As a chronic disease, therapies used to treat MS focus on altering the disease course by reducing disease activity and slowing down the accumulation of disability.
Symptomatic treatment options are also important in helping individuals fulfil their personal, social, and occupational roles and improve quality of life, for as long as possible.
Adapted from Dendrou CA, et al. Nature Reviews Immunology. 2015.
Damage from MS can affect the whole CNS. Autoimmune and inflammatory components can damage myelin, white matter, neurons, axons, and blood vessels. This damage can begin early in the disease.
MS lesions are a hallmark of MS. MS lesions are caused by immune cell infiltration across the blood-brain barrier promoting inflammation, demyelination, gliosis and neuroaxonal degeneration, leading to disruption of neuronal signalling. MS lesions show evidence of invading peripheral immune cells.
Inflammation is more pronounced in the acute stages of MS but can continue into the chronic stages. Peripheral immune cells found to infiltrate MS lesions include macrophages, T cells, B cells, and plasma cells. At later stages of the disease, these cells, along with activated CNS-resident microglia and astrocytes, promote atrophy of grey and white matter.
Remodelling* can occur in MS but may have limited effectiveness. Remodelling may act through multiple potential mechanisms in the CNS and may partially restore or preserve its function.
*Reestablishing or rearranging neural connections.
†Cell type that creates myelin in the CNS.
Neurological signalling pathways are disrupted in MS. These disruptions may inhibit the endogenous functions of the brain, may promote disease related pathways or alternatively inhibit their activation.
*Specialised end of an axon that determines and guides the direction of growth.
Functional connectivity in neural networks can be affected by MS. Recent research into MS has taken a network approach, by making use of functional connectivity to study the response of the brain to MS insults. MS lesions are thought to impact communication networks between different brain regions. These changes in network communication and organisation can alter functional connectivity in MS.
*In a 1-year longitudinal study, patients with early RRMS meeting criteria for no evidence of disease activity (NEDA-3; n = 56) and those with evidence of disease activity (n = 36) showed increases in local cortical connections. This change was not observed in healthy controls (n = 101) over the same period.
Altered functional connectivity has been associated with changes in MS symptoms. Cognitive and motor performance as well as other neurologic dysfunctions (e.g. fatigue, visual problems, depression, and sleep disturbance) are often associated with alterations in functional connectivity or change in network coherence.
Once diagnosed, there are several different types of MS including relapsing remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS).
Relapses are episodes of neurologic deficits that can coincide with inflammation and demyelination which are typically discernible by MRI as white matter lesions. Relapse intensity can vary from mild to severe with complete or incomplete neurological recovery, and the symptoms they cause can vary from patient to patient.
Relapse rate and measures of disability including the EDSS (Expanded Disability Status Scale) score are typical primary outcome measures in clinical trials for the approval of MS disease modifying treatments (DMTs). Relapse rate serves as a measure of inflammatory activity whereas EDSS score is an indication of the accumulation of clinical disability due to inflammatory or neurodegenerative processes. These two measures reflect distinct pathological processes occurring in patients with MS.
Often the reduction of relapses and lesions is prioritised in treatment decisions, however for patients, symptom management remains an important aspect of their therapy for MS.