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Background/Aim: Nowadays, Machine Learning (ML) algorithms have demonstrated remarkable progress in image-recognition tasks and could be useful for the new concept of precision medicine in order to help physicians in the choice of therapeutic strategies for brain tumours. Previous data suggest that, in the central nervous system (CNS) tumours, amino acid PET may more accurately demarcate the active disease than paramagnetic enhanced MRI, which is currently the standard method of evaluation in brain tumours and helps in the assessment of disease grading, as a fundamental basis for proper clinical patient management. The aim of this study is to evaluate the feasibility of ML on 11[C]-MET PET/CT scan images and to propose a radiomics workflow using a machine-learning method to create a predictive model capable of discriminating between low-grade and high-grade CNS tumours. Materials and Methods: In this retrospective study, fifty-six patients affected by a primary brain tumour who underwent 11[C]-MET PET/CT were selected from January 2016 to December 2019. Pathological examination was available in all patients to confirm the diagnosis and grading of disease. PET/CT acquisition was performed after 10 min from the administration of 11C-Methionine (401–610 MBq) for a time acquisition of 15 min. 11[C]-MET PET/CT images were acquired using two scanners (24 patients on a Siemens scan and 32 patients on a GE scan). Then, LIFEx software was used to delineate brain tumours using two different semi-automatic and user-independent segmentation approaches and to extract 44 radiomics features for each segmentation. A novel mixed descriptive-inferential sequential approach was used to identify a subset of relevant features that correlate with the grading of disease confirmed by pathological examination and clinical outcome. Finally, a machine learning model based on discriminant analysis was used in the evaluation of grading prediction (low grade CNS vs. high-grade CNS) of 11[C]-MET PET/CT. Results: The proposed machine learning model based on (i) two semi-automatic and user-independent segmentation processes, (ii) an innovative feature selection and reduction process, and (iii) the discriminant analysis, showed good performance in the prediction of tumour grade when the volumetric segmentation was used for feature extraction. In this case, the proposed model obtained an accuracy of ~85% (AUC ~79%) in the subgroup of patients who underwent Siemens tomography scans, of 80.51% (AUC 65.73%) in patients who underwent GE tomography scans, and of 70.31% (AUC 64.13%) in the whole patients’ dataset (Siemens and GE scans). Conclusions: This preliminary study on the use of an ML model demonstrated to be feasible and able to select radiomics features of 11[C]-MET PET with potential value in prediction of grading of disease. Further studies are needed to improve radiomics algorithms to personalize predictive and prognostic models and potentially support the medical decision process.

It is generally accepted that Glioblastoma (GBM) arise from cancer stem cells (CSC), however, there is little evidence on their anatomical distribution. We investigated the expression and distribution of SOX-2-positive and CD133-positive CSCs both in the enhancing nodule (EN) of GBM and in the FLAIR hyperintensity zones on a surgical, histopathological series of 33 GBMs.The inclusion criterion was the intraoperative sampling of different tumor regions individualized thanks to Neuronavigation and positivity to intraoperative fluorescence with the use of 5-aminolevulinic acid (5-ALA). 33 patients (20 males and 13 females with a mean age at diagnosis of 56 years) met the inclusion criterion. A total of 109 histological samples were evaluated, 52 for ENs and 57 for FLAIR hyperintensity zone. Considering the quantitative distribution of levels of intensity of staining (IS), ES (extent score) and immunoreactivity score (IRS), no difference was found between ENs and FLAIR regions for both the SOX-2 biomarker (respectively, IS p=0.851, ES p=0.561, IRS p=1.000) and the CD133 biomarker (IS p=0.653, ES p=0.409, IRS p=0.881). This evidence suggests to recalibrate the target of surgery for FLAIRECTOMY and 5-ALA could improve the possibility to achieve this goal.

Ping-pong fractures have become less frequent, and no definite predictors to determine which fractures will elevate spontaneously and which should undergo surgical treatment have been clearly defined. Herein, the authors present a revision of the literature, in which 54 papers were included, with a total of 228 children studied. Patients who underwent surgery accounted for 30%; elevation through obstetrical vacuum or other aspiration systems was applied in 30%; and spontaneous resolution occurred in 40%; in 4 patients, percutaneous microscrew elevation was applied. Overall, in 96.4% of patients, the outcome was favorable because we found no significant increase in the incidence of post-traumatic seizures or neurologic sequelae with no significant differences between treated patients and spontaneous elevation. Statistical analysis showed no significant differences among the different treatment methods (P = 0.53). Our results suggest that simple compound ping-pong fractures without brain compression, hematomas, or dural tears could benefit from conservative management. In cases of nonspontaneous resolution after 6 months, operative strategies should be performed, considering that there is no evidence of differences between vacuum elevation and surgical elevation.

Cerebellar liponeurocytoma (CL) is an unusual tumor, histologically composed of a mixture of small to medium-sized, rounded neurocytic cells and a variable lipomatous component. Although CL was originally considered as a subtype of medulloblastoma, subsequent molecular studies demonstrated that this tumor was a distinct entity, exhibiting the tumor protein p53 gene (TP53) missense mutations in 20% of cases, chromosome 17 deletion, and the absence of mutations in the adenomatous polyposis coli gene (APC), the protein patched homolog gene (PTCH), the kinase insert domain receptor gene (KDR), and the β-catenin gene (CTNNB). Apart from these molecular features, little is known about the pathogenesis and the genetic landscape of CL to date. In order to characterize the mutational landscape of CL and identify alterations that are driving tumorigenesis, we report a series of three cases, including one recurrent tumor, analysed by next-generation sequencing (NGS), which identified a total of 22 variants, of which four were missense mutations, nine were synonymous variants, and nine were located on intronic regions. In particular, DNA sequencing identified missense mutations in APC, KDR, and TP53 that could be implicated in promoting tumor progression and angiogenesis of CL. Furthermore, the NGS analysis revealed that recurrent CL did not have additional genetic changes compared with the primary tumor. Moreover, the high frequencies of detected mutations suggested that the identified alterations are germline variants. Indeed, an additional NGS on the genomic DNA obtained from one of the three patients confirmed the presence of the variants in the germline DNA. In conclusion, the obtained data support the hypothesis that CL is a distinct pathological entity that does not show specific somatic alterations driving tumorigenesis.

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients’ prognosis and correct surgical/radiotherapy planning.

Post-traumatic orbital meningoencephaloceles related to orbital roof fractures are a challenging clinical entity because of their rarity and difficult differential diagnosis. We report a case of post-traumatic intra-orbital meningoencephalocele in a 69-year-old man, secondary to a likely trapdoor mechanism, treated with a modified one-piece orbitozygomatic craniotomy. We also performed an extensive literature review of traumatic Intra-Orbital Encephalocele related to Orbital Roof Fracture focused on adult patients on electronic databases including Scopus, MEDLINE/PubMed, and Google Scholar. Patient well recovered after surgery with immediate exophthalmos resolution and discharged without visual or neurological deficits. The literature review included 22 papers with a total of 28 patients: 22 males (78.6%) and 6 females (21.4%), with a median age of 34.7 years. Twenty-six patients (92.9%) reported ocular injuries, with associated intracranial complications in 16 cases (61.5%). Twenty-seven patients (96.4%) were surgically treated, 18 of those underwent unilateral or bilateral frontal approach. Most orbital roof fractures can be managed nanoperatively if asymptomatic. Indeed, when the intra-orbital volume decreases, for example due to an encephalocele, the intra-orbital pressure could increase and determine an orbital compartment syndrome. In our case, we performed a one-piece modified orbitozygomatic approach, which has several advantages in comparison to the frequent unilateral or bilateral frontal craniotomy like the better exposure of the brain and orbit and a minimum brain retraction.

