Double cystic brain metastasis in a patient with stable pancreatic intraductal papillary mucinous neoplasm.

BACKGROUND: Brain metastases in pancreatic cancer are a rare condition and are usually seen in case of pancreatic adenocarcinoma. Only few cases of brain metastasis in patients affected by Intraductal papillary mucinous neoplasm (IPMN) are actually reported. CASE DESCRIPTION: We report a patient diagnosed with double cystic brain lesions that the histological examination reveal to be consistent, with pancreatic metastasis. Our patient had an history shown of stable pancreatic IPMN which has never made the oncologist suspicious about neoplastic progression or degeneration into pancreatic carcinoma. Considering the rarity of these metastasis we did a literature review on the topic. CONCLUSIONS: Despite rare, pancreatic origin of a cystic brain metastasis should considered in differential diagnosis in both patient with IPMN or patient with unknown primitive tumor.

The Targeted Therapies Era Beyond the Surgical Point of View: What Spine Surgeons Should Know Before Approaching Spinal Metastases.

In the last few years, the treatment of spinal metastases has significantly changed. This is due to the advancements in surgical technique, radiotherapy, and chemotherapy which have enriched the multidisciplinary management. Above all, the field of molecular biology of tumors is in continuous and prosperous evolution. In this review, the molecular markers and new approaches that have radically modified the chemotherapeutic strategy of the most common metastatic neoplasms will be examined together with clinical and surgical implications. The experience and skills of several different medical professionals are mandatory: an interdisciplinary oncology team represents the winning strategy in the treatment of patients with spinal metastases.

Intraoperative neurophysiological monitoring during spinal surgery: technical review in open and minimally invasive approaches.

Neurophysiological monitoring is of undoubted value for the intraoperative safety of neurosurgical procedures. Widely developed and used for cranial surgery, it is equally as effective, though perhaps less commonly employed, for spinal pathology. The most frequently used techniques for intraoperative monitoring during spinal surgery include somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs) and electromyography, which can either be spontaneous free-running (sEMG) or triggered (tEMG). The knowledge of the benefits and limitations of each modality is essential in optimising the value of intraoperative monitoring during spinal procedures. This review will analyse the single techniques, their anatomical and physiological basis, their use in spinal surgery as reliable indicators of functional injury, their limits and their application to specific procedures in minimally invasive surgery, such as the lateral transpsoas access for interbody fusion and the divergent trajectory for cortico-pedicular screws. In these particular techniques, because of reduced visual exposure, neuromonitoring is indeed essential to exploit the full potential of minimally invasive surgery, while avoiding damage to nervous structures.

The Endoscopic Endonasal Approach to Craniovertebral Junction Pathologies: Surgical Skills and Anatomical Study.

INTRODUCTION: Surgical anterior decompression is the treatment of choice for symptomatic irreducible ventral craniovertebral junction (CVJ) compression. Along with the classic transoral approach, the endoscopic endonasal approach has evolved and is gaining growing success. MATERIALS AND METHODS: In this work we discuss the surgical technique, give a complete step-by-step description of dissection of the craniovertebral junction and report a specific case of endoscopic endonasal odontoidectomy with use of a high-definition (HD) three-dimensional (3D) endoscope. DISCUSSION: The extended endonasal approach exploits an anatomical corridor to the odontoid process, involving only a small incision in the nasopharynx and sparing palate integrity. The most important limitation of the technique is 2D visualization, which hinders correct recognition of anatomical structures. CONCLUSION: The endoscopic endonasal route to the odontoid process has proven to be a feasible, safe and well-tolerated procedure. Anatomical study is very important for better understanding of the 3D anatomy of the CVJ and relation of critical neurovascular structures to specific bony and muscular landmarks.

Supratotal Resection of Glioblastoma: Is Less More?

