Bariatric surgery and dimethyl fumarate-induced lymphopenia in patients with multiple sclerosis.

INTRODUCTION: Lymphopenia is a known side effect of dimethyl fumarate (DMF), a disease-modifying therapy (DMT) for patients with multiple sclerosis (pwMS). A body mass index ≥ 30 kg/m2 has been identified as a protective factor; however, no data are available on lymphopenia in pwMS undergoing to weight loss due to bariatric surgery. METHODS: We described two pwMS with history of bariatric surgery who started DMF as DMT. RESULTS: The two pwMS experienced persistent lymphopenia during DMF-treatment, which was resolved after its discontinuation. CONCLUSIONS: Several mechanisms might modify DMF pharmacokinetic profiles after bariatric surgery and its bioavailability. Absolute lymphocyte count should be monitored in pwMS treated with DMF and history of bariatric surgery and weight loss.

Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs.

BACKGROUND: Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax. OBJECTIVES: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ). METHODS: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use. RESULTS: Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed. CONCLUSION: Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.

Efficacy and safety of tixagevimab-cilgavimab (Evusheld®) in people with Multiple Sclerosis on Ocrelizumab: preliminary evidence.

BACKGROUND: Evusheld (EVS) was authorized by FDA and EMA as pre-exposure prophylaxis (PrEP) in people at high risk of severe Covid-19 outcomes, including people with Multiple Sclerosis (pwMS) on B-cell depleting (BCD) therapies-such as Ocrelizumab (OCR). In this population, no data on possible adverse drug reactions (ADRs) to EVS, B-lymphocytes (CD20 +) counts pre- and post-EVS injection, and comparison of percentage increase of IgG antibodies directed against SARS-CoV-2 trimeric spike protein (anti-TSP IgG) post-EVS and Covid-19 vaccine was available. The aim of this study was to better characterize the efficacy and safety profile of EVS in pwMS on BCD agents. METHODS: 17 pwMS on OCR agreed to receive EVS as PrEP for Covid-19. Sera samples were collected before the first dose of Covid-19 vaccine (T0), 4 weeks after the second dose (T1), 4 weeks after third dose (T2), immediately before (T3) and 4 weeks after (T4) EVS. RESULTS: Covid-19 vaccine ADRs were mild-to-moderate, whereas no ADRs were reported after EVS injection. A significant increase of anti-TSP IgG was found only at T0-T1 (Z = -3.059, p = .002) and T3-T4 (Z = -3.621, p < .001) time-points. The median percentage increase between T3-T4 was significantly higher with respect to the T0-T1(Z = -3.296, p = .001) and T1-T2 (Z = -3.059, p = .002) time-points. CONCLUSIONS: These results further support EVS safety and efficacy in boosting anti-TSP IgG titers in pwMS on OCR, with a statistically greater increase than that observed after completion of a full Covid-19 vaccine cycle, plus a booster dose.

Six-month humoral response to BNT162b2 mRNA COVID-19 vaccine in people with multiple sclerosis treated with natalizumab.

BACKGROUND: Few studies investigated the immune response to SARS-CoV-2 vaccine in patients with multiple sclerosis (pwMS) treated with natalizumab (NTZ) and found a short-term efficient humoral response; however, there are no studies assessing the levels of SARS-CoV-2 IgG antibodies in pwMS treated with NTZ over time. METHODS: Humoral immune response to BNT162b2 mRNA COVID-19 vaccine was assessed in a group of 26 pwMS on NTZ up to 6 months after a full COVID-19 vaccination cycle and compared it with 43 age- and sex-matched group of HC. Serum samples were collected before the first dose (T0), and 4 weeks (T1) and 6 months (T2) after the first dose of BNT162b2 mRNA COVID-19 vaccine. The LIAISON® SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) was employed for the detection of IgG antibodies to SARS-CoV-2 spike protein (cutoff for positive IgG antibodies: 33.8 BAU/mL). RESULTS: At T1 and T2, both groups showed an efficient humoral response to BNT162b2 mRNA COVID-19 vaccine. A significant reduction of IgG antibodies to SARS-CoV-2 spike protein was detected at T2 both in pwMS and in HC, but SARS-CoV-2 IgG antibodies were still above the cutoff limit in all participants. CONCLUSIONS: pwMS on NTZ develop and maintain a long-term humoral response after a full COVID-19 vaccination cycle comparable to their healthy peers, and these findings are relevant for clinicians called to counsel about COVID-19 mRNA vaccine timing and booster doses in pwMS treated with NTZ.

