Mean EDSS Research Articles

Efficacy and safety of cladribine tablets in multiple sclerosis in real-world clinical practice

Cladribine has a well-defined activity against lymphocytes, leading to their selective depletion.Objective: to determine the efficacy and safety of cladribine in the treatment of multiple sclerosis (MS) in real-world clinical practice.Material and methods. The study involved 82 patients (57 women and 25 men, mean age 36.4±9.3 years) with a disease duration of 2.2±1.5 years. Seven (9%) patients had secondary progressive MS (SPMS), 6 (7%) had rapidly progressive MS (RPMS) and 69 (84%) had highly active MS (HAMS). According to the instructions for use, oral therapy with cladribine was administered in two short courses (up to 10 days per year) to achieve a long-term effect on the immune system. The dose of cladribine was calculated based on the body weight.Results. The average frequency of exacerbations per year before starting therapy was 1.6, while it decreased to 0.2 during cladribine therapy. An exacerbation was observed in 18 patients (22%) at the end of the first course of cladribine treatment and in one patient (2.6%) after the second treatment course. Thus, the number of exacerbations decreased by 78% after the first year of treatment and by 97.4% after the second year of treatment. The mean EDSS score was 3.2±2.5 points before the start of treatment, 3.6±2.5 points after the first course of treatment and 3.4±2.5 points after the second course (p>0.05). MRI results showed a decrease in disease activity by 83% after the first course of cladribine therapy and by 97.4% after the second course. No serious adverse events occurred in any of the patients.Conclusion. We demonstrated efficacy and safety of cladribine in real-life clinical practice in MS patients with frequent exacerbations and rapid disability progression (SPMS, RPMS, HAMS).

Coexistence of Epilepsy or Seizure and Multiple Sclerosis; Review of the Literature with a Single Center Experience

ObjectivesThere is evidence that the inflammatory demyelinating disorder in Multiple Sclerosis (MS) is associated with acute seizures and epilepsy. Additionally, the likelihood of developing epilepsy increases with neurodegeneration. This study aims to reveal the clinical and radiological features of MS-epilepsy/seizure coexistence. MethodsAmong all patients diagnosed with MS that we followed in our center between April 2002 and July 2023, patients with a single seizure history or diagnosed with epilepsy (MS-seizure/epilepsy) were randomized 1:1 in terms of age and gender with MS patients without a diagnosis of epilepsy or seizures. Clinical (comorbidities, annual attack rate, disability, seizures during attacks, initial diagnosis, disease duration, disease-modifying therapies (DMTs), refractory epilepsy, anti-seizure drugs), electroencephalography (EEG) and MRI (lesion localization and new lesion(s)) data were retrospectively evaluated. ResultsThe mean EDSS was 4.07±2.81. 29.4% of patients had progressive MS (n=10). Refractory epilepsy was 52.9% (n=18), and SE history was 14.7% (n=5). Pathology was detected in 69.7% (n=23) of patients in the EEG. The most common slow wave activation was detected in 51.5% (n=17). Refractory epilepsy was more common in cases under 45 and patients with lesions in thalamic localization. Lesions in the temporal and thalamic regions and cerebral atrophy were more common in the MS-seizure/epilepsy group. ConclusionPatients with demyelinating lesions in the temporal and thalamic regions should be questioned more carefully for epilepsy, and an EEG should be performed in case of clinical suspicion. Since thalamus lesions are more common in patients with refractory epilepsy, anti-seizure treatment strategies should be applied more carefully. The presence of atrophy on MRI confirms the link between neurodegeneration processes and the development of epilepsy.

Cladribine use trend in Latin America: the changes in patient profile impact in the drug effectiveness.

Cladribine was approved for Multiple Sclerosis (MS) inour country in 2018. A previous study by our group showed that its use among high efficacy therapiesoptions has been increasing along the years. to analyze the cladribineuse trend across time since its approval. A retrospective cohort study was performed. People withMS (pwMS) treated with cladribinewere included. Two periods were defined: P1 = 2018 - 2020 and P2 = 2021 - 2023. A comparative analysis was carry outbetween P1and P2 to assessthe trend of use, clinical/demographic characteristics, and effectiveness. One hundred ninety- seven people with MS (pwMS) were included, mean EDSS: 2.2 ± 3.08, 72.6% female, mean age: 35.2 ± 9years, mean disease duration: 6.6 ± 5.6years, mean time lapse under cladribine: 26.1 ± 12.4months. Regarding patient profile, we found significant differences between P1 and P2 in the MS evolution (p = 0.001) and EDSS (p = 0.018) prior to initiation of cladribine.In the individualized analysis by year, we found a decrease in relapse number in the year prior to starting cladribine (p = 0.02). Ahigher proportion of No Evidence of Disease Activity (NEDA) was found in patients treated at P2 compared to those treated at P1 (p < 0.001). An earlier use of cladribineachieved a significant increase in reaching NEDA. This learning curve in the use of cladribine allows a better identification of the candidate patient and influences the treatment effectiveness.

