A systematic review to explore patients' MS knowledge and MS risk knowledge.

Living with a chronic illness poses particular challenges, including maintaining current disease knowledge to optimise self-management and interaction with health professionals. People with Multiple Sclerosis (MS) are increasingly encouraged to participate in shared decision making. Making informed decisions is likely to rely on adequate knowledge about the condition and its associated risks. The aim of this systematic review is to explore patients' existing MS knowledge and MS risk knowledge, and how these relate to demographic and disease variables. A literature search was conducted using PsycINFO, PubMed and Cochrane Library. Eligible studies were published peer-reviewed reporting quantitative measures of MS knowledge and MS risk knowledge in adult MS patients. Eighteen studies met inclusion criteria comprising a total sample of 4,420 patients. A narrative synthesis was undertaken because studies employed various measures. Suboptimal levels of MS knowledge and MS risk knowledge were generally identified across studies. Greater self-reported adherence and a willingness to take medication were related to higher MS knowledge, while educational level was a significant predictor of both MS knowledge and MS risk knowledge. Associations with other demographic and disease-related variables were mixed for both knowledge domains. Direct comparison of results across studies were limited by methodological, sampling and contextual heterogeneity. The review's findings and implications for future research and clinical practice are considered from this perspective.

Improvements in quality of life over 2 years with cladribine tablets in people with relapsing multiple sclerosis: The CLARIFY-MS study.

BACKGROUND: Multiple sclerosis (MS) negatively affects health-related quality of life (HRQoL). OBJECTIVE: To evaluate HRQoL in people with highly active relapsing MS treated with cladribine tablets (CladT; 3.5 mg/kg cumulative dose over 2 years) in CLARIFY-MS. METHODS: Changes in the MS quality of life (MSQoL)-54 scores were analysed using a repeated mixed-effects linear model. Subgroup analyses were performed for participants who were pretreatment-naïve and those pretreated with disease-modifying therapies (DMTs) before initiating CladT. Safety and tolerability of CladT were also assessed. RESULTS: MSQoL-54 physical (mean change = 4.86; 95% confidence interval (CI) = 3.18, 6.53) and mental health (4.80; 95% CI = 3.13, 6.46) composite scores (primary endpoints) showed significant improvement at Month 24 versus Baseline (p < 0.0001). Changes in the MSQoL-54 scores were consistent across the pretreatment-naïve and DMT-pretreated subgroups. No new severe or opportunistic infections occurred. Most post-baseline lymphopenia events were Grade 1-2 in severity. Transient Grade-3 lymphopenia was observed in 19.7% (95/482) of participants. Grade-4 lymphopenia was not observed. CONCLUSIONS: CladT treatment significantly improved the mean MSQoL-54 physical and mental health composite scores over 2 years. CladT efficacy in HRQoL, relapse rates and Expanded Disability Status Scale scores demonstrates its multidimensional effects in MS treatment.

Measuring disability in multiple sclerosis: the WHODAS 2.0.

INTRODUCTION: Reliable measurement of disability in multiple sclerosis (MS) using a comprehensive, patient self-reported scale, such as the World Health Organization Disability Assessment Schedule (WHODAS) 2.0, would be of clinical and research benefit. METHODS: In the Trajectories of Outcome in Neurological Conditions-MS study, WHODAS 2.0 (WHODAS-36 items for working, WHODAS-32 items if not working, WHODAS-12 items short-form) was examined using Rasch analysis in 5809 people with MS. RESULTS: The 36- and 32-item parallel forms, and the cognitive and physical domains, showed reliability consistent with individual or group use. The 12-item short-form is valid for group use only. Interval level measurement for parametric statistics can be derived from all three scales which showed medium to strong effect sizes for discrimination across characteristics such as age, subtype, and disease duration. Smallest detectable difference for each scale was < 6 on the standardised metric of 0-100 so < 6% of the total range. There was no substantial differential item functioning (DIF) by age, gender, education, working full/part-time, or disease duration; the finding of no DIF for time or sample supports the use of WHODAS 2.0 for longitudinal studies, with the 36- and 32-item versions and the physical and cognitive domains valid for individual patient follow-up. CONCLUSIONS: Disability in MS can be comprehensively measured at interval level by the WHODAS 2.0, and validly monitored over time. Routine use of this self-reported measure in clinical and research practice would give valuable information on the trajectories of disability of individuals and groups.

