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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: 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.

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.

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.

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: 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.

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: Most contemporary data concerning the frequency and causes of multiple sclerosis (MS) misdiagnosis are from North America and Europe with different healthcare system structure and resources than countries in Latin America. We sought to determine the frequency, and potential contributors to MS misdiagnosis in patients evaluated at an MS referral center in Argentina., Methods: The study was a retrospective medical record review. We included patients evaluated at the MS Clinic at Fleni between April 2013 and March 2021. Diagnoses prior to consultation, final diagnoses after consultation, demographic, clinical and paraclinical data, and treatment were extracted and classified., Results: Seven hundred thirty-six patients were identified. Five hundred seventy-two presented with an established diagnosis of MS and after evaluation, misdiagnosis was identified in 89 (16%). Women were at 83% greater risk of misdiagnosis ( p  = 0.034). The most frequent alternative diagnoses were cerebrovascular disease, radiological isolated syndrome (RIS), and headache. Seventy-four (83%) of misdiagnosed patients presented with a syndrome atypical for demyelination, 62 (70%) had an atypical brain magnetic resonance imaging (MRI), and 54 (61%) were prescribed disease-modifying therapy., Conclusion: Sixteen percent of patients with established MS were subsequently found to have been misdiagnosed. Women were at higher risk for misdiagnosis. Expert application of the McDonald criteria may prevent misdiagnosis and its associated morbidity and healthcare system cost.

Background: Few studies have addressed the results of educational efforts concerning proper use of McDonald criteria (MC) revisions outside multiple sclerosis (MS) subspecialty centers. Neurology residents and MS subspecialist neurologists demonstrated knowledge gaps for core elements of the MC in a recent prior study., Objective: To assess comprehension and application of MC core elements by non-MS specialist neurologists in the United States who routinely diagnose MS., Methods: Through a cross-sectional study design, a previously developed survey instrument was distributed online., Results: A total of 222 neurologists completed the study survey. Syndromes atypical for MS were frequently incorrectly considered "typical" MS presentations. Fourteen percent correctly identified definitions of both "periventricular" and "juxtacortical" lesions and 2% correctly applied these terms to 9/9 images. Twenty-four percent correctly identified all four central nervous system (CNS) regions for satisfaction of magnetic resonance imaging (MRI) dissemination in space. In two presented cases, 61% and 71% correctly identified dissemination in time (DIT) was not fulfilled, and 85% and 86% subsequently accepted nonspecific historical symptoms without objective evidence for DIT fulfillment., Conclusion: The high rate of knowledge deficiencies and application errors of core elements of the MC demonstrated by participants in this study raise pressing questions concerning adequacy of dissemination and educational efforts upon publication of revisions to MC.

Objective: To assess comprehension and application of the McDonald criteria., Background: Studies suggest that knowledge gaps for specific core elements of the McDonald criteria may contribute to multiple sclerosis (MS) misdiagnosis., Methods: Neurology residents (NR) and multiple sclerosis specialists (MSS) in North America completed a web-based survey., Results: A total of 160 participants were included: 72 NR and 88 MSS. Syndromes incorrectly identified as typical of MS included: complete transverse myelopathy (35% NR and 15% MSS), intractable vomiting/nausea/hiccoughs (20% NR and 5% MSS), and bilateral optic neuritis/unilateral optic neuritis with poor visual recovery (17% NR and 10% MSS). Periventricular magnetic resonance imaging (MRI) lesions were correctly identified by 39% NR and 52% MSS, and juxtacortical lesions were correctly identified by 28% NR and 53% MSS. The correct definition of "periventricular" was chosen by 38% NR and 61% MSS, and that of "juxtacortical" was chosen by 19% NR and 54% MSS. Regions incorrectly identified for MRI dissemination in space fulfillment included the optic nerve (31% NR and 26% MSS) and the subcortical white matter (11% NR and 18% MSS). The majority of participants assessed previous non-specific neurological symptoms without objective evidence of a central nervous system (CNS) lesion as sufficient for clinical dissemination in time., Conclusion: The McDonald criteria are often misunderstood and misapplied. Concerted educational efforts may prevent MS misdiagnosis.

Background: The importance of supporting pregnancy-related decisions in multiple sclerosis (MS) patients has increasingly been recognized and hence the need for prospective data on pregnancy and pediatric outcomes in this patient population., Objective: To assess prospective growth and developmental outcomes of infants born to mothers with multiple sclerosis (IMS)., Methods: PREG-MS is a prospective multicenter cohort study in New England, United States. We followed 65 women with MS and their infants with up to 12 months consistent pediatric follow-up. Pediatric, neurologic, and demographic information was obtained via structured telephone interviews and validated with medical records., Results: No differences in infant weights and lengths with World Health Organization (WHO) 50th percentile standards were observed ( p  > 0.05). However, larger head circumference (HC) measurements than WHO standards were reported in cohort infants ( p  < 0.05). There was no association between HC and markers of maternal MS activity, demographic, or social factors. No irreversible pediatric developmental abnormalities were observed., Conclusion: This first prospective study on pediatric anthropometry in IMS suggests a possible increase in HC compared to WHO standards without an increase in irreversible developmental abnormalities. The observations are exploratory and require confirmation with larger prospective studies in diverse groups of MS patients.

