Feline spongiform encephalopathy: first clinical case in Switzerland

A six-year-old female Birman cat was referred to our clinic because of chronic progressive changes in behavior. Additionally, generalized vestibular ataxia and psychomotor seizures were noticed. A multifocal lesion in the forebrain as well as brainstem was suspected. Ancillary investigations such as complete blood cell count, serum biochemistry profile, urinalysis and cerebrospinal fluid examination revealed no significant abnormalities. Electroencephalography showed diffuse changes in the cortical activity. Feline spongiform encephalopathy was confirmed by histological brain examination and positive immunohistochemistry for PrPSc. This is the first time that a case of feline spongiform encephalopathy is diagnosed in Switzerland.     

Renal (uremic) encephalopathy in a goat

Renal encephalopathy was diagnosed in a 2-year-old male boar goat with a history of chronic weight loss and ataxia. Histopathological examination of the brain revealed a striking myelin vacuolation distributed mainly in two patterns: (i) along the junction of the neocortex and corona radiata, and (ii) in the bundles of the internal capsule as it dissects through the basal nuclei. The kidneys had diffuse severe tubular and glomerular necrosis and degeneration. The neural lesions are consistent with renal (uremic) encephalopathy. To the authors' knowledge, this is the first report of renal encephalopathy in a goat.     

Spongiform encephalopathy in a captive puma (Felis concolor).

A captive adult puma developed ataxia, a hypermetric gait and whole body tremor. The signs progressed over a period of six weeks. Histopathological examination following euthanasia demonstrated spongiform encephalopathy, gliosis and mild non-suppurative meningoencephalitis. Immunostaining with a polyclonal antiserum revealed prion protein (PrP) associated with these changes in sections of cervical spinal cord and medulla. This is the first confirmed case of a scrapie-like spongiform encephalopathy described in a non-domestic cat in the United Kingdom.     

Acquired extrahepatic portosystemic shunts in a young dog

A young, male miniature poodle was presented with severe neurological problems. Laboratory tests and ultrasonograph examination were consistent with extrahepatic portosystemic shunts, resulting in hepatic encephalopathy. When surgical correction proved not to be a viable option, the dog was euthanized. Postmortem examination revealed multiple shunts likely acquired after severe hepatitis.     

Ataxia and weakness as uncommon primary manifestations of hepatic encephalopathy in a 15‐year‐old trotter gelding

A 15‐year‐old trotter gelding was evaluated because of an acute onset of ataxia in all 4 limbs. There was no known history of trauma. The gelding showed grade 2/5 ataxia in all 4 limbs, which was localised after clinical neurological examination to the cervical vertebral spinal cord. Initial therapy consisted of oral anti‐inflammatory doses of prednisolone and antimicrobial treatment with potentiated sulphonamides. The ataxia progressed to grade 3/5 at Day 10 of hospitalisation. Additionally, the horse was slightly depressed and showed spontaneous yawning during examination. Facial sensation was blunted. Blood chemistry revealed a marked elevation of liver specific enzymes and blood ammonia levels. Transcutaneous abdominal ultrasonography revealed hepatomegaly. Due to a guarded prognosis, the horse was subjected to euthanasia. At necropsy the left lateral liver lobe was markedly enlarged and showed a firm texture, whereas the cranial part and the right and quadratic liver lobe displayed a severe and diffuse atrophy. Histopathologically, the left lateral liver lobe revealed a moderate to severe cirrhosis with a severe, diffuse hepatocellular iron‐accumulation. Increased numbers of Alzheimer type II astrocytes in the cerebral cortex and cerebral white matter vacuolisation were indicative for encephalopathy. These findings were interpreted as haemosiderosis and cirrhosis of the liver with consecutive hepatic encephalopathy. Aetiologically, haemosiderosis should be considered as a cause of liver cirrhosis with consecutive hepatic encephalopathy. Although hepatic encephalopathy in horses usually presents with predominating cerebral signs, it has to be taken into account as a differential diagnosis in cases of acute onset generalised ataxia.     

Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu (Tragelaphus strepsiceros)

Clinical, pathological and epidemiological details of scrapie-like encephalopathies are described in an arabian oryx and a greater kudu. Clinical signs included ataxia and loss of condition with a short, progressive clinical course (22 and three days, respectively). Histopathological examination of the brains revealed spongiform encephalopathy characteristic of that observed in scrapie and bovine spongiform encephalopathy (BSE). It seems probable that these cases have a common aetiology with BSE. Scrapie-like spongiform encephalopathies have now been described in five species of exotic artiodactyls in Britain indicating a, hitherto inapparent, wider range of ruminant species as natural hosts for these diseases.     

