Results
AFIP Wednesday Slide Conference - No. 27
26 April 2000

Conference Moderator:
MAJ Jo Lynne Raymond
Department of Veterinary Pathology
Armed Forces Institute of Pathology
Washington, DC 20306-6000

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Case I - 99/1240 (AFIP 2694720)

 

Signalment: Three to four-year-old ox.

 

History: Six out of 65 intensively housed cattle, 1-4 years old, kept in different pens, developed severe nervous symptoms characterised by staggering, circling, blindness, head-pressing and collapse within 2-3 days of receiving a home-mixed salt lick consisting of 50% coarse feed-grade sodium chloride and 50% calcium diphosphate.

 

The outbreak occurred during mid-winter, when the feeding of salt lick was resumed after an interval of about 2 months during which time lick constituents were unavailable on the farm. A concentrated production ration containing 1% salt was fed during the same period. As far as could be established, there was also restricted access to drinking water in some of the pens. Three of the most severely affected animals were euthanized by intravenous injections of barbiturate for necropsy, histopathological and toxicological examinations.

 

The remaining 3 animals were successfully treated by parenteral administration of diuretics, corticosteroids, B-complex vitamins, as well as by dosing regulated quantities of water and supportive oral remedies via stomach tube. In the latter animals the nervous symptoms and blindness persisted for about 2 weeks after which complete recovery occurred.

 

Gross Pathology: There was marked congestion and edema of the brain and meninges, as well as petechiae and ecchymoses within the gray- and white matter of the cerebrum, cerebellum and brain stem, and a moderate to severe congestion of the abomasal mucosa.

 

Laboratory Results: Sodium levels were determined in the brain of 3 cases by atomic absorption photospectrometry. In 2 cases, the levels were exceedingly high, viz. 3060 ppm and 3885 ppm, and in the third slightly high, 1839 ppm. According to Osweiler, levels of >2000 ppm is supportive of sodium toxicosis.

 

Determinations for organophosphate and organochlorine pesticides and lead, as well as bacteriological examinations on the brain of one of the animals were negative.

Contributor's Diagnosis and Comments: HE stained transverse sections (3 different sections, marked A, B and C) of the dorsolateral cerebrum, approximately at the level of the midbrain are presented.

 

Morphologic Diagnosis: Poliomalacia, multifocal, acute, moderate, with vasculitis, fibrinoid, multifocal, moderate and leucocytosis, (neutrophilic and monocytic); microhaemorrhages, scattered, multifocal, mild.

 

Histopathological changes are present within the meninges and gray and white matter and comprised varying degrees of vasculitis and edema with accompanying neuronal and glial cell changes. The vascular changes included: endothelial cell swelling, medial fibrinoid change and accumulation of a homogenous eosinophilic material within lumens of capillaries, venules and arterioles, mononuclear leucocyte (neutrophil and occasionally eosinophil) infiltrations into the walls of some vessels (more pronounced in sections marked 99/1240 C), or extravasations into the extravascular spaces.

 

Marked edema with dilatation of perivascular spaces, vacuolation of gray and white matter, as well as eosinophilic degeneration and necrosis of neurons, and glial cell cytoplasmic swelling are evident within the gray matter of the cerebral and cerebellar cortices. Degenerative and necrotic changes of neurons comprise swelling, chromatolysis, increased eosinophilia, fading of nuclear membranes and nuclear pyknosis. Perivascular and neuropil hemorrhages are occasionally present in both the gray and white matter.

 

The clinical signs and histopathological changes of the poliomalacia described here, appear to be similar to those of cerebrocortical necrosis (CCN) associated with thiamine deficiency in cattle and sheep, as well as lead poisoning in cattle. However, the extremely high levels of sodium detected in the brains of two of three of the animals that were euthanized together with a history of salt engorgement as well as possible water deprivation, favors a diagnosis of water deprivation/sodium ion toxicosis.

 

In contrast to pigs where eosinophilic meningoencephalitis is common and together with laminar neuronal changes is regarded to be pathognomonic for salt poisoning in this species, eosinophils are only rarely encountered in cases of salt poisoning in cattle and sheep.

 

The pathogenesis of the edema underlying the poliomalacia is attributed to passive diffusion of sodium into the brain substance from the blood and cerebrospinal fluid when the sodium levels in these compartments rise. This is counteracted by an energy dependent process (anaerobic glycolysis), which is inhibited by high levels of sodium entering the brain, resulting in trapping of sodium ions within the brain. When water intake and renal excretion of sodium reduces the blood sodium levels to normal, an osmotic gradient results which leads to cerebral edema.

