Clinical signs of EPM may include seizures, depression, muscle atrophy, the inability to coordinate voluntary muscle activity and paralysis. Many of these symptoms are similar to other equine diseases that affect the CNS, thus making EPM difficult to diagnose. In addition, the clinical signs of EPM can be subtle or severe. Clinical signs may progress rapidly, or in other cases progression may be slow and signs may even diminish. Although the chances of being seropositive increase with age, the incidence of clinical disease peaks between 15 months and five years.
Stress appears to play an important role in clinical cases and the incubation period is variable.
If left untreated, an infection by S. neurona may remain in the horse's system indefinitely. Which horses will display clinical signs and which horses won't is yet unexplained. The organism that causes EPM is mainly transmitted to horses by the opossum. The opossum releases infective sporocysts into the environment through its feces. The horse ingests the sporocysts via contaminated feed or water.