Multiple Sclerosis Clinical Care Research Articles

Association of Anxiety with Uncinate Fasciculus Lesion Burden in Multiple Sclerosis.

Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects 2.4 million people world-wide, and up to 60% experience anxiety. We investigated how anxiety in MS is associated with white matter lesion burden in the uncinate fasciculus (UF). Retrospective case-control study of participants who received research-quality 3-tesla (3T) neuroimaging as part of MS clinical care from 2010-2018. Analyses were performed from June 1 st to September 30 th , 2024. Single-center academic medical specialty MS clinic. Participants were identified from the electronic medical record. All participants were diagnosed by an MS specialist and completed research-quality MRI at 3T. After excluding participants with poor image quality, 372 were stratified into three groups which were balanced for age and sex: 1) MS without anxiety (MS+noA, n=99); 2) MS with mild anxiety (MS+mildA, n=249); and 3) MS with severe anxiety (MS+severeA, n=24). Anxiety diagnosis and anxiolytic medication. We first evaluated whether MS+severeA patients had greater lesion burden in the UF than MS+noA. Next, we examined whether increasing anxiety severity was associated with greater UF lesion burden. Generalized additive models were employed, with the burden of lesions (e.g. proportion of fascicle impacted) within the UF as the outcome measure and sex and spline of age as covariates. UF burden was higher in MS+severeA as compared to MS+noA (T=2.02, P=0.045, Cohen's f 2 =0.19). A dose-response effect was also found, where higher mean UF burden was associated with higher anxiety severity (T=2.08, P=0.038, Cohen's f 2 =0.10). We demonstrate that overall lesion burden in UF was associated with the presence and severity of anxiety in patients with MS. Future studies linking white matter lesion burden in UF with treatment prognosis are warranted. Question: Are white matter lesions that impact the uncinate fasciculus (UF) associated with anxiety in patients with multiple sclerosis (MS)?Findings: This retrospective, case-control study of 372 patients with MS included 3 anxiety severity groups: 1) MS without anxiety (MS+noA, n=99); 2) MS with mild anxiety (MS+mildA, n=249); and 3) MS with severe anxiety (MS+severeA, n=24). We identified associations between anxiety and UF lesion burden. Specifically, we showed that MS+severeA had higher UF lesion burden than MS+noA, and worsening anxiety severity increased with greater UF burden.Meaning: Lesion burden in the UF may contribute to anxiety comorbidity in MS.

Use of smartphone-based remote assessments of multiple sclerosis in Floodlight Open, a global, prospective, open-access study

Floodlight Open was a global, open-access, digital-only study designed to understand the drivers and barriers in deployment and use of a smartphone app in a naturalistic setting and broad study population of people with and without multiple sclerosis (MS). The study utilised the Floodlight Open app: a ‘bring-your-own-device’ solution that remotely measures a user’s mood, cognition, hand motor function, and gait and postural stability via smartphone sensor-based tests requiring active user input (‘active tests’). Levels of mobility of study participants (‘life-space measurement’) were passively measured. Study data from these tests were made available via an open-access platform. Data from 1350 participants with self-declared MS and 1133 participants with self-declared non-MS from 17 countries across four continents were included in this report. Overall, MS participants provided active test data for a mean duration of 5.6 weeks or a mean duration of 19 non-consecutive days. This duration increased among MS participants who persisted beyond the first week to a mean of 10.3 weeks or 36.5 non-consecutive days. Passively collected life-space measurement data were generated by MS participants for a mean duration of 9.8 weeks or 50.6 non-consecutive days. This duration increased to 16.3 weeks/85.1 non-consecutive days among MS participants who persisted beyond the first week. Older age, self-declared MS disease status, and clinical supervision as part of concomitant clinical research were all significantly associated with higher persistence of the use of the Floodlight Open app. MS participants performed significantly worse than non-MS participants on four out of seven active tests. The findings from this multinational study inform future research to improve the dynamics of persistence of use of digital monitoring tools and further highlight challenges and opportunities in applying them to support MS clinical care.

Emerging imaging and liquid biomarkers in multiple sclerosis.

The advent of highly effective disease modifying therapy has transformed the landscape of multiple sclerosis (MS) care over the last two decades. However, there remains a critical, unmet need for sensitive and specific biomarkers to aid in diagnosis, prognosis, treatment monitoring, and the development of new interventions, particularly for people with progressive disease. This review evaluates the current data for several emerging imaging and liquid biomarkers in people with MS. MRI findings such as the central vein sign and paramagnetic rim lesions may improve MS diagnostic accuracy and evaluation of therapy efficacy in progressive disease. Serum and cerebrospinal fluid levels of several neuroglial proteins, such as neurofilament light chain and glial fibrillary acidic protein, show potential to be sensitive biomarkers of pathologic processes such as neuro-axonal injury or glial-inflammation. Additional promising biomarkers, including optical coherence tomography, cytokines and chemokines, microRNAs, and extracellular vesicles/exosomes, are also reviewed, among others. Beyond their potential integration into MS clinical care and interventional trials, several of these biomarkers may be informative of MS pathogenesis and help elucidate novel targets for treatment strategies.

