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The clinical presentation of repetitive choreiform involuntary movements of the anterior abdominal wall was first introduced as “belly dancer’s dyskinesia.” Etiologies of this rare condition include idiopathic causes, medication inducement, or post-abdominal surgery. We report a case of orobuccal stereotypic movements and abdominal wall dyskinesia secondary to prochlorperazine intake. The movements began 2 weeks after cessation of prochlorperazine. The patient took this dopamine receptor-blocking medication for 6 months to treat nausea due to chemotherapy. To our knowledge, abdominal wall dyskinesia as a tardive syndrome of prochlorperazine has not been previously reported.

The effect of feeding graded levels (0, 5, 10, 15, 20, 25 and 30%) of untreated African star apple kernel meal (ASAKM) on the performance and blood profile of broilers was investigated in an 8-week trial. Two hundred and ten oneweek-old Cobb strain broiler chicks were randomly allotted to 7 diets with 3 replicates of 10 chicks per replicate in a completely randomized design. Data on minerals, vitamins, amino acids and quantification of some anti-nutrients were assayed. The results showed that the kernel was high in nutrients, especially carbohydrate as a source of energy but contains high levels of anti-nutritional or toxic factors. Performance traits (p0.05). Increasing levels of ASAKM in diets caused elevation of AST, ALT, ALP and a significant increase in blood urea levels in the raw kernel meal based diets relative to the control diet (p

Except for a small subset of patients with angina whose survival is improved with coronary artery bypass surgery, chronic stable angina can be appropriately managed with medical therapy in the vast majority of patients. Drug therapy includes aspirin, beta-adrenergic blockers, cholesterol-lowering agents and other anti-ischemic drugs that can ameliorate angina and improve the patient's quality of life. Understanding how and when to use these medicines involves knowledge of the mechanisms of these drugs as well as familiarity with the literature supporting their efficacy in various patient populations. [ABSTRACT FROM AUTHOR]

There are currently no reported cardiac indices for the Nigerian dog. The aim of the study was to obtain breed specific echocardiographic indices for Nigerian local dogs. M– mode measurements of the left ventricle of 20 healthy dogs were obtained from short axis right parasternal view. The result of the study showed that posterior wall thickness in diastole and systole (PWTd, PWTs), septal wall thickness in diastole and systole (SWTd, SWTs), and left ventricular internal diameter in diastole and systole (LVIDd LVIDs) were positively and significantly correlated with body weight. Except PWT and functional indices like ejection fraction (EF) and fractional shortening (FS) whose values were higher than some breeds in literature, all other indices were within the range of values obtained in breeds previously studied. There was no significant correlation between PWTd PWTs, SWTd, SWTs and cardiac function indices such as EF, FS, enddiastolic volume (EDV), end- systolic volume (ESV) and stroke volume (SV). Although LVIDd had positive correlation with EDV, ESV, and SV, it did not correlate with FS and EF. The study revealed that cardiac function indices like FS and EF are not dependent on septal and wall thickness but rather on ventriclular volume and diameter in systole. Since cardiac function indices are also not dependent on body size, the Nigerian mongrels could serve as a useful model for cardiac studies because of their functional homogenous heart.

Abstract Background HIV-1 infection of the thymus contributes to the defective regeneration and loss of CD4+ T cells in HIV-1-infected individuals. As thymic dendritic cells (DC) are permissive to infection by HIV-1, we examined the ability of thymic DC to enhance infection of thymocytes which may contribute to the overall depletion of CD4+ T cells. We compared productive infection in isolated human thymic and blood CD11c+ myeloid DC (mDC) and CD123+ plasmacytoid DC (pDC) using enhanced green fluorescent protein (EGFP) CCR5 (R5)-tropic NL(AD8) and CXCR4 (X4)-tropic NL4-3 HIV-1 reporter viruses. Transfer of productive HIV-1 infection from thymic mDC and pDC was determined by culturing these DC subsets either alone or with sorted thymocytes. Results Productive infection was observed in both thymic pDC and mDC following exposure to R5 HIV-1 and X4 HIV-1. Thymic pDC were more frequently productively infected by both R5 and X4 HIV-1 than thymic mDC (p = 0.03; n = 6). Thymic pDC efficiently transferred productive R5 HIV-1 infection to both CD3hi (p = 0.01; mean fold increase of 6.5; n = 6) and CD3lo thymocytes (mean fold increase of 1.6; n = 2). In comparison, transfer of productive infection by thymic mDC was not observed for either X4 or R5 HIV-1. Conclusions The capacity of thymic pDC to efficiently transfer R5 HIV-1 to both mature and immature thymocytes that are otherwise refractory to R5 virus may represent a pathway to early infection and impaired production of thymocytes and CD4+ T cells in HIV-1-infected individuals.

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., (© 2024 American Society of Neuroimaging.)

