Advanced MRI Techniques: Diagnosis and Follow-Up of Multiple Sclerosis.

Brain and spinal cord imaging plays a pivotal role in aiding clinicians with the diagnosis and monitoring of multiple sclerosis. Nevertheless, the significance of magnetic resonance imaging in MS extends beyond its clinical utility. Advanced imaging modalities have facilitated the in vivo detection of various components of MS pathogenesis, and, in recent years, MRI biomarkers have been utilized to assess the response of patients with relapsing-remitting MS to the available treatments. Similarly, MRI indicators of neurodegeneration demonstrate potential as primary and secondary endpoints in clinical trials targeting progressive phenotypes. This review aims to provide an overview of the latest advancements in brain and spinal cord neuroimaging in MS.

Treatment modifiers across different regimens of natalizumab treatment in MS: An Italian real-world experience.

Despite its widespread use in clinical practice, the effectiveness of natalizumab extended interval dosing (EID) adopted from treatment start across different treatment intervals and individual modifiers (body mass index - BMI) is still under-investigated. Here, seven-hundred and forty-five multiple sclerosis (MS) patients, exposed to natalizumab for 3.30 â€‹± â€‹1.34 years, were retrospectively enrolled in an observational multicenter study. After stratifying patients in EID or standard interval dosing (SID), we assessed differences in time to relapse, MRI activity and Expanded Disability Status Scale (EDSS) progression. The primary analysis was conducted on patients exposed to EID interval from 5 weeks and 1 day to 7 weeks, while a secondary analysis included also EID periods up to 8 weeks. An additional analysis explored the impact of BMI. No differences in time to first relapse, time to radiological activity, time to EDSS progression or time to EDA (evidence of disease activity) were detected between SID and EID group (EID interval from 5 weeks to 1 day to 7 weeks). When including EID periods from 7 weeks and 1 day to 8 weeks, the EID group showed a trend towards higher risk of experience clinical relapses than the SID group. A higher EDA risk was also identified in EID patients with BMI above median. In conclusion, a higher risk of relapses seems to occur for EID above 7 weeks. Independently from the EID scheme adopted, higher BMI increases the risk of EDA in these patients.

Should we treat pediatric radiologically isolated syndrome? An 18-year follow-up case report.

Background: Radiologically isolated syndrome (RIS) describes asymptomatic individuals with incidental radiologic abnormalities suggestive of multiple sclerosis (MS). Much of RIS literature is about adult-onset cases. Treatment of RIS is controversial, especially in pediatric age, but early treatment in selected patients might improve long-term outcomes. Case presentation: We report a single RIS patient who followed up for 18 years in our MS center. At first, she was only monitored with follow-up MRIs. Then, as the lesion load increased, she was treated with a first-line disease-modifying treatment (DMT) reaching MRI stability. Conclusion: This report highlights how treatment can be an appropriate choice in pediatric forms of RIS.

Safety and effectiveness of the booster dose of mRNA COVID-19 vaccines in people with multiple sclerosis: A monocentric experience.

BACKGROUND: Long-term data on the effectiveness and safety of the booster dose of anti-SARS-CoV-2 vaccines in people affected by multiple sclerosis (pwMS) are lacking, hence a retrospective monocentric study exploring these issues was undertaken. MATERIALS AND METHODS: PwMS who had received the booster dose of anti-COVID19 mRNA vaccines (either Comirnaty or Spikevax) according to the national regulation were included. The occurrence of adverse events or disease reactivation and SARS-CoV-2 infection were recorded up to last follow-up. Factors predictive of COVID-19 were explored using logistic regression analyses. A two-tailed p-value <0.05 was considered significant. RESULTS: One hundred and fourteen pwMS were included: 80 females (70%); median age at the booster dose 42 years (range 21 - 73); 106/114 patients (93%) were receiving a disease-modifying treatment at vaccination. The median follow-up after the booster dose was 6 (range 2 - 7) months. Adverse events were experienced in 58% of the patients, being mild to moderate in most cases; 4 reactivations of MS were observed, two of which occurring within 4 weeks after the booster. SARS-CoV-2 infection was reported in 24/114 (21%) cases, occurring a median of 74 days (5-162) after the booster dose and requiring hospitalisation in 2 patients. Six cases received direct antiviral drugs. Age at vaccination and time between the primary vaccination cycle and the booster dose were independently and inversely associated with the risk of COVID-19 (HR 0.95 and 0.98, respectively). CONCLUSIONS: The administration of the booster dose in pwMS showed an overall good safety profile and protected 79% of the patients from SARS-CoV-2 infection. The observed association between the risk of infection after the booster dose and both younger age at vaccination and shorter interval period to the booster dose suggest that unobserved confounders, possibly including behavioural and social factors, play a relevant role in determining the individual propensity to get infected with COVID-19.

