Coping and psychological well-being among persons with relapsing-remitting multiple sclerosis: The role of perceived self-efficacy.

OBJECTIVE: To explore self-efficacy as a possible mediator in the relationship between adaptive coping and psychological well-being (PWB) in persons with relapsing-remitting multiple sclerosis (RRMS). METHOD: 174 persons with RRMS (91% Female) completed an online survey consisting of psychosocial questionnaires. The COPE Inventory was used to create an adaptive coping composite that accounts for the relative contributions of both active and avoidant coping. Self-efficacy was measured using the General Self-Efficacy Scale. The Ryff Psychological Well-Being Scales captured several domains of PWB: Positive relations with others, autonomy, purpose in life, environmental mastery, self-acceptance, and personal growth. The SPSS PROCESS macro was used to test whether self-efficacy mediated the association between adaptive coping and each PWB subscale, using 5,000 bootstrap samples to estimate confidence intervals. RESULTS: In each mediational model, adaptive coping was significantly associated with each PWB subscale and self-efficacy (all p's ≤ 0.001). Self-efficacy was also significantly associated with each PWB subscale (p ≤ 0.001). After controlling for self-efficacy, the associations between adaptive coping and positive relations with others (indirect effect = 0.021, 95% CI [0.011, 0.033]) and autonomy (indirect effect = 0.019, 95% CI [0.011, 0.028]) became non-significant. The separate associations between adaptive coping and purpose in life (p = .004), self-acceptance (p = .026), and personal growth (p < .001) remained significant, despite controlling for self-efficacy. CONCLUSIONS: Self-efficacy fully mediated the relationships between adaptive coping and positive relations with others and autonomy in our sample of persons with RRMS. Interventions aimed at increasing adaptive coping skills and self-efficacy may improve relations with others and autonomy among persons with MS.

Predicting clinical progression and cognitive decline in patients with relapsing-remitting multiple sclerosis: a 6-year follow-up study.

INTRODUCTION: Cognitive impairment occurs from the earliest stages of multiple sclerosis (MS) and progresses over time. The introduction of disease modifying therapies (DMTs) has changed the prognosis for MS patients, offering a potential opportunity for improvement in the cognitive arena as well. MATERIAL AND METHODS: 41 patients with relapsing-remitting multiple sclerosis (MS) were recruited to the study. Thirty patients were available for final follow-up and were included in the analysis. Baseline (BL) brain MRI including volumetry and neuropsychological tests were performed. Blood samples were collected at BL and follow-up (FU) and were tested for: vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM1), soluble platelet-endothelial CAM-1 (sPECAM1), and soluble intercellular CAM-1 (sICAM-1). Patients were invited for a final neuropsychological follow-up after a median of 6 years. Disease activity (relapses, EDSS increase, new/active brain lesions on MRI) was analysed between BL and FU. RESULTS: The study group deteriorated in the Rey-Osterrieth Complex Figure (ROCF) test (p = 0.001), but improved significantly in three other tests, i.e. semantic fluency test (p = 0.013), California Verbal Learning Test (CVLT, p = 0.016), and Word Comprehension Test (WCT, p < 0.001). EDSS increase correlated negatively with semantic fluency and WCT scores (r = -0.579, p = 0.001 and r = -0.391, p = 0.033, respectively). Improvements in semantic fluency test and WCT correlated positively with baseline deep grey matter, grey matter, and cortical volumes (p < 0.05, r > 0). Higher EDSS on FU correlated significantly negatively with baseline left and right pallidum, right caudate, right putamen, right accumbens, and cortical volume (p < 0.05, r < 0). No significant relationship was found between the number of relapses and EDSS on FU or neuropsychological deteriorations. Improvements in WCT and CVLT correlated positively with baseline sPECAM1 and sVCAM1 results, respectively (r > 0, p < 0.05). Deterioration in ROCF test correlated significantly with higher levels of baseline VEGF and sVCAM1 (p < 0.05). CONCLUSIONS: Brain volume is an important predictor of future EDSS and cognitive functions outcome. MS patients have a potential for improving in neuropsychological tests over time. It remains to be established whether this is related to successful disease modification with immunotherapy. Baseline volumetric measures are stronger predictors of cognitive performance than relapse activity, which yet again highlights the importance of atrophy in MS prognosis.

Identifying and understanding cognitive profiles in multiple sclerosis: a role for visuospatial memory functioning.

