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Intracranial aneurysms (IAs) are localized dilations of the cerebral vasculature, representing the leading cause for non-traumatic subarachnoid hemorrhage and an important source of morbidity and mortality. Despite it being a frequent pathology and most often diagnosed incidentally, IAs in infants are a very rare occurrence, and the ruptured variant is exceptional. A 4-month-old boy with a negative family history was brought to our department because of several episodes of incoercible vomiting and fever. Upon examination, the child was somnolent, without any noticeable deficit. Transfontanellar ultrasonography and CT angiography revealed a ruptured aneurysm of the anterior communicating artery (AComA), whereas the pre-clipping MRI showed thin, almost angiographically invisible anterior cerebral arteries (ACAs) on both sides due to vasospasm. We intervened surgically by placing an external ventricular shunt in an emergency setting, followed by clipping of the IA in a delayed manner. The child was discharged a month after admission with no deficit, despite the paradoxical aspect of the ACA. Ruptured IAs can be safely treated via microsurgery, even in infants. However, this requires a great amount of experience and surgical expertise. Furthermore, the lack of proper management would most likely result in a severe deficit in the long term. Lastly, the lack of visibility of the ACA on angiographic studies may not have neurological consequences if they occur in this age group.

Introduction. Brain vascular malformations (BVMs) are congenital lesions with evolutive properties that possess a considerable chance of causing intracranial haemorrhage. The most common types are arteriovenous malformations (AVMs), aberrant entanglements of deformed vessels that shunt blood from the arteries directly into the veins, and cavernous malformations (CMs), being mulberry-shaped sinusoid spaces filled with blood. The rate of hemorrhagic stroke varies between these two types of lesions, being the most common form of symptomatic presentation for AVMs, but a much rarer occurrence for CMs. The purpose of our pilot study was to test whether the incidence of intracranial haemorrhage from BVMs varies between seasons, as well as examining a possible causality for this event. Material and methods. We performed a retrospective analysis on the cases of ruptured BVMs of the brain operated by the senior surgeon in our department between January 2008 and December 2019. We then divided the patients according to the type of lesion and gender, based on the month of the year when their pathologies caused the hemorrhagic stroke. We performed Pearson’s chi-square test to verify the relationship between season and rate of rupture of AVMs and CMs, individual month and rate of rupture, season and gender, and individual month and gender. Results. There were 87 ruptured vascular malformations, out of which 71 were AVMs and 16 were CMs. There were 51 males (40 AVMs, 11 CMs) and 36 females (31 AVMs, 5 CMs). The majority of hemorrhagic strokes occurred in the months of July (10 AVVMs, 2 CMs) and December (10 AVMs, 1 CM). We obtained a statistically significant correlation between the summer season and presentation with ruptured cavernous malformation, as well as the male sex and presentation with a ruptured AVM in December, whereas the female sex presented a correlation with ruptured AVMs in the month of March. We also obtained a correlation between the male sex and presenting with a ruptured vascular malformation of any kind in December, as well as the female gender and hemorrhagic stroke from any vascular malformation in the months of January and August. Conclusion. Despite promising statistical results, the relatively low number of cases may not be applicable to a larger patient population. It seems probable that meteorological conditions, especially extreme temperatures, might act as an additional risk factor for hemorrhagic stroke from vascular malformations, however, these findings should be corroborated with supplementary case series from other centres or a large prospective trial.

Cavernous malformations (CMs) are either congenital or acquired vascular lesions comprised of sinusoid spaces filled with either blood or its breakdown products. They possess a relatively reduced risk of hemorrhage, yet placement within the posterior fossa and especially the brainstem heightens their likelihood to rupture, making them a likely cause of permanent and debilitating neurological deficit, as well as a veritable surgical challenge. Although the incidence of rupture varies with age among reported case series, it is undoubtable that the severity of this occurrence is the highest while the brain is as its most vulnerable period, i.e. during infancy. We present two patients, both female, 6.5- and 5-months-old respectively, who presented with brainstem hemorrhage from CM. They suffered from a sudden onset of hemiparesis and were subjected to surgical removal of their lesions and resulting hematomas. Both patients were discharged in a favorable neurological status and are currently alive and in good health. Microsurgical treatment of brainstem CMs in infants is not only possible with minimal deficit, but also advisable if the lesions are symptomatic. Nevertheless, this requires substantial patience and experience to prevent significant loss of blood and injury to the structures of the posterior fossa. We argue that the safest method to prevent further damage from brainstem CM rebleed is to remove these lesions shortly after the initial hemorrhage.