The Inferior Fronto-Occipital fascicle (IFOF) is a multitasking white matter (WM) bundle bridging frontal, temporal, parietal and occipital lobe. Many papers describe its role in the physiology of language, attention and affective behavior but its anatomical components and cortical terminations remain unclear. We analyze the surgical anatomy of the IFOF in the light of our experience with awake surgery, anatomical dissection on 10 human adult hemispheres (Klingler method) and literature review. Dissecting the specimens from lateral to medial we can describe 3 segments: a vertical segment that runs along the frontal lobe; an horizontal segment that runs along frontal lobe; an horizontal segment that runs from the limen insulae, passes into to the temporal stem and arrives at the parietal and occipital lobes. We retrospectively analyzed also 23 awake surgeries. 2 responses were elicited at subcortical stimulation at the third segment of the IFOF; stimulation gave paraphasias on the first segment of the IFOF in one case. All IFOF responses were founded in the left hemisphere. Anatomical knowledge is the cornerstone of surgical orientation, it allows eloquent structures to be reached quickly and it is of primary importance in awake surgery to avoid patient fatigue with lack of concentration.

Background Extent of tumor resection (EOTR) in glioblastoma surgery plays an important role in improving survival. Objective To analyze the efficacy, safety and reliability of fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images used to guide glioblastoma resection (FLAIRectomy) and to volumetrically measure postoperative EOTR, which was correlated with clinical outcome and survival. Methods A total of 68 glioblastoma patients (29 males, mean age 65.8) were prospectively enrolled. Hyperintense areas on FLAIR images, surrounding gadolinium-enhancing tissue on T1-weighted MR images, were screened for signal changes suggesting tumor infiltration and evaluated for supramaximal resection. The surgical protocol included 5-aminolevulinic acid (5-ALA) fluorescence, neuromonitoring, and intraoperative imaging tools. 5-ALA fluorescence intensity was analyzed and matched with the different sites on navigated MR, both on postcontrast T1-weighted and FLAIR images. Volumetric evaluation of EOTR on T1-weighted and FLAIR sequences was compared. Results FLAIR MR volumetric evaluation documented larger tumor volume than that assessed on contrast-enhancing T1 MR (72.6 vs 54.9 cc); residual tumor was seen in 43 patients; postcontrast T1 MR volumetric analysis showed complete resection in 64 cases. O6-methylguanine-DNA methyltransferase promoter was methylated in 8/68 (11.7%) cases; wild type Isocytrate Dehydrogenase-1 (IDH-1) was found in 66/68 patients. Progression free survival and overall survival (PFS and OS) were 17.43 and 25.11 mo, respectively. Multiple regression analysis showed a significant correlation between EOTR based on FLAIR, PFS (R2 = 0.46), and OS (R2 = 0.68). Conclusion EOTR based on FLAIR and 5-ALA fluorescence is feasible. Safety of resection relies on the use of neuromonitoring and intraoperative multimodal imaging tools. FLAIR-based EOTR appears to be a stronger survival predictor compared to gadolinium-enhancing, T1-based resection.

Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential.

OBJECTIVENo consensus exists on the best treatment for recurrent high-grade glioma (HGG), particularly in terms of surgical indications, and scant data are available on the integrated use of multiple technologies to overcome intraoperative limits and pitfalls related to artifacts secondary to previous surgery and radiotherapy. Here, the authors report on their experience with the integration of multiple intraoperative tools in recurrent HGG surgery, analyzing their pros and cons as well as their effectiveness in increasing the extent of tumor resection. In addition, they present a review of the relevant literature on this topic.METHODSThe authors reviewed all cases in which recurrent HGG had been histologically diagnosed after a first surgery and the patient had undergone a second surgery involving neuronavigation with MRI, intraoperative CT (iCT), 11C-methionine–positron emission tomography (11C-MET-PET), 5-aminolevulinic acid (5-ALA) fluorescence, intraoperative neurophysiological monitoring (IONM), and intraoperative navigated ultrasound (iUS). All cases were classified according to tumor functional grade (1, noneloquent area; 2, near an eloquent area; 3, eloquent area).RESULTSTwenty patients with recurrent HGG were operated on using a multimodal protocol. The recurrent tumor functional grade was 1 in 4 patients, 2 in 8 patients, and 3 in the remaining 8 patients. In all patients but 2, 100% EOTR was obtained. Intraoperative 5-ALA fluorescence and navigated iUS showed low specificity and sensitivity. iCT detected tumor remnants in 3 cases. Postoperatively, 6 patients (30%) had worsening neurological conditions: 4 recovered within 90 days, 1 partially recovered, and 1 experienced a permanent deficit. The median Karnofsky Performance Status remained substantially unchanged over the follow-up period. The mean progression-free survival after the second surgery was 7.7 months (range 2–11 months). The mean overall survival was 25.4 months (range 10–52 months), excluding 2 long survivors. Two patients died within 60 days after surgery, and 3 patients were still under follow-up at the end of this study.CONCLUSIONSThis is the first study reporting the integration of neuronavigation, 5-ALA fluorescence, iUS, iCT, 11C-MET-PET, and IOM during microsurgical resection of recurrent glioma. The authors believe that the proposed multimodal protocol is useful to increase the safety, effectiveness, and EOTR in patients with recurrent HGG and brain alterations secondary to radio- and chemotherapy.

Background One of the greatest neuro-oncological concern remains the lack of knowledge about the etiopathogenesis and physiopathology of gliomas. Several studies reported a strict correlation between radiological features and biological behaviour of gliomas; in this way the velocity of diametric expansion (VDE) correlate with lower grade glioma aggressiveness. However, there are no the same strong evidences for high grade gliomas (HGG) because of the lack of several preoperative MRI. Patients and methods We describe a series of 4 patients affected by HGG followed from 2014 to January 2019. Two patients are male and two female; two had a pathological diagnosis of glioblastoma (GBM), one of anaplastic astrocytoma (AA) and one had a neuroradiological diagnosis of GBM. The VDE and the acceleration time (AT) was calculated for fluid attenuated inversion recovery (FLAIR) volume and for the enhancing nodule (EN). Every patients underwent sequential MRI study along a mean period of 413 days. Results Mean VDE evaluated on FLAIR volume was 39.91 mm/year. Mean percentage ratio between peak values and mean value of acceleration was 282.7%. Median appearance time of EN after first MRI scan was 432 days. Mean VDE was 45.02 mm/year. Mean percentage ratio between peak values and mean value of acceleration was 257.52%. Conclusions To our knowledge, this is the first report on VDE and acceleration growth in HGG confirming their strong aggressiveness. In a case in which we need to repeat an MRI, time between consecutive scans should be reduced to a maximum of 15–20 days and surgery should be executed as soon as possible.

