Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation

Abstract

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system (CNS) and the major cause of non-traumatic disability in young adults. Fatigue is a frequent symptom reported by the majority of MS patients during their disease course and drastically affects their quality of life. Despite its significant prevalence and impact, the underlying pathophysiological mechanisms are not well elucidated. MS fatigue is still considered the result of multifactorial and complex constellations, and is commonly classified into “primary” fatigue related to the pathological changes of the disease itself, and “secondary” fatigue attributed to mimicking symptoms, comorbid sleep and mood disorders, and medications side effects. Radiological, physiological, and endocrine data have raised hypotheses regarding the origin of this symptom, some of which have succeeded in identifying an association between MS fatigue and structural or functional abnormalities within various brain networks. Hence, the aim of this work is to reappraise the neural correlates of MS fatigue and to discuss the rationale for the emergent use of noninvasive brain stimulation (NIBS) techniques as potential treatments. This will include a presentation of the various NIBS modalities and a suggestion of their potential mechanisms of action in this context. Specific issues related to the value of transcranial direct current stimulation (tDCS) will be addressed.

Fatigue in multiple sclerosis – Insights into evaluation and management

“…Here, we will briefly describe the various pathophysiological mechanisms that have been evoked in this field. For a more detailed review, please refer to [24].…”

“…Therefore, combining pharmacological and alternative therapies would be the key toward an optimal management plan. A variety of alternative therapies has been assessed in this setting such as exercise [84], cognitive behavioral therapies [232], cryostimulation [130], and noninvasive brain stimulation (NIBS) [24,152] -and the list goes on. For the sake of this review, we will only focus on NIBS techniques.…”

Are Modular Activations Altered in Lower Limb Muscles of Persons with Multiple Sclerosis during Walking? Evidence from Muscle Synergies and Biomechanical Analysis

“…Their gait deficit is a major contributor to decreased quality of life, diminished activities of daily living, and loss of employment (Chalah et al, 2015). The mediating efficient communication between the central nervous system (CNS) and neuromotor components, needed to perform the movement, is compromised in persons with Multiple Sclerosis as a consequence of the immune-mediated inflammatory destruction of myelin sheaths, axons, and neurons in cortical and subcortical structures (Haines et al, 2011).…”

Fatigue and Affective Manifestations in Multiple Sclerosis—A Cluster Approach

“…The scientific and medical community considers MS fatigue a complex and multifaceted symptom. In fact, its definition remained vague for a long period of time until the MS council for clinical practice guidelines set a clear description of this complaint and has defined it as 'a subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual and desired activities' [2]. Hence, fatigue reported by MS patients differ from the 'classical' tiredness experienced by healthy individuals in that it seriously impedes daily activities and can be lessened or heightened by cold or hot weather, respectively [2].…”

“…From a pathophysiological standpoint, MS-related abnormalities have been incriminated in the generation of fatigue and have been largely studied and described over the past decade. Other factors seem to be implicated, such as inflammatory mediators (i.e., TNF-α, IFN-γ, and IL-1β), neuro-immune and neuro-endocrine mechanisms (i.e., hypothalamo-pituitary-adrenal axis) [2,3].…”