Phd in CLINICAL EXPERIMENTAL NEUROSCIENCE AND PSYCHIATRY

Thesis title: Frailty in Multiple Sclerosis: a cross-sectional and longitudinal evaluation.

Background: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with Multiple Sclerosis (MS). Objectives: To investigate the relationship between frailty and the clinical manifestations of MS. Methods: We consecutively enrolled 745 MS patients at five tertiary dedicated services. Then, 471 patients were longitudinally evaluated after 1 year of follow-up. Patients completing and not completing the follow-up were similar in terms of sociodemographic and clinical features (i.e., age, sex, disease duration). Clinical and demographic data were collected: MS phenotypes were identified; disability and fatigue were assessed. At 1-year of follow-up we collected the total number of experienced relapses including clinical, and/or radiological activity. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits. Results: In the cross-sectional evaluation the median FI value was 0.12 (interquartile range=0.05–0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype. Thirty-five MS patients (33 RRMS and 2 SPMS) experienced a clinical and/or radiological relapse during the follow-up, and a negative association between FI and MS relapse activity was demonstrated. None of the patients experienced more than one relapse during the observed period. No significant modification of MS phenotypes occurred during the follow-up period. Conclusion: Frailty is significantly associated with major characteristics of MS. Furthermore, higher frailty degrees are associated with reduced relapse activity in MS patients. This observation suggests that frailty may play a role in the phenotypic expression and progression of the disease. Further studies, with longer follow-ups and specifically investigating the secondary progression of RRMS are needed to confirm and expand our findings.