Diagnosis of Multiple Sclerosis.

The diagnosis of multiple sclerosis (MS) can be made based on clinical symptoms and signs alone or a combination of clinical and paraclinical features. Diagnostic criteria for MS have evolved over time, and the latest version facilitates earlier diagnosis of MS in those presenting with typical clinical syndromes. This article summarizes the current diagnostic criteria for MS, typical and atypical presentations of MS, and when diagnostic criteria should be applied with caution. The most recent version of the MS diagnostic criteria has the benefits of simplicity and greater sensitivity in comparison to previous iterations. However, misdiagnosis remains a significant issue in MS clinical care, even at MS specialty centers. It is, therefore, evident that careful clinical application of the current version of the diagnostic criteria is necessary and that tools improving the diagnostic accuracy of MS would be of substantial clinical utility. Emerging diagnostic biomarkers that may be useful in this regard, including the central vein sign, paramagnetic rim lesions, and fluid biomarkers, are discussed. Current MS diagnostic criteria facilitate the early diagnosis of MS in people presenting with typical clinical syndromes but should be used cautiously in those presenting with atypical syndromes and in special populations. Clinical judgment and existing paraclinical tools, including sequential MRIs of the neuraxis and laboratory tests, are useful in minimizing misdiagnosis and facilitating the accurate diagnosis of MS. Diagnostic biomarkers that may facilitate or refute a diagnosis of MS in these settings, and emerging imaging and fluid biomarkers may eventually become available for use in clinical settings.

Impact of an anti-infective screening and monitoring protocol together with infectious disease consultation in preventing infective adverse events in patients treated with anti-CD20/CD52 agents for multiple sclerosis

BackgroundMonoclonal antibodies have been a milestone in the treatment of multiple sclerosis (MS). Infective complications have been observed in patients on agents targeting lymphoid cells’ surface antigens, namely anti-CD52 (alemtuzumab) and anti-CD20 agents (ocrelizumab and rituximab). Despite increasing emerging data, there is no standardized consensus regarding pre-treatment testing, vaccinations, and patient education before and during MS therapy or optimal infection-control strategies. MethodsWe led a retrospective/prospective real-life study to evaluate the effectiveness of a program of screening and prophylaxis for infective adverse events in patients with multiple sclerosis and related disorders treated with drugs directed against CD20/52 antigens. All patients referring to the MS Clinical Care and Research Center, University of Naples “Federico II”, who started on alemtuzumab, ocrelizumab or rituximab (off-label use) from 1 November 2015 to 30 June 2019 were recruited. From the 1st of February 2018 patients underwent a microbiological screening and were evaluated by an infectious disease specialist (IDs) before monoclonal antibodies infusion to rule out active infections. We evaluated incidence of infective complications and predictors before (retrospectively)and after (prospectively) the introduction of the above-mentioned anti-infective program. ResultsWe enrolled 275 patients, 104 retrospectively (pre-intervention group, PRE) and 171 prospectively (post-intervention group, POST). In PRE group, most patients were treated with alemtuzumab (58% vs 32%, p < 0.001), were more frequently DMT naïve (48% vs 36%, p = 0.044) or had received fingolimod in the past (48% vs 28%, p = 0.044) and the follow-up period was longer than in POST group (750 vs 191 days, p < 0.001). In POST group, patients were older (median age 47 vs 42 years, p = 0.030) and mostly received OCR (54% vs 14%, p < 0.001). Lymphopenia at baseline was significantly more commonly observed in PRE arm (47% vs 8%, p < 0.001). A total of 39 patients (38%) in PRE arm and 42 patients (25% in POST) group experienced one or more infections (p = 0.022); severe infections were significantly more common in PRE patients (23% vs 14%, p = 0.022). Our anti-infective program was associated with a lower IAE incidence both at univariate and multivariate analysis (aHR of infective events in PRE group: 3.652 [CI: 9.03-94.19], p < 0.001). Moreover, DMT naïve patients significantly experienced fewer infective complications (aHR: 0.470, [CI: 1.02-2.55], p = 0.040). ConclusionsA risk mitigation program including infectious disease consultation and standardized screening and prophylactic protocols was effective in reducing infective adverse events in patients receiving anti CD20/CD52 agents for MS.

Interferon beta for the treatment of multiple sclerosis in the Campania Region of Italy: Merging the real-life to routinely collected healthcare data.

