Object: The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods: The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results: A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions: Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

Background and Purpose—: The biological mechanisms predisposing intracranial saccular aneurysms to growth and rupture are not yet fully understood. Mural cell loss is a histological hallmark of ruptured cerebral aneurysms. It remains unclear whether mural cell loss predisposes to aneurysm growth and eventual rupture. Methods—: Sodium dodecyl sulfate decellularized and nondecellularized saccular aneurysm from syngeneic thoracic aortas were transplanted to the abdominal aorta of Wistar rats. Aneurysm patency and growth was followed up for 1 month with contrast-enhanced serial magnetic resonance angiographies. Endoscopy and histology of the aneurysms were used to assess the role of periadventitial environment, aneurysm wall, and thrombus remodeling. Results—: Nondecellularized aneurysms (n=12) showed a linear course of thrombosis and remained stable. Decellularized aneurysms (n=12) exhibited a heterogeneous pattern of thrombosis, thrombus recanalization, and growth. Three of the growing aneurysms (n=5) ruptured during the observation period. Growing and ruptured aneurysms demonstrated marked adventitial fibrosis and inflammation, complete wall disruption, and increased neutrophil accumulation in unorganized intraluminal thrombus. Conclusions—: In the presented experimental setting, complete loss of mural cells acts as a driving force for aneurysm growth and rupture. The findings suggest that aneurysms missing mural cells are incapable to organize a luminal thrombus, leading to recanalization, increased inflammatory reaction, severe wall degeneration, and eventual rupture.

Object. Animal models provide a basis for clarifying the complex pathogenesis of delayed cerebral vasospasm (DCVS) and for screening of potential therapeutic approaches. Arbitrary use of experimental parameters in current models can lead to results of uncertain relevance. The aim of this work was to identify and analyze the most consistent and feasible models and their parameters for each animal. Methods. An online search of the MEDLINE PubMed and EMBASE medical databases (1969 to week 21 of 2007) was performed using the key words “canine”, “mice”, “rabbit”, “pig”, “rat”, “cat”, and “primate” in combination with “subarachnoid hemorrhage”, “model”, and “vasospasm”. Cross references of each model were checked. Analysis of identified publications was considered in accordance with predetermined eligibility criteria. Results. 1254 abstracts were reviewed and 516 studies were included in the analysis. Then, 66 models in 7 animals were identified. Most often used blood amounts (ml) lead to degree (% vessel narrowing) and peak onset (day) of DCVS within animal models as follows: mice endovascular puncture (various, day 3, 20–62%); rat single injection (0.3 ml, day 2, 19–29%); rat double injection (2x0.3 ml, day 7, 28–47%); rabbit single injection (3 ml, day 3, 19–55%); rabbit double injection (not established, day 5, not established); dog double injection (2x4–5 ml, day 7, 45–66%); primate clot placement (5 ml, day 7, 32–52%). Conclusions. Among the great number of experimental SAH methods and associated parameters only a fistful reliable and consistent models can be identified and recommended. Implementation of more standardized experimental techniques could increase the relevance of future experimental studies.

Previous studies have shown the individual benefits of 5-aminolevulinic acid (5-ALA) and intraoperative (i)MRI in enhancing survival for patients with high-grade glioma. In this retrospective study, we compare rates of progression-free and overall survival between patients who underwent surgical resection with the combination of 5-ALA and iMRI and a control group without iMRI. In 200 consecutive patients with high-grade gliomas, we recorded age, sex, World Health Organization tumor grade, and pre- and postoperative Karnofsky performance status (good ≥80 and poor <80). A 0.15-Tesla magnet was used for iMRI; all patients operated on with iMRI received 5-ALA. Overall and progression-free survival rates were compared using multivariable regression analysis. Median overall survival was 13.8 months in the non-iMRI group and 17.9 months in the iMRI group (P = .043). However, on identifying confounding variables (ie, KPS and resection status) in this univariate analysis, we then adjusted for these confounders in multivariate analysis and eliminated this distinction in overall survival (hazard ratio: 1.23, P = .34, 95% CI: 0.81, 1.86). Although 5-ALA enhanced the achievement of gross total resection (odds ratio: 3.19, P = .01, 95% CI: 1.28, 7.93), it offered no effect on overall or progression-free survival when adjusted for resection status. Gross total resection is the key surgical variable that influences progression and survival in patients with high-grade glioma and more likely when surgical adjuncts, such as iMRI in combination with 5-ALA, are used to enhance resection.

Object: Both anterior cervical discectomy with fusion (ACDF) and anterior cervical corpectomy with fusion (ACCF) are used to treat cervical spondylotic myelopathy; however, there is currently no evidence for the superiority of one over the other in terms of patient-rated outcomes. This comparative effectiveness study compared the patient-rated and radiographic outcomes of 2-level ACDF versus 1-level ACCF. Methods: This single-center study was nested within the EuroSpine Spine Tango data acquisition system. Inclusion criteria were the following: consecutive patients presenting with signs of cervical spondylotic myelopathy who underwent 2-level ACDF or 1-level ACCF between 2004 and 2011. Before and 12 months after surgery, patients completed the multidimensional Core Outcome Measures Index (COMI) and also rated global treatment outcome and satisfaction with care on 5-point Likert scales. Cervical lordosis, segmental height, and fusion rate were assessed radiographically before and immediately after surgery and at the last follow-up (20.4 ± 13.7 months, mean ± SD). Results: In total, 118 consecutive patients (80 in the ACDF group and 38 in the ACCF group) were included. Age, sex, comorbidity, baseline symptoms, baseline radiographic data, operation duration, and complication rates did not differ significantly between the 2 groups. Blood loss was significantly (p < 0.04) lower in the ACDF group. Postoperative mean segmental height was significantly (p = 0.0006) greater for ACDF (42.0 ± 4.2 mm, mean ± SD) than for ACCF (39.0 ± 4.0 mm), and global average lordosis improved to a significantly (p = 0.003) greater extent in ACDF (by 1.6° ± 4.1°) than in ACCF (by −1.0° ± 4.0°). Fusion rates for ACDF were 97.5% and for ACCF were 94.7% (p = 0.59). The 12-month patient-rated outcomes did not differ significantly between ACDF and ACCF: 82.4% and 68.6% had a good global outcome (operation helped/helped a lot) (p = 0.10), 86.5% and 82.9% were satisfied/very satisfied with care (p = 0.62), and the reduction in the multidimensional COMI was 2.8 ± 2.7 and 2.2 ± 3 points (p = 0.30), respectively. The postoperative increase in lordosis angle showed low but significant correlations with the improvement in arm pain (r = 0.25, p = 0.014), highest pain (r = 0.25, p = 0.013), and function (r = 0.24, p = 0.016). Conclusions: Both ACDF and ACCF are safe and effective in the treatment of cervical spondylotic myelopathy, indicated by similarly good patient-rated outcomes 1 year after surgery. This precludes any conclusions regarding the superiority of one technique over the other, although it should be noted that ACDF resulted in less blood loss and greater improvements in cervical lordosis and segmental height than ACCF. Patients with improved lordosis angle had a better clinical outcome.