A coffee enriched with guarana, selenium, and l-carnitine (GSC) has nutrigenomic effects on oxi-inflammatory markers of relapsing-remitting multiple sclerosis patients: A pilot study.

Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical course of multiple sclerosis (MS), characterized by a chronic inflammatory state and elevated levels of oxidative markers. Food supplements with potential anti-inflammatory, antioxidant and neuroprotective effects have been tested as possible adjuvants in the treatment of MS. In this sense, this pilot study was carried out with the aim of verifying whether a minimum daily dose of a guarana, selenium and l-carnitine (GSC) based multi supplement, mixed in cappuccino-type coffee, administered for 12 weeks to 28 patients with RRMS could differentially modulate oxidative blood markers (lipoperoxidation, protein carbonylation and DNA oxidation) and inflammatory blood markers (protein levels of cytokines IL-1ß, IL-6, TNF-α, IFN-γ, IL-10, gene expression of these cytokines, and NLRP3 and CASP-1 molecules, and C-reactive protein levels). The results indicate that a low concentration of GSC is capable of decreasing the plasma levels of oxidized DNA and pro-inflammatory cytokines of RRMS patients. The results support further research into the action of GSC on clinical symptoms, not only in patients with MS, but also with other neurological conditions.

Serum 25(OH) vitamin D level in Relapsing-Remitting Multiple Sclerosis and clinically isolated syndrome groups.

OBJECTIVES: Vitamin D is an important regulator of the immune system, and it has been shown that deficiency of vitamin D is significant environmental factor in some immune-mediated diseases such as Multiple Sclerosis (MS). In this study, we have compared serum 25 hydroxyvitamin (OH) D levels in Relapsing-Remitting Multiple Sclerosis (RRMS), clinically isolated syndrome (CIS), and control groups. METHODS: Forty patients with CIS and 60 patients who have been diagnosed RRMS between age 18-45, respectively, and followed up at Pamukkale University Faculty of Medicine, Department of Neurology, and 60 healthy individuals have been included in this study. Serum 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, parathormone, insulin, and fasting blood glucose levels were studied for all three groups. RESULTS: A statistically significant difference was determined in the comparison of three groups for mean 25(OH) vitamin D levels. In the intergroup comparison of mean 25(OH) vitamin D; mean 25(OH) vitamin D level was determined to be statistically significantly lower in both RRMS and CIS groups compared to control group (p<0.05). CONCLUSIONS: Since vitamin D deficiency poses a problem from the early stage of disease spectrum in both CIS patients and MS patients, 25(OH) vitamin D level should be routinely controlled, and replacement should be administered upon any deficiency state.

Cortical Thickness and Serum NfL Explain Cognitive Dysfunction in Newly Diagnosed Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: To determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS). METHODS: Thirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment. RESULTS: Compared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT. DISCUSSION: Thalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS.

In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing-remitting multiple sclerosis.

The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease-modifying therapies. Proton MRS (1 H-MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ-aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1 H-MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N-acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing-remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross-sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate (F2,65 = 3.424, p = 0.04; 12.40 ± 0.62 mM versus control 13.17 ± 0.95 mM, p = 0.03) but not glutamine (F2,65 = 0.352, p = 0.7; 4.71 ± 0.35 mM versus control 4.84 ± 0.42 mM), reduced GABA (F2,65 = 3.89, p = 0.03; 1.29 ± 0.23 mM versus control 1.47 ± 0.25 mM, p = 0.05), and possibly reduced glutathione (F2,65 = 0.352, p = 0.056; 2.23 ± 0.46 mM versus control 2.51 ± 0.48 mM, p < 0.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA (ρ = -0.4, p = 0.02) but not glutamine or glutathione. Alone, only relapsing-remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA (ρ = -0.5, p = 0.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing-remitting multiple sclerosis.

High-dose vitamin B supplementation for persistent visual deficit in multiple sclerosis: a pilot study.