BACKGROUND: A relationship between the extent of resection (EOR) and survival has been demonstrated in patients with glioblastomas (GBMs). However, despite gross total resection (GTR) of the enhancing nodule (EN), GBMs usually relapse, generally near the surgical cavity. OBJECTIVE: The aim of this study was to determine the prognostic role of FLAIR resection of GBMs by analyzing pre- and post-operative MRIs to estimate the EOR of EN, FLAIR-hyperintense regions and total tumor volume (TTV). METHODS: Radiologic and clinical outcomes were analyzed retrospectively. Pre- and post-operative EN volume, pre- and postoperative FLAIR volume (POFV), and pre- and postoperative TTV were analyzed. EOR was then calculated for each component. Time-dependent ROC curves and cut-off values for pre- and post-operative volumes and EOR were calculated. A Kaplan-Meier analysis with the log-rank test and Cox regression analysis were then used to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: We did not find any correlation between EOR of FLAIR-altered regions and patient survival. On the other hand, there were statistically significant relationships between the prognosis and both a preoperative EN volume less than 31.35 cm3 (p=0.032) and a postoperative EN volume less than 0.57 cm3 (p=0.015). Moreover, an EOR of EN greater than 96% was significantly associated with the prognosis (p=0.0051 for OS and p=0.022 for PFS). CONCLUSION: Our retrospective, multi-center study suggests that survival in patients with GBM is not affected by the extent of resection of FLAIR-hyperintense areas.

Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy

Spinal cord injury (SCI) constitutes an inestimable public health issue. The most crucial phase in the pathophysiological process of SCI concerns the well-known secondary injury, which is the uncontrolled and destructive cascade occurring later with aberrant molecular signaling, inflammation, vascular changes, and secondary cellular dysfunctions. The use of mesenchymal stem cells (MSCs) represents one of the most important and promising tested strategies. Their appeal, among the other sources and types of stem cells, increased because of their ease of isolation/preservation and their properties. Nevertheless, encouraging promise from preclinical studies was followed by weak and conflicting results in clinical trials. In this review, the therapeutic role of MSCs is discussed, together with their properties, application, limitations, and future perspectives.

Tumor location and patient age predict biological signatures of high-grade gliomas.

Prognostic factors for high-grade gliomas include patient age, IDH1 mutation, MGMT methylation, and Ki67 value. We assessed the predictive role of topographic location of gliomas for their biological signatures. Collecting all neuroradiological and histological data of patients with histologically proven HGG, we performed a retrospective monocentric study. A predictive value of frontal location for a lower Ki67 value (especially in the left hemisphere) and mutation of IDH1 (especially in the right hemisphere) was found. Temporal location was predictive for IDH1 wild-type. Involvement of the parietal lobe was found to be predictive of methylated MGMT, while insular lobe involvement predicted an unmethylated MGMT. There was no statistically significant difference of IDH1 mutation and MGMT methylation between left and right sides.

Cortical bone trajectory screws for circumferential arthrodesis in lumbar degenerative spine: clinical and radiological outcomes of 101 cases.

PURPOSE: The use of cortical bone trajectory (CBT) pedicle screws for circumferential interbody fusion represents a viable alternative for single-level procedure with reduced invasiveness and less tissue destruction than the traditional technique. In addition, CBT screws have a potentially stronger pullout strength because of the greater amount of cortical bone intercepted. Only few series exist evaluating clinical and radiological outcomes of CBT screws. METHODS: This is a retrospective cohort study. All patients that underwent circumferential lumbar interbody fusion with CBT screws in our institution from 2014 to 2017 were reviewed. Patient demographics, clinical outcome with visual analogue scale (VAS) and Oswestry Disability Index (ODI), radiological data such as fusion, lordosis and muscle trauma, operative blood loss, hospital stay and use of fluoroscopy were evaluated. RESULTS: A total of 101 patients undergoing CBT-arthrodesis for degenerative lumbo-sacral disease were reviewed. Mean procedural time was 187 min. The mean operative blood loss and X-ray dose per procedure was 383 ml and 1.60 mg cm2, respectively. The mean hospital stay was 3.47 days. The mean follow-up was 18.23 months. Mean lordosis increment at the treated level was 4.2°. When the follow-up was longer than 12 months (53% of patients), fusion was obtained in 94% of cases. Mean ODI and VAS index improved with statistical significance. CONCLUSIONS: This is to our knowledge that the largest available study regarding CBT for circumferential arthrodesis. Results underlined the safety of this technique and the promising clinical and radiological outcomes that will need a longer follow-up. These slides can be retrieved under Electronic Supplementary material.

Intra-Operative Ultrasound: Tips and Tricks for Making the Most in Neurosurgery.

