Catálogo de publicaciones - revistas

<jats:sec><jats:title>Background:</jats:title><jats:p> Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS). </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Prospective 2-year study including two cohorts of young (18–35 years) and elderly (⩾50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration ( p = 0.05), smoking ( p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT ( p = 0.00007), high-efficacy therapies ( p = 0.001), brain lesion volume (BLV) ( p = 0.011), and number of T2 lesions ( p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm<jats:sup>3</jats:sup> and white matter volume 1.78 cm<jats:sup>3</jats:sup>. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> Evidence on the impact of dimethyl fumarate (DMF) during pregnancy in women with multiple sclerosis (MS) is limited. </jats:p></jats:sec><jats:sec><jats:title>Objectives:</jats:title><jats:p> To investigate disease activity and pregnancy outcomes in a retrospective cohort of women exposed to DMF in early pregnancy. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Women discontinuing DMF after pregnancy confirmation were identified from 29 Italian MS Centers. Disease activity 12 months before conception, during pregnancy, and 12 months postpartum were recorded, exploring reactivation predictors. Pregnancy and fetal outcomes were assessed. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> The study analyzed 137 pregnancies (12 pregnancy losses, 125 live births) from 137 women (mean age 32.9 ± 4.7 years), discontinuing DMF within a median (interquartile range (IQR)) interval of 4.9 (3.7–5.7) weeks from conception. In live birth pregnancies, annualized relapse rate (ARR) significantly decreased during pregnancy (ARR = 0.07, 95% confidence interval (CI): 0.03–0.14, p = 0.021) compared to pre-conception (ARR = 0.21 (95% CI: 0.14–0.30)) and increased postpartum ((ARR = 0.22 (95% CI: 0.15–0.32), p = 0.006). Median time to first relapse (TTFR) was 3.16 (IQR: 1:87–5.42) months. Higher pre-conception relapse number (hazard ratio (HR) = 2.33, 95% CI: 1.08–5.02) and Expanded Disability Status Scale (EDSS; HR = 1.81, 95% CI: 1.17-2.74) were associated with shorter TTFR, while treatment resumption with longer TTFR (HR = 0.29, 95% CI: 0.11–0.74). Fetal outcomes were unaffected by DMF exposure. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> DMF discontinuation does not increase relapse risk during pregnancy. Early therapy restart prevents postpartum relapses. Early DMF exposure shows no adverse fetal outcomes. </jats:p></jats:sec>

<jats:p> Healthcare breakthroughs are extending the lives of multiple sclerosis (MS) patients and cancer survivors, creating a growing cohort of individuals navigating a dual diagnosis. Determining the relationship between MS and cancer risk remains challenging, with inconclusive findings confounded by age, risk exposures, comorbidities, genetics and the ongoing introduction of new MS disease-modifying therapies (DMTs) across study periods. </jats:p><jats:p> This research places significant emphasis on cancer survival, with less attention given to the impact on MS outcomes. Our review explores the existing literature on MS, cancer risk and the intersection of DMTs and cancer treatments. We aim to navigate the complexities of managing MS in cancer survivors to optimise outcomes for both conditions. Continuous research and the formulation of treatment guidelines are essential for guiding future care. Collaboration between neuro-immunology and oncology is crucial, with a need to establish databases for retrospective and ultimately prospective analysis of outcomes in these rapidly evolving fields. </jats:p>