Regional changes in thalamic shape and volume are related to cognitive performance in multiple sclerosis.

BACKGROUND: The relationship between cognitive performance and regional thalamic atrophy in multiple sclerosis (MS) has been investigated in recent studies. OBJECTIVE AND METHODS: To further assess this relationship, 118 relapsing-remitting MS patients and 52 healthy controls underwent a neuropsychological assessment and a 3T-MRI (3-Tesla magnetic resonance imaging). Cognitive performances were correlated with thalamic shape changes by using Vertex Analysis. RESULTS: Information processing speed performance correlated with atrophy of frontal/motor-connected thalamic sub-regions. Inhibitory control performance correlated with atrophy of all thalamic sub-regions. Global cognitive status correlated with atrophy of frontal/temporal-connected sub-regions. CONCLUSIONS: These findings support the hypothesis that, within the thalamus, the damage of the anterior regions is most relevant for cognitive dysfunction.

Oligoclonal IgM bands in the cerebrospinal fluid of patients with relapsing MS to inform long-term MS disability.

BACKGROUND: Prognostic markers are needed to guide multiple sclerosis (MS) management in the context of large availability of disease-modifying drugs (DMDs). OBJECTIVE: To investigate the role of cerebrospinal fluid (CSF) markers to inform long-term MS outcomes. METHODS: Demographic features, IgM index, oligoclonal IgM bands (OCMB), lipid-specific OCMB, CSF neurofilament light chain protein levels, expanded disability status scale (EDSS), relapses and DMD use over the study period and peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIPL) thicknesses in non-optic neuritis eyes (end of follow-up) were collected from relapsing MS (RMS) patients with CSF obtained ⩽2 years after MS onset prospectively followed at the Hospital Clinic of Barcelona. We assessed associations between CSF markers and MS outcomes using multivariable models. RESULTS: A total of 89 patients (71 females; median 32.9 years of age) followed over a median of 9.6 years were included. OCMB were associated with a 33% increase in the annualized relapse rate (ARR; p = 0.06), higher odds for high-efficacy DMDs use (OR = 4.8; 95% CI = (1.5, 16.1)), thinner pRNFL (ß = -4.4; 95% CI = (-8.6, -0.2)) and GCIPL (ß = -2.9; 95% CI = (-5.9, +0.05)), and higher rates to EDSS ⩾ 3.0 (HR = 4.4; 95% CI = (1.6, 11.8)) and EDSS ⩾ 4.0 (HR = 5.4; 95% CI = (1.1, 27.1)). No overall associations were found for other CSF markers. CONCLUSION: The presence of OCMB was associated with unfavorable long-term outcomes. OCMB should be determined in RMS to inform long-term prognosis.

Preliminary evidence of blunted humoral response to SARS-CoV-2 mRNA vaccine in multiple sclerosis patients treated with ocrelizumab.

OBJECTIVES: Several concerns regard the immunogenicity of SARS-CoV-2 vaccines in people with multiple sclerosis (pwMS), since the majority of them is treated with immunomodulating/immunosuppressive disease modifying therapies. Here we report the first data on the humoral response to mRNA SARS-CoV-2 vaccine in a case series of 4 pwMS treated with ocrelizumab (OCR) as compared to a group of healthy subjects (HS). METHODS: We collected serum samples at 0, 14, 21 days after the first dose and 7 days after the second dose of BNT162b2-mRNA-Covid-19 vaccine from 55 health-care workers and 4 relapsing pwMS on OCR, with no history of Covid-19 infection. Sera were tested using the LIAISON®SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgGtiters were expressed in Binding Antibody Units (BAU), an international standard unit. RESULTS: At baseline all subjects were negative for anti-spike IgG. Seven days after the second dose of vaccine all HS mounted a significant humoral response (geometric mean 2010.4 BAU/mL C.I. 95% 1512.7-2672) while the 4 pwMS showed a lower response (range <4.81-175 BAU/mL). DISCUSSION: Humoral response to BNT162b2-mRNA-vaccine in pwMS treated with OCR was clearly blunted. Further data are urgently needed to confirm and expand these preliminary results and to develop strategies to optimize the response to SARSCoV-2 vaccines in pwMS on OCR.

