History
A 4-month-old 30.4-kg (66.9-lb) Boer goat buck was examined because of a 24-hour history of signs of depression, weakness, and the inability to rise. The goat was bottle-fed whole milk after birth because the doe developed postpartum mastitis and metritis. The goat had been weaned 2 weeks prior to the examination and had more recently been fed a diet of commercial goat chow along with grass hay and leaves. This goat had not been vaccinated but had been dewormed once monthly with morantel tartrate administered in a feed premix. The 2 other goats on the property were apparently healthy.
Clinical and Gross Findings
On physical examination, the goat was obtunded and had bruxism. Both pupils were dilated. Direct and indirect pupillary light reflexes were absent or markedly delayed in both eyes. The left eye had dorsomedial strabismus. Plasma lactate concentration was high (2.5 mmol/L; reference range in sheep, 1 to 1.3 mmol/L). Intravenous fluid therapy and potassium, calcium, and thiamine supplementation were initiated. Shortly after treatment was started, the goat had a seizure and died.
At necropsy, the brain was removed and there were diffuse petechial hemorrhages throughout the leptomeninges of the cerebrum and cerebellum. There was mild coning of the cerebellum. The brain was coronally sectioned; examination under UV light revealed bilateral and symmetric fluorescence of the cerebral cortical gray matter (Figure 1). The rumen was distended, and ruminal contents included grain, roughage, and leaves. There were no additional gross lesions at necropsy.
Photograph of a cut section of the brain (illuminated with UV light) of a 4-month-old Boer goat buck that was evaluated because of a 24-hour history of signs of depression, weakness, and the inability to rise. Despite initiation of treatment, the goat had a seizure and died. Notice the cerebrocortical autofluorescence under UV light. Affected areas of the frontal lobe appear bilaterally symmetric and have a light blue to turquoise luminescence, compared with the adjacent darker, subcortical white matter.
Citation: Journal of the American Veterinary Medical Association 252, 9; 10.2460/javma.252.9.1067
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page—
Histopathologic Findings
Representative tissue samples, including tissues from the lungs, heart, various parts of the gastrointestinal tract, liver, kidneys, and adrenal glands and multiple sections of brain, were fixed in neutral-buffered 10% formalin and routinely processed for histologic examination. Within the cerebrum, there was severe, multifocal degeneration and necrosis of deep laminar cortical neurons characterized by cytoplasmic hypereosinophilia, shrunken cell bodies with angular borders, nuclear pyknosis, and frequent rarefaction of the surrounding neuroparenchyma. The frontal lobes, especially along the midline, were most severely affected, and in these regions, most neurons were necrotic (Figures 2 and 3).
Photomicrograph of a section of cerebral tissue from the frontal lobe of the brain of the goat in Figure 1. Laminar rarefaction and edema are present within the deep cortical neuroparenchyma giving the zone a pale, washed out appearance. H&E stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 252, 9; 10.2460/javma.252.9.1067
Photomicrograph of another section of cerebral tissue from the frontal lobe of the brain of the goat in Figure 1. Necrosis of cerebral cortical neurons is characterized by hypereosinophilic, shrunken cell bodies with angular cell borders. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 252, 9; 10.2460/javma.252.9.1067
Within the rumen wall, the epithelium was diffusely parakeratotic and most epithelial cells had a moderate amount of lightly basophilic cytoplasm. Occasionally, surface keratinocytes had deeply basophilic, finely granular, cytoplasmic deposits (mineral). Frequently, the basal epithelial layer was lifted off the underlying lamina propria and an eosinophilic to amphophilic, homogenous, acellular, proteinaceous fluid had filled this space (Figure 4).
Photomicrograph of a section of the rumen wall of the goat in Figure 1. There is diffuse, prominent parakeratosis. Keratinocytes frequently have a moderate amount of lightly basophilic, mucinous cytoplasm or occasionally deeply basophilic, granular cytoplasm (mineral). Frequently, the basal layer of epithelial cells has lifted off the underlying lamina propria and an eosinophilic to amphophilic, homogenous, acellular proteinaceous fluid frequently has filled this space. These findings are characteristic of subacute ruminal acidosis. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 252, 9; 10.2460/javma.252.9.1067
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: severe, acute, multifocal, cortical, laminar neuronal necrosis and moderate, diffuse ruminal parakeratotic hyperkeratosis with multifocal mineralization.
Case summary: polioencephalomalacia (PEM) and concurrent subacute ruminal acidosis in a goat.
