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Striving to Limit the Impact: Parenting an Adult Child Who Has Multiple Sclerosis—A Grounded Theory Study

Fatigue is a common and debilitating symptom of multiple sclerosis (MS). Prior work suggests that the prevalence of fatigue is higher in progressive MS (PMS) than relapsing MS (RRMS). No patient-reported outcomes of fatigue have been validated specifically for individuals with PMS, despite evidence that they characterize fatigue differently than individuals with RRMS. Therefore, the objective of this study was to characterize fatigue in both the RRMS and PMS subtypes and determine the convergent validity of the Fatigue Symptoms and Impacts Questionnaire (FSIQ) for individuals with PMS.

A nationwide survey yielded 806 (637 RRMS, 169 PMS) complete responses. The survey collected demographic information and self-reported disease severity, as well as measures of fatigue, health-related quality of life, and self-reported functioning.

People with PMS reported significantly more severe fatigue than those with RRMS (

 < .001). The FSIQ subdomains of physical, cognitive/emotional, and coping demonstrated moderate (

More severe fatigue in people with PMS as compared to those with RRMS underscores the importance of using validated tools to capture fatigue in persons with PMS. The FSIQ is a valid and freely available tool to capture the physical, mental, and emotional fatigue of individuals with PMS.

From the Neuroimaging and Neurorehabilitation Laboratory (JF, ZA-R, NF), Department of Health Care Sciences (NF), and Department of Neurology (NF), Wayne State University, Detroit, MI; Department of Physical Therapy, MGH Institute for Health Professions, Boston MA (PP). 

 Nora Fritz, PhD, PT, DPT, NCS, 259 Mack Avenue, #2324, Detroit MI 48201; 

We would like to thank the National Multiple Sclerosis Society for their assistance with survey distribution.

 Prudence Plummer, PhD, PT, BPhysio(Hons), has research funding from the National Multiple Sclerosis Society and has active contracts with Helius Medical Technologies, Inc, and the Shepherd Center. Nora Fritz, PhD, PT, DPT, NCS, has research funding from the National Institutes of Health, the National Multiple Sclerosis Society, and Teva Pharmaceutical Industries that is unrelated to the submitted work. Fritz serves as member at large for the Consortium of Multiple Sclerosis Centers and receives travel funds to support attendance at its annual meeting.

One of the most common symptoms in multiple sclerosis (MS) is fatigue, with up to 92% of individuals reporting fatigue

 that manifests as lack of energy, exhaustion, or worsening of MS symptoms and ultimately contributes to increasing disability.

 Fatigue is common in both the relapsing and progressive phenotypes of MS. Due to the higher prevalence of relapsing-remitting MS (RRMS), the majority of fatigue research has focused on this phenotype. However, it has been recently suggested that fatigue may be more prevalent in progressive forms of the disease (PMS).

 Currently, there are very few measures of fatigue for patients with PMS. A recent systematic review

 recommended the following fatigue measures for individuals with MS based on available psychometrics: Fatigue Impact Scale, Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), Neurological Fatigue Index-MS, and Unidimensional Fatigue Impact Scale. However, none of the studies included in the review exclusively examined the psychometrics in PMS; all had mixed samples with more individuals with relapsing than progressive phenotypes. Thus, the psychometric properties of the recommended and most widely used fatigue measurement scales for people with PMS are largely unknown.

Recent work has developed and examined psychometrics of a fatigue scale specifically for persons with RRMS, the Fatigue Symptoms and Impacts Questionnaire (FSIQ).

 FSIQ development included interviews with individuals with MS to determine fatigue-related symptoms and impacts and cognitive interviews with additional people with RRMS using a draft questionnaire. Next, content confirmation interviews with people with PMS were conducted, followed by item reduction, which resulted in 7 symptom items and 13 impact items. Critically, this comprehensive measure includes physical, mental, and emotional subscales, while many existing measures fail to capture all 3 domains. In a recent qualitative study, individuals with PMS identified physical and mental concepts of fatigue separately and characterized fatigue as occurring daily with negative impacts on quality of life.

 Concept mapping to existing patient-reported outcome measures supported the FSIQ as the most suitable exiting option for assessing fatigue in persons with PMS.

 The validity and minimal detectable change of this measure and its physical, mental, and emotional subscales in individuals with progressive disease are not known. Further, convergent validity of the FSIQ with other commonly used measures of fatigue (eg, FSS or MFIS) or with common clinical symptoms (ie, depression, anxiety) has not been established for individuals with either RRMS or PMS. Valid measures of fatigue for people with RRMS and people with PMS are critically needed to monitor change over time and with intervention.

Therefore, the objectives of this study were to characterize fatigue in both the RRMS and PMS subtypes and to determine the convergent validity of the FSIQ for people with PMS compared with those with RRMS. Furthermore, we examined the relations between fatigue and other self-reported symptoms (eg, depression, sleep, anxiety, pain, stress, physical activity, cognition, and quality of life) in people with RRMS and PMS.