 

Sodium chloride poisoning has been classified as acute/direct salt poisoning where there has been ingestion of excessive salt in feed or drinking water or as delayed/indirect when there has been a restriction in water intake with or without ingestion of excessive salt. These cases probably resemble indirect salt poisoning due to the delay in onset of clinical symptoms (a few days) and gastrointestinal symptoms, although there was no definite evidence of water restriction in all the cases affected.

 

Hypernatremia with resultant brain edema and neurological disease has also been induced in calves by injudicious use of sodium bicarbonate and oral electrolyte solutions during treatment of diarrhoea with dehydration and acidosis.

 

AFIP Diagnosis: Cerebral cortex: Neuronal necrosis, laminar and segmental, with fibrinoid vascular necrosis and edema, breed not specified, bovine.

 

Conference Note: The contributor has provided an excellent discussion of this case.

 

Contributor: Pathology Section PO Box 12502 Onderstepoort 0110 South Africa.

 

References:

1. Angelos JM, Smith BP, George LW: Treatment of hypernatremia in an acidotic neonatal calf. J Amer Vet Med Assoc 214:1364-1367, 1999

2. Butler R: Salt poisoning/water deprivation in sheep? Control & Therapy series: Post Graduate Foundation in Veterinary Science of the University of Sydney, Australia: Mailing 207:1078, 1999

3. Jubb KVF, Huxtable CR: The Nervous System. In: Pathology of Domestic Animals, eds Jubb KVF, Kennedy PC, Palmer N, vol 1, 4th ed, pp. 340-347. Academic Press, San Diego, 1993

4. Osweiler GD, Carr TF, Sanderson TL: Water deprivation-sodium ion toxicosis in cattle. J Vet Diag Invest 7:583-585, 1995

5. Osweiler GD: Toxicoses resulting from sodium-water imbalance. In: Toxicology, pp. 355-357. Williams & Wilkins, Philadelphia, USA, 1996

6. Penrith M-L: A case of salt poisoning in grower pigs. Newsletter of the Veterinary Laboratory Diagnosticians Group S Afri Vet Assoc 3:2-3, 1995

7. Scarratt WK, Collins TJ, Sponenberg DP: Water deprivation-sodium chloride intoxication in a group of feeder lambs. J Amer Vet Med Assoc 186:977-978, 1985

8. Summers BA, Cummings JF and De Lahunta A: Salt poisoning. In: Veterinary Neuropathology, pp. 254-255. Mosby, St Louis, MO, 1995

9. Trueman KF, Clague DC: Sodium chloride poisoning in cattle. Aust Vet J 5: 89-93, 1978

10. Van Leeuwen JA: Salt poisoning in beef cattle on coastal pasture on Prince Edward Island. Can Vet J 40: 347-348, 1999

 

 

Case II - TAMU 99-1 (AFIP 2694696)

 

Signalment: Five-year-old, Aberdeen Angus bull

 

History: Lesions of 3 months duration on all four distal limbs

 

Gross Pathology: Gray, proliferative, symmetric, moist lesions were observed in circumferential bands extending 15-cm proximally from the coronary band on both front feet. Nodular, dry alopecic lesions were seen on the fetlocks of both rear limbs and the distal scrotal skin. Serpentiginous, dry alopecic lesions were on the sternal skin.

 

Contributor's Diagnosis and Comments: Chronic proliferative dermatitis/pododermatitis with epithelial and mesenchymal proliferation, epidermal hydropic degeneration, focal vasculitis and intraepithelial inclusion bodies, hyperkeratosis, bacterial colonies

Etiology: uncharacterized bovine parapoxvirus

 

This case represents a good example of an unpublished condition! There are numerous parapox virions in the lesions (parapox are different in appearance from other poxviruses on EM), and the lesions are typical of poxvirus diseases. Of course, cutaneous lesions are not usually described in cattle with parapoxvirus. The recognized parapoxviruses include: contagious ecthyma of sheep, bovine papular stomatitis, parapoxvirus of red deer and pseudocowpoxvirus.

