Update on Equine Protozoal Myeloencephalitis (EPM)
Veterinary research has come a long way in diagnosing and treating EPM. Here's what horse owners need to know.
Sarah E. Coleman |
January 6, 2016
In years past, a horse’s diagnosis of Equine Protozoal Myeloencephalitis, better known as EPM, left owners with a feeling of panic and foreboding as they worried they would watch their beloved equines travel down a path of neurologic issues sure to end in death.
While there is still no vaccine on the horizon, EPM doesn’t have to be considered a catastrophic illness. In actuality, if caught early and treated aggressively, horses with EPM may continue to have long competitive careers.
The Signs and Symptoms
Most horses affected by the disease have some ataxia (incoordination) with weakness, abnormal gaits and lameness; some will have muscle atrophy to go along with this. Other horses may have paralysis of the face or mouth, or abnormal sweating patterns. Other, more severe cases, may have an abnormal head tilt, or difficulty swallowing, others may have seizures and collapse.
The true difficulty with this disease is that it can mimic so many other health problems in horses and can hard to diagnose.
"The key is to know your horse well, so that you can identify any signs which deviate from normal,” stressed Dr. Clara Fenger of Equine Integrated Medicine in Georgetown, Ky. "Any change from normal for your horse might not be related to neurologic disease. They could represent early signs of lameness or any other disease, most of which are more readily treated if addressed early in the course of disease,” says Fenger.
Prevalence of EPM Diagnoses
"EPM diagnosis and treatment has gone through quite a few changes over the last two decades,” says Dr. Clara Fenger, "changing from the ‘diagnosis of the moment’ to a condition that is considered overdiagnosed at every turn. In my personal practice, the prevalence has been remained stable over the last 20 years.”
Fenger believes that the condition is "simultaneously over and underdiagnosed, probably because the signs can be subtle and are easily confused with other difficult-to-diagnose diseases.”
Dr. Fenger one of the world’s foremost authorities on all things EPM. Fenger graduated with her veterinary degree from the University of California at Davis in 1988, and after briefly practicing in California, she went on to an Internal Medicine residency and Master’s Degree program in Equine Exercise Physiology at the Ohio State University.
EPM captured her interest during her study of equine Internal Medicine, and led her to pursue a Ph.D. studying EPM at the University of Kentucky. It was Dr. Fenger's groundbreaking research that identified the opossum as the definitive host and source of infection for horses affected with this debilitating protozoal infection. During her graduate studies at UK, she developed a passion for the sport of horse racing, and currently practices in Central Kentucky specializing in Thoroughbred and Standardbred racehorses, as well as other performance disciplines. She owns Thoroughbred racehorses at her Spooky Hollow Racing.
When Fenger began her Ph.D. research in the 1990s, the standard procedure for EPM diagnosis was:
- Thorough physical and neurologic examination
- Cerebrospinal fluid sampling (CSF or spinal tap), with complete cytologic (cellular) analysis, and testing for EPM antibodies by Western Blot
- Ruling out other conditions, including Wobbler's Disease, Equine Herpes Myelitis, Equine Degenerative Myelopathy, Equine Lower Motor Neuron Disease, aberrant parasite migration, or odd lamenesses such as sacroiliac arthritis.
"The reasons for such expensive and comprehensive diagnostics were that EPM was considered a relatively rare disease and the treatment was expensive and prolonged,” Dr. Fenger explains. "The cost of the pyrimethamine (Daraprim(R)) [the standard treatment for EPM at the time] alone was $800 a month and the treatment stretched on for 6 to 8 months.”
A Shift in Diagnosis
As compounded pyrimethamine and sulfa became a standard treatment, the cost of the medication dropped to a range of $200 to $300 per month and even less in recent years. At the same time, the veterinary community began to understand that EPM was by far the most common cause of neurologic disease in young horses, Fenger notes. When this happened, the approach to diagnosis started to shift to a more affordable and less-invasive method.
Added to this was the gradual recognition that false positives on the CSF Western Blot EPM test were not uncommon, explains Fenger. The expensive diagnostic approach to EPM changed to diagnosis by response to therapy.
"Simply put, if the horse was treated for EPM, and he/she improved in clinical signs, then it must be EPM,” says Fenger.
"This approach is very useful in most cases, but can also be fraught with its own problems,” Fenger adds. "Occasionally, simply treating a horse for EPM might delay treatment for a different disease, and this possibility must be considered every time diagnostics are deferred or declined.”
It has also been discovered that there are two different protozoa that cause EPM. "The predominant protozoa implicated in EPM is Sarcocystis neurona, but a second, less common but closely related protozoa has also been identified: Neospora hughesi. Neospora only represents about 7 percent of EPM cases, but the clinical signs are essentially identical,” explains Fenger.
Though the protozoa that cause the disease may be different, treatment of EPM caused by either of them remains the same.
In addition to hands-on, physical tests for EPM, blood tests have been developed to identify exposure for both EPM-causing protozoa. That being said, the spinal tap test has also improved dramatically over the last few years. To date, the most accurate EPM test is the CSF/serum ratio test, which identifies horses that are actively producing EPM antibodies within the central nervous system.
What We Learn from EPM Tests
The different testing options offer different information, says Fenger. The original testing method was testing by Western Blot. "The pattern and intensity of reactivity of the horse serum on the blot would then be interpreted against a known positive horse to determine if the horse has antibodies to EPM.”
ELISA and IFAT testing report a "titer" or relative strength of the response, which can denote a specific strain of EPM.
Regardless of which test you run, Western Blot, ELISA or IFAT, blood tests only provide evidence of exposure, not infection. A blood test can only reflect exposure to the protozoa, and not clinical disease.
