Spectrotemporal cortical dynamics and semantic control during sentence completion.

OBJECTIVE: To investigate cortical oscillations during a sentence completion task (SC) using magnetoencephalography (MEG), focusing on the semantic control network (SCN), its leftward asymmetry, and the effects of semantic control load. METHODS: Twenty right-handed adults underwent MEG while performing SC, consisting of low cloze (LC: multiple responses) and high cloze (HC: single response) stimuli. Spectrotemporal power modulations as event-related synchronizations (ERS) and desynchronizations (ERD) were analyzed: first, at the whole-brain level; second, in key SCN regions, posterior middle/inferior temporal gyri (pMTG/ITG) and inferior frontal gyri (IFG), under different semantic control loads. RESULTS: Three cortical response patterns emerged: early (0-200 ms) theta-band occipital ERS; intermediate (200-700 ms) semantic network alpha/beta-band ERD; late (700-3000 ms) dorsal language stream alpha/beta/gamma-band ERD. Under high semantic control load (LC), pMTG/ITG showed prolonged left-sided engagement (ERD) and right-sided inhibition (ERS). Left IFG exhibited heightened late (2500-2550 ms) beta-band ERD with increased semantic control load (LC vs. HC). CONCLUSIONS: SC involves distinct cortical responses and depends on the left IFG and asymmetric engagement of the pMTG/ITG for semantic control. SIGNIFICANCE: Future use of SC in neuromagnetic preoperative language mapping and for understanding the pathophysiology of language disorders in neurological conditions.

Diagnosis and endovascular management of vasospasm after aneurysmal subarachnoid hemorrhage - survey of real-life practices.

BACKGROUND: Vasospasm and delayed cerebral ischemia (DCI) are the leading causes of morbidity and mortality after intracranial aneurysmal subarachnoid hemorrhage (aSAH). Vasospasm detection, prevention and management, especially endovascular management varies from center to center and lacks standardization. We aimed to evaluate this variability via an international survey of how neurointerventionalists approach vasospasm diagnosis and endovascular management. METHODS: We designed an anonymous online survey with 100 questions to evaluate practice patterns between December 2021 and September 2022. We contacted endovascular neurosurgeons, neuroradiologists and neurologists via email and via two professional societies - the Society of NeuroInterventional Surgery (SNIS) and the European Society of Minimally Invasive Neurological Therapy (ESMINT). We recorded the physicians' responses to the survey questions. RESULTS: A total of 201 physicians (25% [50/201] USA and 75% non-USA) completed the survey over 10 months, 42% had >7 years of experience, 92% were male, median age was 40 (IQR 35-46). Both high-volume and low-volume centers were represented. Daily transcranial Doppler was the most common screening method (75%) for vasospasm. In cases of symptomatic vasospasm despite optimal medical management, endovascular treatment was directly considered by 58% of physicians. The most common reason to initiate endovascular treatment was clinical deficits associated with proven vasospasm/DCI in 89%. The choice of endovascular treatment and its efficacy was highly variable. Nimodipine was the most common first-line intra-arterial therapy (40%). Mechanical angioplasty was considered the most effective endovascular treatment by 65% of neurointerventionalists. CONCLUSION: Our study highlights the considerable heterogeneity among the neurointerventional community regarding vasospasm diagnosis and endovascular management. Randomized trials and guidelines are needed to improve standard of care, determine optimal management approaches and track outcomes.

Cell Surface Vimentin Detection in Cancer Cells by Peptide-Based Monoclonal Antibody.

Background: Vimentin is a prominent Intermediate Filaments (IFs) protein expressed in different mesenchymal origin cell types. Besides a wide range of cellular function roles associated with vimentin expression, its dysregulation and cell surface expression in the induction of malignancy properties have been reported extensively, making it a promising cancer-specific target. Therefore, this study aimed to generate and characterize anti-vimentin monoclonal antibodies. Methods: A 14-mer synthetic peptide from vimentin was conjugated to Keyhole Limpet Hemocyanin (KLH) and used for immunization of Blab/C mice and monoclonal production by conventional hybridoma technology. The monoclonal antibody was purified using affinity chromatography of supernatants from the selected hybridoma cells. ELISA, Immunoprecipitation-Western blotting (IP-WB), Immunocytochemistry (ICC), and flow cytometry were employed to characterize the produced monoclonal antibody in terms of interaction with vimentin immunizing peptide as well as vimentin protein. Results: Amid the several obtained producing anti-vimentin antibody hybridomas, the 7C11-D9 clone (IgG1 isotype with kappa light chain) showed higher reactivity with the immunizing peptide, and led to its selection for purification and characterization. The purified antibody could detect vimentin protein in IP-WB, ICC and flow cytometry of the normal and cancerous cells with different origin. No vimentin expression was found in normal healthy Peripheral Blood Mononuclear Cell (PBMC). Conclusion: Taken together, 7C11-D9 anti-vimentin monoclonal antibody might be used as immune diagnostic or immune therapeutic tool where detection or targeting of vimentin in a wide range of organisms is required.

