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Some diseases are easy to spot. Unique clinical signs can be directly associated with disease, skin fungus for example. It’s hard to ignore your horse when he squints a tearing and swollen eye, those are hallmark signs of a painful corneal ulcer! Fortunately, some diseases have definitive tests.

There are also diseases that aren’t so easily recognize. The veterinarian makes a diagnosis by evaluating the clinical signs and narrowing down the possible disease list with an array of laboratory testing. Yet, some difficult-to-diagnose diseases don’t have definitive tests to get them onto or off the differential diagnosis list.

What can make the definitive diagnosis of some diseases elusive is a fundamental principle: the body reacts to multiple insults by using a few selective, well differentiated pathways. Innate immunity is a quick, generic response system and is a first line of defense against infections. A more refined, specific, and later developing response is called adaptive immunity. An adaptive response results in specific antibody molecules and sensitized T-cells that are “trained” to recognize a distinct infectious agent. Innate immune responses are non-specific and common to infections while adaptive immune responses are the bodies red flags that may used for a definitive diagnosis.

We are going to explain why polyneuritis equi, that is primarily a dysfunction of the inflammatory response system, can be difficult to recognize. To understand PNE, one must have a brief understanding of how inflammation causes clinical signs.

In polyneuritis the thing that is different is that the immune system is now attacking something it shouldn’t. The first step in the immune process is the inflammatory response. Inflammation is a very early response. Even though it is very early it is possible to pick up some nonspecific inflammatory elements in a blood sample. In the PNE disease process abnormal values are associated with subclinical signs. Subclinical means that the signs are generally too subtle to be picked up on a physical exam.

It is important for the body to react quickly to infections. Rapid reactions employed by the innate immune system require communication between several first responding cells to the infection. The blood stream serves as a rapid transit system for the First Responders that are white blood cells (WBC) in innate immunity. These circulating cells are trained in surveillance and at the first encounter with foreign entities they sound the alarm. The signals they use are cytokines. Cytokines are chemicals that exert an effect on individual cells and sometimes on tissues.

The immune system is very economical. Sometimes cytokines turn things off and sometimes cytokines turn things on. Cytokines can turn one pathway in a cell on and at the same time turn off a pathway in the same cell. Think of a switching station along a railroad, pulling one lever changes the destination of the train to a meeting in New York or a party in Florida. Knowing when to pull the lever is important and that is context. Cytokines receive context from other reactions and other cells that let the immune response know where the party is happening.

Innate immune (early and quick) reactions start with inflammation. The five hallmark signs of inflammation are heat, pain, redness, swelling, and loss of function. These signs occur on a large, gross, as well as a microscopic or cellular level. The current discussion focuses on cellular reactions responsible for the gross signs seen in the horse. Inflammation yields changes in measurable clinical laboratory values that may help with a diagnosis of inflammation. Remember that these early, acute reactions are not specific to a specific disease but the response to infection.

Initially, subtle microscopic changes set in motion by cytokines have no outward effect on the horse. The effect is sub-clinical. Yet the ability to measure very minute amounts (or in some cases changes in amounts) of cytokines are accomplished in the laboratory. As the effects of cytokine reactions progress to larger areas of tissues the clinical signs will be noticeable in the horse.

Horses with PNE usually have normal WBC counts. Testing for specific antibodies against bacteria and protozoa will often be negative. Antibody against myelin P2 protein can be absent (early) or present (during fulminant disease). The following discussion will explain why when you test and the context of testing are important for diagnosis and perhaps prognosis of PNE.

End-stage disease, when a horse is beyond help, is where the current recognition of PNE stands. We want to change that. Late in disease, a transrectal ultrasound scan may show swelling of the sacral nerves as they exit the ventral sacral foramina. A biopsy of the sacrocaudalis dorsalis lateralis muscle was useful in one published case. In this case, the horse had no feeling in the tail (clinical signs were paresis or paralysis of the tail and decreased sensitivity). A biopsy showed that WBC’s had infiltrated the tissues and obliterated the nerve structure, but not the muscle fibers. Even in this end-stage case an attempt at healing myelin was observed. In some areas that were examined under the microscope, there was new myelin but in other areas, damaged nerves were covered with fibrotic tissue, the process of fibrosis.