To evaluate clinical response after external lumbar drainage (ELD) and ventriculoperitoneal shunting (VPS) in a cohort of patients with idiopathic normal pressure hydrocephalus associated with parkinsonism (iNPH-P), considering parkinsonism as clinical primary outcome. Patients underwent long-term 72-h intracranial pressure-controlled CSF ELD. Clinical motor response before and after ELD was evaluated using changes in UPDRS-ME as outcome measure. A standardized cognitive assessment was also performed. iNPH-P patients who underwent VPS were clinically followed-up after surgery. Fourteen iNPH-P patients (age: 69.3 ± 11.6 years) were studied. The time of evaluation after ELD removal was 3.5 ± 1.8 days. We observed a significant motor improvement after the drainage in eight (57.1%) patients. Percent clinical motor response was 18.4 ± 6.7%. Twelve (85.7%) patients underwent VPS. Nine patients were examined after surgery at 31.6 ± 7 months. Four (44.4%) patients presented a clinically detectable improvement in motor response after VPS. No significant changes in cognitive performances were detected. A clinically detectable motor response on parkinsonian signs was observed in a consistent part of iNPH-P patients few days after ELD as well as over two and half years after VPS. Parkinsonism should be considered as outcome measure for the clinical management of patients with iNPH-P.

This case report describes a fatal case of a young woman with superior sagittal, transverse and sigmoid sinus thrombosis after administration of the ChAdOx1 nCov-19 vaccination. Eleven days post-vaccination she was found unconscious and transferred to the Emergency Department. Blood parameters showed low platelets, and a CT scan showed an extensive left intracranial hemorrhage and the presence of an occlusive thrombus of the superior sagittal sinus. She under-went a craniectomy, but after the intervention, she remained in a comatose state. After a few days, her clinical conditions worsened, and she died. A complete autopsy was performed which showed a thrombosis of the cerebral venous district, of the upper and lower limbs. A blood sample was also performed to carry out a gene study about the predisposition to thrombosis. The organ samples were studied through light microscope both in hematoxylin-eosin and immunohistochemical examination, and showed a strong inflammatory response in all samples and at the site of thrombosis. Our study aims to provide a proper autopsy technique to study the entire cerebral venous system through a multidisciplinary approach (anatomical dissection and neurosurgery) in post-vaccine venous thrombosis.

Spinal infection (SI) is defined as an infectious disease affecting the vertebral body, the intervertebral disc, and/or adjacent paraspinal tissue and represents 2–7% of all musculoskeletal infections. There are numerous factors, which may facilitate the development of SI including not only advanced patient age and comorbidities but also spinal surgery. Due to the low specificity of signs, the delay in diagnosis of SI remains an important issue and poor outcome is frequently seen. Diagnosis should always be supported by clinical, laboratory, and imaging findings, magnetic resonance imaging (MRI) remaining the most reliable method. Management of SI depends on the location of the infection (i.e., intraspinal, intervertebral, paraspinal), on the disease progression, and of course on the patient’s general condition, considering age and comorbidities. Conservative treatment mostly is reasonable in early stages with no or minor neurologic deficits and in case of severe comorbidities, which limit surgical options. Nevertheless, solely medical treatment often fails. Therefore, in case of doubt, surgical treatment should be considered. The final result in conservative as well as in surgical treatment always is bony fusion. Furthermore, both options require a concomitant antimicrobial therapy, initially applied intravenously and administered orally thereafter. The optimal duration of antibiotic therapy remains controversial, but should never undercut 6 weeks. Due to a heterogeneous and often comorbid patient population and the wide variety of treatment options, no generally applicable guidelines for SI exist and management remains a challenge. Thus, future prospective randomized trials are necessary to substantiate treatment strategies.

Introduction Glioblastoma treatment requires a multidisciplinary approach involving oncologists, radiotherapists and surgeons. Surgery constitutes the initial step of the therapeutic strategy and its efficacy is dependent on the extent of resection (EOR). Over the last decade, the goal of surgical treatment was the resection of the contrast enhancement on T1 MRI, defined as gross-total resection (GTR). More recently, an increasing number of studies reports a positive impact on survival parameters of a more aggressive surgical strategy aiming to resect all peri-tumoral infiltrated areas. These areas are histologically characterized by the presence of pathological cells infiltrating normal white matter and surround the neoplastic core of glioblastoma identified by gadolinium enhancement in T1-weighted MR. Intuitively, the major risk of the so called supramarginal resection is related to the possibility of resecting functionally eloquent brain tissue. Several strategies have been proposed to maximize the safety of resection and minimize the occurrence of postoperative functional deficits. The aim of this review was to focus on the clinical impact of supramarginal resection of glioblastomas, highlighting the role of image-guided surgery combined with neuromonitoring to increase surgical safety and efficacy. Evidence acquisition The MEDLINE database has been queried for the literature research. Evidence synthesis Ten studies matched the inclusion criteria, reporting a global number of 3221 patients. Conclusions The current evidence suggests a positive correlation between a more extensive resection based on FLAIR abnormal areas and overall survival.

Objective Analyzing occlusion, complications rate, and clinical results in unruptured saccular middle cerebral artery aneurysms (MCAAs) comparing clipping with the most advance and newer endovascular techniques. Methods We conducted a literature research from January 2009 to December 2018 to evaluate the efficacy and safety of microsurgical clipping or endovascular treatment with new devices (such as Flow-diverter or Woven EndoBridge) in patients with unruptured MCAAs. We extracted data involved: study and intervention features, occlusion rate; time of occlusion assessment; and clinical outcome. Results A total of 29 studies and 1552 patients with unruptured saccular MCAAs were included in our analysis (464 patients included in the endovascular group, 1088 patients in the surgical group). Overall, the rate of long-term complete/near-complete occlusion was 78.1% (311/405, 95% confidence interval [CI], 69%–87.1%) and 95.7% (113/118, 95% CI, 92%–99.3%) after endovascular and surgical treatments, respectively (P = 0.001). The long-term complete occlusion rate was 60% (153/405, 95% CI, 45%–74%) and 95% (112/118, 95% CI, 90%–98%) after endovascular and surgical treatments, respectively (P = 0.001). The overall rate of treatment-related complications was 5.6% (33/464, 95% CI, 3.6%–7.7%) and 2.9% (37/1088, 95% CI, 0.8%–5%) among the endovascular and surgical groups, respectively (P = 0.001). Endovascular treatments were associated with higher rates of good neurologic outcome (283/293 [97%], 95% CI, 95%–98% vs. 570/716 [84%], 95% CI, 67%–98%; P = 0.001). No difference was found for the mortality (3/464 [1.5%], 95% CI, 0.4%–2.6% vs. 1/1088, 95% CI, 0.1%–0.6%; P = 0.5). Conclusions Treatment-related complication and mortality are comparable among these techniques and the risk of aneurysm rupture seems very low for both strategies. The endovascular approach seems to increase the probability of good functional outcome after treatment, compared with surgery.

OBJECTIVEApproximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients.METHODSClinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score.RESULTSSurvival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell’s c-index of 0.75 (95% CI 0.76–0.81).CONCLUSIONSThe CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

Background In the modern era evidence-based medicine, guidelines and recommendations represent a key-point of daily activity. The Spinal Section of the Italian Society of Neurosurgery introduced some recommendations regarding Degenerative Lumbar Spine Stenosis based on those of the Spine Committee of World Federation of Neurosurgical Societies, revising them on the basis of Italian common practice. Methods In June 2019, a Committee of 21 spine surgeons met in Rome to validate the recommendations of the WFNS. Furthermore, they decided to review the ones that did not reach a consensus to create Italian Recommendations on Degenerative Lumbar Spine Stenosis. A literature review of the last ten years was performed and the statements were voted using the Delphi method. Results 41 statements were discussed and 7 statements were voted again to reach a consensus with respect to those of the WFNS. A total of 40 statements reached a consensus, of which 36 reached a positive consensus and 4 a negative consensus, while no consensus was reached in 1 case. Conclusions Conservative multimodal therapy, tailored on the patient, is a reasonable and effective first option choice for the treatment of LSS patients with tolerable moderate symptoms. Surgical treatment is reserved for symptomatic patients non-responding to conservative treatment or with neurological deficits. The best surgical technique to use depends on personal experience; modern MISS techniques are equivalent to open decompressive surgery with some advantages and higher cost-effectiveness. Fusion surgery and mobility preserving surgery only have a marginal role in the treatment of DLSS without instability.

Background Angioleiomyoma (ALM) is a soft tissue neoplasm rarely described in the intracranial site. Because of their uncommon presentation, atypical neuroradiologic and pathologic features, ALMs are often misdiagnosed. Case Description We describe the neuroradiologic, clinical, and pathologic data of a 37-year-old male patient suffering from a tentorial ALM. He was admitted at our hospital because of a posterior cranial fossa mass. Magnetic resonance imaging (MRI) showed a left tentorial tumor, hypointense on T1-weighted sequences, with heterogeneous contrast enhancement after gadolinium injection (“salt-and-pepper” fashion) and slightly hyperintense signal on T2-weighted sequence. After surgery, pathological examination showed a tumor composed of several thick-walled blood vessels mixed with a population of deeply eosinophilic spindle-shaped smooth muscle cells arranged in bundles. Necrosis was absent. Neither cellular pleomorphism nor mitoses were detected. Immuno-histochemical analysis confirmed the smooth muscle phenotype of the spindle cell component: diffuse and strong positivity for alpha-smooth muscle actin, desmin, and h-caldesmon. Based on both morphologic and immunohistochemical findings, a diagnosis of primary intracranial ALM was rendered. Conclusions We add to the literature the tenth case of this exceedingly rare tumor and submit that ALM should be suspected when a tentorial mass with a “flame-like” time-dependent pattern of contrast enhancement on MRI, a “salt-and-pepper” post-contrast appearance on MRI T1-weighted sequences, and a relation with large intracranial feeding vessels are present.

A retro-odontoid pseudotumour compressing the spinal cord and causing myelopathy is often associated with an inflammatory condition such as rheumatoid arthritis. A degenerative non-inflammatory retro-odontoid pseudotumour responsible for clinically relevant spinal cord compression is a rare condition described in small clinical series and is likely associated with craniovertebral junction hypermobility or instability-like conditions. For several years, direct removal of the lesion through an anterior or lateral approach has been advocated as the best surgical option. However, in the last decade the posterior approach to the craniovertebral junction, to perform C1-C2 fixation and C1 laminectomy without removal of the retro-odontoid tissue, has demonstrated its efficacy in reducing retro-odontoid pannus as well as in obtaining improvement of myelopathy.In this paper we analyse the clinical and radiological outcomes of seven patients (five males and two females) treated with posterior C1-C2 fixation and C1 laminectomy for a degenerative non-inflammatory retro-odontoid pseudotumour responsible for spinal cord compression. C1 laminectomy provided immediate spinal cord decompression. We also review the relevant literature focusing on associated cervical degenerative conditions that may contribute to triggering or acceleration of atlantoaxial hypermobility or 'instability', causing formation of the retro-odontoid tissue.The mean follow-up period (of six followed-up patients) was 55.8 months (range 10-96 months). In all cases the Nurick score at the latest follow-up visit demonstrated clinical improvement; magnetic resonance imaging during follow-up demonstrated progressive reduction of the retro-odontoid pseudotumour in all but one patient, who died of surgery-unrelated disease in the early postoperative period. No vascular or neural damage secondary to C1-C2 fixation was observed.C1-C2 fixation associated with C1 laminectomy is an effective surgical option to treat myelopathy secondary to a degenerative retro-odontoid pseudotumour. In these cases, direct removal of intracanalar tissue compressing the spinal cord is not required, as C1-C2 fixation is sufficient to cause its disappearance.

Background Anterior cervical discectomy and fusion (ACDF) remains one of the most commonly taught procedures during residency and one of the most frequently performed by neurosurgeons. Neurosurgeons use microscopes to perform surgery and to train other surgeons. Although the microscope provides excellent illumination and magnification, its use will be limited to 2 people: the surgeon and the assistant. Consequently, the scrub nurse and residents watching 2-dimensional images on monitors will have a reduced perception of the surgical field depth and anatomical details. The exoscope has been introduced as an alternative to microscopes and endoscopes. We used a 3-dimensional (3D), high-definition exoscope (3D Vitom [Karl Storz, Tuttlingen, Germany]) in 2 patients undergoing 2-level ACDF for cervical myeloradiculopathy. Methods The exoscope was used during soft tissue dissection, discectomy, osteophytectomy, and cage insertion. Microsurgical drilling of the posterior osteophytes, which will usually require adequate magnification and proper microscope angulation, was also performed using the exoscope. Results The exoscope provided a 3D view of the surgical field similar to that provided by a microscope and allowed us to effectively and safely perform the required surgical steps. The main advantage of 3D exoscope-assisted surgery, compared with microscope-assisted surgery, is the possibility to generate videos with a similar view and image quality as perceived by the surgeon. Therefore, the didactic capabilities of exoscopic videos are greater than those provided by microscopic videos. Exoscopes are also smaller compared with microscopes, allowing for comfortable use from the early surgical steps to device implantation. Conclusion We believe that exoscope-assisted surgery could become a safe and effective alternative to microscope-assisted surgery in ACDF.

Background Awake surgery is an effective technique to improve safety in surgical resection of lesions involving eloquent areas of the brain. Intraoperative imaging guidance and neuronavigation are widely applied in neurosurgical procedures. However, data on the application of intraoperative imaging to awake craniotomies are limited. We report our experience with intraoperative computed tomography (i-CT) during awake surgery, focusing on technical feasibility and effectiveness. Methods and Results Four patients with a lesion located in an eloquent area of the brain—1 with a cavernous hemangioma, 1 with a high-grade glioma, and 2 with a low-grade glioma (LGG)—underwent awake surgery with neuronavigation guidance. In all patients, i-CT was used to evaluate the completeness of resection or the extent of residual tumor. Intraoperative ultrasound was also used during microsurgery to verify the presence of residual tumor. The use of i-CT us allowed to obtain updated images for neuronavigation and to correct for brain shift. Conclusions i-CT in awake surgery is reliable and effective. It does not significantly affect the duration of surgery and does not add stress for the patient. The possibility to correct for brain shift also in awake patients can increase the precision and accuracy of surgery, particularly in cases of LGG, avoiding the resection of normal white matter or tumor remnants in noneloquent areas.

