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Published Work

SymptoMScreen: A Tool for Rapid Assessment of Symptom Severity in MS Across Multiple Domains.

2016 Apr 14

Appl Neuropsychol Adult. 2017 Mar-Apr;24(2):183-189. doi: 10.1080/23279095.2015.1125905. Epub 2016 Apr 14.

The objective of this study was to describe SymptoMScreen, an in-house developed tool for rapid assessment of MS symptom severity in routine clinical practice, and to validate SymptoMScreen against Performance Scales (PS). MS patients typically experience symptoms in many neurologic domains. A tool that would enable MS patients to efficiently relay their symptom severity across multiple domains to the healthcare providers could lead to improved symptom management. We developed "SymptoMScreen," a battery of 7-point Likert scales for 12 distinct domains commonly affected by MS: mobility, dexterity, body pain, sensation, bladder function, fatigue, vision, dizziness, cognition, depression, and anxiety. We administered SymptoMScreen and PS scales to consecutive MS patients at a specialty MS Care Center. We assessed the criterion and construct validity of SymptoMScreen by calculating Spearmen rank correlations between the SymptoMScreen composite score and PS composite score, and between SymptoMScreen subscale and the respective PS subscale scores, where applicable. A total of 410 patients with MS (age 46.6 ± 12.9 years; 74% female; mean disease duration 12.2 ± 8.7 years) completed the SymptoMScreen and PSs during their clinic visit. Composite SymptoMScreen score correlated strongly with combined PS score (r = 0.88, p < 0.0001). SymptoMScreen sub scores correlated strongly with the criterion measures of the respective PS (r = 0.69-0.87, p < 0.0001). Test-retest reliability of SymptoMScreen and its subscales was excellent (r = 0.71-0.94, p < .0001). SymptoMScreen is a single-page battery of Likert scales that assesses symptom impact in 12 domains commonly affected in MS. It has excellent criterion and construct validity. SymptoMScreen is patient and clinician friendly, takes approximately one minute to complete, and can help better document, understand, and manage patients' symptoms in routine clinical practice. SymptoMScreen is freely available to clinicians and researchers.

Which symptoms contribute the most to patients' perception of health in multiple sclerosis?

2017 Sep 5

Mult Scler J Exp Transl Clin. 2017 Sep 5;3(3):2055217317728301. doi: 10.1177/2055217317728301. eCollection 2017 Jul-Sep


Multiple sclerosis is a polysymptomatic disease. Little is known about relative contributions of the different multiple sclerosissymptoms to self-perception of health.


To investigate the relationship between symptom severity in 11 domains affected by multiple sclerosis and self-rated health.


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.


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).


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.


Multiple sclerosis; disability; self-rated health; self-report; symptom

Body mass index correlates with multiple sclerosis disease and symptom severity in women, but not in men

Jan 2017

Objective: To assess correlations between Body Mass Index (BMI) and Patient-derived Multiple Sclerosis Severity Score (P-MSSS), and BMI and SymptoMScreen scores in men and women with Multiple Sclerosis (MS). Background: Higher BMI during adolescence and young adulthood is a risk factor for MS, but data is conflicting concerning the relationship between BMI and disease severity in MS. Methods: BMI, Patient Determined Disease Steps (PDDS), and SymptoMScreen were recorded in consecutive clinic MS patients at the NYU MS Care Center (New York, NY) and Barnabas MS Care Center (Livingston, NJ) who were relapse-free for ≥3 months. P-MSSS was calculated based on PDDS and disease duration using a published reference table. Pearson correlation coefficients between P-MSSS and BMI, as well as between SymptoMScreen scores and BMI, were calculated independently for men and women. Separate logistic regression analyses were performed to evaluate the effect of age, sex, site of care and BMI on P-MSSS and symptom severity in 11 distinct domains. Results: 1,024 patients (74.9% women) with clinician-confirmed MS were included in the study. Men and women were similar with respect to age, BMI and disease severity scores, but men had slightly shorter disease duration than women. BMI showed a positive correlation with disease severity (P-MSSS) among women (r=0.106, p=0.0043), but not among men (r= -0.037, p=0.585). In a multiple regression model accounting for BMI, age, site of care and sex, BMI and age were the only significant predictors of disease severity (p<0.01). BMI and age were also the only significant predictors (p<0.01) of symptom severity in the domains of mobility, bodily pain, sensation, vision, depression, and anxiety. Conclusions: In this cross-sectional study, BMI showed a modest correlation with MS severity and symptom burden in women. In men, only anxiety score correlated with BMI. Further study is required to determine why BMI has a sexually dimorphic effect on disease and symptom severity

Validation of the SymptoMScreen with performance-based or clinician-assessed outcomes.

