Publications by authors named "Alex Rovira"

252 Publications

Effect of Changes in MS Diagnostic Criteria Over 25 Years on Time to Treatment and Prognosis in Patients With Clinically Isolated Syndrome.

Neurology 2021 Sep 14. Epub 2021 Sep 14.

Centre d'Esclerosi Múltiple de Catalunya (Cemcat). Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron. Universitat Autònoma de Barcelona. Barcelona, Spain.

Objectives: To explore whether time to diagnosis, time to treatment initiation and age to reach disability milestones has changed in patients with clinically isolated syndrome (CIS) according to different multiple sclerosis (MS)-diagnostic criteria periods.

Methods: Retrospective study based on data prospective collected from the Barcelona-CIS cohort between 1994 and 2020. Patients were classified into five periods according to different MS criteria, and the time to MS diagnosis and treatment initiation were evaluated. The age at which MS patients reached an EDSS ≥3.0 was assessed by Cox regression analysis according to diagnostic criteria periods. Finally, in order to remove the classical "Will Rogers" phenomenon by which the use of different MS criteria over time might result on changes of prognosis, 2017 McDonald criteria were applied and age at EDSS ≥ 3.0 was also assessed by Cox regression.

Results: 1174 patients were included. The median time from CIS to MS diagnosis, and from CIS to treatment initiation showed a 77% and 82 reduction from the Poser to the McDonald 2017 diagnostic criteria periods, respectively. Patients of a given age diagnosed in more recent diagnostic criteria periods had a lower risk of reaching EDSS ≥3.0 than patients of the same age diagnosed in earlier diagnostic periods (reference category Poser period): Adjusted hazard ratio (aHR) 0.47 (95% confidence interval 0.24-0.90) for McDonald 2001, aHR 0.25 (0.12-0.54) for McDonald 2005, aHR 0.30 (0.12-0.75) for McDonald 2010 and aHR 0.07 (0.01-0.45) for McDonald 2017. Early-treatment patients displayed an aHR of 0.53 (0.33-0.85) of reaching age at EDSS ≥3.0 compared to late-treatment. Changes in prognosis together with early-treatment effect were maintained after excluding possible bias derived from the use of different diagnostic criteria over time (so called, "Will Rogers" phenomenon) CONCLUSION: A continuous decrease in the time to MS diagnosis and treatment initiation were observed across diagnostic criteria periods. Overall, patients diagnosed in more recent diagnostic criteria periods displayed a lower risk of reaching disability. Importantly, the prognostic improvement is maintained after discarding the "Will Rogers" phenomenon, and early treatment appears to be the most likely contributing factor.
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http://dx.doi.org/10.1212/WNL.0000000000012726DOI Listing
September 2021

Quantification of Cervical Cord Cross-Sectional Area: Which Acquisition, Vertebra Level, and Analysis Software? A Multicenter Repeatability Study on a Traveling Healthy Volunteer.

Front Neurol 2021 4;12:693333. Epub 2021 Aug 4.

Department of Radiology and Nuclear Medicine, Multiple Sclerosis Center Amsterdam, Amsterdam Neuroscience Amsterdam University Medical Centers (UMC), Vrije Universiteit Medical Center (VUmc), Amsterdam, Netherlands.

Considerable spinal cord (SC) atrophy occurs in multiple sclerosis (MS). While MRI-based techniques for SC cross-sectional area (CSA) quantification have improved over time, there is no common agreement on whether to measure at single vertebral levels or across larger regions and whether upper SC CSA can be reliably measured from brain images. To compare in a multicenter setting three CSA measurement methods in terms of repeatability at different anatomical levels. To analyze the agreement between measurements performed on the cervical cord and on brain MRI. One healthy volunteer was scanned three times on the same day in six sites (three scanner vendors) using a 3T MRI protocol including sagittal 3D T1-weighted imaging of the brain (covering the upper cervical cord) and of the SC. Images were analyzed using two semiautomated methods [NeuroQLab (NQL) and the Active Surface Model (ASM)] and the fully automated Spinal Cord Toolbox (SCT) on different vertebral levels (C1-C2; C2/3) on SC and brain images and the entire cervical cord (C1-C7) on SC images only. CSA estimates were significantly smaller using SCT compared to NQL and ASM ( < 0.001), regardless of the cord level. Inter-scanner repeatability was best in C1-C7: coefficients of variation for NQL, ASM, and SCT: 0.4, 0.6, and 1.0%, respectively. CSAs estimated in brain MRI were slightly lower than in SC MRI (all ≤ 0.006 at the C1-C2 level). Despite protocol harmonization between the centers with regard to image resolution and use of high-contrast 3D T1-weighted sequences, the variability of CSA was partly scanner dependent probably due to differences in scanner geometry, coil design, and details of the MRI parameter settings. For CSA quantification, dedicated isotropic SC MRI should be acquired, which yielded best repeatability in the entire cervical cord. In the upper part of the cervical cord, use of brain MRI scans entailed only a minor loss of CSA repeatability compared to SC MRI. Due to systematic differences between scanners and the CSA quantification software, both should be kept constant within a study. The MRI dataset of this study is available publicly to test new analysis approaches.
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http://dx.doi.org/10.3389/fneur.2021.693333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371197PMC
August 2021

Generic acquisition protocol for quantitative MRI of the spinal cord.

Nat Protoc 2021 Aug 16. Epub 2021 Aug 16.

MR Clinical Science, Philips Healthcare, Markham, Ontario, Canada.