The differential diagnosis of suspected multiple sclerosis has been developed using data from North America, northern Europe, and Australasia, with a focus on White populations. People from minority ethnic and racial backgrounds in regions where prevalence of multiple sclerosis is high are more often negatively affected by social determinants of health, compared with White people in these regions. A better understanding of changing demographics, the clinical characteristics of people from minority ethnic or racial backgrounds, and the social challenges they face might facilitate equitable clinical approaches when considering a diagnosis of multiple sclerosis. Neuromyelitis optica, systemic lupus erythematous, neurosarcoidosis, infections, and cerebrovascular conditions (eg, hypertension) should be considered in the differential diagnosis of multiple sclerosis for people from minority ethnic and racial backgrounds in North America, northern Europe, and Australasia. The diagnosis of multiple sclerosis in people from a minority ethnic or racial background in these regions requires a comprehensive approach that considers the complex interplay of immigration, diagnostic inequity, and social determinants of health., Competing Interests: Declaration of interests LA has received research support from the National Multiple Sclerosis Society, National Institutes of Health National Institute of Neurological Disorders and Stroke, Bristol Myers Squibb Foundation, Race to Erase MS Foundation, and Biogen Idec; is a local Principal Investigator for commercial trials funded by Genentech, Sanofi, and Genzyme; and declares consulting fees from Biogen Idec, Novartis, Genentech, and EMD Serono. DR has received research support from MS Canada, the National Multiple Sclerosis Society, Consortium of Multiple Sclerosis Centers, University of Toronto Division of Neurology, and Roche Canada; and has received speaker or consultant fees from Alexion, Biogen, EMD Serono, Horizon Therapeutics, Novartis, Roche, and Sanofi Aventis. OC is a member of the data and safety monitoring board for Novartis, has served on one advisory board for Biogen, and has received a speaker honorarium from Merck. DO has received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, and Novartis; and has received consulting fees from Biogen Idec, Bristol Myers Squibb, Genentech/Roche, Genzyme, Janssen, Novartis, and Merck. MM has served on scientific advisory boards for Sanofi, Novartis, and Merck; and received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, and Bristol Myers Squibb. VR has received honoraria from the Autonomous University of Barcelona, Roche, Corne Neurosciences, and the Multiple Sclerosis Association of America; and is a consultant (Expert Opinion Program) for Teladoc Health International. DK has served as a consultant for CVS Health. RD has received research support from the UK MS Society, National Multiple Sclerosis Society, BMA Foundation, Horne Family Charitable Foundation, Biogen, and Merck; and has received honoraria for advisory boards and educational activities from Biogen, Novartis, Sandoz, Roche, Janssen, and Merck. MW is a co-investigator for a study funded by Genentech; has received honoraria and consulting fees from Alexion, Biogen Idec, Novartis, Genentech, Horizon Therapeutics, EMD Serono, Octave Biosciences, TG Therapeutics, and Sanofi/Genzyme; and has participated in speakers bureau for Biogen Idec, Genentech, EMD Serono, and TG Therapeutics. RAM is a co-investigator on a study funded in part by Biogen and Roche (no funds to her or her institution). JAC has received personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI; and serves as an Editor for Multiple Sclerosis. BB served as a consultant for Novartis, Roche, and UCB; and is funded by the National Multiple Sclerosis Society and National Institutes of Health for work unrelated to this paper. BH served on scientific advisory boards for Novartis; and has served as a data and safety monitoring board member for AllergyCare, Sandoz, Polpharma, Biocon and TG therapeutics; and his institution has received institutional research grants from Roche. BH has received honoraria for counselling for the Gerson Lehrmann Group; and holds part of two patents: (1) the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis, and (2) genetic determinants of neutralising antibodies to interferon. SDN reports grants or contracts from Biogen, Roche, Genentech, National Multiple Sclerosis Society, Department of Defense, and Patient Centered Outcomes Research Institute; reports personal compensation for consulting for Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and participates on a data safety monitoring board and advisory board for MedDay Pharmaceuticals; and reports support from the Stiff Person Syndrome Research Foundation. AJS reports grant funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, and Bristol Myers Squibb; is contracted for research with Sanofi, Biogen, Novartis, Actelion, and Genentec; has received personal compensation for consulting from EMD Serono and Octave Bioscience; has received payment or honoraria for lectures for EMD Serono; has been called for expert testimony by The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; participates on a data safety monitoring board for Patient Centered Outcomes Research Institute and Yale University; participates on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is content Chair for the American Academy of Neurology Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. WR3rd has research grant support from the National Institutes of Health and the Veterans Administration; reports honoraria, consulting fees, and support for advisory activities for the Consortium of Multiple Sclerosis Centers, the University of Maryland, the University of Calgary, Temple University, Thomas Jefferson University, the Chan Zuckerberg Initiative, the American Association for Cancer Research, and the Alzheimer's Association of Georgia; and receives compensation for serving as Director of specialty programming for Mediflix. AS and BT declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe., Competing Interests: Declaration of interests JC declares receiving grants or research contracts from Biogen and Merck; personal compensation for consulting from Merck; payment or honoraria for lectures from Biogen, Merck, Bristol Myers Squibb, Novartis, and Roche; and support for attending meetings and travel from Merck. JC is a deputy chair International Medical and Scientific Board of Multiple sclerosis International Federation (MSIF), unpaid; and has received equipment, materials, drugs, medical writing, gifts, or other services from Novartis (Investigator initiated award). AJS declares receiving grant funding from National Institute of Neurological Disorders and Stroke, National Institutes of Health and Bristol Myers Squibb (investigator initiated award); has done contracted research with Sanofi, Biogen, Novartis, Actelion, and Genentech; has received personal compensation for consulting from Emmanuel Merck, Darmstadt, Serono and Octave Bioscience; has received payments or honoraria for lectures from Emmanuel Merck, Darmstadt, Serono; has received expert testimony from The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; is a participant on a Data Safety Monitoring Board for the Patient Centered Research Institute, and Yale University; declares participation on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is a content Chair for the American Academy of Neurology (AAN) Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. JAC declares personal compensation for consulting from Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiND Therapeutics, INMune, and Sandoz; and serving as an editor of Multiple Sclerosis Journal. BLB is funded by the National Multiple Sclerosis Society, and National Institute of Health; is a consultant for Roche, and Sanofi; and is a Board Director AAN (unpaid). TG has served as a consultant and received compensation from Genentech, Horizon, Sanofi, Alexion, and Greenwich Biosciences. BH declares grants from the European Union, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft; received personal compensation for consulting from Sandoz, Novartis, and GLG consulting; holds patents for antibodies against KIR4·1 in a subpopulation of patients with multiple sclerosis (2012) and genetic determinants of neutralising antibodies to interferon (filed 2010); and participated in a Data Safety and Monitoring Board for Novartis, Allergy Care DSMB, TG Therapeutics, and Polpharma, and Advisory Board for Novartis. HJK declares a research grant from the National Research Foundation of Korea and research support from Aprilbio, UCB, and Eisai; has received consultancy fees from Altos Biologics, AstraZeneca, Biogen, Daewoong, Kaigene, Kolon Life Science, MDimune, Merck Serono, and Roche; declares honoraria for lectures from Alexion, Eisai, GCPharma, Handok, Mitsubishi Tanabe Pharma, and Sanofi Genzyme; has received personal compensation for participation on a Data Safety Monitoring Board from Sanofi-Genzyme; has received compensation as Co-editor for the Multiple Sclerosis Journal and Associate Editor for the Journal of Clinical Neurology; and is a Vice President of Pan-Asian Committee on Treatment and Research in Multiple Sclerosis (unpaid). RAM declares grants or contracts from Biogen, Idec, and Roche. FM has received research funding to her institution from Sumaira Foundation, Genentech, Biogen, Horizon Therapeutics, US National Histitute Institute of Health, US Department of State, Foundation Pierre Fabre, and Novartis; has received consulting fees from Alexion, EMD Serono, Genentech, TG Therapeutics, and Horizon Therapeutics; and declares shares of the startup company Brain Capture (not related to the content of this manuscript). SDN declares grants or contracts (paid directly to institution) from Biogen, Roche, Genentech, National MS Society, Department of Defense, and Patient Centered Outcomes Research Institute; has received personal compensation for consulting from Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and is a study lead principal investigator for a Roche clinical trial programme. MAS declares personal honoraria for lectures from Roche, Biogen, Cinnagen, NanoAlvand, Merck, Novartis, and Abidi. DKS declares grants or research contracts from CNPq / Brazil 425331/2016–4 and 308636/2019–8, and Brazilian National Council for Scientific and Technological Development; has received investigator initiated awards from TEVA, Merck, and Biogen; has received personal compensation for consulting from Roche, and Alexion; declares personal honoraria for lectures from Roche, Alexion, Horizon, Merck, Americas Health Foundation; and is a member of International Society of Neuroimmunology, International Advisory Board (unpaid), and Academia Brasileira de Neurologia, Educational Committee (unpaid). DS declares a pilot research grant from the National MS Society paid to the Institution; declares receipt of personal honoraria for lecturing from Roche Pharmaceuticals; declares travel support from Roche Pharmaceutical; and is a Committee member and chair of Multiple Sclerosis International Federation (unpaid). AS has received grants or contracts from the Turkish MS Society, Istanbul University-Cerrahpasa Research Support Funds, and The Scientific and Technological Research Council of Türkiye Health Sciences Research Grants; has received consulting fees from Roche, Merck-Serono, Biogen Idec/Gen Pharma of Turkey , Sanofi-Genzyme, Novartis, and Alexion; has received honoraria for lectures from Sanofi-Genzyme, Novartis, TEVA, and Roche; and has received support for attending meetings from Sanofi-Genzyme, Roche, Merck-Serono, and Alexion. KT declares personal consulting fees from Merck and Eisai; declares payment for lectures from Merck, Eisai, Roche, and Terumo Blood and Cell Technology; and is a member of the Organizing Committee Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid). MW has received publication royalties from Springer and Elsevier; has received consultancy honoraria from Icometrix, Imcyse, Novartis, Sanofi, Merck, and Biologix; declares personal compensation for lectures or presentations from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, Icometrix, Merck-Serono, Novartis, Roche, and Sanofi-Genzyme; and declares support for attending meetings from Merck-Serono. BGW declares royalties from RSR, Hospices Civils de Lyon, MVZ Labor PD Dr Volkmann und Kollegen GbR , and Oxford University; declares personal consulting fees from Roche, Horizon Therapeutics, Cambridge Pharmaceuticals, and Mitsubishi Tanabe; has received payments for lecture presentations from Roche and Horizon; has a patent planned for NMO-IgG for diagnosis of neuromyelitis optica; and declares participation on a Data Safety Monitoring Board and Advisory borads for Alexion MedImmune/VielaBio/Horizon, and UCB Biosciences. KF declares grants from Ministry of Education, Culture, Sports, Science and Technology of Japan and Ministry of Health, Welfare and Labor of Japan; has received personal compensation for consulting from Merck Biopharma, Japan Tobacco, and Abbvie; has received payment or honoraria forlectures and presentations from Biogen, Eisai, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, Teijin, Asahi Kasei Medical, Merck, and Takeda; declares participation in an Advisory Board for Biogen, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, and UCB; serves as President of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid), President of the Japanese Society of Neuroimmunology (unpaid), is a Board Member of the Japan Multiple Sclerosis Society (unpaid), is a board member of theEuropean Charcot Foundation (unpaid), and is a Member of the International Medical and Scientific Board, MSIF (unpaid). All other authors declared no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Diagnostic errors in multiple sclerosis (MS) impact patients and healthcare systems., Objectives: This study aimed to determine the prevalence of MS misdiagnosis and underdiagnosis, time delay in reaching a correct diagnosis and potential impact of sex., Methods: Systematic review and meta-analysis on MS diagnostic errors., Results: Out of 3910 studies, we included 62 for a qualitative synthesis and 24 for meta-analyses. Frequency of misdiagnosis (incorrect assignment of an MS diagnosis) ranged from 5% to 41%, with a pooled proportion based on six studies of 15% (95% CI: 9%-26%, n = 1621). The delay to rectify a misdiagnosis ranged from 0.3 to 15.9 years. Conversely, underdiagnosis (unrecognized diagnosis of MS) ranged from 3% to 58%, with a pooled proportion in four studies of 36% (95% CI: 20%-55%, n = 728). Pooling seven studies comprising 2851 individuals suggested a diagnostic delay to establish a correct MS diagnosis of 17.3 months (95% CI: 11.9-22.7) in patients underdiagnosed. In a meta-analysis of five studies, women were 2.1 times more likely to be misdiagnosed with MS compared to men (odds ratio, 95% CI: 1.53-2.86)., Conclusion: This study provides summary-level evidence for the high prevalence of MS misdiagnosis and underdiagnosis. Future studies are needed to understand the causes of these diagnostic challenges in MS care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: F.P. declares research grants outside of this study from Janssen, Merck KGaA and UCB, and fees for serving on Data Monitoring Committee in clinical trials with Chugai, Lundbeck and Roche and expert testimony for Novartis. A.J.S. declares consulting for Octave Bioscience, TG Therapeutics and Kiniksa Pharmaceuticals; served on advisory board for Genentech, Horizon Therapeutics; provided non-promotional Speaking for EMD Serono; site PI for contract research for Sanofi, Actelion, Genentech/Roche and Novartis; received research funding from Bristol Myers Squibb. B.V.I. declares non-promotional Speaking for CSL Behring. The other authors declare no conflicts of interest.

Paroxysmal neurological symptoms in patients with multiple sclerosis (MS) have long been acknowledged. However, consideration of whether such symptoms are a clinical attack and sufficient for fulfillment of MS diagnostic criteria has varied as criteria have evolved over time. Previous studies and anecdotal reports indicate that some patients with MS first present with syndromes such as trigeminal neuralgia, Lhermitte's phenomenon, tonic spasm, and seizure years before an attack typical of MS such as optic neuritis or myelitis. We discuss four patients with presumed MS who initially presented with these syndromes with evidence of a corresponding central nervous system (CNS) lesion who, were these symptoms considered an attack, could have been diagnosed with relapsing remitting MS or clinically isolated syndrome. This case series aims to highlight the unmet need for data for such patient presentations and for clinical guidance from future MS diagnostic criteria to optimize care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KDH: reports no conflicts. CRH: consulting fees from Horizon (now Amgen) and Sanofi. AJS received compensation for consulting for Octave Bioscience, TG Therapeutics and Kiniksa Pharmaceuticals, an advisory board for Genentech, Bristol Meyers Squibb, and Horizon Therapeutics and provided non-promotional Speaking for EMD Serono. He is site PI for contract research for Sanofi, Actelion, Genentech/Roche, Novartis and received research funding from Bristol Meyers Squibb.

