Pragmatic implementation of comprehensive dementia care management: The Cedars-Sinai C.A.R.E.S. Program preliminary data.

BACKGROUND: The United States faces a growing challenge with over 6.5 million people living with dementia (PLwD). PLwD and their caregivers struggle with cognitive, functional, behavioral, and psychosocial issues. As dementia care shifts to home settings, caregivers receive inadequate support but bear increasing responsibilities, leading to higher healthcare costs. In response, the Centers for Medicare & Medicaid Services (CMS) introduced the Guiding an Improving Dementia Experience (GUIDE) Model. The study explores the real-world implementation of the Cedars-Sinai C.A.R.E.S. Program, a pragmatic dementia care model, detailing its recruitment process and initial outcomes. METHODS: The Cedars-Sinai C.A.R.E.S. Program was integrated into the Epic electronic health record system and focused on proactive patient identification, engagement, interdisciplinary collaboration, care transitions, and ongoing care management. Eligible patients with a dementia diagnosis were identified through electronic health record and invited to join the program. Nurse practitioners with specialized training in dementia care performed comprehensive assessments using the CEDARS-6 tool, leading to personalized care plans developed in consultation with primary care providers. Patients benefited from a multidisciplinary team and support from care navigators. RESULTS: Of the 781 eligible patients identified, 431 were enrolled in the C.A.R.E.S. PROGRAM: Enrollees were racially diverse, with lower caregiver strain and patient behavioral and psychological symptoms of dementia (BPSD) severity compared to other programs dementia care programs. Healthcare utilization, including hospitalizations, emergency department (ED) admissions, and urgent care visits showed a downward trend over time. Completion of advanced directives and Physician Order of Life-Sustaining Treatment (POLST) increased after enrollment. CONCLUSION: The Cedars-Sinai C.A.R.E.S. Program offers a promising approach to dementia care. Its real-world implementation demonstrates the feasibility of enrolling a diverse population and achieving positive outcomes for PLwD and their caregivers, supporting the goals of national dementia care initiatives.

Choroid plexus volume differentiates MS from its mimics.

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.

Imaging chronic active lesions in multiple sclerosis: a consensus statement.

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis (MS) and have implications for non-relapsing biological progression. In recent years, the discovery of innovative magnetic resonance imaging (MRI) and PET derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with MS, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted (T1-w) and T2-w scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification, and monitoring is lacking. To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a Consensus Statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this Consensus Statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge.

A multicenter pilot study evaluating simplified central vein assessment for the diagnosis of multiple sclerosis.

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.

Alerting providers to hospitalized persons with dementia using the electronic health record.

BACKGROUND: While patients with dementia entering the hospital have worse outcomes than those without dementia, early detection of dementia in the inpatient setting is less than 50%. We developed and assessed the positive predictive value (PPV) and feasibility of a novel electronic health record (EHR) banner to identify patients with dementia who present to the inpatient setting using data from the medical record. METHODS: We developed and implemented an EHR algorithm to flag hospitalized patients age ≥65 years with potential cognitive impairment in the Epic EHR system using dementia ICD-10 codes, FDA-approved medications, and the use of the term "dementia" in the emergency department physician note. Medical records were reviewed for all patients who were flagged with an EHR banner from October 2022 to May 2023. RESULTS: A total of 344 individuals were identified who had a banner on their chart of which 280 (81.4%) were either diagnosed with dementia or were on an FDA-approved dementia medication. Forty-three individuals who had confirmed dementia were identified by a medication only (15.4%). Of the patients without confirmed dementia, the majority (N = 33, 9.6%) had a diagnosis of altered mental status, cognitive dysfunction, or mild cognitive impairment. Only 31 individuals (9.0%) had no indication of dementia or cognitive decline in their problem list, past medical history, or medication list. CONCLUSIONS: We found that it was feasible to implement an EHR algorithm for prospective dementia identification with a high PPV. These types of algorithms provide an opportunity to accurately identify hospitalized older individuals for inclusion in quality improvement projects, clinical trials, pay-for-performance programs, and other initiatives.

Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and mortality. Despite its clinical relevance, there are few treatment options for depression associated with multiple sclerosis and confirmatory trials are scarce. We aimed to evaluate the safety and efficacy of a multiple sclerosis-specific, internet-based cognitive behavioural therapy (iCBT) programme for the treatment of depressive symptoms associated with the disease. METHODS: This parallel-group, randomised, controlled, phase 3 trial of an iCBT programme to reduce depressive symptoms in patients with multiple sclerosis was carried out at five academic centres with large outpatient care units in Germany and the USA. Patients with a neurologist-confirmed diagnosis of multiple sclerosis and depressive symptoms were randomly assigned (1:1:1; automated assignment, concealed allocation, no stratification, no blocking) to receive treatment as usual plus one of two versions of the iCBT programme Amiria (stand-alone or therapist-guided) or to a control condition, in which participants received treatment as usual and were offered access to the iCBT programme after 6 months. Masking of participants to group assignment between active treatment and control was not possible, although raters were masked to group assignment. The predefined primary endpoint, which was analysed in the intention-to-treat population, was severity of depressive symptoms as measured by the Beck Depression Inventory-II (BDI-II) at week 12 after randomisation. This trial is registered at ClinicalTrials.gov, NCT02740361, and is complete. FINDINGS: Between May 3, 2017, and Nov 4, 2020, we screened 485 patients for eligibility. 279 participants were enrolled, of whom 101 were allocated to receive stand-alone iCBT, 85 to receive guided iCBT, and 93 to the control condition. The dropout rate at week 12 was 18% (50 participants). Both versions of the iCBT programme significantly reduced depressive symptoms compared with the control group (BDI-II between-group mean differences: control vs stand-alone iCBT 6·32 points [95% CI 3·37-9·27], p<0·0001, effect size d=0·97 [95% CI 0·64-1·30]; control vs guided iCBT 5·80 points [2·71-8·88], p<0·0001, effect size d=0·96 [0·62-1·30]). Clinically relevant worsening of depressive symptoms was observed in three participants in the control group, one in the stand-alone iCBT group, and none in the guided iCBT group. No occurrences of suicidality were observed during the trial and there were no deaths. INTERPRETATION: This trial provides evidence for the safety and efficacy of a multiple sclerosis-specific iCBT tool to reduce depressive symptoms in patients with the disease. This remote-access, scalable intervention increases the therapeutic options in this patient group and could help to overcome treatment barriers. FUNDING: National Multiple Sclerosis Society (USA).

Direct synthesis of multi-contrast brain MR images from MR multitasking spatial factors using deep learning.

PURPOSE: To develop a deep learning method to synthesize conventional contrast-weighted images in the brain from MR multitasking spatial factors. METHODS: Eighteen subjects were imaged using a whole-brain quantitative T1 -T2 -T1ρ MR multitasking sequence. Conventional contrast-weighted images consisting of T1 MPRAGE, T1 gradient echo, and T2 fluid-attenuated inversion recovery were acquired as target images. A 2D U-Net-based neural network was trained to synthesize conventional weighted images from MR multitasking spatial factors. Quantitative assessment and image quality rating by two radiologists were performed to evaluate the quality of deep-learning-based synthesis, in comparison with Bloch-equation-based synthesis from MR multitasking quantitative maps. RESULTS: The deep-learning synthetic images showed comparable contrasts of brain tissues with the reference images from true acquisitions and were substantially better than the Bloch-equation-based synthesis results. Averaging on the three contrasts, the deep learning synthesis achieved normalized root mean square error = 0.184 ± 0.075, peak SNR = 28.14 ± 2.51, and structural-similarity index = 0.918 ± 0.034, which were significantly better than Bloch-equation-based synthesis (p < 0.05). Radiologists' rating results show that compared with true acquisitions, deep learning synthesis had no notable quality degradation and was better than Bloch-equation-based synthesis. CONCLUSION: A deep learning technique was developed to synthesize conventional weighted images from MR multitasking spatial factors in the brain, enabling the simultaneous acquisition of multiparametric quantitative maps and clinical contrast-weighted images in a single scan.

