Prediction of disease activity and treatment failure in relapsing-remitting MS patients initiating daily oral DMTs.

BACKGROUND: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS). OBJECTIVES: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing-remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials. METHODS: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation. At 36 months, we examined their ability to predict evidence of disease activity (EDA) components and treatment failure by logistic regression analysis. RESULTS: Notably, 218 patients (62.4% females) initiating dimethyl fumarate, teriflunomide, and fingolimod were included. At 36 months, the RS high-risk group predicted evidence of clinical activity (odds ratio (OR) 10 [2.7-36.9]) and treatment failure (OR 10.6 [3.4-32.5]) but did not predict radiological activity (OR 1.9 [0.7-5]). The mRS non-responders group did not predict EDA and treatment failure. RS, mRS, and MAGNIMS 0 categories showed significantly lower EDA and treatment failure than the remainder. CONCLUSION: Scoring systems present different predictive abilities for disease activity parameters at 36 months in MS patients initiating daily oral therapies, warranting further adjustments (i.e. introduction of fluid biomarkers) to depict disease activity status fully.

Trans-Synaptic Degeneration in the Visual Pathway in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: We aimed to assess the presence of retinal neurodegeneration independent of optic neuritis (ON) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the development of trans-synaptic anterograde degeneration in these patients after ON. METHODS: Cross-sectional, retrospective study of 34 adult patients with MOGAD and 23 healthy controls (HC). Clinical, optical coherence tomography (OCT), and MRI data were collected. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GCIPL) were obtained using Heidelberg Spectralis. FreeSurfer7 was used to obtain the lateral geniculate nucleus (LGN), occipital volume fractions (to total estimated intracranial volume), and occipital cortical thickness. For the anterior visual pathway, the analysis was conducted using eyes, classified based on the history of ON (Eye-ON and Eye-NON) and compared with Eye-HC. The analysis of OCT and brain volumetric measures was conducted comparing MOGAD-ON, MOGAD-NON, and HC groups. The analysis of covariance with a Bonferroni-adjusted post hoc test was used to test differences between groups and linear regression analysis to evaluate OCT/MRI associations; age and sex were considered as covariates. RESULTS: 24 (70.5%) patients had a prior ON. Median pRNFL and GCIPL thickness (um) was significantly reduced in Eye-ON vs EyeNON and HC (pRNFL: 69.4 (17.3), 89.6 (13.7), 98.2 (11.7), p < 0.001; GCIPL: 55.8 (8.7), 67.39 (8.7), 72.6 (4.5), p < 0.001). pRNFL and GCIPL thickness had a negative correlation with the number of ON episodes (p = 0.025 and p = 0.031, respectively). LGN volume fraction was significantly lower in patients with MOGAD-ON than in HC (0.33 (0.05) vs 0.39 (0.04), p = 0.002). The occipital cortical thickness was lower in MOGAD-ON compared with MOGAD-NON and HC (p = 0.010). In patients with MOGAD-ON, pRNFL correlated with LGN volume (p = 0.006), occipital thickness (p = 0.002), and the medial occipital cortex (p = 0.002), but not the lateral occipital lobe. DISCUSSION: Compared with HC, MOGAD-ON exhibits reduced retinal thickness, primarily influenced by the presence and the number of prior ON episodes. Moreover, MOGAD-ON demonstrates significant atrophy in the retinal, subcortical, and cortical regions of the visual pathway, distinguishing them from MOGAD-NON and HC. These findings suggest that in patients with MOGAD neurodegeneration is tightly correlated with damage to the involved pathway.

Go Green in Neuroradiology: towards reducing the environmental impact of its practice.

