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J Vet Clin 2024; 41(2): 95-100

https://doi.org/10.17555/jvc.2024.41.2.95

Published online April 30, 2024

Successful Management of Post-Attenuation Neurologic Signs and Portal Hypertension in a Dog with Congenital Portoazygos Shunt

Jin-Young Kim , Kun-Ho Song , Joong-Hyun Song*

Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National University, Daejeon 34143, South Korea

Correspondence to:*jh.song@cnu.ac.kr

Received: January 10, 2024; Revised: February 12, 2024; Accepted: March 9, 2024

Copyright © The Korean Society of Veterinary Clinics.

A 6-year-old neutered male Poodle with a body weight of 2.7 kg was diagnosed with a congenital extrahepatic portoazygos shunt presented with progressive hepatic encephalopathy. Five days after surgical attenuation, the patient showed post-attenuation neurological signs (PANS) such as generalized tonic-clonic seizure, dull mentation, and tremor. PANS were successfully managed with antiepileptic drugs, but third-space fluid accumulation (ascites and peripheral edema) and phlebectasia were newly identified, suggesting marked portal hypertension (PHT). Telmisartan, spironolactone, carvedilol, and prednisolone were sequentially administered. Three months after surgery, both abnormal clinicopathological values such as anemia and hypoalbuminemia, and clinical signs completely resolved. Herein, we report successful management strategies for PANS and PHT in a dog following surgical attenuation of a congenital portoazygos shunt.

Keywords: case report, hepatic encephalopathy, phlebectasia, portosystemic shunt, post-attenuation seizures

Post-attenuation neurological signs (PANS) encompass all neurological symptoms occurring from the time of portosystemic shunt (PSS) attenuation surgery until discharge, typically manifesting within 7 days post-surgery (7). The clinical signs include depression, ataxia, tremors, and seizures. PANS has an incidence rate ranging from 2.6-27.3% (7). Although several hypotheses exist regarding its etiology, such as central nervous system disease, perioperative hypoglycemia, perioperative electrolyte disturbances, perioperative portal hypertension (PHT), and infectious cause, none have been definitively proven (7). Importantly, unlike hepatic encephalopathy (HE), PANS occurs independently of hyperammonemia.

Secondary portal hypertension (PHT) may occur after PSS ligation. Evaluation typically involves monitoring signs of ascites, anemia, hyperammonemia, and portal-vein blood flow velocity using ultrasonography (2,13). Currently, no specific guidelines are available in veterinary medicine for the treatment of PHT in dogs, particularly regarding secondary PHT resulting from PSS attenuation.

In this report, we describe the case in which congenital portoazygos shunt was ligated, leading to the development of PANS and secondary PHT. We specifically focus on combinations of medications that have rarely been reported in veterinary medicine for the treatment of secondary portal hypertension. Furthermore, although the exact mechanisms of PANS remain unclear, we aim to describe the clinical features and disease progression that can result from attenuation of portoazygos shunts, a recognized risk factor.

A 6-year-old neutered male Poodle with a body weight of 2.7 kg presented with chief complaints of lethargy, salivation, vomiting, and mental dullness. The dog had previously been diagnosed with congenital PSS a few years ago at a local animal hospital and treatment for HE had been administered from the diagnosis. However, as time passed, clinical signs such as vomiting, and lethargy progressively worsened and referred to our institution. There were no remarkable findings in the physical examination. Complete blood count (CBC) using a ProCyte Dx Hematology Analyzer (IDEXX Laboratories, Westbrook, ME, USA) revealed low hematocrit (HCT) (34.7%; reference range [RI], 37.3-61.7) and low mean corpuscular volume (47.2 fL; RI, 61.6-73.5). Hyperammonemia (162 umol/L; RI, 0-98) and hypoglycemia (64 mg/dL; RI, 74-143 was identified using a Catalyst Dx Chemistry Analyzer (IDEXX Laboratories). Computed tomography (CT) was performed using a 32-detector-row CT scanner (Alexion; Toshiba Medical Systems, Tokyo, Japan), which confirmed the presence of a 5.0-mm extrahepatic portoazygos shunt and portal-vein hypoplasia with a diameter of 1.7 mm (Fig. 1).

