Read-Only Case Details Reviewed: May 2008

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2023

N-V05 (NP)

Signalment (JPC Accession #1327071): Mouse, strain unspecified.

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Whole mouse, parasagittal section, cerebrum: Diffusely the neuropil is vacuolated (spongiosis) and blood vessels are congested. Multifocally, few scattered neurons are swollen with loss of Nissl substance and large vacuoles that distend the perikaryon (degeneration), while other neurons occasionally have hypereosinophilic, shrunken cytoplasm, angular borders, and a pyknotic nucleus (necrosis) and are sometimes surrounded by glial cells (satellitosis) or surrounded and replaced by microglia (neuronophagia). There is diffuse, marked gliosis with moderate numbers of gemistocytic astrocytes. Multifocally within the white matter there are dilated myelin sheaths that contain gitter cells (digestion chambers, ellipsoids).

MORPHOLOGIC DIAGNOSIS: Cerebrum: Neuronal necrosis, multifocal, moderate, with neuronophagia, spongiosis, and gliosis, strain unspecified, mouse.

ETIOLOGIC DIAGNOSIS: Picornaviral encephalitis

CAUSE: Mouse encephalomyelitis virus (MEV)

ETIOLOGY SYNONYMS: Theilovirus (ThV), Theiler’s murine encephalomyelitis virus (TMEV)

CONDITION: Mouse polio

GENERAL DISCUSSION:

Single-stranded RNA virus; genus: Cardiovirus; family: Picornaviridae
An enteric virus with numerous strains that infects wild and laboratory mice
Neurologic disease is unusual
1. Usually restricted to particular viral strains and immunodeficient mice
2. Highly neurovirulent viral strains (GDVII, FA) cause severe fatal encephalitis, regardless of inoculation route
3. Less virulent viral strains (TO, BeAn, DA) cause a biphasic disease – acute poliomyelitis followed by late-onset demyelinating disease
Used as an animal model for human poliomyelitis (acute poliomyelitis) and multiple sclerosis (late-onset demyelination)

PATHOGENESIS:

Natural transmission via fecal‑oral route; not very contagious
Virus replicates in enterocytes
Transient viremia is limited by host immune response
Endothelial cells may facilitate entry into brain à virus targets neurons and glia of hippocampus, thalamus, brainstem, and spinal cord à demyelination results from the host immune response to the infected white matter in the spinal cord, brainstem, and cerebellum
Persists in the white matter (macrophages, leukocytes, astrocytes, oligodendrocytes) for up to a year

TYPICAL CLINICAL FINDINGS:

Clinical disease is rare in immunocompetent mice under natural conditions
Acute poliomyelitis results in flaccid paralysis and high morbidity and mortality in exposed immunodeficient mice
Gait disorders, tremors, ataxia, extensor spasm, and urinary incontinence in late-onset demyelination phase

TYPICAL GROSS FINDINGS:

None

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Acute phase (poliomyelitis):
- Neuronal necrosis, neuronophagia, microgliosis, nonsuppurative meningitis, and perivasculitis most prevalent in brainstem and ventral horns of spinal cord
- In SCID and nude mice, marked neuronal vacuolation and enlargement, vacuolation of adjacent astrocytes and oligodendrocytes, and minimal to no inflammation
Late phase (demyelination):
- Nonsuppurative spinal meningitis and leukomyelitis
- Multifocal white matter spongiosis, spheroids, and gitter cells
- Acute myositis and focal myocarditis with IP inoculation

ULTRASTRUCTURAL FINDINGS:

Nonenveloped, 27nm diameter, icosahedral virions in paracrystalline arrays
Vesicular degeneration of myelin and stripping by macrophages

ADDITIONAL DIAGNOSTIC TESTS:

Serology (hemagglutination-inhibition, neutralization, enzyme immunoassay) – extensive cross reactivity with encephalomyocarditis virus (EMCV)
Virus isolation
Immunohistochemistry

DIFFERENTIAL DIAGNOSIS:

For microscopic findings:

Mouse hepatitis virus (D-V04; Coronaviridae; coronavirus): Neurotropic strains cause non-suppurative encephalitis with spongiosis and demyelination in brainstem; viral-induced leukocytic, endothelial, or parenchymal syncytia in target organs
Lactate dehydrogenase elevating virus (Coronaviridae; arterivirus): Non-suppurative encephalitis and scattered neuronal necrosis in ventral and dorsal horns of spinal cord of immunosuppressed C58 and AKR mice; non-suppurative meningitis, myelitis, and radiculitis without clinical signs in C57 mice
Polyomavirus (Papovaviridae): Nude mice develop infection of oligodendroglia with demyelination
Reovirus-3 (Reoviridae; orthoreovirus): Acute diffuse encephalitis, focal necrotizing myocarditis and hepatitis, lymphoid necrosis, pancreatitis, and sialodacryoadenitis in experimentally-inoculated neonatal mice
Encephalomyocarditis virus (C-V02; Picornaviridae; cardiovirus): Rodents are natural reservoir; rarely causes encephalomyelitis in wild rodents but is not known to infect laboratory mice

COMPARATIVE PATHOLOGY:

Important Picornaviridae:

GENUS	VIRUS	SPECIES AFFECTED	DISEASE
Aphthovirus	Foot and Mouth Disease Virus	Wild & domestic ruminants, swine	Foot and Mouth Disease
Enterovirus	Swine Vesicular Disease Virus	Swine	Swine Vesicular Disease
	Avian Encephalomyelitis Virus	Chickens, quail, turkeys, pheasants	Avian Encephalomyelitis/Epidemic Tremor
	Duck Hepatitis Virus	Ducks	Duck Hepatitis
	Polioviruses 1-3	Humans, apes	Poliomyelitis
	Coxsackieviruses	Humans, apes	Hand-Foot-and-Mouth Disease
Cardiovirus	Encephalomyocarditis Virus	Primarily swine, African elephants; also humans, monkeys, cattle, horses	Encephalomyocarditis
	Theiler's Murine Encephalomyelitis Virus	Mice	Murine Poliomyelitis
Hepatovirus	Simian Hepatitis A Virus	Monkeys	Hepatitis
	Human Hepatitis A Virus	Humans	Hepatitis
Rhinovirus	Human Rhinoviruses	Humans, apes	Common Cold
Teschovirus	Porcine Teschoviruses	Swine	Teschen/Talfan Disease; Benign Enzootic Paresis

References:

1. Cantile C., Youssef S. Nervous system. In: Maxie, MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol I. 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:372-373.

2. Lowenstine LJ, McManamon R, Terio KA. Apes. In: In: Terio KA, McAloose D, St. Leger JA, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 389-390.

3. Matz-Rensing K, Lowenstine LJ. New World and Old World monkeys. In: In: Terio KA, McAloose D, St. Leger JA, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 356.

4. McAloose D, Stalis IH. Prosimians. In: Terio KA, McAloose D, St. Leger JA, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 334.

5. Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing Professional. 2016: 20-21, 25, 27, 29, 35-36.

6. Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6^th ed. St. Louis, MO: Elsevier; 2016:43.

7. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6^th ed. St. Louis, MO: Elsevier; 2016:117-119, 121.