Self-reported Reasons for Changes in Performance of Daily Activities During a 2-Year Multidisciplinary Multiple Sclerosis Rehabilitation.

Background: Few multidisciplinary rehabilitation studies with a heterogeneous design have focused on individuals with multiple sclerosis (MS). This study compared subjective-reported changes in performance and satisfaction with daily activities among moderately and severely disabled individuals with MS during a 2-year, multidisciplinary, group-based, outpatient rehabilitation program comprising education in self-management and compensatory techniques, exercise, and guided peer support. Methods: Thirty-eight adults with moderate disability (Expanded Disability Status Scale [EDSS] score of 4.0-5.5, 74% women, mean age of 48) and 41 individuals with severe disability (EDSS 6.0-8.5, 63% women, mean age of 48) were assessed at baseline and after 12 and 21 months of outpatient rehabilitation using the Canadian Occupational Performance Measure (COPM). Group × time interactions were analyzed using mixed analysis of variance. Participants' explanations of reasons for changes in activity performance were collected via semistructured interviews and analyzed content. Results: Statistically significant improvements in COPM performance and satisfaction scores were reported in both groups from baseline to 21 months of rehabilitation. No significant between-group differences in improvement were observed. The self-reported reasons for improvement were mainly linked to environmental factors. Conclusions: The outpatient rehabilitation program, including 4 themes-cognition, mood, energy conservation, and body control-improved the self-reported performance of patients with MS with moderate and severe disabilities. Environmental factors warrant consideration during rehabilitation.

Validation of the Finnish version of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and evaluation of the applicability of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) and the Fatigue Scale for Motor and Cognitive Functions (FSMC).

OBJECTIVES: Cognitive impairment is frequent in multiple sclerosis (MS) as approximately half of the patients manifest some degree of cognitive impairment. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been designed for brief cognitive evaluation. The purpose of the study was to validate the BICAMS along with the Finnish versions of one self-rating questionnaire each for cognition and fatigue. METHODS: A total of 65 MS patients and 45 healthy controls (HC) were assessed with the BICAMS, the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), and the Fatigue Scale for Motor and Cognitive Functions (FSMC) twice, approximately within nine days. RESULTS: MS patients scored markedly lower than the HCs on each of the three tests of the BICAMS. Of the patients, 60% scored at least 1.5 SD below the mean of the HCs on at least one test; 49% on the SDMT, 26% on the CVLT-II, and 28% on the BVMT-R. Correlation coefficients for the repeated measurement were between 0.75 and 0.89 for the three tests in the whole study sample. MS patients reported more cognitive symptoms and more fatigue than the HCs. Cronbach's alpha was 0.94 for the MSNQ and 0.98 for the FSMC. Correlation coefficient for the repeated measurement was 0.91 for the MSNQ and between 0.92 and 0.94 for the FSMC scores for the whole study sample. CONCLUSIONS: The present study supports the validity of the Finnish version of the BICAMS. The SDMT was the most sensitive of the three BICAMS tests and showed cognitive impairment in half of the patients. The Finnish versions of the MSNQ and the FSMC proved useful tools in approaching concerns related to cognition and fatigue.

Research on lower extremity health in patients with multiple sclerosis: a systematic scoping review.

BACKGROUND: Multiple sclerosis (MS) often affects ambulation and the function of the lower limbs. However, little is known about how much research has been conducted on lower extremity health in patients with MS. OBJECTIVE: To analyse empirical studies and their evidence on lower extremity health in patients with MS, in order to identify the need for future studies in key areas. METHODS: A systematic scoping review was conducted. A literature search of Medline (PubMed), CINAHL (EBSCO) and the Cochrane Library databases was performed. The search covered the period up to 15 January 2020 from the earliest records available. This led to the inclusion of 42 empirical articles. The data were analysed using content analysis and quantification techniques. RESULTS: The research on lower extremity health focused primarily on two main areas: gait and lower extremity muscle strength. Lower extremity health was assessed using a variety of methods, most of which consisted of objective physical tests and gait analysis. Patients with MS had many problems with the health of their lower extremities, which manifested in walking difficulties, balance problems, muscle weaknesses and spasticity. In the feet, pes cavus, claw toes, oedema and altered foot sensation were common. CONCLUSIONS: MS affects lower limb and foot health, and these problems can affect patients' daily lives. However, the extent of these problems is poorly understood, partly due to the dearth of research on lower limb and foot health. Therefore, further research is warranted in order to better understand the impact of MS on foot and lower limb health in everyday life.