Scrapie-like encephalopathy in a greater kudu (Tragelaphus strepsiceros) which had not been fed ruminant-derived protein.

A 19-month-old greater kudu (Tragelaphus strepsiceros), whose dam had died 15 months earlier with spongiform encephalopathy, required euthanasia after developing severe ataxia and depression with an apparently sudden onset. No macroscopic abnormalities were detected on post mortem examination but a scrapie-like spongiform encephalomyelopathy was apparent on histopathological examination of brain and segments of spinal cord. Negative stain electron microscopy of proteinase K-treated detergent extracts of tissue from the brain stem revealed the presence of scrapie associated fibrils, and a 25 to 28 kDa band comparable with that identified as abnormal PrP (prion protein) from the brains of domestic cattle with spongiform encephalopathy was detected using rabbit antiserum raised against mouse PrP. The animal was born nine months after the statutory ban on the inclusion of ruminant-derived protein in ruminant feeds and, as no other possible sources of the disease were apparent, it appears likely that the infection was acquired from the dam.     

Hepatic encephalopathy in a pregnant mare: identification of histopathological changes in the brain of a mare and fetus

An 11-year-old Thoroughbred broodmare was evaluated for suspected hepatic dysfunction. Clinical signs of hepatic encephalopathy were evident at admission. Hepatic ultrasonographic evaluation revealed an increase in hepatic size, rounded borders and normal echogenicity. There was no evidence of cholelithiasis or bile duct distention. Increased activity of hepatic enzymes, increased bile acid and bilirubin concentration and an increased ammonia concentration were supportive of a diagnosis of hepatic disease and hepatic encephalopathy. Histopathological evaluation of a liver biopsy specimen was consistent with chronic active hepatitis. The mare was treated with intravenous fluids and antimicrobials, pentoxyfilline, branched-chain amino acids and dietary manipulation. Clinical improvement was observed initially; however, 3 weeks later, deterioration in the mare's condition necessitated euthanasia. Pathological lesions at necropsy were restricted to the liver and brain. The liver was diffusely firm with a prominent reticular pattern on the cut surface. A large choledocholith was present in the main bile duct of the left liver lobe. Histopathological examination of the liver revealed severe fibrosis, with hyperplastic bile ducts and mononuclear and neutrophilic inflammation. Pathological changes consistent with hepatic encephalopathy, (Alzheimer type II cells), were evident in the cerebrum of both the mare and the fetus.     

Severe involvement of cerebral neopallidum in a dog with hepatic encephalopathy

This report describes a unique distribution of cerebral cortical necrotic lesion, which was diagnosed as hepatic encephalopathy in a 2-year-old Maltese dog. The dog showed splenocaval shunt and small liver with marked hepatocellular fatty degeneration. Histopathologic examination revealed that diffuse laminar cortical necrosis composed of neuronal necrosis, marked infiltration of gitter macrophages, and astrogliosis were found bilaterally in the dorsolateral area of the cerebrum. No necrotic lesions were observed in the cerebral paleopallium and archipallium, the central gray matter, cerebellum, and brain stem. Astrocytes with large and pale nuclei (Alzheimer type II astrocytes) were apparent throughout the brain. Immunohistochemically, a decrease of immunostains for glutamine synthetase and glutamate transporter antibodies was seen in Alzheimer type II astrocytes and neuropil. This is, to our knowledge, the first report of extensive involvement of cerebral neopallidum in canine hepatic encephalopathy.     

Spongiform neurodegenerative disease in a Persian kitten

A congenital encephalopathy with spongiform degeneration and prominent neuronal apoptosis was observed in a 4-month-old Persian male cat with a history of depressed mental status and ataxia. On clinical examination, signs included right head tilt, ventroflexion of the head and neck, and tetraparesis. Histological examination of the central nervous system revealed multifocal, bilateral and symmetrical vacuolar degeneration of the neuropil, mainly involving the cerebellar and vestibular nuclei area, the caudal colliculi, the mesencephalic nuclei, the tegmental area and the deeper layer of the cerebral cortex. Accumulation of phosphorylated neurofilaments was detected in neuronal perikarya of the deep cortical layers, hippocampus and thalamus. Numerous pyknotic and apoptotic neurons were also observed in the cerebral cortex. These neuropathological changes differ from those observed in previous reports of spongiform degeneration of the grey matter in cats and were suggestive of a congenital neurodegenerative disease.     

