Outcome of brain metastases from adrenocortical carcinoma: a pooled analysis.

PURPOSE: Brain metastases rarely complicate the natural history of patients with adrenocortical carcinoma (ACC). No information is available regarding the life expectancy and efficacy of treatments in ACC patients with brain involvement. METHODS: A pooled analysis was performed by searching on PubMed and using the keywords: "brain metastases in adrenocortical carcinoma", and "leptomeningeal metastases in adrenocortical carcinoma". Four patients diagnosed at Spedali Civili Hospital in Brescia were added to the analysis. Data concerning demographic, disease characteristics, adopted treatments and patient prognosis were collected. RESULTS: A total of 27 patients (18 adults and 9 children) were included in this study, 22 of them had an adequate follow-up. Brain metastases occurred late in the natural history of adult patients but not in that of children. Surgery plus/minus radiation therapy was the treatment of choice. Adult patients with brain metastases had a poor prognosis with a median progression-free survival (PFS) and overall survival (OS) of 2 and 7 months, respectively. Median PFS and OS were not attained in children. CONCLUSION: Brain metastases in ACC patients are rare and are associated with poor prognosis, particularly in adults. Surgery plus/minus radiotherapy is the only therapeutic approach that can offer patients a chance to obtain durable local disease control.

A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

Quantification and comparison of neurosurgical approaches in the preclinical setting: literature review.

There is a growing awareness of the need for evidence-based surgery and of the issues that are specific to research in surgery. Well-conducted anatomical studies can represent the first, preclinical step for evidence-based surgical innovation and evaluation. In the last two decades, various reports have quantified and compared neurosurgical approaches in the anatomy laboratory using different methods and technology. The aim of this study was to critically review these papers. A PubMed and Scopus search was performed to select articles that quantified and compared different neurosurgical approaches in the preclinical setting. The basic characteristics that anatomically define a surgical approach were defined. Each study was analyzed for measured features and quantification method and technique. Ninety-nine papers, published from 1990 to 2013, were included in this review. A heterogeneous use of terms to define the features of a surgical approach was evident. Different methods to study these features have been reported; they are generally based on quantification of distances, angles, and areas. Measuring tools have evolved from the simple ruler to frameless stereotactic devices. The reported methods have each specific advantages and limits; a common limitation is the lack of 3D visualization and surgical volume quantification. There is a need for a uniform nomenclature in anatomical studies. Frameless stereotactic devices provide a powerful tool for anatomical studies. Volume quantification and 3D visualization of the surgical approach is not provided with most available methods.

Role of Nitric Oxide in Glioblastoma Therapy: Another Step to Resolve the Terrible Puzzle ?

Glioblastoma Multiforme, the most common and aggressive primary brain tumor, remains incurable despite of the advent of modern surgical and medical treatments. This poor prognosis depends by the recurrence after surgery and intrinsic or acquired resistance to chemotherapy and radiotherapy. Nitric oxide is a small molecule that plays a key roles in glioma pathophysiology. Many researches showing that NO is involved in induction of apoptosis, radiosensitization and chemosensitization. Therefore, NO role, if clarified, may improve the knowledge about this unsolved puzzle called GBM.

Advantages and disadvantages of intraoperative language tasks in awake surgery: a three-task approach for prefrontal tumors.

Multidisciplinary efforts are being made to provide surgical teams with sensitive and specific tasks for language mapping in awake surgery. Researchers and clinicians have elaborated different tasks over time. A fair amount of work has been directed to study the neurofunctional correlates of some of these tasks, and there is recent interest in their standardization. However, little discussion exists on the advantages and disadvantages that each task poses from the perspective of the cognitive neuroscience of language. Such an approach may be a relevant step to assess task validity, to avoid using tasks that tap onto similar processes, and to provide patients with a surgical treatment that ensures maximal tumor resection while avoiding postoperative language deficits. An understanding of the language components that each task entails may also be relevant to improve the current assessments and the ways in which tasks are administered, and to disentangle neurofunctional questions. We reviewed 17 language mapping tasks that have been used in awake surgery. Overt production tasks have been a preferred choice over comprehension tasks. Tasks tapping lexico-semantic processes, particularly object-naming, maintain their role as gold standards. Automated speech tasks are used to detect speech errors and to set the amplitude of the stimulator. Comprehension tasks, reading and writing tasks, and tasks that assess grammatical aspects of language may be regularly administered in the near future. We provide examples of a three-task approach we are administering to patients with prefrontal lesions. We believe that future advances in this area are contingent upon reviewing gold standards and introducing new assessment tools.