A multicenter multinational study to evaluate different aspects of the relationship between MS and pregnancy

BackgroundTo investigate the pregnancy-related issues in females with multiple sclerosis (MS) from Turkiye, Egypt, Kuwait, and Iran. Methods1692 pregnancies of 701 females with MS were evaluated in this retrospective multicenter, international project. Demographics, clinical features, pregnancy outcomes, relapses, effects of exposure to disease-modifying drugs on pregnancy and fetus, and worries about pregnancy decisions were investigated. Results85.9 % of females were diagnosed with relapsing-remitting multiple sclerosis. The mean age was 39.0 ± 9.0 years (min 20, max 68). The mean EDSS score was 2.26 ± 1.8. The number of conceptions was inversely correlated with the level of education with significance (p<0.05). Among the concerns related to pregnancy, 31.7 % pertain to disability progression, 14.4 % are associated with relapses, and 7.3 % involve the cessation of treatment. Additionally, 82.3 % of females with MS experienced no relapses during both pregnancy and the postpartum period. Most of the relapses (22.9 %) occurred in the postpartum period. Higher EDSS scores were detected in patients who have higher numbers of pre-MS period pregnancies (p= 0.042; r:0.2591). A similar correlation was found between the total number of pregnancies and higher EDSS levels (p=0.003, r:0.2614). Considering the relationship between EDSS score and the number of pregnancies after MS diagnosis, no significance was found (p = 0.595). The age at first pregnancy did not affect the onset age of MS. Significant positive correlation was found between the age of onset and the total number of pregnancies and pre-MS pregnancies. As the number of pregnancies increased, the disease onset was at a later age (correlation = 0.4258). ConclusionPresence of pre-MS pregnancies increased the age of onset of MS and caused more disability. The reduction in the number of pregnancies following the diagnosis of MS was related with a consistent hesitancy among patients in this regard.

Individualized activity recommendation based on a physical fitness assessment increases short- and long-term regular physical activity in people with multiple sclerosis in a retrospective cohort study.

Despite the evidence of beneficial effects of physical activity (PA), people with multiple sclerosis (pwMS) are less physically active than the general population. To increase PA in pwMS, we developed a structured individually tailored PA promotion program which is conducted within clinical practice in a university-based outpatient clinic since 2016. This study serves as retrospective quality control of this program. In a retrospective cohort study, we assessed the physical fitness of pwMS and the impact of the program on short- and long-term PA changes and behavioral determinants. The program consisted of four appointments each 2-4 weeks apart. Spiroergometric test results of female pwMS were compared to female non-MS controls who underwent a voluntary physical fitness analysis. The short version of the Freiburger questionnaire, self-developed questions and the modified Physical activity screening questionnaire (PASQ) were sent to all participants assessing the PA levels before the program, 3 months after the program (short-term), and at the time of the survey (long-term). Additionally, established questionnaires assessed behavioral determinants before the program and long-term. A total of 166 participants [mean age 38.32 (± 10.61 SD), mean EDSS 2.30 (±1.29 SD)] and mostly females (63.3%, n = 105) were included in the study and started the program. A total of 136 participants completed the program. Out of these 63.9% (n = 87) answered the questionnaires in 12.38 (±11.34 SD) months after finishing the program. At baseline female pwMS (n = 100) showed a lower physical fitness in comparison to non-MS controls (n = 26) (maximal workload (Watts): 138.86 ± 37.85 vs. 191.73 ± 45.25, p < 0.001; peak oxygen consumption (ml min-1 kg-1): 26.40 ± 7.23 vs. 31.56 ± 10.10, p = 0.020). pwMS were more regularly active in short- (62.1%) and long-term (55.2%) compared to baseline (24.2%, p < 0.001). Among the activated participants, we observed improved internal motivation (p = 0.002) and decreased perception of barriers (p = 0.006) compared to baseline. PwMS showed a lower physical fitness in comparison to non-MS controls. An individually tailored PA promotion program might improve behavioral determinants and thereby increase short- and long-term PA levels of pwMS.

