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

Christine Toedebusch, M. D. Bachrach, V. B. Garcia, G. C. Johnson, M. L. Katz, G. Shaw, J. R. Coates, M. L. Garcia

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)513-520
Number of pages8
JournalJournal of Veterinary Internal Medicine
Volume31
Issue number2
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

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Intermediate Filaments
Spinal Cord Diseases
cerebrospinal fluid
Cerebrospinal Fluid
Canidae
dogs
confidence interval
biomarkers
Dogs
Biomarkers
nervous system diseases
Confidence Intervals
ROC Curve
diagnostic techniques
Serum
enzyme-linked immunosorbent assay
Nervous System Diseases
Routine Diagnostic Tests
Cohort Studies
animals

Keywords

  • Amyotrophic lateral sclerosis
  • Biomarker
  • Dog
  • Neurodegenerative disease

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Cerebrospinal Fluid Levels of Phosphorylated Neurofilament Heavy as a Diagnostic Marker of Canine Degenerative Myelopathy. / Toedebusch, Christine; Bachrach, M. D.; Garcia, V. B.; Johnson, G. C.; Katz, M. L.; Shaw, G.; Coates, J. R.; Garcia, M. L.

In: Journal of Veterinary Internal Medicine, Vol. 31, No. 2, 01.03.2017, p. 513-520.

Research output: Contribution to journalArticle

Toedebusch, Christine ; Bachrach, M. D. ; Garcia, V. B. ; Johnson, G. C. ; Katz, M. L. ; Shaw, G. ; Coates, J. R. ; Garcia, M. L. / Cerebrospinal Fluid Levels of Phosphorylated Neurofilament Heavy as a Diagnostic Marker of Canine Degenerative Myelopathy. In: Journal of Veterinary Internal Medicine. 2017 ; Vol. 31, No. 2. pp. 513-520.
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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.",
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author = "Christine Toedebusch and Bachrach, {M. D.} and Garcia, {V. B.} and Johnson, {G. C.} and Katz, {M. L.} and G. Shaw and Coates, {J. R.} and Garcia, {M. L.}",
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AU - Toedebusch, Christine

AU - Bachrach, M. D.

AU - Garcia, V. B.

AU - Johnson, G. C.

AU - Katz, M. L.

AU - Shaw, G.

AU - Coates, J. R.

AU - Garcia, M. L.

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N2 - 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.

AB - 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.

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