Posterolateral approaches to the thoracic spine for calcific disc herniation: is wider exposure always better?

OBJECTIVE: To compare the costotransversectomy (CTV) and transpedicular (TP) approaches versus the transfacet (TF) approach for the surgical treatment of calcific thoracic spine herniations (cTDH), in terms of surgical and clinical outcomes. BACKGROUND: Surgical approaches for cTDH are debated. Anterior approaches are recommended, while posterolateral approaches are preferred for non-calcific, paramedian, and lateral hernias. Currently, there is limited evidence about the superiority of a more invasive surgical approach, such as CTV or TP, over TF, a relatively less invasive approach, in terms of neurological outcome, pain, and surgical complications, for the treatment of cTDH. METHODS: A retrospective, observational, monocentric study was conducted on patients who underwent posterolateral thoracic approaches for symptomatic cTDH, between 2010 and 2023, at our institute. Three groups were drafted, based on the surgical approach used: TF, TP, and CTV. All procedures were assisted by intraoperative CT scan, spinal neuronavigation, and intraoperative neuromonitoring. Analyzed factors include duration of surgery, amount of bone removal, intraoperative blood loss, CSF leak, need of instrumentation for iatrogenic instability, degree of disc herniation removal, myelopathy recovery. Afterwards, a statistical analysis was performed to investigate the bony resection of the superior posterior edge of the vertebral soma. The primary outcome was the partial or total herniation removal. RESULTS: This study consecutively enrolled 65 patients who underwent posterolateral thoracic surgery for cTDH. The TF approach taking the least, and the CTV the longest time (p < 0.01). No statistical difference was observed between the three mentioned approaches, in terms of intraoperative blood loss, dural leakage, post-resection instrumentation, total herniation removal, or myelopathy recovery. An additional somatic bony resection was successful in achieving total herniation removal (p < 0.01), and the extent of bony resection was directly proportional to the extent of hernia removal (p < 0.01). CONCLUSIONS: No statistically significant differences were highlighted between the TP, TF, and CTV regarding the extent of cTDH removal, the postoperative complications, and the neurological improvement. The described somatic bone resection achieved significant total herniation removal and was directly proportional to the preop against postop anteroposterior diameter difference.

The Goutallier Classification System: How Does Paravertebral Adipose Degeneration Change in Patients With Symptomatic Lumbar Spinal Stenosis?

STUDY DESIGN: Retrospective, observational study. OBJECTIVE: To determine the relationship between the Goutallier classification system (GS) and anthropometric, clinical, and radiologic features in 168 patients with lumbar spinal stenosis (LSS). BACKGROUND: There is no agreement on a classification system that is both reliable and easy to use for describing the severity of fatty degeneration in the paravertebral muscles of the lower back in patients with symptomatic LSS. This study aimed to determine the statistical relationship between the GS and anthropometric, clinical, and radiologic factors in 168 patients with LSS. MATERIALS AND METHODS: This study was conducted on 168 patients with LSS scheduled for elective decompressive surgery. A control group of 110 healthy individuals was enrolled. The study assessed paralumbar musculature fatty infiltration using GS on preoperative magnetic resonance imaging. The authors evaluated the statistical association between patient age, body mass index (BMI), preoperative Oswestry disability index (ODI) questionnaire, and cross-sectional areas (CSAs) of the dural sac and lumbar paraspinal muscles. Multivariate analysis was performed to adjust for confounding. RESULTS: This study enrolled 168 patients with symptomatic LSS (95 men, 73 women); mean±SD age: 67.81±9.38 (range: 32.78-92.34) years; BMI: 28.29±3.36 (19.95-38.10) kg/m 2 . The control group was comprised of 110 healthy patients (61 men and 49 women). Age, sex, BMI, and erector spinae (ES)-CSA were not significantly different between the two groups. The authors found a direct relationship between GS grade and age and an inverse relationship between GS grade and dural sac-, multifidus lumbaris (LM)-, ES-, and psoas muscle (PM)-CSAs. Univariate analyses showed the variables statistically related to a higher GS grade included patient age ( P <0.001), ODI ( P =0.136), dural sac-CSA ( P =0.011), LM-CSA ( P < 0.001), ES-CSA ( P <0.001), and PM-CSA ( P <0.001). Multivariate least squares analysis showed the GS grade to be influenced by patient age ( P =0.01), LM-CSA ( P =0.002), ES-CSA ( P =0.002), and PM-CSA ( P =0.003). CONCLUSIONS: GS shows great potential as a tool for evaluating fat infiltration in the paralumbar muscles. This measure does not correlate with the ODI and BMI but is related to all radiologic parameters and patient age. Further prospective studies are required to establish a link between preoperative and postoperative outcomes in the setting of paraspinal fat infiltration.