Psychometric properties of the modified reaching performance scale in persons with multiple sclerosis

BackgroundA valid and reliable assessment tool to describe the quality of the movement pattern of reaching can provide valuable insights into motor performance deficits in persons with MS (pwMS). The Reaching Performance Scale, developed for stroke, is a promising scale to assess movement patterns in pwMS. However, psychometric properties of the scale are lacking in pwMS. ObjectivesFirstly, to investigate the content validity of the modified Reaching Performance Scale for application in patients with MS (mRPS). Secondly, to investigate the psychometric properties (within- and between-session reliability and concurrent validity) of the mRPS for pwMS. MethodsForty-five pwMS (mean EDSS 6.6 pt, IQR 6–7.5) executed the mRPS that rates the quality of movement patterns and compensations during reach to grasp tasks. The content validity was determined by an expert panel based on observations of subjects performing the RPS. The reliability was based on five repetitions within one day, and between two days. For the concurrent validity, outcome measures at two levels of the International Classification of Functioning were correlated with the mRPS: Body Structure and Function level: Fugl-Meyer Assessment of the Upper Limb (FMA-UL), maximal isometric hand grip strength (HGS; Activity level: Action Research Arm Test (ARAT), Box and Blocks Test (BBT), Nine Hole Peg Test (NHPT) and Trunk Impairment Scale 2.0 (TIS 2.0) as well as perceived performance by the Manual Ability Measure-36 (MAM-36). ResultsScale modifications were made only on the ratings of the trunk displacement subscale. The mRPS had excellent agreement scores for within-session reliability (range of Kappa between 0.85 and 0.98) and moderate-to-excellent agreement scores for between-session reliability (K: 0.66–1.00). Regarding validity, the mRPS was highly correlated with the ARAT (rho=0.74, p < 0.001), followed by moderate correlations with trunk performance (TIS 2.0, rho= 0.61, p < 0.001), hand function (BBT: rho=0.64, p < 0.001; NHPT: rho=-0.61, p < 0.001) and perceived performance (MAM36 rho= 0.53, p < 0.001). ConclusionThe mRPS is a reliable measurement tool to describe the movement pattern quality and motor compensations used during reaching in pwMS. Concerning concurrent validity, the mRPS is partially related to other measures of upper limb and trunk performance.

Non-Modifiable Factors Associated with Progression to Irreversible Disability in Multiple Sclerosis Patients

Introduction: Multiple sclerosis (MS) is the leading cause of acquired motor disability in young adults. The increase in disability follows the progression of the disease and imposes on those affected a permanent multidimensional handicap. The identification of the factors associated with the evolution towards an irreversible handicap is important for an adequate therapeutic management. Objective: Identify the non-modifiable factors associated with progression to irreversible disability in patients with MS. Material and Methods: This is a prospective collection study that was carried out in the physical medicine and rehabilitation departments of the University Hospital of Oran and the HMRU of Oran, between January 2017 and December 2019. For the main analysis, we retained an EDSS score (Expanded Disability Status Scale) for the patient if he had the same functional status during the last six months. Results/Discussion: This study included 103 MS cases, including 72 women and 31 men, with a mean age at onset of symptoms of 31.83 years and a mean EDSS of 5.12 ± 1.97. The progression of the disability assessed by the EDSS scale is related to: male gender, age at advanced onset and progressive form of MS. we did not find a correlation between the severity of the handicap and the place of birth and/or residence. Our results are unanimous in the literature for certain parameters, and the same is not true for others. Conclusion: Non-modifiable factors in MS, such as age, gender and place of birth and/or residence, are important predictors of disability and should alert the clinician to appropriate and specific management even at an early stage of the disease.

Spinal cord MRI activity in multiple sclerosis: Predictive value for relapses and impact on treatment decisions

IntroductionEmerging evidence suggests the prognostic value of spinal cord (SC) pathology in multiple sclerosis (MS). However, the 2021 MAGNIMS-CMSC-NAIMS guidelines don't recommend routine SC MRI for disease monitoring. This study investigates the frequency of new asymptomatic and isolated SC lesions, exploring their potential to predict clinical activity and guide treatment decisions. MethodsWe enrolled relapsing-remitting MS (RRMS) patients who underwent brain and SC MRI at baseline and after 12 months. New, enlarged, or gadolinium-enhanced (Gd+) lesions on MRI were considered disease activity markers. Clinical relapses and treatment changes observed 3 months after the 12-month MRI were analyzed using regression analysis, evaluating their association with worsening SC findings. ResultsA total of 201 RRMS patients (56 males, 27.9%, mean age 42.5 ± 12.1 years, mean EDSS 2.7 ± 1.9) were included. Isolated worsening of T2 lesion burden in the SC occurred in 16 patients (8%), and 12 (6%) had Gd + lesions. Among patients without brain MRI activity (n = 138), regression analysis revealed a significant association between new Gd + SC lesions and clinical relapses within 3 months of the 12-month MRI (p = 0.024). Worsening SC findings (p = 0.021) and SC lesion enhancement (p = 0.046) emerged as key factors influencing disease-modifying therapy changes within 3 months in these patients. Notably, even without clinical symptoms, worsening SC findings significantly predicted treatment changes (p = 0.003). ConclusionOur findings highlight the independent value of SC MRI findings in MS monitoring. Importantly, isolated and asymptomatic SC worsening significantly impacted treatment decisions.