Background Penetrating aortic trauma remains one of the most challenging injuries with a high mortality rate if left untreated, or if the surgical treatment is delayed. We present an uncommon case of a late diagnosed abdominal firearm injury, in which the bullet partially penetrated the wall of the aorta, creating a plug that prevented immediate death due to massive bleeding. Case presentation A 26-year-old Libyan man was a victim of a firearm wound, with a bullet penetrating his abdominal wall from the left to right side. After the assault, the victim, spent up to 20 days crossing the Mediterranean Sea to leave his country of origin. Abdominal radiography revealed the presence of a bullet located anteriorly to the second lumbar vertebra, while computed tomography angiography, unexpectedly, demonstrated that the bullet penetrated partially into the aortic wall at the level of the left renal artery. The bullet penetrated the aortic wall for half of its length, creating a plug that avoided immediate life-threatening bleeding at the time of the gunshot injury. The bullet was removed and the aortic lesion was repaired. The patient was discharged 6 days after the surgical procedure, in good health. Conclusions We presented a very rare case of late diagnosis of aortic injury caused by a gunshot lesion, in which the particular trajectory of the bullet helped avoid immediate life-threatening bleeding and, probably, saved the patient’s life. Electronic supplementary material The online version of this article (10.1186/s12893-018-0337-z) contains supplementary material, which is available to authorized users.

To report our early experience with minimally invasive surgery (MIS) in low-dysplastic lumbosacral lytic spondylolisthesis (LDLLS), and to analyze the impact of surgery on postoperative spino-pelvic and sacro-pelvic parameters. Eight patients (mean age 47.6 years) underwent MIS for LDLLS involving in all but one the L5–S1 level. VAS and ODI were used for clinical assessment. Imaging included pre-operative X-rays, CT and MRI scans. Post-operatively, all patients underwent X-rays and CT-scans. Pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS) values as well as lumbar lordosis (LL) have been derived from pre- and post-operative standard X-rays. Mean follow-up is 30.12 months (range 15–42). No complications related to the surgical procedure were observed. Patients reported a satisfactory clinical outcome, as demonstrated by variation in mean VAS (from 9.1 to 3.6) and ODI (from 70.50 to 28.25 %) scores. Comparison between pre- and post-operative sacro-pelvic parameters documented moderate changes, with reduction of PT and increase of SS in all but one patient. Overall sagittal balance of the spine has been evaluated using the sagittal vertical axis (SVA), obtained from post-operative X-rays. Mean value of SVA demonstrated a good sagittal balance of the spine. This series demonstrates that MIS is feasible and effective for LDLLS, as witnesses by the satisfactory clinical results maintained at medium-term follow-up. We submit that TLIF is a valid option but an adequately sized and positioned interbody cage is a key factor to allow satisfactory restoration of segmental lordosis.

Objective Chronic subdural hematoma (CSH) is a common neurosurgical disease among elderly population with concomitant degenerative neurological disorders. This is a retrospective series-control analysis of prospectively collected data, aiming to show advantages and indications of a minimally invasive, percutaneous drainage system for CSH. Patients and methods We retrospectively analyse the clinical and radiological data of a minimally invasive, percutaneous draining system (Integra ™) used in fifteen patients (Group A; mean age: 75.7) with CSH, and compare them with those obtained from two retrospective series of patients: the first one (Group B 15 patients, mean age 77.1) treated with standard, single-burr hole technique for subdural drainage under general anaesthesia; the second one (Group C 15 patients, mean age 76.4) treated with standard, single-burr hole technique for subdural drainage under local anaesthesia and mild sedation. All The percutaneous procedures (Group A) were performed under local anaesthesia. Results Mean follow-up was 10.9 (range 3–14), 18.2 (range 10–29) and 15.2 (range 8–28) months in Group A, B and C respectively. Three of 15 and in Group B experienced a worsening of pre-existing neurodegenerative disorders after general anaesthesia. One patient in group C suffering from Parkinson’s disease experienced a worsening of gait disturbances. Post-operative CT scans were performed at 48 h and 21 days after the operation. An early post-operative CT-scan, obtained immediately after surgical procedure, was performed in all Group A patients. No differences in CSH evacuation were observed comparing the three groups. Two recurrent hematomas, one in group A and one in group B, required revision. Post-operative hospitalization was similar (5.1 vs 5.7 vs 5.6 days, respectively, in group A, B and C) but analgesics use was lower in Group A. Conclusion Pre-operative evaluation of radiological features of CSDHs is crucial in determining the right indication for a minimally invasive drainage. Minimally invasive treatments of CSH may reduce the use of anaesthetic drugs and worsening of pre-existing neurodegenerative disorders.

Minimally invasive spine surgery (MISS), including percutaneous pedicle-screw fixation (PPSF), mini-open transforaminal lumbar interbody fusion (m-open TLIF), vertebroplasty, and stentoplasty, allows the preservation of neurological function and the restoration of spine stability, while reducing associated risks and complications. This study aimed to analyze the safety and efficacy of MISS in elderly patients suffering from degenerative or traumatic thoracolumbar diseases. Forty-five patients (28 females), with a mean age of 73 years (range 65-89), suffering from osteoporotic vertebral fractures (24), degenerative spondylolisthesis (15), and lumbar canal stenosis with instability and/or de novo scoliosis (6) were included.Twenty-one patients underwent PPSF and m-open TLIF. The remaining patients received PPSF without interbody fusion, and in six of these fenestrated screws were used for vertebral body cement augmentation.Functional evaluation was obtained with a visual analog scale (VAS) and the Oswestry Disability Index (ODI) pre- and postoperatively. Preoperative imaging included X-rays, computed tomography (CT), and magnetic resonance imaging (MRI). Patients were followed-up with X-rays, and a CT scan was also obtained at the last follow-up. Follow-up ranged from 6 to 59 months (mean 28 months). Follow-up CT scan documented intersomatic fusion in only 14 % of patients treated with m-open TLIF. Despite the high incidence of non-union, mean VAS and ODI scores showed a significant improvement, with a reduction of mean VAS from 9 to 4 and a reduction of mean ODI from 76.33 to 38.15 %. Only three patients developed postoperative complications. No patients showed neurological deficits.Minimally invasive spine surgery for degenerative and traumatic spinal diseases is a safe and effective treatment also in elderly patients.