Antithrombotic therapy and spinal surgery: a retrospective cohort study of 289 consecutive elderly patients with degenerative lumbar stenosis.

OBJECTIVE: Lumbar spinal stenosis (LSS) is a disabling degenerative process of the spine, mainly affecting older patients. LSS manifests with low-back and leg pain and neurogenic claudication. Disability and impairment in activities of daily living are consequences of the progressive narrowing of the lumbar spinal canal. Surgical decompression has been shown to be superior to conservative management. Nonetheless, intraoperative and postoperative blood loss in elderly patients taking antiplatelet or anticoagulant drugs owing to cardiovascular comorbidities may be a special issue. This study describes and compares early outcomes after surgical procedures in different groups of patients receiving antithrombotic drugs. METHODS: The authors' study retrospectively recruited 289 consecutive patients aged ≥ 65 years who received lumbar decompression for spinal stenosis between January 2021 and May 2022. First, 183 patients taking antiplatelet therapy were divided into two groups according to the rationale for use: primary versus secondary prophylaxis of cardiovascular events (group 1 vs group 2). Primary prevention was stopped preoperatively, or secondary prevention was not discontinued during the perioperative period. Secondly, 106 patients who were not taking antiplatelet mediation were divided into two groups, depending on whether preoperative low-molecular-weight heparin had not been administered or had been (group A vs group B). Intraoperative blood loss, surgical time, and postoperative hospitalization were analyzed. RESULTS: No significant statistical differences were observed between groups 1 and 2 in terms of intraoperative blood loss and time of surgery, or between groups A and B in terms of all analyzed variables. No early or delayed complications were observed, perioperatively or during the postoperative 3-month follow-up period. CONCLUSIONS: The results of this study suggest that the use of anticoagulant and antiplatelet therapies in elective decompressive surgery could be devoid of early complications and could be safely continued perioperatively.

Multiple univariate analysis of radiologic and clinical features on 168 patients with lumbar spinal stenosis: what is the role of the erector spinae in the development of a patient's disability?

BACKGROUND: The weakening of paraspinal muscles in the paravertebral area may play a role in developing central lumbar spinal stenosis, resulting in lower back discomfort. OBJECTIVE: The study thoroughly examined the correlation between the Oswestry Disability Index, Dural Sac cross-sectional area, Schizas grading Scale, Body Mass Index, and the cross-sectional areas of Erector Spinae, Multifidus, and Psoas muscles. The findings were also compared between patients with central Lumbar Spinal Stenosis and healthy individuals. STUDY DESIGN: Retrospective monocentric observational study. METHODS: The study recruited 168 consecutive patients aged 60 or older diagnosed with central Lumbar Spinal Stenosis between January 2020 and July 2022. The patients' condition was evaluated by administering a preoperative Oswestry Disability Index questionnaire, measuring their Body Mass Index, and performing preoperative Magnetic Resonance Imaging. The analyzed parameters were the cross-sectional area of paraspinal muscles at the L4-L5 level, dural sac cross-sectional area, and Schizas grading Scale at the most stenotic level, using multiple linear univariate analyses. Two groups of healthy individuals were recruited: Group A (under 60 years old) and Group B (over 60 years old). The same data extrapolated from these groups were compared with those of patients with central lumbar stenosis using a two-tailed Mann-Whitney test. RESULTS: As the Erector Spinae degenerates, the Oswestry Disability Index tends to increase. Similarly, an increase in Body Mass Index is often accompanied by a decrease in the cross-sectional area of the Erector Spinae. Low dural sac cross-sectional area is statistically linked to a reduced Multifidus cross-sectional area. Interestingly, the Schizas grading scale does not appear to correlate with changes in the cross-sectional area of the paraspinal muscles. Additionally, there is no significant difference in the cross-sectional area of the Psoas muscle between individuals with central lumbar spinal stenosis and healthy individuals. CONCLUSIONS: Our study found that degeneration of the Erector Spinae plays a crucial role in the progression of perceived disability in Lumbar Spinal Stenosis. Prospective studies should investigate the long-term evolution of paraspinal muscles in decompressed patients.