Fibrosis is interesting, it is the body’s attempt to cover nerves that have lost nerve-insulating myelin due to chronic inflammation. The body can remyelinate nerves if inflammation is turned off, but if the repair process is thwarted by chronic inflammation, fibrosis takes over. Myelin allows rapid conduction of messages through the nerve whereas fibrin does not. The clinical signs will not respond to any treatment in late-stage disease when nerves are fibrosed. The antibody response to myelin may be absent because the reactive areas of the nerve are covered by fibrosis. The net results is a horse may produce an overabundant amount of granulation tissue that potentiates instead of controls the inflammatory reaction.

Observing remyelination in the presence of inflammation is good news, if fibrosis hasn’t occurred. Depressing the initial inflammatory reaction may reverse the clinical signs of disease. The propensity of the horse to have inflammation may be an anatomical difference in this species because horses have significantly more myelin P2 than other species.

A more in-depth view of the process of disease rests in the type of cells that are responding. Inflammatory T-cells and antibody producing cells (CD20+) infiltrate the damaged neural tissues. The infiltrating cells are macrophages (CD11a+ and c+), immunoreactive CD8+, cytotoxic T-lymphocytes, and a few CD4+ helper T-lymphocytes and CD3+ T-cells.

The bottom line is histopathology supports an adaptive immune response to inflammation caused by virus, chronic protozoal exposure, rickettsial infections, and immune-mediated diseases. We’re not the first ones to ask if PNE is a result of multiple etiologies that set the immune system into motion via common pathways.

PNE was described in the literature (medical books and journals) a long time ago. There are other things that can look like PNE to the clinician examining a horse with neurologic deficits. Many of the published reports were written before the development of the sensitive molecular tools we have today. There were no diagnostic tools to differentiate PNE from some of the other causes of neuromuscular disease. This meant the reports sometimes muddled the various findings. This in no way means the reports weren’t good, they were. The books and the papers are not wrong, they’re just outdated or incomplete. They don’t include the precision with which we can define the disease today. Still, a lot of their findings are valuable. Remember that PNE had no cure and it was often diagnosed late in the disease process. The changes were end stage disease that were found by microscopic examination after an animal was destroyed.

Some published reports cite the involvement of tissues encasing the cerebellum and cerebral hemispheres, although most agree the disease involves the peripheral nervous system and not the central nervous system. In chronic PNE the branches of trigeminal nerves show lesions, again infiltration by inflammatory cells and perineural fibrosis. The spinal column can show reddening and swelling with peridural edema. Lymphocytic infiltrations can be present in various nerves, the femoral nerve or cranial nerves. Horses with long-term disease can also have calcification of spinal nerve roots and extensive perineural fat. The results of these lesions are paresis or paralysis, sensitivity, muscle wasting, gait anomalies, tripping, and dropping feed.

When researchers attempted to find the causes of PNE, it was difficult. It’s a rare disease. They looked for infections and signs of trauma. Recall that in the past, at the time of diagnosis, PNE was already advanced. If there was an infection that started the process, that infection was already cleared by the immune system, long before the late signs of PNE appeared. There are other causes of nerve demyelination. Since PNE is the result of the immune response, it doesn’t matter too much what sets innate immunity into motion. It matters that the immune system has “seen” the myelin and now sets out to destroy it.

Normally reactive myelin P2 exists inside the Schwann cells membrane. The macrophages (white blood cells) exist in the blood. The myelin P2 is not exposed to the blood stream, so the immune system doesn’t know it is there. That’s the way it is supposed to work. What can happen, though, is that there’s a disruption in the normal Schwann cells integrity and the myelin P2 is exposed to the bloodstream resulting in inflammation. Let me digress for a moment.

There are speculations as to the etiology of polyneuritis equi. The problem is that the disease isn’t reproduceable using organisms or trauma. By the time chronic inflammation sets in the body has exterminated the organisms sometimes leaving only the residual antibody responses.

Polyneuritis equi is a primary demyelination disease. Primary demyelination can occur without inflammation, this can occur in lead poisoning. Primary demyelination can occur with inflammation where the inflammatory cells are mainly lymphocytes and macrophages. Inflammatory demyelination is thought to have an autoimmune pathogenesis, but the reaction isn’t necessarily against “self”. We discussed the up-regulation of certain antibody binding areas on myelin P2 as a response to T-cell stimulation in another section.

It was proposed that antigens, or “self”-proteins that reach the peripheral nervous system attract and activate lymphocytes and macrophages. These cells become a nonspecific cause of a primary or even secondary demyelination. This is called a “bystander” mechanism. Finding an infectious cause of PNE is unexpected in this scenario.