 

At necropsy, the serpentiginous lesions of the sternal skin made us suggest parapoxvirus in the gross report (honest!). Some of the gross lesions looked like papillomas, and the moist lesions of the front limb were reminiscent of the lesions in cattle attributed variably to spirochetes (none seen) or papillomavirus. Vasculitis can be seen with lumpy skin disease and bovine papular stomatitis and is seen in this case. In order to find out if this is a new parapox disease, samples have to be typed, but the lab that does this is in New Zealand, and we could not legally send the material into that country.

 

A couple of interesting features of ovine parapoxvirus infection are that the virus is resistant to both alpha and gamma interferon, and is believed capable of modulating the Th-1 immune response of the infected host through an IL-10-like gene product of the virus. The virus also makes an endothelial growth factor. Parapoxviruses are suggested to occur in musk ox, gray seals, and the Japanese serow (these have not been confirmed in THE lab). This group of viruses is responsible for a nuisance category (due to the mild signs) of zoonoses called "farmyard pox". This type of human pox is described to occur also in handlers of reindeer and other cervids.

 

AFIP Diagnosis: Haired skin: Dermatitis, proliferative, chronic-active, focally extensive, severe, with hyperkeratosis, epithelial ballooning degeneration, and eosinophilic intracytoplasmic inclusion bodies, Aberdeen Angus bull, bovine.

 

Conference Note: Parapoxvirus is a genus of the family Poxviridae. Parapoxviruses are large, enveloped, highly epitheliotropic, DNA viruses that are cocoon shaped and measures 260 x 160 nm. There are over 100 polypeptides in the virion. The core proteins include a transcriptase and several other enzymes. There is extensive cross-neutralization and cross-protection between viruses belonging to the same genus, but not between those of different genera. Even though parapoxviruses exhibit a highly restricted host range, most can infect humans, producing generally benign cutaneous lesions limited to the site of inoculation.

 

By electron microscopy parapoxviruses are ovoid with a regular spiral arrangement of "tubules" (surface rodlets) on the outer membrane. There is no nucleocapsid conforming to either icosahedral or helical symmetry; hence it is called a "complex" virion. An outer membrane encloses a dumbbell-shaped (biconcave) central core and two "lateral bodies" of unknown nature.

 

Some sections contain an organizing thrombus in the subcutis.

 

Contributor: Texas A&M University, Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4467.

 

References:

1. Haig DM: Poxvirus interference with the host cytokine response. Vet Immunol & Immunopath 63(1-2):149-56, 1998

2. Haig DM, Mercer AA: Ovine diseases. Orf. Vet Res. 29(3-4):311-26, 1998

3. Murphy FA, Gibbs EBJ, Horzinek MC, Studdert MJ: Veterinary Virology, 3rd ed., pp. 278-291. Academic Press, San Diego, CA, 1999

4. Robinson AJ, Mercer AA: Parapoxvirus of red deer: Evidence for its inclusion as a new member in the Genus Parapoxvirus. Virolo 208(2):812-815, 1995

5. Smith KJ, Skelton HG, James WD, Lupton GP: Parapoxvirus infections acquired after exposure to wildlife. Arch of Dermatol 127(1):79-82, 1991

 

 

Case III - 989-4037 (AFIP 2694690)

 

Signalment: Tissue is from a 5-year-old female mule deer (Odocoileus hemionus).

 

History: This mule deer was showing signs of weakness, excessive salivation and emaciation.

 

Gross Pathology: Gross lesions included extensive serous atrophy of adipose tissues, mild muscular atrophy, bronchopneumonia, mild gastric ulceration and enlarged adrenal glands.

 

Laboratory Results: Pasteurella sp. was isolated from the pneumonic portion of the lung. No significant growth was cultured from the gastric ulcer.

 

Immunohistochem Mab89/160.1.5

Case 27-3. This photomicrograph is of the dorsal motor nucleus of the vagus nerve of this deer stained with a monoclonal antibody (Mab 89/160.1.5). The positive red staining is interpreted to be scrapie-associated prion protein or an antigenically similar protein that has been found with chronic wasting disease of deer and elk. (Legend and image from Colorado State University Diagnostic Lab, Ft. Collins, CO, USA and reproduced with permission.)

 

Contributor's Diagnosis and Comments: Spongiform encephalopathy, severe, brain, compatible with chronic wasting disease (etiology-thought to be a prion protein).

