Fatigue Scale For Motor And Cognitive Functions Research Articles

A comparative study of fatigue and processing speed in patients with multiple sclerosis treated with natalizumab or rituximab.

Fatigue is the most debilitating symptom in patients with multiple sclerosis (MS). Natalizumab and rituximab are the most used MS disease modifying therapies in Sweden, but comparative data on the effect on fatigue is sparse. Primary objective was to compare fatigue levels between patients on natalizumab and rituximab. As secondary objective, we assessed processing speed, an attention domain quality, between treatment groups. In this Swedish multicentre cross-sectional study, patients with relapsing-remitting MS and >24 months treatment duration were identified in the Swedish MS-registry. Fatigue was assessed using the Fatigue Scale for Motor and Cognitive functions (FSMC) and processing speed using Symbol Digit Modalities Test (SDMT). 128 patients were enrolled (natalizumab: 56, rituximab: 72). No significant differences in FSMC were found when adjusting for potential confounders (p = 0.936), with age having the biggest impact, correlating with increased fatigue. Individuals on natalizumab performed significantly better on SDMT at cross-section (natalizumab 64.7, rituximab 56.2; p = 0.003), with an improvement from treatment initiation, compared to rituximab (change: natalizumab 8.9, rituximab -1.0; p = 0.002). We found no difference in fatigue levels between natalizumab and rituximab cohorts. Patients treated with natalizumab showed significantly better results on SDMT than patients on rituximab.

The Cortical Silent Period and Its Association with Fatigue in Multiple Sclerosis: The Need for Standardized Data Collection.

The cortical silent period (CSP), assessed with transcranial magnetic stimulation (TMS), provides insights into motor cortex excitability. Alterations in the CSP have been observed in multiple sclerosis (MS), although a comparison of the sometimes contradictory results is difficult due to methodological differences. The aim of this study is to provide a more profound neurophysiological understanding of fatigue's pathophysiology and its relationship to the CSP. Twenty-three patients with MS, along with a matched control group, underwent comprehensive CSP measurements at four intensities (125, 150, 175, and 200% resting motor threshold), while their fatigue levels were assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC) and its motor and cognitive subscore. MS patients exhibited a significantly increased CSP duration compared to controls (p = 0.02), but CSP duration was not associated with the total FSMC, or the motor or cognitive subscore. Our data suggest a systematic difference in MS patients compared to healthy controls in the CSP but no association with fatigue when measured with the FSMC. Based on these results, and considering the heterogeneous literature in the field, our study highlights the need for a more standardized approach to neurophysiological data collection and validation. This standardization is crucial for exploring the link between TMS and clinical impairments in diseases like MS.

"No association between disease modifying treatment and fatigue in multiple sclerosis".

Fatigue affects 60-90% of people with multiple sclerosis (MS). It reduces quality of life and the ability to work. The cause of fatigue in MS remains unknown. Several disease-modifying treatments (DMTs) slow the disease process in relapsing MS by suppressing neuroinflammation. We aimed to investigate if treatment with a DMT is associated with lower rates of fatigue. In this cross-sectional study of the MS population in three counties in Norway, we used the Fatigue Scale for Motor and Cognitive Functions (FSMC) and the Hospital Anxiety and Depression Scale (HADS) to assess patient-reported fatigue, anxiety and depression. Clinical data were retrieved from the electronic patient record system. We categorized DMTs as high-efficacy therapy or moderate-efficacy therapy. High-efficacy drugs included fingolimod, natalizumab, ocrelizumab, rituximab, alemtuzumab, daclizumab, and autologous hematopoietic stem cell transplantation. Moderate-efficacy drugs included interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. We included persons with relapsing MS only. Of 1142 patients, 80% had fatigue. Fifty-six percent of the patients were on DMTs (25% on moderate-efficacy treatment and 30% on high-efficacy treatment), 18% had discontinued treatment and 26% had never received any DMT. Sex, level of disability as measured by the Multiple Sclerosis Severity Score, anxiety and depression were independently associated with fatigue. Moderate-efficacy treatment was associated with less fatigue, but not after adjustment for other variables. There was no association between high-efficacy treatment and fatigue. We found no independent relationship between the use of disease-modifying treatment and fatigue in MS.

