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

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.