The Extremely Brilliant Source storage ring of the European Synchrotron Radiation Facility.

The Extremely Brilliant Source (EBS) is the experimental implementation of the novel Hybrid Multi Bend Achromat (HMBA) storage ring magnetic lattice concept, which has been realised at European Synchrotron Radiation Facility. We present its successful commissioning and first operation. We highlight the strengths of the HMBA design and compare them to the previous designs, on which most operational synchrotron X-ray sources are based. We report on the EBS storage ring's significantly improved horizontal electron beam emittance and other key beam parameters. EBS extends the reach of synchrotron X-ray science confirming the HMBA concept for future facility upgrades and new constructions.

Photon-shot-noise-limited transient absorption soft X-ray spectroscopy at the European XFEL.

Femtosecond transient soft X-ray absorption spectroscopy (XAS) is a very promising technique that can be employed at X-ray free-electron lasers (FELs) to investigate out-of-equilibrium dynamics for material and energy research. Here, a dedicated setup for soft X-rays available at the Spectroscopy and Coherent Scattering (SCS) instrument at the European X-ray Free-Electron Laser (European XFEL) is presented. It consists of a beam-splitting off-axis zone plate (BOZ) used in transmission to create three copies of the incoming beam, which are used to measure the transmitted intensity through the excited and unexcited sample, as well as to monitor the incoming intensity. Since these three intensity signals are detected shot by shot and simultaneously, this setup allows normalized shot-by-shot analysis of the transmission. For photon detection, an imaging detector capable of recording up to 800 images at 4.5 MHz frame rate during the FEL burst is employed, and allows a photon-shot-noise-limited sensitivity to be approached. The setup and its capabilities are reviewed as well as the online and offline analysis tools provided to users.

Subpial technique in supratentorial glioma resection: state of the art and analysis of costs and effectiveness in a single institute experience.

BACKGROUND: Many neurosurgeons advocate subpial technique as the best technique to remove supratentorial gliomas. However, few authors clearly defined advantages and features of this technique. The aim of our study is to describe microsurgical subpial technique related to glioma surgery, with regard to its safety and cost effectiveness. METHODS: We analyzed retrospectively all consecutive patients surgically treated for supratentorial glioma from January 2017 to April 2018 at Neurosurgery Department of Neuromed Institute. All patients underwent to surgical glioma resection performing microsurgical subpial technique. Extent of resection and neurological complications were evaluated as primary outcomes; Karnofsky Performance Status and postoperative edema extent were secondary outcomes. Statistical analysis was obtained. RESULTS: The study included 70 patients. Gross Total Removal was obtained in 91.3% of patients with low grade glioma (LGG) and in 81% of patients with high grade glioma. Neurological complications amounted to 34% at early assessment in LGG patients, which were permanent at 3 months in 17% of patients. In high grade glioma patients, neurological complications amounted to 51% at early assessment, which were permanent at 3 months in 25% of them. CONCLUSIONS: We obtained good postoperative results with regard to the extent of tumor resection using this technique. Subpial resection is an effective surgical technique to get a safer and more complete tumor resection. It should be combined with other modern neurosurgical tools such as neuronavigation, ultrasound and cortical mapping to obtain the best tumor resection and functional neurological preservation.

Cervical spine arachnoid cyst complicated by spontaneous intracystic hemorrhage: Case report and review of the literature.

