Background: To evaluate retinal vessel density (VD) in macular and in peripapillary regions in patients with recent onset of multiple sclerosis, at initial demyelinating event (IDE) and in matched relapsing-remitting multiple sclerosis (RRMS) patients.Methods: We evaluated VD in superficial capillary plexus, deep capillary plexus, choriocapillaris and radial peripapillary capillary plexus in IDE, RRMS patients and in matched healthy controls (HCs) through Optical Coherence Tomography Angiography (OCT-A). Clinical history, including history of optic neuritis, Expanded Disability Status scale and disease duration of patients were collected.Results: Thirty patients (20 with IDE and 10 with RRMS) and 15 HCs were enrolled. IDE patients showed a lower VD in radial peripapillary capillary plexus compared with controls (coeff. β = −3.578; p = 0.002). RRMS patients displayed a lower VD in both superficial capillary plexus and radial peripapillary capillary plexus compared with HCs (coeff. β = −4.955; p = 0.002, and coeff. β = −7.446; p < 0.001, respectively). Furthermore, RRMS patients showed a decreased VD in radial peripapillary capillary plexus compared with IDE patients (coeff. β = −3.868; p = 0.003).Conclusions: Peripapillary region vessel density reduction, revealed through OCT-A, might be considered as an early event in MS, and might be relevant as a biomarker of disease pathology.

We used structural equation modeling to explore the relationship between mental distress, disability and coping strategies in the Italian population with multiple sclerosis (MS) under lockdown. A total of 845 people (497 with MS and 348 controls) participated in our web survey; in this population, the MS group had higher scores than the control group for depression ( P = 0.005). According to the structural equation modeling, which explained 74% of the variance observed in depression scores, favoring exercise would enhance active attitude and its positive impact on mental well‐being while, at the same time, reducing the negative impact of disability on depression, representing a valuable tool in facing COVID‐19‐related mental distress.

Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and sixty patients were enrolled. Median dose interval (MDI) following 24th infusion was 4.7 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Two hundred and sixteen patients were in the SID group (MDI = 4.3 weeks) and 144 in the EID group (MDI 6.2 weeks). Annualized relapse rate was 0.060 (95% CI = 0.033-0.087) in the SID group and 0.039 (95% CI = 0.017-0.063) in the EID group. The non-inferiority of EID versus SID was satisfied. In conclusion, there is no evidence of a reduced efficacy of natalizumab in an EID setting. This observation confirms previous results and together with the emerging evidence of a reduced risk of PML associated to an EID, supports the need of a randomized study to assess the need to change the standard of the natalizumab dosing schedule.

Clinical trials in multiple sclerosis (MS) have been including digital technology tools to overcome limitations in treatment delivery and disease monitoring. In March 2020, we conducted a systematic search on pubmed.gov and clinicaltrials.gov databases (with no restrictions) to identify all relevant published and unpublished clinical trials, in English language, including MS patients, in which digital technology was applied. We used “multiple sclerosis” and “clinical trial” as the main search words, and “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Digital technology has been used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms (e.g., electronic recording of motor performance). Other clinical trials have been using digital technology for monitoring symptoms that would be otherwise difficult to detect (e.g., fatigue, balance), for measuring treatment adherence and side effects, and for self-assessment purposes. Collection of outcome measures is progressively shifting from paper-based on site, to internet-based on site, and, in the future, to internet-based at home, with the detection of clinical and treatment features that would have remained otherwise invisible. Similarly, remote interventions provide new possibilities of motor and cognitive rehabilitation.

Background and purpose Cardiovascular risk factors and comorbidities can affect the prognosis of multiple sclerosis (MS). The Framingham risk score is an algorithm that can estimate the 10‐year risk of developing macrovascular disease. Our objectives were to evaluate the possible association between the Framingham risk score at baseline and MS relapses, disability, and disease‐modifying therapy (DMT) choices over a 5‐year follow‐up. Methods This is a retrospective cohort study including 251 MS subjects. At baseline, we calculated the Framingham risk score considering the following variables: age, sex, diabetes, smoking, systolic blood pressure, and body mass index. MS outcomes including relapses, disability, and treatments were collected over 5 years. Cox proportional regression models were employed to estimate hazard ratios (HRs). Results A one‐point increase in the Framingham risk score was associated with 31% higher risk of relapse (HR = 1.31; 95% confidence interval [CI] = 1.03, 1.68), 19% higher risk of reaching of EDSS 6.0 (HR = 1.19; 95% CI = 1.05, 3.01), and 62% higher risk of DMT escalation (HR = 1.62; 95% CI = 1.22, 3.01). Conclusions Higher cardiovascular risk was associated with higher risk of relapses, disability, and DMT escalation in MS. Early identification, correction, and treatment of cardiovascular comorbidities should be carefully considered within MS management.