Background Intradural epidermoid tumors of the spinal cord are commonly associated with spinal cord dysraphism or invasive procedures. We report the particular relationships between spinal subarachnoid compartments and thoracic intradural-extramedullary epidermoid tumor, highlighting the relevant anatomic changes that may influence microsurgery. Methods A 40-year-old woman from compressive myelopathy owing to a thoracic epidermoid tumor extending from T3 to T4 and not associated with spina bifida, trauma, previous surgery, or lumbar spinal puncture underwent microsurgical excision. Accurate tumor membrane dissection, respecting spinal arachnoidal compartments, was performed. Reposition of a laminoplasty plateau helped in restoring thoracic spine anatomic integrity. Results Safe gross total tumor resection was achieved. Complete neurologic recovery as well as absence of recurrent tumor was documented at 4-year follow-up. A literature review revealed only 2 other cases of “isolated” thoracic spine epidermoid tumor. However, description of the relationship between tumor membranes and spinal subarachnoid compartments was not available in either case. Conclusions A thorough knowledge of spinal subarachnoid space anatomy is helpful to distinguish between tumor membranes and arachnoidal planes and to achieve a safe and complete resection to avoid recurrences.

In multilevel degenerative conditions posterior approaches are often preferred, but anterior approaches provide comparable clinical results and better alignment. Anterior plating entails higher rates of soft tissue injuries and dysphagia, particularly in multilevel cases. This study evaluates efficacy and safety of zero-profile devices in 3- and 4-level anterior cervical diskectomy and fusion, analyzing patients' clinical and radiologic long-term outcomes.We prospectively enrolled 24 patients with cervical spondylotic myeloradiculopathy who underwent 3- and 4-level anterior cervical diskectomy and fusion with the zero-profile device. Mean follow-up was 39 months (range 24-72). Nurick grading was used for myelopathy, Neck Disability Index and Visual Analog Scale scores for arm and neck pain, and Short Form 36 survey for physical and mental health status. Postoperative radiograph and computed tomography were obtained after surgery, at 6 and 12 months, and at last follow-up to assess fusion rate and complications. Cervical alignment was measured by Cobb angle. Incidence of postoperative dysphagia was monitored according to Bazaz dysphagia index.On last computed tomography scan, fusion was present in 49% of spaces (40 of 82). Mean neck and arm pain visual analog scale decreased from 6.7-1.6 (P0.01) and 5.9-0.9 (P0.01), respectively. Improvements in the Short Form 36 survey and Neck Disability Index were documented (P0.01). Lordosis was restored in all patients. Five of 24 patients complained of mild dysphagia (20.8%): in three (12.5%) short-term dysphagia and in two (8.3%) medium-term dysphagia. No long-term dysphagia (≥6 months) was observed.Anterior cervical diskectomy and fusion with a zero-profile device is effective and safe for 3- and 4-level cervical spondylotic myeloradiculopathy. It allows to restore cervical lordosis and achieve long-term satisfactory clinical outcome.

Percutaneous techniques have increasingly gained popularity in recent years. The application of technological innovation, including neuromonitoring techniques, has the potential to increase the safety and efficacy of these procedures.Thirty patients suffering from osteoporotic dorsolumbar burst fracture were prospectively enrolled in this study. The patients underwent percutaneous fenestrated pedicle screw fixation augmented with polymethylmethacrylate (PMMA) injection. A novel surgeon-dedicated neuromonitoring device was used in order to increase the safety and the accuracy of the screw insertion. A second group of 30 patients who did not undergo neuromonitoring during percutaneous pedicle screw placement, matched for demographic characteristics, constituted the control group.A total of 296 screws were inserted. All treated patients had a good outcome, documented by an improvement in visual analogue scale (VAS) scores. Excellent trajectories were achieved in all patients. Cobb's angle and anterior vertebral height were satisfactorily restored in all study group patients. Three misplaced screws in three patients and a case of PMMA leakage without neurological deficits were observed in the control group, whereas no complication was recorded in the study group (p = 0.03).Neuromonitoring in cement-augmented percutaneous pedicle screw placement appears to improve surgeon confidence during surgery, reducing the risk of screw misplacement or cement leakage.

Background: Percutaneous techniques have increasingly gained popularity in recent years. The application of technological innovation, including neuromonitoring techniques, has the potential to increase the safety and efficacy of these procedures. Methods: Thirty patients suffering from osteoporotic dorsolumbar burst fracture were prospectively enrolled in this study. The patients underwent percutaneous fenestrated pedicle screw fixation augmented with polymethylmethacrylate (PMMA) injection. A novel surgeon-dedicated neuromonitoring device was used in order to increase the safety and the accuracy of the screw insertion. A second group of 30 patients who did not undergo neuromonitoring during percutaneous pedicle screw placement, matched for demographic characteristics, constituted the control group. Findings: A total of 296 screws were inserted. All treated patients had a good outcome, documented by an improvement in visual analogue scale (VAS) scores. Excellent trajectories were achieved in all patients. Cobb’s angle and anterior vertebral height were satisfactorily restored in all study group patients. Three misplaced screws in three patients and a case of PMMA leakage without neurological deficits were observed in the control group, whereas no complication was recorded in the study group (p = 0.03). Conclusions: Neuromonitoring in cement-augmented percutaneous pedicle screw placement appears to improve surgeon confidence during surgery, reducing the risk of screw misplacement or cement leakage.

Atypical meningiomas have a greater propensity to recur than benign meningiomas and the benefits of early adjuvant radiotherapy are unclear. Existing studies report conflicting results. This retrospective cohort study evaluated the role of early adjuvant radiotherapy following surgical resection of atypical meningioma. A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I-III) or subtotal resection (STR; Simpson Grade IV-V). Survival analysis was performed using the Kaplan-Meier method. One hundred thirty-three patients were identified with a median age of 62years (range 22-86years) and median follow-up of 57.4months (range 0.1-152.2months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5year PFS 81.2% versus 40.08%, log-rank=11.117, p=0.001) but not overall survival (OS) (5year OS 76.6% versus 39.7%, log-rank=3.652, p=0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5year OS 77.0% versus 75.7%, log-rank=0.075, p=0.784) or PFS (5year PFS 82.0% versus 79.3%, log-rank=0.059, p=0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned.

Introduction Colloid cysts are rare benign intracranial lesions classically described as "third ventricle colloid cysts" because of their location within the third ventricle. These lesions' clinical and diagnostic features are mainly related to intermittent or persistent obstruction of foramina of Monro causing cerebrospinal fluid (CSF) circulation impairment and symptoms of raised intracranial pressure. Few reports on colloid cysts located outside the third ventricle have been published over the years. This paper aims to review the existing literature on out-of-third ventricle colloid cysts, and introduces a new illustrative case of lateral ventricle colloid cyst surgically managed with endoscopic technique. Evidence acquisition A literature review was performed through a Medline web-search, using "colloid cysts," "lateral ventricle colloid cysts," "fourth ventricle colloid cysts," "brain colloid cyst," "spinal colloid cysts" as keywords. All retrieved abstracts were screened and full-length text of papers suitable for inclusion were examined. An illustrative case has been added to the existing literature. A 45-year-old man complaining of recurrent headache underwent conservative treatment for 4 years. The unusual headache features as well as the uncommon onset and association with episodic mental impairment led to an initial diagnosis of anxiety disorder triggering the headache. A further worsening of headache and the lack of significant clinical benefit prompted further investigation. Computed-tomography (CT) of the brain showed asymmetrical dilatation of the right lateral ventricle, due to the presence of a cystic mass obstructing the foramen of Monroe. Patient underwent endoscopic resection of the cyst. Evidence synthesis The literature review revealed 16 papers reported between 1952 and 2016. In all cases included histological diagnosis of colloid cyst had been obtained. Clinical and radiological features, as well as surgical management in each case have been analyzed. In the case here reported, histological examination documented a colloid cyst. The postoperative course was uneventful, with progressive resolution of headache. Conclusions Despite third ventricle colloid cysts are related to typical clinical and diagnostic features, non-third ventricle colloid cysts may be responsible for unusual clinical presentation, so making a correct diagnostic approach challenging. We submit that in cases of recurrent headache with unusual features and lacking signs of neurological deficits, a rare neurosurgical condition as an "ectopic" colloid cyst should be included in the differential diagnosis.