BOLD fMRI and DTI fiber tracking for preoperative mapping of eloquent cerebral regions in brain tumor patients: impact on surgical approach and outcome.

PURPOSE: Task-based BOLD fMRI and DTI-fiber tracking have become part of the routine presurgical work-up of brain tumor patients in many institutions. However, their potential impact on both surgical treatment and neurologic outcome remains unclear, in despite of the high costs and complex implementation. METHODS: We retrospectively investigated whether performing fMRI and DTI-ft preoperatively substantially impacted surgical planning and patient outcome in a series of brain tumor patients. We assessed (i) the quality of fMRI and DTI-ft results, by using a scale of 0-2 (0 = failed mapping; 1 = intermediate confidence; 2 = good confidence), (ii) whether functional planning substantially contributed to defining the surgical strategy to be undertaken (i.e., no surgery, biopsy, or resection, with or without ESM), the surgical entry point and extent of resection, and (iii) the incidence of neurological deficits post-operatively. RESULTS: Twenty-seven patients constituted the study population. The mean confidence rating was 1.9/2 for fMRI localization of the eloquent cortex and lateralization of the language function and 1.7/2 for DTI-ft results. Treatment strategy was altered in 33% (9/27) of cases. Surgical entry point was modified in 8% (2/25) of cases. The extent of resection was modified in 40% (10/25). One patient (1/25, 4%) developed one new functional deficit post-operatively. CONCLUSION: Functional MR mapping - which must not be considered an alternative to ESM - has a critical role preoperatively, potentially modifying treatment strategy or increasing the neurosurgeons' confidence in the surgical approach hypothesized based on conventional imaging.

An Anti-TAZ Monoclonal Antibody Recognizing Cell Surface Expressed TAZ Protein in Human Tumor Cells.

Background: WWTR1 or TAZ is a transcriptional co-activator protein expressed in cytoplasm which functions as the main downstream effector of the Hippo signaling pathway. This pathway is an evolutionally conserved signal cascade, which plays a pivotal role in organ size control and tumorigenesis. Ectopic expression of TAZ has already been observed in many malignancies, while the ectopic localization of TAZ is reported for the first time. The aim of this study was to produce a specific monoclonal antibody (mAb) against a synthetic peptide derived from WWTR1 protein to be used as a research tool in human carcinomas. Methods: A 21-mer synthetic peptide (derived from human TAZ protein) was used for immunization of BALB/c mice after conjugation with Keyhole Limpet Haemocyanin (KLH) using hybridoma technology. The generated mAb reacted with the immunizing peptide employing ELISA assay. The reactivity of the antibody with native TAZ protein was assessed through Western blot, immunocytochemistry, and flow cytometry using different cancer cell lines. Results: The produced mAb could recognize the immunizing peptide in ELISA and Kaff was 0.6×10-9 M. The produced anti-TAZ mAb unlike available commercial anti-TAZ antibody, was capable of specifically recognizing cell surface TAZ in human carcinoma cell lines including MCF-7, Raji, and A431 in Western blot, immunocytochemistry, and flow cytometry assays. As expected, no reactivity was observed using normal Peripheral Blood Mononuclear Cell (PBMC) from healthy donors. Conclusion: Based on the results, TAZ is ectopically expressed on the surface of tumor cell lines which is not the case in normal cells. The generated mAb has a potential to be used as a research tool in studying the expression of TAZ in human carcinomas in different applications.

