Diagnosis- What’s your diagnosis #6

What’s your diagnosis #6

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History: a 15 month old Angus steer went down acutely and was euthanized.

Gross findings were unremarkable.

Histopathology:

Brain: In the gray and white matter of the caudal cerebrum, midbrain, and cerebellar peduncle there are multifocal perivascular infiltrates of lymphocytes and fewer neutrophils. There are randomly scattered multifocal areas of necrosis with moderate numbers of neutrophils, lymphocytes, macrophages, microglia and astrocytes (microabscesses). There is a single arteriole with a predominantly eosinophilic infiltrate with fewer lymphocytes.

Brainstem:  There are bilaterally symmetric focal areas of severe necrosis with large numbers of macrophages, neutrophils, lymphocytes, and a few multinucleated giant cells. The meninges are multifocally thickened with moderate numbers of lymphocytes and macrophages. Within areas of necrosis are large expanses of spongiosis with myelin sheath swelling, axonal spheroid formation and digestion chambers with Gitter cells (foamy macrophages).

Brain: At low power there are multifocal areas of necrosis and suppurative inflammation, and perivascular cuffing

Brain: At high power the neuropil is fragmented, and neurons are not visible, instead there is cell debris and neutrophils and increased numbers of glial cells including microglia

Brain: Some areas have large macrophages, or reactive astrocytes with abundant eosinophilic cytoplasm which are cleaning up and repairing the damaged neuropil

Brain: Some areas have focal gliosis, which is interpreted as a region of healing (glial scarring)

Brain: Perivascular cuffing ins prominent in some areas; cells consist of lymphocytes, macrophages and some neutrophils.

Brainstem: At low power there are areas of spongiosis (clear spaces; swollen myelin sheaths).

Brainstem: At higher power there is loss of axons, and numerous clear spaces containing large eosinophilic spheroids (swollen damaged axons), and Gitter cells in axonal spaces.

Morphologic Diagnosis:

Brain and brainstem: Meningoencephalitis, necrotizing, suppurative, multifocal, severe, with lymphocytic cuffing

Immunohistochemistry:

Immunostaining revealed the presence of Listeria monocytogenes in the CNS microabscesses.

Brain, Immunohistochemistry: The red foci indicate positive staining for Listeria monocytogenes

Diagnosis: Listeriosis

Comment:

Listeria sp are Gram-positive facultative anaerobic bacilli found in the environment. It is hardy, and able to survive in temperatures ranging from 4-45 degrees C. It is an intracellular pathogen of macrophages, neutrophils,  and epithelial cells. Virulence factors include the surface protein internalin,  which internalizes with E-cadherin to overcome the intestinal, placental, and blood brain barriers. It also has a cholesterol-binding hemolysin to lyse phagosomes and escape into the cytoplasm. The organism proliferates in the host cytoplasm and migrates against the cell membrane to form protrusions that can be taken up by other cells. It can use the host cell actin filaments to help cell-cell transfer.

Disease syndromes usually dont overlap. Infection can cause abortions, septicemia, and encephalitis. Septicemia Listeriosis occurs in fetuses, neonates and young large animals up to 1 year of age resulting in generalized visceral abscesses.  Encephalitis is almost solely found in adult ruminants, and may be sporadic or associated with outbreaks.  Listeria can grow in spoiled silage that is incompletely fermented. It invades the oral mucosa and invades the trigeminal nerves traveling to the brain.  Lesions not seen in this case include vasculitis.

Of the competing differentials most can be confirmed by histopathology.

BSE: Histologic lesions include vacuolation of brainstem neurons and immunohistochemical confirmation is possible.

Polioencephalomalacia: Characteristic laminar cortical necrosis, with possible mild endothelial hypertrophy, and perivascular histiocytic cells. The same lesion occurs with thiamine deficiency and lead toxicity.

Rabies: Characteristic Negri bodies (eosinophilic intracytoplasmic inclusions) in neurons with perivascular lymphocyte cuffing.

Urea/Ammonia toxicity: There are no characteristic histologic lesions that I am aware of. In horses ammonia toxicity causes Type II Alzheimer cells, which are a type of reactive astrocyte. This has not been described as a feature of cattle with ammonia toxicity. The alkaline rumen pH may have made this a consideration.  7.4 is pretty alkaline for the rumen, and may indicate the presence of ammonia, the by product of urea metabolism by rumen flora.