Effects of inpatient energy management education and high-intensity interval training on health-related quality of life in persons with multiple sclerosis: A randomized controlled superiority trial with six-month follow-up.

Fatigue is one of the most frequent symptoms in persons with multiple sclerosis (pwMS) and impacts health-related quality of life (HRQoL). A multidisciplinary rehabilitation approach is recommended for the treatment of fatigue in pwMS. However, high-quality evidence exists only for unimodal interventions, such as physical therapies/exercise or energy/fatigue management programmes. The primary objective of the current study was to test the hypothesis that a combination of inpatient energy management education (IEME) and high-intensity interval training (HIIT) is superior to a combination of progressive muscle relaxation (PMR) and moderate continuous training (MCT) for improving HRQoL at 6-month follow-up in fatigued pwMS. A randomized (1:1) controlled superiority trial with fatigued pwMS >18 years of age, with Expanded Disability Status Scale (EDSS) score ≤6.5, recruited at the Valens clinic, Switzerland. Participants in the experimental group performed IEME twice and HIIT 3 times per week and those in the usual care group performed PMR twice and MCT 3 times per week, during a 3-week inpatient rehabilitation stay. Primary outcome was HRQoL (Physical and Mental Component Scales of the Medical Outcome Study 36-item Short Form Health Survey (SF-36)), assessed at entry to the clinic (T0), after 3 weeks' rehabilitation (T1) and 4 (T2) and 6 (T3) months after T0. Secondary outcomes included SF-36 subscales, fatigue (Fatigue Scale for Motor and Cognitive Functions (FSMC)), mood (Hospital Anxiety and Depression Scale (HADS)), self-efficacy for performing energy conservation strategies (Self-Efficacy for Performing Energy Conservation Strategies Assessment (SEPECSA)), self-perceived competence in activities of daily living (Occupational Self Assessment (OSA)) and cardiorespiratory fitness (peak oxygen consumption (VȮ2peak)). Data were analysed using a mixed model for repeated measures approach. A total of 106 pwMS (age (years): 49.75 (9.87), 66% female, EDSS: 4.64 (1.32)) were recruited. There were no significant group×time interaction effects in the primary and secondary outcomes. There were significant between-group differences in the pairwise comparisons of the group×time interaction in favour of the IEME+HIIT group at: (i) T1 in cardiorespiratory fitness (p=0.011) and SEPECSA (p=0.032); (ii) T2 in SF-36 mental health subscale (p=0.022), HADS anxiety subscale (p=0.014) and SEPECSA (p=0.040); (iii) T3 in SF-36 physical functioning subscale (p=0.012) and SEPECSA (p=0.003). IEME+HIIT was not superior to PMR+MCT regarding the effects on HRQoL (SF-36 Physical and Mental Component Scales) at 6-month follow-up in pwMS. However, there were significant between-group differences in favour of IEME+HIIT in physical functioning and mental health (SF-36 subscales), anxiety (HADS), cardiorespiratory fitness (VȮ2peak) and self-efficacy (SEPECSA) at different measurement time-points that need to be considered in clinical practice.

Physical activity is related to disease severity and fatigue, but not to relapse rate in persons with relapsing remitting multiple sclerosis - a self-reported questionnaire based study.

Based on theoretical models, physical activity has been introduced as a promoting method to mitigate the disease severity, fatigue and relapse rate in multiple sclerosis. The primary objective of the study was to investigate the relation between self-reported physical activity level and disease severity, fatigue and relapse rate in persons with relapsing remitting multiple sclerosis (RRMS). A survey was offered to persons with RRMS from March 2019 to August 2021 (n = 253). Physical activity level, fatigue and disease severity were determined using the Godin Leisure-Time Questionnaire (GLTEQ), the Patient Determined Disease Steps (PDDS) scale and the Fatigue Scale for Motor and Cognitive Functions (FSMC). Additionally, participants' relapse rate was recorded. Bivariate correlations revealed an inverse relation between physical activity level and PDDS (ρ = -0.279; p < 0.001) as well as between physical activity and FSMC (r = -0.213, p < 0.001), but not between physical activity and relapse rate (r = 0.033, p > 0.05). Multiple linear regression analyses explained 12.6% and 5.2% of the variance of PDDS and FSMC. Our findings confirm a relation between self-reported physical activity, disease severity and fatigue in persons with RRMS. However, self-reported physical activity level does not seem to affect the annualised relapse rate.

Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort.

Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort. Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors. Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4). Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.

Association between improved metabolic risk factors and perceived fatigue during dietary intervention trial in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES trial.

Preliminary dietary intervention trials with the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets have shown favorable effects on fatigue among people with multiple sclerosis (MS); however, their impact on metabolic health is unknown. To evaluate the impact of the Swank and Wahls diets on markers of metabolic health and to determine the association and mediation effect between changes in metabolic health and perceived fatigue among people with relapsing-remitting MS (RRMS). As part of a randomized parallel-arm trial, vital signs, blood metabolic biomarkers, and the fatigue scale for motor and cognitive functions (FSMC) were collected from participants with relapsing-remitting MS (n = 77) at four study visits spaced 12 weeks apart: (1) run-in, (2) baseline, (3) 12-weeks, and (4) 24-weeks. Participants followed their usual diet at run-in, then were randomized at baseline to either the Swank or Wahls diets and followed for 24 weeks. Both groups had significant reductions in weight, body mass index (BMI), total cholesterol, and low-density lipoprotein (LDL) at 12- and 24-weeks compared to respective baseline values (p ≤ 0.04 for all). The Swank group also had a significant reduction in high-density lipoprotein (HDL) at 12- and 24-weeks (p = 0.0001 and p = 0.02, respectively), while the Wahls group had significant reductions in diastolic blood pressure (DBP). In addition, both groups had significant reductions in FSMC total perceived fatigue and the motor and cognitive fatigue subscales at 12- and 24-weeks (p ≤ 0.01 for all); however, change in the cognitive subscale was not significant at 12-weeks in the Swank group (p = 0.06). Furthermore, the favorable effects, of both diets, on markers of metabolic health were not associated with and did not mediate the effect of the diets on perceived fatigue (p > 0.05 for all). Both diets lead to significant reductions in perceived fatigue, weight, BMI, total cholesterol, and LDL, but the significant reductions in perceived fatigue were independent of changes in markers of metabolic health.

High-intensity resistance training in people with multiple sclerosis experiencing fatigue: A randomised controlled trial

BackgroundExercise studies including only fatigued persons with multiple sclerosis (PwMS) with fatigue as primary endpoint are lacking. ObjectiveTo evaluate the effects of high-intensity resistance training (HIRT) on self-reported fatigue in fatigued PwMS in a single center randomised controlled trial. MethodsWe recruited 71 PwMS scoring ≥ 53 on the Fatigue Scale for Motor and Cognitive Functions (FSMC), who were randomised 1:1 to either twice (group A) or once (group B) weekly supervised HIRT for twelve weeks. A non-randomised FSMC score-matched group (n=69) served as non-intervention control. ResultsBetween HIRT-group differences were non-significant for primary and most secondary endpoints. Mean difference in FSMC score (95% confidence intervals) was -10.9 (-14.8; -6.9) in group A and -9.8 (-13.2; -6.3) in group B. Corresponding values for combined HIRT groups vs non-intervention control were -10.3 (-12.9; -7.7) and 1.5 (-0.6;3.6), respectively, p<0.001. Secondary endpoints also improved in both HIRT groups, though only Hospital Anxiety and Depression Scale anxiety and MS Impact Scale-29 psychological subscales significantly favoured the twice a week HIRT (group A). As an exploratory endpoint, changes in plasma inflammatory protein markers were associated with reduced FSMC scores in the pooled material. ConclusionThe finding that HIRT in fatigued PwMS leads to clinically relevant reductions in self-reported fatigue, associated with changes in plasma inflammatory protein levels, provide evidence for recommending HIRT for fatigued PwMS.

The Seasonal Fluctuation of Fatigue in Multiple Sclerosis.

BackgroundFatigue is a common symptom in patients with multiple sclerosis. Several studies suggest that outdoor temperature can impact fatigue severity, but a systematic study of seasonal variations is lacking.MethodsFatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC) in a temperate climatic zone with an average outdoor temperature of 8.8°C. This study included 258 patients with multiple sclerosis from 572 visits temporally distributed over the year. The data were adjusted for age, sex, cognition, depression, disease severity, and follow-up time. Linear regression models were performed to determine whether the temporal course of fatigue was time-independent, linearly time dependent, or non-linearly time dependent.ResultsFatigue was lowest during January (mean FSMC: 49.84) and highest during August (mean FSMC: 53.88). The regression analysis showed the best fit with a model that included months + months2, which was a non-linear time dependency. Mean FSMC per month correlated significantly with the average monthly temperature (ρ = 0.972; p < 0.001).ConclusionIn multiple sclerosis, fatigue showed a natural temporal fluctuation. Fatigue was higher during summer compared to winter, with a significant relationship of fatigue with outdoor temperature. This finding should be carefully taken into account when clinically monitoring patients over time to not interpret higher or lower scores independent of seasonal aspects.

