Expanded Disability Scale Score Research Articles

Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: DISCOVER study

BackgroundPeople with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. MethodsDISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. ResultsA total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6–6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score.Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. ConclusionsPwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.

Neutrophil-to-Lymphocyte Ratio, ESR, and CRP Have No Roles as Markers for Disease Severity and Prognosis in Patients with RRMS.

Up to now, there is no definitive prognostic factor for patients with multiple sclerosis. This study aimed to evaluate the neutrophil-to-lymphocyte ratio (N/L ratio) as a cheap, available, and noninvasive marker for disease activity and prognosis. A total of 112 patients, who were diagnosed with relapsing-remitting multiple sclerosis (RRMS), and 61 healthy controls were considered. We evaluated N/L ratio, ESR, CRP in the control, and patients in the first attack of the onset of the disease, 1 month and 6 months later during remission. All patients received interferon or Glatiramer acetate as disease-modifying therapies. The correlation of parameters with Expanded Disability Scale Score (EDSS) and Functional System (FS) involvement was evaluated. The N/L ratio was increased significantly in patients with MS in the relapse phase (mean: 2.44 ± 0.68) compared to the healthy controls (mean: 1.84 ± 0.67) (P = 0.04). Also, we found a significant increase in CRP among the aforementioned groups (P = 0.028). A significant correlation was not found between NLR, ESR, or CRP and patient's EDSS during 6 months of follow-up. For ESR and the type of functional system, a significant difference was found between favorable and unfavorable categories, while the median (IQR) of ESR in the favorable group was 7.7 (4-12) and among unfavorable ones was 13.8 (6-17.75) (P = 0.008). The results showed the effect of the innate immune system and inflammation during MS attacks. We considered that neutrophils, ESR, and CRP cannot predict disease severity or prognosis at least without a combination of other biomarkers.

Using instrumental variables to correct for bias in real-world cohort studies of the effects of disease-modifying treatment in MS

Background: Estimating the effect of disease-modifying treatment of MS in observational studies is impaired by bias from unmeasured confounders, in particular indication bias. Objective: To show how instrumental variables (IVs) reduce bias. Methods: All patients with relapsing onset of MS 1996–2010, identified by the nationwide Danish Multiple Sclerosis Registry, were followed from onset. Exposure was treatment index throughout the first 12 years from onset, defined as a cumulative function of months without and with medium- or high-efficacy treatment, and outcomes were hazard ratios (HRs) per unit treatment index for sustained Expanded Disability Scale Score (EDSS) 4 and 6 adjusted for age at onset and sex, without and with an IV. We used the onset cohort (1996–2000; 2001–2005; 2006–2010) as an IV because treatment index increased across the cohorts. Results: We included 6014 patients. With conventional Cox regression, HRs for EDSS 4 and 6 were 1.15 [95% CI: 1.13–1.18] and 1.17 [1.13–1.20] per unit treatment index. Only with IVs, we confirmed a beneficial effect of treatment with HRs of 0.86 [0.81–0.91] and 0.82 [0.74–0.90]. Conclusion: The use of IVs eliminates indication bias and confirms that treatment is effective in delaying disability. IVs could, under some circumstances, be an alternative to marginal structural models.

Countermovement Jumps Detect Subtle Motor Deficits in People with Multiple Sclerosis below the Clinical Threshold.

In the early stages of multiple sclerosis (MS), there are currently no sensitive assessments to evaluate complex motor functions. The countermovement jump (CMJ), a high-challenge task in form of a maximal vertical bipedal jump, has already been investigated as a reliable assessment in healthy subjects for lower extremity motor function. The aim was to investigate whether it is possible to use CMJ to identify subthreshold motor deficits in people with multiple sclerosis (pwMS). All participants (99 pwMS and 33 healthy controls) performed three maximal CMJs on a force plate. PwMS with full motor function and healthy controls (HC) did not differ significantly in age, disease duration, Body Mass Index and the Expanded Disability Scale Score. In comparison to HC, pwMS with full motor function demonstrated a significantly decreased CMJ performance in almost all observed kinetic, temporal and performance parameters (p < 0.05). With increasing disability in pwMS, it was also observed that jump performance decreased significantly. This study showed that the CMJ, as a high challenge task, could detect motor deficits in pwMS below the clinical threshold of careful neurological examination. Longitudinal studies are pending to evaluate whether the CMJ can be used as a standardized measure of disease progression.