All data were collected and managed using an online survey designed in Research Electronic Data Capture (REDCap). REDCap is a secure, Health Insurance Portability and Accountability Act–compliant, web-based software platform designed to support data capture for research studies hosted at Wayne State University

 and available via a link distributed through the National Multiple Sclerosis Society electronic newsletter. Participants anonymously responded to the survey and did not report identifying or personal health information. Participants were included if they endorsed a diagnosis of RRMS or PMS, were age 18 years or older, and were able to read and write in English. Participants were excluded if they were unable to complete or consent to the survey. All study procedures were approved by the Wayne State University Institutional Review Board. The survey collected demographic information and self-reported disease severity with the Patient-Determined Disease Steps (PDDS) scale, as well as measures of fatigue, health-related quality of life, and self-reported functioning.

Fatigue was assessed with a battery of self-report questionnaires; in all cases, higher scores indicate greater fatigue.

The FSIQ assesses fatigue-related symptoms, as well as fatigue-related impacts, in physical, cognitive, emotional, and coping domains. The FSIQ has established validity for RRMS.

The FSS is a 9-item scale measuring severity of physical fatigue and its impact on activity and lifestyle. The FSS has moderate test-retest reliability and excellent convergent validity with self-reported walking function on the MS Walking Scale-12 (MSWS-12).

The MFIS is a 21-item scale with physical, cognitive, and psychosocial subscores.

 The MFIS has excellent test-retest reliability

 and excellent concurrent validity with the FSS.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue-MS is an 8-question scale examining fatigue frequency and interference with physical functioning in people with MS.

 The PROMIS Fatigue-MS has excellent test-retest reliability in MS.

The Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue is an 8-item standardized measure of fatigue with established reliability in people with neurologic conditions.

The MS Quality of Life 54 (MSQOL-54) is a 54-item multidimensional health-related quality-of-life measure that combines generic items from the Short Form Health Survey and MS-specific items for scores in both physical and mental health dimensions, with higher scores indicating better quality of life. The MSQOL-54 has established reliability and validity in MS.

Self-reported functioning in domains other than fatigue and quality of life was assessed with valid and reliable measures including PROMIS Depression 8a

; PROMIS Pain Interference 4a and Pain Intensity 3a

; National Institutes of Health (NIH) Toolbox Item Bank – Perceived Stress

; Godin Leisure-Time Exercise Questionnaire

 T scores were used for analyses for all PROMIS and NIH measures. MSWS-12 scores were converted to a 0 to 100 scale.

Data analyses were performed using IBM SPSS Statistics version 28.0.1. Responses were screened for inclusion criteria and analyzed for total and individual MS subtypes. In all analyses, individuals who endorsed having primary progressive MS or secondary progressive MS were combined into a single PMS group. Mann-Whitney U tests were used to examine differences in fatigue among people with RRMS and PMS. Spearman correlation was used to assess the convergent validity of the FSIQ with other measures of fatigue in both RRMS and PMS phenotypes. Spearman correlation was also used to assess the divergent validity of the FSIQ with other measures of MS symptoms, including pain, mobility, mood, and quality of life. Correlation coefficients of less than 0.25 were interpreted as little or no relation, greater than or equal to 0.25 to less than or equal to 0.5 as a fair relation, greater than or equal to 0.5 to less than or equal to 0.75 as a moderate to good relation, and greater than or equal to 0.75 as a good to excellent relation.

 greater than or equal to 0.50 for reporting results.

Of the 1224 responses received, 806 (65.8%) participants consented and completed full demographic information. Of these, 637 (79.0%) self-reported as having RRMS, and 169 (21.0%) self-reported as having a progressive form of MS (109 [13.5%] secondary progressive MS; 60 [7.4%] primary progressive MS). A majority of participants were female (83%) and White (85.2%), with an average age of 50.5 years and a symptom duration of 3.6 years (

). Participants who reported PMS were, on average, older with a longer average symptom duration and reported an increased level of disability compared with those with RRMS (Table S1).

Comparing Fatigue Domains and Severity in RRMS and PMS Subtypes 

Compared to people with RRMS, people with progressive forms of MS reported significantly higher scores (ie, more severe fatigue) in all domains of the FSIQ except the cognitive domain (

). Participants with PMS reported significantly greater fatigue severity on the FSS (P < .001), and greater physical and psychosocial impacts of fatigue on the MFIS (P < .001). As observed with the cognitive domain of the FSIQ, there was no significant difference in cognitive fatigue on the MFIS between participants with RRMS and PMS. Additionally, participants with PMS self-reported increased symptoms of fatigue through the PROMIS fatigue scale (P < .001), and significantly greater impact of fatigue on quality of life in the Neuro-QOL fatigue scale (P < .001).

All subsections of the FSIQ demonstrated moderate to excellent convergent validity with the FSS, MFIS Physical, MFIS Cognitive, MFIS Psychosocial, MFIS Total, PROMIS Fatigue, and Neuro-QOL Fatigue in persons with RRMS (

There were significant correlations between the FSIQ Physical and all other measures for both RRMS and PMS (Table 1); however, all correlations were stronger for the RRMS cohort than the PMS cohort. Further, the FSIQ Physical had the weakest correlations with the MFIS Cognitive in both MS types. Together, these findings demonstrate good convergent validity of the FSIQ Physical as a measure of physical fatigue in people with PMS and suggest that there are modest to null associations between physical fatigue and cognitive fatigue in PMS.

The FSIQ Cognitive demonstrated strong and significant correlations with the MFIS Cognitive and good correlations with the MFIS Psychosocial in both RRMS and PMS. There were also good strength correlations between the FSIQ Cognitive with all other measures and the MFIS Physical for both MS phenotype groups (Table 1).

