Saturday, April 27, 2013

Equine Protozoal Myeloencephalitis; A Veterinarian's Perspective



EPM has plagued horse owners for several decades with an estimated clinical prevalence of less than 5% of horses being affected, causing not only a potential loss of function and performance but also high costs to the owner in terms of diagnostics and treatment.  When I was in vet school, the disease was first being clinically recognized and treated.  In those days, we saw the worst of the cases that were admitted into the veterinary school and many of these horses were recumbent and unable to stand or even turn themselves.  As students on the late night watch, we were often given the chore of hooking these horses to overhead hoists and physically turning them every few hours to minimize bed sores.  It seemed futile in many cases as often, they were unable to eat due to body positioning, which contributed to the body wasting and further muscle weakness.

Cause:
The disease is caused by a parasite called Sarcocystis neurona, which gains entrance the body and then targets peripheral nerves or the central nervous system, eliciting an inflammatory reaction which impairs nerve function.  The parasite is thought to be transmitted by the opossum primarily, but barn cats and various birds have also been implicated in the past, with the horse inevitably being exposed while grazing on pasture or through contaminated feed.  The horse is considered an aberrant host and once infected, they are not a risk to spreading the parasite to other horses.

Prevalence:
In my practice, the exact prevalence of the disease amongst our patients was less than 5%, but may be higher in other regions of the country.  Blood testing of horses has indicated a positive antibody titer in up to 80% of horses (in my practice area), but the majority of these do not demonstrate clinical signs. A positive serum Western Blot simply implies exposure to the parasite and does not define clinical infection. It seems as if the prevalence of the disease, at least in my area, has actually declined over the past several years or quite possibly, they are just not being recognized as having a problem by their owners.

Clinical Signs:
When I was a student, we saw the worst of the worst when it came to EPM cases.  Upon graduation, often we were misled in thinking that they always presented this way.  With more clinical practice years under my belt,  I learned that there were many clinical presentations with the majority of them being mild.  In many cases, mild EPM cases have presented as an unexplained or ‘shifting’ lameness.  The lameness may be present in one limb one day then the next in another area.  If I was presented with a lameness that I could not pinpoint or localize, we would often screen for EPM.  The clinical examination involves not only a full physical exam, but evaluation of neurological function.  Peripheral and cranial nerves are evaluated for deficits, which may help us in localizing the disease.  Limbs may be flexed and evaluated for lameness, but they will also be evaluated for conscious proprioception (CP) by crossing the limbs at times.  In most cases, when limbs are crossed over, they are quickly replaced to normal position by the horse.  Those with neurological impairment may have a delayed or no response.  Tail and anal tone are also evaluated, in addition to the tail pull to determine if there is muscle weakness present. The parasitic infection generally targets nerves and with this, we can have many types of presentation with varying degrees of severity. The condition is progressive in most cases, with time being of the essence in terms of best outcomes for treatment. The most common types of presentations would involve one of the following

  • ·         Lameness

  • ·         Muscle weakness / atrophy

  • ·         Poor performance/intolerance

  • ·         Ataxia (uncoordination)

  • ·         Stumbling or tripping

  • ·         Recumbency/unable to stand

  • ·         Difficulty eating/swallowing or ‘choke’

  • ·         Head tilt

  • ·         Behavioral changes


Diagnosis:
The diagnosis of EPM can be tricky, but in most cases we base the diagnosis upon the combination of clinical signs in addition to other laboratory data.  In our patients, if there is a suspicion of EPM, we would submit a blood antibody titer (Western Blot) to rule in or out the disease.  A positive test on blood is NOT confirmative for a diagnosis of EPM, but a negative result generally rules out the parasite.  If the blood test is positive, which equates to a history of exposure to the parasite, often the next step is to perform a spinal tap in the lumbar region, again looking for antibodies or parasite DNA (PCR) in the spinal fluid. In more recent years, technology has allowed for more refined antibody testing of serum in order to obtain specific titers, which may help to differentiate between exposure and actual clinical disease.

Several issues have risen over the past few years regarding spinal taps.  First thing to remember is that there is risk to the procedure for both the patient and veterinarian.  It can be painful at times, resulting in a horse kicking out to the side which may injure people around the horse.  In other cases, horses have been known to buckle upon insertion of the needle, resulting in potential injuries.  Spinal taps may also potentially worsen ataxia or uncoordination in clinical horses and may be difficult to perform successfully in recumbent animals. The biggest problem with spinal taps is blood contamination of the sample.  If a horse is positive, they will have antibodies present in the bloodstream.  In order to perform a spinal tap in the horse, the needle actually has to pass through several inches of muscle, which are saturated with blood.  The current thought process is that there is a potential for the needle to be exposed to the blood, gather antibodies and thus produce a positive spinal fluid sample.  In the end, it is hard to prove that a positive spinal tap is not due to blood contamination and thus a false positive.

Due to this fact, we stopped performing spinal taps several years ago and have more or less relied on clinical signs along with a positive blood antibody titer.  It certainly is not 100% definitive, but is safer and less expensive in the short run to gather data and assess for a response to medications.

Differential Diagnosis:
Other considerations for a horse demonstrating neurological clinical signs includes toxicity, herpes viral infection, Easter/Western encephalitis, West Nile, Rabies, equine degenerative myelopathy, equine lower motor neuron disease and cervical vertebral stenosis (wobbler syndrome).  Either clinical signs or further testing can help to rule in or out these diagnoses.