Two-year macular volume assessment in multiple sclerosis patients treated with fingolimod.

BACKGROUND: Fingolimod (FNG) is associated with the development of symptomatic macular edema (ME) in a small subset of multiple sclerosis (MS) patients. By using spectral domain optical coherence tomography (SD-OCT), an increase in the total macular volume (TMV) was rarely detected during the first months of treatment. OBJECTIVES: The objective of this study is to assess whether FNG treatment leads to long-term macular changes in a real-life setting. METHODS: Sixty RRMS patients starting FNG, according to therapeutic indication, were enrolled at three Italian MS centers and followed for 2 years. RESULTS: The mean TMV did not change between baseline and the follow-up. No patients experienced visual acuity drop during the follow-up. CONCLUSIONS: Initiation of FNG in MS is associated with a modest, not significant, increase in macular volume followed by no further significant changes over 2 years, highlighting the good safety profile of such treatment in MS.

Fatigue in multiple sclerosis: The contribution of resting-state functional connectivity reorganization.

OBJECTIVES: To investigate resting-state functional connectivity (RS-FC) of the default-mode network (DMN) and of sensorimotor network (SMN) network in relapsing remitting (RR) multiple sclerosis (MS) patients with fatigue (F) and without fatigue(NF). METHODS: In all, 59 RRMS patients and 29 healthy controls (HC) underwent magnetic resonance imaging (MRI) protocol including resting-state fMRI (RS-fMRI). Functional connectivity of the DMN and SMN was evaluated by independent component analysis (ICA). A linear regression analysis was performed to explore whether fatigue was mainly driven by changes observed in the DMN or in the SMN. Regional gray matter atrophy was assessed by voxel-based morphometry (VBM). RESULTS: Compared to HC, F-MS patients showed a stronger RS-FC in the posterior cingulate cortex (PCC) and a reduced RS-FC in the anterior cingulated cortex (ACC) of the DMN. F-MS patients, compared to NF-MS patients, revealed (1) an increased RS-FC in the PCC and a reduced RS-FC in the ACC of the DMN and (2) an increased RS-FC in the primary motor cortex and in the supplementary motor cortex of the SMN. The regression analysis suggested that fatigue is mainly driven by RS-FC changes of the DMN. CONCLUSIONS: Fatigue in RRMS is mainly associated to a functional rearrangement of non-motor RS networks.

Report on Non-fatal events cardio-cerebro-vascular to ten years in a Southern Italy cohort.

BACKGROUND: Data relating to non-fatal cardiovascular events are poor but these data are essential to organize targeted interventions on the territory and to understand their effectiveness. METHODS: We calculated the rates of morbidity from cardiovascular events covering the period 1998/99-2008/09, in a cohort of 1200 persons (600 men and 600 women) aged 25 to 74 years. Data were standardized using the European standard population. RESULTS: The incidence of events to ten years of non-fatal myocardial infarc.ion was 2.2% in men and of 1.8% in women. PCI interventions to ten year have been 3.3% in men and 3.4% in women, the interventions of aorto-coronary bypass have been 2.4% and 0.5% for men and women respectively. While all major cardiovascular events have been more frequent in men, in women there was a higher incidence of stroke (1.6% vs 0.9%). CONCLUSION: Although by comparison with other European countries Italy is among the countries considered at low-risk of coronary heart disease, in Campania cardiovascular diseases reach higher rates than the rest of the country. Our results are in keeping with the literature data and confirm that cardiovascular diseases are a major public health problem. Local analysis are useful in providing additional information for planning prevention interventions targeted to its own territory.

