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We describe 2 patients with spinal cord compression that occurred in the course of biopsy-proven giant cell arteritis (GCA). One case was due to an epidural tumorlike inflammatory lesion, the other to a concentric inflammatory thickening of the meninges. Both patients were highly corticodependent; they had low-titer anti-neutrophil cytoplasmic antibodies but no antimyeloperoxidase or antiproteinase 3 autoantibodies. The diagnosis was established by surgical biopsy. The histological pattern was reminiscent of Wegener granulomatosis. Both patients experienced relapse, despite high doses of corticosteroids, and experienced remission after the introduction of cyclophosphamide. Intravenous immunoglobulin perfusions were added for 1 patient. To our knowledge, spinal cord compression by a spinal pseudotumor or inflammatory meningitis has not been reported in the course of GCA. An overlap syndrome between GCA and Wegener granulomatosis is discussed. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since magnetic resonance spectroscopic imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM., Methods: In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter., Results: One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% CI [42.5; 45.5]), median OS was 22.6 months (95% CI [18.9; 25.4]) versus 22.2 months (95% CI [18.3; 27.8]) for HD, and median progression-free survival was 8.6 (95% CI [6.8; 10.8]) versus 7.8 months (95% CI [6.3; 8.6]), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% CI [23.2; NR]) for HD patients versus 28.5 months (95% CI [21.1; 35.7]) for SD patients., Conclusion: The additional MRSI-guided irradiation dose totaling 72 Gy was well tolerated but did not improve OS in newly diagnosed GBM., Trial Registration: NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&rank=1., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Although perfusion magnetic resonance imaging (MRI) is widely used to identify pseudoprogression, this advanced technique lacks clinical reliability. Our aim was to develop a parameter assessing the hypervascularized fraction of glioblastomas based on volume analysis of dynamic susceptibility contrast-enhanced MRI and evaluate its performance in the diagnosis of pseudoprogression., Methods: Patients with primary glioblastoma showing lesion progression on the first follow-up MRI after chemoradiotherapy were enrolled retrospectively. On both initial and first follow-up MRIs, the leakage-corrected cerebral blood volume (CBV) maps were post-processed using the conventional hot-spot method and a volume method, after manual segmentation of the contrast-enhanced delineated lesion. The maximum CBV (rCBVmax) was calculated with both methods. Secondly, the threshold of 2 was applied to the CBV values contained in the entire segmented volume, defining our new parameter: %rCBV>2. The probability of pseudoprogression based on rCBVmax and %rCBV>2 was calculated in logistic regression models and diagnostic performance assessed by receiving operator characteristic curves., Results: Out of 25 patients, 11 (44%) were classified with pseudoprogression and 14 (56%) with true progression based on the Response Assessement in Neuro-Oncology criteria. rCBVmax was lower for pseudoprogression (3.4 vs. 7.6; p = 0.033) on early follow-up MRI. %rCBV>2, was lower for pseudoprogression on both initial (57.5% vs. 71.3%; p = 0.033) and early follow-up MRIs (22.1% vs. 51.8%; p = 0.0006). On early follow-up MRI, %rCBV>2 had the largest area under the curve for the diagnosis of pseudoprogression: 0.909 [0.725-0.986]., Conclusion: The fraction of hypervascularization of glioblastomas as assessed by %rCBV>2 was lower in tumours that subsequently developed pseudoprogression both on the initial and early follow-up MRIs. This fractional parameter may help identify pseudoprogression with greater accuracy than rCBVmax., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Despite a high variability, the hotspot method is widely used to calculate the cerebral blood volume (CBV) of glioblastomas on DSC-MRI. Our aim was to investigate inter- and intra-observer reproducibility of parameters calculated with the hotspot or a volume method and that of an original parameter assessing the fraction of pixels in the tumour volume displaying rCBV > 2: %rCBV > 2., Methods: Twenty-seven consecutive patients with untreated glioblastoma (age: 63, women: 11) were retrospectively included. Three observers calculated the maximum tumour CBV value (rCBVmax) normalized with a reference ROI in the contralateral white matter (CBVWM) with (i) the hotspot method and (ii) with a volume method following tumour segmentation on 3D contrast-enhanced T1-WI. From this volume