Different quantification algorithms may lead to different results: a comparison using proton MRS lipid signals.

Proton magnetic resonance spectroscopy (MRS) is a sensitive method for investigating the biochemical compounds in a tissue. The interpretation of the data relies on the quantification algorithms applied to MR spectra. Each of these algorithms has certain underlying assumptions and may allow one to incorporate prior knowledge, which could influence the quality of the fit. The most commonly considered types of prior knowledge include the line-shape model (Lorentzian, Gaussian, Voigt), knowledge of the resonating frequencies, modeling of the baseline, constraints on the damping factors and phase, etc. In this article, we study whether the statistical outcome of a biological investigation can be influenced by the quantification method used. We chose to study lipid signals because of their emerging role in the investigation of metabolic disorders. Lipid spectra, in particular, are characterized by peaks that are in most cases not Lorentzian, because measurements are often performed in difficult body locations, e.g. in visceral fats close to peristaltic movements in humans or very small areas close to different tissues in animals. This leads to spectra with several peak distortions. Linear combination of Model spectra (LCModel), Advanced Method for Accurate Robust and Efficient Spectral fitting (AMARES), quantitation based on QUantum ESTimation (QUEST), Automated Quantification of Short Echo-time MRS (AQSES)-Lineshape and Integration were applied to simulated spectra, and area under the curve (AUC) values, which are proportional to the quantity of the resonating molecules in the tissue, were compared with true values. A comparison between techniques was also carried out on lipid signals from obese and lean Zucker rats, for which the polyunsaturation value expressed in white adipose tissue should be statistically different, as confirmed by high-resolution NMR measurements (considered the gold standard) on the same animals. LCModel, AQSES-Lineshape, QUEST and Integration gave the best results in at least one of the considered groups of simulated or in vivo lipid signals. These outcomes highlight the fact that quantification methods can influence the final result and its statistical significance.

Factors affecting formation and rupture of intracranial saccular aneurysms.

Unruptured intracranial aneurysms represent a decisional challenge. Treatment risks have to be balanced against an unknown probability of rupture. A better understanding of the physiopathology is the basis for a better prediction of the natural history of an individual patient. Knowledge about the possible determining factors arises from a careful comparison between ruptured versus unruptured aneurysms and from the prospective observation and analysis of unbiased series with untreated, unruptured aneurysms. The key point is the correct identification of the determining variables for the fate of a specific aneurysm in a given individual. Thus, the increased knowledge of mechanisms of formation and eventual rupture of aneurysms should provide significant clues to the identification of rupture-prone aneurysms. Factors like structural vessel wall defects, local hemodynamic stress determined also by peculiar geometric configurations, and inflammation as trigger of a wall remodeling are crucial. In this sense the study of genetic modifiers of inflammatory responses together with the computational study of the vessel tree might contribute to identify aneurysms prone to rupture. The aim of this article is to underline the value of a unifying hypothesis that merges the role of geometry, with that of hemodynamics and of genetics as concerns vessel wall structure and inflammatory pathways.

Genetic and cellular basis of cerebral cavernous malformations: implications for clinical management.

Cerebral cavernous malformations (CCMs) are a diffuse cerebrovascular disease affecting approximately 0.5% of the population. A CCM is characterized by abnormally enlarged and leaky capillaries arranged in mulberry-like structures with no clear flow pattern. The lesion might predispose to seizures, focal neurological deficits or fatal intracerebral hemorrhage. However, a CCM can also remain neurologically silent. It might either occur sporadically or as an inherited disorder with incomplete penetrance and variable expressivity. Due to advances in imaging techniques, the incidence of CCM diagnoses are increasing, and the patient must be managed on a multidisciplinary basis: genetic counselling, treatment if needed, and follow-up. Advances have been made using radiological and pathological correlates of CCM lesions adding to the accumulated knowledge of this disease, although management of these patients is very variable among centers. This review is aimed at providing an update in genetic and molecular insights of this condition. Included are implications for genetic counselling, and possible approaches to prevention and treatment that derive from the understanding of pathogenetic mechanisms.

Stem cells based therapy in high grade glioma: why the intraventricular route should be preferred?

