MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Intracranial dural based marginal zone MALT-type B-cell lymphoma: a case - Based update and literature review.

OBJECTIVES: Dural based Marginal Zone MALT-type B-Cell Lymphoma (MZBCL) is an intracranial tumor that can mimicking meningioma both from a clinical and a radiological point of view. A standard treatment protocol is still lacking. Aim of the present work is to provide an update of the present literature regarding this rare neoplasia. PATIENTS AND METHODS: We report the case of a patient with a dural-based lesion mimicking a meningioma of the tentorium. After surgical treatment, the diagnosis was of MZBCL. A literature review is performed to highlight the typical characteristics of this rare intracranial lesion and to define the best therapeutic approach. RESULTS: Literature review included 38 articles describing 126 cases of intracranial dural-based MZBCL. No clinical trial has been found. Clinical and histopathological features are properly collected to provide a guide for future cases. Different treatment options have been attempted. Combination of surgery with adjuvant radiation therapy is the most used option. CONCLUSIONS: MZBCL should be considered in differential diagnosis for dural-based intracranial lesion. Surgery followed by radiation therapy is the most reported treatment. As a consequence of the rarity of this disease, of its indolent progression and of the lack of adequate follow-up, it is not possible to define it is the best treatment option.

Delayed intracranial hemorrhage after mild traumatic brain injury in patients on oral anticoagulants: is the juice worth the squeeze?

OBJECTIVE: Mild Traumatic Brain Injury (MTBI) in anticoagulated patients is a common challenge for Emergency Department (ED) Physicians. Anticoagulation is considered a risk factor for developing delayed intracranial hemorrhage (ICH) after MTBI. The occurrence of this event in patients on Vitamin K Antagonists (VKA) or Direct Oral Anticoagulants (DOACs) remains unclear. Primary endpoint: to analyze the role of anticoagulants as risk factors for developing delayed ICH after MTBI and evaluate the indications to repeat a cranial computed tomography (CT) after a period of observation. Secondary endpoint: to assess the difference in the prevalence rate of delayed ICH in patients on VKA versus those on DOACs. PATIENTS AND METHODS: We evaluated all consecutive patients admitted to our ED for MTBI, which had a control CT for late ICH after a negative CT at admission. We used a propensity score match (PSM) on factors affecting the need for oral anticoagulation to adjust the comparison between anticoagulated vs. non-anticoagulated patients for the baseline clinical characteristics. RESULTS: Among 685 patients enrolled, 15 (2.2%) developed ICH at control CT. After PSM, the incidence of ICH, although slightly higher, was not statistically different in anticoagulated patients vs. non-anticoagulated (2.3% vs. 0.6%, p=0.371). Among the 111 patients on VKA, 5 (4.5%) had a late ICH, compared to 4 out of 99 (4.0%) on DOACs; the difference was not statistically significant (p=0.868). CONCLUSIONS: The risk of developing delayed ICH after MTBI in patients on anticoagulation therapy is low. After correction for baseline covariates, the risk does not appear higher compared to non-anticoagulated patients. Thus, a routine control CT scan seems advisable only for patients presenting a clinical deterioration. Larger, prospective trials are required to clarify the safety profile of DOACs vs. VKA in MTBI.

Parietal interhemispheric transfalcine transtentorial approach for posterior incisural space lesions: from the lab to the operative room.

The operative approach to the posterior incisural space is challenging because of its deep location, the surrounding eloquent areas, and the intimate relationship with the deep veins. Several approaches have been proposed to manage the lesions in this region: supratentorial, infratentorial and a combination of them. Brain retraction, injury to the occipital lobe and corpus callosum, and venous bleeding are the principle drawbacks of these routes. We performed anatomical dissection study using 10 embalmed human cadaver specimens injected with colored latex exploring a different route, parietal interhemispheric transfalcine transtentorial (PITT). Then we used a PITT approach on two patients with posterior incisural space (PIS) lesions. The PITT approach led to successful and safe complete removal of PIS lesions in our cases. No complications were reported. The present approach could be a valuable option in case of PIS lesions, especially those associated with downward displacement of the deep venous complex; thanks to the gravity it reduce the complications related to the occipital lobe retraction and manipulation. Moreover, cutting the superior-anterior edge of the tentorium, the sub-tentorial space could be reached.

