thrombosis (five patients). Magnetic resonance imaging of the brain and cervical spine detected one cervical ependymoma. Factors that may contribute to SAH, such as antiplatelet agent use and drug use, were found in 13 patients (13%). Adjunctive laboratory studies alerted practitioners to modifiable risk factors. CONCLUSION These data suggest useful modifications to current diagnostic paradigms for patients with angiographically negative spontaneous SAH.

To assess the utility, technical factors, and complications associated with the use of Onyx (Micro Therapeutics, Inc., Irvine, CA) for preoperative embolization of cranial and spinal tumors.We reviewed a prospectively accumulated database for patients in whom Onyx was used for preoperative embolization of cranial and spinal tumors over a 19-month period. The patients' demographic characteristics, tumor type and location, embolic agents used, arteries catheterized, and associated complications were assessed. Specific attention was focused on technical factors associated with the use of Onyx that differed from the use of other commonly used embolic materials.Ten patients (four female and six male; age range, 11-60 yr) underwent preoperative embolization with Onyx before cranial or spinal tumor resection. Tumors included three juvenile nasal angiofibromas, two meningiomas, two hemangioblastomas, two metastases (renal cell and thyroid), and one giant cell tumor. Onyx embolization was performed in 43 vessels over 11 treatment sessions. There were no complications related to the embolization procedures. Deep penetration of the embolic agent into the tumor was documented through preoperative imaging or surgical pathological specimens.Preoperative embolization of cranial and spinal tumors can be performed safely. Specific technical advantages of Onyx included deep penetration of lesions producing extensive tumor infarction, the ability to embolize extensive portions of the tumors through fewer arterial catheterizations, and the safety of catheter withdrawal despite often substantial reflux along the embolic catheter.

Intracranial venous hypertension is known to be associated with venous outflow obstruction. We discuss the diagnosis and treatment of mechanical venous outflow obstruction causing pseudotumor cerebri.We report 2 patients presenting with central venous outflow obstruction secondary to osseous compression of the internal jugular veins at the craniocervical junction. The point of jugular compression was between the lateral tubercle of C1 and a prominent, posteriorly located styloid process. In both cases, catheter venography showed high-grade jugular stenosis at the level of C1 with an associated pressure gradient. The dominant jugular vein was decompressed after the styloid process was resected. Postoperative imaging confirmed resolution of the jugular stenosis and normalization of preoperative pressure gradients. In both cases, the symptoms of intracranial hypertension resolved.Intracranial venous hypertension may result from extrinsic osseous compression of the jugular veins at the skull base. Although rare, this phenomenon is important to recognize because primary stenting not only is ineffective but also may actually exacerbate the outflow obstruction. The osseous impingement of the dominant jugular vein can be relieved via a decompressive styloidectomy, and the clinical results can be excellent.

INTRODUCTION Recent developments in optical science and image processing have miniaturized the components required for confocal microscopy. Clinical confocal imaging applications have emerged, including assessment of colonic mucosal dysplasia during colonoscopy. We present our initial experience with handheld, miniaturized confocal imaging in a murine brain tumor model. METHODS Twelve C57/BL6 mice were implanted intracranially with 105 GL261 glioblastoma cells. The brains of 6 anesthetized mice each at 14 and 21 days after implantation were exposed surgically, and the brain surface was imaged using a handheld confocal probe affixed to a stereotactic frame. The probe was moved systematically over regions of normal and tumor-containing tissue. Intravenous fluorescein and topical acriflavine contrast agents were used. Biopsies were obtained at each imaging site beneath the probe and assessed histologically. Mice were killed after imaging. RESULTS Handheld confocal imaging produced exquisite images, well-correlated with corresponding histologic sections, of cellular shape and tissue architecture in murine brain infiltrated by glial neoplasm. Reproducible patterns of cortical vasculature, as well as normal gray and white matter, were identified. Imaging effectively distinguished between tumor and nontumor tissue, including infiltrative tumor margins. Margins were easily identified by observers without prior neuropathology training after minimum experience with the technology. CONCLUSION Miniaturized handheld confocal imaging may assist neurosurgeons in detecting infiltrative brain tumor margins during surgery. It may help to avoid sampling error during biopsy of heterogeneous glial neoplasms, with the potential to supplement conventional intraoperative frozen section pathology. Clinical trials are warranted on the basis of these promising initial results.

Identification and complete interruption of fistulae are essential but not always obvious during the surgical treatment of spinal dural arteriovenous fistulae (dAVFs). We examined cases in which we identified and confirmed surgical obliteration of a spinal dAVF with the aid of microscope-integrated near-infrared indocyanine green (ICG) videoangiography.ICG videoangiography was performed during 6 surgical interventions in which 6 intradural dorsal AVFs (type I) were interrupted. An operating microscope-integrated light source containing infrared excitation light illuminated the operating field and was used to visualize an intravenous bolus of ICG. The locations of fistulae, feeding arteries, and draining veins and documentation of occlusion of the fistulae were compared with findings on preoperative and postoperative digital subtraction angiography.ICG videoangiography identified the fistulous point(s), feeding arteries, and draining veins in all 6 cases, as confirmed by immediate postoperative selective spinal angiography. In 1 case, intraoperative ICG ruled out an additional questionable fistula at a contiguous level suspected on the preoperative angiography.Microscope-based ICG videoangiography is simple and provides real-time information about the precise location of spinal dAVFs. During spinal dAVF surgery, this technique can be useful as an independent form of angiography or as an adjunct to intra or postoperative digital subtraction angiography. Larger series are needed to determine whether use of this modality could reduce the need for immediate postoperative spinal angiography after obliteration of intradural dorsal AVFs.

In Brief OBJECTIVE This is the largest contemporary series of distal posterior cerebral artery (PCA) aneurysms treated by use of endovascular coiling and stenting as well as surgical clipping, clip wrapping, and bypass techniques. We propose a new treatment paradigm. METHODS The location, size, type of aneurysm, clinical presentation, treatment, complications, and outcomes associated with 34 distal PCA aneurysms in 33 patients (15 females, 18 males; mean age, 44 years) were reviewed retrospectively. RESULTS The most common presenting symptom was headache in 19 (58%) followed by contralateral weakness or numbness in 6 (18%) and visual changes in 4 (12%). Eight aneurysms were giant. Of the remaining 26 aneurysms, 17 were fusiform/dissecting, 5 were saccular, and 4 were mycotic. Treatment was primarily endovascular in 22 patients, 12 of whom also had a concomitant surgical bypass procedure. Nine patients underwent microsurgical clipping, and 3 underwent combined treatment of clipping and coiling and/or stenting. There were no significant differences in outcomes between the groups (P = .078). The recurrence rate in patients undergoing coiling was 22% and 0% in patients undergoing clipping. Fourteen aneurysms (41%) involved treatment with an occipital artery-to-PCA bypass or an onlay graft. Compared with their preoperative status, these patients had significantly worse outcomes than those without a bypass (P = .013). CONCLUSION Bypass techniques for the treatment of distal PCA aneurysms are associated with a higher rate of complications than once thought. In our new treatment paradigm, bypass is a last resort and reserved for patients in whom balloon-test occlusion fails, who refuse parent-vessel sacrifice, and who cannot undergo primary stenting with coiling or clip wrapping. OBJECTIVE: We report the largest contemporary series of distal posterior cerebral artery (PCA) aneurysms treated by use of endovascular coiling and stenting as well as surgical clipping, clip wrapping, and bypass techniques. We propose a new treatment paradigm. METHODS: The location, size, type of aneurysm, clinical presentation, treatment, complications, and outcomes associated with 34 distal PCA aneurysms in 33 patients (15 females, 18 males; mean age, 44 years) were reviewed retrospectively. RESULTS: Presenting symptoms were headache in 19 (58%), contralateral weakness or numbness in 6 (18%) and visual changes in 4 (12%). Eight aneurysms were giant. Of the remaining 26 aneurysms, 17 were fusiform/dissecting, 5 were saccular, and 4 were mycotic. Treatment was primarily endovascular in 22 patients, 12 of whom also had a concomitant surgical bypass procedure. Nine patients underwent microsurgical clipping, and 3 underwent combined treatment of clipping and coiling and/or stenting. There were no significant differences in outcomes between the groups (P =.078). The recurrence rate in patients undergoing coiling was 22% and 0% in patients undergoing clipping. Fourteen aneurysms (41%) involved treatment with an occipital artery-to-PCA bypass or an onlay graft. Compared with their preoperative status, these patients had significantly worse outcomes than those without a bypass (P =.013). CONCLUSION: Bypass techniques for the treatment of distal PCA aneurysms are associated with a higher rate of complications than once thought. In our new treatment paradigm, bypass is a last resort and reserved for patients in whom balloon-test occlusion fails, who refuse parent-vessel sacrifice, and who cannot undergo primary stenting with coiling or clip wrapping.

