A real-world single-centre analysis of the safety and efficacy of cladribine tablets for relapsing multiple sclerosis

Abstract

Introduction: Damage of frontal cortico-subcortical networks contributes to fatigue and dual-task impairment in multiple sclerosis (MS). However, the mechanisms underlying these clinical deficits in progressive (P) MS still need to be fully explored. Objectives and Aims: In this study, we investigated the associations between structural and functional MRI abnormalities of frontal cortico-subcortical circuits and fatigue and dual-task performance in PMS. Methods: Brain structural and functional MRI scans, Modified Fatigue Impact Scale (MFIS) and dual-task performances were obtained from 57 PMS patients with impaired processing speed from 4 centers and 10 healthy controls (HC). The associations of thalamic, caudate nucleus and dorsolateral prefrontal cortex (DLPFC) atrophy, microstructural abnormalities of their connecting tracts and their resting state effective connectivity (RS EC) with fatigue, single-and dual-task performances were investigated. Results: Compared to HC, PMS patients had higher fatigue (p⩽0.027) and worse dual-task performance (p<0.001). Compared to non-fatigued (MFIS<38), PMS patients with fatigue (MFIS⩾38) had lower RS EC from left-caudate nucleus to left-DLPFC (p=0.007). In PMS, higher MFIS-physical and MFIS-psychosocial scores were predicted by lower RS EC from left-caudate nucleus to left-DLPFC (R 2 =0.112, p=0.027) and higher RS EC from right-thalamus to right-DLPFC (R 2 =0.102, p=0.046), respectively. Dual-task motor performances were predicted by lower RS EC from left-DLPFC to left-thalamus (R 2 ⩾0.137, p⩽0.032). Several structural MRI measures independently predicted dual-task correct response rates (R 2 =0.307, p⩽0.010) and dual-task cognitive cost (R 2 =0.188, p=0.002). Fatigue impact was not associated with single-and dual-task performances. Conclusions: Frontal cortico-subcortical structural and functional MRI abnormalities differently contribute to fatigue impact and single-and dual-task performance in PMS.