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Introduction: Depression and the presence of a disability emerge as noteworthy predictors of the quality of life (QoL) in patients with multiple sclerosis (MS). In this article, we explore the relationship between disability status, depression, and quality of life in individuals with multiple sclerosis., Methods: A total of 150 patients participated in this cross-sectional study. A Persian translation of the Multiple Sclerosis Quality of Life-54 questionnaire was utilized to assess their health-related quality of life (QoL), while the patients' disability levels were measured using the Expanded Disability Status Scale. Additionally, we assessed patients' depression levels using the 21-item BDI-II scale. The questionnaire data were analyzed using SPSS version 25., Results: A total of 150 MS patients participated in the study, with a mean age of 33.4 years (SD = 3.1). The majority were female (n = 71.2 %). The mean EDSS score was 3.7 (SD = 1.8). In the correlation analysis, we found that EDSS scores were not significantly correlated with mental QoL (r = -0.180, p = 0.109), but were significantly correlated with lower physical QoL (r = -0.393, p 0.001). Depression scores were significantly correlated with mental QoL (r = -0.776, P 0.001) and physical QoL (r = -0. 726, P 0.001). The results reveal that both EDSS and Beck scores significantly affect mental and physical health, explaining 62 % and 60 % of their variances, respectively., Conclusion: Our findings indicate a significant relationship between physical quality of life and EDSS scores in MS patients. Higher EDSS scores consistently corresponded to more significant physical impact, as evidenced by higher impact ratings. Conversely, there was no clear association between EDSS scores and mental quality of life. Furthermore, increased depression levels were linked to reduced levels of both mental and physical well-being. These results emphasize the intricate interplay between the physical aspects of quality of life and their implications for the progression and severity of MS in patients., Competing Interests: Declaration of competing interest M.A.S and A.N.M: I have received educational, research grants, lecture honorarium, travel supports to attend scientific meetings from Biogen-Idec, Merck-Serono, Cinnagen, Zistdaru, Zahravi and Genzyme. The other authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cognitive impairments in patients with multiple sclerosis (MS) are suggested as a prognostic factor for disease development, and consequently higher disability and more deficits in daily and social activities. In this regard, we aimed to investigate the association between quality of life (QOL) and cognitive function in patients with MS. Methods: We conducted a cross-sectional study on patients with relapsing-remitting MS (RRMS). General characteristic variables were carried out, and then all patients underwent assessments such as Multiple Sclerosis Quality of Life-54 (MSQOL-54), Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS), Expanded Disability Status Scale (EDSS), Beck Depression Inventory-II (BDI-II), and North American Adult Reading Test (NAART). Results: In the present study, a total of 92 patients, including 76 women with a mean disease duration of 6.82 ± 4.80 years were involved. Results of simple Pearson correlation revealed a significant positive relation between California Verbal Learning Test (CVLT) total learning with MSQOL mental health (r = 0.267, P = 0.017) and physical health (r = 0.299, P = 0.007). After adjusting for potential confounders, there was a negative correlation between MSQOL mental health with Delis-Kaplan Executive Function System (D-KEFS) (r = -0.303, P = 0.015) and Judgment of Line Orientation (JLO) (r = -0.310, P = 0.013). Besides, MSQOL physical health was negatively associated with Brief Visuospatial Memory Test-Revised (BVMT-R) in the adjusted model (r = -0.270, P = 0.031). Conclusion: There is a statistically significant association between specific aspects of cognitive decline and QOL. Therefore, more attention should be paid to cognitive impairment in patients with MS as based on our findings, it is significantly associated with QOL., Competing Interests: The authors declare no conflict of interest in this study., (Copyright © 2022 Iranian Neurological Association, and Tehran University of Medical Sciences Published by Tehran University of Medical Sciences.)