MicroRNAs (miRNAs) are now recognized as the primary RNAs involved in the purposeful silencing of the cell's own message. In addition to the established role of miRNAs as developmental regulators of normal cellular function, they have recently been shown to be important players in pathological states such as cancer. The authors review the literature on the role of miRNAs in the formation and propagation of gliomas and medulloblastomas, highlighting the potential of these molecules and their inhibitors as therapeutics.

Blister aneurysms of the internal carotid artery (ICA) are uncommon. There is a paucity of data on the long-term outcomes of patients.To review our experience with the treatment of these lesions.We retrospectively reviewed all aneurysms treated at our institution between 1994 and 2005. Relevant operative notes, radiology reports, and inpatient/outpatient records were reviewed.Seventeen patients (3 male, 14 female) with 18 blister aneurysms of the ICA were identified. The mean age was 44.6 years (range, 17-72; median, 42 years). Twelve patients (70.6%) presented with aneurysmal subarachnoid hemorrhage. The mean admission Glasgow Outcome Scale score was 4.3 (range, 2-5; median, 5). All patients were initially treated using microsurgical technique with direct clipping (n = 15; 83.3%) or clip-wrapping with Gore-Tex (n = 3, 16.7%). There were 4 cases of intraoperative rupture, all associated with attempted direct clipping; all 4 cases were successfully clipped. Two cases rebled post-treatment. Both rebleeding episodes were managed with endovascular stenting. Follow-up angiography was available for 14 patients and revealed a new aneurysm adjacent to the site of clipping in 1 patient and in-stent stenosis in 2. At the mean follow-up of 74.5 months (median, 73; range, 7-165), the mean Glasgow Outcome Scale score was 4.6 (range, 2-5; median, 5).Microsurgical treatment of blister aneurysms of the ICA results in excellent outcome. In the evolution of treating these friable aneurysms, we have modified our clip-wrapping technique and use this technique when direct clipping is not feasible.

Hypothalamic hamartomas (HHs) are devastating lesions causing refractory epilepsy, rage attacks, social ineptitude, and precocious puberty. Microsurgical and/or endoscopic resection offers an excellent risk/benefit profile for cure or improvement of epilepsy.The authors reviewed a prospective database maintained during the first 7 years of the Barrow Hypothalamic Hamartoma program. They describe and illustrate their surgical methods, and they review data from several previous publications regarding surgical outcome.To date, the authors have performed surgery in 165 patients for symptomatic HHs. Patients underwent an endoscopic, transcallosal, or skull base approach, or multiple approaches. Twenty-six patients (15.8%) required more than 1 treatment for their HH.Microsurgical and endoscopic resection of symptomatic HHs are technically demanding but can be performed safely with excellent results and an acceptable risk profile. Meticulous attention to the subtleties of surgical management helps optimize outcomes.

Object Data regarding the time course of recovery after poor-grade subarachnoid hemorrhage (SAH) is lacking. Most SAH studies assess outcome at a single time point, often as early as 3 or 6 months following SAH. The authors hypothesized that recovery following poor-grade SAH is a dynamic process and that early outcomes may not always approximate long-term outcomes. To test this hypothesis, they analyzed long-term outcome data from a cohort of patients with poor-grade aneurysmal SAH to determine the incidence and predictors of early and delayed neurological improvement. Methods The authors reviewed outcome data from 88 poor-grade SAH patients enrolled in a prospective SAH treatment trial (the Barrow Ruptured Aneurysm Trial). They assessed modified Rankin Scale (mRS) scores at discharge, 6 months, 12 months, and 36 months after treatment to determine the incidence and predictors of neurological improvement during each interval. Results The mean aggregate mRS scores at 6 months (3.31 ± 2.1), 12 months (3.28 ± 2.2), and 36 months (3.17 ± 2.3) improved significantly compared with the mean score at hospital discharge (4.33 ± 1.3, p &lt; 0.001), but they did not differ significantly among themselves. Between discharge and 6 months, 61% of patients improved on the mRS. The incidence of improvement between 6–12 months and 12–36 months was 18% and 19%, respectively. Hunt and Hess Grade IV versus V (OR 6.20, 95% CI 2.11–18.25, p &lt; 0.001) and the absence of large (&gt; 4 cm) (OR 2.76, 95% CI 1.02–7.55, p = 0.05) or eloquent (OR 5.17, 95% CI 1.89–14.10, p &lt; 0.01) stroke were associated with improvement up to 6 months. Age ≤ 65 years (OR 5.56, 95% CI 1.17–26.42, p = 0.02), Hunt and Hess Grade IV versus V (OR 4.17, 95% CI 1.10–15.85, p = 0.03), and absence of a large (OR 8.97, 95% CI 2.65–30.40, p &lt; 0.001) or eloquent (OR 4.54, 95% CI 1.46–14.08, p = 0.01) stroke were associated with improvement beyond 6 months. Improvement beyond 1 year was most strongly predicted by the absence of a large stroke (OR 7.62, 95% CI 1.55–37.30, p &lt; 0.01). Conclusions A substantial minority of poor-grade SAH patients will experience delayed recovery beyond the point at which most studies assess outcome. Younger patients, those presenting in better clinical condition, and those without CT evidence of large or eloquent stroke demonstrated the highest capacity for delayed recovery.

Relative cerebral blood volume, as measured by T2*-weighted dynamic susceptibility-weighted contrast-enhanced MRI, represents the most robust and widely used perfusion MR imaging metric in neuro-oncology. Our aim was to determine whether differences in modeling implementation will impact the correction of leakage effects (from blood-brain barrier disruption) and the accuracy of relative CBV calculations as measured on T2*-weighted dynamic susceptibility-weighted contrast-enhanced MR imaging at 3T field strength.This study included 52 patients with glioma undergoing DSC MR imaging. Thirty-six patients underwent both non-preload dose- and preload dose-corrected DSC acquisitions, with 16 patients undergoing preload dose-corrected acquisitions only. For each acquisition, we generated 2 sets of relative CBV metrics by using 2 separate, widely published, FDA-approved commercial software packages: IB Neuro and nordicICE. We calculated 4 relative CBV metrics within tumor volumes: mean relative CBV, mode relative CBV, percentage of voxels with relative CBV > 1.75, and percentage of voxels with relative CBV > 1.0 (fractional tumor burden). We determined Pearson (r) and Spearman (ρ) correlations between non-preload dose- and preload dose-corrected metrics. In a subset of patients with recurrent glioblastoma (n = 25), we determined receiver operating characteristic area under the curve for fractional tumor burden accuracy to predict the tissue diagnosis of tumor recurrence versus posttreatment effect. We also determined correlations between rCBV and microvessel area from stereotactic biopsies (n = 29) in 12 patients.With IB Neuro, relative CBV metrics correlated highly between non-preload dose- and preload dose-corrected conditions for fractional tumor burden (r = 0.96, ρ = 0.94), percentage > 1.75 (r = 0.93, ρ = 0.91), mean (r = 0.87, ρ = 0.86), and mode (r = 0.78, ρ = 0.76). These correlations dropped substantially with nordicICE. With fractional tumor burden, IB Neuro was more accurate than nordicICE in diagnosing tumor versus posttreatment effect (area under the curve = 0.85 versus 0.67) (P < .01). The highest relative CBV-microvessel area correlations required preload dose and IB Neuro (r = 0.64, ρ = 0.58, P = .001).Different implementations of perfusion MR imaging software modeling can impact the accuracy of leakage correction, relative CBV calculation, and correlations with histologic benchmarks.

Object Patient-reported quality-of-life (QOL) end points are becoming increasingly important health care metrics. To date, no nasal morbidity instrument specifically designed for patients undergoing endonasal skull base surgery has been developed. In this study, the authors describe the development and validation of a site-specific nasal morbidity instrument to assess patient-reported rhinological outcomes following endonasal skull base surgery. Methods Eligible patients included those with planned endonasal transsphenoidal surgery for sellar pathology identified in outpatient neurosurgical clinics of 3 skull base centers from October 2011 to July 2012. An initial 23-question pool was developed by subject matter experts, review of the literature, and from the results of a previous validation study to assess for common rhinological complaints. Symptoms were ranked by patients from “No Problem” to “Severe Problem” on a 6-point Likert scale. Exploratory factor analysis, change scores, and importance rank were calculated to define the final instrument consisting of 12 items (The Anterior Skull Base Nasal Inventory-12, or ASK Nasal-12). Psychometric validation of the final instrument was performed using standard statistical techniques. Results One hundred four patients enrolled in the study. All patients completed the preoperative survey and 100 patients (96%) completed the survey 2–4 weeks after surgery. Internal consistency of the final instrument was 0.88. Concurrent validity measures demonstrated a strong correlation between overall nasal functioning and total scores (p &lt; 0.001). Test-retest reliability measures demonstrated a significant intraclass correlation between responses (p &lt; 0.001). Effect size as calculated by standardized response mean suggested a large effect (0.84). Discriminant validity calculations demonstrated that the instrument was able to discriminate between preoperative and postoperative patients (p &lt; 0.001). Conclusions This prospective study demonstrates that the ASK Nasal-12 is a validated, site-specific, unidimensional rhinological outcomes tool sensitive to clinical change. It can be used in conjunction with multidimensional QOL instruments to assess patient-reported nasal perceptions in endonasal skull base surgery. This instrument is being used as a primary outcome measure in an ongoing multicenter nasal morbidity study. Clinical trial registration no.: NCT01504399 ( ClinicalTrials.gov ).

