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Neurofilament light chain as a biomarker of meningoencephalitis of unknown etiology in dogs - PubMed

. 2021 Jul;35(4):1865-1872.

doi: 10.1111/jvim.16184. Epub 2021 Jun 10.

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Neurofilament light chain as a biomarker of meningoencephalitis of unknown etiology in dogs

Taesik Yun et al. J Vet Intern Med. 2021 Jul.

Abstract

Background: Neurofilament light chain (NfL) is a neuron-specific cytoskeletal protein expressed in axons. Damaged axons of the central nervous system release NfLs into the cerebrospinal fluid (CSF) and the blood. In humans with neurologic diseases, NfL is used as a biomarker.

Objectives: To identify the potential of NfL as a supportive tool for the diagnosis, prognosis, and monitoring of meningoencephalitis of unknown etiology (MUE) in dogs.

Animals: Twenty-six client-owned healthy dogs, 10 normal Beagle dogs, and 38 client-owned MUE dogs.

Methods: Cohort study. The concentrations of NfL in serum and CSF were measured using single-molecule array technology.

Results: Median NfL concentration was significantly higher in MUE dogs (serum, 125 pg/mL; CSF, 14 700 pg/mL) than in healthy dogs (serum, 11.8 pg/mL, P < .0001; CSF, 1410 pg/mL, P = .0002). The areas under the receiver operating characteristic curves of serum and CSF NfL concentrations were 0.99 and 0.95, respectively. The cut-off values were 41.5 pg/mL (serum) and 4005 pg/mL (CSF) for differentiating between healthy and MUE dogs, with sensitivities of 89.19% and 90%, respectively, and specificities of 96.97% and 100%, respectively. The NfL concentration showed a significant decrease (pretreatment, 122 pg/mL; posttreatment, 36.6 pg/mL; P = .02) in the good treatment-response group and a significant increase (pretreatment, 292.5 pg/mL; posttreatment, 1880 pg/mL, P = .03) in the poor treatment-response group.

Conclusions and clinical importance: Neurofilament light chain is a potential biomarker for diagnosing MUE and evaluating response to treatment.

Keywords: MUE; MUO; NfL; cerebrospinal fluid (CSF); serum; single-molecule array (Simoa).

© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.

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Conflict of interest statement

Authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1

NfL concentrations in the serum (A) and CSF (B) samples of healthy dogs and dogs with MUE. A, There was a statistically significant difference in the serum NfL concentration between the healthy dogs (n = 33) and dogs with MUE (n = 37). B, There was a statistically significant difference in the CSF NfL concentration between the healthy dogs (n = 10) and dogs with MUE (n = 10). The horizontal bars show the medians and interquartile ranges from the first to the third quartile. The Mann‐Whitney U test. ***P < .001; ****P < .0001. CSF, cerebrospinal fluid; MUE, meningoencephalitis of unknown etiology; NfL, neurofilament light chain

FIGURE 2
FIGURE 2

ROC curve predicting MUE based on the concentration of NfL in serum (A) and CSF (B) samples of dogs. The thick diagonal line shows a 50% chance. A, The AUC of the serum NfL concentration was 0.99 (95% CI = 0.9676‐1.000). The point of intersection represents the optimal cut‐off value of 41.5 pg/mL for the differentiation of healthy dogs from dogs with MUE, with sensitivity and specificity of 89.19% (95% CI = 75.29‐95.71%) and 96.97% (95% CI = 84.68‐99.84%), respectively. B, The AUC of the CSF NfL concentration was 0.95 (95% CI = 0.8477‐1.000). The point of intersection represents the optimal cut‐off value of 4005 pg/mL for the differentiation of healthy dogs from dogs with MUE, with sensitivity and specificity of 90% (95% CI = 59.58‐99.49%) and 100% (95% CI = 72.25‐100.0%), respectively. AUC, area under the receiver operating characteristic curve; CI, confidence interval; CSF, cerebrospinal fluid; MUE, meningoencephalitis of unknown etiology; NfL, neurofilament light chain; ROC, receiver operating characteristic

FIGURE 3
FIGURE 3

Correlations between the NfL concentrations and the ratio of lesion volume to the entire brain volume in dogs with MUE (serum: A, n = 32, P = .14, r = 0.27; CSF: B, n = 7, P = .3, r = 0.46). Dotted lines represent the 95% confidence intervals. Spearman's rank test. CSF, cerebrospinal fluid; MUE, meningoencephalitis of unknown etiology; NfL, neurofilament light chain

FIGURE 4
FIGURE 4

Serum (A) and CSF (B) NfL concentrations in dogs with MUE depending on the presence of seizure. A, The concentration of serum NfL in MUE dogs with seizure (n = 22) was relatively higher than that in MUE dogs without seizure (n = 15); however, there was no significant difference. B, The concentration of CSF NfL in MUE dogs with seizure (n = 6) was relatively higher than that in MUE dogs without seizure (n = 4); however, there was no significant difference. The horizontal bars show the medians and interquartile ranges from the first to the third quartile. Mann‐Whitney U test. CSF, cerebrospinal fluid; MUE, meningoencephalitis of unknown etiology; NfL, neurofilament light chain

FIGURE 5
FIGURE 5

Alterations in serum NfL concentration posttreatment in dogs with MUE according to therapeutic response. A, There was a significant decrease in NfL concentration in the good treatment‐response group (n = 7) at 6 months after commencement of treatment. B, There was a significant increase in NfL concentration in the poor treatment‐response group (n = 6) just before death or euthanasia. Wilcoxon‐signed rank sum test. *P < .05. MUE, meningoencephalitis of unknown etiology; NfL, neurofilament light chain

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