Impact of multiple sclerosis phenotypes on burden of disease in Finland.

Aims: The aim of this study was to quantify how multiple sclerosis (MS) phenotypes differ from each other in respect of costs and quality-of-life.Materials and methods: The study is based on survey data from Finnish patients with MS (n = 553). The information contained disease type, disease severity according to self-reported Expanded Disease Severity Scale (EDSS), healthcare resource use, and medication use. In addition, information related to employment and early retirement was collected. EQ-5D-VAS and Multiple Sclerosis Impact Scale-29 (MSIS-29) instruments were used to collect quality-of-life data, and Fatigue Severity Scale (FSS) instrument for evaluating fatigue. Patients were stratified based on their disease type (relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS)) and disease severity. The data were primarily analyzed using summary statistics.Results: SPMS had the highest annual total cost (71,177€) followed by PPMS (51,082€) and RRMS (36,492€). Early retirement covered the greatest share of costs in RRMS (39%) and SPMS (43%). In PPMS, early retirement and professional care were the two most equally important cost drivers, contributing together 56% of the total costs. Direct healthcare costs were responsible for 33%, 19%, and 18% of total costs in RRMS, SPMS, and PPMS. The mean EDSS in RRMS, SPMS, and PPMS were 2.5, 5.5, and 5.9, respectively. Differences in the quality-of-life were observed with both disease specific (MSIS-29) and generic (EQ-5D-VAS) instruments. The mean utility value from EQ-5D among patients with RRMS, SPMS, and PPMS was 0.76, 0.52, and 0.49, respectively. In addition, patients with SPMS and PPMS were more likely to report fatigue than patients with RRMS.Conclusions: MS phenotype has an impact on costs and quality-of-life of the patients. Early retirement seems to be one of the most important contributors to MS-related costs.

Cost Assessment Modelling of Treatments for Highly Active Relapsing Multiple Sclerosis.

INTRODUCTION: Cost assessment modelling (CAM) of treatments in highly active relapsing multiple sclerosis was conducted. METHODS: The CAM was developed using the R programming language. The PICOSTEPS health technology assessment framework was applied in the CAM. Modelled patients were 280 adults with highly active relapsing multiple sclerosis eligible for disease-modifying treatment. Intervention was cladribine tablets, a new and reimbursed oral treatment for highly active relapsing multiple sclerosis in Finland. Comparators included fingolimod, the most used oral reimbursed treatment for the highly active disease, and natalizumab, the most used intravenous treatment, and a treatment mix (80% use fingolimod, 20% use natalizumab) in Finland. Outcomes presented expected annual and cumulative drug-associated costs in the overall population and per patient. Setting was modelled public specialist care in Finland. Time was set to 4 years, without discounting. Effects covered expected drug-associated costs (screening, acquisition, administration, monitoring, adverse events, travelling, productivity). Perspective was a limited societal perspective. Sensitivity analyses regarding all PICOSTEPS components were conducted. RESULTS: Cladribine tablets were projected to be cost saving in comparison to fingolimod, natalizumab and treatment mix. The respective modelled savings were €4,598,742, €16,249,701 and €6,928,934 in the overall population, and €16,424, €58,035 and €24,746 per patient, respectively, during the 4 years. The most important cost driver was drug costs, representing 96.3%, 96.0% and 83.4% of modelled costs associated with cladribine tablets, fingolimod and natalizumab, respectively. Cladribine tablets sustained their affordability in the sensitivity analyses. From the perspective of health care payer, cladribine tablets' savings were projected to be €4,514,509, €15,145,366 and €6,640,680 in the overall population, and €16,123, €54,091 and €23,717 per patient in comparison to fingolimod, natalizumab and treatment mix, respectively. CONCLUSION: Based on the CAM, cladribine tablets were projected to robustly save modelled drug-associated costs in comparison to fingolimod, natalizumab and their mix in Finland.

