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BackgroundIn chronic neurological diseases, especially in multiple sclerosis (MS), clinical assessment of motor dysfunction is crucial to monitor the disease in patients. Traditional scales are not sensitive enough to detect slight changes. Video recordings of patient performance are more accurate and increase the reliability of severity ratings. When these recordings are automated, quantitative disability assessments by machine learning algorithms can be created. Creation of these algorithms involves non–health care professionals, which is a challenge for maintaining data privacy. However, autoencoders can address this issue. ObjectiveThe aim of this proof-of-concept study was to test whether coded frame vectors of autoencoders contain relevant information for analyzing videos of the motor performance of patients with MS. MethodsIn this study, 20 pre-rated videos of patients performing the finger-to-nose test were recorded. An autoencoder created encoded frame vectors from the original videos and decoded the videos again. The original and decoded videos were shown to 10 neurologists at an academic MS center in Basel, Switzerland. The neurologists tested whether the 200 videos were human-readable after decoding and rated the severity grade of each original and decoded video according to the Neurostatus-Expanded Disability Status Scale definitions of limb ataxia. Furthermore, the neurologists tested whether ratings were equivalent between the original and decoded videos. ResultsIn total, 172 of 200 (86.0%) videos were of sufficient quality to be ratable. The intrarater agreement between the original and decoded videos was 0.317 (Cohen weighted kappa). The average difference in the ratings between the original and decoded videos was 0.26, in which the original videos were rated as more severe. The interrater agreement between the original videos was 0.459 and that between the decoded videos was 0.302. The agreement was higher when no deficits or very severe deficits were present. ConclusionsThe vast majority of videos (172/200, 86.0%) decoded by the autoencoder contained clinically relevant information and had fair intrarater agreement with the original videos. Autoencoders are a potential method for enabling the use of patient videos while preserving data privacy, especially when non–health-care professionals are involved.

BackgroundSensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. ObjectiveTo test the usability and acceptability of ASSESS MS with health professionals and patients with MS. MethodsA prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. ResultsAll health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. ConclusionsIn typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment.

BackgroundIn multiple sclerosis (MS) patients, symptoms of anxiety, depression, pain, and cognitive impairment are highly prevalent and contribute to lower wellbeing. As these physical and psychological symptoms of distress often stay unnoticed, regular screening could offer possibilities to identify and refer impaired patients to appropriate care. ObjectiveThe aim of our study was to pilot a new computer-based method in 43 MS patients to efficiently screen for a variety of psychological and physical symptoms of distress. MethodsData on feasibility and psychological and physical distress (anxiety, depression, fatigue, physical disability, cognitive functioning) were collected via a touch screen computer. Referral to psychosocial care and rehabilitation was retrospectively checked. ResultsThe results demonstrated that most patients (35/40, 88%) considered the screening meaningful and the system easily usable (37/40, 93%). Average completion time of the screening was below 8 minutes. Many patients (35/40, 88%) had elevated distress levels, of whom the majority was referred. ConclusionsThese findings imply that computer-based screening for MS-related distress incorporated in clinical care is feasible and aids to identify psychological or physical needs. A randomized controlled trial with follow-up should address whether this screening method could be more effective than routine care, and whether it can improve costs and efficiency of care.

Background: Literature on the intricate relationship between self-reported and objectively assessed cognitive functioning suggests a discrepancy between self-reported cognitive complaints (SCC) and actual test performance. Objectives: To investigate the interplay between patient-reported outcome measures (PROMs) and objective cognitive functioning using network analysis in people with multiple sclerosis (PwMS). Methods: We collected PROMs on anxiety, depression, fatigue and SCC, and cognitive functioning across six domains (n = 703 PwMS; 71% female, mean age = 46.3 ± 11.2 years). We constructed cognitive symptom networks using Gaussian Graphical Models, in which the aforementioned variables were presented as nodes linked by regularized partial correlations. We compared global network strength between relevant subgroups. Results: The networks primarily showed clustering of PROMs and cognitive domains into two separate modules, with weaker links connecting both modules. Global network strength was lower for PwMS with impaired information processing speed (IPS; indicating lower symptom interrelatedness) compared to those with preserved IPS (3.57 versus 4.51, p = 0.001), but not when comparing SCC subgroups (p = 0.140). Conclusions: Cognitive symptom networks deepen our understanding of the discrepancy between self-reported and objectively assessed cognitive functioning. Lower symptom interrelatedness in PwMS with impaired IPS might suggest a nonlinear relation between PROMs and cognitive domains, which depends on the cognitive status. [ABSTRACT FROM AUTHOR]

