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It is an ill wind that bloweth no man goodJohn Haywood 1562

Autoimmune polyneuritis is a disease that causes weakness and ataxia in horses.  It is related to horses diagnosed and treated for EPM. It is not a new disease but hasn't been in the EPM-discussion.  This post explains polyneuritis equi and using CRP levels to monitor the disease process.

A Little History The possibility of contracting variant Cruetzfeld-Jakob disease (the human form of bovine spongiform encephalopathy) was recognized when Mad Cow disease blew into Europe.  Risk spurred scientists to replace the well-characterized bovine neural tissues that were used in MS (multiple sclerosis) research with equine tissues. The flurry of equine experiments led to some very useful information.  In 1981, scientists raised the possibility that circulating antibodies to myelin protein played a role in neuritis of the cauda equina in horses.  An ELISA test was reported in 1987 for the differential diagnosis of cauda equina neuritis and other neuropathies in horses. Polyneuritis equi (PE) is the more correct term for neuritis of the cauda equina. Ellison 2015 MPP MP2 Assay ELISA Submission Form Pathogenes Testing Options

Several diseases are encompassed by the term polyneuritis equi. That complicates the understanding of this syndrome.  Suffice to say, much research is needed to determine cause and effect as well as the pathogenesis of polyneuritis equi in horses.

The pathology of polyneuritis equi is characterized by inflammation of the nerve roots that form the cauda equina (typical) and any other peripheral nerves (atypical) that are involved.  Histological examination of the affected nerves can show areas of demyelination and remyelination. These lesions are similar to experimental allergic neuritis.  Horses with clinically and pathologically diagnosed polyneuritis equi  had circulating antibodies against myelin protein that were similar to lesions in the experimental model. When it becomes necessary there is a procedure that may be used to confirm the diagnosis. Aleman 2009 PNE

The cause of polyneuritis equi is elusive.  A viral or an immune-mediate etiology are each possible.  These two theories may not be incompatible because an infectious agent may initiate an immune-mediated condition that stimulates a common pathologic pathway.

The distinction between chronic inflammatory demyelinating polyradiculoneuropathy and acute inflammatory demyelinating polyradiculoneuropathy and several disease-associated polyradiculoneuropathies (cancer, diabetes, liver disease) is important in human and equine medicine because the course of disease and prognosis are different.

Our approach to investigating polyneuritis in horses is by serum testing for MPP and MP2 antibodies followed by observing a response to treatment. We hypothesize that polyneuritis in horses is immune-mediated and it is not specific to cause.  For example, sarcocystosis due to S. neurona or S. fayeri can stimulate polyneuritis.  So can Borellia, the agent of Lyme disease. The pathway that results in clinical signs and pathology are the same, the stimuli are different.  Because the pathogenesis of disease is by a common pathway, the initial treatment of polyneuritis equi is the same, irrespective of the stimulus.  However, the identification of the etiology is important to treat the underlying cause of the proinflammatory-stimulating pathway.

The immune response is over reacting to an infection. Most of the time an immune response turns off once an infection resolves.  In some horses with polyneuritis, a chronic inflammatory condition results because the immune system is stuck in the “IL6 <-> CRP” cycle, each molecule stimulating the production of the other.  No “turn off” switch is initiated when the pathway is stuck.  Just the opposite happens.  The end result of molecular reactions turn on the reactions to stimulate the cycle again. Our approach is resetting this cycle using a protocol that prevents the short term production of IL6 receptors.

The proposed pathogenesis of polyneuritis equi. The immune response in polyneuritis equi is possibly via an IL6 (pro-inflammatory) pathway. Our reasoning is that:

  • innate immune responses stimulate IL6 production;
  • myelin protein displays IL6 receptors.

An experiment demonstrated horses with abnormal IL6 pathways do not get signs of polyneuritis equi, as opposed to horses with normal IL6 pathways, when given the same stimulus.

  • Horses treated for abnormal IL6 reactions resolve their clinical signs with treatment.
  • Untreated horses with chronic polyneuritis (atypical polyneuritis equi) get worse.
  • Untreated chronic polyneuritis progress to an immune mediated demyelinating neuropathy.

The waxing and waning of the immune mediated disease eventually results in microscopic calcium deposition on nerves. This terminal condition, classical polyneuritis equi, has no treatment in horses. The recommendation for classical cases of polyneuritis equi, once the diagnosis is confirmed, is euthanasia due to the poor prognosis and intensive nursing care required, even for symptomatic support. We do not recommend euthanasia until a response to treatment is investigated.