Exploring the relationship between disability status, depression, and quality of life in individuals with multiple sclerosis

IntroductionDepression 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. MethodsA 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. ResultsA 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. ConclusionOur 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.

ACTIVE-FIT program: Assessment of sleep quality and its relationship with physical activity in patients with relapsing-remitting multiple sclerosis

BackgroundMultiple sclerosis (MS) causes sleep disturbances in up to 70 % of individuals. These problems are linked to fatigue, mood and cognitive performance, thereby affecting the quality of life in people with MS (PwMS). The frequent and debilitating side effects of sleep medications prompt the exploration of alternative therapies.Physical activity has shown benefits in improving sleep, reducing fatigue, and enhancing quality of life. Combined with a controlled exercise program tailored for PwMS, the study aims to analyze the impact of moderate physical exercise on sleep quality, cognitive function, quality of life, mood, and fatigue. MethodsA single-center prospective cohort study was designed to assess the impact of a 12-week physical exercise program on patients with relapsing-remitting multiple sclerosis. Changes in sleep and activity parameters are evaluated using an actigraph and cognitive, quality of life, fatigue and mood changes are assessed through specific questionnaires before, during, and after the exercise program application. Results23 patients completed the study (women = 84.6 %) Mean age was 37.2 years (SD 7.5). The mean EDSS score was 1.9, and 80.8 % were diagnosed within the last six years.Significant improvements were noted in sleep efficiency between baseline and final measurements (χ2 = 27.5; p.adj = 0.004), sleep latency (χ2 = 275; p.adj = 0.000), sleep duration (χ2 = 251; p.adj = 0.001) and in the number of awakenings (χ2 = 269.5; p.adj = 0.000), with a decreased in total time in bed from 8.5 h to 7.35 h post-intervention. Regarding activity variables, an increase in caloric expenditure and an increase in the time participants engaged in light activity were observed. We found significant improvements in fatigue, quality of life and mood. Concerning neuropsychological exploration results, improvements were observed in all studied parameters, with statistically significant improvement in Verbal SRT (χ2 = 43; p = 0.022). ConclusionOur study showed a positive impact of a 12-week physical exercise program on sleep performance, cognition and mood in PwMS. The observed improvements underscore the potential of tailored exercise interventions in promoting a more comprehensive and holistic care paradigm for PwMS.

The role of ethnicity and native-country income in multiple sclerosis: the Italian multicentre study (MS-MigIT)

ObjectiveMultiple sclerosis (MS) is a complex disorder in which environmental and genetic factors interact modifying disease risk and course. This multicentre, case–control study involving 18 Italian MS Centres investigated MS course by ethnicity and native-country economic status in foreign-born patients living in Italy.MethodsWe identified 457 MS patients who migrated to Italy and 893 age- and sex-matched native-born Italian patients. In our population, 1225 (93.2%) subjects were White Europeans and White Northern Americans (WENA) and 89 (6.8%) patients were from other ethnical groups (OEG); 1109 (82.1%) patients were born in a high-income (HI) Country and 241 (17.9%) in a low-middle-income (LMI) Country. Medical records and patients interviews were used to collect demographic and disease data.ResultsWe included 1350 individuals (973 women and 377 men); mean (SD) age was 45.0 (11.7) years. At onset, 25.45% OEG patients vs 12.47% WENA (p = 0.039) had > 3 STIR spine lesions. At recruitment, the same group featured mean (SD) EDSS score of 2.85 (2.23) vs 2.64 (2.28) (p = 0.044) reached in 8.9 (9.0) vs 12.0 (9.0) years (p = 0.018) and underwent 1.10 (4.44) vs. 0.99 (0.40) annual MRI examinations (p = 0.035). At disease onset, patients from LMI countries had higher EDSS score than HI patients (2.40 (1.43) vs 1.99 (1.17); p = 0.032).DiscussionOur results suggested that both ethnicity and socio-economic status of native country shape MS presentation and course and should be considered for an appropriate management of patients. To the best of our knowledge, this is the first study reporting on the impact of ethnicity in MS at an individual level and beyond an ecological population-perspective.

Is impairment of facial emotion recognition independent of cognitive dysfunction in multiple sclerosis?

