Multiple Sclerosis In Clinical Practice Research Articles

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis: A Multiregional Population-Based Study

It is not possible to fully establish the safety of a disease-modifying drug (DMD) for multiple sclerosis (MS) from randomized controlled trials as only very common adverse events occurring over the short-term can be captured, and the quality of reporting has been variable. We examined the relationship between the DMDs for MS and potential adverse events in a multiregion population-based study. We identified people with MS using linked administrative health data from 4 Canadian provinces. MS cases were followed from the most recent of first MS or related demyelinating disease event on January 1, 1996, until the earliest of emigration, death, or December 31, 2017. DMD exposure primarily comprised β-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab. We examined associations between DMD exposure and infection-related hospitalizations and physician visits using recurrent events proportional means models and between DMD exposure and 15 broad categories of incident adverse events using stratified multivariate Cox proportional hazard models. We identified 35,894 people with MS. While virtually all DMDs were associated with a 42%-61% lower risk of infection-related hospitalizations, there was a modest increase in infection-related physician visits by 10%-33% for select DMDs. For incident adverse events, most elevated risks involved a second-generation DMD, with alemtuzumab's hazard of thyroid disorders being 19.42 (95% CI 9.29-36.51), hypertension 4.96 (95% CI 1.78-13.84), and cardiovascular disease 3.72 (95% CI 2.12-6.53). Natalizumab's highest risk was for cardiovascular disease (adjusted hazard ratio [aHR] 1.61; 95% CI 1.24-2.10). For the oral DMDs, fingolimod was associated with higher hazards of cerebrovascular (aHR 2.04; 95% CI 1.27-3.30) and ischemic heart diseases (aHR 1.64; 95% CI 1.10-2.44) and hypertension (aHR 1.73; 95% CI 1.30-2.31); teriflunomide with higher hazards of thyroid disorders (aHR 2.30; 95% CI 1.11-4.74), chronic liver disease (aHR 1.94; 95% CI 1.19-3.18), hypertension (aHR 1.76; 95% CI 1.32-2.37), and hyperlipidemia (aHR 1.61; 95% CI 1.07-2.44); and from complementary analyses (in 1 province), dimethyl fumarate with acute liver injury (aHR 6.55; 95% CI 1.96-21.87). Our study provides an extensive safety profile of several different DMDs used to treat MS in the real-world setting. Our findings not only complement those observed in short-term clinical trials but also provide new insights that help inform the risk-benefit profile of the DMDs used to treat MS in clinical practice. The results of this study highlight the continued need for long-term, independent safety studies of the DMDs used to treat MS. This study provides Class III evidence that for patients with MS, while DMD exposure reduces the risk of infection-related hospitalizations, there are increased risks of infection-related physician visits and incident adverse events for select DMDs.

A Closed-Loop Falls Monitoring and Prevention App for Multiple Sclerosis Clinical Practice: Human-Centered Design of the Multiple Sclerosis Falls InsightTrack.

