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

Yun, Taesik; Koo, Yoonhoi; Chae, Yeon; Lee, Dohee; Kim, Hakhyun; Kim, Soochong; Chang, Dongwoo; Na, Ki-Jeong; Yang, Mhan‐Pyo; Kang, Byeong‐Teck

doi:10.1111/jvim.16184

Cited by 11 publications

(33 citation statements)

References 34 publications

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“…Meningoencephalitis of unknown origin in dogs is a debilitating disease and, despite appropriate treatment, 25% to 33% of dogs die within a week of diagnosis 5,6 . Several studies have evaluated short and long‐term outcome in dogs with MUO, but all have focused on survival at different time points 5‐14 . The use of survival as an outcome measure for MUO patients is flawed because affected dogs often are euthanized, and owners may elect for euthanasia at different time points based on a variety of complex underlying factors including financial constraints, difficulties managing chronic disease and views on what constitutes acceptable quality of life.…”

Section: Introductionmentioning

confidence: 99%

Development of a reliable clinical assessment tool for meningoencephalitis in dogs: The neurodisability scale

Gonçalves

Maddox

Phillipps

et al. 2023

Veterinary Internal Medicne

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Background Meningoencephalitis of unknown origin (MUO) comprises a group of debilitating inflammatory diseases affecting the central nervous system of dogs. Currently, no validated clinical scale is available for the objective assessment of MUO severity. Objectives Design a neurodisability scale (NDS) to grade clinical severity and determine its reliability and whether or not the score at presentation correlates with outcome. Animals One hundred dogs with MUO were included for retrospective review and 31 dogs were subsequently enrolled for prospective evaluation. Methods Medical records were retrospectively reviewed for 100 dogs diagnosed with MUO to identify the most frequent neurological examination findings. The NDS was designed based on these results and evaluated for prospective and retrospective use in a new population of MUO patients (n = 31) by different groups of independent blinded assessors, including calculation of interobserver agreement and association with outcome. Results The most common clinical signs in MUO patients were used to inform categories for scoring in the NDS: seizure activity, ambulatory status, posture and cerebral, cerebellar, brainstem, and visual functions. The intraclass correlation coefficient (ICC) for prospective use of the NDS was 0.83 (95% confidence interval [CI], 0.68‐0.91) indicating good agreement, and moderate agreement was found between prospective and retrospective assessors (ICC, 0.71; 95% CI, 0.56‐0.83). No association was found between NDS score and long‐term outcome. Conclusions and Clinical Importance The NDS is a novel clinical measure for objective assessment of neurological dysfunction and showed good reliability when used prospectively in MUO patients but, in this small population, no association with outcome could be identified.

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Section: Introductionmentioning

confidence: 99%

Development of a reliable clinical assessment tool for meningoencephalitis in dogs: The neurodisability scale

Gonçalves

Maddox

Phillipps

et al. 2023

Veterinary Internal Medicne

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“…However, this approach remains laborious (a few biomarkers out of thousands of possible candidates are typically tested at one time on a small number of affected dogs), access to CNS tissue to compare circulating and in situ biomarkers is rare, and most markers lack specificity, as highlighted by Andersen-Ranberg et al ( 103 ). Since that review, five further studies ( 104 – 108 ) revisited blood neutrophil-to-lymphocyte ratio or various biomarkers that showed promise. In general, many biomarker comparisons have been made but few studies have examined sensitivity and specificity (rather than simple statistical tests of difference).…”

Section: Discussionmentioning

confidence: 99%

New insights into the treatment of meningoencephalomyelitis of unknown origin since 2009: A review of 671 cases

Jeffery

Granger

2023

Front. Vet. Sci.