Predictors of Participation and Autonomy in People With Multiple Sclerosis.

IMPORTANCE: Because multiple sclerosis (MS) affects many life areas, it is important to know how participation and autonomy are associated with the perceived impact of MS on everyday life. OBJECTIVE: To investigate how perceived quality of life, disease impact, gender, and disease severity predict participation and autonomy in people with MS. DESIGN: Cross-sectional study in which structural equation modeling was used to evaluate relationships between measured variables. SETTINGS: Outpatient clinics in three areas and one inpatient rehabilitation center in Finland. PARTICIPANTS: Convenience sample of 194 people with MS. OUTCOMES AND MEASURES: Participants completed the Impact on Participation and Autonomy (IPA), the World Health Organization Quality of Life-Brief measure (WHOQOL-BREF), and the Multiple Sclerosis Impact Scale (MSIS-29). The Expanded Disability Status Scale (EDSS) was administered by a neurologist. RESULTS: The final model showed good fit to the data. All the goodness-of-fit indexes except χ² supported the model, χ²(30, N = 194) = 46.729, p < .026; comparative fit index = .983; Tucker-Lewis index = .969; root mean square error of approximation = .054; standardized root mean square residual = .039. Quality of life (WHOQOL-BREF) and the impact of multiple sclerosis (MSIS-29) were the main predictors of participation and autonomy. Disease severity influenced only the IPA Autonomy Indoors domain. Gender was not associated with participation and autonomy. CONCLUSION AND RELEVANCE: Experiences of participation and autonomy appear to be closely associated with perceived quality of life and impact of the disease. Findings support the importance of assessing participation and autonomy and planning interventions using this information. WHAT THIS ARTICLE ADDS: The IPA appears to be an appropriate measure for assessing participation and autonomy and planning occupational therapy interventions for people with MS. In particular, environmental factors affecting participation and autonomy should be considered when planning interventions to promote participation and autonomy.

Validity and reliability of the Finnish version of the Multiple Sclerosis Impact Scale-29.

BACKGROUND: The Multiple Sclerosis Impact Scale-29 (MSIS-29) has been increasingly used to evaluate the self-perceived impact of multiple sclerosis (MS) on a patient. OBJECTIVES: The aim of this study was to evaluate the psychometric properties of the Finnish version of MSIS-29 in patients with MS. METHODS: A total of 553 patients with MS completed the MSIS-29 and self-administered questionnaires capturing information on demographics, disease characteristics and severity, perceived quality of life (EuroQol 5D-3L instrument), and fatigue (Fatigue Severity Scale). RESULTS: The data quality for MSIS-29 was excellent, with 99.5% computable scores for the MSIS-29 physical scale and 99.3% for the MSIS-29 psychological scale. Floor and ceiling effects were minimal. Excellent Cronbach's alpha values of 0.97 and 0.90 were seen for MSIS-29 physical and psychological subscales, respectively. The physical subscale showed highest correlations with measures of physical functioning, such as disease severity and the mobility domain of the quality of life. Similarly, the psychological subscale showed highest correlations with self-reported fatigue and the anxiety/depression domains of the quality of life. MSIS-29 physical scores related strongly to disease severity, whereas the MSIS-29 psychological scores increased in mild disease but declined in more severe disease forms. CONCLUSION: The Finnish version of MSIS-29 has satisfactory psychometric properties. Consistent with the previous recommendations, the use of two MSIS-29 subscale scores instead of a total score was supported.

Validity and reliability of the Fatigue Severity Scale in Finnish multiple sclerosis patients.