Background: Spinal intradural extramedullary arachnoid cysts represent about 1-3% of all primary spinal space-occupying lesions often causing spinal cord and/or radicular nerve compression. Spontaneous intralesional hemorrhages are extremely rare and are typically found within intracranial arachnoid cysts. Here, a 55-year-old female presented with a spontaneous hemorrhage into a cervical spine arachnoid cyst warranting surgical intervention (i.e., fenestration/excision/occlusion). Case Description: A 55-year-old female presented with 3 weeks of dull pain in the cervicothoracic region. She subsequently developed paresthesias and progressive lower extremity weakness with (urinary incontinence. The cervical magnetic resonance revealed a right anterolateral intradural extramedullary "cystic" lesion extending from C7 to T2; it contained a heterogeneous signalon T2W sequences, and a fluid-fluid level was documented on the T2-GRE and FLAIR sequences. At surgery, consisting of a laminectomy, two hemorrhagic cystic lesions were identified and removed. Histological findings were consistent with hemorrhagic into an arachnoid cyst. Conclusion: Only rarely hemorrhages develop in intraspinal intradural extramedullary spinal arachnoid cysts.

Continuous subcortical monitoring of motor pathways during glioma surgery with ultrasonic surgical aspirator: technical description in a single institute experience.

BACKGROUND: Actual challenge in surgical treatment of intra-axial gliomas involving eloquent areas is maximal safe resection. Mapping and monitoring of cortical and subcortical motor functionsare important tools to avoid postoperative deficits. In the present study, we present our experiencewith a continuous dynamic motor mapping technique pairing a traditional monopolar stimulatorwith a Cavitron Ultrasonic Surgical Aspirator (CUSA) to perform a continuous stimulation ofthe white matter avoiding removal interruption. METHODS: We describe a single center retrospective analysis of 1-year consecutive patients with intraxial tumors located adjacent to corticospinal tract and treated with surgical resection adopting "continuous dynamic mapping technique". With the support of a reconstruction software (3D Slicer), we classified the Extent Of Resection (EOR) as Gross Total Resection (GTR) (>98%), Sub-Total Resection (STR) (from 90% to 97%), and Partial Resection (<90%). Medical Research Council (MRC) grading was adopted to evaluate neurological outcomes (from 0 to 5), assessed on 1st post-operative day, at 1 week, 1 month and 3 months. RESULTS: From July 2017 to July 2018, 29 patients underwent to surgical removal of intraxial tumor adjacent to motor areas, using continuous dynamic subcortical mapping. Median age was 54 years old (range 12-75 years). At pre-operative MRI tractography reconstruction, mean distance between tumor and corticospinal tract was 4,4 mm (range At 1 week post-operative assessment, motor deficits were still present in 12 patients (41%). At 1 month, 10 patients (35%) had persisting deficits, which required admission to rehabilitation department. At 3 months, 4 patients (14%) had persistent motor impairment and overall 28 patients (98%) were able to walk by themselves. CONCLUSIONS: Our early experience showed that a combination of dynamic subcortical mapping with transcranial and cortical strip MEP (Motor Evoked Potentials) monitoring is useful in tumors close to motor eloquent areas to extend surgical resection avoiding permanent consequences. However, we need for further experience to consolidate and improve this technique.

Is age an additional factor in the treatment of elderly patients with glioblastoma? A new stratification model: an Italian Multicenter Study.

OBJECTIVE: Approximately 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. METHODS: Clinical, 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. RESULTS: Survival 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). CONCLUSIONS: The 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%.

Interplay among work function, electronic structure and stoichiometry in nanostructured VOx films.

The work function is the parameter of greatest interest in many technological applications involving charge exchange mechanisms at the surface. The possibility to produce samples with a controlled work function is then particularly interesting, albeit challenging. We synthetized nanostructured vanadium oxide films by a room temperature supersonic cluster beam deposition method, obtaining samples with tunable stoichiometry and work function (3.7-7 eV). We present an investigation of the electronic structure of several vanadium oxide films as a function of the oxygen content via in situ Auger, valence-band photoemission spectroscopy and work function measurements. The experiments probed the partial 3d density of states, highlighting the presence of strong V 3d-O 2p and V 3d-V 4s hybridizations which influence 3d occupation. We show how controlling the stoichiometry of the sample implies control over work function, and that the access to nanoscale quantum confinement can be exploited to increase the work function of the sample relative to the bulk analogue. In general, the knowledge of the interplay among work function, electronic structure, and stoichiometry is strategic to match nanostructured oxides to their target applications.