Effect of GBCA Use on Detection and Diagnostic Performance of the Central Vein Sign: Evaluation Using a 3-T FLAIR* Sequence in Patients With Suspected Multiple Sclerosis.

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.

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.

Consensus Curriculum for Fellowship Training in Multiple Sclerosis and Neuroimmunology.

Management of multiple sclerosis and neuroimmunologic disorders has become increasingly complex because of the expanding number of recognized neuroimmune disorders, increased number of therapeutic options, and multidisciplinary care management needs of people with multiple sclerosis and neuroimmunologic disorders. More subspecialists are needed to optimize care of these patients, and many fellowship programs have been created or expanded to increase the subspecialty workforce. Consequently, defining the scope and standardizing fellowship training is essential to ensure that trainees receive high-quality training. A workgroup was created to develop a consensus fellowship curriculum to serve as a resource for all current and future training programs. This curriculum may also serve as a basis for future accreditation efforts.

Deep grey matter injury in multiple sclerosis: a NAIMS consensus statement.

Although multiple sclerosis has traditionally been considered a white matter disease, extensive research documents the presence and importance of grey matter injury including cortical and deep regions. The deep grey matter exhibits a broad range of pathology and is uniquely suited to study the mechanisms and clinical relevance of tissue injury in multiple sclerosis using magnetic resonance techniques. Deep grey matter injury has been associated with clinical and cognitive disability. Recently, MRI characterization of deep grey matter properties, such as thalamic volume, have been tested as potential clinical trial end points associated with neurodegenerative aspects of multiple sclerosis. Given this emerging area of interest and its potential clinical trial relevance, the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative held a workshop and reached consensus on imaging topics related to deep grey matter. Herein, we review current knowledge regarding deep grey matter injury in multiple sclerosis from an imaging perspective, including insights from histopathology, image acquisition and post-processing for deep grey matter. We discuss the clinical relevance of deep grey matter injury and specific regions of interest within the deep grey matter. We highlight unanswered questions and propose future directions, with the aim of focusing research priorities towards better methods, analysis, and interpretation of results.

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.

Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis: Recommendations of the National Multiple Sclerosis Society.

Importance: Autologous hematopoietic stem cell transplant (AHSCT) for multiple sclerosis has gained increasing interest in recent years. Despite the availability of many US Food and Drug Administration-approved disease-modifying therapies, some patients do not respond adequately and others may have very early aggressive disease that prompts consideration of alternative, highly effective, long-lasting therapy. The National Medical Advisory Committee of the National Multiple Sclerosis Society has reviewed recent literature on AHSCT for the purpose of making recommendations about its use based on current knowledge, as well as pointing out areas of controversy and issues requiring further research. Observations: Studies on AHSCT have repeatedly demonstrated high efficacy and a durable outcome in people with relapsing multiple sclerosis. Recent studies have shown considerable improvement in the safety of the procedure, with much lower mortality rates than were reported earlier. Consensus is emerging about the characteristics of the best candidates for the procedure. Questions remain about the ideal protocol, particularly about the best conditioning regimen to be used to kill immune cells. Larger randomized clinical trials are needed to address the question of whether AHSCT has advantages over the most efficacious disease-modifying agents currently available. One such trial (Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis [BEAT-MS) is currently in progress. Conclusions and Relevance: The National Multiple Sclerosis Society believes that AHSCT may be a useful treatment option for people with relapsing multiple sclerosis who demonstrate substantial breakthrough disease activity (ie, new inflammatory central nervous system lesions and/or clinical relapses) despite treatment with high-efficacy disease-modifying therapy or have contraindications to high-efficacy disease-modifying therapies. The best candidates are likely people younger than 50 years with shorter durations of disease (<10 years). The procedure should only be performed at centers with substantial experience and expertise. Ideally, recipients of the procedure should be entered into a single database, and further research is needed to establish ideal cell mobilization and immune-conditioning regimens.

Imaging Mechanisms of Disease Progression in Multiple Sclerosis: Beyond Brain Atrophy.

