Long-term trajectories of ambulatory impairment in multiple sclerosis.

BACKGROUND: Ambulatory impairment is a common and complex manifestation of multiple sclerosis (MS), and longitudinal patterns are not well understood. OBJECTIVE: To characterize longitudinal walking speed trajectories in a general MS patient population and in those with early disease (⩽ 5 years from onset), identify subgroups with similar patterns, and examine associations with individual attributes. METHODS: Using a retrospective cohort study design, latent class growth analysis was applied to longitudinal timed 25-foot walk (T25-FW) data from 7683 MS patients, to determine T25-FW trajectories. Associations were evaluated between trajectory assignment and individual attributes. Analyses were repeated for 2591 patients with early disease. RESULTS: In the general patient population, six trajectories were discerned, ranging from very minimal to very high impairment at baseline, with variability in impairment accrual. The clusters with moderate to very high walking impairment were associated with being female, older and Black American, longer symptom duration, progressive course, and depressive symptoms. In the early disease subset, eight trajectories were discerned that included two subgroups that rapidly accrued impairment. CONCLUSION: We identified novel subgroups of MS patients will distinct long-term T25-FW trajectories. These results underscore that socially disadvantaged and economically marginalized MS patients are the most vulnerable for severe ambulatory impairment.

Stopping disease-modifying therapy in relapsing and progressive multiple sclerosis.

PURPOSE OF REVIEW: To assess the reasons for considering discontinuation of disease-modifying therapies (DMTs)in patients with multiple sclerosis (MS). Relevant aspects of the natural history, pathology, and immunology are analyzed. RECENT FINDINGS: A number of retrospective observational studies in aggregate indicate that stopping DMTs may be attempted in older individuals with stable disease. Prognostic factors have been identified informing about the risk of recurrence of disease activity after DMT discontinuation. SUMMARY: Several clinical scenarios provide a rationale to stop DMTs in people with MS. Cumulative evidence has been gathered recently allowing us to more precisely weigh the risks against the benefits. This information aids in the decision process.

The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability.

BACKGROUND: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. OBJECTIVES: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. METHODS: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. CONCLUSION: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS ( http://www.cdisc.org/therapeutic#MS ) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.

Prevalence and Predictors of Depression Among Patients With Epilepsy, Stroke, and Multiple Sclerosis Using the Cleveland Clinic Knowledge Program Within the Neurological Institute.

BACKGROUND: Neurological conditions carry a high risk of depression. Given this risk, the Neurological Institute (NI) at Cleveland Clinic has initiated systematic screening for depression using the 9-item Patient Health Questionnaire-9 (PHQ-9) embedded within its electronic medical record and its data capture system, the Knowledge Program (KP)1. OBJECTIVE: We sought to (1) estimate the prevalence of depression among patients with epilepsy, stroke, and multiple sclerosis (MS); (2) identify risk factors for depression within each disease; and (3) determine differential risks and predictors across neurological disorders. METHODS: The KP1 database provided information on approximately 23,000 visits involving 7946 outpatients with epilepsy, stroke, or MS seen in neurology specialty clinics. The primary outcome measure was depression as defined as a PHQ-9 ≥ 10. RESULTS: Overall, the point prevalence of depression was 29.0%. For stroke, epilepsy, and MS, prevalence of depression was 23% (95% CI: 21-25%), 33% (95% CI: 31-35%), and 29% (95% CI: 28-30%), respectively. For all 3 conditions, increasing disease severity and decreased health-related quality of life were independent predictors of depression. In multivariable models, there was a significant interaction between age and condition, and condition with disease severity. In stroke and MS, increasing age was associated with reduced odds for depression, whereas in epilepsy, increasing age was associated with an increased odds for depression. CONCLUSIONS: Although depression is common among patients with neurological disorders, our data suggest that predictors of depression such as age and disease severity varied by condition, supporting important possible phenomenological and pathophysiological differences of depression across these neurological conditions.

Processing speed test: Validation of a self-administered, iPad®-based tool for screening cognitive dysfunction in a clinic setting.