 

This slide is from the obex region of the medulla oblongata of the brain stem of a 5-year-old female mule deer. The primary histological lesions at this level of the medulla oblongata are found within the dorsal motor nucleus of the vagus nerve with milder lesions of the hypoglossal nucleus, nucleus of the spinal tract of the trigeminal nerve, nucleus ambiguus and the olivary nuclei. The histological lesions are characterized by intracytoplasmic neuronal vacuolation, microcavitation of the neuropil and mild astrocytosis. Many of the sections contain variably-sized areas of mineralization at the vagal nucleus. This is a common incidental finding with no known association with the observed vacuolar changes. This condition is confined to North Central Colorado and Southeast Wyoming.

 

20x obj

Case 27-3. Brain stem. Multifocally, neurons and neuropil contains round clear vacuoles (spongiform degeneration). There is focal perivascular hemorrhage (probably an artifact) and mild gliosis.

 

AFIP Diagnosis: Brain stem, medulla oblongata: Neuronal degeneration, vacuolation, and loss, with spongiform change of gray matter neuropil, and astrocytosis, consistent with spongiform encephalopathy, mule deer (Odocoileus hemionus), cervid.

Conference Note: Chronic Wasting Disease (CWD) is classified as a transmissible spongiform encephalopathy (TSE). As early as 1967 chronic wasting disease was diagnosed in captive mule deer and mule deer / white-tailed deer hybrids. It was later discovered in captive elk and white-tailed deer and within the last few years it has been diagnosed in significant numbers of free-ranging deer and elk. CWD shares many epizootiologic, clinical and pathologic features of other TSE's (scrapie, bovine spongiform encephalopathy (BSE), etc.).

 

Although the cause of these diseases is still speculative and controversial, prions (proteinaceous infectious particles) are generally accepted as the etiologic agents. Prions are isoforms of a normal cell surface sialoglycoprotein, prion protein (PrP), that are protease-resistant and differ in conformation from the normal PrP. The normal prion protein (PrP) consists of alpha helices, which are regions in which the molecular backbone twists into a specific kind of spiral. The abnormal form contains beta strands, which are regions in which the backbone is fully extended and form beta sheets when aggregated. The abnormal conformation may result from a mutation, which predisposes the aberrant PrP to "flip", or from the physical interaction between the abnormal and normal PrP. For these reasons, spongiform encephalopathies are considered inherited as well as communicable diseases.

 

The exact mechanism of infection is still controversial and speculative. It is generally accepted that BSE is caused by the accumulation of abnormal protease-resistant PrP within neurons. This occurs either via a mutational alteration of the PrP gene and subsequent translation of abnormal PrP, or by infection of abnormal PrP which then causes a cascading conformational alteration of normal PrP. In the infectious scenario, the abnormal PrP replicates in lymphoid tissues and lower intestinal tract. The agent continues to replicate in the lymphoid tissues and intestine for months to years. It then spreads via hematogenous and/or axonal routes to the central nervous system (CNS) where it localizes in the medulla oblongata and diencephalon. The reason for this tropism is unclear, but retrograde migration via visceral and peripheral nerves has been proposed. It later spreads to other parts of the CNS, replicates and causes clinical disease usually at three to four years of age. Recent studies suggest that lysosomes are the site of abnormal PrP production, and it is the accumulation of this abnormal PrP, which eventually leads to rupture of the lysosomal membrane. The liberation of hydrolytic lysosomal enzymes is proposed to cause the characteristic spongiform change. Like scrapie, transmission is thought to occur most commonly by ingestion. CNS and placental tissue are especially rich in abnormal PrP.

 

Even though the TSE's are a heterogenous group of neurodegenerative disorders, the common feature of deposition of a shared abnormal isoform of a native sialoglycoprotein (prion protein), has resulted in the development of reliable immunohistochemical markers. These markers yield positive results with both formalin fixed and autolytic tissues.

 

Contributor: Colorado State University, Department of Pathology, Ft. Collins, CO 80523 USA.

 

References:

1. Clark WW, Hourrigan JL, Hadlow WJ: Encephalopathy in cattle experimentally infected with the scrapie agent. Am J Vet Res 56(5): 606-612, 1995

2. Kuezius T, Haist I, Groschup MH: Molecular analysis of bovine spongiform encephalopathy and scrapie strain variation, J Infect Dis 178(3): 693-699, 1998

3. O'Rourke KI, Baszler TV, Miller JM, Spraker TR, Sadler-Riggleman I, Knowles DP: Monoclonal antibody F89/160.1.5 defines a conserve epitope on the ruminant prior protein. J Clin Microbiol 36:1750-1755, 1998

4. Spraker TR, Miller MW, Williams ES, Getzy DM, Adrian WJ, Schoonvelt GG, Spowart RA, O'Rourke KI, and Merz PA: Spongiform encephalopathy in free-ranging mule deer, white-tailed deer and Rocky Mountain elk. J Wildl Dis 33:1-6, 1997

5. Williams ES, Young S: Chronic Wasting Disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 16:89-98, 1980

 

 

Case IV- 17077-99 (AFIP 2689003)

 

Signalment: Perinate, crossbred, domestic pig

 

History: An entire litter of pigs was born with generalized skin lesions. No other litters had been affected previously and none have been affected since this litter had been born.

