Increased α‐tocopherol metabolism in horses with equine neuroaxonal dystrophy

Hales, Erin N.; Habib, Hadi; Favro, Gianna; Katzman, Scott A.; Sakai, R. Russell; Marquardt, Sabin A.; Bordbari, Matthew H.; Ming‐Whitfield, Brittni; Peterson, Janel; Dahlgren, Anna R.; Rivas, Victor N.; Ramirez, Carolina Alanis; Peng, Sichong; Donnelly, Callum G.; Dizmang, Bobbi Sue; Kallenberg, Angelica; Grahn, Robert A.; Miller, Andrew D.; Woolard, Kevin D.; Moeller, Benjamin C.; Puschner, Birgit; Finno, Carrie J.

doi:10.1111/jvim.16233

Cited by 8 publications

(24 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it seems likely that genetic factors are important, and recent work suggests that horses with eNAD might metabolize vitamin E abnormally, increasing susceptibility to disease 21. Although horses in our study frequently had vita-…”

mentioning

confidence: 65%

Clinical and histopathological features in horses with neuroaxonal degeneration: 100 cases (2017‐2021)

Brown,

Bender,

Johnson

2023

Veterinary Internal Medicne

View full text Add to dashboard Cite

BackgroundAdult horses with proprioceptive ataxia and behavior changes that have histologic lesions consistent with neurodegenerative disease have been increasingly recognized.Hypothesis/ObjectivesDescribe the history, clinical findings and histopathologic features of horses presented to a referral institution with neuroaxonal degeneration.AnimalsOne hundred horses with a necropsy diagnosis of neuroaxonal degeneration compatible with neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM).MethodsRetrospective study of horses presented to the University of Pennsylvania, New Bolton Center, between 2017 and 2021 with a necropsy diagnosis of eNAD/EDM.ResultsAffected horses had a median age of 8 years (range, 1‐22), and the majority were Warmbloods (72). Sixty‐eight horses had behavioral changes, and all 100 had proprioceptive ataxia (median grade, 2/5). Fifty‐seven horses had abnormal findings on cervical vertebral radiographs, and 14 had myelographic findings consistent with compressive myelopathy. No antemortem diagnostic test results were consistently associated with necropsy diagnosis of neurodegenerative disease. All 100 horses had degenerative lesions characteristic of eNAD in the brainstem gray matter, and 24 had concurrent degenerative features of EDM in the spinal cord white matter.Conclusions and Clinical ImportanceClinical and histopathologic findings in this large group of horses with neurodegenerative disease were most consistent with eNAD/EDM, but with a different signalment and clinical presentation from earlier descriptions. The increasing occurrence of neurodegenerative disease in horses and the safety risk posed emphasize the importance of focused research in affected horses.

show abstract

mentioning

confidence: 65%

Clinical and histopathological features in horses with neuroaxonal degeneration: 100 cases (2017‐2021)

Brown,

Bender,

Johnson

2023

Veterinary Internal Medicne

View full text Add to dashboard Cite

show abstract

“…Histopathologic features consistent with eNAD include axonal swelling and spheroids in the cuneate and gracile spinocerebellar tracts 1 . Recent advances have been made towards the antemortem diagnosis of the condition using biomarkers of axonal degeneration and metabolites of α‐tocopherol 9,10 . Phosphorylated neurofilament heavy (pNfH) has shown promise as a diagnostic aid for animals suspected of eNAD 9 .…”

Section: Introductionmentioning

confidence: 99%

Vitamin E depletion is associated with subclinical axonal degeneration in juvenile horses

Donnelly

Finno

2023

Equine Veterinary Journal

Self Cite

View full text Add to dashboard Cite

BackgroundPhosphorylated neurofilament heavy, a marker of neuroaxonal damage, is increased in horses with equine neuroaxonal dystrophy. However, the temporal dynamics of this biomarker during the post‐natal risk period are not understood.ObjectiveTo measure serum and cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile foals across the post‐natal window of susceptibility for equine neuroaxonal dystrophy.Study designCase–control in vivo experimental study.MethodsConcentrations of phosphorylated neurofilament heavy were measured using frozen serum and cerebrospinal fluid collected from 13 foals raised in a vitamin E deficient environment from 1 to 6 months of age. Four of these foals were produced by equine neuroaxonal dystrophy‐affected dams, developed clinical signs consistent with equine neuroaxonal dystrophy and had a diagnosis confirmed by histopathology. The remaining nine foals, produced by healthy mares, were vitamin E depleted and remained clinically healthy. An additional cohort of foals, produced by healthy mares, were supplemented with vitamin E (α‐tocopherol; α‐TOH) from birth and sampled similarly.ResultsSerum α‐TOH concentrations were significantly higher in vitamin E supplemented healthy foals. Serum phosphorylated neurofilament heavy concentrations did not differ significantly between groups at any time point. Cerebrospinal fluid phosphorylated neurofilament heavy concentrations increased with age in healthy vitamin E depleted foals (p < 0.001); an effect that was not observed in healthy vitamin E supplemented foals.Main limitationsA genetically susceptible cohort supplemented with vitamin E was not available for comparison.ConclusionWe demonstrate that vitamin E depletion may elevate cerebrospinal fluid phosphorylated neurofilament heavy in otherwise healthy juvenile foals by 6 months of age. We highlight an important cofactor to consider when interpreting cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile horses.

show abstract

“…2 Additionally, no definitive diagnostic test is available for the second most common cause of spinal ataxia, eNAD/EDM. 3 , 4 As such, definitive diagnosis in many cases of spinal ataxia can only be achieved by necropsy. Inability to accurately diagnose spinal ataxia antemortem is an important financial burden for horse owners, trainers, and insurance underwriters.…”

Section: Introductionmentioning

confidence: 99%

“…These imaging techniques are used primarily to exclude CVCM, but the poor sensitivity and presence of nonrelevant background lesions limit their utility 2 . Additionally, no definitive diagnostic test is available for the second most common cause of spinal ataxia, eNAD/EDM 3,4 . As such, definitive diagnosis in many cases of spinal ataxia can only be achieved by necropsy.…”

Section: Introductionmentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Increased α‐tocopherol metabolism in horses with equine neuroaxonal dystrophy

Cited by 8 publications

References 36 publications

Clinical and histopathological features in horses with neuroaxonal degeneration: 100 cases (2017‐2021)

Clinical and histopathological features in horses with neuroaxonal degeneration: 100 cases (2017‐2021)

Vitamin E depletion is associated with subclinical axonal degeneration in juvenile horses

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

Contact Info

Product

Resources

About