Clinicians involved with different aspects of the care of persons with multiple sclerosis (MS) and scientists with expertise on clinical and imaging techniques convened in Dallas, TX, USA on February 27, 2019 at a North American Imaging in Multiple Sclerosis Cooperative workshop meeting. The aim of the workshop was to discuss cardinal pathobiological mechanisms implicated in the progression of MS and novel imaging techniques, beyond brain atrophy, to unravel these pathologies. Indeed, although brain volume assessment demonstrates changes linked to disease progression, identifying the biological mechanisms leading up to that volume loss are key for understanding disease mechanisms. To this end, the workshop focused on the application of advanced magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging techniques to assess and measure disease progression in both the brain and the spinal cord. Clinical translation of quantitative MRI was recognized as of vital importance, although the need to maintain a relatively short acquisition time mandated by most radiology departments remains the major obstacle toward this effort. Regarding PET, the panel agreed upon its utility to identify ongoing pathological processes. However, due to costs, required expertise, and the use of ionizing radiation, PET was not considered to be a viable option for ongoing care of persons with MS. Collaborative efforts fostering robust study designs and imaging technique standardization across scanners and centers are needed to unravel disease mechanisms leading to progression and discovering medications halting neurodegeneration and/or promoting repair.

Microglia in Multiple Sclerosis: Friend or Foe?

Microglia originate from myeloid progenitors in the embryonic yolk sac and play an integral role in central nervous system (CNS) development, immune surveillance and repair. The role of microglia in multiple sclerosis (MS) has been complex and controversial, with evidence suggesting that these cells play key roles in both active inflammation and remyelination. Here we will review the most recent histological classification of MS lesions as well as the evidence supporting both inflammatory and reparative functions of these cells. We will also review how microglia may yield new biomarkers for MS activity and serve as a potential target for therapy.

Education Research: Multiple sclerosis and neuroimmunology fellowship training status in the United States.

OBJECTIVE: To investigate the current status of postgraduate training in neuroimmunology and multiple sclerosis (NI/MS) in the United States. METHODS: We developed a questionnaire to collect information on fellowship training focus, duration of training, number of fellows, funding application process, rotations, visa sponsorship, and an open-ended question about challenges facing training in NI/MS. We identified target programs and sent the questionnaires electronically to fellowship program directors. RESULTS: We identified and sent the questionnaire to 69 NI/MS fellowship programs. We successfully obtained data from 64 programs. Most programs were small, matriculating 1-2 fellows per year, and incorporated both NI and MS training into the curriculum. Most programs were flexible in their duration, typically lasting 1-2 years, and offered opportunities for research during training. Only 56% reported the ability to sponsor nonimmigrant visas. Most institutions reported having some internal funding, although the availability of these funds varied from year to year. Several program directors identified funding availability and the current absence of national subspecialty certification as major challenges facing NI/MS training. CONCLUSION: Our study is the first to describe the current status of NI/MS training in the United States. We found many similarities across programs. We anticipate that these data will serve as a first step towards developing a standard NI/MS curriculum and help identify areas where shared resources could enhance trainee education despite differences in training environments. We identified funding availability, certification status, and nonimmigrant visa sponsorship as potential barriers to future growth in the field.

New imaging approaches for precision diagnosis and disease staging of MS?

Magnetic resonance imaging (MRI) has revolutionized the diagnosis and management of people living with multiple sclerosis (MS). However, conventional MRI sequences and measures currently used in clinical practice have limitations in the appropriate diagnosis, prediction of future disability, and monitoring of disease activity in MS. A specific challenge is the accurate and timely diagnosis of progressive subtypes of MS. This article will summarize emerging MRI measures that may be of utility as clinical tools in diagnosis and prediction in MS. Although a wide range of MRI techniques have different strengths and weaknesses, those that will be discussed in this article include the "central vein sign," leptomeningeal inflammation/enhancement, conventional and quantitative spinal cord imaging, susceptibility-weighted imaging, and high-field MRI techniques. There are a number of novel and emerging MRI techniques that hold promise in improving diagnosis, prediction, and disease monitoring in MS.

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD.

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD.