Faculty Bibliography

Pathophysiology of multiple sclerosis (MS) lesions is dynamic and changes over time. The purpose of this exploratory study was to determine the longitudinal changes in MS lesions over time on ultra-high field MR imaging. Nine patients with MS underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo-T2*-weighted imaging on 7T MRI at baseline and after ~2.4 years of follow-up. Morphologic imaging characteristics, signal intensity patterns and quantitative susceptibility mapping (QSM) values of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on T2*-weighted images and/or SWI as well as hyperintense signal on QSM. Lesions were considered "non-iron-laden" if they were hyperintense on T2*/SWI and isointense or hyperintense on QSM. Total of 162 non-iron-laden and 29 iron-laden lesions were observed at baseline. No change in baseline lesion size during follow up was recorded in 92.7%; no change in lesion-vessel relationship in 86.5%; and no change in signal intensity pattern in 96.9% of lesions. Three lesions which were non-iron-laden at baseline, exhibited iron at follow-up. In two iron-laden lesions, redistribution of iron content was observed at follow-up. Two-thirds of these iron-laden lesions showed an increase in QSM at follow-up relative to baseline, and the remaining one-third exhibited decrease in QSM. Most of the newly formed lesions (11/13, 84.6%) at follow-up were iron-laden. 7T multiparametric MRI is a useful tool for tracking the evolution of MS lesions, especially with regard to changes in iron content.

Background/UNASSIGNED:Short-term disease progression is well documented in clinical trials, but there are limited published data on disease course in real-life practice. Methods/UNASSIGNED:Patient-Determined Disease Steps (PDDS). Clinicians recorded disease subtype and relapse status at each visit, but did not rate disability. PMSSS change from the first to the last visit was calculated for the cohort as a whole and for subgroups of interest. Multivariable regression models were constructed for predicting final PMSSS based on readily available predictor variables collected at the initial visit and relapse history during follow up. Results/UNASSIGNED:0.28). The only major predictor of final PMSSS was the initial PMSSS. Demographic variables (age, sex, race) or relapse status did not predict final severity score. Conclusions/UNASSIGNED:Baseline disability in two MS clinics was much lower than in the reference population from which PMSSS was derived. We observed no discernable slowing of disability accumulation during the short-term follow up in our cohort compared with the reference cohort. Overwhelmingly the most important predictor of final disease severity rank score was the initial disease severity rank score.

Whether disease course in Hispanic Americans (HA) with multiple sclerosis (MS) is different from Caucasian Americans (CA) or African Americans (AA) is unknown. We compared MS severity in the three main ethnic populations in our tertiary MS clinics using disease duration-adjusted rank score of disability: Patient-Derived Multiple Sclerosis Severity Score (P-MSSS). The age- and gender-adjusted P-MSSS was significantly higher in HA (3.9 +/- 2.6) and AA (4.5 +/- 3.0) compared to CA (3.4 +/- 2.6; p < 0.0001 for both). Adjusting for insurance did not change these results. These findings suggest that HA, as AA, have more rapid disability accumulation than CA.

Background: MS patients often stop disease-modifying therapy (DMT). MSBase, a 50,000-patient, global observational MS registry, provides a unique opportunity to identify predictors of relapses and disease progression after DMTs are stopped. Objectives: To identify predictors of relapse and confirmed disability progression after stopping DMTs. Methods: We included MS patients who, at the time of stopping DMT, were >=18 years and were on a DMT continuously for >=1 year. We also required that, after stopping DMT, each patient be followed for >2 years; did not restart DMT for > 6 months (to exclude therapy 'switchers'); and did not become pregnant for >1 year. Predictors of time to first relapse and 3-month confirmed progression (1.5 EDSS steps for baseline EDSS 0; 0.5-for baseline EDSS 6-6.5; 1-for all others) were analyzed using Cox proportional hazards regression. Hazard proportionality was assessed with scaled Schoenfeld residuals; p< 0.05 was considered significant. Results: We identified 4,842 patients in the MSBase who met our inclusion criteria (74% female; mean (SD) age 40.7 years (10.4); mean (SD) disease duration 11.6 years (7.7)). Median (IQR) EDSS at baseline was 3 (1.5, 5.5). The discontinued DMTs were: IFNb-1a sc in 28%; IFNb-1b-26%; IFNb-1a im-20%; glatiramer acetate 18%; natalizumab-6%; fingolimod 3%. Most common reasons for discontinuation, recorded for 48% patients, were adverse events (9%), inconvenience (7%) and intolerance (7%). Post-DMT follow up was 31,691 patient-years. Post-DMT annualized relapse rate (ARR) was 0.22 and was lowest post-IFNb-1b (ARR=0.19) and highest post-Natalizumab (ARR=0.32). Disability data was available for 2,678 patients. The incidence of post-DMT confirmed disability progression was 8.23 per 100 person-years (95% CI: 7.72, 8.76); it was lowest post-IFNb-1a (6.40 (5.45, 7.51)) and highest post-Natalizumab (12.55 (10.04, 15.69). DMT was restarted by 2,984 (61.6%) patients after a median (IQR) of 18.22 months (IQR 10.97, 36.60). For each DMT, we will present predictors of time to relapse and confirmed disability progression, and DMT restart based on Cox regression model. Conclusions: Understanding risk factors for post-DMT relapses and disability accumulation after cessation of DMTs may allow clinicians to identify patients at low risk of disease worsening, who may choose to safely discontinue a particular DMT, and those at high risk, who would be well advised to continue on therapy