Background: The present study aimed to address the effect of Rituximab on the cognitive impairment in patients with secondary progressive MS (SPMS)., Methods: The present interventional study used a convenience sampling method to select the study participants from SPMS patients. All these patients had progressive disability over the last two years before being admitted in the study. Prior to the administration of Rituximab, the minimal assessment of cognitive function in the multiple sclerosis (MACFIMS) test was performed for each patient who was a candidate to be included in this study. This test was repeated by passing 6 and 12 months from the initial treatment with Rituximab. Since the data needed for this study were obtained at different time intervals, so a linear mixed model was used for their analysis. Analysis of variance (ANOVA) was also used to investigate whether time and sex generally affect the cognitive impairments in SPMS patients. A p-value <0.05 was considered as statistically significant in this study., Results: Of the total 35 patients, 34% and 66% were men and women with a mean age of 41.33 and 41.39 years old, respectively. Rituximab showed a significant positive effect on a number of subgroups of MACFIMS test, including Controlled Oral Word Association Test (COWAT) (P-value: 0.038) and Brief Visuospatial Memory Test (BVMT-total) (P: 0.019)., Conclusion: The present study revealed that Rituximab has a positive effect on the cognitive impairment resulted from MS in secondary progressive patients., Competing Interests: Abdorreza Naser Moghadasi and Mohammad Ali Sahraian have received speaker’s honoraria from AryoGen Pharmed. The other authors do not have any conflict of interest.

Background: One of the most concerning features that involves 40-70% of patients with multiple sclerosis (MS) is cognitive impairment. Moreover, it affects various aspects of patients' life. In this regard, this study was conducted to find independent predictors of cognitive function., Method: We performed a cross-sectional analysis on 92 patients chosen from MS clinic of Sina hospital, Iran. After completing a general questionnaire of demographic and various clinical features, the included participants (patients with RRMS) underwent neuropsychological assessment using Minimal Assessment of Cognitive function in Multiple Sclerosis (MACFIMS), Expanded disability Status Scale (EDSS), Beck Depression Inventory II (BDI-II), and National American Adult Reading Test (NAART). An un-weighted average of MACFIMS subscales z-scores was reported as cognitive index. In order to find the association between CI and different factors, each variable was entered in a simple regression model first. Then, a univariate multiple regression model was invoked to evaluate the predictors of cognitive index in patients., Results: Simple regression for cognitive index of 92 patients (86% female) with a mean age of 33.4±7.6 years old suffering of RRMS for 6.8±4.8 years revealed patients with history of former smoking (p=0.001), sole visual symptoms as the presentation sign of the study (β=-0.341, p=0.001), lower EDSS score (β=-0.299, p=0.005), higher NAART score (β=0.416, p≤0.0001), and college education (p=0.001), had better cognitive function in our study population. Such factors including age, educational status, BDI-II score, EDSS score, and disease duration were fixed and the other significant factors entered once separately and then simultaneously in the univariate multiple linear regression model. It was revealed that former smoking (β=-0.372, p≤0.0001), NAART (β=0.304, p=0.002), and EDSS (β= -0.185, P=0.045) are associated significantly with the cognitive function of patients with multiple sclerosis., Conclusion: This study demonstrated NAART, as a proxy of premorbid intelligence, history of former smoking, and EDSS score may have effects on cognitive function in MS. Future studies need to be invoked for the evaluation of the causality relation of these factors., (Copyright © 2021. Published by Elsevier B.V.)