ADAPTED MEDITERRANEAN DIET IMPACT ON THE SYMPTOMS OF CHRONIC FATIGUE, SERUM LEVELS OF OMEGA-3 POLYUNSATURATED FATTY ACIDS (PUFAS) AND INTERLEUKIN 17 (IL-17) IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS UNDERGOING DISEASE-MODIFYING THERAPY: A PILOT STUDY

Purpose: This pilot study was designed to investigate the impact of a moderate-calorie Mediterranean diet compared to a regular diet with omega-3 PUFAs (eicosapentaenoic and docosahexaenoic acids) supplementation on fatigue symptoms in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the optional benefit of the diet on their quality of life. Material/Methods: This 12-month pilot study was conducted in 2021 at the Department of Neurology, Medical University – Pleven, Bulgaria. A total of 60 patients with RRMS aged 18-64 were selected from the database of the Neurology Clinic at the University Hospital "Dr Georgi Stranski" – Pleven. From the selected patients, only 30 were included in the pilot phase and respectively assigned to the nutritional arms. Blood samples were collected twice – at the first and second visit in 3 months, for metabolic and dietary parameters analysis. Symptoms of fatigue were assessed with Fatigue Scale for Motor and Cognitive Functions (FSMC) and Modified Fatigue Impact Scale (MFIS). Results: From the 30 participants included in the study, 17 patients attended the clinic centre for complete follow-up; the remaining 13 were only partially observed. The dynamics of the followed-up parameters showed a statistically significant change in the body mass index (BMI), the fatigue symptoms in the FSMC and MFIS scales, total cholesterol and triglycerides levels, and the serum concentrations of IL17A, EPA and DHA. The metabolic caloric values were also found to be significantly changed. Conclusions: Despite the small study size limitation, this pilot study might be of benefit for further extensive research on the potential favorable impact of diet and lifestyle modifications on the symptoms of fatigue in multiple sclerosis patients.

Disentangling self-reported fatigue, depression, and cognitive impairment in people with multiple sclerosis

BackgroundFatigue is a common problem among people with multiple sclerosis (MS) and can have a negative effect on mental, physical, and social function. Self-reported measures of MS fatigue are often operationalized as a multi-dimensional symptom. However, questions remain about how best to account for the multi-dimensional aspects of self-reported fatigue and whether these aspects are distinct entities. Thus, the purpose of this study was to explore the overlap and distinctions between self-reported measures of the severity and impact of fatigue, between mental and physical fatigue, and between mental fatigue, depressive symptoms, and cognitive impairment. MethodsAn observational study was conducted with 289 participants with MS . The questionnaires were the Unidimensional Fatigue Impact Scale (UFIS), the Chalder Fatigue Scale (CFS), the Fatigue Scale for Motor and Cognitive Functions (FSMC), the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNSQ), and the Quality of Life in Neurological Disorders short form for depression (Neuro-QoL). Spearman's correlation coefficient was used to examine the bivariate correlations between composite and subscale scores. Exploratory structural equation modeling (ESEM) was used to determine the factor structure under a pre-specified number of factors to retain in the modeling of multiple items across questionnaires and examine model fit. Subsequently for poor fitting models in an iterative procedure to determine a better fitting multidimensional model, we posited a bifactor confirmatory factor analysis model. ResultsThe bivariate correlation analysis revealed that subscales from the same questionnaire measuring different aspects of fatigue had the highest correlations (r = 0.61–0.68), subscales from different questionnaires measuring the same aspect of fatigue had the next highest correlations (r = 0.43–0.60), and subscales from different questionnaires measuring different aspects of fatigue had the lowest correlations (r = 0.34–0.40). Bifactor models with a general fatigue factor and subdomains pertaining to impact, severity, and mental and physical fatigue had relatively good model fits compared to models omitting the subdomains. However, an ESEM model using subscales from the CFS and FSMC fit poorly and did not adequately identify separate factors for mental and physical fatigue. An ESEM model with separate factors for self-reported mental fatigue, depressive symptoms, and cognitive impairment was a good fit. ConclusionsThe working study hypothesis that fatigue constructs would be moderately correlated yet distinct entities was generally supported by the results of the study. However, we found that our hypothesized separation into a latent dimension existed only when the items or subscales came from the same questionnaire, in which case their level of specificity in terms of target, action, context, and time elements for measuring fatigue were consistent. The implications for the principle of compatibility in measuring self-reported MS fatigue are discussed.

