Equine protozoal myeloencephalitis (EPM) is an important neurologic disease of horses most commonly caused by infection of the central nervous system by the protozoa, Sarcocystis neurona. Clinical signs can be focal or multifocal and are attributed to damage to neural tissues by invasion of the protozoa and concurrent inflammation. Many horses will test seropositive, however, only a small percentage will exhibit clinical signs which implies horses with a compromised immune system are susceptible to infection while horses with a healthy immune system are able to clear the parasitic infection without treatment. Traditional Chinese Veterinary Medicine theory views this disease pattern as a Zheng Qi Deficiency with Qi and Blood Stagnation. Premortem diagnosis in both Eastern and Western Veterinary Medicine involves a thorough neurologic exam and response to treatment. Treatment with acupuncture and herbal therapy alone or in conjunction with pharmaceuticals has a favorable prognosis. Food therapy and rehabilitation can assist the horse to return to full function. Recrudescence and reinfection when the immune system is challenged is a common sequela, therefore, long term care of EPM horses should include TCVM treatment during times when the Zheng Qi may be challenged.
Introduction and Background
Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses unique to North and South America first described in the 1970s. It is most commonly caused by infection with the protozoa, Sarcocystis neurona but infections with Neospora hughesi and Sarcocystis fayeri have been reported. Unlike S.neurona, S. fayeri forms muscle cysts which can release endotoxins that elicit a dysfunctional inflammatory immune response indistinguishable from S.neurona infection. Equine Muscular Sarcocystis (EMS) caused by S.fayeri has been reported in horses world wide and is not unique to the Americas.1
The definitive host for S. neurona is the opossum, Didelphis virginiana, a marsupial who’s range extends from the Eastern US to the rockies and into Central America. Though not native to the West coast, the opossum was introduced in the 1930s and its range is slowly extending northward into Canada. EPM has been reported in all parts of the United States with a similar prevalence.
The horse is an intermediate dead end host and can be infected by ingesting sporocysts in food or water contaminated with opossum feces. Horizontal transmission is not possible and horses can not transmit S.neurona infection to other horses or other intermediate hosts.
Sporocysts hatch and release sporozoites into the lumen of the intestinal tract. The sporozoites penetrate the epithelium and enter the muscle tissue where they undergo asexual reproduction to become merozoites which then enter the bloodstream and eventually cross the blood-brain barrier to infect neural cells in both the white and grey matter in the central nervous system (CNS).2
The mechanism to cross the blood-brain barrier is unknown but is thought to involve merozoite infection of encephalitogenic T cells. Encephalitogenic T cells are leukocytes with the ability to cross the blood-brain barrier. Molecular imaging techniques have shown encephalitogenic T cells adhere to the epithelium of the CNS microvasculature and migrate along the luminal surface until they are able to find an entry point.3
Many horses will test positive for the protozoa but few progress to neurologic disease. Reported seroprevalence varies widely from 15% to as high as 89% however horses with active disease is far lower. The factors contributing to the progression are unclear. Stress, vaccination and other concurrent disease have been implicated. Animal models of Experimental Allergic Encephalitis (EAE) which are used to help understand human neurologic diseases with an autoimmune component such as Multiple Sclerosis have shown that the gut microbiome has some influence on the ability of encephalitogenic T cells to cross into the CNS
Retrospective studies found some predisposing factors for horses at a higher risk of developing EPM which included age, season, presence of opossums and a stressful lifestyle. Young horses between the age of 1 to 5 years and horses
older than 13 years had a higher prevalence. Horses were three times as likely to be diagnosed with EPM in the Spring and Summer and six times as likely to be diagnosed with EPM in the Fall as compared to Winter. A large opossum population in the area correlated with a higher prevalence of disease. Racing and Competition horses had a higher risk of developing disease as compared to pleasure and breeding horses.
Clinical Signs
EPM commonly presents as a progressive neurologic disease with an insidious onset of focal or multifocal signs depending on what part of the spinal cord, brainstem and/or brain is involved.
Some cases have presented with acute signs with severe ataxia, seizures and recumbency while others have mild signs over a long period of time with intermittent episodes of relapse and recovery.
