Delayed cerebral vasospasm has classically been considered the most important and treatable cause of mortality and morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Secondary ischemia (or delayed ischemic neurological deficit, DIND) has been shown to be the leading determinant of poor clinical outcome in patients with aSAH surviving the early phase and cerebral vasospasm has been attributed to being primarily responsible. Recently, various clinical trials aimed at treating vasospasm have produced disappointing results. DIND seems to have a multifactorial etiology and vasospasm may simply represent one contributing factor and not the major determinant. Increasing evidence shows that a series of early secondary cerebral insults may occur following aneurysm rupture (the so-calledearly brain injury). This further aggravates the initial insult and actually determines the functional outcome. A better understanding of these mechanisms and their prevention in the very early phase is needed to improve the prognosis. The aim of this review is to summarize the existing literature on this topic and so to illustrate how the presence of cerebral vasospasm may not necessarily be a prerequisite for DIND development. The various factors determining DIND that worsen functional outcome and prognosis are then discussed.

Objectives. We performed a systematic literature review to analyze the clinical application and the safety of mifepristone, a prominent antiprogesterone agent, in meningioma patients.Materials and Methods. A systematic search was performed through Medline, Cochrane, and clinicaltrials.gov databases from 1960 to 2014.Study Selection. Studies were selected through a PICO approach. Population was meningioma patients, meningioma cells cultures, and animal models. Intervention was mifepristone administration. Control was placebo administration or any other drug tested. Outcomes were clinical and radiological responsiveness, safety profile, and cell growth inhibition.Results. A total of 7 preclinical and 6 clinical studies and one abstract were included. Encouraging results were found in preclinical studies. Concerning clinical studies, the response rate to mifepristone in terms of radiological regression and symptomatic improvement/stability in patients with inoperable meningioma was low. In meningiomatosis, favorable preliminary results were recorded. The safety profile was good. Limitations were as follows. The tumoral expression of progesterone receptors was not analyzed systematically in every study considered.Conclusions. No clear evidence exists to recommend mifepristone in inoperable meningiomas. Preliminary encouraging results were found in diffuse meningiomatosis. Mifepristone is a well-tolerated treatment. Patients’ selection and hormonal profile analysis in meningiomas are fundamental for a better understanding of its benefit. Multicenter placebo-controlled trials are required.

Aneurysmal subarachnoid hemorrhage (aSAH) provokes a cascade reaction that is responsible for early and delayed brain injuries mediated by intracranial hypertension, hydrocephalus, cerebral vasospasm (CV), and delayed cerebral ischemia (DCI), which result in increased morbidity and mortality. During open microsurgical repair, cisternal access is achieved essentially to gain proximal vascular control and aneurysm exposition. Cisternostomy also allows brain relaxation, removal of cisternal clots, and restoration of the CSF dynamics through the communication between the anterior and posterior circulation cisterns and the ventricular system, with the opening of the Membrane of Liliequist and lamina terminalis, respectively. Continuous postoperative CSF drainage through a cisternal drain (CD) is a valuable option for treating acute hydrocephalus and intracranial hypertension. Moreover, it efficiently removes the blood and toxic degradation products, with a potential benefit on CV, DCI, and shunt-dependent hydrocephalus. Finally, the CD is an effective pathway to administer vasoactive, fibrinolytic, and anti-oxidant agents and shows promising results in decreasing CV and DCI rates while minimizing systemic effects. We performed a comprehensive review to establish the adjuvant role of cisternostomy and CD performed in cases of direct surgical repair for ruptured intracranial aneurysms and their role in the prevention and treatment of aSAH complications.

Background and aim: About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates. Methods: We performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas’ classification as primary outcomes. Secondary outcomes included the TPS’ relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis. Results: Eighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas’ classification, we found that “proliferative” cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80–18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98–14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10–0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence. Conclusions: PD-L1 expression was associated with proliferative grades of Trouillas’ classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.