Background: Detection of a "central vein sign" (CVS) on FLAIR* magnetic resonance imaging (MRI) is highly specific and sensitive for multiple sclerosis (MS). We evaluated the specificity and sensitivity of simplified CVS algorithms for MS diagnosis., Methods: MRIs from 10 participants with MS without additional comorbidities for MRI white matter abnormalities; 10 with MS and additional comorbidities for white matter abnormalities; 10 with migraine, white matter abnormalities, and no additional comorbidities; and 10 who had previously been erroneously diagnosed with MS were evaluated. 3T MRI T2-FLAIR and T2*-weighted sequences were acquired to create FLAIR* images. Three MS physician reviewers, blinded to diagnosis, evaluated two different algorithms: (1) three lesions pre-selected on FLAIR were subsequently evaluated for CVS on FLAIR*( select3). (2) FLAIR* was evaluated for up to three lesions with CVS ( select3*)., Results: For select3, average specificity across reviewers for MS was 0.98 and sensitivity 0.52 and a correct prediction of diagnosis demonstrated kappa = 0.29. For select3*, specificity was 0.81, sensitivity was 0.83, and kappa was 0.31., Conclusion: A simplified determination of CVS in three white matter lesions on 3T FLAIR* MRI demonstrated good specificity and sensitivity and fair inter-rater reliability for a diagnosis of MS and with further study, may be a candidate for clinical application.

Background: Patients facing a high-stakes clinical decision are often confronted with an overwhelming array of options. High-quality decisions about treatment should reflect patients' preferences as well as their clinical characteristics. Preference-assessment instruments typically focus on pre-selected clinical outcomes and attributes chosen by the investigator., Objective: We sought to develop a patient-centered approach to elicit and compare the treatment goals of patients with multiple sclerosis (MS) and healthcare providers (HCPs)., Methods: We conducted five nominal group technique (NGT) meetings to elicit and prioritize treatment goals from patients and HCPs. Five to nine participants in each group responded silently to one question about their treatment goals. Responses were shared, consolidated, and ranked to develop a prioritized list for each group. The ranked lists were combined. Goals were rated and sorted into categories. Multidimensional scaling and hierarchical cluster analysis were used to derive a visual representation, or cognitive map, of the data and to identify conceptual clusters, reflecting how frequently items were sorted into the same category., Results: Five NGT groups yielded 34 unique patient-generated treatment goals and 31 unique HCP-generated goals. There were differences between patients and HCPs in the goals generated and how they were clustered. Patients' goals tended to focus on the impact of specific symptoms on their day-to-day lives, whereas providers' goals focused on slowing down the course of disease progression., Conclusions: Differences between the treatment goals of patients and HCPs underscore the limitations of using HCP- or investigator-identified goals. This new adaptation of cognitive mapping is a patient-centered approach that can be used to generate and organize the outcomes and attributes for values clarification exercises while minimizing investigator bias and maximizing relevance to patients.

Background: Pharmaceutical industry financial support of physicians, physician practices, and academic departments involved in multicenter industry-sponsored clinical trials of novel therapeutic agents is a relatively new and infrequently acknowledged source of potential physician conflict of interest. Detailed disclosure of these relationships to study participants is not uniformly a part of informed consent and documentation practices., Objective: To understand attitudes of patients with multiple sclerosis concerning disclosure of potential physician-industry conflicts of interest created by clinical trials and how such disclosures may influence study participation, Methods: An anonymous online instrument was developed., Results: 597 people with multiple sclerosis participated in the study. The study found that detailed disclosure of conflicts of interest is important to potential participants in industry-sponsored clinical trials for multiple sclerosis therapies and that the presence of these conflicts of interest may influence patients' decisions to participate in these studies., Conclusions: Findings from this study support a call for uniform guidelines regarding disclosure of physician-industry relationships to prospective research participants for industry-sponsored clinical trials., (© The Author(s), 2015.)

Background: TNF alpha inhibitor (TNFAI) therapy has been associated with inflammatory neurological syndromes., Objectives: To present 10 new cases of TNFAI associated neurological disease and a review of the literature., Methods: The design and methods were based on case series collected from Oregon Health & Sciences University and the Department of Veterans Affairs Hospital in Portland, Oregon and PubMed review., Results: We describe eight demyelinating central nervous system syndromes and two peripheral nervous system syndromes associated with TNFAI therapy. Characteristics from these cases are analyzed with data from 141 additional cases from the literature. Onset was between the ages of 36 and 65 years in 84% of CNS cases, distinguishing TNFAI-associated disease from sporadic multiple sclerosis. Symptoms occurred within one year of TNFAI therapy in 71%. Etanercept therapy was reported in the majority of cases of CNS syndromes and infliximab therapy in the majority of neuromuscular syndromes. Significant disability remained in 67% of cases although 82% had been followed for less than one year., Conclusions: Our case series and literature review demonstrates an association between TNFAI therapy and inflammatory neurological disease. While a causal relationship is suggested, this remains uncertain. TNFAI-associated neurological syndromes are associated with significant disability and longer follow-up is needed to better determine natural history and evaluate appropriate treatment interventions.