Measuring coping in multiple sclerosis: The Coping Index-MS.

BACKGROUND: Coping in multiple sclerosis (MS) refers to cognitive and behavioural efforts to manage stresses imposed by the illness. Existing generic and disease-specific coping scales do not meet modern guidelines for scale development and cannot produce interval-level metrics to allow for change scores. OBJECTIVE: The main aim of this study was to develop a brief patient-reported outcome measure for coping in MS, capable of interval-level measurement. METHODS: Qualitative work in 43 people with MS leads to a draft scale which was administered to 5747 participants, with longitudinal collection in 2290. A calibration sample of 1000 subjects split into development and validation sets was used to generate three scales consistent with Rasch model expectations. RESULTS: The total Coping Index-MS (CI-MS-T), CI-MS-Internal (CI-MS-I) and CI-MS-External (CI-MS-E) cover total, internal and externally focused coping. All three scales are capable of interval-level measurement. Trajectory analysis of 9000 questionnaires showed two trajectories in CI-MS-T: Group 1 showed a low level of coping with slight decline over 40 months, while Group 2 had a better and stable level of coping due to improving CI-MS-I which compensated for the deteriorating CI-MS-E over time. CI-MS-T < 30 identified group membership at baseline. CONCLUSION: The CI-MS-T, CI-MS-I and CI-MS-E, comprising 20 items, provide interval-level measurement and are free-for-use in not-for-profit settings.

Identifying Progression in Multiple Sclerosis: New Perspectives.

The identification of progression in multiple sclerosis is typically retrospective. Given the profound burden of progressive multiple sclerosis, and the recent development of effective treatments for these patients, there is a need to establish measures capable of identifying progressive multiple sclerosis early in the disease course. Starting from recent pathological findings, this review assesses the state of the art of potential measures able to predict progressive multiple sclerosis. Future promising biomarkers that might shed light on mechanisms of progression are also discussed. Finally, expansion of the concept of progressive multiple sclerosis, by including an assessment of cognition, patient-reported outcomes, and comorbidities, is considered. ANN NEUROL 2020;88:438-452.

A novel in-home digital treatment to improve processing speed in people with multiple sclerosis: A pilot study.

OBJECTIVE: To assess whether a videogame-like digital treatment is superior to a control in improving processing speed in adults with multiple sclerosis (MS). METHODS: Adults with MS and baseline Symbol Digit Modalities Test (SDMT) z-scores between -2 and 0 were enrolled in a double-blind randomized controlled clinical trial. After completing a baseline in-clinic evaluation (Visit 1), they were randomized to complete an in-home, tablet-based videogame-like digital treatment (AKL-T03) or control word game (AKL-T09) for up to 25 minutes/day, 5 days/week, for 6 weeks. A repeat in-clinic evaluation occurred at 6 weeks (Visit 2), and again 8 weeks later to determine persistence of effects (Visit 3). The pre-specified primary outcome was change in SDMT score between Visits 1 and 2. RESULTS: SDMT increased at Visit 2 for participants randomized to both AKL-T03 (p < 0.001) and AKL-T09 (p = 0.024). These respective mean improvements were +6.10 and +3.55 (comparison p = 0.21). At Visit 3, 70% of participants randomized to AKL-T03 maintained a clinically meaningful 4+-point increase in SDMT above their baseline, compared with 37% for AKL-T09 (p = 0.038). CONCLUSION: This in-home digital intervention resulted in substantial and durable improvements in processing speed. A larger randomized controlled clinical trial is planned. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov under "NCT03569618," https://clinicaltrials.gov/ct2/show/NCT03569618.