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Cerebral abscess in a foal- Streptococcus equi

Cerebral Abscess in a foal- Streptococcus equi

History:

A 4 month old intact female Quarterhorse with nasal discharge and mandibular lymphadenopathy. Despite treatment the foal became neurologic: ataxia, wobbly, and head pressing.  Neurologic exam revealed an intention tremor when head raised and no left menace but direct PLRs were normal. A CBC revealed 600mg/dl fibrinogen and 11,100/ul neutrophils. A CT scan performed 7/14/09 revealed large mass in the right cranium. The owner elected euthanasia.

There is a current strangles outbreak on the farm. The brain mass indicates strong suspicion of abscess as complication to strangles.

Gross Findings:

The carcass was in good body condition, fresh with no autolytic changes. The guttural pouches bilaterally were filled with thick, firm inspissated pus.

Guttural pouches, ventral view (rostral is left): in the center you can see a thick solidified pasty yellow mass extruding from the guttural pouch.

The mandibular and retropharyngeal lymph nodes were enlarged bilaterally and several were completely effaced with purulent material, and had fibrous capsules enclosing the pus.

Lymph node: several lymph nodes were effaced by thick pale yellow to white pus with some fibrous tissue surrounding them, indicating prolonged timecourse.

The right caudal lung lobe had a focal 2cm firm nodule elevating the pleural surface of the dorsal and medial aspect of the lung lobe. The nodule was composed of a thick fibrous capsule surrounding a 2 mm diameter central zone containing yellow purulent material.

Lungs, dorsal view: The right dorsal aspect of the middle and caudal lobes have a poorly defined expanded area corresponding to a chronic abscess. Rhodococcus equi was cultured.

The right cerebral hemisphere was swollen, with flattened sulci and gyri and contained a 5 cm x 4 cm elliptical abscess filled with yellow to light green pasty pus.

Brain, dorsal view: The right cerebrum is expanded and fluctuant, with flattening of sulci and gyri (Abscess)

Brain lateral view: The right hemisphere is yellowed multifocally with obvious flattening of sulci and gyri

Brain, cross sectioned: THe right cerebrum is effaced by a well circumscribed abscess filled with pasty purulent material (asbcess). cerebral grey matter and white matter tracts are effaced, and the lateral ventricles are mildly dilated. There is deviation of the midbrain to the left.

Brain, cross section with pus removed. The rim of the abscess is composed of some yellow tissue corresponding to suppurative infiltrate and astrocyte proliferation histologically. The red areas are neovascularization in response to the inflammation.

The small intestine contained  moderate numbers of large roundworms (Ascarids) (incidental finding)

Small intestine, opened: The lumen contains large nematodes- (Ascarids), presumably Parascaris equorum

The non-glandular gastric mucos had multifocal to coalescing ulcers.

Stomach: Non-glandular portion is on top, and at the Margo plicatus, and extending upward are multiple coalescing areas of ulceration. Presumably stress related.

Gross Diagnosis:

1. Brain: Focal cerebral abscess, unilateral

2. Mandibular and retropharyngeal lymph nodes: Suppurative lymphadenitis, multifocal, severe, chronic

3. Guttural pouch: Bilateral empyema, severe, chronic

4. Lung: Focal chronic abscess, unilateral

5. Small intestine: intra-luminal ascarids, moderate

Comments:

The gross findings are consistent with bastard strangles, a disseminated form of Streptococcus equi infection. Typical strangles results in empyema and lymphadenitis of the retropharyngeal lymph nodes. If the infection progresses, septicemia can seed other organs. In this case the brain abscess resulted in severe neurologic disease and euthanasia was elected.  The lung abscess was originally presumed to be a Streptococcus equi infections, however cultures identified only Rhodococcus equi.  This is a common location for Rhodococcus equi infections, and these may be clinically silent for a long time.

Other complications of Streptococcus equi infections include Purpura hemorrhagica, which is a Type III hypersensitivity to certain anitgens related to this bacteria. This conditions requires a first infection that sensitizes the horse to the bacteria, and then when re0infection happens antigens released systemically form complexes with circulating antibodies that lodge in small vessels, activate complement, recruit neutrophils, and cause a leukocytoclastic vasculitis with petechial hemorrhage and edema. Hemorrhages may only be visible in the gingival mucosa. Edema can be seen in the head, neck, and chest.

Ancillary testing:

Bacteriology:

Lung: Rhodococcus equi

Brain, swab: Streptococcus equi

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Tularemia in a cat and capybara

Tularemia in a cat and capybara

This post combines two cases Tularemia: the cat and capybara have no relation

History: A 2 year-old male DSH cat had a leg wound 1 week prior, then stopped eating and drinking, became laterally recumbent and depressed.  Temperature, pulse and respiration were within normal limits, PCV was 22% with a neutrophilic leukocytosis and left shift.   The capybara was a captive zoo animal living with several capybaras. Several had severe bloody diarrhea and one died.  It was necropsied by the referring veterinarian who described necrotizing enteritis as the primary gross lesion and submitted fixed tissues for histopathology.