Among people with PMS, the FSIQ Coping demonstrated excellent correlation with the Neuro-QOL fatigue measure, the PROMIS fatigue measure, and the MFIS Total, and good strength correlations with all other measures (Table 1). The weakest association of the FSIQ Coping for people with PMS was with the MFIS Cognitive, but this was also the weakest for people with RRMS. Of note, the correlations for the FSIQ Coping tended to be higher than those for the FSIQ Physical for people with PMS, suggesting that the coping questions may be particularly relevant for assessing the impact of fatigue in PMS (and RRMS). Again, the strength of associations was stronger for the RRMS cohort than the PMS, which may be due to differences in sample size. Nonetheless, all associations were acceptable to excellent for demonstrating convergent validity in PMS.

Finally, the FSIQ Daily also demonstrated good to excellent correlations in RRMS (Table 1) and moderate to good correlations among people with PMS.

The FSIQ Physical demonstrated a moderate to excellent correlation with health-related quality of life (MSQOL physical), self-reported physical functioning (PROMIS Physical), and self-reported walking function (MSWS-12) in individuals with RRMS and individuals with PMS. The fair relation with sleep and the moderate relation with cognition observed in RRMS were not found in the PMS cohort (

In the PMS group, the FSIQ Cognitive demonstrated a moderate correlation with the MSQOL physical and mental, as well as self-reported depression, cognition, anxiety, and pain, which was similar to the findings for the RRMS group (Table 2).

Finally, both the FSIQ Coping and FSIQ Daily demonstrated moderate correlations with the MSQOL physical and mental, as well as self-reported depression, anxiety, stress, cognition, and pain, which was similar to the findings for the RRMS group (Table 2).

Compared with people with RRMS, we found that people with PMS, on average and across all measures, reported more severe fatigue. Considering the different types of fatigue across all included measures, people with PMS reported more severe physical and psychosocial fatigue than people with RRMS. There were no differences between the RRMS and PMS groups in cognitive fatigue measured by either the FSIQ Cognitive/Emotional scale or the MFIS Cognitive scale. This may be because cognitive fatigue was relatively mild in both groups on both cognitive fatigue measures. Indeed, among the different fatigue domains, physical fatigue was the most severe, especially in people with PMS. It has been reported that fatigue is more prevalent in people with progressive forms of MS.

 Our findings suggest that it is not only more prevalent, but it is also more severe and predominantly driven by the subjective experience of physical fatigue. The current findings also suggest that it may be important to rate physical fatigue separately from other types of fatigue. In this regard, the FSIQ and the MFIS, which provide physical and cognitive subscores, may be optimal.

Overall, the FSIQ subdomains (physical fatigue, cognitive fatigue, and coping) demonstrated good to excellent convergent validity with other more established measures of self-reported fatigue in people with PMS (Neuro-QOL fatigue, PROMIS fatigue, MFIS total, FSS), as well as the respective physical and cognitive subdomains of the MFIS. The finding that the FSIQ Physical was least strongly related to cognitive fatigue on the MFIS Cognitive subscale provides further evidence that physical and cognitive/emotional dimensions of fatigue are discrete entities and may need to be measured separately (in both RRMS and PMS). Indeed, when talking spontaneously about fatigue, people with PMS characterize physical and mental aspects of fatigue separately.

 Thus, instruments that help clinicians differentiate whether perceptions of fatigue and fatigability are associated with physical and/or cognitive/emotional impacts, such as the FSIQ and MFIS, may have greater clinical value over other fatigue measures that generate a single overall fatigue score. The current data provide new evidence that the FSIQ has good to excellent validity in people with PMS.

The FSIQ Coping Impacts subdomain had the strongest convergent validity for people with PMS compared with the other FSIQ subdomains. The exception was that the FSIQ Coping score demonstrated weaker correlations with MFIS Cognitive scores than with the FSIQ Cognitive scores. The high convergent validity of the FSIQ Coping Impacts also suggests that this subdomain may be particularly relevant to evaluating self-reported fatigue in people with PMS. The FSIQ Coping section includes questions that ask about both difficulty (motivation to perform routine daily activities, taking part in social activities) as well as frequency of needing to take a nap, take a break, and rearrange plans. Two of the 5 items of the FSIQ Coping subdomain are also included in the FSIQ Physical fatigue score, which may explain their similarly strong correlations with other existing fatigue measures. However, 4 of 5 items on the FSIQ Physical Activity rate difficulty rather than frequency. It may be the combination of both symptom frequency and its associated difficulty that makes the FSIQ Coping particularly sensitive to detecting fatigue in people with PMS.

The strong relation between the FSIQ Physical and other physical symptom self-rating scales (MSQOL Physical, PROMIS Physical, and MSWS-12) is consistent with prior research that physical fatigue is associated with perceived limitations in physical performance.

 Based on the current data, this appears to be true for both RRMS and PMS. Interestingly, however, despite the perceived link between physical fatigue and physical function, meta-analyses of the effects of exercise interventions on fatigue indicate substantial heterogeneity.

 That is, improving physical function or exercise capacity does not consistently result in improved ratings of fatigue. Indeed, treatment of fatigue in MS remains a considerable challenge. This is most likely due to our limited understanding of fatigue mechanisms and because fatigue is a dynamic phenomenon that can vary greatly both among and within individuals.