It is apparent from the discussion that two processes may be at play. There is an innate immune response that is a quick inflammatory defense against infections. The infection can be a bacterium, a virus, or a protozoan. After the acute phase reaction, the body equilibrates, and the cytokines facilitate a robust adaptive immune response. Normally, acute inflammation switches off while an adaptive reaction is switched on, a cytokine success.

Occasionally the acute inflammatory reaction doesn’t turn off. It becomes dysregulated. The cytokines forget context and keep the acute reaction in play. The reaction becomes chronic. The cytokines and their end-products keep the reactions going in an endless cycle. As chronic inflammation (T-cells) continue to destroy myelin an adaptive reaction against “self”-myelin ensues. At this point anti-myelin P2 antibodies are measurable.

It is important to recognize where in the cycle the disease is manifesting. We do that by measuring an acute phase cytokine, C reactive protein (CRP), and adaptive reactions against two areas of myelin P2. The cytokine CRP is one “turn-on” signal for acute inflammation.

To recap here, a horse will have clinical signs and acute inflammation, elevated CRP and no measurable P2 antibody and it is treatable. As disease progresses a little more, we measure antibodies against whole myelin P2. Further along, with more progressive disease, the horse may become refractory to the whole P2 protein, those antibodies decline, and only the T-cell stimulating protein antibodies (neuritogenic peptide) linger, most horses are still treatable and need management. Once the body fibroses damaged nerves and myelin is no longer exposed, the the antimyelin P2 antibodies decline. Nerves can’t conduct signals yielding clinical signs that are progressively worse. And the horse is untreatable.



The nervous system is composed of a central and peripheral system. The peripheral nervous system is the part of the nervous system that consists of the nerves and bundles of nerve cells on the outside of the brain and spinal cord. A picture is worth a thousand words, look at the picture and let’s fast forward to myelin. Myelin is made of proteins, proteins are made up of amino acids. Groups of amino acids are called peptides, peptides can be as small as two amino acids.

Myelin insulates axons, the axon is a long threadlike part of a nerve cell along which impulses are conducted from the cell body to other cells. If myelin, made up of proteins, is damaged then messages are not transmitted to cells. Myelin proteins are highly similar, conserved, between species. And that is important to the study of polyneuritis equi (PNE).

When scientists (primarily the English and French) were investigating all manner of neurodegenerative diseases in people they got huge amounts of myelin from the spinal cords of cows because all animals have the same protein structure for myelin. This phenomenon is called conservation. Unfortunately, in 1984 an English cow developed strange signs that turned out to be the first recognition of Mad Cow disease.

Let’s digress, I like this part of history and what it gave us. The source of Mad Cow disease was animal feed. Specifically, animal feed contaminated with bits of protein called “prions”. First, disease was linked to sheep--but now some believe human bone might have gotten into the British animal feed. Doctors Alan and Nancy Colchester write that Indian and Pakistani peasants sometimes gather large bones from land and rivers to sell, and that "Hindus believe that it is essential for their remains after death to be disposed of in a river, preferably the Ganges. The ideal is for the body to be burned, but most people cannot afford enough wood for full cremation." During the 1960s and 1970s, the U.K. got a lot of raw material for fertilizers from Bangladesh, Pakistan, and India. Humans were known to have Creutzfeldt-Jakob disease, the infection passed to cows through ground-up bones in animal feed, and then the cows gave it back to people. Fearful of Mad Cow scientists turned to the horse as a source of tissue for their research. This vast body of knowledge gave us a leg up on polyneuritis equi.

There were some distinct differences in the equine protein and the bovine protein. It is molecularly heavier because it has 3 more amino acids. Ok big deal, I’m being thorough. But an unexpected result was horses have more, much more, basic myelin P2 protein (lets call it P2) in their central nervous system tissue. And P2 protein makes up 2-15% of the peripheral nervous system protein. The amount and distribution of P2 is a big deal because disease affecting this protein will be more apparent in horses. Myelin P2’s function is in lipid transport and storage in the cell responsible to myelinate nerves. The take home message here is that it was possible to test these myelin making cells (Schwann cells) for damage. If Schwann cells are damaged myelin production would decrease measurably.

Progressive neurological disease was induced in experimental animals by injecting myelin protein. This was important because a model using laboratory animals allowed controlled experiments. In the case of P2, an animal model for Guillian-Barre syndrome, a demyelinating disease of the human peripheral nervous system, was produced. If Schwann cells are damaged myelin production would decrease measurably in the model animals.