Trans-sulcal versus trans-parenchymal approach in supratentorial cavernomas. A multicentric experience.

OBJECTIVES: Cavernous malformations (CM) are low-flow vascular lesions that can cause significant symptoms and neurological deficits. Different intraoperative surgical approaches have been developed. Aim of the present investigation is the comparison between the trans-sulcal approach (TS) and the trans-parenchymal neuronavigation-assisted approach (TPN) in a surgical series from two neurosurgical centers. The technique and clinical outcomes are discussed, with a specific focus on seizure outcome. PATIENTS AND METHODS: Clinical and radiological data from two neurosurgical centers ("A. Gemelli" Hospital in Rome and A.O.U. Città della Salute e della Scienza in Turin) were retrospectively reviewed in order to evaluate the different outcome of TS and TPN approach for cavernous malformation treatment. RESULTS: A total of 177 patients underwent surgical intervention for supratentorial CM, 130 patients with TPN approach and 47 with TS approach. TS approach was associated with higher rate of seizure in early post-operative period both in epileptic patients (p < 0,001) and in patients without history of seizures before surgery (p = 0,002). Moreover, length of incision (p < 0,001), area of craniotomy (p < 0,001) and corticectomy (p < 0,001) were bigger in TS than in TPN approach. Brain contusion (p < 0,001) and fluid collection (p < 0,001) were more likely to be discovered after TS approach. CONCLUSIONS: TPN is a valuable approach for resection of CM. Minor complications are significantly lower in TPN approach when compared with TS approach. In addition, it is associated with lower rate of early post-operative seizure and shorter length of stay.

Contrast enhanced ultrasound (CEUS) applications in neurosurgical and neurological settings - New scenarios for brain and spinal cord ultrasonography. A systematic review.

Contrast-enhanced ultrasound (CEUS) is a real-time, feasible technique. Both intraoperatively and bedside, it satisfies the need for serial assessment and easy performability. Initially employed in neuro-oncology, it has recently overcome this first application. We aimed to evaluate the literature and give a comprehensive view of its use in the fields listed below. A systematic review of all pertinent literature was performed via PubMed access according PRISMA P guidelines. Studies not involving human adults and not reporting original data were excluded. Cross-check of references of selected articles was performed to complete bibliographical research. 67 articles were then grouped by field of application: Oncology (26 articles) further subdivided in a) cranial tumors (23 articles) and b) spinal tumors (3 articles); Vascular (31 articles), divided in three sections: a) aneurysms, AVMs and AVFs surgery (6 articles), b) cerebral perfusion assessment and acute stroke patients management (15 articles), c) carotid plaques treatment (10 articles); TBI (2 articles); Pediatrics (4 articles); Peripheral nerve surgery (2 articles) and others (2 articles). CEUS versatility across the aforementioned areas was analyzed, underlining its complementarity to other well-settled imaging techniques. This review is focused on reporting CEUS advantages and disadvantages, suggesting a further broadening of the already numerous applications.

Diagnosis and management of dural arteriovenous fistulas: a 10 years single-center experience.

OBJECTIVES: Dural arteriovenous fistulas (DAVFs) are a challenging condition in vascular neurosurgery. Disease natural history and its management is still debated. In the present paper we report our center series on DAVFs over a period of 10 years. Our data were compared with relevant literature. PATIENT AND METHODS: Our series includes 45 cases: 14 cavernous sinus, 11 transverse-sigmoid, 8 patients tentorial, 6 anterior cranial fossa, 5 patients spinal, 1 patient foramen magnum. RESULTS AND CONCLUSIONS: DVAFs distribution, clinical presentation and hemorrhagic risk are discussed. Cavernous sinus DAVFs are the most common site in our series. Other locations in order of frequency are transverse-sigmoid sinus, tentorial, anterior cranial fossa, spinal and foramen magnum. The majority of patients presented with non-aggressive symptoms. 18% presented with intracranial hemorrhage: all the hemorrhages occurred in high-grade DAVFs. For most patients, endovascular treatment, transarterial or transvenous, was the first option. Surgery was performed for the anterior cranial fossa DAVFs and other complex lesions draining mostly transverse-sigmoid sinus and tentorium. In 7% of cases a combination of endovascular+surgical treatment was used. Our series has been carefully analyzed in comparison 'side by side' with most relevant literature on DVAFs, focusing particularly on management strategies, therapeutic options and risks related to treatment.