Falls are common in people with multiple sclerosis (MS), causing injuries, fear of falling, and loss of independence. Although targeted interventions (physical therapy) can help, patients underreport and clinicians undertreat this issue. Patient-generated data, combined with clinical data, can support the prediction of falls and lead to timely intervention (including referral to specialized physical therapy). To be actionable, such data must be efficiently delivered to clinicians, with care customized to the patient's specific context. This study aims to describe the iterative process of the design and development of Multiple Sclerosis Falls InsightTrack (MS-FIT), identifying the clinical and technological features of this closed-loop app designed to support streamlined falls reporting, timely falls evaluation, and comprehensive and sustained falls prevention efforts. Stakeholders were engaged in a double diamond process of human-centered design to ensure that technological features aligned with users' needs. Patient and clinician interviews were designed to elicit insight around ability blockers and boosters using the capability, opportunity, motivation, and behavior (COM-B) framework to facilitate subsequent mapping to the Behavior Change Wheel. To support generalizability, patients and experts from other clinical conditions associated with falls (geriatrics, orthopedics, and Parkinson disease) were also engaged. Designs were iterated based on each round of feedback, and final mock-ups were tested during routine clinical visits. A sample of 30 patients and 14 clinicians provided at least 1 round of feedback. To support falls reporting, patients favored a simple biweekly survey built using REDCap (Research Electronic Data Capture; Vanderbilt University) to support bring-your-own-device accessibility-with optional additional context (the severity and location of falls). To support the evaluation and prevention of falls, clinicians favored a clinical dashboard featuring several key visualization widgets: a longitudinal falls display coded by the time of data capture, severity, and context; a comprehensive, multidisciplinary, and evidence-based checklist of actions intended to evaluate and prevent falls; and MS resources local to a patient's community. In-basket messaging alerts clinicians of severe falls. The tool scored highly for usability, likability, usefulness, and perceived effectiveness (based on the Health IT Usability Evaluation Model scoring). To our knowledge, this is the first falls app designed using human-centered design to prioritize behavior change and, while being accessible at home for patients, to deliver actionable data to clinicians at the point of care. MS-FIT streamlines data delivery to clinicians via an electronic health record-embedded window, aligning with the 5 rights approach. Leveraging MS-FIT for data processing and algorithms minimizes clinician load while boosting care quality. Our innovation seamlessly integrates real-world patient-generated data as well as clinical and community-level factors, empowering self-care and addressing the impact of falls in people with MS. Preliminary findings indicate wider relevance, extending to other neurological conditions associated with falls and their consequences.

Současná doporučení pro využití MR u onemocnění roztroušené sklerózy v klinické praxi

Současná doporučení pro využití MR u onemocnění roztroušené sklerózy v klinické praxi

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

Multiple Sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system. It is a complex and heterogeneous disease, and its pathogenesis is still not completely understood. Precision medicine, which involves the use of advanced technologies such as genomics, proteomics, metabolomics, and imaging to identify specific biomarkers and disease subtypes, is a promising approach to the management of multiple sclerosis. Precision medicine in MS includes the development of targeted therapies that aim to modulate specific immune pathways involved in MS pathogenesis. This review article aims to provide an overview of the current status and future directions of precision medicine in MS. The article discusses the importance of precision diagnostics in MS, including the identification of biomarkers and imaging techniques for MS, as well as the challenges and opportunities of personalized treatment in MS. Targeted therapies in MS are also discussed, including the challenges of developing and implementing these therapies. The article highlights the potential of combination therapies in MS, and the role of AI and ML in improving biomarker identification. The challenges of implementing precision medicine in clinical practice are also addressed, including the standardization of diagnostic criteria and treatment guidelines, and the ethical and legal considerations of personalized treatment. Overall, precision medicine represents a promising approach to the management of MS, with the potential to improve diagnosis, prognosis, and treatment outcomes. However, the implementation of precision medicine in MS clinical practice requires addressing several challenges, including the standardization of diagnostic criteria and treatment guidelines, and the development of affordable and accessible technologies and therapies. With continued research and advances in technology, precision medicine has the potential to transform the field of MS research and clinical practice.

Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis

ABSTRACT Predicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.4 y. Worsening (with EDSS-Plus) occurred in 39/95 patients (outcome undetermined for 16 individuals). The inflammation-associated, dysbiotic Bacteroides 2 enterotype (Bact2) was detected at baseline in 43.6% of worsened patients, while only 16.1% of non-worsened patients harbored Bact2. This association was independent of identified confounders, and Bact2 was more strongly associated with EDSS-Plus than neurofilament light chain (NfL) plasma levels. Furthermore, using fecal sampling performed 3 months post-baseline, we observed Bact2 to be relatively stable, suggesting its potential use as a prognostic biomarker in MS clinical practice.

Development of an international, multidisciplinary, patient-centered Standard Outcome Set for Multiple Sclerosis: The S.O.S.MS project.

