- It can be difficult to differentiate between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) during diagnosis. A correct diagnosis is important as some MS treatments are harmful in NMOSD.
- Researchers funded by MS Australia found the profile of certain lipids (fats) in cerebrospinal fluid (CSF) are different between NMOSD and MS. This could be a useful method to distinguish between the two diseases during diagnosis.
- The researchers also found some lipids are strongly linked to the level of disability in MS and could be useful biomarkers for monitoring disease progression and assessing treatment effectiveness.
What do NMOSD and MS have to do with lipids?
Neuromyelitis optica spectrum disorder (NMOSD) is a neuroinflammatory disorder that is easily mistaken for MS in its earlier stages. A wrong diagnosis is a problem, as treating NMOSD with some MS treatments can make NMOSD worse. Measuring serum aquaporin-4 (AQP4) antibodies is the standard method of diagnosing NMOSD, but 20-40 per cent of people living with NMOSD are negative for AQP4 antibodies.
Myelin, the protective coating around nerves, is composed of 70-80 per cent of lipids (fats). Two such lipids are sphingolipids and cholesterol esters, which could potentially act as biomarkers (biological signs) for disease. The profile of lipids in cerebrospinal fluid (CSF) changes in people with MS as the disease progresses and may differ with other neurological conditions.
Given that myelin is composed primarily of lipids, it is hypothesised that demyelinating diseases such as MS and NMOSD would have different levels of lipids in CSF compared to other neurological conditions. Additionally, there are no validated lipid biomarkers that can track disease severity or distinguish between MS and NMOSD.
What did the researchers do?
MS Australia-supported researchers, Associate Professors Todd Hardy, Laura Piccio and Anthony Don from Charles Perkins Centre, Brain and Mind Centre and Concord Hospital, measured different types of lipids in the CSF of people with relapsing remitting MS, NMOSD, other inflammatory neurological diseases and non-inflammatory neurological diseases (NIND). They then compared these measurements across these different groups and analysed the lipids against disability levels, active inflammation in the brain and triggers of inflammation.
None of the participants were receiving treatment for their conditions.
What did the researchers find?
Published in the Journal of Neurology, Neurosurgery and Psychiatry, the study found that a large number of CSF lipids were significantly higher in people with NMOSD compared to people with MS or NIND. In particular, a combination of three sphingolipids were able to distinguish between NMOSD and MS with good accuracy. There were no differences in lipid profiles between people with MS or NIND.
Many of the lipids that could distinguish between NMOSD and MS/NIND also correlated with markers of inflammation.
Additionally, higher levels of cholesterol esters were associated with lower levels of disability in people with MS. In contrast, higher levels of inflammatory markers were associated with higher levels of disability.
No reliable association between active inflammation in the brain and CSF lipid profiles was found in people living with MS – this is an area that requires more study to confirm if there is a link.
Why is this important?
This study suggests that CSF sphingolipids may be useful way to distinguish between MS and NMOSD during diagnosis. This could help ensure people with NMOSD, who are often misdiagnosed with MS, are diagnosed correctly and obtain the correct treatment earlier.
Additionally, CSF sphingolipids and cholesterol esters show potential as biomarkers for monitoring disease progression and assessing treatment effectiveness in MS.
Additional research is needed to confirm these findings and to better understand how these can be integrated into clinical practice for improved outcomes.