Adding the Optic Nerve in Multiple Sclerosis Diagnostic Criteria: A Longitudinal, Prospective, Multicenter Study

BACKGROUND AND OBJECTIVES: The optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort. METHODS: MAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the fifth area of the CNS. A risk assessment analysis and the performance of the different DIS criteria were analyzed using the diagnosis of MS according to the 2017 McDonald criteria as the primary outcome and new T2 lesions and/or a second relapse as the secondary outcome. RESULTS: We included 157 patients with CIS from 5 MAGNIMS centers; 60/157 (38.2%) patients presented with optic neuritis. Optic nerve involvement on ON-MRI was found in 40.2% patients at study entry and in 72.5% of those with optic neuritis.At follow-up (mean 27.9 months, SD 14.5), 111/157 patients (70.7%) were diagnosed with MS according to the 2017 McDonald criteria. Fulfilling either 2017 DIS or any modified DIS criteria conferred a similar high risk for reaching primary and secondary outcomes. The modified DIS criteria had higher sensitivity (92.5% [with ON-MRI] vs 88.2%), but slightly lower specificity (80.0% [with GCIPL IEA ≥4 µm] vs 82.2%), with overall similar accuracy (86.6% [with ON-MRI] vs 86.5%) than 2017 DIS criteria. Consistent results were found for secondary outcomes. DISCUSSION: In patients with CIS, the presence of an optic nerve lesion defined by MRI, OCT, or VEP is frequently detected, especially when presenting with optic neuritis. Our study supports the addition of the optic nerve as a fifth topography to fulfill DIS criteria.

The safety of statins in children.

UNLABELLED: Current American Academy of Pediatrics Guidelines recommended that statins should be considered as a first-line agent in children as early as 8 years of age. The aim of our work is to assess the safety of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in children with hypercholesterolaemia. CONCLUSION: Controlled studies in children show that statin monotherapy is efficacious, well tolerated and safe in the short-time. Unfortunately, these studies have relatively short-term follow-up periods, and therefore, long-term safety remains unclear.

[Ten year cardio-cerebro-vascular mortality and morbidity in a Southern Italy cohort: the VIP Project data]. / Mortalità e morbilità cardio-cerebro-vascolare a dieci anni (1998/99 - 2008/09) in una coorte di popolazione adulta dell'Italia meridionale: i dati del Progetto VIP.

RATIONALE: In Italy the mortality data were obtained almost exclusively from the data RENCAM (Name Causes of Death Register), while there are few prospective surveys. In order to assess whether there are particular epidemiological conditions in the geographical area of Mercato S. Severino, in Southern Italy, we have studied, and reassessed at ten years (1998/99 - 2008/09), a cohort of adult general population in a project of cardiovascular epidemiology and prevention. MATERIALS AND METHODS: We calculated the rates of mortality and morbidity from cardiovascular events covering the period 1998/99 - 2008/09, in a cohort of 1200 persons (600 men and 600 women) aged 25 to 74 years. Data were standardized using the European standard population. RESULTS: Mortality from cardiovascular causes was 46.5% in men and 48.7% in women; it was mainly concentrated in the age group 65-74 years where it occurred on 62.9% of deaths in men and 66.7% in women. Regarding morbidity, the incidence of events to ten years of non-fatal myocardial infarction was 2.2% in men and of 1.8% in women. PTCA interventions to ten year have been 3.3% in men and 3.4% in women, the interventions of aorto-coronary bypass have been 2.4% and 0.5% for men and women respectively. While all major cardiovascular events have been more frequent in men, in women there was a higher incidence of stroke (1.6% vs 0.9%). CONCLUSIONS: Although by comparison with other European countries Italy is among the countries considered at low-risk of coronary heart disease, in Campania cardiovascular diseases reach higher rates than the rest of the country. Our results are in line with the literature data and confirm that cardiovascular diseases are a major public health problem. Local analysis to propose means to provide useful information for planning prevention interventions targeted to their own territory.

Quality of care provided by Multiple Sclerosis Centers during Covid-19 pandemic: Results of an Italian multicenter patient-centered survey.