Neurosurgery, a demanding specialty, involves many microsurgical procedures that require complex skills, including open surgical treatment of intracranial aneurysms. Simulation or practice models may be useful for acquiring these skills before trainees perform surgery on human patients.To describe a human placenta model for the creation and clipping of aneurysms.Placental vessels from 40 human placentas that were dimensionally comparable to the sizes of appropriate cerebral vessels were isolated to create aneurysms of different shapes. The placentas were then prepared for vascular microsurgery exercises. Sylvian fissure--like dissection technique and clipping of large- and small-necked aneurysms were practiced on human placentas with and without pulsatile flow. A surgical field designed to resemble a real craniotomy was reproduced in the model.The human placenta has a plethora of vessels that are of the proper dimensions to allow the creation of aneurysms with dome and neck dimensions similar to those of human saccular and fusiform cerebral aneurysms. These anatomic scenarios allowed aneurysm inspection, manipulation, and clipping practice. Technical microsurgical procedures include simulation of sylvian fissure dissection, unruptured aneurysm clipping, ruptured aneurysm clipping, and wrapping; all were reproduced with high fidelity to the haptics of live human surgery. Skill-training exercises realistically reproduced aneurysm clipping.Human placenta provides an inexpensive, widely available, convenient biological tissue that can be used to create models of cerebral aneurysms of different morphologies. Neurosurgical trainees may benefit from the preoperative use of a realistic model to gain familiarity and practice with critical surgical techniques for treating aneurysms.

The endoscopic supracerebellar-infratentorial (SCIT) approach is a viable method to access pathology of the posterior incisura, but a narrow working space and frequent instrument conflict can potentially limit its surgical efficacy. Until now, no rigorous studies were available comparing surgical freedom and angle of attack for four previously well-described approaches to pineal region targets. Four formalin-fixed cadaver heads were dissected bilaterally (eight sides). A midline approach and three progressively lateral approaches to the pineal region were performed (paramedian, lateral, extreme lateral), and anatomical targets were identified. Utilizing frameless stereotaxy, we calculated surgical freedom using the vector cross-product method for all approaches for the exposed area and for three anatomical targets (pineal gland, ipsilateral superior colliculus, splenium). The mean and maximum possible angles of attack were calculated in the axial and sagittal planes. Point target surgical freedom, exposed area surgical freedom, and angle of attack for each individual pineal region target can be maximized depending on the medial-to-lateral location of the craniotomy. For endoscopic-controlled approaches, the extreme lateral approach provides the largest surgical freedom when accessing the ipsilateral superior colliculus (P < 0.0001), the lateral approach provides the largest surgical freedom to the pineal gland (P < 0.0001), and the paramedian craniotomy provides the largest surgical freedom when accessing the splenium (P < 0.0001). The extreme lateral approach to the pineal gland provided the largest horizontal angle of attack (P < 0.0001), and the extreme lateral approach to the ipsilateral superior colliculus provided the largest vertical angle of attack (P < 0.001). The microscope provides marginally increased surgical freedom and a better angle of attack to specific anatomical targets in the paramedian and extreme lateral approach compared with those provided by the endoscope, but these differences are negligible during intraoperative application. Presurgical planning and a detailed understanding of the important neurovascular structures in the pineal region are paramount to safe and successful surgical execution. Our current cadaveric study indicates that the medial-to-lateral location of craniotomy can maximize access to pineal region targets. Furthermore, the endoscope is a viable alternative to the microscope for identifying pathology of the posterior incisura. These differences in surgical freedom and angle of attack to the pineal region may be useful to consider when planning minimal-access approaches.

BACKGROUND: Indocyanine green (ICG) angiography is commonly used to map the vascular configuration of cerebral arteriovenous malformations (AVMs) during resection. OBJECTIVE: To determine whether ICG improves rates of resection and clinical outcomes. METHODS: A retrospective chart review was done for all patients undergoing resection of an AVM by the senior author (R.F.S.) between 2007 and 2011. Operative reports, hospital records, and radiographic imaging were used to determine the use of ICG, the incidence of residual disease, and clinical outcomes. RESULTS: A total of 130 cases (56 ICG, 74 non-ICG) were identified. Average AVM grade (2.2 vs 2.4) and size (2.7 vs 2.7 cm) were similar between the ICG and non-ICG groups, respectively. ICG was more often used when the AVM nidus was close to the cortical surface (71.4% vs 17.6%; P = .001) or lobar (82.1% vs 54.1%; P = .008). Eighteen patients (13.8%) were noted to have residual disease. Reoperation rates and change in modified Rankin Scale score were not different between the 2 groups (12.5% vs 14.9%, P = .8; 0.6 vs 0.4, P = .17). There were no ICG-attributable complications. CONCLUSION: ICG videoangiography is a quick and safe method of intraoperatively mapping the angioarchitecture of superficial AVMs, but it is less helpful for deep-seated lesions. This modality alone does not improve the identification of residual disease or clinical outcomes. Surgeon experience with extensive study of preoperative vascular imaging is paramount to achieving acceptable clinical outcomes. Formal angiography remains the gold standard for the evaluation of AVM obliteration. ABBREVIATIONS: AVM, arteriovenous malformation DSA, digital subtraction angiography ICG, indocyanine green

Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it to an operating microscope (OPMI) equipped with a fluorescence module and to a benchtop confocal laser scanning microscope (CLSM). 5-Aminolevulinic acid–induced PpIX fluorescence was assessed in GL261-Luc2 cells in vitro and in vivo after implantation in mouse brains, at an invading glioma growth stage, simulating residual tumor. Intraoperative fluorescence of high and low PpIX concentrations in normal brain and tumor regions with SFE, OPMI, CLSM, and histopathology were compared. SFE imaging of PpIX correlated to CLSM at the cellular level. PpIX accumulated in normal brain cells but significantly less than in glioma cells. SFE was more sensitive to accumulated PpIX in fluorescent brain areas than OPMI (P < 0.01) and dramatically increased imaging time (>6×) before tumor-to-background contrast was diminished because of photobleaching. SFE provides new endoscopic capabilities to view PpIX-fluorescing tumor regions at cellular resolution. SFE may allow accurate imaging of 5-aminolevulinic acid labeling of gliomas and other tumor types when current detection techniques have failed to provide reliable visualization. SFE was significantly more sensitive than OPMI to low PpIX concentrations, which is relevant to identifying the leading edge or metastasizing cells of malignant glioma or to treating low-grade gliomas. This new application has the potential to benefit surgical outcomes.

OBJECTIVE Hemangiopericytomas (HPCs) are rare tumors widely recognized for their aggressive clinical behavior, high recurrence rates, and distant and extracranial metastases even after a gross-total resection. The authors report a large multicenter study, through the International Gamma Knife Research Foundation (IGKRF), reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly discovered HPCs. METHODS Eight centers participating in the IGKRF participated in this study. A total of 90 patients harboring 133 tumors were identified. Patients were included if they had a histologically diagnosed HPC managed with SRS during the period 1988–2014 and had a minimum of 6 months' clinical and radiological follow-up. A de-identified database was created. The patients' median age was 48.5 years (range 13–80 years). Prior treatments included embolization (n = 8), chemotherapy (n = 2), and fractionated radiotherapy (n = 34). The median tumor volume at the time of SRS was 4.9 cm 3 (range 0.2–42.4 cm 3 ). WHO Grade II (typical) HPCs formed 78.9% of the cohort (n = 71). The median margin and maximum doses delivered were 15 Gy (range 2.8–24 Gy) and 32 Gy (range 8–51 Gy), respectively. The median clinical and radiographic follow-up periods were 59 months (range 6–190 months) and 59 months (range 6–183 months), respectively. Prognostic variables associated with local tumor control and post-SRS survival were evaluated using Cox univariate and multivariate analysis. Actuarial survival after SRS was analyzed using the Kaplan-Meier method. RESULTS Imaging studies performed at last follow-up demonstrated local tumor control in 55% of tumors and 62.2% of patients. New remote intracranial tumors were found in 27.8% of patients, and 24.4% of patients developed extracranial metastases. Adverse radiation effects were noted in 6.7% of patients. During the study period, 32.2% of the patients (n = 29) died. The actuarial overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression–free survival (PFS) was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Review of these 76 treated tumors showed that 17 presented as an in-field recurrence and 59 were defined as an out-of-field recurrence. Margin dose greater than 16 Gy (p = 0.037) and tumor grade (p = 0.006) were shown to influence PFS. The development of extracranial metastases was shown to influence overall survival (p = 0.029) in terms of PFS; repeat (multiple) SRS showed additional benefit. CONCLUSIONS SRS provides a reasonable rate of local tumor control and a low risk of adverse effects. It also leads to neurological stability or improvement in the majority of patients. Long-term close clinical and imaging follow-up is necessary due to the high probability of local recurrence and distant metastases. Repeat SRS is often effective for treating new or recurrent HPCs.