Comments
Thiamine deficiency is a known cause of PEM in ruminants. Clinical signs suggestive of PEM include ataxia, opisthotonus, head pressing, seizures, blindness, and death. For the 4-month-old Boer goat buck of the present report, a diagnosis of PEM with subacute ruminal acidosis was made.
A deficiency in thiamine can be primary or secondary. Herbivores, in particular ruminants, have low dietary thiamine requirements owing to the presence of thiamine-producing bacteria in the rumen. A primary thiamine deficiency develops in neonates fed thiamine-deficient milk replacer. Secondary thiamine deficiency results from the destruction of microbe-derived ruminal thiamine by thiaminases and has been associated with ingestion of high-concentrate diets, thiaminase-containing plants (nardoo [Marsilea drummondii], bracken [Pteridium aquilinum], and rock ferns [Cheilanthes sieberi]), and excess dietary sulfur.1–3 Consumption of diets with high concentrations of grain results in rapid carbohydrate fermentation and the production of large amounts of lactic acid. This lowers the pH and changes the microbial population in the rumen. The ruminal flora alter from thiamine-producing bacteria to thiaminase-producing bacteria including Clostridium thiaminolyticum, Clostridium sporogenes, and Bacillus aneurinolyticum.4,5
Thiamine is required for aerobic cellular respiration, and a deficiency results in a shift to anaerobic metabolism. In thiamine-deficient animals, high plasma pyruvate, lactate, and pyruvate kinase concentrations have been reported. It is thought that a decrease in glucose utilization by the brain results in focal lactic acidosis, which ultimately damages susceptible areas of the brain and causes cerebrocortical edema and necrosis. The dorsally symmetric distribution of cerebral cortical necrosis within the frontal lobe in the case described in the present report may have been compounded by an increase in intracranial pressure and compression of the middle cerebral artery, thereby leading to ischemic change in the dependent cerebral cortex.6
The histologic lesions associated with thiamine deficiency are PEM or necrosis of the deep laminar cerebral cortical neurons. However, this type of lesion is relatively nonspecific, and it is associated with various other conditions. Polioencephalomalacia in animals treated with anthelmintics (thiabendazole or levamisole) and coccidiostats (amprolium) has been reported.4,7 There have also been reports1,2 of PEM in animals that have developed thiamine-independent PEM as a result of excessive dietary sodium, lead, or sulfur.8
In a retrospective study9 of neurologic lesions in goats from 3 veterinary diagnostic laboratories, necrosis of neurons within the cerebral cortex with no or very minimal nonsuppurative inflammation was the second most commonly diagnosed lesion (30/139 [21.6%] cases) after lesions associated with listeriosis. These findings in the cerebral cortex were reported as PEM, laminar cerebrocortical necrosis, and cerebral cortical necrosis in 23, 5, and 2 cases, respectively. In that study,9 the fewest PEM cases were recorded during the winter months. Neurologic tissue samples (fresh or fixed) from 17 of those cases were examined under UV light; in 13 (76.5%) of those cases, fluorescence of cortical gray matter was reported.9
Although 4 goats with PEM in the aforementioned retrospective study9 had concurrent bronchopneumonia (presumed aspiration pneumonia), none were reported to have concurrent subacute ruminal acidosis. Subacute ruminal acidosis is defined as repetitive, prolonged periods of decreased ruminal pH to values between 5.6 and 5.2 and is the result of feeding excessive quantities of concentrate with low levels of fibrous roughage. The histologically characteristic parakeratosis associated with subacute ruminal acidosis is a result of high ruminal concentrations of volatile fatty acids, particularly butyric and propionic acids, which stimulate epithelial turnover (Figure 4). Subacute ruminal acidosis fosters alterations in the rumen microbiota and, potentially, an overproduction of thiaminases.10 A diagnosis of PEM attributable to thiamine deficiency can be made on the basis of history; clinical signs; low erythrocyte transketolase activity; high serum or plasma lactate, pyruvate, and pyruvate kinase activities; and clinical response to thiamine supplementation. Thiamine deficiency results in a deficiency of thiamine pyrophosphate, which is a required cofactor for transketolase in many cell types, including erythrocytes.11 Thus, low erythrocyte transketolase activity may be used as a surrogate marker for low systemic thiamine concentration and may be a useful diagnostic assessment in some cases. It is recommended that every neonatal ruminant with CNS signs should be treated with thiamine, and often response to early treatment is favorable. Thiamine-deficient PEM can be prevented with adequate dietary roughage and thiamine supplementation. Ruminant diets that have excessively high amounts of concentrates should be avoided or supplemented with thiamine.
References
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