While relapsing-remitting multiple sclerosis (MS) has many therapeutic options, progressive forms of MS remain largely untreatable. Phase 2 clinical trials are our main tool to advance new treatments for progressive MS. Given the complexities of progressive MS, it will likely require many phase 2 trials to improve its treatment. To conduct informative and efficient phase 2 trials, it is important that such trials are designed in a way that they can identify a successful treatment as quickly and with as few participants as possible. In this topical review, we discuss cohort selection, outcome selection, cohort enrichment, and dosing selection as strategies to optimize the efficiency of phase 2 clinical trials in progressive MS. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to describe the intensity and patterns of antibiotic drug use among people with multiple sclerosis (pwMS) in the Netherlands. Methods: People with prevalent MS between 1 January 2018 and 31 December 2020 were identified using ambulatory hospital records from the PHARMO Database Network that contains routinely collected healthcare data from the Netherlands. Out‐patient pharmacy dispensing data were used to assess type of antibiotic, dosage, and amounts dispensed. Antibiotic intensity in defined daily doses (DDD)/1000 patient‐days (PD) was calculated together with frequency of dispensing of the same (prolongation) or different (switch) antibiotic up to 3 days after the end of the last antibiotic prescription; and stratified by sex, age, polypharmacy (use of > 4 out‐patient prescription drugs for > 29 days), type of disease‐modifying treatment, and Sars‐CoV‐2‐related lockdown. Results: A total of 1960 (37.8%) out of 5179 pwMS were dispensed ≥ 1 antibiotic. Of the 8762 dispensing events, 27.6%% were part of a prolongation, and 16.3% of a switch. Overall antibiotic use among pwMS was 18.8 DDD/1000 PD (95% confidence interval [95% CI]: 18.7–19.0) compared to 7.77–8.90 DDD/1000 PD in the general out‐patient population, as reported by the Dutch Working Party on Antibiotic Policy. Antibiotic use was higher among women, increased with age, and was higher in people with polypharmacy and lower during lockdown. Nitrofurantoin was the most commonly dispensed antibiotic (41.7%). Conclusions: The intensity of antibiotic use is considerably higher among pwMS than the general population. This reflects the burden of infection in this susceptible population. [ABSTRACT FROM AUTHOR]

Background and objectives: Serum neurofilament light (sNfL) is a biomarker for neuro-axonal damage in multiple sclerosis (MS). Clinical implementation remains limited. We investigated the impact of implementation on clinical decisions using questionnaires at the MS Center Amsterdam, a tertiary outpatient clinic. Methods: sNfL assessments were added to routine clinical practice (August 2021–December 2022). Before and after the results, clinicians filled in questionnaires on context of testing, clinical decisions, certainty herein, expectation of magnetic resonance imaging (MRI) activity, urgency, and motivation to receive the sNfL result and perceived value of sNfL. Results: sNfL was assessed in 166 cases (age 41 ± 12 years, 68% female, 64% disease-modifying therapy (DMT) use) for the following contexts: "DMT monitoring" (55%), "new symptoms" (18%), "differential diagnosis" (17%), and "DMT baseline" (11%). Clinical decisions changed in 19.3% of cases post-disclosure, particularly in context "new symptoms" (38%) and with higher sNfL levels (β = 0.03, p = 0.04). Certainty increased (p = 0.004), while expectation of MRI activity decreased with disclosure of low sNfL levels (p = 0.01). Motivation was highest in context "differential diagnosis" (p < 0.001); perceived value and urgency were highest in context "new symptoms" (p = 0.02). Conclusion: In this study, sNfL implementation had considerable impact on clinical decision-making and certainty herein. Standard implementation may complement patient care but warrants caution and more exploration in diverse clinical settings [ABSTRACT FROM AUTHOR]

BackgroundThere is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis.ObjectiveBuild a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course.MethodsSerially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)).Results and conclusionWe provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

ObjectiveTo investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial (n = 487; clinicaltrials.gov NCT00731692).MethodsMagnetic resonance imaging scans were collected annually. Brain volume loss was determined using SIENA. Patients were stratified by baseline normalized brain volume after adjusting for demographic and disease-burden covariates.ResultsBaseline normalized brain volume was predictive of disability worsening: Risk of 3-month confirmed disability progression was reduced by 36% for high versus low baseline normalized brain volume (Cox's model hazard ratio 0.64, P = 0.0339; log-rank test: P = 0.0297). Moreover, on-study brain volume loss was significantly associated with disability worsening (P = 0.012) and was evident in patients with or without new lesions or relapses. Brain volume loss depended significantly on baseline T2 lesion volume (P