Fatigue and activity-dependent conduction block in neuromuscular disorders

ObjectiveFatigue is a major disabling problem in patients with neuromuscular disorders. Both nerve demyelination and increased axonal branching associated with collateral sprouting reduce the safety factor for impulse transmission and could cause activity-dependent hyperpolarization and conduction block during voluntary contraction, and thus fatigue. This study aimed to investigate whether activity-dependent conduction block is associated with fatigue in demyelinating neuropathies and lower motor neuron disorders. MethodsThis study included 31 patients (17 with chronic inflammatory demyelinating polyneuropathy [CIDP] and 14 with spinal and bulbar muscular atrophy [SBMA]). Sixteen healthy subjects served as normal controls. Fatigue was assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Compound muscle action potential (CMAP) recording and nerve excitability testing after median nerve stimulation in the wrist were performed before and after maximal voluntary contraction of the abductor pollicis brevis for 1 min. ResultsPatients with CIDP/SBMA had prominent fatigue with higher FSMC motor scores (P < 0.0001) than normal controls. After voluntary contractions, CMAP amplitudes decreased significantly in four of the 17 patients with CIDP and one of the 14 patients with SBMA. The reduction in CMAP amplitude was associated with the fatigue score in the motor but not in the cognitive domain. After voluntary contraction, excitability testing showed axonal hyperpolarization in the normal and CIDP/SBMA groups. ConclusionsIn CIDP or SBMA, fatigue is caused by voluntary contraction-induced membrane hyperpolarization and conduction block, presumably due to the critically lowered safety factor due to demyelination or increased axonal branching. SignificancePeripheral fatigue can be objectively assessed using CMAP amplitudes and nerve excitability testing.

The aerobic capacity – fatigue relationship in persons with Multiple Sclerosis is not reproducible in a pooled analysis of two randomized controlled trials

BackgroundFatigue is one of the most frequent symptoms of persons with Multiple Sclerosis (pwMS) but has limited treatment options. Aerobic capacity and endurance training have been discussed as relevant factors to improve fatigue. However, over the last decades, results have been equivocal. This secondary analysis of two pooled parallel group RCTs of three weeks of endurance training (high intensity interval training (HIIT) and moderate continuous training (MCT)) for pwMS aimed to (I) reproduce reported associations between aerobic capacity and fatigue on a cross-sectional and interventional level. The analysis further aimed to (II) investigate intervention effects on fatigue in a severely fatigued subgroup and (III) analyze differences in changes of fatigue between peak oxygen uptake (VO2peak) responders and non-responders. MethodsBoth RCTs were conducted in the same inpatient rehabilitation clinic in Valens, Switzerland. Original primary outcomes were cognitive function (RCT1) and change in proportion of circulating regulatory T-cells (RCT2). PwMS (n = 131) with a relapsing-remitting or secondary progressive MS phenotype and Expanded Disability Status Scale score between 1 - 6.5 were eligible. Over the two studies participants exercised 3 - 5 times per week on cycle ergometers at intensities of 65 - 70% of maximum heart rate (HRmax) for 30 min (MCT groups) or three times per week with five 90 – 180 s intervals at intensities of 85% – 100% of HRmax and 90 s rest intervals (HIIT groups). Main outcome measures for the present secondary analysis were VO2peak measured during a cardiopulmonary exercise test and the Fatigue Scale for Motor and Cognitive Functions (FSMC), both assessed at the start and end of inpatient rehabilitation. ResultsBaseline correlations did not reveal a significant association between VO2peak and FSMC. There were no significant improvements in fatigue after the HIIT and MCT in the overall sample or the subsample of severely fatigued pwMS and no significant differences in fatigue changes between VO2peak-responders and non-responders. ConclusionsOur analysis did not confirm the aerobic capacity - fatigue relationship on a cross-sectional and experimental level, even when analyzing subgroups that should benefit the most according to proposed hypotheses.

