Improved risk stratification in younger IDH wild-type glioblastoma patients by combining a 4-miRNA signature with MGMT promoter methylation status.

BACKGROUND: The potential benefit of risk stratification using a 4-miRNA signature in combination with MGMT promoter methylation in IDH1/2 wild-type glioblastoma patients was assessed. METHODS: Primary tumors from 102 patients with comparable treatment from the LMU Munich (n = 37), the University Hospital Düsseldorf (n = 33), and The Cancer Genome Atlas (n = 32) were included. Risk groups were built using expressions of hsa-let-7a-5p, hsa-let-7b-5p, hsa-miR-615-5p, and hsa-miR-125a-5p to assess prognostic performance in overall survival (OS). MGMT promoter methylation and age were considered as cofactors. Integrated miRNA, DNA methylome, and transcriptome analysis were used to explore the functional impact of signature miRNAs. RESULTS: The 4-miRNA signature defined high-risk (n = 46, median OS: 15.8 months) and low-risk patients (n = 56, median OS: 20.7 months; univariable Cox proportional hazard analysis: hazard ratio [HR]: 1.8, 95% confidence interval [CI]: 1.14-2.83, P = .01). The multivariable Cox proportional hazard model including the 4-miRNA signature (P = .161), MGMT promoter methylation (P < .001), and age (P = .034) significantly predicted OS (Log-rank P < .0001). Likewise to clinical routine, analysis was performed for younger (≤60 years, n = 50, median OS: 20.2 months) and older patients (>60 years, n = 52, median OS: 15.8) separately. In younger patients, the 4-miRNA signature had prognostic value (HR: 1.92, 95% CI: 0.93-3.93, P = .076). Particularly, younger, MGMT methylated, 4-miRNA signature low-risk patients (n = 18, median OS: 37.4 months) showed significantly improved survival, compared to other younger patients (n = 32, OS 18.5 months; HR: 0.33, 95% CI: 0.15-0.71, P = .003). Integrated data analysis revealed 4-miRNA signature-associated genes and pathways. CONCLUSION: The prognostic 4-miRNA signature in combination with MGMT promoter methylation improved risk stratification with the potential for therapeutic substratification, especially of younger patients.

Calcifying Pseudoneoplasm of Neuraxis (CAPNON) in the Posterior Third Ventricle-Challenge for Neuroendoscopy.

BACKGROUND: We report the first case of a purely intraventricular calcifying pseudoneoplasm of neuraxis (CAPNON) in the posterior third ventricle. CASE DESCRIPTION: A 63-year-old male without any previous medical history presented with Hakim triad. Imaging showed a calcified lesion of the posterior third ventricle with hydrocephalus. An endoscopic third ventriculostomy was performed. Endoscopic removal or debulking of the lesion was impossible due to its rock-hard consistency, and thus the procedure was aborted after biopsy. CONCLUSIONS: When encountering such calcified lesions within the ventricular system, especially in proximity to eloquent regions, the decision making process should include the hard consistency and parenchymal adhesions as obstacles to neuroendoscopic removal. Even for biopsy, a higher morbidity rate compared with typical soft tumors should be assumed. Although data on intraventricular CAPNON is limited, biopsy of the lesion and treatment of associated hydrocephalus appear to be the primary neurosurgical goals, followed by imaging surveillance.

Natural History of De Novo Aneurysm Formation in Patients with Treated Aneurysmatic Subarachnoid Hemorrhage: A Ten-Year Follow-Up.

BACKGROUND: De novo aneurysm formation after completely occluded aneurysms via clipping or coiling has not been well studied. Although known to occur several years after initial aneurysm management, the natural history of de novo aneurysms is obscure. We investigated the formation of new aneurysms in patients who had previously undergone treatment of intracranial aneurysms. METHODS: In a retrospective, single-institutional series, eligible patients who had undergone treatment of ruptured cerebral aneurysms from 2000 to 2011 were included. The primary outcome measure was the development of de novo aneurysms during long-term follow-up. RESULTS: Overall, 130 patients (63% women) who had undergone microsurgical clipping (n = 63; 48.5%) or endovascular coiling (n = 67%; 51.5%) for ruptured aneurysms were included. The average follow-up time for our cohort was 10 ± 2.7 years. De novo aneurysms occurred in 10 of 130 patients (7.7%), with a mean time of 7.9 years for aneurysm detection. No association between the formation of de novo aneurysms and the location of the treated aneurysms, smoking status, hypertension, age, or gender was found. Follow-up imaging studies were performed every 2 years. De novo aneurysms had formed in 2 patients within 2-5 years, 7 patients after 5-10 years, and 1 patient after 10 years of follow-up. In 2 of 10 patients, the de novo aneurysm had ruptured and led to subarachnoid haemorrhage. CONCLUSION: The rate of de novo aneurysm occurrence was 7.6%, with a mean time to development of 7.9 years. This underscores the significance of long-term monitoring of patients with intracranial aneurysms. In our series, most new aneurysms had occurred after 5 years of follow-up.

Contrast enhancement of vascular walls of intracranial high flow malformations in black blood MRI indicates high inflammatory activity.

BACKGROUND: There are controversies concerning the natural history of arteriovenous malformations (AVMs) in literature and it is not clear which AVMs should be treated and which should be just observed. Objective criteria beyond growth in serial MRIs or angiographies are needed. The use of black blood MRI is currently under investigation for evaluating the rupture risk of cerebral aneurysms, however its use for assessment of AVMs has yet to be evaluated. We therefore conducted a feasibility study on the application of black blood MRI (bbMRI) in AVMs to assess rupture risk. METHODS: Retrospective study of 10 patients with intracranial AVMs and 4 patients with arteriovenous fistulas who received a black blood MRI before treatment. RESULTS: AVM niduses (9/10) show contrast enhancement irrespective of rupture or size. All arteriovenous fistulas (4 / 4) were contrast enhancing irrespective of rupture. CONCLUSION: High flow malformations are in a permanent stage of inflammation which does not seem to allow conclusions on their rupture risk at the current stage. BbMRI is a feasible method of identifying inflammation in AVMs and arteriovenous fistulas. However, future prospective studies are needed to evaluate whether bbMRI contrast enhancement correlates with rupture risk.