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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.


Once upon a time there was a small village on the edge of a river. The people there were good and life in the village was good. One day a villager noticed a baby floating down the river. The villager quickly swam out to save the baby from drowning. The next day this same villager noticed two babies in the river. He called for help, and both babies were rescued from the swift waters. And the following day four babies were seen caught in the turbulent current. And then eight, then more, and still more!

The villagers organized themselves quickly, setting up watchtowers and training teams of swimmers who could resist the swift waters and rescue babies. Rescue squads were soon working 24 hours a day. And each day the number of helpless babies floating down the river increased. The villagers organized themselves efficiently. The rescue squads were now snatching many children each day. While not all the babies, now very numerous, could be saved, the villagers felt they were doing well to save as many as they could each day. Indeed, the village priest blessed them in their good work. And life in the village continued on that basis.

One day, however, someone raised the question, “But where are all these babies coming from? Let’s organize a team to head upstream to find out who’s throwing all of these babies into the river in the first place!”

We’ve heard this story many times so the source is lost, but the message is true.  The presence of inflammation and it’s association with EPM is as old as the discovery of the disease itself.  Neuroinflammation associated with EPM is minimally responsive to steroid and non-steroidal anti-inflammatory drugs, NSAID's target prostaglandin mediated inflammation.  We have had success treating EPM-associated neuroinflammation by modulating the immune system directed by non-prostaglandin pathways.

We clearly showed that serum amyloid A (SAA) was elevated in horses with EPM, however this inflammatory marker was elevated very late in the course of disease. This makes SAA unattractive to help us identify a horse with EPM. We are closer to understanding what happens in S. neurona infections in horses when we concentrate on innate immune pathways.

Because C-reactive protein (CRP) is closely associated with IL6, a molecule found on nervous tissue linings, we measure CRP in suspect cases of EPM. Eighty percent of horses with an incomplete response or relapse case of EPM have highly elevated CRP values, the average value in this group of horses is more than 39 micrograms/ml of serum!  When the CRP was elevated prior to treatment in a horse with sarcocystosis, the value dropped post treatment.

A poor predictor of survival is no response to treatment and a CRP value that remains elevated.  Clinical signs remain the most important parameter for evaluating EPM cases, however CRP is useful to determine response to inflammation in the cases we are monitoring.

Why does cytokine-targeted treatment relieve the signs of EPM?  We turned to the human literature where IL6 receptor signaling is an active area of research.  What we found is that there are soluble cytokines (IL6 has a soluble receptor that can cross the blood brain barrier in many species)—why not in horses?

While there aren’t cells that are actively making IL6 in the central nervous system in EPM horses, the soluble IL6 receptor can bind cells that lack this receptor.  Once the IL6 receptor attaches to the cell, the cell binds molecules that ultimately turn on inflammation.  That may be how there are clinical signs without parasites in many cases of EPM. It was shown that there aren’t any detectable IL6 cytokine gene expression in the brain tissues of horses with EPM.  The only way our theory makes sense with this cytokine is via a circulating receptor that can bind receptor-less cells, as shown in humans.  There could be another cytokine, and even if we are are on the right track with IL6, it isn’t a solo act.  We can measure IL6 so it is our first target, IL6 stimulates C-reactive protein and that is easy to measure.

Our goal is a treatment that goes to the head of the inflammatory stream to turn off the pro-inflammatory cells off by preventing the synthesis of IL6 receptors. Once the signal pathway is blocked the signs of inflammation recede.