BACKGROUND: The heterogeneous nature of cognitive impairment in people with multiple sclerosis (PwMS) hampers understanding of the underlying mechanisms and developing patient-tailored interventions. We aim to identify and classify cognitive profiles in PwMS, comparing these to cognitive status (preserved versus impaired). METHODS: We included 1213 PwMS (72% female, age 45.4 ± 10.7 years, 83% relapsing-remitting MS). Cognitive test scores were converted to Z-scores compared to healthy controls for the functions: attention, inhibition, information processing speed (IPS), verbal fluency and verbal/visuospatial memory. Concerning cognitive status, impaired cognition (CI) was defined as performing at Z ≤ - 1.5 SD on ≥ 2 functions. Cognitive profiles were constructed using latent profile analysis on all cognitive functions. Cognitive profiles or status was classified using gradient boosting decision trees, providing the importance of each feature (demographics, clinical, cognitive and psychological functioning) for the overall classification. RESULTS: Six profiles were identified, showing variations in overall performance and specific deficits (attention, inhibition, IPS, verbal fluency, verbal memory and visuospatial memory). Across the profiles, IPS was the most impaired function (%CI most preserved profile, Profile 1 = 22.4%; %CI most impaired profile, Profile 6 = 76.6%). Cognitive impairment varied from 11.8% in Profile 1 to 95.3% in Profile 6. Of all cognitive functions, visuospatial memory was most important in classifying profiles and IPS the least (area under the curve (AUC) = 0.910). For cognitive status, IPS was the most important classifier (AUC = 0.997). CONCLUSIONS: This study demonstrated that cognitive heterogeneity in MS reflects a continuum of cognitive severity, distinguishable by distinct cognitive profiles, primarily explained by variations in visuospatial memory functioning.

Meaningful Change Thresholds and Fatigue Severity Points on Patient-Reported Outcomes by the Fatigue Symptoms and Impacts Questionnaire in Patients With Relapsing Multiple Sclerosis.

OBJECTIVES: The Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) is a new content-valid, concise, and reliable 20-item patient-reported outcome measure to evaluate the symptoms and impacts of fatigue in patients with relapsing forms of multiple sclerosis. Analyses were performed to derive meaningful change thresholds (MCTs) on patient-reported outcomes as measured by FSIQ-RMS and generate receiver operating characteristic (ROC) curves to determine fatigue severity cut points at baseline and change in severity at post-baseline and supplement the anchor-based MCT results. METHODS: Analyses were based on data from the OPTIMUM trial (NCT02425644). An anchor-based approach using uncollapsed changes on the Patient Global Impression of Severity at week 108 were used to determine the MCT for only the FSIQ-RMS Symptoms domain; distribution-based MCT estimations were conducted using baseline FSIQ-RMS Impacts scores. ROC curves with calculation of area under the curve were used to identify the best cut point. RESULTS: Based on the evidence provided by the anchor-based analyses using the Patient Global Impression of Severity as an anchor for the FSIQ-RMS Symptoms domain, meaningful score changes for improvement and deterioration were -6.3 and 6.3, respectively. Meaningful score changes for the FSIQ-RMS Physical, Cognitive/Emotional, and Coping Impacts domains using distribution-based methods were 10.8, 8.4, and 9.8, respectively. These results are supported by the ROC analyses. CONCLUSIONS: Thresholds to support interpretation of the FSIQ-RMS, such as MCTs, can be used to determine and categorize patients who have experienced a meaningful change in their MS-related fatigue (eg, responder analyses) in future clinical research studies.

Is impairment of facial emotion recognition independent of cognitive dysfunction in multiple sclerosis?