Background and Purpose: The central vein sign (CVS) is a proposed diagnostic imaging biomarker for multiple sclerosis (MS). The proportion of white matter lesions exhibiting the CVS (CVS+) is higher in patients with MS compared to its radiological mimics. Evaluation for CVS+ lesions in prior studies have been performed by manual rating, an approach that is time-consuming and has variable inter-rater reliability. Accurate automated methods would facilitate efficient assessment for CVS. The objective of this study was to compare the performance of an automated CVS detection method with manual rating for the diagnosis of MS., Materials and Methods: 3T MRI was acquired in 86 participants undergoing evaluation for MS in a 9-site multicenter study. Participants presented with either typical or atypical clinical syndromes for MS. An automated CVS detection method was employed and compared to manual rating, including total CVS+ proportion and a simplified counting method in which experts visually identified up to 6 CVS+ lesions using FLAIR* contrast (a voxel-wise product of T 2 FLAIR and post-contrast T 2 *-EPI images)., Results: Automated CVS processing was completed in 79 of 86 participants (91%), of whom 28 (35%) fulfilled the 2017 McDonald criteria at the time of imaging. The area under the receiver-operator characteristic curve (AUC) for discrimination between participants with and without MS for the automated CVS approach was 0.78 (95% confidence interval: [0.67,0.88]). This was not significantly different from simplified manual counting methods (select6*) (0.80 [0.69,0.91]) or manual assessment of total CVS+ proportion (0.89 [0.82,0.96]). In a sensitivity analysis excluding 11 participants whose MRI exhibited motion artifact, the AUC for the automated method was 0.81 [0.70,0.91], which was not statistically different from that for select6* (0.79 [0.68,0.92]) or manual assessment of total CVS+ proportion (0.89 [0.81,0.97])., Conclusions: Automated CVS assessment was comparable to manual CVS scoring for differentiating patients with MS from those with other diagnoses. Large, prospective, multicenter studies utilizing automated methods and enrolling the breadth of disorders referred for suspicion of MS are needed to determine optimal approaches for clinical implementation of an automated CVS detection method., Abbreviations: CVS= central vein sign; CVS+ = white matter lesions exhibiting the CVS; MRI = magnetic resonance imaging; MS = multiple sclerosis; T 2 FLAIR = T 2 fluid-attenuated inversion recovery; T 2 *-EPI = T 2 *-weighted 3D echo planar imaging; FLAIR* = a voxel-wise product of T 2 FLAIR and post-contrast T 2 *-EPI images; select6* = simplified counting method in which experts visually identified up to 6 CVS+ lesions on FLAIR* imaging., Competing Interests: Disclosures: D.S. Reich’s lab has received research support from Abata Therapeutics and Sanofi-Genzyme. A.J. Solomon reports consulting or advisory board compensation for Octave Bioscience, TG Therapeutics, Kiniksa Pharmaceuticals, Genentech, and Horizon Therapeutics, non-promotional speaking for EMD Serono, contracted research for Sanofi, Actelion, Genentech/Roche, Novartis, and research funding from Bristol Meyers Squibb., (© 2024 by American Journal of Neuroradiology.)

Importance: While the typical onset of multiple sclerosis (MS) occurs in early adulthood, 2% to 10% of cases initially present prior to age 18 years, and approximately 5% after age 50 years. Guidance on approaches to differential diagnosis in suspected MS specific to these 2 age groups is needed., Observations: There are unique biological factors in children younger than 18 years and in adults older than age 50 years compared to typical adult-onset MS. These biological differences, particularly immunological and hormonal, may influence the clinical presentation of MS, resilience to neuronal injury, and differential diagnosis. While mimics of MS at the typical age at onset have been described, a comprehensive approach focused on the younger and older ends of the age spectrum has not been previously published., Conclusions and Relevance: An international committee of MS experts in pediatric and adult MS was formed to provide consensus guidance on diagnostic approaches and key clinical and paraclinical red flags for non-MS diagnosis in children and older adults.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Karlo Toljan: Training grant: National MS Society (FP-2207-39855).Lynn Daboul: Research support: NIH Medical Research Scholars Program.Praneeta Raza: Nothing to disclose.Melissa L. Martin: Nothing to disclose.Quy Cao: Nothing to disclose.Carly M. O’Donnell: Nothing to disclose.Paulo Rodrigues: Employed by and holds options of QMENTA.John Derbyshire: Nothing to disclose.Christina J. Azevedo: Research support: National Multiple Sclerosis Society, National Institutes of Health. Consulting: Genentech, EMD Serono, Alexion Pharmaceuticals, Sanofi Genzyme, Horizon Therapeutics.Amit Bar-Or: Consulting: Accure, Atara Biotherapeutics, Biogen, Bristol Myers Squibb, GlaxoSmithKline, Gossamer, Janssen, AstraZeneca, EMD Serono, Novartis, Genentech, Sanofi. Research support: Biogen, Genentech, EMD Serono, Novartis.Eduardo Caverzasi: Nothing to disclose.Peter A Calabresi: Research support: Genentech. Advisory board: Lilly, Novartis, Idorsia, and Project Efflux.Bruce A. C. Cree: Consulting: Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon, Immunic AG, Kyverna, Neuron23, Novartis, Sanofi, and TG Therapeutics; research support from Genentech.Leorah Freeman: Advisory board: Genentech, Novartis, Celgene. Consulting: EMD Serono, Celgene, Biogen. Program sponsorship: Biogen, EMD Serono.Roland G. Henry: Consulting: Neurona, Roche, Novartis, Sanofi, QIA, Celgene/BMS, Atara, Medday, Boston Pharma. Research support: Roche, Atara.Erin E Longbrake: Consulting: Genentech, Sanofi, Alexion, Biogen, EMD Serono, Bristol Myers Squibb.Jiwon Oh: Research support: Biogen, Roche, EMD Serono. Consulting: EMD Serono, Sanofi, Biogen, Roche, Celgene, Novartis.Nico Papinutto: Research support: Race to Erase MS Foundation.Daniel Pelletier: Consulting: Sanofi, Roche, Novartis.Rohini D. Samudralwar: Advisory board: Biogen, EMD Serono, Sanofi. Consulting: EMD Serono, Biogen.Matthew K. Schindler: Nothing to disclose.Elias S. Sotirchos: Consulting for Alexion, Viela Bio, Horizon Therapeutics, Genentech, Ad Scientiam. Honoraria: Alexion, Viela Bio, Biogen.Nancy L. Sicotte: Research support: NIH, National MS Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Biogen.Andrew J. Solomon: Advisory board: Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics. Consulting: Octave Bioscience. Non-promotional speaking: EMD Serono. Research support: Bristol Myers Squibb, Sanofi, Biogen, Novartis, Janssen, Genentech. Trainee funding: Biogen.Russell T. Shinohara: Consulting: Octave Bioscience. Research support: NIH, National MS Society.Daniel S. Reich: Supported by Intramural Research Program of NINDS. Research support: Abata, Sanofi.Pascal Sati: Research support: NIH, National MS Society, Erwin Rautenberg Foundation.Daniel Ontaneda: Research support: NIH, National MS Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Bristol Myers Squibb, Genentech, Sanofi, Novartis. Consulting: Biogen, Bristol Myers Squibb, Genentech, Sanofi, Janssen, Novartis, Pipeline Therapeutics, and Merck.

