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Beagles & CD-1 Mouse - spontaneous axonal spheroids

SIGNALMENT:

• D2M: 4.5 yr, Beagle, male, canine, (Canis familiaris)
• D10M: 4.5 yr, Beagle, male, canine, (Canis familiaris)
• D5F: 1.5 yr, Beagle, female, canine, (Canis familiaris)
• M46M: 9.5 mos, CD-1 (R), male, mouse, (Mus musculus)

HISTORY:
Untreated control dogs and mouse maintained in a barrier facility.

GROSS PATHOLOGY:
None.

LABORATORY RESULTS:
None.

What's Your Diagnosis? Provide your possible etiologies in the comment section below. Member login is required to comment.

R41a: D10M (canine) medulla (4x). Cross section of the brain at the level of the myelencephalon (cuneate nucleus) containing a single homogeneously bright eosinophilic swollen axon (spheroid) in the neuropil.	R41b. D10M (canine) medulla. Higher magnification (40x) of the axonal spheroid in the 4x view of D10M-medulla which is adjacent to and compressing a neuron.
R41c. D2M (canine) thalamus (4x): Cross section of the brain at the level of the diencephalon (thalamus) containing two larger and three smaller homogeneously bright eosinophilic swollen axons (spheroids) in the neuropil.	R41d. D2M (canine) thalamus: Higher magnification (40x) of the cluster of axonal spheroids in D2M-thalamus-4x.
R41e. D5F (canine) cochlear: Cross section of the brain at the level of the metencephalon (cochlear nucleus) containing three homogeneous, moderately eosinophilic, swollen axons (spheroids) in the neurophil; 4x.	R41f. D5F (canine) cochlear-10x: Higher magnification (10x) of two of the three axonal spheroids in D5F-cochlear-4x.
R41g. M46M (mouse) medulla: Cross section of the brain at the level of the myelencephalon (gracilis nucleus) containing two brightly eosinophilic swollen axons (spheroids) in the neuropil; 4x.	R41h. M46M (mouse) medulla: Higher magnification (40x) of one of the two axonal spheroids in M46M-medulla-4x.
R41i. M46M (mouse) medulla: Higher magnification (40x) of the other axonal spheroid in M46M-medulla-4x, which has a more granular eosinophilic appearance.

MORPHOLOGIC DIAGNOSI(E)S AND ETIOLOGY:
Axonal spheroids, etiology unknown.

CONTRIBUTOR:
Schering Plough Research Institute, Lafayette, NJ, USA.

CONTRIBUTOR'S COMMENTS:

Focal axonal swellings (spheroids) have been found in the brain and/or spinal cord of normal dogs (1, 2, 3), foals (4), cats (5), rats (6), and rabbits (7). In addition, the frequency of finding axonal spheroids in the CNS (cuneate and gracilis nuclei of the medulla oblongata) and autonomic ganglia of animals increases with age. (8, 2, 4) Ultrastructurally, spheroids are found in myelinated or unmyelinated fibers near the axon terminations of primary sensory neurons. (9) These swellings can be comprised of a number of cellular elements: tangles of neurofilaments and microtubules, abundant smooth endoplasmic reticulum or other tubulovesicular bodies, mitochondria, degenerate organelles, and/or amorphous dense bodies. (4)

We demonstrate spheroids in the brain of normal control dogs and mice. No spheroids were found in the spinal cord or autonomic ganglia of the small intestine. Of the three regions of the brain examined (diencephalon, metencephalon, myelencephalon), the myelencephalon (cuneate and gracilis nuclei of the medulla) had the highest incidence of axonal swellings. The enlarged axons were often bilateral and symmetrical, few in number to rare (single), variable in size (15-80um), round to oval or scalloped, homogeneous, moderate to deeply eosinophilic, and sometimes granular or vacuolated. The cause or composition of these spheroids is undetermined. However, they are common incidental background findings in numerous laboratory species and must be taken into consideration when evaluating neural tissues especially of aged animals.

REFERENCES:

1. Newberne JW, Robinson VB, Estill L, Brinkman DC: Granular structures in the brain of apparently normal dogs. Am J Vet Res 21:782-786, 1960.
2. Suzuki Y, Suu S: Spheroids (axonal dystrophy) in the central nervous system of the dog. I. Light microscopic observations. Jpn J Vet Sci 40:325-334, 1978.
3. Slayter MV, Summers BA, Meade RP, Anderson CA: Axonal spheroids in the cochlear nucleus of normal beagle dogs. Vet Pathol 35: 150-153, 1998.
4. Summers BA, Cummings JF, de Lahunta A: Veterinary Neuropathology, pp. 50-51. Mosby, St. Louis, MO, 1995.
5. Saito K: Spheroids and altered axons in the spinal gray matter of the normal cat: an electron-mircoscopic study. Acta Neuropathol (Berl) 52: 213-222, 1980.
6. Steenis van G, Kroes R: Changes in the nervous system and musculature of old rats. Vet Pathol 8: 320-332, 1971.
7. Leonhardt H: "Axonal spheroids" in the spinal cord of normal rabbits. Cell Tissue Res 174(1): 99-108, Oct 22, 1976.
8. Schmidt RE, Plurad SB, Modert CW: Neuroaxonal dystrophy in the autonomic ganglia of aged rats. J Neuropathol Exp Neurol 32: 376-390, 1983.
9. Fujisawa K. Study of axonal dystrophy. III. Posterior funiculus and posterior column of ageing and old rats. Acta Neuropathol (Berl) 76(2): 115-127, 1988.

SUMMARY REPORT (R041) - by Moderator Dr. Byron Boysen

Dogs, Beagle, CD-1, Axonal Spheroids, Spontaneous

LIGHT MICROSCOPIC DIAGNOSES:

1. Axonal spheroids, diencephalon (thalamus), metencephalon (cochlear nucleus), and myelencephalon (cuneate nucleus), Beagle dog.
2. Axonal spheroids, myelencephalon (gracilis nucleus), CD-1 mouse.

CONFERENCE NOTES:
The contributor has provided a brief summary of the appearance and occurrence of axonal spheroids based upon a complete and up to date list of references.

The real importance of axonal spheroids is not well understood, but they appear to represent nonspecific degenerative changes in axons of the central, peripheral and autonomic nervous system⁽¹⁾. It is proposed that they start at a single focus in the axon and then progress both distally and proximally in the axon⁽¹⁾. Spheroids may be found in low numbers in animals of all ages, and increase in number with increase in age of the animal. They tend to be found more often in gray matter than white matter and are especially common in the nucleus gracilis and nucleus cuneatus in the medulla.

Axonal spheroids are encountered infrequently in laboratory animals on regulatory toxicology studies but can present an interpretive problem when they are found. They should be recorded in the data when observed to ensure that an accurate historical incidence of these lesions in untreated control animals is available in the laboratory. In toxicology studies, group incidences of these lesions in treated groups should be compared to incidences in the control group and to historical data from your laboratory to determine if treatment-related effects exist. Without the historical data, one might inadvertently identify a treatment-related effect that should be considered background. The references provided by the contributor of his case may also provide insight and support for your conclusion.

REFERENCES: (provided by the contributor or moderator)

1. Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology, 1995, Mosby, St. Louis, MO, pp. 50-51.