<jats:sec><jats:title>Background:</jats:title><jats:p> Scarce data are available on the long-term immunological effects of multiple sclerosis (MS) disease-modifying treatments (DMTs). </jats:p></jats:sec><jats:sec><jats:title>Objectives:</jats:title><jats:p> This study aimed to investigate the long-term modifications of the peripheral immune repertoire on interruption of a sequestering DMT (natalizumab, fingolimod) and switch to another high-efficacy DMT. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Lymphocyte subpopulations were assessed, every 6 months up to 48 months, in patients switched from fingolimod or natalizumab to ocrelizumab, and in patients switched from fingolimod to natalizumab, compared to patients switched to ocrelizumab or natalizumab from a moderate-efficacy DMT and to naive patients. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> We included 389 MS patients (200 ocrelizumab and 189 natalizumab). After adjusting for baseline variables, patients switched from fingolimod to ocrelizumab showed lower CD3 + and CD4 + lymphocytes up to 48 months after switch (with lower percentage of naive CD4 +), and increased odds of total, CD3+, CD4+ lymphopenia. Patients switched from natalizumab to ocrelizumab showed higher CD3 + lymphocytes up to 36 months after switch, and higher CD4+, CD8+ lymphocytes up to 24 months. The frequency of infections was not influenced by previous treatment. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> A long-term persistence of the residual effects of the exposure to sequestering DMTs (fingolimod and less natalizumab) on the peripheral immune repertoire was observed after switching to another high-efficacy DMT. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> Cognitive impairment is common in neurologic diseases. Precise measurement of cognitive change over time is necessary for isolating disease-related patterns from normal age-related decline. Existing measures of subjective cognition, however, focus on present status. There is, to our knowledge, no currently available self-report measure of cognitive change. We therefore developed the Cognitive Change Scale (CCS), which assesses perceived cognitive change in neurologic populations. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> A systematic mixed-methods process was followed for the scale design and validation. Associations of CCS responses to demographics, mood, and fatigue were examined in 131 persons with multiple sclerosis. A total of 46 participants also completed a cognitive test battery. Correlations of test scores with CCS responses were calculated. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> The 17-item CCS showed good reliability and validity. Results of exploratory and confirmatory factor analyses supported a four-factor structure, with items reflecting change in (1) general cognition, (2) language and executive function, (3) external feedback, and (4) use of coping strategies. Positive relationships of CCS scores with fatigue, depression, and anxiety were observed. Correlations of CCS scores with cognitive test performance did not reach significance. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> The CCS may be a useful cognitive outcome tool for treatment trials in neurologic populations. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> A digital adaptation of the nine-hole peg test (9HPT) was developed with the potential to provide novel disability features for patients with multiple sclerosis (PwMS). </jats:p></jats:sec><jats:sec><jats:title>Objectives:</jats:title><jats:p> The objectives were to evaluate the 9HPT features based on reliability, prognosis, and discrimination between treatment groups. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> The MS partners Advancing Technology and Health Solutions (MS PATHS) cohort data were used to derive new features including completion time and speed. Association and reliability between features and clinical outcomes were tested by intraclass correlation coefficients (ICCs) with repeated measures. The added prognostic value of the features for a clinically meaningful decline was assessed by time-to-event analyses with likelihood ratio tests. The estimated effect size between treatment efficacy groups was acquired from linear mixed-effects models. Sample size was calculated for a hypothetical randomized clinical trial. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> For the 10,843 PwMS, speed and completion time were associated with MS disability. Compared with time, speed showed higher reliability (ICC = 0.78 vs 0.74), added benefits in predicting disability worsening ( p &lt; 0.001), better discrimination between high- and low-efficacy groups (effect size: 0.035 vs 0.015), and an 18% reduction in required sample size for a 1-year clinical trial. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Integrating horizontal hand distances traveled over the 9HPT pegboard can be a more reliable measure of hand function. </jats:p></jats:sec>

<jats:p> Recognizing neuromyelitis optica spectrum disorder (NMOSD) and differentiating NMOSD from multiple sclerosis (MS) and other disorders can be challenging yet it is extremely important to prevent misdiagnosis, defined in this review as the incorrect diagnosis of patients who truly have NMOSD, particularly in aquaporin-4-IgG (AQP4-IgG)-seronegative cases. The heterogeneity of clinical presentations and wide range of differential diagnoses often lead to missed diagnoses of NMOSD. Misapplication of the 2015 NMOSD criteria and misinterpretation of clinical and neuroradiological findings are relevant factors associated with misdiagnosis in clinical practice. Despite the presence of a specific biomarker for NMOSD (AQP4-IgG), misdiagnosis rates have been reported as high as 35%. Studies indicate that misdiagnosed patients often undergo unnecessary prolonged immunotherapy, leading to health risks and increased morbidity. Accurate definitive diagnosis is crucial as long-term outcomes and treatment approaches differ based on the correct diagnosis, and inappropriate immunotherapy can lead to disability in NMOSD patients. This review outlines factors linked to NMOSD misdiagnosis and briefly discusses strategies to reduce misdiagnosis. </jats:p>

