Clinical Course Of Multiple Sclerosis Research Articles

Rola androgenów w patogenezie i przebiegu klinicznym stwardnienia rozsianego. Nowe możliwości terapii

Rola androgenów w patogenezie i przebiegu klinicznym stwardnienia rozsianego. Nowe możliwości terapii

3. Functional MRI in the diagnosis and prognosis of multiple sclerosis

Whereas morphological MR imaging provides clear evidence of white and gray matter lesions reflecting multiple sclerosis (MS) pathology, functional MRI (fMRI) studies of the motor, visual and cognitive networks in MS patients have provided evidence of more diffuse cortical changes. Compared with healthy subjects, fMRI changes are characterized by expansion within physiological task-related networks, such as more prominent participation of higher-level areas or recruitment of additional areas, as well as differences in resting state networks and disrupted within-network connectivity. Longitudinal fMRI studies have demonstrated that the observed abnormalities vary over the course of the disease, even in patients in disease remission (i.e., outside of relapses). Treatment interventions, such as treatment of leg spasticity with intramuscular botulinum toxin, may cause notable, even if transient, normalization of task-related networks. Functional MRI changes in MS reflect morphological MRI abnormalities, especially when more sensitive techniques are applied to detect normal-appearing white and gray matter of the brain and spinal cord. This phenomenon fits in the more widely described mechanism of increased recruitment within functional networks to at least partially compensate for structural damage in brain diseases as diverse as stroke and amyotrophic lateral sclerosis ( Weiller et al., 2006 ). While notable progress has been made to improve prognosis of the clinical course of MS using sophisticated morphological markers, e.g., ( Kalincik et al., 2012 , Zivadinov et al., 2013 ), functional MRI might also contribute to improve disease monitoring prognosis. Finally, functional MRI may be used to study the effects of different therapies on central nervous system engagement ( Filippi and Rocca, 2013 ).

Association of cerebrospinal fluid levels of lateral olfactory tract usher substance (LOTUS) with disease activity in multiple sclerosis.

Although multiple sclerosis (MS) is generally considered an autoimmune demyelinating disorder of the central nervous system, axonal degeneration through Nogo receptor-1 signaling was recently recognized as an important pathological feature. Our previous identification of lateral olfactory tract usher substance (LOTUS), an endogenous Nogo receptor-1 antagonist, prompted us to analyze the relationship between LOTUS levels of cerebrospinal fluid and the clinical course of MS to evaluate whether LOTUS could be a useful biomarker for MS. To examine variations in LOTUS concentrations in the cerebrospinal fluid of patients with MS in accordance with their clinical course. Cerebrospinal fluid samples were obtained retrospectively from normal controls (NCs; n = 27) and patients with MS (n = 40), amyotrophic lateral sclerosis (n = 22), and multiple system atrophy (n = 10) between January 1, 2008, and January 1, 2014. Patients with MS were divided into relapsing-remitting MS (RRMS; n = 30) and secondary progressive MS (n = 10). Patients with RRMS were further divided into relapse and remission groups. The LOTUS concentration in cerebropsinal fluid was quantitatively detected by immunoblotting using a specific LOTUS antibody and the concentrations compared in accordance with the patients' clinical course, such as remission and relapse groups in RRMS and secondary progressive MS. The mean (SD) cerebrospinal fluid LOTUS concentration in the relapse group of RRMS (9.3 [3.6] µg/dL) was lower than that of NCs (19.2 [4.7] µg/dL; P < .001) whereas the level in the remission group of RRMS (19.6 [5.8] µg/dL) was similar to that of NCs. The LOTUS concentration in SPMS (6.7 [1.4] µg/dL; P < .001) was lower than that of NCs and the remission group of RRMS. The LOTUS levels in other neurodegenerative diseases, such as amyotrophic lateral sclerosis and multiple system atrophy, were normal. Variations in LOTUS concentrations were correlated with disease activity in MS. Therefore, LOTUS concentration may be useful as a possible biomarker for MS. Low LOTUS concentrations may be possibly involved in Nogo receptor-1 signaling, which may induce axonal degeneration in the relapse phase of RRMS and secondary progressive MS.

