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<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>