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1.
Role of diet in regulating the gut microbiota and multiple sclerosis.
Sanchez, JMS, DePaula-Silva, AB, Libbey, JE, Fujinami, RS
Clinical immunology (Orlando, Fla.). 2022;:108379
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2.
Short-term laboratory and related safety outcomes for the multiple sclerosis oral disease-modifying therapies: an observational study.
Kingwell, E, Zhang, T, Zhu, F, Walld, R, Carruthers, R, Evans, C, Marrie, RA, Tremlett, H
Expert opinion on drug safety. 2021;(4):481-487
Abstract
BACKGROUND Real-world safety data for the oral multiple sclerosis (MS) disease-modifying therapies (DMTs), dimethyl fumarate (DMF), fingolimod, and teriflunomide are important. We examined laboratory test abnormalities and adverse health conditions in new users. METHODS Linked laboratory and administrative health data were accessed for all persons with MS (PwMS) filling their first oral DMT prescription in two Canadian provinces. PwMS were followed from first prescription fill until discontinuation, death, emigration or study end. Proportions of PwMS, and incidence rates (IR)/100 person-years, were calculated for ≥1 event of elevated alanine aminotransferase (ALT) (>the upper limit of normal [ULN]; all DMTs), liver toxicity (ALT>3xULN; fingolimod); lymphopenia and proteinuria (DMF), and cardiac arrhythmia, hypertension and pneumonia (all DMTs). RESULTS Overall, 1,140 PwMS were followed for up to 2 years. De novo elevated alanine aminotransferase affected 13.2% (DMF), 12.4% (teriflunomide), and 30.0% (fingolimod) of users. Liver toxicity affected 2.8% of fingolimod, lymphopenia 3.1% of DMF, and proteinuria 2.9% of DMF users. The incidences of cardiac arrhythmia, pneumonia and hypertension ranged from <1 to 1.86/100 person-years depending on the DMT. CONCLUSIONS The short-term, real-world incidences of abnormal laboratory results or adverse events were consistent with the pivotal clinical trial findings. Longer-term safety data are still needed.
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3.
The Relationship Between Walking Speed and the Energetic Cost of Walking in Persons With Multiple Sclerosis and Healthy Controls: A Systematic Review.
Theunissen, K, Plasqui, G, Boonen, A, Brauwers, B, Timmermans, A, Meyns, P, Meijer, K, Feys, P
Neurorehabilitation and neural repair. 2021;(6):486-500
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Abstract
BACKGROUND Persons with multiple sclerosis (pwMS) experience walking impairments, characterized by decreased walking speeds. In healthy subjects, the self-selected walking speed is the energetically most optimal. In pwMS, the energetically most optimal walking speed remains underexposed. Therefore, this review aimed to determine the relationship between walking speed and energetic cost of walking (Cw) in pwMS, compared with healthy subjects, thereby assessing the walking speed with the lowest energetic cost. As it is unclear whether the Cw in pwMS differs between overground and treadmill walking, as reported in healthy subjects, a second review aim was to compare both conditions. METHOD PubMed and Web of Science were systematically searched. Studies assessing pwMS, reporting walking speed (converted to meters per second), and reporting oxygen consumption were included. Study quality was assessed with a modified National Heart, Lung and Blood Institute checklist. The relationship between Cw and walking speed was calculated with a second-order polynomial function and compared between groups and conditions. RESULTS Twenty-nine studies were included (n = 1535 pwMS) of which 8 included healthy subjects (n = 179 healthy subjects). PwMS showed a similar energetically most optimal walking speed of 1.44 m/s with a Cw of 0.16, compared with 0.14 mL O2/kg/m in healthy subjects. The most optimal walking speed in treadmill was 1.48 m/s, compared with 1.28 m/s in overground walking with a similar Cw. CONCLUSION Overall, the Cw is elevated in pwMS but with a similar energetically most optimal walking speed, compared with healthy subjects. Treadmill walking showed a similar most optimal Cw but a higher speed, compared with overground walking.