Currently, outcomes of Multiple Sclerosis (MS) are not standardized and it is unclear which outcomes matter most to people living with MS. A consensus between patients and healthcare professionals on which outcomes to measure and how, would facilitate a move towards value-based MS care. to develop an internationally accepted, patient-relevant Standard Outcome Set for MS (S.O.S.MS). A mixed-method design was used, including a systematic literature review, four patient focus groups (n=30) and a RAND-modified Delphi process with seventeen MS experts of five disciplines from seven countries (the Netherlands, United States of America, Portugal, Ireland, India, New Zealand, Switzerland and Turkey). A standard outcome set for MS was defined, consisting of fourteen outcomes divided in four domains: disease activity (n=3), symptoms (n=4), functional status (n=6), and quality of life (n=1). For each outcome, an outcome measure was selected and the measurement protocol was defined. In addition, seven case-mix variables were selected. This standard outcome set provides a guideline for measuring outcomes of MS in clinical practice and research. Using this set to monitor and (inter)nationally benchmark real-world outcomes of MS can support improvement of patient value and ultimately guide the transition towards value-based MS care.

Sensitivity of conventional cognitive tests in multiple sclerosis: Application of item response theory.

Cognitive impairment (CI) is common in Multiple Sclerosis (MS), and its prevalence rate ranges between 22% and 70%. Because CI significantly impacts vocational status, caregiver burden, and quality of life, an accurate neuropsychological assessment is required. Three widely used and validated batteries for MS-associated CI are the Brief Repeatable Neuropsychological Battery (BRN-B), the Minimal Assessment of Cognitive Function (MACFIMS), and the Brief International Cognitive Assessment (BICAMS). Although similar, these batteries differ in time-consuming and in specific tests employed. This study aims to assess the sensitivity of cognitive tests included in these batteries through an Item Response Theory approach. Ninety-seven patients with MS and 91 demographically matched controls (HC) were consecutively assessed using the three neuropsychological batteries (i.e., BRN-B, MACFIMS, and BICAMS). Continuous Response Model (CRM) was used to identify the cognitive test(s) that best discriminate patients with MS from HC. Receiver Operating Characteristic (ROC) curve analysis was used to determine the accuracy of the CRM results. Cognitive tests loaded on two different latent variables: the 'higher-order executive functioning,' consisting of tests assessing concept formation, problem-solving, and inhibitory control, and the 'memory and information processing speed,' comprising tests assessing long-term, working memory, and information processing speed. The Delis Kaplan Executive Functioning System-Sorting Test and the Stroop Test were the most sensitive tests in differentiating cognitive functioning between MS and HC. This study confirms the importance of including a more extensive executive assessment in MS clinical practice since higher-order executive functions (e.g., abstraction and inhibitory control) significantly impact patients' quality of life and functional autonomy. Clinical implications of careful dissection of executive functioning in MS neuropsychological assessment are discussed.

A Scoping Review on Body Fluid Biomarkers for Prognosis and Disease Activity in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a complex demyelinating disease of the central nervous system, presenting with different clinical forms, including clinically isolated syndrome (CIS), which is a first clinical episode suggestive of demyelination. Several molecules have been proposed as prognostic biomarkers in MS. We aimed to perform a scoping review of the potential use of prognostic biomarkers in MS clinical practice. We searched MEDLINE up to 25 November 2021 for review articles assessing body fluid biomarkers for prognostic purposes, including any type of biomarkers, cell types and tissues. Original articles were obtained to confirm and detail the data reported by the review authors. We evaluated the reliability of the biomarkers based on the sample size used by various studies. Fifty-two review articles were included. We identified 110 molecules proposed as prognostic biomarkers. Only six studies had an adequate sample size to explore the risk of conversion from CIS to MS. These confirm the role of oligoclonal bands, immunoglobulin free light chain and chitinase CHI3L1 in CSF and of serum vitamin D in the prediction of conversion from CIS to clinically definite MS. Other prognostic markers are not yet explored in adequately powered samples. Serum and CSF levels of neurofilaments represent a promising biomarker.

Improving Detection of Change in Motor Functioning in Multiple Sclerosis Using Video-Assisted Composite Measures.

