Earlier detection of multiple sclerosis may mean better treatment options. A diagnostic test for nerve molecules should enable early detection of MS flare-ups.
Multiple sclerosis, or MS for short, is a disease that strikes people early in life and usually without warning. It devastates many people’s life plans.
What’s more stressful about the nervous disease is that it’s impossible to predict when the disease will become more active in the coming years and when the typical symptoms will reappear: blurred vision, arm and leg coordination problems, tingling or burning on the skin, rapid fatigability, or incontinence.
Neurofilaments in the blood should close this diagnostic gap, allowing for early detection.
Nerve cells’ skeleton is made up of proteins, which act as disease indicators in this circumstance. When nerve cells die as a result of an MS flare-up, the body breaks down the remaining cells swiftly. A portion of the neurofilament known as the light chain, on the other hand, does not dissipate as quickly and may thus be measured in the blood.
A study conducted in Switzerland and Sweden suggests that neurofilaments may be used to improve disease prediction. This would allow the therapy to be adjusted as necessary. After all, MS affects approximately one million people in the United States, with 200 new cases diagnosed every week.
The researchers used more than 10,000 blood samples from 5,390 healthy persons to identify neurofilament limit ranges and generate so-called percentile curves, which are similar to growth curves for children. The concentration of neurofilaments is affected not only by age but also by body weight.
The values in the blood samples of 5654 MS patients were determined in a second stage. The researchers wanted to see if neurofilament levels may signal whether or not the disease was growing more aggressive.
When interpreting the personal situation of the patient is also decisive
In fact, higher neurofilament counts were seen in both patients who had recently relapsed and those who had a higher degree of disability, and more damage in the brain was detected by magnetic resonance imaging (MRI) – all indicators of higher disease activity.
The neurofilament values were also an indication of how well the different MS medications worked. In those patients treated with potent antibodies over an average of 5.6 years, neurofilament counts returned to the normal range. Therapy with moderately effective tablets also caused the values to drop, but not as much.
With the weak-acting interferons and glatiramer acetate, the levels fell in the first year but then rose again and ended up being almost as high as in patients who had not received any therapy.
How meaningful the neurofilaments are, however, also depends on the personal situation of the individual patient. The marker shows very specifically that nerve cells have perished, but not why. Elevated values were then also detected in various other neurological diseases, such as dementia, stroke, brain injuries or Parkinson’s.
“If I see high neurofilament values in an MS patient and he tells me that he has had a stroke or works as a professional boxer, the neurofilaments cannot be interpreted at the time,” says Jens Kuhle, head of the MS center at the University Hospital Basel and Lead author of the new study.
Even if the patient has diabetes, you have to be careful with an interpretation. Because diabetes can also cause the neurofilaments to increase, presumably due to diabetes-related damage to the nerves. In this case, an intensification of diabetes therapy would make sense. In many cases, however, the value can help with therapy decisions, says Kuhle.
For example, when the disease appears to be getting worse but imaging shows little or no change. If the neurofilaments were in the normal range in such a case, he would advise waiting and checking. However, if the value were above the statistically critical value, the so-called 90th percentile, he would advocate treatment with a stronger drug.
So this study cannot yet give the green light for blood-based early detection of an MS flare-up. In retrospective studies like this one, in which the connection between neurofilaments, disease signs and effectiveness of the therapy was shown afterwards, causal connections cannot be proven.
A prospective, randomized study would be more meaningful in which the neurofilaments are regularly determined in some of the patients, not in some at the moment, and then in the months and years that follow how the disease progresses.
MRI not dispensable
Bernhard Hemmer, Director of Neurology at the Technical University in Munich, is critical: “Before the value can be included in the routine, it must first be validated and it must be ensured that different laboratories deliver the same result.”
The proof that the neurofilaments are more informative than the imaging in the MRI.
“We can see changes very clearly in the images as an indication of increased disease activity, and these are then also specific to MS,” says Hemmer.
In any case, one cannot do without an MRI in certain cases. For example, if a patient suddenly can no longer move his leg well. This could be a new attack, but also a small stroke. In both cases, the neurofilaments would increase.
“If I do without an MRI in such a case and give stronger medication because I suspect a flare-up, I will miss the stroke and run the risk of unnecessary side effects,” adds the neurologist.
It is similarly difficult to assess when a patient has a Virus infection of the brain sick. This can also be similar to an MS attack and cause the neurofilaments to increase, so here too the question is whether the increase is caused by a new MS attack or by the viral infection.
“That would be fatal, because the antibody drugs against MS could drive the virus disease forward,” says Hemmer.
He sees the neurofilaments more as an upstream marker for the MRI.
“If the value is normal and the patient has no symptoms, we could wait and maybe do the MRI for a year,” he says.
Conversely, if the neurofilaments were increased in a check-up, he would immediately check with an MRI.
Under no circumstances would he make therapy decisions based solely on neurofilaments.
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