PAOLA Valentino (Italy)
catanzaro neurologyAuthor Of 4 Presentations
LONG-TERM DISABILITY PROGRESSION IN CHILDHOOD AND ADOLESCENT ONSET MULTIPLE SCLEROSIS PATIENTS
- Ermelinda De Meo (Italy)
Abstract
Background and Aims:
Early onset pediatric multiple sclerosis (MS) is extremely rare, occurring in 0.2-0.6% of all MS cases. The aim of this study is to describe and compare disease course and prognosis of early and late (ie, disease onset before and after age 11 years) onset pediatric MS.
Methods:
Prospectively collected clinical information from Italian MS Register from 1993 pediatric MS patients, of whom 172 with early onset, was analyzed. Cox proportional hazards regression models adjusted for sex and disease-modifying treatments (DMT) exposure were used to assess the risk of reaching confirmed Expanded Disability Status Scale (EDSS) scores of 3, 4, and 6 in early vs late onset pediatric MS, along with prognostic factors.
Results:
A greater proportion of males, isolated brainstem involvement, and longer time to first relapse was observed in early vs late onset pediatric MS patients. Compared to late onset, early onset pediatric MS patients took longer time from disease onset to convert to a secondary progressive phenotype and to reach all 3 disability milestones, thus reaching them at the same age. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease and DMT exposure were independent predictors for long-term disability in early onset pediatric MS patients.
Conclusions:
The different natural history of early vs late onset pediatric MS underscores the existence of specific pathophysiological mechanisms as well as a greater capability to counteract damage in early onset pediatric MS patients.
EXIT-STRATEGIES IN NATALIZUMAB RESPONDERS RRMS PATIENTS: AN ITALIAN COMPARISON AMONG OCRELIZUMAB, RETUXIMAB AND CLADRIBINE
- Emanuele D'Amico (Italy)
Abstract
Background and Aims:
The main aim of the study is to evaluate the efficacy and safety profile of Ocrelizumab (OCR), Rituximab (RTX), and Cladribine (CLA), employed as Natalizumab (NTZ) exit-strategies in Relapsing-Remitting Multiple Sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML).
Methods:
This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX and CLA from January 1st, 2019 to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and Magnetic Resonance Imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs).
Results:
Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX and 20 to CLA. Patients from the three groups did not shown differences for baseline characteristics, also after post-hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpB OCR 0.485, CI 95% 0.264-0.893, p=.020). This result was confirmed also for 12-months MRI activity (ExpB OCR 0.248 CI 95% 0.065-0.948, p=.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the three groups.
Conclusions:
Anti-CD20 drugs revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile
PROGRESSION INDEPENDENT OF RELAPSE ACTIVITY IN EARLY MULTIPLE SCLEROSIS PATIENTS
- Emilio Portaccio (Italy)
Abstract
Background and Aims:
Disability accrual in multiple sclerosis (MS) may occur as relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). We investigated the contribution of RAW and PIRA to confirmed disability accumulation (CDA) in patients with clinically isolated syndrome (CIS) and early relapsing-remitting (RR) MS.
Methods:
Relapsing-onset MS patients assessed within one year from onset and with follow-up >/= 5 years (n=5,340) were extracted from the Italian MS Registry. CDA was defined by an increase in Expanded Disability Status Scale (EDSS) score confirmed at 6 months, and classified per temporal association with relapses. Predictors of PIRA and RAW were assessed using multivariable Cox regression models.
Results:
PIRA occurred in 1472 (27.6%) and RAW in 240 (17.6%) patients. Predictors of PIRA were older age (HR=1.02;95%CI 1.02-1.03,p<0.001), RR course (HR=1.46;95%CI 1.30-1.64,p<0.001), longer disease duration (HR=1.49;95%CI 1.22-1.82,p<0.001), lower EDSS (HR=0.89;95%CI 0.85-0.93,p<0.001), lower number of relapses before the event (HR=0.93;95%CI 0.91-0.95,p<0.001). RAW was associated with younger age (HR=0.99;95%CI 0.98-0.99,p<0.001), RR course (HR=1.56; 95%CI 1.35-1.80,p<0.001), lower EDSS (HR=0.92;95%CI 0.87-0.97,p=0.002), higher number of relapses before the event (HR=1.07;95%CI 1.05-1.09,p<0.001). Longer exposure to disease modifying drugs (DMD) reduced the risk of both PIRA and RAW (p<0.001).
Conclusions:
in this early relapsing-onset MS cohort, PIRA was an important contributor to CDA. Our findings indicate that insidious progression appears even in the earliest phases of the disease, suggesting that inflammation and neurodegeneration can represent a single disease continuum. The analysis on progression independent of relapse and radiological activity is ongoing.
MICROSTRUCTURAL ALTERATIONS OF THE SPINOTHALAMIC TRACT AND NEUROPATHIC PAIN: A DIFFUSION TENSOR IMAGING STUDY IN RELAPSING REMITTING MULTIPLE SCLEROSIS
- Alessia Sarica (Italy)
Abstract
Background and Aims:
Neuropathic pain (NP) is frequently underestimated in Multiple Sclerosis (MS). The aim of this work is to evaluate for the first time the relationship between NP and spinothalamic tract (STT) microstructural integrity in Relapsing Remitting MS (RR-MS) patients through tractography reconstruction from Diffusion Tensor Imaging.
Methods:
A cohort of 35 RR-MS patients, and 15 healthy controls was enrolled and acquired on 3T scanner, including T1, T2, FLAIR and DTI. All participants underwent a complete clinical comprising pain evaluation (DN4) and cognitive assessment. Five ROIs (Fig1.A) were manually traced on controls DTI to obtain STT probabilistic masks, and to create STT template (Fig1.B). Diffusion metrics (FA, MD, AD, RD) of all participants were extracted from template and their laterality index (LI). ANCOVA corrected for age and gender was used for comparing the STT diffusion LI between controls and patients, while partial correlation was employed for assessing the relationships between alterations in LI and clinical/cognitive scores (p <0.05).
Results:
Results of the ANCOVA were reported in Fig2.A. The LI of FA was significant higher in RR-MS patients than controls (Fig2.B). Moreover, there was a positive correlation between the LI of MD and AD and FSS and between LI of MD, AD and RD with DN4 (Fig.2.C).
Conclusions:
We demonstrated that RR-MS patients had higher asymmetry than controls and more interestingly this abnormal STT laterality had a significant association with higher levels of fatigue and NP. In conclusion, we provided a first evidence of neuroanatomic correlate of the NP in RR-MS with STT microstructural alterations.