BackgroundEmotions expressed on the face play a key role in social cognition and communication by providing inner emotional experiences. This study aimed to evaluate facial emotion identification and discrimination and empathy abilities in patients with MS and whether it is related to cognitive dysfunction.MethodsOne hundred twenty patients with relapsing–remitting MS and age- and sex-matched 120 healthy controls were enrolled in the study. All the subjects were evaluated with the Facial Emotion Identification Test (FEIT), Facial Emotion Discrimination Test (FEIDT), and Empathy Quotient (EQ). We used the Beck Depression Inventory (BDI) for depression and detailed cognitive tests, including the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Paced Auditory Serial Addition Test (PASAT). The quality of life was assessed with Multiple Sclerosis Quality of Life-54 (MSQL-54).ResultsPatients with MS were 37.6 ± 9.5 years old, had a mean disease duration of 8.8 ± 6.6 (8–28) years, and a mean EDSS score of 1.6 ± 1.3 (0–4.5). We found significant differences in the identification of facial emotions, discrimination of facial emotions, and empathy in MS patients compared to controls (p < 0.05). Especially the recognition of feelings of sadness, fear, and shame was significantly lower in MS patients. The multivariate logistic regression analysis showed low SDMT and FEIDT scores which showed an independent association with MS.ConclusionsOur findings indicate that facial emotion recognition and identification deficits are remarkable among patients with MS and emotion recognition is impaired together with and independently of cognitive dysfunction in MS patients.

Influence of cognition on the correlation between objective and subjective upper limb measures in people with multiple sclerosis.

A comprehensive assessment of upper limb (UL) function is mandatory in people with multiple sclerosis (PwMS), and the use of multiple objective and subjective measures is advisable. Findings on the role of cognitive impairment on the assessment of UL function are scant and inconclusive. The present study investigated the influence of cognitive function on the distribution of objective and subjective UL measures and on their association. In the cross-sectional study, subjects with a diagnosis of MS, age ≥ 18years, right-hand dominance, no presence of orthopedic UL impairment, or other neurological diseases were recruited. The assessment protocol included the Nine-Hole Peg Test (9-HPT), Box and Block Test (BBT), and hand grip strength (HGS), a validated PROM (MAM-36), and the Symbol Digit Modalities Test (SDMT). Two hundred forty-six PwMS were recruited (158 females, mean age = 51.65 ± 13.45years; mean EDSS = 5.10 ± 1.88) Subject with mild-to-moderate cognitive impairment (SDMT ≤ - 2 SD of normative values) scored lower on the 9-HPT and higher on the BBT and MAM-36 when compared with subject with no cognitive impairment. Cognitive impairment showed a small but significant effect on the association between 9-HPT scores and the MAM-36. Findings suggest that cognitive impairment is associated with subjects' performance on 9-HPT, BBT, and MAM-36 (but not HGS), resulting in scores indicating a poorer UL function. Interestingly, cognitive impairment slightly affected the congruence between subjective and objective UL measures, although only minor differences in the correlation pattern across groups reporting different cognitive performances emerged.

Lumbar Pain in Patients with Multiple Sclerosis and Knowledge about Physiotherapeutic Methods for Combating Pain

Background: The purpose of this study was to evaluate the intensity and frequency of low back pain (LBP) in people with multiple sclerosis (PwMS) and patients’ knowledge of physiotherapeutic methods for combating LBP. Methods: This study included all MS patients attending consecutive follow-up visits for treatment related to MS between March and May 2023. Only current pain sensations in the lumbar spine were taken into account. The inclusion criteria were age 18–60 years, a definite diagnosis of MS according to the 2017 McDonald criteria, treatment with disease-modifying drugs (DMTs), and consent to participate in the study. This study was carried out using an original survey questionnaire and a Visual Analogue Scale. PwMS were divided into three age groups: 18–30 years, 31–50 years, and over 50 years. Results: Ninety PwMS (68 women and 22 men) were included in the study. The mean duration of the disease was 9.5 ± 4.9 years, and the mean EDSS was 3.5 ± 1.6. Most patients had a relapsing-remitting form of the disease. Overall, 68.9% of PwMS felt low back pain (n = 62). The relationship tested was statistically significant (p &lt; 0.001), and the strength of the relationship was high (rc = 0.695). The average level of low back pain among PwMS was 4.7 out of 10 on the VAS. The prevalence of LBP was higher in female patients (p &lt; 0.001), patients with a secondary progressive form of MS (p &lt; 0.001), and patients with a longer duration of disease (p &lt; 0.05). The most widely used methods for treating LBP were kinesitherapy and manual therapy. Conclusions: LBP is common in patients with multiple sclerosis. Female sex, a secondary progressive form of MS, and a longer duration of disease increase the risk of LBP. It is important to implement properly planned physiotherapy activities and educate patients on how to combat LBP.

The administration of the paper and electronic versions of the Manual Ability Measure-36 (MAM-36) and Fatigue Severity Scale (FSS) is equivalent in people with multiple sclerosis.