A retrospective analysis of the effect of pregnancy on the course of multiple sclerosis

For a long time it was believed that pregnancy worsens the clinical course of multiple sclerosis. In several European countries, there have been several studies that have demonstrated remission of autoimmune aggression during pregnancy. We studied the effect of pregnancy on the course of multiple sclerosi. A retrospective analysis of disease course of 279 patients was performed for the first time in three major Russian centers (Moscow, Novosibirsk, Tyumen). There was a remission of autoimmune aggression during pregnancy. The use of DMT before pregnancy was a predictor of a more favorable course of the disease after delivery. An earlier beginning of DMT after delivery led to a significant risk reduction of relapses.

Vitamin D Deficiency and Possible Role in Multiple Sclerosis

Vitamin D is not only an essential nutrient for bone homeostasis but has also been implicated in many other disorders including cardiovascular disease (CVD) and autoimmune diseases. Here we review the problem of vitamin D deficiency and guidelines to help achieve adequate levels in both the general population and in multiple sclerosis (MS) patients and its role in MS and impact on treatment. Although there is a lack of consensus on vitamin D deficiency and insufficiency, they have been defined as a serum level of 25(OH)D &lt;50 nmol/L or 52.5–72.5 nmol/L, respectively. Deficiency is common in all age groups. Vitamin D is probably involved in the prevention of a number of disease states and 25(OH)D is thought to regulate at least 2,000 genes. Vitamin D toxicity is very rare, with none seen at doses up to 20,000 IU/day. However, the majority of primary care clinicians are not aware of the recommended dose for vitamin D supplementation and optimum serum level in terms of patients with MS. Several organisations have concluded that vitamin D screening cannot be recommended in the general population. Guidelines have been published on treatment and prevention of vitamin D deficiency, particularly for at-risk groups and during pregnancy. There is much evidence for the protective effects of vitamin D in MS. A higher level of sun exposure and intake of vitamin D as well as of serum 25 (OH)D, are associated with a lower risk of MS. It also has a beneficial effect on the clinical course of MS, such as lowering the risk of relapses. Growing evidence indicates that the effects of interferon-beta are additively enhanced by 25(OH)D in MS and this may be due to its modulating vitamin D metabolism.

Objectively Measured Physical Activity Is Associated with Brain Volumetric Measurements in Multiple Sclerosis.

Background. Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS). Purpose. This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI) in MS. Method. 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV), normalized WM volume (NWMV), and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations (pr) controlling for demographic and clinical variables. Results. Moderate-to-vigorous physical activity (MVPA) was significantly associated with NGMV (pr = 0.370, p < 0.05), NWMV (pr = 0.433, p < 0.01), hippocampus (pr = 0.499, p < 0.01), thalamus (pr = 0.380, p < 0.05), caudate (pr = 0.539, p < 0.01), putamen (pr = 0.369, p < 0.05), and pallidum (pr = 0.498, p < 0.01) volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. Conclusion. Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS.

Polymorphism of the osteopontin gene and clinical course of multiple sclerosis in the Polish population.

Osteopontin (OPN) is a key cytokine involved in T-cell activation in multiple sclerosis (MS). We investigated whether polymorphism of the osteopontin gene affects MS occurrence and clinical course in a Polish population. Disability in 100 MS patients was evaluated using the Expanded Disability Status Scale (EDSS). Genotype and allele frequencies at exons 6 and 7 were examined by PCR. Using appropriate statistical tests, the distribution of variables was tested and means ± SD compared. Genotype distribution and allele frequency differences between patients and control individuals were not statistically significant. No association of OPN with susceptibility to MS was found in the Polish population. The EDSS score was higher in 8090 T/T + 9250 C/C patients than in 8090 C/C + 9250 C/C MS patients (p = 0.0120), and the disability in 8090 C/C + 9250 C/T MS patients was higher than in 8090 C/C + 9250 C/C MS patients (p = 0.0137). Logistic regression analysis revealed age to be an independent factor influencing disability. The polymorphisms of the OPN gene in positions 8090 T/T + 9250 C/C, 8090 C/C + 9250 C/T, and 8090 C/T + 9250 C/T were linked with higher levels of disability in MS patients.