Many horses with neuropathy have increased CRP (stimulated by IL6).  That is why CRP is important to monitor the presence of disease.  Sub-clinical disease is diagnosed when CRP levels are elevated and there are no clinical signs.  The CRP levels are useful in monitoring these cases, treatment is needed until the CRP levels are normal.  Again, treatment to decrease inflammation is not useful in chronic cases unless the underlying condition is resolved.

You’re probably reading this because you have a horse that has relapsed multiple times or you are concerned about the CRP value.  Here is our quick reference:

CRP level is trending to a normal value (less than 16):  indicates the inflammatory process is resolved.  If clinical signs are still present they are probably due to a physical cause and more diagnostics are warranted.

CRP level is elevated or going up: indicates the inflammatory process is not resolved, subclinical disease is present.  If the horse is clinically normal, it may be useful to deworm with QUEST.  Quest is required to eliminate encysted small strongyles that may be associated with chronic inflammation.  It’s cheap, safe, and there is nothing to lose.  Have you considered hind gut ulcers?

CRP level is elevated or going up: if the horse is not clinically normal or relapses after treating the inflammatory pathway,  the underlying condition has not been resolved. A possibility is that S. neurona is causing continued exposure and disease; S. fayeri toxin is present and S. fayeri infection has not resolved or there is continued exposure in the environment.  Our ongoing study is designed to distinguish these conditions and is accepting cases.  The study is for 1 year.

CRP level is elevated and MP2/MPP antibodies are present: indicates that autoimmune polyneuritis is present.  This condition will not respond to antiprotozoal drugs.  This condition will require a different treatment protocol.  We are consulting with veterinarians/owners with sick horses about this disease and providing the most up to date protocols. Treatment may resolve clinical signs. CRP is used to detect subclinical disease that should be treated before clinical signs manifest.  If the CRP continues to go up, and clinical signs progress, further diagnostics are indicated.

Chronic relapsing disease with an elevated CRP that is unresponsive to treatment requires additional diagnostic workup. There are some diagnostics to assist in the ante-mortem diagnosis of classical polyneuritis equi. Aleman 2009 PNE The field procedure is a transrectal ultrasound of the extradural sacral nerves.  Also, biopsy of the sacrocaudorsalis dorsalis lateralis (the base of the tail) is useful.  There are  case reports describing the procedures and the results in two cases that may be useful.

We provide new and novel ideas for the treatment of conditions that are previously diagnosed as “EPM”.  Our work also makes sense of some of the most perplexing issues surrounding S. neurona sarcocystosis. Our papers are published and available to everyone.  You may give us a call for guidance with these cases, however to support our work and our time, we ask that you please submit samples for testing.  Our test results and responses to our protocols provides us with information that can lead to new treatments for these very complicated diseases.  There are few veterinarians working and publishing in this area. Supporting our work guarantees there will be more options in the pipeline.

 

Shoestring, loved by everyone that knew him.

Can EPM be prevented with drugs? What are the unintended consequences of continued antiprotozoal therapy?  These are complex questions without simple answers. Equine protozoal myeloencephalitis is a syndrome that involves infection with pathogenic protozoa and, in some horses, the infection can cause neuroinflammation.  It is the inflamed neural tissue that causes  clinical signs.  How is it that few horses that are infected with S. neurona get EPM when the parasites can infect organs quickly?  The susceptible horses have an inflammatory response that goes to the central nervous system.

We were taught (Elitsur, 2007) that the lymph nodes of normal horses harbor parasites one day after ingesting infectious stages of S. neurona! The parasites move to the liver (day 2), lungs (day 5), and by day 7 neuroinflammation (but not parasites) can be detected in the brain and spinal cord of susceptible horses. Most horses have antibodies against S. neurona.  It takes a couple of weeks after infection to detect antibodies. A longstanding conundrum with S. neurona infections is that infection rarely results in EPM when EPM is defined as parasites in the brain or spinal cord.  The majority of horse studies established neuroinflammation associated with S. neurona infection as the cause of clinical disease. The presence of antibodies at the time of clinical signs tie the signs with the immune response to the parasites.  Infecting immunodeficient horses (SCID foals) can lead to a parasitemia and no clinical signs because these horses lack specific inflammation producing cells. Good evidence that the immune cells can transport parasites and produce molecules that result in clinical disease.  Immunocompetent horses quickly clear parasites but continue to have clinical signs.  Good evidence indicating that inflammation doesn’t resolve when parasites are removed.

