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BACKGROUND: Cerebrospinal fluid (CSF) oligoclonal bands (OCB) are a diagnostic biomarker in multiple sclerosis (MS). The central vein sign (CVS) is an imaging biomarker for MS that may improve diagnostic accuracy. OBJECTIVES: The objective of the study is to examine the diagnostic performance of simplified CVS methods in comparison to OCB in participants with clinical or radiological suspicion for MS. METHODS: Participants from the CentrAl Vein Sign in MS (CAVS-MS) pilot study with CSF testing were included. Select-3 and Select-6 (counting up to three or six CVS+ lesions per scan) were rated on post-gadolinium FLAIR* images. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value for Select-3, Select-6, OCB, and combinations thereof were calculated for MS diagnosis at baseline and at 12 months. RESULTS: Of 53 participants, 25 were OCB+. At baseline, sensitivity for MS diagnosis was 0.75 for OCB, 0.83 for Select-3, and 0.71 for Select-6. Specificity for MS diagnosis was 0.76 for OCB, 0.48 for Select-3, and 0.86 for Select-6. At 12 months, PPV for MS diagnosis was 0.95 for Select-6 and 1.00 for Select-6 with OCB+ status. DISCUSSION: Results suggest similar diagnostic performance of simplified CVS methods and OCB. Ongoing studies will refine whether CVS could be used in replacement or in conjunction with OCB.

This study aimed to determine whether choroid plexus volume (CPV) could differentiate multiple sclerosis (MS) from its mimics. A secondary analysis of two previously enrolled studies, 50 participants with MS and 64 with alternative diagnoses were included. CPV was automatically segmented from 3T magnetic resonance imaging (MRI), followed by manual review to remove misclassified tissue. Mean normalized choroid plexus volume (nCPV) to intracranial volume demonstrated relatively high specificity for MS participants in each cohort (0.80 and 0.76) with an area under the receiver-operator characteristic curve of 0.71 (95% confidence interval (CI) = 0.55-0.87) and 0.65 (95% CI = 0.52-0.77). In this preliminary study, nCPV differentiated MS from its mimics.

BACKGROUND: The central vein sign (CVS) is a proposed magnetic resonance imaging (MRI) biomarker for multiple sclerosis (MS); the optimal method for abbreviated CVS scoring is not yet established. OBJECTIVE: The aim of this study was to evaluate the performance of a simplified approach to CVS assessment in a multicenter study of patients being evaluated for suspected MS. METHODS: Adults referred for possible MS to 10 sites were recruited. A post-Gd 3D T2*-weighted MRI sequence (FLAIR*) was obtained in each subject. Trained raters at each site identified up to six CVS-positive lesions per FLAIR* scan. Diagnostic performance of CVS was evaluated for a diagnosis of MS which had been confirmed using the 2017 McDonald criteria at thresholds including three positive lesions (Select-3*) and six positive lesions (Select-6*). Inter-rater reliability assessments were performed. RESULTS: Overall, 78 participants were analyzed; 37 (47%) were diagnosed with MS, and 41 (53%) were not. The mean age of participants was 45 (range: 19-64) years, and most were female (n = 55, 71%). The area under the receiver operating characteristic curve (AUROC) for the simplified counting method was 0.83 (95% CI: 0.73-0.93). Select-3* and Select-6* had sensitivity of 81% and 65% and specificity of 68% and 98%, respectively. Inter-rater agreement was 78% for Select-3* and 83% for Select-6*. CONCLUSION: A simplified method for CVS assessment in patients referred for suspected MS demonstrated good diagnostic performance and inter-rater agreement.

ObjectiveTo summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings.MethodsClinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement.ResultsA wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design.ConclusionsImaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms.

Background and Purpose: Paramagnetic rim lesions (PRLs) are an MRI biomarker of chronic inflammation in people with multiple sclerosis (MS). PRLs may aid in the diagnosis and prognosis of MS. However, manual identification of PRLs is time‐consuming and prone to poor interrater reliability. To address these challenges, the Automated Paramagnetic Rim Lesion (APRL) algorithm was developed to automate PRL detection. The primary objective of this study is to evaluate the accuracy of APRL for detecting PRLs in a multicenter setting. Methods: We applied APRL to a multicenter dataset, which included 3‐Tesla MRI acquired in 92 participants (43 with MS, 14 with clinically isolated syndrome [CIS]/radiologically isolated syndrome [RIS], 35 without RIS/CIS/MS). Subsequently, we assessed APRL's performance by comparing its results with manual PRL assessments carried out by a team of trained raters. Results: Among the 92 participants, expert raters identified 5637 white matter lesions and 148 PRLs. The automated segmentation method successfully captured 115 (78%) of the manually identified PRLs. Within these 115 identified lesions, APRL differentiated between manually identified PRLs and non‐PRLs with an area under the curve (AUC) of.73 (95% confidence interval [CI]: [.68,.78]). At the subject level, the count of APRL‐identified PRLs predicted MS diagnosis with an AUC of.69 (95% CI: [.57,.81]). Conclusion: Our study demonstrated APRL's capability to differentiate between PRLs and lesions without paramagnetic rims in a multicenter study. Automated identification of PRLs offers greater efficiency over manual identification and could facilitate large‐scale assessments of PRLs in clinical trials. [ABSTRACT FROM AUTHOR]