Assessing motor functioning is important to monitor the disease course of multiple sclerosis (MS). Video-assisted rating of classic neurologic tests and activities of daily living may improve the detection of changes in motor functioning. We investigated the value of using video-assisted composite measures for the detection of changes in mobility and upper extremity function (UEF). Forty-three patients with MS were recorded performing motor function tests before and during treatment with fampridine. Patients were classified as improved or not improved on mobility composite (MOB-COM) and UEF composite (UEF-COM) measures based on neurologists' ratings of the tests. The proportional agreements between the composite measures and the conventional measures-the Timed 25-Foot Walk test (T25FW) and the Nine-Hole Peg Test (NHPT)-were determined and compared with patient-perceived improvement, which was determined using patient-reported ratings of changes in mobility and UEF. Agreement between MOB-COM and T25FW was 79.5%, and agreement between UEF-COM and NHPT was 82.1%. Twenty-six of 39 patients (66.7%) reported mobility improvement; 6 of these reports were confirmed by both T25FW and MOB-COM, 4 were confirmed by T25FW only, and 2 were confirmed by MOB-COM only. For UEF, 13 of 39 patients (33.3%) reported improvement; 3 of these were confirmed by the NHPT and 3 were confirmed by the UEF-COM. Compared with the conventional NHPT measure, the video-assisted composite measure of UEF detected additional patient-perceived improvement. This was less evident for mobility measures. Video-assisted composite measures may enhance the detection of treatment effects in MS clinical practice and trials.

Neurologists’ views on patient reported outcomes in multiple sclerosis care

BackgroundThe value that patient reported outcomes (PROs) can bring to the clinical encounter is increasingly being recognized. Within the field of Multiple Sclerosis (MS), a number of activities have been initiated internationally with the aim of integrating PROs in MS care. Integration of PROs in MS care will, among other things, require MS neurologists' acceptance of PROs. This qualitative study aimed to explore MS specialized neurologists’ view on the potentials and barriers for the use of PROs in the clinical setting. MethodsEight neurologists specialized in MS participated in a series of individual in-depth semi-structured interviews. Interviews were audio-recorded and transcribed. A thematic analysis was conducted using a reflexive thematic approach to identify meaning units and themes emerging from the interviews. The analysis focused on barriers and potentials for PROs that relate to the specific characteristics of MS. ResultsThree main themes emerged from the data. “The role of PROs in describing the patient's situation” describes how informants perceived MS as a complex disease, and in this context, PROs can bring forth new or otherwise hidden information, but they may also blur the picture. The theme “The validity of PROs reported by MS patients may be questionable” describes how impairments caused by MS, such as cognitive and physical disabilities, were identified as risk factors that could cause unreliable self-reported outcome measures within this patient group. Finally, the theme “Involving the patient” regards how the clinical conversation was viewed as the most important source of patient reported information, but at the same time PROs carry the potential to enhance shared decision making. ConclusionThis study indicates that, according to MS neurologists, integration of PROs in MS clinical practice, though possibly valuable, is not without challenges. Possible benefits of PROs include the ability to bring forth otherwise hidden information on the patient's health status and the enhancement of shared decision making. Barriers include difficulties in capturing the full situation of the patient via PROs due to the complexity of MS as well as the issue of various MS-related impairments compromising the validity of PROs reported by MS patients.

Imaging Features of Adult-Onset Genetic Leukodystrophies Misdiagnosed as Multiple Sclerosis in Clinical Practice (P12-4.002)

Imaging Features of Adult-Onset Genetic Leukodystrophies Misdiagnosed as Multiple Sclerosis in Clinical Practice (P12-4.002)

