Spongiform encephalomyelopathy in a calf with a congenital portosystemic shunt.

A 3-month-old Holstein heifer calf was presented because of an abnormal gait. Further examination revealed cranial nerve deficits, including a severely delayed corneal reflex. The calf was not ataxic and maintained an appetite, but was considerably stunted for her age. A postmortem examination resulted in a diagnosis of a congenital portosystemic shunt.

Encéphalomyélopathie spongiforme chez un veau atteint d'un shunt portosystémique congénital. Une génisse Holstein âgée de 3 mois a été présentée en raison d'une démarche anormale. Un examen a révélé des déficits nerveux crâniens, y compris un réflexe cornéen gravement retardé. Le veau n'était pas ataxique et avait conservé un appétit, mais avait une croissance ralentie pour son âge. Un shunt portosystémique congénital a été diagnostiqué à l'examen post mortem.(Traduit par Isabelle Vallières).

Hepatic Lipodystrophy in Galloway Calves.

Hepatic lipodystrophy in Galloway calves is a fatal liver disease affecting a small proportion of the Galloway breed described in different parts of Europe and North America during the past decades. The clinical findings include a diversity of neurological signs. Clinical pathology findings frequently indicate hepatobiliary disease. Postmortem examination reveals an enlarged, pale yellow, and firm liver. Histologic lesions include hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. To date, the etiopathogenesis remains obscure. Infectious causes, intoxications, and a hereditary origin have been considered. We describe hepatic lipodystrophy in Galloway calves from an extensively farmed cow-calf operation in southern Germany. Main clinical findings in 6 calves were consistent with hepatic encephalopathy. Clinical pathology findings in 5 of 6 tested animals revealed increased concentration of total bilirubin (maximum value [MV], 54 µmol/l; reference range [RR], <8.5 µmol/l), direct bilirubin (MV, 20 µmol/l; RR, <3.4 µmol/l), increased activity of gamma glutamyl transferase (MV, 162 U/l; RR, <36 U/l) and glutamate dehydrogenase (MV, 420 U/l; RR, <16 U/l). In addition, activity of glutathione peroxidase was decreased in all tested ( n = 5) animals (MV, 61 U/g hemoglobin [Hb]; RR, >250 U/g Hb). Postmortem examination in 6 calves revealed a firm, diffusely enlarged yellow liver with a finely nodular surface. Histologic lesions included hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. Our findings add to the existing data on hepatic lipodystrophy in the Galloway breed and outline a protocol to aid in the diagnosis of this disorder.

Use of bee venom in preventive medicine: An experimental hepatic encephalopathy study in rats.

OBJECTIVES: Bee venom is used for medicinal purposes, including the treatment of neurological and liver diseases, but its use as a primary health care approach for preventive purposes requires further exploration. The aim of this study was to provide the first investigation into the possible protective effects of bee venom against hepatic encephalopathy, a serious neurodegenerative disease. MATERIALS AND METHODS: An experimental animal study was conducted in which healthy albino Sprague-Dawley rats were randomized into three groups: healthy, control and bee venom groups. All rats were tested for locomotor activity at the beginning and end of the study. No intervention was made in the healthy group, whereas hepatic encephalopathy was induced in the control and bee venom groups by the administration of thioacetamide (TAA) (200 mg/kg/day). The bee venom group also received bee venom (5 mg/kg/day) subcutaneously every day for 14 days prior to the TAA administration. RESULTS: The results for the final locomotor activity tests were statistically better in the bee venom group than in the control group, supporting a beneficial effect of prophylactic bee venom application. Blood ammonia levels and liver weights, determined as indicators of inflammation, were lower in the bee venom group than in the control group and were close to levels in the healthy group, but not statistically significant. CONCLUSIONS: Bee venom administration has protective effects against the development of hepatic encephalopathy and offers a promising therapeutic opportunity in preventive medicine.

Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

Dogs with congenital porto-systemic shunting (cPSS) and hepatic encephalopathy have higher serum concentrations of C-reactive protein than asymptomatic dogs with cPSS.

