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.

Encefalopatía hepática por shunt porto-sistémico congénito: una entidad de presentación variable / No disponible

No disponible

Valoración del tratamiento del shunt portosistémico congénito en el adulto en función de la sintomatología asociada / Appreciation of the treatment in adult patients with congenital portosystemic connections in relation with their symptoms

Introducción: las comunicaciones porto-sistémicas congénitas intrahepáticas (síndrome de Abernethy) son variantes anatómicas muy poco frecuentes, estando clasificadas en función del tipo de unión que exista entre la vena porta y el sistema venoso central. En el adulto, su diagnóstico suele ser incidental, aunque algunos casos puede presentarse con clínica de encefalopatía en pacientes sin hepatopatía asociada. Casos clínicos: presentamos dos casos de shunt porto-sistémico, uno con desarrollo de encefalopatía y otro hallado de forma casual. Su tratamiento, por medio de radiología intervencionista se decidió en función de si presentaban o no sintomatología. Ambos casos (tratado y control) se presentan al control en consultas externas asintomáticos, sin asociar complicaciones derivadas de la decisión terapéutica. Este control se realiza anualmente con pruebas de imagen (ecografía/TAC) y análisis sanguíneo. Discusión: dada la escasa prevalencia de este tipo de malformación y su diagnóstico habitual en edades más tempranas (asociada a importantes alteraciones cognitivas) su tratamiento en adultos no está protocolizado. En estos casos la decisión del tratamiento estaría condicionada a la sintomatología asociada, siendo el tratamiento mínimamente invasivo mediante radiología intervencionista una opción terapéutica a valorar en el adulto sintomático. Por su parte la observación por medio de pruebas de imagen y control en consultas externas, sin tratamiento asociado, seria de elección en adultos en los que no se presenta sintomatología asociada

Background: portosystemic intrahepatic venous connections (Abernethy syndrome) are rare anatomical variants, which are classified according to the type of union between the portal venous circulation and the central venous system. In adults, the diagnosis is often incidental, although some cases can be presented with an encephalopathy without associated liver disease. Case reports: here we present two cases of portosystemic shunt, one with encephalopathy development, and the other casually caught. Its treatment by interventionist radiology, was decided in function of clinic symptoms. Both patients were asymptomatic at controls in the outpatient consultation. No complications derived from the therapeutic decision. The control is carried out annually with image tests and blood analysis. Discussion: given the low prevalence of malformation and its usual diagnosis at younger ages (associated with important cognitive alterations) its treatment in adults is not protocolized. In these cases the decision of the treatment would be conditioned to the associated symptomatology, being the minimally invasive treatment (by interventional radiology) a therapeutic option in the symptomatic adult. Observation by imaging tests and control in outpatient consultation (without associated treatment) would be a choice in asymptomatic adults

Attenuation of congenital portosystemic shunt reduces inflammation in dogs.

Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder.

Congenital portosystemic shunts and hepatic encephalopathy in goat kids in California: 11 cases (1999-2012).

Between 1999 and 2012, 11 cases of congenital portosystemic shunts (cPSS) resulting in hepatic encephalopathy were diagnosed in goat kids necropsied at the California Animal Health and Food Safety Laboratory System and at the Department of Pathology, Immunology & Microbiology, School of Veterinary Medicine, University of California-Davis. Affected animals included 6 females and 5 males of various breeds including Boer (5/11), Nigerian Dwarf (1/11), Saanen (1/11), Toggenburg (1/11), and mixed-breed (3/11) aged between 1.5 months and 11 months, submitted live (2/11) or dead (9/11) for necropsy. The most frequent clinical signs in these goats were ataxia, blindness, tremors, head bobbing, head pressing, seizures, circling, weakness, and ill thrift. Bile acids were measured in 2 animals, and were elevated in both cases (134 and 209 µmol/l, reference interval = 0-50 µmol/l). Necropsy findings were poor to fair body condition. Grossly, the livers of 4 animals were subjectively small. Microscopic lesions included portal spaces with increased numbers of arteriolar profiles and hypoplastic or absent portal veins, diffuse atrophy of the hepatic parenchyma with the presence of small hepatocytes and, in some cases, multifocal hepatocellular macrovesicular vacuolation. In the brain and spinal cord of all animals, there was bilateral and symmetric spongy degeneration affecting the cerebrum, mesencephalon, cerebellum, brainstem, and cervical spinal cord. In all cases, the brain lesions were consistent with hepatic encephalopathy. Congenital portosystemic shunts should be considered in the differential diagnosis of young goats with a history of ill thrift, and nonspecific neurological signs.

