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Exclusionary Diagnostics or 99 diseases your horse doesn’t have


lab opossum

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.