Longitudinal myelin content measures of slowly expanding lesions using 7T MRI in multiple sclerosis.

BACKGROUND AND PURPOSE: Slowly expanding lesions (SELs) are thought to represent a subset of chronic active lesions and have been associated with clinical disability, severity, and disease progression. The purpose of this study was to characterize SELs using advanced magnetic resonance imaging (MRI) measures related to myelin and neurite density on 7 Tesla (T) MRI. METHODS: The study design was retrospective, longitudinal, observational cohort with multiple sclerosis (n = 15). Magnetom 7T scanner was used to acquire magnetization-prepared 2 rapid acquisition gradient echo and advanced MRI including visualization of short transverse relaxation time component (ViSTa) for myelin, quantitative magnetization transfer (qMT) for myelin, and neurite orientation dispersion density imaging (NODDI). SELs were defined as lesions showing ≥12% of growth over 12 months on serial MRI. Comparisons of quantitative measures in SELs and non-SELs were performed at baseline and over time. Statistical analyses included two-sample t-test, analysis of variance, and mixed-effects linear model for MRI metrics between lesion types. RESULTS: A total of 1075 lesions were evaluated. Two hundred twenty-four lesions (21%) were SELs, and 216 (96%) of the SELs were black holes. At baseline, compared to non-SELs, SELs showed significantly lower ViSTa (1.38 vs. 1.53, p < .001) and qMT (2.47 vs. 2.97, p < .001) but not in NODDI measures (p > .27). Longitudinally, only ViSTa showed a greater loss when comparing SEL and non-SEL (p = .03). CONCLUSIONS: SELs have a lower myelin content relative to non-SELs without a difference in neurite measures. SELs showed a longitudinal decrease in apparent myelin water fraction reflecting greater tissue injury.

The patient-reported wearing-off phenomenon with monoclonal antibody treatments for multiple sclerosis.

Background: Many patients report a wearing-off phenomenon with monoclonal antibody treatment for multiple sclerosis in which perceived benefits wear off before the next dose is due. Objectives: To determine prevalence of the wearing-off effect, symptoms experienced, impact on treatment satisfaction, and associated patient characteristics. Methods: Patients receiving natalizumab, ocrelizumab, ofatumumab, or rituximab at a tertiary multiple sclerosis center were invited to take an online survey interrogating their monoclonal antibody experience. Additional history and patient characteristic data were collected. Logistic regression was used to determine if patient characteristics predicted the wearing-off effect and linear regression to evaluate the impact of the wearing-off effect on treatment satisfaction. The models were adjusted for age, disease duration, race, sex, body mass index, education, and depression as measured by the Patient Health Questionnaire-9. Results: We received 258 qualifying responses and 141 (54.7%) patients reported the wearing-off phenomenon. The most common symptom was fatigue (47.7%). Higher Patient Health Questionnaire-9 scores were significantly associated with the wearing-off phenomenon (OR = 1.02, p = 0.005). The wearing-off effect (ß = -0.52, p = 0.04) and higher Patient Health Questionnaire-9 (ß = -0.09, p < 0.01) scores were associated with significantly reduced treatment satisfaction. Conclusion: The wearing-off phenomenon is common, associated with depression, and reduces treatment satisfaction. Research addressing mitigation strategies is needed.

Progressive Encephalomyelopathy in an Older Man: A Case Report From the National Multiple Sclerosis Society Case Conference Proceedings.

We present a case of subacute onset progressive encephalomyelopathy in a 77-year-old man with symmetric lateral column signal abnormalities on spinal MRI. We discuss the differential and presumptive final diagnosis along with a review of the postulated disease immunopathogenesis.

Common Social and Health Disparities Contribute to Racial Differences in Ambulatory Impairment in Multiple Sclerosis.