Hepatic encephalopathy (HE) is a cause of significant morbidity and mortality in patients with liver disorders and a wide range of rodent models of HE have been described to facilitate studies into the pathogenesis and treatment of HE. However, it is widely acknowledged that no individual model perfectly mimics human HE and there is a particular need for spontaneous, larger animal models. One common congenital abnormality in dogs is the portosystemic shunt (cPSS) which causes clinical signs that are similar to human HE such as ataxia, disorientation, lethargy and occasionally coma. As inflammation has recently been shown to be associated with HE in humans, we hypothesised that inflammation would similarly be associated with HE in dogs with cPSS. To examine this hypothesis we measured C-reactive protein (CRP) in 30 healthy dogs, 19 dogs with a cPSS and no HE and 27 dogs with a cPSS and overt HE. There was a significant difference in CRP concentration between healthy dogs and dogs with HE (p < 0.001) and between dogs with HE and without HE (p < 0.05). The novel finding that there is an association between inflammation and canine HE strengthens the concept that HE in dogs with cPSS shares a similar pathogenesis to humans with HE. Consequently, dogs with a cPSS may be a good spontaneous model of human HE in which to further examine the role of inflammation and development of HE.

Computed tomographic features of portal vein thrombosis in two cats with splenosystemic shunts.

Two spayed female cats presented with hepatic encephalopathy due to hyperammonaemia. On abdominal ultrasound, concurrent portal vein thrombosis and splenosystemic shunts were suspected in both cats. Computed tomographic angiography clearly detected thrombi as non-contrast enhancing intraluminal structures in the main portal vein of both cats. Additionally, splenorenal shunts were revealed in both cats. Follow-up computed tomographic angiography for portal vein thrombosis was performed in both cats, only one of whom received anticoagulant therapy. In the untreated cat, portal vein thrombosis had progressed with the development of an aberrant tortuous vessel. In the cat treated with low-molecular-weight heparin, the thrombus progressively decreased in size and disappeared on follow-up diagnostic imaging. Computed tomographic angiography might be useful for the diagnosis and follow-up of portal vein thrombosis in cats.

Successful management of clinical signs associated with hepatic encephalopathy with manual therapeutic plasma exchange in a dog.

OBJECTIVE: To describe the use of manual therapeutic plasma exchange (TPE) to manage hepatic encephalopathy (HE) in a dog. CASE SUMMARY: A 9-year-old neutered female Dachshund presented for HE secondary to a previously diagnosed portosystemic shunt. The hyperammonemia and severe clinical signs of HE persisted despite extensive medical management. Therapeutic plasma exchange was performed for stabilization prior to surgical shunt ligation. A total of 1 plasma volume was processed during a single manual TPE session. The ammonia immediately prior to TPE was 235 µmol/L (reference interval, 10-30 µmol/L) and decreased to 117 µmol/L by the end of the session. The dog showed significant improvement in clinical signs shortly after the session and remained stable thereafter. Shunt ligation was performed 5 days later with no complications observed with TPE or postoperatively. The dog was discharged 3 days after surgery with no neurological signs and was doing well 100 days after surgery. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first published report of manual TPE to manage HE in veterinary medicine. Therapeutic plasma exchange should be further investigated as a possible strategy to manage clinical signs of HE in patients that are refractory to medical management. Achieving this with manual TPE may be considered in patients that are too small for conventional TPE due to extracorporeal volume or in situations where conventional TPE is not available.

Serum melatonin in dogs with congenital portosystemic shunting, with and without hepatic encephalopathy.

BACKGROUND: Melatonin is a hormone produced and secreted primarily by the pineal gland and mainly metabolised in the liver. Increased melatonin concentrations have been reported in human cirrhosis and hepatic encephalopathy (HE), a syndrome of neurological dysfunction. The pathogenesis of canine HE is incompletely understood. Melatonin has been hypothesised as a contributor to the development of HE. The aim of this study was to investigate whether serum melatonin concentrations are increased in canine congenital portosystemic shunting (cPSS), with and without HE. METHODS: Medical records were retrospectively reviewed, for which archived (-80°C) serum samples were available. A canine competitive ELISA was used to measure melatonin in two cohorts: dogs with a final diagnosis of cPSS (n=23) with and without clinical signs of HE, and healthy dogs (n=15). RESULTS: Melatonin concentrations were not significantly different (P=0.81) between healthy controls (median 27.2 pg/mL, range 19.8-161.5 pg/mL) and dogs with cPSS (median 25.7 pg/mL, range 18.5-244.9 pg/mL). Serum melatonin did not differ between cPSS patients with and without clinical signs of HE (P>0.99). No correlation was found between serum melatonin and blood ammonia (Spearman rank correlation coefficient, rs =-0.41, P=0.08). CONCLUSION: Serum melatonin is not increased in canine cPSS with and without HE. We found no evidence that altered melatonin metabolism plays a role in the pathogenesis of cPSS-associated HE.