Spinal cord grey matter atrophy in Multiple Sclerosis clinical practice

PurposeSeveral studies have indicated the relevance of spinal cord grey matter atrophy for Multiple Sclerosis (MS) related disability. This work aimed at evaluating feasibility and clinical relevance of MRI-derived estimations of spinal cord grey matter atrophy in clinical practice. MethodsA convenience sample of MS patients (n=48) and healthy controls (HC, n=11) was scanned using brain sagittal 3D T1w (MPRAGE) and transverse T2w-FLAIR, and transverse single-slice spinal cord 2D heavily T1w (PSIR: phase-sensitive inversion recovery) sequences. An experienced technician with neuroradiological supervision used a semiautomated thresholding method implemented in JIM software on PSIR sequences to obtain cross-sectional area (CSA) of the spinal canal (CSAcanal), whole cord (CSAcord), grey (CSAgm) and white matter (CSAwm) at C2-C3. MPRAGE and T2w-FLAIR sequences were used to obtain brain parenchymal, grey and white matter fractions (BPF, GMF and WMF) using the Statistical Parametric Mapping software. Appropriate statistical tests were used before and after age and sex adjustment. ResultsCSAgm and CSAwm could be obtained in all HC, but only 18 patients (37.5%) due to presence of lesions at C2-C3. Significant univariate associations between EDSS and BPF (rho =−0.376, p=0.015), GMF (rho =−0.287, p=0.069), CSAcanal (rho =−0.310, p=0.049), CSAcord (rho =−0.533 p<0.001) and CSAgm (rho =−0.511, p=0.062) were detected. After age/sex adjustment trends were observed for CSAcanal and CSAcord. ConclusionIn a clinical practice setting, relevance of spinal cord grey matter is confirmed, but cervical cord lesions could greatly hamper its application. Clinical associations with disability have been observed and seem stronger for spinal cord than for brain atrophy measures.

Lifestyle and complementary therapies in multiple sclerosis guidelines: Systematic review

Management of multiple sclerosis (MS) may comprise clinical interventions and self-management strategies, including complementary therapies and modifiable lifestyle factors such as exercise and smoking cessation. Lifestyle modifications and complementary therapies with proven safety and efficacy are essential as part of best-practice MS management, especially when faced with limited access to healthcare services. However, it is unclear to what extent MS clinical practice guidelines and consensus statements address these strategies. A systematic review was conducted, wherein MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, Web of Science, guideline databases and developer sites were searched for guidelines and consensus statements that addressed lifestyle modifications and complementary therapies of interest. Two researchers independently screened articles, extracted data and assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation version II. Thirty-one guidelines and consensus statements were included. Quality was high for 'clarity of presentation' (77%) and 'scope and purpose' (73%), moderate for 'stakeholder development' (56%), 'rigour of development' (48%) and 'editorial independence' (47%), and low for 'applicability' (29%). Two guidelines, related to physical activity and exercise, mindfulness, smoking cessation, and vitamin D and polyunsaturated fatty acid supplementation, scored high in all domains. These guidelines were two of only four guidelines intended for use by people with MS. High-quality guidelines and consensus statements to guide lifestyle modifications and complementary therapies in MS management are limited. Our findings indicate the need for more guidelines intended for use by people with MS, and a further focus on implementation resources.

Role of artificial intelligence in MS clinical practice

Machine learning (ML) and its subset, deep learning (DL), are branches of artificial intelligence (AI) showing promising findings in the medical field, especially when applied to imaging data. Given the substantial role of MRI in the diagnosis and management of patients with multiple sclerosis (MS), this disease is an ideal candidate for the application of AI techniques. In this narrative review, we are going to discuss the potential applications of AI for MS clinical practice, together with their limitations. Among their several advantages, ML algorithms are able to automate repetitive tasks, to analyze more data in less time and to achieve higher accuracy and reproducibility than the human counterpart. To date, these algorithms have been applied to MS diagnosis, prognosis, disease and treatment monitoring. Other fields of application have been improvement of MRI protocols as well as automated lesion and tissue segmentation. However, several challenges remain, including a better understanding of the information selected by AI algorithms, appropriate multicenter and longitudinal validations of results and practical aspects regarding hardware and software integration. Finally, one cannot overemphasize the paramount importance of human supervision, in order to optimize the use and take full advantage of the potential of AI approaches.

CAM recommendations in multiple sclerosis clinical practice guidelines: A systematic review

CAM recommendations in multiple sclerosis clinical practice guidelines: A systematic review

Rim lesions are demonstrated in early relapsing\u2013remitting multiple sclerosis using 3\xa0T-based susceptibility-weighted imaging in a multi-institutional setting