Novel c.191C>G (p.Pro64Arg) MPV17 mutation identified in two pairs of unrelated Polish siblings with mitochondrial hepatoencephalopathy.

This study reports clinical, biochemical and histopathological findings associated with a novel homozygous MPV17 mutation in four patients with mitochondrial depletion syndrome. The severe course of the disease, which started in the first weeks of life, was dominated by a failure to thrive, hypotonia and liver dysfunction, with relatively mild neurological involvement. All affected infants died by 1 year of age. Laboratory findings included progressive liver failure (hypertransaminasaemia, icterus, and coagulopathy), recurrent hypoglycaemia, lactic acidaemia, hyperferritinaemia, and increased transferrin saturation. Histological and ultrastructural analyses uncovered significant lipid accumulation in hepatocytes and myocytes. A severe decrease in the mitochondrial/nuclear DNA (mtDNA/nDNA) ratio was found post-mortem in the livers (and in one muscle specimen) of both examined patients. Oxidative phosphorylation system (OXPHOS) Western blotting revealed low levels of complexes I, III and IV subunits. The highlights of our findings are as follows: (i) The novel p.Pro64Arg mutation is the second recurrent MPV17 mutation reported. The phenotype associated with the p.Pro64Arg mutation differs from the phenotype of the relatively common p.Arg50Gln mutation, suggesting the existence of a genotype-phenotype correlation. (ii) Tissues collected from patients during autopsy may be useful for both mtDNA/nDNA ratio assessment and OXPHOS Western blotting.

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.

RE: Endovascular Treatment of Congenital Intrahepatic Portosystemic Shunts with Amplatzer Plugs

No abstract available.

Congenital intrahepatic portosystemic venous shunt and liver mass in a child patient: successful endovascular treatment with an amplatzer vascular plug (AVP).

A congenital intrahepatic portosystemic shunt is a rare anomaly; but, the number of diagnosed cases has increased with advanced imaging tools. Symptomatic portosystemic shunts, especially those that include hyperammonemia, should be treated; and various endovascular treatment methods other than surgery have been reported. Hepatic masses with either an intra- or extrahepatic shunt also have been reported, and the mass is another reason for treatment. Authors report a case of a congenital intrahepatic portosystemic shunt with a hepatic mass that was successfully treated using a percutaneous endovascular approach with vascular plugs. By the time the first short-term follow-up was conducted, the hepatic mass had disappeared.

Congenital Intrahepatic Portosystemic Venous Shunt and Liver Mass in a Child Patient: Successful Endovascular Treatment with an Amplatzer Vascular Plug (AVP)

A congenital intrahepatic portosystemic shunt is a rare anomaly; but, the number of diagnosed cases has increased with advanced imaging tools. Symptomatic portosystemic shunts, especially those that include hyperammonemia, should be treated; and various endovascular treatment methods other than surgery have been reported. Hepatic masses with either an intra- or extrahepatic shunt also have been reported, and the mass is another reason for treatment. Authors report a case of a congenital intrahepatic portosystemic shunt with a hepatic mass that was successfully treated using a percutaneous endovascular approach with vascular plugs. By the time the first short-term follow-up was conducted, the hepatic mass had disappeared.

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.

Simultaneous congenital and acquired extrahepatic portosystemic shunts in two dogs.