Alertness-Grundmessung als stärkster Prädiktor für den Erwerbsstatus bei Patienten mit MS sechs Monate nach der Rehabilitation

Baseline alertness as the strongest predictor of employment status in patients with MS 6 months after rehabilitationS. Marchione, C. Dettmers, A. Weimer-Jaekel, B. Godde, M. JoebgesAbstractIntroduction: Fatigue is a dominant impairment in multiple sclerosis, which often also limits the professional performance of patients with MS (PwMS). In clini-cal practice fatigue is often difficult to assess. The question of our study was whether the objective cognitive fatigability – measured as reaction time or tonic alertness – or the subjective self-assessment of the patient – recorded by the Fatigue Scale for Motor and Cognitive Functions (FSMC) – predicts employment status 6 months after discharge from rehabilitation.Methods: PwMS whose rehabilitation measures were paid for by the government pension fund, and who had doubts about maintaining their professional per-formance in terms of their workload, underwent further testing. Tonic alertness from the test battery TAP-M was used as an indicator of cognitive fatigability. Participants were tested in the morning at 8:00 a.m., after standardized exer-cise at 11:00 a.m., and in the afternoon at 2:00 p.m. In addition, fatigue was determined using a self-assessment questionnaire (FSMC). Six months after discharge from neurological rehabilitation, their employment status was classi-fied through a telephone interview and also compared with our socio-medical performance assessment. Results: A complete data set was collected from 64 patients (43 female; age 48.9 ± 8.7 years; duration of illness 14.7 ± 9.5 years; EDSS 3.8 ± 1.3; 67 % relapsing remitting, 16 % secondary progressive, 17 % primary progressive). According to the International Standard Classification of Occupations (ISCO) code, 86 % were “white collar” workers, for example, in service, office and non-manual jobs. Six months after discharge from the rehabilitation clinic, 15 (23 %) out of 64 PwMS reported working less than 3 hours per day, 35 (55 %) PwMS reported 3 to 6 hours, and the remaining 14 (22 %) PwMS were full-time employees. The mean total value of the FSMC questionnaire for cognition was 38.9 ± 7.4, which was equivalent to severe cognitive fatigue. Eleven of the 14 full-time employees had severe fatigue. The morning alert-ness measurement (alertness1) (β = -.985; p= .003) and, the decline in alert-ness from morning to noon (alertness difference21; β = -.590; p= .033) and from noon to afternoon (alertness difference32; β =-.709; p= .020) were sig-nificant predictors for employment status. A reduction in alertness (increase in reaction time) by 1 SD on the alertness scale increases the probability of not working full-time by a factor of 2.67. Likewise, the probability of not working full-time increases by a factor of 1.80 if fatigability is increased by 1 SD from morning to noon. If fatigability increases by 1 SD from noon to eve-ning, the probability of not working full-time increases by a factor of 2.03. Discussion: The FSMC has no prognostic value for employment status 6 months after discharge from rehabilitation. The morning alertness measurement has the highest predictive value. However, an above average decline in alertness over the course of the day also reduces the probability of working full-time. Keywords: fatigue, fatigability, MS, alertness, employment status, prognostic factor

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).

ObjectivesCognitive 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.MethodsA 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.ResultsMS 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.ConclusionsThe 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.

High prevalence of fatigue in contemporary patients with multiple sclerosis.

ObjectiveThe prevalence of multiple sclerosis (MS)-related fatigue may have changed due to new diagnostic criteria and new disease modifying drugs. We aimed to assess the prevalence of fatigue in a contemporary MS cohort, and to explore associations between fatigue and clinical and demographic factors.MethodsThis is a cross-sectional study of the MS population in three Norwegian counties. Fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC). We also assessed self-reported anxiety, depression and daytime sleepiness.ResultsThe response rate was 64% (1599/2512). The mean age of the participants was 52 ± 13 years, median EDSS was 2.5 (IQR 1.5-3.0) and median disease duration from onset was 16 years (IQR 8-25). We found a prevalence of fatigue of 81%. Women had a higher prevalence of fatigue than men (83% vs 78%, p = 0.02). The prevalence increased with age (p < 0.001) and with increasing disease severity (p < 0.001), but in multivariate analyses, only sex and disease severity remained independent determinants of fatigue. Anxiety, depression, and daytime sleepiness were more prevalent in patients with fatigue than in those without fatigue (all p-values < 0.001).ConclusionThe prevalence of fatigue is high in contemporary patients with MS. Fatigue is associated with female sex and level of disability, as well as with anxiety, depression and excessive daytime sleepiness.