Gross findings: 

Cat: The sclera was icteric, and the left hind-limb hada  2 cm ulcer over the left lateral aspect of the tarsus and tibia with swollen subcutis.  The spleen contained many 1mm diameter white foci that were ell-circumscribed. The liver contained many 1mm white foci. The lung was edematous, dark red, and contained many 2-3mm white foci.  The intestines contained tarry black feces but no other lesions. Many lymph nodes were necrotic with white foci.

Spleen from cat: The capsular surface is raised by well-demarcated white foci that extend into the parenchyma diffusely

Histopathology:

Cat: 

Spleen: Multifocal random necrotizing suppurative splenitis, severe

Spleen, low power magnification, HE stain: At low power there are multifocal random areas of necrosis and suppurative inflammation (purple foci). These dead cells are most likely neutrophils that migrated into the spleen, or pre-existing lymphocytes.

Spleen from cat, HE stain: The white foci seen grossly correspond to these areas of necrotic debris consisting of necrotic and lysed neutrophils, lymhpocytes and red blood cells and splenic stromal cells lined by a rim of intact neutrophils and macrophages

Liver: Multifocal necro-suppurative hepatitis, moderate, generalized

Cat liver at high magnification, HE stain: The liver also contained grossly visible white foci corresponding to these areas of necrotic neutrophils mixed with necrotic hepatocyte debris. These foci are also circumscribed by macrophages and intact neutrophils.

Skin: Focal necrotizing panniculitis, and ulcerative dermatitis with vascular thrombosis

Skin, low power from the cat: The leg wound had severe necrotizing and suppurative cellulitis involving the panniculus, muscle and dermis, with vascular thrombosis (lower right corner)

Lymph nodes: Diffuse necro-suppurative lymphadenitis, severe

Lungs: Multifocal necro-suppurative pneumonia

Stomach: Suppurative gastritis, multifocal, mild

Large intestine: Intraluminal hemorrhage, severe

Capybara: 

Intestine: Diffuse transmural necrotizing enteritis, severe

Lungs: Multifocal necrotizing pneumonia, moderate, generalized

Lymph nodes: Diffuse necrotizing lymphadenitis, severe

Immunohistochemistry:

All affected tissues in the capybara and cat were positive with IHC for Francisella tularensis.

Ancillary findings:

Cat: Francisella tularensis cultured positive

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Pathology of the distal third metacarpal/metatarsal bone and incidence of lateral condylar fractures in New York State Thoroughbred race horses:42 cases from 2013-2014

Pathology of the distal third metacarpal/metatarsal bone and incidence of lateral condylar fractures in New York State Thoroughbred race horses:42 cases from 2013-2014

N-14 ACVP Atlanta, GA 2014

Brian G Caserto, Cornell University College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY

Abstract:

Degenerative changes in the distal metacarpus/metatarsus are commonly recognized in racehorses. Grading is based on the appearance of the surface cartilage which has limitations in evaluating the underlying subchondral and epiphyseal bone. Progressive changes in the bone density of the distal metacarpal condyles can be observed and categorized by gross examination of longitudinal sections through the midpoint of the condyles. In this series, condylar fractures occurred in lateral condyles only. Condyles from thirty-nine (42) racehorses from 2013-2014 were graded according to an established scoring system, and were additionally categorized by newly described patterns of epiphyseal sclerosis; Normal, Focal subchondral, Bridging , or Diffuse.  Eight horses with 9 lateral condylar fractures (4 left unilateral; 3 right unilateral; 1 bilateral) were found with 77.8% (7/9) of fractured condyles having Bridging epiphyseal sclerosis and 22.2% (2/9) having Focal subchondral sclerosis. No condylar fractures occurred in horses having normal epiphyseal trabecular bone density or diffuse epiphyseal sclerosis. Pre-existing pathology is often cited as a risk factor for catastrophic musculoskeletal injury in racing horses. In this series, grade of condylar arthrosis had no correlation to the pattern of subchondral sclerosis, epiphyseal bone density, or incidence of fracture.  However, gross examination of distal metacarpal/metatarsal condyles is able to  subjectively categorize the pattern of epiphyseal sclerosis, and the large proportion of bridging sclerotic condyles incurring catastrophic fractures suggests that this maladaptive change in bone density is a possible risk factor for lateral condylar fractures resulting in breakdowns in New York State Thoroughbred race horses.