It wasn’t long before a connection was made to neuritis of the cauda equina, now called polyneuritis equi, a neurodegenerative disease in horses. Another similarity between Guillian-Barre and P2 neuritis was paralysis of the trigeminal and facial nerves. Cranial nerve involvement was also recognized in horses.

As an aside, this work was going on in 2005, some purified myelin protein became available. Horse neurologists got some purified spinal protein, injected it into a few horses, but didn’t get disease. Case closed. No more work on cauda equina induction by myelin protein. This small experiment closed the door to a model and produced a bias against this line of research that continues today. Did they use P2? And as you are going to see, different parts of myelin P2 can give different results in laboratory animals.

Back in Europe scientists purified equine myelin P2 and crystallized the protein giving them a highly refined molecule. There was another unexpected result of the P2 experiments that may relate to the small horse study. Myelin P2 was snipped (chemically) into peptides, different peptides and disease depended on the peptides that were used in the experiment. Some peptides did not cause disease whereas the whole purified protein did. The conclusion was that there must be a disease-inducing region of the protein. One peptide caused neuromuscular disease and weakness that would resolve, untreated. Another neuritogenic (disease causing) peptide consistently induced disease. Animals could become desensitized to disease-causing injections of the whole protein P2, but not to the neuritogenic peptide.

And, normal animals that were given blood cells (T-cells) from diseased animals (passive transfer) got disease! The disease was produced from immune cells from animals, not the protein itself. This raised several questions, but we’re going to cut to the chase. It wasn’t a malfunction of the cells that put myelin around axons. The myelinating cells did not change the proteins they made, nor did they change the capacity to remyelinate damaged axons in the face of disease.

What changed was the transfer of sensitized cells to a healthy animal. Researchers found that the sensitized cells induced the production of another protein, an immunoglobulin-binding protein on nerves that increased during the clinical deficit. The net result was now there was an increase in the ability of inflammatory cells to bind nerve cells. The nerve cells became the target of the body’s immune system.

What about that neuritogenic peptide? The neuritogenic peptide of P2, the myelin protein that wraps around axons, turned out to contain an inflammatory receptor that is recognized by the immune system. It participates in inflammatory reactions regulating cells that are involved in cell-to-cell signaling by molecules called cytokines.

In health, the neuritogenic peptide of P2 (and P2) are not exposed to the body’s immune system. When myelin is damaged and P2 is exposed disease ensues. Clinical signs manifest because the exposed peptides sensitize T-cells that stimulate a protein to bind immunoglobulin and make peripheral nerves a target of inflammation.

What’s myelin and why is it important?

For this we need some background.

When we think of the nervous system, we generally think of two parts, first there’s the brain, called the Central Nervous System, CNS. Then there is the part that passes information to and from the brain. We call this the Peripheral Nervous System, PNS.

Nerve impulses from the body are passed along nerves by shifting chemicals. It is a slow process. Some nerves are fine with slow impulses, the nerves that cause your intestines to move food along, for instance. Then there are the nerves that must pass information very quickly.

clip_image002Imagine placing a hand on a hot stove. It wouldn’t do for the information to take a long time to get to the brain then a long time for the brain to communicate to the muscles to move the hand. The quicker the better. To do that, the fast nerves have a method to move the impulses quickly down a nerve. What happens is that the nerve is insulated with a sheath, this allows the impulse to rapidly skip down the nerve jumping long distances across the insulated portions. This insulation is called a myelin sheath.

If the myelin sheath doesn’t work properly, the nerve impulses don’t go quickly. This makes the myelin sheath extremely important. To coordinate complicated actions such as walking, running, and chewing, for examples, muscle groups need to work in complex coordinated patterns. Each muscle or set of muscles needs to contract in the proper sequence and exactly on cue. Any interruption or delay has severe consequences.

Animals and people have these important rapid transit nerves. Unfortunately, this myelin sheath can be damaged. Generally, it is the body’s own defense system that attacks this myelin sheath. It’s the same defense system that helps you conquer disease, and ward off infections. The body has a way of defining what is part of the body, named “self”, and what doesn’t belong, “non-self” which includes invading bacteria, virus, or protozoa. The body routinely attacks any “non-self” invaders and destroys them.