BACKGROUND: Emotions expressed on the face play a key role in social cognition and communication by providing inner emotional experiences. This study aimed to evaluate facial emotion identification and discrimination and empathy abilities in patients with MS and whether it is related to cognitive dysfunction. METHODS: One hundred twenty patients with relapsing-remitting MS and age- and sex-matched 120 healthy controls were enrolled in the study. All the subjects were evaluated with the Facial Emotion Identification Test (FEIT), Facial Emotion Discrimination Test (FEIDT), and Empathy Quotient (EQ). We used the Beck Depression Inventory (BDI) for depression and detailed cognitive tests, including the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Paced Auditory Serial Addition Test (PASAT). The quality of life was assessed with Multiple Sclerosis Quality of Life-54 (MSQL-54). RESULTS: Patients with MS were 37.6 ± 9.5 years old, had a mean disease duration of 8.8 ± 6.6 (8-28) years, and a mean EDSS score of 1.6 ± 1.3 (0-4.5). We found significant differences in the identification of facial emotions, discrimination of facial emotions, and empathy in MS patients compared to controls (p < 0.05). Especially the recognition of feelings of sadness, fear, and shame was significantly lower in MS patients. The multivariate logistic regression analysis showed low SDMT and FEIDT scores which showed an independent association with MS. CONCLUSIONS: Our findings indicate that facial emotion recognition and identification deficits are remarkable among patients with MS and emotion recognition is impaired together with and independently of cognitive dysfunction in MS patients.

Impulsivity and attention deficit-hyperactivity symptoms among patients with relapsing-remitting multiple sclerosis: a case-control study.

BACKGROUND AND OBJECTIVES: Multiple sclerosis(MS) is a progressive, autoimmune, neurodegenerative disease.Studies have suggested that autoimmune diseases play a role in the pathogenesis of Attention deficit and hyperactivity disorder(ADHD).We aim to evaluate ADHD symptoms among patients with RRMS(pwRRMS). METHODS: The study included 48 RRMS patients and 54 healthy controls. ADHD symptoms were assessed by self-report questionnaires and performance tests.Beck Depression Inventory (BDI), Turgay's Turkish version of Adult-ADD/ADHD (A-ADHD), Barratt Impulsivity Scale (BIS-11), and World Health Organization Quality of Life-Short Form (WHOQoL-Bref) were completed by the participants.Stroop Colour and Word Interference Test - TBAG Form (SCWT); was used for assessing cognitive function by a trained psychiatrist. Fatigue Severity Scale (FSS) and Expanded Disability Status Scale (EDSS) were used to evaluate by pwRRMS. RESULTS: PwRRMS had significantly higher attention-deficit scores and poor performance in all SCWT subtests.All SCWT scores were positively correlated with MS duration.A-ADHD-Total scores were negatively correlated with the age of MS diagnosis.A moderate positive correlation was found between falls and A-ADHD-total scores, and psychomotor speed.A moderate negative correlation was found between WHOQoL-Bref scores and BID, FSS, ADHD-Attention Deficit, SCWT-3, SCWT-5, and SCWT-interference.In multivariate linear regression analyzes, attention-deficit predicted EDSS positively, while depressive symptoms, attention-deficit, and psychomotor speed time were negative predictors of physical health quality. CONCLUSIONS: In pwRRMS, cognitive dysfunctions such as response inhibition and intervention control, which are symptoms of attention deficit and impulsivity, have been shown to reduce the overall QoL. Among the strategies to reduce the impact of RRMS disease on patients' lives, it is essential to implement programs to prevent depression and increase cognitive reserve.

[Cognitive impairment in multiple sclerosis: when to think about it?] / Troubles cognitifs dans la sclérose en plaques : quand y penser ?

Cognitive disorders are present in 30 to 45% of relapsing-remitting forms of multiple sclerosis and in up to 50-75% of progressive forms. They bear a negative impact on the quality of life and predict an unfavorable disease progression. According to guidelines, screening based on objective measurement such as the Single Digit Modality Test (SDMT) should be performed at the time of diagnosis and then on an annual basis. Confirmation of diagnosis and management are performed in collaboration with neuropsychologists. Increased awareness from patients and healthcare professionals is important to ensure earlier management and prevent negative consequences on the patients professional and family life.

Les troubles cognitifs sont présents chez 30 à 45 % des patients souffrant d'une forme poussée-rémission de sclérose en plaques (SEP) et chez jusqu'à 50-75 % de ceux souffrant des formes progressives. Ces troubles cognitifs impactent négativement la qualité de vie et sont associés à une progression défavorable de la SEP elle-même. Les recommandations proposent un dépistage au moment du diagnostic, puis annuellement, à l'aide d'un test objectif tel que le Single Digit Modality Test (SDMT) ou équivalents. La confirmation du diagnostic et la prise en charge se font en collaboration avec les neuropsychologues. Une meilleure sensibilisation des patients et des professionnels de santé est nécessaire pour assurer une prise en charge plus précoce et limiter les conséquences négatives sur la vie professionnelle et familiale des patients.

