Laboratory evaluation for the differential diagnosis of possible multiple sclerosis in the United States: A physician survey.

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.

An Update on Diagnostic Laboratory Biomarkers for Multiple Sclerosis.

PURPOSE: For many patients, the multiple sclerosis (MS) diagnostic process can be lengthy, costly, and fraught with error. Recent research aims to address the unmet need for an accurate and simple diagnostic process through discovery of novel diagnostic biomarkers. This review summarizes recent studies on MS diagnostic fluid biomarkers, with a focus on blood biomarkers, and includes discussion of technical limitations and practical applicability. RECENT FINDINGS: This line of research is in its early days. Accurate and easily obtainable biomarkers for MS have not yet been identified and validated, but several approaches to uncover them are underway. Continue efforts to define laboratory diagnostic biomarkers are likely to play an increasingly important role in defining MS at the earliest stages, leading to better long-term clinical outcomes.

Multiple sclerosis diagnosis: Knowledge gaps and opportunities for educational intervention in neurologists in the United States.

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.

Preventing multiple sclerosis misdiagnosis using the "central vein sign": A real-world study.

BACKGROUND: Misdiagnosis of multiple sclerosis (MS) is common and often occurs due to misattribution of non-MS magnetic resonance imaging (MRI) lesions to MS demyelination. A recently developed MRI biomarker, the central vein sign (CVS), has demonstrated high specificity for MS lesions and may thus help prevent misdiagnosis. OBJECTIVE: This study explores the potential "real world" diagnostic value of CVS by comparing CVS in patients with MS and patients previously misdiagnosed with MS. METHODS: Fifteen patients with MS and 15 misdiagnosed with MS were prospectively recruited to undergo 3T brain MRI. T2-weighted fluid-attenuated inversion recovery (FLAIR) and T2*-weighted segmented echo-planar-imaging (T2*-EPI) were acquired. The generated FLAIR* images were analyzed by two independent raters. The percentage of lesions with CVS was calculated for each patient. RESULTS: A CVS lesion threshold of 29% or higher resulted in high sensitivity (0.79) and specificity (0.88) for MS and correctly identified 87% of patients previously misdiagnosed with MS. Interrater reliability for CVS was high with a Cohen's kappa coefficient of 0.86. CONCLUSION: This study demonstrates the ability of CVS to differentiate between patients with MS and patients with an MS misdiagnosis resulting from standard MRI and clinical evaluation. Clinical application of CVS may reduce MS misdiagnosis.

Three-dimensional whole-brain simultaneous T1, T2, and T1ρ quantification using MR Multitasking: Method and initial clinical experience in tissue characterization of multiple sclerosis.

PURPOSE: To develop a 3D whole-brain simultaneous T1/T2/T1ρ quantification method with MR Multitasking that provides high quality, co-registered multiparametric maps in 9 min. METHODS: MR Multitasking conceptualizes T1/T2/T1ρ relaxations as different time dimensions, simultaneously resolving all three dimensions with a low-rank tensor image model. The proposed method was validated on a phantom and in healthy volunteers, comparing quantitative measurements against corresponding reference methods and evaluating the scan-rescan repeatability. Initial clinical validation was performed in age-matched relapsing-remitting multiple sclerosis (RRMS) patients to examine the feasibility of quantitative tissue characterization and to compare with the healthy control cohort. The feasibility of synthesizing six contrast-weighted images was also examined. RESULTS: Our framework produced high quality, co-registered T1/T2/T1ρ maps that closely resemble the reference maps. Multitasking T1/T2/T1ρ measurements showed substantial agreement with reference measurements on the phantom and in healthy controls. Bland-Altman analysis indicated good in vivo repeatability of all three parameters. In RRMS patients, lesions were conspicuously delineated on all three maps and on four synthetic weighted images (T2-weighted, T2-FLAIR, double inversion recovery, and a novel "T1ρ-FLAIR" contrast). T1 and T2 showed significant differences for normal appearing white matter between patients and controls, while T1ρ showed significant differences for normal appearing white matter, cortical gray matter, and deep gray matter. The combination of three parameters significantly improved the differentiation between RRMS patients and healthy controls, compared to using any single parameter alone. CONCLUSION: MR Multitasking simultaneously quantifies whole-brain T1/T2/T1ρ and is clinically promising for quantitative tissue characterization of neurological diseases, such as MS.

Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers.

