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J Vet Intern Med. 2017 Mar;31(2):513-520. doi: 10.1111/jvim.14659. Epub 2017 Feb 10.

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

Author information

1
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO.
2
Division of Biological Sciences, Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO.
3
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO.
4
Mason Eye Institute, School of Medicine, University of Missouri-Columbia, Columbia, MO.
5
EnCor Biotechnology Inc, Gainesville, FL.

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.

KEYWORDS:

Amyotrophic lateral sclerosis; Biomarker; Dog; Neurodegenerative disease

PMID:
28186658
PMCID:
PMC5354061
DOI:
10.1111/jvim.14659
[Indexed for MEDLINE]
Free PMC Article

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