Background

Cardiovascular (CV) risk factors have been associated with changes in clinical and MRI outcomes in patients with multiple sclerosis (MS). However, previous studies have not set an age-limit, while older patients may be affected by cerebral small vessel disease-related damage in addition to MS.

Objectives

To investigate the impact of cardiovascular risk factors on brain atrophy in patients with multiple sclerosis under the age of 50.

Methods

One-hundred and twenty-four (79 relapsing-remitting, 45 progressive) MS patients (74 females, age 36 ± 8, range 18 – 50), and 95 age- and sex-matched healthy controls (HC) (47 females, age 35 ± 8, range 18 – 50) underwent brain 3T MRI with pulse sequences for assessing lesions and atrophy, and complete neurological examination. Traditional CV risk factors were assessed: having smoked ≥5 pack-years (py), and presence of hypertension, dyslipidemia, diabetes/prediabetes. More stringent cut-offs were also assessed: having smoked ≥10py, and hypertension, dyslipidemia or diabetes under treatment. Linear models adjusted for age, sex, disease duration, phenotype and treatment were used to determine the impact of CV risk factors on MRI variables.

Results

Nineteen HC and 48 MS patients had one traditional CV risk factor, 4 HC and 15 MS patients had more than one. Ten HC and 30 MS patients had one stringent CV risk factor, 3 and 8 had more than one. Most of our subjects had a smoking history as a CV risk factor (16 HC and 42 MS patients among traditional, 8 HC and 23 MS patients among stringent). In MS patients, the presence of at least two traditional CV risk factors was associated with reduced normalized grey matter volume (NGMV) (p=0.01), white matter volume (NWMV) (p=0.03) and brain volume (NBV) (p=0.003), and not with T2-lesion volume (T2-LV) (p=0.27). Among traditional CV risk factors, only hypertension (n=8) was associated with MRI measures (NWMV and NBV). In MS patients, the presence of one stringent CV risk factor was associated with reduced NGMV (p=0.006), NWMV (p=0.003) and NBV (p<0.001), and higher T2-LV (p=0.03). In HC, no differences were observed according to either traditional or stringent risk factor presence.

Conclusions

The presence of CV risk factors is associated with brain atrophy in MS patients, even under age 50. CV risk factors seem to have synergistic effects, determining brain atrophy even for levels of exposure that may often be overlooked by clinicians, when present in combination.

Background

The advent of oral first-line disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has expanded considerably the therapeutic landscape. However, here is an important need to gather real-world evidence data regarding long-term treatment effectiveness and safety in comparison to the old first-line injectables DMTs.

Objectives

To compare old injectable and oral first line DMTs for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation in a cohort of RRMS patients extracted from the Italian MS Registry.

Methods

Multicentre, observational, retrospectively acquired and propensity-adjusted cohort study of RRMS-naïve patients in the Italian MS Register starting injective or oral first line DMTs between 1 January 2010 and 31 December 2017 to evaluate their impact on disability outcomes in patients. Enrolled patients were divided into two groups: injectable group (IG) and oral group (OG).

Results

From a cohort of 11,416 patients, 4,602 were enrolled (3,919 on IG and 683 on OG). IG had higher rate of women (67.3% vs 63.4%, p<.05) and a lower mean age (36.1±10.9 vs 38.9±11.8, p<.001). For the event time to first relapse, Cox models after PS adjustment revealed a lower risk for OG patients (HR 0.58 CI95% 0.47-0.70, p<0.001). About the risk of CDP, no differences were found in the two groups (HR 1.14 CI95% 0.88-1.48, p=0.306). About the risk of DMT discontinuation, OG patients showed lower risk (HR 0.70 CI95% 0.57-0.86 p=0.001) than IG patients.

Conclusions

Real-world data from the Italian MS registry suggest that first line oral DMTs are associated to lower risks of experiencing a new relapse and of therapy discontinuation in comparison to injectable DMTs.

