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Diagnosing an autoimmune reaction in a sidewinding horse can lead to effective treatment!  Pathogenes Testing Options

Sidewinder is a term that describes the clinical presentation of a horse with a unilateral weakness/hemiparesis causing the hind quarter to track either side of the front quarter. Cauda equina neuritis (CEN) is an uncommon condition in the horse clinically characterized by paresis/paralysis of the tail, rectum, and bladder and a loss of sensation in the sacral dermatome with a surrounding zone of hyperesthesia and can be seen in sidewinding horses. Frequently, CEN is associated with cranial nerve paralysis, hindquarter muscle wasting, and an abnormal gait.

The disease in sidewinders describes a syndrome with characteristic clinical signs, predictable outcomes, and no recognized necropsy findings.  It is termed idiopathic. Often clinical signs are due to peripheral and central nervous system (CNS) inflammation, central lesions may indicate the presence of encephalomyelitis. The inflammatory pathological lesions of CEN is similar to those described in allergic neuritis. Experimental allergic encephalitis (EAE) is an induced autoimmune disease of the CNS that is readily induced in many mammalian species by immunization with CNS tissues.

Horses with serum antibody to specific proteins correlate well with clinical and pathologically diagnosed disease and indicate the pathogenesis of disease is immune mediated. The purpose of our current investigation is to determine the presence of antibodies against specific proteins in serum of horses with a diagnosis of idiopathic encephalomyelitis that present with a sidewinding gait. Give us a call to see if your case qualifies for free testing.  We may have your sample on file if it was submitted within the last 6 months, if we tested your horse for S. neurona antibody, that was clinically a sidewinder, we will go back and run our new test on the saved serum.

Several things are important to us.  The degree of disease based on the modified Rostami scale (a number between 0 and 3).  The score is 0 = a normal animal; 1 = is mild (more than 5% weight loss and a flaccid tail; 2 = moderate; and 3= severe with paraplegia or tetraplegia; a typical sidewinding gait.  The distinction between a central and peripheral lesion that is causing the signs is an important factor in diagnosis and treatment expectations.  While there can be both central and peripheral lesions, we want to discriminate between the two populations of horses if a distinction exists.

Email us the answer to the following questions (give a numerical score for the first assessment; circle the presence of any other signs) :

  • Clinical assessment (numerical score)
  • Ataxic, gait anomaly, sidewinder
  • Weight loss
  • Signs attributable to central lesion
  • Behavior change
  • Muscle wasting: back muscles
  • Muscle wasting: gluteal
  • Muscle wasting: masseter muscles
  • Tail paresis
  • Urinary incontinence
  • Rectal dysfunction
  • Perianal analgesia
  • Cranial nerve neuropathy
  • Muzzle twist
  • Eye lid paresis
  • Facial paresis

Update: 2018 ELISA Submission Form

Determining the cause of polyneuritis equi and autoimmune polyneuritis may be possible.  There are no published protocols for polyneuritis equi, our treatment protocol is available to veterinarians when they are faced with a horse with antibodies against myelin protein.  Our next step is in staging disease.  Our autoimmune tests, MPP/MP2 can help us do that.  Call for details.


Between the dark and the daylight,

When the sun is ascending to power,

Comes a pause in the day's occupation

That is known as the Scientist's Hour.

It is dawn in tiny Fairfield, Florida, but Pathogenes is not sleeping in. Before daybreak, we begin to answer the emails which slithered in overnight when nobody was looking. It's also time to send out the documents which had gone directly to spam and to watch videos of ataxic horses from every state but Hawaii and Alaska, not to mention a few from our friends up North. We make early phone calls to our team of advisors across the country, wishing we had been more alert in Geography so that we'd recall that it is two hours earlier in the Mountain Time Zone. We are repaid for this failing later in the day when other poor Geography students telephone us at Pathogenes from Sacramento at ten p. m.

Our drop box at the end of the gated driveway oftentimes offers up samples from local vets and these are carried back to the lab. FedEx runs an early delivery route before the regular noon call so the gates must be opened well before eight a. m. The team arrives beginning at nine, a courier is dispatched to the small Farifield Post Office forthwith and the delivery trucks begin rolling in, culminating with UPS, the final visitor of the day, at seven p.m.