BACKGROUND: Cognitive dysfunction is common in multiple sclerosis (MS) patients and has important consequences for daily activities, yet, unlike motor function, is not routinely assessed in the clinic setting. We developed the Processing Speed Test (PST), a self-administered iPad®-based tool to measure MS-related deficits in processing speed. OBJECTIVE: To determine whether the PST is valid for screening cognitive dysfunction by comparing it to the paper-and-pencil Symbol Digit Modalities Test (SDMT). METHODS: We assessed PST test-retest reliability, sensitivity of PST and SDMT in discriminating MS patients from healthy controls (HC), convergent validity between PST and SDMT, correlations between T2 lesion load and PST and SDMT, and PST performance with and without technician present during administration. RESULTS: PST had excellent test-retest reliability, was highly correlated with SDMT, was slightly more sensitive than SDMT in discriminating MS from HC groups, and correlated better with cerebral T2 lesion load than did SDMT. Finally, PST performance was no different with or without a technician in the testing environment. CONCLUSION: PST has advantages over SDMT because of its efficient administration, scoring, and potential for medical record or research database integration. PST is a practical tool for routine screening of processing speed deficits in the MS clinic.

Idio Scale Judgment: evaluation of a new method for estimating responder thresholds.

PURPOSE: To pilot the newly developed Idio Scale Judgment method for estimating the amount of score change that matters to patients (i.e., change thresholds). METHODS: An online panel of 500 participants diagnosed with multiple sclerosis (MS) responded to the Neuro-QoL fatigue scale and to demographic and clinical questions. Participants compared their own fatigue to that represented by seven short form summaries (SFSs) that were located relatively close to their own fatigue levels. They judged these as representing the same, greater, or less fatigue than their own. We calculated the distances between patients' own levels of fatigue and the location of SFSs they endorsed as a change that would make a difference in daily life. These distances were used as estimates of change thresholds. Logically inconsistent judgments were tabulated and associations with clinical and demographic variables were estimated. RESULTS: Change thresholds based on mean individual thresholds for consequential change were calculated for improvement (-3.5) and worsening (3.2). The majority of participants had no logically inconsistent judgments (69%). Having one or more reversals in judgment was not significantly associated with education or fatigue score, but was weakly associated with age, gender, and MS type and moderately associated with ratings of confidence in SFS comparisons. CONCLUSIONS: As piloted, Idio Scale Judgment had a number of design strengths. Participants made comparisons to levels of fatigue that were within range of their own, and their judgments were contextualized in personally relevant consequences. The design lends itself to collection of data in large samples allowing evaluation of the range of judgments. Some study limitations could be mitigated with modifications. We concluded that the Idio Scale Judgment has substantial promise as a new tool for estimating change thresholds.

Validating Neuro-QoL short forms and targeted scales with people who have multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic, progressive, and disabling disease of the central nervous system with dramatic variations in the combination and severity of symptoms it can produce. The lack of reliable disease-specific health-related quality of life (HRQL) measures for use in clinical trials prompted the development of the Neurology Quality of Life (Neuro-QOL) instrument, which includes 13 scales that assess physical, emotional, cognitive, and social domains, for use in a variety of neurological illnesses. OBJECTIVE: The objective of this research paper is to conduct an initial assessment of the reliability and validation of the Neuro-QOL short forms (SFs) in MS. METHODS: We assessed reliability, concurrent validity, known groups validity, and responsiveness between cross-sectional and longitudinal data in 161 recruited MS patients. RESULTS: Internal consistency was high for all measures (α = 0.81-0.95) and ICCs were within the acceptable range (0.76-0.91); concurrent and known groups validity were highest with the Global HRQL question. Longitudinal assessment was limited by the lack of disease progression in the group. CONCLUSIONS: The Neuro-QOL SFs demonstrate good internal consistency, test-re-test reliability, and concurrent and known groups validity in this MS population, supporting the validity of Neuro-QOL in adults with MS.

Factors associated with clinically significant increased walking time in multiple sclerosis: results of a survival analysis of short-term follow-up data from a clinical database.

