Equine Leukoencephalomalacia

Robert J. MacKay

Equine leukoencephalomalacia (ELEM) is a fatal CNS intoxica­tion of horses caused by ingestion of fumonisin toxins on corn or corn by-products.^1-3 Fumonisin toxins (B₁, B₂, and B₃), produced by the fungi Fusarium Verticillioides and Fusarium proliferatum (previously known together as Fusarium monili- forme), interfere with sphingolipid metabolism, disrupting endothelial cell walls and basement membranes.⁴ Although all three are toxic, B₁ is the most common and most thoroughly studied.

■ Clinical Signs The onset of ELEM is usually sudden. In previously healthy animals, the first indication may be death, but most affected horses show abnormal neurologic signs for hours to days before death.^5,6 These include obtundation to the point of stupor and dementia manifested as compulsive walking in large circles, head pressing, and hyperesthesia. Blindness and lack of menace response, as well as reduced reaction to touch around the face, may be present. Movements of the muzzle, lips, and tongue may be weak and ineffectual. Signs are typically asymmetric. Muscle fasciculations occur over the neck and withers and in antigravity muscles, and limb ataxia and weakness are prominent in the terminal phase. Seizures are common after affected horses become recumbent, and many affected horses die while convulsing. The few horses that survive ELEM usually have permanent neurologic dysfunc­tion. Hepatic involvement occurs in many cases, as evidenced by high serum levels of liver enzymes, although hepatic failure is uncommon.^4,7 Signs of liver disease include icterus, petechia- tion on mucous membranes, and swelling of the muzzle or lips. Fatal outbreaks of liver disease without brain involvement have been reported.⁴ Cardiovascular abnormalities are also described in horses with experimental ELEM and include decreases in cardiac contractility, heart rate, and arterial pulse pressure and increases in systemic vascular resistance.⁸

Fumonisin toxins cause a variety of clinical syndromes in other species, including pulmonary edema in swine, but horses appear to be the most susceptible domestic animal species and can show signs when exposed to toxin concentrations as low as 5 to 10 ppm.⁴ Regulatory guidance issued by the U.S.

■ Clinical Pathology and Diagnosis No findings on routine bloodwork are unique to ELEM. Serum levels of liver enzymes (i.e., aspartate transaminase, γ-glutamyltransferase, and sorbitol dehydrogenase) and bilirubin are often high. Anemia, leukocytosis, and leukopenia all have been reported, but none is a consistent finding. Markedly high protein concentration (i.e., >100 mg/dL) with normal nucleated cell count is a typical CSF finding in affected horses.⁹ High serum sphinganine level, sphingosine level, and sphinganine-to-sphingosine ratio suggest acute fumonisin toxicosis,⁸ but the assays for these substances are available only at research laboratories. In practice, antemortem diagnosis relies on recognition and demonstration of fumonisin (Bi, B₂, and B₃) concentrations greater than 10 ppm in feed. Fumonisin assays are widely available through diagnostic laboratories, and turnaround should be rapid.

Differential diagnoses include traumatic brain injury, the arboviral encephalitides, hepatic encephalopathy, EPM, and botulism.

■ Epidemiology Leukoencephalomalacia occurs worldwide. Corn becomes contaminated during growth rather than in storage, and climatic factors that stress the plants, such as drought followed by high rainfall, increase the likelihood of mold development. The fungus is introduced into the growing corn by insects such as the western flower thrip, which enters the ear and damages the kernel as it feeds.¹⁰ Cereal grains and baled hay similarly may be contaminated.¹¹ Most cases of related equine disease occur during the winter and early spring.¹ Repeated exposure to the toxin, rather than a single large dose, seems to be associated with the development of clinical signs.¹² Experimental studies with infected corn demonstrated an onset of clinical signs on the ninth day after the beginning of the feeding period, but the reported delay between exposure and signs in outbreaks has ranged between 4 and 180 days.

The rates of disease in exposed horses vary widely, from 14% to 100% in some reports; the rate of lethality is close to 100%.

■ Pathology The major pathologic features in the CNS result from the vascular damage caused by fumonisin toxins, including Iiquefactive necrosis and degeneration or malacia of the white matter of one or both cerebral hemispheres.^5,13 The lesions may vary from grossly inapparent in peracute cases to complete subcortical cerebral necrosis. Flattening of the cortical gyri, enlargement of the cerebral cortex, vascular congestion, cortical softening, yellowish discoloration of the white matter, hemorrhage, and cavitation of the cerebral cortex may be present.¹ A gelatinous fluid can be observed in many of the cavitary lesions. Hemorrhage in the CNS has also been reported. Lesions in the visceral organs, including hepatic congestion, centrilobular hepatic necrosis, hemorrhagic enteritis, and cystitis, are found in some affected horses. The relationship between these lesions in the CNS and those in the liver, urinary bladder, and GI tract is unknown.

■ Treatment Specific treatment is not available, and early euthanasia is usually the most humane option. Because of cerebral edema, it is rational to administer IV antiedema drugs, including corticosteroids (e.g., dexamethasone 0.1 mg/kg daily), DMSO (1 g/kg as a 10% solution), hypertonic saline (4 mL/ kg of 7.2% NaCl every 4 hours), or mannitol (1 g/kg as a 20% solution). Nonsteroidal antiinflammatory drugs (e.g., flunixin meglumine 1.1 mg/kg PO or IV bid), once or twice daily antioxidants (DMSO, α-tocopherol, 20 IU/kg PO), ascorbic acid (25 mg/kg in IV fluids), and thiamine (5 mg/kg, slowly IV) can all be tried to limit secondary brain injury, but none of these treatments is likely to be effective.