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Isocitrate dehydrogenase (IDH) is a key enzyme in normal metabolism and homeostasis. However, mutant forms of IDH are also defining features of a subset of diffuse gliomas. In this review, we highlight current techniques targeting IDH-mutated gliomas and summarize current and completed clinical trials exploring these strategies. We discuss clinical data from peptide vaccines, mutant IDH (mIDH) inhibitors, and PARP inhibitors. Peptide vaccines have the unique advantage of targeting the specific epitope of a patient’s tumor, inducing a highly tumor-specific CD4+ T-cell response. mIDH-inhibitors, on the other hand, specifically target mutant IDH proteins in cancer cell metabolism and thus help halt gliomagenesis. We also explore PARP inhibitors and their role in treating diffuse gliomas, which exploit IDH mutant diffuse gliomas by allowing the persistence of unrepaired DNA complexes. We summarize various completed and current trials targeting IDH1 and IDH2 mutations in diffuse gliomas. Therapies targeting mutant IDH have significant promise treating progressive or recurrent IDH-mutant gliomas and may significantly change treatment paradigms in the next decade.

Craniofacial fibrous dysplasia (CFD) typically occurs in the facial bones and anterior cranial vault and can produce both disfigurement and functional limitations for patients disfigurement. Treatment consists of reducing the abnormal bone. Bone contouring can become challenging when the exposure does not extend to the corresponding normal contralateral structures for comparison or when normal landmarks are not available, which may compromise the overall aesthetic outcome. We describe a technique using dynamic mirroring to accurately contour the involved part of the cranium in a case of giant CFD.A 49-year-old male presented with a giant deforming fibrous dysplasia of the right mastoid and parieto-temporo-occiput that was causing functional limitations due to the size of the bony mass. This was managed with multidisciplinary bony reduction. Several neurovascular structures were in proximity to the areas of planned drilling of the expansile lesion, and dynamic mirroring of the uninvolved left skull was utilized to maximize safety and symmetry of reduction. High-speed drilling of the right occipital bone was performed until the navigation system alerted the surgeon that symmetric depth had been achieved. There were no complications from the procedure and this technique maximized the limits of symmetric reduction without significantly increasing surgical complexity or duration.Dynamic mirroring of bony structures in the posterior cranium is not commonly employed in neurosurgical practice. This technique may help improve the aesthetic outcomes of bony reduction in craniofacial dysplasia and a variety of similarly managed bony lesions, contour cranioplasties, and in unilateral craniosynostosis surgery.

Background Immunoglobulin-G4-related hypophysitis is a rare inflammatory disease that can present as a tumefactive pituitary lesion mimicking hypophyseal neoplasms such as pituitary adenoma or craniopharyngioma. The literature on this entity is sparse, with fewer than 100 cases reported across 19 publications; a recent review found only 24 cases published from 2007 to 2018. Previous reports have described demographic differences, with immunoglobulin-G4-related hypophysitis in females tending to present in the second and third decades in association with other autoimmune disease, while males tend to present in the fifth and sixth decades of life without an autoimmune history. Case presentation In contrast to the reported demographic trends, here we describe a unique case of immunoglobulin-G4-related hypophysitis in a 63-year-old white female with no history of autoimmune disease who presented with a rapidly enlarging sellar and hypothalamic mass causing headaches and cranial nerve palsies, prompting biopsy for diagnosis. The patient experienced rapid response to treatment with high-dose steroids and rituximab. Conclusion The case contributes to the growing clinicopathologic description of immunoglobulin-G4-related hypophysitis and illustrates that this diagnosis should be a consideration even outside the conventional demographic setting.

The literature includes many studies examining the genetic abnormalities that influence pituitary adenomas (PAs). We aimed to state the collective knowledge on the genetic underpinnings of PAs by organizing, summarizing, and consolidating the literature to serve as a comprehensive review for scientists and clinicians of the most up-to-date information underlying the genetic landscape of PAs.The PubMed and Google Scholar databases were searched using multiple key words and combined Medical Subject Headings terms; only articles published in English between January 2000 and January 2022 were included. Articles in which the focus did not relate to genetics, that included mainly anecdotal evidence, or that were single case studies were eliminated.PAs are one of the most common intracranial neoplasms. However, the genetic underpinnings for these tumors are not yet fully elucidated. There are several categories of PAs: clinically significant versus not clinically significant, functional versus nonfunctional, and germline-derived versus sporadic origin. Each of these disease subcategories is characterized by unique genetic aberrations. Recently, more genes and other types of genetic aberrations have been identified as possible causes of PAs, such as copy number variations and altered levels of microRNAs.This review serves to consolidate and summarize the literature discussing the genetic motifs of PAs to help physicians and scientists deliver patient-centered therapies.