Objective To illustrate the usefulness of intraoperative indocyanine green videoangiography (ICG-VA) to identify the nidus and feeders of a small cerebellar AVM resembling a cavernous hemangioma. To review the unique features regarding the overlay between these two vascular malformations and to highlight the importance to identify with ICG-VA, and treat accordingly, the arterial and venous vessels of the AVM. Methods A 36-year old man presented with bilateral cerebellar hemorrhage. MRI was equivocal in showing an underlying vascular malformation but angiography demonstrated a small, Spetzler–Martin grade I AVM. Surgical resection of the AVM with the aid of intraoperative ICG-VA was performed. After hematoma evacuation, pre-resection ICG-VA did not reveal tortuous arterial and venous vessels in keeping with a typical AVM but rather an unusual blackberry-like image resembling a cavernous hemangioma, with tiny surrounding vessels. Such intraoperative appearance, which could also be the consequence of a “leakage” of fluorescent dye from the nidal pathological vessels, with absent blood-brain barrier, into the surrounding parenchymal pathological capillary network, is important to be recognized as an unusual AVM appearance. Results Post-resection ICG-VA confirmed the AVM removal, as also shown by postoperative and 3-month follow-up DSAs. Conclusions Despite technical limitations associated with ICG-VA in post-hemorrhage AVMs, this case together with the intraoperative video, demonstrates the useful role of ICG-VA in identifying small AVMs with peculiar features.

We describe a technical variation used to enhance intraoperative safety and efficiency in multilevel percutaneous pedicle screw fixation (PPSFs) and mini-open transforaminal lumbar interbody fusion (m-TLIFs). A review of the literature on percutaneous screw insertion techniques and related pitfalls is presented. PPSFs and m-TLIFs are increasingly used techniques in multilevel lumbar degenerative disease. Facetectomy and TLIF are usually performed before inserting ipsilateral pedicle screws. Such techniques can cause unintended violation of the pedicle and injure the dura or neural structures, particularly in multilevel cases. A literature review revealed a lack of intraoperative and fluoroscopic images detailing the technique for multilevel PPSF and m-TLIF(s) performed through tubular, expandable retractors. Thirteen patients with two- to four-level disease underwent multilevel PPSF and m-TLIF (one to four levels). The Kirschner Cage Screw (KCS) technique, consisting of early insertion of K-wires in all pedicles followed by facetectomy and m-TLIF(s) and, finally, screw insertion, was used in order to minimize the risk of dural/neural injuries. Neither CSF (cerebrospinal fluid) leaks nor nerve root injuries nor technique-related complications were encountered with a follow-up ranging from 7 to 38 months (mean 23.6). In conclusion, the KCS technique allows safe identification of the pedicles without opening the canal during m-TLIF(s). Moreover, by visualizing the K-wires inside the retractor, the surgeon can check the pedicle position during facetectomy, and screws can be introduced with a minimal risk of neural or dural injuries. We believe that the proposed technique increases the safety and ease of the procedure, particularly in multilevel cases.

Object The objective of this study was to report the authors' experience with the long-term administration of temozolomide (TMZ; > 6 cycles, up to 101) in patients with newly diagnosed glioblastoma and to analyze its feasibility and safety as well as its impact on survival. The authors also compared data obtained from the group of patients undergoing long-term TMZ treatment with data from patients treated with a standard TMZ protocol. Methods A retrospective analysis was conducted of 37 patients who underwent operations for glioblastoma between 2004 and 2012. Volumetric analysis of postoperative Gd-enhanced MR images, obtained within 48 hours, confirmed tumor gross-total resection (GTR) in all but 2 patients. All patients received the first cycle of TMZ at a dosage of 150 mg/m2 starting on the second or third postsurgical day. Afterward, patients received concomitant radiochemotherapy according to the Stupp protocol. With regard to adjuvant TMZ therapy, the 19 patients in Group A, aged 30–72 years (mean 56.1 years), received 150 mg/m2 for 5 days every 28 days for more than 6 cycles (range 7–101 cycles). The 18 patients in Group B, aged 46–82 years (mean 64.8 years), received the same dose, but for no more than 6 cycles. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was analyzed for both groups and correlated with overall survival (OS) and progression-free survival (PFS). The impact of age, sex, Karnofsky Performance Scale score, and Ki 67 staining were also considered. Results All patients but 1 in Group A survived at least 18 months (range 18–101 months), and patients in Group B survived no more than 17 months (range 2–17 months). The long-term survivors (Group A), defined as patients who survived at least 12 months after diagnosis, were 51.3% of the total (19/37). Kaplan-Meier curve analysis showed that patients treated with more than 6 TMZ cycles had OS and PFS that was significantly longer than patients receiving standard treatment (median OS 28 months vs 8 months, respectively; p = 0.0001; median PFS 20 months vs 4 months, respectively; p = 0.0002). By univariate and multivariate Cox proportional hazard regression analysis, MGMT methylation status and number of TMZ cycles appeared to be survival prognostic factors in patients with glioblastoma. After controlling for MGMT status, highly significant differences related to OS and PFS between patients with standard and long-term TMZ treatment were still detected. Furthermore, in Group A and B, the statistical correlation of MGMT status to the number of TMZ cycles showed a significant difference only in Group A patients, suggesting that MGMT promoter methylation was predictive of response for long-term TMZ treatment. Prolonged therapy did not confer hematological toxicity or opportunistic infections in either patient group. Conclusions This study describes the longest experience so far reported with TMZ in patients with newly diagnosed glioblastomas, with as many as 101 cycles, who were treated using GTR. Statistically significant data confirm that median survival correlates with MGMT promoter methylation status as well as with the number of TMZ cycles administered. Long-term TMZ therapy appears feasible and safe.

