Elevated levels of phosphorylated neurofilament heavy subunit in the cerebrospinal fluid of patients with lumbar spinal stenosis: preliminary findings

Abstract

Background contextThe phosphorylated neurofilament heavy subunit (pNfH) is an axon fiber structural protein that is released into the cerebrospinal fluid (CSF) after nerve damage. Although the previous studies have reported elevated CSF levels of pNfH in various neurological diseases, including amyotrophic lateral sclerosis, these levels have not been examined in patients with spinal stenosis. PurposeThe purpose of this study was to investigate the CSF levels of pNfH in patients with lumbar spinal stenosis (LSS) and to examine the relationship between CSF levels of pNfH and the severity of LSS. Study designThis is a prospective observational study. Patient sampleWe included consecutive patients with LSS who were undergoing myelography for preoperative evaluation. The CSF samples from patients with idiopathic scoliosis were used as the controls. Outcome measuresPhysiological measures: CSF levels of pNfH were measured using an enzyme-linked immunosorbent assay. The Zurich Claudication Questionnaire (ZCQ) and the Numerical Rating Scale (NRS) for sciatic pain were used to assess the clinical severity of LSS, and patients were grouped into tertiles according to their symptom severity and pain grading. Axial magnetic resonance imaging was used to evaluate the morphological severity of LSS, and patients were classified into three groups based on their morphological grading (using the CSF/rootlet ratio). MethodsAnalysis of variance was used to examine the relationship between the CSF levels of pNfH and the severity of LSS. ResultsThirty-three patients with LSS were included (13 men and 20 women and mean age 73.2 [range 58–88] years). Most patients (n=32) were positive for pNfH in their CSF (mean 1,344 [149–9,250] pg/mL), whereas all control subjects were negative for pNfH in their CSF. Regarding the association with clinical severity, patients in the third tertiles of ZCQ and NRS tended to have higher levels of pNfH compared with the other groups. There was no association between the CSF level of pNfH and the morphological severity of LSS. ConclusionsThis study detected elevated pNfH levels in the CSF of patients with LSS. Patients with severe clinical symptoms were more likely to exhibit high levels of pNfH. Our results indicate the potential usefulness of pNfH as a biomarker for compressive spinal disorders.