Can preventing infection prevent neuroinflammation in the EPM susceptible horse?  Perhaps the first question relating to preventive therapy is how one decides if a horse is at risk for EPM?

Which horse do you select for prevention treatment? Very few horses get S. neurona in the brain and spinal cord.  Yet serological surveys show over 80% of horses in the US have been infected.  Our evidence that antibody against S. neurona does not indicate  protozoa made it into the central nervous system.  It is probably early immune responses that prevent parasites migrating into the central nervous system.  Antibodies indicate an immune response to S. neurona infection, and once produced antibodies can remain for many months after parasites are gone.

The immune responses initiated by infection thwart parasite migration and infection of the CNS.  However, in some horses the immune system causes clinical signs because inflammatory molecules enter the central nervous system.  Anti-protozoals won’t affect the clinical course of immune mediated neuroinflammation.  That said, the overwhelming scenario is that horses are clinically normal after infection.  Therefore, one must assume that the majority of horses produce immune reactions, in addition to antibodies, that are protective against disease.  A horse should have clinical signs as well as antibodies against protozoa to justify treatment with an antiprotozoal.  It only makes sense to treat prophylactically if an animal has a history of multiple infections.  It would not make sense to treat seropositive, clinically normal animals or an animal that has resolved EPM.

Some horses exhibit signs attributed to EPM but have other conditions.  Many of these horses are treated for EPM and are being treated for the wrong disease.  The unintended consequences of antiprotozoal treatment in a horse with another condition is worsening of the underlying condition and no response to treatment.

The horse that needs prevention therapy is one that has chronic relapsing disease, is seropositive after becoming seronegative post-treatment, and responded to anti-protozoal therapy.  The horse that needs prevention is one that other causes of disease have been ruled out.  There are several serum tests that can point out other neuroinflammatory conditions.  We find the CRP, Lyme, S. fayeri, MPP, and MP2 (anti-myelin protein antibody) tests useful.

There may be unintended consequences of prophylaxis.  Treating all S. neurona exposed horses may thwart protective immunity. In vivo experiments have shown that mice treated with 10 mg diclazuril/kg, before and continuing for 10 days after infection, did not develop protective immunity whereas mice treated with 1 mg of diclazuril/kg survived challenge exposure. Perhaps there is inefficient and incomplete removal of parasites. A chronic infection stimulates protective immunity.  The authors showed in vitro treatment of host cells with 10,000 nanograms of diclazuril,  used for 24 hours, did not kill all the parasites.  One thousand nanograms of diclazuril in similarly treated host cells resulted in killing only 31% of the parasites.  There were plenty of parasites left to infect an animal.

Ponazuril experiments had the same results. The dose required for protection and no relapse of infection in mice was 10 and 20 mg/kg per day before and for 10 days after exposure.  Although death was prevented in mice using 10 and 20 mg/kg ponazuril given 3 and 6 days after exposure, parasite DNA was found in the brains of these mice. You could expect these results because horse experiments showed that parasites were already in the lymph nodes, liver, and lungs by day 6!  Based on the mouse and horse experiments  treating a horse once every seven days makes no sense.  Also, take into account how long it takes to get effective drug levels into the animal.  It only took 1 day for the parasite to enter a cell willing to transport it to the lymph nodes.  Prophylaxis will require daily treatment and then it must be instituted before infection.

What about horses?  It was convincingly shown ten years ago that horses “treated with ponazuril at 5 mg/kg minimized, but does not eliminate infection and clinical signs of EPM in horses”.  These horses were treated 7 days before infection and continuing until 28 days after infection. However, seroconversion was significantly decreased in the treated horses.

Reducing antibodies against S. neurona does not equate to preventing EPM. A recent publication cites a reduction in antibodies to S. neurona in foals treated daily with diclazuril.  The foals were born to mares that had antibodies to S. neurona.  This is evidence that S. neurona is in the environment.  There was no correlation between the serum antibodies and disease on the farm.  Foals nor mares were subjected to CSF analysis.  The take home message was that daily treatment of foals (daily for 11 months) reduced serum antibody production by the foals.  This study doesn’t answer the question of antibody reduction and disease.

The studies that show the effectiveness of EPM-prevention by delaying or reducing antibodies against S. neurona requires giving anti-protozoal drugs to horses followed by S. neurona challenge. There have not been, and probably won’t be, published studies showing that diclazuril or ponazuril prevents EPM in a challenge model. The challenge studies show just the opposite, disease was not prevented.