Tratamiento sintomático y del brote de esclerosis múltiple

In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients’ quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high–dose methylprednisolone and plasmapheresis

Physical activity and health-related quality of life over time in adults with multiple sclerosis.

This prospective panel study examined the relationship between changes in physical activity and health-related quality of life (HRQOL) across a 6-month period in persons with multiple sclerosis (MS). Adults with a definite diagnosis of MS completed a battery of questionnaires that included the Godin Leisure-Time Exercise Questionnaire (Godin & Shephard, 1985) and the 36-item Medical Outcomes Study Short-Form Health Survey (SF-36; Ware & Sherbourne, 1992) at baseline (n = 292) and 6-month follow-up (n = 276). The data were analyzed using panel analysis in Mplus 6.0. The panel model represented an acceptable fit for the data (χ2 = 140.72, df = 56, standardized root mean square residual = 0.06, comparative fit index = 0.98). The standardized path coefficients were statistically significant between follow-up physical activity and follow-up Physical Function (β = .12, p < .005), Role-Emotional (β = .16, p < .01), Vitality (β = .13, p < .001), and Social Function (β = .12, p < .05). Those who reported a change (increase or decrease) in levels of physical activity over 6 months reported a change (improving or worsening, respectively) in HRQOL on 4 of 8 domains on the SF-36, independent of disability status, MS clinical course and duration, age, and sex. The observed pattern of relationships supports the possibility that changing physical activity through an intervention might yield desirable changes in HRQOL, particularly domains representing the mental component.

The influence of immunomodulatory treatment on the clinical course of multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease of the central nervous system. One of the major questions concerning the clinical progression of MS, still insufficiently elaborated or confirmed, is if it can be slowed down or augmented by external factors. Immunomodulatory treatment is a disease modifiable factor shown to influence disease progression of various medical conditions. To investigate if treatment affects the long-term clinical progression of MS, measured as time from diagnosis to score of 4 or higher of Expanded Disability Status Scale (EDSS). Longitudinal, prospective data concerning treatment status and EDSS were collected by health professionals in the Swedish MS Registry. Study cohort comprised new diagnosed MS patients at Karolinska Hospital between 2001 and 2005. Survival analysis adjusted for suspected confounders was used with the outcome variable time from diagnosis to EDSS ≥ 4. Early treatment was correlated with longer time from diagnosis to EDSS ≥ 4 (HR: 1.77; 95 % CI: 1.15-2.73; p = 0.01). Additionally, the influence of the covariates-age at onset and the baseline EDSS, which were statistically significant with hazard ratios of 1.03 and 2.1, respectively, was found. Early treatment was associated with a better clinical outcome.

Further validation of the Six-Spot Step Test as a measure of ambulation in multiple sclerosis

BackgroundThere is preliminary evidence regarding the validity of the Six-Spot Step Test (SSST) as a promising measure of ambulatory function in persons with multiple sclerosis (MS). To date, this assessment has not been subject to the same rigor and extent of psychometric evaluation as other widely-accepted measures of ambulatory (e.g., timed 25-foot walk (T25FW)). ObjectiveThis study aimed to provide additional validity evidence for the SSST in 96 persons with MS, based on construct validity and precision. Construct validity involves examining the pattern of associations between the SSST and other measures, and precision involves comparing SSST performance relative to other valid measures of ambulation for differentiating between levels of disability status, MS clinical course, and fall risk based on balance confidence. MethodsAll participants completed the SSST, T25FW, Timed Up-and-Go (TUG), six-minute walk, Multiple Sclerosis Walking Scale-12, Late-Life Function and Disability Inventory, Activities-specific Balance Confidence, and Paced Auditory Serial Addition Test. All participants further underwent a neurological examination for generating EDSS scores, and then wore an ActiGraph accelerometer for the waking hours of a 7-day period. ResultsSSST performance was strongly associated with other valid measures of ambulation (|ρ|=.65–.90) and disability status (ρ=.73), moderately-to-strongly associated with balance confidence (ρ=.58), and weakly-to-moderately associated with cognitive processing speed and non-ambulatory measures (|ρ|=.35–.39). The SSST demonstrated stronger relative precision in discriminating between levels of disability status, MS clinical course, and fall risk based on balance confidence than the T25FW and TUG. ConclusionsWe provide comprehensive validity evidence for the SSST that supports its consideration for inclusion alongside other highly-regarded objective measures of ambulatory function for clinical research and practice in persons with MS.

