JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2026

N-M21 (NP)

SIGNALMENT (JPC #2013034): Military working dog, age unspecified.

HISTORY: Incidental finding

HISTOPATHOLOGIC DESCRIPTION: Brain, cerebellum and brainstem: Diffusely in the cerebellar molecular layer there are moderate numbers of 10-20 µm diameter, round to oblong, often-bulbous structures with a blue-gray, finely granular core surrounded by a 2-4 µm wide light amphophilic, finely granular zone and further outlined by a 1 µm thin zone of eosinophilic material (peripheralized axoplasm). Moderate numbers of neurons in the brainstem contain intracytoplasmic, often perinuclear, yellow-gold pigment (lipofuscin).

MORPHOLOGIC DIAGNOSIS: Brain, cerebellum, molecular layer: Polyglucosan bodies, numerous, breed unspecified, canine.

CONDITION: Incidental Lafora-like bodies

SYNONYMS: Lafora bodies; neuronal glycoproteinosis

GENERAL DISCUSSION:

• Lafora bodies (LBs), corpora amylacea, and amylopectin bodies are all intracytoplasmic inclusions composed of complex glycoprotein polymers (polyglucosan bodies)
• Incidental LBs are the most common form of LBs and occurs in neurons of aging animals
• Lafora-like disease of dogs: rare; associated with severe myoclonus epilepsy; LBs occur in high numbers through the brain, intracytoplasmic within neuron soma, dendrites, and less frequently in axons; most numerous in Purkinje cells and neurons of the caudate, thalamic, and periventricular nuclei

PATHOGENESIS:

• Lafora-like disease of dogs is caused by repeat expansion (triplet repeat disorder) of the EPM2B gene (encodes malin)
• Malin normally ubiquitinates laforin for degradation; also forms a complex with laforin to ubiquinate other enzymes involved in glycogen synthesis
• Inability to degrade laforin 🡪 accumulation of glycogen and glycosaminoglycans 🡪 widespread, primary intraneuronal formation of polyglucosan bodies 🡪 late stage and progressive myoclonus/epilepsy

TYPICAL CLINICAL FINDINGS:

• Myoclonic epilepsy with progressive neurologic deterioration
• Severity of clinical signs does not correlate with number of Lafora bodies
• Basset hounds, beagles, poodles, and high incidence among miniature wirehaired dachshunds affected

TYPICAL GROSS FINDINGS:

• No significant gross lesions

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lafora body: 5-20 µm, homogenous, basophilic to amphophilic, non-membrane-bound, spherical inclusion with a central basophilic core and a peripheral halo of radiating filaments; may be incidental finding throughout brain and spinal cord
• Lafora-like disease: LBs in neuron soma, dendrites, and less frequently in axons; reported in the hypothalamus and cerebellum; other reported sites include heart, skeletal muscle, liver, apocrine sweat gland, smooth muscle layer of the urinary bladder, peripheral nerves

ULTRASTRUCTURAL FINDINGS:

• Non-membrane-bound admixture of 9 nm diameter interwoven filaments, electron-dense bodies, and glycogen
• Appears to be associated with rough endoplasmic reticulum and Golgi

ADDITIONAL DIAGNOSTIC TESTS:

• Histochemical staining:
  • LBs are positive for PAS (diastase resistant), Alcian blue, Best’s carmine, methenamine silver, Weil’s; binding is to lectin concavalin A
  • LBs are negative for glycogen, lipid, mineral, and nucleic acid stains
• Immunohistochemistry: immunoreactive for calbindin, laforin, hsp70, alpha/beta synuclein, ubiquitin, LC3, p62

DIFFERENTIAL DIAGNOSIS:

• Polyglucosan bodies (LBs, corpora amylacea, amylopectin bodies) must be discriminated from Buscaino bodies (post mortem artifact, may be PAS positive, glassy gray-blue), edema, or storage disorders
• Corpora amylacea: found in normal aging cells in most tissues; located in astrocytes and axons, not in perikaryon; immunoreactive for both human PGBs and neurofilaments suggesting a mixed neuronal-glial origin
• Amylopectin bodies: morphologically similar to LBs/corpora amylacea, but found in tissues of patients with glycogen storage disease type IV or glycogen branching enzyme deficiency

COMPARATIVE PATHOLOGY:

• Lafora disease in humans is due to autosomal recessive mutation (not a repeat expansion mutation) in the EPM2A gene (encodes laforin) or the EPM2B gene (encodes malin); LBs have similar immunohistochemical properties between dogs and humans
• Occasionally reported in cats, ox, fennec fox, chickens and psittacines
• Incidental LBs reported in a raccoon, cats, and cattle
• Polyglucosan bodies are unusually abundant in the cerebellar molecular and Purkinje cell layers and cerebellar peduncles of captive-bred and wild-caught Montserrat orioles, but are likely a normal (non-pathogenic) finding in aging birds (Spiro et al, 2025).

References:

1. Cantile C, Miller AD, Youssef S. Nervous System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 7th ed. St. Louis, MO: Elsevier; 2026:255-256, 292.
2. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier. 2018:233.
3. Spiro S, Pereira M, Bates KA, et al. Incidence and characterization of polyglucosan bodies in the cerebella of montserrat orioles (Icterus oberi). Vet Pathol. 2025;62(4):581-585.
4. Struthers JD, Schmidt RE. Nervous system. In: Schmidt R, Struthers JD, Phalen DN, eds. Pathology of Pet and Aviary Birds. 3rd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2024:375-376
5. Valentine BA. Skeletal Muscle. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th ed. St. Louis, MO: Elsevier. 2022:1035, 1002.e2.

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