BACKGROUND: Covid-19 pandemic impacted on management of people with Multiple Sclerosis (pwMS). Level of satisfaction of pwMS regarding the care received by the staff of Multiple Sclerosis Centers (MSCs) during the pandemic was not fully investigated. In a large patient-centered multicenter study, the therapeutic adherence and quality of care of MSCs was assessed. METHODS: In April-May 2021, an online survey was widespread by 16 Italian MSCs. Frequencies, percentages and/or means and standard deviations were calculated to describe the sample. ANOVAs were performed to evaluate the effect of sociodemographic and clinical variables on overall pwMS' rating of MSC assistance. RESULTS: 1670 pwMS completed the survey (67.3% women). During the pandemic, 88% did not change their disease modifying therapy schedule, and 89.1% reached their MSCs with no or little difficulties. Even if only 1.3% of participants underwent a tele-health follow-up visit with their MSC staff, the 80.1% believed that tele-health services should be improved regardless of pandemic. 92% of participants were satisfied of how their MSC took charge of their needs; ANOVAs revealed an effect of disease duration on pwMS' level of satisfaction on MSCs management during the pandemic. CONCLUSIONS: The results revealed an efficient MSCs response to Covid-19 pandemic and provided the basis for the implementing of tele-health services that would further improve the taking charge of patients, particularly those with longer disease, higher disability, and/or living far from their MSC.

[Chronic kidney disease prevalence and trends (1998-2008) in an area of southern Italy. The data of the VIP project]. / Prevalenza e trend (1998-2008) dell'insufficienza renale cronica in un'area dell'Italia meridionale: i dati del progetto VIP.

Chronic kidney disease (CKD) is a common disorder whose prevalence is increasing worldwide. In Italy the prevalence of CKD, especially the early stages, is still not exactly known. Our study examines the prevalence and trends in ten years (1200 subjects in 1998-1999 and 1200 subjects in 2008-2009) of the estimated glomerular filtration rate (eGFR) in a population of southern Italy. We analyzed, within the VIP project, the prevalence of CKD (eGFR <60) in our area and its relationship to diabetes and hypertension as well as the trend between the years 1998-1999 and 2008-2009. The estimate of the GFR was obtained with the Cockcroft-Gault formula corrected for body surface area. The prevalence of CKD, stratified by the population of Campania, was about 5.9% in males and 3.9% in females in the years 1998-1999; ten years later (2008-2009) it had increased to 6.2% in males and 4.5% in females. The differences between males and females and between the two decades are not statistically significant although the trend shows a clear increase in subjects affected by CKD among both sexes. Among the male population the prevalence of CKD in persons with hypertension or diabetes, in those with both diseases, and in those free from these diseases was 11.2%, 12%, 13.8% and 6.3% (p=0.018), respectively. The same groups among females showed a CKD prevalence of 8%, 9.2%, 9.7% and 4.4%, respectively (p=0.042). Our work provides a picture of the prevalence of CKD in an area of southern Italy. It highlights the increase in CKD and calls upon a greater use of renal function tests in clinical practice, so that individuals at increased risk of developing cardiovascular complications may be detected as early as possible.

The psychological impact of Covid-19 pandemic on people with Multiple Sclerosis: A meta-analysis.

BACKGROUND: Covid-19 pandemic caused relevant psychological consequences in the general population. Since people with Multiple Sclerosis (pwMS) are usually at higher risk of psychological distress than age-matched healthy controls (HC), a meta-analytic study was conducted, aimed at evaluating i) differences between pwMS and HC in the psychological variables during the pandemic, ii) differences in the levels of anxiety, depression, stress, sleep disturbances and quality of life before and during the Covid-19 pandemic in pwMS. METHODS: The literature search on three electronic databases yielded 196 studies (113 after the duplicates removal). Seven studies compared psychological variables between pwMS and HC during the pandemic, while seven studies evaluated the pre- vs during the pandemic differences in pwMS. The following outcomes were selected: depression, anxiety, physical QoL, mental QoL, stress, sleep quality/disturbances. Mean weighted effect sizes (ES) were calculated using Hedges'g, via Prometa3 software. RESULTS: During the pandemic, pwMS showed higher levels of depression (g = 0.51, p=.001), anxiety (g = 0.41, p=.032), and stress (g = 0.51, p=.016) compared to HC. The comparison on psychological outcomes before and during the pandemic in pwMS revealed no significant increase during the pandemic on levels of anxiety (g = 0.08, p=.380), depression (g = 0.02, p=.772), mental QoL (g= -0.14, p=.060), physical QoL (g = 0.00, p=.986), whereas sleep quality deteriorated during the pandemic (g = 0.52, p<.001). CONCLUSIONS: In agreement with pre-pandemic literature, pwMS showed higher levels of psychological distress than HC also during the Covid-19 pandemic. Contrariwise, longitudinal studies revealed that, in pwMS, the only psychological-associated variable that worsened significantly was the sleep quality, but this outcome was evaluated only in two studies. Future studies will have to assess/evaluate the long-term psychological consequences of the pandemic on pwMS.

