A 2-year-old Thoroughbred filly in race training was found in its stall with signs of lethargy and periorbital swelling and a corneal ulcer in the left eye; there appeared to be no vision in that eye. These signs were attributed to unobserved head trauma. Over a 3-day period, medical management of the ulcer with topical administration of antimicrobials and atropine was unsuccessful, and the horse was referred for further evaluation. The horse had been treated with acupuncture 2 months earlier for suspected pelvic limb weakness. At the referral examination, the upper eyelid of the left eye was swollen with chemosis and hyperemia of conjunctival and scleral vessels. There was a 10 × 5-mm ulcer in the ventral aspect of the cornea and hyperemia of the left portion of the optic disk. Atrophy of the left masseter muscle and left parotidoauricularis muscle was present. The mandible deviated to the right. Other general physical examination findings were unremarkable.
Neurologic examination
What is the problem? Where is the lesion? What are the most probable causes of this problem? What is your plan to establish a diagnosis? Please turn the page.
Assessment
Anatomic diagnosis
| Problem | Rule out location |
|---|---|
| Blindness, negative menace response, and negative direct and indirect pupillary light reflex in left eye | Cranial nerve II on the left side |
| Facial paralysis of the left side (ptosis, muzzle deviation, ear droop, and loss of facial component of the cervicofacial reflex) | Nucleus (medulla oblongata), root, or nerve of cranial nerve VII on the left side |
| Deviation of mandible to the right and left masseter muscle atrophy | Motor nucleus (pons), root, or nerve of cranial nerve V (motor division of trigeminal nerve) on the left side |
| Quadriparesis and upper motor neuron deficit | Upper motor neuron (brainstem nuclei and descending motor tracts), midbrain to T2 spinal cord segment (asymmetric, multifocal, or diffuse lesion) |
| Head turn to the right without a tilt | Right or left aspect of the forebrain (diencephalon or telencephalon); atypical right- or left-sided central vestibular disease |
| Head tilt to the left when blindfolded | Cranial nerve VIII (peripheral and left-sided location or central, right, or left location) |
| Ventral strabismus and exaggerated eye drop in left eye | Cranial nerve III, cranial nerve VIII, or extraocular muscles (all left side) |
| Left parotidoauricularis muscle atrophy | Cranial nerve VII (central or peripheral location) |
| Collapse in pelvic limbs with slight dorsal pressure | L3 to S2 lower motor neurons, ventral horn gray matter, ventral nerve roots, or peripheral motor nerves |
| Obtundation | Ascending reticular activating system of the brainstem or diffuse forebrain disease |
| Absence of physiologic nystagmus in the left eye only | Cranial nerve III (controls adduction of medial rectus muscle during normal nystagmus), cranial nerve VI (controls abduction of lateral rectus muscle during normal nystagmus), or extraocular muscles |
| Negative left eye retraction | Cranial nerve VI, nucleus (pons) or peripheral; sensory component of cranial nerve V, central or peripheral; or extraocular muscles of left eye |
Likely location of one lesion
| These signs cannot be explained by 1 lesion but are consistent with a minimum of 2 lesions: obtundation (ascending reticular-activating system); dysfunction of cranial nerves II, III, V, VI, VII, and VIII; and limb ataxia or quadriparesis (upper motor neuron or spinocerebellar tracts) with at least 1 extensive asymmetric lesion in the brainstem (left > right; extending from diencephalon to medulla); and collapse of pelvic limbs in response to mild dorsal pressure with at least 1 lesion affecting lower motor neurons of the lumbosacral intumescence (L3-S2). If these lesions are caused by a single disease, then the finding of obtundation excludes diseases that only involve nerve roots or peripheral nerves. |
Etiologic diagnosis—Differential diagnoses included equine protozoal myeloencephalitis (EPM), trauma to the skull or a spinal injury, infectious meningoencephalomyelitis (bacterial or verminous), viral encephalomyelitis (eastern equine encephalomyelitis virus or West Nile virus infection), abscess (focal or multifocal), neoplasia (focal or multifocal), or vascular infarcts. The diagnostic plan included a CBC and plasma biochemical analysis (to detect underlying systemic pathological changes), analysis (including cytologic examination) of a CSF sample (to evaluate for bacterial, viral, verminous, or protozoal inflammation or neoplasia), analysis of a serum sample via ELISA to enable assessment of the serum-to-CSF concentration ratio for snSAG2,4/3 antibodies (to rule out EPM), radiography or CT of the head (to assess for evidence of trauma), MRI of the head (to assess and characterize any structural abnormalities within the brain), and serologic assessment via IgM ELISA (to detect antibodies against eastern equine encephalomyelitis and West Nile viruses).