Figure 1.Preoperative 3D reconstruction computed tomography (CT) images of the case dog (B), compared to a normal canine model (A), and postoperative transverse plane CT images showing the porta hepatis level (C, D) and splenic shunt level (E, F). In the patient, compared to a healthy dog, there is significant hypoplasia of the portal vein (highlighted in orange), making its structure nearly indiscernible. The extrahepatic portal vein is in pink, the gastroduodenal vein is in green, and the extrahepatic portoazygos shunt vessel is in white. The CT images on postoperative days 11 (C, E) and 28 (D, F) were compared. The red arrow indicates the shunt vessel, the blue arrow represents the portal vein, and the yellow arrow indicates the caudal vena cava. The shunt vessel diameter decreased from 5.0 mm preoperatively to 3.5 mm postoperatively, while the portal-vein diameter increased from 1.7 mm preoperatively to 3.7 mm postoperatively.

The patient underwent PSS ligation surgery using a 4.4-mm ameroid constrictor. Five days after attenuation, the patient showed generalized tonic-clonic seizures, vomiting, obtunded mentation, tremor, and vocalization, which prompted suspicion of PANS. On postoperative day (POD) 7, CBC revealed a significant decrease in HCT (14.2%) compared to the previous day (23%). Also, hypoalbuminemia (1.5 g/dL; RI, 2.3-4.0), hypoglycemia (48 mg/dL; RI, 74-143 mg/dL), and low creatinine (0.4 mg/dL; RI, 0.5-1.8) were identified. However, postoperative measurements revealed that the ammonia levels were within the reference range (0 umol/L). To resolve hypoglycemia, intravenous fluid therapy containing dextrose was administered. However, tremor, depressed mentation, and vocalization persisted.

Abdominal ultrasonography was performed using an ultrasound device (IU 22; Philips Healthcare, Best, Netherlands). Gastrointestinal hypomotility and ascites were observed. Total protein of ascitic fluid was less than 2 g/dL, and the total nucleated cell count was 280, confirming a pure transudate. A small portal-vein diameter made it challenging to measure the blood flow velocity in the portal vein.

To resolve PANS, treatment with phenobarbital (Jeil Phenobarbital inj; Jeil Pharmaceutical, Seoul, South Korea) (2 mg/kg intravenously every 12 h [q 12 h]), levetiracetam (Keppra inj; UCB Pharma, Brussels, Belgium) (40 mg/kg intravenously q 8 h), and midazolam (Midazolam inj; Bukwang Pharma, Seoul, South Korea) (0.1-0.3 mg/kg/h constant rate infusion [CRI] for 3 days) were initiated, and CRI was discontinued on POD 10. Following the administration of midazolam CRI, no additional seizures were observed from POD 7. However, mental depression, tremors, and vocalization persisted. Therefore, CT and magnetic resonance imaging (MRI) scanning were performed without anesthesia on POD 11 to assess the brain and PHT.

CT revealed portal-vein hypoplasia, and no changes were observed in the diameter of the portal vein and shunt vessel. MRI was performed using a 1.5-T Vantage Elan system (Canon Medical Systems, Otawara, Japan). On the transverse plane of the T2-weighted image at the level of the interthalamic adhesion, extensive bilateral hyperintense lesions were observed (Fig. 2). Furthermore, a decrease in the height of the interthalamic adhesion, along with widened sulci, were observed. Based on these findings, a tentative diagnosis of hepatic encephalopathy with cerebral cortical necrosis and brain atrophy has been made.

Figure 2.Transverse plane magnetic resonance imaging of the interthalamic adhesion level in T2-weighted (A), T1-weighted (B), and fluid-attenuated inversion recovery sequences (C). Bilateral hyperintense lesions were observed in the cerebral cortex (red arrow), indicating overall brain atrophy (A). Widened sulci were also noted (yellow arrow), along with a decrease in the height of interthalamic adhesion (blue arrow), confirming the presence of brain atrophy (A, B, C).

After the administration of aforementioned antiepileptic drugs, the patient’s mental status returned to normal on POD 12 and tetraparesis resolved on POD 15. However peripheral edema and phlebectasia were identified and progressively worsened, indicating further exacerbation of PHT.