BACKGROUND: We previously reported more rapid accrual of ambulatory impairments in Black compared to White individuals with relapsing remitting multiple sclerosis (RRMS) and higher body mass index (BMI). Hypertension and lower neighborhood socioeconomic status (SES) were associated with greater impairment, irrespective of race. We hypothesize that these common social and health inequities may explain a substantial portion of the racial differences in ambulation in American individuals with RRMS. METHODS: Causal mediation analyses investigated baseline and change-over-time mediators of ambulatory impairment differences between 1795 Black and White individuals with RRMS using a retrospective cohort study comprised of electronic health record data from 8491 clinical encounters between 2008 and 2015 where Timed 25-Foot Walk (T25FW) speeds without assistive devices were recorded. The hypothesis was that BMI, neighborhood SES, and hypertension were possible mediators. RESULTS: At baseline, Black individuals with RRMS (n = 175) had significantly slower T25FW speeds (5.78 vs 5.27 ft/s), higher BMI, a higher prevalence of hypertension, and they were more likely to live in lower-income neighborhoods than White individuals (n = 1,620). At baseline, a significant proportion (33.7%; 95% CI, 18.9%-59.4%) of the T25FW difference between Black and White individuals was indirectly due to a higher BMI (12.5%), hypertension burden (9.5%), and living in lower-income neighborhoods (11.2%). Once baseline mediation relationships were accounted for, there were no significant longitudinal mediation relationships. CONCLUSIONS: The findings implicate social and health disparities as prominent drivers of ambulatory differences between Black and White individuals with RRMS, suggesting that wellness and health promotion are essential components of MS care, particularly for Black individuals.

Predicting disability and mortality in CV2/CRMP5-IgG associated paraneoplastic neurologic disorders.

BACKGROUND: We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND). METHODS: This is a retrospective study of patients with CV2/CRMP5-IgG PND evaluated between 2002-2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan-Meier estimates were used to determine the probability of survival. RESULTS: Twenty-seven patients (56% female) with CV2/CRMP5-IgG PND were identified with a median follow-up of 54 months (IQR = 11-102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow-up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87-30.64, P = 0.005). Moderate-severe mRS = 3-5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18-41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55-93.04, P < 0.001) was significantly associated with mortality, while thymoma was not. INTERPRETATION: In this retrospective longitudinal study of CV2/CRMP5-IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population.

Detecting isolated cognitive relapses in persons with MS.

BACKGROUND: The existence of isolated cognitive relapses (ICRs) in persons with MS (PwMS) has been debated. OBJECTIVE: To examine relapses with decline on Symbol Digit Modalities Test (SDMT) but no change on Expanded Disability Status Scale (EDSS). METHODS: This 3-year prospective cohort study identified PwMS experiencing a relapse with decrease on SDMT. Participants with SDMT decline/stable EDSS were labeled "ICR," while those with a corresponding decrease on EDSS were classified "Relapse with Cognitive Decline (RCD)." Two definitions of SDMT decline were explored: (1) ⩾ 8 points, and (2) ⩾ 4 points. Logistic regression was used to analyze the relationship between ICR and RCD. RESULTS: The full cohort had 592 participants: 83 experienced relapses; 22 (26.5%) had an SDMT decrease of ⩾ 8 points; 14 (63.6%) met ICR criteria. Logistic regression (X2(1) = 5.112, p = 0.024) using demographics and disease characteristics explained 28.4% of the variance in ICR versus RCD. Only the MS Neuropsychological Questionnaire was associated with ICR (odds ratio (OR): 8.6; 95% confidence interval (CI): 1.1-16.4) 40 relapsing participants with SDMT decrease of ⩾ 4 points were identified: 26 (65%) had a stable EDSS (ICR). Logistic regression did not find any variable predictive of ICR. CONCLUSION: This prospective study demonstrates evidence of ICR in PwMS.

The impact of cigarette smoking on cognitive processing speed and brain atrophy in multiple sclerosis.

BACKGROUND: Smoking is associated with an increased risk of multiple sclerosis (MS) and disability worsening. The relationship between smoking, cognitive processing speed, and brain atrophy remains uncertain. OBJECTIVE: To quantify the impact of smoking on processing speed and brain volume in MS and to explore the longitudinal relationship between smoking and changes in processing speed. METHODS: A retrospective study of MS patients who completed the processing speed test (PST) between September 2015 and March 2020. Demographics, disease characteristics, smoking history, and quantitative magnetic resonance imaging (MRI) were collected. Cross-sectional associations between smoking, PST performance, whole-brain fraction (WBF), gray matter fraction (GMF), and thalamic fraction (TF) were assessed using multivariable linear regression. The longitudinal relationship between smoking and PST performance was assessed by linear mixed modeling. RESULTS: The analysis included 5536 subjects of whom 1314 had quantitative MRI within 90 days of PST assessment. Current smokers had lower PST scores than never smokers at baseline, and this difference persisted over time. Smoking was associated with reduced GMF but not with WBF or TF. CONCLUSION: Smoking has an adverse relationship with cognition and GMF. Although causality is not demonstrated, these observations support the importance of smoking cessation counseling in MS management.