Our interpretations of the results from samples sent to us are the culmination of more than forty years of lab and field experience and fourteen years dedicated to EPM. And now we have yet another addition to the team. We call him Hal 9000P and he is tasked with test result interpretations and reporting.


Hal 9000’s people skills are renowned-- earning a top 100 award in his previous career, see his resume on Wikipedia. Hal 9000-P is a Cracker Jack at numbers, especially the numbers -1, 0 and 1. True/false and “not null” are Hal’s forte…beyond that Hal 9000 doesn’t read or speak. Austin trained Hal 9000-P to use our algorithm.

Submission Forms The submission form accompanies serum samples and gives us all the data we need to help you with your case of EPM. Our interpretation, coupled with a veterinarian’s neurological exam and field experience, simplifies treating equine protozoal myeloencephalitis. Sometimes, we find no submission form in the box, just a blood sample. Careful sleuthing by the lab crew can often reveal the source from the return address sticker. Failing that, we wait. Eventually, someone will call for the results.

Gait Assessment Score The veterinary exams are critical to a meaningful interpretation of our test. A trigger for “no interpretation” is absence of information on the submission form. A horse name and reporting email won’t give us anything to interpret—it may even trigger an email from Hal 9000.

It is well known that most horses in the United States are exposed to S. neurona resulting in serum antibodies, but yet there is no disease. This conundrum plagued EPM diagnosis for 25 years. We rely heavily on the gait assessment score (GAS), our hands are tied if there is no GAS on the form. A behavior problem should be scored as a “1”, issues such as head shaking and Horner’s (syndrome) make sense to us but Hal 9000 doesn’t interpret comments. He can evaluate a “1” listed as “Normal-deficit”, just check the box. We also need the submission form signed in order to use it for our FDA endeavors. You will get an interpretation without a signed submission, but the data is lost to our research. Be sure and download our newest, easy to fill out form on the services tab.

Send pre- and post treatment samples The follow-up sample is also critical to our analysis. If the second submission isn’t available, we won’t know how drugs. We hear that the once Grade 4 ataxic horse is now happily galloping in the meadow and can’t be caught…to us that is a treatment failure. We need that second signed submission form and blood sample.

Treatment response Initially our logic is based on the horse’s treatment history. If the horse has not been treated with an anti-protozoal AND there are antibodies to S. neurona then we want how the animal did clinically after treatment. Send us a quick email and let us know the response! Alternately, if there are no antibodies to S. neurona we still want your veterinarian to understand the disease process, this will lead to treatment options.

No S. neurona antibodies, GAS >0 We base our recommendations on statistics. We have tested and evaluated thousands of horses. We realize that some horses have no antibody; there are several situations could exist. No antibodies to S. neurona can indicate early infection (less than 17 days) or the horse has been exposed to anti-protozoals. Less likely reasons for lack of specific antibodies are that the animal has no ability to respond due to a defective immune system. This is a long held myth that there is a genetic predisposition to develop EPM—we don’t believe that. There is another theory…there are many unrecognized to S. neurona strains, thus all Sarcocystis may cause EPM—this is the Great Divide between our testing (specific) and the others (non-specific tests).

And, here is the most logical reason: it isn’t EPM. Yes, the horse can have neuroinflammation but not have active infection. In these cases we believe that a past infection with S. neurona, treatment of protozoa and not inflammation, is the problem. Our statistics show that in 80% of the cases without specific antibodies there is no infection. These cases can be treated. The numbers also indicate that 20% of the time we would miss early infections. When there is an early infection a post treatment test can determine active infection. A fourfold rise in titer (antibodies in the serum) indicates that there was active infection. The treatment decision is based on the veterinarian’s experience and risk assessment.

If a veterinarian is risk-averse, we offer C-reactive protein (CRP) testing. If the inflammation is due to ongoing S. neurona, Lyme, enteritis, gastritis, colitis, respiratory disease, tumor or other cause of inflammation the CRP will be high.

Treated The best time to retest is 8 weeks following treatment. We want to see that the antibodies are down to the undetected range. However, it the GAS is > 0 after treatment, we suggest determining the CRP and further treatment.