Metacarpal arthrosis vs Palmar/Plantar Osteochondral Disease:

Pathology involving the palmar/plantar aspect of the subchondral bone has been called a variety of names including “metacarpal arthrosis” and palmar/plantar osteochondral disease”. Whichever term is used this refers to several progressive degenerative changes occurring on the palmar apical region of the distal metacarpal/metatarsal condyles of athletic horses. This suite of changes begins with suhchondral sclerosis in a semi-circular pattern:

Distal condyle, early subchondral sclerosis in a focal pattern, with relatively porous (normal) epiphyseal bone

From here several things can happen:

1) The epiphysis progresses to bridging or diffuse sclerosis with no osteochondral disease:

Advanced case of bridging sclerosis, nearly progressed to diffuse, but as yet no subchondral bone defect

Severe bridging sclerosis also with no osteochondral disease

Or:

2) The subchondral bone becomes damaged by repeated impact during exercise. What happens to the subchondral bone progresses in stages:

- Microcracks can form in the zone of mineralized cartilage and subchondral bone, and shrunken vascular spaces are damaged causing hemorrhage and localized hypoxia.

Microcracks form in the subchondral bone and zone of mineralized cartilage adding to the devitalization of the subchondral bone, that prevents proper repair.

 

 

Larger cracks and fissures form as a precursor to morselization

Hemorrhage within vascular spaces is an early lesion of repetitive injury

-Followed by disruption of the subchondral bone into many small pieces called “morselization” – This grossly looks yellow to brown due to hemorrhage and necrosis.

The subchodnral bone is fragmented into many small pieces by repeated impact trauma. The overlying cartilage is relatively normal.

 

-  This often causes a depression, flattening or defect in the overlying articular cartilage since the subhcondral bone plate is destroyed focally.

Grade 3 arthrosis/osteochondral disease in both condyles. The discoloration is due to the hemorrhage and necrosis of the underlying bone.

Severe subchondral necrosis (osteochondral disease) in a diffusely sclerotic epiphysis. The surface is flattened, and the bone has only begun to heal.

What Happens to these lesions over time?

- Over time these regions can become re-vascularized and begin to heal:

1) first resorbing the crushed subchondral bone, and forming new dense trabeculae in its place.

Early remodeling of moralized subchondral bone, showing reversal lines perpendicular to the lamellar bone, with woven born added to it

 

-Healing may take place before collapse of the articular surface, and in mild cases the surface may retain its shape and contour with no lasting effects.

-In more severe cases, the articular surface is changed permanently.

 

Secondary changes to the overlying cartilage include initially thickening of the cartilage, as it swells with absorbed joint fluid. This then becomes softer, and more prone to mechanical damage, and results eventually in fibrillation or a flap forming.

Late stage of osteochondral disease with fibrillation of the articular cartilage. Notice the subchondral bone is composed of woven osteoid indicating proliferative response and attempt at repair. In this case the contour of the surface is relatively unchanged

In some cases the cartilage collapses and dips into the subchondral bone forming a fold:

Aging healing osteochondral defect with a folding of the articular cartilage and a small rim of brown discoloration indicating past hemorrhage

 

A gross image of the above lesion, an advanced case of arthrosis/osteochondral disease. On the left side there is swelling of the overlying cartilage secondary to subchondral bone changes. On the right the surface is collapse as seen in the cross section above.

Progressive degenerative joint disease is possible in the long term, however these are nearly clinically undetectable without CT or MRI, and in most cases do not affect racing performance or cause lameness.

The pathogenesis of these lesions is a subject of debate. Increased bone density is thought to lead to ischemia of the bone. However ischemic bone is still structurally sound, so by itself the reduction in vascular supply secondary to sclerosis is only a predisposing factor.

Microcracks in the zones of mineralized cartilage, and subchondral bone often occur at the periphery of the morselized regions, and in my opinion are a precursor to moreselization.  Increased bone density does lead to reduced size of vascular channels, and rigid brittle bone, which predisposes these regions for micro cracks without healing, and further moreselization that will occur.

Epiphyseal Bone Density

In this case series I focused on the gross appearance of the lateral condyles. Serial longitudinal sections through lateral and medial condyles of the right and left limbs provided insights into the variety of progressive bone changes in the epiphyses of these bones.