Raising public awareness about the relevance of supporting sustainable practices is required owing to the phenomena of global warming caused by the rising production of greenhouse gases. The healthcare sector generates a relevant proportion of the total carbon emissions in developed countries, and radiology is estimated to be a major contributor to this carbon footprint. Neuroradiology markedly contributes to this negative environmental effect, as this radiological subspecialty generates a high proportion of diagnostic and interventional imaging procedures, the majority of them requiring high energy-intensive equipment. Therefore, neuroradiologists and neuroradiological departments are especially responsible for implementing decisions and initiatives able to reduce the unfavourable environmental effects of their activities, by focusing on four strategic pillars-reducing energy, water, and helium use; properly recycling and/or disposing of waste and residues (including contrast media); encouraging environmentally friendly behaviour; and reducing the effects of ionizing radiation on the environment. The purpose of this article is to alert neuroradiologists about their environmental responsibilities and to analyse the most productive strategic axes, goals, and lines of action that contribute to reducing the environmental impact associated with their professional activities.

T1/T2-weighted ratio: A feasible MRI biomarker in multiple sclerosis.

T1/T2-weighted ratio is a novel magnetic resonance imaging (MRI) biomarker based on conventional sequences, related to microstructural integrity and with increasing use in multiple sclerosis (MS) research. Different from other advanced MRI techniques, this method has the advantage of being based on routinely acquired MRI sequences, a feature that enables analysis of retrospective cohorts with considerable clinical value. This article provides an overview of this method, describing the previous cross-sectional and longitudinal findings in the main MS clinical phenotypes and in different brain tissues: focal white matter (WM) lesions, normal-appearing white matter (NAWM), cortical gray matter (GM), and deep normal-appearing gray matter (NAGM). We also discuss the clinical associations, possible reasons for conflicting results, correlations with other MRI-based measures, and histopathological associations. We highlight the limitations of the biomarker itself and the methodology of each study. Finally, we update the reader on its potential use as an imaging biomarker in research.

Late/delayed gadolinium enhancement in MRI after intravenous administration of extracellular gadolinium-based contrast agents: is it worth waiting?

The acquisition of images minutes or even hours after intravenous extracellular gadolinium-based contrast agents (GBCA) administration ("Late/Delayed Gadolinium Enhancement" imaging; in this review, further termed LGE) has gained significant prominence in recent years in magnetic resonance imaging. The major limitation of LGE is the long examination time; thus, it becomes necessary to understand when it is worth waiting time after the intravenous injection of GBCA and which additional information comes from LGE. LGE can potentially be applied to various anatomical sites, such as heart, arterial vessels, lung, brain, abdomen, breast, and the musculoskeletal system, with different pathophysiological mechanisms. One of the most popular clinical applications of LGE regards the assessment of myocardial tissue thanks to its ability to highlight areas of acute myocardial damage and fibrotic tissues. Other frequently applied clinical contexts involve the study of the urinary tract with magnetic resonance urography and identifying pathological abdominal processes characterized by high fibrous stroma, such as biliary tract tumors, autoimmune pancreatitis, or intestinal fibrosis in Crohn's disease. One of the current areas of heightened research interest revolves around the possibility of non-invasively studying the dynamics of neurofluids in the brain (the glymphatic system), the disruption of which could underlie many neurological disorders.

Defining a standard set of health outcomes for patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Standardizing health outcomes is challenging in clinical management, but it also holds the potential for creating a healthcare system that is both more effective and efficient. The aim of the present study is to define a standardized set of health outcomes for managing Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: The project was led and coordinated by a multidisciplinary scientific committee (SC), which included a literature review, a patient-focused group, three nominal group meetings, and two SC meetings. RESULTS: 36 outcome variables were included in the standard set: 24 clinical (including weight, smoking habit, comorbidities, disability, mobility, diagnosis of secondary progressive multiple sclerosis, relapsed-related variables, radiological variables, cognitive status and disease-related symptoms), nine treatment-related (pharmacological and non-pharmacological information), and 3 related to the impact of RRMS on the patient's life (quality of life, pregnancy desire, work-related difficulties). In addition, experts also agreed to collect 10 case-mix variables that may affect but cannot be controlled as part of the management of the condition: 4 sociodemographic (age, sex, race, and employment status) and 6 clinical (height, date of diagnosis and first episode, serological status, early symptoms, and number of relapses pre-diagnosis). CONCLUSION: The information provided through the present standard set of outcome variables can improve the management of RRMS and promote patient-centred quality care.

Optic nerve topography in multiple sclerosis diagnostic criteria: Existing knowledge and future directions.