This “self” identification system is usually perfect. Not always, though. If the body misidentifies something that should be “self” as “non-self”, the body attacks the “non-self” with all the resources it has available. In general, it’s the immune system that is called into action. There’s also the inflammatory system which works hand in hand with the immune system to destroy invaders.

So how can this happen?

The body breaks down the invaders into small pieces. The body identifies each of these pieces, classifies them as “non-self” and produces antibodies against these pieces. This way the body can wipe out the invaders by attaching antibodies at many places. Think of an antibody like a hook. Each antibody is very specific and only attaches to the piece that it is meant to attack. The body produces a sea of these antibody hooks. If the target piece exists, the antibody hooks automatically attach and the rest of the immune system uses these hooks to help destroy the invaders.

Now suppose the system that determines “self” and “non-self” gets mixed up- or even duped. Suppose an invader doesn’t get classified as “non-self”. The body will not recognize it as an invader and will not attack it. Some bacteria will take advantage of this, they’ll coat themselves with materials that the body doesn’t recognize as foreign. Parasites disguise themselves by changing the way they present themselves, varying the expression of genes. Sometimes parasites are masters of disguise and hijack “self”-proteins in order to manipulate the immune system. The result is that if the body misinterprets what should be “self” as “non-self”, those antibody hooks will attach to normal tissue and the immune system will attack it.

This can happen with the myelin. There are several ways it can happen. Once it does happen, the immune system will break down the myelin sheaths. When that happens, myelin fragments are released into the blood stream. We test the blood for antibodies against myelin to see if those fragments are present. If they are present, we know that there is a problem.

Suppose one has a horse and that horse develops a coordination problem. Suppose it doesn’t walk well, it staggers and falls. If we test the blood and find the myelin fragments, that goes a very long way toward telling us why the horse has a problem and what to do about it.

If myelin is attacked by the immune system, all the myelin is attacked. We won’t generally see a single problem, we’ll see an array of signs-diffuse over the body. We call this array of signs “polyneuritis”. “Poly” means many, neuritis means the nerves are affected. If we’re talking about a horse, we tack on the word “equi” so we know we’re talking about the horse.

Introduction and purpose equi (PNE) is an uncommon neurological disease of mature horses and ponies.  Historically, PNE is recognized as untreatable.  Unfortunately, veterinarians aren’t trained to consider the possibility polyneuritis equi underlies the clinical signs seen in horses before untreatable disease manifests.  Our purpose is to present a set of white papers to inform and educate those interested in PNE. Eventually, we will combine the papers into an eBook.

If you are interested in polyneuritis equi, you probably have an afflicted horse or know a person that has a horse suffering from the disease.  Polyneuritis equi is rare, less than 50, 000 horses a year are diagnosed with PNE. That means there isn’t much information out there on this orphan disease and there are few groups conducting studies that will solve problems associated with PNE.

We collected information from published literature and studies that we conduct to write these white papers. Some of our studies were conducted under the most rigorous conditions, blinded and placebo controlled.  Some studies used cases from field veterinarians.  Some field cases could not be used, there just wasn’t enough documentation.  More often, case reports and collaboration allowed us to generalize, statistically evaluate parameters, and the body of data moved our work forward. Reports in the literature are for one or several cases and statistical analysis just isn’t possible.

It is our goal to share our knowledge, bring awareness to this disease in horses and license treatments that can control the clinicals signs of PNE.

Our view is that polyneuritis equi isn’t recognized early in the course of disease, when it is treatable. The current dogma surrounding PNE leaves no option other than humane euthanasia because clinical signs attributed to this disease relate to end-stage pathology. However, polyneuritis equi can have an insidious onset, horses present with subtle clinical signs that can be transient and they are progressive.  We believe these signs are treatable.  Frustratingly, these early signs can accompany other diseases and that makes diagnosis difficult. Scientists are looking at the cellular and molecular aspects of PNE and that gives us hope that we can achieve our goals.

This book is organized into ten stand-alone sections. An extremely brief but relevant overview of the nervous system forms the basis of understanding PNE. The section Relating clinical signs of PNE to pathology explains the underlying pathophysiology of disease.  The Case Reports section is from the few reported cases in literature and current cases we follow. The discussion is approached using a standard scoring system for PNE.  Clinical Scoring system for PNE highlights what may be relevant to evaluating field cases. The section on Considerations for a Differential Diagnosis of PNE explores the current thinking about diseases with similar signs.  This section will highlight the relationship between etiology and pathophysiology of disease.  Research Past and Present is a roadmap to current thinking about PNE. Diagnostic Testing for PNE is written to help alleviate the frustration with using inclusionary and exclusionary diagnostics to get to the root of disease. Treatment and a molecular based approach to treatment gets to our fundamental understanding: PNE is an inflammatory problem. The last sections Summary and How you can be involved in PNE research contains links to important support for the owners of horses with PNE.