The aim of this study is to investigate the potential neuroprotective effect of high-doses vitamins B1, B6 and B12 in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent visual loss after acute optic neuritis (AON). Sixteen patients (20 eyes) diagnosed with RRMS and visual permanent disability following AON were enrolled for the present open, pilot study. Each patient was treated with oral high-doses 300 mg of vitamin B1, 450 mg of vitamin B6 and 1,500 mcg of vitamin B12, as add-on treatment to concomitant disease-modifying therapies (DMTs) for consecutive 90 days. Outcome measures were to determine changes from baseline to month three in visual acuity (VA) and visual field (VF) testing, with correlations with clinical parameters. Logistical regression was performed to evaluate predictors of final VA. A statistically significant improvement was registered in visual acuity (p = 0.002) and foveal sensitivity threshold (FT) (p = 0.006) at follow-up compared to baseline. A similar trend was demonstrated for mean deviation (MD) (p < 0.0001), and pattern standard deviation (PSD) (p < 0.0001). Age at the time of inclusion was positively correlated with latency time (rho = 0.47, p = 0.03), while showing a negative correlation with visual acuity (rho = - 0.45, p = 0.04) and foveal sensitivity threshold (rho = - 0.6, p = 0.005) at follow up. A statistically significant correlation was demonstrated between foveal sensitivity threshold and visual acuity at baseline (rho = 0.79, p < 0.0001). In a linear regression model, the main predictor of visual acuity at follow up was the foveal sensitivity threshold (B = 1.39; p < 0.0001). Supplemental high-dose vitamins B1, B6 and B12 resulted as effective therapy to improve visual function parameters in MS-related visual persistent disability.

Relapses During High-Dose Biotin Treatment in Progressive Multiple Sclerosis: a Case-Crossover and Propensity Score-Adjusted Prospective Cohort.

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Some reports have suggested that HDB treatment may be associated with an increased risk of relapse. We evaluate the relationship between exposure to HDB for treating PMS and the risk of relapse. We screened for PMS patients prospectively registered in a French regional cohort being part of the OFSEP national registry. In a case-crossover design among patients who received HDB, we first compared number of relapses before and after initiation of HDB. Second, time to the first clinical relapse was compared between patients who received HDB (biotin group) and a control group using a Cox survival analysis after a propensity score (PS) matching (1:1) and inverse probability of treatment weighting (IPTW) method. In the 42 PMS patients who received HDB, the number of relapses was statistically and clinically significant higher after biotin initiation than before biotin initiation (incident rate ratio [IRR] 7.4, 95% confidence interval [CI] 3.5-15.9, p < 0.0001). With the PS matching method, the risk of relapse was significantly higher in the biotin group compared to the control group (hazard ratio [HR] 4.3, 95% CI 1.4-13.3, p = 0.01). The IPTW method with 440 control patients revealed consistent results (HR 5.1, 95% CI 2.3-11.3, p < 0.0001). In our non-randomized study, HDB treatment for PMS was associated with an increased risk of relapse. The follow-up of PMS patients initiating HDB should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.

The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients.

BACKGROUND: Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS. METHODS: A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI). RESULTS: State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups. CONCLUSIONS: EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.