Background

Polypharmacy adds many variables in the relapsing-remitting Multiple Sclerosis (RRMS) therapeutic algorithms. The choice of first Disease-Modifying Therapy (DMT) should also take into account the presence of concomitant medical illnesses and the use of other medications that can expose patients to adverse drug reactions, and drug-drug or drug-disease interactions.

Objectives

To examine the frequency of polypharmacy in a large cohort of patients at the time of RRMS diagnosis and to explore its effects on disease course after three years from the beginning of the first DMT assessed by the score no evidence of disease activity (NEDA-3).

Methods

We enrolled RRMS patients starting their first DMT between January 1^st, 2013 and December 31^st, 2015. According to the number of medicines prescribed (except DMTs) we divided patients in three groups: no-Poly-RRMS, minor-Poly-RRMS (from one to three medications) and major Poly-RRMS (>3 medications).

Results

392 RRMS patients were enrolled (mean age 41.1). Minor-Poly-RRMS were 61 (15.6%) and major-Poly-RRMS were 112 (28.6%). Minor and major-poly-RRMS were older (p=0.00) and with higher median Body Mass Index (BMI)(p=0.00) than no-poly-RRMS patients.

At multivariate regression analysis, higher age at onset was associated with minor and major-poly-RRMS (OR 1.050, CI 1.0-1-2, p=.015 and OR 1.063, CI 1.0-1.1, respectively). BMI was associated with major poly-RRMS (OR 1.186, CI 1.18-1.29, p=.000). Polypharmacy was not associated with disease activity after three years.

Conclusions

In our cohort of newly diagnosed RRMS, polypharmacy was associated with older age and higher BMI at the time of diagnosis. Polypharmacy represents an emerging challenge in medical management in the worldwide population, especially in the elderly.

Background

Cardiovascular comorbidities are one of the most leading causes of disability in the general population, and hypertension is one comorbid condi­tion that is prevalent and impactful among patients with Multiple Sclerosis (MS). Furthermore, sedentary behavior has been associated with putative outcomes of disability status in patients with MS.

Objectives

The aim of the study is the association between cardiovascular risk (measured with Framingham risk score (FRS)), sedentary behaviors (measured with Godin Leisure-Time Excercise Questionnaire (GLTEQ)) and disease activity in MS patients.

Methods

Patients with Relapsing Remitting MS (RRMS) consecutively admitted to the MS center of Catania from October 2019 to February 2020 were enrolled. According to the reason of access to the MS center, patients were divided in: active patients (patients with clinical relapses and/or radiological activity) and non-active patients (scheduled visit). The assessment included collection of demographical and clinical outcomes. To analyse any association between disease activity and FRS and GLTEQ a binary logistic regression model was built.

Results

432 patients were enrolled. Out of them, 334 (77.8%) were active and 98 (22.2%) were non active. Active patients were younger, with higher number of relapses in the year before enrolment and higher level of disability (p<.05 for all). About FRS, no differences were found between the two groups in low (54.3% vs 54.1), intermediate (34% vs 34.2%) and high risk (11% vs 11.7%) rates. About GLTEQ, no differences were found between the two groups in rates of full active (16% vs 19.5%), sufficiently active (53.2% vs 57.7%) and inactive (30.9% vs 22.8%) patients.

At logistic regression model, there was a correlation between a high GLTEQ value and disease activity (ExpB 2.462, IC 1.000-6.094, p = .049). No correlations were found with other clinical variables or with FRS.

Conclusions

Our study revealed that sedentary behaviors should be associated with higher level of disease activity. Cardiovascular comorbidities deserve attention in all MS cohort. Further studies are needed.

Background

Cardiovascular comorbidities are one of the most leading causes of disability in the general population, and hypertension is one comorbid condi­tion that is prevalent and impactful among patients with Multiple Sclerosis (MS). Furthermore, sedentary behavior has been associated with putative outcomes of disability status in patients with MS.