Purpose of Review: Misdiagnosis of multiple sclerosis (MS) is a prevalent worldwide problem. This review discusses how MS misdiagnosis has evolved over time and focuses on contemporary challenges and potential strategies for its prevention., Recent Findings: Recent studies report cohorts with a range of misdiagnosis between 5 and 18%. Common disorders are frequently misdiagnosed as MS. Overreliance on MRI findings and misapplication of MS diagnostic criteria are often associated with misdiagnosis. Emerging imaging biomarkers, including the central vein sign and paramagnetic rim lesions, may aid diagnostic accuracy when evaluating patients for suspected MS. MS misdiagnosis can have harmful consequences for patients and healthcare systems. Further research is needed to better understand its causes. Concerted and novel educational efforts to ensure accurate and widespread implementation of MS diagnostic criteria remain an unmet need. The incorporation of diagnostic biomarkers highly specific for MS in the future may prevent misdiagnosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Supraventricular tachycardia (SVT) is commonly evaluated in the emergency department (ED). While troponin has been shown to be elevated in SVT, its usefulness for predicting coronary artery disease and future adverse cardiovascular outcomes has not been shown., Objectives: We aimed to evaluate the prognostic utility of troponin measurement as part of SVT management in the ED., Methods: We performed a literature search in the PubMed and Scopus databases from inception to August 30, 2023, including all studies reporting troponin measurements in adult patients (age > 18 years) presenting to the ED with supraventricular tachycardia. The primary outcome of interest for this study was the prevalence of elevated troponin in patients with SVT. Secondary outcomes included the prevalence of major adverse cardiac events (MACE) and additional cardiac testing with significant findings., Results: We included 7 studies (500 patients) in our analysis. Six studies reported the number of patients with SVT and elevated troponin, with a pooled prevalence of 46% (95% CI 27-66%, I 2 93%). The pooled prevalence of all MACE in our study was 6% (95% CI 1-25%), while the prevalence for MACE among patients with elevated serum troponin levels was 11% (95% CI 4-27%)., Conclusions: Troponin levels are frequently ordered for ED patients with SVT and are often elevated. However, this review suggests that they have low prognostic value in predicting MACE., Competing Interests: Declaration of competing interest The authors do not have a financial interest or relationship to disclose regarding this research project., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: People with multiple sclerosis (pwMS) struggle with whether, how, and how much to disclose their diagnosis. They often expend resources to conceal their diagnosis, and hold beliefs that it may negatively affect their personal relationships and/or professional opportunities. To better understand these effects, we developed a measure to quantify concealment behaviors and disclosure beliefs. Our main objective is to evaluate relationships of DISCO-MS responses to health and quality of life in a multinational cohort., Methods: Survey responses were obtained for DISCO-MS and PROMIS-MS scales: global health, communication, social roles participation, anxiety, depression, emotional / behavioral dyscontrol, fatigue, lower extremity function, positive affect / well-being, social roles satisfaction, sleep, stigma, upper extremity function, cognitive function, bladder control, bowel control, visual function. Simple linear regression assessed associations., Results: 263 pwMS were include. Higher concealment was associated with higher anxiety (beta= 0.15 [0.07, 0.23]), depression (beta = 0.13 [0.05, 0.21]), emotional dyscontrol (beta = 0.12 [0.04, 0.20]), lower affect / well-being (beta = -0.13 [-0.21, - 0.05]). Higher anticipation of negative consequences of disclosure was associated with lower self-reported physical (beta = -0.15) and mental health (beta = -0.14), lower positive affect / well-being, social roles satisfaction, higher anxiety, depression, emotional dyscontrol, sleep disturbance, and higher perceived stigma., Discussion: These results reveal potential consequences of diagnosis concealment for physical and mental health and quality of life. Raising awareness and implementing interventions may mitigate negative repercussions of concealment., Competing Interests: Declaration of competing interest Disclosures: VML: Speaker honoraria: American Academy of Neurology. Compensation for reviewing: National Institutes of Health, United States Department of Defense. Advisory Board: Biogen. CB: No disclosures to report. RTS: Consulting: Octave Bioscience. Compensation for reviewing: American Medical Association, National Institutes of Health, Department of Defense, Emerson Collective. SMW: No disclosures to report. HS: No disclosures to report. SMA: No disclosures to report. AS: Advisory Board: Almirall, Merck. Non-promotional speaking: Merck, Neurotalk. AJS: Advisory Board: Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics. Consulting: Octave Bioscience. Non-promotional speaking: EMD Serono. Research support: Bristol Myers Squibb. Trainee funding: Biogen. Contracted Research: Sanofi, Biogen, Novartis, Actelion, Genentech/Roche. Expert witness testimony., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.L. has no relevant disclosures. Z.R. has relevant disclosures. V.G. has no relevant disclosures. In the last 3 years, Dr C.J.A. has received consulting fees from Horizon Therapeutics, Genentech, Sanofi Genzyme, TG Therapeutics, and EMD Serono. She has received grant support from the National Institutes of Health and the National Multiple Sclerosis Society. P.A.C. is PI on grants to JHU from the Myelin Repair Foundation and Genentech. He has received consulting fees from Lilly, Idorsia, and Novartis. B.A.C.C. has no relevant disclosures. L.F. has received fees for consultancy and/or advisory board participation from Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Sanofi, Horizon Therapeutics, and TG Therapeutics; has received honorarium for participation in educational programs from Medscape, Inc., the MS Association of America and Impact Education; has received program sponsorship from EMD Serono; and grant support from NIH/NINDS, PCORI, Genentech, and EMD Serono through her institution. E.E.L. has received honoraria for consulting from Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, TG Therapeutics, Janssen, and NGM Bio. She has received research from Biogen and Genentech. J.O. is none relevant to this manuscript. M.K.S. has no relevant disclosures. N.L.S. received grant funding from NIH, PCORI, and NMSS. D.S.R. received research funding from Abata and Sanofi. D.O. received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, Bristol Myers Squibb, and Novartis, and also received consulting fees from Biogen Idec, Bristol Myers Squibb, Genentech/Roche, Novartis, Pipeline Therapeutics, and Merck. P.S. received support from the National Institutes of Health, Department of Defense, National Multiple Sclerosis Society and the Erwin Rautenberg Foundation. Q.C. has no relevant disclosures. R.T.S. received consulting income from Octave Bioscience and compensation for scientific reviewing from the American Medical Association. A.J.S. as consulting or advisory board: Genentech, Octave Bioscience, Horizon Therapeutics, Kiniksa Pharmaceuticals, and TG Therapeutics; non-promotional speaking: EMD Serono; research funding: Bristol Meyers Squibb; and contract research: Sanofi, Actelion, Genentech, and Novartis.

Objective: Infrapopliteal peripheral vascular interventions (PVIs) for claudication are still performed in the USA. This study aimed to evaluate whether infrapopliteal PVI is associated with worse long term outcomes than isolated femoropopliteal PVI for treatment of claudication., Methods: A retrospective analysis of fee for service claims in a national administrative database was conducted using 100% of the Medicare fee for service claims between 2017 and 2019 to capture all Medicare beneficiaries who underwent an index infra-inguinal PVI for claudication. Hierarchical Cox proportional hazards models were performed to assess the association of infrapopliteal PVI with conversion to chronic limb threatening ischaemia (CLTI), repeat PVI, and major amputation., Results: In total, 36 147 patients (41.1% female; 89.7% age ≥ 65 years; 79.0% non-Hispanic White ethnicity) underwent an index PVI for claudication, of whom 32.6% (n = 11 790) received an infrapopliteal PVI. Of these, 61.4% (n = 7 245) received a concomitant femoropopliteal PVI and 38.6% (n = 4 545) received an isolated infrapopliteal PVI. The median follow up time was 3.5 years (interquartile range 2.7, 4.3). Patients receiving infrapopliteal PVI had a higher three year cumulative incidence of conversion to CLTI (26.0%; 95% confidence interval [CI] 24.9 - 27.2% vs. 19.9%; 95% CI 19.1 - 20.7%), repeat PVI (56.0%; 95% CI 54.8 - 57.3% vs. 45.7%; 95% CI 44.9 - 46.6%), and major amputation (2.2%; 95% CI 1.8 - 2.6% vs. 1.3%; 95% CI 1.1 - 1.5%) compared with patients receiving isolated femoropopliteal PVI. After adjusting for patient and physician level characteristics, the risk of conversion to CLTI (adjusted hazard ratio [aHR] 1.31, 95% CI 1.23 - 1.39), repeat PVI (aHR 1.12, 95% CI 1.05 - 1.20), and major amputation (aHR 1.72, 95% CI 1.42 - 2.07) remained significantly higher for patients receiving infrapopliteal PVI. An increasing number of infrapopliteal vessels treated during the index intervention was associated with increasingly poor outcomes (p < .001 for trend)., Conclusion: Infrapopliteal PVI for claudication is associated with worse long term outcomes relative to isolated femoropopliteal PVI., (Copyright © 2024 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: There are limited data supporting or opposing the use of infrapopliteal peripheral vascular interventions (PVI) for the treatment of claudication., Objectives: We aimed to evaluate the association of infrapopliteal PVI with long-term outcomes compared with isolated femoropopliteal PVI for the treatment of claudication., Methods: We conducted a retrospective analysis of all patients in the Medicare-matched Vascular Quality Initiative database who underwent an index infrainguinal PVI for claudication from January 2004-December 2019 using Cox proportional hazards models., Results: Of 14,261 patients (39.9% female; 85.6% age ≥65 years, 87.7% non-Hispanic white) who underwent an index infrainguinal PVI for claudication, 16.6% (N=2,369) received an infrapopliteal PVI. The median follow-up after index PVI was 3.7 years (IQR 2.1-6.1). Compared to patients who underwent isolated femoropopliteal PVI, patients receiving any infrapopliteal PVI had a higher 3-year cumulative incidence of conversion to CLTI (33.3% vs. 23.8%; P<0.001); repeat PVI (41.0% vs. 38.2%; P<0.01); and amputation (8.1% vs. 2.8%; P<0.001). After risk-adjustment, patients undergoing infrapopliteal PVI had a higher risk of conversion to CLTI (aHR 1.39, 95% CI, 1.25-1.53); repeat PVI (aHR 1.10, 95% CI, 1.01-1.19); and amputation (aHR 2.18, 95% CI, 1.77-2.67). Findings were consistent after adjusting for competing risk of death; in a 1:1 propensity-matched analysis; and in subgroup analyses stratified by TASC disease, diabetes, and end-stage kidney disease., Conclusions: Infrapopliteal PVI is associated with worse long-term outcomes than femoropopliteal PVI for claudication. These risks should be discussed with patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.C.H. declares no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. A.J.S. consulting for Octave Bioscience and Kiniksa Pharmaceuticals; served on advisory board for TG Therapeutics, Horizon Therapeutics, and Bristol Meyers Squibb; provided non-promotional Speaking for EMD Serono; site PI for contract research for Sanofi, Actelion, Genentech/Roche, and Novartis; and received research funding from Bristol Meyers Squibb.