 Evaluating fatigue on comprehensive instruments such as the FSIQ may be an important step in guiding person-centered interventions for fatigue.

Although sleep disturbance may appear as a cluster of symptoms that exacerbate fatigue,

 neither physical fatigue nor cognitive fatigue (FSIQ) had any association with sleep (PROMIS Sleep) in people with PMS and little to no relation in people with RRMS. The statistical significance of the weak relation between FSIQ Physical and FSIQ Cognitive scores and PROMIS Sleep in people with RRMS (r < 0.22) is likely due to the large RRMS group sample size and simply indicates that the weak relation has a high probability of being real (ie, very low probability of Type II error), though recent work suggests that subjective reports of sleep may not correlate with fatigue.

 It is possible that subjective reports of sleep disturbance do not adequately capture the relation between sleep and fatigue,

 necessitating the use of objective measures of sleep that better align with fatigue.

 Whereas FSIQ Cognitive/Emotional fatigue scores did not correlate with physical fatigue scores, they were associated with physical aspects of health-related quality of life, albeit only moderately for people with PMS. Cognitive fatigue was also associated with depression, lower mental health–related quality of life, and self-rated cognitive function. Fatigue arising from depression, anxiety, and pain may decrease the ability to cope with the disease and have an impact on daily living.

 Our findings suggest that subjective reports of cognitive function may be influenced by depression and fatigue, emphasizing the importance of cognitive, mood, and fatigue screening in routine clinical care.

The key strengths of this study were the large sample sizes for the 2 MS phenotypes, the use of multiple existing patient-reported outcomes, and the comparisons between people with PMS and RRMS. Our study had some limitations. Due to the survey nature of the study, we were not able to capture any functional measures of performance or objective measures of fatigability. The study also assessed fatigue at a single point in time, and it is well known that fatigue is a dynamic phenomenon that can vary dramatically both individually and among individuals on a daily basis.

 It is possible that some individuals were unaware of progressing from RRMS to secondary progressive MS, so future studies examining differences in fatigue between MS subtypes should consider confirming diagnosis prior to participation. Nevertheless, this study provides compelling evidence to support the validity and use of the FSIQ in people with PMS.

Mean fatigue ratings were higher in people with PMS than RRMS; furthermore, persons with PMS endorse both greater mental and physical fatigue. Measuring these subdomains of fatigue with a valid tool is critical for the development of targeted interventions and longitudinal monitoring. In the absence of a gold standard for subjective fatigue in people with MS, it is not possible to establish concurrent validity; however, the FSIQ is a valid and freely available tool with excellent convergent validity to capture the physical, mental, and emotional fatigue of people with PMS.

Characterizing Fatigue by Multiple Sclerosis Subtype and Determining Validity of a Fatigue Scale Specific to Persons With Progressive Multiple Sclerosis

Patient-generated data are a cornerstone of individualized multiple sclerosis (MS) treatment. MyMS, an interface for patient-reported outcomes (PROs) was developed by the Finnish MS Register to enable systematic collection of PROs.

MyMS collects data on demographics, lifestyle factors, disease-related factors, and validated questionnaires, including the Quality of Life Questionnaire (15D), the Multiple Sclerosis Impact Scale (MSIS-29), and the Fatigue Severity Scale (FSS). At the end of 2020, the patient-reported Expanded Disability Status Scale (PREDSS), the EuroQOL-5 Dimension (EQ-5D), the Fatigue Scale for Motor and Cognitive Functions (FSMC), and the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) were added.

As of January 1, 2023, 1201 individuals with MS (79% female) have added data to MyMS. Of the validated PRO measures (PROMs), the 15D, MSIS-29, and FSS are the most used. The mean PREDSS score is 3.0 and median disease duration is 6.4 years. According to the existing PROMs, patients report mildly compromised quality of life and problems with fatigue and cognition.

The patient interface of the Finnish MS Register consists of data from 17 of 21 counties with well-being services. The interface is used by 10% of Finnish individuals with MS. The addition of the PREDSS, EQ-5D, FSMC, and MSNQ to the interface has increased health care professional and patient interest in the use of PROMs. We suggest that PROs should be integrated into electronic health records to improve shared decision-making and diminish documentation burden.

From the Department of Psychology and Speech-Language Pathology (PH), Department of Mathematics and Statistics (MV), Division of Clinical Neurosciences (JR, MS-H), University of Turku, Turku, Finland; The Finnish Neuro Society, Masku, Finland (PH, JR); StellarQ Ltd, Turku, Finland (PH, MV); Department of Neurology, Tampere University Hospital, Tampere, Finland (HK); Department of Health and Social Management, University of Eastern Finland, Kuopio, Finland (HK); Turku University Hospital Neurocenter, Turku, Finland (JR, MS-H). 

 Päivi Hämäläinen, PhD, StellarQ Ltd, Eerikinkatu 3 A, 20100 Turku, Finland; 

paivi.hamalainen@neuroliitto.fi, paivi.hamalainen@stellarq.com.

The authors gratefully acknowledge the contribution of the StellarQ IT team that built and continuously refines the Finnish MS Register platform. All members of the steering committee of the Finnish MS registry as well as patients who have participated in the development of MyMS are gratefully acknowledged.