What happens when triazine agents are given to infected horses, ones with EPM?  A paper in 2013 states “the results of in vitro and in vivo studies of triazine agents with various apicomplexan parasites clearly indicate that removal of triazines after appropriate treatment time results in regrowth of the parasites.  This suggests that although some stages are killed, other stages are inhibited and retain the ability to begin development again once the drug is removed.”  The author speculated that “the intact immune responses can likely remove most of the inhibited stages in cases of successful treatment.  In unsuccessful cases, relapse can occur because of failure of the removal of some of these stages by the drug or by (failure of) the immune system (to remove parasites).”

If antibodies are an indication of immune response to infection, what other protective immune responses are inhibited?  Is it possible to make horses susceptible by trying to prevent infections because a protective immune response is never initiated?

Another Prophylaxis study design is available.  It is possible to document recurrent disease in horses.  We look for antibodies to S. neurona in horses that also have clinical signs due to neuroinflammation.  The chronic cases are recognized by observing several “relapses”, usually over several years.  These horses may respond to antiprotozoal treatment.  In this study each animal must serve as its own control.  This was the approach used in studies conducted to support licensing Marquis and Protazil (FOI for each product) for the treatment of EPM so there should be no issues with study design.

In our Prophylaxis study the horses are identified by clinical exam, antibody testing, and response to treatment.  The main criteria for entrance to the Prophylaxis study is chronic relapsing disease due to EPM.  The selected animals receive  prophylaxis and then they are monitored over the course of a year.  The outcome variable, the measured response, is by veterinary exam.  The history of relapse and treatment responses are critical to make this study meaningful.  Our Prophylaxis study is ongoing and conducted by veterinarians that have these cases.  If you have an interest in this study contact us at Pathogenes.  We can tell you if your case qualifies.

Can overuse of antiprotozoal drugs lead to resistance? Treating horses empirically makes no sense. Drug resistance is a huge issue.  Is it a reasonable to assume that drug resistance will not be induced in an intermediate host?  The horse harbors the asexual stage of the parasite and selection of an organism due to resistance should not be possible.  Harboring a resistant strain is only an issue for that horse because the horse is a dead end host. However, when enough drug is in the environment, or inadvertently ingested by a definitive host, drug resistance becomes possible.  Wherever the definitive host sheds virulent drug-resistant strains of oocysts the susceptible horse will have no treatment options.

The methods used to select drug resistant strains in vitro are easily accomplished.  A small amount of drug is added to the culture.  Increasing amounts of drug are added until a resistant population remains. This sounds eerily similar to some treatment protocols used in the field for EPM.

Alternatively, drug resistance is identified by growth of the parasite in the face of treatment.  Using triazine drugs parasites regrow when the drug is removed.  This is due to stage related susceptibility to the drug, most likely not drug resistance.  To find a triazine resistant strain the organism would be isolated while the horse is being treated.  This is accomplished in a laboratory setting.

Thoughts de jourPreventing EPM makes sense in horses that have chronic relapsing disease due to protozoa and the disease is responsive to anti-protozoal therapy.  It is critical to identify these horses and limit treatment to this group.

It is counterproductive and expensive to treat all horses with drugs.  It boarders on harmful because this will foster resistance. It is important to monitor serum antibodies in horses with chronic, relapsing EPM.  It’s also important to monitor inflammation.

Can EPM be prevented?  We prevented EPM in a merozoite challenge model and related the protective response by a serum antibody titer (Ellison 2009). Yes, it can be done with a vaccine.  What we found was that vaccine effectiveness was strain specific.  Using very common antigens for vaccine is a way around strain specificity but opens the door for initiating inflammation.

Preventing disease with vaccine was based on inducing protective immunity. Can the same be done with drugs?  A study that first identifies horses with chronic relapsing EPM differentiating disease from other conditions that mimic EPM is critical.  Measuring disease over time and response to treatment will answer the questions in susceptible horses.  To us prevention only makes sense on a case-by-case basis.

A Sidewinder is a term describing a neurologic older horse that has an unusual clinical presentation.  The horse has a lateral hemi-paresis that results in a gait that makes them list to one side or the other. Most Sidewinders are depressed.  The clinical presentation  (because they are depressed) classifies them having a multi-focal, diffuse neurologic disease (encephalomyelitis) of undetermined etiology.  In our consulting practice we saw a pattern to the clinical presentation of these idiopathic encephalopathies and wrote about them in a blog posted in February of 2012. Sidewinding horses have recently reached the level of recognition of clinicians at one university, we expect more discussion will be forthcoming.