BSE infection in bovine PrP transgenic mice leads to hyperphosphorylation of tau-protein

We observed the changes in the central nervous system (CNS) of transgenic mice expressing bovine prion protein (Bo-PrP) as a contribution to our knowledge of the pathogenesis of bovine spongiform encephalopathy (BSE). The main result was the detection of hyperphosphorylated tau. This protein was detected for the first time, using immunohistochemical techniques, in the neurons and glial cells of mice experimentally infected with BSE. The results highlighted the involvement of tau protein in the pathogenesis of BSE and the close link between hyperphosphorylated tau deposits and prion protein. Ultrastructural examination revealed a novel arrangement of intraneuronal tau deposits not hitherto reported.     

Gastric adenocarcinoma in a horse with portal vein metastasis and thrombosis: a novel cause of hepatic encephalopathy

A 17-year-old Quarter horse mare was referred to Cornell University for postmortem examination after 72 hours of encephalopathy that consisted of depression, mania, and blindness. A plasma sample and cerebral spinal fluid demonstrated hyperammonemia. Gross necropsy examination findings included the following: mild icterus, a transmural mass in the glandular portion of the gastric fundus, multiple masses throughout the liver, and a large tumor thrombus in the portal vein. Microscopically, the gastric mass, hepatic masses, and portal vein thrombus were composed of similar neoplastic epithelial cells that formed variably sized acini and branching cords separated by a dense desmoplastic stroma. Throughout the cerebral frontal cortex were numerous Alzheimer type II astrocytes. Hepatic encephalopathy was caused by gastric adenocarcinoma, with metastasis to the liver and the portal vein. The clinical and pathologic lesions from this unique case, as well as hyperammonemia and portal vein thrombosis in the pathogenesis of hepatic encephalopathy, are discussed.     

Colchicine treatment in a dog with hepatoportal fibrosis

A two-year-old female spayed English setter with hepatic encephalopathy was found to have hepatoportal fibrosis and acquired portosystemic shunts on laparotomy and liver biopsy. The dog was treated symptomatically with a low-protein diet, lactulose and metronidazole, while colchicine was given as antifibrotic therapy. There was a gradual improvement in clinical signs and liver function until 30 months after first presentation, when the dog developed severe haematuria caused by renal infarction of unknown aetiology. Post mortem examination revealed hepatic fibrosis to be unchanged. This case illustrates that long term survival may be possible in canine hepatoportal fibrosis and suggests that colchicine may be effective in improving liver function and slowing progression of hepatic fibrosis.     

Putative uremic encephalopathy in horses: five cases (1978-1998)

OBJECTIVE: To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. PROCEDURE: Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. RESULTS: Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.     

Gait deficits in liver disease: Hepatic encephalopathy and hepatic myelopathy

In this issue, the unusual clinical presentation of a horse diagnosed is described with severe liver cirrhosis and hepatic encephalopathy. The horse initially presented for thoracic and pelvic limb ataxia and weakness, and signs of forebrain disease were not apparent until later in the disease process. The typical pathology of central nervous system disease associated with liver disease is related to encephalopathy and forebrain disease; however, the spinal cord is occasionally also involved. Hepatic myelopathy is a rare syndrome usually associated with surgical or acquired portosystemic shunts, liver cirrhosis and/or portal hypertension in man. Where a gliopathy is the most prominent pathological feature seen in hepatic encephalopathy, in hepatic myelopathy the most remarkable feature is demyelination of the corticospinal tracts of the distal cervical and thoracic spinal cord with occasional axon loss. The clinical signs of hepatic myelopathy are spastic paresis/paralysis with normal sensory findings and preserved sphincter function. The prognosis for hepatic myelopathy is generally poor. In summary, in severe liver disease, motor deficits can occur secondary to the encephalopathy, but motor deficits can also occur as a result of spinal cord pathology such as seen in hepatic myelopathy. In examination of horses with myelopathies, liver disease as a cause of myelopathy should be included in our list of differentials.     

Presumptive Iatrogenic Microcystin‐Associated Liver Failure and Encephalopathy in a Holsteiner Gelding

An 8‐year‐old Holsteiner gelding was presented for evaluation of anorexia, obtundation, icterus, and mild colic signs of 48 hours duration. History, physical examination, and initial diagnostics were suggestive of hepatic disease and encephalopathy. Microcystin toxicosis was suspected based on historical administration of a cyanobacteria supplement, associated serum biochemistry abnormalities, and characteristic histopathological changes. Microcystin contamination was confirmed in both supplement containers fed to the horse. Fulminant hepatic failure and encephalopathy progressed resulting in euthanasia. Necropsy findings were consistent with microcystin induced liver failure.     