 The study was financially supported by Janssen-Cilag Oy. The funder had no role in or influence on any aspect of the study, including data collection, data analysis, writing of the manuscript, and decision to publish. Preparation of this manuscript was funded in part by the Strategic Research Council within the Academy of Finland (funding No. 358415). Efforts to increase the use of the Finnish MS registry have received funding from Biogen Idec, Merck, Novartis, Sanofi Genzyme, Roche, Teva, and Business Finland.

 Päivi Hämäläinen and Matias Viitala are employees of StellarQ Ltd. The other authors of this manuscript do not declare any conflicts of interest related to this study.

High-quality patient registers are needed to improve the monitoring and treatment of progressive diseases such as multiple sclerosis (MS). MS registers are in use in many European countries,

 and the need to further develop register-based data collection is recognized worldwide.

 Registers allow individualized follow-up by providing systematic data on disease history, real-world data on the natural history of the disease, as well as data on treatment effectiveness, tolerability, and safety.

 They may also be used to predict an individual’s risk of conversion to secondary progressive multiple sclerosis (SPMS).

 Optimally, registers combine patient-reported data with data contributed by health care professionals (HCPs).

Along with the development of clinician-based registers, there is a growing need to implement patient engagement options, combining objective disease data with subjective patient-reported outcomes (PROs). This would promote patient autonomy, shared decision-making, and cost-effective individualized care.

 A PRO is any report of the status of an individual’s condition that comes directly from the individual, without interpretation by anyone, such as a clinician. PRO measures (PROMs) are standardized tools such as surveys, scales, or single-item measures. It is important that HCPs and the treatment team know how individuals perceive their disease, quality of life (QOL), treatment effects, and adverse events, and that means measuring outcomes that matter most to people with MS.

 Systematic collection, storage, and use of PRO data are likely to improve disease management and help the treatment team and the patient determine the best treatment options together.

Finland’s national MS register was launched in 2014

 to enable systematic disease monitoring as well as to monitor disease incidence, prevalence, and progression. A PRO interface was added in 2017 to enhance patient-centeredness and autonomy. Individuals are able to record data on medication usage, suspected relapses, lifestyle factors, and QOL, as well as keep track of disease severity, symptoms, and impact. The interface allows patients to follow their disease in a visual format and acts as a communication tool with the treatment team.

The objective of this study was to describe the contents and status of MyMS, the PRO interface of the Finnish national MS register. We illustrate the core variables and data collected by MyMS at the beginning of 2023. We also discuss future challenges, perspectives, and needs related to PRO-based data collection.

The Finnish MS Register is a browser-based register for public health care organizations.

 During the patient visit, it is the neurologist’s primary user interface, integrated into the hospital’s electronic patient record (EPR) system. HCPs log on to the MS register via the hospital’s EPR system with a single sign-on identifier, which automatically redirects them to the individual’s registry view. It is also possible for the structured patient narrative to automatically transfer to the neurology interleaf of the EPR, which avoids having to record patient information in 2 different systems. The PRO data in the patient interface are displayed directly on the clinician’s interface.

The use of the register is voluntary, and each county with well-being services decides whether to acquire it. The development of the register, the steering committee, and the core features of the clinician-based register are described elsewhere.

 As of January 2023, 17 of 21 of Finland’s counties with well-being services, which includes all 5 university hospitals, use the register, and most of them have integrated it into their EPR system. In January 2023, the number of patients in the register was 11,349, which was approximately 90% of individuals with MS in Finland. Register funding is based on licensing fees paid by the counties to the software service provider, StellarQ Ltd (stellarq.com).

The interface for PROs is available to all patients who have enrolled in the national MS register. MyMS is a secure log-in service with a user-friendly and graphically illustrative interface (

). It includes the following PROs: identification data (name, date of birth, sex), background data (heredity, education, employment), lifestyle factors (smoking, use of alcohol), suspected relapse notation, medications, comorbidities, and requests for assistance and rehabilitation, as well as standardized questionnaires on disease severity, impact, symptoms, disability, and QOL. The standardized PROMs include the patient-reported Expanded Disability Status Scale (PREDSS),

 the Quality of Life Questionnaire (15D),

 the Multiple Sclerosis Impact Scale-29 (MSIS-29),

 the Fatigue Scale for Motor and Cognitive Functions (FSMC),

 and the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ).

 In case of interruption, it is possible to complete a questionnaire within 24 hours. At the end of 2020, the PREDSS, the EQ-5D, the FSMC, and the MSNQ were added to the register; all the other measures were present from the launch of the interface. Approximately 10% of Finnish individuals with MS use MyMS.

Individuals with MS learn about MyMS mainly from MS nurses working in hospital MS clinics. The nurses are provided with written instructions on how to introduce the interface and the PROs, and written instructions are also available as handouts. The Finnish MS associations also tell their members about using MyMS to follow their disease and participate in their treatment.

National level patient-reported data were collected from the real-time pseudonymous database. Patients permit data utilization for study purposes, as long as data are reported in aggregated, anonymous form. This is ensured via a formal consent that is collected through MyMS when the patient begins to use the interface. Data extraction also includes date of MS diagnosis, which is mandatory clinical information to get access to the patient interface. StellarQ is the data processor for all data extracted.