Baseline characteristics and effects of fingolimod on cognitive performance in patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Studies reporting the baseline determinants of cognitive performance and treatment effect on cognition in patients with multiple sclerosis (MS) are limited. We investigated the baseline correlates of cognition and the long-term treatment effects of fingolimod 0.5 mg once daily on cognitive processing speed and attention in patients with relapsing-remitting MS. METHODS: This post hoc analysis pooled data from the phase 3 FREEDOMS and FREEDOMS II trials (N = 1556). We assessed the correlation between baseline patient demographic and disease characteristics and baseline 3-second Paced Auditory Serial Addition Test (PASAT-3) scores (Spearman's rank test) and the changes from baseline in PASAT-3 (mixed model repeated measures model) in the fingolimod and placebo (up to 24 months) or placebo-fingolimod switched (from Month 24 up to 120 months) groups. Additionally, the predictive value of PASAT-3 score for future disease outcomes was assessed (Cox or logistic regression models). RESULTS: Among the variables assessed, lower PASAT-3 score at baseline correlated with higher disease burden (total brain volume, T2 lesion volume, and Expanded Disability Status Scale score), longer disease duration and older age (p < 0.0001 for all). Fingolimod significantly improved PASAT-3 scores from baseline versus placebo at 6 (1.3; p = 0.0007), 12 (1.1; p = 0.0044) and 24 months (1.1; p = 0.0028), with a sustained effect (overall treatment effect p = 0.0012) up to 120 months. Improvements were seen regardless of baseline cognitive status (PASAT quartile). Baseline PASAT-3 score was predictive of both clinical and magnetic resonance imaging measures of disease activity at Month 24 (p < 0.001 for all). CONCLUSION: Early fingolimod treatment may offer long-term cognitive benefit in patients with relapsing-remitting MS.

Polish validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS battery): correlation of cognitive impairment with mood disorders and fatigue.

BACKGROUND: Cognitive impairment is recognised as a significant clinical issue in Multiple Sclerosis (MS). It can occur at any stage of the disease, affecting quality of life, occupational activity, and adherence to therapy. This makes the availability of a validated assessment tool for detecting and monitoring cognitive dysfunction in multiple sclerosis essential. The Brief International Cognitive Assessment for Multiple Sclerosis is a practical and simple means of administering a battery of three neuropsychological tests, and does not require any formal neuropsychological training. OBJECTIVE: To establish the validity of BICAMS in the Polish MS population; to assess the correlations of cognitive status with demographic and clinical factors, including affective symptoms and fatigue. METHODS: BICAMS was administered to 61 MS patients and 61 HC subjects. Examination of 20 participants with MS was repeated after one to three weeks to assess test-retest reliability. The patients with MS and HC subjects also completed the Hospital Anxiety and Depression Scale (HADS) and Modified Fatigue Impact Scale (MFIS). RESULTS: The MS group performed worse than the HC group in all three BICAMS components, obtaining the following values respectively: 51.7 and 56.1 (p = 0.02) for CVLT, 25 and 28 (p = 0.03) for BVMT-R, and 48.8 and 57.2 (p < 0.001) for SDMT. All BICAMS tests had very significant correlations in test-retest reliability (r = 0.83, p < 0.001 for CVLT; r = 0.84, p < 0.001 for BVMTR; r = 0.9, p < 0.001 for SDMT). 34% of MS patients presented cognitive dysfunction based on the criterion of one or more test scores below the 5th percentile value of the HC group. Significant anxiety and depressive symptoms were reported by 31.1% and 18.0% of MS patients. 31.1% of PwMS reported significant fatigue. BICAMS test results were not associated with HADS or MFIS scores. CONCLUSIONS: The Polish version of BICAMS is a valid and reliable tool for the assessment of cognitive impairment in patients with MS.

Learning ability correlates with brain atrophy and disability progression in RRMS.

OBJECTIVE: To assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis. METHODS: We compared screening (day -14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years. RESULTS: The mean PASAT score at screening was 45.38, increasing on average by 3.18 from day -14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates. CONCLUSIONS: Short-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment.

The effect of self-assessed fatigue and subjective cognitive impairment on work capacity: The case of multiple sclerosis.

OBJECTIVES: The impact of physical disability in multiple sclerosis on employment is well documented but the effect of neurological symptoms has been less well studied. We investigated the independent effect of self-reported fatigue and cognitive difficulties on work. METHODS: In a large European cost of illness survey, self-reported fatigue, subjective cognitive impairment (SCI), and productivity at work were assessed with visual analogue scales (VAS 0-10). The analysis controlled for country, age, age at diagnosis, gender, education, and physical disability. RESULTS: A total of 13,796 patients were of working age and 6,598 were working. Physical disability had a powerful impact on the probability of working, as did education. The probability of working was reduced by 8.7% and 4.4% for each point increase on the VAS for SCI and fatigue, respectively ( p < 0.0001). Regular work hours decreased linearly with increasing severity of fatigue and cognitive problems, while sick leave during the 3 months preceding the assessment increased. Finally, the severity of both symptoms was associated with the level at which productivity at work was affected ( p < 0.0001). CONCLUSION: Our results confirm the independent contribution of self-reported fatigue and SCI on work capacity and highlight the importance of assessment in clinical practice.