OBJECTIVE The objective of this retrospective study was to compare the survival of patients with biopsy-proven skull base chordoma who had undergone stereotactic radiosurgery (SRS) with versus without prior fractionated radiation therapy (RT). METHODS Relevant articles from database inception to September 2021 were retrieved from the PubMed, Scopus, Web of Science, and Cochrane databases for a systematic review of treatment protocols. Studies were included if they 1) involved adult patients (age ≥ 18 years) with histologically and radiologically confirmed chordomas located within the clival skull base region and treated with SRS; 2) reported data on clinical features, SRS protocols, and outcomes; and 3) were written in the English language. Studies were excluded if they 1) were literature reviews, case reports, technical notes, abstracts, or autopsy reports; 2) did not clearly differentiate the data of patients with chordomas from the data of patients with different tumors or the data of patients with chordomas in locations other than the skull base; or 3) lacked histological confirmation or treatment and outcome data. Extracted data included the following: study author and publication year, patient age and sex, symptoms, cranial nerve involvement, invaded structures, lesion size, treatment modality, surgical details, histopathological type, RT modality, SRS parameters, complications, postradiosurgery outcomes, complications, and survival outcomes. RESULTS After the selection process, 15 articles describing 130 patients met the study eligibility criteria, including 94 patients who had undergone postresection SRS (NoRT group) and 36 who had undergone postresection fractionated RT and subsequent SRS (RT group). The NoRT and RT groups were comparable in age (51.3 vs 47.4 years, respectively), sex (57.1% vs 58.3% male), tumor volume (9.5 vs 11.2 cm3), SRS treatment parameters (maximum dose: 35.4 vs 42.2 Gy, marginal dose: 19.6 vs 20.6 Gy, treatment isodose line: 60.2% vs 65.2%), and SRS adverse effects (10.9% vs 17.6%). For the entire cohort, the 3-, 5-, and 10-year progression-free survival (PFS) rates were 23%, 9%, and 3%, respectively, and the overall survival (OS) rates were 94%, 82%, and 76%, respectively. In the NoRT group, SRS was adjuvant treatment after resection in 38 patients (40.4%), salvage treatment for recurrent tumor treated with resection alone in 10 (10.6%), and not specified in 46 (48.9%). In the RT group, SRS was boost treatment in 9 patients (25.0%), salvage treatment after recurrence in 22 (61.1%), and not specified in 5 (13.9%). There was no difference between the two groups in terms of median PFS (24.0 months [Q1 34.0, Q3 15.0] vs 23.8 months [34.0, 18.0], respectively; p = 0.8) or median OS (293.0 months [not reached, 137.4] vs not reached [not reached, 48.0], respectively; p = 0.36). The adverse radiation effect rates were comparable between the groups (10.9% vs 17.6%, respectively; p = 0.4). CONCLUSIONS The role of SRS in the management of skull base chordomas is still evolving. This systematic literature review of biopsy-proven chordoma revealed that tumor control and survival rates for SRS alone after chordoma surgery were not inferior to those encountered after SRS plus fractionated RT.

Toxoplasma gondii is one the most prevalent opportunist infections worldwide and can cause a severe and potentially fatal encephalitis. Toxoplasma encephalitis (TE) often presents in the setting of acquired immunodeficiency syndrome (AIDS), however, diagnosing TE can be challenging in patients with no signs of being immunocompromised. Here we report unusual presentations of TE in an immunocompetent patient, a patient four years post orthotopic liver transplantation, and two patients with undiagnosed AIDS that underwent prolonged workup for lesions that mimicked intracranial neoplasm. This report highlights the difficulties in diagnosing TE in patients with atypical presentations and unknown risk factors. A high clinical suspicion should be maintained to allow rapid treatment and to avoid significant morbidity and mortality.

