Author Of 1 Presentation
YI02.03 - Identifying distinct cognitive phenotypes in multiple sclerosis
Abstract
Background
Cognitive impairment is one of the most disabling symptoms of multiple sclerosis (MS), affecting about 50% of patients.
Objectives
We sought to define homogeneous cognitive phenotypes in a large cohort of MS patients by using a data-driven approach, and to assess their distinctive clinical and MRI features.
Methods
A cohort of 1212 MS patients and 196 healthy controls (HC) from 8 Italian MS centers underwent cognitive evaluation with Rao’s Brief Repeatable Battery and Stroop Color Word Test. A subgroup (172 MS patients and 50 HC) also underwent a 3T MRI examination, including 3D T1-weighted and dual-echo sequences. Latent-profile analysis was used on cognitive tests’ z-scores for identifying cognitive phenotypes. Linear regression and mixed effects models were used to define the clinical and MRI features of each phenotype.
Results
Five cognitive phenotypes were identified, characterized by “preserved-cognition” (19%), “mild verbal memory/semantic fluency” impairment (30%), “mild-multi-domain” impairment (19%), “severe-attention/executive” impairment with mild impairment of other domains (14%), and “severe-multi-domain” impairment (18%). “Preserved-cognition” patients had shorter disease duration and lower Expanded Disability Status Scale (EDSS) score than all other groups, and mildly impaired phenotypes included patients with shorter disease duration and less likely progressive disease compared to severely impaired groups. However, the “preserved-cognition” group also included patients with progressive disease and high EDSS scores, and severely impaired phenotypes were also represented in early MS stages. Comparing each phenotype to “preserved-cognition” group, distinctive MRI features emerged: “mild verbal memory/semantic fluency” patients had reduced hippocampal volume (p=0.02), “mild-multi-domain” reduced cortical gray matter volume (p=0.04), “severe-attention/executive” higher lesion volume (p=0.04) and severe-multi-domain” extensive brain damage (p<0.01 for lesion, brain, gray matter and thalamic volumes).
Conclusions
We identified five cognitive phenotypes of MS patients, with distinctive MRI substrates. By defining homogenous and clinically meaningful groups, this characterization may be useful for future research on cognitive impairment in MS, and for defining personalized management approaches and rehabilitative strategies in clinical practice.
Author Of 1 Presentation
P0161 - Short-term evaluation of alemtuzumab to ocrelizumab switch in MS patients with disease activity after alemtuzumab: an Italian multicentric study. (ID 1603)
Abstract
Background
the management of MS patients (pts) who show disease activity after 2 alemtuzumab (ALM) courses represents an unsolved issue. No real-life data about the switch to ocrelizumab (OCR) have been reported yet.
Objectives
To describe efficacy and safety outcome of OCR patients switching from ALM due to persistence of disease activity after ALM
Methods
MS pts who switched from ALM to OCR from March 2019 to March 2020 were retro- and prospectively recruited from different Italian MS Centers. Clinical, immunological and neuroradiological data about ALM treatment period, ALM-OCR interval and OCR treatment period were collected.
Results
we recruited 23 MS pts [mean age: 35.7(SD±6.8); female, 40.1%; Relapsing Remitting, (RR): 75.8%, active Secondary progressive, (aSP): 24.2%; mean time interval (days) from II ALM course: 87.4(SD±108); cumulative number of relapses: 21; mean number of new T2 and Gd+ lesions: 4.1(SD±4.5) and 1.6(SD±3.1); median EDSS:3(range 1-7)]. The mean follow-up (FU) from OCR start was 7.9±7.4 months. Efficacy: 4 (17.4%) pts had a relapse after OCR start (1 pt relapsed between the first and the second OCR infusion and 3 pts after 3, 11 and 15 months from OCR start respectively), with complete recovery after steroid treatment. 4 (17.4%) pts showed radiological activity with no clinical correlates at 3 months (n=2), 4 months (n=1) and 9 months (n=1). EDSS was stable except for 1 aSP patient who showed 1-year disability progression. Safety: I) Infusion Associated Reactions (IARs) occurrence was significantly lower with respect to alemtuzumab courses (p<0.05); (ii) infections: mild upper airways (n=1), urinary infections (n=1), appendicectomy (n=1) and fever due to probable Sars-Cov2 infection (n=1). For 12 pts, data about immunophenotype were available. Of them, no pts showed T CD4+ cell count decrease <200 cell/mm3 at 3, 6-months and 1-year FU; complete B CD19+ cell depletion (<5 cell/mm3) was confirmed at 3, 6-months and 1-year FU. 10 (43.4%) pts developed hypogammaglobulinemia without developing associated infectious events. C) Autoimmunity: no alemtuzumab-related new complications occurred.
Conclusions
short-term FU seems to suggest that the switch to OCR in MS patients who showed disease activity after 2 ALM courses is characterized by a good safety and efficacy profile, although clinical and neuroradiological activity can be detected both in an early and in a later phase of treatment. Longer follow-up is warranted and recruitment is still ongoing.