Quantitative spinal cord (SC) magnetic resonance imaging (MRI) presents many challenges, including a lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for users of 3T MRI systems from the three main manufacturers: GE, Philips and Siemens. The protocol provides guidance for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area computation, multi-echo gradient echo for gray matter cross-sectional area, and magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. In a companion paper from the same authors, the spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects. The key details of the spine generic protocol are also available in an open-access document that can be found at https://github.com/spine-generic/protocols . The protocol will serve as a starting point for researchers and clinicians implementing new SC imaging initiatives so that, in the future, inclusion of the SC in neuroimaging protocols will be more common. The protocol could be implemented by any trained MR technician or by a researcher/clinician familiar with MRI acquisition.
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http://dx.doi.org/10.1038/s41596-021-00588-0DOI Listing
August 2021

Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers.

Sci Data 2021 08 16;8(1):219. Epub 2021 Aug 16.

MR Clinical Science, Philips Healthcare, Markham, ON, Canada.

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/ . The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.
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http://dx.doi.org/10.1038/s41597-021-00941-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368310PMC
August 2021

Magnetic resonance imaging findings in focal-onset status epilepticus.

Eur J Neurol 2021 Aug 14. Epub 2021 Aug 14.

Neuroradiology Section, Radiology Department, Vall d'Hebron Hospital, Barcelona, Spain.

Background And Purpose: Magnetic resonance imaging (MRI) is commonly used in the diagnostic work-up for status epilepticus (SE). The purpose of this study was to characterize MRI features in SE patients and determine their association with clinical and electroencephalography (EEG) findings. The mid-term consequences of baseline MRI features were also analysed.

Methods: This is a prospective study including consecutive patients with SE who underwent brain MRI within 240 h after SE onset. The MRI protocol included T1-weighted (T1WI), T2-weighted (T2W), fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences. Follow-up MRI was performed after SE resolution in some patients.

Results: Sixty patients (56.7% men, mean age 58.3 years) were included. SE-related MRI abnormalities were seen in 31 (51.7%), manifesting as hyperintensities on T2W/FLAIR imaging (58.1%) and DWI (74.2%) sequences. Hippocampal and pulvinar involvement was seen in 58.0% and 25.8% of patients, respectively. MRI abnormalities were associated with a longer SE duration (p = 0.013) and the presence of lateralized periodic discharges (LPDs) on EEG (p < 0.001). Amongst the 33 follow-up MRIs, nine (27.3%) showed mesial temporal sclerosis (MTS), which was associated with severe clinical status (p = 0.031), hippocampal oedema (p = 0.001) and LPDs (p = 0.001) at baseline. A poorer clinical outcome was associated with baseline T2W/FLAIR imaging hyperintensities (p = 0.003).

Conclusion: MRI showed abnormalities in more than half of SE patients. A longer SE duration and LPDs on EEG were associated with SE-related MRI abnormalities and the development of MTS.
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http://dx.doi.org/10.1111/ene.15065DOI Listing
August 2021

Drug-related demyelinating syndromes: understanding risk factors, pathophysiological mechanisms and magnetic resonance imaging findings.

Mult Scler Relat Disord 2021 Jul 21;55:103146. Epub 2021 Jul 21.

Departamento de Radiologia e Oncologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. Electronic address:

Some drugs and medications can precipitate immune system deregulations, which might be confused with recurrent demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMO), exacerbations of an existing disease, neoplastic lesions or other conditions. In this narrative review we describe some of the most relevant drugs and medications associated with iatrogenic demyelination. The anthelminthic agent levamisole is a frequent cocaine adulterant and can precipitate an exacerbated immune response attacking the central nervous system (CNS). High-efficacy multiple sclerosis (MS) drugs might induce a selective CNS immunosuppression, making it susceptible for opportunistic infections that course with demyelination, such as progressive multifocal leukoencephalopathy. Sometimes, the interruption of a high-efficacy drug to treat MS can induce a rapid CNS reentry of lymphocytes, exacerbating demyelinating processes and triggering rebound syndromes. Furthermore, selective cytokines inhibition, such as anti-TNFα agents, might induce an imbalance between cell death and proliferation inducing a paradoxical increase of CNS tumor necrosis factor (TNF), affecting the activity of lymphocytes, microglia and macrophages, triggering aberrant inflammation and demyelination. Immune checkpoint inhibitors are a new class of antineoplastic drugs that enhance the immune response against tumor cells by an upregulation of T-cell activity. However, this hyperactivation of the immune system might be associated with induction of unwanted autoimmune responses. In this paper we review the risk factors, the possible pathological mechanisms and the magnetic resonance imaging (MRI) findings of these drug-related demyelinating syndromes.
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http://dx.doi.org/10.1016/j.msard.2021.103146DOI Listing
July 2021

Beyond McDonald: updated perspectives on MRI diagnosis of multiple sclerosis.

Expert Rev Neurother 2021 Aug 27;21(8):895-911. Epub 2021 Jul 27.

Section of Neuroradiology (Department of Radiology), Hospital Universitari Vall d'Hebron, Universitat Autònoma De Barcelona, Barcelona, Spain.

Introduction: Magnetic resonance imaging (MRI) is an essential paraclinical test to establish an accurate and early diagnosis of multiple sclerosis (MS), which is based on the application of the McDonald criteria.

Areas Covered: The objective of this article is to analyze, based on publicly available database since the publication of the 2017 McDonald diagnostic criteria, the clinical impact of these criteria, to discuss the potential inclusion within these criteria of the optic nerve to demonstrate dissemination in space, and to guide the acquisition and interpretation of MRI scans for diagnostic purposes. Finally, the authors will review emerging MRI features that could improve the specificity of MRI in the diagnosis of MS and consequently minimize the misdiagnosis of this disease.