To facilitate the veterinary interests and research community we are providing access to our database of the cases we have gathered data over several years.  This syndrome is recognized by clinical presentation and is a non-reportable disease.  The limits of our data are similar to all statistical databases, which includes under reporting and misclassification of disease.  Our data is captured by state of residence and not where the animal was exposed.  These cases are reported by veterinarians from field observations and are therefore termed anecdotal.

Three years ago our impression was that horses diagnosed with EPM were part of a larger group of ataxic horses and the weakness/hemi-paresis group were due to a subset of horses with an inflammatory syndrome.  Most of the horses are presumably diagnosed as suspect EPM, some of them have antibodies to S. neurona in the serum and some don’t.  There is usually a history of extensive clinical work up, referral to a university, CSF fluid analysis, and treatment for protozoa.  Generally these horses don’t respond to NSAID’s, steroids, or anti-protozoal drugs and show progressive disease.  The treatment protocol varies from the standard EPM treatment.

Clinically recognizable features are signalment (age is the only statistically related factor, 20-35 years old), depression, and a twisted gait.  Often the horse will use a stall wall for balance.  A complete blood count and clinical chemistry values are generally normal.   Antibody against S. neurona is not a significant factor.  There can be a varied and incomplete response to anti-protozoal drugs, anti-protozoal treatment does not maintain the horses and they are considered treatment failures.  An elevated C reactive protein is present in most, but not all of the animals and may be a significant factor.

We have not yet found the causal molecule in sidewinding horses. Histopathology was unremarkable in 4 cases (we concentrated on the choroid plexus), one case showed mild Wallerian degeneration.  A small percent of animals show signs related to vaccination and vaccination accompanied by specific treatment prevented recurrence of signs in these horses.  The resolution of signs with treatment can be directly associated with vaccination, there is no correlation with a specific adjuvant or manufacturer.  Note that vaccination is not the precipitating factor in most horses.

Some treated horses remained symptom free post-treatment and were had a good quality of life.  Due to the age of these animals most are trail riding, breeding stallions, and pasture pets.  Some animals show recurrence of signs after 12-15 months.

Our interpretation is that Sidewinders are a subset of neuromuscular diseases in horses, 20-35 years old with chronic inflammation due to unidentified causes.  Our differentials include infectious, metabolic, and immune mediated causes.  Infectious causes include chronic protozoa infection or chronic herpes viral infection.

Equine protozoal myeloencephalitis (EPM) is a syndrome that includes neuroinflammation. Recognizing the inflammatory component of the syndrome may make EPM a treatable disease, of course supporting a presumptive diagnosis requires a clinical examination and ruling out other causes of disease. Ruling out other diseases begins with a physical and neurological exam. Diagnostic tests can include radiographs and immunodiagnostics. Primary complaints that are related to an abnormal gait indicate a standard lameness exam (that includes nerve and joint blocks) should be performed. After routine diagnostic procedures, some veterinarians use a response to treatment to support a diagnosis.

When ataxia is apparent, ruling in/out the location of the problem is useful. Localizing the lesion is an achievable art. In early S. neurona infections vestibular disease is recognizable and can involve the peripheral or central vestibular system, brainstem, or cervical vertebrae. When localizing a lesion to the clinical signs an important consideration-- is it one lesion or a multifocal issue? The onset of signs can be sudden and indicate trauma, infections, inflammation, toxicity, or idiopathic causes. Chronic and non-progressive disease make trauma or infections more likely. A thorough examination and diagnostic testing can rule out or point to an etiology.

Induced EPM infections cause ataxia in horses. Prior to ataxia, central vestibular disease is apparent. Since publication of Early Signs of Equine Protozoal myeloencephalitis (Ellison, Kennedy, Brown, 2003. Journal of Applied Research in Veterinary Medicine p.272-278) the observations in 44 ataxic horses were documented. The determination of disease in horses in these blinded, placebo controlled studies was by a grade 2 ataxia. Observing the signs indicated in the chart below suggested central lesions quickly after S. neurona challenge.