On POD 7, HCT decreased from 23 to 14.2 compared to the previous day. No visually suspected skin or urinary bleeding was confirmed, and no hematochezia or melena was observed. However, considering the overall clinical presentation of the patient and the extent of the decrease in HCT, secondary gastropathy due to portal hypertension was primarily considered. To manage portal hypertension-induced gastropathy, blood transfusion, almagate (Almagate suspension; Yuhan, Seoul, South Korea) (3 mL orally q 12 h), esomeprazole (Nexium inj.; AstraZeneca, Cambridge, UK) (1 mg/kg intravenously q 12 h), maropitant (Cerenia; Zoetis KR, Seoul, South Korea) (1 mg/kg intravenously q 24 h), metoclopramide (Meckool inj., Jeil Pharmaceutical) (0.04 mg/kg/h intravenously CRI for 5 days) were administered, and vitamin K1 (Vitamin K1 inj.; Daihan Pharma, Seoul, South Korea) (0.5 mg/kg subcutaneously q 12 h) and cyanocobalamin (Shin Poong Pharmaceutical, Seoul, South Korea) (25 μg/kg subcutaneously every week for 6 weeks) was added for supplementation. The quantity of ascitic fluid progressively increased, and on the POD 22, the dog showed respiratory distress, with an inhalation-to-exhalation ratio of approximately 3:1. To alleviate the respiratory distress, abdominocentesis was performed. To resolve hypoalbuminemia, dietary intake was increased. However, albumin levels remained at 1.5 g/dL with no improvement observed. Consequently, albumin transfusion was administered, but there was no significant improvement. Telmisartan (Ilyang Telmisartan Tab.; Il-Yang Pharmaceutical, Yongin, South Korea) (1 mg/kg orally q 24 h), spironolactone (Spirodactone Tab.; Guju Pharma Co., Seoul, South Korea) (0.5 mg/kg orally q 12 h), and carvedilol (Alvogen Carvedilol Tab.; Alvogen Korea, Seoul, South Korea) (0.3 mg/kg orally q 12 h) were added on postoperative days 12, 21, and 25, respectively (Fig. 3). Since spironolactone works slowly to mobilize fluid, it may take time to show its effects, and to prevent side effects due to overdosing, the dosage was maintained without any increases (2).

Figure 3.Changes in HCT, TS, albumin, and glucose levels at different timepoints after medication administration. HCT, hematocrit; TS, total solid; POD, postoperative day.

On the CT scan performed on POD 28, an increase in the diameter of the portal vein and a decrease in the diameter of the shunt vessel were observed (Fig. 1). However, since ascites and phlebectasia still appeared severe, prednisolone (Solondo Tab. Yuhan Corp., Seoul, Korea) (0.5 mg/kg orally q 12 h) was added on the same day to further prolong the time until the alleviation of PHT, and was discharged (Fig. 3). On POD 43, the patient became even more alert than before the surgery and HCT (38.5%) and TS (6.7 g/dL) levels normalized (Fig. 3). Furthermore, the ascites, edema, and phlebectasia resolved on the same day. However, left-sided head tilt and ventrolateral positional strabismus of the left eye persisted. On POD 70, the albumin level was within the reference range (2.3 g/dL) (Fig. 3). Three months after surgery, CT did not reveal any evidence of acquired PSS, indicating successful management.

In veterinary medicine, several risk factors for PANS have been reported in dogs, including increasing age, HE immediately before surgery, extrahepatic PSS morphology, and breed (7). In this case, the patient underwent PSS attenuation surgery at the age of 6. Considering that the dog presented clinical signs such as lethargy, hypersalivation, and vomiting a few years before the presentation, the prolonged presence of HE before surgery may have precipitated the development of PANS. In addition, the presence of a portoazyos shunt can serve as a risk factor for PANS, possibly because of its diagnosis at a later stage of life (7). These findings highlight the importance of identifying these factors in future studies.

In veterinary medicine, PHT is often indirectly assessed using ultrasonography (2). However, in cases such as this, where the portal vein is difficult to detect because of pre-existing hypoplasia, it may not be effective. In such cases, gastrointestinal hypomotility, gastropathy, protein-losing enteropathy (PLE), peripheral edema, ascites, or phlebectasia can be used to infer the possibility of PHT (2).

In the presence of PHT, there is general constriction of the blood vessels within the liver, while the splanchnic vasculature undergoes progressive vasodilation (7). Increased hydrostatic pressure in the portal vasculature leads to ascites, peripheral edema, and PLE. Furthermore, dogs with pre-existing hepatic disease are at an increased risk of gastrointestinal ulceration, which may be attributed to thrombosis of the mesenteric veins and alterations in gastrointestinal motility (4,11).

Currently, there are no well-established guidelines for the treatment of PHT in veterinary medicine. In this case, we successfully employed telmisartan, carvedilol and prednisolone that have not been widely reported for the management of secondary PHT.