Potential Protective Role of Pregnancy and Breastfeeding in Delaying Onset Symptoms Related to Multiple Sclerosis.

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation.

Hematopoietic Stem Cell Transplantation in People With Active Secondary Progressive Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Uncontrolled evidence suggests that autologous hematopoietic stem cell transplantation (AHSCT) can be effective in people with active secondary progressive multiple sclerosis (SPMS). In this study, we compared the effect of AHSCT with that of other anti-inflammatory disease-modifying therapies (DMTs) on long-term disability worsening in active SPMS. METHODS: We collected data from the Italian Bone Marrow Transplantation Study Group and the Italian Multiple Sclerosis Register. Patients were considered eligible if treatment had been started after the diagnosis of SPMS. Disability worsening was assessed by the cumulative proportion of patients with a 6-month confirmed disability progression (CDP) according to the Expanded Disability Status Scale (EDSS) score. Key secondary endpoints were the EDSS time trend after treatment start and the prevalence of disability improvement over time. Time to first CDP was assessed by means of proportional hazard Cox regression models. A linear mixed model with a time × treatment group interaction was used to assess the longitudinal EDSS time trends. Prevalence of improvement was estimated using a modified Kaplan-Meier estimator and compared between groups by bootstrapping the area under the curve. RESULTS: Seventy-nine AHSCT-treated patients and 1975 patients treated with other DMTs (beta interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, and alemtuzumab) were matched to reduce treatment selection bias using propensity score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (hazard ratio [HR] = 0.50; 95% CI = 0.31-0.81; p = 0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time trend over 10 years was higher in patients treated with other DMTs than in AHSCT-treated patients (+0.157 EDSS points per year compared with -0.013 EDSS points per year; interaction p < 0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant vs 4.6% of patients treated by other DMTs (p < 0.001). DISCUSSION: The use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared with standard immunotherapy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to CDP compared with other DMTs.

CNS inflammatory demyelinating events after COVID-19 vaccines: A case series and systematic review.

Background: Vaccinations provided the most effective tool to fight the SARS-CoV-2 pandemic. It is now well established that COVID-19 vaccines are safe for the general population; however, some cases of rare adverse events following immunization have been described, including CNS Inflammatory Demyelinating Events (CIDEs). Although observational studies are showing that these events are rare and vaccines' benefits highly outweigh the risks, collecting and characterizing post-COVID-19 vaccine CIDEs might be relevant to single out potential risk factors and suggest possible underlying mechanisms. Methods: Here we describe six CIDEs, including two acute transverse myelitis (ATM), three multiple sclerosis (MS), and one neuromyelitis optica spectrum disorder (NMOSD), occurring between 8 and 35 days from a COVID-19 vaccine. Moreover, we performed a systematic literature search of post-COVID-19 vaccines CIDEs, including ATM, ADEM, MS, and NMOSD/MOGAD, published worldwide between December 2020 and December 2021, during 1 year of the vaccination campaign. Clinical/MRI and CSF/serum characteristics were extracted from reviewed studies and pooled-analyzed. Results: Forty-nine studies were included in the systematic review, reporting a total amount of 85 CIDEs. Considering our additional six cases, 91 CIDEs were summarized, including 24 ATM, 11 ADEM, 47 MS, and nine NMOSD/MOGAD. Overall, CIDEs occurred after both mRNA (n = 46), adenoviral-vectored (n = 37), and inactivated vaccines (n = 8). Adenoviral-vectored vaccines accounted for the majority of ADEM (55%) and NMOSD/MOGAD (56%), while mRNA vaccines were more frequent in MS new diagnoses (87%) and relapses (56%). Age was heterogeneous (19-88) and the female sex was prevalent. Time from vaccine to symptoms onset was notably variable: ADEM and NMOSD/MOGAD had a longer median time of onset (12.5 and 10 days) compared to ATM and MS (6 and 7 days) and further timing differences were observed between events following different vaccine types, with ATM and MS after mRNA-vaccines occurring earlier than those following adenoviral-vectored ones. Conclusion: Both the prevalence of vaccine types for certain CIDEs and the heterogeneity in time of onset suggest that different mechanisms-with distinct dynamic/kinetic-might underly these events. While epidemiological studies have assessed the safety of COVID-19 vaccines, descriptions and pooled analyses of sporadic cases may still be valuable to gain insights into CIDE's pathophysiology.