Expert Opinion: Although the optic nerve has not been included as one of the topographies required to demonstrate demyelinating lesion disseminated in space in the 2017 McDonald criteria, new studies seem to show some improvement in the sensitivity of these criteria when this topography is considered. New radiological findings such as the central vein sign and iron rims, should be considered within the typical MRI features of this disease with the objective of minimizing MRI-based diagnostic errors.
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http://dx.doi.org/10.1080/14737175.2021.1957832DOI Listing
August 2021

Cortical metabolic and structural differences in patients with chronic migraine. An exploratory FDG-PET and MRI study.

J Headache Pain 2021 Jul 17;22(1):75. Epub 2021 Jul 17.

Headache and Craniofacial Pain Unit, Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain.

Background: To describe interictal brain structural and metabolic differences between patients with episodic migraine (EM), chronic migraine (CM) and healthy controls (HC).

Methods: This is an exploratory study including right-handed age-matched women with EM, CM and HC. On the same day, a sequential interictal scan was performed with FDG-PET and MRI. 3D T1-weighted images were segmented with FreeSurfer, normalized to a reference atlas and the mean values of metabolism, cortical thickness (CTh) and local gyrification index (IGI) were determined. Groups were compared using age-adjusted linear models, corrected for multiple comparisons. FDG-PET measurements between groups were also analysed adjusting by patient's age, CTh and lGI. The variables independently associated with diagnosis were obtained using a logistic regression analysis.

Results: Fifteen patients (8 EM, 7 CM) and 11 HC were included. Morphometric data showed an increased CTh in 6 frontal areas (L/R-Caudal Middle Frontal, L/R-Rostral Middle Frontal, L-Medial Orbitofrontal and L-Superior Frontal) in CM patients compared to HC without differences for IGI. The structural adjusted analysis in CM showed a statistically significantly hypometabolism in 9 frontal areas (L-Lateral Orbitofrontal, L/R-Medial Orbitofrontal, L-Frontal Superior, R-Frontal pole, R-Parts Triangularis, L/R-Paracentral and R-Precentral) and 7 temporal areas (L/R-Insula, L/R-Inferior temporal, L/R-Temporal pole and R-Banks superior temporal sulcus) compared to HC. EM patients presented intermediate metabolic values ​​between EM and HC (non-significant).

Conclusions: CM patients showed frontotemporal hypometabolism and increased frontal cortical thickness when compared to HC that may explain some cognitive and behavioural pain-processing and sensory integration alterations in CM patients. Combined information from sequential or simultaneous PET and MRI could optimize the study of complex functional neurological disorders such as migraine.
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http://dx.doi.org/10.1186/s10194-021-01289-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285838PMC
July 2021

2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis.

Lancet Neurol 2021 08 14;20(8):653-670. Epub 2021 Jun 14.

Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address:

The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centres guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial relevant advances in knowledge, including the 2017 revisions of the McDonald diagnostic criteria, renewed safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MRI for diagnostic, prognostic, and monitoring purposes. These developments suggest a changing role of MRI for the management of patients with multiple sclerosis. This 2021 revision of the previous guidelines on MRI use for patients with multiple sclerosis merges recommendations from the Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centres, and North American Imaging in Multiple Sclerosis Cooperative, and translates research findings into clinical practice to improve the use of MRI for diagnosis, prognosis, and monitoring of individuals with multiple sclerosis. We recommend changes in MRI acquisition protocols, such as emphasising the value of three dimensional-fluid-attenuated inversion recovery as the core brain pulse sequence to improve diagnostic accuracy and ability to identify new lesions to monitor treatment effectiveness, and we provide recommendations for the judicious use of gadolinium-based contrast agents for specific clinical purposes. Additionally, we extend the recommendations to the use of MRI in patients with multiple sclerosis in childhood, during pregnancy, and in the post-partum period. Finally, we discuss promising MRI approaches that might deserve introduction into clinical practice in the near future.
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http://dx.doi.org/10.1016/S1474-4422(21)00095-8DOI Listing
August 2021

Assessing the Accuracy and Reproducibility of PARIETAL: A Deep Learning Brain Extraction Algorithm.

J Magn Reson Imaging 2021 Jun 16. Epub 2021 Jun 16.

Research Institute of Computer Vision and Robotics, University of Girona, Girona, Spain.

Background: Manual brain extraction from magnetic resonance (MR) images is time-consuming and prone to intra- and inter-rater variability. Several automated approaches have been developed to alleviate these constraints, including deep learning pipelines. However, these methods tend to reduce their performance in unseen magnetic resonance imaging (MRI) scanner vendors and different imaging protocols.

Purpose: To present and evaluate for clinical use PARIETAL, a pre-trained deep learning brain extraction method. We compare its reproducibility in a scan/rescan analysis and its robustness among scanners of different manufacturers.

Study Type: Retrospective.

Population: Twenty-one subjects (12 women) with age range 22-48 years acquired using three different MRI scanner machines including scan/rescan in each of them.

Field Strength/sequence: T1-weighted images acquired in a 3-T Siemens with magnetization prepared rapid gradient-echo sequence and two 1.5 T scanners, Philips and GE, with spin-echo and spoiled gradient-recalled (SPGR) sequences, respectively.

Assessment: Analysis of the intracranial cavity volumes obtained for each subject on the three different scanners and the scan/rescan acquisitions.

Statistical Tests: Parametric permutation tests of the differences in volumes to rank and statistically evaluate the performance of PARIETAL compared to state-of-the-art methods.

Results: The mean absolute intracranial volume differences obtained by PARIETAL in the scan/rescan analysis were 1.88 mL, 3.91 mL, and 4.71 mL for Siemens, GE, and Philips scanners, respectively. PARIETAL was the best-ranked method on Siemens and GE scanners, while decreasing to Rank 2 on the Philips images. Intracranial differences for the same subject between scanners were 5.46 mL, 27.16 mL, and 30.44 mL for GE/Philips, Siemens/Philips, and Siemens/GE comparison, respectively. The permutation tests revealed that PARIETAL was always in Rank 1, obtaining the most similar volumetric results between scanners.