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Possible Role of Butyrylcholinesterase in Fat Loss and Decreases in Inflammatory Levels in Patients with Multiple Sclerosis after Treatment with Epigallocatechin Gallate and Coconut Oil: A Pilot Study.
de la Rubia Ortí, JE, Platero, JL, Yang, IH, Ceron, JJ, Tvarijonaviciute, A, Sabater, PS, Benlloch, M, Sancho-Cantus, D, Sancho, S
Nutrients. 2021;(9)
Abstract
(1) Background. Multiple sclerosis (MS) is characterised by the loss of muscle throughout the course of the disease, which in many cases is accompanied by obesity and related to inflammation. Nonetheless, consuming epigallocatechin gallate (EGCG) and ketone bodies (especially β-hydroxybutyrate (βHB)) produced after metabolising coconut oil, have exhibited anti-inflammatory effects and a decrease in body fat. In addition, butyrylcholinesterase (BuChE), seems to be related to the pathogenesis of the disease associated with inflammation, and serum concentrations have been related to lipid metabolism. Objective. The aim of the study was to determine the role of BuChE in the changes caused after treatment with EGCG and ketone bodies on the levels of body fat and inflammation state in MS patients. (2) Methods. A pilot study was conducted for 4 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. Fat percentage and concentrations of the butyrylcholinesterase enzyme (BuChE), paraoxonase 1 (PON1) activity, triglycerides, interleukin 6 (IL-6), albumin and βHB in serum were measured. (3) Results. The intervention group exhibited significant decreases in IL-6 and fat percentage and significant increases in BuChE, βHB, PON1, albumin and functional capacity (determined by the Expanded Disability Status Scale (EDSS)). On the other hand, the control group only exhibited a decrease in IL-6. After the intervention, BuChE was positively correlated with the activity of PON1, fat percentage and triglycerides in the intervention group, whereas these correlations were not observed in the control group (4). Conclusions. BuChE seems to have an important role in lipolytic activity and the inflammation state in MS patients, evidenced after administering EGCG and coconut oil as a βHB source.
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[Evaluation of the impact of lockdown on the health and lifestyle of users of the Fundacio Esclerosi Multiple's neurorehabilitation centres in Lleida and Reus].
Zabay-Neiro, MC, Nieves-Collado, M, Carrés-Gonzalez, G, Curto-Estupiñà, G, Gargallo-Noval, M, Martínez-Lerín, N, Torres-Calvo, S, Yaya-Tur, G
Revista de neurologia. 2021;(7):249-257
Abstract
INTRODUCTION On 13 March 2020, a state of alarm was declared due to the COVID-19 pandemic, resulting in total lockdown in Spain. The neurorehabilitation centres of the Fundacio Esclerosi Multiple (FEM) provide care for people diagnosed with neuroprogressive diseases with significant health deficits. We look at how lockdown can affect their way of life. AIMS To assess and manage the impact of lockdown on persons with multiple sclerosis (MS) and other neurodegenerative diseases. PATIENTS AND METHODS Analytical observational study. An anonymous questionnaire was administered to all the patients undergoing comprehensive rehabilitation treatment at two of the FEM centres; the survey included questions on the demographic and clinical characteristics of the subjects, and an assessment of the impact of the pandemic on the physical, social and psychological spheres. RESULTS A total of 202 surveys were analysed. The average age of the participants was 49.09 years and 77.8% had MS, while 22.2% had other conditions. The most frequently reported physical symptoms were muscle weakness, loss of balance and fatigue. The study population remained active during lockdown. More than half of them did not report any increase in cognitive symptoms, but they did mention an increased sense of worry on an emotional level. CONCLUSIONS We can state that the actions deployed by the FEM to reduce the consequences of lockdown have been effective and have minimised the occurrence of maladaptive behaviours. The study has also opened the door for us to add new lines of intervention.
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Onset of Marine-Lenhart syndrome and Graves' ophthalmopathy in a female patient treated with alemtuzumab for multiple sclerosis.