The relationship between cognition, education, and employment in multiple sclerosis patients.

Background: Processing speed decline is a common manifestation of multiple sclerosis (MS). The processing speed test (PST) is a validated electronic cognitive assessment based on the Symbol-Digit Modalities Test, which is routinely administered as part of the multi-institutional Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) initiative. The longitudinal relationship between education, processing speed, and employment is unclear. Objectives: Determine the longitudinal impact of educational attainment on processing speed and employment. Methods: MS PATHS data through March 2020 were analyzed. Repeat PST assessments at 1, 2, and 3 years were classified as improved, worsened, or stable. Linear regression was used to evaluate the relationship between education and baseline PST performance and logistic regression was used to determine the odds of PST worsening by educational attainment. Employment outcomes were analyzed by PST status and educational level. Results: There were 13,732 patients analyzed. Education impacted baseline PST scores, but had a limited effect on PST performance over time. Education was protective with respect to employment in the setting of both PST worsening and improvement. Conclusion: Greater education results in better baseline processing speed and is protective with respect to employment status. Its impact on processing speed over time is marginal.

Racial disparities in hypertension management among multiple sclerosis patients.

BACKGROUND: Hypertension adversely impacts the multiple sclerosis (MS) disease course and is more common among Black Americans. Disparities in care due to structural racism may lead to suboptimal hypertension detection and control in Black American MS patients. OBJECTIVES: To determine if uncontrolled hypertension is more common in Black or White Americans with MS and whether race impacts the likelihood of receiving anti-hypertensive treatment. METHODS: A retrospective cohort study was conducted using longitudinal data from American participants in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) multi-institutional registry. Data was collected from 7 sites in the United States between May 2015 and November 2020. Patients with uncontrolled hypertension, defined as ≥2 blood pressure measurements ≥140/90 mmHg, were identified in the dataset. Racial differences in uncontrolled hypertension and odds of anti-hypertensive treatment were evaluated using logistic regression. Predictors of anti-hypertensive treatment in those with uncontrolled hypertension were determined by race. RESULTS: The analysis included 10,673 MS patients, of whom 1,442 (13.5%) were Black Americans. Despite a lower mean age (45.7 vs. 49.2 years), Black Americans had a 31% increased odds of uncontrolled hypertension compared to White Americans. After adjustment for relevant covariates, mean systolic blood pressure was 1.84 mmHg (95% confidence interval=1.07-2.61) higher in Black Americans than White Americans, and mean diastolic blood pressure was 1.28 mmHg (95% confidence interval=0.74-1.82) higher. Black Americans were also more likely to be on anti-hypertensive therapy (OR=1.68, 95% confidence interval=1.30-2.18) and were exposed to an adjusted average of 0.61 (95% confidence interval=0.45-0.78) more anti-hypertensive treatments than White Americans (p<0.001). Age, comorbid diabetes mellitus, and comorbid hyperlipidemia were positively associated with use of anti-hypertensive treatments in all patients with uncontrolled hypertension. CONCLUSION: Black American MS patients have significantly increased odds of uncontrolled hypertension, but also higher odds of receiving anti-hypertensive treatment.

Interpreting change on the Symbol Digit Modalities Test in people with relapsing multiple sclerosis using the reliable change methodology.

BACKGROUND: The Symbol Digit Modalities Test (SDMT) is increasingly utilized in clinical trials. A SDMT score change of 4 points is considered clinically important, based on association with employment anchors. Optimal thresholds for statistically reliable SDMT changes, accounting for test reliability and measurement error, are yet to be applied to individual cases. OBJECTIVE: The aim of this study was to derive a statistically reliable marker of individual change on the SDMT. METHODS: This prospective, case-control study enrolled 166 patients with multiple sclerosis (MS). SDMT scores at baseline, relapse, and 3-month follow-up were compared between relapsing and stable patient groups. Using data from the stable group and three previously published studies, candidate thresholds for reliable decline were calculated and validated against other tests and a clinically meaningful anchor-cognitive relapse. RESULTS: Candidate thresholds for reliable decline at the 80% confidence level varied between 6 and 11 points. An SDMT change of 8 or more raw score points was deemed to offer the best balance of discriminatory power and external validity for estimating cognitive decline. CONCLUSION: This study illustrates the feasibility and usefulness of reliable change methodology for identifying statistically meaningful cognitive decline that could be implemented to identify change in individual patients, for both clinical management and clinical trial outcomes.

