In progressive chronic illnesses such as multiple sclerosis (MS), it is important for physicians and researchers alike to know exactly when patients develop symptoms that cross the threshold into disability. Treatment strategy fundamentally changes when patients become unable to carry out day-to-day functions and require assistance for basic tasks.
In 2001, the World Health Organization set forth an umbrella definition of disability that incorporates impairment in body structure or function, difficulties in carrying out a task or action, and impediments in participating in life situations.
Nehra and colleagues believed that neurological disability, in particular, is vastly underestimated in terms of its prevalence and the mortality it causes. “There is a need for a comprehensive format for neurological disabilities assessment which would also include objective neuropsychological assessments,” they wrote in Neurology India.
Lublin and colleagues recently published a study on how patients with multiple sclerosis (MS) reach and face disability. As the development of disability is a devastating experience for even the most well-prepared of patients, the team managed to produce a paper that is equally informative and empathetic.
The Expanded Disability Status Scale
The Expanded Disability Status Scale (EDSS) is the key scale used to measure disability in MS. It was developed in the early 1980s to do the important job of objectively defining endpoints for clinical studies.
The scale ranges from 0 to 10, with 0 being normal neurological function and 10 being death from MS. In the lower range, the EDSS measures impairment in 8 functional systems; in the middle range it measures ambulatory function; and in the upper range, it focuses on the patient’s ability to carry out day-to-day activities.
“In clinical practice, it [the scale] is mainly used in specialist multiple sclerosis centers, while nonspecialists may use the EDSS as a basis for their assessments,” Uitdehaag wrote in a study published in CNS Drugs.
Read more about multiple sclerosis treatment
The main advantage of the EDSS is that it is widely used: a medical researcher can communicate the intended range of disability in a different language and be understood by researchers across the world. However, its shortcomings are also well-recognized: it has limited sensitivity, insufficient assessment domains, and records high levels of variability between patients.
Relapse, Incomplete Recovery Contribute to Disability
Lublin and colleagues used the EDSS in their sweeping study on how patients with MS reach the level of disability. “Using the Novartis-Oxford MS (NO.MS) data pool spanning all multiple sclerosis phenotypes and pediatric multiple sclerosis, we evaluated ~200,000 EDSS transitions from >27,000 patients with ≤15 years follow-up,” they explained.
Their main finding was that MS patients acquire disability through 2 main means: relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). The research team discovered that PIRA started early in relapsing-remitting MS and was the primary driver of disability accumulation over the course of the disease.
Read more about multiple sclerosis patient education
The research team also discovered that relapses have a significant impact on all-cause disability. They were found to be most common in patients with relapsing-remitting MS, followed by secondary progressive multiple sclerosis. When relapses occur, incomplete recovery is a further contributor to the accumulation of disability. The most important and consistent risk factors for incomplete relapse recovery were pre-existing disability and the age of the patient at the time of relapse.
Lublin and colleagues also compared how disease-modifying therapies (DMTs) affected disability outcomes in randomized placebo-controlled phase 3 trials. “Data show DMTs reduced the proportions of patients who relapsed and those who had all-cause disability worsening events, with the strongest effect in relapsing-remitting multiple sclerosis,” they reported.
One interesting finding highlighted by Lublin et al is that disease progression can often be underestimated as a factor contributing to the accumulation of disability, especially in relapsing-remitting MS. This is in part due to the inconsistent ways in which physicians monitor disease progression (with some conducting formal routine assessments while others do not).
In addition, worsening neurological symptoms in an MS patient can sometimes be wrongly attributed to a relapse. The key difference between a relapse and a progressive worsening of symptoms is that the latter is permanent, even after any acute episodes have been resolved.
Three Takeaways for Clinicians
There are a few things that clinicians learn from this study. The first is that disability can be difficult to quantify, especially if it happens progressively. It is not uncommon for both clinicians and patients to miss out on worsening symptoms, since they can happen so gradually.
Second, relapses contribute significantly to the acquisition of disability and should therefore be managed as effectively as possible.
The third takeaway is that current treatments do play a role in delaying the onset of disability. Lublin and colleagues wrote, “Our study demonstrated that time to disability milestones can be delayed by several years with treatment, with the highest potential to gain time in the youngest, least disabled patients with multiple sclerosis.”
The best thing physicians can do is to educate their patients on potential disability progression and to use all the tools at their disposal, including the EDSS and DMTs, to delay its onset for as long as possible.
Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;awac016. doi:10.1093/brain/awac016
Uitdehaag BMJ. Disability outcome measures in phase III clinical trials in multiple sclerosis. CNS Drugs. 2018;32(6):543-558. doi:10.1007/s40263-018-0530-8
Nehra A, Tripathi M, Srivastava MVP. Neuropsychological disability: A hidden epidemic of neurological conditions. Neurol India. 2020;68(1):154-158. doi:10.4103/0028-3886.279709