Protective effect of external ventricular drainage on cerebral vasospasm. A retrospective study on aneurysmal SAH treated endovascularly.

OBJECTIVE: Cerebral vasospasm (VS) is one of the factors that can most significantly worsen the prognosis after aneurysmal subarachnoid hemorrhage (SAH). A substantial body of evidence supports the idea that CSF diversion could prevent VS, even if this issue is still much debated. External ventricular drainage (EVD) is the recommended procedure for post-hemorrhagic hydrocephalus. In this study we analyzed whether EVD, placed for acute hydrocephalus, is effective in reducing the incidence of clinical and radiological cerebral vasospasm in patients who underwent endovascular treatment for aneurysmal SAH. PATIENTS AND METHODS: We retrospectively studied the incidence of radiologically confirmed VS in 141 patients treated endovascularly for aneurysmal SAH: 80 underwent EVD for hydrocephalus, 61 did not undergo EVD. RESULTS: VS occurred in 8.75% of cases (7 patients) in the first groups, while in 22.95% (14 patients) in the second group. In addition, patients not treated with EVD display a prevalence of VS in lower Fisher grades compared to the other group. CONCLUSION: Our data indicate that CSF drainage reduces the risk of vasospasms in patients with endovascular treatment for aneurysmal SAH.

Indocyanine green video-angiography in neurosurgery: a glance beyond vascular applications.

OBJECTIVE: Indocyanine green video angiography (ICG-VA) is a non invasive, easy to use and a very useful tool for various neurosurgical procedures. Initially introduced in vascular neurosurgery since 2003, it's applications have broadened over time, both in vascular applications and in other neurosurgical fields. The objective of our study is to review all published literature about ICG-VA, cataloguing its different applications. METHODS: A systematic review of all pertinent literature articles published from January 2003 to May 2014 using Pubmed access was performed using pertinent keywords; cross check of references of selected articles was performed in order to complete bibliographical research. Results of research were grouped by pathology. RESULTS AND CONCLUSIONS: The paper systematically analyses ICG-VA different applications in neurosurgery, from vascular neurosurgery to tumor resection and endoscopic applications, focusing on reported advantages and disadvantages, and discussing future perspectives.

Laminoplasty is better of laminectomy in cervical stenotic myelopathy: myth or truth?

INTRODUCTION: Laminoplasty has been proposed as a treatment for cervical stenotic myelopathy (CSM) as an alternative to standard laminectomy as this has been considered directly associated with an increased risk of postoperative deformity. METHODS: We retrospective reviewed postoperative results of open door laminoplasty (unilateral approach technique) compared with laminectomy in terms of clinical/electophysiological results (somatosensory evoked potentials - SSEP, and motor evoked potentials - MEP); in addition the rate of subsequent spinal deformities was analyzed in both techniques. RESULTS: Postoperative results in terms of late follow up neurological assessment and neurophysiological improvement was substantially comparable in both groups. Postoperative dynamic cervical X-rays showed a kyphotic deformity in (12.5%) in patients undergoing laminectomy; none was unstable. No case of kypothic deformity occurred in patients undergoing open door laminoplasty. Complication rate was similar in both groups. DISCUSSION AND CONCLUSIONS: Standard laminectomy seems to be associated to late cervical spine deformities in a more relevant percentage of patients, possibly leading to severe forms of kyphosis and segmental instability over time compared with open-door expansive laminoplasty. The unilateral approach represents an evolution to standard open door technique that further spares posterior elements, may decrease the incidence of progressive spinal deformity and prevent the need for subsequent spinal stabilization.