Hydrocephalus is a complex pathology that can have a significant impact on the quality of life in all age groups. Cerebrospinal fluid (CSF) diversions from the lateral ventricle to the peritoneal cavity are regarded as the treatment of first intent, but they have a high revision rate, and there are multiple factors which can impair their proper insertion and function. One of the many alternatives to peritoneal shunting is redirecting the CSF towards the renal system. A literature search was conducted to identify the particularities of these types of shunts and what clinical context rendered them feasible in pediatric and adult patient populations. Twenty-eight studies were found to meet the selection criteria. The shunts were classified into ventriculopyeloureteral, ventriculoureteral, and ventriculovesical. Their main advantage was that they did not depend on absorption properties of the tissues, like in the case of the peritoneum. However, several issues with ascending infections, bladder pressure imbalance, distal shunt migration, and calculus formation were noted. Literature suggests that the urinary tract can have the potential of diverting CSF when the peritoneum or atrium is not available, but further research is required to establish their proper role in current practice.

Background: Brain arteriovenous malformations (BAVMs) and cerebral cavernous malformations (CCMs) are rare developmental anomalies of the intracranial vasculature, with an irregular tendency to rupture, and as of yet incompletely deciphered pathophysiology. Because of their variety in location, morphology, and size, as well as unpredictable natural history, they represent a management challenge. MicroRNAs (miRNAs) are strands of non-coding RNA of around 20 nucleotides that are able to modulate the expression of target genes by binding completely or partially to their respective complementary sequences. Recent breakthroughs have been made on elucidating their contribution to BAVM and CCM occurrence, growth, and evolution; however, there are still countless gaps in our understanding of the mechanisms involved. Methods: We have searched the Medline (PubMed; PubMed Central) database for pertinent articles on miRNAs and their putative implications in BAVMs and CCMs. To this purpose, we employed various permutations of the terms and idioms: ‘arteriovenous malformation’, ‘AVM’, and ‘BAVM’, or ‘cavernous malformation’, ‘cavernoma’, and ‘cavernous angioma’ on the one hand; and ‘microRNA’, ‘miRNA’, and ‘miR’ on the other. Using cross-reference search; we then investigated additional articles concerning the individual miRNAs identified in other cerebral diseases. Results: Seven miRNAs were discovered to play a role in BAVMs, three of which were downregulated (miR-18a, miR-137, and miR-195*) and four upregulated (miR-7-5p, miR-199a-5p, miR-200b-3p, and let-7b-3p). Similarly, eight miRNAs were identified in CCM in humans and experimental animal models, two being upregulated (miR-27a and mmu-miR-3472a), and six downregulated (miR-125a, miR-361-5p, miR-370-3p, miR-181a-2-3p, miR-95-3p, and let-7b-3p). Conclusions: The following literature review endeavored to address the recent discoveries related to the various implications of miRNAs in the formation and growth of BAVMs and CCMs. Additionally, by presenting other cerebral pathologies correlated with these miRNAs, it aimed to emphasize the potential directions of upcoming research and biological therapies.