Relapse A relapse of EPM defined by us as insufficient treatment of IL6 mediated inflammation. Bute and banamine don’t work to treat this inflammatory path. A relapse can be due to incomplete removal of S. neurona, re-infection with S. neurona, or a reaction to another cause of IL6 mediated inflammation. We are documenting other reasons for IL6 inflammation, we recognize vaccination can induced ataxia in 0.3% of disease reported on our submission forms.

It’s the end of the day…we’ve used our lifetime of acquired knowledge to help you with your horse. We encourage you to forward your questions to Hal 9000…he’s waiting…

“A lie told often enough becomes the truth”. --Vladimir Lenin

If you’re not talking about inflammation, then-- by exclusion-- you’re lying about equine protozoal myeloencephalitis.  Reviewing only the causative agents (protozoa), life-cycle of the parasite, antibody testing, and treatment perpetuates misunderstanding.  Old ideas (EPM is enzootic and effectively untreatable, most horses are doomed to relapse) repeated often enough become a self-fulfilling prophesy.

Instead of viewing EPM as a population of horses infected with S. neurona containing a sub-group of untreatable, relapsing horses, chew on this.  View the population of ataxic horses as the whole pie (data set).  Ataxia is ubiquitous in horses and ataxia has several etiologies.  Sometimes ataxia in horses is caused by S. neurona.  Our data associates ataxia and S. neurona  in 54% of ataxic horses.

The ideas are very similar, however the practical difference between the views is that we can treat the latter group successfully—we are all too familiar with the treatment success of the former group.  Treating inflammation appropriately is key.  Understanding and managing the two components of EPM, inflammation and infection, are important to long term success.  The successful management of a horse with EPM will not be achieved by treatment alone, management takes an understanding the disease process.  It takes some work and it isn’t hard.

We make the association based on a gait assessment score, GAS, and the presence of specific serum antibody to the predominant surface antigens of S. neurona-SAG 1, 5, or 6.  A GAS of >1 and an ELISA SAG 1, 5, or 6 titer >8 attributes the ataxia to S. neurona.  A response to treatment supports the diagnosis.

Horses that do not have antibodies to S. neurona, with a positive GAS, are considered the rest of the pie, 46%. Just for arguments sake, call this group of animals IE-- disease due to inflammatory encephalitis.

If licensed anti-protozoal drugs are used for treatment the treatment efficacy is (published) 58%.  The difference in treating inflammation along with an anti-protozoal in suspect cases of EPM is 35%.  Are we just treating IE horses with an effective immune modulator or is there reason to think S. neurona played a role in disease? That is an experimental question for scientists, horse owners and veterinarians want results.

When horses show signs after "EPM" treatment they are called “relapses”.  Relapses are attributed to ineffective killing of anti-protozoals or re-infection.  The relapse rate with conventional antiprotozoal drugs are reported as 25% (ReBalance) and 20% (Triazines)—all of these drugs decrease the detectable antibodies in serum leaving, on average, 17% of horses in the IE category—ataxic with no antibodies--these are post-treatment IE cases but are attributable to S. neurona.  The rate of relapse (inflammation post-treatment) is three times higher in horses in which the inflammation was not addressed at the time of protozoal killing. Seventy one percent of ataxic horses with a presumptive diagnosis of EPM (no alternate diagnosis) had a root cause of inflammation that was most likely due to S. neurona infections.  This should be the topic of conversation about EPM.

The math leaves us to believe that 22% of horses with IE are horses with inflammation with an undetermined cause.  In some cases, we detect the effectiveness treatment for IE by serum CRP.  The anticipated treatment failure rate of treating inflammation and ignoring the inciting infectious cause, including S. neurona, would be high.  Our data indicates that S. neurona is a significant cause of IE in horses and should be a top consideration in treatment options.  Our research indicates that inflammation is the larger issue.  When treatment fails other obvious causes of IE should be investigated.

A long held belief is that a horse with EPM has antibodies to Sarcocystis neurona. Along with that idea is that spinal fluid (CSF) can improve the diagnosis of EPM--logic says if one detects antibody made in the CNS then organisms must be there. The antibodies are a response to local infection. The discussion quickly proceeds to the antigens used to detect antibodies--which are are most useful? Not up for debate is the question of active versus past infections. We already know that no antibody test can make that distinction. And that is because Equine Protozoal Myeloencephalitis is a disease, a syndrome, with infection and inflammation and both need to be recognized and treated.