BACKGROUND: Because multiple sclerosis (MS) is variable and unpredictable, if symptom worsening could be predicted, patients may feel better prepared to manage changes in function. OBJECTIVE: The objective of this paper is to study the prediction of walking impairment in MS. METHODS: We retrieved data for all MS patients at our center (2008-2009), including baseline and follow-up timed 25-foot walk (T25FW) times. We assessed the incidence of ≥20% worsening in T25FW by developing two survival models: (1) disease course and (2) Multiple Sclerosis Performance Scales (MSPS) score. The outcome was days until ≥20% worsening in T25FW. Covariates were disease subtype, years since diagnosis, Patient Health Questionnaire-9 (PHQ-9) score, and demographics. Data were interval censored; missing data were handled with multiple imputation. RESULTS: Of 1544 patients, 309 (20%) experienced ≥20% worsening T25FW. For disease course, time to worsening was significantly shorter for secondary progressive vs. relapsing-remitting disease (p < 0.001). For MSPS, patients with lower baseline MSPS scores progressed more slowly (p = 0.001). In both models, sex, baseline T25W, and time since diagnosis were significantly associated with worsening. In the disease course model, PHQ 9 score may be related to worsening (p = 0.07). CONCLUSION: These findings suggest factors associated with worsening in T25FW and a potential approach to establishing indicators associated with clinically significant change.

Vision in a phase 3 trial of natalizumab for multiple sclerosis: relation to disability and quality of life.

BACKGROUND: Low-contrast visual acuity (LCVA), a sensitive measure of visual function in multiple sclerosis (MS), demonstrated treatment effects as a secondary outcome measure in the Phase 3 trial of natalizumab, AFFIRM. In these posttrial analyses, we studied the relation of visual function to quality of life (QOL), magnetic resonance imaging (MRI) measures, and Expanded Disability Status Scale (EDSS) scores. METHODS: At baseline and at 52 and 104 weeks in AFFIRM, patients underwent binocular testing of LCVA (1.25% and 2.5% contrast) and high-contrast visual acuity (HCVA). Vision-specific QOL was assessed by the Impact of Visual Impairment Scale (IVIS), whereas the SF-36 Health Survey and Visual Analog Scale were administered as generic QOL measures and the EDSS as a measure of neurologic impairment. RESULTS: Among QOL measures, IVIS scores showed the most significant correlations with visual dysfunction at all time points in the trial (r= -0.25 to -0.45, P < 0.0001 for LCVA and HCVA). Higher MRI T1- and T2-lesion volumes were also associated with worse vision scores at all time points (P < 0.0001). Clinically meaningful worsening (progression) of LCVA was noted in substantial proportions of patients in AFFIRM and was prevalent even among those without EDSS progression over 2 years (21.9% with LCVA progression at 2.5% contrast; 26.2% at 1.25% contrast). HCVA worsened in only 3.7% of patients without EDSS progression. CONCLUSIONS: Loss of visual function, particularly as measured by LCVA, was common in AFFIRM, occurring in >20% of patients. Both LCVA and HCVA scores reflect vision-specific aspects of QOL, but LCVA provides information about disability progression not entirely captured by the EDSS. Vision represents a key dimension of outcome assessment for MS and adds valuable information on disability and QOL that can be useful to clinicians.

Comparison of time to clinically meaningful improvement in quality of life in neurological disorders in patients treated with natalizumab versus ocrelizumab.

Aim: To assess time to improvement in Quality of Life in Neurological Disorders (Neuro-QoL) domains for patients treated with natalizumab versus ocrelizumab. Methods: Patients enrolled in the MS PATHS network who initiated treatment with either natalizumab or ocrelizumab rated the Neuro-QoL domains of physical function, symptoms, emotional health, cognitive function and social ability. Results: Time to clinically meaningful improvement was significantly shorter with natalizumab versus ocrelizumab for cognitive function (event time ratio [95% CI]: 0.37 [0.24-0.57]; p < 0.001), sleep disturbance (0.45 [0.28-0.72]; p = 0.001), social role participation (0.37 [0.21-0.66]; p = 0.001) and social role satisfaction (0.5 [0.31-0.8]; p = 0.004). Conclusion: Natalizumab had shorter time to clinically meaningful improvement in cognitive, sleep, and social role Neuro-QoL domains versus ocrelizumab.

