EPM Diagnosis and Treatment Recommendations

Have you ever wished you could pull all the scientific recommendations on equine protozoal myeloencephalitis (EPM) diagnosis and treatment together in one place? Done! At the 2009 American Association of Equine Practitioners Convention, held Dec. 5-9 in Las Vegas, Nev., one practitioner summarized the available literature on EPM diagnosis and treatment for a large crowd of equine veterinarians.

"Sarcocystis neurona (a species of protozoa) infection is the most common cause of EPM," began Amy L. Johnson, DVM, Dipl. ACVIM-LAIM, lecturer in clinical studies at the University of Pennsylvania. "This neurologic disease presents a diagnostic challenge to practitioners because many horses are exposed to the protozoa and clinical signs can mimic many other conditions. Treatment is also challenging because several medications are available and response to treatment is not consistent among horses."

Diagnosis

Diagnosing EPM in a live horse is challenging because no test is 100% accurate; the gold standard for diagnosis is finding the protozoan parasite in the spinal cord, which can only be sampled after the horse is euthanized. So for live horses, diagnostics include a complete neurologic exam, exclusion of other common neurologic conditions, and confirmation of exposure to S. neurona through analysis of serum (clear fluid portion of the blood) or cerebrospinal fluid (CSF, the fluid surrounding the brain and spinal cord).

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Dr. Amy Johnson talks about the challenges of diagnosing EPM.
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"If clinical signs cannot be attributed to lesions in one or more regions of the central nervous system (CNS), EPM should not be considered," Johnson advised. "However, EPM can mimic almost any neurologic disease and cause signs ranging from a single cranial or peripheral neuropathy to diffuse CNS dysfunction. Certain patterns, such as multifocal signs, mixed lower motor neuron and upper motor neuron signs (e.g., both muscle atrophy and spinal proprioceptive ataxia), and asymmetric signs are more commonly observed with EPM than other neurologic diseases."

Tests for EPM in live horses include the Western blot, indirect fluorescent antibody test (IFAT), and surface antigen-1 ELISA test (SAG-1 ELISA). All detect the presence of antibodies in the horse's serum or CSF, but keep in mind that a positive test on any of them does not necessarily mean the horse has clinical EPM. Antibodies just confirm that he has been exposed to S. neurona.

The Western blot test was the first one to be commercially available, and it has shown variable sensitivity for detecting S. neurona (accurate identification of positive horses is 80-89%, depending on the study cited) and variable specificity (accurate identification of negative cases, 38-71%). Thus, only a few positive horses will be missed, but more often negative horses will receive false positive results. Very low levels of blood contamination in a CSF sample can yield a false positive.

A modified Western blot test has shown better sensitivity and specificity results, but the study on it was very small and did not evaluate horses that had been exposed to the parasite, but were not clinically ill.

The IFAT has shown comparable sensitivity and better specificity, and it is less affected by blood contamination. However, evaluations of the IFAT share the modified Western blot evaluation issues of small numbers of positive cases evaluated. Also, this test might give positive results for the protozoa S. fayeri, which might or might not cause disease in the horse.

The newest test, the SAG-1 ELISA, has shown mixed results, depending on the study and population tested. The test looks for the presence of a particular surface protein of S. neurona, as its name implies, but not all strains express this particular protein. Thus, the test might be effective in detecting strains that express the SAG-1 protein, but it misses strains that do not. Therefore, false negative results (misdiagnosing horses that truly have EPM as being free of the disease) are common.

Treatment

"None of the available/approved treatments are obviously superior; all have shown about a 60% success rate in clinical trials," reported Johnson.

She explained that sulfadiazine/pyrimethamine combination (Rebalance), ponazuril (Marquis), and nitazoxanide (Navigator) medications are the approved treatments that have been commercially available, while diclazuril is approved for EPM treatment, but is not yet marketed. Navigator manufacture was discontinued in the spring of 2009, she noted.

Sulfadiazine/pyrimethamine interrupts folic acid metabolism, and this treatment is usually given for 90-270 days. It was successful at eradicating antibodies to the protozoa from CSF and/or improving neurological signs by at least two grades in 61.5% of horses in one study. Side effects can include fever, anemia, anorexia, depression, worsening of ataxia (incoordination), and abortion.

Ponazuril inhibits energy metabolism in the protozoa, and it is given for 28 days. The published study on its use found 62% of horses had at least one grade of improvement of neurological signs and/or no longer had antibodies to the protozoa in their CSF. Side effects are rare, but a few treated horses had blisters on the nose and mouth, skin rash or hives, loose stools, mild colic, and one horse had a seizure.

Nitazoxanide (no longer available) inhibits a step of anaerobic (without oxygen) energy metabolism in the parasite. Improvement of at least one grade in neurologic signs was seen in 57% of horses in one study and 81% in a second study that was "less stringent" in selecting affected horses. Adverse reactions can potentially be more significant with this medication, including the possibility of fatal enterocolitis (inflammation of the small intestine and colon) at the recommended dose. Milder adverse effects included fever, anorexia, and lethargy/depression.

Diclazuril's mode of action is unknown, but might be similar to that of the related medication ponazuril; it is also given for 28 days. In one study, 67% of affected horses improved by at least one neurologic grade and/or no longer had antibodies to protozoa in their CSF after treatment. Adverse effects observed might or might not have been due to diclazuril, and included laminitis and deteriorating neurologic status.

Recent research has investigated one more option, Johnson reported--that of toltrazuril sulfone or ponazuril given at a loading dose along with dimethyl sulfoxide (DMSO) to improve uptake of the medications. She noted that with this strategy, high levels of the medications show up in the CSF in about a day, possibly resulting in quicker action of the medications and a shorter duration of treatment/less risk of adverse effects.

"Prospective, randomized, blinded clinical trials would aid in assessing if one drug shows superior efficacy," Johnson concluded. "Based on reported side effects, ponazuril and diclazuril seem to have the fewest reported adverse effects."

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.

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