We aim to overcome limitations of previous clinical and population-based studies by merging a clinical registry to routinely-collected healthcare data, and to specifically describe differences in clinical outcomes, healthcare resource utilization and costs between interferon beta formulations for multiple sclerosis (MS). We included 850 patients with MS treated with interferon beta formulations, from 2015 to 2019, seen at the MS Clinical Care and Research Centre (Federico II University of Naples, Italy) and with linkage to routinely-collected healthcare data (prescription data, hospital admissions, outpatient services). We extracted and computed clinical outcomes (relapses, 6-month EDSS progression using a roving EDSS as reference), persistence (time spent on a specific interferon beta formulation), adherence (medication possession ratio (MPR)), healthcare resource utilization and costs (annualized hospitalization rate (AHR), costs for hospital admissions and DMTs). To evaluate differences between interferon beta formulations, we used linear regression (adherence), Poisson regression (AHR), mixed-effect regression (costs), and Cox-regression models (time varying variables); covariates were age, sex, treatment duration, baseline EDSS and adherence. Looking at clinical outcomes, rates of relapses and EDSS progression were lower than studies run on previous cohorts; there was no differences in relapse risk between interferon beta formulations. Risk of discontinuation was higher for Betaferon®/Extavia® (HR = 3.28; 95%CI = 2.11, 5.12; p<0.01). Adherence was lower for Betaferon®/Extavia® (Coeff = -0.05; 95%CI = -0.10, -0.01; p = 0.02), and Avonex® (Coeff = -0.06; 95%CI = -0.11, -0.02; p<0.01), when compared with Rebif® and Plegridy® (Coeff = 0.08; 95%CI = 0.01, 0.16; p = 0.02). AHR and costs for MS hospital admissions were higher for Betaferon®/Extavia® (IRR = 2.38; 95%CI = 1.01, 5.55; p = 0.04; Coeff = 14.95; 95%CI = 1.39, 28.51; p = 0.03). We have showed the feasibility of merging routinely-collected healthcare data to a clinical registry for future MS research, and have confirmed interferon beta formulations play an important role in the management of MS, with positive clinical outcomes. Differences between interferon beta formulations are mostly driven by adherence and healthcare resource utilization.

Cognitive assessment in multiple sclerosis clinical care: A qualitative evaluation of stakeholder perceptions and preferences

ABSTRACT There is a growing consensus that cognitive assessments should form part of routine clinical care in Multiple Sclerosis (MS). However, what remains unclear is which assessments are preferred by “stakeholders” (including people with MS, family members, charity volunteers, clinicians, and healthcare commissioners), in which contexts, and in which formats. Therefore, the aim of this study was to collect and synthesize stakeholders’ perceptions of the assessments that are acceptable and feasible for routine administration in the UK healthcare system. We interviewed 44 stakeholders and held one focus group (n = 5). We asked stakeholders about their experience with cognitive impairment and assessment and their views on how cognitive assessment could be implemented within routine clinical care. Using framework analysis, we summarized three themes: the current cognitive screening situation; the suitability of commonly used assessments; and feasibility aspects, including modality and location of testing. All participants acknowledged that cognitive impairment could have a significant impact on the quality of life, but that assessment and monitoring are not routinely performed in clinics. Barriers and enablers were described, and most participants reported that brief, routine screening with tests such as symbol substitution was acceptable. Electronic, self-administration of cognitive screening would be beneficial in minimizing clinic attendance and staff time.

Telehealth in Multiple Sclerosis Clinical Care and Research.

Purpose of ReviewThe COVID-19 pandemic has provided us with a unique opportunity to experiment with telehealth and evaluate its benefits and limitations. This review discusses the impact of telehealth on multiple sclerosis (MS) care and research in adults and children.Recent FindingsTelehealth visits for MS patients have been shown to reduce missed workdays and costs for patients. Brief telephone-based counseling may be associated with better adherence to disease-modifying therapy, although results of multiple home-based tele-rehabilitation for people with MS have been equivocal. Overall, patients and providers have reported high levels of satisfactions with telehealth. Several remote disability measures and numerous other technological tools have emerged for use in remote MS research and care. Major challenges of telehealth include limitations to performing a complete neurologic exam and disparities in access to telehealth amongst vulnerable populations with limited access to virtual platforms.SummaryFollowing the rapid expansion of telehealth during the pandemic, it is highly likely that we will continue to embrace the benefits of this valuable tool. Future directions for improving telehealth should include more evidence-based research on the diagnostic accuracy in neuroimmunology and reducing disparities in the access to telehealth.