Eating Hubs in Multiple Sclerosis: Exploring the Relationship Between Mediterranean Diet and Disability Status in Italy.

Background: Multiple Sclerosis (MS) is a complex disease in which multiple factors contribute to disability accrual. Mediterranean Diet (MeDi) has shown beneficial effects across neurodegenerative diseases. We hypothesize that specific food habits, rather than global adherence to MeDi, might impact on MS. We aimed to (i) evaluate differences in adherence to MeDi between people living with MS (PwMS) and healthy controls (HC); (ii) characterize eating patterns in PwMS and HC, identifying the most influential MeDi items for each group by the use of network analysis; (iii) explore the relationship between patients' eating habits and disability. Materials and Methods: In this cross-sectional study, we consecutively recruited 424 PwMS and 165 matched HC. Data were obtained through the administration of self-reported questionnaires. Expanded Disability Status Scale (EDSS) and Fatigue Severity Scale (FSS) were evaluated in the MS population. We performed between-groups comparisons via unpaired two-sample t-test and X2 test as appropriate. We calculated food networks in both MS cases and HC using and tested the association between hub nodes and disability. Finally, we conducted a post-hoc analysis, investigating the relationship between food items, lifestyle factors (smoking, exercise) and clinical outcomes. Results: Most participants adhered sufficiently to MeDi. Exploring each group separately, fruit, vegetables, cereal, and fish were identified as hubs in PwMS, while meat and alcohol were identified as hubs in HC. Hubs were all inter-correlated, indicating that eating habits of PwMS include a large intake of all the foods identified as hubs. EDSS was predicted by the intake of vegetables (beta = -0.36, p < 0.03) and fish (beta = -0.34, p < 0.02). The model including smoking pack/year, International Physical Activity Questionnaire (IPAQ) score and intake of "negative foods" predicted 6% of the variance in EDSS (p < 0.001), while the model including smoking pack/year and IPAQ score predicted 4% of the variance in FSS (p < 0.001). Conclusions: We identified a sufficient adherence to MeDi in our population. PwMS showed overall a healthier dietary pattern than HC. Vegetables and fish intake were associated with disability outcomes. Future longitudinal studies applying integrated approaches are needed to understand lifestyle added value to the use of standard pharmacological therapies.

Case Report: Multiple Sclerosis Relapses After Vaccination Against SARS-CoV2: A Series of Clinical Cases.

Objective: To describe a temporal association between COVID-19 vaccine administration and multiple sclerosis (MS) relapses. Methods: This case series study was collected in four MS Centres in Central Italy, using data from 16 MS patients who received COVID-19 vaccination and presented both clinically and radiologically confirmed relapses between March and June 2021. We collected patients' relevant medical history, including demographics, MS clinical course, disease-modifying treatment (DMT) received (if applicable), and data from MRI scans obtained after the COVID-19 vaccination. Results: Three out of 16 patients received a diagnosis of MS with a first episode occurring after COVID-19 vaccination; 13 had already a diagnosis of MS and, among them, 9 were on treatment with DMTs. Ten patients received BNT162b2/Pfizer-BioNTech, 2 patients mRNA-1273/Moderna, and 4 patients ChAdOx1 nCoV-19/AstraZeneca. All MS relapses occurred from 3 days to 3 weeks after receiving the first dose of the COVID-19 vaccination or the booster. All patients had evidence of radiological activity on MRI. Discussion: Clinical and radiological findings in these cohort of MS patients confirmed disease re/activation and suggested a temporal association between disease activity and COVID-19 vaccination. The nature of this temporal association, whether causative or incidental, remains to be established.