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“Meningoencephalomyelitis of unknown origin” (MUO)—a collective term for a group of clinically-indistinguishable (but pathologically distinct) autoimmune diseases of the CNS—has become increasingly commonly recognized throughout the world. In the 1960s−1980s the focus was primarily on the pathological description of these conditions and, largely anecdotally, their response to glucocorticoids. The subsequent availability of magnetic resonance imaging for companion animals led to a focus on imaging characteristics and response of MUO to various immunosuppressive medications. Previous reviews have not found clear evidence of superiority of any specific treatment regimen. Here, we review outcomes in a further 671 dogs treated with various combinations of glucocorticoids and immunosuppressive drugs and reported since 2009, aiming to determine whether recommendations can be drawn from the material published during more recent decades. We observe that: (i) there is more complete information on outcome of MUO-affected dogs solely receiving glucocorticoids and these reports provide evidence to undermine the dogma that MUO inevitably requires treatment with glucocorticoids plus an immunosuppressive drug; (ii) there is far more information on the pharmacokinetics of cytarabine delivered by a variety of routes, revealing that previous dosing and duration of administration in dogs with MUO may not have been optimal; and, (iii) there is a large number of cases that could be available for entry into multi-institutional randomized controlled trials. Finally, we suggest new research avenues that might aid future clinical trials in MUO through improved understanding of etiological triggers and individual patterns of immune response, such as the impact of the gut microbiome, the potential of CSF flow cytometry, and the establishment of robust clinical scores for evaluation of treatment success.

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Section: Discussionmentioning

confidence: 99%

“…In dogs, use of this technology allowed for the quantification of NEFL in serum or plasma and CSF at picogram concentrations and showed promise as a diagnostic, prognostic, and treatment response biomarker. [26][27][28][29] In addition to NEFL, other proteins that are under evaluation as biomarkers in neurologic diseases of humans were detected. These included Dickkoph-1 (DDK1), an important inhibitor of WNT signaling.…”

Section: Discussionmentioning

confidence: 99%

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Cerebrospinal fluid and serum proteomic profiles accurately distinguish neuroaxonal dystrophy from cervical vertebral compressive myelopathy in horses

Donnelly

Johnson

Reed

et al. 2023

Veterinary Internal Medicne

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Background Cervical vertebral compressive myelopathy (CVCM) and equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) are leading causes of spinal ataxia in horses. The conditions can be difficult to differentiate, and there is currently no diagnostic modality that offers a definitive antemortem diagnosis. Objective Evaluate novel proteomic techniques and machine learning algorithms to predict biomarkers that can aid in the antemortem diagnosis of noninfectious spinal ataxia in horses. Animals Banked serum and cerebrospinal fluid (CSF) samples from necropsy‐confirmed adult eNAD/EDM (n = 47) and CVCM (n = 25) horses and neurologically normal adult horses (n = 45). Methods . A subset of serum and CSF samples from eNAD/EDM (n = 5) and normal (n = 5) horses was used to evaluate the proximity extension assay (PEA). All samples were assayed by PEA for 368 neurologically relevant proteins. Data were analyzed using machine learning algorithms to define potential diagnostic biomarkers. Results Of the 368 proteins, 84 were detected in CSF and 146 in serum. Eighteen of 84 proteins in CSF and 30/146 in serum were differentially abundant among the 3 groups, after correction for multiple testing. Modeling indicated that a 2‐protein test using CSF had the highest accuracy for discriminating among all 3 groups. Cerebrospinal fluid R‐spondin 1 (RSPO1) and neurofilament‐light (NEFL), in parallel, predicted normal horses with an accuracy of 87.18%, CVCM with 84.62%, and eNAD/EDM with 73.5%. Main Limitations Cross‐species platform. Uneven sample size. Conclusions and Clinical Importance Proximity extension assay technology allows for rapid screening of equine biologic matrices for potential protein biomarkers. Machine learning analysis allows for unbiased selection of highly accurate biomarkers from high‐dimensional data.

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

Cited by 11 publications

References 34 publications

Development of a reliable clinical assessment tool for meningoencephalitis in dogs: The neurodisability scale

Development of a reliable clinical assessment tool for meningoencephalitis in dogs: The neurodisability scale

New insights into the treatment of meningoencephalomyelitis of unknown origin since 2009: A review of 671 cases

Cerebrospinal fluid and serum proteomic profiles accurately distinguish neuroaxonal dystrophy from cervical vertebral compressive myelopathy in horses

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