The mobile device diffusion has increasingly highlighted the opportunity to collect patient-reported outcomes (PROs) through electronic patient-reported outcomes measurements (ePROMs) during the clinical routine. Despite the ePROMs promises and advantages, the equivalence when a PRO measure is moved from the original paper-and-pencil to the electronic version is still little investigated. This study aims at evaluating equivalence between PROMs and ePROMs self-administration in people with multiple sclerosis (PwMS); in addition, preference of self-administration type was evaluated. The Manual Ability Measure-36 (MAM-36) and Fatigue Severity Scale (FSS) were selected for the equivalence test. The app ABOUTCOME was developed through a user-centered design approach to administer the questionnaires on tablet. Both paper-and-pencil and electronic versions were randomly self-administered. Intrarater reliability between both versions was evaluated through the intraclass correlation coefficient (ICC, excellent for values ≥ 0.75). Fifty PwMS (35 females) participated to the study (mean age: 54.7±11.0 years, disease course: 27 relapsing-remitting and 23 progressive; mean EDSS: 4.7±1.9; mean disease duration: 13.3±9.5 years). No statistically significant differences were found for the means total scores of MAM-36 (p = 0.61) and FSS (p = 0.78). The ICC value for MAM-36 and FSS was excellent (0.98 and 0.94, respectively). Most of participants preferred the tablet version (84%). The results of the study provide evidence about the equivalence between the paper-and-pencil and electronic versions of PROs administration. In addition, PwMS prefer electronic methods rather than paper because the information can be provided more efficiently and accurately. The results could be easily extended to other MS PROs.

Real-life safety and effectiveness outcomes of teriflunomide in patients with relapsing–remitting multiple sclerosis: The TERICAM study

Introduction and objectiveTeriflunomide is an oral immunomodulatory agent approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). We examined teriflunomide outcomes in patients with RRMS under clinical practice conditions in Spain. Material and methodsNon-interventional, retrospective study at 15 sites in the Autonomous Region of Madrid and nearby regions. Effectiveness (relapses, EDSS, gadolinium-enhancing T1 lesions and new/enlarged T2-weighted lesions), safety (adverse events), and reasons for discontinuation during the 24 months after teriflunomide initiation were reported. ResultsA total of 776 patients were included (mean [SD] age was 43.3 (9.8) years; 69.3% were female). Two-thirds (67.7%) of patients had received a prior treatment, with beta-interferons or glatiramer acetate (BRACE) as the most frequent (93.5%) treatment. After 24 months, teriflunomide significantly reduced the annualized relapse rate (ARR) by 72% (mean [95% confidence interval] 0.12 [0.10, 0.14] vs 0.43 [0.40, 0.47] at baseline; P<.0001) and 81.8% of patients were relapse-free. The number of patients with gadolinium-enhancing T1 lesions and new/enlarged lesions on T2 was also reduced after 24 months of teriflunomide treatment (P<.001). Mean EDSS (SD) score was 1.9 (1.5) at teriflunomide initiation and 2.0 (1.6) at month 24. Half of patients (n=388) reported at least 1 adverse event (AE; gastrointestinal disorders: 26.2%; hair thinning: 25%; and elevation of ALT values: 12.9%). Most patients (91.5%) did not show fatigue increase during teriflunomide treatment. Among patients who discontinued treatment (n=262; 34.2%), the most common reasons were lack of effectiveness (58.0%), AEs (31.9%; n=82), and pregnancy desire (6.6%; n=17). ConclusionsMost RRMS patients treated with teriflunomide in clinical practice had received prior treatments. Teriflunomide resulted in decreased clinical and radiological activity and disability stabilization. AE frequency and type were in line with prior reports. Most patients did not experience fatigue increases after teriflunomide initiation.

Health behaviors of people with multiple sclerosis and its associations with MS related outcomes: a German clinical cohort.