Narrative recall in relapsing-remitting multiple sclerosis: A potentially useful speech task for detecting subtle cognitive changes.

Our research studied relapsing-remitting multiple sclerosis (RRMS). In half of the RRMS cases, mild cognitive difficulties are present, but often remain undetected despite their adverse effects on individuals' daily life. Detecting subtle cognitive alterations using speech analysis have rarely been implemented in MS research. We applied automatic speech recognition technology to devise a speech task with potential diagnostic value. Therefore, we used two narrative tasks adjusted for the neural and cognitive characteristics of RRMS; namely narrative recall and personal narrative. In addition to speech analysis, we examined the information processing speed, working memory, verbal fluency, and naming skills. Twenty-one participants with RRMS and 21 gender-, age-, and education-matched healthy controls took part in the study. All the participants with RRMS achieved a normal performance on Addenbrooke's Cognitive Examination. The following parameters of speech were measured: articulation and speech rate, the proportion, duration, frequency, and average length of silent and filled pauses. We found significant differences in the temporal parameters between groups and speech tasks. ROC analysis produced high classification accuracy for the narrative recall task (0.877 and 0.866), but low accuracy for the personal narrative task (0.617 and 0.592). The information processing speed affected the speech of the RRMS group but not that of the control group. The higher cognitive load of the narrative recall task may be the cause of significant changes in the speech of the RRMS group relative to the controls. Results suggest that narrative recall task may be effective for detecting subtle cognitive changes in RRMS.

Are we ready to define cognitive worsening in MS? How different cutoffs detect future cognitive worsening after six years of follow-up.

BACKGROUND: Although cognitive evaluation has been incorporated in recent MS clinical trials, the definition of cognitive progression is not clear and recent data are questioning the 4-point cutoff using the SDMT at the individual level. We aimed to evaluate the behavior of cognitive performance over time using different cutoffs. METHODS: Cognitive performance over six years was analyzed in a cohort of 42 relapsing-remitting MS patients and 30 controls using verbal/visual memory and information processing speed tests. Fixed cutoffs were: 10% and 20% change (all tests) and a 4- and 8-point change (SDMT). The relative cutoff established by regression-based models was a 1SD change. RESULTS: The distributions of "worsening", "stability", and "improvement" showed low concordance rates across the cutoffs (p < 0.001 for most comparisons). Most patients classified with worsening initially using fixed cutoffs had subsequent improvement in all cognitive tests, yielding a low sensitivity to predict later cognitive worsening. Using the relative cutoff, the proportion of patients with subsequent improvement was noticeably smaller. CONCLUSIONS: Fixed cutoffs classify a high proportion of patients with cognitive improvement. Most patients categorized with worsening initially presented subsequent improvement. Instead, the relative cutoff generally had a better performance. These data raise concerns about how we are defining cognitive worsening so far, especially at the individual level.

Network analysis characterizes key associations between subjective fatigue and specific depressive symptoms in early relapsing-remitting multiple sclerosis.

BACKGROUND: Fatigue is common and disabling in multiple sclerosis (MS), yet its mechanisms are poorly understood. In particular, overlap in measures of fatigue and depression complicates interpretation. We applied a multivariate network approach to quantify relationships between fatigue and other variables in early MS. METHODS: Data were collected from patients with newly diagnosed immunotherapy-naïve relapsing-remitting MS at baseline and month 12 follow-up in FutureMS, a Scottish nationally representative cohort. Subjective fatigue was assessed by Fatigue Severity Scale. Detailed phenotyping included measures assessing each of physical disability, affective disorders, cognitive performance, sleep quality, and structural brain imaging. Network analysis was conducted to estimate partial correlations between variables. Baseline networks were compared between those with persistent and remitted fatigue at one-year follow up. RESULTS: Data from 322 participants at baseline, and 323 at month 12, were included. At baseline, 154 patients (47.8%) reported clinically significant fatigue. In the network analysis, fatigue severity showed strongest connections with depression, followed by Expanded Disability Status Scale. Conversely, fatigue severity was not linked to objective cognitive performance or brain imaging variables. Even after controlling for measurement of "tiredness" in our measure of depression, four specific depressive symptoms remained linked to fatigue. Results were consistent at baseline and month 12. Overall network strength was not significantly different between groups with persistent and remitted fatigue (4.89 vs 2.90, p = 0.11). CONCLUSIONS: Our findings support robust links between subjective fatigue and depression in early relapsing-remitting MS. Shared mechanisms between specific depressive symptoms and fatigue could be key targets of treatment and research in MS-related fatigue.