Subarachnoid hemorrhage (SAH) from ruptured posterior inferior cerebellar artery (PICA) aneurysms is uncommon, and long-term outcome data for patients who have suffered such hemorrhages is lacking. This study investigated in-hospital and long-term clinical data from a prospective cohort of patients with SAH from ruptured PICA aneurysms enrolled in a randomized trial; their outcomes were compared with those of SAH patients who were treated for other types of ruptured intracranial aneurysms. The authors hypothesize that PICA patients fare worse than those with aneurysms in other locations and this difference is related to the high rate of lower cranial nerve dysfunction in PICA patients.The authors analyzed data for 472 patients enrolled in the Barrow Ruptured Aneurysm Trial (BRAT) and retrospectively reviewed vasospasm data not collected prospectively. In the initial cohort, 57 patients were considered angiographically negative for aneurysmal SAH source and did not receive treatment for aneurysms, leaving 415 patients with aneurysmal SAH.Of 415 patients with aneurysmal SAH, 22 (5.3%) harbored a ruptured PICA aneurysm. Eight of them had dissecting/fusiform-type aneurysms while 14 had saccular-type aneurysms. Nineteen PICA patients were treated with clipping (1 crossover from coiling), 2 were treated with coiling, and 1 died before treatment. When comparing PICA patients to all other aneurysm patients in the study cohort, there were no statistically significant differences in age (mean 57.6 ± 11.8 vs 53.9 ± 11.8 years, p = 0.17), Hunt and Hess grade median III [IQR II-IV] vs III [IQR II-III], p = 0.15), Fisher grade median 3 [IQR 3-3] vs 3 [IQR 3-3], p = 0.53), aneurysm size (mean 6.2 ± 3.0 vs 6.7 ± 4.0 mm, p = 0.55), radiographic vasospasm (53% vs 50%, p = 0.88), or clinical vasospasm (12% vs 23%, p = 0.38). PICA patients were more likely to have a fusiform aneurysm (36% vs 12%, p = 0.004) and had a higher incidence of lower cranial nerve dysfunction and higher rate of tracheostomy/percutaneous endoscopic gastrostomy placement compared with non-PICA patients (50% vs 16%, p < 0.001). PICA patients had a significantly higher incidence of poor outcome at discharge (91% vs 67%, p = 0.017), 1-year follow-up (63% vs 29%, p = 0.002), and 3-year follow-up (63% vs 32%, p = 0.006).Patients with ruptured PICA aneurysms had a similar rate of radiographic vasospasm, equivalent admission Fisher grade and Hunt and Hess scores, but poorer clinical outcomes at discharge and at 1- and 3-year follow-up when compared with the rest of the BRAT SAH patients with ruptured aneurysms. The PICA's location at the medulla and the resultant high rate of lower cranial nerve dysfunction may play a role in the poor outcome for these patients. Furthermore, PICA aneurysms were more likely to be fusiform than saccular, compared with non-PICA aneurysms; the complex nature of these aneurysms may also contribute to their poorer outcome.

There has been a progressive decrease in the indications for cerebral revascularization during the past 30 years, particularly with the advance of endovascular techniques. Our objective was to define indications for and evaluate outcomes of patients treated with bypass surgery in the modern endovascular era. We retrospectively reviewed the charts of all patients who underwent direct cerebral revascularization procedures between January 2006 and March 2013. In total, 121 patients underwent 131 direct microsurgical revascularization procedures. The indications for bypass surgery were moyamoya angiopathy (40 patients, 47 bypasses), complex aneurysms (54 patients, 56 bypasses), and occlusive vascular disease (27 patients, 28 bypasses). Revascularization resulted in improvement of symptoms in 77.5% of patients with moyamoya angiopathy (mean clinical follow-up 18.8 months) and 55.5% of patients with occlusive vascular disease (mean clinical follow-up 10.4 months). Among the aneurysm patients treated with revascularization, 81.5% had a favorable outcome (Glasgow Outcome Scale score 4–5) at long-term follow-up (mean clinical followup 18.5 months). Although microvascular cerebral revascularization is no longer performed as commonly as in the past, it remains an essential part of the skill set required to treat select vascular pathologies. Complex aneurysms are the single largest indication for direct bypass procedures. Moyamoya disease is by far the largest indication if indirect bypass procedures are included in the analysis. In experienced hands, the morbidity and mortality of patients undergoing cerebral revascularization procedures are low and long-term outcomes generally excellent.

The three-dimensional (3D) endoscope is a novel tool that provides stereoscopic vision and may allow for improved dexterity and safety during surgical resection of ventral skull base lesions. We describe here the cumulative experience available in the neurosurgical literature.A PubMed literature review was performed to identify and analyze all studies pertaining to 3D endoscopic endonasal skull base surgery.We identified 26 articles: 14 clinical articles, 5 simulated environment studies, 5 human cadaveric studies, and 2 expert opinions. In all the clinical studies, 262 patients were treated for the following 257 pathologies listed in the articles: 190 suprasellar/parasellar lesions (73.9%), 41 ventral skull base lesions (16.0%), 19 sinonasal pathologies (7.4%), and 7 cerebrospinal fluid leak repairs (2.7%). Complication rates, operative time, length of hospital stay, and extent of tumor resection were equivalent between two-dimensional (2D) and 3D endoscopy. However, all studies reported that subjective depth perception and spatial orientation were markedly improved with 3D technology. In 3 studies (11.5%), it was concluded that there was no clinically significant surgical benefit in switching from 2D to 3D endoscopy. All cadaveric studies and expert opinions concluded that 3D endoscopy improved the identification of key anatomical structures and was superior to 2D endoscopy. Simulated environment studies demonstrated that 3D endoscopy improved speed and accuracy of endonasal tasks, more so in novice surgeons.Our findings suggest that 3D endoscopy provides improved surgical dexterity by affording the surgeon with depth perception when manipulating tissue and maneuvering the endoscope in the endonasal corridor.

OBJECTIVE Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas. METHODS Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression. RESULTS Nineteen patients (median age 64.5 years, range 50–78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1–3) and 2 (range 1–4), respectively; the median preoperative tumor volume was 11.3 cm 3 (range 0.9–92.0 cm 3 ). The median radiation dose from BT was 63 Gy (range 54–80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03–47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9–321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically. CONCLUSIONS R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

Background: Technological innovations based on light amplification created by stimulated emission of radiation (LASER) have been used extensively in the field of neurosurgery.Methods: We reviewed the medical literature to identify current laser-based technological applications for surgical, diagnostic, and therapeutic uses in neurosurgery.Results: Surgical applications of laser technology reported in the literature include percutaneous laser ablation of brain tissue, the use of surgical lasers in open and endoscopic cranial surgeries, laser-assisted microanastomosis, and photodynamic therapy for brain tumors.Laser systems are also used for intervertebral disk degeneration treatment, therapeutic applications of laser energy for transcranial laser therapy and nerve regeneration, and novel diagnostic laser-based technologies (e.g., laser scanning endomicroscopy and Raman spectroscopy) that are used for interrogation of pathological tissue.Conclusion: Despite controversy over the use of lasers for treatment, the surgical application of lasers for minimally invasive procedures shows promising results and merits further investigation.Laser-based microscopy imaging devices have been developed and miniaturized to be used intraoperatively for rapid pathological diagnosis.The multitude of ways that lasers are used in neurosurgery and in related neuroclinical situations is a testament to the technological advancements and practicality of laser science.

