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.

Improving MS patients' understanding of treatment risks and benefits in clinical consultations: A randomised crossover trial.

BACKGROUND: Multiple Sclerosis (MS) patients find it difficult to understand the complex risk-benefit profiles of disease-modifying drugs. An evidence-based protocol was designed to improve patient's understanding of treatment information: Benefit and Risk Information for Medication in Multiple Sclerosis (BRIMMS). OBJECTIVE: A feasibility study to evaluate whether the BRIMMS protocol can improve MS patients' treatment understanding and reduce conflict in treatment decisions compared to consultation as usual. DESIGN: Single-blind 4-condition 4-period randomised crossover trial. Hypothetical treatment information was presented to MS patients in a faux 20 minute consultation session using the BRIMMS protocol (aural and visual) or as a usual consultation (aural and visual). Patients were randomised to the order in which they received the four consultation styles. PARTICIPANTS: 24 patients diagnosed with relapsing-remitting MS. MEASURES: Patients were assessed on their comprehension of treatment information, decisional conflict and feedback on consultation styles. Disease and demographic information was also collected. RESULTS: Treatment understanding was greater for both BRIMMS visual and BRIMMS aural, compared to usual consultations in visual or aural format. Similarly, BRIMMS visual and BRIMMS aural reduced decisional conflict compared to usual consultations in visual or aural formats. All comparisons were p<0.001. Cognitive status was not related to understanding in the BRIMMS protocol, but was negatively related with usual consultation. Conversely, mood influenced understanding on the BRIMMS protocol but not for usual consultation. CONCLUSIONS: BRIMMS protocol offers an effective, evidence-based tool for presenting treatment information in consultations with MS patients and is not influenced by cognition. TRIAL REGISTRATION: ISRCTN17318966.

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.

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.

Multiple sclerosis patients' understanding and preferences for risks and benefits of disease-modifying drugs: A systematic review.

BACKGROUND: Multiple sclerosis (MS) patients are faced with complex risk-benefit profiles of disease-modifying drugs (DMDs) when making treatment decisions. For effective shared decision-making, MS patients should understand the risks and benefits of DMDs and make treatment decisions based on personal preferences. METHODS: This is an inclusive systematic review to primarily assess current understanding of MS patients for information about DMDs provided during the standard healthcare system. The secondary aim assesses MS patients' preferences for specific risks and benefits of treatments. A systematic search was conducted using PubMed, Embase and Google Scholar. A total of 22 studies were reviewed across both aims. Relevant quantitative and qualitative data was extracted by two authors. A narrative synthesis was conducted due to heterogeneity of research findings. RESULTS: There was a trend for DMD risks to be generally underestimated and DMD benefits to be generally overestimated by MS patients. Treatments that could potentially offer substantial symptom improvement, delay in disease progression, or reduction in relapses were preferred even at the expense of higher risks. CONCLUSIONS: Many patients' experience of information during the standard healthcare system does not provide satisfactory understanding of the risks and benefits of DMDs. Effective ways to communicate risk and benefit DMD information when making shared treatment decisions needs to be identified. Patient preferences of DMD risks and benefits should also be taken into account.

Interventions to support risk and benefit understanding of disease-modifying drugs in Multiple Sclerosis patients: A systematic review.

OBJECTIVE: The present review evaluates interventions that have been designed to improve understanding of the complex risk-benefit profiles of disease-modifying drugs (DMDs) in patients with Multiple Sclerosis (MS). METHODS: A systematic search conducted using PubMed, Embase, Google Scholar and PsycINFO identified 15 studies. Interventions which provided treatment information were present across a range of study designs. A narrative synthesis was conducted due to heterogeneity of research findings. RESULTS: Interventions providing treatment information ranged from comprehensive education programmes to booklets of a few pages. MS patients favoured the interventions they received. Understanding of overall treatment information and treatment risks specifically, generally improved following interventions. Yet overestimation of treatment benefits persisted. There was no conclusive effect on DMD decisions. No superior intervention was identified. CONCLUSION: Interventions designed to improve understanding of DMD risk and benefit information are moderately successful. PRACTICE IMPLICATIONS: Additional support provided to MS patients beyond routine healthcare can generally improve understanding of the complex risk-benefit profiles of DMDs. Future interventions need to ensure that patients with symptoms that may confound understanding can also benefit from this additional information.

The Hungarian validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery and the correlation of cognitive impairment with fatigue and quality of life.

BACKGROUND: Multiple Sclerosis (MS) causes not only somatic, but also cognitive impairment regardless of the patients׳ age or the course of the disease. The Brief International Cognitive Assessment for MS (BICAMS) test, published in 2011, is a short cognitive questionnaire: a fast, reliable, sensitive and specific tool for the evaluation of the patients׳ cognitive state. OBJECTIVES: Our primary objective was to assess the validity of the Hungarian version of the BICAMS test. Our secondary objective was to evaluate the impact of the cognitive impairment on the patient׳s quality of life and fatigue׳s impact on the patients׳ cognitive state. METHODS: 65 RR-MS patients and 65 age, sex and education matched healthy control (HC) subjects completed the test and were retested after 3 weeks. The patients also completed the MS Quality of Life 54 (MSQoL54) and the Fatigue Impact Scale (FIS) assessments. Group differences were calculated by paired sample T-tests. The test-retest reliability was measured by intraclass correlation coefficients. To analyze the difference between the test-retest performances of the two groups we used two-way repeated measures ANOVA where the BICAMS battery was the single composite outcome and one-way repeated measures ANOVA. To assess the impact of the cognitive decline on the patients׳ quality of life and fatigue׳s impact on the cognitive state, we examined the correlations between results in the BICAMS and the MSQoL54 and FIS. RESULTS: We found significant difference (p ≤ 0.001, p = 0.017 in the first CVLT-II assessment) between MS patients and members of the HC group in all four evaluated parameters of BICAMS test in both sessions. The correlation coefficients were very strong between the tests and retests (r > 0.8; p < 0.001; r = 0.678, p < 0.001 between the CVLT-II assessments). We found that the HC group performed significantly (p = 0.020) better in the retest sessions as compared to their original performance than the patients did and this difference is solely due to the difference between the CVLT-II performances. We have found significant negative correlation between the patients׳ cognitive function and the fatigue score (r < -0.3, p < 0.05). Seven of the MSQoL-54 subscales correlated with the BICAMS performance (r > 0.3; < 0 .05). CONCLUSIONS: The Hungarian version of the BICAMS test is a valid and reliable method for the evaluation of MS patients׳ cognitive function. It seems that because of the short retest period, the members of the HC group remembered the CVLT-II words thus performed better than the patients did. Also apparently fatigue can have a negative impact on the patients׳ cognitive state, and cognitive impairment could worsen the patients׳ quality of life.

