There is no single measure of multiple sclerosis (MS). This glossary provides simple explanations for some of the terms used to define how multiple sclerosis can be measured.
Annualised Relapse Rate (ARR)
The average number of relapses a group of patients in a clinical study have in one year.1
Brain Volume Loss
The overall decline in brain volume due to MS disease activity, which can be measured with MRI. Also referred to as “atrophy”, brain volume loss is associated with permanent disability.2
Composite Confirmed Disability Progression
Measures the risk of a persons’s disability getting worse based on any one of three disability endpoints – confirmed disability progression (CDP), walking speed (T25-FW) and hand function (9-HPT).
Confirmed Disability Progression (CDP)
Measures the increase in a person’s EDSS score (see below) that is sustained over a pre-determined time period, which means a person’s physical disability has increased.3
The loss of abilities that results from damage to the central nervous system (CNS) as MS progresses and may be irreversible.4
No matter what course of MS a person has, relapsing or progressive forms of MS may be active or inactive at different points in time. Disease activity may be outwardly apparent with new or worsening signs or symptoms (relapses).5 There can also be underlying disease activity (inflammation or damage to the central nervous system) that is detected with special equipment like magnetic resonance imaging (MRI) – even when clinical symptoms aren’t apparent or don’t appear to be getting worse. Disease activity may lead to disability progression.
Expanded Disability Status Scale (EDSS)
Measures the degree of physical disability based on a neurological exam of seven functional systems throughout the body, plus a person’s walking ability. The EDSS and its predecessor DSS have been used in nearly every MS clinical trial in the last 40 years.6
Gadolinium-enhanced T1-weighted MRI
Shows active lesions that appear bright white on an MRI scan after administration of an intravenous imaging contrast agent (gadolinium).7
Multiple Sclerosis Functional Composite (MSFC)
A combined measure of three separate disability assessments that was first introduced in the late 1990s. The MSFC is calculated based on leg, hand and cognitive function (T25-FW, 9-HPT, PASAT).8
No Evidence of Disease Activity (NEDA)
A combined measure of disease activity based on relapses, disability progression and MRI results. If someone meets NEDA criteria, they are free from measurable disease activity over a defined period of time.9
No Evidence of Progression or Active Disease (NEPAD)
A novel composite endpoint that measures the combined absence of disease activity (relapses and MRI activity) and progression (disability). NEPAD is similar to NEDA, but uses a composite endpoint (no confirmed disability progression by EDSS, 20% progression on T25-FW, and 20% progression on 9-HPT) to measure disability. This may represent a more comprehensive measurement of overall disease activity and progression for people with PPMS.
No Evidence of Progression (NEP)
A novel composite endpoint that measures the proportion of people with no confirmed progression of disability status (EDSS), walking speed (T25-FW) and upper extremity function (9-HPT) and may represent a new outcome for people with PPMS.
Nine-Hole Peg Test (9-HPT)
Measures arm, wrist and hand function by timing the speed in which a person can move nine pegs into nine holes and then remove them, using one hand at a time.10
Paced Auditory Serial Addition (PASAT)
Measures cognitive function by testing thinking speed and calculation ability.11
Progression Independent of Relapse Activity (PIRA)
Measures a person’s disability getting worse independently of a relapse and based on a composite disability score of confirmed disability progression (CDP), walking speed (T25-FW) and hand/arm function (9-HPT). This may be an indicator of underlying disease progression.
New or worsening signs and symptoms caused by inflammation in the central nervous system (CNS). These episodes develop quickly, last at least 24 hours and can continue for several days to weeks. Relapses can be followed by a full recovery or some continuing disability.12
Slowly Evolving Lesion (SEL)
Chronic inflammation in the brain is present in lesions and normal-appearing tissue and is more likely to occur in people with progressive MS. Recent scientific advances have suggested that SELs may be measured with conventional brain MRI. SELs may represent a measure of ongoing chronic tissue damage in pre-existing lesions of the brain.14
Shows all lesions, both active and chronic. These appear bright white and can be tracked over time to measure how a person’s MS is progressing.7
Timed 25-Foot Walk (T25-FW)
Determines walking speed by measuring how fast a person with MS can walk 25 feet.13
Bermel, RA, et al. The measurement and clinical relevance of brain atrophy in multiple sclerosis. The Lancet Neurology. 2006; 5(2):158 – 170.
Wiendl H, Meuth SG. Pharmacological Approaches to Delaying Disability Progression in Patients with Multiple Sclerosis. Drugs. 2015;75(9):947-977.
Giovannoni, G, et al. Brain Health: Time Matters in Multiple Sclerosis. 2015; pp 14.
Lublin FD, et al. Defining the clinical course of multiple sclerosis. Neurology. 2014; 83(3):278 – 86.
Sethi V, et al. Slowly eroding lesions in multiple sclerosis. Mult Scler. 2017 Mar;23(3):464-472.