Health behaviors in persons with multiple sclerosis (pwMS) have been associated with MS-related disease outcomes. The aim of the study was to gain knowledge about current patient health behaviors in a convenience sample representative for pwMS presenting to a large university-based outpatient clinic and to investigate associations between modifiable risk factors with physical impairment, quality of life (QoL) and cardiovascular comorbidities. A questionnaire was administered at the MS Outpatient Clinic of the University Medical Center Hamburg Eppendorf asking for health behaviors regarding dietary habits assessed with the German adaptation of the validated Spanish short Diet Quality Screener (sDQS), level of physical activity assessed with the Godin Leisure Time Questionnaire (GLTEQ) and tobacco smoking. Participants were asked to report cardiovascular comorbidities using items from the Self-Report Comorbidity Questionnaire for Multiple Sclerosis. Additionally, cardiovascular risk factors like blood pressure, height and weight (to calculate BMI) and waist circumference were measured. MS specific clinical data, e.g., disease course, duration, disability and MS-specific QoL were collected from the clinical database. Descriptive analyses were performed and multivariate regression analyses for complete cases were carried out for each of the three outcome variables including all mentioned modifiable risk factors (dietary behavior, smoking, physical activity and BMI) as independent variables. In this sample of 399 pwMS the mean age was 42 years (SD 12.8) with a mean disease duration since diagnosis of 7.4 years (SD 8.4) and a mean EDSS of 2.8 (SD 1.9). 24% were current smokers, 44% were insufficiently physically active and 54% did not follow a healthy dietary pattern. 49% of this relatively young clinical population was overweight and 27% reported one or more cardiovascular comorbidities. Most modifiable risk factors showed no convincing associations with MS-related disease outcomes in the multiple regression analyses. This clinical cohort of pwMS shows a high prevalence of critical health behaviors and comorbidities and emphasizes the need for monitoring, education and assistance for behavior change in this population.

SARS-CoV-2 pandemic as a model to assess the relationship between intercurrent viral infections and disease activity in Multiple Sclerosis: A propensity score matched case-control study.

An association between intercurrent viral respiratory infections and exacerbations of Multiple Sclerosis (MS) disease activity has been proposed by several studies. Considering the rapid spread of SARS-CoV2 worldwide and the systematic effort to immediately detect all incident cases with specific diagnostic tests, the pandemic can represent an interesting experimental model to assess the relationship between viral respiratory infections and MS disease activity. In this study, we have performed a propensity score matched case-control study with a prospective clinical/MRI follow-up, on a cohort of relapsing-remitting MS (RRMS) patients who tested positive for SARS-CoV2 in the period 2020-2022, with the aim to evaluate if the SARS-CoV2 infection influences the short-term risk of disease activity. Controls (RRMS patients not exposed to SARS-CoV-2, using 2019 as the reference period) were matched 1:1 with cases for age, EDSS, sex and disease-modifying treatment (DMT) (moderate efficacy vs high efficacy). Differences in relapses, MRI disease activity and confirmed disabilty worsening (CDW) between cases in the 6 months following the SARS-CoV-2 infection, and controls in a similar 6 months reference period in 2019 were compared. We identified 150 cases of SARS-CoV2 infection in the period March 2020 - March 2022, out of a total population of approximately 1500 MS patients, matched with 150 MS patients not exposed to SARS-CoV2 (controls). Mean age was 40.9±12.0 years in cases and 42.0±10.9 years in controls, mean EDSS was 2.54±1.36 in cases and 2.60±1.32 in controls. All patients were treated with a DMT, and a considerable proportion with a high efficacy DMT (65.3% in cases and 66% in controls), reflecting a typical real world RRMS population. 52.8% of patients in this cohort had been vaccinated with a mRNA Covid-19 vaccine. We did not observe a significant difference in relapses (4.0% cases, 5.3% controls; p=0.774), MRI disease activity (9.3% cases, 8.0% controls; p=0.838), CDW (5.3% cases, 6.7% controls; p=0.782) in the 6 months after SARS-CoV-2 infection between cases and controls. Using a propensity score matching design and including both clinical and MRI data, this study does not suggest an increased risk of MS disease activity following SARS-CoV-2 infection. All MS patients in this cohort were treated with a DMT, and a considerable number with a high efficacy DMT. These results therefore may not be applicable to untreated patients, for which the risk of increased MS disease activity after SARS-CoV-2 infection may not be excluded. A possible hypothesis explaining these results could be that SARS-CoV2 is less prone, compared to other viruses, to induce exacerbations of MS disease activity; another possible interpretation of these data might be that DMT is able to effectively suppress the increase of disease activity triggered by SARS-CoV2 infection.

A real-life study of alemtuzumab in persons with multiple sclerosis: Kuwait's experience.

