JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2017

N-M21 (NP)

 

SIGNALMENT (JPC #2013034):  Military working dog

 

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: Lafora disease

 

SYNONYMS:  Lafora-like bodies; Lafora bodies; neuronal glycoproteinosis

 

GENERAL DISCUSSION:

·       Intracytoplasmic inclusions are composed of complex glycoprotein polymers

·       Incidental finding in the CNS of aged dogs and cats (>8 years); two main types of polyglucosan bodies:

·       Lafora-like bodies: located within neuronal perikarya, neuropil, and axons

·       Widely distributed in CNS

·       Corpora amylacea: located in astrocytes and axons, not in perikaryon;

·       Also found in normal aging cells in most tissues

·       Lafora’s-like disease is similar to the human Lafora’s disease

·       Affected canine breeds include: Basset hounds, beagles, and poodles

·       High incidence among miniature wirehaired dachshunds

·       In 2014, 50% of a study cohort, carried at least one copy of the EPM2B mutation which is responsible for Lafora’s-like disease

·       First triplet repeat (genetic) disorder ever discovered in domestic animals 

 

PATHOGENESIS:

·       Abnormality of carbohydrate metabolism >  produces glucose polymers (polyglucosans) >  widespread, primary intraneuronal storage or accumulation of polyglucosan > in animals, the late stage manifests as a progressive myoclonus epilepsy

·       In humans, Lafora disease is caused by a mutation in the EPM2A gene that encodes for laforin and the EPM2B gene that encodes for malin

 

TYPICAL CLINICAL FINDINGS:

·       Often incidental finding in aged animals

·       Inherited late-onset Lafora disease: myoclonic epilepsy with progressive neurologic deterioration

·       Severity of clinical signs does not correlate with number of Lafora bodies

 

TYPICAL GROSS FINDINGS:

·       No significant gross lesions

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Lafora body: 5-20 µm, basophilic, intraneuronal inclusion with radial pattern in the outer zone (sunburst appearance), with varying density (dense to laminated)

·       Occurs in the neuronal perikaryon, dendrites, or axons

·       Found throughout the brain (cerebellar Purkinje cells and thalamic neurons) and spinal cord (caudal lumbar, sacral, and caudal segments)

·       Other reported sites include:

·       Most prominently the liver and heart

·       Also reported in the sweat glands, peripheral nerves, and voluntary muscle

 

ULTRASTRUCTURAL FINDINGS:

·       Admixture of branching filaments, non-membrane bound electron-dense bodies, and glycogen

·       Appears to be associated with rough endoplasmic reticulum and Golgi

 

ADDITIONAL DIAGNOSTIC TESTS:

·       Positive staining: PAS (intense, diastase-resistant), alcian blue, Best’s carmine, methenamine silver, Weil’s; concanavalin A (a lectin; indicates the presence of mannose and glucose)

·       Negative for glycogen, lipids, minerals, and nucleic acid

 

DIFFERENTIAL DIAGNOSIS:

·       Amylopectin bodies:  A third type of polyglucosan body very similar morphologically to Lafora bodies and corpora amylacea, but found in tissues of patients with glycogen storage disease type IV or glycogen branching enzyme deficiency

 

COMPARATIVE PATHOLOGY:

·       Occasional case reports in other species including: Feline, ox, fennec fox, and gray-headed flying fox

·       Reported avian species include: cockatiels, juvenile parrots, chickens and psittacine

 

References:

1.      Cantile C, et al.  Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: 255, 292.

2.      Frosch MP, et al. The central nervous system. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier; 2015: 1253.

3.      Gabor LJ, et al. Polyglucosan inclusions (Lafora bodies) in a gray-headed flying fox (Pteropus poliocephalus). J Vet Diagn Invest. 2010; 22(2):303-304.

4.      Hamir AN. Pathology of neurologic disorders of raccoons (Procyon lotor). J Vet Diagn Invest. 2011; 23 (5): 873-884.

5.      Honnold SP, et al. Lafora's-like disease in a fennec fox (Vulpes zerda). J Zoo Wildl Med. 2010; 41(3):530-534.

6.      Miller AD, et al. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016: 952.

7.      Sainsbury R. DNA screening for Lafora's disease in miniature wire-haired dachshunds. Vet Rec. 2014; 175(22):568.

8.      Stent A, et al. Giant axonal neuropathy–like disease in an Alexandrine parrot (Psittacula eupatria). J Vet Diagn Invest. 2015; 27(5): 611-615.

9.      Vandevelde M, et al. Veterinary Neuropathology. Ames, IA: Wiley-Blackwell; 2012: 181-182.

 

 


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