Multiple sclerosis fatigue, its neural correlates, and its modulation with tDCS

Multiple sclerosis (MS) is a chronic progressive and inflammatory disease of the central nervous system and causes high rates of non-traumatic disability in young adults. Fatigue is frequently reported by a major part of patients during the disease course and dramatically increases the burden of illness. Despite the high prevalence of fatigue and its enormous impact on quality of life, its pathophysiological mechanisms are still unclear. Its etiology is multifactorial and complex, and is usually classified into 'primary' fatigue resulting from the pathological brain changes versus 'secondary' fatigue following disease symptoms, sleep disturbances, mood disorders, and side effects of medication. Hypotheses concerning the pathophysiology of this symptom are based on radiological, physiological, and endocrine data. It has been suggested that fatigue refers to structural and functional changes in a variety of neuronal networks. Over the past years, non-invasive brain stimulation methods were used to modulate brain function, especially transcranial direct current stimulation (tDCS) has proven to impact neuronal connectivity; however evidence is still sparse due to the pilot character of the studies. In this review we aim at discussing the neuronal correlates of fatigue and the potential influence of tDCS in the modulation of the symptoms.