Fatigue in multiple sclerosis: a clinical and MRI studi

Fatigue is a very common symptom in multiple sclerosis (MS), described as an overwhelming sense of tiredness, lack of energy and feeling of exhaustion. Several electrophysiological and imaging studies have shown an abnormal recruitment of cortical and subcortical networks in MS patients with fatigue, supporting the hypothesis of a central genesis of this symptom. Although the specific central nervous system regions involved have not been clearly identified, there is some evidence that the precentral gyrus, cingulate gyrus, insula and cerebellum are involved. The main purpose of this study is to define the functional MRI (f-MRI) activation pattern of brain areas in MS patients with fatigue during resting state and during a motor task. MS patients will be selected from the MS Outpatients Clinic at G. Rossi Hospital, Verona, aged 18-55 years, with a relapsing-remitting (RR) course, Expanded Disability Status Scale (EDSS) score ≤4.5, complaint of fatigue for ≥50% of days for >6 weeks, and mean Fatigue Severity Scale (FSS) score ≥5.0. Patients will be selected for right-hand dominance. A group of RRMS patients without fatigue and with mean FSS score <5.0, matched by age, sex and EDSS score to patients with fatigue, will be included in the study. Selected patients will need to be free from any functional impairment of the right upper limb interfering with the motor task required for f-MRI. A score>=17 at the Montgomery and Asberg Depression Rating Scale will be an exclusion criteria. Patients on therapy with anti-fatigue drugs (amantadine and 4-aminopyridine) within the previous month will be excluded. A group of healthy subjects, age- and gender-matched to MS patients, will be enrolled as controls for MRI evaluation. Patients and controls will undergo conventional and f-MRI scans. T1 lesion load, T2 lesion load will be calculated on conventional MRI scans. Functional MRI will be performed in resting state and during a simple motor task. To date, twelve MS patients, six with and six without fatigue, and three healthy controls have undergone MRI. MS patients showed activation related to motor-task in primary somatosensory area bilaterally, supplementary motor area, inferior frontal gyrus and cerebellum bilaterally. Moreover, patients complaining fatigue appeared to activate more motor brain areas compared to both MS patients without fatigue and controls.