A novel ADC targeting cell surface fibromodulin in a mouse model of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancers (TNBCs) are highly aggressive and metastatic. To date, finding efficacious targeted therapy molecules might be the only window of hope to cure cancer. Fibromodulin (FMOD), is ectopically highly expressed on the surface of Chronic Lymphocytic Leukemia (CLL) and bladder carcinoma cells; thus, it could be a promising molecule for targeted therapy of cancer. The objective of this study was to evaluate cell surface expression of FMOD in two TNBC cell lines and develop an antibody-drug conjugate (ADC) to target FMOD positive TNBC in vitro and in vivo. MATERIALS AND METHODS: Two TNBC-derived cell lines 4T1 and MDA-MB-231 were used in this study. The specific binding of anti-FMOD monoclonal antibody (mAb) was evaluated by flow cytometry and its internalization was verified using phAb amine reactive dye. A microtubulin inhibitor Mertansine (DM1) was used for conjugation to anti-FMOD mAb. The binding efficacy of FMOD-ADC was assessed by immunocytochemistry technique. The anti-FMOD mAb and FMOD-ADC apoptosis induction were measured using Annexin V-FITC and flow cytometry. Tumor growth inhibition of anti-FMOD mAb and FMOD-ADC was evaluated using BALB/c mice injected with 4T1 cells. RESULTS: Our results indicate that both anti-FMOD mAb and FMOD-ADC recognize cell surface FMOD molecules. FMOD-ADC could induce apoptosis in 4T1 and MDA-MB-231 cells in vitro. In vivo tumor growth inhibition was observed using FMOD-ADC in 4T1 inoculated BALB/c mice. CONCLUSION: Our results suggests high cell surface FMOD expression could be a novel bio-marker TNBCs. Furthermore, FMOD-ADC could be a promising candidate for targeting TNBCs.

Monoclonal Antibody Against Sortilin Induces Apoptosis in Human Breast Cancer Cells.

Background: Sortilin has an important role in various malignances and can be used as a promising target to eradicate cancer cells. Methods: In this study, the expression of sortilin in 4T1 and MDA-MB231 cell lines was evaluated by flow cytometry and immunocytochemistry. Apoptosis assay was also applied to evaluate apoptosis induction in 4T1 and MDA-MB231 cell lines. Results: Based on cell surface flow cytometry results, anti-sortilin (2D8-E3) mAb could recognize sortilin molecules in 79.2% and 90.3% of 4T1 and MDA-MB231 cell-lines, respectively. The immunocytochemistry staining results confirmed sortilin surface expression. Apoptosis assay indicated that anti-sortilin mAb could induce apoptosis in 4T1 and MDA-MB231 cell lines. Conclusion: Our study revealed the important role of surface sortilin in breast carcinoma cell survival and its possible application as a therapeutic agent in cancer targeted therapies.

Diagnostic and Therapeutic Implications of Sortilin Expressed on the Surface of Bladder Carcinoma Cells.

Background & Objective: Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as a target for developing diagnostic and therapeutic agents against bladder carcinoma. Methods: The protein expression of sortilin in bladder cancer tissues and cell lines (5637 and EJ138) was investigated by immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry. Furthermore, the capability of anti-sortilin mAb in apoptosis induction in bladder cancer cells was evaluated. Results: A high expression level was observed in bladder carcinoma tissues (P≤0.001) and cell lines, using IHC and ICC, respectively. Flow cytometry results showed cell surface expression of 27.5±3% (P≤0.01), 74.4±7.8% (P≤0.001), and 4.2±0.4% of sortilin in EJ138, 5637, and HFFF cells, respectively. In EJ138 anti-sortilin mAb induced apoptosis in 25.2±11.5% (P≤0.05) (early) and 4.5±1.1% (P>0.05) (late) after 6 h incubation, while for 12 h, the values of 11.6±3.8% (P>0.05) and 20.7±4.4% (P≤0.05) were achieved. In 5637 cells, 6 h incubation resulted in 10.2±0.3% (P>0.05) and 6.6±1.4% (P>0.05) apoptosis induction, while these values were 12.1±0.8% (P>0.05) and 27.4±4.5% (P≤0.01) after 12 h. The HFFF cells did not show significant apoptosis. Conclusion: The overexpression of sortilin in bladder tumor cells and its potential in inducing apoptosis via directed targeting with the specific monoclonal antibody may represent this protein as a potential candidate of targeted therapy in bladder carcinoma.