Sclerosis of the condylar epiphyseal trabeculae was grouped into 4 categories with. Osteochondral defects were not considered in these categories and were treated separately

Mechanical forces acting on the condyles influence the degree of bone density and the pattern of progression. In most horses the medial condyles are larger, wider, and progress to increased bone density faster than the lateral condyles. Undoubtedly there are conformational factors affecting the weight distribution onto the condyles that affect the forces and therefor the bone remodeling in the distal metacarpal bones.

Fractures occurred in the lateral condyles only in these horses, with roughly equal distribution between left and right forelimbs, and the right hind limbs in 3 cases.

Often the degree of density is directly related to the time in training, and not necessarily to age. Based on my observations, I can see several patterns of increased bone density. Young horses with only 1-2 years of training often have a mild increase in bone density, with the bone appearing porous throughout the epiphysis. This I categorized as “Normal”.

With more high speed training a focal region corresponding to the palmar apical area becomes sclerotic, and is distinctly less vascular, and appears as a continuous white region beneath the cartilage. This can occur with or without arthrosis. This pattern I have categorized as Focal subchondral sclerosis, or “Focal”.

In several cases, it can be demonstrated that  with more exercise, the focal regions can extend through the epiphysis, widening and eventually bridging the opposite side of the condyle at the dorsal base of the condyle. This pattern often excludes the subchondral bone adjacent to the palmar apical crescent, and because of this I call this a “Bridging” pattern.   This pattern can eventual progress to  the next category.

The final category can arise in two ways. First, it can progress from the bridging sclerotic change. Secondly it can also develop without going through the bridging phase, and arise simply as a uniform increase in bone density throughout the epiphysis.   The reason for this I believe is simply a mechanical influence resulting from conformation and training.

Osteochondral disease and the relationship to lateral condylar fractures

All lateral condyles were graded, in the left and right limbs of each horse examined. Fractures decreased in incidence as the prevalence of each grade decreased. Most horses fell into the grade 0 category, and the least number in grade 3.

Fracture incidence by sclerotic pattern

Lateral condyles were compared in both left and right limbs. The majority of these were categorized as diffuse sclerosis, having sufficiently dense bone throughout the epiphysis. The next frequent categories were focal, and normal, and these two had the least number of fractures. By far the smallest category was bridging, but it had the majority of fractures, and these outnumbered the cases of bridging sclerosis where no fracture occurred.

Conclusions

Bridging sclerosis may be a risk factor for lateral condylar fractures that could potentially be identified by CT or MRI.  Several studies, and also a poster in this conference have studied the subchondral osteochondral disease in racehorses and attempted to correlate the grade of arthrosis with indigence of fractures or breakdowns. I think the focus on these defects is not warranted based on the above results. Rather, the entire epiphysis should be examined since it seems to have a better predictive value for lateral condylar fractures.

 

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What’s Your Diagnosis #6

What’s your diagnosis #6

History: A 15 month old Angus steer became recumbent and could not rise.

What are some differential diagnoses for acute weakness and recumbency in cattle?

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The steer was treated with thiamine and penicillin, but  was eventually euthanized for diagnostic purposes. Three other animals have died acutely.

Gross Necropsy Findings:

The steer was in good body condition. The rumen contained coarse plant fibers and chopped cornstalks, with no grain. The rumen pH was 7.4. The brain did not fluoresce under UV light.

There were no significant gross lesions.

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Differential Diagnoses for acute recumbency:

Neurologic:

Polioencephalomalacia (thiamine deficiency, lead toxicity)

Lymphoma (spinal)

Listeriosis

Thrombotic Meningoencephalitis

Rabies

BSE

Septic meningitis

Metabolic: 

Calcium deficiency

Magnesium deficiency (grass tetany)

Salt toxicity/water deprivation

Musculoskeletal:

Blackleg (Clostridium chauvoei)

Fracture

Osteochondrosis

Arthritis

Other:

Urea toxicity

Nervous Ketosis

Nervous Coccidiosis

Abomasal displacement

Peritonitis

Systemic bacteremia

Comment:

Considering the signalment and gross necropsy findings many of these diseases can be ruled out or down.  This is not a lactating cow (its a steer), so hypocalcemia, and hypomagnesemia are less likely. There is no evidence of septic peritonitis, abomasal bloat, or meningitis.  There is no enteritis suggesting coccidiosis, and no rumen acidosis. There was no sign of skeletal muscle necrosis, fractures, or joint diseases, and no sign of lymphoma.

Remaining differentials include: Polioencephalomalacia, Urea toxicity, BSE, Rabies, Listeriosis, or TME

What would you expect to see histologically in each of these conditions?

Stay tuned for histopath…

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