Monitoring disease activity in individuals with multiple sclerosis, either to predict flare-ups or to check treatment response, might be done with a simple blood test that measures levels of a nerve protein, according to a new study from Norway.
The findings, which have now been published in the journal Neurology: Neuroimmunology & Neuroinflammation, are the work of Dr. Kristin N. Varhaug, of the University of Bergen in Norway, and her colleagues.
“Since MS varies so much from person to person,” says Dr. Varhaug, “and is so unpredictable in how the disease will progress and how people will respond to treatment, identifying a biomarker like this that can help us make predictions would be very helpful.”
MS develops when the immune system attacks healthy tissue in the central nervous system, which is a part of the body that includes the brain, spinal cord, and optic nerves.
In MS, immune attacks destroy the myelin sheath that protects the nerves, resulting in disruption to the electrical signals that they carry to and from the brain and the rest of the body.
Depending on which parts of the central nervous system come under attack, the symptoms can vary from person to person and vary at different times in the same person. In relapsing-remitting MS, the symptoms flare up unexpectedly and then go away. In progressive MS, they remain and gradually get worse.
Symptoms of MS may include: blurred or double vision; blindness; fatigue; muscle weakness; problems with balance and coordination; numbness and prickling sensations; dizziness; pain; tremors; speech impediments; hearing loss; paralysis; and difficulty remembering and concentrating.
Because doctors in the United States do not have to report new cases of MS to the Centers for Disease Control and Prevention (CDC), it is not easy to arrive at an accurate figure of how many people may be living with the disease nationwide.
Some estimates, based on research that was done before MRI scans were introduced to diagnose MS, suggest that there might be around 2.5 million people worldwide with MS, including an estimated 300,000–400,000 in the U.S.
Preliminary findings of a recent study, however, suggest that the numbers are much higher, instead proposing that there are around 1 million people in the U.S. living with MS.
The new study looks at a nerve protein called “neurofilament light chain” (NFL), which is shed into the cerebrospinal fluid that surrounds the brain and spinal cord when nerve cells and fibers are damaged.
It is, however, possible to detect even low concentrations of NFL in the bloodstream. Therefore, Dr. Varhaug and her colleagues wanted to investigate whether using blood levels of NFL might offer a suitable clinical way to monitor disease activity in relapsing-remitting MS.
Testing for an MS biomarker in blood samples would be preferable to taking samples of spinal fluid “as lumbar puncture is invasive and not appropriate for repetitive sampling and long-time follow-up,” they note.
They recruited 85 people with the relapsing-remitting form of MS and followed them for 2 years. During this time, they did not receive any treatment for 6 months and then received 18 months of treatment with interferon-beta 1a, which is given to MS patients to reduce flare-ups and slow buildup of brain lesions.
Over the 2 years of the study, the subjects also underwent various assessments of their condition, including disability status (scored at baseline and then every 6 months) and MRI scans (at baseline and then every month for 9 months, and then at the end of the first and second years).
The researchers collected blood samples from the participants at baseline and after 3, 6, 12, and 24 months. They measured levels of NFL in the samples and then used various statistical tools to compare them with the other assessments of disease activity.
The results showed that blood NFL levels were higher when the MRI scans showed new areas of damage in the brain known as T1 and T2 lesions.
The blood level of NFL was 37.3 picograms per milliliter in people with new T1 lesions compared with only 28 picograms per milliliter in people without new T1 lesions.
People with new T2 lesions had 37.3 picograms per milliliter of NFL in their blood compared with 27.7 picograms per milliliter in those without new T2 lesions.
The raised levels of NFL persisted for 3 months as new lesions developed. They then fell once the subjects began their treatment with interferon-beta 1a.
The statistical analysis calculated that for every 10-picogram per milliliter increase in blood NFL, there was a 48 percent raised risk of a new T1 and a 62 percent raised risk of a new T2 lesion.
The team also checked whether or not another protein, called chitinase 3-like 1 (CHI3L1), might also serve as a blood biomarker for MS. Raised levels of CHI3L1 have been found in several inflammatory conditions and studies have proposed it as a biomarker for MS.
However, in this study, the results showed that changes in “CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment.”
Summarizing the findings, Dr. Varhaug says that they found that levels of NFL “were higher when people had new disease activity and lower when they took medication to reduce the number of symptom flare-ups.”
“These blood tests could provide a low-cost alternative to MRI for monitoring disease activity.”
Dr. Kristin N. Varhaug