What are equine neuroaxonal dystrophy and equine degenerative myeloencephalopathy?
Equine neuroaxonal dystrophy (eNAD) and equine degenerative myeloencephalopathy (EDM) result from abnormalities of specific neurons in the brainstem and spinal cord. Research suggests that eNAD is the underlying basis for EDM, which is the more advanced form of the disease. Cases have been reported in many breeds and the incidence in closely related horses suggests a genetic basis. Studies have indicated an autosomal dominant mode of inheritance with incomplete penetrance. A causative mutation has not been identified, so there is currently no genetic test, but research is ongoing.
Although there is a genetic component, an environmental trigger in the form of dietary vitamin E deficiency during specific developmental stages is required for the onset of clinical signs. In particular, affected horses often have low vitamin E concentrations in the blood. Vitamin E is a biological antioxidant that helps maintain normal neurological function by limiting the damage caused by oxidative stress and free radicals. The best source of this nutrient is fresh green grass (when it is cut for hay, the vitamin E begins to degrade). Horses that do not have sufficient access to lush green pasture are often deficient in this essential mineral, which leaves them vulnerable to eNAD/EDM.
What are the clinical signs of equine neuroaxonal dystrophy and equine degenerative myeloencephalopathy?
The two conditions are clinically indistinguishable from one another. Clinical signs vary among horses, ranging from mild performance issues to severe debilitation, and often arise at a young age (6 to 24 months of age). In some cases, however, signs do not appear until middle age (5-10 years of age).
Clinical signs include ataxia (mild to severe gait abnormalities) on both sides of the body (symmetric), with horses consequently appearing uncoordinated and not knowing where to place their feet. They may have an abnormal stance while at rest, with their legs too close to one another or too far apart. They may have difficulty negotiating how to step up on hills or curbs, and lack coordination in tight turns while walking.
How are equine neuroaxonal dystrophy and equine degenerative myeloencephalopathy diagnosed?
Currently, the only way to definitively diagnose eNAD/EDM is by postmortem identification of lesions by examining the brainstem and spinal cord under the microscope. Antemortem eNAD/EDM diagnosis requires that a veterinarian rule out other possible causes for the neurological deficits such as cervical vertebral compressive myelopathy (CVCM) - also known as “wobbler” syndrome, equine protozoal myeloencephalitis (EPM), West Nile Virus, trauma, and equine herpesvirus-1 myeloencephalopathy (EHV-1/EHM). This may be combined with a history of neurological disease, low levels of vitamin E in the blood, and knowledge that the horse had limited access to lush green pasture.
A biomarker test has recently been developed at UC Davis to aid in antemortem diagnosis. The equine pNF-H phosphorylated neurofilament ELISA represents the first diagnostic antemortem testing available for eNAD/EDM. The test measures a biomarker of axon damage, phosphorylated neurofilament heavy subunit (pNF-H,) in serum and/or cerebrospinal fluid (CSF).
How are equine neuroaxonal dystrophy and equine degenerative myeloencephalopathy treated?
Once clinical signs of eNAD/EDM are observed, the progression of the neurological deficits can be slowed or halted through dietary vitamin E supplementation, but they cannot be reversed. Clinical signs of the disease typically stabilize on their own at approximately two years of age in most horses.
What is the prognosis for equine neuroaxonal dystrophy and equine degenerative myeloencephalopathy?
An ataxic horse is not suitable for riding. Since eNAD/EDM has a genetic basis, affected individuals are also not suitable for breeding. Affected horses with mild clinical signs may be kept as pasture pets, but those with severe clinical signs are often euthanized.
How can equine neuroaxonal dystrophy and equine degenerative myeloencephalopathy be prevented?
Since there is no effective treatment for eNAD/EDM, prevention is the best approach. If horses are not able to access fresh pastures year-round, vitamin E must be supplemented in their diet.
All vitamin E supplements consist of alpha(α)-tocopherol, the most biologically available isoform of vitamin E. The National Research Council (NRC) recommends a daily vitamin E supplement to be 1-2 international units (IU)/ kilogram of the horse’s body weight. A 1,000-pound horse would require 450-900 IU of supplementary vitamin E daily. However, it is important to test blood vitamin E levels before initiating a supplementation program. Some horses may require higher doses of supplementation than others, and it is difficult to tailor dosing without knowing a baseline vitamin E level. Healthy grazing horses maintain a blood vitamin E level between 3-4 µg/mL, so that is the target.
Historically, there was little concern associated with providing too much vitamin E. This was mainly due to the fact that most vitamin E supplements were not very well absorbed in the horse and the NRC levels were based on these synthetic vitamin E supplements. With newer formulations, however, excessive supplementation can occur. High dosages can lead to bleeding disorders, so it is critical to check blood vitamin E levels regularly to ensure the dose does not exceed the recommended range.
Not all vitamin E supplements are created equal. The first generation of supplements were termed “synthetic vitamin E”, in that they contained α-tocopherol (specifically dl-α-tocopherol, also called all-rac-α-tocopherol), the main antioxidant component of vitamin E, in all of its different chemical configurations. Later research demonstrated that only the “natural” form of vitamin E, or the one containing only one particular highly bioavailable configuration (d-α-tocopherol), was highly effective at increasing vitamin E levels in the blood of horses. Since then, additional alcohol-based vitamin E supplements, termed “water-dispersible,” have been developed for use in horses. These are the most effective of all vitamin E supplements in that the water-dispersible formulation is readily absorbed and the natural vitamin E quickly increases blood and tissue levels in most horses.
Horses in different conditions and different stages of life may require varying levels of supplementation. Additionally, dosing is based on the type of vitamin E formula used (synthetic powder/pellet, “natural” powder/pellet or “natural” water dispersible). After assessing baseline blood concentrations and identifying deficiencies, pregnant mares should be given 5,000 IU/day of the natural water-dispersible vitamin E and foals should receive 500 IU/day (i.e. 10 IU/kg as the foal grows) of the same product as soon as the foal is born to decrease the risk of eNAD. Blood levels should be checked frequently to ensure that they remain in the normal range. It is important for horse owners to discuss what level would be best for their horse with their veterinarian before implementing any supplements into their horse’s diet.
For more information:
Center for Equine Health Horse Report, Fall 2018: https://ceh.vetmed.ucdavis.edu/sites/g/files/dgvnsk4536/files/inline-files/Horse_Report_Fall_2018_web.pdf
UC Davis, Dr. Carrie Finno Laboratory: https://www.vetmed.ucdavis.edu/labs/finno-laboratory/equine-neuroaxonal-dystrophy-enad
Clinical signs of equine neuroaxonal dystrophy (video): https://www.youtube.com/watch?v=5q4L0v-vIiM
An Evening with Vet Med - Management Considerations for California Horses: https://ucdsvm.mediasite.com/Mediasite/Play/1fd1820ca7aa49078095c5741d8d456a1d
UC Davis Science and Climate blog: When in Drought: Horses and Vitamin E: https://climatechange.ucdavis.edu/what-can-i-do/when-in-drought-horses-and-vitamin-e/
Edwards, L.A., Donnelly, C.G., Reed, S., M., Valberg, S., Chigerwe, M., Johnson, A.L., Finno, C.J. 2021. Serum and cerebrospinal fluid phosphorylated neurofilament heavy protein concentrations in equine neurodegenerative diseases. Equine Vet J. 2021 May 9. doi: 10.1111/evj.13452. Epub ahead of print.
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