Current diagnostic criteria for multiple sclerosis (MS) do not consider the optic nerve as a typical topography for establishing the diagnosis. Recent studies have proved the utility of optic nerve magnetic resonance imaging, optical coherence tomography and visual evoked potentials in detecting optic nerve lesions during the early stages of MS. In addition, emerging evidence supports the inclusion of optic nerve topography as a fifth region to fulfil the dissemination in space criteria. Anticipating a modification in the McDonald criteria, it is crucial for neurologists to familiarize with the diagnostic properties of each test in detecting optic nerve lesions and understand how to incorporate them into the MS diagnostic process. Therefore, the objective of this article is to review the existing evidence supporting the use of these tests in the diagnostic process of MS and provide a practical algorithm that can serve as a valuable guide for clinical practice.

Adding the Optic Nerve in Multiple Sclerosis Diagnostic Criteria: A Longitudinal, Prospective, Multicenter Study

BACKGROUND AND OBJECTIVES: The optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort. METHODS: MAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the fifth area of the CNS. A risk assessment analysis and the performance of the different DIS criteria were analyzed using the diagnosis of MS according to the 2017 McDonald criteria as the primary outcome and new T2 lesions and/or a second relapse as the secondary outcome. RESULTS: We included 157 patients with CIS from 5 MAGNIMS centers; 60/157 (38.2%) patients presented with optic neuritis. Optic nerve involvement on ON-MRI was found in 40.2% patients at study entry and in 72.5% of those with optic neuritis.At follow-up (mean 27.9 months, SD 14.5), 111/157 patients (70.7%) were diagnosed with MS according to the 2017 McDonald criteria. Fulfilling either 2017 DIS or any modified DIS criteria conferred a similar high risk for reaching primary and secondary outcomes. The modified DIS criteria had higher sensitivity (92.5% [with ON-MRI] vs 88.2%), but slightly lower specificity (80.0% [with GCIPL IEA ≥4 µm] vs 82.2%), with overall similar accuracy (86.6% [with ON-MRI] vs 86.5%) than 2017 DIS criteria. Consistent results were found for secondary outcomes. DISCUSSION: In patients with CIS, the presence of an optic nerve lesion defined by MRI, OCT, or VEP is frequently detected, especially when presenting with optic neuritis. Our study supports the addition of the optic nerve as a fifth topography to fulfill DIS criteria.

Optic chiasm manual and automated measurements in sub-acute optic neuritis with OCT and MRI correlations.

PURPOSE: The optic chiasm (OC) is a central structure in the visual pathway and can be visualized in conventional MRI, but no consensus regarding its measurement has been defined. We aim to investigate the most reproducible manual approach to OC measurement and to explore associations of OC with optical coherence tomography (OCT) parameters, and automatic brain segmentation (FreeSurfer) in subacute optic neuritis (sON), multiple sclerosis without optic neuritis (MSwoON), and healthy subjects (HS). MATERIALS AND METHODS: We reproduced two previously reported methodologies and implemented a new proposed simplified approach, entitled optic chiasm mean area (OCMA). The intra and inter-rater reliability and reproducibility were assessed through the intraclass correlation (ICC) and Dice similarity (DSC) coefficients. Partial correlations were calculated to gauge the associations between OCMA fraction (OCMA divided by total intracranial volume), brain regional segmentations derived from FreeSurfer, and OCT parameters. RESULTS: We have analysed 43 sON, 20 MSwoON, and 20 HS. OCMA presented better results for reliability in both intra- and inter-rater analysis (excellent ICC and DSC with over 80% overlap between masks), as compared to the other two approaches. OCMA fraction was associated with OC volume fraction obtained with Freesurfer in all groups, brain parenchymal fraction, and OCT parameters in MSwoON. CONCLUSIONS: The OCMA is a simplified approach to measure OC atrophy, has a higher reliability than the current approaches and shows association with an automated method. OC-derived measures seem to reflect diffuse neurodegenerative damage, whereas, in patients with subacute ON, it may be associated with local damage.

Assessing treatment response to oral drugs for multiple sclerosis in real-world setting: a MAGNIMS Study.