Objective Previous work categorized skull base chordoma (SBC) into three genetic risk groups based on 1p36 and homozygous 9p21(p16) deletions, accounting for a wide variability in prognosis (A = low-risk, B = intermediate-risk, C = high-risk). However, it remains unclear how these groups could guide management. Study Design By integrating surgical outcome and adjuvant radiation (AdjXRT) information with genetic data on 152 tumors, we sought to develop an evidence-based management algorithm for SBC. Results Gross total resections (GTRs) were associated with improved progression free survival (PFS) in all genetic groups. For Group C tumors, GTR and AdjXRT independently contributed to PFS (multivariate Cox proportional hazard ratio [HR] = 0.14, p = 0.002, and HR = 0.40, p = 0.047, respectively). For Group B tumors, AdjXRT improved outcomes only when GTR was not feasible (log-rank p = 0.008), but not following GTR (log-rank p = 0.54). However, 24 of 25 Group A tumors underwent GTR, and AdjXRT for these did not confer any benefit (log-Rank p = 0.285). The high GTR rates in Group A could be explained by smaller tumor sizes (mean = 0.98cc/4.08cc/4.92cc for Group A/B/C, respectively, p = 0.031) and lack of invasiveness. Group A tumors were also more frequently diagnosed in young people (p = 0.002) as asymptomatic lesions (p = 0.001), suggesting that they could be precursors to tumors in higher risk groups. Conclusion Genotypic grouping by 1p36 and homozygous 9p21(p16) deletions can predict prognosis in SBC and guide management. GTR remains the cornerstone of SBC treatment and can be sufficient without AdjXRT in low and intermediate risk tumors. Low-risk tumors are associated with a less invasive phenotype, which makes them more amenable to GTR.

Intraoperative distinction of pituitary adenoma from normal gland is critical in maximizing tumor resection without compromising pituitary function. Contact endoscopy provides a noninvasive technique that allows for real-time in vivo visualization of differences in tissue vascularity. Two illustrative cases of endoscopic endonasal approaches (EEAs) for resection of pituitary adenoma illustrate the use of contact endoscopy in identifying tumor from gland and differentiating a thin section of normal gland draped over the underlying tumor, thereby allowing for safe extracapsular tumor resection. Contact endoscopy may be used as an adjunct for intraoperative, in vivo differentiation of pituitary gland and adenoma. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21199

Background: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids is a rare disorder that presents with subacute brainstem symptoms such as ataxia, facial paresthesias, and episodic diplopia, thought to be due to a T-cell medicated perivascular inflammatory process. A supratentorial variant, Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS), has been described in only three patients. Case Description: A 71-year-old male presented with word-finding difficulties, confusion, and left leg weakness. Radiographic workup demonstrated multiple supratentorial ring-enhancing lesions. PET/CT demonstrated hypermetabolism and susceptibility-weighted imaging demonstrated a hemorrhagic component. Frozen pathology revealed a predominately T-cell and monocyte inflammatory infiltrate. He demonstrated interval improvement to dexamethasone therapy, but then demonstrated worsening of his symptoms following discontinuation. Conclusion: Given his dramatic response to corticosteroids, he was diagnosed with SLIPPERS. SLIPPERS is an underrecognized diagnostic entity to consider in patients with ring-enhancing lesions and can present with hypermetabolic lesions on PET/CT.

OBJECTIVE Pediatric patients are at risk for the recurrence of brain arteriovenous malformation (AVM) after resection. While there is general consensus on the importance of follow-up after surgical removal of an AVM, there is a lack of consistency in the duration of that follow-up. The object of this systematic review was to examine the role of follow-up imaging in detecting AVM recurrence early and preventing AVM rupture. METHODS This systematic review was performed using articles obtained through a search of the literature contained in the MeSH database, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS Search results revealed 1052 articles, 13 of which described 31 cases of AVM recurrence meeting the criteria for inclusion in this study. Detection of AVM occurred significantly earlier (mean ± SD, 3.56 ± 3.67 years) in patients with follow-up imaging than in those without (mean 8.86 ± 5.61 years; p = 0.0169). While 13.34% of patients who underwent follow-up imaging presented with rupture of a recurrent AVM, 57.14% of those without follow-up imaging presented with a ruptured recurrence (p = 0.0377). CONCLUSIONS Follow-up imaging has an integral role after AVM resection and is sometimes not performed for a sufficient period, leading to delayed detection of recurrence and an increased likelihood of a ruptured recurrent AVM.

