A Randomized Computer-Assisted Rehabilitation Trial of Attention in Pediatric Multiple Sclerosis: A Post Hoc Analysis

Cognitive impairment (CI) is a remarkable feature in pediatric-onset multiple sclerosis (POMS). The Symbol Digit Modalities Test (SDMT) is increasingly used to explore CI in MS. Recently, a four-point worsening on the SDMT score has been demonstrated to correlate with a clinically meaningful cognitive worsening in adult MS. We conducted a post hoc analysis of a randomized computer-assisted rehabilitation trial for attention impairment in POMS to test the clinical meaningfulness of the changes in SDMT scores at the end of the trial (delta SDMT). A four-point SDMT cut-off was applied. POMS patients exposed to specific computer training (ST) and non-specific training (nST) were compared. Data of 16 POMS (9 females, age 15.75 +/- 1.74 years) patients were analyzed. At the end of the trial, 25% of patients reported no clinically significant changes (-3 to 3), 12.5% a clinically significant worsening (<=-4) and 62.5% a clinically significant improvement (>= 4) in the delta SDMT. The proportion of patients reporting a clinically meaningful improvement was significantly (p = 0.008) higher (100%) in patients exposed to ST in comparison to those (25%) exposed to nST. The use of the four-point SDMT cut-off may be useful to assess the clinical meaningfulness of results from cognitive rehabilitation trials

Long-term comparative analysis of no evidence of disease activity (NEDA-3) status between multiple sclerosis patients treated with natalizumab and fingolimod for up to 4 years

Comparative effectiveness of natalizumab and fingolimod over a follow-up longer than 2 years has been not addressed yet

Типологія синтаксичних конструкцій в німецькій та українській мовах

Німецька та українська мови є односистемними мовами: обидві належать до індоєвропейської мовної сім’ї. Спільні корені та тривалий період ізольованого розвитку, вказують на те, що вказані мови мають характеристики подібності та відмінності в своій внутрішній будові. Німецька та українська належать до синтетичного типу флективних мов. Це означає, що граматичне значення слів у них виражається, здебільшого, за допомогою системи флексій і реалізується в межах одного графічного слова. Але флективна система німецької мови бідніша, ніж у слов’янських мовах.Немецкий и украинский языки являются односистемными языками: оба принадлежат к индоевропейской языковой семье. Общие корни и длительный период изолированного развития, указывают на то, что указанные языки имеют характеристики сходства и различия в своем внутреннем строении. Немецкий и украинский принадлежат к синтетическому типу флективных языков. Это означает, что грамматическое значение слов в них выражается, в основном, с помощью системы флексий и реализуется в пределах одного графического слова. Но флективная система немецкого языка беднее, чем в славянских языках.German and Ukrainian are single-system languages: both belong to the Indo-European language family. Common roots and a long period of isolated development, indicate that these languages ​​have characteristics of similarity and differences in their internal structure. German and Ukrainian belong to the synthetic type of inflectional languages. This means that the grammatical meaning of words in them is expressed, mainly, with the help of a system of inflexions and is realized within a single graphic word. But the inflectional system of the German language is poorer than in the Slavic languages

Impact of Natalizumab on Cognitive Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label, Two Years Observational Study

Background and Objectives: Natalizumab reduces the relapse rate and magnetic resonance imaging activity in patients with Relapsing-Remitting Multiple Sclerosis (RRMS). So far the influence of natalizumab on cognitive functions and fatigue in MS remains uncertain. The aim of this prospective, open-label, observational study was to evaluate the possible effects of natalizumab on cognition and fatigue measures in RRMS patients treated for up to two years. Methods: Cognitive performances were examined by the Rao’s Brief Repeatable Battery (BRB), the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months. Patients who failed in at least 3 tests of the BRB and the ST were classified as cognitively impaired (CI). Fatigue Severity Scale (FSS) was administered every 12 months to assess patient’s selfreported fatigue. One hundred and 53 patients completed 1 and 2 year-natalizumab treatment, respectively. Results: After 1 year of treatment the percentage of CI patients decreased from 29 % (29/100) at baseline to 19 % (19/100) (p = 0.031) and the mean baseline values of CII (13.5266.85) and FSS (4.0161.63) scores were significantly reduced (10.4867.12, p,0.0001 and 3.6161.56, p = 0.008). These significant effects were confirmed in the subgroup of patients treated up to two years. Conclusions: These results demonstrate that a short-term NTZ treatment may significantly improve cognitive performance

Effectiveness of fingolimod in real-world relapsing-remitting multiple sclerosis Italian patients: the GENIUS study

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Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis

Introduction Natalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population. Materials and methods This retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the ’Italian MS Register’. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment. Results Out of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups. Discussion The use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety

Disability assessment using Google Maps

Objectives To evaluate the concordance between Google Maps  application (GM ) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). Materials and methods This is a cross-sectional multicenter study. AS and EDSS were calculated using GM  and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. Results Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM  and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1–7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01–1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04–1.17, p = 0.002) were associated with discrepancies between GM  and routine clinical scoring. Conclusion GM  could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM  should be considered for validation in further clinical studies

Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies

Background and aims: No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC). Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups. Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19, p = 0.03) at 1 year to 0.30 (0.07-0.53, p = 0.009) at 5 years and to 0.67 (0.31-1.03, p = 0.0003) at 10 years. Conclusion: Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time

Risk of Getting COVID-19 in People With Multiple Sclerosis

Background and Objectives Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). Methods Acase-control (1:2) studywas set up. Cases included PwMSwith a confirmed diagnosis ofCOVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administeredDMT, previousDMTsequences, or the place where the last treatment was administered. Results A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02)with a higher risk of contractingCOVID-19. Patients receiving natalizumab as last DMT(OR[95%CI]: 2.38 [1.66–3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34–2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. Discussion This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. Classification of Evidence This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective

Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression

Objectives: We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS). Methods: Relapsing-onset MS patients with follow-up > / = 5 years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score. Sustained disability accumulation (SDA) was a CDA with no EDSS improvement in all subsequent visits. Predictors of PIRA and RAW and the association between final EDSS score and type of CDA were assessed using logistic multivariable regression and multivariable ordinal regression models, respectively. Results: Over 11.8 ± 5.4 years, 16,731 CDA events occurred in 8998 (55.8%) patients. PIRA (12,175) accounted for 72.3% of CDA. SDA occurred in 8912 (73.2%) PIRA and 2583 (56.7%) RAW (p < 0.001). 4453 (27.6%) patients transitioned to SPMS, 4010 (73.2%) out of 5476 patients with sustained PIRA and 443 (24.8%) out of 1790 patients with non-sustained PIRA. In the multivariable ordinal regression analysis, higher final EDSS score was associated with PIRA (estimated coefficient 0.349, 95% CI 0.120-0.577, p = 0.003). Discussion: In this real-world relapsing-onset MS cohort, PIRA was the main driver of disability accumulation and was associated with higher disability in the long term. Sustained PIRA was linked to transition to SP and could represent a more accurate PIRA definition and a criterion to mark the putative onset of the progressive phase