Knowledge of treatment-related benefits associated with medication choices, including improvement of quality of life (QoL), are strong influential factors for patients to start and continue their therapies. Little is known about patient-reported time to onset of functional improvement upon the initiation of medications for multiple sclerosis (MS). The Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network, a repository of collaborative international data on routine MS management, includes patient-reported information on the health-related QoL using the Quality of Life in Neurological Disorders (Neuro-QoL) measure. This study included data from 883 eligible patients enrolled in MS PATHS, with the aim of assessing and comparing the time to improvement in physical, mental and social health for patients treated with natalizumab versus ocrelizumab using Neuro-QoL. Natalizumab and ocrelizumab are both high-efficacy treatment options for relapsing forms of MS. The results demonstrated that, compared with ocrelizumab, natalizumab treatment led to faster effect on mental and social health, as well as quicker improvements in physical functioning in the arms and hands. Overall, it took shorter time for natalizumab-treated patients to achieve better QoL compared with ocrelizumab. These findings highlight the importance of QoL in disease management and provide a patient perspective for healthcare providers when making decisions about high-efficacy treatments for their patients with MS.

Long term benefit of multiple sclerosis treatment: an investigation using a novel data collection technique.

BACKGROUND: The Knowledge Program (KP) is an initiative to collect self-reported patient data and objective clinician assessments electronically at each outpatient clinical encounter. Available outcomes include the EuroQoL-5D (EQ5D), Patient Health Questionnaire-9 (PHQ9), Multiple Sclerosis Performance Scales (MSPS), and the timed 25-foot walk (T25FW). OBJECTIVE: This study was designed to use the KP to investigate the long-term benefits of early treatment (ET) in multiple sclerosis (MS). METHODS: The KP was queried for patients with relapsing-remitting MS or secondary progressive MS who were ≥ 5 years from symptom onset. ET was defined as treatment with an approved agent for ≥ 3 of the first five years after symptom onset. Propensity scores for ET were calculated based on early clinical characteristics. Patients were divided into propensity score quintiles and linear regression models were constructed to determine the treatment effect sizes and confidence intervals. RESULTS: From the 1082 patients that met entry criteria, 453 patients (41.9%) received ET. Those patients receiving ET showed significantly better scores on the EQ5D index, PHQ9, and MSPS, but only in the upper three propensity quintiles. For the T25FW, ET did not result in significantly better times in any quintile. CONCLUSIONS: These results suggest that ET of MS is beneficial but the effect appears modest.

Implementing patient-reported outcomes assessment in clinical practice: a review of the options and considerations.

PURPOSE: While clinical care is frequently directed at making patients "feel better," patients' reports on their functioning and well-being (patient-reported outcomes [PROs]) are rarely collected in routine clinical practice. The International Society for Quality of Life Research (ISOQOL) has developed a User's Guide for Implementing Patient-Reported Outcomes Assessment in Clinical Practice. This paper summarizes the key issues from the User's Guide. METHODS: Using the literature, an ISOQOL team outlined considerations for using PROs in clinical practice; options for designing the intervention; and strengths, weaknesses, and resource requirements associated with each option. RESULTS: Implementing routine PRO assessment involves a number of methodological and practical decisions, including (1) identifying the goals for collecting PROs in clinical practice, (2) selecting the patients, setting, and timing of assessments, (3) determining which questionnaire(s) to use, (4) choosing a mode for administering and scoring the questionnaire, (5) designing processes for reporting results, (6) identifying aids to facilitate score interpretation, (7) developing strategies for responding to issues identified by the questionnaires, and (8) evaluating the impact of the PRO intervention on the practice. CONCLUSIONS: Integrating PROs in clinical practice has the potential to enhance patient-centered care. The online version of the User's Guide will be updated periodically.

Clinical perspective on clinical outcome assessments in neurosarcoidosis.

BACKGROUND: There are no validated clinical outcome assessments (COAs) used in neurosarcoidosis. OBJECTIVE: We surveyed clinicians who treat patients with neurosarcoidosis to determine: 1) current approaches to assessment of neurologic impairment, and 2) clinicians' needs regarding future COA development. METHODS: Physician contacts from the Foundation for Sarcoidosis Research and Neurosarcoidosis Consortium Group were sent an online survey. RESULTS: For 43/143 responders, COAs were used in a minority of settings. Apart from time for administration, the biggest barriers to implementation were lack of validated, disease-specific measures. CONCLUSIONS: Lack of validated, disease-specific measures is a barrier to monitoring neurological impairment in neurosarcoidosis.

Association of socioeconomic disadvantage and neighborhood disparities with clinical outcomes in multiple sclerosis patients.

