JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2023

N-P05 (NP)

 

Signalment (JPC #1590828): Mouse

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Multifocally within the grey matter there are several distinct, 500 µm diameter, multilobulated, expansile, protist cysts that have a 1-2 µm eosinophilic wall and contain numerous crescentic, 2x5 µm, basophilic bradyzoites. Focally within the hippocampus there is a 500 µm diameter granuloma with a central core of eosinophilic debris surrounded by epithelioid macrophages and rare foreign-body type multinucleated giant cells, further bounded by low numbers of lymphocytes and plasma cells. Multifocally, surrounding small vessels and expanding Virchow-Robin spaces are low numbers of lymphocytes and plasma cells. Similar infiltrates surround meningeal vessels. Focally there is a perivascular aggregate of moderate numbers of macrophages with abundant foamy cytoplasm.

 

MORPHOLOGIC DIAGNOSIS: Cerebrum: Meningoencephalitis, lymphoplasmacytic, multifocal, mild, with multifocal multilobulated protist cysts and a focal granuloma, mouse, rodent.

 

ETIOLOGIC DIAGNOSIS: Cerebral frenkeliosis

 

CAUSE: Frenkelia sp.

 

GENERAL DISCUSSION: 

• Frenkelia is an apicomplexan, coccidian protist (previously protozoan) that forms large tissue cysts in the central nervous system of small rodents (intermediate hosts) and forms oocysts within the intestines of the definitive hosts (hawks and buzzards)
• Two species are identified, F. microti and F. glareoli
  • F. glareoli is found in Europe and is distinguished by its strict intermediate host specificity (bank voles) and its non-lobate cysts
  • F. microti occurs in many areas of the northern hemisphere; has a wide intermediate host range (various rodents and small mammals)
• Differentiation of Frenkelia from Sarcocystis is based on location and morphology of asexual stages in the intermediate hosts; both genera share many similar phenotypical characteristics and genetic analysis does not support separate genera, some consider Frenkelia and Sarcocystis to be synonymous;  Frenkelia is phylogenetically related to Sarcocystis neurona

 

LIFE CYCLE:

• Indirect lifecycle involving intermediate hosts (rodents and small mammals) and definitive hosts (buzzards and hawks (Buteo spp.))
• Intermediate hosts (rodents, small mammals; extraintestinal cycle) are infected by ingestion of sporulated oocysts (sporocysts) > schizogony with formation of tachyzoites occurs in hepatocytes and Kupffer cells, with subsequent formation of large, multilobulated cysts (filled with bradyzoites) in the CNS > ingestion of cysts by definitive hosts (hawks, buzzards; intestinal/typical coccidian cycle) > gametogony and sporontogony in the lamina propria of the definitive host small intestine > sporulated oocysts are passed in the feces

 

TYPICAL CLINICAL FINDINGS:

 

TYPICAL GROSS FINDINGS: 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lobulated, thin-walled cysts with thin septa up to 1mm in diameter packed with crescentic bradyzoites in the central nervous system
• There is usually no host reaction to mature cysts
• Focal hepatocellular necrosis and lymphoplasmacytic perivascular inflammation in many organs is associated with development of first generation meronts in the rodent host
• Developing cysts compress the adjacent nervous tissue with resulting pressure necrosis and lymphoplasmacytic perivascular and meningeal inflammation
• Granulomatous reactions may occur with cyst rupture

 

ULTRASTRUCTURAL FINDINGS:

 

DIFFERENTIAL DIAGNOSIS: 

• Sarcocystis: These cysts very similar and are found in skeletal/cardiac muscle and occasionally brain; the two genera are very closely related
• Besnoitia: Cysts similar in size, ovoid; usually in skin/subcutis
• Toxoplasma (N-P02): Cysts are small (30-100µm), spherical
• Hammondia: These cysts are ovoid, up to 100x300µm, and in skeletal and cardiac muscle; cysts are rarely seen in brain, where they are usually small (20-25µm)

 

COMPARATIVE PATHOLOGY:

 

References:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016.:151
2. Gardiner CH, Fayer R, Dubey JP. An Atlas of Protozoal Parasites in Animal Tissues. 2nd ed. Washington, DC: Armed Forces Institute of Pathology;1998:47-48.
3. Hoberg EP, Cawthorn RJ, Hedstrom OR. Enteric coccidian (Apicomplexa) in the small intestine of the northern spotted owl (Strix occidentalis caurina). J Wildl Dis. 1993;29(3):495-497.
4. Jones TC. Diseases due to protozoa. In: Jones TC, Hunt RD, King NW, eds. Veterinary Pathology. 6th ed. Baltimore, MD: Williams & Wilkins;1997:569.
5. Laakkonen J, Henttonen H. Ultrastructure of Frenkelia spp from a Norwegian lemming in Finland. J Wildl Dis. 2000;36(2):362-366.
6. Mugridge NB, Morrison DA, Johnson AM, Luton K, Dubey JP, Votypka J, Tenter AM.  Phylogenetic relationships of the genus Frenkelia:  A review of its history and new knowledge gained from comparison of large subunit ribosomal ribonucleic acid gene sequences. Int Jour Parasitol. 1999;29:957-972.
7. Upton SJ, McKown RD. The red-tailed hawk, Buteo jamaicensis, a native definitive host of Frenkelia microti (Apicomplexa) in North America. J Wildl Dis. 1992;28(1):85-90.
8. Wunschmann A, Armien AG, Hofle U, Kinne J, Lowenstine LL, Shivaprasad HL. Birds of Prey. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:717-740.

 

 

 

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