MRI of Acute Low Back Pain: About an Uncommon Pitfall.

Posteriorly migrated disc extrusion may mimic tumoral masses on MRI with contrast; still, this diagnosis must be evoked in patients presenting acute low back pain with a posterior epidural mass. We describe a case of epidural posterior migration of an inflammatory lumbar disc herniation in a young patient with acute lumbosciatica. MRI showed an intracanalar mass with intense global enhancement, which is an uncommon feature of this rare condition.

Detection of cerebral hypoperfusion with a dynamic hyperoxia test using brain oxygenation pressure monitoring.

INTRODUCTION: Brain multimodal monitoring including intracranial pressure (ICP) and brain tissue oxygen pressure (PbtO2) is more accurate than ICP alone in detecting cerebral hypoperfusion after traumatic brain injury (TBI). No data are available for the predictive role of a dynamic hyperoxia test in brain-injured patients from diverse etiology. AIM: To examine the accuracy of ICP, PbtO2 and the oxygen ratio (OxR) in detecting regional cerebral hypoperfusion, assessed using perfusion cerebral computed tomography (CTP) in patients with acute brain injury. METHODS: Single-center study including patients with TBI, subarachnoid hemorrhage (SAH) and intracranial hemorrhage (ICH) undergoing cerebral blood flow (CBF) measurements using CTP, concomitantly to ICP and PbtO2 monitoring. Before CTP, FiO2 was increased directly from baseline to 100% for a period of 20 min under stable conditions to test the PbtO2 catheter, as a standard of care. Cerebral monitoring data were recorded and samples were taken, allowing the measurement of arterial oxygen pressure (PaO2) and PbtO2 at FiO2 100% as well as calculation of OxR (= ΔPbtO2/ΔPaO2). Regional CBF (rCBF) was measured using CTP in the tissue area around intracranial monitoring by an independent radiologist, who was blind to the PbtO2 values. The accuracy of different monitoring tools to predict cerebral hypoperfusion (i.e., CBF < 35 mL/100 g × min) was assessed using area under the receiver-operating characteristic curves (AUCs). RESULTS: Eighty-seven CTPs were performed in 53 patients (median age 52 [41-63] years-TBI, n = 17; SAH, n = 29; ICH, n = 7). Cerebral hypoperfusion was observed in 56 (64%) CTPs: ICP, PbtO2 and OxR were significantly different between CTP with and without hypoperfusion. Also, rCBF was correlated with ICP (r = - 0.27; p = 0.01), PbtO2 (r = 0.36; p < 0.01) and OxR (r = 0.57; p < 0.01). Compared with ICP alone (AUC = 0.65 [95% CI, 0.53-0.76]), monitoring ICP + PbO2 (AUC = 0.78 [0.68-0.87]) or ICP + PbtO2 + OxR (AUC = 0.80 (0.70-0.91) was significantly more accurate in predicting cerebral hypoperfusion. The accuracy was not significantly different among different etiologies of brain injury. CONCLUSIONS: The combination of ICP and PbtO2 monitoring provides a better detection of cerebral hypoperfusion than ICP alone in patients with acute brain injury. The use of dynamic hyperoxia test could not significantly increase the diagnostic accuracy.

The Association of Cell Surface Fibromodulin Expression and Bladder Carcinoma.

BACKGROUND: Fibromodulin (FMOD) is a secretory protein which is considered a major component of extracellular matrix. Its dysregulation in different types of cancer implies it as a promising target for cancer therapy. Within the scope of its rather wide expression in different tumors, we studied expression of FMOD and effect of anti-FMOD antibody in bladder cancer cells in order to identify new target for diagnostic and therapeutic interventions. We report here for the first time the expression of FMOD in bladder cancer cell lines in comparison to the normal cell line and tissues. METHODS: A peptide-based produced anti-FMOD murine monoclonal antibody (mAb) (clone 2C2-A1) was applied for evaluation of FMOD expression in bladder cancer and normal tissues by immunohistochemistry (IHC) staining. Furthermore, the expression of FMOD was examined in human bladder cell lines, 5637 and EJ138, as well as a non-cancerous human cell line, human fetal foreskin fibroblast (HFFF), by immunocytochemistry (ICC) and flow cytometry. The apoptosis induction of anti-FMOD mAb was also evaluated in bladder cancer cells. RESULTS: IHC and ICC analyses revealed that the qualitative expression of FMOD in bladder cancer tissues and cell lines is higher than in normal tissues and cell lines. Flow cytometry analyses revealed that 2C2-A1 mAb could recognize FMOD expression in 84.05 ± 1.85%, 46.1 ± .4% , and 2.56 ± 1.26% of 5637, EJ138, and HFFF cells, respectively. An effective apoptosis induction was detected in 5637 and EJ138 cells with no significant effect on HFFF cell. CONCLUSION: To our knowledge, this is for the first time reporting surface expression of FMOD in bladder cancer. This significant surface expression of FMOD in bladder cancer with no expression in normal bladder tissues and the capacity of inducing apoptosis through directed targeting of FMOD with specific monoclonal antibody might candidates FMOD as a diagnostic marker as well as a potential immunotargeting with monoclonal antibody.