Diagnostic test findings—Routine CBC, plasma biochemical analysis, and cytologic examination of a CSF sample were not performed because the filly was euthanized soon after examination because of poor prognosis for complete recovery and future performance. With the consent of the owner, further diagnostic assessments and necropsy were performed. The serum-to-CSF concentration ratio for snSAG2,4/3 antibodies was 25; values of < 100 are indicative of intrathecal antibody production and consistent with a diagnosis of EPM.1 Contrast-enhanced CT revealed no evidence of skull fractures or other trauma. These findings along with atrophy of the masseter and parotidoauricularis muscles were not consistent with a presumed traumatic event 3 days prior. Moreover, EPM is strongly suspected when neurologic signs cannot be explained by 1 lesion. Immediately following euthanasia, MRIa of the head was performed and images were obtained from the following sequences: sagittal, transverse, and dorsal plane T2-weighted fast spin echo; transverse plane T1-weighted spin echo; transverse plane T2–weighted fluid attenuation inversion recovery; and transverse plane T2*-weighted and transverse plane proton density–weighted fast spin echo. The MRI examination revealed a large, expansile, contiguous area of increased signal in the midbrain, pons, cerebellum, and medulla, which was more severe on the left side (Figure 1). Gross necropsy findings included evidence of encephalitis involving the midbrain, pons, and cerebellum, which was consistent with a diagnosis of EPM. Results of histologic examination of sections of the CNS confirmed the diagnosis of EPM and revealed severe, chronic, necrotizing encephalomyelitis with intralesional merozoites as well as neuronal and axonal degeneration in the brain and spinal cord at the level of the C1 vertebra. Spinal cord segments caudal to the C5 vertebra were not examined histologically because of marked autolysis. The result of a PCR assay to detect internal transcribed spacer-1 of S neurona2 in a brain lesion specimen was positive.
Sagittal T2–weighted MRI image of the brain of a horse that was examined because of obtundation and blindness in the left eye. The image was obtained after euthanasia. Notice the large expansile area of increased signal intensity (arrow) present in the midbrain, pons, medulla, cerebellum, and brainstem. Rostral is to the left, and dorsal is toward the top of the image.
Citation: Journal of the American Veterinary Medical Association 243, 6; 10.2460/javma.243.6.779
Comments
Equine protozoal myeloencephalitis is a neurologic disease that affects many horses in the Americas and is most often caused by the protozoan S neurona.3 Spinal ataxia and weakness appear to be the most common signs associated with EPM,4 although signs are variable among horses and are dependent on the area of the CNS that is affected.3 Onset of clinical signs can be sudden or insidious, and signs are usually progressive. For the horse of the present report, onset of clinical signs likely occurred at least 2 months before referral, when pelvic limb weakness was suspected. After a period of apparent quiescence, signs then progressed to involve the brainstem. Diagnosing EPM can be difficult, and the diagnosis must be considered tentative in living horses.4 A definitive diagnosis can only be made after death or euthanasia on the basis of histologic detection of the organism in CNS tissue sections or results of immunohistochemical analysis, PCR assay, or culture of brain or spinal cord samples. In the case described in this report, a diagnosis of EPM was supported initially by clinical signs and the result of the snSAG2,4/3 ELISA.1 Confirmation was made at the time of necropsy after intralesional merozoites were observed and the PCR assay to detect internal transcribed spacer-1 of S neurona yielded a positive result. Ponazuril is an FDA-approved treatment for EPM with a reported 62% likelihood of improvement with treatment.5 Other FDA-approved treatments are diclazuril and a combination of sulfadiazine and pyrimethamine.3
Toshiba Titan high-field 1.5-Tesla unit, Otawara-Shi, Tochigi-Ken, Japan.
References
1. Johnson AL, Morrow JK, Sweeny RW. Indirect fluorescent antibody test and surface antigen ELISAs for antemortem diagnosis of equine protozoal myeloencephalitis. J Vet Intern Med 2013;27: 596–599.
2. Marsh AE, Barr BC, Tell L, et al. Comparison of the internal transcribed spacer, ITS-1, from Sarcocystis falcatula isolates and Sarcocystis neurona. J Parasitol 1999;85: 750–757.
3. Dubey J, Lindsay D, Saville W, et al. A review of Sarcocystis neurona and equine protozoal myeloencephalitis (EPM). Vet Parasitol 2001;95: 89–131.
4. Furr M, MacKay R, Granstrom D, et al. Clinical diagnosis of equine protozoal myeloencephalitis (EPM). J Vet Intern Med 2002;16: 618–621.
5. Furr M, Kennedy T, MacKay R, et al. Efficacy of ponazuril 15% oral paste as a treatment for equine protozoal myeloencephalitis. Vet Ther 2001;2: 215–222.