Astrocyte lesions in cerebral cortex and cerebellum of dogs with congenital ortosystemic shunting.

BACKGROUND: Congenital portosystemic shunt (cPSS) is one of the most common congenital disorders diagnosed in dogs. Hepatic encephalopathy (HE) is a frequent complication in dogs with a cPSS and is a major cause of morbidity and mortality. Despite HE been a major cause of morbidity in dogs with a cPSS, little is known about the cellular changes that occur in the central nervous system of dogs with a cPSS. OBJECTIVES: The objective of this study was to characterise the histological changes in the cerebral cortex and cerebellum of dogs with cPSS with particular emphasis on astrocyte morphology. METHODS: Eight dogs with a confirmed cPSS were included in the study. RESULTS: Six dogs had substantial numbers of Alzheimer type II astrocytes and all cases had increased immunoreactivity for glial fibrillary acidic protein in the cerebral cortex, even if there were minimal other morphological changes. CONCLUSIONS: This study demonstrates that dogs with a cPSS have marked cellular changes in the cerebral cortex and cerebellum. The cellular changes that occur in the cerebral cortex and cerebellum of dogs with spontaneously arising HE are similar to changes which occur in humans with HE, further validating dogs with a cPSS as a good model for human HE.

Comparative accuracy and precision of two commercial laboratory analyzers for the quantification of ammonia in cerebrospinal fluid.

BACKGROUND: Hyperammonemia is one of the contributing factors of hepatic encephalopathy (HE). Although blood ammonia concentrations are frequently measured in patients suspected of HE, systemic levels do not necessarily reflect the amount of ammonia in the central nervous system. Measuring ammonia in cerebrospinal fluid (CSF) can help to understand HE better and potentially improve the diagnosis and follow-up of patients with HE. OBJECTIVES: The objectives of this technical report were to evaluate the accuracy and precision of two commercial blood ammonia analyzers (Catalyst Dx, CatDX and Pocket Chem BA, PocBA) to measure CSF ammonia concentrations. METHODS: A pool of normal equine CSF was spiked with concentrated ammonia, and a series of six spiked samples were measured in parallel with both CatDx and PocBA. RESULTS: CatDx and PocBA data correlated excellently with but differed significantly from the spiked ammonia concentrations. These differences were smaller when ammonia CSF concentrations were measured with the PocBA than with the CatDx. In addition, values obtained with the PocBA were more precise than those measured with the CatDx, especially for low ammonia concentrations. CONCLUSION: This in-house comparative study shows that ammonia concentrations in spiked equine CSF correlate well with those measured by two commercial blood ammonia analyzers. Nevertheless, concentrations obtained with the PocBA are more accurate and more precise than those obtained with the CatDx, making the former device the preferred choice for clinical veterinary applications.

Outcome of non-surgical dietary treatment with or without lactulose in dogs with congenital portosystemic shunts.

Background: Congenital portosystemic shunts (CPSS) are vascular anomalies, allowing portal blood to bypass the hepatic parenchyma, thereby accumulating toxic substances such as ammonia in the systemic circulation resulting in hepatic encephalopathy.Aim: To evaluate the outcome of non-surgically treated dogs with a CPSS.Methods: Case records of 78 dogs with a single congenital CPSS confirmed by ultrasound and/or computed tomography between September 2003 and February 2015 were reviewed. Median age at diagnosis of CPSS in dogs was 10.8 months (range 2-133 months). Non-surgical treatment was started as an adjusted diet (a diet restricted in protein) with or without lactulose. Owners were contacted by telephone to determine survival time and presumed cause of death, if applicable. In addition, a questionnaire was used to retrospectively assess quality of life (QoL) and CPSS scores in 37 dogs before and during non-surgical treatment. Differences between Kaplan-Meier curves were tested by a Log rank test.Results: Overall estimated median survival time (EMST) was 38.5 months (range 1 day - 91 months; 78 dogs). No significant differences between EMSTs were found between dogs with extra- (n = 48) or intrahepatic (n = 29) shunts, nor between treatment with only an adjusted diet, or an adjusted diet combined with lactulose. During non-surgical treatment, significant improvement in perceived QoL and CPSS scores were found (P < 0.01).Conclusion: Our study demonstrated that an overall median EMST of 3.2 years was reached and that owners retrospectively perceived that non-surgical treatment resulted in an improved QoL and clinical performance, irrespective of intrahepatic or extrahepatic CPSS location.