Multiple sclerosis (MS) misdiagnosis in the form of an incorrect diagnosis of MS, as well as delayed diagnosis in patients who do have MS, both influence patient clinical outcomes. Contemporary studies have reported data on factors associated with these diagnostic challenges and their frequency. Expediting diagnosis in patients with MS and reducing MS misdiagnosis in patients who do not have MS may be aided by educational efforts surrounding early MS symptoms and proper application of MS diagnostic criteria. Emerging novel MS diagnostic biomarkers may aid early and accurate diagnosis of MS in the future., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Postural instability is associated with disease status and fall risk in Persons with Multiple Sclerosis (PwMS). However, assessments of postural instability, known as postural sway, leverage force platforms or wearable accelerometers, and are most often conducted in laboratory environments and are thus not broadly accessible. Remote measures of postural sway captured during daily life may provide a more accessible alterative, but their ability to capture disease status and fall risk has not yet been established. We explored the utility of remote measures of postural sway in a sample of 33 PwMS. Remote measures of sway differed significantly from lab-based measures, but still demonstrated moderately strong associations with patient-reported measures of balance and mobility impairment. Machine learning models for predicting fall risk trained on lab data provided an Area Under Curve (AUC) of 0.79, while remote data only achieved an AUC of 0.51. Remote model performance improved to an AUC of 0.74 after a new, subject-specific k-means clustering approach was applied for identifying the remote data most appropriate for modelling. This cluster-based approach for analyzing remote data also strengthened associations with patient-reported measures, increasing their strength above those observed in the lab. This work introduces a new framework for analyzing data from remote patient monitoring technologies and demonstrates the promise of remote postural sway assessment for assessing fall risk and characterizing balance impairment in PwMS.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.D., C.M.O.D, M.A., J.D., E.C., P.Ra., and M.K.S. have declared no conflicts of interest. P.Ro. employed by and holds stocks in QMENTA. C.A. received consulting fees for scientific advisory boards for Genentech, EMD Serono, Alexion Pharmaceuticals, and Sanofi Genzyme. A.B.O. has received personal fees for advisory board participation and consulting from Abata, Accure, Atara Biotherapeutics, Biogen, BMS/Celgene/Receptos, GlaxoSmithKline, Gossamer, Horizon Therapeutics, Immunic, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, Sangamo, Sanofi Genzyme, Viracta; and grant support to the University of Pennsylvania from Biogen Idec, Roche/Genentech, Merck/EMD Serono, and Novartis. P.A.C. is a PI on grants to JHU from Biogen and Annexon and served on scientific advisory boards for Disarm Therapeutics and Biogen. B.A.C.C. received compensation for consulting from Alexion, Atara, Biogen, EMD Serono, Novartis, Sanofi, and TG Therapeutics. L.F. received fees for consultancy and advisory board participation from Genentech, Novartis, Celgene/Bristol Myers Squibb, EMD Serono, and TG Therapeutics; received fees for educational activities from Medscape, LLC, and the MS Association of America; program sponsorship to UT from EMD Serono; and grant support to UT from NIH/NINDS, PCORI, Genentech, and EMD Serono. R.G.H. received research support from Roche, Genentech, Atara, and MedDay and consulting for Novartis, Sanofi/Genzyme, Roche/Genentech, QIA, and Neurona. E.E.L. received research support from Genentech, Biogen and consulting for Genentech, Janssen, TG Therapeutics, NGM Bio, Bristol Myers Squibb, and EMD Serono. J.O. received research support from Biogen Idec, Roche, and EMD Serono; consulting compensation from EMD Serono, Sanofi/Genzyme, Biogen Idec, Roche, Celgene, and Novartis. N.P. received research support from the Race to Erase MS Foundation. D.P. received consulting compensation from EMD Serono, Sanofi Genzyme, Roche, and Novartis. V.P. employed by and holds stocks in QMENTA. M.R. employed by and holds stock options in QMENTA. R.D.S. received fees for advisory board participation (Biogen, EMD Serono, Sanofi Genzyme) and consulting (EMD Serono, Biogen). E.S. received fees for scientific advisory boards and consulting for Alexion, Viela Bio, Horizon Therapeutics, Genentech, and Ad Scientiam; speaking honoraria from Alexion, Viela Bio, and Biogen. N.L.S. received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Race to Erase MS Foundation, and Biogen Idec. A.J.S. received fees for consulting: Greenwich Biosciences, Horizon Therapeutics, Kiniksa Pharmaceuticals, Octave Bioscience, TG Therapeutics; non-promotional speaking: EMD Serono; research funding: Bristol Myers Squibb; contracted research: Sanofi, Novartis, Actelion, Genentech/Roche. R.T.S. supported NIH R01NS112274, R01MH112847, and R01MH123550 and received consulting income from Octave Bioscience. D.S.R. supported by the Intramural Research Program of NINDS; received additional research support from Vertex Pharmaceuticals, Sanofi Genzyme, and Abata Therapeutics. P.S. received research support from the National Institutes of Health and the National Multiple Sclerosis Society. D.O. received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, and Novartis; consulting fees from Biogen Idec, Genentech/Roche, Genzyme, Novartis, and Merck.

Background: Disease modifying therapies (DMTs) offer opportunities to improve the course of multiple sclerosis (MS), but decisions about treatment are difficult. People with multiple sclerosis (pwMS) want more involvement in decisions about DMTs, but new approaches are needed to support shared decision-making (SDM) because of the number of treatment options and the range of outcomes affected by treatment. We designed a patient-centered tool, MS-SUPPORT, to facilitate SDM for pwMS. We sought to evaluate the feasibility and impact of MS-SUPPORT on decisions about disease modifying treatments (DMTs), SDM processes, and quality-of-life., Methods: This multisite randomized controlled trial compared the SDM intervention (MS-SUPPORT) to control (usual care) over a 12-month period. English-speaking adults with relapsing MS were eligible if they had an upcoming MS appointment and an email address. To evaluate clinician perspectives, participants' MS clinicians were invited to participate. Patients were referred between November 11, 2019 and October 23, 2020 by their MS clinician or a patient advocacy organization (the Multiple Sclerosis Association of America). MS-SUPPORT is an online, interactive, evidence-based decision aid that was co-created with pwMS. It clarifies patient treatment goals and values and provides tailored information about MS, DMTs, and adherence. Viewed by patients before their clinic appointment, MS-SUPPORT generates a personalized summary of the patient's treatment goals and preferences, adherence, DMT use, and clinical situation to share with their MS clinician. Outcomes (DMT utilization, adherence, quality-of-life, and SDM) were assessed at enrollment, post-MS-SUPPORT, post-appointment, and quarterly for 1 year., Results: Participants included 501 adults with MS from across the USA (84.6% female, 83% white) and 34 of their MS clinicians (47% neurologists, 41% Nurse Practitioners, 12% Physician Assistants). Among the 203 patients who completed MS-SUPPORT, most (88.2%) reported they would recommend it to others and that it helped them talk to their doctor (85.2%), understand their options (82.3%) and the importance of taking DMTs as prescribed (82.3%). Among non-users of DMTs at baseline, the probability ratio of current DMT use consistently trended higher over one-year follow-up in the MS-SUPPORT group (1.30 [0.86-1.96]), as did the cumulative probability of starting a DMT within 6-months, with shorter time-to-start (46 vs 90 days, p=0.24). Among the 222 responses from 34 participating clinicians, more clinicians in the MS-SUPPORT group (vs control) trended towards recommending their patient start a DMT (9 of 108 (8%) vs 5 of 109 (5%), respectively, p=0.26). Adherence (no missed doses) to daily-dosed DMTs was higher in the MS-SUPPORT group (81.25% vs 56.41%, p=.026). Fewer patients forgot their doses (p=.046). The MS-SUPPORT group (vs control) reported 1.7 fewer days/month of poor mental health (p=0.02)., Conclusions: MS-SUPPORT was strongly endorsed by patients and is feasible to use in clinical settings. MS-SUPPORT increased the short-term probability of taking and adhering to a DMT, and improved long-term mental health. Study limitations include selection bias, response bias, social desirability bias, and recall bias. Exploring approaches to reinforcement and monitoring its implementation in real-world settings should provide further insights into the value and utility of this new SDM tool., Competing Interests: Declaration of Competing Interest Funding for this research was provided by EMD Serono Inc., USA, an affiliate of Merck KGaA, Darmstadt, Germany, through MS-LINK, a scientific consortium with a mission to improve patient outcomes by advancing MS science to generate actionable real-world data and patient-centered solutions. Further research supported by MS-LINK is designed to close existing scientific gaps identified by the MS community to advance discovery, care, and outcomes for patients with MS. NC: reports research grants and payment for participation in Advisory Board from EMD Serono, Inc., an affiliate of Merck KGaA, Darmstadt, Germany, during the conduct of the study; grants from Pfizer, grants from Biogen, grants from Edwards Lifesciences, LLC, and grants from MSAA (Multiple Sclerosis Association of America). EA: reports consultation or advisory fees for Alexion, Biogen, Celgene/BMS, EMD Serono/Merck, Genentech/Roche, Horizon, Motric Bio, Novartis, Sanofi, and TG Therapeutics; and funding or grants from: Biogen, Genentech/Roche, Novartis, TG Therapeutics, Patient-Centered Outcomes Research Institute, National Multiple Sclerosis Society, National Institutes of Health, and Rocky Mountain MS Center, LP: has nothing to disclose. CI: (Carolina) has received research support from Riccio Neuroscience Fund and compensation from Sanofi Genzyme and Bristol Myers Squibb for advisory board participation. IBM: has nothing to disclose. AJS: reports funding by NIH/NINDS K02NS109340; compensation for consulting or advisory boards from EMD Serono, Genentech, Biogen, Alexion, Celgene, Octave Bioscience, and Greenwich Biosciences, compensation for nonpromotional speaking from EMD Serono, and research support from Biogen; and participated in contracted research with Biogen, Novartis, Actelion, and Genentech. CK: Consultant for EMD Serono, Biogen, Genzyme, BMS, Amgen, Teva, and Alexion. TL: is an employee of EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany, JC: reports personal fees from EMD Serono, Inc., an affiliate of Merck KGaA, Darmstadt, Germany, Biogen, Allergan, and Biohaven, CIw (Crystal): has nothing to disclose. HC: has nothing to disclose. LN: has nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a chronic, immune-mediated, neurodegenerative condition of the central nervous system, with distinct challenges due to its heterogeneous presentation, prognostic uncertainty, and variable clinical course of neurological and non-neurological symptoms and disability. Although there have been significant advances in management of MS, many patients experience disability progression. Despite MS being a frequent cause of neurological disability, particularly in young persons, involvement of palliative care physicians in the care of patients with MS has been limited. This article provides ten tips for palliative clinicians for caring for patients with MS and their care partners.