BACKGROUND: Multiple Sclerosis (MS) specialists routinely evaluate misdiagnosed patients, or patients incorrectly assigned a diagnosis of MS. Misdiagnosis has significant implications for patient morbidity and healthcare costs, yet its contemporary incidence is unknown. We examined the incidence of MS misdiagnosis in new patients referred to two academic MS referral centers, their most common alternate diagnoses, and factors associated with misdiagnosis. METHODS: Demographic data, comorbidities, neurological examination findings, radiographic and laboratory results, a determination of 2010 McDonald Criteria fulfillment, and final diagnoses were collected from all new patient evaluations completed at the Cedars-Sinai Medical Center and the University of California, Los Angeles MS clinics over twelve months. RESULTS: Of the 241 new patients referred with an established diagnosis of MS, 17% at Cedars-Sinai and 19% at UCLA were identified as having been misdiagnosed. The most common alternative diagnoses were migraine (16%), radiologically isolated syndrome (9%), spondylopathy (7%), and neuropathy (7%). Clinical syndromes and radiographic findings atypical for MS were both associated with misdiagnosis. The misdiagnosed group received approximately 110 patient-years of unnecessary MS disease modifying therapy. CONCLUSION: MS misdiagnosis is common; in our combined cohort, almost 1 in 5 patients who carried an established diagnosis of MS did not fulfill contemporary McDonald Criteria and had a more likely alternate diagnosis.

Multiple sclerosis management and reproductive changes: A guide for general neurologists.

PURPOSE OF REVIEW: Multiple sclerosis (MS) disease activity and symptoms are tied to hormonal changes. This review explains the current standard of care in MS at various stages of a woman's reproductive life and helps neurologists answer patients' most common questions surrounding MS care and fertility, pregnancy, and menopause. RECENT FINDINGS: Recent work has focused on MS risk and exacerbation with variables related to reproductive health. Management of disease-modifying therapies prenatally and postnatally is also a focus. SUMMARY: This review is a concise, practical guide for general neurologists caring for women with MS. MS is a disease that requires adaptation of management as a woman moves through reproductive stages. With proper planning and management, pregnancy is safe for women with MS. We describe the current standard of care based on trials, when available, and on expert opinion.

A dementia care management intervention: which components improve quality?

OBJECTIVES: To analyze whether types of providers and frequency of encounters are associated with higher quality of care within a coordinated dementia care management (CM) program for patients and caregivers. DESIGN: Secondary analysis of intervention-arm data from a dementia CM cluster-randomized trial, where intervention participants interacted with healthcare organization care managers (HOCMs), community agency care managers (CACMs), and/ or healthcare organization primary care providers (HOPCPs) over 18 months. METHODS: Encounters of 238 patient/caregivers (dyads) with HOCMs, CACMs, and HOPCPs were abstracted from care management electronic records. The quality domains of assessment, treatment, education/support, and safety were measured from medical record abstractions and caregiver surveys. Mean percentages of met quality indicators associated with exposures to each provider type and frequency were analyzed using multivariable regression, adjusting for participant characteristics and baseline quality. RESULTS: As anticipated, for all 4 domains, the mean percentage of met dementia quality indicators was 15.5 to 47.2 percentage points higher for dyads with HOCM--only exposure than for dyads with none (all P < .008); not anticipated were higher mean percentages with increasing combinations of provider-type exposure-up to 73.7 percentage points higher for safety (95% confidence interval 65.2%-82.1%) with exposure to all 3 provider types compared with no exposure. While greater frequency of HOCM-dyad encounters was associated with higher quality (P < .04), this was not so for other provider types. CONCLUSIONS: HOCMs' interactions with dyads was essential for dementia care quality improvement. Additional coordinated interactions with primary care and community agency staff yielded even higher quality.

Predictors of acceptance of offered care management intervention services in a quality improvement trial for dementia.

OBJECTIVE: Care management approaches have been proven to improve outcomes for patients with dementia and their family caregivers (dyads). However, acceptance of services in these programs is incomplete, impacting effectiveness. Acceptance may be related to dyad as well as healthcare system characteristics, but knowledge about factors associated with program acceptance is lacking. This study investigates patient, caregiver, and healthcare system characteristics associated with acceptance of offered care management services. METHODS: This study analyzed data from the intervention arm of a cluster randomized controlled trial of a comprehensive dementia care management intervention. There were 408 patient-caregiver dyads enrolled in the study, of which 238 dyads were randomized to the intervention. Caregiver, patient, and health system factors associated with participation in offered care management services were assessed through bivariate and multivariate regression analyses. RESULTS: Out of the 238 dyads, 9 were ineligible for this analysis, leaving data of 229 dyads in this sample. Of these, 185 dyads accepted offered care management services, and 44 dyads did not. Multivariate analyses showed that higher likelihood of acceptance of care management services was uniquely associated with cohabitation of caregiver and patient (p < 0.001), lesser severity of dementia (p = 0.03), and higher patient comorbidity (p = 0.03); it also varied across healthcare organization sites. CONCLUSIONS: Understanding factors that influence care management participation could result in increased adoption of successful programs to improve quality of care. Using these factors to revise both program design as well as program promotion may also benefit external validity of future quality improvement research trials.