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Difficult Neurologic Cases

 

Some horses with equine protozoal myeloencephalitis (EPM) resolve their issues with treatment, these cases are simple.  Some horses continue to have gait problems that span years, they “relapse” year after year.  These are complex cases.  One common strategy is to treat the EPM-suspect horse and see what happens.  If the horse fails on treatment or “relapses” some suggest that the relapses “must reflect either new infections or reactivation of latent  infections” (MacKay 2008).

The comments about treating relapses states: “there is no obvious rationale for using a different drug to treat recrudescent EPM than was used to treat the primary presentation.  In my (MacKay) experience, regardless of the drug used, the response to treatment of each successive relapse is incrementally less complete.”  This approach leads veterinarians to extend the course of therapy, use higher doses of the same therapy, combine antiprotozoal, switch from one approved drug to another, institute “maintenance” antiprotozoal drug therapy…

Complex neurologic cases may be difficult to treat, not due to a lack of treatment effectiveness, but rather a lack of understanding of the pathogenesis of disease and the the drugs that should be used for the disease process.  Treatment response is a part of elucidating the disease in horses.Testing is critical to understanding what the disease process is in the horse.

Diagnosis of EPM is difficult and it is common knowledge that there are no “EPM” tests.   EPM is a syndrome that involves protozoal infection and signs that result from Sarcocystis-associated  infection.  An antibody test that detects protozoa won’t diagnose the inflammatory component of disease.  The presence or absence of antibodies can rule in or rule out the involvement of Sarcocystis. The inflammatory processes can linger long after the horses immune system resolved the active infection.  Inflammation makes EPM complicated to detect and treat.  The inflammatory process is not detected by circulating or CSF antibodies.

We are piecing together puzzling aspects of neuromuscular disease in horses and can help you understand some of those difficult cases.  Important aspects to consider are the presence/absence of Sarcocystis neurona antibodies, the serotype of the S. neurona infection, the host’s inflammatory response to protozoal infections, the presence of Sarcocystis fayeri toxins in horses, autoimmune antibodies, and the pharmacodynamics of treatment on both the horse and the parasites.

Published data clearly showed the clinical difference between the S. neurona challenged immune-competent horse and the S. neurona challenged immune-deficient horse.  Immune-competent horses cleared parasites from the blood and suffered clinical signs of disease.  The immune-deficient horses were unable to clear the parasitemia and surprisingly, did not show any signs of disease (Sellon 2004)! One take home message was that immune cells were involved in parasite clearance as well and clinical signs.  Interestingly, the immuno-competent horses did not have parasites that could be recovered indicating the parasites were eliminated.  Parasites were recovered from the immune-deficient horses. Understanding disease involves animal models, these horse experiments show the immune system impacts the results of infection. We have a disease model that makes a normal horse act like an immune-deficient horse and that helps us understand the disease processes and the effects of some treatments.

Another telling experiment showed that anti-protozoal drugs can delay the production antibodies--but not prevent disease (Furr).  The message is that antibodies are not a measure of disease, but they are a method to associate disease to a particular organism.  Horses on “maintenance” doses of antiprotozoal drugs may test negative for antibodies yet have treatable disease.  One reason that antibodies are decreased (or delayed) is that some anti-protozoal drugs alter the protozoa’s expression of antigens that are used as markers in antibody tests. Using antiprotozoals to prevent antibody production is not a rational approach to preventing “EPM”.

A recent topic is the contribution of Sarcocystis fayeri to neuromuscular disease in horses.  Previously S. fayeri was considered a common and benign muscle infection in horses.  Researchers at UC Davis and Pathogenes believe that Fayeri may not be so benign. The UC Davis group associated a slight increase in muscle cysts in horses with neuromuscular disease (over the number of cysts found in clinically normal horses) while we associated neuromuscular disease with inflammation and S. fayeri antitoxin.

We have determined that autoimmune antibodies, not detected by S. neurona antibody assays, are present in some “relapse” horses.  These horses are not effectively treated with antiprotozoal drugs.  They respond to judicious use of steroids.  It is this disease process that showed us the obvious rationale for using a different drug to treat recrudescent EPM than was used to treat the primary presentation.  Of course, testing and defining the presence of autoimmune antibodies is as critical as the proper treatment.

No doubt these additional conditions found in the “EPM” horse are rare.  In our experience these diseases account for 50% of the horses that are diagnosed with the rare condition EPM.  We assayed sera from 7601 horses with neuromuscular disease and found only 3745 were “EPM” suspect.  The other 3856 were clinically ill due to undetermined causes that included autoimmune disease and S. fayeri toxins.

In the past two years we have identified 195 horses with autoimmune disease that have not, and would not, respond to any antiprotozoal treatment protocol.  We also identified 121 horses presumably suffering from S. fayeri toxins.  These horses become worse with some antiprotozoal treatment protocols.

It is important to understand the components of equine neuromuscular disease and focus less on branding these cases as EPM.  When EPM is the correct diagnosis understanding the inflammatory component of the disease process is important because pathological inflammation goes hand-in-hand with infection.

Call us with questions, we are happy to share our approach with you.

 

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