Data Conclusion: PARIETAL accurately segments the brain and it generalizes to images acquired at different sites without the need of training or fine-tuning it again. PARIETAL is publicly available.

Level Of Evidence: 2 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27776DOI Listing
June 2021

Quantitative comparison of subcortical and ventricular volumetry derived from MPRAGE and MP2RAGE images using different brain morphometry software.

MAGMA 2021 May 29. Epub 2021 May 29.

Neuroradiology Section, Department of Radiology (Institut de Diagnòstic per la Imatge), Vall d'Hebron Hospital Universitari, Pg Vall d'Hebron 119-129, 08035, Barcelona, Spain.

Objective: In brain volume assessment with MR imaging, it is of interest to know the effects of the pulse sequence and software used, to determine whether they provide equivalent data. The aim of this study was to compare cross-sectional volumes of subcortical and ventricular structures and their repeatability derived from MP2RAGE and MPRAGE images using MorphoBox, and FIRST or ALVIN.

Materials And Methods: MPRAGE and MP2RAGE T1-weighted images were obtained from 24 healthy volunteers. Back-to-back scans were performed in 12 of them. Volumes, coefficients of variation, concordance, and correlations were determined.

Results: Significant differences were found for volumes derived from MorphoBox and FIRST. Ventricular volumes determined by MorphoBox and ALVIN were similar. Differences between volumes obtained using MPRAGE and MP2RAGE were significant for a few regions. Coefficients of variation, ranged from 0.2 to 9.1%, showed a significant inverse correlation with the mean volume. There was a correlation between volume measures, but agreement was rated as poor for most regions.

Conclusion: MP2RAGE sequences and MorphoBox are valid options for assessing subcortical and ventricular volumes, in the same way as MPRAGE and FIRST or ALVIN, accepted tools for clinical research. However, caution is needed when comparing volumes obtained with different tools.
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http://dx.doi.org/10.1007/s10334-021-00933-0DOI Listing
May 2021

Transductive Transfer Learning for Domain Adaptation in Brain Magnetic Resonance Image Segmentation.

Front Neurosci 2021 29;15:608808. Epub 2021 Apr 29.

Institute of Computer Vision and Robotics, University of Girona, Girona, Spain.

Segmentation of brain images from Magnetic Resonance Images (MRI) is an indispensable step in clinical practice. Morphological changes of sub-cortical brain structures and quantification of brain lesions are considered biomarkers of neurological and neurodegenerative disorders and used for diagnosis, treatment planning, and monitoring disease progression. In recent years, deep learning methods showed an outstanding performance in medical image segmentation. However, these methods suffer from generalisability problem due to inter-centre and inter-scanner variabilities of the MRI images. The main objective of the study is to develop an automated deep learning segmentation approach that is accurate and robust to the variabilities in scanner and acquisition protocols. In this paper, we propose a transductive transfer learning approach for domain adaptation to reduce the domain-shift effect in brain MRI segmentation. The transductive scenario assumes that there are sets of images from two different domains: (1) source-images with manually annotated labels; and (2) target-images without expert annotations. Then, the network is jointly optimised integrating both source and target images into the transductive training process to segment the regions of interest and to minimise the domain-shift effect. We proposed to use a histogram loss in the feature level to carry out the latter optimisation problem. In order to demonstrate the benefit of the proposed approach, the method has been tested in two different brain MRI image segmentation problems using multi-centre and multi-scanner databases for: (1) sub-cortical brain structure segmentation; and (2) white matter hyperintensities segmentation. The experiments showed that the segmentation performance of a pre-trained model could be significantly improved by up to 10%. For the first segmentation problem it was possible to achieve a maximum improvement from 0.680 to 0.799 in average Dice Similarity Coefficient (DSC) metric and for the second problem the average DSC improved from 0.504 to 0.602. Moreover, the improvements after domain adaptation were on par or showed better performance compared to the commonly used traditional unsupervised segmentation methods (FIRST and LST), also achieving faster execution time. Taking this into account, this work presents one more step toward the practical implementation of deep learning algorithms into the clinical routine.
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http://dx.doi.org/10.3389/fnins.2021.608808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116893PMC
April 2021

Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis.

Brain 2021 06;144(5):1296-1311

Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.

Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response.
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http://dx.doi.org/10.1093/brain/awab029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219362PMC
June 2021

Identification of patients with relapsing multiple sclerosis eligible for high-efficacy therapies.

Neurodegener Dis Manag 2021 06 10;11(3):251-261. Epub 2021 May 10.

Neurology Department, Hospital Universitario de Cruces, Barakaldo, 48903, Spain.

Relapsing multiple sclerosis (RMS) presents a highly variable clinical evolution among patients, and its management should be personalized. Although there is no cure at present, effective disease-modifying therapies (DMTs) are available. Selection of the most appropriate DMT for each patient is influenced by several clinical, radiological and demographic aspects as well as personal preferences that, at times, are not covered in the regulatory criteria. This may be a source of difficulty, especially in certain situations where so-called 'high-efficacy DMTs' (usually considered second-line) could be of greater benefit to the patient. In this narrative review, we discuss evidence and experience, and propose a pragmatic guidance on decision-making with respect to the indication and management of high-efficacy DMT in adult patients with RMS based on expert opinion.
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http://dx.doi.org/10.2217/nmt-2020-0049DOI Listing
June 2021

CSF chitinase 3-like 1 is associated with iron rims in patients with a first demyelinating event.

Mult Scler 2021 Apr 19:13524585211010082. Epub 2021 Apr 19.

Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background: Chronic active lesions with iron rims have prognostic implications in patients with multiple sclerosis.