Characterizing relapsing remitting multiple sclerosis patients burdened with hypertension, hyperlipidemia, and asthma.

BACKGROUND: Hypertension, hyperlipidemia, and asthma are common in multiple sclerosis (MS) patients and adversely impact physical and mental health independent of sociodemographic and clinical attributes. Characterizing MS patients with these comorbidities is necessary for informing comorbidity screening and managed care in vulnerable patient subgroups; however, there is sparse data currently available. METHODS: We conducted cross-sectional analyses of 2,012 relapsing remitting (RR) MS patients. Separate multivariable logistic regression models were conducted for the presence of hypertension, hyperlipidemia, and asthma. Independent variables included age, sex, race, MS duration, body mass index classification, insurance payer, smoking status, median income by residence ZIP code, disease modifying therapies, and the other comorbidities. RESULTS: Hypertension was more common in RRMS patients who were older, obese/severely obese, had hyperlipidemia, were asthmatics, living in neighborhoods with the lowest income, and who were Black Americans. RRMS patients with hyperlipidemia were more likely to be male, older, overweight/obese/severely obese, hypertensive, asthmatics, and White American. Asthmatic RRMS patients were more likely to be female, obese, hypertensive, and living in neighborhood of medium/low income, and less likely to be on interferons or glatiramer acetate. CONCLUSION: We identified factors independently associated with common comorbidity burden in RRMS patients, which will inform risk-stratification efforts aimed at mitigating the adverse impact of these conditions in MS patients. Our results are consistent with what is known about the determinants of hypertension, hyperlipidemia, and asthma in the non-MS patient population, and therefore disparities that exist in screening and management in the general U.S. population may likely exist in U.S. MS patients. It is also possible that there may be unique differences in specific MS patient subgroups, which warrants further investigation and detailed characterization.

Impact of Switching to Fingolimod Versus Injectable Disease-Modifying Therapy Cycling on Risk of Multiple Sclerosis-Related Relapses: A Retrospective Analysis.

BACKGROUND: Clinical and real-world studies have shown significant reductions in multiple sclerosis (MS) relapses with fingolimod versus injectable disease-modifying therapies (DMTs). Multiple sclerosis relapse rate and incidence were compared in patients switching from an injectable DMT to fingolimod and those cycling from one injectable DMT to another or remaining on their original injectable DMT. METHODS: Retrospective analysis was performed using Commercial and Medicare Supplemental claims data (July 1, 2010, to June 30, 2016) of adults with MS receiving ≥1 injectable DMT. Relapses were identified from MS-related hospitalization, outpatient emergency department or office visit, and corticosteroid administration. Annualized relapse rate ratio was estimated. RESULTS: Of 16,352 patients, 1110 were switchers to fingolimod, 908 were injectable DMT cyclers, and 14,334 were nonswitchers. At baseline, rate and incidence of MS relapses were higher in switchers and injectable DMT cyclers versus nonswitchers (P < .001); mean ± SD relapse rates declined from 0.4 ± 0.7, 0.4 ± 0.7, and 0.2 ± 0.5 at baseline to 0.2 ± 0.5, 0.3 ± 0.6, and 0.1 ± 0.4 after follow-up in switchers, injectable DMT cyclers, and nonswitchers, respectively. Relapse incidence declined in each cohort. The highest reductions in relapse rate and incidence were in switchers to fingolimod, where relapse risk was significantly reduced versus injectable DMT cyclers (22%, P = .0433) and nonswitchers (47%, P < .001). CONCLUSIONS: This study provides evidence that patients switching from an injectable DMT to fingolimod have the highest reductions in annualized rate and incidence of MS relapses and significantly reduced risk of relapse versus injectable DMT cyclers and nonswitchers.

Integrating patient-reported outcomes and quantitative timed tasks to identify relapsing remitting multiple sclerosis patient subgroups: a latent profile analysis.