Multiple sclerosis clinical course and cardiovascular disease risk - Swedish cohort study.

Cardiovascular disease (CVD) risk amongst multiple sclerosis (MS) patients appears raised, but few studies have examined CVD risk amongst an unselected MS patient group. MS course may be relevant for CVD risk. Our aim was to assess CVD risk and variation by course in MS patients. The Multiple Sclerosis Register identified 7667 patients who received an MS diagnosis between 1964 and 2005. They were matched by age, period, region and sex with 76045 members of the general population without MS using Swedish registers. Poisson regression compared the two cohorts to estimate the relative risk for CVD, overall, as well as grouped and individual CVD diagnoses. MS patients had an increased adjusted relative risk (with 95% confidence intervals; number of MS cohort events) for CVD of 1.31 (1.22-1.41; n=847), with some variation by course: relapsing-remitting 1.38 (1.17-1.62; n=168); secondary progressive 1.30 (1.18-1.53; n=405) and primary progressive 1.15 (0.93-1.41; n=108). The association for the relapsing-remitting course was not significant after excluding the first year of follow-up. Overall incidence rates per 1000 person-years for CVD are 11.8 (11.06-12.66) for the MS cohort and 8.8 (8.60-9.05) for the non-MS cohort. The most pronounced association was for deep vein thrombosis: relapsing-remitting 2.16 (1.21-3.87; n=14), secondary progressive 3.41 (2.45-4.75; n=52) and primary progressive 3.57 (1.95-6.56; n=15). MS was associated with ischaemic stroke but largely during the first year of follow-up. MS was associated with a decreased relative risk for angina pectoris and atrial fibrillation. There is a significantly increased relative risk for CVD in MS, particularly for venous thromboembolic disorders in progressive MS, suggesting immobility as a possible factor. An increased frequency of ischaemic stroke in MS is most probably due to surveillance bias resulting from diagnostic investigations for MS. There is no increased relative risk for ischaemic heart disease in MS and atrial fibrillation appears to be less common than amongst the general population.

EBV &amp; HHV6 reactivation is infrequent and not associated with MS clinical course

Among the environmental factors associated with multiple sclerosis (MS) causation, some of the strongest associations are with Epstein-Barr virus (EBV), and to a lesser extent human herpesvirus 6 (HHV6). Associations with clinical course are less conclusive, however. We evaluated serum anti-EBV-EA-R IgG and anti-HHV6 IgM, and EBV and HHV6 viral load (VL) for their associations with relapse, disability, and progression in disability in a prospective cohort of 198 participants with clinically definite MS. Anti-EBV-EA-R IgG was detected in 81.8% of cases at study entry, and titers remained essentially unchanged during the study. Anti-HHV6 IgM was detected in only one participant, and EBV-VL (29%) and HHV6-VL (1.8%) were detected in a minority of samples, and where detected levels were low. Our previously demonstrated association between anti-HHV6 IgG and relapse hazard was not affected by adjustment for parameters of reactivation. We found no evidence that any of the viral markers were associated with disability or progression in disability. In relation to relapse, only EBV-VL was positively associated, although this was strongly influenced by a single individual. Using a prospective cohort design, we found no convincing evidence that reactivation parameters of EBV or HHV6 were associated with subsequent MS relapse hazard or progression in disability, confirming previous findings, and indicating that herpesvirus reactivation is not an important driver of relapse or disability in this established MS population.