Background: Many patients with multiple sclerosis (MS) endure cognitive impairment, which affects their everyday life and lowers their life quality. It has been demonstrated that obesity can result in poor cognitive performance in healthy individuals through various mechanisms. Therefore, we aimed at assessing the association between body mass index (BMI) and cognitive function in MS patients, using minimal assessment of cognitive functions in MS (MACFIMS) battery., Method: This study included eighty-one patients with relapsing-remitting MS (RRMS). After collecting the demographic data, patients' height and weight were measured in order to calculate BMI. Then, MACFIMS battery was administered in one session, after obtaining information using expanded disability status scale (EDSS)., Results: Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT) scores were negatively correlated with BMI (P values are equal to 0.005 and 0.037, respectively). PASAT score correlated with BMI after controlling for sex, age, and EDSS, but SDMT score did not correlate. Nevertheless, no significant variation was observed in the BMI level among individuals having MS with or without cognitive deficit., Conclusion: We have shown that, BMI is associated with poor cognitive performance in some tests which, MACFIMS battery was included. This could suggest that obesity might be an important factor, which have effect on the cognitive performance., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Complement system activation products are present in areas of neuroinflammation, demyelination, and neurodegeneration in brains of patients with multiple sclerosis (MS). C3 is a central element in the activation of complement cascades. A common coding variant in the C3 gene (rs2230199, C3R102G) affects C3 activity., Objectives: To assess the effects of rs2230199 on MS severity using clinical, cognitive, and imaging measures., Methods: In total, 161 relapse-onset MS patients (Expanded Disability Status Scale (EDSS) ≤ 6) underwent physical assessments, cognitive tests (Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and California Verbal Learning Test (CVLT)), and magnetic resonance imaging (MRI). Lesion volumes were quantified semi-automatically. Voxel-wise analyses were performed to assess the effects of rs2230199 genotype on gray matter (GM) atrophy ( n = 155), white matter (WM) fractional anisotropy (FA; n = 105), and WM magnetization transfer ratio (MTR; n = 90)., Results: While rs2230199 minor-allele dosage (C3-102G) showed no significant effect on EDSS and Multiple Sclerosis Functional Composite (MSFC), it was associated with worse cognitive performance ( p = 0.02), lower brain parenchymal fraction ( p = 0.003), and higher lesion burden ( p = 0.02). Moreover, voxel-wise analyses showed lower GM volume in subcortical structures and insula, and lower FA and MTR in several WM areas with higher copies of rs2230199 minor allele., Conclusion: C3-rs2230199 affects white and GM damage as well as cognitive impairment in MS patients. Our findings support a causal role for complement system activity in the pathophysiology of MS.

Background: Mesenchymal stem cells (MSCs) are a potential therapy for various diseases. Here, the results of intrathecal injection of MSCs in multiple sclerosis (MS) patients are reported., Materials and Methods: Four patients were enrolled in the study. Three were male and one was female. There were three secondary-progressive MS patients and one relapsing-remitting MS patient. An amount of 50-80 ml of bone marrow was collected from the patients. MSC cultures were collected for each microbiological examination at each change of medium and passage as well as at the time of sample injection. Then, MSCs were injected into the patients by the intrathecal method. In two patients, the injection was replicated in 1 year., Results: All the patients were followed up for 2 years. Three patients who had secondary progression did not show disease progress after the injection, and the disease entered a stable state. A degree of recovery was observed in two patients. The relapsing-remitting patient suffered an attack that led to corticosteroid injection. None of the patients reported side effects. In terms of magnetic resonance imaging, there were no new plaques or enhanced plaques., Conclusion: This study suggests that injection of MSC can be a suitable method, especially for secondary-progressive patients. It seems that reinjection of these stem cells can be safe and sustaining it positively increases the effects of this therapeutic approach.

Background: In combined high median and ulnar nerve injury, transfer of the posterior interosseous nerve branches to the motor branch of the ulnar nerve (MUN) is previously described in order to restore intrinsic hand function. In this operation a segment of sural nerve graft is required to close the gap between the donor and recipient nerves. However the thenar muscles are not innervated by this nerve transfer. The aim of the present study was to evaluate whether the superficial radial nerve (SRN) can be used as an "in situ vascular nerve graft" to connect the donor nerves to the MUN and the motor branch of median nerve (MMN) at the same time in order to address all denervated intrinsic and thenar muscles., Methods: Twenty fresh male cadavers were dissected in order to evaluate the feasibility of this modification of technique. The size of nerve branches, the number of axons and the tension at repair site were evaluated., Results: This nerve transfer was technically feasible in all specimens. There was no significant size mismatch between the donor and recipient nerves Conclusions: The possible advantages of this modification include innervation of both median and ulnar nerve innervated intrinsic muscles, preservation of vascularity of the nerve graft which might accelerate the nerve regeneration, avoidance of leg incision and therefore the possibility of performing surgery under regional instead of general anesthesia. Briefly, this novel technique is a viable option which can be used instead of conventional nerve graft in some brachial plexus or combined high median and ulnar nerve injuries when restoration of intrinsic hand function by transfer of posterior interosseous nerve branches is attempted.

