Multiple sclerosis is a devastating disease; it is highly heterogeneous, and a large percentage of patients acquire some form of life-altering disability. 

Nearly a million individuals in the United States are affected by multiple sclerosis, and this condition is typically diagnosed when patients are in their 20s and 30s. The effects can be devastating: deteriorating physical functioning, poorer quality of life, and an inability to stay employed. 

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Although we understand multiple sclerosis to be an autoimmune disorder of the central nervous system characterized by axonal transection and inflammatory demyelination, its exact etiology remains unclear. Some propose a genetic cause; others think that environmental factors are more likely, such as vitamin D deficiency. In addition, Epstein-Barr viral infection has been associated with this disease, and so has a history of tobacco smoking. 

“Current treatment for [multiple sclerosis] consists of a multidisciplinary approach including disease-modifying therapies, symptomatic treatment, lifestyle modifications, psychological support, and rehabilitation interventions,” McGinely and colleagues wrote in JAMA. 

A quick list of the common signs of multiple sclerosis and what they mean to patients elucidate the devastating effects of this diagnosis. In optic neuritis associated with multiple sclerosis, patients typically experience pain with eye movements and decreased visual acuity evolving over hours/days. In partial myelitis, patients may experience impaired sensation in their torso and their extremities, as well as ever-worsening hyperreflexia. 

Lhermitte phenomenon is a particularly unpleasant complication of multiple sclerosis, involving sensations of electric shock that radiates from the neck down to the spine/extremities. Patients with multiple sclerosis also typically experience lesions in distinct anatomical locations within the central nervous system, and risk developing new central nervous lesions over time. 

A multiple sclerosis relapse is defined as “a monophasic clinical episode with patient-reported symptoms and objective findings reflecting a focal or multifocal inflammatory demyelinating event in the [central nervous system], developing acutely or subacutely, with a duration of at least 24 h with or without recovery and in the absence of fever or infection,” McGinely et al wrote. 

In addition, patients with multiple sclerosis may experience “pseudo relapses”, defined as the transient worsening of neurological symptoms not caused by new disease activity. 

Acquiring Disability 

There is no doubt that a diagnosis of multiple sclerosis opens up a world of suffering. However, how exactly do patients with multiple sclerosis acquire disability? 

“There are two main mechanisms by which patients with multiple sclerosis acquire disability: (i) step-wise accrual of impairment due to incomplete recovery from a relapse; and (ii) progression independent of relapse activity,” Lublin and colleagues wrote in Brain. 

The first cause of disability is rather straightforward — a relapse occurs, and a failure of treatment (or a lack thereof) results in permanent disability. However, the second cause of disability is less straightforward and far more insidious. They tend to progress to primary and secondary progressive multiple sclerosis. 

Lublin et al conducted a study in which their endpoints included multiple sclerosis relapses (defined as the appearance of new neurological abnormalities or worsening of preexisting neurological abnormalities), as well as confirmed/sustained disability worsening (defined as a worsening of the Expanded Disability Status Scale (EDSS)). 

The study confirmed that relapses were a common cause for disability in both relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis. However, the research team reported that relapses held no prognostic value for further disability worsening. 

The results of this study indicate that disease-modifying therapies can reduce the percentage of patients who experience relapses; they also reduce the proportion of patients experiencing all-cause disability worsening events, particularly in patients with relapsing-remitting multiple sclerosis. 

This study also validated other research that states that incomplete recovery from relapses contribute to the accumulation of disability. This was most pronounced in relapsing-remitting multiple sclerosis, followed by secondary progressive multiple sclerosis, and finally, primary-progressive multiple sclerosis. 

“This included all investigator-reported relapses, irrespective of an EDSS-based confirmation,” the study authors noted. 

The research team also discovered that patients with preexisting disabilities (as indicated by EDSS scores) prior to relapse were least likely to completely recover from relapses. This was especially the case for older adults with preexisting disabilities. 

In contrast, individuals who were most likely to make a complete relapse recovery were young patients, particularly those with the least disabling relapsing-remitting multiple sclerosis.

Read more about multiple sclerosis treatment 

The researchers also investigated an interesting angle in how patients with multiple sclerosis acquire disability — the time to reach milestone disability and the impact of treatment. They reported that patients who were on disease-modifying therapy took 12.5 years to reach a particular disability threshold; in patients who were given a placebo and had an average EDSS of 4, the time was shortened to 9 years. 

“Our study confirmed that relapses are a significant and clinically meaningful contributor to all-cause disability worsening,” the study authors concluded. “This is in line with observations that relapses frequently lead to residual deficits, and that persistent focal inflammatory activity early in the disease is predictive of severe EDSS worsening.” 

In light of this evidence, physicians should educate patients on how to avoid relapses, and present them with facts about how disability in multiple sclerosis is required. Although multiple sclerosis remains in many aspects a disabling disease, continued research into novel therapeutics may offer patients hope in the near future. 


McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis. JAMA. Published online February 23, 2022.

Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disabilityBrain. Published online February 1, 2022. doi:10.1093/brain/awac016