method, %rCBV > 2 was also assessed. After 8-12 weeks, one observer repeated all delineations. Intraclass (ICC) and Lin's (LCC) correlation coefficients were used to determine reproducibility., Results: Inter-observer reproducibility of rCBVmax was fair with the hotspot and good with the volume method (ICC = 0.46 vs 0.65, p > 0.05). For CBVWM, it was fair with the hotspot and excellent with the volume method (0.53 vs 0.84, p < 0.05). Reproducibility of one pairwise combination of observers was significantly better for both rCBVmax and CBVWM (LCC = 0.33 vs 0.75; 0.52 vs 0.89, p < 0.05). %rCBV > 2 showed excellent inter- and intra-observer reproducibility (ICC = 0.94 and 0.91)., Conclusion: Calculated in glioblastomas with a volume method, rCBVmax and CBVWM yielded good to excellent reproducibility but only fair with the hotspot method. Overall, the volume analysis offers a highly reproducible parameter, %rCBV > 2, that could be promising during the follow-up of such heterogeneous tumours., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The purpose of this study was to investigate the possible benefit of repeat surgery on overall survival for patients with recurrent glioblastoma multiforme (GBM)., Methods: We performed a retrospective analysis of data from patients who presented with recurrent GBM over a 5-year period ( n = 157), comparing baseline characteristics and survival for patients who had at least 1 new tumor resection followed by chemotherapy (reoperation group, n = 59) and those who received medical treatment only (no-reoperation group, n = 98) for recurrence., Results: The baseline characteristics of the two groups differed in terms of WHO performance status (better in the reoperation group), mean age (60 years in the reoperation group vs. 65 years in the no-reoperation group), mean interval to recurrence (3 months later in the reoperation group than in the no-reoperation group) and more gross total resections in the reoperation group. Nevertheless, the patients in the reoperation group had a higher rate [32.8%] of sensorimotor deficits than those of the no-reoperation group [14.2]. There was no significant difference in sex; tumor localization, side, or extent; MGMT status; MIB-1 labeling index; or Karnofsky Performance Status [KPS] score. After adjustment for age, the WHO performance status, interval of recurrence, and extent of resection at the first operation, multivariate analysis showed that median survival was significantly better in the reoperation group than in the no-reoperation group (22.9 vs. 14.61 months, P < 0.05). After a total of 69 repeat operations in 59 patients (10 had 2 repeat surgeries), we noted 13 temporary and 20 permanent adverse postoperative events, yielding a permanent complication rate of 28.99% (20/69). There was also a statistically significant ( P = 0.029, Student's t -test) decrease in the mean KPS score after reoperation (mean preoperative KPS score of 89.34 vs. mean postoperative score of 84.91)., Conclusion: Our retrospective study suggests that repeat surgery may be beneficial for patients with GBM recurrence who have good functional status (WHO performance status 0 and 1), although the potential benefits must be weighed against the risk of permanent complications, which occurred in almost 30% of the patients who underwent repeat resection in this series., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Asian Journal of Neurosurgery.)

Background: Multiple sclerosis (MS) patients represent a population potentially affected by the intracerebral accumulation of gadolinium-based contrast agents (GBCA) due to repeated magnetic resonance imaging (MRI) performed during their lifetime; however, MRI is still the best tool to monitor MS inflammatory activity., Objective: This study aimed to evaluate the relevance of GBCA injections during the MRI follow-up of MS patients under natalizumab (Tysabri) treatment., Methods: The MRI data results were retrospectively reviewed in a monocentric study (University Hospital of Toulouse, France) from all consecutive patients treated with natalizumab from January 2014 to January 2017. For each examination during the whole MRI follow-up, new lesions (enhancing and non-enhancing) were analyzed., Results: A total of 129 patients were included in this study (65% female, mean age = 41 years, mean treatment duration 6.5 years, 50% positive for John Cunningham virus) and benefited from 735 MRIs with GBCA. Only 3 MRIs showed a new enhancing lesion, systematically encountered after treatment discontinuation., Conclusion: According to this study based on the clinical and radiological practice, the systematic use of GBCA seems of limited relevance in the MRI follow-up of asymptomatic patients treated continuously with natalizumab.