OBJECTIVE To present an alternative surgical technique in treating cases of Chiari I Malformation with mild-to-moderate syringomyelia after decompressive suboccipital craniectomy: incising only the outer layer of the dura mater, then dissecting it from the inner layer without opening the latter. PATIENTS AND METHODS We utilized this technique in a short series of three cases who were admitted to our department for mild symptoms such as intermittent headache and dissociated sensory loss in the upper limbs, caused by a Chiari Malformation Type I. The patients were placed in the sitting position. We performed a reduced median suboccipital craniectomy and resection of the posterior arch of C1 adapted to the level of tonsil descent, from a limited superior half to complete resection. Afterward, we incised the outer dural layer, while sparing the inner one. Using a fine dissector, we then split apart the outer and inner layers to the margin of the craniectomy. Through the transparency of the inner layer and the arachnoid, the cerebellum and the medulla were visible and pulsating. An autologous fascia duraplasty was then performed. RESULTS The postoperative course was favorable in all cases, the patients being discharged without any deficits and with complete symptom resolution. Follow-up at 3, 6, and 12 months after surgery revealed a significant reduction in brainstem compression and syringomyelia. CONCLUSIONS Interlayer dural split technique can be used effectively in treating symptomatic cases of type I Chiari malformation in adults, with mild-to-moderate syringomyelia. It is less invasive than opening the dura and possibly more effective than decompressive craniectomy and C1 laminectomy alone. This technique must be validated in a larger case-control series.

Background and Objectives: Brain arteriovenous malformations AVMs have been consistently regarded as congenital malformations of the cerebral vasculature. However, recent case reports describing “de novo AVMs” have sparked a growing debate on the nature of these lesions. Materials and Methods: We have performed a systematic review of the literature concerning de novo AVMs utilizing the PubMed and Google Academic databases. Termes used in the search were “AVM,” “arteriovenous,” “de novo,” and “acquired,” in all possible combinations. Results: 53 articles including a total of 58 patients harboring allegedly acquired AVMs were identified by researching the literature. Of these, 32 were male (55.17%), and 25 were female (43.10%). Mean age at de novo AVM diagnosis was 27.833 years (standard deviation (SD) of 21.215 years and a 95% confidence interval (CI) of 22.3 to 33.3). Most de novo AVMs were managed via microsurgical resection (20 out of 58, 34.48%), followed by radiosurgery and conservative treatment for 11 patients (18.97%) each, endovascular embolization combined with resection for five patients (8.62%), and embolization alone for three (5.17%), the remaining eight cases (13.79%) having an unspecified therapy. Conclusions: Increasing evidence suggests that some of the AVMs discovered develop some time after birth. We are still a long way from finally elucidating their true nature, though there is reason to believe that they can also appear after birth. Thus, we reason that the de novo AVMs are the result of a ‘second hit’ of a variable type, such as a previous intracranial hemorrhage or vascular pathology. The congenital or acquired characteristic of AVMs may have a tremendous impact on prognosis, risk of hemorrhage, and short and long-term management.

In the context of hydrocephalus, there are a multitude of therapeutic options that can be explored in order to improve patient outcomes. Although the peritoneum is the current elected clinical solution, various receptacles have been utilized when experiencing contraindications. Along with the ventriculoatrial or ventriculopleural, the ventriculocholecystic shunt was also described as an alternative. In order to make a decision on a place for drainage, the surgeon must be knowledgeable on details from modern literature. The main target of this review was to summarize the currently available information on this topic and assess the status of the gallbladder as a viable option for cerebrospinal fluid diversion.

