Neurophysiological and neuroradiological correlates of fatigue in non-disabled multiple sclerosis patients

Background. Fatigue is a well-known and very often reported symptom in multiple sclerosis (MS) patients, even when neurological disability is still not clinically evident. In spite of its high prevalence, the pathophysiology of fatigue is still unclear and often concealed by the presence of motor pathway damage due to the demyelinating process and/or concomitant psychiatric diseases. Aim of this work was to evaluate a possible correlation between neuroradiological and neurophysiological findings in non-disabled MS patients. Matherials and Methods. A group of patients was selected with the following inclusion criteria: diagnosis of relapsing-remitting MS, absence of neurological disability (EDSS ≥ 1.5 with pyramidal FS score ≥ 1), no involvement of cere bellar sensitive sphincter FS, absence of concomitant mood disorders (as assessed by MADRS), absence of steroid treatment and/or MS relapse in the previous month. After inclusion patients were divided into 2 groups differentiated by presence (F) or absence (NF) of fatigue as assessed by the Fatigue Severity Scale (FSS). Following these criteria we identified two groups of subjects (15F, 15NF) matched by age, sex, disease duration and EDSS. Both groups underwent MEPs and brain MRI scan. Following the same selection criteria we evaluated the desynchronization/synchronization (ERD/ERS) of EEG rythms during a self-paced movement of the right thumb, in a group of 13 F and 18 NF MS patients and in 12 normal subjects. All clinical, neurophysiological and neuroradiological data were statistically analyzed. Results. MEP analysis revealed a higher prevalence of abnormalities in F patients than in the NF group for all the four limbs tested even if they didn't reach statistical significance. Median MRI total lesion burden was higher in F patients than in NF patients and it was significantly correlated to the FSS score (SRCC = 0.5; P <0,005). Significantly higher regional burden values for F than for NF patients were found in the parietal lobe, internal capsule and periventricular (PV) areas. The EEG rhythm evaluation performed with ERD/ERS analysis, revealed a significant reduction in post-movement ERS over the contralateral cortical central area in F patients as compared with NF. Conclusions. Our data suggest that the demyelinating damage located in critical areas of brain white matter could lead to a disturbance in the neural conduction expressed with abnormal activation in the pre-motor cortical areas as detected with ERD/ERS analysis. This phenomenon seems to lead to a secondary disturbance in movement control that could be responsible for the MEP abnormalities and clinical symptoms of fatigue in non-disabled MS patients.