Treatment:
For many years, we have used a combination of antibiotics; sulfatrimethoprim with rifampin, to help manage the parasite infection.  The combination was often fairly successful, but required many months of therapy.  Over the past decade, we have seen some improvement in therapies, which include a medications such as diclazuril, toltrazuril, ponazuril and NTZ, which have all shown promise and require less time for treatment.


Results from therapy can be variable with noted improvement in less than 75% of cases and a full recovery in less than 25%.  In some cases, the patients would actually get worse during therapy for a brief period due to the parasite being killed off and eliciting an inflammatory type reaction.  In many cases, the patients would recover but continue to have neurological issues or deficits resulting in loss of use, decreased performance and even euthanasia in some cases.

One of the biggest problems when treating an EPM horse are relapses, which can be quite high.  In many situations, horses would appear to recover, only to demonstrate clinical signs again within the next 6-12 months.  This is not only frustrating but expensive for the owner as it often entailed another course of medication.

Other therapies often used adjunctively include non-steroidal anti-inflammatories, corticosteroids, DMSO and antioxidants, with vitamin E being most commonly used.

Thoughts / Prevention:
Many years back, an astute veterinarian raised the question as to how the parasite was gaining access to the systemic circulation.  After all, most bacteria and parasites are killed off by high acid levels in the stomach or by other factors in the gut.  In order for the parasite to gain access, there would have to be a breakdown in the gut barrier in some shape or form.  Upon further exploration of this theory, it was proposed that many of these clinical horses had gastric ulcers, which may be allowing the parasite to gain access to the body.  There are many theories out there, many of them still unproven, but this ulcer theory opens the door to many questions.

If we blood test 10 horses for antibody titers, approximately 8 of them will be positive and maybe 1-2 of those 8 will actually be clinically sick.  Why?  What makes those 1-2 horses different or more susceptible to clinical disease?  When we look at the ‘ulcer theory’, this raises the question regarding the impact of stress on the body, which may be hindering the immune response.  The body creates many barriers to prevent invasion by bacteria, viruses and other parasites, but the immune system is ultimately responsible for detecting and eliminating invaders into the body.  So, what potentially causes a deficiency in the immune response?  This can be a genetic cause, dietary related, stress induced….the list goes on.  It has been noted that stress and immune compromise increase the susceptibility to a horse contracting EPM.  Likewise, the incidence of EPM also appears to be higher in competitive horses, which may be undergoing increased levels of stress.

What I have found and explore with these patients is the status of the immune response.  In all of our cases, I have submitted what is termed a CBC (complete blood count), which is fairly routine.  What I am looking for is the level or status of the white blood cells, specifically the lymphocyte.  I have noticed that many EPM cases have lowered lymphocyte levels upon presentation. Those horses with lowered lymphocyte counts also appear to be more likely to experience relapses.  It is potentially a crude means of evaluating the immune response and predicting relapse rates, but none the less is valuable in my opinion.

When we were first treating these patients years ago, I would almost always add in some type of immune supplement along with traditional therapies.  Originally, I would use a cattle dewormer called Levamisole, which has demonstrated immune enhancing properties.  It would help in most cases, but there was always a need for something better.  Several years later, I discovered and researched medicinal mushrooms and their impact on immune health.  There are several types of mushrooms that demonstrate immune enhancing capabilities and have been researched for decades with verifiable results.  We soon developed and began to utilize what became our EQ Immune &Repair formula in our EPM cases and noted a tremendous impact along with traditional therapies.  The patients did better overall and recovered more completely. 

Aside from the immune component, we have to remember that there is also a strong inflammatory reaction that is occurring and contributing to neurological deficits.  In many severe cases, especially in recumbent horses, clinicians would utilize a steroid or DMSO to help combat the inflammation.  The steroid would help in a high percentage of cases, but potentially came at a cost due to a high incidence of side effects, including gastric ulcers, further immune suppression and even laminitis.  We used these steroids in some of our cases, but needed something more complete, gentler and more effective for systemic inflammation.  We began to utilize our EQ Plus  formula in our EPM cases to combat inflammation as well as provide antioxidants in addition to our Immune & Repair formulas, alongside of the traditional therapies.  Again, we noted a more complete and quicker recovery in a high percentage of cases.  In some cases, due to the expense of pharmaceutical medications, many owners were unable to afford traditional therapies and we were forced to manage them using our EQ Plus and Immune & Repair formulas.  It was stunning to see that a high percentage of these horses recovered and obtained remission without the need for anti-parasitic medications.  The results were achieved based on improving overall immune health and managing inflammation.

Our results have been confirmed by many of our Cur-OST® customers, stating an enhanced recovery as a standalone therapy or even in cases that have relapsed and were no longer responsive to traditional therapies.

Prevention of EPM from my point of view is rather simple. We can make attempts to 'clean up' the environment and make it less attractive to the Opossum, but it is next to impossible to eliminate the parasite completely from the environment.  We can, however, enhance overall health in these patients by improving immune function and controlling ongoing inflammation.  Factors such as stress, lifestyle, diet, genetics and many others directly contribute to inflammation, which then potentially impacts immune health.  It becomes obvious in many EPM cases that inflammation was a preliminary problem as many of these horse have other concurrent issues such as lameness, poor performance, laminitis, COPD and even insulin resistance.  We need to look at the patient as a whole to get a better understanding on how poor health influences the prevalence of these diseases.

In the end, EPM is a complex condition with a multitude of opinions on how to treat and manage.  We need to stop looking to pharmaceutical medications as being the end all be all answer and start looking at the patient as a whole, including their environment and lifestyle.  

All my best,

Tom Schell, D.V.M.
www.curost.com

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