Objective: To assess the relationship between iron rims and levels of chitinase 3-like 1 (CHI3L1), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with a first demyelinating event.

Methods: Iron rims were identified using 3T susceptibility-weighted imaging. Serum NfL and GFAP levels were measured by single-molecule array assays. CSF (cerebrospinal fluid) CHI3L1 levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Sixty-one patients were included in the study. The presence of iron rims was associated with higher T2 lesion volume and higher number of gadolinium-enhancing lesions. In univariable analysis, having ⩾2 iron rims (vs 0) was associated with increased CSF CHI3L1 levels (β = 1.41; 95% confidence interval (CI) = 1.10-1.79; < 0.01) and serum NfL levels (β = 2.30; 95% CI = 1.47-3.60; < 0.01). In multivariable analysis, however, only CSF CHI3L1 levels remained significantly associated with the presence of iron rim lesions (β = 1.45; 95% CI = 1.11-1.90; < 0.01). The presence of ⩾2 iron rims was not associated with increased serum GFAP levels in univariable or multivariable analyses.

Conclusion: These findings support an important contribution of activated microglia/macrophages to the pathophysiology of chronic active lesions with iron rims in patients with a first demyelinating event.
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http://dx.doi.org/10.1177/13524585211010082DOI Listing
April 2021

MRI findings in cervical spondylotic myelopathy with gadolinium enhancement: Review of seven cases.

BJR Case Rep 2021 Apr 5;7(2):20200133. Epub 2021 Jan 5.

Hospital Universitario Vall d'Hebron, Barcelona, Spain.

Cervical spondylotic myelopathy (CSM) is a clinical syndrome secondary to a spinal cord compression due to cervical spondylosis. In some cases, conventional MRI typically shows an intramedullary hyperintense signal on T2W imaging and contrast enhancement on post-gadolinium T1W imaging. We report a series of seven patients with CSM who had typical clinical presentation and imaging findings on T2W and contrast-enhanced T1W sequences. The imaging findings included degenerative changes of the cervical spine, intramedullary T2-signal hyperintensity, and an intramedullary enhancement on post-gadolinium T1W images. Our results support the statement that the presence of an intramedullary gadolinium-enhancement with a flat transverse pancake-like pattern (on sagittal images) and a circumferential pattern (on axial images), located within a T2-signal abnormality, in patients with cervical spondylosis and clinical myelopathy is indicative of spondylosis as the cause of the myelopathy.
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http://dx.doi.org/10.1259/bjrcr.20200133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008469PMC
April 2021

Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA-ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.
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http://dx.doi.org/10.3390/jcm10050989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957864PMC
March 2021

Scoring the 10-year risk of ambulatory disability in multiple sclerosis: the RoAD score.

Eur J Neurol 2021 08 19;28(8):2533-2542. Epub 2021 Apr 19.

Centre d'Esclerosi Multiple de Catalunya (Cemcat), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.

Background And Purpose: Both baseline prognostic factors and short-term predictors of treatment response can influence the long-term risk of disability accumulation in patients with relapsing-remitting multiple sclerosis (RRMS). The objective was to develop and validate a scoring system combining baseline prognostic factors and 1-year variables of treatment response into a single numeric score predicting the long-term risk of disability.

Methods: We analysed two independent datasets of patients with RRMS who started interferon beta or glatiramer acetate, had an Expanded Disability Status Scale (EDSS) score <4.0 at treatment start and were followed for at least 10 years. The first dataset ('training set') included patients attending three MS centres in Italy and served as a framework to create the so-called RoAD score (Risk of Ambulatory Disability). The second ('validation set') included a cohort of patients followed in Barcelona, Spain, to explore the performance of the RoAD score in predicting the risk of reaching an EDSS score ≥6.0.

Results: The RoAD score (ranging from 0 to 8) derived from the training set (n = 1225), was based on demographic (age), clinical baseline prognostic factors (disease duration, EDSS) and 1-year predictors of treatment response (number of relapses, presence of gadolinium enhancement and new T2 lesions). The best cut-off score for discriminating patients at higher risk of reaching the disability milestone was ≥4. When applied to the validation set (n = 296), patients with a RoAD score ≥4 had an approximately 4-fold increased risk for reaching the disability milestone (p < 0.001).

Discussion: The RoAD score is proposed as an useful tool to predict individual prognosis and optimize treatment strategy of patients with RRMS.
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http://dx.doi.org/10.1111/ene.14845DOI Listing
August 2021

Menopause does not modify disability trajectories in a longitudinal cohort of women with clinically isolated syndrome and multiple sclerosis followed from disease onset.

Eur J Neurol 2021 Feb 20. Epub 2021 Feb 20.

Neurology-Neuroimmunology Department, Centro de Esclerosis Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background And Purpose: To evaluate the effect of menopause on disability accumulation in women followed from their clinically isolated syndrome (CIS).

Methods: We examined the longitudinal changes in Expanded Disability Status Scale (EDSS) scores from CIS until the last follow-up in women belonging to the Barcelona CIS prospective cohort, followed through their menopausal transition. The analysis is based on 13,718 EDSS measurements, with an average of 28 EDSS measurements per patient. Differences in EDSS trajectories between menopausal and nonmenopausal women, controlling for age and disease duration, were evaluated. We performed two sensitivity analyses in women with confirmed MS and in those experiencing early menopause.

Results: From 764 eligible women, 496 (65%) responded to the questionnaire, and 74 (14.9%) reached menopause over the follow-up. We did not find a significant inflection point in EDSS trajectories around menopause (slope change -0.009; 95% CI -0.066; 0.046). The annual increase in EDSS over the complete course of the disease was significantly higher in menopausal women (0.049; 95% CI, 0.026-0.074) versus nonmenopausal (0.019; 95% CI, 0.008-0.031; interaction p value 0.025). This difference was lost when controlling for age and disease duration (EDSS annual increase of 0.059; 95% CI, 0.025-0.094 vs. 0.038; 95% CI, 0.021-0.057, respectively; interaction p value 0.321). No inflection point was detected when the analysis was restricted to women with confirmed MS or with earlier menopause.