While venous congestion in the peripheral vasculature has been described and accepted, intracranial venous congestion remains poorly understood. The characteristics, pathophysiology, and management of cerebral venous stasis, venous hypertension and venous congestion remain controversial, and a unifying conceptual schema is absent. The cerebral venous and lymphatic systems are part of a complex and dynamic interaction between the intracranial compartments, with interplay between the parenchyma, veins, arteries, cerebrospinal fluid, and recently characterized lymphatic-like systems in the brain. Each component contributes towards intracranial pressure, occupying space within the fixed calvarial volume. This article proposes a framework to consider conditions resulting in brain and neck venous congestion, and seeks to expedite further study of cerebral venous diagnoses, mechanisms, symptomatology, and treatments.A multi-institution retrospective review was performed to identify unique patient cases, complemented with a published case series to assess a spectrum of disease states with components of venous congestion affecting the brain. These diseases were organized according to anatomical location and purported mechanisms. Outcomes of treatments were also analyzed. Illustrative cases were identified in the venous treatment databases of the authors.This framework is the first clinically structured description of venous pathologies resulting in intracranial venous and cerebrospinal fluid hypertension. Our proposed system highlights unique clinical symptoms and features critical for appropriate diagnostic work-up and potential treatment. This novel schema allows clinicians effectively to approach cases of intracranial hypertension secondary to venous etiologies, and furthermore provides a framework by which researchers can better understand this developing area of cerebrovascular disease.

The circumstances of failure for nonoperative management of blunt traumatic brain injury have been poorly defined. In this study, all trauma patients identified over a 12-year period with progression of neurologic injury requiring craniotomy were retrospectively reviewed.Data collected included demographic information, mechanism of injury, field and admission vital signs, and Glasgow Coma Scale score, medications, associated injuries, and coagulopathy. Head computed tomographic scans were reviewed, and anatomic findings were correlated with clinical changes (change in mental status or elevation of intracranial pressure) that led to subsequent CT scan and craniotomy.Of 20,100 patients, there were 852 who had computed tomographic scans with acute intracranial injuries on admission; 462 patients were managed nonoperatively. Fifty-seven patients had progression of neurologic injury (34 < 24 hours = early; 23 > 24 hours = late) that required surgery.Of the variables investigated, only anatomic location of injury was found to be predictive of early failure of nonoperative management. Frontal intraparenchymal hematomas are particularly prone to early failure. Clinical examination and intracranial pressure monitoring are equally important in detecting failure and should be an integral part of nonoperative management.

OBJECTIVE To describe a modification of the pterional approach (PT), the minipterional craniotomy (MPT), and compare the anatomic exposure provided by these two approaches. METHODS The anatomic exposure offered by the MPT and PT were compared in eight sides of cadaver heads using a computerized tracking system, a robotic microscope, and an image-guidance system. The area of surgical exposure, angular exposure, and anatomic limits of each craniotomy were evaluated. Three recently operated clinical cases (EGF) are also reported. RESULTS There were no statistical differences in the total area of surgical exposure between the two craniotomies (PT, 1524.7 ± 305 mm2; MPT, 1469.7 ± 380.3 mm2; P > 0.05) or among the ipsilateral, middle, and contralateral components of the area (P > 0.05). There were no differences in angular exposure along the longitudinal and transverse axis angles for the three selected targets, the bifurcations of internal carotid and middle cerebral arteries, and the anterior communicating artery (P > 0.05). Except for the distal portion of the operculoinsular compartment of the sylvian fissure, no significant differences in the limits of the surgical exposure through the PT and MPT were apparent on the image-guidance system. CONCLUSION The MPT craniotomy provides comparable surgical exposure to that offered by the PT. The advantages of the MPT include reduction of tissue trauma and bony removal, a decrease in surgical time, and improved cosmetic outcomes.

Spinal dural arteriovenous fistulae (dAVFs), are lesions involving an aberrant connection between a radicular feeding artery and the venous system of the spinal cord at the dural sleeve of the nerve root. When rare dAVFs are occult on digitally subtracted catheter-based angiography, they present a diagnostic and therapeutic challenge.We report 3 cases of angiographically occult spinal dAVFs that were evaluated during surgery with indocyanine green (ICG) fluorescent microscope-integrated angiography.Three patients with clinical and magnetic resonance imaging features suggestive of a spinal dAVF but no abnormality on digital subtraction angiography underwent surgical exploration with the aid of microscope-integrated ICG videoangiography.In all 3 cases, ICG identified the intradural vein draining the fistula, clearly distinguishing it from an artery or uninvolved medullary vein.ICG angiography can rapidly identify a draining vein as it enters the spinal canal even in dAVFs not identifiable on catheter-based digital subtraction angiography.

As a general principle, sacrifice of cerebral veins at surgery is avoided. However, at times sacrifice of a vein may be desirable to increase surgical exposure. At present, no method exists to predict whether such sacrifice will be accommodated by the presence of collateral venous drainage. We show a simple technique to examine cerebral venous blood flow using indocyanine green videoangiography.In two patients, parasagittal meningiomas were found to be associated with paramedian veins that impeded complete removal of the tumors. The suitability of veins removal was assessed by applying a temporary aneurysm clip and performing an indocyanine green videoangiogram.In one patient, stasis was observed in the vein. In the second patient, a collateral flow allowed the venous blood to drain. The former test was considered a counterindication for venous sacrifice, whereas the latter supported its feasibility. The vein was preserved in the former case and coagulated in the latter. In both cases, the patients did well.Although our limited study cannot prove that venous congestion or infarction can be avoided with this technique, it does provide direct evidence of the presence or absence of collaterals that can help guide intraoperative surgical decision-making.

Placement of external ventricular drains subjects patients to risks of injury, intracerebral hematoma, and failure from improper placement. Traditional free-hand placement has been associated with a relatively frequent occurrence of these complications. We sought to assess the accuracy of ventriculostomy when performed using image-navigation technology in the intensive care unit (ICU). Thirty-five patients were consecutively enrolled in a single-arm trial evaluating the accuracy and complications from ventriculostomies performed at the ICU bedside using electromagnetic image guidance technology. The duration of any additional imaging and the length of the total procedure were also quantified. There were no unacceptably placed ventriculostomy catheters; only two catheters were not perfectly placed in the ipsilateral frontal horn. There was only one patient with tract hemorrhage. The use of image guidance technology added approximately 36 minutes to the time from when the need was identified to when successful drainage was achieved (p = 0.002), but added only 4 minutes of operative time (p = 0.12). Accuracy of placement demonstrated a statistically significant improvement in the accuracy of ventriculostomy over historical data. There were two registration failures which were converted to the traditional technique; there were no other complications arising from the use of image-guided technology. Electromagnetic image guidance is feasible and accurate. Image guidance technology eliminated unacceptably placed catheters and may reduce the risk of catheter-associated intracerebral hemorrhages.

BACKGROUND: External ventricular drains (EVDs) are valuable adjuncts in the management of neurosurgical patients but are associated with a significant risk of cerebrospinal fluid (CSF) infection (range, 0% to 27%); a review of 23 studies reported a mean of 8.8%. OBJECTIVE: To compare the efficacy of 2 different antibiotic-impregnated EVD catheters in preventing CSF infections. METHODS: Patients were prospectively enrolled in an Institutional Review Board–approved study. During alternating 3-month periods, all patients received either a minocycline/rifampin-impregnated (M/R) ventricular catheter or a clindamycin/rifampin-impregnated (C/R) EVD catheter. CSF cultures were collected at the time of insertion and twice weekly. Positive cultures were defined a priori as growth of the same bacteria on 2 media (eg, blood agar and broth) or 2 cultures of the same bacteria on 1 medium (eg, broth). RESULTS: Altogether, 129 patients (mean age, 58.4 years; 55 male) received 65 C/R catheters and 64 M/R catheters. The most common indications for EVD placement were aneurysmal subarachnoid hemorrhage (48.1%), spontaneous intraparenchymal hemorrhage (13.2%), and tumor (11.6%). The mean duration of ventriculostomy drainage was 11.8 and 12.7 days in the C/R and M/R groups, respectively. No positive CSF cultures were identified in either cohort. CONCLUSIONS: The use of antibiotic-impregnated catheters was associated with an extremely low risk of CSF infection compared with the reported mean of nearly 9% for standard EVD catheters. Infection rates for both C/R and M/R EVD catheters were zero. These results support the use of antibiotic-impregnated EVD catheters in routine clinical practice.