BACKGROUND: Socioeconomic disadvantage may be an important contributor to clinical outcomes in MS but is not well understood. Our objective was to examine the associations between Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage, with clinical outcomes. METHODS: We assessed the longitudinal association between MS Performance Test (MSPT) and quality of life in Neurological Disorders (Neuro-QoL) measures with ADI quartiles (Q1: lowest deprivation - Q4 highest deprivation) in relapsing remitting MS (RRMS) and progressive MS cohorts. RESULTS: Our study included 2,921 patients (65.8% RRMS and 34.1% progressive MS) with 13,715 visits. Patients living in the most disadvantaged areas had almost universal worsening on baseline MSPT and Neuro-QoL scores (p < 0.05) when compared to patients living in areas of lowest deprivation. Manual Dexterity Test (MDT) illustrated particular disparity as RRMS patients living in the greatest area of deprivation had MDT score which averaged 2.9 seconds longer than someone living in areas of least deprivation. Longitudinal analysis illustrated less favorable MSPT and Neuro-QoL outcomes across visits between Q1 versus Q4 ADI quartiles within in the RRMS cohort but not within the progressive MS cohort. After adjustment, linearly increasing area deprivation scores reflected less favorable Processing Speed Test (PST) and six Neuro-QoL outcomes among the RRMS cohort. Within the progressive cohort, higher deprivation was associated less favorable MDT, PST and 11 of 12 Neuro-QoL outcome measures. CONCLUSIONS: This study provides evidence for socioeconomic disadvantage as a risk factor for disability accrual in MS and may be targeted to improve care while informing resource allocation.

Components of a successful community-based exercise program for individuals with Parkinson's disease: Results from a participant survey.

OBJECTIVES: The aim of the project was to examine the personal beliefs, motivators, and barriers in people with Parkinson's disease (PwPD) relating to their participation in a year-round community-based cycling program, Pedaling for Parkinson's (PFP). DESIGN: Cross-sectional survey from a 12-month pragmatic study. SETTING: Five community-based PFP sites. MAIN OUTCOME MEASURES: A survey was designed to capture the attitudes and beliefs of those participating in a PFP program. Survey responses were rated on a 5-point Likert scale (1-5; higher number representing a more positive response) assessing the subdomains of Personal Beliefs and Knowledge, Health and Disability, Program, and Fitness Environment following a 12-month exercise observational period. RESULTS: A total of 40 PwPD completed the survey. Mean subdomain scores were as follows: 4.37 (0.41) for Personal Beliefs and Knowledge, 4.25 (0.65) for Health and Disability, 4.11 (0.53) for Program, and 4.35 (0.44) for Fitness Environment. There were no significant correlations between survey subdomains and demographic variables (age, years of education, years since diagnosis, years attending the PFP program, and disease severity) or subdomains and exercise behavior (cadence, attendance, and heart rate). CONCLUSIONS: Regardless of demographic variables and disease severity, PwPD who attended a PFP program enjoyed the class, felt that their PD symptoms benefited from exercise, and were motivated to exercise by their PD diagnosis. Factors such as location of the gym, cost, and transportation were important. With the growing body of PD literature supporting the role of exercise in potentially altering the disease trajectory, it is critical that communities adopt and implement exercise programs that meet the needs of PwPD and facilitate compliance.

Web-based self-management for patients with multiple sclerosis: a practical, randomized trial.

OBJECTIVE: No studies have addressed the use of electronic personal health records (e-PHRs) for self-management in complex neurological disorders. We assessed and tested an Internet-based self-management system that utilized the e-PHR and determined its impact on self-assessed well-being, clinician-assessed well-being, and healthcare utilization in patients with multiple sclerosis (MS). MATERIALS AND METHODS: Subjects were randomized to usual care (a secure Web-based messaging system) or active intervention, which included secure messaging, self-monitoring, self-management of MS symptoms, and communication about upcoming clinic visits. Computers and Internet access were provided. Subjects were included if they had MS, lived within the county or region surrounding our MS center, had at least two appointments at our center in the previous 12 months, and demonstrated basic typing and computer skills. Study duration was 12 months. RESULTS: Of 220 subjects completing informed consent, 206 met the inclusion criteria. At the study's end, 83 subjects remained in the usual care group and 84 in the enhanced care group. Both groups used the available system components. The groups did not significantly differ on the primary endpoints or healthcare utilization. CONCLUSIONS: Self-management support is an emerging aspect of chronic care management. We established the feasibility of conducting a randomized, controlled trial using e-PHRs for patient self-management. We did not find that e-PHR-enabled self-management augmented multidisciplinary MS center-based care, possibly because the differences between interventions were not great enough.