Conclusions: Menopause is not associated with an increased risk of disability in a CIS population, considering EDSS trajectories throughout the course of the disease together with age and disease duration.
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http://dx.doi.org/10.1111/ene.14782DOI Listing
February 2021

The frequency and characteristics of MS misdiagnosis in patients referred to the multiple sclerosis centre of Catalonia.

Mult Scler 2021 05 10;27(6):913-921. Epub 2021 Feb 10.

Section of Neuroradiology, Radiology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background: Multiple sclerosis (MS) misdiagnosis may cause physical and emotional damage to patients.

Objectives: The objective of this study is to determine the frequency and characteristics of MS misdiagnosis in patients referred to the Multiple Sclerosis Centre of Catalonia.

Methods: We designed a prospective study including all new consecutive patients referred to our centre between July 2017 and June 2018. Instances of misdiagnosis were identified, and referral diagnosis and final diagnosis were compared after 1 year of follow-up. Association of misdiagnosis with magnetic resonance imaging (MRI) findings, presence of comorbidities and family history of autoimmunity were assessed.

Results: A total of 354 patients were referred to our centre within the study period, 112 (31.8%) with 'established MS'. Misdiagnosis was identified in eight out of 112 cases (7.1%). MRI identified multifocal white matter lesions, deemed non-specific or not suggestive of MS in all misdiagnosed cases. Patients with MS misdiagnosis had more comorbidities in general than patients with MS ( = 0.026) as well as a personal history of autoimmunity ( < 0.001).

Conclusion: A low frequency of MS misdiagnosis was found in our clinical setting. Multifocal non-specific white matter lesions in referral MRI examinations and the presence of comorbidities, including a personal history of autoimmunity, seem to be contributing factors to misdiagnosis.
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http://dx.doi.org/10.1177/1352458520988148DOI Listing
May 2021

Differential effect of vascularity between long- and short-term survivors with IDH1/2 wild-type glioblastoma.

NMR Biomed 2021 04 19;34(4):e4462. Epub 2021 Jan 19.

ITACA, Universitat Politècnica de València, Valencia, Spain.

Introduction: IDH1/2 wt glioblastoma (GB) represents the most lethal tumour of the central nervous system. Tumour vascularity is associated with overall survival (OS), and the clinical relevance of vascular markers, such as rCBV, has already been validated. Nevertheless, molecular and clinical factors may have different influences on the beneficial effect of a favourable vascular signature.

Purpose: To evaluate the association between the rCBV and OS of IDH1/2 wt GB patients for long-term survivors (LTSs) and short-term survivors (STSs). Given that initial high rCBV may affect the patient's OS in follow-up stages, we will assess whether a moderate vascularity is beneficial for OS in both groups of patients.

Materials And Methods: Ninety-nine IDH1/2 wt GB patients were divided into LTSs (OS ≥ 400 days) and STSs (OS < 400 days). Mann-Whitney and Fisher, uni- and multiparametric Cox, Aalen's additive regression and Kaplan-Meier tests were carried out. Tumour vascularity was represented by the mean rCBV of the high angiogenic tumour (HAT) habitat computed through the haemodynamic tissue signature methodology (available on the ONCOhabitats platform).

Results: For LTSs, we found a significant association between a moderate value of rCBV and higher OS (uni- and multiparametric Cox and Aalen's regression) (p = 0.0140, HR = 1.19; p = 0.0085, HR = 1.22) and significant stratification capability (p = 0.0343). For the STS group, no association between rCBV and survival was observed. Moreover, no significant differences (p > 0.05) in gender, age, resection status, chemoradiation, or MGMT methylation were observed between LTSs and STSs.

Conclusion: We have found different prognostic and stratification effects of the vascular marker for the LTS and STS groups. We propose the use of rCBV at HAT as a vascular marker clinically relevant for LTSs with IDH1/2 wt GB and maybe as a potential target for randomized clinical trials focused on this group of patients.
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http://dx.doi.org/10.1002/nbm.4462DOI Listing
April 2021

Association of Gray Matter Atrophy Patterns With Clinical Phenotype and Progression in Multiple Sclerosis.

Neurology 2021 03 13;96(11):e1561-e1573. Epub 2021 Jan 13.

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.), Division of Neuroscience, Neurology Unit (M.A.R., P.P., M.F.), Neurorehabilitation Unit, and Neurophysiology Service (M.F.), IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University (M.A.R., M.F.), Milan, Italy; Multiple Sclerosis Center (C.G., C.Z.), Department of Neurology, Neurocenter of Southern Switzerland, Civic Hospital; Faculty of Biomedical Sciences Università della Svizzera Italiana (C.G., C.Z.), Lugano, Switzerland; Section of Neuroradiology (A.R.), Department of Radiology, and Department of Neurology/Neuroimmunology (J.S.-G.), Multiple Sclerosis Center of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences (A.G., A.B.) and 3T MRI-Center (A.G., A.B.), University of Campania Luigi Vanvitelli, Naples, Italy; Institute of Neuroradiology at the Department of Radiology and Nuclear Medicine (C.L., B.B.), St. Josef Hospital, Ruhr University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience Amsterdam UMC, location VUmc, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.

Objectives: Gay matter (GM) involvement is clinically relevant in multiple sclerosis (MS). Using source-based morphometry (SBM), we characterized GM atrophy and its 1-year evolution across different MS phenotypes.