Background: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS. Objective: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS. Methods: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants. Results: The number of subjects included at each time point ranged from 23,917 subjects in 2008 to 55,797 subjects in 2021. In 2021, subjects with CNS-active polypharmacy were more likely to be 46–65 years of age and have CNS-related comorbidities compared to those without CNS-active polypharmacy. From 2008 to 2021, the age-adjusted prevalence of CNS-active polypharmacy among female subjects increased from 19.8% (95% confidence interval (CI) = 19.1–20.4) to 26.4% (95% CI = 25.9–26.8) versus 15.9% (95% CI = 14.8–17.0) to 18.6% (95% CI = 17.9–19.2) in male subjects. Conclusion: The prevalence of CNS-active polypharmacy has increased among people with MS with a growing disparity by sex. [ABSTRACT FROM AUTHOR]

Background: Effective and safe treatment options for multiple sclerosis (MS) are still needed. Montelukast, a leukotriene receptor antagonist (LTRA) currently indicated for asthma or allergic rhinitis, may provide an additional therapeutic approach. Objective: The study aimed to evaluate the effects of montelukast on the relapses of people with MS (pwMS). Methods: In this retrospective case–control study, two independent longitudinal claims datasets were used to emulate randomized clinical trials (RCTs). We identified pwMS aged 18–65 years, on MS disease-modifying therapies concomitantly, in de-identified claims from Optum's Clinformatics® Data Mart (CDM) and IQVIA PharMetrics® Plus for Academics. Cases included 483 pwMS on montelukast and with medication adherence in CDM and 208 in PharMetrics Plus for Academics. We randomly sampled controls from 35,330 pwMS without montelukast prescriptions in CDM and 10,128 in PharMetrics Plus for Academics. Relapses were measured over a 2-year period through inpatient hospitalization and corticosteroid claims. A doubly robust causal inference model estimated the effects of montelukast, adjusting for confounders and censored patients. Results: pwMS treated with montelukast demonstrated a statistically significant 23.6% reduction in relapses compared to non-users in 67.3% of emulated RCTs. Conclusion: Real-world evidence suggested that montelukast reduces MS relapses, warranting future clinical trials and further research on LTRAs' potential mechanism in MS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Multiple sclerosis (MS) typically presents in young adulthood. Recent data show the highest prevalence of MS in people aged 55 to 64 years; however, there are limited studies of this population. METHODS: Administrative US claims data from IBM-Truven MarketScan commercial and Medicare databases (2011-2017) were analyzed. People with MS 50 years or older were assigned to the aging MS cohort (n = 10,746). The matched controls were people 50 years or older without MS (n = 10,746). Multivariable models compared outcomes between groups. RESULTS: Infections were more frequent in the aging MS cohort vs matched controls (61% vs 45%; P < .0001); urinary tract, acute upper respiratory tract, and herpes zoster were the most frequent infection types. Malignancy rates were 20% for both groups (P = .8167); skin, breast, and prostate malignancies were the most frequent types. Skilled nursing facilities (aging MS cohort, 12%; matched controls, 3%; P < .0001) and MRI (aging MS cohort, 87%; matched controls, 37%; P < .0001) were used more frequently in the aging MS cohort; brain and spine were the most frequent types of MRI in the aging MS cohort. Time to first cane/walker or wheelchair use was shorter in the aging MS cohort (cane/walker use: HR, 2.1; 95% CI, 1.9-2.3; P < .0001; wheelchair use: HR, 6.9; 95% CI, 6.0-8.1; P < .0001). CONCLUSIONS: In people 50 years or older, measures typically associated with worse health primarily resulted from having MS rather than being a consequence of aging alone. [ABSTRACT FROM AUTHOR]

Background and purpose: Cerebellar damage is a valuable predictor of disability, particularly in progressive multiple sclerosis. It is not clear if it could be an equally useful predictor of motor disability worsening in the relapsing‐remitting phenotype. Aim: We aimed to determine whether cerebellar damage is an equally useful predictor of motor disability worsening in the relapsing‐remitting phenotype. Methods: Cerebellar lesion loads and volumes were estimated using baseline magnetic resonance imaging from the CombiRx trial (n = 838). The relationship between cerebellar damage and time to disability worsening (confirmed disability progression [CDP], timed 25‐foot walk test [T25FWT] score worsening, nine‐hole peg test [9HPT] score worsening) was tested in stagewise and stepwise Cox proportional hazards models, accounting for demographics and supratentorial damage. Results: Shorter time to 9HPT score worsening was associated with higher baseline Expanded Disability Status Scale (EDSS) score (hazard ratio [HR] 1.408, p = 0.0042) and higher volume of supratentorial and cerebellar T2 lesions (HR 1.005 p = 0.0196 and HR 2.211, p = 0.0002, respectively). Shorter time to T25FWT score worsening was associated with higher baseline EDSS (HR 1.232, p = 0.0006). Shorter time to CDP was associated with older age (HR 1.026, p = 0.0010), lower baseline EDSS score (HR 0.428, p < 0.0001) and higher volume of supratentorial T2 lesions (HR 1.024, p < 0.0001). Conclusion: Among the explored outcomes, single time‐point evaluation of cerebellar damage only allows the prediction of manual dexterity worsening. In clinical studies the selection of imaging biomarkers should be informed by the outcome of interest. [ABSTRACT FROM AUTHOR]