PurposeRim lesions, characterised by a paramagnetic rim on susceptibility-based MRI, have been suggested to reflect chronic inflammatory demyelination in multiple sclerosis (MS) patients. Here, we assess, through susceptibility-weighted imaging (SWI), the prevalence, longitudinal volume evolution and clinical associations of rim lesions in subjects with early relapsing–remitting MS (RRMS).MethodsSubjects (n = 44) with recently diagnosed RRMS underwent 3 T MRI at baseline (M0) and 1 year (M12) as part of a multi-centre study. SWI was acquired at M12 using a 3D segmented gradient-echo echo-planar imaging sequence. Rim lesions identified on SWI were manually segmented on FLAIR images at both time points for volumetric analysis.ResultsTwelve subjects (27%) had at least one rim lesion at M12. A linear mixed-effects model, with ‘subject’ as a random factor, revealed mixed evidence for the difference in longitudinal volume change between rim lesions and non-rim lesions (p = 0.0350 and p = 0.0556 for subjects with and without rim lesions, respectively). All 25 rim lesions identified showed T1-weighted hypointense signal. Subjects with and without rim lesions did not differ significantly with respect to age, disease duration or clinical measures of disability (p > 0.05).ConclusionWe demonstrate that rim lesions are detectable in early-stage RRMS on 3 T MRI across multiple centres, although their relationship to lesion enlargement is equivocal in this small cohort. Identification of SWI rims was subjective. Agreed criteria for defining rim lesions and their further validation as a biomarker of chronic inflammation are required for translation of SWI into routine MS clinical practice.

Effect of virtual height exposure on postural control

The value that patient reported outcomes (PROs) can bring to the clinical encounter is increasingly being recognized. Within the field of Multiple Sclerosis (MS), a number of activities have been initiated internationally with the aim of integrating PROs in MS care. Integration of PROs in MS care will, among other things, require MS neurologists' acceptance of PROs. This qualitative study aimed to explore MS specialized neurologists’ view on the potentials and barriers for the use of PROs in the clinical setting.Eight neurologists specialized in MS participated in a series of individual in-depth semi-structured interviews. Interviews were audio-recorded and transcribed. A thematic analysis was conducted using a reflexive thematic approach to identify meaning units and themes emerging from the interviews. The analysis focused on barriers and potentials for PROs that relate to the specific characteristics of MS.Three main themes emerged from the data. “The role of PROs in describing the patient's situation” describes how informants perceived MS as a complex disease, and in this context, PROs can bring forth new or otherwise hidden information, but they may also blur the picture. The theme “The validity of PROs reported by MS patients may be questionable” describes how impairments caused by MS, such as cognitive and physical disabilities, were identified as risk factors that could cause unreliable self-reported outcome measures within this patient group. Finally, the theme “Involving the patient” regards how the clinical conversation was viewed as the most important source of patient reported information, but at the same time PROs carry the potential to enhance shared decision making.This study indicates that, according to MS neurologists, integration of PROs in MS clinical practice, though possibly valuable, is not without challenges. Possible benefits of PROs include the ability to bring forth otherwise hidden information on the patient's health status and the enhancement of shared decision making. Barriers include difficulties in capturing the full situation of the patient via PROs due to the complexity of MS as well as the issue of various MS-related impairments compromising the validity of PROs reported by MS patients.

Integrated Management of Multiple Sclerosis Spasticity and Associated Symptoms Using the Spasticity-Plus Syndrome Concept: Results of a Structured Specialists' Discussion Using the Workmat® Methodology.

