JPC SYSTEMIC PATHOLOGY
NERVOUS SYSTEM
March 2023
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, neuronal cell bodies with pyknotic nuclei (neuronal necrosis) and there is 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:
- Chronic ingestion of T. divaricata or T. laxa causes severe neurologic disease and lipofuscinosis in sheep, horses, goats, and pigs
- T. divaricata is indigenous to the arid regions of South Africa and Australia
PATHOGENESIS:
- An induced storage disease associated with intense lipofuscin storage in all central and peripheral neurons, but toxic principle and relationship of the lipofuscin to clinical disease is unknown
TYPICAL CLINICAL FINDINGS:
- Progressive, irreversible weakness
TYPICAL GROSS FINDINGS:
- Variable rusty‑brown discoloration of central gray nuclei and peripheral ganglia
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Abundant perinuclear yellowish‑brown to dark brown granules (lipofuscin) in the cytoplasm of all neurons throughout the central and peripheral nervous systems
- Similar granules can be found in Kupffer cells, hepatocytes, intestinal lamina propria macrophages, renal tubular epithelial cells
ULTRASTRUCTURAL FINDINGS:
- Identical to lipofuscin
ADDITIONAL DIAGNOSTIC TESTS:
- Lipofuscin: PAS-positive due to carbohydrate content; autofluorescent (excitation wavelength of 320-480 nm, emission wavelength of 460-630 nm); reacts to lipid stains due to lipid content (e.g. Sudan black B, Oil Red O)
DIFFERENTIAL DIAGNOSIS:
- Other induced neuronal storage diseases in livestock/horses include:
- Phalaris toxicosis: sheep and cattle, rarely horses in Australia, New Zealand, South Africa, Argentina, California, and West Virginia; grazing on Phalaris spp. grasses (especially P. aquatica, P. arundinacea); cause staggers syndrome (chronic, acute, and/or delayed)
- Microscopic findings: Perinuclear green-brown pigment deposition in neurons (brainstem nuclei, spinal gray matter, dorsal root ganglia), macrophages in CSF, and renal tubular epithelial cells; degeneration within long descending motor tracts in spinal cord; reactive astrocytosis
- Two acute neurologic syndromes: Sudden death due to cardiac arrhythmia (sheep and horses) from serotonin related toxin’s methyl tryptamine and β-carboline indoleamines OR polioencephalomalacia-like syndrome (sheep) due to edema in the deep cortical gray matter laminae with severe astrocytic edema suggestive of peracute ammonia toxicity (see N-M17)
- Locoweed (Swainsonine) toxicosis (N-T01): grazing livestock in North America, Brazil, and Mozambique; swainsonine compounds (indolizidine alkaloids) inhibit lysosomal α-mannosidase as well as Golgi α-mannosidase II; any grazing livestock
- Prominent neuronal swelling and vacuolation (foamy or finely vacuolated)
- Similar changes in multiple other cells throughout body
COMPARATIVE PATHOLOGY:
Other diseases with intraneuronal accumulation of lipofuscin or lipofuscin-like material:
- Gomen disease (N-M12): Unknown environmental toxin in horses from New Caledonia with lipofuscin storage in neurons; cerebellar neuronal degeneration
- Inherited neuronal ceroid-lipofuscinosis (N-M12): Due to an autosomal recessive trait; reported in cattle (Beefmaster), sheep (South Hampshire), dogs (dachshunds, Chihuahua, English setters), and cats; neurons at all levels contain variably sized, colorless or slightly eosinophilic (H&E) cytoplasmic granules that are PAS positive and Luxol fast blue positive
References:
- 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: Elsevier; 2016: 292-293.
- Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 940-941.