The effect of self-acupressure on quality of life, physical and cognitive function in relapsing remitting multiple sclerosis patients: A randomized controlled study.

OBJECTIVE: This study was conducted to evaluate the effectiveness of self-acupressure on quality of life, physical and cognitive functions in individuals with Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: In our randomized controlled study; participants in the study group were asked to perform self-acupressure on 6 points. They were asked to perform a total of 16 sessions, 2 days a week, for an average of 27 min each session in the morning and evening. No intervention was made in the control group during the study. Data were collected using Descriptive Information Form, Multiple Sclerosis Functional Composite Test (MSFC), and Multiple Sclerosis Quality of Life 54 Scale (MSQL-54). RESULTS: Thirty-one individuals with RRMS in each group, 25 women in the study group and 21 women in the control group, were included in the study. After the self-acupressure application, a positive and significant difference was detected in all MSFC sub-parameters (9-Hole Peg Test, Timed 25-foot Walk Test, Paced Auditory Serial Addition Test) values of the study group compared to the control group. In addition, after self-acupressure application, the study group was found to have statistically significantly higher scores in both the combined physical health and composite mental health sub-parameters of MSQOL-54 compared to the control group (p < 0.05). CONCLUSION: We found that self-acupressure was effective in improving physical function, cognitive function and quality of life in RRMS patients. Additionally, self-acupressure is a feasible, accessible and inexpensive method in the disease management of multiple sclerosis, which needs to be treated or supported continuously.

Brain volume loss and physical and cognitive impairment in naive multiple sclerosis patients treated with fingolimod: prospective cohort study in Buenos Aires, Argentina.

BACKGROUND: The percentage of brain volume loss (PBVL) has been classically considered as a biomarker in multiple sclerosis (MS). OBJECTIVE: The objective of the present study was to analyze if the PBVL during the 1st year after the onset of the disease predicts physical and cognitive impairment (CI). METHODS: Prospective study that included naïve patients without cognitive impairment who initiated MS treatment with fingolimod. Patients were followed for 3 years and relapses, expanded disability status scale (EDSS) progression (defined as worsening of 1 point on the EDSS), the annual PBVL (evaluated by structural image evaluation using normalization of atrophy [SIENA]), and the presence of CI were evaluated. Cognitive impairment was defined in patients who scored at least 2 standard deviations (SDs) below controls on at least 2 domains. The PBVL after 1 year of treatment with fingolimod was used as an independent variable, while CI and EDSS progression at the 3rd year of follow-up as dependent variables. RESULTS: A total of 71 patients were included, with a mean age of 35.4 ± 3 years old. At the 3rd year, 14% of the patients were classified as CI and 6.2% had EDSS progression. In the CI group, the PBVL during the 1st year was - 0.52 (±0.07) versus -0.42 (±0.04) in the no CI group (p < 0.01; odds ratio [OR] = 2.24; 95% confidence interval [CI]: 1.72-2.44). In the group that showed EDSS progression, the PBVL during the 1st year was - 0.59 (±0.05) versus - 0.42 (±0.03) (p < 0.01; OR = 2.33; 95%CI: 1.60-2.55). CONCLUSIONS: A higher PBVL during the 1st year in naïve MS patients was independently associated with a significant risk of CI and EDSS progression.