Pneumatic artificial muscle-based stimulator for passive functional magnetic resonance imaging sensorimotor mapping in patients with brain tumours.

BACKGROUND: Two concerns with respect to pre-operative task-based motor functional magnetic resonance imaging (fMRI) in patients with brain tumours are inadequate performance due to patients' impaired motor function and head motion artefacts. NEW METHOD: In the present study we validate the use of a stimulator based on a pneumatic artificial muscle (PAM) for fMRI mapping of the primary sensorimotor (SM1) cortex in twenty patients with rolandic or perirolandic brain tumours. All patients underwent both active and passive motor block-design fMRI paradigms, performing comparable active and passive PAM-induced flexion-extensions of the icontralesional index finger. RESULTS: PAM-induced movements resulted in a significant BOLD signal increase in contralateral primary motor (M1) and somatosensory (S1) cortices in 18/20 and 19/20 (p<.05 FWE corrected in 16/18 and 18/19) patients, versus 18/20 and 16/20 (p<.05 FWE corrected) during active movements. The two patients in whom the PAM-based stimulator failed to induce any significant BOLD signal change in the contralateral M1 cortex differed from the two in whom active motion was conversely ineffective. At the group level, no significant difference in contrast magnitude was observed within the contralateral SM1 cortex when comparing active with passive movements. During passive movements, head motion was significantly reduced. Comparison with existing method(s) As compared to the several robotic devices for passive motion that were introduced in the past decades, our PAM-based stimulator appears smaller, handier, and easier to use. CONCLUSION: The use of PAM-based stimulators should be included in routine pre-operative fMRI protocols along with active paradigms in such patients' population.

Remote Intracranial Hemorrhage after Cranio-Spinal Surgery. Report of Two Cases.

Post-operative intracranial bleeding at a distance from the surgical site is a rare complication of both cranial and spinal surgeries and is referred to as remote intracranial hemorrhage (RIH). Bleeding typically occurs in the cerebellum. Simultaneous hemorrhages in different cranial compartments have been rarely observed. We herein report two cases of RIH, which showed different imaging patterns and clinical signs and symptoms. RIH are typically self-limiting and do not usually require treatment. Physicians must be aware of this benign entity which needs not be misdiagnosed with other conditions. Teaching point: Remote intracranial hemorrhage is a rare but worthy of note complication of cranio-spinal surgery.

Monoclonal Antibody Against ROR1 Induces Apoptosis in Human Bladder Carcinoma Cells.

BACKGROUND: Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is one of the promising cell surface antigens for targeting cancer cells. The aim of this study was to evaluate ROR1 cell surface expression in bladder cancer cells using a murine anti-ROR1 monoclonal antibody (mAb) called 5F1-B10 as well as investigate its potential in apoptosis induction. METHODS: Expression of ROR1 in two human bladder cell lines, 5637 and EJ138, as well as a non-cancerous human cell line, Human Fetal Foreskin Fibroblast (HFFF), was examined by flow cytometry and immunocytochemistry. Immunohistochemical staining of cancer and normal bladder tissues was also performed. RESULTS: The flow cytometry results showed that 5F1-B10 mAb could recognize ROR1 molecules in 86.1% and 45.6% of 5637 and EJ138 cells, respectively. The expression level of ROR1 was 5.49% in HFFF cells. The immunocytochemistry and immunohistochemistry staining results also confirmed the presence of ROR1 on the surface of both bladder cancer cells and tissues, respectively. The obtained data from apoptosis assay demonstrated that 5F1-B10 mAb could induce apoptosis in both 5637 and EJ138 cell lines. CONCLUSION: Taken together, our finding indicates the role of ROR1 in bladder cancer cell survival and suggests this receptor might be a promising target for developing novel therapeutic agents against bladder carcinoma.