Systemic heparinization has become the mainstay anticoagulant in neurointerventional procedures to prevent thromboembolic complications. Its benefit during endovascular therapy for acute stroke however has not been established. The purpose of this study is to retrospectively evaluate the impact of heparin during endovascular therapy for acute ischemic stroke (AIS).We performed a retrospective review of our interventional stroke database from February 2009 to September 2012 for patients with anterior circulation AIS with ICA-T or MCA M1 occlusions. 76 patients were categorized into 2 groups: intraprocedural vs. no intraprocedural heparin use. Outcomes measured included reperfusion (modified TICI scale), cerebral hemorrhages (ECASS criteria), and 90-day outcomes (modified Rankin scale).Baseline characteristics were similar between heparin and non-heparin treated patients, except for presence of CAD (6% vs. 30%, p=0.01), Coumadin (0% vs. 11%, p=0.04), and NIHSS (15.6±5.0 vs. 18.1±4.6, p=0.03). There was a nonsignificantly higher reperfusion rate achieved in heparin-treated patients compared to non heparin-treated patients (63% vs. 50%, p=0.35). Patients who received heparin had significantly lower rates of hemorrhage (p=0.02). Multivariate logistic regression for good outcome revealed only age (OR 0.86; 95% CI 0.78-0.95; p0.01), ASPECTS (OR 2.14; 95% CI 1.01-4.50; p=0.04), and successful reperfusion (OR 19.25; 95% CI 2.37-155.95; p0.01) independently associated with mRS 0-2 at 90 days.The use of intraprocedural heparin in patients with AIS from MCA M1 or ICA-T occlusion was found safe. The impact of heparinization is unclear and warrants further evaluation.

Introduction Intracranial Langerhans Cell Histiocytosis (LCH) is a rare disease caused by the proliferation and dissemination of antigen presenting cells in the skin. Few cases have been reported on to date and there is a lack of consensus on the most effective means of diagnosis and treatment of these lesions. This paper will serve as a review of this malady. Methods MeSH database search was performed to include all relevant studies on intracranial LCH. Results A total of 146 studies with 192 patients were included in our review. Men were more commonly affected and the average age of diagnosis was 31.6 and 28.0 in men and women respectively. CT and MRI were the most common imaging modalities. The majority of the case reports performed biopsies and the most common lesion location was the hypothalamus-pituitary axis. All studies used surgical resection, radiotherapy, chemotherapy or combination therapy as means of treatment, with resection plus chemotherapy being the most successful. 74 cases were successful in preventing recurrence. Conclusion LCH rarely affects the brain as primary or secondary focus. Biopsy is required for precise diagnosis and exclusion of other intracranial lesions. There is no standard treatment for LCH of the central nervous system, but this review may serve as a guide to chronicle previous efficacious therapeutics strategies.

OBJECTIVEBlood-blister aneurysms (BBAs) of the internal carotid artery (ICA) have a poor natural history associated with high morbidity and mortality. Currently, both surgical and endovascular techniques are employed to treat BBAs; thus, the authors sought to perform a meta-analysis to compare the efficacy and safety of these approaches.METHODSA literature search of PubMed, MEDLINE, and Google Scholar online databases was performed to include pertinent English-language studies from 2005 to 2015 that discussed the efficacy and safety of either surgical or endovascular therapies to treat BBAs.RESULTSThirty-six papers describing 256 patients with BBAs treated endovascularly (122 procedures) or surgically (139 procedures) were examined for data related to therapeutic efficacy and safety. Pooled analysis of 9 papers demonstrated immediate and late (mean 20.9 months) aneurysm occlusion rates of 88.9% (95% CI 77.6%–94.8%) and 88.4% (95% CI 76.7%–94.6%), respectively, in surgically treated patients. Pooled analysis of 12 papers revealed immediate and late aneurysm obliteration rates of 63.9% (95% CI 52.3%–74.1%) and 75.9% (95% CI 65.9%–83.7%), respectively, in endovascularly treated aneurysms. Procedure-related complications and overall poor neurological outcomes were slightly greater in the surgically treated cases than in the endovascularly treated cases (27.8% [95% CI 19.6%–37.8%] vs 26.2% [95% CI 18.4%–35.8%]), indicating that endovascular therapy may provide better outcomes.CONCLUSIONSBlood-blister aneurysms are rare, challenging lesions with a poor prognosis. Although surgical management potentially offers superior aneurysm obliteration rates immediately after treatment and at the long-term follow-up, endovascular therapy may have a better safety profile and provide better functional outcomes than surgery. A registry of patients treated for BBAs may be warranted to better document the natural course of the disease as well as treatment outcomes.