BACKGROUND: Fatigue is one of the most debilitating symptoms in multiple sclerosis (MS) considerably interfering with patients' daily functioning. Both researchers and clinicians need psychometrically robust methods to evaluate fatigue in MS. OBJECTIVES: The objective of this study was (i) to evaluate the psychometric properties of the Finnish version of the Fatigue Severity Scale (FSS) and (ii) to describe the results among patients with MS. METHODS: In total, 553 patients with MS (mean age, 53.8 years; standard deviation [SD], 11.4; 79% women: mean patient-defined disease severity, Expanded Disability Status Scale [EDSS] 4.0, SD, 2.5) completed the self-administered questionnaires including the FSS. A standard procedure was used for the translation of the FSS. RESULTS: The mean (SD) score for the FSS was 4.5 (1.7); in 65% of the patients, the score was ≥4.0. The data quality of the FSS was excellent, with 99.6% of computable scale scores. Floor and ceiling effects were minimal. The FSS showed high internal consistency (Cronbach's alpha, 0.95). Unidimensionality was supported based on confirmatory factor analysis with the comparative fit index being 0.94. The FSS showed moderate/high correlations with the perceived burden of the disease, quality of life and disease severity, whereas, age or gender did not have a significant effect on the FSS score. CONCLUSIONS: The Finnish version of the FSS showed satisfactory reliability and validity and thus can be regarded as a feasible measure of self-reported fatigue.

Psychometric evaluation of the Finnish version of the impact on participation and autonomy questionnaire in persons with multiple sclerosis.

OBJECTIVE: The objective of this study was to evaluate the psychometric properties of the impact on participation and autonomy (IPA) questionnaire. The Finnish version of IPA (IPAFin) was translated into Finnish using the protocol for linguistic validation for patient-reported outcomes instruments. METHODS: A total of 194 persons with multiple sclerosis (MS) (mean age 50 years SD 9, 72% female) with moderate to severe disability participated in this study. A confirmatory factor analysis (CFA) was used to confirm the four factor structure of the IPAFin. The work and educational opportunities domain was excluded from analysis, because it was only applicable to 51 persons. Internal consistency was investigated by calculating Cronbach's alpha. RESULTS: CFA confirmed the construct validity of the IPA (standardized root mean square residual (SRMR) = 0.06, comparative fit index (CFI) = 0.93, Tucker-Lewis index =0.93, root mean square error of approximation (RMSEA) = 0.06), indicating a good fit to the model. There was no difference in the models for females and males. Cronbach's alpha for the domains ranged between 0.80 and 0.91, indicating good homogeneity. CONCLUSIONS: The construct validity and reliability of the IPAFin is acceptable. IPAFin is a suitable measure of participation in persons with MS.

Burden of illness in multiple sclerosis (DEFENSE) study: the costs and quality-of-life of Finnish patients with multiple sclerosis.

OBJECTIVE: Although multiple sclerosis (MS) is one of the most common causes of non-traumatic disability among young adults, no published data on its economic and health-related quality-of-life (HRQoL) burden is available from Finland. The DEFENSE study aimed to estimate the costs and HRQoL of patients with MS (PwMS) in Finland and explore how these variables are influenced by disease severity and relapses. METHODS: Overall, 553 PwMS registered with the Finnish Neuro Society, a national patient association in Finland, completed a self-administered questionnaire capturing information on demographics, disease characteristics and severity (Expanded Disease Severity Scale [EDSS]), relapses, resource consumption and HRQoL. RESULTS: The PwMS had a mean EDSS score of 4.0. Overall, 44.1% had relapsing-remitting form of the disease (RRMS). The mean age was 53.8 years and 55.7% had retired prematurely due to MS. Disease-modifying therapies (DMTs) were used by 42.7% of the study population, and 21.5% across all disease types and severities had experienced relapses during the previous year. The mean total annual cost of MS was €46,994, which increased with advancing disease from €10,835 (EDSS score = 0) to €109,901 (EDSS score = 8-9). The mean utility was 0.644. HRQoL decreased with increasing disease severity. Relapses imposed an additional utility decrement among the PwMS with RRMS and EDSS ≤5 and had a trend-like effect on total costs. LIMITATIONS: The cross-sectional setting did not allow assessment of the significance of relapses in early MS or the use of DMTs on the prognosis of the disease. CONCLUSION: The study confirms previous findings from other countries regarding a significant disease burden associated with MS and provides, for the first time, published numerical estimates from Finland. Treatments that slow disease progression and help PwMS retain employment for a longer duration have the highest potential to reduce the disease burden associated with MS.

[Update on Current Care Guideline: Multiple sclerosis]. / Kaypa hoite-suosituksen paivitystiivistelma. MS-tauti.

