ECG, hematology, serum biochemistry, and rumen contents were reportedly within normal limits. It initially responded to supportive therapy, but deteriorated and died the following day. The calf was submitted to ADDL for necropsy. The owners indicated that white snakeroot was present in the pasture grazed by the herd, and that the dam had also developed muscle tremors and subsequently recovered.
Gross findings: Significant gross lesions were not observed.
Histopathologic findings: Samples of the quadriceps femoris and shoulder muscles contained focally extensive areas of degeneration characterized by myocyte swelling with sarcoplasmic hyalinization, fragmentation, and loss of cross striations. Rarely, myocytes were segmentally mineralized. The interstitium was expanded by edema, numerous macrophages and fewer neutrophils. Variable numbers of macrophages infiltrated the remnants of degenerate myocytes. Regenerative myofibers with basophilic sarcoplasm and large, centrally located nuclei (myotubes) were scattered throughout the damaged muscle tissue.
Toxicology: Rumen contents from the calf were submitted for microscopic analysis. Toxic plants or seeds were not identified in the rumen contents.
Discussion: White snakeroot (Eupatorium rugosum) is a member of the daisy family that can cause severe toxicities in livestock and humans. The perennial herb grows 1-3 feet tall from a shallow mat of fibrous roots, has oval, opposite, serrated leaves with pointed tips, and clusters of small white tubular flowers that bloom in late summer. White snakeroot is common throughout Indiana and the eastern United States. The plant is found in low, moist, shady areas and in clearings and thickets bordering woodlands. Consumption of 0.5-2.0% of body weight in green plant is associated with signs of intoxication in livestock. The toxic effect is cumulative. All parts of the leaves and stems are toxic. Tremetol content is highest in the green plant and remains toxic even when dried in hay. Frost does not inactivate the toxin. Following ingestion, plant components presumably become toxic after microsomal activation by cytochrome P-450 enzymes in the liver. The apparent toxic principle in white snakeroot may be tremetol (or its ketone, tremetone), a fat-soluble, high molecular weight alcohol. Crude tremetol has been experimentally separated into a toxic fraction and a nontoxic sterol fraction. Tremetol is fat soluble and excreted in the milk of lactating animals. Lactating animals are generally slower to show clinical signs of toxicity, although their nursing young will be affected.
In cattle, white snakeroot intoxication has been called "trembles" because of the characteristic muscle tremors. Clinical signs in cattle and other ruminants include depression, lethargy, listlessness, acetone breath (ketosis), constipation, and weakness that often progresses to recumbency, coma, and death in 2-10 days. Muscle tremors are most severe in the muzzle and legs and tend to occur after exercise.
In horses, white snakeroot intoxication is associated with congestive heart failure. Clinical signs include sweating, stumbling, depression, jugular pulses, tachycardia, cardiac arrythmias, and difficulty swallowing. Electrocardiogram changes include increased heart rate, ST elevation, variable QRS complexes, and ventricular premature beats. Muscle tremors are inconsistently observed in horses with white snakeroot poisoning.
White snakeroot intoxication was the cause of "milk sickness" in 18th and 19th century America. Milk sickness in humans begins as weakness, loss of appetite, abdominal pain, and violent vomiting followed by constipation, severe thirst, vomiting, tremors, acetone breath, prostration, delirium, coma, and death. Abraham Lincoln's mother reportedly died from milk sickness in 1818 after drinking milk from a cow that had been grazed on white snakeroot. Although tremetol is not inactivated by pasteurization, human disease is uncommon today due to current practices of animal husbandry and the pooling of milk from many producers.
Mortality in livestock is high. Treatment consists of supportive care, including extra bedding in stalls to prevent development of pressure sores in recumbent animals. Exercise and excitement should be avoided. Lactating animals should be frequently milked out and the milk discarded. Cattle, horses, and other livestock should be restricted from access to pastures containing white snakeroot.
There are no specific routine diagnostic tests for tremetol (or tremetone). Diagnosis is based on clinical signs, presence of white snakeroot in the hay or pasture, elevated muscle enzymes (CK, ALP and AST), histologic evidence of cardiac and/or skeletal muscle degeneration and rule-out of other causes. Rumen or stomach contents may be submitted for microscopic identification of white snakeroot leaves. Gross lesions associated with white snakeroot and other toxic myopathies are often unremarkable, and may be difficult to distinguish microscopically from acute nutritional or exertional myopathies.
Differential diagnoses include botulism, organophosphate intoxication, nutri-tional or exertional myopathies, other toxic myopathies, rabies and esophageal obstruction in horses. Other plants that cause tremorgenic syndromes in livestock include dallies grass, rayless goldenrod (Isocoma wrightii), Jimmy fern (Notholaena sinuate) and western mountain laurel (Sophora secundiflora). Most of these plants are found in the southern and southwestern United States.
-by Dr. Kim Maratea, ADDL Graduate Student
Beier RC et al: 1987. Microsomal activation of constituents of white snakeroot (Eupatorium rugosum Houtt) to form toxic products. Am J Vet Res 48(4): 583-585.
Nicholson SS: 1989. Tremorgenic syndromes in livestock. Vet Clin No Amer: Food An Pract 5(2): 291-301.
Panter, KE and Janes LF: 1990. Natural plant intoxicants in milk: A review. J Anim Sci 68: 892-904.