BACKGROUND: Multiple sclerosis (MS) patients experience wide-ranging symptoms with varied severity, and approaches that integrate patient-reported outcomes and objective quantitative measures will present opportunities for advancing clinical profiling. The primary objective of the current study was to conduct exploratory data analysis using latent variable modeling to empirically identify clusters of relapsing remitting (RR) MS patients with shared impairment patterns across three patient-reported outcomes and two timed task measures. METHODS: Latent profile analyses and impairment data for 2,012 RRMS patients identified distinct patient clusters using timed task measures of upper and lower limb performance, and patient-reported outcomes measuring quality of life, depression symptom severity, and perceived global disability. Multinomial logistic regression models were used to characterize associations between socio-demographic attributes and assignment to the patient clusters. RESULTS: There were 6 distinct clusters of RRMS patients that differed by symptom patterns, and by their socio-demographic attributes. Most notable were were no differences in age, sex, or disease duration between the least and most impaired classes, representing 14% and 4% of patients, respectively. Patients in the most impaired class were much more likely to be Black American, have a history of smoking, have a higher body mass index, and be of lower socioeconomic status than the least impaired class. There were positive relationships between age and classification to clusters of increasing moderately severe impairment but not the most severe clusters. CONCLUSION: We present a framework for discerning phenotypic impairment clusters in RRMS. The results demonstrate opportunities for advancing clinical profiling, which is necessary for optimizing personalized MS care models and clinical research.

Age of hypertension onset in multiple sclerosis patients.

BACKGROUND/OBJECTIVE: Hypertension (HTN) is common in multiple sclerosis (MS), and it is associated with poorer outcomes. We sought to characterize HTN age at onset (AAO) by MS status. METHODS/RESULTS: There were 130,050 incident HTN patients, among whom there were 892 MS patients. We conducted multivariable linear regression adjusting for patient attributes. Sex- and race-stratified models were conducted. HTN AAO did not differ in patients with and without MS (p = 0.17). Similar null associations were observed in the sex- and race-specific analyses. CONCLUSION: While there are complex relationships between HTN and MS, there are no differences in HTN AAO by MS status.

Vascular comorbidity is associated with lower brain volumes and lower neuroperformance in a large multiple sclerosis cohort.

OBJECTIVE: The objective of this study is to assess the association between vascular comorbidity burden with clinical and imaging features of disease burden in a large population of people with multiple sclerosis (MS). METHODS: We included participants from the MS Partners Advancing Technology Health Solutions (MS PATHS) cohort. We evaluated if vascular comorbidities (diabetes, hypertension, and dyslipidemia) or a composite sum of comorbidities was associated with MS characteristics, including objective neurologic function assessments and quantitative brain magnetic resonance imaging (MRI) measurements in propensity score-weighted models. RESULTS: In total, 11,506 participants (6409 (55%) with brain MRI) were included. Individuals with 2+ vascular comorbidities had slower walking speed (standard deviation (SD) = -0.49; 95% confidence interval (CI) = -0.78, -0.19; p = 0.001), slower manual dexterity (SD = -0.41; 95% CI = -0.57, -0.26; p < 0.0001), and fewer correct scores on cognitive processing speed (SD = -0.11; 95% CI = -0.20, -0.02; p = 0.02) versus those with no comorbidities. Those with 2+ had lower brain parenchymal (-0.41%, 95% CI = -0.64, -0.17) and gray matter fractions (-0.30%, 95% CI = -0.49, -0.10), including reduced cortical (-10.10 mL, 95% CI = -15.42, -4.78) and deep (-0.44 mL, 95% CI = -0.84, -0.04) gray matter volumes versus those with no comorbidity. CONCLUSION: Increased vascular comorbidity burden was associated with clinical and imaging markers of neurologic dysfunction and neurodegeneration in MS. Strategies to optimize comorbidity management in people with MS are warranted.

Measures of Thalamic Integrity are Associated with Cognitive Functioning in Fingolimod-treated Multiple Sclerosis Patients.