Background: Brain arteriovenous malformations (AVMs) are a relatively infrequent vascular pathology of unknown etiology that, despite their rarity, cause the highest number of hemorrhagic strokes under the age of 30 years. They pose a challenge to all forms of treatment due to their variable morphology, location, size, and, last but not least, evolving nature. MicroRNAs (miRNAs) are non-coding RNA strands that may suppress the expression of target genes by binding completely or partially to their complementary sequences. Single nucleotide polymorphisms (SNPs), as the name implies, are variations in a single nucleotide in the DNA, usually found in the non-coding segments. Although the majority of SNPs are harmless, some located in the proximity of candidate genes may result in altered expression or function of these genes and cause diseases or affect how different pathologies react to treatment. The roles miRNAs and certain SNPs play in the development and growth of AVMs are currently uncertain, yet progress in deciphering the minutiae of this pathology is already visible. Methods and Results: We performed an electronic Medline (PubMed, PubMed Central) and Google Academic exploration using permutations of the terms: "arteriovenous malformations," "single nucleotide polymorphisms," "microRNA," "non-coding RNA," and "genetic mutations." The findings were then divided into two categories, namely the miRNAs and the candidate gene SNPs associated with AVMs respectively. 6 miRNAs and 12 candidate gene SNPs were identified and discussed. Conclusions: The following literature review focuses on the discoveries made in ascertaining the different implications of miRNAs and candidate gene SNPs in the formation and evolution of brain AVMs, as well as highlighting the possible directions of future research and biological treatment. Abbreviations: ACVRL1/ALK1: activin receptor-like kinase 1; Akt: protein kinase B; ANGPTL4: angiopoietin-like 4; ANRIL: antisense noncoding RNA in the INK4 locus; AVM: arteriovenous malformation; AVM-BEC: arteriovenous malformation brain endothelial cell; BRCA1: breast cancer type 1 susceptibility protein; CCS: case-control study; CDKN2A/B: cyclin-dependent kinase inhibitor 2A/B; CLTC: clathrin heavy chain; DNA: deoxyribonucleic acid; ERK: extracellular signal-regulated kinase; GPR124: probable G-protein coupled receptor 124; GWAS: genome-wide association study; HHT: hereditary hemorrhagic telangiectasia; HIF1A: hypoxia-inducible factor 1A; IA: intracranial aneurysm; ICH: intracranial hemorrhage; Id-1: inhibitor of DNA-binding protein A; IL-17: interleukin 17; MAP4K3: mitogen-activated protein kinase kinase kinase kinase 3; miRNA: microRNA; MMP: matrix metalloproteinase; NFkB: nuclear factor kappa-light-chain of activated B cells; NOTCH: neurogenic locus notch homolog; p38MAPK: p38 mitogen-activated protein kinase; PI3K: phosphoinositide 3-kinase; RBBP8: retinoblastoma-binding protein 8; RNA: ribonucleic acid; SNAI1: Snail Family Transcriptional Repressor 1; SNP: single nucleotide polymorphism; SOX-17: SRY-related HMG-box; TGF-β: transformation growth factor β; TGFR: transformation growth factor receptor; TIMP-4, tissue inhibitor of metalloproteinase 4; TSP-1: thrombospondin-1; UTR: untranslated region; VEGF: Vascular Endothelial Growth Factor; VSMC: vascular smooth muscle cell; Wnt1: Wnt family member 1.

Patient: Male, 55-year-old Final Diagnosis: Right frontal arteriovenous malformation, partially calcified • multiple generalised epileptic seizures • chronic headache Symptoms: Epilectic seizure • headache Medication: — Clinical Procedure: Neurosurgical resection of the right frontal AVM Specialty: Neurosurgery Objective: Rare disease Background: Brain arteriovenous malformations (AVMs) are benign intracranial vascular anomalies that, under certain circumstances, may become life-threatening. Diffuse calcifications found in the vessel walls, interposing tissue or adjacent cerebral parenchyma are not uncommon, however, intense calcifications of AVMs that render them into veritable “brain stones” are scarcely reported in the literature and a genuine neurosurgical nightmare. Case Report: A 55 years-old male patient lacking any personal history of serious morbidities or surgical interventions was referred to our department for several epileptic seizures and severe chronic headache in the parieto-occipital region. Upon clinical examination, the patient was aware, right-handed, and had no motor or sensory deficits. Computed tomography angiography scan showed a large densely calcified frontal AVM. The patient was subjected to neurosurgical removal of the lesion and was discharged a week later with a minor motor deficit of the left arm. Conclusions: Intracranial AVMs are a rare pathology, but a genuine microsurgical trial. The difficulty level soars when the malformed vessels become atherosclerotic and calcified, rendering bipolar ligation or permanent clipping un-feasible. An incomplete resection in the case of a highly calcified lesion can only result in an uncontrollable hemorrhage.

Optic pathway gliomas (OPG) represent an important cause of visual loss in pediatric population. The indication of treatment is based on clinical or neuroimaging progression. Visual acuity loss is the most important symptom of disease progression, but children with OPG are frequently unable to complete the testing of visual function. Optical coherence tomography (OCT) was suggested as an objective tool for visual assessment. A literature review was performed in order to determine the role of retinal OCT as a surrogate marker of vision in children with OPG. The search was performed using PubMed, Embase, and Web of Science databases and was restricted to articles published in English between 2000 and 2016, with a minimum of ten participants enrolled. Eleven studies met the eligibility criteria and were included in the present review. Both neurofibromatosis-1 associated and sporadic OPG were investigated. Retinal OCT is a promising tool to be considered as a screening or follow-up test in children with OPG, and further multicenter research is encouraged.

Trigeminal schwannomas (TS) are rare tumors that are located in the posterior and middle cranial fossae in about a quarter of the cases. The presentation pattern is different according to the involved compartment and the goal of surgery is complete removal. We present the case of a 35-year old woman who presented a left sided TS extending from the posterior to the middle fossa and cavernous sinus. We review the relevant literature regarding diagnosis and surgical treatment of these tumors.

Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.

Complex scalp defects with poor recipient vessels represent a challenge for plastic surgeons. In these cases, free flaps are the last resort for solving the problem. The authors present 5 difficult cases with complex large scalp and calvarium defects with unsuitable small recipient vessels for anastomoses. For these cases, the lesser saphenous vein was harvested and used as an interposition graft between the external carotid artery, the jugular vein, and the flap. Latissimus Dorsi, Anterolateral Thigh, and serratus anterior were the flaps used for reconstruction. Cranioplasty was simultaneously performed in 4 cases. The scalp defects varied from 83 to 288 cm. All flaps survived. In 1 case (extended Latissimus Dorsi) there was local infection and wound dehiscence with marginal flap necrosis that required flap readvancement. In conclusion, end-to-end anastomosis to the external carotid artery offers strong outflow through the vein graft and flap. A large vein graft allows good outflow and is more resistant to the pressure of the skin envelope. Anastomosis to large neck vessels (internal or external jugular) facilitates drainage since there is also an aspiration effect due to the venous flow circulation through it.

Introduction: Metformin (MET), an old anti-diabetic drug, has proven unexpected anti-glioblastoma effects, by impacting cell proliferation, migration and invasion. However, its remarkable anti-cancer efficacy is mainly limited to the use of high millimolar concentrations in in vitro studies, which are hard to be attained in the clinical setting. Aim: The aim of this paper was to synthetize gold nanoparticles loaded with MET and to test if an enhanced drug delivery via nanotechnology could overcome the limitations of small drug concentrations. Materials and Methods: Gold nanoparticles were functionalized with chitosan (GNPc) and loaded with 80 μM of MET. Their size, zeta potential and stability were characterized and their internalization within tumor cells was assayed through dark field microscopy. Three primary glioblastoma stem cell lines were treated with 5, 10 and 20 μg/mL concentrations of nanoparticles and irradiated. The anti-tumoral effect was evaluated through the MTT cell viability assay. Results: MET-GNPc are easily synthetized and have a positive zeta potential, spherical shape and a median size of 26 nm. MET-GNPc have an increased cell internalization and affect the viability of all three glioblastoma cell lines used compared to control and free MET. However, their anti-cancer effect is not statistically different when compared to GNPc, although a slight tendency to a better response may be observed. Conclusion:Despite an increased cell internalization, the small micromolar concentrations of metformin does not bring an additional benefit to chitosan-based GNPs. Novel delivery methods being able to carry a higher drug concentration of metformin should be tested.

Cerebral hemispherectomy is a neurosurgical procedure that involves surgically removing one hemisphere of the brain, used as a therapeutic option in severe cases of intractable epilepsy. Several animal models have contributed to our understanding of the underlying neuromechanisms. The review was based on a PubMed search using the terms "hemispherectomy" and "mouse" or "rat" or "rodent", with no limitation of year of study or language. We identified a series of elements that were collected and analyzed that add up to our contemporary knowledge of this procedure. Our search returned 29 articles out of which only 15 are relevant to our purposes. Most of the current literature is concerned with the different molecular and electrophysiological issues of neuroplasticity, exhibiting the neurochemical background on which brain plasticity is founded. Experimental neurosurgery is quintessential in understanding the process in which various pathologies respond to in vivo animal models and recreating conditions otherwise difficult or impossible to obtain in humans. The aim of our study was to evaluate the current literature on the modern comprehension that animal models offer for histopathological, neurochemical and microsurgical research. In addition, the review is focused on the neuroplastic/compensatory mechanisms developed after hemispherectomy. Further research is of vital importance in exploring neurotherapeutical aspects of neuroplasticity in central nervous system (CNS) diseases.