Glioblastoma (GBM) is the most common and deadly form of brain tumor. After standard treatment of resection, radiotherapy, and chemotherapy, the 5-year survival is5%. In recent years, research has uncovered several potential targets within the Notch signaling pathway, which may lead to improved patient outcomes.A literature search was performed for articles containing the terms "Glioblastoma" and "Receptors, Notch" between 2003 and July 2015. Of the 62 articles retrieved, 46 met our criteria and were included in our review. Nine articles were identified from other sources and were subsequently included, leaving 55 articles reviewed.Of the 55 articles reviewed, 47 used established human GBM cell lines. Seventeen articles used human GBM surgical samples. Forty-five of 48 articles that assessed Notch activity showed increased expression in GBM cell lines. Targeting the Notch pathway was carried out through Notch knockdown and overexpression and targeting δ-like ligand, Jagged, γ-secretase, ADAM10, ADAM17, and Mastermindlike protein 1. Arsenic trioxide, microRNAs, and several other compounds were shown to have an effect on the Notch pathway in GBM. Notch activity in GBM was also shown to be associated with hypoxia and certain cancer-related molecular pathways such as PI3K/AKT/mTOR and ERK/MAPK. Most articles concluded that Notch activity amplifies malignant characteristics in GBM and targeting this pathway can bring about amelioration of these effects.Recent literature suggests targeting the Notch pathway has great potential for future therapies for GBM.

Objectives: Despite the aggressive standard of care for patients with glioblastoma multiforme, survival rates typically do not exceed 2 years. Therefore, current research is focusing on discovering new therapeutics or rediscovering older medications that may increase the overall survival of patients with glioblastoma. Curcumin, a component of the Indian natural spice, turmeric, also known for its antioxidant and anti-inflammatory properties, has been found to be an effective inhibitor of proliferation and inducer of apoptosis in many cancers. The goal of this study was to investigate the expanded utility of curcumin as an antiglioma agent. Methods: Using the PubMed MeSH database, we conducted a systematic review of the literature to include pertinent studies on the growth inhibitory effects of curcumin on glioblastoma cell lines based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 19 in vitro and five in vivo studies were analyzed. All of the studies indicated that curcumin decreased glioblastoma cell viability through various pathways (i.e. decrease in prosurvival proteins such as nuclear factor κB, activator protein 1, and phosphoinositide 3 kinase, and upregulation of apoptotic pathways like p21, p53, and executor caspase 3). Curcumin treatment also increased animal survival compared with control groups. Conclusions: Curcumin inhibits proliferation and induces apoptosis in certain subpopulations of glioblastoma tumors, and its ability to target multiple signaling pathways involved in cell death makes it an attractive therapeutic agent. As such, it should be considered as a potent anticancer treatment. Further experiments are warranted to elucidate the use of a bioavailable form of curcumin in clinical trials.