ANTECEDENTES: A porcentagem de perda de volume cerebral (PPVC) é um biomarcador na esclerose múltipla (EM). OBJETIVO: Analisar se a PPVC durante o 1° ano após o início da doença prediz deterioração física (DF) e cognitiva (DC) em pacientes com EM. MéTODOS: Estudo de coorte prospectivo que incluiu pacientes recém-diagnosticados sem comprometimento cognitivo que iniciaram tratamento com fingolimode. Os pacientes foram acompanhados por 3 anos, sendo avaliados a presença de recidivas, progressão da Escala Expandida do Estado de Incapacidade (EDSS, na sigla em inglês) (definida como agravamento de 1 ponto na EDSS), o PPVC anual (avaliado pela avaliação de imagem estrutural de atrofia normalizada [SIENA, na sigla em inglês) e a presença de DC (avaliada no início do estudo e nos 2° e 3° anos). O PPVC no 1° ano de tratamento com fingolimode foi utilizado como variável independente. RESULTADOS: foram incluídos 71 pacientes com idade média de 35,4 ± 3 anos. No 3° ano, 14% dos pacientes tiveram DC e 6,2% tiveram progressão de EDSS. No grupo DC, o PPVC durante o 1o ano foi - 0,52 (±0,07) versus - 0,42 (±0,04) no grupo sem DC (p < 0,01; razão de probabilidades [OR, na sigla em inglês] = 2,24; intervalo de confiança [IC] de 95%: 1,72­2,44). No grupo que apresentou progressão da EDSS, o PPVC durante o 1° ano foi de - 0,59 (±0,05) versus - 0,42 (±0,03) (p < 0,01; OR = 2,33; IC95%: 1,60­2,55). CONCLUSõES: Um maior PPVC durante o 1° ano foi associado a um risco significativo de progressão de DC e EDSS durante o seguimento.

Validation of a brief cross-cultural cognitive screening test in Multiple Sclerosis.

BACKGROUND: Several batteries have been developed for the cognitive assessment of people with multiple sclerosis (MS). However, all these tests have some limitations in general clinical practice and from a cross-cultural perspective. In this study, we aimed to validate a novel cognitive screening test, the Cross-Cultural Dementia screening test (CCD), in pwMS. METHODS: Seventy-five participants with relapsing-remitting MS and 75 healthy controls were enrolled and completed a comprehensive neuropsychological battery and the CCD. Intergroup comparisons, effect sizes, and correlations with previously validated tests were calculated for a majority and a pilot study of a minority sample. ROC curves were estimated, and random forest classification models were developed. RESULTS: There were statistically significant differences between cognitively impaired MS (MS-CI) group and healthy controls, and between MS-CI and non-cognitively impaired MS group in all subtests of CCD with medium to large effect sizes. Correlations with standardized neuropsychological tests were moderate to high, supporting concurrent validity. These results were replicated in the minority sample. The random forest models showed a very accurate classification using the CCD. This test showed good psychometric properties compared with SDMT. CONCLUSIONS: Our study validates the CCD for cognitive impairment screening in MS, showing advantages over other routinely used cognitive tests.

Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits.

BACKGROUND: Dietary changes impact human physiology and immune function and have potential as therapeutic strategies. OBJECTIVE: Assess the tolerability of a ketogenic diet (KD) in patients with relapsing multiple sclerosis (MS) and define the impact on laboratory and clinical outcome metrics. METHODS: Sixty-five subjects with relapsing MS enrolled into a 6-month prospective, intention-to-treat KD intervention. Adherence was monitored with daily urine ketone testing. At baseline, fatigue, depression and quality of life (QoL) scores were obtained in addition to fasting adipokines and MS-related clinical outcome metrics. Baseline metrics were repeated at 3 and/or 6 months on-diet. RESULTS: Eighty-three percent of participants adhered to the KD for the study duration. Subjects exhibited significant reductions in fat mass and showed a nearly 50% decline in self-reported fatigue and depression scores. MS QoL physical health (67±16 vs 79±12, p<0.001) and mental health (71±17 vs 82±11, p<0.001) composite scores increased on-diet. Significant improvements were noted in Expanded Disability Status Scale scores (2.3±0.9 vs 1.9±1.1, p<0.001), 6-minute walk (1631±302 vs 1733±330 ft, p<0.001) and Nine-Hole Peg Test (21.5±3.6 vs 20.3±3.7 s, p<0.001). Serum leptin was lower (25.5±15.7 vs 14.0±11.7 ng/mL, p<0.001) and adiponectin was higher (11.4±7.8 vs 13.5±8.4 µg/mL, p=0.002) on the KD. CONCLUSION: KDs are safe and tolerable over a 6-month study period and yield improvements in body composition, fatigue, depression, QoL, neurological disability and adipose-related inflammation in persons living with relapsing MS. TRIAL REGISTRATION INFORMATION: Registered on ClinicalTrials.gov under registration number NCT03718247, posted on 24 October 2018. First patient enrolment date: 1 November 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1.