BACKGROUND: Multiple sclerosis is a polysymptomatic disease. Little is known about relative contributions of the different multiple sclerosis symptoms to self-perception of health. OBJECTIVES: To investigate the relationship between symptom severity in 11 domains affected by multiple sclerosis and self-rated health. METHODS: Multiple sclerosis patients in two multiple sclerosis centers assessed self-rated health with a validated instrument and symptom burden with symptoMScreen, a validated battery of Likert scales for 11 domains commonly affected by multiple sclerosis. Pearson correlations and multivariate linear regressions were used to investigate the relationship between symptoMScreen scores and self-rated health. RESULTS: Among 1865 multiple sclerosis outpatients (68% women, 78% with relapsing-remitting multiple sclerosis, mean age 46.38 +/- 12.47 years, disease duration 13.43 +/- 10.04 years), average self-rated health score was 2.30 ('moderate to good'). Symptom burden (composite symptoMScreen score) highly correlated with self-rated health (r = 0.68, P < 0.0001) as did each of the symptoMScreen domain subscores. In regression analysis, pain (t = 7.00), ambulation (t = 6.91), and fatigue (t = 5.85) contributed the highest amount of variance in self-rated health (P < 0.001). CONCLUSIONS: Pain contributed the most to multiple sclerosis outpatients' perception of health, followed by gait dysfunction and fatigue. These findings suggest that 'invisible disability' may be more important to patients' sense of wellbeing than physical disability, and challenge the notion that physical disability should be the primary outcome measure in multiple sclerosis.

Objective: To investigate indications for and outcomes of total hip and knee arthroplasty in patients with multiple sclerosis (MS). Background: MS patients may need joint replacement due to MS-related factors, such as falls or avascular necrosis, or for unrelated indications (eg primary/secondary osteoarthritis). Literature on outcomes of total joint replacement in MS patients is limited to case reports that highlight surgical complications or unusual presentations. There are no systematic reviews of indications for and short- and long-term outcomes of hip and knee arthroplasty in MS patients. Design/Methods: Retrospective chart review of NYU MS Center patients who underwent hip or knee arthroplasty after MS onset. Results: 13 MS patients followed at NYU MS Care Center underwent hip (N=8) or knee (N=5) replacement at NYU. Average age at surgery was 56+/-11 years (range 35-69 years) and MS duration was 16+/-9 years; 10/13 were female. 3 patients had prior joint trauma and 1 had avascular necrosis of the hip presumably from steroid use; the remainder suffered from osteoarthritis. Ambulatory status before surgery was: 4-walking unassisted, 7 - cane, 2 - bilateral assistance. Ambulatory status after surgery at last follow up was: 8 walking unassisted, 3 using a cane, and 2 using a walker. Perioperative complications included acute blood loss in 4, pneumonia in 2, DVT in 1, and urinary retention in 1. Reoperation was required in 1 patient for recurrent hip dislocation. Conclusions: Orthopaedic literature focuses on perioperative complications after total joint arthroplasty in MS patients, but our data on unselected patients show that the surgery appears to benefit most of them, though (mostly) non-neurologic complications were seen in approximately half of the cases. These data can help optimize selection and surgical management of MS patients who are considering knee or hip replacement. We intend to present additional data on our patients that will include patient-reported outcomes