Spontaneous Cardiovagal Baroreflex Sensitivity in Females with Multiple Sclerosis

Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system that is known to disrupt autonomic function. Females with MS are at an increased risk of cardiovascular disease partly due to altered autonomic regulation of arterial blood pressure. Longitudinal data suggest that low spontaneous cardiovagal baroreflex sensitivity is a predictor of cardiovascular disease. Therefore, the purpose of this investigation is to test the hypothesis that spontaneous cardiovagal baroreflex sensitivity (cBRS) is less in females with MS compared to healthy controls. Electrocardiogram (ECG) and beat‐to‐beat blood pressure (Finometer) were continuously recorded during 10 minutes of quiet supine rest in 3 females with relapsing‐remitting MS (Expanded Disability Scale Score &lt; 6.0) and 3 sex‐, age‐, height‐, weight‐ and race‐ matched healthy controls. Spontaneous cBRS was determined using the sequence method (CardioSeries v2.7). Spontaneous cBRS gain is calculated as the average slope of the relationship between R‐R interval and systolic blood pressure from individual sequences of 3 or more consecutive cardiac cycles where both variables are increasing (up‐up sequences) or decreasing (down‐down sequences). Females with MS had similar resting mean arterial pressures (P=0.55), systolic blood pressures (P=0.53) and heart rates (P=0.18) compared to healthy controls. Overall spontaneous cBRS gain was greater in females with MS compared to healthy controls (27.1 ± 6.3 ms/mmHg vs. 18.8 ± 1.1 ms/mmHg respectively; P=0.04). Spontaneous cBRS gain from up‐up sequences was also greater in females with MS compared to healthy controls (27.6 ± 5.1 ms/mmHg vs. 17.1 ± 2.1 ms/mmHg respectively; P=0.01). Spontaneous cBRS gain from down‐down sequences trended to be greater in females with MS compared to healthy controls but was not statistically significant (27.2 ± 7.8 ms/mmHg vs. 20.1 ± 2.4 ms/mmHg respectively; P=0.10). Counter to our hypothesis, these preliminary findings in a small sample suggest that females with MS have increased spontaneous cBRS compared to healthy controls. If this relationship continues with additional data collection, it may indicate that females with MS have enhanced cardiac responses to regulate arterial blood pressure.

Alterations of subset and cytokine profile of peripheral T helper cells in PBMCs from Multiple Sclerosis patients or from individuals with MS risk SNPs near genes CYP27B1 and CYP24A1

T helper cells play an important role in the aetiology of Multiple Sclerosis (MS). Vitamin D has an anti-inflammatory effect on T helper cells and can affect onset and pathogenesis of MS. Two genes of the metabolic Vitamin D pathway expressed by activated T helper (Th) cells have been identified as MS risk genes by genome-wide association studies, CYP27B1 (25(OH)D3 1-alpha-hydroxylase) and CYP24A1 (1,25(OH)2D3 24-alpha-hydroxylase). Therefore, we hypothesize that the MS risk alleles around gene CYP27B1 and CYP24A1 are associated with the altered inflammatory profile of peripheral Th cells in PBMCs both ex vivo and in vitro potentially influencing the pathogenesis of MS. PBMCs from MS patients (41 RRMS patients in their remitting stage and 4 SPMS patients) and 12 healthy controls were collected, subpopulation of Th cells in PBMCs and cytokine profile were tested by Flow cytometry and Cytometric Bead Array (CBA), respectively. MS risk SNPs were genotyped by allele-specific PCR analysis. Data were analysed using nonparametric tests and linear regression for adjusting multiple factors. The proportion of Th17.1, Th17 and Th1 cells were all associated with MS while the proportions of Th2 (significant) and Th17 (near significant) cells were correlated with the expanded disability scale score of MS patients. Additionally, we found a MS-specific dysregulation in the IL-6 and TNF production of Th cells in Concanavalin A-stimulated PBMCs. Furthermore, the risk allele rs2248359-C (near gene CYP24A1) showed a consistent inhibitory effect on the proportions of Th1 and Th17.1 cells, and the presence of the homozygous risk allele rs703842-AA (near gene CYP27B1) reduced the production of IL-2. In conclusion, both MS disease and its risk alleles near Vitamin D metabolism genes influence the inflammatory profile of T helper cells in PBMCs.

Clinical characteristics of middle-aged and older patients with MS treated with interferon beta-1b: post-hoc analysis of a 2-year, prospective, international, observational study

BackgroundDespite trends towards the increased age of patients living with multiple sclerosis (MS), little is known about the response of older adults with MS to disease-modifying therapies (DMTs). Thus, a post-hoc analysis was undertaken using data from a 2-year, international, non-interventional, prospective cohort study (NCT00787657; BEACON: BEtaferon prospective study on Adherence, COping and Nurse support) of patients above the age of 40 years with MS and starting interferon beta-1b (IFNB-1b) treatment within 6 months before study entry.MethodsMiddle-aged and older patients with MS were divided into two sub-groups: 41–50 years and > 50 years. Treatment with IFNB-1b started within 6 months before study entry. Patients were followed-up for a 2-year observation period. Assessments included disease history and course, annualised relapse rate (ARR), Expanded Disability Scale Score (EDSS), treatment adherence, Hospital Anxiety and Depression Scale (HADS), and adverse events (AE).ResultsAt baseline, the intention-to-treat (ITT) population (n = 481) aged 41–50 years (n = 327) and > 50 years (n = 154), had mean (standard deviation [SD]) ages of 45.1 (2.8) and 56.2 (4.2) years, maximum age of 72 years, and duration of MS since onset of symptoms of 3.9 (5.2) and 5.9 (7.1) years, respectively. At baseline, the proportion of patients with relapsing–remitting MS (RRMS) was 96.3 and 94.9 %, and secondary progressive MS (SPMS) was 3.7 and 5.1 %, in the 41–50 and > 50 years sub-groups, respectively. The ARR in the 2 years before study start was 0.93 (0.48) and 0.86 (0.54) for the 41–50 and > 50 years groups, respectively, and decreased since study start to 0.20 (1.09) and 0.07 (0.37), respectively. The percentage of patients with anxiety and depression, as measured by HADS, were stable over the study period. Polypharmacy (five or more medications) was seen in 32.3 and 41.2 % of patients aged 41–50 and > 50 years. No unexpected AEs were reported.ConclusionsThis study provides observational data on patients between 40 and 72 years of age, suggesting that IFNB-1b can be an effective and well-tolerated treatment option in MS patients of advanced age.Trial registrationClinicalTrials.gov, NCT00787657.

20680 Characterization of Clinical and Immunological Laboratory Features in Multiple Sclerosis Patients with COVID-19

ABSTRACT IMPACT: Better understanding of the factors impacting disease severity and immunological response of MS patients on disease modifying therapy will enable better recommendations for vaccination options and risk mitigation strategies OBJECTIVES/GOALS: The Coronavirus Disease 2019 (COVID-19) and global health crisis has raised health concerns for patients with multiple sclerosis (MS). We aim to study the clinical characteristics, immunological laboratory data, and immunoglobulin response in patients with MS and COVID-19, to identify factors impacting disease severity and immune response. METHODS/STUDY POPULATION: Database search was done using DataDirect to search for MS patients who had tested positive for COVID-19 at the University of Michigan hospital. Patients with a positive nasopharyngeal swab polymerase chain reaction (PCR) for COVID-19 between March 1 and September 2020 were included. The primary outcome was the immunological laboratory data and immunoglobulin levels and the secondary outcome was their disease severity. We collected demographics, neurological history, MS treatment, Expanded Disability Scale Score (EDSS), comorbidities, and COVID-19 characteristics. A 7-point ordinal scale previously used to assess disease severity was used. Univariate and multivariate analyses will be performed to assess relationships between the collected variables. RESULTS/ANTICIPATED RESULTS: A total of 17 patients, mean age 53 (SD 11.6) years, mean disease duration, 6.2(SD 4.1) years were analyzed. 41% of patients had relapsing remitting multiple sclerosis, 17% had primary progressive MS. (88%) patients were on Disease Modifying Therapy (DMT) at the time of COVID-19 diagnosis. 2 patients died from COVID-19 complications. There was a higher proportion of patients with higher disease severity receiving Ocrelizumab. Only one patient showed positive IgG to SARS-CoV-2 after the resolution of infection. CBC with differential was obtained and a longitudinal follow-up of labs will be done. Regression analysis will be done to check the association between the use of DMT, immunological response, and COVID disease severity in them. The impact of COVID-19 on MS relapse, EDSS, and MRI activities will also be studied. DISCUSSION/SIGNIFICANCE OF FINDINGS: Recommendations to continue current DMT have been made, however, the immune response has not been correlated with the individual’s risk profile. Certain therapies may interfere with mounting a protective immune response of COVID-19 and this knowledge is crucial when advising patients regarding the choice of vaccine and risk mitigation strategies.

Intravenous immunoglobulin as the rescue treatment in NMOSD patients.

Intravenous immunoglobulin (IVIg) has been used for neuromyelitis optica spectrum disorder (NMOSD) patients to prevent relapses in several studies. However, efficacy of the rescue treatment of IVIG was just assessed in a small sample research. The aim of this study is to investigate the efficacy of IVIG in NMOSD as a rescue treatment and whether it could reduce the relapse rate. We retrospectively reviewed patients with NMOSD in the First and Second Affiliated Hospital of Wenzhou Medical University. Clinical parameters were extracted from the medical records, such as expanded disability scale score (EDSS) and time to next relapse. Thirty-one events of 20 NMOSD patients were included in the intravenous methylprednisolone (IVMT) + IVIG group and 72 events of 39 patients in the IVMT group. IVMT therapy combined with IVIG could improve the neurological disability when discharged (p < 0.001), whereas patients first attacked did not show a similar trend. Patients who were treated with IVMT + IVIG (17.39 ± 2.75months) show a longer time to next relapse compared to patients who were treated with IVMT (9.50 ± 0.79months) (log rank test p = 0.002), especially in relapsed patients or anti-aquaporin-4 antibody (AQP4-Ab) seropositive patients. IVIG might be helpful for NMOSD patients as the rescue treatment and might bring a longer remission, especially for patients with relapse and AQP4-ab seropositive patients.

Multiple Sclerosis: Treadmill Versus Cycle Ergometry Maximal Exercise Test Responses

ABSTRACT Background: Multiple sclerosis (MS) is an autoimmune disease that impacts the central nervous system. MS generally results in decreased mobility and work capacity. Our objective was to determine exercise testing responses on both a treadmill and cycle ergometer among individuals with MS who were able to ambulate freely. Methods: Twenty-six individuals with MS participated in a cross-sectional study (44 ± 11 years; body mass index 26.8 ± 6.2 kg·m−2; expanded disability scale score 3.1 ± 0.9), with 24 individuals with complete test data for both treadmill and cycle ergometry tests. Peak aerobic capacity (VO2peak) for both treadmill and cycle ergometry tests were measured with indirect calorimetry. Results: Participants safely completed both treadmill and cycle ergometry tests, and treadmill testing yielded higher values (26.7 ± 6.4 mL·kg−1·min−1) compared with cycle ergometry (23.7 ± 5.7 mL·kg−1·min−1), with values ~12% greater for treadmill. When comparing tests to their respected predicted values within modality, treadmill tests were 8% lower and cycle ergometry tests were 10% lower than predicted. Conclusions: While peak aerobic capacity was very low for this population, treadmill tests were still higher than cycle ergometry data, with this difference between modes being similar to that observed in healthy adult populations. Additional research is required to determine if these findings are impacted by participation in physical activity or regular exercise.

Subjective visual vertical and visual dependency in patients with multiple sclerosis

BackgroundSpatial orientation is an inherent ability governed by the complex integration of visual, vestibular and proprioceptive inputs. The degree to which an individual relies upon visual cues, as opposed to the vestibular or proprioceptive cues, is termed visual dependence. Although abnormal visual dependence has been documented in other neurological disorders, it is not known whether MS leads to visual dependence, and if so whether this is related to disease progression, clinical disability, or neuro-inflammatory burden in the central nervous system. ObjectiveTo evaluate SVV and visual dependence using a novel mobile virtual reality-based system for subjective visual vertical assessment (VIRVEST) and evaluate its relationship with the Expanded Disability Scale Score (EDSS), MS course and clinical findings. MethodsThe study included 59 patients with MS and 59 controls. Four tests were integrated in VIRVEST system and performed by each patient: a static SVV, dynamic SVV with clockwise and counter-clockwise background stimulus rotation, and SVV in a virtual reality background – a boat floating in the wavy water - to be adjusted vertically. Visual dependence was evaluated as a function of dynamic SVV. ResultsPatients with MS manifest larger biases in both static and dynamic SVV than healthy controls (p<0.001), in addition to higher visual dependence scores (p<0.05). MS patients with an EDSS score >4.5 had larger values of dynamic SVV and when compared to MS patients with lower EDSS scores (p<0.01), and visual dependence was related to disease severity. Patients with progressive MS disease course demonstrated statistically significantly larger dynamic SVV and visual dependence scores when compared to MS patients with relapsing-remitting disease (p<0.01). The mean System Usability Scores for the VIRVEST system corresponded to a patient perceived adjective rating of ``excellent''. ConclusionWe have evaluated the application of a novel virtual reality-based SVV test in patients with MS. We identified greater dynamic SVV errors suggestive of visual dependence in patients with MS versus controls and show that dynamic SVV abnormalities are related to disability measures. We suggest that this paradigm is effective at identifying visual dependence in neurological patients, and may have application in clinical settings, given high system usability scores.

A cross-sectional study of alexithymia in patients with relapse remitting form of multiple sclerosis.

Background:Alexithymia is one's incapacity to identify, comprehend, and describe emotions. There is almost no literature data about the levels of alexithymia among patients with relapse remitting type of multiple sclerosis.Aim:The objective of the present study was to assess the levels of alexithymia in patients with relapse remitting type of multiple sclerosis in relation to their sociodemographic variables and clinical characteristics of the disease.Methods:This cross-sectional study included 106 consecutively assessed patients with relapse remitting type of multiple sclerosis. In addition to the data regarding disease duration, number of demyelinating relapses, and degree of neurological disability, assessed by the expanded disability scale score (EDSS), we used Toronto alexithymia scale (TAS), fatigue severity scale (FSS) and, Hamilton scale for the assessment of anxiety and depression and sociodemographic questionnaire.Results:Study included 74 female and 32 male patients, with a median age of 44 years, median disease duration 90 months, and median EDSS 4. About 29.55% of patients had alexithymia and borderline alexithymia was observed in 31.15% patients. Alexithymia correlated with anxiety and depression (P < 0.01) on all TAS subscales. Higher levels of neurological disability based on EDSS, severe fatigue based on FSS scores, and severe relapse remitting type of multiple sclerosis with more relapses and longer disease duration correlated with alexithymia (P < 0.01), depression (P < 0.01), and anxiety (P < 0.01). Higher rates of alexithymia were noticed in older, unemployed, single patients, and those having fewer children.Conclusions:Alexithymia was found in a relatively high percentage in patients with relapse remitting type of multiple sclerosis.

High levels of alexithymia in patients with multiple sclerosis.

Alexithymia is a personality trait characterized by difficulties identifying and describing feelings. Some researchers describe high levels of alexithymia among patients with multiple sclerosis (MS) but literature data on this subject are scarce.Objective:The objective of the present study was to characterize findings of alexithymia in patients with MS.Methods:This cross-sectional case-control study included 180 patients with MS and a matched control group. Data for patients with MS included disease duration, number of demyelinating relapses and degree of neurological disability, as assessed by the Expanded Disability Scale Score (EDSS). In addition, the Hospital Anxiety and Depression (HAD) scale and the Toronto Alexithymia Scale (TAS) were used.Results:There were 126 women and 54 men in each group, with median age of 37 years and median education of 16 years. Patients with MS had higher degrees of depression (p<0.01), anxiety (p=0.01) and alexithymia (p<0.01) than did control subjects. For individuals with MS, depressive traits (p<0.01), anxious traits (p=0.03), higher age (p=0.02), lower education level (p=0.02), higher degree of disability (p<0.01) and not being actively employed (p=0.03) were associated with higher rates of alexithymia.Conclusion:Alexithymia was a relevant finding in patients with MS.

Analysis of HLA-DRB1*1501 in Multiple Sclerosis Patients in Khuzestan Province, Iran

Background: Multiple sclerosis (MS) is a demyelinating, autoimmune and neurodegenerative disease of the central nervous system (CNS). The pathogenesis of this disease is still unknown, although there are evidences of environmental factors affecting subjects with genetic predisposition factors. The contribution of HLA-DRB1*1501 to MS risk has been replicated and confirmed in most population-based studies. Since there are no data with respect to the association of HLA-DRB1*1501 and MS in Khuzestan province. Objectives: The aim of this study was to investigate the correlation of this allele with MS in Khuzestan province. Methods: In this case-control study, DRB1*1501 allele was analyzed by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 200 MS patients and 200 unrelated healthy individuals, without any autoimmune disease from the same geographical region. The frequencies of the mentioned allele were compared between the patients and control group using SPSS 16 statistical software and the chi square test. Results: The results demonstrated that distribution of DRB1*1501 allele was statistically different between patient and control (41.5% vs. 22.81%, P < 0.001); significant correlation was observed among these allele with both Arab (28.84% vs. 50.84%, P = 0.005) and Persian (15.87% vs. 35.55%, P = 0.018) ethnicities; although no association was revealed between mentioned allele and disease clinical course (relapsing-remitting, secondary-progressive, progressive-relapsing and primary-progressive), expanded disability scale score (EDSS) and gender. Conclusions: The study presents association of susceptibility to multiple sclerosis in southwest of Iran with HLA-DRB1*1501 allele in both Arab and Persian ethnic; although DRB1*1501 may be is not involved in the pathogenesis of different MS disease subtypes. The results are consistent with most of the other studies in Iran; and also most studies in European populations.

Cigarette Smoking, Alcohol Consumption and Overweight in Multiple Sclerosis: Disability Progression

The rate at which disability progresses in multiple sclerosis (MS), and its severity, have been associated with modifiable lifestyle habits. To investigate the risk of disability progression in MS patients according to tobacco and alcohol consumption and to the presence of overweight. This was a follow-up of MS cases from a concluded case-control study (National Institute of Neurology and Neurosurgery, Mexico 2010-2013). The evolution in EDSS (Expanded Disability Scale Score) units was followed through a medical record review. Kaplan Meier statistics and multivariate Cox regression analysis were performed. Of 181 cases, 63.5% were women and 82.5% had relapsing remitting MS. Study duration was 19.95±15.24months. The disease progressed faster in daily smokers than in non-smokers (p=0.0168). In overweight patients, disability progressed faster than in normal weight patients (p=0.0249). Ex-consumers of alcohol had lower risk of progression than current consumers (HR=0.33 CI 95%=0.14-0.83, p=0.019) and both daily and ex-smokers presented higher risk of progression than non-smokers (HR=2.32 CI 95%=1.14-4.72, p=0.020 and HR=3.56, CI 95%=1.21-10.46, p=0.021). Stratifying by gender, the effects of smoking and overweight were only found in men. Smoking is associated with rapid disability progression in MS. Our results suggest that cessation of tobacco and alcohol consumption could be clinically beneficial. Although there is association between overweight and disability progression in men, a further exploration of gender differences is necessary to corroborate this finding.

Real-life experience with fampridine (Fampyra®) for patients with multiple sclerosis and gait disorders.

Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS). To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group. Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine. The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients. Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders.

COGNITIVE IMPAIRMENT IN MULTIPLE SCLEROSIS: ASSOCIATION WITH THE ACTIVITY OF INFLAMMATORY PROCESS AND SEVERITY OF DISABILITY

Background: Multiple sclerosis is the most common neurological disease leading to disability in young and productive patients. One of available methods of control over the course of the disease and detection of its progression is neuropsychological testing. However, selection of the most informative tests, as well as the search for interpretation of their results is still ongoing. Aim: To study cognitive functions in multiple sclerosis patients depending on the disease activity and degree of disability. Materials and methods: Fifty patients with multiple sclerosis were evaluated during their remissions and 15 of them were additionally assessed during an exacerbation. During neuropsychological testing a computer test “Selection of figures” was used for assessment of attention, productivity, frontal functions and visual neglect. We studied potential dependency of the parameters obtained from degree of disability and disease stage (exacerbation or remission). The control group comprised 12 healthy subjects. Results: Compared to healthy subjects, the multiple sclerosis patients had a prolonged time of test performance, decreased learning, and statistically significant decrease of the working efficacy (p < 0.05). During an attack, there was a decreased conceptualization (48 answers compared to 51.5 at remission stage); more than 3-fold (from 1,3 to 4,4) increase in the number of figures missed in one visual field, that could indirectly indicate visual neglect. Also, changes in frontal functions were noted as a tendency to almost 2-fold higher numbers of perseverative answers, more frequent categorical escape and learning abnormality. There was a positive correlation between expanded disability scale score (EDSS) and working efficacy (r = 0.453, p = 0.001), and a negative correlation between EDSS and mental stability (r = 0.4055, p = 0.0035). Conclusion: Patients with multiple sclerosis had abnormal rate and accuracy of test performance, compared to those in healthy subjects. During an exacerbation of the disease, there was a deterioration of the parameters compared to those registered in the remission. Also, a negative association with disease severity assessed by EDSS, was found. The data obtained documents feasibility of the computer test “Selection of figures” for dynamic control in multiple sclerosis patients.

Diagnostic and Prognostic Value of the Cerebrospinal Fluid Concentration of Immunoglobulin Free Light Chains in Clinically Isolated Syndrome with Conversion to Multiple Sclerosis.

Background and objectiveIn this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS).MethodsWe compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients.ResultsThe levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056).ConclusionThe concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression.

Should plasma exchange be offered to patients with multiple sclerosis-associated optic neuritis?

Should plasma exchange be offered to patients with multiple sclerosis-associated optic neuritis?

Neuromyelitis Optica With Onset in Childhood and Adolescence

BackgroundNeuromyelitis optica with onset before the age of 18 years is a relatively rare, yet potentially devastating condition. The objective of the present study was to contribute to the study of early-onset neuromyelitis optica with a case series. PatientsData were collected from medical records of Brazilian neurologists caring for patients with neuromyelitis optica occurring in childhood and adolescence. ResultsTwenty-nine patients with neuromyelitis optica occurring before the age of 18 years and fulfilling the diagnostic criteria were identified. The average age at disease onset was 13 years and the patients had had an average disease duration of 6 years. The expanded disability scale score at the latest consultation was, on average, 4.7, and one patient had died from the disease. The 29 patients had had an average 4.5 relapses during the disease, accounting for 0.75 relapses per year, irrespective of the medication used. All patients were using one or more of the following medications: azathioprine, prednisone, immunoglobulin, and glatiramer acetate. ConclusionsNeuromyelitis optica with onset in childhood and adolescence is a poorly understood condition that is often disabling and difficult to manage.