First, telmisartan is a medication widely used in veterinary medicine for the treatment of systemic hypertension or proteinuria. Telmisartan but also effectively alleviates liver fibrosis and PHT while providing neuroprotection and may prevent the progression of chronic kidney disease (5,15). Secondly, in human medicine, the use of non-selective beta-blockers is often considered for PHT (2). However, propranolol was ineffective in some dogs (6,14). Carvedilol is 2-3 times more potent than propranolol and acts not only as a non-selective beta-blocker but also as an alpha-1 blocker, providing the additional benefit of reducing intrahepatic resistance (1,12). Third, in cases where other medications demonstrate limited efficacy, prednisolone has been reported as an effective treatment for PHT in humans (11). However, glucocorticoids can induce hypercoagulability in clinical settings (9). Therefore, the vigilant monitoring of coagulation systems is crucial. Other methods to treat PHT include abdominocentesis and albumin transfusion. Blood transfusion, almagate, esomeprazole, and maropitant should be considered for the treatment of portal hypertensive gastropathy. Moreover, the administration of metoclopramide, vitamin K1, and cyanocobalamin to compensate for the impaired liver and gastrointestinal function has been regarded as a successful therapeutic strategy in this dog.

The MRI findings in this patient such as brain atrophy, ventriculomegaly, widened sulci, and cerebrocortical necrosis were consistent with the characteristics observed in dogs with HE caused by PSS (10). In humans, significant HE can lead to irreversible cell damage, directly affecting astrocytes and neurons (8). Furthermore, in human patients with overt HE, damage to brain connectivity has been observed (8). The severity of such cellular damage is associated with profound cognitive impairment that may persist permanently (8). In the present case, the left-sided head tilt and ventrolateral positional strabismus persisted, indicating permanent brain damage. Therefore, in cases where portal-vein hypoplasia is present and PSS is diagnosed at a later age, continuous monitoring of various neurological clinical manifestations such as seizures is required.

Absence of a liver biopsy during the PSS ligation surgery may be considered a limitation of this case report. To assess potential precipitating factors for PHT, such as microvascular dysplasia, in addition to the suspected primary hypoplasia of the portal vein and congenital PSS ligation, liver biopsy would be required. Furthermore, observed improvement after administration of anti-inflammatory dose of prednisolone does not definitively rule out the possibility of glucocorticoid-responsive hepatopathy. However, considering the patient’s history and the diagnostic imaging results, this possibility is considered low. Another limitation could be the absence of endoscopy and biopsy results to confirm the cause of hypoalbuminemia such as lymphangiectasia. However, considering the overall condition of the patient, additional anesthesia would not be suitable. Furthermore, given the concurrent presence of panhypoproteinemia and hypocholesterolemia, PLE was strongly suspected as the main cause of hypoalbuminemia, indirectly indicating the presence of secondary portal hypertension.

It is important to recognize the risk factors of PANS and consider them before surgery. If gastrointestinal hypomotility, anemia, PLE, peripheral edema, ascites, and phlebectasia are observed after ligation of congenital extrahepatic PSS, PHT should be suspected. In such cases, telmisartan, carvedilol, and prednisolone may be considered as therapeutic options. Additionally, in situations in which chronic HE persists, continuous monitoring of neurological symptoms is necessary even after PSS attenuation.

Conceptualization: Kim JY; Data curation: Song KH, Song JH; Writing - original draft: Kim JY; Writing - review & editing: Song KH, Song JH.

This study was supported by the National Research Foundation of Korea and funded by a grant from the Korean Government (NRF-2022R1G1A10036821131482092640101), and the Basic Science Research Program through the NRF, funded by the Ministry of Education (RS-2023-0021971031482092640001).

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Article

Case Report

J Vet Clin 2024; 41(2): 95-100

Published online April 30, 2024 https://doi.org/10.17555/jvc.2024.41.2.95

Copyright © The Korean Society of Veterinary Clinics.

Successful Management of Post-Attenuation Neurologic Signs and Portal Hypertension in a Dog with Congenital Portoazygos Shunt

Jin-Young Kim , Kun-Ho Song , Joong-Hyun Song*

Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National University, Daejeon 34143, South Korea

Correspondence to:*jh.song@cnu.ac.kr

Received: January 10, 2024; Revised: February 12, 2024; Accepted: March 9, 2024

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A 6-year-old neutered male Poodle with a body weight of 2.7 kg was diagnosed with a congenital extrahepatic portoazygos shunt presented with progressive hepatic encephalopathy. Five days after surgical attenuation, the patient showed post-attenuation neurological signs (PANS) such as generalized tonic-clonic seizure, dull mentation, and tremor. PANS were successfully managed with antiepileptic drugs, but third-space fluid accumulation (ascites and peripheral edema) and phlebectasia were newly identified, suggesting marked portal hypertension (PHT). Telmisartan, spironolactone, carvedilol, and prednisolone were sequentially administered. Three months after surgery, both abnormal clinicopathological values such as anemia and hypoalbuminemia, and clinical signs completely resolved. Herein, we report successful management strategies for PANS and PHT in a dog following surgical attenuation of a congenital portoazygos shunt.