Data extraction included patient-reported data from January 1, 2017, through December 31, 2022. Data counts and percentages of patients with data in MyMS as well as mean, standard deviation, median, and quartiles for the latest scores were calculated using nonmissing data. No imputation was needed. Date of first data entry in the patient interface was considered the index date to calculate age, disease duration, and user count progression. All data analyses were done using RStudio (version 2023.03.0).

A total of 11,349 MS patients (G35) and 692 patients with unspecified demyelinating disease of the central nervous system (G37.9) were registered with the Finnish MS Register as of January 2023. There are 4 well-being services counties that do not use the MS register (

; coded as 1, 7, 8, and 19). In 12 counties, MyMS is considered inactive (ie, coverage under 10%). There are 3 counties (3, 6, 14) with MyMS coverage exceeding 20%.

MyMS was used by 1201 patients in January 2023. The number of MyMS users has increased linearly since it was launched in 2017. The 

 shows the cumulative progression of MyMS users as well as the cumulative progression of filled documents from 2017 to the beginning of 2023.

Of the 1201 MyMS users, 79% are women, and there was a median disease duration of 6.4 years and 13.9 mean years of education based on self-report. 

 describes the MyMS variables, how many times the variable has been recorded in the register, and the percentage of patients who have the information included in their data file. The most actively reported PROs were lifestyle factors and background information. The PROMs that were included since the launch of the patient interface have been used the most; 74.6% of respondents with MS have filled out the 15D, 52% the MSIS-29, and 51% the FSS. The scales added in the register later have been filled out by individuals with MS as follows: the PREDSS by 39.4%, the FSMC by 35.0%, the EQ-5D by 31.6%, and the MSNQ by 18.1%.

The mean PREDSS score (n = 473) is 3.0, which means the average patient has no walking ability limitations, but has other significant MS-related problems that limit daily activities (

). The mean EQ-5D (n = 380) and 15D scores (n = 896) were both 0.8, indicating mildly compromised QOL.

 The mean MSIS-29 scores (n = 624) were between 26.2 and 28.5, which indicates few problems

 The mean FSS score (n = 613) was 4.2, equating to mild self-perceived fatigue.

 In contrast, the FSMC scores (n = 420) seemed to indicate severe overall fatigue (mean score 63.1) as well as moderate motor (means core 31.4) and cognitive fatigue (mean score 31.7).

 The mean MSNQ score (n = 217) was 35.3, which means that the patient perceives problems with cognitive functions.

Seven years after its launch, the Finnish MS Register covers the majority of Finnish MS patients. It is increasingly being adopted as a part of clinical practice following the national treatment guidelines,

 and efforts to achieve complete coverage are ongoing. PROMs, especially standardized and validated ones, are growing in importance because individualized patient-centered treatment is the gold standard of high-quality care.

 has highlighted the need to improve communication between patients and HCPs to promote patient participation and self-management, as well as to enable access to high-quality information.

There are several national MS registries in Europe that differ from each other with respect to objectives, structure, collected data, and patient and clinician involvement.

 The registries were established between 1956 (Denmark) and 2014 (Finland). In 2017, the number of patients in the registries varied from 1000 to approximately 50,000.

 Registries are typically kept by academic research institutions, patient organizations, or health care organizations.

 Based on a review published in 2014, physician-based outcome measures such as the Expanded Disability Status Scale (EDSS) were used in all 20 identified European registries, whereas data from patients’ perspectives were only collected in 6 registries.

 According to results of a more recent survey published in 2019, 7 of 19 identified MS registries include patient-derived measures.

 The MSIS-29 was used in all 7 registries, and 6 registries included PROMs on fatigue, 4 of those the FSS. The North American Research Committee on Multiple Sclerosis (NARCOMS) registry is one of the few patient-driven registries. In NARCOMS, patients fill out questionnaires online or by mail to a coordinating center.

 In contrast to the patient interface of the Finnish national MS registry, data collection in NARCOMS initially occurred only at enrollment, and longitudinal semiannual data collection began in 2020.

 electronic health technologies could play an increasing role in the systematic use of PRO data. The patient interface of the Finnish MS Register is a good example of an e-health solution that enables systematic collection of patient experience. Active use of the data in MyMS together with that in the clinician-based MS register is 1 way to improve shared decision-making. Systematic self-report is a way to empower patients to take responsibility for their disease and commit to treatment, rehabilitation, and beneficial lifestyle choices.

 When the patient uses MyMS, the treatment team can compare the clinician-rated EDSS

 score with the corresponding PROM and the PREDSS

 and then discuss any discrepancies with the patient. The PREDSS has shown high correlation with the clinician-rated EDSS.

 Moreover, the information on patient-perceived symptoms and impact of the disease is readily available to the team, as it is displayed on the clinician interface.

Because many MS-related symptoms are invisible and difficult to diagnose in their early phases, patient reports are critical. Based on a European registry sample of almost 14,000 individuals with MS, Kobelt and colleagues

 showed that self-reported fatigue and cognitive symptoms reduce working capacity. In MyMS, patients have the opportunity to fill out the MSNQ

 to evaluate and follow their cognitive symptoms, the FSS

 to evaluate fatigue severity, and the FSMC

 to evaluate the characteristics of their self-perceived fatigue. The clinician can combine the MSNQ with the results on the objective measure of information processing speed, the Symbol Digit Modalities Test,

 which is recorded in the clinician-based register. Thus, MyMS may help identify patients who need support to manage invisible symptoms such as fatigue and cognitive problems. At best, longitudinal and systematic patient reporting is a pathway to react to treatment urgencies without delay.