Reflections on scrapie and related disorders,with consideration of the possibility of a viral aetiology

The transmissible spongiform encephalopathies of domesticated animals, scrapie in-sheep and bovine spongiform encephalopathy (BSE), and transmissible mink encephalopathy are more than a scientific curiosity; under certain circumstances their impact on commercial activities can be calamitous. Knowledge of their causation and pathogenesis is still rudimentary, but many consider than an unconventional agent, the prion (a brain protein, PrP), that is not associated with nucleic acid is involved in both. Others believe that conventional viruses, which replicate by virtue of their nucleic acid-defined genes, are involved in the causation and progression of the encephalopathies but that technical problems have prevented their identification. Others postulate even more exotic causative agents. While this paper will particularly address the possibility of a viral aetiology for these diseases, it is also emphasized that our knowledge of the state of the immune system in animals with encephalopathy needs broadening. There are remarkable gaps in our knowledge of the histopathology of these diseases, particularly the nature of the characteristic vacuoles. Much further work is needed on the biochemical changes in the brain and the serum, particularly of the latter as it could lead to an additional means of recognizing clinical cases without waiting for the animal to die with subsequent examination of the brain for characteristic lesions and the presence of protease-K-resistant PrP.Abbreviations AI artificial insemination - BSE bovine spongiform encephalopathy - CJD Creutzfeldt-Jakob disease - ET embryo transfer - GSSD Gerstmann-Sträussler-Scheinker disease - HDV hepatitis delta virus - MCF mink cell focus - PK proteinase K - PrP prion protein - PrPSc scrapie prion protein - PrP-C the proteinase-K sensitive homologue in normal brain - SAF scrapie-associated fibrils - TME transmissible mink encephalopathy     

Subacute necrotising encephalopathy in an Alaskan husky

A 29-month-old female Alaskan husky was presented recumbent, tetraparetic and in a state of dementia, with blindness and cranial nerve deficits. The dog's progress was followed for over two months, as the signs resolved to an non-progressive mild hypermetria with slight proprioceptive ataxia, a diminished menace response and inability to prehend food. Magnetic resonance imaging (MRI) revealed bilateral cavitation extending from the thalamus to the medulla, with less pronounced degenerative lesions in the caudate nucleus, putamen and claustrum. Cerebrospinal fluid lactate and pyruvate concentrations were in their normal ranges. Necropsy and histological examination confirmed the MRI findings as well as neuronal degeneration of the cerebellar cortex in the vermis and degenerative changes in the neocortex at the depths of the cerebral sulci. In view of the similarity of lesions to subacute necrotising encephalomyelopathy, known as Leigh's disease in humans, a tentative diagnosis of a mitochondrial encephalopathy was made.     

Hepatic lipodystrophy of pedigree Galloway calves

Hepatic lipodystrophy has been recognised in pedigree Galloway calves since 1965. Between 1975 and 1984 15 cases from five farms were examined. The calves initially appear normal and in good bodily condition but invariably die by five months of age. The characteristic clinical and neurological changes lead to body tremors, opisthotonus, and dyspnoea before the animals become recumbent and die. On postmortem examination the most significant finding in all cases was an enlarged, pale and mottled liver weighing up to 2.75 kg. Limited histopathological examinations of the brain and liver revealed changes suggestive of hepatic encephalopathy. Exhaustive investigations of the farms failed to reveal any significant findings and the small number of cases made it impossible to determine whether the disease was genetically determined; limited evidence suggests that a 'storage disease' cannot be excluded.     

A case of spongiform encephalopathy ("cattle madness") in a cow in Switzerland

Spongiform encephalopathies occur in humans and several domestic animal species. Among them, the bovine spongiform encephalopathy (BSE) has aroused considerable interest because of a massive outbreak of this disease in Great Britain, which is thought to result from feeding meat and bone meal contaminated with the spongiform encephalopathy agent. We observed the first case of BSE in Switzerland, which is also the first case on the European continent. A 6 year old cow suffered from progressive neurological disease. On neuropathological examination typical spongiform changes and neuronal vacuolation were found. The origin of the infection remains unknown. It cannot be excluded that the animal was exposed to cattle feed derived from Great Britain. It is possible that additional sporadic cases may occur in Switzerland, an outbreak such as in England is unlikely to happen.