Humoral response and safety of the third booster dose of BNT162b2 mRNA COVID-19 vaccine in patients with multiple sclerosis treated with ocrelizumab or fingolimod.

BACKGROUND: The assessment of the safety and the humoral response to a third booster dose of the BNT162b2 mRNA COVID-19 vaccine is relevant in patients with Multiple Sclerosis (pwMS) treated with Ocrelizumab (OCR) or Fingolimod (FNG). METHODS: Serum samples were collected from Healthy controls (HCs) and pwMS treated with OCR or FNG at the following time-points: before the first of two vaccine doses (T0); 8 (T1), 16 (T2), 24 (T3) weeks after the first dose; within 8 weeks before (T0b) and after (T1b) the booster dose. IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) were quantified and expressed as binding antibody units (BAU)/mL. RESULTS: 40 HCs, 28 pwMS on OCR and 19 on FNG were included. At T0b 12 (42.9%) pwMS on OCR and 6 (31.6%) on FNG were still positive while, at T1b 16 (57.14%) pwMS on OCR and 16 (84.2%) on FNG, passed the threshold of positivity. The increase of Anti-TSP IgG levels at T1b was higher for: (i) HCs with respect to OCR (p < 0.001) and FNG (p = 0.032) groups; (ii) pwMS on FNG compared with pwMS on OCR (p < 0.001). No socio-demographic, clinical or laboratory variables were able to predict the anti-TSP IgG increase between T0b and T1b. Neither clinical relapses nor severe adverse events were reported in pwMS after each dose of vaccine. CONCLUSIONS: The third booster dose of BNT162b2 mRNA vaccine to OCR- and FNG-treated pwMS revives the humoral response, independently of any clinical variable, and manifests a good safety and tolerability profile.

Impact of post-contrast MRI in the definition of active multiple sclerosis.

BACKGROUND: For multiple sclerosis (MS) phenotypes classification, the presence of "disease activity" can be defined by clinical relapses and/or by magnetic resonance imaging (MRI) through gadolinium-enhancing (Gd+) lesions or new/enlarged T2 lesions. Recent MRI and pathology findings have demonstrated Gd deposition in the brain, suggesting to avoid Gd administration when dispensable. In this scenario, we aimed to evaluate the contribution of post-contrast MRIs to the definition of "active" MS phenotype. METHODS: We retrospectively selected 84 "active" relapsing-remitting MS (RRMS) patients according to Lublin 2013, calculating both the number of Gd+ lesions not detectable as new/unequivocally enlarged on T2 images and the proportion of patients who would be still correctly classified as "active" without Gd administration. RESULTS: 13 out of 164 (7.9%) Gd+ lesions did not correspond to a new/enlarged T2 lesion. Gd administration did not modify the classification of MS as "active" in 83 out of 84 subjects (98.8%). CONCLUSION: The contribution of Gd+ lesions to the correct classification of RRMS patients as "active" is marginal, thus limiting the need of routine Gd administration for this scope. Further studies are warranted to support these conclusions.

Six-month humoral response to mRNA SARS-CoV-2 vaccination in patients with multiple sclerosis treated with ocrelizumab and fingolimod.