The cat with neurological manifestations of systemic disease. Key conditions impacting on the CNS.

PRACTICAL RELEVANCE: A number of systemic diseases are associated with neurological deficits. Most systemic diseases that impact on the nervous system result in multifocal neurological signs; however, isolated deficits can also be observed. This article reviews the clinical signs, pathophysiology, diagnosis, treatment and prognosis of four important systemic diseases with neurological consequences: feline infectious peritonitis, toxoplasmosis, hypertension and hepatic encephalopathy. CLINICAL CHALLENGES: Early recognition of systemic signs of illness in conjunction with neurological deficits will allow for prompt diagnosis and treatment. While neurological examination of the feline patient can undoubtedly be challenging, hopefully the accompanying articles in this special issue will enable the clinician to approach these cases with more confidence. EVIDENCE BASE: The veterinary literature contains numerous reports detailing the impact of systemic disease on the nervous system. Unfortunately, very few references provide detailed descriptions of large cohorts of affected cats. This review summarises the literature underpinning the four key diseases under discussion.

Bilateral laryngeal paralysis associated with hepatic dysfunction and hepatic encephalopathy in six ponies and four horses.

Six ponies and four horses with a mean (sd) age of 15.9 (6.0) years developed sudden-onset bilateral laryngeal paralysis (BLP) in association with hepatic dysfunction. Nine of them had been referred for the investigation of respiratory distress, and one pony had been referred for weight loss before BLP developed. Nine of the animals had clinicopathological evidence of liver disease, and nine had histological evidence of liver disease. All of the animals had one or more of the following: hepatic encephalopathy (in eight), hyperammonaemia (in six) and endoscopic evidence of BLP (in nine). Three of the animals had signs of pituitary pars intermedia dysfunction, a diagnosis supported in two by endocrine function testing, and in two by histopathological examination. Histopathological examination of the intrinsic laryngeal musculature and recurrent laryngeal nerves of four of the horses and of the region of the nucleus ambiguus of two did not reveal any abnormalities. Three of the animals were euthanased after they had first been examined, and one improved temporarily before the condition recurred. A temporary tracheostomy was performed in six of the animals, five of which subsequently died or were euthanased; one pony recovered.

Computed Tomography of Lobular Dissecting Hepatitis in a Young Golden Retriever.

A 9 mo old female intact golden retriever presented for evaluation of chronic lethargy and decreased appetite. The serum biochemistry profile revealed increased liver enzymes consistent with a mixed hepatocellular and cholestatic pattern. A multiphase computed tomography angiography was performed to evaluate for a portosystemic shunt. Numerous hyperattenuating nodules were identified throughout the liver on the noncontrast-enhanced series. Histologic evaluation of percutaneous needle biopsy samples of a liver nodule showed a rare form of hepatitis called lobular dissecting hepatitis. Lobular dissecting hepatitis should be considered as a differential in young dogs with precontrast hyperattenuating hepatic nodules on noncontrast-enhanced computed tomography.

Protective role of chrysin on thioacetamide-induced hepatic encephalopathy in rats.

Hepatic encephalopathy (HE) is a serious neuropsychiatric syndrome due to either acute or chronic hepatic failure. This study aimed to investigate the possible neuroprotective effect of chrysin, a natural flavenoid on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. HE was induced in Wistar rats by intraperitoneal (i.p.) injection of TAA (200 mg/kg) for three alternative days. Normal and control groups received the vehicle for 21 days. Chrysin was administered orally for 21 days (25, 50, 100 mg/kg) and starting from day 17, rats received i.p. dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were conducted. Chrysin improved TAA-induced motor incoordination as it reduced final falling latency time in rotarod test, ameliorated cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes namely, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Hepatic encephalopathy in two goat kids with common paternity.