The wide spectrum of symptoms and radiographic findings in patients with Chiari I malformation makes the decision to proceed with intervention controversial. We evaluated symptomatic outcomes using diverse surgical techniques in 104 patients who underwent decompression surgery. The symptoms of most patients improved. Patients with syringomyelia showed less symptomatic improvement; however, syringomyelia was not associated with postoperative symptomatic worsening. Durotomy was performed in 97.1% and arachnoid opening was performed in 60.6% with visualization of the fourth ventricle in 51.9% of patients. Neither arachnoid opening nor fourth ventricle visualization was associated with the clinical outcome. Duraplasty was performed in 94.2% of patients. A Chiari plate was used in 13.4% of patients and was associated with favorable outcomes. Use of postoperative steroids or muscle relaxants was not associated with outcome. Syringomyelia showed a 62.5% improvement rate on postoperative MRI. In conclusion, bony decompression and dural opening are important aspects of Chiari I surgery, with symptomatic improvement observed in most patients.

Recent studies have questioned the utility of surgical resection of unruptured brain arteriovenous malformations (bAVMs).We performed an assessment of outcomes and complications of surgical resection of low-grade bAVMs (Spetzler-Martin grade I or II) at a single high-volume neurosurgical center.We reviewed all unruptured low-grade bAVMs treated with surgery (with or without preoperative embolization) between January 2004 and January 2014. Stroke rate, mortality, and clinical and radiographic outcomes were examined.Of 95 patients treated surgically, 85 (25 grade I, 60 grade II) met inclusion criteria, and all achieved radiographic cure postoperatively. Ten patients (11.8%) were lost to follow-up; the mean follow-up of the remaining 85 was 3.3 years. Three patients (3.5%) with grade II bAVMs experienced a stroke; no patients died. Although 20 patients (23.5%) had temporary postoperative neurological deficit, only 3 (3.5%) had new clinical impairment (modified Rankin Scale score ≥2) at last follow-up. Eight of the 13 patients (61.5%) with preexisting clinical impairment had improved modified Rankin Scale scores of 0 or 1; and 17 of 30 patients (56.7%) with preoperative seizures were seizure-free without antiepileptic medication postoperatively. No significant differences existed in stroke rate or clinical outcome between grades I and II patients at follow-up (Fisher exact test, P = .55 and P > .99, respectively).Surgical resection of low-grade unruptured bAVMs is safe, with a high rate of improvement in functional status and seizure reduction. Although transient postoperative neurological deficit was observed in some patients, permanent treatment-related neurological morbidity was rare.ARUBA, A Randomized Trial of Unruptured Brain Arteriovenous MalformationsbAVM, brain arteriovenous malformationmRS, modified Rankin Scale.

BACKGROUND: Microscopic and endoscopic transsphenoidal approaches to the sellar are well established. Surgical freedom is an important skull base principle that can be measured objectively and used to compare approaches. OBJECTIVE: To compare the surgical freedom of 4 transsphenoidal approaches to the sella turcica to aid in surgical approach selection. METHODS: Four transsphenoidal approaches to the sella were performed on 8 silicon-injected cadaveric heads. Surgical freedom was determined with stereotactic image guidance using previously established techniques. The results are presented as the area of surgical freedom and angular surgical freedom (angle of attack) in the axial and sagittal planes. RESULTS: Mean total exposed area surgical freedom for the microscopic sublabial, endoscopic binostril, endoscopic uninostril, and microscopic endonasal approaches were 102 ± 13, 89 ± 6, 81 ± 4, and 69 ± 10 cm2, respectively. The endoscopic binostril approach had the greatest surgical freedom at the pituitary gland and ipsilateral and contralateral internal carotid arteries (25.7 ± 5.4, 28.0 ± 4.0, and 23.0 ± 3.0 cm2) compared with the microscopic sublabial (21.8 ± 3.5, 21.3 ± 2.4, and 19.5 ± 6.3 cm2), microscopic endonasal (14.2 ± 2.7, 14.1 ± 3.2, and 16.3 ± 4.0 cm2), and endoscopic uninostril (19.7 ± 4.8, 22.4 ± 2.3, and 19.5 ± 2.9 cm2) approaches. Axial angle of attack was greatest for the microscopic sublabial approach to the same targets (14.7 ± 1.3°, 11.0 ± 1.5°, and 11.8 ± 1.1°). For the sagittal angle of attack, the endoscopic binostril approach was superior for all 3 targets (16.6 ± 1.7°, 17.2 ± 0.70°, and 15.5 ± 1.2°). CONCLUSION: Microscopic sublabial and endoscopic binostril approaches provided superior surgical freedom compared with the endonasal microscopic and uninostril endoscopic approaches. This work provides objective baseline values for the quantification and evaluation of future refinements in surgical technique or instrumentation. ABBREVIATIONS: cICA, cavernous internal carotid artery pICA, petrous internal carotid artery

<b>Objective</b> Endoscopic ipsilateral endonasal transmaxillary, contralateral endonasal transseptal transmaxillary, and Caldwell-Luc approaches can access lesions within the retromaxillary space and pterygopalatine fossa. We compared the exposure and surgical freedom of these transmaxillary approaches to assist with surgical decision making. <b>Design</b> Four cadaveric heads were dissected bilaterally using the three approaches just described. Prior to dissection, stereotactic computed tomography (CT) scans were obtained on each head to obtain anatomical measurements. Surgical freedom and area of exposure were determined by stereotaxis. <b>Main Outcome Measures</b> Area of exposure was calculated as the extent of the orbital floor, maxillary sinus floor, nasal floor, and mandibular ramus exposed through each approach. Surgical freedom was the area through which the proximal end of the endoscope could be freely moved while moving the tip of the endoscope to the edges of the exposed area. <b>Results</b> The mean exposed area was similar: 9.9 ± 2.5 cm² (Caldwell-Luc), 10.4 ± 2.6 cm² (ipsilateral endonasal), and 10.1 ± 2.1 cm² (contralateral transseptal) (<i>p</i> > 0.05). The surgical freedom of the Caldwell-Luc approach (113 ± 7 cm²) was greater than for either endonasal approach, 76 cm²± 15 (<i>p</i> = 0.001) (ipsilateral endonasal) and 83 cm² ± 15 (<i>p</i> = 0.003) contralateral transseptal. <b>Conclusions</b> Our work demonstrates that the Caldwell-Luc endonasal approach offers greater surgical freedom than either approach for anterolateral skull base targets, although these approaches offer similar exposure.

OBJECTIVE Cerebral venous pressure gradient (CVPG) from dural venous sinus stenosis is implicated in headache syndromes such as idiopathic intracranial hypertension (IIH). The incidence of CVPG in headache patients has not been reported. METHODS The authors reviewed all cerebral venograms with manometry performed for headache between January 2008 and May 2015. Patient demographics, headache etiology, intracranial pressure (ICP) measurements, and radiographic and manometric results were recorded. CVPG was defined as a difference ≥ 8 mm Hg by venographic manometry. RESULTS One hundred sixty-four venograms were performed in 155 patients. There were no procedural complications. Ninety-six procedures (58.5%) were for patients with IIH. The overall incidence of CVPG was 25.6% (42 of 164 procedures): 35.4% (34 of 96 procedures) in IIH patients and 11.8% (8 of 68 procedures) in non-IIH patients. Sixty procedures (36.6%) were performed in patients with preexisting shunts. Seventy-seven patients (49.7%) had procedures preceded by an ICP measurement within 4 weeks of venography, and in 66 (85.7%) of these patients, the ICP had been found to be elevated. CVPG was seen in 8.3% (n = 5) of the procedures in the 60 patients with a preexisting shunt and in 0% (n = 0) of the 11 procedures in the 77 patients with normal ICP (p < 0.001 for both). Noninvasive imaging (MR venography, CT venography) was assessed prior to venography in 112 (68.3%) of 164 cases, and dural venous sinus abnormalities were demonstrated in 73 (65.2%) of these cases; there was a trend toward CVPG (p = 0.07). Multivariate analysis demonstrated an increased likelihood of CVPG in patients with IIH (OR 4.97, 95% CI 1.71-14.47) and a decreased likelihood in patients with a preexisting shunt (OR 0.09, 95% CI 0.02-0.44). CONCLUSIONS CVPG is uncommon in IIH patients, rare in those with preexisting shunts, and absent in those with normal ICP.