Background: Cortical lesion subtypes' occurrence and distribution across networks may shed light on cognitive impairment (CI) in multiple sclerosis (MS). Methods: In 332 people with MS, lesions were classified as intracortical, leukocortical or juxtacortical based on artificially generated double inversion-recovery images. Results: CI-related leukocortical lesion count increases were greatest within sensorimotor and cognitive networks (p < 0.001). Only intracortical lesion count could distinguish between cognitive groups (p = 0.024). Effect sizes were two- to four-fold larger than differences between MS phenotypes. Conclusion: In CI-MS, leukocortical lesions predominate, whereas intracortical lesions distinguish cognitive groups. Lesions' grey matter (GM) involvement might be decisive for cognition in MS, surpassing overall disease burden. [ABSTRACT FROM AUTHOR]

Background: Higher age is associated with less inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS). It is unknown whether age itself or disease duration underlies this association. Objectives: This study investigated the effects of age, disease duration, and inflammatory disease activity in people with RRMS. Methods: Individual patient-level data from five large phase III randomized controlled trials (RCTs) was utilized to investigate the association of both age and disease duration with annualized relapse rate (ARR), contrast-enhancing lesions (CELs), and new T2 lesions on magnetic resonance imaging (MRI) at baseline and follow-up. Results: The data set included 5626 participants. Higher age was associated with lower ARRs, lower CEL number on MRI at baseline and follow-up, and lower new T2 lesion numbers at follow-up. This effect was present in all disease duration groups. For example, we found a lower number of new T2 lesions on MRI during follow-up in higher age groups compared to lower age groups, independent of disease duration. Conclusion: Aging in RRMS is associated with a lower risk of inflammatory disease activity, across different disease durations. Age should be taken into account when designing clinical trials and future research should investigate how age should be integrated into personalized predictions of treatment response and risk profiling. [ABSTRACT FROM AUTHOR]

BACKGROUND: Individuals with advanced multiple sclerosis (MS) have complex care requirements and are more likely to use long-term facilities. This study determined the associations between mood and social care--related quality of life (SCRQOL), and health-related quality of life (HRQOL) and examined the association between HRQOL and SCRQOL. METHODS: Baseline data from a cohort study were used. Patients completed questionnaires, including the Hospital Anxiety and Depression Scale (HADS), Adult Social Care Outcomes Toolkit (ASCOT), and EuroQOL 5D-5L (EQ-5D-5L) and EQ-Visual Analogue Scale (EQ-VAS). Linear regression analyses were employed to assess the relationships between mood and both outcomes of QOL while controlling for relevant confounding factors (βs; 95% CI). The cross-sectional association between SCRQOL and HRQOL was examined using Pearson correlation coefficients (r). RESULTS: A total of 75 patients, with a mean age of 56.1 years and a disease duration of 17.3 years, were enrolled from a long-term care facility in the Netherlands. Results showed that after controlling for confounders, HADS is an independent determinant of ASCOT (βs = -.368; 95% CI, -.581 to -.154) and EQ-5D-5L (βs = -.297; 95% CI, -.507 to -.087). Also, there are significant but weak correlations between ASCOT and EQ-5D-5L (r = 0.242; 95% CI, .015-.468), between ASCOT and EQ-VAS (r = 0.230; 95% CI, .003-.457) and between EQ-5D-5L and EQ-VAS (r = 0.227; 95% CI, .000-.454). CONCLUSIONS: Mood, especially the depression component, is an important determinant of both HRQOL and SCRQOL in advanced MS. Focusing on mood in health care and social care may contribute to the improvement of QOL in a broader sense. [ABSTRACT FROM AUTHOR]

The relationship between being overweight during early life and disease course in multiple sclerosis (MS) is unresolved. We investigated the association between being overweight or obese during early life (childhood and adolescence) and MS case status, age of first symptom onset and onset type in people with MS (pwMS) of the same birth year. We enrolled 363 PwMS and 125 healthy controls (HC) from Project Y, a Dutch population-based cross-sectional cohort study including all PwMS born in 1966 and age and sex-matched HC. The associations between weight during childhood and adolescence (non-overweight vs. overweight or obese) and MS, age at symptom onset and onset type (relapsing vs. progressive) were assessed using logistic and linear regressions. In addition, sex-separated associations were explored. Being overweight or obese during childhood (OR = 2.82, 95% CI 1.17–6.80) and adolescence (OR = 2.45, 95% CI 1.13–5.34) was associated with developing MS. Furthermore, being overweight or obese during adolescence was associated with a younger age of onset (β = −0.11, p = 0.041). Of all 47 patients with a primary progressive (PP) onset type, only one patient (2.1%) was overweight or obese during childhood, whereas 45 patients with a relapsing remitting (RR) onset (14.3%) were overweight or obese during childhood (PP vs. RR p = 0.017; PP vs. HC p = 0.676; RR vs. HC, p = 0.015). However, using logistic regression analysis we did not find evidence of a significant association. In a nationwide population-based birth year cohort, being overweight or obese during childhood or adolescence is associated with MS prevalence and an earlier age of onset, but does not seem to associate with the type of onset. [ABSTRACT FROM AUTHOR]