We know, by experiment, that using CSF along with serum antibodies does not enhance the diagnosis of clinical EPM. In several randomized, controlled, masked studies (using horses) we determined that there was no statistical significance when CSF was used to diagnose disease. We used serial serum and CSF tested by SAG 1 ELISA (we used a SAG 1 challenge so that is our gold standard), and western blot (EBI, Lexington KY). Western blot was the test de jour and we added it to our testing to be complete.  We have discussed that topic in prior posts.

Another factor affecting antibody as a diagnostic aid is the horses’ prior history.  If a horse is naïve (the first infection) the antibody titer will be low and get higher as the infection continues.  An experienced horse, this is usually an older animal, develops a higher titer in a shorter period of time.  Antibody is detected by day 17 after infection.  These observations were statistically significant in randomized, controlled, masked studies (using horses).  We also know, and have discussed, that treatment (with triazine drugs) will delay an antibody response, again observed in randomized, controlled, masked studies. It takes very little drug to delay an antibody response, the serum levels are posted on our archived web page.  We suspect that other antiprotozoal drugs have the same quelling effect on antibody (but not clinical signs) but the data has not been published.  These confounding factors (an animals exposure and treatment history) change our diagnostic decision tree.

The first factor we look at is the exposure to antiprotozoal drugs.  Classically, the animal would not have a treatment history (and that would have to include no other animal served as an environmental contaminator).  When we look at submission forms a treatment history is included, but we are unsure of low level drug exposure.  The next most important factor is the presence of clinical signs.  If there are no antibodies (on our test a titer of <8) we look for a treatment response and recheck the horse at the end of treatment.  If there is a treatment response and no rise in titer we give a tentative diagnosis treatment-responsive inflammation.  Horses that respond to treatment a fourfold rise in titer increases the probability signs were due to active S. neurona.

Of course our diagnostic job is easier if the horse starts with an antibody titer (on our test >8).  If we see a response to treatment we just like to look for antibody again in 6-8 weeks to make sure the levels are <2 (on our test).  If we get a partial--or no response to treatment we look to inflammatory disease or seek other causes of the clinical signs.  A young horse (<2 would be a candidate for neck radiographs while an old horse would be a candidate for vitamin E treatment for equine motor neuron disease).  The expertise of the field veterinarian is important here.

The other half of our decision tree deals with inflammatory disease.  We use C-reactive protein, and in some instances serum IL6, to decide what the treatment steps are going forward.  A response to treatment indicates treatment-responsive inflammation--with or without S. neurona infection.  This is when an antibody response is useful developing a treatment plan.  When there is a treatment response and the CRP is falling to normal levels (we need serial testing to determine this) our follow up treatment if there are more issues.

The situation in which there is no response to treatment, the gait score is >2 and deteriorating, with a serum CRP concentration of >16 micrograms per ml further drastic measures are in order.  The first thing we try is using a treatment for encysted small strongyles that has good efficacy for this stage of parasite and rechecking the CRP in 7 days after de-worming.  In a few cases treating for Lyme, despite a negative test run at Cornell, has improved  horses clinical signs.  Sadly, in the other cases, we hit a dead end.  These cases are rare for us .03% of the submissions.  It may be useful to do a standing nerve biopsy.  A pre-mortem diagnosis can confirm untreatable disease in some of these horses.

What makes our approach to analysis of a case different is our first question—treatment--we don’t start our analysis with antibody—the confounding factors are too complex.  We start with treatment history and move to treatment response.  The serum testing is invaluable and is in our analysis so testing is critical and adds to our analysis.  The CRP is useful, it changes our treatment decisions in many cases.



Previously posted on June 7, 2011

EPM has three definitions depending on who you are talking to.  “Gold Standard” disease is defined  as Sarcocystis neurona residing in the central nervous system of a horse displaying neurological signs attributed to lesions in one or more regions of the central nervous system. For a definitive diagnosis, the organism must be isolated from the CNS. Isolation of the pathogen is post mortem evidence that the horse had EPM. Less stringency is used by clinicians at university equine hospitals. In these clinics EPM is recognized by the organism in the tissues or by PCR (polymerase chain reaction).