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, has been approved as a treatment in persons with active relapsing-remitting multiple sclerosis (RRMS). Real-world data in middle east is very limited. We aimed to evaluate the effectiveness and safety of alemtuzumab in a real-world clinical setting. This observational, registry based study assessed persons with multiple sclerosis (PwMS) who were treated with alemtuzumab and completed at least follow up one year after second course. Baseline clinical and radiological characteristics within one year prior to alemtuzumab initiation were collected. The relapse rate, disability measures, radiological activity and adverse events at last follow-up visits were assessed. Data of seventy-three persons with multiple sclerosis (MS) was analyzed, of which 53 (72.6%) were females. Mean age and mean disease duration were 34.25±7.62 and 9.23±6.20 years respectively. Alemtuzumab was started in32(43.8%)naïve patientsdue tohighly active disease and in 25 (34.2%) (PwMS) who were on prior therapies andin 16 (22%) patients due to adverse events on prior medications. Mean follow-up period was 4±1.67 years. In the last follow-up visits, most of our cohort was relapse free (79.5% vs. 17.8%; p<0.001) compared to baseline before alemtuzumab treatment while mean EDSS score was reduced (2.21±2.15vs. 2.41±1.85; p<0.059). The proportion of PwMS who had MRI activity (new T2/ Gd-enhancing) lesions were significantly reduced compared to baseline (15.1% vs. 82.2%; p<0.001). NEDA-3 was achieved in 57.5% of (PwMS). NEDA-3 was significantly better in naïve patients (78% versus. 41.5%; p<0.002) and in patients with disease duration < 5 years, (82.6% v 43.2%; p<0.002). Several adverse events such as infusion reactions (75.3%), autoimmune thyroiditis (16.4%) and glomerulonephritis (2.7%) were reported. The effectiveness and safety profile of alemtuzumab in this cohort were consistent with data of clinical trials. Early initiation of Alemtuzumab is associated with favorable outcome.

A randomized, controlled trial of low-fat diet for fatigue in multiple sclerosis (P6-3.008)

<h3>Objective:</h3> Determine if a low-fat diet is effective at ameliorating fatigue in people with multiple sclerosis (PwMS) through a randomized controlled trial (RCT). Primary outcome is reduction in fatigue assessed via Modified Fatigue Impact Scale (MFIS) at 16 weeks. <h3>Background:</h3> Fatigue is a common, disabling symptom of multiple sclerosis (MS). A dietary intervention to improve fatigue is desirable given the minimal risk of adverse events. <h3>Design/Methods:</h3> PwMS were assigned to a low-fat diet (active) or wait-list (control) group. The active group received 4 weeks of data collection/nutrition counseling followed by adherence to the diet for 12 weeks. We measured diet adherence using monthly Food Frequency Questionnaire and 24-hr food recall. The principal statistical analysis used linear mixed models, with a random effect for subject to account for the within-subject correlation, in an intent-to-treat (ITT) framework to determine the effect of diet on the outcomes of MFIS and Fatigue Severity Scale (FSS). Sensitivity analysis was conducted by excluding potential outliers in both groups. <h3>Results:</h3> 39 participants were recruited with 20 in the active group and 19 in the control group. At baseline, participants’ mean age was 50 years (±12 years), mean BMI was 31 kg/m² (±7 kg/m²), and mean EDSS was 3.8 (±1.4). Mean MFIS decreased by −4.00 (95% CI: −12.04, 4.04) and mean FSS decreased by −0.41 (95% CI: −1.18, 0.36) from baseline to the end of the RCT in active group compared to control. Sensitivity analysis strengthened the magnitude of association with a mean MFIS decrease of −13.93 (95% CI: −20.65, −7.20) and mean FSS decrease of −1.22 (95% CI: −1.94, −0.50) in active group compared to control. Percent calories from fat decreased by 10.56% (95% CI: −18.50%, −2.97%) in active group compared to control. <h3>Conclusions:</h3> This 16-week long low-fat dietary intervention reduced the fatigue score significantly in the active group compared to controls. <b>Disclosure:</b> Dr. Chen has received research support from OHSU Foundation. Mrs. Chase has nothing to disclose. Dr. Lane has nothing to disclose. The institution of Dr. Wooliscroft has received research support from National Institutes of Health. Claire Adams has nothing to disclose. Mrs. Srikanth has nothing to disclose. Dr. Silbermann has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. Dr. Silbermann has received research support from VA. Dr. Rice has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Pharmaceuticals. Dr. Hollen has nothing to disclose. Allison Fryman has nothing to disclose. Dr. Martin has received research support from Tartar Trust. The institution of Dr. Martin has received research support from OHSU Foundation. Ms. Vong has nothing to disclose. Anna Orban has nothing to disclose. Dr. Khan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dompe Pharmaceuticals. The institution of Dr. Khan has received research support from United Therapeutics. The institution of Dr. Khan has received research support from Janssen pharmaceuticals. The institution of Dr. Khan has received research support from Eli Lilly. The institution of Dr. Khan has received research support from 4D Medical. The institution of Dr. Khan has received research support from Regeneron Pharmaceuticals. The institution of Dr. Khan has received research support from BOA Medical. Dr. Horgan has nothing to disclose. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb Foundation. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD-Serono . The institution of Dr. Yadav has received research support from Department of Veterans Affairs. Dr. Yadav has received research support from NIH. Dr. Yadav has received research support from PCORI. Dr. Yadav has received research support from NMSS. The institution of Dr. Yadav has received research support from Department of Veterans Affairs. The institution of Dr. Yadav has received research support from Tykeson Family Foundation Endowed Professorship.