Background: Emotional intelligence refers to a process through which an individual is not only capable of understanding his/her/others' emotions, but also is able to manage them. Emotional intelligence can get disturbed due to different neurological diseases. Since cognition and emotion are directly and closely related, the present study aims to evaluate the relationship between emotional intelligence and cognitive disorders in patients with Multiple Sclerosis (MS). Methods: The demographic data of 92 MS patients participating in this study were recorded. The emotional intelligence and cognitive disorders were studied using the Bradberry-Greaves, and MS Neuropsychological Questionnaire (MSNQ) tests, respectively. Results: 16 men and 76 women were considered in this study. The mean age of the participants was 33.4 years, the mean duration of the disease was 6.8 years, the mean of Expanded Disability Status Scale (EDSS) was 1.97, the mean MSNQ was 21.58, and the mean emotional quotient (EQ) of the patients was 74.18. The MSNQ had a significant relationship with the total EQ and its sub-categories (P < 0.05). Conclusion: This study showed that EQ and cognitive disorders are directly relevant to each other; as cognitive disorder increases, the EQ rate decreases. Therefore, cognitive rehabilitation might be effective in enhancing the EQ in these patients.

Background: Trauma and ventilator-induced lung injury is often associated with endothelial-epithelial barriers breakdown, which may lead to multiple system organ failure (MSOF) and death in critically ill patients. Although molecular mechanism involved in MSOF is not known, junctional opening is believed to happen. In vitro, thyroid hormones inhibit myosin light chain (MLC) phosphorylation and may, thus, inhibit cellular contraction and junctional opening. Trauma is also associated with tissue hypo-thyroid state. Therefore, we examined the effects of thyroid function on expression of phospho-MLC (pp-MLC) and claudin 4 (Clud4), key proteins involved in regulation of junctional tightness, in lung injury., Methods: Rats were rendered hypo-thyroid (Hypo) or hyperthyroid (Hyper) by adding methimazole or levo-thyroxine, respectively, to their drinking water. Untreated euthyroid (Eue) animals were used as control. Lung pp-MLC and Clud4 proteins were assessed by western blotting and in situ immunodetection, respectively. Lung injury was induced by high tidal volume mechanical ventilation., Results: Lung injury was significantly enhanced in Hypo animals and attenuated in Hyper animals. Parallel changes in expression of lung pp-MLC were detected. Alterations in lung histomorphology correlated with the level of pp-MLC. Expression of alveolar and bronchiolar Clud4 protein was differentially affected by the state of thyroid gland., Conclusions: Our data suggest that thyroid function plays significant role in lung injury perhaps by modulating expression of the proteins involved in junctional tightness. Besides, they strongly support the idea that the tissue hypo-thyroid state may contribute to endothelial-epithelial barriers breakdown associated with trauma., (© 2015 John Wiley & Sons Ltd.)