Predictive validity of NEDA in the 16- and 21-year follow-up from the pivotal trial of interferon beta-1b.

BACKGROUND: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS). OBJECTIVE: To examine the predictive validity of different NEDA definitions. METHODS: Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed. NEDA in the first 2 years was defined as follows: clinical NEDA: no relapses or Expanded Disability Status Scale (EDSS) progression from baseline to Year 2; NEDA-3a: no relapses, no confirmed ⩾1-point EDSS progression, and no new T2-active lesions; NEDA-3b: no relapses, no EDSS progression, and no increase in T2 burden of disease (T2-BOD); and NEDA-4: no relapses, no EDSS progression, and no increase in T2-BOD or atrophy. NDOs were defined as death, need for wheelchair, EDSS ⩾6, or progressive MS. RESULTS: A total of 245 and 371 patients were evaluated at 16 and 21 years, respectively. Clinical NEDA predicted NDOs ( p = 0.0029), as did baseline EDSS ( p < 0.0001), baseline T2-BOD ( p < 0.0001), and change in T2-BOD ( p = 0.0033). IFNB-1b treatment ( p = 0.0251), relapse rate in the 2 years before study start ( p = 0.0260), T2-BOD at baseline ( p = 0.0014), and change in T2-BOD ( p = 0.0129) predicted survival at 21 years. CONCLUSION: Clinical NEDA predicted long-term disability outcome. By contrast, definitions of NEDA that included on-therapy changes in magnetic resonance imaging variables did not increase the predictive validity.

Influence of different rehabilitative aerobic exercise programs on (anti-) inflammatory immune signalling, cognitive and functional capacity in persons with MS - study protocol of a randomized controlled trial.

BACKGROUND: Studies have shown positive effects of therapeutic exercise on motor- and cognitive function as well as on psychosocial outcomes in persons with multiple sclerosis (MS). A reduction of inflammatory stress through physical exercise has been suspected as one key mechanism, mediating the positive effects of exercise in the context of MS. The primary objective of this trial is to investigate the acute and chronic effects of different exercise modalities on (anti-)inflammatory immune signalling as well as on cognitive and functional capacity in persons with MS. METHODS: A two armed single-blind randomized controlled design will investigate 72 persons with relapsing remitting or secondary progressive MS (EDSS 3.0-6.0), during 3 weeks of inpatient rehabilitation. Participants will be randomized into either a high-intensity interval training (HIIT) or a moderate continuous training group; the latter represents the local standard therapy (ST). Both groups will exercise 3x per week. The HIIT group will perform 5 × 1.5-min high-intensive exercise bouts at 95-100% of their maximum heart rate (HRmax) followed by active breaks of unloaded pedalling (60% HRmax) for 2 min. In contrast, the ST group will exercise for 24 min continuously at 65% of HRmax. The proportion of circulating regulatory T-cells will be measured as primary outcome. Secondary outcomes comprise numbers and proportions of further immune cells including Th17-cells, soluble factors ((anti-) inflammatory cytokines, tryptophan metabolites), endurance capacity, cognitive performance, processing skills for activities of daily living, fatigue, depression and healthcare-related quality of life. Outcomes will be assessed before (T0) and after (T3) the 3-week exercise intervention program. Blood samples of T0 will be taken immediately before the first exercise session. Additionally, blood samples for the soluble factors will be collected immediately after (T1) and three hours (T2) after the first exercise session of each group. DISCUSSION: This study will be the first to investigate both acute and chronic effects of aerobic exercise on immune function and disease associated biomarkers in persons with MS. Combining biological analyses with cognitive and functional capacity assessments may contribute to a better understanding of responses to rehabilitative training, needed to improve exercise recommendations for persons with MS. TRIAL REGISTRATION: This trial was prospectively registered at ClinicalTrials.gov ( NCT03652519 ; 29 August 2018).

Usability of Health Information Websites Designed for Adolescents: Systematic Review, Neurodevelopmental Model, and Design Brief.

