Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial
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PROVIDER: S-EPMC10617283 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo compare the effect of the modified Paleolithic elimination (Wahls) and low-saturated fat (Swank) diets in relapsing-remitting MS (RRMS).MethodsIndividuals (n = 87) with RRMS were randomized to the Swank or Wahls diets in a parallel group clinical trial consisting of four timepoints: 1) run-in, 2) baseline, 3) 12-weeks, and 4) 24-weeks.Results77 participants completed 12 weeks and 72 completed 24 weeks. The 12-week change from baseline in fatigue was -0.94 ± 0.18 (FSS) and -9.87 ± 1.93 (MFIS; both p < 0.0001) for Swank, and -0.71 ± 0.24 (FSS; p = 0.004) and -14.41 ± 2.22 (MFIS; p ≤ 0.0001) for Wahls. Physical MSQoL scores improved by 6.04 ± 2.18 (p = 0.006) for Swank and by 14.5 ± 2.63 (p < 0.0001) for Wahls. Mental MSQoL scores improved by 11.3 ± at 2.79 (p < 0.0001) for Wahls while the Swank did not change (3.85 ± 2.63; p = 0.14). Neither group showed significant changes in 6-minute walking distance at 12 weeks. All outcomes were maintained or further improved at 24 weeks.ConclusionsBoth diets were associated with clinically meaningful within-group reductions in fatigue and improvements in QoL.Trial Registration: Clinicaltrials.gov Identifier: NCT02914964.
| S-EPMC8326636 | biostudies-literature
Project description:BackgroundPreliminary 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.ObjectiveTo 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).MethodsAs 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.ResultsBoth 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).ConclusionBoth 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.
| S-EPMC9892773 | biostudies-literature
Project description:ImportanceMultiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown.ObjectiveTo understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS.Design, setting, and participantsIn this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014.Main outcomes and measuresVoxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores).ResultsAmong the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations.Conclusions and relevanceThese biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.
| S-EPMC6415681 | biostudies-literature
Project description:Cognitive dysfunction affects 40-65% of multiple sclerosis (MS) patients and can occur in the early stages of the disease. This study aimed to explore cognitive functions by means of the Italian version of the minimal assessment of cognitive function in MS (MACFIMS) in relapsing-remitting MS (RRMS) patients with very mild clinical disability to identify the primarily involved cognitive functions. Ninety-two consecutive RRMS patients with Expanded Disability Status Scale (EDSS) scores ≤ 2.5 and forty-two healthy controls (HC) were investigated. Our results show that 51.1% of MS patients have cognitive dysfunction compared to HC. An impairment of verbal and visual memory, working memory, and executive functions was found in the RRMS group. After subgrouping RRMS by EDSS, group 1 (EDSS ≤ 1.5) showed involvement of verbal memory and executive functions; moreover, group 2 (2 ≤ EDSS ≤ 2.5) patients were also impaired in information processing speed and visual memory. Our results show that utilizing a comprehensive neuropsychological assessment, approximately half of MS patients with very mild physical disability exhibit cognitive impairment with a primary involvement of prefrontal cognitive functions. Detecting impairment of executive functions at an early clinical stage of disease could be useful to promptly enroll MS patients in targeted rehabilitation.
| S-EPMC5574272 | biostudies-literature
Project description:ObjectiveWe tested whether it is possible to differentiate relapsing-remitting (RR) from secondary progressive (SP) disease stages in patients with multiple sclerosis (MS) using a combination of nuclear magnetic resonance (NMR) metabolomics and partial least squares discriminant analysis (PLS-DA) of biofluids, which makes no assumptions on the underlying mechanisms of disease.MethodsSerum samples were obtained from patients with primary progressive MS (PPMS), SPMS, and RRMS; patients with other neurodegenerative conditions; and age-matched controls. Samples were analyzed by NMR and PLS-DA models were derived to separate disease groups.ResultsThe PLS-DA models for serum samples from patients with MS enabled reliable differentiation between RRMS and SPMS. This approach also identified significant differences between the metabolite profiles of each of the MS groups (PP, SP, and RR) and the healthy controls, as well as predicting disease group membership with high specificity and sensitivity.ConclusionsNMR metabolomics analysis of serum is a sensitive and robust method for differentiating between different stages of MS, yielding diagnostic markers without a priori knowledge of disease pathogenesis. Critically, this study identified and validated a type II biomarker for the RR to SP transition in patients with MS. This approach may be of considerable benefit in categorizing patients for treatment and as an outcome measure in future clinical trials.Classification of evidenceThis study provides Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of MS.
| S-EPMC4222850 | biostudies-literature
Project description:To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.