Apr 2019

Mult Scler Relat Disord. 2019 Jan 24;29:86-93. doi: 10.1016/j.msard.2019.01.031. [Epub ahead of print]

BACKGROUND: People with multiple sclerosis (MS) experience symptoms in multiple domains. High-quality patient-reported outcomes(PROs) that assess multiple domains can aid healthcare providers in assessing these symptoms and may support remote disease monitoring. The "SymptoMScreen" PRO correlates with other PROs in MS; however, whether the SymptoMScreen or its component domains are associated with performance-based or clinician-assessed outcomes is unknown.

OBJECTIVES: To validate SymptoMScreen and its domains against performance-based, clinician-assessed measures or other well-validated diagnostic tools.

METHODS: We recruited participants with MS from a large tertiary care center. At routine clinic visits participants completed the MS performance test (MSPT), which is an iPad-based application that objectively assesses walking speed, manual dexterity, processing speed, and low contrast letter acuity. Expanded Disability Status Scale (EDSS) scores were assessed in a subset. Participants also completed an online SymptoMScreen following clinic visits. We assessed criterion and construct validity by calculating Spearman rank correlations between the 12 SymptoMScreen domains and respective clinical outcomes. We evaluated test-retest reliability using intra-class correlation coefficients [ICC], and internal consistency reliability using Cronbach's alpha.

RESULTS: The 102 participants were predominantly female (78%), of average age [standard deviation]: 47.6 [12.3] years, with an average disease duration: 13.1 [10.0] years); 60 participants completed the SymptoMScreen and EDSS. Composite SymptoMScreen scores were associated with EDSS (r = 0.71; 95% CI 0.54, 0.83). For individual domains, strong correlations were observed between mobility scores and walking speed (r = 0.63; 95% CI: 0.48, 0.75) and hand function scores with manual dexterity (r = 0.52; 95% CI: 0.36, 0.65). More moderate correlations were detected for the cognition domain with processing speed (r=-0.37; 95% CI: -0.53, -0.18) and for the visual function domain with low contrast letter acuity at 2.5% contrast (r=-0.33; 95% CI -0.54, -0.08). Both test-retest and internal consistency reliability measures for overall SymptoMScreen scores were high (ICC: 0.88; 95% CI: 0.80, 0.93; Cronbach's alpha: 0.93; 95% CI: 0.90, 96).

CONCLUSIONS: The SymptoMScreen is practical outcome measure whose subscales may provide a valid assessment of corresponding performance-based and clinician-assessed measures among people with MS with mild-to-moderate disability.


A longitudinal study of symptom botheration in Multiple Sclerosis.

Nov 2020

Background: It is well documented that ambulatory disability in MS worsens over time, but there is a dearth of information on symptom evolution in other domains commonly affected by MS.

Methods: SymptoMScreen (SyMS) is a validated tool for assessing symptom severity in 12 domains commonly affected by MS. Patients who attended two specialized MS centers filled out SyMS at each visit. We included in the study patients with neurologist-diagnosed MS who completed two SyMS questionnaires separated at least 12 months. We used the first and final assessment and adjusted for time on study, baseline SyMS score, age, sex, race, MS type, disability strata, and site. Changes over time were also examined using Markov chain estimates of moving from one level of botheration to another for each domain over 1-year periods.

Results: A total of 1,014 MS patients met the inclusion criteria. Mean composite SyMS score was 1.4 (±1.16) at baseline and increased by 0.084 (±0.73) points during 21.0 (±5.5) months of followup (p<0.0001). The initial mean composite SyMS score correlated strongly with the final mean composite SyMS score (r=0.81). Individual domain SyMS scores at baseline were highest for fatigue: 2.2 (±1.7), and lowest for vision: 1.1 (±1.3) and dexterity: 1.1 (±1.4). Small but significant increases during followup were seen in dexterity, bladder, vision, and pain domains, while significant decreases were seen in anxiety and sensory domains. We observed a high degree of inter-individual variability in symptom severity with the more extreme scores tending to resolve over time.

Conclusions: Symptom botheration increases modestly year-to-year, as would be expected in a slowly progressive disease that evolves over decades. Initial symptom burden strongly correlated with final symptom burden, but there was a high degree of individual variability in symptom severity.

Comparing the MSIS-29 and the Health Utilities Index Mark III in Multiple Sclerosis

Dec 2021

Front. Neurol., 17 December 2021 Sec. Multiple Sclerosis and Neuroimmunology. |

Objective: Since the properties of health-related quality of life measures vary across samples, studies directly comparing the properties of different measures can be useful in understanding their relative strengths and limitations. We aimed to compare the psychometric properties of the Health Utilities Index Mark III (HUI3) and the Multiple Sclerosis Impact Scale-29 (MSIS-29).

