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

The reality of multiple sclerosis assessment in middle-income countries

To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.

Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper. We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis. We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.

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.

BACKGROUND. The central vein sign (CVS) is a proposed MRI biomarker of multiple sclerosis (MS). The impact of gadolinium-based contrast agent (GBCA) administration on CVS evaluation remains poorly investigated. OBJECTIVE. The purpose of this study was to assess the effect of GBCA use on CVS detection and on the diagnostic performance of the CVS for MS using a 3-T FLAIR* sequence. METHODS. This study was a secondary analysis of data from the pilot study for the prospective multicenter Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), which recruited adults with suspected MS from April 2018 to February 2020. Participants underwent 3-T brain MRI including FLAIR and precontrast and post-contrast echo-planar imaging T2*-weighted acquisitions. Postprocessing was used to generate combined FLAIR and T2*-weighted images (hereafter, FLAIR*). MS diagnoses were established using the 2017 McDonald criteria. Thirty participants (23 women, seven men; mean age, 45 years) were randomly selected from the CAVS-MS pilot study cohort. White matter lesions (WMLs) were marked using FLAIR* images. A single observer, blinded to clinical data and GBCA use, reviewed marked WMLs on FLAIR* images for the presence of the CVS. RESULTS. Thirteen of 30 participants had MS. Across participants, on precontrast FLAIR* imaging, 218 CVS-positive and 517 CVS-negative WMLs were identified; on post-contrast FLAIR* imaging, 269 CVS-positive and 459 CVS-negative WMLs were identified. The fraction of WMLs that were CVS-positive on precontrast and postcontrast images was 48% and 58% in participants with MS and 7% and 10% in participants without MS, respectively. The median patient-level CVS-positivity rate on precontrast and postcontrast images was 43% and 67% for participants with MS and 4% and 8% for participants without MS, respectively. In a binomial model adjusting for MS diagnoses, GBCA use was associated with an increased likelihood of at least one CVS-positive WML (odds ratio, 1.6; p < .001). At a 40% CVS-positivity threshold, the sensitivity of the CVS for MS increased from 62% on precontrast images to 92% on postcontrast images (p = .046). Specificity was not significantly different between precontrast (88%) and postcontrast (82%) images (p = .32). CONCLUSION. GBCA use increased CVS detection on FLAIR* images, thereby increasing the sensitivity of the CVS for MS diagnoses. CLINICAL IMPACT. The postcontrast FLAIR* sequence should be considered for CVS evaluation in future investigational trials and clinical practice.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Multiple sclerosis in childhood: Report of 15 cases

Magnetic resonance imaging is recognized as the most important diagnostic test in the diagnosis of multiple sclerosis,differential diagnosis and evaluation of progression/therapeutic response. However, to make optimal use of magnetic resonance imagingin multiple sclerosis, the use of a standard, reproducible and comparable imaging protocol is of uttermost importance. In thiscontext, the Portuguese Society of Neuroradiology and the Group of Studies of Multiple Sclerosis, after a joint discussion, appointed acommittee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiplesclerosis. This document represents the second part of the first Portuguese consensus recommendations on the use of magnetic resonanceimaging in multiple sclerosis in clinical practice. The Portuguese Society of Neuroradiology and the Group of Studies of Multiple Sclerosis, after discussing thetopic in national meetings and after a working group meeting held in Figueira da Foz, May 2017, appointed a committee of experts thathave developed several standard protocols on the use of magnetic resonance imaging on multiple sclerosis by consensus. The documentobtained was based on the best scientific evidence and expert opinion. Portuguese multiple sclerosis consultants and departmentsof neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Standardizedstrategies of magnetic resonance imaging referral in clinical practice for diagnosis and follow-up of multiple sclerosis were publishedin the first part of this paper. We provide magnetic resonance imaging acquisition protocols regarding multiple sclerosis diagnostic and monitoring and theinformation to be included in the report for application across Portuguese healthcare institutions. We hope that these first Portuguese magnetic resonance imaging guidelines will contribute to optimize multiple sclerosismanagement and improve patient care in Portugal.

Gadolinium Retention in Human Brain, Bone, and Skin.

The presentation of multiple sclerosis (MS) in childhood has traditionally been thought to be rare. However, more paediatric cases are now being reported, as a result of progress in diagnostic techniques with the use of sensitive imaging modalities of the brain and spinal cord. Management from an early age and the availability of new treatment options have changed the outcome of paediatric MS. Drugs currently available for treatment, such as beta-interferons, copolymer-1 and intravenous immunoglobulin G, have been found to reduce relapse rate, disease severity and progression to disability in adults, but have not been investigated in children and adolescents. The overall outcome of MS in children is apparently no worse than in adults and the disease may even be less aggressive in children. In juvenile MS, disease progression does not appear to be related to age of onset, severity of neurological involvement or mono/polysymptomatic involvement at presentation. The potential to treat MS has significantly changed the prognosis. Early diagnosis is important, as early treatment can prevent or delay the development of disability.