| S-EPMC6406712 | biostudies-literature
Project description: Not available
| S-EPMC10401910 | biostudies-literature
Project description:Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life. To elucidate the relationship between depression and fatigue and brain connectivity in pwRRMS we conducted a systematic review. Searched databases were PubMed, Web-of-Science and Scopus. Inclusion criteria were: studied participants with RRMS (n ≥ 20; ≥ 18 years old) and differentiated between MS subtypes; published between 2001-01-01 and 2023-01-18; used fatigue and depression assessments validated for MS; included brain structural, functional magnetic resonance imaging (fMRI) or diffusion MRI (dMRI). Sixty studies met the criteria: 18 dMRI (15 fatigue, 5 depression) and 22 fMRI (20 fatigue, 5 depression) studies. The literature was heterogeneous; half of studies reported no correlation between brain connectivity measures and fatigue or depression. Positive findings showed that abnormal cortico-limbic structural and functional connectivity was associated with depression. Fatigue was linked to connectivity measures in cortico-thalamic-basal-ganglial networks. Additionally, both depression and fatigue were related to altered cingulum structural connectivity, and functional connectivity involving thalamus, cerebellum, frontal lobe, ventral tegmental area, striatum, default mode and attention networks, and supramarginal, precentral, and postcentral gyri. Qualitative analysis suggests structural and functional connectivity changes, possibly due to axonal and/or myelin loss, in the cortico-thalamic-basal-ganglial and cortico-limbic network may underlie fatigue and depression in pwRRMS, respectively, but the overall results were inconclusive, possibly explained by heterogeneity and limited number of studies. This highlights the need for further studies including advanced MRI to detect more subtle brain changes in association with depression and fatigue. Future studies using optimised imaging protocols and validated depression and fatigue measures are required to clarify the substrates underlying these symptoms in pwRRMS.
| S-EPMC10980255 | biostudies-literature
Project description:Changes of intestinal permeability (IP) have been extensively investigated in inflammatory bowel diseases (IBD) and celiac disease (CD), underpinned by a known unbalance between microbiota, IP and immune responses in the gut. Recently the influence of IP on brain function has greatly been appreciated. Previous works showed an increased IP that preceded experimental autoimmune encephalomyelitis development and worsened during disease with disruption of TJ. Moreover, studying co-morbidity between Crohn's disease and MS, a report described increased IP in a minority of cases with MS. In a recent work we found that an alteration of IP is a relatively frequent event in relapsing-remitting MS, with a possible genetic influence on the determinants of IP changes (as inferable from data on twins); IP changes included a deficit of the active mechanism of absorption from intestinal lumen. The results led us to hypothesize that gut may contribute to the development of MS, as suggested by another previous work of our group: a population of CD8+CD161high T cells, belonging to the mucosal-associated invariant T (MAIT) cells, a gut- and liver-homing subset, proved to be of relevance for MS pathogenesis. We eventually suggest future lines of research on IP in MS: studies on IP changes in patients under first-line oral drugs may result useful to improve their therapeutic index; correlating IP and microbiota changes, or IP and blood-brain barrier changes may help clarify disease pathogenesis; exploiting the IP data to disclose co-morbidities in MS, especially with CD and IBD, may be important for patient care.
| S-EPMC5794695 | biostudies-literature
Project description:Multiple Sclerosis (MS) is the most common chronic inflammatory and neurodegenerative disease of the central nervous system (CNS), which can lead to severe cognitive impairment over time. Magnetic resonance imaging (MRI) is currently the best available biomarker to track MS pathophysiology in vivo and examine the link to clinical disability. However, conventional MRI metrics have limited sensitivity and specificity to detect direct associations between symptoms and their underlying CNS substrates. In this study, we aimed to investigate structural and resting state functional connectomes and subnetworks associated with neuropsychological (NP) performance using a graph theoretical approach. A comprehensive NP test battery was administered in a sample of patients with relapsing remitting MS (RRMS) and mild disability [n = 33, F/M = 20/13, age = 40.9 ± 9.7, median [Expanded Disability Status Scale] (EDSS) = 2, range =0-4] and compared to healthy controls (HC) [n = 29, F/M = 19/10, age = 41.0 ± 8.5] closely matched for age, sex, and level of education. The NP battery comprised the most relevant domains of cognitive dysfunction in MS including attention, processing speed, verbal and spatial learning and memory, and executive function. While standard MRI metrics showed good correlations with TAP Alertness test, disease duration and neurological exams, structural networks showed closer associations with 9-hole peg test and cognitive performances. Decreased graph strength was associated with two out of the 5 NP tests in the spatial learning and memory domain specified by BVMT [Sum 1-3] and BVMT [Recall], and with also SDMT which is one out of the 9 NP tests in the attention/processing speed domain, while no correlation was found between these scores and functional connectivity. Nodal strength was decreased in all subnetworks based on Yeo atlas in patients compared to HC; however, no difference was observed in nodal level of functional connectivity between the groups. The difference in structural and functional nodal connectivity between the groups was also observed in the relationship between structural and functional connectivity within the groups; the relationship between nodal degree and nodal strength was reversed in patients but positive in controls. On a nodal level, structural and functional networks (mainly the default mode network) were correlated with more than one cognitive domain rather than one specific network for each domain within patients. Interestingly, poorer cognitive performance was mostly correlated with increased functional connectivity but decreased structural connectivity in patients. Increased functional connectivity in the default mode network had both positive as well as negative associations with verbal and spatial learning and memory, possibly indicating adaptive and maladaptive mechanisms. In conclusion, our results suggest that cognitive performance, even in patients with RRMS and very mild disability, may reflect a loss of structural connectivity. In contrast, widespread increases in functional connectivity may be the result of maladaptive processes.
| S-EPMC6997626 | biostudies-literature