BACKGROUND: Adolescence is a unique developmental period characterized by biological, social, and cognitive changes, as well as an interest in managing one's own health care. Many adolescents use the internet to seek health care information. However, young people face barriers before they can understand and apply the health information that they access on the web. It is essential that usability of adolescent health websites on the internet is improved to help adolescents overcome these barriers and allow them to engage successfully with web-based health care content. OBJECTIVE: The aim of this review was to synthesize the usability of specific health information websites. These findings were mapped onto the adolescent neurodevelopmental profile, and a design brief based on the findings was developed to tailor future websites for specific adolescent requirements. METHODS: A systematic search conducted using PubMed, PsycINFO, and Education Resources Information Center (ERIC) identified 25 studies that assessed the usability of health information websites. Adolescent feedback was collected by a mixture of surveys, focus groups, interviews, and think-aloud procedures. RESULTS: A majority of the information websites were developed for specific health issues that may be relevant to adolescents. The most preferred website features were interactive content such as games and quizzes, as well as videos, images, audio clips, and animations. Participants also preferred communicating with other adolescents with similar conditions or learning about their experience through real stories and testimonials. Adolescents found it difficult to use health information websites if they contained too much text, were too cluttered, or had features that made it difficult to access. The findings are considered in the context of adolescent social processes, low tolerance of delayed gratification, and attraction to novelty and mapped onto a neurodevelopmental model of adolescence. CONCLUSIONS: Young people's feedback can determine usability and content that make a health information website easy or informative to use. Neurodevelopmental profiles and the users' specific preferences and skills should be addressed in future development of health information websites for adolescents.

Cognitive impairment in pediatric-onset multiple sclerosis is detected by the Brief International Cognitive Assessment for Multiple Sclerosis and computerized cognitive testing.

BACKGROUND: Cognitive impairment is a common and troubling feature of pediatric-onset multiple sclerosis (POMS). Brief cognitive assessment in the outpatient setting can identify and longitudinally monitor cognitive involvement so that early intervention is possible. OBJECTIVES: The goal of this study was to measure the sensitivity of two cognitive assessment approaches that are brief, repeatable, and suitable for clinical practice and for multicenter investigation. METHODS: Participants with POMS ( n = 69) were consecutively evaluated as part of outpatient neurologic visits and compared to healthy control participants (HC, n = 66) using the Brief International Cognitive Assessment for MS (BICAMS) approach and timed information processing measures from Cogstate, a computer-based assessment. RESULTS: There was strong agreement in the detection rate of impairment between both assessments, with 26% for the BICAMS and 27% for Cogstate. Two of the Cogstate tasks were the most sensitive individual measures. CONCLUSION: Both the BICAMS and Cogstate timed processing measures offer practical, sensitive, and standardized approaches for cognitive screening assessment in POMS.

High-intensity interval exercise improves cognitive performance and reduces matrix metalloproteinases-2 serum levels in persons with multiple sclerosis: A randomized controlled trial.

BACKGROUND: Aerobic exercise can improve cognitive performance in healthy elderly people. OBJECTIVE: The aim of this study was to investigate the influence of a 3-week high-intensity aerobic exercise programme (high-intensity training group (HIT)) on cognitive performance in persons with multiple sclerosis (MS) compared with a standard exercise programme (control training (CT)). METHODS: A total of 60 persons with MS (Expanded Disability Status Scale (EDSS): 1.0-6.5) were randomized to a HIT group (3×/week for 20 minutes, including five 3-minute exercise intervals at 80% of peak oxygen uptake (VO2-peak)) or a CT group (continuously 5×/week for 30 minutes/session at 65% of VO2-peak). Cognitive performance was assessed using the Brief International Cognitive Assessment for MS at entry ( t0) and discharge ( t1). Furthermore, VO2-peak, brain-derived neurotrophic factor, serotonin and matrix metalloproteinases (MMP)-2 and -9 were measured. RESULTS: Compared to CT, HIT significantly improved verbal memory. Significant improvements over time in executive functions were found in both groups. Secondary outcomes indicated significant improvements in VO2-peak and a significant reduction in MMP-2 in the HIT group only. CONCLUSION: HIT represents a promising strategy to improve verbal memory and physical fitness in persons with MS. Further research is needed to determine the impact of exercise on biomarkers in MS.

Best Methods of Communicating Clinical Trial Data to Improve Understanding of Treatments for Patients with Multiple Sclerosis.