Background: There is limited evidence and lack of guidelines for diagnostic laboratory evaluation of patients with possible multiple sclerosis (MS)., Objective: To survey neurologists on their practice of laboratory testing in patients with possible MS., Methods: An online survey was developed to query the frequency of serum and cerebrospinal fluid (CSF) studies ordered in the routine evaluation of patients with possible MS, and in three hypothetical clinical cases. Non-MS specialist neurologists who evaluate patients for MS in their practice were invited to participate by MedSurvey (a medical market research company)., Results: The survey was completed by 190 neurologists. A mean of 17.2 (SD: 17.0) tests in serum and CSF were reported "always" ordered in the evaluation of patients with possible MS. CSF oligoclonal bands was the most frequently selected ("always" among 73.7% of participants). Antinuclear antibody (43.2%), erythrocyte sedimentation rate (34.2%), and thyroid stimulating hormone (31.6%) were also among the most frequently ordered., Discussion: Extensive laboratory evaluations are often completed in the evaluation of possible MS. However, many of these tests have poor specificity and false positive results could yield unnecessary increased costs, diagnostic delay, and potentially misdiagnosis. Further research is needed to identify optimal laboratory approaches for possible MS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Misdiagnosis of multiple sclerosis (MS) is common and can have harmful effects on patients and healthcare systems. Identification of factors associated with misdiagnosis may aid development of prevention strategies., Objective: To identify clinical and radiological predictors of MS misdiagnosis., Methods: We retrospectively reviewed medical records of all patients who were referred to Johns Hopkins MS Center from January 2018 to June 2019. Patients who carried a diagnosis of MS were classified as correctly diagnosed or misdiagnosed with MS by the Johns Hopkins clinician. Demographics, clinical, laboratory, and radiologic data were collected. Differences between the two groups were evaluated, and a regression model was constructed to identify predictors of misdiagnosis., Results: Out of 338 patients who were previously diagnosed with MS, 41 (12%) had been misdiagnosed. An alternative diagnosis was confirmed in 28 (68%) of the misdiagnosed patients; cerebrovascular disease was the most common alternate diagnosis. Characteristics associated with misdiagnosis were female sex (odds ratio (OR): 5.81 (95% confidence interval (CI): 1.60, 21.05)) and non-specific brain magnetic resonance imaging (MRI) lesions (OR: 7.66 (3.42, 17.16))., Conclusion: Misdiagnosis is a frequent problem in MS care. Non-specific brain lesions were the most significant predictor of misdiagnosis. Interventions aimed to reduce over-reliance on imaging findings and misapplication of the McDonald criteria may prevent MS misdiagnosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Y.W. discloses research funding from Genentech. N.B.R. has no disclosures. J.K. has no disclosures. R.G. has no disclosures. M.A. has no disclosures. D.L. has no disclosures. A.J.S. discloses contracted research with Sanofi, Biogen, Novartis, Actelion, and Genentech/Roche; research support from Bristol Myers Squibb; personal compensation for consulting from Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, Horizon Therapeutics, TG Therapeutics, and Octave Bioscience; and personal compensation for non-promotional speaking from EMD Serono. E.M.M. discloses research funding from Biogen, Genentech, and Teva; consulting for Be Care Link, LLC; and royalties for editorial duties from UpToDate.

Background and Objectives: Recent data suggest increasing global prevalence of multiple sclerosis (MS). Early diagnosis of MS reduces the burden of disability-adjusted life years and associated health care costs. Yet diagnostic delays persist in MS care and even within national health care systems with robust resources, comprehensive registries, and MS subspecialist referral networks. The global prevalence and characteristics of barriers to expedited MS diagnosis, particularly in resource-restricted regions, have not been extensively studied. Recent revisions to MS diagnostic criteria demonstrate potential to facilitate earlier diagnosis, but global implementation remains largely unknown., Methods: The Multiple Sclerosis International Federation third edition of the Atlas of MS was a survey that assessed the current global state of diagnosis including adoption of MS diagnostic criteria; barriers to diagnosis with respect to the patient, health care provider, and health system; and existence of national guidelines or national standards for speed of MS diagnosis., Results: Coordinators from 107 countries (representing approximately 82% of the world population), participated. Eighty-three percent reported at least 1 "major barrier" to early MS diagnosis. The most frequently reported barriers included the following: "lack of awareness of MS symptoms among general public" (68%), "lack of awareness of MS symptoms among health care professionals" (59%), and "lack of availability of health care professionals with knowledge to diagnose MS" (44%). One-third reported lack of "specialist medical equipment or diagnostic tests." Thirty-four percent reported the use of only 2017 McDonald criteria (McD-C) for diagnosis, and 79% reported 2017 McD-C as the "most commonly used criteria." Sixty-six percent reported at least 1 barrier to the adoption of 2017 McD-C, including "neurologists lack awareness or training" by 45%. There was no significant association between national guidelines pertaining to MS diagnosis or practice standards addressing the speed of diagnosis and presence of barriers to early MS diagnosis and implementation of 2017 McD-C., Discussion: This study finds pervasive consistent global barriers to early diagnosis of MS. While these barriers reflected a lack of resources in many countries, data also suggest that interventions designed to develop and implement accessible education and training can provide cost-effective opportunities to improve access to early MS diagnosis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Accurate diagnosis of multiple sclerosis requires careful attention to its differential diagnosis-many disorders can mimic the clinical manifestations and paraclinical findings of this disease. A collaborative effort, organised by The International Advisory Committee on Clinical Trials in Multiple Sclerosis in 2008, provided diagnostic approaches to multiple sclerosis and identified clinical and paraclinical findings (so-called red flags) suggestive of alternative diagnoses. Since then, knowledge of disorders in the differential diagnosis of multiple sclerosis has expanded substantially. For example, CNS inflammatory disorders that present with syndromes overlapping with multiple sclerosis can increasingly be distinguished from multiple sclerosis with the aid of specific clinical, MRI, and laboratory findings; studies of people misdiagnosed with multiple sclerosis have also provided insights into clinical presentations for which extra caution is warranted. Considering these data, an update to the recommended diagnostic approaches to common clinical presentations and key clinical and paraclinical red flags is warranted to inform the contemporary clinical evaluation of patients with suspected multiple sclerosis., Competing Interests: Declaration of interests AJS reports grant funding from National Institute of Neurological Disorders and Stroke, National Institutes of Health, and Bristol Myers Squibb; contracted research with Sanofi, Biogen, Novartis, Actelion, and Genentec; personal compensation for consulting from EMD Serono and Octave Bioscience; payment or honoraria for lectures from EMD Serono; expert testimony from The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; participation on a Data Safety Monitoring Board for Patient Centered Research Institute and Yale University; participation on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics. AJS is also content Chair for the American Academy of Neurology Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. GA reports a grant from FIS PI19/01590 from Instituto de Salud Carlos III, Spain; personal compensation for consulting from Sanofi; payment or honoraria for lectures from Merck, Roche, and Novartis; support for attending meetings or travel from Merck, Novartis, European Committee for Treatment and Research in Multiple Sclerosis, and European Academy of Neurology; participation on a Data Safety Monitoring Board or Advisory Board for Merck, Roche, Horizon Therapeutics. GA is editor for Europe of Multiple Sclerosis Journal—Experimental, Translational and Clinical. GA is also executive committee member of International Women in Multiple Sclerosis network and steering committee member of European Biomarkers in Multiple Sclerosis consortium. WJB reports personal compensation for consulting from Biogen, Jannsen, Merck, Novartis, Roche, Sanofi, and Viatris; and payment or honoraria for lectures from Biogen, Jannsen, Merck, Novartis and Roche. EPF reports grant funding from the National Institutes of Health; personal compensation for consulting from Alexion, Genentech, UCB, and Horizon Therapeutics; and payment or honoraria for lectures from Pharmacy Times. EPF also served as site primary investigator in a randomised clinical trial on inebilizumab in neuromyelitis optica spectrum disorder sponsored by Medimmune/Viela-Bio/Horizon Therapeutics. EPF is also employed at the Mayo Clinic where commercial MOG-IgG, aquaporin-4-IgG and other antibodies are tested but does not receive any royalties from this testing. MPA reports grants or contracts with Biogen, Merck, Sanofi, Genzyme, Roche, Novartis, and Celgene/Bristol Myers Squibb; payment or honoraria for lectures from Biogen, Merck, Sanofi, Genzyme, Roche, Novartis, and Celgene/Bristol Myers Squibb; and participation on a Data Safety Monitoring Board or Advisory Board for Biogen, Merck, Sanofi, Genzyme, Roche, Novartis, and Celgene/Bristol Myers Squibb. BLB reports a grant from the National Multiple Sclerosis Society; personal compensation for consulting from Roche, Sanofi, Novartis, and UCB; and serves on the American Academy of Neurology Board of Directors and the International Medical and Scientific Advisory Board for the Multiple Sclerosis International Federation (MSIF). FB reports a grant from EU-IMI; personal compensation for consulting from Merck, Biogen, Roche, Combinostics, and IXICO; participation on a Data Safety Monitoring Board or Advisory Board for Prothena and EISAI; and stock options for QSA LTD. QSA is a contract research organization that provides imaging analysis services to the pharmaceutical industry. FB notes that his work with QSA has no relationship with his work as a diagnostic neuroradiologist nor with the content of the Personal View. JRC reports grants or contracts from the National Multiple Sclerosis Society, Patient Centered Outcomes Research Institute, EMD Serono, and Med Day; payment or honoraria for lectures from ECTRIMS European Charcot Foundation, Emory University, University of Chicago, MS XChange, and The Ohio State University. JRC also reports expert testimony for Mylan; participation on a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb; and serves as Medical Director of Rocky Mountain Multiple sclerosis Center. JC reports grants or contracts from Biogen and Merck; payment or honoraria for lectures from Biogen, Merck, Sanofi, Bristol Myers Squibb, Novartis, Roche, and Jansen; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Novartis. KF reports grants from Ministry of Education, Culture, Sports, Science and Technology of Japan, and from Ministry of Health, Welfare and Labor of Japan. KF also reports personal compensation for consulting from Merck Biopharma, Japan Tobacco, and Abbvie; payment or honoraria for lectures and presentations from Biogen, Eisai, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon, Therapeutics, Teijin, Asahi Kasei Medical, Merck, and Takeda; participation on an Advisory Board for Biogen, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, and UCB. KF serves as President of Pan-Asian Committee for Treatment and Research in Multiple Sclerosis, President of the Japanese Society of Neuroimmunology, Board Member of Japan Multiple Sclerosis Society and European Charcot Foundation, and Committee and Board member Executive Committee, International Medical and Scientific Board, MSIF. BH reports support from the European Union, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft; personal compensation for consulting from Sandoz and Biocom; patents for antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis (2012) and genetic determinants of neutralizing antibodies to interferon (filed 2010); and participation on a Data Safety Monitoring Board for TG Therapeutics and Polpharma and an Advisory Board for Novartis. RAM reports grants or contracts from Biogen Idec and Roche. SDN reports grants or contracts from Biogen, Roche, Genentech, National Multiple Sclerosis Society, Department of Defense, and Patient Centered Outcomes Research Institute; personal compensation for consulting from Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, and Horizon Therapeutics; and participation on a Data Safety Monitoring Board or Advisory Board for MedDay Pharmaceuticals. SDN also reports support from the Stiff Person Syndrome Research Foundation. MAR reports grants or contracts from Multiple Sclerosis Society of Canada and Fondazione Italiana Sclerosi Multipla; personal compensation for consulting from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, and Roche; payment or honoraria for lectures from Bayer, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Merck Healthcare Germany, Merck Serono SpA, Novartis, Roche, and Teva. MAR also serves as Associate Editor for Multiple Sclerosis and Related Disorders. BY serves on the MSIF scientific advisory board and as President of MENACTRIMS. BY also reports personal compensation for consulting from Merck, Biogen, Novartis, Roche, Sanofi, and Bayer. JAC reports personal compensation for consulting from Biogen, Convelo, EMD Serono, Gossamer Bio, and PSI; serves as President of the Americas Committee on Treatment and Research in Multiple Sclerosis; and receives personal compensation for working as the Editor of Multiple Sclerosis Journal. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates., Objectives: This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes., Design: The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028)., Methods: Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts., Results: Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% ( n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume ( R = 0.29, p = 0.01) and total white matter volume ( R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness ( R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses., Conclusion: Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations., Competing Interests: AS contracted Research with Sanofi, Biogen, Novartis, Actelion, Genentech/Roche. Consulting fees from Octave Bioscience. Research support from Bristol Myers Squibb. Personal compensation for consulting for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics and OctavemBioscience. Personal compensation non-promotional speaking for EMD Serono. Participationin ma Data Safety and Monitoring Board for NCT03073603, and NCT04877457. MF received a grant from Sanofi-Genzyme Canada. Honoraria or consultation fees from Alexion/Astra Zeneca, BiogenIdec, EMD Inc./EMD Serono/Merck Serono, Find Therapeutics, Hoffman La-Roche, Novartis, Quanterix, Sanofi-Genzyme, Teva Canada Innovation. Member of a company advisory board or board of directors for Alexion/Astra Zeneca, Atara Biotherapeutics, Bayer Healthcare, Celestra Health, EMD Inc./Merck Serono, Find Therapeutics, Hoffman La-Roche, Actelion/Janssen (J&J), Novartis, Sanofi-Genzyme, Setpoint Medical. Participation in a company sponsored speaker's bureau: Sanofi-Genzyme, EMD Serono. PR contracted research with Biogen, Genentech, Novartis, Sanofi. Consulting honoraria: Banner, BristolMyersSquibb, EMD Serono, Genentech, Novartis, Sanofi, TG therapeutics. Speaker honoraria: Biogen, BristolMyersSquibb, Genentech, Novartis, Sanofi, TG therapeutics. OS serves on the editorial boards of Therapeutic Advances in Neurological Disorders, has served on data monitoring committees for Genentech-Roche, Pfizer, Novartis, and TG Therapeutics without monetary compensation, has advised EMD Serono, Novartis, and VYNE, receives grant support from EMD Serono, is a 2021 recipient of a Grant for Multiple Sclerosis Innovation (GMSI), Merck KGaA, is funded by a Merit Review grant (federal award document number (FAIN) BX005664-01 from the United States (U.S.) Department of Veterans Affairs, Biomedical Laboratory Research and Development, is funded by RFA-2203-39314 (PI) and RFA-2203-39305 (co-PI) grants from the National Multiple Sclerosis Society (NMSS). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Spain, Hildebrand, Waslo, Rooney, Emmons, Schwartz, Freedman, Paz Soldan, Repovic, Solomon, Rinker, Wallin, Haselkorn, Stuve, Gross and Turner.)