Aerobic exercise increases irisin serum levels and improves depression and fatigue in patients with relapsing remitting multiple sclerosis: A randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic progressive neurodegenerative disease of the central nervous system. Although there is increasing evidence that aerobic exercise has a positive effect on both cognitive and psychological functioning, there is limited evidence for Relapsing-Remitting MS (RRMS) patients. Moreover, it is unclear at what exercise modality and intensity the irisin, the cleaved and circulating form of the exercise-associated membrane protein Fibronectin Type III Domain Containing 5, is induced in patients with MS. This study aimed to investigate the effect of a regular aerobic exercise program on irisin serum level, depression, fatigue, and cognitive performance in patients with MS. METHODS: Thirty-two individuals with RRMS were randomized into 2 groups as control and study groups (mean EDSS score 1.69 and 1.97, respectively). While the Study Group received a combined exercise training consisting of three sessions of aerobic exercise and Frenkel Coordination Exercises per week for 6 weeks, the Control Group received only Frenkel Coordination Exercise training. Before and after the study, the cognitive performance of the participants were evaluated with the Paced Auditory Serial Addition Test with 3-second stimulus (PASAT-3), their maximum aerobic capacity with the Fitmate Pro® (VO2max), their fatigue status with the Fatigue Impact Scale (FIS), and their depression status with the Beck Depression Inventory (BDI). Irisin serum levels were analyzed with Enzyme-Linked ImmunoSorbent Assay (ELISA) test from the serum samples of individuals. RESULTS: Our results revealed that the irisin serum level significantly increased in the Study Group. Significant improvement in aerobic capacity, PASAT-3, FIS, and BDI values was observed in the Study Group compared to the Control Group. When the ΔIrisin, ΔVO2max, ΔFIS, and ΔBDI values between the groups were compared, a significant difference was found in favor of the study group. CONCLUSION: The aerobic exercise revealed significant changes in depression, fatigue and irisin serum levels in MS patients. We think that this study, in which a significant increase in irisin serum level, significant improvement in depression, cognitive performance and fatigue states were obtained in the Study Group, will be a pioneering study for the future studies aiming to investigate the effects of irisin serum level on these symptoms in detail.

Physical exercise may improve problem-solving skills and emotional intelligence in patients with relapsing-remitting multiple sclerosis: A cross-sectional study.

BACKGROUND: Multiple sclerosis is a disease that can reduce the quality of life with a physical disability, neuropsychiatric disorders, and cognitive dysfunctions. Therefore, multiple sclerosis treatment should include treatments for cognitive and neuropsychiatric disorders and pharmacological treatments. This study aimed to examine the effects of exercise on neuropsychiatric disorders, problem-solving skills, and emotional intelligence in multiple sclerosis patients. METHODS: Thirty-six female relapsing-remitting multiple sclerosis patients aged between 18 and 45 years, with an Expanded Disability Status Scale between 1 and 3, who were diagnosed with definitive multiple sclerosis according to the revised McDonald criteria were included in the study. Participants completed outcome measures before and after the 12-week exercise program. Demographic/clinical information of the participants was obtained at baseline, neurological examinations were performed, and graded exercise testing on a bicycle ergometer was performed to determine aerobic capacity. Short Form-12 Version 2, Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale, Problem-Solving Inventory, Emotional Intelligence Scale were evaluated before and after the exercise program of the participants. RESULTS: While a significant increase was observed in the HRpeak values ​​of the participants after the exercise (p < 0.05), the VO2max values also showed a highly significant difference compared to the pre-treatment values. (p < 0.01). While a significant difference was detected in the mental subparameter of Short Form-12 (p < 0.05), a high level of significant difference was found in the physical subparameter (p < 0.01). While no significant difference was observed in the Hospital Anxiety and Depression Scale anxiety subparameter (p > 0.05), a significant difference was found in the depression subparameter (p < 0.01). There was a significant difference in Modified Fatigue Impact Scale physical and cognitive subparameters compared to pre-treatment (p < 0.01). A significant difference was observed in the Emotional Intelligence Scale total score after the treatment (p < 0.01). CONCLUSIONS: The results of our study showed that exercise in relapsing-remitting multiple sclerosis patients provided significant improvements in emotional intelligence, improved neuropsychiatric parameters, and increased problem-solving skills. In addition, to the best of our knowledge, this study is the first study in the literature to investigate the effect of physical activity exercises on problem-solving skills in multiple sclerosis patients.

Reduction in Cognitive Processing Speed Surrounding Multiple Sclerosis Relapse.

