AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

March 2017

N-T09 (NP)

 

SIGNALMENT (JPC #2077579):  Two-year-old castrated male Merino sheep

 

HISTORY:  This was one of 50 animals affected from a flock of 600 mixed-aged sheep grazing partially cleared bush country.  Losses occurred over three months.  Affected animals were first observed to stagger and collapse when driven and eventually became weak and permanently recumbent, although they remained alert and responsive.  None recovered.

 

HISTOPATHOLOGIC DESCRIPTION:  Brainstem:  Multifocally, approximately 80% of neuronal cell bodies contain variable amounts of a yellow to brown granular, intracytoplasmic, often perinuclear pigment (lipofuscin).  There are rare shrunken, hypereosinophilic, pyknotic neuronal cell bodies (necrosis) and mild gliosis.

 

MORPHOLOGIC DIAGNOSIS:  Brain stem, neuronal cell bodies:  Lipofuscinosis, cytoplasmic, multifocal, moderate, Merino, ovine.

 

ETIOLOGIC DIAGNOSIS:  Toxic encephalopathy

 

CAUSE:  Trachyandra divaricata ingestion

 

GENERAL DISCUSSION:

·       Trachyandra divaricata is indigenous to the arid regions of South Africa and Western Australia and has spread to North America and New Zealand

·       It is commonly known as branched onion weed, and has more recently been called strapweed or dune onion weed

·       Animals are forced to eat Trachyandra sp. in overgrazing, poor management, or drought conditions  

·       Horses, goats, sheep, cattle, and pigs can be affected

·       Similar syndromes have been associated with Trachyandra laxa

 

PATHOGENESIS:

·       The toxic principle is unknown

·       Associated with intense lipofuscin storage in all central and peripheral neurons

·       Clinical signs appear to be irreversible

·       Toxicity results in lipofuscin storage in neurons of the CNS, peripheral ganglia, enteric neurons, hepatocytes, Kupffer’s cells, and renal tubular epithelium

·       Four to six weeks of ingestion of this plant is necessary

 


TYPICAL CLINICAL FINDINGS:

·       Progressive ataxia, weakness, staggering gait, paresis, and paralysis

·       Seizures, varying degrees of hypersensitivity, and muscle fasiculations

·       Death occurs due to starvation, exposure, or secondary complications one to three months after the onset of symptoms

 

TYPICAL GROSS FINDINGS:

·       Variable yellowish‑brown to rusty‑brown discoloration of central gray nuclei and peripheral ganglia

·       Mild pigmentation of the liver, renal cortex, and lymph nodes

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Abundant perinuclear yellowish‑brown to dark brown granules (lipofuscin) in the cytoplasm of neurons throughout the brain, spinal cord and autonomic ganglion

·       Similar granules can be found in Kupffer cells, hepatocytes, lymph node and intestinal lamina propria macrophages, splenic red pulp, and renal tubular epithelial cells

 

ULTRASTRUCTURAL FINDINGS:

·       Similar to lipofuscin:  Membrane bound dense granular and lamellated material

 

ADDITIONAL DIAGNOSTIC TESTS:

·       Granules stain positive with PAS

 

DIFFERENTIAL DIAGNOSIS:

·       Other induced neuronal storage diseases in sheep and cattle include:  Phalaris poisoning and Swainsonine toxicosis

·       "Phalarisstaggers" Sheep and rarely cattle can be affected by eating Phalaris sp. grasses in the United States, Australia, New Zealand, and South Africa

·       Toxic agents include methyl tryptamine and Beta-Carboline indoleamines (chemically related to serotonin)

·       Perinuclear green brown pigment deposition in neurons (brainstem nuclei, spinal gray matter, dorsal root ganglia)

·       Intoxication associated with grazing lush green pastures for 3 to 10 days

·       Two syndromes:

·       Sudden death due to cardiac arrhythmia

·       Chronic neurologic disease  (polioencephalomalacia like syndrome due to edema)

·       Swainsonine (Oxytropis, Astragalus, and Swainsona sp.) toxicity cause inhibition of lysosomal alpha-mannosidase and Golgi mannosidase-II with intraneuronal accumulation of alpha-mannosyl residues and mannose rich oligosaccharides 

·       Clinical differentials are numerous and include:  Nutritional (copper deficiency, Vitamin E/selenium disorders), toxic (Ryegrass staggers (Corynetoxins), Paspalum staggers (mycotoxin), nitrate poisoning), infectious (Rabies, Listeria sp.), and genetic (abiotrophy, storage diseases)

 

COMPARATIVE PATHOLOGY:

·       Gomen disease Unknown environmental toxin in horses from New Caledonia with lipofuscin storage in neurons; cerebellar neuronal degeneration

·       Inherited ceroid-lipofuscinosis:  Due to an autosomal recessive trait; reported in cattle (Beefmaster), sheep (South Hampshire), dogs (dachshunds, Chihuahua, English setters) and cats

o   Neurons at all levels contain variably sized colorless or slightly eosinophilic on H&E and are PAS positive  

 

References: 

1.      Bourke C. The clinical differentiation of nervous and muscular locomotor disorders of sheep in

1.      Australia. Aust Vet J. 1995;72:228-234.

2.      Bourke C, Carrigan M.  Mechanisms underlying Phalaris aquatica "sudden death" syndrome in

3.      sheep. Aust Vet J. 1992;69:165-167.

4.      Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Saunders Elsevier; 2016: 292-293.

5.      Huxtable C, Chapman H, Main D, Vass D, Pearse B, Hilbert B. Neurological disease and

6.      lipofuscinosis in horses and sheep grazing Trachyandra divaricata (branched onion weed) in southwestern Australia. Aust Vet J. 1987;64:105-108.

7.      Miller AD, Zachary JF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 853-854.

8.      Newsholme SJ, Schneider DJ, Reid C.  A suspected lipofuscin storage disease of sheep associated with ingestion of the plant, Trachyandra divaricata. Onderstepoort J Vet Res. 1985;52:87-92.  

9.      Radostits OM, Gay CC, Hinchcliff KW, Constable PD. Diseases associated with toxins in plants, fungi, cyanobacteria, plant-associated bacteria, and venoms in ticks and vertebrate animals.  In: Radostits OM, Gay CC, Hinchcliff KW, Constable PD, eds. Veterinary Medicine a Textbook of the Diseases of Cattle, Horses, Sheep, Pigs and Goats. 10th ed. Philadelphia, PA: Saunders Elsevier; 2007:1868-1871.

10.   Summers BA, Cummings JF, de Lahunta A. Degenerative diseases of the central nervous system. In: Veterinary Neuropathology. St. Louis, MO: Mosby-Year Book Inc; 1995:233-236.

 

 

 

 


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