BACKGROUND: Cognitive impairment is common in relapsing-remitting multiple sclerosis (RRMS) and multiple domains are affected, including information processing speed, episodic memory, and executive function. Damage to the thalamus appears to be related to cognitive functioning in MS. Fingolimod is a disease-modifying therapy for RRMS, which has been shown to have a protective effect on thalamic volume. OBJECTIVE: To determine the relationship between cognitive measures and the thalamus in fingolimod-treated RRMS patients and healthy controls using ultra high-field magnetic resonance imaging (MRI). METHODS: Fingolimod-treated RRMS and healthy participants were recruited from a single center to undergo neuropsychological testing and 7 tesla MRI. These assessments were performed at baseline, 6 months, and 12 months. The neuropsychological testing included the Brief Visuospatial Memory Test-Revised (BVMTR), the Symbol Digit Modalities Test (SDMT), the Selective Reminding Test (SRT), and the Delis-Kaplan Executive Function System (DKEFS). MRI metrics included thalamic volume, thalamic myelin density, thalamic axon density, T2 lesion volume, brain parenchymal fraction, and cortical thickness. Mixed-effects linear regression was used to determine the relationship between MRI parameters and neuropsychological test performance over time. Rates of change in patients and controls were compared using two-sample t-tests. RESULTS: We enrolled 15 RRMS patients and 5 healthy controls. Controls performed better than patients at baseline, but this difference was only significant for the letter fluency subtest of the DKEFS and for long-term storage as assessed by the SRT. Thalamic volume and thalamic myelin density were significantly associated with visuospatial (BVMTR) and verbal memory (SRT). Thalamic volume alone was also associated with inhibitory control (Color word interference subtest of the DKEFS) and cognitive flexibility (Number letter switching subtest of the DKEFS), whereas thalamic myelin density alone was associated with semantic knowledge (Verbal fluency subtest of the DKEFS). There were no significant changes in the rates of change in neurometric test performance or MRI metrics between patients and controls from baseline to 6 months and baseline to 12 months. CONCLUSIONS: Thalamic injury is associated with cognitive performance in several domains. Fingolimod-treated RRMS patients evolved similarly to healthy controls over one year with regards to neuropsychological test performance and changes on MRI.

Quantifying cognition and fatigue to enhance the sensitivity of the EDSS during relapses.

BACKGROUND: Cognition is affected by relapses in persons with multiple sclerosis (PwMS), yet the Expanded Disability Status Scale (EDSS) does not readily detect cognitive changes. OBJECTIVE: The objective of this study is to improve the detection of cognitive decline during relapses, by incorporating the Symbol Digit Modalities Test (SDMT) into the cerebral Functional System Score (CFSS) of the EDSS. METHODS: This prospective study recruited PwMS from three dedicated MS centers. All subjects had EDSS, SDMT, and Fatigue Severity Scale (FSS) administered. Subjects experiencing a relapse were assigned to the relapse group (RG). Matched controls from the larger cohort were assigned to the stable group (SG). RG and SG subjects underwent the same evaluation at relapse and 3 months later. Our main outcomes were a modified CFSS (m-CFSS) and modified EDSS (m-EDSS), incorporating SDMT and FSS, accounting for cognitive performance and fatigue rating, during relapse. RESULTS: The full cohort included 592 subjects; 80 qualified for RG and 72 were matched to the SG. The m-CFSS was significantly higher than CFSS at baseline (median = 2 vs. median = 0, p < 0.001) and relapse (median = 2 vs. median = 1, p < 0.001). The m-EDSS was higher than EDSS (median 3.0 vs. 2.5, p = 0.02) at relapse, where 35 RG subjects (43.8%) had higher m-EDSS than EDSS at relapse. CONCLUSION: This study demonstrates that incorporating the SDMT and FSS improves the accuracy of the EDSS, by accounting for cognitive changes, during relapse activity.

Patient reported outcomes and performance metrics at diagnosis of secondary progressive multiple sclerosis.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) usually evolves into secondary progressive multiple sclerosis (SPMS). Recognition of SPMS is important because of prognostic and treatment implications. OBJECTIVE: The objective of this study is to determine distributions of patient-reported outcomes (PROs) and the Timed 25-Foot Walk (T25FW) at SPMS diagnosis and describe the evolution of these metrics in patients with SPMS. METHODS: A tertiary MS center clinical database was queried to identify patients with RRMS and SPMS. PRO data including performance scales (PS), Patient Health Questionnaire-9 (PHQ-9), European Quality of Life-5-Dimensions (EQ-5D), and the T25FW were extracted. Descriptive statistics were calculated at SPMS diagnosis, and score trajectories were modeled. Cox proportional hazards modeling was used to estimate hazard ratios for time to SPMS diagnosis. RESULTS: Among 5,558 patients identified, 164 were diagnosed with SPMS between January 2008 and June 2016. At SPMS diagnosis, the mean outcome values were T25FW = 12.5 seconds (standard deviation, SD = 10.7), PS = 15.6 (SD = 6.5), PHQ-9 = 6.8 (SD = 4.2), and EQ-5D = 0.63 (SD = 0.20). Distinct patterns were observed in the measures leading up to SPMS diagnosis. Higher age, male gender, longer disease duration, and greater disability were associated with an increased hazard of SPMS diagnosis. CONCLUSION: Longitudinal monitoring of PROs and performance metrics may help identify those at higher risk of near-term SPMS.