The present sample represents most of the counties in Finland with well-being services, although the coverage is uneven. Women are more active MyMS users than men. MyMS users reported mild disability as rated with the PREDSS (mean score 3.0). QOL was reported by both the 15D and the EQ-5D to be mildly compromised. The MSIS-29 showed mild physical and psychological disease impact. Contrary to the FSS showing mild self-perceived fatigue, the FSMC showed severe overall fatigue and moderate motor and cognitive fatigue.

 At the end of 2020, new validated instruments were implemented into MyMS mainly to help evaluate invisible symptoms, such as fatigue with the FSMC and cognitive problems with the MSNQ. It is possible that patients who filled out the measures added in 2020, the PREDSS,

 have more pronounced cognitive and fatigue concerns, which would explain why the FSMC shows more severe fatigue than the FSS. Further, the FSMC covers cognitive and physical aspects of fatigue equally, whereas the FSS focuses on physical aspects of fatigue. This may be another reason for the discrepancies in the results of the fatigue questionnaires.

Patients can use MyMS whenever they want. The interest in self-reporting is growing alongside the need for and interest in early intervention and shared decision-making, especially due to the increasing number of treatments. Patients increasingly look to PROMs to convey their lived experiences and multifaceted challenges. The lack of knowledge on the use of PROMs and difficulties utilizing PROM data in often fast-paced clinical decision-making may have previously hindered the use of patient reporting.

Efforts to improve user experience, including the development of a mobile application, are ongoing. By adding feedback and guidance on the validated questionnaires, MyMS could become a source of reliable information and a self-management tool. Implementation of patient-reported experience measures to evaluate treatment satisfaction is also a future milestone in the development of the patient interface.

As yet, there is no systematic national procedure to present MyMS to MS patients in neurology clinics. Some clinics do have a systematic approach, particularly in southwestern and eastern Finland, and these clinics also ask patients to update PROs, such as the PREDSS and QOL measures, annually to provide insights into long-term changes. This may have led to the higher use of MyMS in these areas, and there are efforts to spread these practices nationwide via education and educational materials.

Successful treatment of MS relies on evidence-based medicine. High-quality health information is built from the knowledge and experience of HCPs combined with data from the lived experience of patients. The Finnish MS Register with MyMS is a clinical and patient interface, a unique e-health platform for this kind of data collection, and this is the first paper to report on it. There are numerous opportunities to further develop the collection and utilization of patient-generated data to improve the quality of care and increase patient participation. As more individuals with MS use the platform, the generalizability of the results increases, and research questions regarding the self-perceived symptomatology, disability, usage experiences, and other factors that are crucial in shared decision-making can be more efficiently addressed.

MyMS: An Interface for Patient-Reported Outcomes for Finnish Individuals With Multiple Sclerosis

The multiple sclerosis (MS) diagnostic process can be lengthy and result in psychological distress and treatment delays. The 2024 revised McDonald diagnostic criteria incorporate the central vein sign (CVS) and paramagnetic rim lesions (PRL), radiological biomarkers that offer the potential to improve the diagnostic pathway.

The study aims were to: (1) investigate the experiences of people with MS and health care professionals (HCPs) regarding the current diagnostic process, and (2) identify the barriers and facilitators to implementing the revised diagnostic criteria. Semistructured individual interviews and focus groups were conducted with 10 HCPs and 9 people with MS. Framework analysis, applying normalization process theory, was employed.

Interviews revealed 4 themes: current challenges for the diagnostic pathway, CVS/PRL implementation barriers, the benefits of CVS/PRL implementation, and suggestions for overcoming implementation barriers and improving the diagnostic pathway . Challenges to implementation include pathway inefficiencies, care delivery inequality, insufficient communication, financial constraints, capacity limitations, and clinician hesitancy with the revised criteria. Suggested strategies for implementation and improvement included HCP training, enhancing interdisciplinary collaboration, evaluating implemented changes, and delivering emotional and practical support during diagnosis. Benefits for CVS/PRL implementation included reduced reliance on lumbar punctures, improved patient experience, cost-effectiveness, and enhanced diagnostic accuracy.

Despite patient enthusiasm, implementing the revised diagnostic criteria will be challenging and possibly delayed unless HCP concerns are appropriately addressed.

From the School of Medicine, University of Nottingham, Nottingham, United Kingdom (CG, CCSS, MC, LT, NE); Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom (CG, TP, NE); Nottingham Hospitals Charity, Nottingham, United Kingdom (TP); NIHR Nottingham Biomedical Research Centre, Nottingham, United Kingdom (BDP, LT); and the Centre for Rehabilitation and Ageing Research, School of Medicine, University of Nottingham, Nottingham, United Kingdom (BDP). 

Christopher Gilmartin, MB BChir, MRCP, Mental Health and Clinical Neurosciences Academic Unit, School of Medicine, University of Nottingham, UK, NG7 2UH; 

We would like to thank the individuals with MS and the health care professionals who gave their time to support this study. We are also grateful for the support of the National Institute for Health and Care Research (NIHR), European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the MS Society. Christopher Gilmartin, MB BChir, MRCP, is an NIHR Academic Clinical Fellow; Margareta Clarke, PhD, is a 2023 ECTRIMS Research Fellow; and Blanca de Dios Pérez, PhD, is a senior research fellow with grant support from the MS Society.