Most cases involve a bright, alert horse with a gait abnormality and asymmetric ataxia with muscle wasting, however, signs can be variable depending on location. Involvement of the cerebrum may cause depression, behavior changes or seizures. Lesions in the brainstem may cause cranial nerve deficits and involvement of the cerebellum may cause muscle spasticity and a “Shivers – like” presentation. In the spinal cord, signs of gray matter involvement include muscle weakness followed by muscle atrophy because the neuronal cell bodies are damaged. The quadricep, gluteal and temporalis muscles are often affected. White matter involvement results in ataxia and weakness or hypertonia in limbs caudal to the site of infection because the communication between neurons is damaged. Experimentally induced horses show loss of appetite, decreased tongue tone and facial paralysis Early signs of EPM such as stumbling and frequent interference between limbs can be confused with lameness.
Conventional Diagnosis
Definitive diagnosis requires post mortem conformation of parasites in the CNS, however in up to 50% of cases, diagnosis was made presumptively on the characteristic inflammatory pattern without detection of parasites.2
In practice, if after a thorough neurologic examination, EPM is high on the differential diagnosis list, there are testing options available. Western Blot (WB), indirect fluorescent antibody tests (IFAT) and enzyme-linked immunosorbent assay (ELISA) assays for the parasite surface antigens SAG 1, 5 and 6 on blood and/or spinal fluid can be used independently or read as a ratio of CSF titers to Serum titers. A positive response to treatment is also used for a presumptive diagnosis with or without laboratory testing.2
Conventional Treatment
Historically it was believed that infection of the parasite caused focal mechanical damage to the neural tissues, but current research shows that parasite induced inflammation of the nerves causes the majority of clinical signs, therefore, current treatment therapies focus on two goals, to eliminate the parasite and to reduce inflammation.6
Oroquin-10 (FP), decoquinate at 0.5 mg/kg combined with levamasole at 1 mg/kg for 10 days showed improvement of clinical signs in 93.6 % of horses. Decoquinate is highly efficient at eliminating the protozoa, while levamasole is an immune modulator that reduces inflammation and helps to restore immune balance.7
Three other common commercially available treatments address the elimination of the parasite :
Marquis (BAH), ponazuril at 5 mg/kg per day for 28 days has shown decrease in clinical signs and does cross the BBB to reach the CNS.8 Some protocols recommend a loading dose of 15 mg/kg day to achieve steady state concentrations in the CNS within 28 hours. Efficacy of this treatment, defined as improvement of clinical signs by one grade, is 60% with 8% of those cases relapsing within 90 days.
Protazil (MAH), diclazuril at 1 mg/kg per day for 28 days also improved clinical signs by one grade in 58% of horses.
Rebalance (PRN) sulfadiazine at 20 mg/kg and 1 mg/kg pyrimethamine per day for 90 days improved clinical signs in 61.5 % of treatment horses. Because sulfadiazine and pyrimethamine are folate inhibitors, side effects such as bone marrow suppression have been documented.
Conventional treatments are usually prescribed with concurrent NSAID or steroid therapy to address inflammation along with 5000 – 7000 IU Vitamin E as an antioxidant.11
Symptoms associated with EPM
• Hypersensitivity-sensitivity to noise, touch, tremors.
• Wormy, pot belly appearance, gastric and/or colonic ulcers
• Moving short strided, especially in the rear
• Low stamina, weakness
• Adverse reactions to wormers or vaccinations
• Chronic allergies
• Unusual sensitivity at the girth
• Stiffness in the rear, most often the right hind
• Tightness in the muscles inside the upper legs and groin, causing a cow-hocked or knock-kneed appearance, splayed-out or toed-out feet especially hind feet
• Reluctance to pick feet up
• Hopping, changing leads at the canter, tripping
• Lameness most noticeable at the walk and the canter
• muscle spasms
• Toe dragging, landing more on toe, toe stabbing
• Right hind swings out
What is the best alternative treatment for EPM diseases.
TCM formulations including strong antiparasitic/protozoa herbal formulations and also Tonify Qi and enhancing the immune system.
Best used with conventional medicine for lasting and successful results.