<jats:sec><jats:title>Background:</jats:title><jats:p> In the DISCOMS (DISCOntinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS)) randomized clinical trial, we could not demonstrate that discontinuing MS DMTs in older, stable adults was not inferior to continuing DMTs. Relapses were rare in both groups, and most new disease activity was one to two new brain magnetic resonance imaging (MRI) lesions unassociated with clinical changes. </jats:p></jats:sec><jats:sec><jats:title>Objective/Aims:</jats:title><jats:p> Describe results of the DISCOMS extension study. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Among 10/19 of the original sites, we enrolled patients who completed DISCOMS; did not reach the primary endpoint during the original trial; and retained original randomized assignment. Participants completed one study visit and brain MRI at least 30 months after original enrollment in DISCOMS. Primary endpoint was time from entry into the primary study to relapse or new brain MRI activity. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Mean (SD) total follow-up was 40 (11.7) months. There were no relapses, and new brain MRI lesions (1/30 continuer, 2/44 discontinuers) were uncommon during the extension. Time from primary trial entry to disease event was significantly shorter for subjects in the discontinue group ( p = 0.043 from log-rank test). </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> From entry into DISCOMS extension study, time to new MS activity remained shorter in discontinuers, but relapses were absent and new brain MRI lesions were rare. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> Little is known about how multiple sclerosis (MS) presents in Hispanic/Latinx (HL) people with MS (pwMS). </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> Compare age at onset (AAO) and onset severity between HL versus non-Hispanic White (NHW) pwMS. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> A cross-sectional study leveraged the MS PATHS registry spanning seven US tertiary care institutions. HL was subcategorized as HL White (HLW) and HL Other (HLO; all other races). Multivariable models examined relationships between ethnoracial variables and AAO and self-reported presenting disease course. Models were repeated restricting to those born ⩾1970. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> The study population included 8231 pwMS, including 540 HL (200 HLW, 340 HLO). The sex distribution did not differ across ethnoracial subgroups. From the statistical models (1) HLO pwMS had an earlier AAO and a higher prevalence of initial progressive disease course than NHW pwMS; (2) among all HL pwMS, irrespective of race, AAO did not differ by sex or between relapsing and progressive MS at onset. In younger HLO adults (born ⩾1970), those with progressive MS at onset had an earlier AAO than those with relapsing MS; and (3) in HL pwMS there was no sex-bias in presenting disease course. </jats:p></jats:sec><jats:sec><jats:title>Discussion:</jats:title><jats:p> Distinct differences in the presentation of MS in HL compared with NHW individuals were observed. </jats:p></jats:sec>

<jats:sec><jats:title>Background:</jats:title><jats:p> Predicting treatment response and disease progression in multiple sclerosis (MS) is challenging. Treatment Response Scoring Systems (TRSS) are potentially useful, but their utility in patients receiving high-efficacy therapies and very high-efficacy therapies (HET/vHET) remains unclear. </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> This study aimed to evaluate the performance of TRSS in patients treated with HET/vHET. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We retrospectively studied MS patients treated with HET/vHET in an MS specialized centre. TRSS, including the Rio Score, modified Rio Score and MAGNIMS score, were applied to assess response to treatment. We evaluated the predictive value of the TRSS on disease activity and disability progression. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> TRSS effectively predicted disease activity and progression of disability in patients treated with HET/vHET. Patients with high TRSS scores at 12 months post-HET/vHET initiation had a significantly increased risk of relapses, new lesions on magnetic resonance imaging (MRI) scans and progression of disability at 4 years. </jats:p></jats:sec><jats:sec><jats:title>Discussion:</jats:title><jats:p> Our findings highlight the importance of personalized treatment strategies in MS. TRSS are valuable tools for monitoring treatment response, guiding clinical decision-making and optimizing patient care. </jats:p></jats:sec>