Objectives

The aim of the study is the association between cardiovascular risk (measured with Framingham risk score (FRS)), sedentary behaviors (measured with Godin Leisure-Time Excercise Questionnaire (GLTEQ)) and disease activity in MS patients.

Methods

Patients with Relapsing Remitting MS (RRMS) consecutively admitted to the MS center of Catania from October 2019 to February 2020 were enrolled. According to the reason of access to the MS center, patients were divided in: active patients (patients with clinical relapses and/or radiological activity) and non-active patients (scheduled visit). The assessment included collection of demographical and clinical outcomes. To analyse any association between disease activity and FRS and GLTEQ a binary logistic regression model was built.

Results

432 patients were enrolled. Out of them, 334 (77.8%) were active and 98 (22.2%) were non active. Active patients were younger, with higher number of relapses in the year before enrolment and higher level of disability (p<.05 for all). About FRS, no differences were found between the two groups in low (54.3% vs 54.1), intermediate (34% vs 34.2%) and high risk (11% vs 11.7%) rates. About GLTEQ, no differences were found between the two groups in rates of full active (16% vs 19.5%), sufficiently active (53.2% vs 57.7%) and inactive (30.9% vs 22.8%) patients.

At logistic regression model, there was a correlation between a high GLTEQ value and disease activity (ExpB 2.462, IC 1.000-6.094, p = .049). No correlations were found with other clinical variables or with FRS.

Conclusions

Our study revealed that sedentary behaviors should be associated with higher level of disease activity. Cardiovascular comorbidities deserve attention in all MS cohort. Further studies are needed.

Background

The subventricular zone (SVZ), a 2-mm layer alongside brain lateral ventricles, is the largest neural stem cells niche in adult humans. It is likely to exert a neuroprotective role on striatal neurons and its damage has been associated with cognitive decline after brain radiation. Multiple sclerosis (MS) can be considered as a disease-related model of SVZ injury, since periventricular lesions involve this region. In MS, cognitive dysfunction is common and information processing speed is affected from the earliest phases of the disease despite relatively low lesion volume (LV) and atrophy.

Objectives

In this study, we characterized SVZ damage in terms of focal lesions and microstructural alterations in MS and assessed its association with striatal atrophy and cognitive dysfunction, evaluated with the Symbol Digit Modalities Test (SDMT).

Methods

3.0 T brain MRI scans were acquired from 97 MS patients and 43 age- and sex-matched healthy controls (HC). After lesion refilling, normalized (N-) brain volumes and cortical thickness (CT) were obtained. According to anatomical references, SVZ mask was segmented on T1-weighted images in the Montreal Neurological Institute space and then registered on fractional anisotropy (FA) and mean diffusivity (MD) maps. Age- and sex-adjusted linear models, partial correlations, and stepwise multiple linear regressions were used to assess SVZ damage and to identify predictors of N-striatal volume and SDMT scores.

Results

In MS, mean SVZ percentage LV was 4.2%. Compared to HC, SVZ normal appearing (NA) tissue was characterized by increased MD (0.89 vs 0.86, p=0.04) and preserved FA values. N-striatal volume correlated with all measures of brain damage (p range: <0.0001-0.02, r absolute values range: 0.24-0.70), while SDMT correlated with SVZ damage (percentage LV, lesional FA , NA MD, p range:0.028-0.0028, r absolute values range: 0.33-0.36) and brain T2-weighted LV (p=0.0051, r=-0.37). N-brain volume (p<0.0001), white matter MD (p=0.0236), SVZ percentage LV (p=0.0052), and mean CT (p=0.0354) were independent predictors of N-striatal volume (R²=0.67). SVZ percentage LV was selected as the only predictor of SDMT performance (p=0.0018, R²=0.26).

Conclusions

SVZ damage is associated with striatal atrophy and cognitive dysfunction in MS. These results might provide a novel key lecture on cognitive impairment in this disease, suggesting a possible role of periventricular injury in MS cognition.