5-aminolevulinic acid (5-ALA) has been used for the last 5 years to increase the extent of resection in adult brain tumors, mostly glioblastomas, but it is not approved yet as standard adjuvant treatment in the pediatric population. We report three different cases of pediatric brain tumors (two glioblastomas and one medulloblastoma) recently operated using 5-ALA fluorescence guidance, highlighting how useful it is in pediatric high-grade glioma (but not in medulloblastoma) also and confirming the lack of 5-ALA-related side effects. The first glioma was a recurrent GBM, whilst the second was a primary tumor. In all children, 5-ALA was administrated after discussing its use, including pros and cons, with the parents. 5-ALA fluorescence was a very useful tool to better identify tumor tissue and achieve gross-total tumor resection in GBMs, as confirmed by postoperative magnetic resonance imaging (MRI). In the medulloblastoma case no useful 5-ALA fluorescence was identified. No hematological or dermatological complications nor other side effects related to use of 5-ALA were observed. We submit that 5-ALA fluorescence guided surgery can be safe and useful in pediatric high-grade glioma, although its use in children still remains an off-label indication and requires validation through larger studies.

To analyze the prospectively collected data in a series of patients treated with single- or multilevel ACDF with a stand-alone, zero-profile device, focusing on clinico-radiological outcome, complications and technical hints, and to review the literature on such new devices.Eighty-five patients harboring symptomatic DDD underwent ACDF with the Zero-P cage-plate: 29 at 1-level and 56 at 2-4 levels (total 162 devices). In the multilevel group, 9 patients received a combination of Zero-P and stand-alone cages (hybrid implants). This study focuses on 32 patients with follow-up ranging from 20 to 48 months. NDI, SF-36 and arm pain VAS scores were registered preoperatively and at follow-up visits. Dysphagia was assessed using the Bazaz score. Imaging included X-rays, CT and MRI, also to assess the presence of vertebral body fractures in multilevel cases. Paired Student t test was used for statistical analysis.SF-36 and NDI showed a statistically significant improvement (p0.01) and mean arm pain VAS score decreased from 79 to 41. X-rays and CT demonstrated, respectively, a 94.5 % and a 92 % fusion rate. Three patients complained of moderate and two of mild transient dysphagia (15.5 %). No device-related complications occurred and no fractures, secondary to four screws insertion in one vertebral body (i.e., swiss cheese effect), were detected in multilevel cases. In patients with extensive anterior osteophytes only a "focal spondylectomy" was required.The Zero-P device is safe and efficient, even in multilevel cases. Dysphagia is minimal, extensive anterior osteophytectomy is unnecessary and technical hints may ease the surgical workflow. This is the largest series, with the longest follow-up, reported.

Retro-odontoid pseudotumor, not related to inflammatory or traumatic conditions, is an uncommon pathology. Atlanto-axial instability has been advocated to explain the pathophysiology of retro-odontoid pseudotumor's formation and growth. Despite pseudotumor direct removal through transoral or lateral approach represented the main surgical strategy for a long time, in the last decade several authors highlighted the possibility to treat retro-odontoid pseudotumor by occipito-cervical or C1-C2 fixation without removal of the intracanalar tissue. The goal of this study is to analyze the data collected in a series of patients suffering from cervical myelopathy due to non-inflammatory, degenerative retro-odontoid pannus and treated by posterior C1-C2 fixation. The relevant literature is also reviewed.Five patients, not suffering from inflammatory diseases, were treated between 2009 and 2012. Abnormalities of cranio-cervical junction and/or lower cervical spondylotic degeneration were observed in all patients. No evidence of atlanto-axial instability was demonstrated. Clinical and radiological evaluation included pre- and post-operative Nurick score as well as pre- and post-operative X-rays, CT and MRI. In one case, CT scan highlighted an eggshell calcification of the pannus. All patients underwent either a C1-C2 fixation (C1 lateral mass and C2 isthmus-pedicle screws) or occipito-cervical fixation (2 patients) in cases of C0-C1 fusion.Follow-up ranges from 22 to 45 months (mean 32) in four patients. One patient died of surgery-unrelated disease. Nurick score changes suggest a clinical improvement in four cases. Neuro-radiological evaluation shows a progressive but incomplete reduction of thickness of retro-odontoid pseudotumor in one patient, and its disappearance in the other three cases. A second-stage transoral or posterior lateral approach was not required.Although the etiopathogenesis of non-inflammatory, i.e., degenerative, retro-odontoid pseudotumor is still controversial, our series (the second largest on degenerative retro-odontoid pannus in the literature) confirms that a posterior approach may be sufficient and transoral surgery is not required.

OBJECTIVE: Intracerebral hemorrhage (ICH) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its long-lasting analog, darbepoetin alfa, have been demonstrated to be neuroprotective in several models of neuronal insult. The objectives of this study were to analyze whether the systemic administration of recombinant human EPO (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery and brain damage in a rat model of ICH. METHODS: Experimental ICH was induced in rats by injecting autologous blood into the right striatum under stereotactic guidance. Subsequently, animals underwent placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. Animals were killed 14 days after injury. RESULTS: Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment after injury, as assessed by the neurological tasks performed. rHuEPO- and darbepoetin alfa-treated animals exhibited a restricted brain injury with nearly normal parenchymal architecture. In contrast, the saline-treated group exhibited extensive cerebral cytoarchitectural disruption and edema. The number of surviving NeuN-positive neurons was significantly higher in the rats treated with rHuEPO and darbepoetin alfa compared with those that received saline (P < 0.05). CONCLUSION: These results demonstrate that weekly administered darbepoetin alfa confers behavioral and histological neuroprotection after ICH in rats similar to that of daily EPO administration. Administration of EPO and its long-lasting recombinant forms affords significant neuroprotection in an ICH model and may hold promise for future clinical applications.

This video demonstrates the minimally invasive surgical technique used in a 56-year-old woman suffering from L-5 spondylolysis and grade 2 L5–S1 spondylolisthesis. The first author used expandable tubular retractors bilaterally to perform neural decompression, mini-open TLIF, spondylolysthesis reduction and L5–S1 pedicle screw fixation. L-5 cement augmentation was performed through cannulated and fenestrated screws to enhance resistance to screw pull-out secondary to reduction maneuvers.Sequential surgical steps related to microsurgery, spondylolysthesis reduction and instrumentation are shown and commented.We submit that in cases of lythic spondylolisthesis a bilateral traversing and exiting nerve roots decompression is a safer option prior to performing the deformity reduction and fixation; the proposed minimally invasive technique may help in reducing surgical morbidity and improving postoperative recovery.The video can be found here: http://youtu.be/G4Qdg-A-Y3M.

Summary Background Patients with trigeminal neuralgia (TN) and persistent or recurrent facial pain after microvascular decompression (MVD) typically undergo less invasive procedures in the hope of providing pain relief. However, re-operation should be considered in selected patients. Case Report A 48-year-old woman presented with recurrent trigeminal neuralgia (TN) 3 years following microvascular decompression (MVD). The patient underwent brain magnetic resonance angiography (MRA), which did not reveal neurovascular compression; therefore surgical re-exploration was carried out. During the operation, the fifth cranial nerve was seen without impingement from any blood vessels; however, a very firm tissue was observed and identified as the muscle fragment from the previous MVD procedure. The fifth cranial nerve was carefully separated from the muscle. Thereafter, the right SCA was dissected out from the muscle and suspended by a periosteum tape sutured to the nearby dura. Conclusions Our findings, along with similar cases reported in the literature, support the development of new inert materials and alternative surgical strategies that can limit TN recurrence.