BACKGROUND: Patients' understanding of treatment risks and benefits is a prerequisite for shared decision making. Yet, patients with multiple sclerosis (MS) do not accurately understand treatment information provided in regular clinical consultations. OBJECTIVES: To identify the best methods of communicating clinical trial data to improve the understanding of treatments among patients with MS and to also examine the relationship between patients' understanding with decisional conflict, individual traits, and MS symptoms. METHODS: A repeated-measures study was used. A sample of relapsing-remitting patients with MS was recruited from National Health Service sites in the United Kingdom. Patients were presented with hypothetical treatment risks and benefits from faux clinical trials. Treatments were communicated using absolute terms, relative terms, and numbers needed to treat/harm. The presence of baseline information with each method was also manipulated. Patients' understanding and conflict in treatment decisions were assessed. Individual traits and MS symptoms were also recorded. RESULTS: Understanding was better when treatments were communicated in absolute terms (mean 3.99 ± 0.93) compared with relative terms (mean 2.93 ± 0.91; P < 0.001) and numbers needed to treat/harm (mean 2.89 ± 0.88; P < 0.001). Adding baseline information to all methods significantly improved understanding (mean 5.04 ± 0.96) compared with no baseline information (mean 1.50 ± 0.74; P < 0.001). Understanding was not related to conflict in treatment decisions (r = -0.131; P = 0.391). Numeracy, IQ, and cognitive impairments were significantly related to patients' understanding of treatments. CONCLUSIONS: Treatment risks and benefits should ideally be communicated using absolute terms, alongside baseline information. Patients with MS with low numeracy, low IQ, and reduced cognitive skills should be supported during treatment education.

Validation of the brief international cognitive assessment for multiple sclerosis (BICAMS) in the Portuguese population with multiple sclerosis.

BACKGROUND: The validation of international cognitive batteries in different multiple sclerosis (MS) populations is essential. Our objective was to obtain normative data for the Portuguese population of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and assess its reliability. METHODS: The BICAMS was applied to 105 MS patients and 60 age, gender and education matched healthy controls (HC). In order to test its reliability, BICAMS was re-administered in a subset of 25 patients after a 7-month interval. RESULTS: Most participants were women, with a mean age of 37, 21 years and a mean of 14,08 years of education. The vast majority of the MS patients (92.4%) had the relapsing remitting type, 58.1% were professionally active, mean disease duration was 6.52 years, median EDSS score was 1.5 (range: 0-6.0) and the median MSSS score was 2.01 (IQR range: 3.83). The MS group presented significantly higher scores of anxiety and depression than HC and 47,4% had fatigue. The MS group performed significantly worse than the control group across the three neuropsychological tests, yielding the following values: SDMT: t(165) = 3.77, p = .000; CVLT-II: t(165) = 2.98, p = .003; and BVMT-R: t(165) = 2.94, p = .004. The mean raw scores for Portuguese normative data were as follows: SDMT: 58.68 ± 10.02; CVLT-II: 60.47 ± 10.12; and BVMT-R: 24.68 ± 5.52. Finally, test-retest reliability coefficients for each test were as follows: SDMT: r = .90; CVLT-II: r = .71; and BVMT-R: r = .84. CONCLUSIONS: The Portuguese version of BICAMS here in described is a reliable monitoring instrument for identifying MS patients with cognitive impairment.

The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS): normative values with gender, age and education corrections in the Italian population.

BACKGROUND: BICAMS (Brief International Cognitive Assessment for Multiple Sclerosis) has been recently developed as brief, practical and universal assessment tool for cognitive impairment in MS subjects. It includes the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT2) and the Brief Visuospatial Memory Test-Revised (BVMT-R) . In this study we aimed at gathering regression based normative data for the BICAMS battery in the Italian population. METHODS: Healthy subjects were consecutively recruited among patient friends and relatives. Corrections for demographics were calculated using multivariable linear regression models. Test-retest reliability was assessed using the Pearson correlation coefficient. RESULTS: The BICAMS battery was administered to 273 healthy subjects (180 women, mean age 38.9 ± 13.0 years, mean education 14.9 ± 3.0 years). Test-retest reliability was good for all the tests. CONCLUSIONS: The study provided normative data of the BICAMS for the Italian population confirming good test-retest reliability which can facilitate the use of the battery in clinical practice, also for longitudinal patient assessments.