The focus of EPM research is on the pathogenesis of protozoal encephalomyelitis. Vestibular disease is part of the disease process, as shown by documenting signs in challenged horses. In field cases, the most common causes of vestibular disease are trauma or infection. The clinical signs in horses are often acute. Management and treatment of these cases can be difficult. Central and peripheral lesions are treated differently with different prognosis and that makes differentiation between these two conditions important. Central vestibular disease (affecting the brainstem or ventral portion of the cerebellum) often results in severe signs including trouble eating, ataxia, and paresis in multiple limbs, or even recumbence. Central vestibular disease is often observed in cases of EPM. Early recognition of central vestibular disease associated with EPM combined with effective treatment can resolve clinical signs returning a horse to use.

The location of the protozoa in active EPM cases is currently under debate. Some practitioners argue that protozoa must be in the CNS to cause the observed inflammatory signs of disease. We argue that protozoa can occupy the CNS, breaching the blood brain barrier inside white blood cells (Trojan Horse model), but assert that this scenario is rare. Undoubtedly there are cases in which protozoa are found post mortem in horse with a diagnosis of EPM. The far more common condition is that protozoa are not found in histological samples. Histological specimens are rife with inflammatory lesions, considered evidence of protozoal infection. However, these lesions are not described as pathopneumonic. The term is idiopathic if a definitive diagnosis is not made.

The basis for our opinion is that protozoa are not found in the majority cases of suspect EPM that undergo post mortem examination. Even in the stress model used to induce EPM (Saville et al 2001. Veterinary Parasitology 211-222) the researchers were unable to demonstrate protozoa in the CNS of the challenged horses. Alleviation of signs can occur rapidly with treatment. Should necrotic lesions (due to parasites) be present in the CNS one would expect a long period for recovery including an aftermath of signs that could not be resolved.  A rapid response to treatment and return to use in suspect EPM cases is our goal.  Our goal is facilitated by an early recognition of central vestibular signs. No doubt EPM is a difficult disease to identify, treat, and manage. Our view is based on available literature, experiment, and clinical observations made by veterinarians. The optimistic view is that EPM is treatable because a large part of the disease syndrome is inflammation. Until scientific evidence shows us an alternative, defensible view, we will continue suggesting treating neuroinflammation as a practical approach to treating EPM.

RESEARCH NOTE:  PLEASE COMPLETE AND EMAIL THE APPROPRIATE TRIAL DOCUMENTS (OWNER CONSENT; GAIT SCORE; VIDEO) AFTER REVIEWING THE INCLUSION CRITERIA FOR EACH STUDY.  ALL FIELD STUDIES REQUIRE THE PARTICIPATION OF A QUALIFIED VETERINARIAN.

The idea that EPM is primarily an immune mediated disease, perhaps obvious, is not readily accepted.  Parasites were isolated from brain tissue in experimentally infected horses (Ellison.  Intern. J. App. Res. Vet Med. 2004. p 79-89).  In this experiment, immuno-affinity beads were used to trap parasites from large volumes of neurological tissues—a technique that was key to proving the success of this model.  A highly virulent strain of S. neurona was employed in these studies. The organism was passed through a horse (with re-isolation) to increase the organisms virulence for horses.  Passing the organism through other species (such as a raccoon) result in parasites that are less virulent for horses.

The evidence that parasites (S. neurona) are associated with brain lesions is lacking in the majority of clinically diseased animals as well as experimentally infected horses (Saville. Vet Parasitol. 2001. Feb; p 211-22). What was clearly demonstrated in the Saville model is that clinical signs are associated with inflammation—not protozoa. Therefore it is generally accepted that clinical signs (neuroinflammation) and the presence of S. neurona antibodies define a horse with EPM pre-mortem. Even post-mortem diagnosis of EPM does not depend on demonstration of the protozoa (Saville).

Treating a horse with antiprotozoal drugs for EPM can result in elimination of antibodies and, in some cases, incomplete resolution of clinical signs.  Treating specific neuroinflammation can result in resolution of disease in these horses.  There are several inflammatory molecules that play a role in the modulation of the early immune response  to parasitic protozoa.  Molecules and their receptors are active areas of research.

We found data from a recent paper showing levels of specific neuroinflammatory molecules (found in brain and blood) distinguished between treated animals that had cleared systemic parasites, but not those in the brain, interesting.  It will take years of research to apply these tests to horses with EPM, should researchers even take on the work.  The first step in investigating the inflammatory component of EPM is recognizing the importance of neuroinflammation in disease. However, these tests may be instrumental in accruing more evidence that the vast majority of horses with EPM don’t have active parasites in the CNS.  Certainly the outcome will change the approach to treating EPM.