Definition and Etiology
Robert J. MacKay • Lisle W. George
Locoism (Swainsonine Toxicity)
Chronic ingestion of various plants worldwide can result in an acquired neurovisceral storage disease. Plants incriminated so far include members of Astragalus and Oxytropis genera (locoweeds) in the western United States, Canada, Africa, Asia, and Australia; Ipomoea carnea in Mozambique; the darling pea in Australia (Swainsona spp.); and Ipomoea spp., Turbina cordata, and Sida acuta (also known as S.
carpinifolia) in Brazil.1-8 The disease was also diagnosed in a horse in Belgium; however, the causative plant was not identified.9 Horses are most susceptible, but cattle, sheep, goats, and deer can also be affected.10Conditions that promote locoweed poisoning are hot, dry weather and a scarcity of alternative forage. Horses may be more prone to graze on locoweed than are cattle, particularly when other green forage is scarce, and may increase their consumption over a single season.10 Chronically exposed livestock become addicted to locoweeds and feed selectively on the plant over successive grazing seasons.11
Locoweeds represent only a small proportion of the species in the Astragalus or Oxytropis genera; many Astragalus spp. contain nitrotoxins or are selenium accumulators, and many other members of both genera are nontoxic. The indolizidine alkaloid swainsonine (also known as locoine) has been identified as the cause of locoism. Swainsonine acts by potent inhibition of mammalian α-D-mannosidase and of Golgi mannosidase II.5,12 Swainsonine synthesis in Astragalus and Oxytropis plants is dependent on the fungal endophyte Undifilum oxytropis or closely related Undifilum spp.13,14 Swainsonine, along with slaframine (slobber toxin), is also produced by Rhizoctonia leguminicola, a fungus that causes black patch disease of red clover.15 Whether plants other than Astragalus and Oxytropis spp.
are also colonized by swainsonine-producing fungi has not yet been clarified. Other toxins identified in locoweeds have included β-galactosidase and β-glucosidase; aminonitrile, a toxin that causes abortion and teratogenesis; and miserotoxin, a cause of respiratory disease.Oxytropis and Astragalus plants are legumes that have herbaceous stems and alternate pinnately compound leaves.16 The fruits are characteristic leguminous pods that contain kidneyshaped seeds with pods marked by characteristic longitudinal grooves. The plant is eaten because it is the first vegetation available in the spring. Neurologic signs do not usually develop in cattle until 3 weeks after the animals first begin grazing on the plant and may not occur until long after ingestion of the plant has stopped. In parallel with changes in the concentration of endophyte in locoweeds, toxicity may vary from year to year and even within one season.17
■ Clinical Signs Experimentally and naturally poisoned horses show clinical signs by 2 to 3 weeks after continuous ingestion of locoweed.2,10 The clinical signs include ataxia and obtundation alternating with periods of frenzied or manic activity.7 Some affected horses demonstrate a high-stepping gait suggestive of cerebellar dysfunction.7 At rest, there is intention tremor of the head; flaccidity of the nose and lips; repetitive, dystonic movements of the lips and tongue; and dysphagia. The clinical signs worsen when affected horses are handled or transported. Signs in goats are similar, including ataxia, hypermetria, hyperesthesia, and muscle tremors.1,2 When the chin is raised for 30 seconds and then suddenly released, even mildly affected goats fall into recumbency with additional signs of nystagmus, opisthotonos, tetanic spasms, and seizures. Sedation is usually ineffective for controlling the hyperexcitability of locoism. Horses that survive locoweed poisoning retain altered behavior and an irregular gait.
Abortions, stillbirths, and neonatal deaths can occur in all species exposed to these toxic plants, regardless of whether the dams have clinical signs of neurologic disease.2,3,18Neurologic signs in adult cattle include ataxia, limb hypermetria and weakness, obtundation, dull staring eyes, and loss of herding instinct. Heavy losses from abortions or malformed calves have also been described. The indolizidine alkaloids are secreted in the milk and may cause unthriftiness and weak suckling behavior in calves. Calves that have been exposed to the toxin in utero are weak and fail to thrive. Some may have flexural contractions of the limbs and lateral rotation of the carpus.8,19,20 Ingestion of locoweed by certain cattle at high altitudes may result in the development of cor pulmonale.21 Many cattle with mild signs of locoweed poisoning recover completely by 60 days after removal from the involved pastures. Poisoned sheep have a stargazing attitude and appear to be blind, nervous, and stiff. The normal flocking behavior is absent.12 Affected sheep may salivate excessively. Testicular atrophy has been reported in affected rams.22 The immunosuppressive actions of swainsonine predispose affected animals to pyogenic infections such as pneumonia, keratoconjunctivitis, and foot rot.
■ Clinical Pathology Microscopic examination of stained blood smears may reveal cytoplasmic vacuolation of lymphocytes. These changes are found in the majority of lysosomal storage disorders but might be considered diagnostic of locoweed poisoning in animals with characteristic clinical signs and historical evidence of exposure. Serum activities of alkaline phosphatase and AST are high; elevated concentrations reflect liver dysfunction in association with prominent vacuolation of hepatocytes.23 Definitive diagnosis can be established by assays of blood from affected animals for α-D-mannosidase activity and swainsonine concentration.
The half-life of swainsonine in the serum is 16 to 20 hours.24 This means that an animal suspected of locoweed poisoning must have a blood sample taken within 2 days of eating locoweed for swainsonine to be detected.■ Pathology The microscopic abnormalities of the soft tissues of acutely poisoned animals are similar to those of the inherited lysosomal storage diseases of cattle, including cytoplasmic vacuolation of neurons, particularly cerebellar Purkinje cells, and cells in various other tissues.2,7 Paraffin- embedded tissues can be examined with lectin photochemistry testing to characterize the stored material within the vacuoles.25 Vacuolation of renal tubular epithelial cells may occur as early as 4 days after the start of daily feeding of 0.34 kg of locoweed to horses and may be present in animals exposed to toxic plants but clinically normal.26 Pulmonary lesions associated with chronic ingestion of locoweed that may predispose to high-altitude disease (brisket disease) in cattle include alveolar emphysema, bronchiolar constriction and hypertrophy, and interlobular edema and fibrosis. Pyloric or gastric ulcers have been reported in affected cattle.8,26 Placental edema, fetal ascites, and hydrops allantois have been described in exposed pregnant cattle.
■ Treatment There is no known effective long-term therapy for locoweed poisoning. Animals remain affected for a prolonged period or even permanently after removal of the plants. One author recommends tranylcypromine (60 mg PO), a monoamine oxidase inhibitor, and protryptyline (60 mg PO) or reserpine (1.25 mg PO per animal once daily) for treatment of chronically affected animals.27 The efficacy of these treatments is unknown. Addition of a mineral supplement and a natural clay (clinoptilolite) to the diet of cattle ingesting locoweed did not prevent toxicity.28
■ Prevention Nonaddicted livestock normally do not eat locoweed if other forage is available. The condition may be prevented by supplemental feeding during the early spring and late summer. One report has described conditioning aversion to locoweed in horses with lithium chloride administered simultaneously with grazing on Oxytropis sericea.2 Whether this is a practical management tool in large numbers of animals has yet to be determined.