BACKGROUND: The assessment of treatment response is a crucial step for patients with relapsing-remitting multiple sclerosis on disease-modifying therapies (DMTs). We explored whether a scoring system developed within the MAGNIMS (MRI in Multiple Sclerosis) network to evaluate treatment response to injectable drugs can be adopted also to oral DMTs. METHODS: A multicentre dataset of 1200 patients who started three oral DMTs (fingolimod, teriflunomide and dimethyl fumarate) was collected within the MAGNIMS network. Disease activity after the first year was classified by the 'MAGNIMS' score based on the combination of relapses (0-≥2) and/or new T2 lesions (<3 or ≥3) on brain MRI. We explored the association of this score with the following 3-year outcomes: (1) confirmed disability worsening (CDW); (2) treatment failure (TFL); (3) relapse count between years 1 and 3. The additional value of contrast-enhancing lesions (CELs) and lesion location was explored. RESULTS: At 3 years, 160 patients experienced CDW: 12% of them scored '0' (reference), 18% scored '1' (HR=1.82, 95% CI 1.20 to 2.76, p=0.005) and 37% scored '2' (HR=2.74, 95% CI 1.41 to 5.36, p=0.003) at 1 year. The analysis of other outcomes provided similar findings. Considering the location of new T2 lesions (supratentorial vs infratentorial/spinal cord) and the presence of CELs improved the prediction of CDW and TFL, respectively, in patients with minimal MRI activity alone (one or two new T2 lesions). CONCLUSIONS: Early relapses and substantial MRI activity in the first year of treatment are associated with worse short-term outcomes in patients treated with some of the oral DMTs.

Prognostic value of single-subject grey matter networks in early multiple sclerosis.

The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict 5-year Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from MRI, outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for 5 years (mean follow-up = 5.0 ± 0.6 years). EDSS was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again 1 year after baseline. Grey matter atrophy over 1 year and white matter lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on grey matter atrophy measures derived from a statistical parameter mapping-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for grey matter atrophy and white matter lesion load, and the network measures and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over 5 years through lower values for network degree [H(2) = 30.0, P < 0.001] and global efficiency [H(2) = 31.3, P < 0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups [H(2) = 1.5, P = 0.474]. Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of grey matter atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over grey matter atrophy and white matter lesion load in predicting EDSS worsening (all P-values < 0.05). Our findings provide evidence that grey matter network reorganization over 1 year discloses relevant information about subsequent clinical worsening in RRMS. Early grey matter restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors.

The role of gadolinium-based contrast agents in magnetic resonance imaging structured reporting and data systems (RADS).

Among the 28 reporting and data systems (RADS) available in the literature, we identified 15 RADS that can be used in Magnetic Resonance Imaging (MRI). Performing examinations without using gadolinium-based contrast agents (GBCA) has benefits, but GBCA administration is often required to achieve an early and accurate diagnosis. The aim of the present review is to summarize the current role of GBCA in MRI RADS. This overview suggests that GBCA are today required in most of the current RADS and are expected to be used in most MRIs performed in patients with cancer. Dynamic contrast enhancement is required for correct scores calculation in PI-RADS and VI-RADS, although scientific evidence may lead in the future to avoid the GBCA administration in these two RADS. In Bone-RADS, contrast enhancement can be required to classify an aggressive lesion. In RADS scoring on whole body-MRI datasets (MET-RADS-P, MY-RADS and ONCO-RADS), in NS-RADS and in Node-RADS, GBCA administration is optional thanks to the intrinsic high contrast resolution of MRI. Future studies are needed to evaluate the impact of the high T1 relaxivity GBCA on the assignment of RADS scores.

Use of gadolinium-based contrast agents in multiple sclerosis: a review by the ESMRMB-GREC and ESNR Multiple Sclerosis Working Group.