OBJECTIVE: The purpose of this study was to explore the longitudinal relationship between multiple sclerosis (MS) relapses and information processing efficiency among persons with relapsing-remitting MS. METHODS: We conducted a Swedish nationwide cohort study of persons with incident relapsing-remitting MS (2001-2019). Relapse information and symbol digit modalities test (SDMT) scores were obtained from the Swedish MS Registry. Follow-up was categorized into 2 periods based on relapse status: "relapse" (90 days pre-relapse to 730 days post-relapse, subdivided into 10 periods) and "remission." Linear mixed models compared SDMT scores during the relapse periods to SDMT scores recorded during remission (reference) with results reported as ß-coefficients and 95% confidence intervals (CIs), adjusted for age, sex, SDMT type (written vs oral), time-varying, disease-modifying therapy exposure and sequence of SDMT. RESULTS: Over a mean (SD) follow-up of 10.7 (4.3) years, 31,529 distinct SDMTs were recorded among 3,877 persons with MS. There was a significant decline in information processing efficiency that lasted from 30 days pre-relapse up to 550 days post-relapse, with the largest decline occurring 0 to 30 days post-relapse (ß-coefficient: -4.00 (95% CI = -4.61 to -3.39), relative to the period of remission. INTERPRETATION: We found evidence of cognitive change up to 1 month prior to relapse onset. The reduction in SDMT lasted 1.5 years and was clinically significant up to 3 months post-relapse. These results suggest that the effects of a relapse on cognition are longer than previously thought and highlight the importance of reducing relapse rates as a potential means of preserving cognitive function. ANN NEUROL 2022;91:417-423.

Cognitive function and oral health in relapsing-remitting multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is often associated with reduced cognitive function, and there is also emerging evidence of a heightened vulnerability to oral health problems. However, although links between cognitive function and oral health have been identified in other special populations, it remains to be established whether this relationship is also evident for people with MS. The aim of this study was to provide the first empirical test of whether there is a relationship between cognitive function and oral health in people diagnosed with relapsing-remitting multiple sclerosis (RRMS). METHODS: One hundred and eleven individuals were evaluated: 56 people diagnosed with RRMS and 55 demographically matched healthy controls. All participants completed an objective oral health assessment as well as a standardized battery that assessed six distinct neurocognitive domains. RESULTS: Relative to controls, people with RRMS presented with higher rates of decayed teeth and mild gingivitis, and also performed more poorly in three of the six neurocognitive domains assessed (language, complex attention, and executive function). However, for the RRMS group, no associations emerged between oral health with performance on any of the six neurocognitive domains. CONCLUSIONS: These data cross-validate previous research which shows people with RRMS are more likely to present with both reduced cognitive function and poorer oral health, but also extends this literature in a meaningful way by additionally showing for the first time that these clinical features are unrelated in RRMS. CLINICAL RELEVANCE: The findings emphasize the need for early assessment of both oral health and cognitive function in people with RRMS so that appropriate interventions and support can be put in place for each of these clinical symptoms.

"I'm walking into the unknown": Qualitative insights into how emotions and lived experience related to multiple sclerosis diagnosis impact on decisions to pursue disease modifying treatment.

INTRODUCTION: People with Relapsing Remitting Multiple Sclerosis (RRMS) are increasingly included as active participants in shared decision making around their treatment options. Choosing a first disease modifying treatment (DMT) is a complex process that often takes place soon after a diagnosis has been given. Patients therefore are often required to make difficult decisions at a time when they are still coming to terms with their illness. This study investigated the views and experiences of recently diagnosed patients with RRMS when they were making their initial DMT choice. METHOD: This was a qualitative study involving in-depth semi-structured interviews with patients with RRMS in a National Health Service (NHS) setting in the United Kingdom. Data were collected from 6 patients and analysis was guided by an Interpretive Phenomenological Analysis (IPA) approach. RESULTS: Initial reactions to diagnosis were characterized by strong emotions and a feeling of despair and hopelessness. Subsequently the DMT decision was shaped by multiple considerations around maintaining normality, and restoring hope and control over one's life whilst reconciling uncertainty around efficacy. Considering the future with a DMT elicited reflections around employment and family planning. CONCLUSION: Emotions and lived experience related to recent MS diagnosis can impact on the initial DMT decision in number of ways. Health care professionals need to understand the lived experience of patients making DMT decisions soon after diagnosis when engaging in shared decision making.