BACKGROUND: Resection of cerebellopontine angle (CPA) meningiomas may result in significant neurological morbidity. Radiosurgery offers a minimally invasive alternative to surgery. OBJECTIVE: To evaluate, in a multicenter cohort study, the outcomes of patients harboring CPA meningiomas who underwent Gamma Knife radiosurgery (GKRS). METHODS: From 7 institutions participating in the North American Gamma Knife Consortium, 177 patients with benign CPA meningiomas treated with GKRS and at least 6 months radiologic follow-up were included for analysis. The mean age was 59 years and 84% were female. Dizziness or imbalance (48%) and cranial nerve (CN) VIII dysfunction (45%) were the most common presenting symptoms. The median tumor volume and prescription dose were 3.6 cc and 13 Gy, respectively. The mean radiologic and clinical follow-up durations were 47 and 46 months, respectively. Multivariate regression analyses were performed to identify the predictors of tumor progression and neurological deterioration. RESULTS: The actuarial rates of progression-free survival at 5 and 10 years were 93% and 77%, respectively. Male sex (P = .014), prior fractionated radiation therapy (P = .010), and ataxia at presentation (P = .002) were independent predictors of tumor progression. Symptomatic adverse radiation effects and permanent neurological deterioration were observed in 1.1% and 9% of patients, respectively. Facial spasms at presentation (P = .007) and lower maximal dose (P = .011) were independently associated with neurological deterioration. CONCLUSION: GKRS is an effective therapy for CPA meningiomas. Depending on the patient and tumor characteristics, radiosurgery can be an adjuvant treatment to initial surgical resection or a standalone procedure that obviates the need for resection in most patients. ABBREVIATIONS: ARE, adverse radiation effect CN, cranial nerve CPA, cerebellopontine angle EBRT, external beam radiation therapy GKRS, Gamma Knife radiosurgery IAC, internal auditory canal NAGKC, North American Gamma knife Consortium PFS, progression-free survival SRS, stereotactic radiosurgery WHO, World Health Organization

Endoscopic approaches are increasingly utilized to treat third ventricular colloid cysts but have been associated with lower rates of complete cyst wall resection. Our objective was to assess the results of colloid cyst resection via an anterolateral endoscopic approach with a dual-instrument technique, with an emphasis on completeness of cyst wall resection.A retrospective review of the senior author's experience with 22 colloid cysts treated with endoscopic resection since 2004 was performed. Initial cyst size, completeness of resection, postoperative radiographic residual, recurrence at follow-up, need for reoperation, and neurologic morbidity were assessed. All cysts were approached from an anterolateral trajectory with two instruments working in concert through a single endoscope.Of 22 patients, near-total resection was obtained in 95%. In 3 cases, a very small, radiographically occult residual was left. Complete cyst wall resection was therefore obtained in 18 (82%). There were no cases of recurrence at follow-up in any patient. No patients required craniotomy or underwent re-resection. Fifteen of 16 (94%) patients with long-term clinical follow-up remained stable or improved.High rates of complete colloid cyst resection, with low morbidity, are possible with an anterolateral endoscopic approach with dual-instrument technique. These results support the findings of other endoscopists that show how technical modifications to traditional endoscopic approaches can produce favorable results.

OBJECTIVE Microvascular anastomosis is a basic neurosurgical technique that should be mastered in the laboratory. Human and bovine placentas have been proposed as convenient surgical practice models; however, the histologic characteristics of these tissues have not been compared with human cerebral vessels, and the models have not been validated as simulation training models. In this study, the authors assessed the construct, face, and content validities of microvascular bypass simulation models that used human and bovine placental vessels. METHODS The characteristics of vessel segments from 30 human and 10 bovine placentas were assessed anatomically and histologically. Microvascular bypasses were performed on the placenta models according to a delineated training module by "trained" participants (10 practicing neurosurgeons and 7 residents with microsurgical experience) and "untrained" participants (10 medical students and 3 residents without experience). Anastomosis performance and impressions of the model were assessed using the Northwestern Objective Microanastomosis Assessment Tool (NOMAT) scale and a posttraining survey. RESULTS Human placental arteries were found to approximate the M2-M4 cerebral and superficial temporal arteries, and bovine placental veins were found to approximate the internal carotid and radial arteries. The mean NOMAT performance score was 37.2 ± 7.0 in the untrained group versus 62.7 ± 6.1 in the trained group (p < 0.01; construct validity). A 50% probability of allocation to either group corresponded to 50 NOMAT points. In the posttraining survey, 16 of 17 of the trained participants (94%) scored the model's replication of real bypass surgery as high, and 16 of 17 (94%) scored the difficulty as "the same" (face validity). All participants, 30 of 30 (100%), answered positively to questions regarding the ability of the model to improve microsurgical technique (content validity). CONCLUSIONS Human placental arteries and bovine placental veins are convenient, anatomically relevant, and beneficial models for microneurosurgical training. Microanastomosis simulation using these models has high face, content, and construct validities. A NOMAT score of more than 50 indicated successful performance of the microanastomosis tasks.

Ethmoidal dural arteriovenous fistulas (dAVFs) have a malignant natural history and an anatomy that make endovascular therapy challenging. Their uniqueness begs for stratified analyses, but this has largely been precluded by their rarity. We sought to summarize the anatomic, presentation, treatment approaches, and clinical outcomes of patients with these lesions.We reviewed our prospectively maintained institutional database to identify patients diagnosed with ethmoidal dAVFs from January 1, 2000, to December 31, 2015. We evaluated demographic, presentation, angiographic, treatment, and follow-up data.In total, 27 patients with ethmoidal dAVFs underwent endovascular and/or surgical treatment. Mean patient age was 62 years old and there was a male sex predilection (67% men; 2:1 male-female ratio). All dAVFs exhibited direct cortical venous drainage; venous ectasia was present in 59% of cases. Of the dAVFs, 30% drained posteriorly into the basal vein of Rosenthal or the sylvian veins. Embolization with casting of the draining vein was successful in 2 of 9 cases (22%), including 1 successful transvenous case. There were no clinical or permanent complications from embolization; specifically, no patients experienced visual loss after treatment. Surgical treatment with successful dAVF obliteration was carried out in 24 of 24 patients (100%). One patient declined surgical treatment after attempted endovascular embolization. There were no permanent complications after surgical treatment and no cases of wound infection or cerebrospinal fluid leakage.Surgical disconnection remains the gold standard in the treatment of ethmoidal dAVFs. Embolization is a consideration for well-selected cases with favorable arterial or venous access anatomy.

Abstract BACKGROUND Ruptured wide-neck aneurysms (WNAs) are difficult to treat and few publications have compared clipping to coiling. OBJECTIVE To determine, using Barrow Ruptured Aneurysm Trial (BRAT) data: (1) How many aneurysms had a wide neck? (2) Did wide-neck status influence treatment? (3) How did clipping compare to coiling for WNAs? METHODS A post hoc analysis was conducted of saccular WNAs in the BRAT. A WNA was defined as maximum neck width ≥ 4 mm or maximum aneurysm dome-diameter–to–neck-width ratio &lt; 2. Both intent-to-treat and as-treated analyses were performed. RESULTS Of the 327 patients analyzed, 177 (54.1%) had a WNA. WNAs were more likely to occur in older patients ( P = .03) with worse presenting clinical grade ( P = .02), were more likely to arise from the middle cerebral artery, basilar tip, or internal carotid artery other than the junction with the posterior communicating artery ( P = .001) and were associated with worse clinical outcomes at all time points ( P ≤ .01). WNAs were equally distributed in assigned treatment groups (clip 56.6% vs coil 51.8%; P = .38), but were overrepresented in the actual clipping group (clip 62.4% vs coil 37.6%, P &lt; .001). Most patients (76.7%) in the coil-to-clip crossover group had a WNA. Comparing clipping to coiling, there was no difference in clinical outcomes at any time point in either analysis ( P ≥ .33). The aneurysm obliteration rate was lower ( P &lt; .001) and the retreatment rate higher ( P &lt; .001) in the actual coiling group. CONCLUSION Wide-neck status significantly impacted treatment strategy in the BRAT, favoring clipping. Clipping and coiling of ruptured WNAs resulted in statistically similar long-term clinical outcomes.

<h2>Abstract</h2> Hemifacial spasm (HFS) due to direct compression of the facial nerve by a dolichoectatic vertebrobasilar artery is rare. Vessels are often non-compliant and tethered by critical brainstem perforators. We set out to determine surgical strategies and outcomes for this challenging disease. All patients undergoing surgery for HFS secondary to vertebrobasilar dolichoectasia were reviewed. Hospital records, clinic notes and radiographic imaging were collected for outcome measures. Seventeen patients (eight males, nine females) were identified. Sixteen patients (94%) were treated with Teflon pledgets (DuPont, Wilmington, DE, USA) and one (6%) patient had a vascular sling placed around a severely diseased vertebral artery. All patients had significant reduction in symptoms and 82% of patients had complete resolution of symptoms (average follow-up: 41.4months). One patient suffered persistent facial nerve paresis and swallowing difficulty. Two other patients suffered a 1 point decrease in the House–Brackmann facial nerve grading scale. Four patients (23%) required re-operation (infection, cerebrospinal fluid leak, and two patients with delayed recurrence of HFS). Of the latter, one patient required repositioning of a Teflon pledget and another patient underwent a sling decompression. There were no perioperative strokes or death. Excellent relief of symptoms with acceptable preoperative morbidity can be achieved using Teflon pledgets alone in most cases. In recalcitrant cases, sling transposition can be used to further augment the decompression. Careful attention must be paid to prevent vascular kinking and preserve brainstem perforators.