PURPOSE: Advances in intraoperative imaging and neuronavigation techniques have positively affected glioma surgery. The desire to reduce brain-shift-related problems while achieving the real-time identification of lesions and residual and anatomical relationships has strongly supported the introduction of intraoperative ultrasound (ioUS) in neuro-oncological surgery. This paper presents tips based on our experience with ioUS in neurosurgery. METHODS: We retrospectively analyzed 264 patients who underwent high-grade glioma (HGG) resection at the University of Turin and 60 patients who were treated at the University of Rome. RESULTS: The main issues are the correct choice of the probe and how to evaluate the anatomy to understand how the information from the three common US planes (axial, sagittal and coronal plane) can be used in each case. It is also important to correctly identify anatomical structures in ioUS imaging. In a normal brain, the sulci, sickle, tentorium, choroid plexus, ependyma and the walls of the vessels are all hyperechoic. In addition, some structures are hypoechoic with a homogeneous acoustic gradient: ventricles, cysts and everything that contains liquor. Tumors are usually hyperechoic in ioUS because of their higher cellularity. Conversely, acute edema that contains fluid is hypoechoic, while chronic edema is hyperechoic. CONCLUSIONS: IoUS is a real-time, accurate and inexpensive imaging method. The difficulties of interpretation can be overcome by experience in US imaging and a better understanding of the interaction between navigation and imaging fusion techniques. Training on a large number of cases is important for the correct assessment of ioUS information to obtain valuable, real-time information during HGG surgery.

Detailed anatomy knowledge: first step to approach petroclival meningiomas through the petrous apex. Anatomy lab experience and surgical series.

Petroclival meningiomas are a challenge for neurosurgeons due to the complex anatomy of the region that is rich of vessels and nerves. A perfect and detailed knowledge of the anatomy is very demanding in neurosurgery, especially in skull base surgery. The authors describe the microsurgical anatomy to perform an anterior petrosectomy based on their anatomical and surgical experience and perform a literature review. The temporal bone is the most complex and fascinating bone of skull base. The apex is located in the angle between the greater wing of the sphenoid and the occipital bone. Removing the petrous apex exposes the clivus. The approach directed through the temporal bone in this anatomical area is referred to as an anterior petrosectomy. The area that must be drilled is the rhomboid fossa that is defined by the Kawase, premeatal, and postmeatal triangles. In Division of Neurosurgery - University of Turin, 130 patients, from August 2013 to September 2015, underwent surgical resection of intracranial meningiomas. In this group, we have operated 7 PCMs and 5 of these were approached performing an anterior petrosectomy with good results. In our conclusions, we feel that this surgery require an advanced knowledge of human anatomy and a specialized training in interpretation of radiological and microsurgical anatomy both in the dissection lab and in the operating room.

Is Pseudotumor Cerebri An Unusual Expression of Chiari Syndrome? A Case Report and Review of the Literature.

The Chiari I malformation (CM-I) is a developmental alteration of the posterior cranial fossa (PCF), radiographically defined as the descent of the cerebellar tonsils ≤ 5 mm below the foramen magnum (FM) inside the cervical canal. Headache is the most frequent symptom associated with CM-I. The association of CM-I and neurological symptoms configures with Chiari syndrome. A rare symptom associated with Chiari syndrome is intracranial hypertension syndrome with cephalea and papilloedema-the typical findings of pseudotumor cerebri (PTC). PTC is a syndrome characterized by signs and symptoms of increased intracranial pressure (ICP) in the absence of space-occupying masses and/or obstruction of the ventricular system detectable by neuroimaging. The most common symptoms are headache and visual disturbances. Literature reports that the association between CM-I and PTC has a prevalence of 2-6%. More recently, a prevalence of 11% has been described in a specific subset of obese or overweight female patients between 20 and 40 years old. Here we report the case of a 38-year-old woman who came to our observation with a clinical picture and neuroradiological examinations compatible with both CM-I and PTC. We discuss the clinical case and the significant improvement after surgical occipito-cervical decompression.

Scalp Metastasis from Glioblastoma Multiforme: A Case Report and Literature Review.

Glioblastoma multiforme (GBM) is a common malignant brain tumor that rarely metastasizes extracranially, despite its aggressive clinical course. This report details the case of a young man presenting with a single subcutaneous localization of GBM that arose six months after initial surgery and recurred after excision. Only six other cases of scalp metastasis of GBM following surgery have been described in the literature, each with peculiar features. Whenever feasible, surgery is the most effective way to obtain local control of disease. However, a correct approach must be carefully planned to minimize the risks of recurrence and wound dehiscence.

