Cerebrospinal Fluid Levels of Phosphorylated Neurofilament Heavy as a Diagnostic Marker of Canine Degenerative Myelopathy

Abstract

Background No definitive, antemortem diagnostic test for canine degenerative myelopathy ( DM ) is available. Phosphorylated neurofilament heavy ( pNF ‐H) is a promising biomarker for nervous system diseases. Hypothesis/Objective Cerebrospinal fluid ( CSF ) and serum pNF ‐H is a detectable biological marker for diagnosis of canine DM . Animals Fifty‐three DM ‐affected, 27 neurologically normal, 7 asymptomatic at‐risk, and 12 DM mimic dogs. Methods Archived CSF and serum pNF ‐H concentrations were determined by a commercially available ELISA . A receiver‐operating characteristic ( ROC ) curve was generated with CSF values. Results Compared with old control dogs, median CSF pNF ‐H concentration was increased in all stages of DM ; old dogs 5.1 ng/mL (interquartile range [ IQR ] 1.4–9.3) versus DM stage 1 23.9 ng/mL ( IQR 20.8–29.6; P < .05) versus DM stage 2 36.8 ng/mL ( IQR 22.9–51.2; P < .0001) versus DM stage 3 25.2 ng/mL ( IQR 20.2–61.8; P < .001) versus DM stage 4 38.0 ng/mL ( IQR 11.6–59.9; P < .01). Degenerative myelopathy stage 1 dogs had increased median CSF pNF ‐H concentrations compared with asymptomatic, at‐risk dogs (3.4 ng/mL [ IQR 1.5–10.9; P < .01]) and DM mimics (6.6 ng/mL [ IQR 3.0–12.3; P < .01]). CSF pNF ‐H concentration >20.25 ng/mL was 80.4% sensitive (confidence interval [ CI ] 66.09–90.64%) and 93.6% specific ( CI 78.58–99.21%) for DM . Area under the ROC curve was 0.9467 ( CI 0.92–0.9974). No differences in serum pNF ‐H concentration were found between control and DM ‐affected dogs. Conclusions and Clinical Importance pNF ‐H concentration in CSF is a sensitive biomarker for diagnosis of DM . Although there was high specificity for DM in this cohort, further study should focus on a larger cohort of DM mimics, particularly other central and peripheral axonopathies.