OBJECT The objective of this study was to describe the surgical anatomy and technical nuances of various vascularized tissue flaps. METHODS The surgical anatomy of various tissue flaps and their vascular pedicles was studied in 5 colored silicone-injected anatomical specimens. Medical records were reviewed of 11 consecutive patients who underwent repair of extensive skull base defects with a combination of various vascularized flaps. RESULTS The supraorbital, supratrochlear, superficial temporal, greater auricular, and occipital arteries contribute to the vascular supply of the pericranium. The pericranial flap can be designed based on an axial blood supply. Laterally, various flaps are supplied by the deep or superficial temporal arteries. The nasoseptal flap is a vascular pedicled flap based on the nasoseptal artery. Patients with extensive skull base defects can undergo effective repair with dual flaps or triple flaps using these pedicled vascularized flaps. CONCLUSIONS Multiple pedicled flaps are available for reconstitution of the skull base. Knowledge of the surgical anatomy of these flaps is crucial for the skull base surgeon. These vascularized tissue flaps can be used effectively as single or combination flaps. Multilayered closure of cranial base defects with vascularized tissue can be used safely and may lead to excellent repair outcomes.

OBJECTIVE Endoscopic transmaxillary approaches (ETMAs) address pathology of the anterolateral skull base, including the cavernous sinus, pterygopalatine fossa, and infratemporal fossa. This anatomically complex region contains branches of the trigeminal nerve and external carotid artery and is in proximity to the internal carotid artery. The authors postulated, on the basis of intraoperative observations, that the infraorbital nerve (ION) is a useful surgical landmark for navigating this region; therefore, they studied the anatomy of the ION and its relationships to critical neurovascular structures and the maxillary nerve (V2) encountered in ETMAs. METHODS Endoscopic anatomical dissections were performed bilaterally in 5 silicone-injected, formalin-fixed cadaveric heads (10 sides). Endonasal transmaxillary and direct transmaxillary (Caldwell-Luc) approaches were performed, and anatomical correlations were analyzed and documented. Stereotactic imaging of each specimen was performed to correlate landmarks and enable precise measurement of each segment. RESULTS The ION was readily identified in the roof of the maxillary sinus at the beginning of the surgical procedure in all specimens. Anatomical dissections of the ION and the maxillary branch of the trigeminal nerve (V2) to the cavernous sinus suggested that the ION/V2 complex has 4 distinct segments that may have implications in endoscopic approaches: 1) Segment I, the cutaneous segment of the ION and its terminal branches (5-11 branches) to the face, distal to the infraorbital foramen; 2) Segment II, the orbitomaxillary segment of the ION within the infraorbital canal from the infraorbital foramen along the infraorbital groove (length 12 ± 3.2 mm); 3) Segment III, the pterygopalatine segment within the pterygopalatine fossa, which starts at the infraorbital groove to the foramen rotundum (13 ± 2.5 mm); and 4) Segment IV, the cavernous segment from the foramen rotundum to the trigeminal ganglion (15 ± 4.1 mm), which passes in the lateral wall of the cavernous sinus. The relationship of the ION/V2 complex to the contents of the cavernous sinus, carotid artery, and pterygopalatine fossa is described in the text. CONCLUSIONS The ION/V2 complex is an easily identifiable and potentially useful surgical landmark to the foramen rotundum, cavernous sinus, carotid artery, pterygopalatine fossa, and anterolateral skull base during ETMAs.

Confocal laser endomicroscopy (CLE) is an advanced optical fluorescence imaging technology that has the potential to increase intraoperative precision, extend resection, and tailor surgery for malignant invasive brain tumors because of its subcellular dimension resolution. Despite its promising diagnostic potential, interpreting the gray tone fluorescence images can be difficult for untrained users. In this review, we provide a detailed description of bioinformatical analysis methodology of CLE images that begins to assist the neurosurgeon and pathologist to rapidly connect on-the-fly intraoperative imaging, pathology, and surgical observation into a conclusionary system within the concept of theranostics. We present an overview and discuss deep learning models for automatic detection of the diagnostic CLE images and discuss various training regimes and ensemble modeling effect on the power of deep learning predictive models. Two major approaches reviewed in this paper include the models that can automatically classify CLE images into diagnostic/nondiagnostic, glioma/nonglioma, tumor/injury/normal categories and models that can localize histological features on the CLE images using weakly supervised methods. We also briefly review advances in the deep learning approaches used for CLE image analysis in other organs. Significant advances in speed and precision of automated diagnostic frame selection would augment the diagnostic potential of CLE, improve operative workflow and integration into brain tumor surgery. Such technology and bioinformatics analytics lend themselves to improved precision, personalization, and theranostics in brain tumor treatment.

Background: Previous studies showed that confocal laser endomicroscopy (CLE) images of brain tumors acquired by a first generation (Gen1) CLE system using fluorescein sodium (FNa) contrast yielded a diagnostic accuracy similar to frozen surgical sections and histologic analysis. We investigated performance improvements of a second generation (Gen2) CLE system designed specifically for neurosurgical use. Methods: Rodent glioma models were used for in vivo and rapid ex vivo CLE imaging. FNa and 5-aminolevulinic acid were used as contrast agents. Gen1 and Gen2 CLE images were compared to distinguish cytoarchitectural features of tumor mass and margin and surrounding and normal brain regions. We assessed imaging parameters (gain, laser power, brightness, scanning speed, imaging depth, and Z-stack [3D image acquisition]) and evaluated optimal values for better neurosurgical imaging performance with Gen2. Results: Efficacy of Gen1 and Gen2 was similar in identifying normal brain tissue, vasculature, and tumor cells in masses or at margins. Gen2 had smaller field of view, but higher image resolution, and sharper, clearer images. Other advantages of the Gen2 were auto-brightness correction, user interface, image metadata handling, and image transfer. CLE imaging with FNa allowed identification of nuclear and cytoplasmic contours in tumor cells. Injection of higher dosages of FNa (20 and 40 mg/kg vs. 0.1-8 mg/kg) resulted in better image clarity and structural identification. When used with 5-aminolevulinic acid, CLE was not able to detect individual glioma cells labeled with protoporphyrin IX, but overall fluorescence intensity was higher (p<0.01) than in the normal hemisphere. Gen2 Z-stack imaging allowed a unique 3D image volume presentation through the focal depth. Conclusion: Compared with Gen1, advantages of Gen2 CLE included a more responsive and intuitive user interface, collection of metadata with each image, automatic Z-stack imaging, sharper images, and a sterile sheath. Shortcomings of Gen2 were a slightly slower maximal imaging speed and smaller field of view. Optimal Gen2 imaging parameters to visualize brain tumor cytoarchitecture with FNa as a fluorescent contrast were defined to aid further neurosurgical clinical in vivo and rapid ex vivo use. Further validation of the Gen2 CLE for microscopic visualization and diagnosis of brain tumors is ongoing.

MR imaging-based modeling of tumor cell density can substantially improve targeted treatment of glioblastoma. Unfortunately, interpatient variability limits the predictive ability of many modeling approaches. We present a transfer learning method that generates individualized patient models, grounded in the wealth of population data, while also detecting and adjusting for interpatient variabilities based on each patient's own histologic data.We recruited patients with primary glioblastoma undergoing image-guided biopsies and preoperative imaging, including contrast-enhanced MR imaging, dynamic susceptibility contrast MR imaging, and diffusion tensor imaging. We calculated relative cerebral blood volume from DSC-MR imaging and mean diffusivity and fractional anisotropy from DTI. Following image coregistration, we assessed tumor cell density for each biopsy and identified corresponding localized MR imaging measurements. We then explored a range of univariate and multivariate predictive models of tumor cell density based on MR imaging measurements in a generalized one-model-fits-all approach. We then implemented both univariate and multivariate individualized transfer learning predictive models, which harness the available population-level data but allow individual variability in their predictions. Finally, we compared Pearson correlation coefficients and mean absolute error between the individualized transfer learning and generalized one-model-fits-all models.Tumor cell density significantly correlated with relative CBV (r = 0.33, P < .001), and T1-weighted postcontrast (r = 0.36, P < .001) on univariate analysis after correcting for multiple comparisons. With single-variable modeling (using relative CBV), transfer learning increased predictive performance (r = 0.53, mean absolute error = 15.19%) compared with one-model-fits-all (r = 0.27, mean absolute error = 17.79%). With multivariate modeling, transfer learning further improved performance (r = 0.88, mean absolute error = 5.66%) compared with one-model-fits-all (r = 0.39, mean absolute error = 16.55%).Transfer learning significantly improves predictive modeling performance for quantifying tumor cell density in glioblastoma.