Magnetic resonance imaging (MRI) is the most sensitive technique for detecting inflammatory demyelinating lesions in multiple sclerosis (MS) and plays a crucial role in diagnosis and monitoring treatment effectiveness, and for predicting the disease course. In clinical practice, detection of MS lesions is mainly based on T2-weighted and contrast-enhanced T1-weighted sequences. Contrast-enhancing lesions (CEL) on T1-weighted sequences are related to (sub)acute inflammation, while new or enlarging T2 lesions reflect the permanent footprint from a previous acute inflammatory demyelinating event. These two types of MRI features provide redundant information, at least in regular monitoring of the disease. Due to the concern of gadolinium deposition after repetitive injections of gadolinium-based contrast agents (GBCAs), scientific organizations and regulatory agencies in Europe and North America have proposed that these contrast agents should be administered only if clinically necessary. In this article, we provide data on the mode of action of GBCAs in MS, the indications of the use of these agents in clinical practice, their value in MS for diagnostic, prognostic, and monitoring purposes, and their use in specific populations (children, pregnant women, and breast-feeders). We discuss imaging strategies that achieve the highest sensitivity for detecting CELs in compliance with the safety regulations established by different regulatory agencies. Finally, we will briefly discuss some alternatives to the use of GBCA for detecting blood-brain barrier disruption in MS lesions. CLINICAL RELEVANCE STATEMENT: Although use of GBCA at diagnostic workup of suspected MS is highly valuable for diagnostic and prognostic purposes, their use in routine monitoring is not mandatory and must be reduced, as detection of disease activity can be based on the identification of new or enlarging lesions on T2-weighted images. KEY POINTS: • Both the EMA and the FDA state that the use of GBCA in medicine should be restricted to clinical scenarios in which the additional information offered by the contrast agent is required. • The use of GBCA is generally recommended in the diagnostic workup in subjects with suspected MS and is generally not necessary for routine monitoring in clinical practice. • Alternative MRI-based approaches for detecting acute focal inflammatory MS lesions are not yet ready to be used in clinical practice.

Energy consumption in MRI: Determinants and management options.

BACKGROUND: Energy consumption awareness is a known concern, and radiology departments have energy-intensive consuming machines. The means of energy consumption management in MRI scanners have yet to be evaluated. PURPOSE: To measure the MRI energy consumption and to evaluate the means to reduce it. MATERIALS AND METHODS: Data was retrieved for two MRI scanners through the hospital's automated energy consumption measurement software. After correlation with picture archiving and communication system (PACS) files, they were segmented by machine and mode (as follows: stand-by, idle and active) and analyzed. Active mode data for a specific brain MRI protocol have been isolated, and equivalent low energy consuming protocol was made. Both were performed on phantom and compared. Same protocol was performed on a phantom using 3.0T 16 and 32 head channels coils. Multiples sequences were acquired on phantom to evaluate power consumption. RESULTS: Stand-by mode accounted for 60 % of machine time and 40 % of energy consumption, active mode accounted for 20 % machine time and 40 % energy consumption, idle mode for 20 % imachine time and 20 % consumption. DWI and TOF sequences were the most consuming in our brain-MRI protocol. The low energy consuming protocol allowed a saving of approximately 10 % of energy consumption, which amounted for 0.20€ for each examination. This difference was mainly due to an energy consumption reduction of the DWI sequence. There were no difference in consumption between a 3.0T 16 and 32 channels head coils. Sequence's active power and duration (especially considering slice thickness) have to be taken into account when trying to optimize energy consumption. CONCLUSION: There are two key factors to consider when trying to reduce MRI scan energy consumption. Stand-by mode energy consumption has to be taken into account when choosing an MRI scan, as it can't be changed further on. Active mode energy consumption is dependent of the MRI protocols used, and can be reduced with sequences adaptation, which must take into account sequence's active power and duration, on top of image quality.

Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis.

Importance: Multiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice. Objective: To quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other conditions showing brain lesions on magnetic resonance imaging (MRI). Design, Setting, and Participants: This was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants' diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 [64.4%] female; mean [SD] age, 41.5 [12.3] years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 [66.8%] female; mean [SD] age, 49.2 [14.5] years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2). Exposures: MS/CIS vs non-MS conditions. Main Outcomes and Measures: Area under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model. Results: The presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 [95% CI, 0.86-0.91]) was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P < .001), and was increased when combining the 2 imaging markers (AUC, 0.92 [95% CI, 0.90-0.94]; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis. Conclusions and Relevance: The findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

Association of magnetic resonance imaging phenotypes and serum biomarker levels with treatment response and long-term disease outcomes in multiple sclerosis patients.

