How MS is measured

A relapse, or attack, is an episode of new or worsening symptoms that lasts at least 24 hours, without a fever or infection to explain it. Trials in relapsing MS usually count relapses per person per year, the annualised relapse rate. Relapse rates in the placebo groups of trials have fallen steadily over the decades, mainly because the people recruited had fewer relapses before they joined. A medicine tested today therefore has less to reduce than one tested in the 1990s.[1][2]

On MRI, lesions show up as bright spots. A lesion that lights up after an injection of gadolinium contrast is a sign of current inflammation, because the dye leaks through a damaged blood-brain barrier. New or enlarging lesions on a later scan show activity since the previous one. Across trials, medicines that reduce new lesions also reduce relapses, which is why early trials in relapsing MS often use MRI to decide which medicines deserve a larger trial.[3]

MRI can also measure how fast the brain is shrinking, known as atrophy. The brain shrinks slowly with age in everyone and faster in MS. Atrophy is linked to disability, but it changes slowly and is hard to measure reliably in one person. Newer MRI signs, such as a rim of iron at the edge of a lesion or a vein at its centre, now support diagnosis and are being studied as markers of smouldering inflammation.[4][5]

The Expanded Disability Status Scale (EDSS) runs from 0, a normal neurological examination, to 10, with half-point steps over most of the scale. It was published in 1983 and is still the main disability measure in trials. In its middle range it depends heavily on how far a person can walk, and it says little about the hands, thinking or vision.[6]

Trials count confirmed disability progression: a rise in the EDSS that is still present at a check three or six months later, so that a temporary worsening during a relapse is not counted. When the worsening happens without a relapse, researchers call it progression independent of relapse activity, or PIRA.[7]

Because the EDSS misses a great deal, trials add timed tests. The timed 25-foot walk measures walking speed, the nine-hole peg test measures hand function, and the Symbol Digit Modalities Test measures how quickly a person processes information, one of the thinking skills most often affected by MS.[8][9]

Neurofilament light chain (NfL) is a protein released into the blood when nerve fibres are damaged. Its level rises with new inflammation and falls on effective treatment, and it can be measured with a blood test. Glial fibrillary acidic protein (GFAP), released by astrocytes, has been linked to later progression in some studies. Neither is yet used on its own to make decisions about one person.[10][14]

Questionnaires such as the Multiple Sclerosis Impact Scale (MSIS-29) ask people how MS affects their daily life, physically and psychologically. They capture effects that scans and examinations can miss.[11]

A medicine can change one measure and not another. In a phase 2 trial in secondary progressive MS, high-dose simvastatin slowed the rate of brain shrinkage. The phase 3 trial that followed, MS-STAT2, with 964 participants, found no effect on disability. Deciding which early signals deserve a large trial is one of the hardest problems in MS research, and the Research section tracks how often those signals have held up.[12][13]