Olfactory Dysfunction in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Disease-Modifying Therapies.

Olfactory dysfunction evaluated with time-consuming tests was more common in patients with multiple sclerosis (MS) than in controls and correlated with neurological deficit. The aim of the present study was to compare olfactory function between patients with relapsing-remitting MS (RRMS) and controls with short and simple screening tool-the Sniffin' Sticks Identification Test (SSIT)-and search for its association with clinical and radiological features of the disease. The study included 30 controls and 30 patients with RRMS treated with disease-modifying therapies-injectables (interferon β or glatiramer acetate, N = 18) and oral drugs (dimethyl fumarate or fingolimod, N = 12). Hyposmia was defined as a score of 6 points or fewer in the SSIT olfactory test. The data concerning number of previous relapses, disability in Expanded Disability Status Scale (EDSS), and recent brain magnetic resonance imaging (MRI) scan were collected. Moreover, thalamic volume and third ventricle width were recorded in every patient. Additionally, cognition and fatigue in patients were evaluated 24 months after olfactory assessment with the Symbol Digit Modalities Test (SDMT) and Fatigue Scale for Motor and Cognitive Functions (FSMC), respectively. Patients with RRMS had a higher risk of hyposmia than controls (66.7% vs 36.7%, OR = 1.82, 95% CI, 1.10-3.67, P = .02). Neither inflammatory (number of previous relapses or new brain MRI lesions) nor neurodegenerative (EDSS, SDMT, and FSMC scores; thalamic volume; third ventricle width) MS features did not correlate with SSIT score (P > .05). In patients treated with oral drugs, olfactory dysfunction correlated with FSMC cognitive subscale (r = -0.90, P = .006). Olfactory dysfunction is nearly twice as common in RRMS as in controls and correlates with fatigue level in patients treated with dimethyl fumarate or fingolimod.

A two-year longitudinal follow-up of cognitive performance assessed by BICAMS in newly diagnosed patients with MS

Background: Cognitive impairment is common in patients with multiple sclerosis (MS) and may occur at any stage and with any subtype of the disease. Screening and monitoring of cognitive function should therefore be implemented into everyday clinical neurology practice. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was developed for this purpose. Although several cross-sectional studies have validated BICAMS, longitudinal studies evaluating its use as part of a clinical follow-up routine are still lacking. Objective: To investigate cognitive function and trajectories of change assessed by the BICAMS test battery in a cohort of newly diagnosed relapsing-remitting MS (RRMS) patients examined at baseline and after 12 and 24 months. Methods: BICAMS was used to assess cognitive function in 58 RRMS patients, who also filled in the Hospital Anxiety and Depression Scale (HADS) and the Fatigue Scale for Motor and Cognitive Functions (FSMC), and underwent standard neurological evaluations at baseline and at the two follow-ups. Results: A total of 27 patients (46.6%) were defined as cognitively impaired at baseline on at least one test, and 22 (37.9%) were defined as impaired at follow-up after 24 months. Throughout the study, 8 (13.8%) and 4 (6.9%) patients were consistently defined as impaired on two or three tests, respectively. The mean raw scores on two BICAMS subtests (SDMT and CVLT-II) improved significantly from baseline to the first follow-up, and then remained stable the next year, whereas the visual memory test (BVMT-R) were overall unchanged from baseline to the end of the study. The correlations between the scores on HADS, FSMC and the BICAMS subtests were non-significant at baseline, but weak to moderate negative correlations were found at the one- and two-year follow-ups. Conclusion: The patients showed improved test results from baseline to the first follow-up examination, indicating that an effect of previous practise should be taken into account when interpreting the results. With results showing both trajectories of stability and change, our study supported the validity of including BICAMS as part of a clinical follow-up routine of RRMS patients. Anxiety, depression, fatigue and cognition should always be assessed at the same time to reveal interaction effects that are expected to affect the daily-life functioning of at least some of the RRMS patients.