Background: In Moyamoya Angioplasty (MMA), increased apparent diffusion coefficient (ADC) in frontal white matter (WM) with a normal appearance has been associated with frontal hypoperfusion and executive dysfunction. Multiple burr-hole surgery enables the revascularization of large frontal areas., Goal: To assess the effect of multiple burr-hole surgery on the ADC and cognitive functions in adults with MMA., Methods: ADC was measured in 26 brain hemispheres of 14 consecutive adults with MMA (9 women, mean age ± SD: 38.1 ± 10.7 years) prior to and 6 months after burr-hole surgery. ADC was obtained from regions of interest located in frontal and posterior (temporo-occipital) normal-appearing WM. Ten patients had neuropsychological assessment that focused on executive and attentional functions before and after surgery., Results: Anterior and posterior ADC values did not differ before surgery (815.8 ± 60.1 vs. 812.1 ± 35.3 mm 2 /s, p = 0.88). After surgery, frontal ADC was lower than prior to surgery (789.9 ± 64.5 vs. 815.8 ± 60.1 mm 2 /s; p <0.001) whereas no change occurred in posterior ADC (p = 0.31). Trail-making test part B median z-score increased from - 1.47 to - 0.21 (p = 0.018), suggesting improved cognitive flexibility., Conclusion: In adults with MMA, indirect revascularization with burr-hole is followed by a decrease of ADC in normal-appearing frontal WM and may have improved some executive functions in the flexibility process. Change in ADC may reflect the improvement in cerebral perfusion after surgery. The measuring of ADC may be a promising tool in exploring potentially reversible microstructural WM damage related to hypoperfusion and cognitive change in MMA.

Background: Glioblastoma, a high-grade glial infiltrating tumor, is the most frequent malignant brain tumor in adults and carries a dismal prognosis. External beam radiotherapy (EBRT) increases overall survival but this is still low due to local relapses, mostly occurring in the irradiation field. As the ratio of spectra of choline/N acetyl aspartate> 2 (CNR2) on MR spectroscopic imaging has been described as predictive for the site of local relapse, we hypothesized that dose escalation on these regions would increase local control and hence global survival., Methods/design: In this multicenter prospective phase III trial for newly diagnosed glioblastoma, 220 patients having undergone biopsy or surgery are planned for randomization to two arms. Arm A is the Stupp protocol (EBRT 60 Gy on contrast enhancement + 2 cm margin with concomitant temozolomide (TMZ) and 6 months of TMZ maintenance); Arm B is the same treatment with an additional simultaneous integrated boost of intensity-modulated radiotherapy (IMRT) of 72Gy/2.4Gy delivered on the MR spectroscopic imaging metabolic volumes of CHO/NAA > 2 and contrast-enhancing lesions or resection cavity. Stratification is performed on surgical and MGMT status., Discussion: This is a dose-painting trial, i.e. delivery of heterogeneous dose guided by metabolic imaging. The principal endpoint is overall survival. An online prospective quality control of volumes and dose is performed in the experimental arm. The study will yield a large amount of longitudinal multimodal MR imaging data including planning CT, radiotherapy dosimetry, MR spectroscopic, diffusion and perfusion imaging., Trial Registration: NCT01507506 , registration date December 20, 2011.

To assess the value of T2* dynamic-susceptibility contrast MRI (DSC-MRI) and diffusion-weighted imaging (DWI) to predict the glioblastoma relapse sites after chemoradiation. From a cohort of 44 patients, primarily treated with radiotherapy (60 Gy) and concomitant temozolomide for glioblastoma, who were included in the reference arm of a prospective clinical trial (NCT01507506), 15 patients relapsed and their imaging data were analyzed. All patients underwent anatomical MRI, DSC-MRI and DWI before radiotherapy and every 2 months thereafter until relapse. Voxels within the sites of relapse were correlated with their perfusion and/or diffusion abnormality (PDA) pretreatment status after rigid co-registration. The relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were used as biomarkers. Several PDA areas were thresholded: hyperperfused voxels using a 1.75 fixed rCBV threshold (HP t ); hypoperfused (hP g ) and hyperperfused (HP g ) voxels using a histogram-based Gaussian method; diffusion-restricted voxels (DR g ); and HP g voxels with diffusion restriction (HP g &DR g ). Two sets of voxels (2,459,483 and 2,073,880) were analyzed according to these thresholding methods. Positive predictive values (PPV) of PDA voxels were low (between 9.5 and 31.9 %). The best PPV was obtained with HP g &DR g voxels within the FLAIR hyperintensity, as 18.3 % of voxels without initial PDA were within relapse sites, versus 31.9 % with initial PDA (p < 0.0001). This prospective study suggests that DSC and/or DWI-MRI do not predict the glioblastoma relapse sites. However, further investigations with new methodological approaches are needed to better understand the role of these modalities in the prediction of glioblastoma relapse sites.