Background: Multiple sclerosis (MS) treatment has radically improved over the last years; however, MS symptom management is still challenging. The novel Spasticity-Plus syndrome was conceptualized to frame several spasticity-related symptoms that can be addressed together with broad-spectrum medication, such as certain cannabinoid-based drugs. The aim of this project was to gain insight into Spanish neurologists' clinical experience on MS spasticity and associated symptoms, and to assess the acknowledgment and applicability of the Spasticity-Plus syndrome concept in patients with MS.Methods: Ten online meetings were conducted using the Workmat® methodology to allow structured discussions. Fifty-five Spanish neurologists, experts in MS management, completed and discussed a set of predefined exercises comprising MS symptom assessment and its management in clinical practice, MS symptoms clustering in clinical practice, and their perception of the Spasticity-Plus syndrome concept. This document presents the quantitative and qualitative results of these discussions.Results: The specialists considered that polytherapy is a common concern in MS and that simplifying the management of MS spasticity and associated manifestations could be useful. They generally agreed that MS spasticity should be diagnosed before moderate or severe forms appear. According to the neurologists' clinical experience, symptoms commonly associated with MS spasticity included spasms/cramps (100% of the specialists), pain (85%), bladder dysfunction (62%), bowel dysfunction (42%), sleep disorders (42%), and sexual dysfunction (40%). The multiple correspondence analysis revealed two main symptom clusters: spasticity-spasms/cramps-pain, and ataxia-instability-vertigo. Twelve out of 16 symptoms (75%) were scored >7 in a 0–10 QoL impact scale by the specialists, representing a moderate–high impact. The MS specialists considered that pain, spasticity, spasms/cramps, bladder dysfunction, and depression should be a treatment priority given their frequency and chance of therapeutic success. The neurologists agreed on the usefulness of the new Spasticity-Plus syndrome concept to manage spasticity and associated symptoms together, and their experience with treatments targeting the cannabinoid system was satisfactory.Conclusions: The applicability of the new concept of Spasticity-Plus in MS clinical practice seems possible and may lead to an integrated management of several MS symptoms, thus reducing the treatment burden of disease symptoms.

Added Value of Susceptibility Weighted Imaging (SWI) in Diagnosis of Multiple Sclerosis (MS)

Abstract Background: There are a number of challenges in MS clinical practice, including the limitations of conventional MRI techniques in the diagnosis, subtyping, predicting disease course, and monitoring of people suffering from MS. Suscep-tibility Weighted Imaging (SWI) is a relatively new MR sequence that has the ability for simultaneous visualization of hyperintense MS lesions and their central veins. Aim of Study: To assess the role of MR susceptibility weighted imaging in comparison with T2 and FLAIR sequences in evaluation of MS lesions. Patients and Methods: In this prospective study, 30 patients with clinical diagnosis of MS were enrolled. All patients were undergone brain MRI consisting T2W, FLAIR and SWI se-quences. All sequences were analyzed for the presence and number of MS plaques. Moreover, the detection of central veins in MS plaques were assessed by SWI. Results: Our study included 30 MS patients: 5 patients (16.7%) had disease duration more than 5 years and 15 patients (83.3%) with disease duration less than 5 years. All obtained sequences showed fewer number of plaques as the disease duration was less (p < 0.05). SWI has also the ability of detection central vein in MS plaques. Conclusion: SWI is an additional sequence, that together to conventional MRI sequences, helps to characterize the white matter lesions detected in multiple sclerosis diagnosis with superiority of detecting central veins which improves the understanding of the MS pathogenesis.

Exploring CSF neurofilament light as a biomarker for MS in clinical practice; a retrospective registry-based study

Background: Neurofilament light (NFL) has been increasingly recognized for prognostic and therapeutic decisions. Objective: To validate the utility of cerebrospinal fluid NFL (cNFL) as a biomarker in clinical practice of relapsing-remitting multiple sclerosis (RRMS). Methods: RRMS patients (n = 757) who had cNFL analyzed as part of the diagnostic work-up in a single academic multiple sclerosis (MS) center, 2001–2018, were retrospectively identified. cNFL concentrations were determined with two different immunoassays and the ratio of means between them was used for normalization. Results: RRMS with relapse had 4.4 times higher median cNFL concentration (1134 [interquartile range (IQR) 499–2744] ng/L) than those without relapse (264 [125–537] ng/L, p < 0.001) and patients with gadolinium-enhancing lesions had 3.3 times higher median NFL (1414 [606.8–3210] ng/L) than those without (426 [IQR 221–851] ng/L, p < 0.001). The sensitivity and specificity of cNFL to detect disease activity was 75% and 98.5%, respectively. High cNFL at MS onset predicted progression to Expanded Disability Status Scale (EDSS) ⩾ 3 (p < 0.001, hazard ratios (HR) = 1.89, 95% CI = 1.44–2.65) and conversion to secondary progressive MS (SPMS, p = 0.001, HR = 2.5, 95% CI = 1.4–4.2). Conclusions: cNFL is a robust and reliable biomarker of disease activity, treatment response, and prediction of disability and conversion from RRMS to SPMS. Our data suggest that cNFL should be included in the assessment of patients at MS-onset.