Treatment for relapsing-remitting multiple sclerosis (RRMS) is initiated upon fulfillment of new McDonald 2010 criteria for RRMS. In addition, lumbar puncture is an essential diagnostic method. Interferon-ß, dimethyl fumarate, glatiramer acetate and teriflunomide are the first-line immunomodulating drugs (IMD) for RRMS. If the disease is active according to clinical or MRI evaluation during the first-line IMD treatment, alemtuzumab, fingolimod or natalizumab may be considered as second-line therapies. IMD treatment is discontinued upon the transition of RRMS to secondary progressive phase. Rehabilitation should be considered at every phase of the disease.

Cognitive performance profile in different phenotypes of MS with cognitive complaints.

BACKGROUND: The relationship between cognitive impairment and disease course and severity of multiple sclerosis (MS) is not well understood. OBJECTIVE: The aim of the study was to evaluate whether cognitive complaints in different clinical phenotypes and severity stages of MS are associated with differences in the profile of cognitive impairment. METHODS: 196 MS patients (relapsing-remitting RRMS n=138; secondary progressive SPMS n=32; primary progressive PPMS n=26) with perceived cognitive deficits underwent neuropsychological assessment with the brief repeatable battery of neuropsychological tests (BRBNT). Mood, impact of the disease, and quality of life were evaluated with self-reports. RESULTS: Only minor differences were observed in the cognitive impairment profile of different disease phenotypes and different disease severity stages. RRMS patients performed better only in one cognitive test of the BRBNT, than patients with progressive disease types. When RRMS, SPMS, and PPMS groups were evaluated separately, PPMS showed more pronounced cognitive impairments than RRMS and SPMS. The relationships between cognitive impairment and severity of disability as well as duration of disease were weak. CONCLUSION: MS patients with cognitive complaints tend to have a relatively similar cognitive impairment profile which is not dependent on the disease course and severity.

The activities and participation categories of the ICF Core Sets for multiple sclerosis from the patient perspective.

PURPOSE: To validate the activities and participation components of The International Classification of Functioning, Disability and Health (ICF). METHODS: In this cross-sectional study, 113 Finnish community-dwelling persons with MS were assessed using a semi-structured interview provided by the Canadian Occupational Performance Measure (COPM) to capture participants' self-perceived problems in everyday activities and participation. Problems were linked to the ICF categories. RESULTS: Participants identified 527 of the most important occupational performance problems. They covered all chapters of the ICF Activities and Participation components. Forty-one categories out of a total 53 ICF activities and participation categories of the Comprehensive ICF Core Set and four out of five categories of the Brief ICF Core Set were reported on by the participants. The most common category in this sample, 'd920 Recreation and leisure' (145 problems/27.5%), is not included in the Brief ICF Core Set. CONCLUSIONS: Most, but not all, ICF activities and participation categories of the ICF Core Sets for MS could be confirmed from the perspective of persons with MS. It is worth considering to add category 'd920 Recreation and leisure' to the Brief ICF Core Set.

The effects of heat stress on physical functioning in persons with multiple sclerosis.

Heat sensitivity is a well-recognised feature in multiple sclerosis (MS). However, little is known about how heat affects physical performance in persons with MS. The objective of the study was to evaluate the effects of short-term heat stress on physical functioning in persons with MS. Twenty-three heat-sensitive MS subjects and 19 healthy controls participated. Moderate heat exposure took place in a dry Finnish sauna. Measures of upper and lower extremity function, static and dynamic balance, and walking capacity were applied. Core body temperature was measured by a telemetric physiological monitoring system. Assessments were conducted before, immediately, 1 hour, and 1 day after the heat exposure. Subjects with MS showed a significantly (P=0.002) higher core body temperature than the controls following the heat stress. Performances in walking (P<0.001), chair rise (P=0.005) and functional reach (P=0.04) were poorer in MS subjects than in controls immediately after the heat. No prolonged heat effects were observed. An increase in ambient temperature causes a higher core body temperature rise in MS subjects than in healthy controls. This rise in temperature is associated with acute, but not prolonged detrimental effects on physical functioning.

Cerebral acetylcholinesterase activity is not decreased in MS patients with cognitive impairment.