 

Case 27-4. This newborn piglet (note umbilical cord) has multiple, diffusely distributed, slightly raised, reddish-brown epidermal papules.

 

Gross Pathology: One dead neonatal pig was submitted. The pig submitted was slightly gaunt. There were multiple ulcers on the skin, which measured approximately 3 to 10 millimeters in diameter and were randomly distributed over the entire body as well as on the palatine surface of the tongue. Several of the hooves were partially sloughed. Small amounts of fibrinous exudate were present in the peritoneal cavity. Individual lung lobules had a dark-red appearance.

 

Laboratory Results: Poxvirus was identified in a homogenate of skin by means of electron microscopy. Streptococcus suis was isolated from an abdominal swab and from the lung.

 

Contributor's Diagnosis and Comments: Severe diffuse suppurative necrotic epidermitis with ballooning degeneration and intracytoplasmic eosinophilic inclusion bodies.

 

There is full thickness necrosis of epithelium, which extends into hair follicles. At the margins of the necrotic epithelium, there is ballooning degeneration of epithelial cells. Numerous eosinophilic intracytoplasmic inclusion bodies can be seen in degenerated epithelial cells. The ulcerated surface is covered by a crust of serum proteins, degenerate inflammatory cells, and mixed bacterial colonies. The dermis is diffusely infiltrated by large numbers of histiocytes, neutrophils, and fewer lymphocytes.

 

This represents an unusual case of swinepox infection, since there had not been a history of prior episodes of swinepox on the farm. There have been no new cases of swinepox in six months since the initial occurrence. Typically, swinepox virus is thought to be transmitted mainly by the sucking louse, Haematopinus suis via mechanical transmission. Pigs on this farm were devoid of louse infestation. Congenital swinepox infection is thought to occur as a result of transplacental infection, although placentas were not available for examination in this case.

 

AFIP Diagnosis: Haired skin: Dermatitis and folliculitis, necrotizing, subacute, focally extensive, severe, with vasculitis, acanthosis, epithelial ballooning degeneration and eosinophilic intracytoplasmic inclusion bodies, crossbred domestic pig, porcine, etiology consistent with a poxvirus.

 

Conference Note: Postnatal infection through contact with Haematopinus suis resulting in mild or subclinical disease is the most common form of swinepox. Congenital infections occur much less frequently. Although all of the piglets in this litter were affected, frequently only one pig in a litter is affected, demonstrating that the compartmentalization of the placenta can restrict spread of infection as it does in many other intrauterine infections.

 

Congenital swinepox cannot be conclusively differentiated from congenital infection with vaccinia virus infection by histopathology, but the presence of intranuclear vacuoles strongly suggests infection with swinepox virus.

 

Contributor: Veterinary Diagnostic Center, Fair Street and East Campus Loop, Lincoln, NE 68583-0907.

 

References:

1. Borst GHA, Kimman TG, Gielkens AU, van der Kamp JS: Four sporadic cases of congenital swinepox. Vet Rec 127:61-63, 1990

2. House JA, House CA: Swine Pox. In: Disease of Swine, ed. Straw BE, 8th ed., pp. 29 1-294. Iowa State University Press, Ames Iowa, 1999

3. Murphy FA, Gibbs EBJ, Horzinek MC, Studdert MJ: Veterinary Virology,
3rd ed., pp. 278-291. Academic Press, San Diego, CA, 1999

4. Neufeld JL: Spontaneous pustular dermatitis in a newborn piglet associated with a poxvirus. Can Vet J 22:156-1 58, 1981

5. Paton DJ, Brown IH, Fitton J, Wrathall AE: Congenital pig pox: A case report. Vet Rec 127:204, 1990

 

 

J Scot Estep, DVM
Captain, United States Army
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202) 782-2615; DSN: 662-2615
Internet: estep@afip.osd.mil

 

* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.

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