OBJECTIVE Long-segment injuries to large peripheral nerves present a challenge to surgeons because insufficient donor tissue limits repair. Multiple supplemental approaches have been investigated, including the use of Schwann cells (SCs). The authors present the first 2 cases using autologous SCs to supplement a peripheral nerve graft repair in humans with long-term follow-up data. METHODS Two patients were enrolled in an FDA-approved trial to assess the safety of using expanded populations of autologous SCs to supplement the repair of long-segment injuries to the sciatic nerve. The mechanism of injury included a boat propeller and a gunshot wound. The SCs were obtained from both the sural nerve and damaged sciatic nerve stump. The SCs were expanded and purified in culture by using heregulin β1 and forskolin. Repair was performed with sural nerve grafts, SCs in suspension, and a Duragen graft to house the construct. Follow-up was 36 and 12 months for the patients in Cases 1 and 2, respectively. RESULTS The patient in Case 1 had a boat propeller injury with complete transection of both sciatic divisions at midthigh. The graft length was approximately 7.5 cm. In the postoperative period the patient regained motor function (Medical Research Council [MRC] Grade 5/5) in the tibial distribution, with partial function in peroneal distribution (MRC Grade 2/5 on dorsiflexion). Partial return of sensory function was also achieved, and neuropathic pain was completely resolved. The patient in Case 2 sustained a gunshot wound to the leg, with partial disruption of the tibial division of the sciatic nerve at the midthigh. The graft length was 5 cm. Postoperatively the patient regained complete motor function of the tibial nerve, with partial return of sensation. Long-term follow-up with both MRI and ultrasound demonstrated nerve graft continuity and the absence of tumor formation at the repair site. CONCLUSIONS Presented here are the first 2 cases in which autologous SCs were used to supplement human peripheral nerve repair in long-segment injury. Both patients had significant improvement in both motor and sensory function with correlative imaging. This study demonstrates preliminary safety and efficacy of SC transplantation for peripheral nerve repair.

Object Pediatric patients are at significant risk for recurrence of brain AVM after resection. While there is general consensus as to the importance of follow-up after surgical resection of an AVM, there is a lack of consistency in follow-up duration. The object of this systematic review is to examine the role of follow-up imaging in detecting AVM recurrence early and preventing AVM rupture. Methods This systematic review was carried out with articles obtained through a search of the literature according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results Search results revealed 1052 articles, of which 13 studies describing 31 cases of AVM recurrence met criteria for inclusion in this study. Patients receiving follow-up imaging experienced AVM detection significantly earlier (mean = 3.56 years, SD = 3.67) than patients with no follow-up (mean = 8.86 years, SD = 5.61; p = 0.0085). While 13.34% of patients that were not receiving follow-up imaging presented with rupture of recurrent AVM, 57.14% of patients that were receiving follow-up imaging presented with ruptured recurrence (p = 0.019). Conclusions Follow-up imaging has an integral role after AVM resection and is sometimes not carried out for a sufficient period of time, leading to delayed detection of recurrence and increased likelihood of recurrent AVM rupture. Disclosures J. Jimenez: None. Z. Gersey: None. J. Wagner: None. B. Snelling: None. S. Ambekar: None. E. Peterson: None.

Background Glioblastoma Multiforme (GBM) is the most common and lethal form of primary brain tumor in adults. Following standard treatment of surgery, radiation and chemotherapy, patients are expected to survive 12–14 months. Theorized cause of disease recurrence in these patients is tumor cell repopulation through the proliferation of treatment-resistant cancer stem cells. Current research has revealed curcumin, the principal ingredient in turmeric, can modulate multiple signaling pathways important for cancer stem cell self-renewal and survival. Methods Following resection, tumor specimens were dissociated and glioblastoma stem cells (GSCs) were propagated in neurosphere media and characterized via immunocytochemistry. Cell viability was determined with MTS assay. GSC proliferation, sphere forming and colony forming assays were conducted through standard counting methods. Reactive oxygen species (ROS) production was examined using the fluorescent molecular probe CM-H2DCFA. Effects on cell signaling pathways were elucidated by western blot. Results We evaluate the effects of curcumin on patient-derived GSC lines. We demonstrate a curcumin-induced dose-dependent decrease in GSC viability with an approximate IC50 of 25 μM. Treatment with sub-toxic levels (2.5 μM) of curcumin significantly decreased GSC proliferation, sphere forming ability and colony forming potential. Curcumin induced ROS, promoted MAPK pathway activation, downregulated STAT3 activity and IAP family members. Inhibition of ROS with the antioxidant N-acetylcysteine reversed these effects indicating a ROS dependent mechanism. Conclusions Discoveries made in this investigation may lead to a non-toxic intervention designed to prevent recurrence in glioblastoma by targeting glioblastoma stem cells. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3058-2) contains supplementary material, which is available to authorized users.