A poor outcome for a horse with EPM demonstrates the complexity of this neurologic disease

Sarcocystis neurona, one of the protozoan parasites that causes equine protozoal myeloencephalitis (EPM), seen within an infected horse’s spinal tissue with associated inflammatory cells. | Courtesy Dr. Rebecca Ruby

Equine protozoal myeloencephalitis (EPM) results from the protozoan parasites Sarcocystis neurona or, less commonly, Neospora hughesi, invading the horse’s central nervous system (CNS). With S. neurona, horses become infected after ingesting the parasite’s sporocysts (the infective egglike stage of development) that contaminate the environment. The opossum is the definitive host and source of these infectious S. neurona sporocysts, which it passes in its feces.

“After a horse ingests the organism, it begins to multiply in the gut, as well as in vascular endothelial cells throughout the horse’s body,” explains Steve Reed, DVM, Dipl. ACVIM, an internal medicine specialist and shareholder at Rood & Riddle Equine Hospital in Lexington, Kentucky. “The organisms are often cleared by the immune system in most but not all horses. How the parasite winds up in the CNS in some horses remains unclear.”

Horses with EPM have neurologic deficits such as weakness, ataxia (incoordination), muscle atrophy (wasting), or cranial nerve deficits such as head tilt, depression, and facial paralysis. The exact clinical signs vary depending on the part of the brain or spinal cord the parasite damages. 

“Typically, the disease has an insidious onset, but some horses may present with acute neurologic deficits that may be severe from the outset,” says Reed.

Meet Magic

The case of Magic, a 6-year-old Belgian Warmblood gelding, demonstrates just how insidious EPM’s onset can be.

“Magic had already been diagnosed with EPM by the primary practitioner, and treatment had been initiated,” recalls Reed. “But the owners wanted to begin a rehabilitation program under direct veterinary supervision. The horse was therefore referred to me.”

Magic was Grade 4 out of 5 ataxic when Reed first assessed him, meaning the horse would fall or nearly fall while walking. Magic also had antibodies against S. neurona detectable in his bloodstream, which Reed says wasn’t surprising.

“It is common to find antibodies in many horses that live in states that have the definitive host, opossums,” he explains. “Reports indicate while 50% to 75% of horses have been exposed to the parasite, very few of those horses ultimately develop EPM. This means that only measuring a blood titer is not sufficient to make a confirmed diagnosis of EPM.”

To determine if the antibodies against S. neurona in the blood were truly indicative of EPM rather than simply exposure to the causative organism, the next step was to measure antibodies to S. neurona in the cerebrospinal fluid (CSF) that bathes the brain and spinal cord. Reed then calculated the blood serum-to-CSF antibody ratio.

“In this case the ratio was 6.25, which is strongly supportive of antibodies being produced by S. neurona located within the CNS,” Reed says. “Using this ratio is better than either the serum or CSF alone. In a validation study of 128 horses that had a post-mortem examination to confirm the cause of their spinal ataxia, the antibody ratio calculation provided the most accurate means of diagnosing EPM in affected horses.”

Another test used to diagnose EPM is an enzyme-linked immunosorbent assay (ELISA). “In all SN (serum neutralization) ELISA testing, surface antigens (1 through 6) can be examined,” says Reed. An antigen is a disease-causing substance that stimulates the immune system. “Some laboratories look at surface antigens 2, 3, and 4, while other labs look only at 1 or 1, 5, and 6. The University of California, Davis, also provides excellent service, and they use a different platform, the indirect fluorescent antibody (IFA). That test provides a titer and a likelihood ratio of whether a horse has EPM based on comparison to known confirmed cases.”

Based on clinical signs of severe ataxia and the high antibody ratio, Reed prescribed Magic a course of Marquis (ponazuril).

Treatment Options for EPM

Marquis is an FDA-approved treatment for EPM. It is one of the two triazines currently available and contains 15% ponazuril. The other approved triazine is Protazil, which contains 1.56% diclazuril. The only other FDA-approved treatment for EPM is ReBalance, a product containing a combination of sulfadiazine and pyrimethamine.

After two months on Marquis, Magic’s ataxia improved to Grade 3, and he showed less weakness, spasticity, and hypermetria (exaggerated limb movements). He could readily perform tight circling with relative ease, which had proved challenging prior to treatment. By the third month of treatment, Magic was classified as Grade 2 ataxic.

“We elected to discontinue the Marquis at that time, instead switching him to a combination of decoquinate and the immunomodulator levamisole,” Reed says. “Decoquinate is an antiparasitic drug similar to the one in Marquis, but in Magic’s case we elected to switch medications because it appeared the organism was very difficult to clear.”

He says in this case the horse’s particular strain of S. neurona might not have been sensitive to ponazuril. While Marquis is almost always his first choice, he adds, “we wanted to try all the antiprotozoal medications we could at that time.”

Although Magic remained bright and alert while on the decoquinate/levamisole combination, his clinical signs worsened. This prompted Reed to again prescribe Marquis for an additional six weeks. Magic improved to a point that he was being hand-walked and longed. The plan was to consider putting a rider on him if this improvement continued. To expedite the process Reed also prescribed Magic Protazil and vitamin E to be administered concurrently with the Marquis.

Magic made great progress over the subsequent eight weeks but continued to exhibit weakness and ataxia while transitioning from a trot to a walk and from a canter to a trot. Working those transitions heavily, Magic was finally at the point where he was exercising with a saddle and weighted dummy. Medications were discontinued except for a single dose of Protazil (1 mg/kg) once weekly.

Magic continued to progress over the next eight weeks, giving the owners hope he might be rideable again. Suddenly, however, Magic suffered a relapse, returning to Grade 4 ataxia. Despite medication, his condition failed to improve, and Magic was humanely euthanized.

Says Reed, “The published information on the FDA-approved medications indicate about 62% effectiveness; however, my colleagues and I think that if the testing was repeated with the tests we use today, the results would be closer to 70% or 75%.”

In Magic’s case, even prolonged therapy was ineffective and, while most horses are considered safe to ride following treatment, this goal did not come to fruition for his owners.

Take-Home Message

Many, if not most, horses are seropositive for S. neurona (have antibodies against the protozoa in their blood). This does not indicate infection or predict which horses will develop EPM. In fact, very few horses do: Only about 1% of seropositive horses have EPM.

“This case reminds us that in some parts of the United States EPM is one of the most common causes of ataxia and is the disease most often treated, regardless of the cause,” says Reed. “This case also shows that despite several good, effective medications, some horses, even with aggressive treatment, do not survive. This is why I always encourage early diagnostic testing followed by rapid initiation of treatment along with medications that support the immune system and enhance healing.”

He adds that vaccine development is under investigation, and selective administration of medications such as Marquis and Protazil might help prevent disease or recurrence of infection post-treatment. None of the current medications, however, are 100% effective.

“There is still room for development of another medicine to treat this and other protozoan infections,” says Reed.