AIM: Mesenchymal stem cells (MSCs) migrate in response to chemokines and possess extensive tropism for experimental glioma. Antitumor effects have been reported following intracranial and intravenous administration of gene-modified MSCs. Among the different routes for cell transplant, the intraventricular (IV) approach found very little employment in comparison with intraparenchymal, intratumoral and intravenous administration protocols. Nevertheless, IV transplantation offers advantages in terms of cells viability and distribution toward target sites, opening interesting opportunities for its clinical application. METHODS: Using a rat glioma model, we investigated migratory capacity, tumor tropism, distribution and differentiation of MSCs following IV administration. RESULTS: Transplanted MSCs create niches of viable cells in the subventricular zone and can be stimulated to migrate to sites of tumor infiltration. MSCs seemed not to be involved in tumor growth and angiogenesis. CONCLUSION: We speculate that the IV route can be used to achieve a kind of reservoir of self-renewal cells, potentially active against the spread of cancer cells. Further studies are needed to shed light on MSCs distribution close to the ventricular wall, in order to define their lifespan and their capacity to migrate towards new-enhancing foci time after implantation.

Recent therapeutic strategies for spinal cord injury treatment: possible role of stem cells.

Spinal cord injury (SCI) often results in significant dysfunction and disability. A series of treatments have been proposed to prevent and overcome the formation of the glial scar and inhibitory factors to axon regrowth. In the last decade, cell therapy has emerged as a new tool for several diseases of the nervous system. Stem cells act as minipumps providing trophic and immunomodulatory factors to enhance axonal growth, to modulate the environment, and to reduce neuroinflammation. This capability can be boosted by genetical manipulation to deliver trophic molecules. Different types of stem cells have been tested, according to their properties and the therapeutic aims. They differ from each other for origin, developmental stage, stage of differentiation, and fate lineage. Related to this, stem cells differentiating into neurons could be used for cell replacement, even though the feasibility that stem cells after transplantation in the adult lesioned spinal cord can differentiate into neurons, integrate within neural circuits, and emit axons reaching the muscle is quite remote. The timing of cell therapy has been variable, and may be summarized in the acute and chronic phases of disease, when stem cells interact with a completely different environment. Even though further experimental studies are needed to elucidate the mechanisms of action, the therapeutic, and the side effects of cell therapy, several clinical protocols have been tested or are under trial. Here, we report the state-of-the-art of cell therapy in SCI, in terms of feasibility, outcome, and side effects.

Luminescence and fluorescence of essential oils. Fluorescence imaging in vivo of wild chamomile oil.

Essential oils are currently of great importance to pharmaceutical companies, cosmetics producers and manufacturers of veterinary products. They are found in perfumes, creams, bath products, and household cleaning substances, and are used for flavouring food and drinks. It is well known that some of them act on the respiratory apparatus. The increasing interest in optical imaging techniques and the development of related technologies have made possible the investigation of the optical properties of several compounds. Luminescent properties of essential oils have not been extensively investigated. We evaluated the luminescent and fluorescent emissions of several essential oils, in order to detect them in living organisms by exploiting their optical properties. Some fluorescent emission data were high enough to be detected in dermal treatments. Consequently, we demonstrated how the fluorescent signal can be monitored for at least three hours on the skin of living mice treated with wild chamomile oil. The results encourage development of this technique to investigate the properties of drugs and cosmetics containing essential oils.

Fast and minimally invasive determination of the unsaturation index of white fat depots by micro-Raman spectroscopy.

In the last 20 years increasing interest has been devoted to the investigation of white adipose tissue (WAT) because hypo- or hyperfunction of WAT is involved in the pathogenesis of obesity and other pathologies. The investigation and discrimination of different characteristics in adipose tissues by means of spectroscopic techniques appears as a topic of current interest, also in view of possible medical-technological applications. The aim of this work was to establish micro-Raman spectroscopy as a tool for the characterization of mammals fat tissue. After preliminary tests aimed at defining a suitable sample preparation protocol, Raman spectra of WAT specimens excised from mice of different ages were recorded in the energy range 750-3,350 cm⁻¹. Quantitative values of the unsaturation index were obtained through the calibration with HR-NMR spectra of lipid extracts. Raman spectroscopy detected a sharp increase in the unsaturation index between 22 and 30 days of age in close correspondence with the weaning of mice (21 days). The present results show that Raman spectroscopy is an inexpensive, fast and robust technique to analyze the unsaturation index of mammals fat tissues that could be routinely used in bioptic samples.