Keywords: case report, hepatic encephalopathy, phlebectasia, portosystemic shunt, post-attenuation seizures

Introduction

Post-attenuation neurological signs (PANS) encompass all neurological symptoms occurring from the time of portosystemic shunt (PSS) attenuation surgery until discharge, typically manifesting within 7 days post-surgery (7). The clinical signs include depression, ataxia, tremors, and seizures. PANS has an incidence rate ranging from 2.6-27.3% (7). Although several hypotheses exist regarding its etiology, such as central nervous system disease, perioperative hypoglycemia, perioperative electrolyte disturbances, perioperative portal hypertension (PHT), and infectious cause, none have been definitively proven (7). Importantly, unlike hepatic encephalopathy (HE), PANS occurs independently of hyperammonemia.

Secondary portal hypertension (PHT) may occur after PSS ligation. Evaluation typically involves monitoring signs of ascites, anemia, hyperammonemia, and portal-vein blood flow velocity using ultrasonography (2,13). Currently, no specific guidelines are available in veterinary medicine for the treatment of PHT in dogs, particularly regarding secondary PHT resulting from PSS attenuation.

In this report, we describe the case in which congenital portoazygos shunt was ligated, leading to the development of PANS and secondary PHT. We specifically focus on combinations of medications that have rarely been reported in veterinary medicine for the treatment of secondary portal hypertension. Furthermore, although the exact mechanisms of PANS remain unclear, we aim to describe the clinical features and disease progression that can result from attenuation of portoazygos shunts, a recognized risk factor.

Case Report

A 6-year-old neutered male Poodle with a body weight of 2.7 kg presented with chief complaints of lethargy, salivation, vomiting, and mental dullness. The dog had previously been diagnosed with congenital PSS a few years ago at a local animal hospital and treatment for HE had been administered from the diagnosis. However, as time passed, clinical signs such as vomiting, and lethargy progressively worsened and referred to our institution. There were no remarkable findings in the physical examination. Complete blood count (CBC) using a ProCyte Dx Hematology Analyzer (IDEXX Laboratories, Westbrook, ME, USA) revealed low hematocrit (HCT) (34.7%; reference range [RI], 37.3-61.7) and low mean corpuscular volume (47.2 fL; RI, 61.6-73.5). Hyperammonemia (162 umol/L; RI, 0-98) and hypoglycemia (64 mg/dL; RI, 74-143 was identified using a Catalyst Dx Chemistry Analyzer (IDEXX Laboratories). Computed tomography (CT) was performed using a 32-detector-row CT scanner (Alexion; Toshiba Medical Systems, Tokyo, Japan), which confirmed the presence of a 5.0-mm extrahepatic portoazygos shunt and portal-vein hypoplasia with a diameter of 1.7 mm (Fig. 1).

Figure 1. Preoperative 3D reconstruction computed tomography (CT) images of the case dog (B), compared to a normal canine model (A), and postoperative transverse plane CT images showing the porta hepatis level (C, D) and splenic shunt level (E, F). In the patient, compared to a healthy dog, there is significant hypoplasia of the portal vein (highlighted in orange), making its structure nearly indiscernible. The extrahepatic portal vein is in pink, the gastroduodenal vein is in green, and the extrahepatic portoazygos shunt vessel is in white. The CT images on postoperative days 11 (C, E) and 28 (D, F) were compared. The red arrow indicates the shunt vessel, the blue arrow represents the portal vein, and the yellow arrow indicates the caudal vena cava. The shunt vessel diameter decreased from 5.0 mm preoperatively to 3.5 mm postoperatively, while the portal-vein diameter increased from 1.7 mm preoperatively to 3.7 mm postoperatively.

The patient underwent PSS ligation surgery using a 4.4-mm ameroid constrictor. Five days after attenuation, the patient showed generalized tonic-clonic seizures, vomiting, obtunded mentation, tremor, and vocalization, which prompted suspicion of PANS. On postoperative day (POD) 7, CBC revealed a significant decrease in HCT (14.2%) compared to the previous day (23%). Also, hypoalbuminemia (1.5 g/dL; RI, 2.3-4.0), hypoglycemia (48 mg/dL; RI, 74-143 mg/dL), and low creatinine (0.4 mg/dL; RI, 0.5-1.8) were identified. However, postoperative measurements revealed that the ammonia levels were within the reference range (0 umol/L). To resolve hypoglycemia, intravenous fluid therapy containing dextrose was administered. However, tremor, depressed mentation, and vocalization persisted.

Abdominal ultrasonography was performed using an ultrasound device (IU 22; Philips Healthcare, Best, Netherlands). