Antemortem (before death) diagnosis of equine protozoal myeloencephalitis (EPM) has been a long-standing source of frustration for equine veterinarians and horse owners. Typically, a diagnosis of EPM has been based on the presence of clinical signs consistent with neurologic disease along with a supportive serologic test demonstrating the presence of antibodies against the primary etiologic agent. Most often this is the protozoan parasite Sarcocystis neurona, although EPM is attributed infrequently to the related parasite Neospora hughesi.
Unfortunately, most any neurologic disease can cause clinical signs similar to those associated with EPM. Moreover, horses are frequently exposed to S. neurona, so simply the presence of antibodies in the blood has little diagnostic value. Given these challenges, it is little wonder that some veterinary practitioners have relied on “response to treatment” as a primary diagnostic criterion. This approach to EPM diagnosis is not only expensive; it can be misleading as well.
Thankfully, it is now possible to view EPM diagnosis with much greater confidence. The development of semi-quantitative assays that can measure antibodies against S. neurona allow for diagnostic methodology that identifies with high accuracy horses suffering from EPM.
Specifically, the assays can be used to demonstrate S. neurona-specific intrathecal antibody production (i.e., antibodies produced in the central nervous system), which indicates that there is active infection. This approach has been used for decades in human medicine and is based on comparing the amount of antigen-specific antibody present in the cerebrospinal fluid (CSF) relative to the blood. Infection in the central nervous system is confirmed when the amount of antibody present in the CSF is greater than anticipated from normal passive transfer across the blood-brain barrier.
A recent multi-investigator collaboration examined 128 horses that were diagnosed by postmortem examination with either EPM or another neurologic disorder (e.g., cervical-vertebral malformation or wobblers). Serum and cerebrospinal fluid (CSF) from each horse were tested with two enzyme-linked immunosorbent assays (ELISAs) that detect antibodies against the conserved S. neurona proteins SnSAG2, SnSAG3, and SnSAG4. Three major conclusions were derived from the results of these analyses:
- The ratio of antibody in serum vs. CSF provides an accurate diagnosis of EPM (about 92% sensitivity and 83% specificity).
- Although less accurate for diagnosis, higher antibody titers in CSF were associated with EPM.
- Serum antibody titers alone were not a good indicator of EPM.
Collectively, the findings from the study confirmed that intrathecal antibody production against S. neurona is a valuable criterion for EPM diagnosis, and the findings highlight the importance of performing spinal taps on suspected EPM cases to allow measurement of antibody in CSF.
The SnSAG2 and SnSAG4/3 ELISAs used for this study are capable of providing an accurate measurement of antibodies against S. neurona, which is critical for showing definitively that there are disproportionate amounts of antibody in the CSF. However, it should be noted that these ELISAs have no magical attributes that make the procedure exclusive to them. Consequently, it should be possible to obtain similar results using other reliable tests that can quantify anti-S. neurona antibodies (e.g., the immunofluorescent antibody test).
In summary, obtaining an accurate antemortem diagnosis of EPM is no longer an exercise in frustration. While it is still important to conduct a careful neurologic examination of a suspect EPM case, the ability to assess the S. neurona neuroinfection status using a supportive test has improved tremendously, thus leading to much greater confidence in a diagnosis. In turn, this leads to better and more timely care for horses suffering from neurologic disease.