Two juvenile, intact, female mixed-breed goats from a common sire were presented for periodic neurologic deficits, seizures, and a generalized loss of body condition that occurred over a 4-6-week period. On physical examination, both goats were thin, obtunded, blind, and ataxic. Laboratory diagnostics revealed increased serum bile acids (95 micromol/l; reference interval: 0-50 micromol/l) in one of the goats. Both goats exhibited progressive physical and mental deterioration, and were eventually euthanized. Upon necropsy, no significant macroscopic lesions were noted. Microscopic examination, however, demonstrated hepatocellular atrophy and anomalies in the hepatic microvasculature, including duplication of hepatic arteries, small-to-indistinct portal veins, and oval cell hyperplasia. In addition, spongiform change was microscopically identified throughout the parenchyma of the brain, most notably within the white matter and along the junction of gray and white matter. The diagnosis of congenital portal vein hypoperfusion (suggestive of a portosystemic shunt) with resultant hepatic encephalopathy was proposed in each case based on the characteristic microscopic lesions in conjunction with the signalment and history of the goats. The observation that the affected kids were sired by the same buck suggests a hereditary basis for the condition in these animals as well.

Measurement of brain trace elements in a dog with a portosystemic shunt: relation between hyperintensity on T1-weighted magnetic resonance images in lentiform nuclei and brain trace elements.

Prior to euthanasia, brain magnetic resonance imaging (MRI) was performed for a five-year-old male Yorkshire Terrier following portosystemic shunt (PSS) surgical attenuation. Hyperintensity was observed on T1W images of the lentiform nuclei. Trace elements in this area were measured by inductively coupled plasma atomic emission spectrometry. The manganese concentration in the lentiform nuclei was four times higher than that in the control group. Therefore, the manganese accumulation would be the substance that causes the hyperintensity on T1W images of the lentiform nuclei in PSS dogs.

Hepatic encephalomyelopathy in a calf with congenital portosystemic shunt (CPSS).

A 4-month-old female Holstein Friesian calf was referred to the Veterinary Teaching Hospital, University of Berne, Switzerland for evaluation of ataxia, weakness, apathy and stunted growth. Clinical examination revealed generalized ataxia, propioceptive deficits, decreased menace response and sensibility. Postmortem examination did not reveal macroscopic changes of major organs. Histologically, the brain and the spinal cord lesions were characterized by polymicrocavitation, preferentially affecting the white matter fibers at the junction of grey and white matter and by the presence of Alzheimer type II cells. The liver revealed lesions consistent with a congenital portosystemic shunt, characterized by increased numbers of arteriolar profiles and hypoplasia to absence of portal veins. The pathological investigations along with the animal history and clinical signs indicated a hepatic encephalomyelopathy due to a congenital portosystemic shunt.

Multiple acquired portosystemic shunts secondary to primary hypoplasia of the portal vein in a cat.

A 6-year 5-month-old spayed female Scottish Fold cat presented with a one-month history of gait abnormalities, increased salivation, and decreased activity. A blood test showed hyperammonemia and increased serum bile acids. Imaging tests revealed multiple shunt vessels indicating acquired portosystemic shunt. Histopathologic analysis of liver biopsy showed features consistent with liver hypoperfusion, such as a barely recognizable portal vein, increased numbers of small arterioles, and diffuse vacuolar degeneration of hepatocytes. These findings supported the diagnosis of primary hypoplasia of the portal vein/microvascular dysplasia, (PHPV/MVD). To our knowledge, this is the first case of feline PHPV/MVD that developed multiple acquired portosystemic shunts and presented with hepatic encephalopathy.

Congenital portosystemic shunts in five mature dogs with neurological signs.

Congenital portosystemic shunts are a common cause of hepatic encephalopathy and are typically first identified when dogs are <2 years of age. This case series describes five dogs with congenital portosystemic shunts; the dogs were presented for severe encephalopathic signs during middle or old age. Three dogs had portoazygos shunts, and four dogs had multifocal and lateralizing neurological abnormalities, including severe gait abnormalities and vestibular signs. All five dogs responded to medical or surgical treatment, demonstrating that older animals can respond to treatment even after exhibiting severe neurological signs.