Identifying Patients With Relapsing-Remitting Multiple Sclerosis Using Algorithms Applied to US Integrated Delivery Network Healthcare Data.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) has a major impact on affected patients; therefore, improved understanding of RRMS is important, particularly in the context of real-world evidence. OBJECTIVES: To develop and validate algorithms for identifying patients with RRMS in both unstructured clinical notes found in electronic health records (EHRs) and structured/coded health care claims data. METHODS: US Integrated Delivery Network data (2010-2014) were queried for study inclusion criteria (possible multiple sclerosis [MS] base cohort): one or more MS diagnosis code, patients aged 18 years or older, 1 year or more baseline history, and no other demyelinating diseases. Sets of algorithms were developed to search narrative text of unstructured clinical notes (EHR clinical notes-based algorithms) and structured/coded data (claims-based algorithms) to identify adult patients with RRMS, excluding patients with evidence of progressive MS. Medical records were reviewed manually for algorithm validation. Positive predictive value was calculated for both EHR clinical notes-based and claims-based algorithms. RESULTS: From a sample of 5308 patients with possible MS, 837 patients with RRMS were identified using only the EHR clinical notes-based algorithms and 2271 patients were identified using only the claims-based algorithms; 779 patients were identified using both algorithms. The positive predictive value was 99.1% (95% confidence interval [CI], 94.2%-100%) for the EHR clinical notes-based algorithms and 94.6% (95% CI, 89.1%-97.8%) to 94.9% (95% CI, 89.8%-97.9%) for the claims-based algorithms. CONCLUSIONS: The algorithms evaluated in this study identified a real-world cohort of patients with RRMS without evidence of progressive MS that can be studied in clinical research with confidence.

Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNß; the SOLARIUM study.

Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D3 supplementation on clinical outcomes in a randomized controlled trial. Here we present the immune regulatory effects, investigated in the SOLARIUM sub-study. Thirty Dutch relapsing remitting (RR) MS patients treated with IFNß-1a received high dose vitamin D3 supplementation and 23 patients received placebo during a period of 48weeks. Lymphocytes were phenotypically characterized by flow cytometry and in vitro cytokine secretion was assessed in the presence or absence of 1,25(OH)2D3 using Luminex technology. Changes in immune regulatory parameters were determined within subjects as well as between treatment groups. The proportion of cells in the immune regulatory cell compartment (nTreg, iTreg and Breg) was not altered upon high dose vitamin D3 supplementation. Proportions of T helper subsets were not affected by vitamin D3, except for the proportion of IL4+ Th cells, which decreased in the placebo but not in the vitamin D3 group. T cell cytokine secretion increased, most pronounced for IL5 and latency activated protein of TGFß, in the placebo group but not in the vitamin D3 group. Lymphocytes remained equally reactive to in vitro 1,25(OH)2D3. In conclusion, high dose vitamin D3 supplementation did not result in a relative increase in lymphocytes with a regulatory phenotype. However, this study supports the hypothesis that vitamin D contributes to the maintenance of immune homeostasis by preventing further disturbance of the T cell compartment early in the disease course of MS.

Effect of Vitamin A Supplementation on fatigue and depression in Multiple Sclerosis patients: A Double-Blind Placebo-Controlled Clinical Trial.

Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis (MS) patients using vitamin A derivatives (retinoic acids) has been well documented. The present study determined the effect of vitamin A supplementation on psychiatric signs in MS patients. The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled randomized clinical trial. The treatment group was administered 25000 IU/d retinyl palmitate (RP) for 6 months followed by 10000 IU/d RP for another 6 months. The results for baseline characteristics, modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study. The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test. (ClinicalTrials.gov Identifiers: NCT01417273). The results showed significant improvement in the treatment group for fatigue (p=0.004) and depression (p=0.01). Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms.

A low vitamin D status at diagnosis is associated with an early conversion to secondary progressive multiple sclerosis.

Low circulating 25-hydroxyvitamin D (25(OH)D) levels have been associated with an increased risk of relapses in relapsing remitting multiple sclerosis (RRMS), but an association with disability progression is uncertain. Lower 25(OH)D levels are found in secondary progressive MS (SPMS) when compared to RRMS. We hypothesized that a poor vitamin D status in RRMS is associated with an increased risk of conversion to SPMS. In a retrospective longitudinal study we measured 25(OH)D levels at the start of a 3-year follow-up, and analyzed whether these levels predict the risk of RRMS to SPMS conversion. In 338 RRMS patients, vitamin D status did not predict the 3-year risk of conversion to SPMS (n=51; OR 0.970; p=0.65). However, in diagnostic blood samples of SPMS patients with a relatively short RRMS duration (n=19) 25(OH)D levels were significantly lower (38nmol/L; Q1-Q3: 24-50) than in diagnostic samples of matched RRMS patients with no progression to SPMS ((n=38; 55nmol/L; Q1-Q3: 40-70) (p<0.01). These data indicate an association between a low vitamin D status at the start of RRMS and the early conversion to SPMS. Therefore, time to SPMS conversion is of interest as clinical measure in (follow-up of) clinical vitamin D supplementation studies.