BACKGROUND AND PURPOSE: The aim was to evaluate whether magnetic resonance imaging (MRI) phenotypes defined by inflammation and neurodegeneration markers correlate with serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in relapsing-remitting multiple sclerosis (RRMS) patients; and to explore the role of radiological phenotypes and biomarker levels on treatment response and long-term prognostic outcomes. METHODS: Magnetic resonance imaging scans from 80 RRMS patients were classified at baseline of interferon-beta (IFNß) treatment into radiological phenotypes defined by high and low inflammation and high and low neurodegeneration, based on the number of contrast-enhancing lesions, brain parenchymal fraction and the relative volume of non-enhancing black holes on T1-weighted images. Serum levels of NfL and GFAP were measured at baseline with single molecule array (Simoa) assays. MRI phenotypes and serum biomarker levels were investigated for their association with IFNß response, and times to second-line therapies, secondary-progressive MS (SPMS) conversion and Expanded Disability Status Scale (EDSS) 6.0. RESULTS: Mean (SD) follow-up was 17 (2.9) years. Serum NfL levels and GFAP were higher in the high inflammation (p = 0.04) and high neurodegeneration phenotypes (p = 0.03), respectively. The high inflammation phenotype was associated with poor response to IFNß treatment (p = 0.04) and with shorter time to second-line therapies (p = 0.04). In contrast, the high neurodegeneration phenotype was associated with shorter time to SPMS (p = 0.006) and a trend towards shorter time to EDSS 6.0 (p = 0.09). High serum NfL levels were associated with poor response to IFNß treatment (p = 0.004). CONCLUSIONS: Magnetic resonance imaging phenotypes defined by inflammation and neurodegeneration correlate with serum biomarker levels, and both have prognostic implications in treatment response and long-term disease outcomes.

Cognitive improvement following endovascular embolization in patients with intracranial dural arteriovenous fistula: The Neuropsychology in dural ArterIal Fistula (NAIF) Study.

BACKGROUND: Cognitive improvement after endovascular embolization of an intracranial dural arteriovenous fistula (dAVF) remains unexplored. We aim to investigate cognitive changes following endovascular embolization of dAVFs. METHODS: Neuropsychology in dural ArterIal Fistula (NAIF) was a prospective multicentric study including patients with an angiographic diagnosis of dAVF who underwent endovascular embolization over the course of 4 years. A complete neuropsychological evaluation comprising five cognitive domains (attention and executive functions, memory, language, praxis, gnosis) was performed at baseline and 3 months follow-up. Mean Z scores for cognitive tests were compared pre- and post-treatment using paired sample t-tests, where higher Z scores indicate better cognition. Effect sizes were computed as Cohen's d. RESULTS: A total of 32 patients (mean age 61.1±15.4 years, 10 (31.3%) females) were included. Patients exhibited improved performance in attention and executive functions: executive functions-attention (+0.282, P=0.009, d=0.29), executive functions-fluencies (+0.283, P=0.029, d=0.4), and executive functions-processing speed (+0.471, P=0.039, d=0.41). There was an increase in memory: verbal learning and verbal delayed recall scores (+0.513, P<0.001, d=0.55, and +0.385, P=0.001, d=0.41, respectively), while verbal recognition parameters (+0.839, P=0.086, d=0.37) and visual memory (delayed recall) (+0.430, P=0.060, d=0.35) displayed trends toward improved performance. Regarding language, there was significant overall improvement (+0.300, P=0.014, d=0.24), but neither praxis nor gnosis changed significantly. These cognitive outcomes were independent of the severity (measured as Cognard classification), and no patient experienced cognitive worsening. CONCLUSION: This study suggests that endovascular embolization confers cognitive benefits on dAVF patients undergoing endovascular embolization and may be beneficial even for patients with a low risk of hemorrhage.