Transient breathing disorders after posterior cervical surgery for degenerative diseases: pathophysiological interpretation.

Central sleep apnea is a breathing disorder that manifests as repetitive cessation of the breath during the sleep. The occurrence of breathing disorders after cervical laminectomy has been exceptionally described as a complication after cervical decompressive laminectomy for cervical stenotic myelopathy. In 1994, Naim-ur-Rahman reported the first case of postoperative central sleep apnea following C3-C6 laminectomy, occurring right after surgery and associated with spyncterial incontinence, that spontaneously recovered three weeks after onset. Recently we described a rare complication of cervical laminectomy for cervical stenotic myelopathy: the onset was delayed from surgery (nearly two weeks later) and cervical stenotic myelopathy was not associated to any other neurological sign of spinal cord damage as demonstrated by the neurophysiological assessment. Possible familiar predisposition can be matter of discussion. No definite interpretation of pathophysiological mechanisms can ultimately explain the occurrence of delayed and isolated central sleep apnea after laminectomy for the treatment of cervical stenotic myelopathy. Such a reversible and benign complication remain unpredictable in the best surgical hands.

Transcriptional profile characterization for the identification of peripheral blood biomarkers in patients with cerebral aneurysms.

We tried to identify molecular markers in peripheral blood to predict high risk of aneurysm rupture. Extraction of the total population of peripheral blood mononuclear cell (PBMC) from total blood volume, total RNA extraction from PBMC and Agilent One Color Gene-expression Oligo-Microarray were performed on peripheral venous blood samples from 45 patients with ruptured, unruptured cerebral aneurysms and control group (15). Mean foreground/ background signal intensities and A (log2(R*G)/2) values were calculated for each spot. Genes with absolute fold change (FC) greater than or equal to plus or minus 1.5 and p-value less than 0.05 were considered differentially expressed in the 3 groups (Student T-test). Genes coding for MMPs were strongly underexpressed in ruptured aneurysms group, suggesting a possible role in aneurysms development more than their rupture. Genes coding for adhesine proteins of the extracellular matrix (ICAM1) and cytoskeleton (WIPF1,TUBA4A) were underexpressed in ruptured aneurysms. Genes coding proteins involved in the regulation of apoptotic processes may be important in aneurysm development and rupture, resulting into an increased rate of remodeling processes in the arterial wall. Fas coding gene, SUMO1, ZFAT, BCL2, CCR5 genes were all over-represented in unruptured aneurysms. The coexisting over-representation of pro-apoptotic genes and the underexpression of cytoskeleton and extracellular matrix genes confirms that aneurysms development and evolution are part of a degenerative process of the arterial wall not involved in aneurysms rupture. MMPs may be involved in repairing chronic damages to the arterial walls and preventing SAH. Unexpectedly, Heat Shock Proteins (HSP90AA1, HSPA1A, HSPB1), G and RAS proteins, generally activated by stress situations were under-represented in aneurysmal walls. Further PCR and Western Blotting studies are needed to confirm such findings and to identify diagnostic and prognostic markers in order to define screening protocols for intracranial aneurysms.

Glioblastoma multiforme intraxial metastasis to the conus medullaris with primary disease under control: a rare unexpected finding.

We report on glioblastoma multiple spinal intraaxial metastases with primary disease radiologically under control. The case highlights glioblastoma biological behavior and spread mechanisms; dissemination may have occurred initially and been controlled by chemotherapy, or more likely, is an indicator that even if radiologically dormant, disease is unlikely biologically inactive.

Modic changes: anatomy, pathophysiology and clinical correlation.

Studying discovertebral complex anatomy is extremely important for the understanding of the pathophysiology of disc degeneration which leads to vertebral endplates signal changes, also known as Modic changes.The sequelae of disc degeneration are among the leading causes of functional incapacity in both sexes and are one of the most common sources of chronic disability in the working years. Even if the presence of degenerative changes in MRI of the spine is by no means an indicator of symptoms, we are concordant in a positive association between Modic changes and low back pain, above all as a relatively specific but insensitive sign of discogenic low back pain.