Neurofilaments support the differentiation of amyotrophic lateral sclerosis from degenerative cervical myelopathy

Abstract The differential diagnosis between degenerative cervical myelopathy (DCM) and early amyotrophic lateral sclerosis (ALS) is often clinically challenging; laboratory tests that support this distinction could be highly valuable. This study examined the concentrations of neurofilament light chain (NfL) and the phosphorylated neurofilament heavy chain (pNfH), in CSF and serum of carefully selected patients with DCM, spinal canal stenosis (SCS) and ALS, after exclusion of major neurological confounders. Patients were assigned to five groups according to MRI findings and ALS diagnosis. All patients were treated in the Department of Neurology, and were only included if a CSF or serum sample was available for retrospective measurement of neurofilaments. Z-scores were used for age-adjusted interpretation of NfL concentrations in CSF and serum. In addition, the albumin quotient (QAlb), as a marker for the integrity of the blood-CSF barrier, was investigated in the five patient groups. The levels of NfL and pNfH, including Z-score distributions, differed significantly. The groups with diagnosed ALS had elevated neurofilaments both in CSF and Serum. Comparison of neurofilament concentrations between patients with isolated spinal canal stenosis and patients with cervical myelopathy revealed no significant difference. The QAlb showed no clear correlation with elevated neurofilaments and provided limited value for differential diagnosis. In summary, we showed that NfL and pNfH in CSF and serum support the differential diagnosis of cervical SCS with and without myelopathy from ALS in carefully selected cohorts. However, since neurofilaments are not specific, they should be used in context with clinical assessment and imaging for individual diagnostic and treatment decisions.