Assessing Access to Five Types of Insurance by People with Multiple Sclerosis Using a Cross-sectional Online Survey.

BACKGROUND: Many individuals with multiple sclerosis (MS) depart the workforce prematurely. In the United States, access to insurance, including health, disability income, long-term care, and life insurance, is largely employment-based or purchased from earnings. Many individuals we see in the clinic experience financial hardship because of a lack of insurance, even if working. We sought to determine the proportion of workers who are financially protected through insurance coverage and the sources of this coverage in a large sample. METHODS: We developed an online survey and opened it to individuals aged 18 to 65 years registered with the North American Research Committee on Multiple Sclerosis, iConquerMS, or the National Multiple Sclerosis Society Minority Advisory Council. Data collected included demographic and disease characteristics, current information about each insurance type (coverage vs no coverage), and when the current insurance policies were obtained relative to MS diagnosis. RESULTS: Of 2507 survey respondents, 82.9% were female, 3.8% Hispanic/Latino, and 91.2% White. The mean ± SD age was 53.5 ± 8.5 years and disease duration was 16.4 ± 8.5 years after diagnosis. The most frequently held insurance types were health (96.3%) and life (58.8%). Only 9.7% of respondents had long-term care insurance. Except for life insurance, most current policies were obtained after MS diagnosis. CONCLUSIONS: Individuals with MS might not prioritize the possible short- and long-term benefits of these types of insurance. Health care providers can direct patients to nonprofit agencies that educate about of these insurance types and emphasize that others with MS have obtained these insurance types after their diagnosis.

Impact of natalizumab on quality of life in a real-world cohort of patients with multiple sclerosis: Results from MS PATHS.

BACKGROUND: Optimizing multiple sclerosis treatment warrants understanding of changes in physical, mental, and social health. OBJECTIVE: To assess the impact of natalizumab on Quality of Life in Neurological Disorders (Neuro-QoL) scores. METHODS: Annualized change in T-scores and likelihood of ≥5-point improvement over baseline were calculated for each Neuro-QoL domain after natalizumab initiation. Comparisons with ocrelizumab-treated patients were conducted after propensity score weighting and adjustment for relevant co-medications, year, and drug-year interaction. RESULTS: Among 164 natalizumab patients analyzed, 8 of 12 Neuro-QoL domains improved significantly, with greater improvement in patients with abnormal baseline Neuro-QoL. In the subgroup comparison of natalizumab-treated (n = 145) and ocrelizumab-treated (n = 520) patients, significant improvement occurred in 9 of 12 and 4 of 12 domains, respectively. The difference between groups was statistically significant for positive affect and well-being (p = 0.02), sleep (p = 0.003), and satisfaction with social roles and activities (SRA) (p = 0.03) in the overall population and for emotional and behavioral dyscontrol (p = 0.01), participation in SRA (p = 0.0001), and satisfaction with SRA (p = 0.02) in patients with abnormal baseline Neuro-QoL. CONCLUSIONS: Natalizumab can produce clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias, as their magnitude exceeded improvements with another high-efficacy therapy, ocrelizumab.

Quality of life in multiple sclerosis: determinants, measurement, and use in clinical practice.

Multiple sclerosis (MS) is a complex demyelinating disease with a relatively unpredictable course. It is well established that MS has a significant impact on health-related quality of life (HRQL) for individuals at all stages of the disease. It is argued that clinicians offer treatment to their patients for three reasons: 1) to increase longevity, 2) to prevent future morbidity, and 3) to make patients feel better. To assess how well they are accomplishing the third of these goals, clinicians have come to depend on the direct measurement of patients' HRQL. We review the many physical and emotional symptoms and other consequences of MS that negatively influence HRQL, how HRQL is measured, the unique information these measures provide compared with clinical parameters, the benefit of treatment interventions, and how to include HRQL assessment and data from other sources in clinical encounters and suggest measures to consider for clinical use.