Relapsing and progressive forms of multiple sclerosis: insights from pathology.

The predominant clinical disease course of multiple sclerosis starts with reversible episodes of neurological disability, which transforms into progressive neurological decline. This review provides insight into the pathological differences during relapsing and progressive phases of multiple sclerosis. The clinical course of multiple sclerosis is variable, and the disease can be classified into relapsing and progressive phases. Pathological studies have been successful in distinguishing between these two forms of the disease and correlate with the clinical findings in terms of cellular responses, the inflammatory environment, and the location of lesions. Available therapies for multiple sclerosis patients, while effective during the relapsing phase, have little benefit for progressive multiple sclerosis patients. Development of therapies to benefit progressive multiple sclerosis patients will require a better understanding of the pathogenesis of progressive multiple sclerosis. This review discusses and compares the pathological findings in relapsing and progressive multiple sclerosis patients.

Defining the clinical course of multiple sclerosis

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

The relationship between familial Mediterranean fever gene (MEFV) mutations and clinical and radiologic parameters in multiple sclerosis patients

Objective: Central nervous system (CNS) involvement in patients with familial Mediterranean fever (FMF) is considerably rare. Patients with FMF may exhibit clinical and radiologic symptoms similar to multiple sclerosis (MS). However, the impact of the Familial Mediterranean Fever Gene (MEFV) mutations on the clinical course of MS is not fully understood as yet. Methods: In our study, we investigated the presence of probable MEFV mutations in patients diagnosed with definite MS and the association of these mutations with the clinical course, radiologic characteristics and disability status of the individuals. A total of 105 patients diagnosed with definite MS according to the McDonald criteria and a control group of 112 non-symptomatic individuals were included in the study. Results: Thirty-seven patients (35.2%) had MEFV gene mutations; three were compound heterozygotes (M694V/E148Q; M694V/V726A; P369S/E148Q) and one was homozygous for P369S. No statistically significant differences were found among patients with MS and healthy individuals with respect to existing mutations. In addition, we did not observe a statistically significant relationship between MEFV mutations and the gender of the patients, oligoclonal band (OCB) positivity, Expanded Disability Status Scale (EDSS), disease onset age, clinical presentation, affected neurologic systems, existence of spinal lesions, response to immunomodulatory treatment, time to reach EDSS scores of 3 and 6, the number of attacks and the average number of lesions on a brain MRI. Conclusion: Our results indicate that MEFV gene mutations do not affect the neurologic prognosis in patients with MS. However, additional research studies involving more patients with MS and clinical forms are warranted to confirm our results.

Клиническая характеристика гендерных различий при разных типах течения рассеянного склероза Сообщение 2

Изучены гендерные различия структурно-функциональной организации этапов рецидивирования (65 больных при рецидивирующем течении (РТ) и 49 больных при вторично-прогредиентном течении (ВПТ)) и прогрессирования (70 больных при ВПТ и 60 больных при первично-прогредиентном течении (ППТ)) при разных типах течения рассеянного склероза (РС). Структурно-функциональная характеристика этапов рецидивирования включала в себя анализ таких клинических показателей, как тяжесть и длительность отдельных рецидивов, темпы формирования клинической симптоматики рецидивов, полнота, продолжительность и стойкость клинических ремиссий между рецидивами; этапов прогрессирования — пути формирования прогрессирования при ВПТ и ППТ, темпы и варианты прогрессирования, особенности периодов стабилизации.В результате проведенных исследований были выделены совокупности клинических факторов риска, отобранных по гендерному признаку, которые определяли характер вероятностного прогноза на последующих этапах заболевания. Предложенный подход уточнил роль гендерного фактора, который существенно возрастает для вероятностного прогноза при ВПТ по сравнению с РТ. После трансформации РТ в ВПТ дальнейшее течение РС у женщин в большинстве случаев является более тяжелым, чем у мужчин. Клинические этапы ППТ также протекают с участием гендерного фактора, который проявляется более тяжелым и неблагоприятным течением заболевания у мужчин.

Automated extraction of clinical traits of multiple sclerosis in electronic medical records

ObjectivesThe clinical course of multiple sclerosis (MS) is highly variable, and research data collection is costly and time consuming. We evaluated natural language processing techniques applied to electronic medical records (EMR) to identify MS patients and the key clinical traits of their disease course.Materials and methodsWe used four algorithms based on ICD-9 codes, text keywords, and medications to identify individuals with MS from a de-identified, research version of the EMR at Vanderbilt University. Using a training dataset of the records of 899 individuals, algorithms were constructed to identify and extract detailed information regarding the clinical course of MS from the text of the medical records, including clinical subtype, presence of oligoclonal bands, year of diagnosis, year and origin of first symptom, Expanded Disability Status Scale (EDSS) scores, timed 25-foot walk scores, and MS medications. Algorithms were evaluated on a test set validated by two independent reviewers.ResultsWe identified 5789 individuals with MS. For all clinical traits extracted, precision was at least 87% and specificity was greater than 80%. Recall values for clinical subtype, EDSS scores, and timed 25-foot walk scores were greater than 80%.Discussion and conclusionThis collection of clinical data represents one of the largest databases of detailed, clinical traits available for research on MS. This work demonstrates that detailed clinical information is recorded in the EMR and can be extracted for research purposes with high reliability.

Genetic burden of common variants in progressive and bout-onset multiple sclerosis

Background: The contribution of genetic variants underlying the susceptibility to different clinical courses of multiple sclerosis (MS) is still unclear. Objective: The aim of the study is to evaluate and compare the proportion of liability explained by common SNPs and the genetic burden of MS-associated SNPs in progressive onset (PrMS) and bout-onset (BOMS) cases. Methods: We estimated the proportion of variance in disease liability explained by 296,391 autosomal SNPs in cohorts of Italian PrMS and BOMS patients using the genome-wide complex trait analysis (GCTA) tool, and we calculated a weighted genetic risk score (wGRS) based on the known MS-associated loci. Results: Our results identified that common SNPs explain a greater proportion of phenotypic variance in BOMS (36.5%±10.1%) than PrMS (20.8%±6.0%) cases, and a trend of decrease was observed when testing primary progressive (PPMS) without brain MRI inflammatory activity (p = 7.9 × 10−3). Similarly, the wGRS and the variance explained by MS-associated SNPs were higher in BOMS than PPMS in males (wGRS: 6.63 vs 6.51, p = 0.04; explained variance: 4.8%±1.5% vs 1.7%±0.6%; p = 0.05). Conclusions: Our results suggest that the liability of disease is better captured by common genetic variants in BOMS than PrMS cases. The absence of inflammatory activity and male gender further raise the difference between clinical courses.

Cognitive impairment among different clinical courses of multiple sclerosis

Background: As of yet, no consensus has been reached regarding cognitive impairment profiles in multiple sclerosis (MS) patients based on the MS type and disease duration.The main objective of this study was to describe cognitive impairment at the early stages of MS.The secondary objective was to compare cognitive performances in patients with relapsing remitting multiple sclerosis (RRMS), secondary progressive (SP) MS and primary progressive (PP) MS.Methods: The study included 128 MS patients and 63 healthy controls (HC). The study constituted five groups: early RR (ERR) (<3 years); late RR (LRR) (>10 years), SP, PP, and healthy Controls (HC). A neuropsychological assessment was performed including information processing speed (IPS), working memory, verbal episodic memory and executive functions.Results: Compared to HC, only impairment in phonemic fluency was observed in ERR. Slowing IPS, impairment in working memory and phonemic fluency were shown in LRR. In progressive forms, deficits were observed in verbal episodic memory, in working memory, in flexibility, in semantic and phonemic fluencies, with a slowing IPS.Conclusion: Verbal fluency is impaired at early stage of RRMS, in this form of MS, impairment increased with MS duration, and distinct cognitive profiles were observed between chronic and progressive forms.