The clinical use of MRI in patients with multiple sclerosis (MS) has advanced markedly over the past few years. Technical improvements and continuously emerging data from clinical trials and observational studies have contributed to the enhanced performance of this tool for achieving a prompt diagnosis in patients with MS. The aim of this article is to provide guidelines for the implementation of MRI of the brain and spinal cord in the diagnosis of patients who are suspected of having MS. These guidelines are based on an extensive review of the recent literature, as well as on the personal experience of the members of the MAGNIMS (Magnetic Resonance Imaging in MS) network. We address the indications, timing, coverage, reporting and interpretation of MRI studies in patients with suspected MS. Our recommendations are intended to help radiologists and neurologists standardize and optimize the use of MRI in clinical practice for the diagnosis of MS.

Practical issues concerning the use of Magnetic Resonance Imaging in Multiple Sclerosis in Latin America: Discussion from 16 centres on behalf of the Foro Latam EM Study Group

Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions — the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating central nervous system disease. Most MS patients develop the disease between 20 and 40 years of age, with a predominance of women being affected. Children before the age of 16 represent an estimated 2.7–5% of individuals with MS, with 0.2–0.7% presenting under the age of 10 year. In Albania, there are currently four paediatric patients (three girls, and one boy) diagnosed with MS, receiving treatment at the Paediatric Neurology Clinic in UHC in Tirana. One of the girls P.GJ. 12 years old started to have some acute symptoms such as numbness of right arm and leg and dysarthria within a 40 days period. The other girl E.XH. 14 years old had first symptoms with visibility reduction within a period of three months, gait problems and fatigue. Both of them with a normal developmental history, without any previous medical history. MRI scan of P.GJ. resulted in multiple cerebral lesions localized in subcortical frontal region, peri trigonal dexter and capsule-thalamic sinister. MRI scan of E.XH. Periventricular multiple lesions of white matter. FO: optic neuritis dexter. There are overall no major differences in the clinical presentation between childhood- and adult-onset MS. Over 95% of childhood-onset MS patients have a relapsing-remitting MS course at onset. Childhood and adolescent-onset MS is characterized by a shorter interval between the first and second demyelinating event, and by a higher relapse frequency compared to adult-onset MS. Glucocorticoids remain the cornerstone of treatment for relapses. Disease-modifying agents (DMA) are moderately effective in reducing relapses and MRI activity. Paediatric-onset MS patients reach disability milestones at a younger age than their adult-onset counterparts. This evokes an increased sense of responsibility to effectively recognize, diagnose, and treat children and adolescents with MS.

Multiple sclerosis (MS) in children and adolescents is a genuine concern of pediatric neurology that specialists in all countries are dealing with. To date, neither the causes of onset nor the individual components of the pathogenesis of the disease have been reliably clarified, and the modern, changing picture of the clinical manifestation of the disease sometimes complicates timely diagnosis even in adult patients. There are more such questions in pediatric MS.Objective: to study the prevalence and clinical features of MS in children in the Republic of Tatarstan.Material and methods. We conducted a survey and data analysis of 128 children and adolescents aged 0 to 18 years inclusive. The examination of patients included neurological examination according to the classical scheme, neuroimaging examination, neurophysiological examination and cerebrospinal fluid examination. The diagnosis was based on the current (as of the time of diagnosis) criteria of McDonald and the International Pediatrics MS Study Group criteria. The severity of the patients' clinical condition was assessed using the Expanded Disability Status Scale (EDSS).Results. MS was diagnosed in 99 cases (77.3%), clinically isolated syndrome – in 10 (7.8%), acute disseminated encephalomyelitis – in 5 (3.9%), bilateral optic neuritis – in two patients (1.6%), disseminated encephalomyelitis – in one case (0.8%); other central nervous system diseases were diagnosed in 11 (8.6%) patients. After a detailed examination, the group “other diseases of the central nervous system” included such conditions as cerebral angiopathy, neurofibromatosis, brain mass, structural focal epilepsy, sequelae of viral encephalitis, and hereditary leukodystrophy. Among the patients, girls aged 15–17 years predominated. Monofocal manifestations were more frequently observed at debut. Moreover, the absolute predominance of the remitting type of course was also noted.Conclusion. The data obtained suggest a predominance of the predominantly remitting course type of MS with a monofocal onset, which is consistent with data from other studies of MS in pediatric practice.