We previously showed that the farnesyl transferase inihibitor, Tipifarnib induced vascularization normalization, oxygenation and radiosensitization in a pre-clinical glioblastoma (GBM) model. The aim of this study was to assess by dynamic-susceptibility-contrast MRI (DSC-MRI) the effect of radiotherapy (RT) and Tipifarnib combination on tumor perfusion in GBM patients. Eighteen patients with newly diagnosed GBM, enrolled in a phase I-II clinical trial associating RT with Tipifarnib, underwent anatomical MR imaging and DSC-MRI before (M0) and two months after treatment (M2). Anatomic volumes of interest (VOIs) were delineated according to contrast-enhanced and hyper-intense signal areas on T1-Gd and T2 images, respectively. Perfusion variations between M0 and M2 were assessed with median relative cerebral blood volume (rCBV) inside these VOIs. Another voxel by voxel analysis of CBV values classified 405,117 tumor voxels into High&#95;, Normal&#95; and Low&#95;CBVTUMOR according to the distribution of CBV in the contralateral normal tissue. These three categories of CBVTUMOR voxels were color-coded over anatomical MRI. Variations of median rCBV were significantly different for two groups of patients (P < 0.013): rCBV decreased when initial rCBV was ≥ 1.0 (Group&#95;rCBV&#95;M0 > 1) and rCBV increased when initial rCBV was < 1.0 (Group&#95;rCBV&#95;M0 < 1). Mapping of color-coded voxels provided additional spatial and quantitative information about tumor perfusion: Group&#95;rCBV&#95;M0 > 1 presented a significant decrease of High&#95;CBVTUMOR volume (P = 0.015) simultaneously with a significant increase of Normal&#95;CBVTUMOR volume (P = 0.009) after treatment. Group&#95;rCBV&#95;M0 < 1 presented a decrease of Low&#95;CBVTUMOR volume with an increase of Normal&#95; and High&#95;CBV TUMOR volume after treatment. Pre and post-treatment CBV measurements with DSC-MRI characterized tumor perfusion evolution in GBM patients treated with RT combined to Tipifarnib; showing variations in favour of tumor perfusion normalization in agreement with our pre-clinical results of vascular normalization.

Purpose: Because lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to-N-acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D-(1)H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM)., Methods and Materials: Fourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis of the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: (1) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N-acetyl-aspartate (NAA) ratio ≥ 2 (CNR2); and (2) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence., Results: A LNR of ≥ 0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different from those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm(3); range: 6-49 cm(3)). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR (P<.01)., Conclusions: Pre-RT LNR-0.4 in GBM indicates tumor areas that are likely to relapse. Further investigations are needed to confirm lactate imaging as a tool to define additional biological target volumes for dose painting., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Purpose: Patterns of DWI findings that predict recurrent ischemic events after TIA are well-established, but similar assessments of intracranial MRA findings are not available. We sought to determine the imaging characteristics of MRA that are predictive of early recurrent stroke/TIA in patients with TIA., Materials and Methods: We performed a retrospective analysis of 129 consecutive patients with a clinical diagnosis of TIA in whom MR imaging was done within 24 hours of symptom onset. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of >50% stenosis or occlusion of symptomatic intracranial arteries for recurrent stroke/TIA at 7 days after TIA. We used logistic regression analysis to adjust for the clinical ABCD(2) score. We performed this analysis for symptomatic steno-occlusive lesions at any site and symptomatic steno-occlusive lesions on proximal large intracranial arteries (internal carotid artery, vertebral artery, basilar artery, and circle of Willis)., Results: Forty-two (32.5%) patients had acute ischemic lesions on DWI; 16 (12.4%) had significant MRA lesions, of which 11 (8.5%) were on proximal vessels. Nine patients had early recurrence (TIA, 7; minor stroke, 2). Only patients with proximal MRA lesions were at higher risk of early recurrence independent of the ABCD(2) score (adjusted odds ratio, 5.5; 95% confidence interval, 1.1-27.8; P = .04)., Conclusions: Proximal lesions of cerebral arteries seen on MRA were predictive of recurrent stroke/TIA at 7 days. These findings suggest that MRA could be used to improve the selection of patients with TIA at high risk of early recurrent stroke/TIA.