Objectives: Multiple Sclerosis is a demyelinating disease that can cause different symptoms by the autoimmune involvement of myelin. CD4+ and CD8+ T-cells as well as B-cells play important roles in MS pathophysiology. Co-existence of other autoimmune diseases and multiple sclerosis has been reported previously in the literature. It is not clear whether this co-existence may change the clinical course of MS or not. In this study we aim to evaluate the prevalence of other autoimmune diseases among patients with MS and if they may play any role in the clinical course of the patients., Patients and Methods: Twenty four patients with multiple sclerosis and another simultaneous autoimmune disease were detected among 1700 patients referred to the MS clinic of Sina Hospital during two years. Sex, age, duration of MS and the autoimmune disease as well as the type of the latter were recorded. For evaluation of disease progression a control group was randomly selected from the same patients referred to the clinic. EDSS was measured and recorded in both groups., Results: The prevalence of concomitant autoimmune disease and multiple sclerosis was 0.014. The mean age of the patients was 35.04±6.45years. There were 18 different autoimmune diseases in the first group. The mean duration of MS and concomitant autoimmune disease were 5.91 and 9.80±7.1years respectively. The mean of EDSS in these patients was 1.62±1.12 and in the control group was 3.33±1.89. One patient had developed secondary progressive course in the first group. The statistical difference between these groups based on EDSS, was significant (P-value: <0.001). The median of EDSS in the first group was 1.5 and in the second one was 2.5. The mean of annual relapse rate in the first group was 0.60 and in the second one was 0.62 (P-value: 0.71)., Conclusion: The present study shows that several other autoimmune diseases may coexist with MS and their presence may modify the course of the disease. This should be re-evaluated in multicenter prospective long term studies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To determine the motor-behavioral and neural correlates of putative functional common variants in the sodium-channel NaV1.8 encoding gene (SCN10A) in vivo in patients with multiple sclerosis (MS)., Methods: We recruited 161 patients with relapsing-onset MS and 94 demographically comparable healthy participants. All patients with MS underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 patients with MS to evaluate differences in cerebellar functional connectivity. All participants were genotyped for 4 potentially functional SCN10A polymorphisms., Results: Two SCN10A polymorphisms in high linkage disequilibrium (r(2) = 0.95) showed significant association with MSFC performance in patients with MS (rs6795970: p = 6.2 × 10(-4); rs6801957: p = 0.0025). Patients with MS with rs6795970(AA) genotype performed significantly worse than rs6795970(G) carriers in MSFC (p = 1.8 × 10(-4)) and all of its subscores. This association was independent of EDSS and cerebellar atrophy. Although the genotype groups showed no difference in regional brain volumes, rs6795970(AA) carriers demonstrated significantly diminished cerebellar functional connectivity with the thalami and midbrain. No significant SCN10A-genotype effect was observed on MSFC performance in healthy participants., Conclusions: Our data suggest that SCN10A variation substantially influences functional status, including prominent effects on motor coordination in patients with MS. These findings were supported by the effects of this variant on a neural system important for motor coordination, namely cerebello-thalamic circuitry. Overall, our findings add to the emerging evidence that suggests that sodium channel NaV1.8 could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS., (© 2016 American Academy of Neurology.)

Introduction: Neuromyelitis optica is a demyelinating disease of the central nervous system with various patterns of brain lesions. Corpus callosum may be involved in both multiple sclerosis and neuromyelitis optica. Previous case reports have demonstrated that callosal lesions in neuromyelitis optica are usually large and edematous and have a heterogeneous intensity showing a "marbled pattern" in the acute phase. Their size and intensity may reduce with time or disappear in the chronic stages., Case Presentation: In this report, we describe a case of a 25-year-old Caucasian man with neuromyelitis optica who presented clinically with optic neuritis and myelitis. His brain magnetic resonance imaging demonstrated linear enhancement of the corpus callosum. Brain images with contrast agent added also showed linear ependymal layer enhancement of the lateral ventricles, which has been reported in this disease previously., Conclusions: Linear enhancement of corpus callosum in magnetic resonance imaging with contrast agent could help in diagnosing neuromyelitis optica and differentiating it from other demyelinating disease, especially multiple sclerosis.

Myosin light chain kinase (MLCK) may play a key role in cellular contraction, paracellular permeability and lung water homeostasis. In vitro, thyroid hormones (THs) potently inhibit MLCK activation and, hence, MLC phosphorylation. Whether similar effect is exerted by THs in in vivo systems is not known. Therefore, we investigated the effects of hypothyroid (HO) and hyperthyroid (HR) states on the level of phospho-MLC, aquaporin 5 (AQP5) protein expression, and water holding capacity in the rat lung. Alterations in thyroid state were induced by adding methimazole or levothyroxine (L-T4) to animals' drinking water. Serum TH concentration and thyroid gland histomorphology were assessed to verify the onset of the thyroid state. Lung phospho-MLC and AQP5 proteins were assessed by Western blotting and immunohistochemistry. Lung extravascular water content was estimated by the tissue wet weight-to-dry weight (W/D) ratio. The HO state induced significant increases in the expression of lung phospho-MLC and AQP5 proteins. In contrast, the HR state caused moderate decreases in lung phospho-MLC and AQP5 proteins. While lung water holding capacity was significantly increased in HO animals, it was significantly reduced in HR animals. The data of this study show that THs are able to modulate MLC phosphorylation in in vivo systems. Besides, they suggest that the circulating level of THs may alter lung fluid balance not only through expression of water channels but also through regulation of cellular contraction and paracellular permeability.