Also included are histopathological lesions consistent with EPM.  The tissues don’t show any S. neurona, but specific inflammatory lesions that are similar to those found in classical disease are used for the diagnosis. This inflammatory criteria was used in all the Ohio model infections and many experiments that examine antibodies in “diseased” animals.

To the rest of us, EPM for practicing veterinarians or “clinical EPM”, suspect EPM horses are surviving animals that have neurologic signs consistent with asymmetric or multifocal central nervous system lesions or both for which other likely differential diagnoses were excluded. Ancillary diagnostics used by practicing veterinarians can include serum testing, CSF testing, and response to treatment.

We all know that the etiologic agent of EPM is Sarcocystis neurona. Only antigen type I or II are involved in EPM, antigen types are defined by 32 markers! The recognition that antigen type I or II are involved in EPM is the major evidence that gives the SAG 1, 5, 6 ELISA credibility to identify infections, determine drug resistance, and response to treatment.

A diagnostic test for EPM isn’t available. Licensing a diagnostic is a long and complicated procedure that can not be achieved for EPM, mainly because signs result from inflammation and not the actual parasite. A diagnostic can be licensed to identify antibody in a sample if it is prepared as a kit. There are high dollar machines that read the tests, ambulatory veterinarians are unlikely to make this investment.  Antibody tests (that detect antibody to S. neurona) do not have to be licensed. These tests are “validated”. Validation is a strict set repeat tests between and in laboratories.

An antibody test detects immune responses to infections.  Infections with S. neurona may lead to EPM–the presence of clinical signs are the key factor. It is an important distinction between an antibody test to detect antibodies against S. neurona and a test for EPM. Antibody tests are used to rule in or rule out the possibility or the probability that a horse has an active infection or even parasites in the CNS, however these tests can have false positives and false negatives.  No antibody test can definitively diagnose EPM.

Sarcocystosis is a visceral infection that causes a measurable immune response in horses. Equine sarcocystosis is caused by S. fayeri, S. bertrami, and S. neurona. Equine sarcocystosis is pretty common. Equine sarcocystosis produces antibodies that are measured by tests such as IFAT, SAG 2, 3-4 ELISA, and Western blot. Tests using SAG 1, 5, and 6 are specific for S. neurona, they don't detect S. fayeri, we have a specific test for measuring a disease-associated protein of S. fayeri.

Apicomplexan parasites, like Sarcocystis, have common, or shared, antigens. These shared SAG’s, 2 and 3 and 4 are surface antigens that are common to all organisms in the genus Sarcocystis.

Sarcocystis falcatula have SAG’s as well. Some are unique. It is the common, or shared, SAG’s that get confused between tests that use common antigens. The shared SAG’s are interspecies markers because they have highly similar nucleic acid sequences and are antigenically identical, close enough so a horse can’t tell them apart. That makes them cross-reactive.

Sarcocystis neurona has distinguishing traits, the ones we use are molecular and can be identified by antibody reaction, these are neurona serotypes. Serotype is defined as antigen type and is represented by one of the mutually exclusive SAG’s that classify S. neurona strains into one of three groups: SnSAG1, SnSAG5, or SnSAG6. Phenotypes are antigenically unique and indicate some virulence and drug resistance factors that occur between strains.

SAG 1, 5, 6 ELISA testing uses recombinant proteins representing the phenotypes of S. neurona (SAG’s 1, 5, and 6) and determines the serotype of the infecting organism in horses, dogs and cats. Mixed infections are common and are detected by our test. Opossums have mixed infections. Opossums shed a mixture of oocysts so it’s no surprise that horses get several infections at the same time. The limits of the SAG ELISA are to serotype. A 2-4 fold increase in titer 3-4 weeks apart indicates active infection.

Other IgG tests include SAG 2-3-4 ELISA, IFAT, Western Blot. These commercial tests detect sarcocystis infections in horses. The limits of these tests are to the genus Sarcocystis. No serotype determination or ability to determine the identification of mixed infections are possible using these tests. Active infection is not distinguished from cyst degradation, possible in S. fayeri infections. Drug resistance can’t be determined using these tests.

Anti-protozoal drug susceptibility is measured by in vitro and in vivo assays. There are differences in the efficacy of anti-protozoal drugs that are demonstrated by dose and phenotype of the challenge infection. This is an important area for phenotype determination.