The most promising test for an actual, true diagnosis of EPM is the use of the CSF/serum ratio test. This is the only test that identifies actual production of antibodies in the central nervous system in response to local presence of protozoa.
Physical Testing: A Non-Invasive Option
If you choose not to run any blood or serum tests, there are still ways your vet may make a more-specific diagnosis. Many vets will want to do these physical tests in addition to a blood or serum test, just to be sure that EPM is what is ailing your equine.
The hallmark of neurologic gait deficits is an irregularly irregular gait, says Fenger. "The lack of proprioception-the sense of position in space- leads to the horse not necessarily knowing where all of its limbs are at any point. He might drag toes or even stumble, not knowing to pick up the feet properly. Or, he may overreach, trying to overcompensate because the ground is not always where it should be.”
In an exam, Fenger listens to the sound of the hoof beats on the hard ground, listening for irregular footfalls. Lameness is usually characterized as a single hoof beat that is fainter than the others. Neurologic gait deficits will have an irregular pattern.
Another test she will perform involves raising the horse’s head. When a horse's head is raised, the proprioceptive receptors in the neck, and the visual horizon, which an uncoordinated horse may use to compensate, are removed. Often, horses that compensate really well for neurologic disease will fall completely apart when they are walked with their heads raised. They may pace, or develop a lateral walk, which results from the decoupling of the signals that travel from the front legs to the back legs. They may develop a markedly irregular footfall pattern, and they may start to markedly overreach with their front limbs to compensate for losing their compensation mechanism. Each of these abnormal ways of traveling will indicate to Fenger that something is neurologically awry.
"Possibly the most sensitive test of proprioception and coordination in horse is the 5 meter circle,” Fenger explains. "Turning in a small, but forward, circle, such as a 5 meter circle, the hind limbs should travel in an arc which matches the size of the circle. In the ataxic horse, the limbs continue on a tangent to the circle, missing the signal that the horse is turning. Then, because the leg is attached to the horse, it will be pulled toward the body, almost involuntarily in an exaggerated arc. This is called circumduction, and can be anywhere from a subtle abnormality to an impressive swinging outward of the outside hind leg.”
Additional tests include walking on hills to assess normal foot placement going up and down, or walking up and down a curb or over cavaletti. The normal horse may hit the cavaletti once, but the ataxic horse, unable to tell his legs how high to lift, may stumble repeatedly over simple obstacles like this. Additional parts of the neurologic exam include testing for weakness, sensation, cranial nerves and conscious proprioception.
"Response to therapy [treating the horse without a definitive diagnosis] is certainly a legitimate diagnostic approach, but it is not without its drawbacks,” Fenger explains. "There are many conditions, such as Herpes Myelitis, which may improve on their own, regardless of what else is done. Additionally, some conditions may wax and wane, such as Wobbler's Disease, leading the horse owner to assume that any improvement is the result of the treatment.”
"FDA-approved medications on the market for EPM are ReBalance (PRN Pharmaceuticals(R)), Marquis (Bayer (R)), and Protazil (Merck (R)). ReBalance is the FDA-approved equivalent of the original pyrimethamine/sulfa combination used for EPM, which has been used successfully in compounded form for at least 20 years. This is a very affordable option for treating EPM, but needs to be used for a number of months, which has led to horse owners looking for alternatives,” says Fenger.
Marquis (ponazuril) was the first FDA-approved medication available for EPM, and is still widely used. The most recent addition to this roster of EPM meds is a related drug, diclazuril, sold under the name Protazil.
It is worth noting here that all medications approved for EPM treatment are not one-shot cure-alls; if the protozoa are not completely eliminated by the full course of treatment, affected horses can have an EPM relapse when exposed to stress of some kind, whether that be showing, shipping, a change in routine or other environmental stressors.
Fenger explains that there is no shortage of medications and combinations of medications that are compounded for EPM. One which has gained momentum of late is the combination of Decoquinate and Levamisole. Levamisole is used to stimulate the horse’s immune system. Decoquinate is used to prevent intestinal infection with coccidia in poultry, and it has most of its effect locally in the intestines.
Potential Treatment Issues
Because of the problems with non-FDA approved medications, it’s always recommended to use FDA-approved medications where possible, Fenger notes. "I have yet to see any data compiled convincingly on the Decoquinate product, and it is a compound that is minimally absorbed, making it highly unlikely to achieve levels high enough in the central nervous system to be effective against EPM.”
So why would horse owners use this drug? "The allure of a 10-day treatment for EPM attracts many horse owners, but with the lack of data to support the use of this medication… the use of this product only delays appropriate treatment, which is a great disservice to the horses.”
Another complication of EPM treatment without definitive diagnosis is that the treatment can be overused, even in horses that do not exhibit signs of EPM. In Thoroughbred racing, some trainers put all their 2-year-olds in training on Marquis; they feel that this is a "preventative” measure that will help the horse not contract EPM, not realizing that what they could do is to making EPM-causing protozoa resistant to the effect of the medicine.
EPM, like any other infections disease, is completely treatable, notes Fenger. The biggest reason she sees why horses do not respond to treatment is that they simply do not have EPM. "The key is to treat the horse and stick with the treatment,” she explains. "Promises of shortcuts … are just promises, and are the protocols which result in horses needing lifelong treatment.”
Sarah Coleman has had two of her show horses diagnosed with EPM, and has been lucky enough to have Dr. Fenger work on each of them. Both her old campaigner and young prospect returned to the show ring with minimal ill effects from the disease, proving that due diligence and a wonderful veterinary team are key to early diagnosis and treatment.
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Update on Equine Protozoal Myeloencephalitis (EPM)