Nikos Evangelou, DPhil, has received research funding from the Patient-Centered Outcomes Research Institute and Roche and personal compensation for speaking, advisory board work, and travel from Biogen, Merck, and Novartis. No other authors report conflicts of interest related to this article.

This study was generously supported by a grant from Nottingham Hospitals Charity (FR-000002298/23GNS025). The authors had full control of the content and made all final decisions.

In the United Kingdom (UK), 150 people are diagnosed with multiple sclerosis (MS) every week.

 MS is a chronic inflammatory disease of the central nervous system, and timely diagnosis is critical to initiate immunosuppressive treatment and reduce long-term disability

; yet, on average, it takes 9 months from referral for people with MS to receive the diagnosis.

 These delays are not unique to the UK but represent an international challenge, partly due to the nonspecific nature of MS symptoms, exacerbated by lengthy diagnostic pathways.

 Prolonged waiting times have been highlighted as a significant contributor to patients’ emotional upheaval during the diagnostic process.

The revised McDonald diagnostic criteria endorse the application of novel MRI biomarkers in clinical practice,

 offering MS services the opportunity to restructure their diagnostic pathway. One of the most significant updates is the inclusion of the central vein sign (CVS), a highly specific feature of MS lesions, which is visible on susceptibility-based sequences.

 This sign reflects the characteristic perivenular distribution of MS lesions.

 For a scan to be considered CVS-positive, 6 lesions are required to have a central vein; if there are fewer than 10 white matter lesions present on MRI, more than half must have a central vein.

 Application of the CVS as a biomarker has consistently shown a specificity of 85% to 98% for MS.

 This high specificity has led to the inclusion of the CVS as a tool supporting the diagnosis of MS, in both those presenting with clinical symptoms typical of MS and those solely with incidental imaging findings. A rarer but highly specific marker, paramagnetic rim lesions (PRLs), are thought to represent a ring of iron-rich macrophages and microglia around chronic lesions.

PRLs have also been included in the revised criteria, albeit with a less prominent role.

Previously, uncertain MS diagnoses would lead to a lumbar puncture (LP). Avoiding an LP and instead receiving an MRI scan for CVS/PRL analysis is highly preferred by most patients.16 LPs have a reported complication rate ranging from 8% to 60%, including a debilitating low-pressure headache in 5% to 36% of those who undergo the procedure.

 People who receive an LP require day-case hospital admission, time off from work, and additional recovery time. This also translates to an increased burden on health care professionals (HCPs) and systems. Replacing LPs with MRI scans, including susceptibility-based sequences, may not only facilitate a faster diagnosis, but also improve the experience for people who are ultimately diagnosed with MS.

The inclusion of CVS/PRL in international guidelines will not necessarily equate to changing clinical practice; previous literature suggests evidence can take up to 17 years to become routine.

 Implementing the revised MS guidelines is likely to take a prolonged period. A study’s results showed that just over half of MS specialist neurologists were correctly able to identify periventricular and juxtacortical lesions, highlighting the scale of the challenge to implement new radiological markers into clinical practice.

To understand how CVS/PRL can be used in clinical practice to diagnose MS, theoretical frameworks such as normalization process theory (NPT) can be beneficial to identify what factors can contribute to ensuring this diagnostic criteria is applied within usual care.

 The 4 constructs of NPT (coherence, cognitive participation, collective action, and reflexive monitoring) can yield information on the barriers and facilitators to implementation in clinical practice.

This study sought to identify barriers and facilitators to implementing the CVS/PRL within an improved diagnostic pathway in the context of current broader challenges within the National Health Service (NHS) MS diagnostic pathway. We included the perspective of people with MS to ensure that any amendments to the diagnostic pathway considered their priorities. Although the study was based in the UK, this work provides insights for all centers considering the implementation of CVS/PRL to aid in the diagnosis of MS.

This study was approved by the University of Nottingham Faculty of Medicine and Health Science Research Ethics Committee (FMHS 274-0824) and Nottingham University Hospitals NHS Trust (24-502C).

Our aim was to learn how to successfully implement CVS/PRL into the MS diagnostic pathway. To do this, we sought to understand the challenges within the current MS diagnostic pathway, including the perspectives of people with MS and their priorities for improving the pathway; identify barriers and facilitators to implementing a new diagnostic pathway using CVS/PRL; and consider the utility of CVS/ PRL in cases of diagnostic uncertainty, including where individuals are referred with a preliminary nonspecific MRI suggestive of demyelination.

Semistructured interviews and focus groups with people with MS and HCPs were conducted online using Microsoft Teams from October 2024 to February 2025. Interviewers (C.C.S.S, C.G., T.P.) received training from experienced qualitative researchers (B.D.P., L.T.). Interviewer characteristics are in 

Two participant groups were recruited: people with MS and HCPs. Eligibility criteria for the MS group were as follows: diagnosed in the last 10 years, 18 years or older, able to communicate in English, and able to provide consent. The inclusion criteria for HCPs were staff currently involved in the MS diagnostic pathway.

Camilla Holden, DClinPsy, MSc, BSc

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