Signs of damage over time may not be needed for MS diagnosis: Study
Evidence of neurological damage in multiple areas, called DIS, likely sufficient
Evidence of neurological damage over time — known as dissemination in time, or DIT — may not be necessary to reach a diagnosis of multiple sclerosis (MS) for all patients, according to a report by U.K. researchers.
Traditionally, an MS diagnosis would typically require both DIT and DIS, or dissemination in space, which means there’s evidence of neurological damage in multiple areas of the central nervous system (CNS), comprised of the brain and spinal cord.
Findings from this new study — which involved more than 200 patients — indicate that for people who strongly meet DIS criteria, with signs of damage in at least four of the five CNS regions typically affected in MS, that criteria alone may be sufficient for a diagnosis.
“Using DIS alone could simplify the workup of patients with suspected MS,” the researchers wrote, noting that this could facilitate more prompt treatment for those found to have the neurodegenerative disease.
The study, “Investigating Whether Dissemination in Time Is Essential to Diagnose Relapsing Multiple Sclerosis,” was published in the journal Neurology.
Revisions already proposed to McDonald criteria for diagnosing MS
In MS, the immune system mistakenly launches inflammatory attacks on healthy parts of the CNS. Lesions, or areas of damage where these inflammatory attacks are occurring or have already occurred, are evident on MRI scans, which are commonly used in the diagnostic process.
For decades, reaching a relapsing MS diagnosis has relied on both DIS and DIT, which marked neurological damage across multiple time points. Under the most recent, 2017, revision of the McDonald criteria — a set of diagnostic guidelines for MS first developed in 2001 — DIS requires that MRI scans show lesions in at least two of four different CNS locations.
DIT, meanwhile, is usually confirmed by a second clinical attack, or by certain evidence of lesions developing at different points in time on MRI scans. The presence of oligoclonal bands (OCBs), antibodies reflective of CNS inflammation that are commonly seen in MS, can be used as a substitute for these other DIT criteria.
More recently, however, researchers have called into question the importance of DIT. Many patients exceed DIS criteria when first evaluated, with several lesions in different CNS regions, which clinicians believe could be enough to diagnose some people.
Importantly, the researchers noted, experts in 2024 proposed revisions to the McDonald criteria, aiming to help doctors make an accurate diagnosis at an earlier stage of the disease. The revisions also include the optic nerve, which transmits signals between the eyes and brain, as a fifth region for demonstrating DIS.
Once formalized, these revisions would not necessarily require DIT to be met as a diagnostic criteria.
In the study, the researchers looked at data from 244 patients, ages 16 and older, who were seen at a hospital in London for clinical symptoms typical of a first MS attack.
Baseline scans — a starting MRI obtained within three months of symptom onset — showed that two-thirds of patients met standard DIS criteria, with lesions in at least two of four regions. Specifically, 45% had lesions in at least three regions while 20% had lesions in all four. Slightly fewer than half of the patients (43%) had evidence of DIT on MRI or were positive for OCBs.
Over a mean follow-up of 11.2 years, 77% of the patients were diagnosed with MS under the 2017 McDonald criteria, with 49% having a second clinical attack and 70% showing new lesions on MRI scans.
Neurological damage over time likely not as critical as amount seen
In their report, the researchers explored the utility of using various DIS requirements alone for reaching a diagnosis without the need for evidence of neurological damage over time.
Requiring a greater number of involved DIS regions led to decreasing diagnostic sensitivity — the ability to positively identify all MS cases — but increasing specificity, or the ability to rule out cases that are not MS.
Sensitivity was 84% when two DIS regions were required, falling to 58% for three regions and 26% for four regions. Specificity, meanwhile, increased from 91% with two regions involved, to 98% with three regions and 100% when all four regions were affected.
When at least three regions were affected, it was nearly 100% certain that MS was present, known as a positive predictive value, or PPV. This more stringent DIS criteria had similar specificity and PPV as the 2017 McDonald criteria requiring both DIS and DIT or OCBs.
When also including the optic nerve as a fifth DIS region, the results showed a similar pattern, with sensitivity becoming lower with an increasing number of regions being required for reaching a diagnosis, but specificity increasing to 100% when four or five regions were required.
Altogether, “these findings suggest that DIS alone … seems sufficient to ‘rule-in’ MS,” the researchers wrote.
The team emphasized, however, that because the sensitivity of the test is relatively low, failing to meet the criteria does not rule out the neurodegenerative disease. Rather, it’s an indication that further follow-up might be needed.
These findings suggest that DIS [neurological damage in multiple areas] alone … seems sufficient to ‘rule-in’ MS. … DIT [such damage over time] … may not be necessary to confirm a diagnosis of MS.
From their findings, the scientists developed an algorithm via which a diagnosis can be made if a person has a first MS-like attack and exhibits MRI lesions in all four typical DIS regions. If that criteria isn’t met, a diagnosis can be reached if four of five regions, including the optic nerve, are affected.
Applying it, the researchers determined that 25%-40% of people with a first demyelinating event could be diagnosed with MS. For people who don’t meet the criteria based on DIS alone, additional evidence — in the form of DIT or OCB presence — would be necessary.
The researchers noted that the algorithm was developed using data specifically from adults with classic signs of relapsing MS. Its utility in other groups, including those with atypical disease presentations, primary progressive MS, or children, remains to be tested.
Overall, according to the researchers, “DIT … may not be necessary to confirm a diagnosis of MS in patients with typical clinical presentations and DIS in [at least] 4 regions, facilitating the application of the criteria in clinical practice and streamlining MS diagnosis.”
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