Does hippotherapy effect use of sensory information for balance in people with multiple sclerosis?

OBJECTIVE: This case-series study aimed to determine if there were observable changes in sensory processing for postural control in individuals with multiple sclerosis (MS) following physical therapy using hippotherapy (HPOT), or changes in balance and functional gait. DESIGN: This pre-test non-randomized design study, with follow-up assessment at 6 weeks, included two females and one male (age range 37-60 years) with diagnoses of relapse-remitting or progressive MS. The intervention consisted of twelve 40-min physical therapy sessions which included HPOT twice a week for 6 weeks. Sensory organization and balance were assessed by the Sensory Organization Test (SOT) and Berg Balance Scale (BBS). Gait was assessed using the Functional Gait Assessment (FGA). RESULTS: Following the intervention period, all three participants showed improvements in SOT (range 1-8 points), BBS (range 2-6 points), and FGA (average 4 points) scores. These improvements were maintained or continued to improve at follow-up assessment. Two of the three participants no longer over-relied on vision and/or somatosensory information as the primary sensory input for postural control, suggesting improved use of sensory information for balance. CONCLUSION: The results indicate that HPOT may be a beneficial physical therapy treatment strategy to improve balance, functional gait, and enhance how some individuals with MS process sensory cues for postural control. Randomized clinical trials will be necessary to validate results of this study.

Effect of high dose vitamin D intake on interleukin-17 levels in multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Vitamin D has immunomodulatory effects in multiple sclerosis (MS). Vitamin D acts through various mechanisms such as secretion of cytokines. Interleukin-17 (IL-17) is a critical interleukin in inflammatory response in MS. OBJECTIVE: This study assessed the effect of oral high dose vitamin D intake on IL-17 levels in MS patients in a double blind randomized clinical trial. METHODS: 94 patients with a diagnosis of relapsing remitting multiple sclerosis (RRMS) were randomized to two groups. One group received 50,000 IU vitamin D3 every five days for 12weeks. The other group was given placebo. Both groups received interferon-ß (IFN-ß) treatment. Serum levels of IL-17 were measured at the beginning of the study and after 12weeks. RESULTS: IL-17 serum levels were 56.75±28.72pg/ml and 30.31±75.85pg/ml in the intervention and placebo group at the beginning of the study, respectively (Median±IQR, p=0.338). After 12weeks, IL-17 levels were 58.93±67.93pg/ml and 46.13±94.70pg/ml in the intervention and placebo group, respectively (Median±IQR, p=0.960). The multiple linear regression analysis indicated that the consumption of vitamin D3 was positively and significantly associated with the logarithm of IL-17 measures (ß=1.719; p=0.002 and R2=0.91), adjusted by EDSS scores. CONCLUSION: IL-17 levels showed significant change in RRMS patients after receiving high dose vitamin D3 for 12weeks.

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

OBJECTIVES: Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. METHODS: Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. RESULTS: While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. CONCLUSIONS: While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

P300 amplitude and response speed relate to preserved cognitive function in relapsing-remitting multiple sclerosis.