Methods: In Spring 2020, North American Research Committee on Multiple Sclerosis (NARCOMS) Registry participants completed the HUI3, MSIS-29, Patient Determined Disease Steps (PDDS) and SymptoMScreen. For the HUI3 and MSIS-29 we assessed floor and ceiling effects, construct validity, and internal consistency reliability. We used relative efficiency to compare the discriminating ability of the two measures with respect to disability.

Results: We included 5,664 participants in the analysis, with mean (SD) age 63 (10.1) years; 4,579 (80.8%) were women. For the HUI3 the mean (SD) score was 0.44 (0.32), for the MSIS-29 physical it was 34.0 (24.2) and for the MSIS-29 psychological it was 25.9 (20.4). Neither of the measures had floor or ceiling effects, and internal consistency reliability was > 0.70 for both. The HUI3 and MSIS-29 physical were strongly correlated (r = −0.78; 95%CI:−0.79,−0.77). The correlation between the HUI3 and MSIS-29 psychological was weaker but remained moderately strong (r = −0.64; 95%CI:−0.66,−0.63). After adjusting for sociodemographic and clinical factors, relative efficiency to discriminate between disability (PDDS) groups was highest for the MSIS-29 physical scale, followed by the HUI3.

Conclusion: Both measures had adequate validity and reliability. The MSIS-29 physical discriminated between disability groups better than the HUI3.

Measuring productivity loss in early relapsing-remitting multiple sclerosis

Feb 2022

Background: Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their autonomy and capacity to maintain employment.

Objective: The aim of this study was to assess the impact on work productivity in early-stage relapsing-remitting multiple sclerosis (RRMS).

Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0–5.5 were included. Absenteeism, presenteeism, and unpaid work loss due to RRMS were measured using the Valuation of Lost Productivity (VOLP) questionnaire. The EDSS, SymptoMScreen, 5-item Modified Fatigue Impact ScaleHospital Anxiety and Depression ScaleSymbol Digit Modalities Test, and Multiple Sclerosis Work Difficulties Questionnaire were used to gather information on disability, patients’ perception of symptom severity, fatigue, mood/anxiety, cognition, and problems in the workplace, respectively. Associations between the VOLP and clinical and work outcomes were analyzed using Spearman's rank correlations.

Results: A total of 189 patients were included. Mean age (SD) was 36.1 ± 9.4 years and 71.4% were female. Mean disease duration was 1.2 ± 0.8 years. Median EDSS score was 1.0 (IQR 0, 2.0). One hundred thirty patients (68.8%) were working for pay or self-employed. Fifty-three patients (40.8%) reported absence from work in the past 3 months with an average of 14.3 absent workdays. Their health problems resulted in the loss of 3.4% of their actual work time in the past 7 days. Thirty patients got help (11.8 h) with their unpaid work activities in the past 7 days. Absenteeism was significantly correlated with anxiety and depression (rho=0.298 and 0.291, p<0.001), fatigue (rho=0.214, p = 0.014), and symptom severity (rho=0.213, p = 0.015). Presenteeism was significantly correlated with fatigue (rho=0.375, p<0.001), symptom severity (rho=0.373, p<0.001), depression (rho=0.263, p = 0.008), and disability (rho=0.215, p = 0.031).

Conclusions: Productivity loss even in a RRMS population with short disease duration stresses the need for more efficient treatment control of disease activity from earlier stages.

Efficacy, safety and patient reported outcomes in patients with active relapsing multiple sclerosis treated with ocrelizumab: Final results from the PRO-MSACTIVE study

Aug 2022

Background: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has been approved in Europe for the treatment of adult patients with active relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), on the basis of previous phase III studies. However, limited data were available on ocrelizumab efficacy in RMS according to the Lublin definition of activity (clinical and/or imaging features) used in the current drug label. The PRO-MSACTIVE study was thus designed to provide additional data on ocrelizumab efficacy according to this definition, and also on safety and patient reported outcomes (PROs).

Methods: PRO-MSACTIVE is a national, multicenter, open-label, single-arm phase IV French study, conducted in patients with active RMS (relapsing-remitting multiple sclerosis, RRMS, or secondary progressive multiple sclerosis, SPMS). The primary endpoint, which was assessed at week (W) 48, was defined as the proportion of patients free of disease activity (defined by no relapses and no T1 gadolinium-enhancing nor new and/or enlarging T2 lesions using brain MRI). Disease activity, disability and PROs using 6 questionnaires for disease severity, quality of life, impact on work productivity, and treatment satisfaction were described at W24 and W48. Adverse events were described until W72.