Frequency-Dependent Intrinsic Electrophysiological Functional Architecture of the Human Verbal Language Network.

Functional magnetic resonance imaging (fMRI) allowed the spatial characterization of the resting-state verbal language network (vLN). While other resting-state networks (RSNs) were matched with their electrophysiological equivalents at rest and could be spectrally defined, such correspondence is lacking for the vLN. This magnetoencephalography (MEG) study aimed at defining the spatio-spectral characteristics of the neuromagnetic intrinsic functional architecture of the vLN. Neuromagnetic activity was recorded at rest in 100 right-handed healthy adults (age range: 18-41 years). Band-limited power envelope correlations were performed within and across frequency bands (θ, α, ß, and low γ) from a seed region placed in the left Broca's area, using static orthogonalization as leakage correction. K-means clustering was used to segregate spatio-spectral clusters of resting-state functional connectivity (rsFC). Remarkably, unlike other RSNs, within-frequency long-range rsFC from the left Broca's area was not driven by one main carrying frequency but was characterized by a specific spatio-spectral pattern segregated along the ventral (predominantly θ and α) and dorsal (ß and low-γ bands) vLN streams. In contrast, spatial patterns of cross-frequency vLN functional integration were spectrally more widespread and involved multiple frequency bands. Moreover, the static intrinsic functional architecture of the neuromagnetic human vLN involved clearly left-hemisphere-dominant vLN interactions as well as cross-network interactions with the executive control network and postero-medial nodes of the DMN. Overall, this study highlighted the involvement of multiple modes of within and cross-frequency power envelope couplings at the basis of long-range electrophysiological vLN functional integration. As such, it lays the foundation for future works aimed at understanding the pathophysiology of language-related disorders.

Intracranial Vessel Wall MRI in Cryptogenic Stroke and Intracranial Vasculitis.

INTRODUCTION: Intracranial vasculopathies easily elude classic stroke work-up. We aim in this work to show that vessel wall-MRI could prove an efficient alternative to digital subtraction angiography for the diagnosis of intracranial vasculopathies by identifying intracranial arterial vessel walls anomalies and contrast enhancement, suggestive of angiitis of the central nervous system. MATERIALS AND METHODS: Clinical and imaging characteristics of stroke patients diagnosed with primary angiitis of the central nervous system based on vessel wall-MRI were retrospectively reviewed and the clinical and imaging features of angiitis associated with intracranial vessel walls anomalies and contrast enhancement detailed. RESULTS: Twenty patients were included (mean age was 59 years old). All patients were admitted for focal neurological deficits of sudden onset that were recurrent in 13 subjects. Cognitive impairment, headache and seizures occurred in, respectively, 13, 5, and 2 patients. Cerebrospinal fluid analysis was abnormal in 15 patients. In MRI, FLAIR sequences showed ischemic infarcts in 20 patients and DWI showed acute infarct in 15 patients. Digital subtraction angiography was performed in 11 patients and disclosed proximal and distal multifocal stenosis in 10 patients along distal irregularities in different vascular territories in 7. For all of our patients, VW-MRI revealed a concentric contrast enhancement of arterial walls, localized in multiple vascular territories, suggesting angiitis. Abnormalities on digital subtraction angiography and/or MR-Angiography, and vessel wall-MRI were consistent in all patients. CONCLUSIONS: This report underlies the added value of vessel wall-MRI to the diagnosis of underlying intracranial vasculopathy, particularly primary angiitis of the central nervous system, without the use of invasive endovascular techniques and the yield of vessel wall-MRI in the work-up of cryptogenic stroke.

Neurosurgical Device Implantation for Neurooncologic Patients: What To Avoid?