BACKGROUND: Neuropsychological studies have extensively described the presence of cognitive dysfunction in MS patients. One possible pharmacological treatment of the impairment could be based on acetylcholinesterase inhibitors (AChEIs), which have shown efficacy in alleviating cognitive impairment in many other disorders. The findings on the efficacy of AChEI medication in MS associated cognitive symptoms are preliminary and no studies concerning cerebral acetylcholinesterase (AChE) activity in these patients have been published. OBJECTIVE: The objective of the study was to examine cerebral AChE activity in cognitively deteriorated MS patients. Cerebral AChE activity of 10 MS patients with secondary progressive disease and marked cognitive impairment, and 10 healthy controls, was studied with positron emission tomography using tracer (11)C-MP4A. METHODS: The cognitive profile of the patients was assessed with CERAD (Consortium to Establish a Registry for Alzheimer's Disease). RESULTS: No differences in cortical AChE activity between MS patients and controls were seen. CONCLUSIONS: In the patient group regional AChE activities had inverse correlations with Word learning and MMSE (Mini-Mental State Examination) scores. In the group of cognitively deteriorated MS patients no change in cerebral AChE activity, compared with controls, was observed, but within the patient group more pronounced cognitive symptoms were associated with higher cerebral AChE activity.

[Update on current care guidelines: diagnostics, treatment and rehabilitation of multiple sclerosis]. / MS-taudin diagnoosi, lääkehoito ja kuntoutus.

Treatment is initiated when the McDonald criteria for relapsing-remitting multiple sclerosis (RRMS) are fulfilled. High-risk patients with clinically isolated syndrome are followed using magnetic resonance imaging for one year after the first imaging. Interferon-beta or glatiramer acetate are the first-line immunomodulating drugs (IMD) for RRMS. MxA protein is measured 12 and 24 months after initiation of Interferon-beta to evaluate possible development of neutralizing antibodies. If MxA protein may not be detected repeatedly interferon-beta treatment is discontinued. If the disease is active in spite of treatment with first-line IMD, natalizumab may be considered as a second-line therapy. IMD is stopped when the transition to secondary progressive phase has occurred (or upon transition to secondary progressive phase).

A follow-up study of chromosome 19q13 in multiple sclerosis susceptibility.

A possible role of allelic variation on chromosome 19q13 in multiple sclerosis (MS) susceptibility has been suggested. We tested association of sixteen 19q13 markers with MS in 459 families. Nominally significant associations were tested in an independent set of 323 families as well as in the pooled set of 782 families. We were not able to confirm previously suggested associations with APOE, GIPR, ZNF45, ILT6 and D19S585. In the screening dataset nominally significant associations were found with D19S867 and with APOE haplotype (p=0.007 in both), but these were not replicated in the independent dataset nor in the pooled analysis of 757 families. Thus, we were not able to detect any statistically significant allelic associations. Re-sequencing based approaches may be required for elucidating the role chromosome 19q13 with MS.

Pupillary function in early multiple sclerosis.

Autonomic pupillary function was assessed with pupillometry in 95 mildly or moderately disabled patients with multiple sclerosis (MS) and 81 healthy subjects. The parasympathetic pupillary function was measured as initial diameter (mm), time to minimum diameter (seconds), reflex amplitude (mm), relative reflex amplitude (%), and maximal constriction velocity (mm/seconds). To reflect the sympathetic pupillary function maximal redilatation velocity (mm/seconds), and time of 75% of redilatation (seconds) were measured. Of MS patients 85-99% were within the reference values of healthy subjects. In MS patients the effect of age was observed in the initial diameter, reflex amplitude, and time of 75% redilatation. There were no such age related effects in healthy subjects. In age adjusted analysis the initial diameter and time of 75% redilatation differed significantly from healthy controls. Autonomic pupillary functions were not associated with fatigue, visual defect, or bladder disturbance, as measured by Fatigue Severity Scale, Kurtzke's Functional System Scales, Expanded Disability Status Scale, or the Multiple Sclerosis Functional Composite. Our results suggest that both parasympathetic and sympathetic pupillary functions are disturbed already early in the course of MS. However, the disturbance is not severe at this stage of the disease. The dysfunction is age-dependent and thus possibly related to the dimished remyelination capacity of the central nervous system.