Complete Characterization of Phase and Amplitude of Bichromatic Extreme Ultraviolet Light.

Intense, mutually coherent beams of multiharmonic extreme ultraviolet light can now be created using seeded free-electron lasers, and the phase difference between harmonics can be tuned with attosecond accuracy. However, the absolute value of the phase is generally not determined. We present a method for determining precisely the absolute phase relationship of a fundamental wavelength and its second harmonic, as well as the amplitude ratio. Only a few easily calculated theoretical parameters are required in addition to the experimental data.

Non-conventional fotemustine schedule as second-line treatment in recurrent malignant gliomas: Survival across disease and treatment subgroup analysis and review of the literature.

Fotemustine (FTM) is a treatment option in recurrent malignant gliomas (MGs) after first-line Stupp treatment. The efficacy and the safety of fractionated FTM schedule proposed by Addeo et al was analysed in the present study in recurrent MGs patients. A retrospective analysis on 40 recurrent MGs patients and second-line fractionated FTM chemotherapy was performed. Response evaluation was assessed using RANO criteria and safety was assessed using CTCAE v.4.03. Subgroup analyses based on MGMT methylation, resurgery and reirradiation were performed. A review of the literature was also performed. The results revealed 5 partial responses (13%) and 19 stable diseases (47%) with a disease-control rate of 60%. Median progression-free survival (PFS) was 4 months, with a PFS of 33% at 6 months and 13% at 1 year. The median overall survival (OS) was 9 months and OS at 6 months was of 55% and at 1 year of 30%. Methylated patients experienced longer mPFS (6 vs. 3 months; p=0.004) and mOS (10 vs. 4 months; p<0.0001) compared with unmethylated patients. Patients treated with reirradiation experienced longer mPFS (5 vs. 3.5 months; p=0.48) and mOS (10 vs. 5 months; p=0.11). No survival benefit with resurgery was observed. Furthermore, the fractioned schedule was well tolerated, only 15% of patients developed severe myelotoxicities. Considering the present findings, fractionated FTM schedule is an efficient second-line option for MGs associated with an acceptable myelotoxicity profile. Additionally, MGMT methylation is associated with improved survival outcomes. However, this study highlights the requirement for further prospective randomized studies on resurgery and reirradiation.

Multiple brain metastases: a surgical series and neurosurgical perspective.

Despite review papers claim for radical treatment of oligometastatic patients, only few surgical series have been published. In this study, we analyze results and actual role of surgical resection for the management of patients with multiple brain metastases. This retrospective study compares surgical results of two groups of patients consecutively treated in our Institute from January 2004 to June 2015. The first group comprises all 32 patients with multiple brain metastases with only 2-3 lesions who underwent surgical resection of all lesions; the second group comprises 30 patients with a single surgically treated brain mestastasis compatible with the first group (match-paired control series). Median survival was 14.6 months for patients with multiple brain metastases (range 1-28 months) and 17.4 months for patients with a single brain metastasis (range 4-38 months); the difference was not statistically significant (P = 0.2). Neurological condition improved in 59.4% of patients with multiple metastases, it remained unchanged in 37.5% and worsened in 3.1%. In our series, selected patients with only 2-3 lesions with well-controlled systemic disease, life expectancy of more than 3 months, Karnofsky's performance status > 60, and surgically accessible lesions, benefited from surgical treatment in terms of survival and quality of life, with reduction or disappearance of significant neurological deficits. The prognosis for these patients is similar to that of patients with a single metastasis. It seems that patients with breast cancer included in our series had the worst prognosis if compared to other histotypes.

Epileptic seizures heralding a relapse in high grade gliomas.

