ALS: Markers for Diagnosis and Prognosis Identified in BloodThe diagnosis of ALS is often made late due to numerous differential diagnoses. NFL is now a biomarker that can detect the disease in the blood.
Even for experienced physicians, patients with amyotrophic lateral sclerosis (ALS) can be difficult to diagnose. The multiple symptoms make it difficult to distinguish from other neurodegenerative diseases. ALS is a progressive neurodegenerative disease of motor neurons that leads to progressive paralysis and ultimately death by respiratory arrest.
Blood test facilitates differential diagnosis
In the meantime, there are promising therapeutic approaches that make early diagnosis all the more important. An international team of researchers with scientists from Ulm University Medicine. The University of Milan has now succeeded in facilitating the differential diagnosis with a blood test. The results of the study were published in the Journal of Neurology, Neurosurgery, and Psychiatry .
Test measures neurofilament concentration in blood
The German-Italian research group developed a test that indicates the concentration of neurofilaments (neurofilament light chain/NFL) in the serum of patients. NFL are proteins that form the scaffold of motor neurons and other nerve cells. If these neurons die during the course of ALS, NFL are released. The increasing concentration of NFL in the serum is detected by the test.
According to this test, an examination of the cerebrospinal fluid is not necessary. This fact makes the test also attractive for the investigation of larger cohorts in studies or for patients for whom a collection of cerebrospinal fluid is not possible.
Simoa technology allows detection of NFL
The new blood test is based on the so-called Single Molecule Array technology (Simoa). This technology is comparable to ELISAs and uses the same reagents, but is much more sensitive.
Study evaluates reliability of the test
The reliability of the test, which is designed to aid clinical, neurophysiological and imaging diagnosis, was investigated in the current study. The study involved 124 ALS patients and 159 controls. The control group included subjects with other neurodegenerative diseases, such as Alzheimer's and Parkinson's, as well as study participants without degenerative or inflammatory neural conditions.
Analyses showed that NFL concentrations were highest in the blood of ALS patients (exception: Creutzfeldt-Jakob disease). A differential diagnosis was thus possible. Through the comparative measurements with the control group, the scientists were also able to establish a diagnostic threshold for ALS.
This is around 62 pg/ml. If the NFL concentration is above this level, ALS is considered probable. The test differentiates with a sensitivity of 85.5% (95% CI, 78% – 91.2%) and a specificity of 81.8% (95% CI 74.9% – 87.4%) between ALS and non-ALS.
Test allows prognosis of the course of the disease
Besides, the measured NFL value correlates with the severity of the disease. "ALS patients with a higher NFL concentration in the blood experience a more rapid clinical deterioration and have a shorter survival time on average," according to Professor Markus Otto of the Ulm University Department of Neurology . The biomarker NFL can be measured shortly after the onset of the first symptoms, and it may also be possible to track the response to therapy with the help of the test, explains Professor Otto.
The researchers plan to conduct further studies to test the reliability of the new blood test in larger, multicenter cohorts and to introduce additional markers into the diagnostic process. This should make the laboratory diagnosis more specific. The research group from Ulm could already show that the biomarker NFL is suitable for early diagnosis in families with the inherited ALS-variant.