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Neurologic deficits are seen in horses with abnormal gaits, changes in behavior or signs that are limited to the cranial nerves.  These horses are difficult to diagnose because the list of etiologies that result in neurologic deficits is long. The list of disease-causing possibilities is long because animals have a short list of responses to infection and injury.

Long ago lowly slime molds and paramecia selected and perfected a group of chemicals that allowed them to achieve movement and the ability to communicate with other organisms. The chemical signaling mechanism that parasitic protozoa and animals use today is based on these evolutionary successes. Redundancy is built into the chemical structures and the way signals reach the target tissues. Redundant molecules also are used to turn off these systems. The basics of the pathways are common to all living things and they are primal.

Signaling pathways are also common to many tissues and they are ubiquitous throughout the body. An infectious agent will set off  a protective primal response in an animal. That response is called “innate immunity,” and this immunity results in signs that are non-specific to a single agent.  Vertebrates have many checks-and-balances regulatory pathways that control these common systems most of the time.  Sometimes the pathways become unregulated. As animals evolved to efficiently use the chemicals (cytokines) involved in protection against infections, parasitic microbes exploited the same systems. These highly successful disease-causing organisms use some pretty nifty  methods to evade or even hijack the innate immune signaling cascade.

The result is that an animal with neurologic disease has a limited repertoire of responses to several insults and they all look the same to the clinician.  We have accrued a vast amount of scientific knowledge about some diseases.  The diagnosis of these diseases is verified by  objective methods.  Some diseases have classically presenting signs that allow a veterinarian to easily rule them in or out. Of course, field experience is valuable in recognizing some classic signs. The diagnostician thins the list of possible causes of disease to the short list.

The short list for neurologic diseases that are found in horses often don’t have definitive diagnostics and that leads to using exclusion to help diagnose the cause. A diagnosis of exclusion  is a diagnosis of a medical condition reached by a process of elimination, which may be necessary if the presence cannot be established with complete confidence from the history, examination or testing. Such elimination of other reasonable possibilities is a major component in performing a differential diagnosis.

Diagnosis by exclusion tends to occur where scientific knowledge is scarce, specifically where the means to verify a diagnosis by an objective method is absent. As a specific diagnosis cannot be confirmed, a fall back position is to exclude that group of known causes that may cause a similar clinical presentation.  Polyneuritis equi (PE) is such a disease.  We have, along with our regulatory partners, put together a list of definitive tests and some that are exclusionary to pinpoint the tests most likely to give us the target population for our polyneuritis equi study.

The PE horse has evidence of neurologic disease that can be identified by neurological exam and those that are treatable have serum antibody against some specific proteins.  These are inclusionary criteria for our study.  The horse may or may not have antibodies against parasitic protozoa. To keep our study uncomplicated, we exclude horses with antibody against S. neurona, a parasitic protozoa that causes equine protozoal myeloencephalitis (EPM). Other exclusionary criteria are no recent history of trauma, no  recent respiratory infection (or a current vaccination for EHV-1 can satisfy this one).  Vaccination for rabies will exclude rabies as a cause.  Of course,  a horse would need to have a normal vitamin E level ( > 1.5 micrograms/ml serum).

Some treatments will exclude horses from our study.  They include anti-inflammatory agents within 3 days and anti-protozoal agents within a time frame that the anti-protozoal is expected to exert its effect.  Each expected effect from licensed anti-protozoal medication is different, some 30 days and some beyond 90 days.

Diagnostics are a major frustration for owners of horses with suspected EPM.  Owners spend many dollars on exclusionary diagnostics and don’t have an answer at the end of it.  Unfortunately, that is the nature of EPM. It is also the nature of Sarcocystis infections to trigger innate immune inflammatory cytokine responses that produce the signs associated with neurological diseases.  That means the horse can have two active pathological processes!  Because the nature of these diseases and the repair mechanisms that are associated with them use similar pathways, it is unlikely that there will be definitive diagnostics.  A good neurological examination by a veterinarian familiar with neurological disease and judicious use of diagnostics to form a short list  is the most successful path to health.