OBJECTIVE: To explore if cognitive impairment in relapsing-remitting multiple sclerosis (RRMS) is associated with abnormal neural function and if there is evidence of neural compensatory mechanisms. METHODS: Seventy-two RRMS patients and 89 healthy control subjects were included in a cross-sectional study. Event-related brain potential (P300) and response time (RT) were recorded with visual and auditory choice reaction tasks. Cognitive function was evaluated with an 18 item test battery. RESULTS: Patients had a decrease in cognitive function (p<0.001 for global score) and increased visual P300 amplitude frontally. P300 amplitude was normal in other brain areas and RT was normal. P300 latency was normal except for an increase in auditory latency occipitally. Cognitive performance correlated positively with parietal P300 amplitude in patients but not in controls. Cognition had stronger correlation (negative) with RT in patients than in controls. CONCLUSIONS: Patients with low P300 amplitude and long RT were more often cognitively impaired. This indicates that general factors such as signal amplitude and speed are limiting for cognitive function in RRMS patients. The increase in frontal P300 amplitude may be a compensatory effect. SIGNIFICANCE: Our findings suggest that high amplitude and fast speed may be protective against cognitive impairment.

Increased thalamic intrinsic oscillation amplitude in relapsing-remitting multiple sclerosis associated with the slowed cognitive processing.

OBJECTIVE: To investigate the relationship between the amplitude of thalamic intrinsic neuronal activity, structural imaging indices, and the clinical neurological scales in relapsing-remitting multiple sclerosis (RRMS). METHODS: Twenty-three patients with RRMS and 23 healthy controls were examined by resting-state fMRI (rs-fMRI) scan. Thalamic intrinsic oscillation amplitude was calculated by amplitude of low frequency fluctuation (ALFF) of rs-fMRI, as well as its correlations with clinical and structural imaging indices. RESULTS: Compared with the healthy controls, RRMS patients showed significantly increased ALFF values in bilateral thalami (P<.05, corrected). In the patient group, positive correlation was found between bilateral ALFF values and paced auditory serial addition test (left: P=.033; right: P=.016). Significant correlation was detected between the ALFF values and fractional anisotropy (FA) values in the left thalamus (r=0.550, P=.007); only tendency increased correlation was detected between the ALFF values and FA values in the right thalamus (P=.114). No correlation was observed between bilateral thalamic ALFF values and disease duration, expanded disability status scale score, brain parenchymal fraction, or total white matter lesion loads (P>.05). CONCLUSION: The increased thalamic intrinsic oscillation amplitude as an ineffective reorganization was responded to microstructural damage in the RRMS patients, as well as it was associated with the slowed cognitive processing in relatively minimally disabled stage.

Randomized controlled trial of a behavioral intervention targeting symptoms and physical activity in multiple sclerosis.

BACKGROUND: Exercise training is beneficial, but most persons with multiple sclerosis (MS) are sedentary and physically inactive. This has prompted a new focus on the promotion of lifestyle physical activity in MS. We previously designed, tested, and refined a behavioral intervention delivered through the Internet that successfully increased lifestyle physical activity in MS, but have not evaluated the effects on secondary symptomatic and health-related quality of life (HRQOL) outcomes. OBJECTIVE: We conducted a 6-month randomized controlled trial (RCT) that examined the efficacy of an Internet-delivered, behavioral intervention for improving outcomes of fatigue, depression, anxiety, pain, sleep quality, and HRQOL in 82 ambulatory persons with MS. The secondary aim was to replicate previous results regarding change in free-living physical activity. RESULTS: There was a significant and positive effect of the intervention on fatigue severity (p=.001, η ρ (2)=.15) and its physical impact (p=.008, η ρ (2)=.09), depression (p=.006, η ρ (2)=.10), and anxiety (p=.006, η ρ (2)=.10). There were non-significant improvements in pain (p=.08, η ρ (2)=.04), sleep quality (p=.06, η ρ (2)=.05), and physical HRQOL (p=.06, η ρ (2)=.05). We replicated our previous results by demonstrating an increase in self-reported physical activity (p=.001, η ρ (2)=.13). CONCLUSIONS: Our results support behavioral interventions targeting lifestyle physical activity as an alternative approach for managing symptoms in MS.