Hydrocephalus represents the pathological elevation of cerebrospinal fluid (CSF) levels as a consequence of various embryological or acquired defects. Although the classic method of treatment is by means of diverting the CSF from the ventricular system towards the peritoneum, there are other sites of diversion that have proven their efficiency through time, in the context of complications related to the more common option of intraperitoneal insertion. The aim of the review is to assess and organize a database of all the types of shunt locations from the oldest shunt attempts until present, using Pubmed and Medline and to underline the particularities related to technique, indications, complications and associated epidemiological background. Current literature reveals up to 36 sites of diversion of CSF with a diverse topography varying from cephalic regions such as venous sinuses or mastoid bone, thoracic elements such as the heart or the pleura and abdominopelvic segments such as the peritoneum or the urinary bladder. Several atypical locations were studied such as the fallopian and intestinal shunts. Although ventriculoperitoneal and ventriculoatrial shunts are the most commonly used shunts today, there are some systems such as the ventriculosinusal and ventriculolymphatic shunts that prove to be equally as efficient. The successful treatment of hydrocephalus requires a complete comprehension of the indications and therapeutic options and a reliable evaluation of the risks and possible complications. The profile of cerebral ventricular shunts is highly dynamic and the spectrum of cerebrospinal fluid diversion offers multiple solutions in the benefit of the patient.

Purpose : Glioblastoma multiforme (GBM) remains one of the most devastating diseases known to mankind and affects more than 17,000 patients in the United States alone every year. This malignancy infiltrates the brain early in its course and makes complete neurosurgical resection almost impossible. Recent years have brought significant advances in tumor biology. Many cancers, including gliomas, appear to be supported by cells with stemlike properties. Nanoparticles are excellent candidates to serve as delivery vectors of drugs or biologically active molecules because of their unique chemical and physical properties that result in specific transportation and deposition of such agents in specific organs and tissues.. In the current study we have investigated the in vitro action of nanostructural systems (temozolomide encapsulated in chitosan and polymer nanostructures) on high-grade gliomaderived cancer stem cells (CSCs), with the intention of developing a new therapy to treat specific brain tumors with increased efficacy and minimal toxicity. In vitro cytotoxicity and apoptosis measurements indicated that the drug/vector combination facilitated the ability of the alkylating drug TMZ to alter the resistance of these cancer stem cells, suggesting a new chemotherapy strategy even for patients diagnosed with inoperable or recurrent malignant gliomas Methods : At the National Institute for R & D of Isotopic and Molecular Technologies form Cluj Napoca were synthesized three types of nanostructures chitosan-TMZ, TMZ-chitosan-PEG (polyethylene glycol), TMZ-chitosan-PPG (polypropylene glycol). Three type of cell lines (Glioma-derived stem, HFL and HUVEC) were treated with the 3 types of nanostructures and the survival rate of the cells was compare to standard therapy (TMZ). Results : The results showed a reduction in the rate of survival of the tumor cells. Cell proliferation assays clearly demonstrate the differences betweenconventional chemotherapy (TMZ) and temozolomide encapsulated in chitosan and polymer nanostructures. Conclusion: Nanostructures like chitosan, PEG, PPG are useful as vectors for drugs transport. Despite combined therapy (surgery, radiotherapy, chemotherapy), currently median patient survival is reduced. The key to improving life expectancy could be an effective therapy targeted, customized for each case. An increasingly important role will be new methods of treatment such as immunotherapy, gene therapy or nanotherapy.