Cognition in multiple sclerosis.

PURPOSE OF REVIEW: A broad overview of cognition in multiple sclerosis (MS) is provided, taking account of its impact on the lives of patients, how cognitive impairment relates to disease and magnetic resonance variables, which cognitive domains are most vulnerable, the influence of depression and fatigue and what treatment options are available. RECENT FINDINGS: The current focus is on cognitive reserve, which seems to offer some protection from the cognitive impact of MS. There is also considerable momentum with new MRI techniques and growing interest in PET studies. SUMMARY: Cognition in MS is a priority for patients. Although understanding of the natural history of MS cognitive deficits is reasonably well understood, treatment options require further work before precise recommendations can be made on an individual basis.

Future-directed thinking and depression in relapsing-remitting multiple sclerosis.

BACKGROUND: Research has shown that depression is associated with a view of the future characterized by reduced anticipation of future positive experiences, but not necessarily increased anticipation of future negative experiences. The aim of the present study was to investigate how participants with relapsing-remitting multiple sclerosis (MS) anticipated their future in terms of positive and negative events. DESIGN: A mixed design compared three groups of participants on a measure of future thinking using an adapted verbal fluency paradigm. METHODS: Depressed MS participants (N=14), non-depressed MS participants (N=28) and healthy control participants (N=26) were assessed on their ability to generate future positive and negative experiences. A content analysis was also conducted on the responses generated by the MS depressed and MS non-depressed groups according to whether or not they were related to MS. RESULTS: The MS depressed group anticipated significantly fewer future positive events than the healthy control group and the MS non-depressed group. The three groups did not differ in the total numbers of anticipated future negative events, though the MS depressed group did anticipate a significantly higher proportion of MS-related negative events. CONCLUSIONS: Like depressed but physically healthy individuals, the MS depressed group was characterized by a lack of positive thoughts about the future, rather than an increased number of negative thoughts. The clinical implications of these findings are discussed along with recommendations for future research.

Does the spelling dyslexic read by recognizing orally spelled words? An investigation of a letter-by-letter reader.

In this single case report we describe our further observations of a patient (ROC) with a classical spelling dyslexia. A word length effect and a script effect were demonstrated. No evidence of semantic processing was obtained with brief tachistoscopic presentations. Single letter identification was unimpaired. In a series of experiments it was shown that her letter-by-letter reading strategy was mediated by explicit letter naming. In particular, it was observed that with successive presentation of the individual letters there was a stepwise function relating her whole word reading to the single letter presentation times. These durations permitted explicit letter naming. When explicit letter naming was prevented by a simultaneous articulatory suppression task, her letter-by-letter reading was significantly impaired. Her performance was compared with a second patient (MRF) who could read but could not spell. His reading was unaffected by articulatory suppression and significantly impaired by a successive presentation of the individual letters of a word. It is argued that explicit letter naming provides an input to the spelling system and thus can be recognized as orally spelled words. We conclude that in the reading-impaired patient there was a lexical deficit compensated for by the operation of a component of her intact spelling system.

Minimal neuropsychological assessment of MS patients: a consensus approach.

Cognitive impairment is common in multiple sclerosis (MS), yet patients seen in MS clinics and neurologic practices are not routinely assessed neuropsychologically. In part, poor utilization of NP services may be attributed to a lack of consensus among neuropsychologists regarding the optimal approach for evaluating MS patients. An expert panel composed of neuropsychologists and psychologists from the United States, Canada, United Kingdom, and Australia was convened by the Consortium of MS Centers (CMSC) in April, 2001. Our objectives were to: (a) propose a minimal neuropsychological (NP) examination for clinical monitoring of MS patients and research, and (b) identify strategies for improving NP assessment of MS patients in the future. The panel reviewed pertinent literature on MS-related cognitive dysfunction, considered psychometric factors relevant to NP assessment, defined the purpose and optimal characteristics of a minimal NP examination in MS, and rated the psychometric and practical properties of 36 candidate NP measures based on available literature. A 90-minute NP battery, the Minimal Assessment of Cognitive Function in MS (MACFIMS), emerged from this discussion. The MACFIMS is composed of seven neuropsychological tests, covering five cognitive domains commonly impaired in MS (processing speed/working memory, learning and memory, executive function, visual-spatial processing, and word retrieval). It is supplemented by a measure of estimated premorbid cognitive ability. Recommendations for assessing other factors that may potentially confound interpretation of NP data (e.g., visual/sensory/motor impairment, fatigue, and depression) are offered, as well as strategies for improving NP assessment of MS patients in the future.