Neuron-specific enolase enzymatic activity as a biomarker to discriminate neurologic and orthopedic gait abnormalities in dogs
Amy Huynh, Michael J Byron, Margret I Lenfest, Furkat Mukhtarov, Rubina Yasmin, Roy Cohen, Mark Rishniw, Alexander J Travis, Yael MerblAbstract
Background
The glycolytic enzyme neuron-specific enolase (NSE) shows high expression in neurons, generating interest as a diagnostic biomarker for neurologic diseases. However, assays measuring NSE protein concentration (NSE-p) have yielded inconsistent diagnostic results.
Hypothesis/Objectives
This was an observational study to investigate NSE enzymatic activity (NSE-a) as a biomarker in dogs to distinguish neurologic vs musculoskeletal causes of gait abnormalities. We hypothesized that NSE-a would be superior to NSE-p for detecting neurologic conditions.
Animals
Client-owned dogs presenting with gait abnormalities were enrolled as: (1) neurology service (n = 10), (2) orthopedic surgery and sports medicine and rehabilitation (SMR) (n = 21), and (3) control dermatology patients without gait abnormalities (n = 3). Inclusion required clinical examination by diplomates or residents of the relevant service and confirmed diagnoses based on radiography, ultrasonography, computed tomography, and magnetic resonance imaging.
Methods
Serum NSE-p was measured using validated commercial ELISA kits for use in dogs. Plasma NSE-a was quantified using an NSE functional activity assay (NSE-FA, TETmedical). A secondary experiment compared the techniques using plasma samples from dogs with neurological gait abnormalities.
Results
Neurologic dogs showed significantly increased plasma NSE-a (median, 0.372; IQR, 0.274-0.407) compared with orthopedic and SMR dogs (median, 0.212; IQR, 0.154-0.259; P = .001) and controls (median, 0.218; IQR, 0.15-0.226; P = .03). Direct comparison indicated that NSE-p fell below detection thresholds whereas NSE-a remained measurable.
Conclusions and clinical importance
Our results suggest that NSE-a is superior to NSE-p for differentiating neurologic from musculoskeletal gait abnormalities. Future research should explore its potential as a point-of-care biomarker for patients with suspected neurologic conditions.