Two dogs with simultaneous congenital and acquired portosystemic shunts are reported. The first dog was an eight-month-old, male Golden Retriever with a history of peritoneal effusion, polyuria/polydipsia, and stunted growth. The dog had a microcytic, hypochromic anemia, a mildly elevated AST, and a moderate to severely elevated preprandial and postprandial serum bile acids. Transcolonic portal scintigraphy confirmed the presence of a portosystemic shunt. An intraoperative mesenteric portogram was performed. Two conjoined congenital extrahepatic portosystemic shunts and multiple acquired extrahepatic portosystemic shunts were identified. The second dog was a five-month-old, mixed breed with two week history of peritoneal effusion. Abdominal ultrasound and transcolonic scintigraphy were used to diagnose a portosystemic shunt. A single extrahepatic portosystemic shunt, portal hypertension, and multiple acquired collateral shunts were identified at surgery. The histologic alterations observed in these dogs were consistent with a portosystemic shunt. In these dogs, the presence of congenital and acquired portosystemic shunts and histopathologic findings are considered to represent a combination of congenital portosystemic shunts and noncirrhotic portal hypertension or portal vein hypoplasia.

Selective alterations of cerebrospinal fluid amino acids in dogs with congenital portosystemic shunts.

Numerous studies suggest that modifications in concentrations of both excitatory and inhibitory amino acids are implicated in the pathophysiology of portal-systemic encephalopathy (PSE), a neuropsychiatric disorder associated with chronic liver disease in humans. In this study, amino acid levels were measured by High Performance Liquid Chromatography (HPLC) in Cerebrospinal Fluid (CSF) of 10 dogs (age range: 3 mo.- 3 yr 4 mo.) exhibiting a congenital portal-systemic shunt, either intra or extra-hepatic, and 8 age-matched control dogs who showed no signs of hepatic or neurologic disorders. Dogs with congenital shunts manifested signs of encephalopathy such as disorientation, head pressing, vocalization, depression, seizures and coma. CSF from dogs with congenital shunts contained significantly increased amounts of glutamate (2 to 3-fold increase, p<0.01), glutamine (6-fold increase, p<0.05) and aromatic amino acids (phenylalanine, tyrosine and tryptophan) compared to CSF of control dogs. Concentrations of GABA and branched chain amino acids (valine, leucine, isoleucine) were within normal limits. Modifications of brain glutamate (an excitatory amino acid) as well as tryptophan (the precursor of serotonin) could contribute to the neurological syndrome characteristic of congenital PSE in dogs.

L-glutamate and gamma-aminobutyric acid uptake in synaptosomes from the cerebral cortex of dogs with congenital chronic hepatic encephalopathy.

High affinity [3H]gamma-aminobutyric acid (GABA) and [3H]L-glutamate uptake were determined in synaptosomes prepared from the cerebral cortex of dogs with congenital hepatic encephalopathy and control dogs. The Km value for GABA uptake was increased by 35% but there was a concomitant 34% increase in Vmax suggesting that GABA uptake capacity was not changed in HE dogs. In contrast, mean Vmax for glutamate uptake in HE dogs was 85% greater than mean Vmax in control dogs; mean Km was increased by 25% in HE dogs. Therefore, overall synaptosomal high affinity glutamate uptake capacity was increased in HE dogs compared to controls.

Canine congenital portosystemic encephalopathy.

The case records of 21 dogs with congenital portosystemic encephalopathy are reviewed. The disorder was most common in Australian cattledogs (blue heelers; 8 cases), Old English sheepdogs (3 cases) and Maltese terriers (3 cases). Extra-hepatic shunts occurred in small breeds, with the exception of 1 cattledog, while intra-hepatic shunts occurred in the medium to large breeds. The most common clinical pathology abnormalities were abnormal ammonia tolerance, mild to moderate increases in plasma alanine aminotransferase or alkaline phosphatase concentrations, decreased total serum protein concentrations, increased fasting ammonia concentrations and ammonium biurate crystalluria. Radiological examination revealed that all the dogs had a small liver. The kidneys were enlarged in 5 of 10 dogs in which kidney size could be estimated. Surgical ligation of an extra-hepatic shunt was successful in 2 of 4 dogs in which it was attempted. Medical management resulted in alleviation of clinical signs in 5 of 8 dogs. The period of successful treatment ranged from a few months to over a year.