Associations of sNfL with clinico-radiological measures in a large MS population.

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice. METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay. RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with sNfL-E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease-modifying therapy was associated with lower odds of sNfL-E. MS participants with sNfL-E exhibited worse neurological function (patient-reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short-term rates of whole brain atrophy in sNfL-E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL-E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age-normative sNfL Z-scores as a continuous variable. INTERPRETATION: Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking.

The impact of cognitive rehabilitation on quality of life in multiple sclerosis: A pilot study.

BACKGROUND: Cognitive impairment in people with multiple sclerosis (pwMS) negatively impacts daily function and quality of life (QoL). Prior studies of cognitive rehabilitation in pwMS have shown limited benefit but many focused on cognitive function scores rather than QoL measures. Studies using QoL metrics primarily evaluated group cognitive rehabilitation, which may be less appropriate due to variable cognitive profiles in pwMS. This study assesses the impact of an individualized cognitive rehabilitation approach on QoL in MS. METHODS: We performed a retrospective chart review of NeuroQoL assessments done by pwMS (n = 12, mean age 47.9 ± 4.0 years, 75% female, 100% White, 75% RRMS) before and after participation in an individualized compensatory cognitive program. We used a comparison group of pwMS who were candidates for the program but did not participate (n = 9, mean age 48.9 ± 4.4 years, 88.9% female, 100% White, 66.7% RRMS). RESULTS: PwMS who participated in the rehabilitation program saw improvements in Sleep Disturbance (50.5 from 55.5, p = 0.005), Fatigue (52.5 from 57.0, p = 0.024), Anxiety (49.8 from 55.4, p = 0.011), and Cognitive Function (39.3 from 36.7, p = 0.049). CONCLUSIONS: Individualized compensatory cognitive rehabilitation appears effective for improving QoL measures in pwMS with cognitive complaints, supporting the need for further randomized controlled prospective analysis of this intervention.

Harnessing Real-World Data to Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS).

Background: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. Methods: MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care. Institutional participation required the following: active MS patient census of ≥500, at least one Siemens 3T magnetic resonance imaging scanner, and willingness to standardize patient assessments, share standardized data for research, and offer universal enrolment to capture a representative sample. The eligible participants have diagnosis of MS, including clinically isolated syndrome, and consent for sharing pseudonymized data for research. MS PATHS incorporates a self-administered patient assessment tool, the Multiple Sclerosis Performance Test, to collect a structured history, patient-reported outcomes, and quantitative testing of cognition, vision, dexterity, and walking speed. Brain magnetic resonance imaging is acquired using standardized acquisition sequences on Siemens 3T scanners. Quantitative measures of brain volume and lesion load are obtained. Using a separate consent, the patients contribute DNA, RNA, and serum for future research. The clinicians retain complete autonomy in using MS PATHS data in patient care. A shared governance model ensures transparent data and sample access for research. Results: As of August 5, 2019, MS PATHS enrolment included participants (n = 16,568) with broad ranges of disease subtypes, duration, and severity. Overall, 14,643 (88.4%) participants contributed data at one or more time points. The average patient contributed 15.6 person-months of follow-up (95% CI: 15.5-15.8); overall, 166,158 person-months of follow-up have been accumulated. Those with relapsing-remitting MS demonstrated more demographic heterogeneity than the participants in six randomized phase 3 MS treatment trials. Across sites, a significant variation was observed in the follow-up frequency and the patterns of disease-modifying therapy use. Conclusions: Through digital health technology, it is feasible to collect standardized, quantitative, and interpretable data from each patient in busy MS practices, facilitating the merger of research and patient care. This approach holds promise for data-driven clinical decisions and accelerated systematic learning.

Comparison of telemedicine versus in-person visits for persons with multiple sclerosis: A randomized crossover study of feasibility, cost, and satisfaction.

BACKGROUND: Telemedicine, the remote delivery of health care services, increases access to care for patients with mobility or geographic limitations. Virtual house calls (VHCs) are one type of telemedicine in which clinical visits are conducted remotely using an audio-visual connection with the patient at home. Use of VHCs is more established in other neurologic disorders but is only recently being formally evaluated in multiple sclerosis (MS). This randomized crossover study systematically assessed VHCs compared with in-clinic visits in persons with MS. METHODS: Recruitment occurred in a university based MS clinic. Each subject completed one VHC and one in-clinic follow-up visit. A 1:1 randomization determined whether the VHC or in-clinic follow-up visit occurred first. Baseline surveys included demographics and MS history; post-visit surveys elicited subject responses regarding each visit type to assess feasibility, satisfaction, and cost differences. Outcomes were compared using t-tests for continuous variables and Fisher's exact test for proportions. RESULTS: Thirty-six participants completed both study visits and both post-visit surveys. VHC feasibility was demonstrated by a lack of statistically significant difference in the number of completed VHCs as compared with in-clinic visits. VHCs provided both cost and time savings to participants. The majority of participants reported that they would recommend telemedicine visits to others (97.1%) and rated it easy to connect via telemedicine (94.3%). In qualitative comments, participants expressed appreciation for VHCs due to convenience and similarity to in-clinic visits. CONCLUSIONS: VHCs were found to be feasible, cost-effective, and appealing to persons with MS and physicians, supporting their utility as a care delivery method for MS.

Fingolimod.

Fingolimod is the first oral disease therapy approved for relapsing-remitting multiple sclerosis (MS). Patients can be switched directly from interferon-ß or glatiramer acetate to fingolimod without a washout period. Fingolimod's potent efficacy, oral route of administration, and generally good safety and tolerability make it appealing to patients and clinicians. However, several adverse effects have already been identified, overall experience with its use is limited compared to other agents, and its novel and complex mechanism of action make predicting adverse effects challenging. Fingolimod's place in the MS treatment algorithm is evolving. We anticipate that once centers have solved the logistical issues associated with fingolimod initiation and if the experience in clinical practice parallels the efficacy, safety, and tolerability demonstrated in the phase 3 trials, fingolimod's routine use will increase.