Background and Purpose: Cortical demyelinated lesions are prevalent in multiple sclerosis (MS), associated with disability, and have recently been incorporated into MS diagnostic criteria. Presently, advanced and ultrahigh-field MRIs-not routinely available in clinical practice-are the most sensitive methods for detection of cortical lesions. Approaches utilizing MRI sequences obtainable in routine clinical practice remain an unmet need. We plan to assess the sensitivity of the ratio of T 1 -weighted and T 2 -weighted (T 1 /T 2 ) signal intensity for focal cortical lesions in comparison to other high-field imaging methods., Methods: 3-Tesla and 7-Tesla MRI collected from 10 adults with MS were included in the study. T 1 /T 2 images were calculated by dividing 3T T 1 -weighted (T 1 w) images by 3T T 2 -weighted (T 2 w) fluid-attenuated inversion recovery images for each participant. A total of 614 cortical lesions were identified using 7T T 2 *w and T 1 w images and corresponding voxels were assessed on registered 3T images. Signal intensities were compared across 3T imaging sequences, including T 1 /T 2 , T 1 w, T 2 w, and inversion recovery susceptibility-weighted imaging with enhanced T 2 weighting (IR-SWIET) images., Results: T 1 /T 2 images demonstrated a larger contrast between median lesional and nonlesional cortical signal intensity (median ratio = 1.29, range: 1.19-1.38) when compared to T 1 w (1.01, 0.97-1.10, p < .002), T 2 w (1.17, 1.07-1.26, p < .002), and IR-SWIET (1.21, 1.01-1.29, p < .03)., Conclusion: T 1 /T 2 images are sensitive to cortical lesions. Approaches incorporating T 1 /T 2 could improve the accessibility of cortical lesion detection in research settings and clinical practice., (© 2023 American Society of Neuroimaging. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Purpose: To evaluate safety and effectiveness of percutaneous biliary endoscopy (PBE) performed on patients ineligible for surgery or endoscopic retrograde cholangiopancreatography., Materials and Methods: Retrospective review was conducted for all patients who underwent PBE at a single academic institution between June 2013 and February 2020; 39 patients underwent 58 choledochoscopy sessions, and 21 patients underwent 48 cholecystoscopy sessions. Choledochoscopy indications included stone removal (23 of 39 patients) or biliary stenosis evaluation (19 of 39 patients). Cholecystoscopy indications included calculous cholecystitis (18 of 21 patients) and symptomatic cholelithiasis (3 of 21 patients). Technical success, procedural and fluoroscopy times, and tube-free survival were assessed., Results: For all PBEs performed for stone clearance, using disposable endoscopes led to shorter mean ± SD procedural (128.7 minutes ± 56.2 vs 240.2 minutes ± 184.6; P < .01) and fluoroscopy times (10.7 minutes ± 7.9 vs 16.5 minutes ± 12.0; P = .01) than using reusable endoscopes. Increasing institutional experience was associated with reduced procedural time (β = -56.73; P < .001). Choledochoscopy technical success was 94.8% with 1 adverse event of bile duct perforation with bile leak requiring drainage. For patients with choledocholithiasis, biliary drains were removed in 14 (60.9%) patients, with a mean tube-free survival of 22.1 months ± 23.8. For cholecystoscopy, technical success was 93.8% with no adverse events. Cholecystostomy tubes were removed in 15 (71.4%) patients, with a mean tube-free survival of 7.5 months ± 8.8., Conclusions: This study supports PBE as a safe and feasible option for nonsurgical patients or those with altered anatomy precluding endoscopic retrograde cholangiopancreatography. Moreover, PBE may result in tube-free survival., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

The association between trigeminal neuralgia (TN) and multiple sclerosis (MS) is well established. Many MS patients with TN have magnetic resonance imaging (MRI) evidence of a symptomatic demyelinating lesion. Although infratentorial presentations are included in the diagnostic criteria for MS, there remains confusion in clinical practice as to whether TN should be considered a clinically isolated syndrome for the application of McDonald criteria. In this case series, we discuss this diagnostic quandary in patients presenting with TN and additional MRI findings suggestive of MS and highlight the unmet need for data in such patients to optimally guide their care.