After sitting many years on the shelves of drug stores as a harmless antidiabetic drug, metformin comes back in the spotlight of the scientific community as a surprisingly effective antineoplastic drug. Metformin targets multiple pathways that play pivotal roles in cancer progression, impacting various cellular processes, such as proliferation, cell death, metabolism, and even the cancer stemness features. The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin's anticancer efficiency. This could indicate a need for tumor genetic profiling in order to identify patients most likely to benefit from metformin treatment. Considering that the majority of experimental models suggest that higher, supra-clinical doses of metformin should be used in order to obtain an antineoplastic effect, new ways of drug delivery could be developed, such as metformin-loaded nanoparticles or incorporation of metformin into microparticles used in transarterial chemoembolization, with the aim of obtaining higher intratumoral drug concentrations and a targeted therapy which will ultimately maximize metformin's efficacy.

Primary brain tumors consist are a heterogenic group of malignancies. Gliomas represent subtypes which include all tumors arising from glial cells. The risk factors for gliomas are until today unclear. The aim of this study was to summarize all possible connections between suspected risk factors and glial brain tumors.

Meningiomas account for more than 30% of all intracranial brain tumors, with 25% of them originating somewhere along the skull base and about 20% of these located in the posterior fossa. The intimate relation of these tumors with neural and vascular structures make them difficult to treat, both surgically and nonsurgically. Their treatment is further hampered by the lack of definitive recommendations, which is partially due to the fact that there is no general accepted model of classification. The present report proposes a new concept of classification of posterior fossa skull base meningiomas, one that takes into account the intimate relation of these tumors with arachnoid structures, simplifies the overcrowded landscape of their systematization and can be extended to oher skull base locations.

The objective of this systematic literature review is to assess the role of retinal optical coherence tomography (OCT) in the evaluation of patients with tumors of the visual pathway. We performed a PubMed database search according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The search was restricted to articles published in English between 2000 and 2016, with at least 10 human adult participants enrolled. Twenty-seven articles met the eligibility criteria. All studies investigated tumors of the anterior visual pathway. Both time-domain and spectral-domain OCT technologies were used and the role of OCT as diagnostic and/or prognostic tool was studied. Retinal OCT provides structural information about ganglion cell axon integrity and is complementary to visual function examination. OCT is a prognostic factor for post-operative visual outcome.

Glioblastoma multiforme (GBM) represents a very aggressive brain tumor. Angiogenesis is the formation of a network of new blood vessels, from preexisting ones. It plays an important role in the formation of the tumor, as it supplies it with oxygen and nutrients. Angiogenesis and inflammation play essential roles in glioblastoma development. These processes are regulated by the balance of a few molecules, acting as pro- or antiangiogenic and pro- or anti-inflammatory factors. The purpose of our study was to evaluate the expression of 7 markers involved in angiogenesis and inflammation pathways in patients with glioblastoma. VEGF, PDGF-bb, IGF-1, TGF-β, TNF-α, IL-6 and IL-8 levels were measured using the ELISA method, in the preoperative sera of 14 patients with histopathologically confirmed glioblastoma multiforme and 32 healthy patients. Serum levels of PDGF-bb, IGF-1 and IL-8 were significantly higher in patients with GBM, compared to the control group (p-value < 0.01). A statistically significant correlation has been found between IGF-1 and IL-6 levels (rho= -0.53, p-value < 0.05) and also between TNF-α and IL-6 levels (rho=0.60, p-value < 0.05). Statistically significant associations have been found between the presence of low levels of IL-8 and the development of coagulation necrosis (p-value < 0.05), high levels of VEGF and development of ischemic necrosis (p-value < 0.01) and high levels of IL-8 and the development of endothelial hyperplasia (p-value < 0.05). We have observed no statistically significant associations between the serum levels of the markers and the survival rates.