Results: Among the 422 analyzed patients (RRMS: 376, SPMS: 46), 63.3% (95% CI [58.5%; 67.9%]) were free of disease activity at W48 (RRMS: 62.2% [57.1%; 67.2%], SPMS: 71.7% [56.5%; 84.0%]). A total of 358 patients (84.8%; RRMS: 84.6%, SPMS: 87.0%) were relapse-free up to W48, and the overall adjusted annualized relapse rate was 0.14 (RRMS: 0.15, SPMS: 0.09). Overall, 67.8% of patients (RRMS: 66.8%, SPMS: 76.1%) had no evidence of MRI activity (no T1 gadolinium-enhancing lesions [83.4%] and no new/enlarging T2 lesions [75.1%]); 58.5% of patients (RRMS: 57.7%, SPMS: 65.2%) achieved No Evidence of Disease Activity (NEDA: no relapses, no confirmed disability progression, and no MRI activity) at W48. All PRO scores were stable between the first dose of ocrelizumab and W48 and better outcomes were seen for patients having an EDSS score ≥4. Overall, 89.3% of patients reported adverse events, 62.3% adverse events assessed as related to ocrelizumab, and 8.5% serious adverse events. No serious infusion-related reactions, opportunistic infections, progressive multifocal leukoencephalopathy, nor deaths were reported. No new safety signal was identified.

Conclusion: These data confirm the efficacy of ocrelizumab in a pragmatic setting and its favorable benefit-risk profile in patients with RMS.

( identifier: NCT03589105; EudraCT identifier: 2018-000780-91).

SAkuraBONSAI: Protocol design of a novel, prospective study to explore clinical, imaging, and biomarker outcomes in patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorder receiving open-label satralizumab

Feb 2023

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD.

Objectives: SAkuraBONSAI will evaluate clinical disease activity measures, patient-reported outcomes (PROs), pharmacokinetics, and safety of satralizumab in AQP4-IgG+ NMOSD. Correlations between imaging markers (magnetic resonance imaging [MRI] and optical coherence tomography [OCT]) and blood and cerebrospinal fluid (CSF) biomarkers will be investigated.

Study design: SAkuraBONSAI is a prospective, open-label, multicenter, international, Phase 4 study that will enroll approximately 100 adults (18–74 years) with AQP4-IgG+ NMOSD. This study includes two patient cohorts: newly diagnosed, treatment-naïve patients (Cohort 1; n = 60); and inadequate responders to recent (<6 months) rituximab infusion (Cohort 2; n = 40). Satralizumab monotherapy (120 mg) will be administered subcutaneously at Weeks 0, 2, 4, and Q4W thereafter for a total of 92 weeks.

Endpoints: Disease activity related to relapses (proportion relapse-free, annualized relapse rate, time to relapse, and relapse severity), disability progression (Expanded Disability Status Scale), cognition (Symbol Digit Modalities Test), and ophthalmological changes (visual acuity; National Eye Institute Visual Function Questionnaire-25) will all be assessed. Peri-papillary retinal nerve fiber layer and ganglion cell complex thickness will be monitored using advanced OCT (retinal nerve fiber layer and ganglion cell plus inner plexiform layer thickness). Lesion activity and atrophy will be monitored by MRI. Pharmacokinetics, PROs, and blood and CSF mechanistic biomarkers will be assessed regularly. Safety outcomes include the incidence and severity of adverse events.

Conclusions: SAkuraBONSAI will incorporate comprehensive imaging, fluid biomarker, and clinical assessments in patients with AQP4-IgG+ NMOSD. SAkuraBONSAI will provide new insights into the mechanism of action of satralizumab in NMOSD, while offering the opportunity to identify clinically relevant neurological, immunological, and imaging markers.

Poster Presentations

Multi-dimensional assessment of symptom severity in matched NMO and MS patients


Patient-Reported SymptoMScreen Baseline Scores in Patients With Relapsing-Remitting Multiple Sclerosis Enrolled In Phase IIIb Studies of Ocrelizumab (ENSEMBLE and CASTING)


Longitudinal study of symptom botheration in Multiple Sclerosis


Tracking symptom impact in MS patients:

longitudinal study of SymptoMScreen scores in patients

attending two large tertiary MS centers


Novel Assessment of Real-World Effectiveness and Safety of Ocrelizumab for Treatment of Patients With Relapsing and Primary Progressive Multiple Sclerosis: Design of a Multicentre Non-Interventional Study (MuSicalE Study)


Construct Validity and Internal Consistency of Patient-Reported Symptomscreen in Phase IIIb Trials of Ocrelizumab in Relapsing Multiple Sclerosis (ENSEMBLE and CASTING)

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