Le Moli, R, Russo, M, Malandrino, P, Vella, V, Belfiore, A, Frasca, F
Hormones (Athens, Greece). 2021;(1):161-165
Abstract
BACKGROUND Immune checkpoint blockade therapy may lead to thyroid dysfunction in 3-7% of treated patients. Alemtuzumab is a CD52 inhibitor leading to thyroid dysfunction in approximately 40% of patients. A female patient was affected by multiple sclerosis (MS) and subclinical hyperthyroidism due to an autonomously functioning thyroid nodule (AFTN). After alemtuzumab treatment, she developed aggressive clinical hyperthyroidism consistent with Marine-Lenhart syndrome. CASE PRESENTATION A 36-year-old woman presented in July 2019 with symptoms of hyperthyroidism and eye complaints. Three years earlier, she was diagnosed with MS. Subclinical hyperthyroidism was diagnosed in April 2017. Thyroid scintigraphy showed an intranodular distribution of 99mTc-pertechnatate consisting of an AFTN in the right lobe of the thyroid. In June 2018, because of the MS, she was treated with alemtuzumab. In November 2018, she was started on methimazole treatment because of the symptoms of hyperthyroidism. In December 2018, thyroid function was normal under methimazole treatment. In June 2019, the patient received a second round of alemtuzumab administration. One month later, she developed symptoms of hyperthyroidism. These symptoms were accompanied by diplopia. Blood tests showed severe hyperthyroidism. Thyroid scintigraphy showed a diffuse distribution of 99mTc-pertechnatate and the presence of a "cool" area in the right lobe of the thyroid, confirmed by ultrasonography. The nodule was diagnosed as a low-risk indeterminate lesion. CONCLUSION We present a case of Graves' disease with active, moderate-to-severe Graves' ophthalmopathy in a patient with pre-existing AFTN presenting with a coexisting, rare case of Marine-Lenhart syndrome associated with immune reconstitution after alemtuzumab treatment.
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The relationship between vitamin D levels and cognitive impairment in patients with multiple sclerosis.
Alhussain, F, Alomar, M, Alenazi, A, Aldraihem, M, Alshiha, L, Bashir, S
European review for medical and pharmacological sciences. 2021;(4):2021-2030
Abstract
OBJECTIVE Neurocognitive impairment is one of the most common manifestations of multiple sclerosis (MS). However, the pathophysiology of this issue is still poorly understood. The objective of this study is to investigate the relationship between vitamin D levels and cognitive function in patients with MS as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB). PATIENTS AND METHODS This was a cross-sectional, case-control study; the subjects were 39 Saudi patients diagnosed with MS. For all participants, demographic information, including age, sex, and educational level, was collected. Participants were also evaluated using the disease steps scale and the PHQ-9 scale. Their vitamin D levels were assessed, and the participants completed a computerized cognitive assessment using the CANTAB. RESULTS From the total sample of 39 patients with MS, 31 (79.5%) were female. Physical disability due to MS was insignificant in 25 (64.1%) of the subjects and significant in 14 (35.9%). Seventeen (43.6%) of the participants had normal vitamin D levels; 22 (56.4%) had low vitamin D levels. The MS patients had lower MOT mean errors than the control group, and this difference was statistically significant (t = -4.313, p < 0.01). Moreover, the scores of the two groups for all subcategories of the memory domain were different at statistically significant levels. Furthermore, the control group had higher PAL total errors (adjusted), PAL total errors (6 shapes, adjusted), and PRM percent correct than the MS patients (p < 0.01). The control group also achieved lower scores on SWM between errors and SWM strategy than the MS patients (p < 0.01). The MOT mean error was found to correlate with the disease steps score (r = 0.394, p < 0.05) and with significant physical disability (r = 0.457, p< 0.01). In the memory domain, PAL total errors (adjusted) correlated with age (r = 0.381, p < 0.05), SWM between errors correlated with age at onset of disease (r = 0.345, p < 0.05), and vitamin D level (r = 0.335, p < 0.05) and SWM strategy correlated with the number of relapses in the past 12 months (r = -0.355, p < 0.05). CONCLUSIONS Cognitive performance was impaired in patients with MS. Vitamin D deficiency, a potentially modifiable risk factor, independently predicted cognitive impairment in MS patients.
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Impact of previous disease-modifying treatment on effectiveness and safety outcomes, among patients with multiple sclerosis treated with alemtuzumab.