PURPOSE: Seizures are a common clinical symptom in high-grade gliomas (HGG). The aim of the study was to investigate the relationship between seizures and HGG relapse (HGG-R). METHODS: We retrospectively evaluated 145 patients who were surgically treated for HGG-R. By analyzing clinical characteristics in these patients (all operated and treated by the same protocol), we identified 37 patients with seizures during follow-up. This cohort was divided into four subgroups according to a) presence or absence of seizures at the time of diagnosis and b) temporal relationship between seizure occurrence and HGG-R during follow-up: subgroup A (25pts) had seizures at follow-up but not at onset, subgroup B (12pts) had seizures both at follow-up and onset, subgroup C (30pts) had seizures before MRI-documented HGG-R, and subgroup D (7pts) had seizures after MRI-documented HGG-R. RESULTS: Although the datum was not statistically significant, survival was longer in patients with seizures during follow-up than in those without seizures (59.3% vs 51.4% alive at 2 years). In 30 patients (subgroup C) seizures heralded HGG-R. In a correlation analysis for this last subgroup, the time interval between seizure and the HGG-R was significantly associated with the number of chemotherapy cycles (r=0.470; p=0.009) and follow-up duration (r=0.566; p=0.001). A linear regression model demonstrated a reciprocal association between the above factors and that it may be possible to estimate the timing of HGG-R by combining these data. CONCLUSIONS: Seizures may herald HGG-R before MRI detection of relapse, thus suggesting that seizures should always be considered a red flag during follow-up.

Emergency decompressive craniectomy after removal of convexity meningiomas.

BACKGROUND: Convexity meningiomas are benign brain tumors that are amenable to complete surgical resection and are associated with a low complication rate. The aim of this study was to identify factors that result in acute postoperative neurological worsening after the removal of convexity meningiomas. METHODS: Clinical evaluation and neuroradiological analysis of patients who underwent removal of a supratentorial convexity meningioma were reviewed. Patients were selected when their postoperative course was complicated by acute neurological deterioration requiring decompressive craniectomy. RESULTS: Six patients (mean age: 43.3 years) underwent surgical removal of a supratentorial convexity meningioma. Brain shift (mean: 9.9 mm) was evident on preoperative imaging due to lesions of varying size and perilesional edema. At various times postoperatively, patient consciousness worsened (up to decerebrate posture) with contralateral paresis and pupillary anisocoria. Computed tomography revealed no postoperative hematoma, however, did indicate increased brain edema and ventricular shift (mean: 12 mm). Emergency decompressive craniectomy and brief ventilator assistance were performed in all patients. Ischemia of the ipsilateral posterior cerebral artery occurred in 3 patients and hydrocephalus occurred in 2 patients. Outcome was good in 2, fair in 2, 1 patient had severe disability, and 1 patient died after 8 months. CONCLUSIONS: Brain shift on preoperative imaging is a substantial risk factor for postoperative neurological worsening in young adult patients after the removal of convexity meningiomas. Emergency decompressive craniectomy must be considered because it is effective in most cases. Other than consciousness impairment, there is no reliable clinical landmark to guide the decision to perform decompressive craniectomy; however, brain ischemia may have already occurred.

Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.

UNLABELLED: The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders.

Transdural Spread of Glioblastoma with Endonasal Growth in a Long-Term Survivor Patient: Case Report and Literature Review.

Glioblastoma (GBM) is the most aggressive primary tumor of the central nervous system (CNS) in adults. Its growth has been always described as locally invasive. This tumor rarely penetrates dura mater and invades extracranial structures. We present a case of GBM, which occurred in a 39-year-old man, with final involvement of the nasal cavity. The patient was operated four times in three years, and a personalized adjuvant chemotherapy regimen was administered in a neo-adjuvant fashion. Histopathological features of the tumor are described. To our knowledge, there are only 9 cases reported in the literature showing this growth pattern and the last case was reported in 1998.

Magnetic resonance diffusion tensor imaging and fiber-tracking diffusion tensor tractography in the management of spinal astrocytomas.

Some specially imaging of magnetic resonance imaging, the diffusion-weighted imaging (DWI), the diffusion tensor imaging and fractional anisotropy (FA), are useful to described, detect, and map the extent of spinal cord lesions. FA measurements may are used to predicting the outcome of patients who have spinal cord lesions. Fiber tracking enable to visualizing the integrity of white matter tracts surrounding some lesions, and this information could be used to formulating a differential diagnosis and planning biopsies or resection. In this article, we will describe the current uses for DWI and fiber tracking and speculate on others in which we believe these techniques will be useful in the future.