Background: Functional characterization of human amniotic fluid (AF) proteome, 845 proteins, has revealed that top three functions are cell proliferation, movement and differentiation, events fundamental to development, and tissue repair. Although these findings fortify the idea that AF components play roles in regeneration-like fetal wound healing, it is not known whether the components endure processing. Therefore, we processed AF and tested its effects on diabetes-impaired wound healing in an animal model., Materials and Methods: Through a germfree procedure, mature and premature AF samples were collected, respectively, from the mothers of full-term and preterm infants. Excisional wounds were generated on the dorsum of diabetic rats. Wounds were treated on day 3 and harvested on day 7 postwounding. Proliferating cell nuclear antigen and alpha-smooth muscles actin, markers for mitosis and angiogenesis, respectively, were assessed by in situ immunodetection method., Results: Significant increases in the rate of wound closure and proliferating cell nuclear antigen-expressing cells were observed in AF-treated wounds when compared with that of sham and control wounds. Likewise, the number of large vessels was significantly increased in the wounds treated with the AF. However, population of myofibroblasts was not affected by the treatment. The mature and premature AF were almost equally effective., Conclusions: Our data, for the first time, show that processed AF accelerates diabetes-impaired wound healing by activating mitosis and angiogenesis, indicating that bioactive molecules in AF may endure processing. We believe that processed forms of this naturally designed "Cocktail" of bioactive molecules may have multiple clinical applications., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The aim of the current study was to evaluate anxiety in patients with multiple sclerosis (MS) and factors which are associated with this symptom. Eighty totals of 180 patients with MS were enrolled in this cross-sectional study. They were asked to answer the valid and reliable Persian version of the Beck depression inventory (BDI) and Beck anxiety inventory (BAI) questionnaires. Demographic characteristics (sex and age), duration of the disease, disease course and Kurtzke Expanded Disability Status Scale (EDSS) were recorded for all participants. Mean BDI was 17.5 ± 11.4 in patients while mean BAI was17.7 ± 12.5 in all participants, respectively. Mean BDI and BAI were not statistically different between male and female participants. Patients with higher levels of disability (higher EDSS) had significant higher BDI and BAI scores and there was significant positive correlation between EDSS and BDI and BAI scores (rho=0.42, P<0.001, rho=0.35, P<0.001). Patients with SP (Secondary progressive) type of disease had significant higher BDI and BAI score. Multiple linear regression analysis showed that depression and disability level were independent predictors of anxiety in patients. Anxiety and factors which are related with this symptom should be considered in MS patients.

Introduction: Several cases of sarcoidosis following treatment with interferon-α have been reported in the literature, but those following interferon-β are very rare. We report the case of a patient with multiple sclerosis who developed pulmonary and cutaneous sarcoidosis following treatment with Betaseron® (interferon-β-1b)., Case Presentation: A 33-year-old Caucasian woman with a history of multiple sclerosis, treated with interferon-β-1b for 2.5 years developed erythema nodosum in her lower limbs, a breast abscess, and unilateral adenopathy of her left lung. A skin biopsy confirmed sarcoidosis. After the discontinuation of interferon-β-1b and treatment with indomethacin and prednisolone, she recovered., Conclusions: Sarcoidosis is considered one of the most common multiple sclerosis imitators with involvement of the central nervous system. However, although rare, sarcoidosis can develop following treatment with interferon-β-1b and should be considered in patients with multiple sclerosis treated with beta-interferons who develop pulmonary or extra-pulmonary manifestations of sarcoidosis. Interferon-β-1b discontinuation is the first and most important step in the treatment of such cases followed by treatment with corticosteroids.

Dream should be considered as a kind of cognitive ability that is formed parallel to other cognitive capabilities like language. On the other hand, multiple sclerosis (MS) is a complex disease that can involve different aspects of our cognition. Therefore, MS may influence patients' dreams. In fact, we do not know what the importance of dream is in MS, but further studies may introduce dream and dreaming as a sign of improvement or progression in MS disease.