Fatigue in Multiple Sclerosis Is Associated With Childhood Adversities

Fatigue is a common and disabling symptom in patients with Multiple Sclerosis (PwMS). Its pathogenesis, however, is still not fully understood. Potential psychological roots, in particular, have received little attention to date. The present study examined the association of childhood adversities, specific trait characteristics, and MS disease characteristics with fatigue symptoms utilizing path analysis. Five hundred and seventy-one PwMS participated in an online survey. Standardized psychometric tools were applied. The Childhood Trauma Questionnaire (CTQ) served to assess childhood adversities. Trait variables were alexithymia (Toronto Alexithymia Scale; TAS-26) and early maladaptive schemas (Young Schema Questionnaire; YSQ). Current pathology comprised depression (Beck’s Depression Inventory FastScreen; BDI-FS) and anxiety symptoms (State-Trait Anxiety Inventory; STAI-state), as well as physical disability (Patient determined Disease Steps; PDDS). The Fatigue Scale for Motor and Cognitive Functions (FSMC) was the primary outcome variable measuring fatigue. PwMS displayed high levels of fatigue and depression (mean FSMC score: 72; mean BDI-II score: 18). The final path model revealed that CTQ emotional neglect and emotional abuse remained as the only significant childhood adversity variables associated with fatigue. There were differential associations for the trait variables and current pathology: TAS-26, the YSQ domain impaired autonomy and performance, as well as all current pathology measures had direct effects on fatigue symptoms, accounting for 28.2% of the FSMC variance. Bayesian estimation also revealed indirect effects from the two CTQ subscales on FSMC. The final model fitted the data well, also after a cross-validation check and after replacing the FSMC with the Chalder Fatigue Questionnaire (CFQ). This study suggests an association psychological factors on fatigue in Multiple Sclerosis. Childhood adversities, as well as specific trait characteristics, seem to be associated with current pathology and fatigue symptoms. The article discusses potential implications and limitations.

Influence Of High-intensity Interval Training On Fatigue, Depression And Anxiety In People With Multiple Sclerosis

Sport and Exercise have been described to promote positive effects on psychosocial symptoms of multiple sclerosis (MS) such as fatigue, depression and anxiety. However, detailed recommendations for intervention programs in the rehabilitation of MS have not been proposed yet. PURPOSE: The present study aims to compare the influence of high intensity interval (HIIT) on fatigue, depression and anxiety in people with relapsing remitting and secondary progressive MS. METHODS: Within the framework of a single- blinded randomized controlled trial, 73 patients with MS conducted 3x/week for three weeks either HIIT (5×1.5 minutes at 95-100% of participants’ maximal heart rate (HRmax)) or moderate continuous aerobic exercise (MC) (24 minutes continuous cycling at 65% of HRmax) on a bicycle ergomete. Before (t0) and after (t1) the training period, fatigue, depression and anxiety were assessed using the multidimensional fatigue scale for motor and cognitive functions (FSMC) and the Hospital and anxiety scale (HADS). Effects of within (t0 vs. t1) - and between (HIIT vs. MC, relapsing remitting type vs. secondary progressive type) - subjects have been analyzed by baseline- adjusted analysis of variance (ANCOVA). RESULTS: At the time of allocation, 68 patients were identified to have mild fatigue (sum score ≥ 43) and were included in the analysis of FSMC. ANCOVA revealed significant time effects for the FSCM sum score (F(1)= 7.188, p= .009). While people with relapsing remitting type of MS improved in both HIIT (p≤.001) and MC (p= .012), no alterations were observed for people with secondary progressive type of MS. However, neither significant group nor interaction effects were revealed for all FSMC outcomes. Regarding HADS, 38 patients with mild depression or anxiety (HADS-TS ≥ 8) at the time of allocation were analyzed. No significant time, group and interaction effect for any outcome was observed. CONCLUSION: There are no differences in the impact of HIIT vs. MC on fatigue, depression and anxiety in people with MS. However, people with relapsing remitting MS tend to react more sensible for positive effects of aerobic exercise in general regarding fatigue than people with secondary progressive MS. Nonetheless, results need to be taken with caution, since no main effect for group and MS type was detected.