Rims, central veins and atrophy

The clinico-radiological paradox

The number and size of lesions on standard MRI match a person's disability poorly. Two people with similar scans can be affected very differently, and lesions can come and go without symptoms. This mismatch has a name, the clinico-radiological paradox.[1] It has several explanations: lesions in some places matter more than in others, cortical lesions and diffuse damage are hard to see, standard scans cannot tell repaired lesions from destroyed ones, and the brain compensates for damage to different degrees. The methods in this lesson try to close that gap.

The central vein sign

Most MS lesions form around a small vein, and on sequences sensitive to veins, such as susceptibility-weighted imaging, the vein can be seen as a thin dark line or dot in the middle of the lesion. White spots from small vessel disease or migraine usually lack it. A North American consensus in 2016 proposed a standard definition and argued that the sign can separate MS from its mimics.[2] The 2024 McDonald criteria now accept the central vein sign, where available, as supporting evidence that adds specificity in defined situations.[3]

Rims of iron

Lesions whose edges are still inflamed carry iron-laden microglia at their rim, which shows as a dark ring on the same sequences (lesson 3.2). In a study at the US National Institutes of Health, 56 per cent of people with MS had at least one rim lesion, and those with four or more reached disability at a younger age.[4] Rim lesions are rare in the diseases that mimic MS, so the 2024 criteria accept them too as supporting evidence.[3] They are also being tested as a measure of whether treatments reach smouldering inflammation.

Atrophy: measuring what has been lost

Everyone's brain shrinks slowly with age. In MS it shrinks faster. In a study that followed people for an average of seven and a half years with the same software, brain volume fell by 0.51 per cent a year in MS against 0.27 per cent in healthy people. A loss of more than 0.37 per cent a year best separated the two groups, but even this cut-off picked out only two thirds of the people with MS.[5] Loss of grey matter, especially in the deep grey matter and the cortex, matches disability better than loss of white matter. The spinal cord shrinks too, and cord atrophy is closely linked to walking problems.

Atrophy is hard to use for one person. Measurements vary between scanners and with hydration, and changes of a few tenths of a per cent are close to the noise. In the first months after starting an effective treatment, brain volume can drop faster as swelling from inflammation resolves, an effect known as pseudo-atrophy. For now atrophy is mainly a trial measure, used especially in progressive MS.

Other methods on the way

Several methods are mostly used in research. Magnetisation transfer and diffusion imaging are sensitive to myelin and to the structure of white matter, and are used in trials of repair. Scanners at 7 tesla show cortical lesions and rims far better than routine machines. PET scans with tracers that bind activated microglia show smouldering inflammation directly. Each could become part of routine care if it proves reliable on ordinary scanners.