Pfeuffer, S, Ruck, T, Pul, R, Rolfes, L, Korsukewitz, C, Pawlitzki, M, Wildemann, B, Klotz, L, Kleinschnitz, C, Scalfari, A, et al
Journal of neurology, neurosurgery, and psychiatry. 2021;(9):1007-1013
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Abstract
OBJECTIVES Alemtuzumab is effective in patients with active multiple sclerosis but has a complex safety profile, including the development of secondary autoimmunity. Most of patients enrolled in randomised clinical trials with alemtuzumab were either treatment naïve or pretreated with injectable substances. Other previous disease-modifying treatments (DMTs) were not used in the study cohorts, and therefore, associated risks might yet remain unidentified. METHODS We retrospectively evaluated a prospective dual-centre alemtuzumab cohort of 170 patients. We examined the baseline characteristics as well as safety and effectiveness outcomes, including the time to first relapse, the time to 3 months confirmed disability worsening and the time to secondary autoimmunity. RESULTS The regression analysis showed that, among all previously used DMTs, the pretreatment with fingolimod (n=33 HRs for the time to first relapse (HR 5.420, 95% CI 2.520 to 11.660; p<0.001)) and for the time to worsening of disability (HR 7.676, 95% CI 2.870 to 20.534; p<0.001). Additionally, patients pretreated with fingolimod were more likely to experience spinal relapses (55% vs 10% among previously naïve patients; p<0.001) and had an increased risk of secondary autoimmunity (HR 5.875, 95% CI 2.126 to 16.27; p<0.001). CONCLUSION In the real-world setting, we demonstrated suboptimal disease control and increased risk of secondary autoimmunity following alemtuzumab, among patients previously treated with fingolimod. These data can provide guidance for improving MS therapeutic management.
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Intermittent Fasting and the Possible Benefits in Obesity, Diabetes, and Multiple Sclerosis: A Systematic Review of Randomized Clinical Trials.
Morales-Suarez-Varela, M, Collado Sánchez, E, Peraita-Costa, I, Llopis-Morales, A, Soriano, JM
Nutrients. 2021;(9)
Abstract
Intermittent fasting has become popular in recent years and is controversially presented as a possible therapeutic adjunct. A bibliographic review of the literature on intermittent fasting and obesity, diabetes, and multiple sclerosis was carried out. The scientific quality of the methodology and the results obtained were evaluated in pairs. Intermittent fasting has beneficial effects on the lipid profile, and it is associated with weight loss and a modification of the distribution of abdominal fat in people with obesity and type 2 diabetes as well as an improvement in the control of glycemic levels. In patients with multiple sclerosis, the data available are too scarce to draw any firm conclusions, but it does appear that intermittent fasting may be a safe and feasible intervention. However, it is necessary to continue investigating its long-term effects since so far, the studies carried out are small and of short duration.
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10.
A common genetic variant rs2821557 in KCNA3 is linked to the severity of multiple sclerosis.
Lioudyno, V, Abdurasulova, I, Negoreeva, I, Stoliarov, I, Kudriavtsev, I, Serebryakova, M, Klimenko, V, Lioudyno, M
Journal of neuroscience research. 2021;(1):200-208
Abstract
The rate of symptom accumulation distinguishes between slowly and rapidly progressing forms of multiple sclerosis (MS). Given that a patient's genetics can affect the rate of disease progression, identification of genetic variants associated with rapid disease progression should provide valuable information for timely prognosis and development of optimal treatment plans. We hypothesized that the polymorphism rs2821557 in the human KCNA3 gene encoding a voltage-gated potassium channel Kv1.3 might be one of these genetic variants, given the role of Kv1.3 in neuroinflammation, as well as the location and gain-of-function effect of this polymorphism. To test this hypothesis we performed an analytic study exploring the relationships between rs2821557 polymorphism and disease progression in a cohort of MS patients. The rs2821557 genotype and the rate of disease progression based on Multiple Sclerosis Severity Score (MSSS) were determined for 101 patients (68 females and 33 males). Peripheral blood CD4+ lymphocyte subpopulations (Tnaive , TCM , TEM ) and the expression of chemokine receptors (CXCR5, CXCR3, CCR6, CCR4) were estimated by flow cytometry. The comparisons between groups by genotype (TT, TC, CC) and allelic approach analysis (T vs. C) revealed a significantly higher incidence of the rapid disease course (MSSS ≥ 7.5) among minor C allele carriers (CC and TC) compared to patients with the TT genotype. Furthermore, C allele carriers had higher counts of CXCR3+ TEM cells than homozygous T allele carriers. In conclusion, accelerated MS progression in C allele carriers is likely linked to enhanced Kv1.3-mediated accumulation of pathogenic CXCR3+ TEM cells and exacerbated neuroinflammation.