Facial Nerve Schwannoma: A Case Report, Radiological Features and Literature Review.

Facial nerve schwannoma localized in the middle fossa is a rare lesion. We report a case of a facial nerve schwannoma in a 30-year-old male presenting with facial nerve palsy. Magnetic resonance imaging (MRI) showed a 3 cm diameter tumor of the right middle fossa. The tumor was removed using a sub-temporal approach. Intraoperative monitoring allowed for identification of the facial nerve, so it was not damaged during the surgical excision. Neurological clinical examination at discharge demonstrated moderate facial nerve improvement (Grade III House-Brackmann).

Multivariate projection method to investigate inflammation associated with secondary insults and outcome after human traumatic brain injury: a pilot study.

BACKGROUND: Neuroinflammation has been proposed as a possible mechanism of brain damage after traumatic brain injury (TBI), but no consensus has been reached on the most relevant molecules. Furthermore, secondary insults occurring after TBI contribute to worsen neurological outcome in addition to the primary injury. We hypothesized that after TBI, a specific pattern of cytokines is related to secondary insults and outcome. METHODS: A prospective observational clinical study was performed. Secondary insults by computerized multimodality monitoring system and systemic value of different cytokines were collected and analysed in the first week after intensive care unit admission. Neurological outcome was assessed at 6 months (GOSe). Multivariate projection technique was applied to analyse major sources of variation and collinearity within the cytokines dataset without a priori selecting potential relevant molecules. RESULTS: Twenty-nine severe traumatic brain injury patients undergoing intracranial pressure monitoring were studied. In this pilot study, we demonstrated that after TBI, patients who suffered of prolonged and severe secondary brain damage are characterised by a specific pattern of cytokines. Patients evolving to brain death exhibited higher levels of inflammatory mediators compared to both patients with favorable and unfavorable neurological outcome at 6 months. Raised ICP and low cerebral perfusion pressure occurred in 21 % of good monitoring time. Furthermore, the principal components selected by multivariate projection technique were powerful predictors of neurological outcome. CONCLUSIONS: The multivariate projection method represents a valuable methodology to study neuroinflammation pattern occurring after secondary brain damage in severe TBI patients, overcoming multiple putative interactions between mediators and avoiding any subjective selection of relevant molecules.

3D HD Endoscopy in Skull Base Surgery: From Darkness to Light.

The introduction of modern endoscopy in neurosurgery brought light to one of the darkest areas: the skull base. In particular, the trans-nasal route allowed skull base surgeons to visualize and dominate the entire midline skull base. We analyzed our surgical series of 199 patients that were affected by several pathologies (pituitary adenomas, clivalchordomas, craniopharyngioma, Rathke's cleft cysts, tuberculum sellaemeningiomas, and craniovertebral junction pathologies with bulbar compression) and treated each by using a 3D-HD endoscope between December 2012 and December 2015 and reviewed the literature. We present our results in terms of tumor resections and decompression inpatients affected by craniovertebral junction pathologies. Analyzing our direct experience, as well as the literature, we can assert that the amount and accuracy of necessary movements in order to achieve a determined target are affected by the screen clarity and image resolution of the device. Additionally, the experience of the surgeon has an important role in the surgical outcome. Moreover, depth perception is critical in order to obtain precise and accurate movements. Our observations and the experts' opinion indicate that this modality provides improved surgical dexterity by affording the surgeon with depth perception while manipulating tissue and maneuvering the endoscope in the endonasal corridor, which is especially crucial in reducing the learning curve of young neurosurgeons.

Vagus nerve stimulation for treatment-resistant mood disorders: a long-term naturalistic study.

BACKGROUND: Limited therapeutic options are available for patients with treatment-refractory major depression who do not respond to routinely available therapies. Vagus nerve stimulation showed adjunctive antidepressant effect in chronic treatment resistant depression, even though available studies rarely exceed 2-year follow up. We report a naturalistic 5-year follow up of five patients who received VNS implant for resistant depression (3 patients with major depressive disorder and 2 with bipolar disorder). METHODS: Response was defined as a reduction of the 17-item HDRS total score ≥50% with respect to baseline, remission as a score ≤7. RESULTS: Response and remission rates were both 40% (2/5) after 1 year, and 60% (3/5) at 5 years. Two patients withdrew from the study because of side effects or inefficacy of stimulation. CONCLUSIONS: Our case series showed that long-term VNS may be effective in reducing severity of depression in a small but significant minority of patients, although two patients had stimulation terminated because of adverse effects and/or refusal to continue the study.