BACKGROUND: Neurooncologic patients frequently require surgery, and neurosurgical devices are often implanted during neurosurgery. These devices could disturb oncologic follow-up by magnetic resonance imaging. METHODS: The authors describe the use of neurosurgical devices, such as bone substitutes, ventriculoperitoneal shunts, and titanium skull fixations, in neurooncologic patients. RESULTS: Acrylic cement cranioplasty, valve of ventriculoperitoneal shunt, and titanium skull fixations produced magnetic artifacts disturbing postoperative magnetic resonance imaging. CONCLUSIONS: The authors highlight the fact that all these neurosurgical devices implanted during surgery should be carefully evaluated to allow appropriate imaging follow-up for neurooncologic patients, which is a problem that remains underreported in the literature.

[Early postsurgical temozolomide treatment in newly diagnosed bad prognosis glioblastoma patients: Feasibility study]. / Administration précoce de témozolomide après chirurgie chez des patients ayant un glioblastome de mauvais pronostic : étude de faisabilité.

INTRODUCTION: Despite the combined adjuvant treatment of radiotherapy plus chemotherapy with temozolomide (TMZ) followed by 6 cycles of temozolomide after surgery, the prognosis of patients with glioblastoma remains poor. We conducted a monocentric prospective study to explore the tolerance and potential efficacy of an early temozolomide cycle after surgery. METHOD: Patients with newly diagnosed glioblastoma (unmutated IDH1) and of poor prognosis (age>50 years, biopsy or partial resection or unmethylated MGMT promoter) were prospectively included from June 2014 to 2017. They all received a cycle of 5 days of temozolomide between surgery and the combined adjuvant treatment. RESULTS: Twelve patients of median age 64.5 years (45-73) were included in the study. The median doses of temozolomide administered were respectively 265mg (225-300) for the early cycle; 130mg (110-150) for the concomitant treatment and 310mg (225-400) for the adjuvant one. Side effects during treatment were grade III lymphopenia, grade III neutropenia, fatigue and nausea/vomiting respectively in 4, 1, 7 and 5 patients. Progression-free survival and overall survival were respectively 90% and 91.7% at 6 months; 58.3 and 71.3% at 12 months; 31.1 and 71.3% at 18 months. CONCLUSION: Early postsurgical temozolomide treatment prior to standard adjuvant therapy for poor prognosis glioblastoma patients in our small prospective series presents toxicity and survival similar to those published in the literature for the general population of glioblastoma. These encouraging results should be confirmed by a multicentric study comparing this regiment with the standard treatment.

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

OBJECTIVES: In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). METHODS: In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. RESULTS: MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. INTERPRETATION: The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294.

Management of supratentorial recurrent low-grade glioma: A multidisciplinary experience in 35 adult patients.

The management of recurrent diffuse low-grade gliomas (LGGs) is controversial. In the present study, the multidisciplinary management of 35 patients with recurrent LGGs was retrospectively analyzed. Tumor progression or recurrence was defined by clinical, radiological and/or metabolic pejorative evolution. All patients were regularly followed up by a multidisciplinary neuro-oncological group at Hôpital Erasme. Patients with histologically confirmed supratentorial LGGs (7 astrocytoma, 22 oligodendrogliomas and 6 oligoastrocytomas) who had undergone surgery between August 2004 and November 2010 were included. A total of 3 patients exhibited no tumor progression (median follow-up (FU), 81 months; range, 68-108 months). Tumor recurrence occurred in the 32 remaining patients [progression-free survival (PFS), 26 months; range, 2-104 months]. In addition, 25/29 (86%) patients who received surgery alone underwent reoperation at the time of tumor recurrence, and high-grade transformation occurred in 6 of these patients (24%). Furthermore, 4/29 (14%) patients were treated with adjuvant therapy alone (3 chemotherapy and 1 radiotherapy). In the 19 patients with no high-grade transformation at reintervention, 3 received adjuvant therapy and 16 were regularly followed up through multimodal imaging. The PFS time of the patients who underwent reoperation with close FU (n=16) and for the patients receiving adjuvant therapy with or without surgery (n=7) at first recurrence was 10 and 24 months (P=0.005), respectively. However, no significant difference was observed for overall survival (P=0.403). At the time of this study, 22 of the 35 patients included were alive following a median FU time of 109 months (range, 55-136). The results of the present study could change the multidisciplinary approach used into a more aggressive approach with adjuvant therapy, with or without surgery, for the treatment of a select subpopulation of patients with LGGs at the first instance of tumor recurrence.