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S. neurona may elicit the JAK/STAT pathway in disease



Tongue paresis following S. neurona infection

Do you wonder why researchers often can't find Sarcocystis neurona in the tissues of a horse with EPM (equine protozoal myeloencephalitis) on post-mortem exams? They can't even find the organisms in experimental infections when the onset of infection is known. Time of infection is a huge advantage because we already know when and where the parasite goes after infectiion. The most obvious answer to the absence of parasites is that they were eliminated by the immune system, just as nature intended.


The forgoing begs the question about "chronic EPM" and "relapsing EPM". We see a number of internet posts about people thinking they are dealing with a horse that had EPM and the signs are due to parasites. We disagree with those conclusions. The horse isn't improving because the diagnosis is incorrect.


Our hypothesis is that the disease associated with EPM is not from the parasites but it is due to a "bystander mechanism". The hosts cells and tissues are injured by immunologic reactions, the cells and tissues are innocent bystanders, although the immunologic reactions were initiated by parasites. The parasites are eliminated, but the inflammation remains. There are several possible mechanisms, one is the development of autoantibodies and the resulting disease is autoimmune; another mechanism is chronic inflammation that isn't turned off. Bystander mechanisms are common in several diseases, for example Lyme Disease, Equine Herpes Virus, Long Covid, and equine sarcocystosis.


The reactive proteins associated with the infecting organisms, antigens, reach the peripheral nervous system attracting and activating lymphocytes and macrophages. The reactive cells remove the offending microbes. However, some of the inflammatory pathways remain engaged and result in chronic inflammation. There are immune rpathways that are prostaglandin mediated, some cytokine mediated, COX2 can be involved, and some use the JAK/STAT pathway. NSAID's don't work on all these pathways and certainly anti-protozoal drugs are not indicated.


The important factors in identifying disease by a bystander mechanisms are ruling out other look-alike diseases. There are many articles that list the differential diagnosis for EPM and we won't review them here. However, one disease that is overlooked is temporohyoid osteoarthropathy (THO). Overlapping signs with EPM include head shaking/tossing, difficulty chewing food, resistance to the bit, behavioral problems, and ear rubbing. Neurological signs may develop as the disease progresses.


Neurological signs associated with THO can include loss of balance, head tilt, and involuntary movement of the eyes (nystagmus). Signs of facial nerve paralysis may include deviation of the muzzle to one side, a droopy ear, and inability to close the eyelids. Damage to nerves that affect the eye can lead to decreased tear production and abnormal blinking, which can cause significant ulceration of the cornea. Radiographs and endoscopy are useful to determine if the horse has THO.


Be sure and get your horse worked up with a full neurological exam and watch for new enrollment into our field studies for new medications to treat bystander disease signs.




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