Increased serum concentrations of neurofilament light chains (NFL), also known as neurofilament light polypeptides, are associated with poorer neurological functions, according to a large real-world study.
Neurofilaments (NF) are like mobile scaffolds for maintaining the structure of axons. Neuronal damage leads to the release of neurofilament components, which enter the cerebrospinal fluid (also known as CSF) and finally the blood. Elevated NF concentrations in cerebrospinal fluid have been described in the context of various Central Nervous System (CNS) diseases with severe nerve damage, such as traumatic brain injury, motor neuron diseases and multiple sclerosis.
Studies in recent years have shown that people with MS have higher levels of NF than people without MS, that levels are elevated after relapses and in relation to MRI lesions, and that the marker may help predict the severity of disease at onset. NF levels in CSF decrease after therapy with highly effective disease-modifying therapies (DMTs).1
The clinical benefit of a cerebrospinal fluid marker would, of course, be limited, since regular cerebrospinal fluid punctures would be necessary. A serum marker would be much better for both practitioners and patients. This approach has been strongly pursued by further work in recent years. In order to be used as a predictive marker, serum NFL must be tested in large, heterogeneous MS populations with different demographics and comorbidities. Real-life data presented at the 2019 ECTRIMS congress in Stockholm, the world's largest congress on MS, provided evidence that supports this concept.2, 3
"Serum NFL is developing into a strong biomarker candidate that correlates with disease severity" and shows "potential for use in disease monitoring and risk stratification," said Prof. Kathryn Fitzgerald of the Johns Hopkins School of Medicine in Baltimore, USA. She presented documented data from almost two thousand MS patients in 10 USA and European centers who took part in the so-called 'MS PATHS' program.3
A quarter of the MS patients studied (25%) had high serum NFL levels and these patients had significantly greater disability: Compared to MS patients with normal NFL levels, their walking speed was 10% slower, their manual dexterity (the speed at which coordinated hand and finger movements can be performed) was 7% lower and their cognitive processing speed was 8% lower. The impairment reported by the patients themselves was also higher.
The most common concomitant diseases were renal failure (38%), obesity (35%), hypertension (28%), hyperlipidemia (17%) and diabetes (6%). For diabetic MS patients, the probability of increased serum NFL was more than double. Prof. Fitzgerald, on the other hand, says the relationship between obesity and serum NFL levels is "complex and varies according to the degree of disability. No association was found with the other comorbidities studied. Since serum NFL increases with age, this was taken into account when establishing threshold values.
"The data confirm the evidence to date that NFL in peripheral blood is a promising candidate as a marker for disease burden in MS patients," summarises Prof. Fitzgerald. Further studies would have to address the question of whether other pre-existing conditions influence the relationship between NFL levels and MS outcomes in the long term.3
Sources:
1. Can blood neurofilaments be used to monitor disease activity? Multiple Sclerosis Research Blog (2017).
2. Serum neurofilament light chain is associated with MS outcomes and comorbidity in a large population of people with multiple sclerosis. ECTRIMS Online Library. Fitzgerald K. Sep 11, 2019; 279375; 23.
3. ECTRIMS2019 - Serum Neurofilament Light Is Potential MS Biomarker. Multiple Sclerosis. News Today / (2019).