Dear editor We have read with great interest the paper of Ketkar-Atre et al,1 in which they have developed a new way of tracking stem cells after transplantation using a magnetic resonance imaging (MRI)-based method. They have proven using high resolution electron microscopy that various types of undifferentiated cells, also known as stem cells, have a differentiation uptake of iron oxide nanoparticles according to their size and proliferation rate. Due to its super-paramagnetic properties, iron oxide is slowly finding its way from the laboratory to the clinic. When combined with MRI, it can very efficiently track a stem cell in vivo, as in the case of autologous transplantation,2,3 but also for other conditions such as Duchenne muscular dystrophy. Undifferentiated cells are slowly changing the way we treat various diseases and transplantation is currently the standard-of-care in hematology and ophthalmology, but these cells are not always the solution for therapy. Sometimes, undifferentiated cells are the cause of disease initiation, progression and resistance to therapy. This is the case of stem-like cells, that have been isolated from a wide variety of malignancies4–6 and have been proven to be responsible for resistance to both chemotherapy and radiation oncology treatment. This most often leads to a dismal prognosis for the patient. Various nanotechnology-based approaches have been developed to specifically target these stem-like cells,7,8 but so far little real progress has been made in the clinic because of late diagnosis of malignancy relapse. Using iron oxide nanoparticles combined with an MRI or positron emission tomography (PET) scan, we may actually identify a very small cluster of stem-like malignant cells and diagnose a tumor relapse before clinical, or preclinical investigations show it. This method has already been published by Marotta et al,9 but further investigation must be carried out in the field.

Summary Background The balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10–100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could improve outcome in these patients. Methods In this international, parallel-group trial undertaken in 78 centres in 27 countries, we compared early surgical haematoma evacuation within 12 h of randomisation plus medical treatment with initial medical treatment alone (later evacuation was allowed if judged necessary). An automatic telephone and internet-based randomisation service was used to assign patients to surgery and initial conservative treatment in a 1:1 ratio. The trial was not masked. The primary outcome was a prognosis-based dichotomised (favourable or unfavourable) outcome of the 8 point Extended Glasgow Outcome Scale (GOSE) obtained by questionnaires posted to patients at 6 months. Analysis was by intention to treat. This trial is registered, number ISRCTN22153967. Findings 307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavourable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3·7% [95% CI −4·3 to 11·6], odds ratio 0·86 [0·62 to 1·20]; p=0·367). Interpretation The STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral haemorrhage without intraventricular haemorrhage. Funding UK Medical Research Council.

Dear editor We have read with great interest the work of Lu et al published recently in the International Journal of Nanomedicine,1 in which the authors describe different strategies for an efficient delivery of drugs to the central nervous system (CNS) across the blood–brain and blood–cerebrospinal fluid barriers. The paper describes in a very organized and efficient manner the current approaches to improve the penetration of various drugs across the blood–brain barrier, of key importance in CNS malignancies. Several methods have been proposed as improved ways to surpass the problems related to poor delivery and resistance of CNS malignancies to chemotherapy. The dose intensity is defined as high-dose chemotherapy followed by an autologous stem cell transplantation, and represents an efficient salvage protocol for a primary CNS malignancy treated with a carmustine-based, carboplatin-based or thiotepa-based regimen, along with autologous stem cell rescue.2,3 The result is reduced mortality and a prolonged disease-free interval. However, the efficiency of dose intensity in pediatric neurooncology is still unknown. Whether defined as high-dose chemotherapy, autologous bone marrow rescue, hematopoietic stem cell rescue, or myeloablative chemotherapy, very conclusive data have yet to be published supporting the superiority of dose intensity over less aggressive consolidation chemotherapy. Myeloablative chemotherapy is somewhat biased regarding the more favorable outcomes, as clinical trials either support or refute these protocols.4,5 This is why further trials, that enroll more patients, are expected to decide the efficacy of this approach, as dose intensity alone seems to lack the strength to treat pediatric CNS malignancy. In the case of neuroblastomas, Kesheleva et al6 have proven that acquired resistance to chemotherapy increases progressively to the intensity of the delivered in vivo dosage. This resistance is probably linked to the number of malignant cells that acquire genetic or epigenetic alterations during standard protocols used in the clinic. Thus, it is important to mention the issue of dose intensity in hematopoietic transplantation in pediatric hematooncology. This is because it seems to be of crucial importance in the treatment of children with primary CNS cancers or resistant disease with various chemoenhancers, as is the case of autologous stem cell transplantation in order to achieve a long-term remission or at least an improved therapeutic ratio.