Objective: At present, no data are available to support the use of tibial interventions in the treatment of claudication. We characterized the practice patterns surrounding tibial peripheral vascular interventions (PVIs) for patients with claudication in the United States., Methods: Using 100% Medicare fee-for-service claims from 2017 to 2019, we conducted a retrospective analysis of all patients who underwent an index PVI for claudication. Patients with any previous PVI, acute limb ischemia, or chronic limb-threatening ischemia in the preceding 12 months were excluded. The primary outcome was the receipt or delivery of tibial revascularization during an index PVI for claudication, defined as tibial PVI with or without concomitant femoropopliteal PVI. Univariable comparisons and multivariable hierarchical logistic regression were used to assess the patient and physician characteristics associated with the use of tibial PVI for claudication., Results: Of 59,930 Medicare patients who underwent an index PVI for claudication between 2017 and 2019, 16,594 (27.7%) underwent a tibial PVI (isolated tibial PVI, 38.5%; tibial PVI with concomitant femoropopliteal PVI, 61.5%). Of the 1542 physicians included in our analysis, the median physician-level tibial PVI rate was 20.0% (interquartile range, 9.1%-37.5%). Hierarchical logistic regression suggested that patient-level characteristics associated with tibial PVI for claudication included male sex (adjusted odds ratio [aOR], 1.23), increasing age (aOR, 1.30-1.96), Black race (aOR, 1.47), Hispanic ethnicity (aOR, 1.86), diabetes (aOR, 1.36), no history of hypertension (aOR, 1.12), and never-smoking status (aOR, 1.64; P < .05 for all). Physician-level characteristics associated with tibial PVI for claudication included early-career status (aOR, 2.97), practice location in the West (aOR, 1.75), high-volume PVI practice (aOR, 1.87), majority of practice in an ambulatory surgery center or office-based laboratory setting (aOR, 2.37), and physician specialty. The odds of vascular surgeons performing tibial PVI were significantly lower compared with radiologists (aOR, 2.98) and cardiologists (aOR, 1.67; P < .05 for all). The average Medicare reimbursement per patient was dramatically higher for physicians performing high rates of tibial PVI (quartile 4 vs quartile 1-3, $12,023.96 vs $692.31 per patient; P < .001)., Conclusions: Tibial PVI for claudication was performed more often by nonvascular surgeons in high-volume practices and high-reimbursement settings. Thus, a critical need exists to reevaluate the indications, education, and reimbursement policies surrounding these procedures., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Impairment in persons with multiple sclerosis (PwMS) can often be attributed to symptoms of motor instability and fatigue. Symptom monitoring and queued interventions often target these symptoms. Clinical metrics are currently limited to objective physician assessments or subjective patient reported measures. Recent research has turned to wearables for improving the objectivity and temporal resolution of assessment. Our group has previously observed wearable assessment of supervised and unsupervised standing transitions to be predictive of fall-risk in PwMS. Here we extend the application of standing transition quantification to longitudinal home monitoring of symptoms. Subjects (N=23) with varying degrees of MS impairment were recruited and monitored with accelerometry for a total of  ∼  6 weeks each. These data were processed using a preexisting framework, applying a deep learning activity classifier to isolate periods of standing transition from which descriptive features were extracted for analysis. Participants completed daily and biweekly assessments describing their symptoms. From these data, Canonical Correlation Analysis was used to derive digital phenotypes of MS instability and fatigue. We find these phenotypes capable of distinguishing fallers from non-fallers, and further that they demonstrate a capacity to characterize symptoms at both daily and sub-daily resolutions. These results represent promising support for future applications of wearables, which may soon augment or replace current metrics in longitudinal monitoring of PwMS.

Importance: Autoimmune encephalitis misdiagnosis can lead to harm., Objective: To determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis., Design, Setting, and Participants: This retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), University of Washington in St Louis (n = 6), and University of Utah (n = 4). Inclusion criteria were adults (age ≥18 years) with a prior autoimmune encephalitis diagnosis at a participating center or other medical facility and a subsequent alternative diagnosis at a participating center. A total of 393 patients were referred with an autoimmune encephalitis diagnosis, and of those, 286 patients with true autoimmune encephalitis were excluded., Main Outcomes and Measures: Data were collected on clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions., Results: A total of 107 patients were misdiagnosed with autoimmune encephalitis, and 77 (72%) did not fulfill diagnostic criteria for autoimmune encephalitis. The median (IQR) age was 48 (35.5-60.5) years and 65 (61%) were female. Correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). Onset was acute/subacute in 56 (52%) or insidious (>3 months) in 51 (48%). Magnetic resonance imaging of the brain was suggestive of encephalitis in 19 of 104 patients (18%) and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). Thyroid peroxidase antibodies were elevated in 24 of 62 patients (39%). Positive neural autoantibodies were more frequent in serum than CSF (48 of 105 [46%] vs 7 of 91 [8%]) and included 1 or more of GAD65 (n = 14), voltage-gated potassium channel complex (LGI1 and CASPR2 negative) (n = 10), N-methyl-d-aspartate receptor by cell-based assay only (n = 10; 6 negative in CSF), and other (n = 18). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). Potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]), misinterpretation of functional/psychiatric, or nonspecific cognitive dysfunction as encephalopathy (41 [38%])., Conclusions and Relevance: When evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria. Autoimmune encephalitis misdiagnosis leads to morbidity from unnecessary immunotherapies and delayed treatment of the correct diagnosis.

Typical assessments of balance impairment are subjective or require data from cumbersome and expensive force platforms. Researchers have utilized lower back (sacrum) accelerometers to enable more accessible, objective measurement of postural sway for use in balance assessment. However, new sensor patches are broadly being deployed on the chest for cardiac monitoring, opening a need to determine if measurements from these devices can similarly inform balance assessment. Our aim in this work is to validate postural sway measurements from a chest accelerometer. To establish concurrent validity, we considered data from 16 persons with multiple sclerosis (PwMS) asked to stand on a force platform while also wearing sensor patches on the sacrum and chest. We found five of 15 postural sway features derived from the chest and sacrum were significantly correlated with force platform-derived features, which is in line with prior sacrum-derived findings. Clinical significance was established using a sample of 39 PwMS who performed eyes-open, eyes-closed, and tandem standing tasks. This cohort was stratified by fall status and completed several patient-reported measures (PRM) of balance and mobility impairment. We also compared sway features derived from a single 30-second period to those derived from a one-minute period with a sliding window to create individualized distributions of each postural sway feature (ID method). We find traditional computation of sway features from the chest is sensitive to changes in PRMs and task differences. Distribution characteristics from the ID method establish additional relationships with PRMs, detect differences in more tasks, and distinguish between fall status groups. Overall, the chest was found to be a valid location to monitor postural sway and we recommend utilizing the ID method over single-observation analyses.

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.

Background: The clinical evaluation of a new diagnosis of MS typically includes serologic testing to evaluate for its many mimics, yet there is little data to guide approaches to such testing., Objective: To evaluate for the frequency and clinical significance of serologic testing for MS diagnostic evaluations., Methods: In a single MS subspeciality center retrospective study, new patient evaluations for MS over the course of a year were identified, and the results of serologic testing and diagnostic evaluation extracted. Retrospective longitudinal diagnostic assessment was performed to confirm the accuracy of initial serological testing assessments., Results: 150 patients had 823 serologic tests. 40 (5%) tests were positive, and resulted in 117 additional serologic tests, 10 radiographs, and 2 biopsies. 77 (51%) patients were diagnosed with a non-demyelinating disorder. Serologic testing results did not change any diagnosis, yet in some patients, it resulted in unnecessary additional testing and diagnostic delay., Conclusions: Serologic testing in the clinical assessment for routine MS resulted in unnecessary diagnostic delay, additional testing, and considerable healthcare cost., Competing Interests: Declaration of Competing Interest Anna A Shah, MD - I have participated in advisory boards through Genentech and TG therapeutics. I have received funding for non-promotional educational programming through NCQA, Novartis and Rocky Mountain MS Center. Brian Callaghan, MD – I receive research contracts and I am on the editorial board for the American Academy of Neurology. I consult for Dynamed. I perform medicolegal consultations including for the Vaccine Injury Compensation Program. Andrew J Solomon, MD - Consulting or Advisory Boards: EMD Serono, Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, Octave Bioscience.  Non-Promotional Speaking: EMD Serono.   Research Funding: Bristol Myers Squibb and Biogen.  Contracted Research:  Sanofi, Biogen, Novartis, Actelion, Genentech/Roche. Medicolegal consultations including expert witness testimony. Colin Lyness, MD, Jessica Piche, MD, and Benjamin Stewart, MD, have no reportable conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Receiving a diagnosis of multiple sclerosis (MS) can be stressful; later, patients may conceal their diagnosis. Here, we aimed to (1) assess prevalence of disclosure and concealment behaviors, and (2) explore whether diagnosis experience is associated with later concealment and if MS provider engagement on this topic modifies concealment., Methods: In a survey-based study, MS patients completed DISCO-MS assessing disclosure and concealment and responded to questions about diagnosis experience and practitioner attention to disclosure. Frequency analysis and Pearson's correlations were used in exploratory analyses., Results: 428 adults with MS participated. 49% (N = 201) conceal their diagnosis. Higher education [t(405) = 3.66, p < 0.001], younger age (r = -0.15, p = 0.002), and shorter disease duration (r = -0.18, p = 0.010) were associated with higher concealment. 39% (N = 159) anticipate negative consequences of disclosure. Individuals reporting positive diagnosis experience (26%, N = 102) were less likely to conceal later in disease course compared to those with negative experience (34%, N = 136) [t(233) = 2.483, p = 0.014]. Patients whose MS providers discussed disclosure (23%, N = 73) anticipated less negative consequences of disclosure [t(323) = 2.475, p = 0.014]., Conclusions: Diagnosis concealment is common in MS. Favorable diagnosis experience and provider attention to the topic of disclosure throughout the MS disease course may influence diagnosis concealment., Competing Interests: Declaration of Competing Interest VML: Advisory Board: Biogen. Non-promotional speaker: Novartis. Compensation for reviewing: National Institutes of Health, Department of Defense. Chief Scientific Officer and cofounder of eSupport Health, PBC. AMK: Nothing to disclose. SMW: Nothing to disclose. RTS: Consulting: Octave Bioscience. Compensation for reviewing: American Medical Association, National Institutes of Health, Department of Defense, Emerson Collective. HS: Nothing to disclose. SMA: Nothing to disclose. AS: Advisory Board: Almirall, Merck. Speaking: Biogen, Merck, Teva. AJS: Advisory Board: Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, Horizon Therapeutics, TG Therapeutics. Consulting: Octave Bioscience. Non-promotional speaking: EMD Serono. Research support: Bristol Myers Squibb. Trainee funding: Biogen. Contracted Research: Sanofi, Biogen, Novartis, Actelion, Genentech/Roche. Expert witness testimony. Funding was provided by the University of Vermont Multiple Sclerosis Center., (Copyright © 2022 Elsevier B.V. All rights reserved.)