Methods: Clinical and MRI data were obtained at 8 European sites from 170 healthy controls (HCs) and 398 patients with MS (34 with clinically isolated syndrome [CIS], 226 with relapsing-remitting MS [RRMS], 95 with secondary progressive MS [SPMS], and 43 with primary progressive MS [PPMS]). Fifty-seven HCs and 144 with MS underwent 1-year follow-up. Baseline GM loss, atrophy progression, and correlations with disability and 1-year clinical worsening were assessed.

Results: SBM identified 26 cerebellar, subcortical, sensory, motor, and cognitive GM components. GM atrophy was found in patients with MS vs HCs in almost all components ( range <0.001-0.04). Compared to HCs, patients with CIS showed circumscribed subcortical, cerebellar, temporal, and salience GM atrophy, while patients with RRMS exhibited widespread GM atrophy. Cerebellar, subcortical, sensorimotor, salience, and frontoparietal GM atrophy was found in patients with PPMS vs HCs and in patients with SPMS vs those with RRMS. At 1 year, 21 (15%) patients had clinically worsened. GM atrophy progressed in MS in subcortical, cerebellar, sensorimotor, and fronto-temporo-parietal components. Baseline higher disability was associated ( = 0.65) with baseline lower normalized brain volume (β = -0.13, = 0.001), greater sensorimotor GM atrophy (β = -0.12, = 0.002), and longer disease duration (β = 0.09, = 0.04). Baseline normalized GM volume (odds ratio 0.98, = 0.008) and cerebellar GM atrophy (odds ratio 0.40, = 0.01) independently predicted clinical worsening (area under the curve 0.83).

Conclusion: GM atrophy differed across disease phenotypes and progressed at 1 year in MS. In addition to global atrophy measures, sensorimotor and cerebellar GM atrophy explained baseline disability and clinical worsening.
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http://dx.doi.org/10.1212/WNL.0000000000011494DOI Listing
March 2021

Mind the gap: from neurons to networks to outcomes in multiple sclerosis.

Nat Rev Neurol 2021 Mar 12;17(3):173-184. Epub 2021 Jan 12.

National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, London, UK.

MRI studies have provided valuable insights into the structure and function of neural networks, particularly in health and in classical neurodegenerative conditions such as Alzheimer disease. However, such work is also highly relevant in other diseases of the CNS, including multiple sclerosis (MS). In this Review, we consider the effects of MS pathology on brain networks, as assessed using MRI, and how these changes to brain networks translate into clinical impairments. We also discuss how this knowledge can inform the targeting of MS treatments and the potential future directions for research in this area. Studying MS is challenging as its pathology involves neurodegenerative and focal inflammatory elements, both of which could disrupt neural networks. The disruption of white matter tracts in MS is reflected in changes in network efficiency, an increasingly random grey matter network topology, relative cortical disconnection, and both increases and decreases in connectivity centred around hubs such as the thalamus and the default mode network. The results of initial longitudinal studies suggest that these changes evolve rather than simply increase over time and are linked with clinical features. Studies have also identified a potential role for treatments that functionally modify neural networks as opposed to altering their structure.
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http://dx.doi.org/10.1038/s41582-020-00439-8DOI Listing
March 2021

Optic Nerve Topography in Multiple Sclerosis Diagnosis: The Utility of Visual Evoked Potentials.

Neurology 2021 01 16;96(4):e482-e490. Epub 2020 Dec 16.

From the Servicio de Neurología-Neuroinmunología (A V.-J., G.A., S.O.-R., J.R., M.C., C.N., J.C., I.G., S.C., B.R.-A., A.Z., L.M., J.S.-G., X.M., M.T.), Centro de Esclerosis Múltiple de Catalunya (Cemcat), Sección de Neuroradiologia (A.R., C.A.), Servei de Radiologia, Servicio de Medicina Preventiva y Epidemiologia (S.O.-R.), and Servicio de Neurofisiología Clínica (D.M., K.R., V.T.), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; and Division of Neurology (X.M.), St. Michael's Hospital. University of Toronto, Ontario, Canada.

Objective: To assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria.

Methods: From the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non-optic neuritis).

Results: The addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non-optic neuritis CIS.

Conclusion: The addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity.
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http://dx.doi.org/10.1212/WNL.0000000000011339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905792PMC
January 2021

Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective: A Review.

JAMA Neurol 2021 Mar;78(3):351-364

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Istituto di Ricovero e di Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.

Importance: Although magnetic resonance imaging (MRI) is useful for monitoring disease dissemination in space and over time and excluding multiple sclerosis (MS) mimics, there has been less application of MRI to progressive MS, including diagnosing primary progressive (PP) MS and identifying patients with relapsing-remitting (RR) MS who are at risk of developing secondary progressive (SP) MS. This review addresses clinical application of MRI for both diagnosis and prognosis of progressive MS.

Observations: Although nonspecific, some spinal cord imaging features (diffuse abnormalities and lesions involving gray matter [GM] and ≥2 white matter columns) are typical of PPMS. In patients with PPMS and those with relapse-onset MS, location of lesions in critical central nervous system regions (spinal cord, infratentorial regions, and GM) and MRI-detected high inflammatory activity in the first years after diagnosis are risk factors for long-term disability and future progressive disease course. These measures are evaluable in clinical practice. In patients with established MS, GM involvement and neurodegeneration are associated with accelerated clinical worsening. Subpial demyelination and slowly expanding lesions are novel indicators of progressive MS.