Rapid transfer of knowledge for multiple sclerosis clinical care during COVID-19: ECHO MS

BackgroundHealthcare providers caring for people with multiple sclerosis (MS) have had significant concerns about the intersection of MS and COVID-19. As a result, there has been an urgency to understand and share information about how to best provide MS clinical care during COVID-19. The Project ECHO model is well-suited for this challenge, as it provides a uniquely efficient and effective approach to sharing information in real-time using real cases. We report on the translation of the Project ECHO model for the rapid sharing of knowledge among MS clinical providers during COVID-19. MethodsThe ECHO MS COVID-19 Response Clinic was a videoconference-based education and case consultation program offered to providers in the U.S. who care for individuals with MS. The Response Clinic was offered as four sessions, each delivered by three regional hubs. Data were collected on participation and the self-reported impact of the program. ResultsA total of 132 unique providers participated in the Response Clinic, which consisted of 11 didactic modules and 43 case consultations. Participant providers overwhelmingly indicated that the program improved their knowledge, attitude, and skills for providing healthcare for people with MS during the COVID-19 pandemic. DiscussionThe Project ECHO model was successfully adapted to serve the needs of the MS community during COVID-19, suggesting the program could be continued or could be expanded to other disease areas for a similar purpose. More research is needed to objectively measure the impact of the program on patient outcomes.

The impact of diagnostic criteria and treatments on the 20-year costs for treating relapsing-remitting multiple sclerosis

ObjectiveTo assess whether the introduction of the new diagnostic criteria and disease modifying therapies (DMTs) is associated with higher cost for treating multiple sclerosis (MS). MethodsThis is a regression-based quasi-experimental study employing interrupted time series analysis, including data from 2229 patients (age 42.1 ± 11.2 years; female 63.34%), with incident diagnosis of relapsing remitting MS (RRMS) and followed up from 1997 to 2017, extracted from the database of the MS Clinical Care and Research Centre of the Federico II University Hospital of Naples (Italy). Annual healthcare costs for DMT (e.g., prescription, staff involved in DMT administration) and management (e.g., neurological consultations, other consultations related to DMT safety, MRI, laboratory exams), were calculated and inflated to the most recent value. ResultsAnnual costs per patient for DMT prescription and management were not affected by the introduction of 2001 and 2005 criteria, but decreased by 0.4% after the introduction of 2011 criteria (PD= -0.4%; 95% C.I. -0.7%/-0.0%; p = 0.023). Annual costs per patient increased by 11.2% after the introduction of Natalizumab in 2007 (PD= 11.2%; 95% C.I.= 9.4%/13.0%; p <0.001), by 10.9% after the introduction of tablets in 2011 (Fingolimod, Teriflunomide and Dimethyl Fumarate) (PD= 10.9%; 95% C.I. 9.2%/12.7%; p<0.001), and by 10.7% after the introduction of Alemtuzumab in 2015 (PD= 10.7%; 95% C.I. 9.0%/12.4%; p< 0.001). DiscussionDMTs remain the main responsible for increased medical direct costs in MS, whilst improved diagnostic skills and subsequent patient profiling can at least in part mitigate costs for MS treatment and management.

Imaging Markers for Monitoring Disease Activity in Multiple Sclerosis.

Multiple sclerosis (MS) is an immune-mediated disease affecting the central nervous system (CNS). Magnetic resonance imaging (MRI) has long been recognized as an important tool in the diagnosis of MS. It is increasingly recognized that in addition to its role in diagnosis, MRI can play a key role as a noninvasive tool for prognostication, disease monitoring, assessment of treatment efficacy, and safety monitoring of disease-modifying therapies (DMTs). A confluence of factors, including increased availability of MRI, development of improved MRI techniques, and increased availability of DMTs have contributed to the expanding role of MRI in MS clinical care. As the clinical use of MRI in MS expands, it is important that MRI protocols amongst clinical centers are standardized. Here, we summarize recent evidence supporting the use of MRI in clinical practice, summarize various clinical guidelines and recommendations for the use of MRI in MS disease monitoring, and provide our recommendations for standardized MRI protocols.

Patients' perspectives on quality of mental health care for people with MS

ObjectiveThe objective was to obtain multiple sclerosis (MS) patients' report on their experience receiving mental health care. MethodsWe convened focus groups at four MS clinical care centers to identify the aspects of mental health care that were important to people with MS. All patients (n=54) had received mental health care in the past year. Data were analyzed by coding comments under specific themes. ResultsPatients wanted prompt intervention after diagnosis and ongoing screening for mental health problems; they prefer providers with knowledge about MS and experience working with people with MS; they appreciated being able to access mental health services that were on-site at their MS center and noted the benefit of inclusion of family members in treatment. ConclusionsMental health care should be provided promptly after diagnosis, with regular screening and interventions that include family members as indicated thereafter. Mental health providers should be familiar with MS, collaborate with neurologic care providers and provide services on-site at MS centers.