Say "no" to spinal cord injury: is nitric oxide an option for therapeutic strategies?

PURPOSE: a literature review was made to investigate the role of nitric oxide (NO) in spinal cord injury, a pathological condition that leads to motor, sensory, and autonomic deficit. Besides, we were interested in potential therapeutic strategies interfering with NO mechanism of secondary damage. MATERIALS: A literature search using PubMed Medline database has been performed. RESULTS: excessive NO production after spinal cord injury promotes oxidative damage perpetuating the injury causing neuronal loss at the injured site and in the surrounding area. CONCLUSION: different therapeutic approaches for contrasting or avoiding NO secondary damage have been studied, these include nitric oxide synthase inhibitors, compounds that interfere with inducible NO synthase expression, and molecules working as antioxidant. Further studies are needed to explain the neuroprotective or cytotoxic role of the different isoforms of NO synthase and the other mediators that take part or influence the NO cascade. In this way, it would be possible to find new therapeutic targets and furthermore to extend the experimentation to humans.

Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection.

Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions.

Association between polymorphisms rs1333040 and rs7865618 of chromosome 9p21 and sporadic brain arteriovenous malformations.

BACKGROUND: The chromosomal locus 9p21 is a novel genetic marker for a variety of cardiovascular and cerebrovascular diseases. In a recent study, we have demonstrated an association between the single nucleotide polymorphism (SNP) rs1333040C>T on chromosome 9p21 and sporadic brain arteriovenous malformations (BAVMs). Here, we extended our analysis to an additional SNP on chromosome 9p21 (rs7865618A>G) and increased our sample size including BAVMs from two different Italian neurosurgical centers. METHODS: We studied 206 patients with sporadic BAVMs and 171 unaffected controls. Genomic DNA was isolated from peripheral blood and the rs1333040C>T and rs7865618A>G polymorphisms were assessed by PCR-RFLP using the BsmI and MspI restriction endonucleases, respectively. For each SNP, we performed dominant, recessive, and additive genetic models. RESULTS: The distribution of the three possible genotypes of rs1333040 (TT, TC and CC) was statistically different between cases and controls (p = 0.0008). The TT genotype was significantly associated with BAVMs both in the dominant (p = 0.013) and recessive (p = 0.012) models. The T allele was significantly associated with BAVMs in the additive model (p = 0.002). Also the distribution of the three possible genotypes of rs7865618 (GG, AG and AA) was statistically different between cases and controls (p = 0.005), and the GG genotype and G allele were significantly associated with BAVMs in the dominant (p = 0.032), recessive (p = 0.007), and additive models (p = 0.009). We also detected a significant association between BAVMs with large nidus size and the GG genotype and G allele of rs7865618 and the TT genotype of rs1333040. A deep venous drainage was instead associated with the TT genotype of the rs1333040 and the GG genotype of the rs7865618. The occurrence of bleeding was associated with the TT genotype and T allele of rs1333040, while the presence of seizures appeared associated with the GG genotype of rs7865618. CONCLUSIONS: SNPs of the 9p21 region, in addition to be genetic markers for coronary artery disease, stroke, and intracranial aneurysms, are associated with sporadic BAVMs. These results extend and strengthen the role of the 9p21 chromosomal region as a common risk factor for cerebrovascular diseases.

Pelvic parameters and global spine balance for spine degenerative disease: the importance of containing for the well being of content.

PURPOSE: Spinal deformities and pathologies of the spinopelvic junction are conditions affecting up to 60-70 % of the general aging population. In this review, we discuss the more recent knowledge on sagittal balance and its clinical implications. METHODS: Review of the literature regarding global spine balance. RESULTS: Global spinal balance and its relationship to the pelvis correlate closely with disability and quality of life. It has been demonstrated that extensive surgery, previously considered to have poor balance between risks and outcomes, causes great improvements in health-related quality of life in the oldest age groups. CONCLUSION: Failure to restore normal sagittal alignment in patients primarily operated for other than deformity results in unacceptable rates of poor results and revision surgery.