Spinal Cord Imaging Emerges as a Crucial Window into Multiple Sclerosis Disability

For many years, multiple sclerosis research largely overlooked the spinal cord. A major review in the Journal of Neurology argues that this narrow strand of nervous tissue, only about fifteen millimetres wide at its broadest point, may be the most important site for explaining why people with MS become disabled. Led by Tal J. Koren and Michael H. Barnett of the University of Sydney with international collaborators, the review brings together nearly four years of work on spinal cord imaging and lands on a clear conclusion: disease progression is concentrated in the cord, while clinicians and trial designers have been measuring it far too little.

The extent of the issue is considerable. MS affects more than 2.9 million people around the world, and spinal cord lesions appear on as many as 85 percent of MRI scans of the cord in newly diagnosed patients. Among people with relapsing-remitting MS, up to 76 percent have at least one cord lesion when the full cord is scanned, rising to 90 percent in progressive disease. Even so, a systematic review cited in the paper found that out of 291 MS clinical trials, only eight planned to use spinal cord MRI measures as outcomes, and only three reported those data. None showed a significant benefit versus placebo for cord atrophy or lesion count.

Studying the cord has been difficult for a series of technical reasons. Because the structure is so small, images need slices of just one to three millimetres to detect lesions reliably. The cord is surrounded by bone and cerebrospinal fluid that moves with each heartbeat, which creates motion artefacts. Differences in magnetic susceptibility between the cord, fluid, bone and air distort the signal, and even slight changes in slice positioning from one scan to the next can make it seem as if the cord has changed when it has not. One researcher’s comparison of routine spinal cord MRI to cave paintings captures just how far the technology has lagged behind brain imaging.

Even with those limitations, the predictive value is strong. Spinal cord lesions can forecast conversion to MS in people with radiologically isolated syndrome, and patients whose first clinical event involves the cord tend to reach a definite diagnosis more quickly. The total lesion volume in the cord at diagnosis is linked to later disability on the Expanded Disability Status Scale, the Nine-Hole Peg Test and the Timed 25-Foot Walk. Just as important, both lesion volume and lesion number at diagnosis are tied to progression independent of relapse activity, the quiet worsening that continues even when inflammatory attacks are controlled. That points to a gap in standard monitoring, which still focuses heavily on the brain.

Atrophy appears to be even more revealing. In healthy adults, spinal cord cross-sectional area shrinks by about 0.06 percent per year, while in MS the rate is roughly 1.78 percent per year. In a retrospective study of more than 360 people with relapsing-remitting MS, those who later developed secondary progressive disease had cord atrophy of 2.19 percent per year over four years, compared with 0.88 percent in those who did not. Cord cross-sectional area tracks disability more closely than brain atrophy, and grey matter loss inside the cord, which is more pronounced in progressive disease, is even more tightly associated with clinical impairment than whole-cord measurements.

Diagnostic practice has also changed with the revised McDonald criteria. The spinal cord now counts as one of five anatomical sites used to show dissemination in space, and in suspected primary progressive MS, two cord lesions are enough to satisfy that requirement without another anatomical region. The criteria also advise looking for cord lesions first in patients over fifty or in those with notable vascular risk factors before attributing white matter abnormalities to small-vessel ischaemia. The shape of lesions is informative too: MS lesions in the cord are usually short, peripheral, cigar-shaped on sagittal images and wedge-shaped on axial views. That pattern helps distinguish MS from neuromyelitis optica spectrum disorder and MOG antibody disease, which more often show longer lesions that run through the centre of the cord or involve grey matter, including the so-called H sign seen in MOGAD.

The differential diagnosis is broader than other inflammatory disorders. Spinal cord infarction can produce owl-eye or pencil-like MRI patterns. Spinal dural arteriovenous fistulas may resemble progressive MS because they can cause slowly worsening myelopathy, and missing them can be dangerous, especially since steroids may worsen the congested cord. Also in the differential are compressive spondylotic myelopathy, vitamin B12 and copper deficiency with the inverted dorsal V sign, infectious myelitides, neurosarcoidosis with its trident sign, and even rare pegivirus-associated cord tractopathy. The review stresses that careful pattern recognition on cord MRI is not only useful for research but also an important diagnostic safeguard.

On the imaging side, agreement is emerging. The 2024 MAGNIMS-CMSC-NAIMS recommendations call for whole-cord imaging using two complementary sagittal sequences, gapless T2 fast spin echo, STIR, PSIR or MP(2)RAGE with slice thickness under three millimetres, plus one axial sequence, while advising against FLAIR for lesion detection in the cord. Moving from 1.5 to 3 Tesla does not provide an overall advantage for detecting cord lesions, because field inhomogeneity, sensitivity to movement and energy deposition offset the expected gain in signal. Newer three-dimensional techniques such as phase-sensitive inversion recovery have proven more sensitive for cervical cord lesions than conventional two-dimensional STIR, and ultra-high-field 7 Tesla imaging has been reported to increase lesion detection by 52 percent while also revealing cord counterparts of the brain’s central vein sign and paramagnetic rim lesions, though these remain research tools.

More advanced quantitative methods are beginning to move toward clinical use. Diffusion tensor imaging shows reduced fractional anisotropy and increased diffusivity extending into tissue that appears normal on conventional scans, and those changes correlate with disability even in patients with relatively few visible lesions. Magnetisation transfer ratio, which reflects myelin integrity, is lower across the cervical cord in recently diagnosed patients even when visible lesions are excluded, suggesting a possible biomarker for progression independent of relapse activity. Myelin water imaging fell by more than ten percent over two years in primary progressive MS, while proton spectroscopy has shown reduced N-acetyl-aspartate, a sign of axonal damage before atrophy is visible. Chemical exchange saturation transfer and sodium MRI point to broader biochemical disruption beyond focal lesions. Artificial intelligence is also starting to help with cord and lesion segmentation through tools such as the open-source Spinal Cord Toolbox, although no model is yet reliable enough for longitudinal lesion tracking and none has regulatory approval as a clinical device.

The authors end with a practical message. They argue that every patient should have high-quality MRI of the full spinal cord at diagnosis, and because many cord lesions cause no symptoms, they suggest routine whole-cord imaging every two to three years, describing this as an expert opinion rather than a formal guideline, in order to detect silent activity before irreversible disability builds. They also recommend that clinical trials include cord lesion burden and atrophy as endpoints, especially in progressive disease where cord pathology drives much of the clinical picture. The evidence base still relies heavily on small, single-centre, cross-sectional studies with inconsistent imaging methods, and most advanced biomarkers remain confined to research. Even so, the trend is unmistakable: the spinal cord is moving from the margins to the centre of MS care, and better imaging may change how the disease is diagnosed, followed and treated.

Subject of Research: Spinal cord MRI biomarkers for diagnosis and progression monitoring in multiple sclerosis

Article Title: Spinal cord imaging in multiple sclerosis: from diagnosis to disease progression

Article References: Spinal cord imaging in multiple sclerosis: from diagnosis to disease progression. (n.d.). https://doi.org/10.1007/s00415-026-14122-3

Image Credits: AI Generated

Keywords: multiple sclerosis, spinal cord, MRI, spinal cord atrophy, McDonald criteria, progression independent of relapse activity, demyelination, magnetisation transfer, diffusion MRI, myelin water imaging, artificial intelligence, disease-modifying therapy