INTRODUCTION: Real-world clinical data suggest an attenuated short-term humoral response to SARS-CoV-2 vaccines in patients with multiple sclerosis (pwMS) receiving high efficacy (HE) disease modifying therapies (DMTs) such as Ocrelizumab (OCR) and Fingolimod (FNG). Long-term humoral response in pwMS treated with these HE-DMTs has been poorly investigated. The aim of our study was to explore: i) the humoral response up to six months after a full cycle of the BNT162b2 mRNA Covid-19 vaccine in pwMS treated with OCR and FNG and to compare it to age- and sex-matched healthy controls (HCs); ii) the relationship between humoral response and clinical and immunological characteristics of the studied population. METHODS: Serum samples were collected from HCs and pwMS treated with OCR or FNG at the following time points: before BNT162b2 mRNA Covid-19 vaccine (T0), and 4 (T1), 8 (T2), 16 (T3) and 24 (T4) weeks after the first dose. Sera were stored at -20 °C and tested for the quantitative detection of IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) expressed in binding antibody units (BAU). At T1 neutralizing antibodies (NAbs) titres were assessed. The relationship between Anti-TSP IgG at each time-point and clinical and laboratoristic analyses were analysed by the Spearman correlation coefficient. RESULTS: 47 HCs and 50 pwMS (28 on OCR and 22 on FNG) were included in the study. All HCs mounted a positive humoral response at T1 and preserved it up to six months. At T1 only 57.1% pwMS on OCR (p < 0.001 compared with HCs) and 40.9% on FNG (p < 0.001) had a positive humoral response at T1, with only 39.3% and 27.3% maintaining a positive response at sixth months (T4), respectively. A strong positive correlation was observed between Nabs titres and Anti-TSP IgG at T1 (rho 0.87, p < 0.0001) with NAbs titres significantly higher in HCs compared with pwMS on OCR and FNG (p<0.0001). We also found a strong positive correlation between time-window since last OCR infusion and anti-TSP IgG titres at all time-points (T1 rho=0.58, p = 0.001; T2 rho=0.59, p = 0.001; T3 rho=0.53, p = 0.004; T4 rho=0.47, p = 0.01). In the FNG group we observed a significant correlation between the humoral response measured from T1 to T4 and: i) treatment duration (T1: rho -0.65, p = 0.001; T2: rho -0.8 p< 0.001; T3: rho -0.72, p=<0.001; T4: rho -0.67, p<0.001), ii) disease duration (T1: rho -0.5, p = 0.017; T2: rho -0.6, p = 0.003; T3: rho -0.58, p = 0.005; T4: rho -0.57, p = 0.006), and iii) baseline total lymphocyte count (T1: rho 0.37, p = 0.08; T2: rho 0.45, p = 0.03; T3: rho 0.43, p = 0.04; T4: rho 0.45, p = 0.03). CONCLUSIONS: Our long-term data show a weakened and short-lasting humoral response to SARS-CoV-2 mRNA vaccine in pwMS treated with OCR and FNG when compared with HCs. MS neurologists should take into account the time elapsed since the last infusion for pwMS on OCR, and the lymphocyte count as well as the disease and treatment duration for those on FNG when called to counsel such pwMS regarding the vaccination with the SARS-CoV-2 mRNA vaccine.

The Burden of Cardio-Cerebrovascular Risk Factors: Differences Between Individual Risk and Population Risk.

INTRODUCTION: Cardio-cerebrovascular (CCV) disease contributes significantly to the global burden of disease, with dramatic consequences in terms of mortality and general health. Mitigate CCV risk factors is the key to reduce individual and population risk of CCV events. Evidence-based medicine and epidemiological investigations of risk factors are essential to optimize actions. AIM: To contribute to the knowledge of the burden of risk factors in determining CCV events in the individual patient and in the community. METHODS: Clinical data and risk factors were collected through a longitudinal survey (1999) as part of a larger epidemiology and cardiovascular prevention project, namely the "VIP (Valle dell'Irno Prevention) Project". We assessed the incidence of major cardiovascular events (MACE) and for each risk factor we calculated: prevalence, absolute risk, odds ratio (OR), additional risk (AR) = risk of exposed to the risk factor - risk of non-exposed, population attributable risk (PAR) = additional risk * prevalence, population attributable risk fraction (PAF) = PAR/total incidence of the disease. RESULTS: Comparing the MACE group with the non-MACE group, a statistically significant difference was found for the following: glomerular filtration rate (GFR), glucose and systolic blood pressure (SBP), BMI, diastolic blood pressure (DBP), cholesterol, triglycerides, creatinine and uric acid. GFR, glucose and SBP showed the highest OR. Age, creatinine, glycemia, SBP and uric acid were independent predictor of MACE. When calculating the PAF, the CCV risk factors with the greatest impact on MACE were: SBP (29.6%), triglyceridemia (19.4%) and metabolic syndrome (18.3%). CONCLUSION: The burden of risk factors on MACE changes substantially according to whether it is calculated in the single patient or in the population. It is crucial for physicians to take these differences into account when applying their own intervention to reduce CCV events.