Signalment:  

Adult, mixed breed, beef cow (Bos taurus). This is a 25-cow herd of adult mixed breed beef cows in late gestation. Several animals developed a staggering gait over weeks and were euthanized.

Gross Description:  

No gross lesions.

Histopathologic Description:

Scattered neurons in the brain stem around the cerebral aqueduct and in the pons contain green-brown granular material in the cytoplasm (Figs. 1, 2). Many neurons contain golden pigment consistent with lipofuscin. Occasional neuronal necrosis is seen. Some sections have axonal degeneration of nerves along the ventral surface of the brain stem.

Morphologic Diagnosis:  

Neuronal pigmentation, brain stem, mild, with axonal degeneration and neuronal necrosis.

Condition:  

Phalaris toxicosis

Contributor Comment:  

The pigment in neurons is consistent with that seen in poisoning by plants of the genus Phalaris. Ultrastructurally, the granules within the neuronal cytoplasm are membrane-bound and composed of concentric membranous lamellae that may be intermingled with fine granular material. They are considered to be lysosomal in nature.(1) The toxic principle is a mix of methyl tryptamine and beta carboline indoleamines that are related to the neurotransmitter serotonin. The experimental administration of these alkaloids to sheep has induced the acute syndrome, presumably by interfering with the function or metabolism of serotonin.

Phalaris toxicosis is typically a disease of sheep causing staggers. Onset of staggers may be rapid following ingestion of the plant or delayed by several months. Most animals recover from the staggering syndrome but some do not. Cattle are occasionally poisoned by Phalaris and develop staggers from which they usually do not recover. Sudden death is another less common manifestation of Phalaris poisoning seen in sheep and occasionally horses.(3)

The Phalaris species likely involved in the poisoning of these cattle is Phalaris arundinacea or reed canarygrass. This plant was found in the pasture grazed by the affected cattle. 

JPC Diagnosis:  

Brainstem: Neuronal pigmentation, multifocal, with mild gliosis.

Conference Comment:  

Conference participants discussed the tinctorial and morphologic differences between lipofuscin and the pigment imparted by Phalaris toxicosis. The distinction is important, because although the wear and tear pigment of lipofuscin indicates free radical and lipid peroxidation of polyunsaturated lipids of subcellular membranes, it is does not generally cause injury to the cell.(2) In Trachyandra intoxication, lipofuscinosis may be intense in central and peripheral neurons; however, the relationship between this storage process and clinical signs is uncertain. The pigment in many of the ceroid lipofuscinoses is not lipofuscin, but rather protein subunit c of mitochondrial ATP synthase.(3)

In this case, tan, globular lipofuscin is predominantly concentrated in the axon hillock of motor nuclei. The storage granules resulting from Phalaris toxicosis are more granular, brown to green, and have a predominantly perinuclear distribution. Similar granules may occur in the renal tubular epithelium of affected animals, and in severe cases the granules impart a grossly visible green discoloration to kidneys and gray matter.(3)

Phalaris toxicosis is one of several induced storage diseases caused by plants. Others include the aforementioned lipofuscinosis associated with Trachyandra toxicosis; Solanum-induced cerebellar neuronal degeneration and loss; Gomen disease, a suspected toxicosis of horses in New Caledonia; and alpha-mannosidosis induced by the indolizadine alkaloid swainsonine, found in a variety of plants, including locoweed (Astragalus sp., Oxytropis sp.), poison pea (Swainsona sp.), and the shrubby morning glory (Ipomoea sp.).(3)

The term staggers, as applied to the clinical manifestation of Phalaris toxicosis, should not be confused with staggering disease, caused by Borna disease virus, or ryegrass staggers, which includes both perennial and annual ryegrass staggers. Annual ryegrass staggers is caused by a corynetoxin produced by the bacterium Corynebacterium rathayi in nematode-induced seed head galls; host plants include annual ryegrass (Lolium rigidum), annual beardgrass (Polypogon monsppeliensis), chewings fescue (Festuca nigrescens), and Pacific bent grass (Agrostis avenacea). The corynetoxin inhibits lipid-linked N-glycosylation of glycoproteins, compromising membrane integrity, and causing increased vascular permeability in multiple organs, including the brain.(3) Perennial ryegrass staggers is caused by tremorgenic mycotoxins (lolitrems) produced by the endophytic fungus Neotyphodium lolii in perennial ryegrass (Lolium perenne); disease is milder than in annual ryegrass staggers and is often reversible.(4)

References:

1. East NE, Higgins RJ: Canary grass (Phalaris sp) toxicosis in sheep in California. JAVMA 192:667-669, 1989
2. Kumar V, Abbas AK, Fausto N, Aster JC: Robbins and Cotran Pathologic Basis of Disease, 8th ed., pp. 36-37. Saunders Elsevier, Philadelphia, PA, 2010
3. Maxie MG, Youssef S: Nervous system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol. 1, p. 331. Elsevier Saunders, Philadelphia, PA, 2007
4. Radostits OM, Gay CC, Hinchcliff KW, Constable PD: Veterinary Medicine, A Textbook of the Diseases of Cattle, Horses, Sheep, and Goats, 10th ed., pp. 1410-1413. Saunders Elsevier, Philadelphia, PA, 2007

A virtual slide is not available for this case.

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2-1. Mesencephalon

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