Conclusions And Relevance: Diagnosis of PPMS is more challenging than diagnosis of RRMS. No qualitative clinical, immunological, histopathological, or neuroimaging features differentiate PPMS and SPMS; both are characterized by imaging findings reflecting neurodegeneration and are also impacted by aging and comorbidities. Unmet diagnostic needs include identification of MRI markers capable of distinguishing PPMS from RRMS and predicting the evolution of RRMS to SPMS. Integration of multiple parameters will likely be essential to achieve these aims.
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http://dx.doi.org/10.1001/jamaneurol.2020.4689DOI Listing
March 2021

Adding brain volume measures into response criteria in multiple sclerosis: the Río-4 score.

Neuroradiology 2021 Jul 25;63(7):1031-1041. Epub 2020 Nov 25.

Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, P. Vall d'Hebron 119-129, 08035, Barcelona, Spain.

Purpose: Brain volume changes (BVC) on therapy in MS are being considered as predictor for treatment response at an individual level. We ought to assess whether adding BVC as a factor to monitor interferon-beta response improves the predictive ability of the (no) evidence of disease activity (EDA-3) and Río score (RS-3) criteria for confirmed disability progression in a historical cohort.

Methods: One hundred one patients from an observational cohort treated with interferon-beta were assessed for different cutoff points of BVC (ranged 0.2-1.2%), presence of active lesions (≥ 1 for EDA/≥ 3 for RS), relapses, and 6-month confirmed disability progression (CDP), measured by the Expanded Disability Status Scale, after 1 year. Sensitivity, specificity, and positive and negative predictive values for predicting confirmed disability progression at 4 years in original EDA (EDA-3) and RS (RS-3) as well as EDA and RS including BVC (EDA-4 and RS-4) were compared.

Results: Adding BVC to EDA slightly increased sensitivity, but not specificity or predictive values, nor the OR for predicting CDP; only EDA-3 showed a trend for predicting CDP (OR 3.701, p = 0.050). Adding BVC to RS-3 (defined as ≥ 2 criteria) helped to improve sensitivity and negative predictive value, and increased OR for predicting CDP using a cutoff of ≤ - 0.86% (RS-3 OR 23.528, p < 0.001; RS-4 for all cutoffs ranged from 15.06 to 32, p < 0.001). RS-4 showed areas under the curve larger than RS-3 for prediction of disability at 4 years.

Conclusion: Addition of BVC to RS improves its prediction of response to interferon-beta.
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http://dx.doi.org/10.1007/s00234-020-02604-8DOI Listing
July 2021

MR imaging findings in primary spinal cord glioblastoma.

Radiol Case Rep 2021 Jan 2;16(1):72-77. Epub 2020 Nov 2.

Section of Neuroradiology, Department of Radiology, Vall d'Hebron University Hospital, Hospital Vall d'Hebron, Passeig de la Vall d'Hebron, 119-129 | 08035, Barcelona, Spain.

Spinal cord glioblastoma is a rare disease, with an aggressive course and a poor prognosis. We describe magnetic resonance imaging (MRI) findings, in 3 adult cases of biopsy-confirmed glioblastoma. Conventional MRI findings were unclear with regard to the differential diagnosis between this rare tumor and other more common spinal cord lesions, including less aggressive tumors such as ependymoma or pilocytic astrocytoma, abscesses or tumefactive demyelinating lesions. After reasonable exclusion of infectious/inflammatory conditions, a final diagnosis of glioblastoma was established based on histopathological analysis. The cases reported reflect the difficulty of early radiological diagnosis of spinal cord glioblastoma, and indicate the need to perform a biopsy once inflammatory-infectious conditions are excluded with appropriate laboratory tests.
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http://dx.doi.org/10.1016/j.radcr.2020.10.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642760PMC
January 2021

REMOTE Ischemic Perconditioning Among Acute Ischemic Stroke Patients in Catalonia: REMOTE-CAT PROJECT.

Front Neurol 2020 25;11:569696. Epub 2020 Sep 25.

Stroke Unit, Hospital de Sant Pau, Barcelona, Spain.

Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection. To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care. A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%. We aim to conduct a multicentre study of pre-hospital RIPerC application in AIS patients. A total of 572 adult patients diagnosed of suspected clinical stroke within 8 h of symptom onset and clinical deficit >0 according to prehospital rapid arterial occlusion evaluation (RACE) scale score will be randomized, in blocks of size 4, to RIPerC or sham. Patients will be stratified by RACE score scale. RIPerC will be started in the ambulance before hospital admission and continued in the hospital if necessary. It will consist of five cycles of electronic tourniquet inflation and deflation (5 min each). The cuff pressure for RIPerC will be 200 mmHg during inflation. Sham will only simulate vibration of the device. The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days. Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS. www.ClinicalTrials.gov, identifier: NCT03375762.
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http://dx.doi.org/10.3389/fneur.2020.569696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546310PMC
September 2020

MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas.

Eur Radiol 2021 Mar 1;31(3):1738-1747. Epub 2020 Oct 1.

Instituto Universitario de Tecnologías de la Información y Comunicaciones, Universitat Politècnica de València, València, Spain.

Objectives: To assess the combined role of tumor vascularity, estimated from perfusion MRI, and MGMT methylation status on overall survival (OS) in patients with glioblastoma.

Methods: A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships between MGMT and perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored by MGMT methylation in terms of OS.

Results: rCBV distributions did not differ significantly (p > 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV < 10.73), MGMT methylation was a positive predictive factor for OS (HR = 2.73, p = 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of MGMT methylation (HR = 1.72, p = 0.10, AUC = 0.56).

Conclusions: Our results indicate the existence of complementary prognostic information provided by MGMT methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from MGMT methylation. Not considering this information may lead to bias in the interpretation of clinical studies.

Key Points: • MRI perfusion provides complementary prognostic information to MGMT methylation. • MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile. • Failure to consider these relations may lead to bias in the interpretation of clinical studies.
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http://dx.doi.org/10.1007/s00330-020-07297-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880975PMC
March 2021
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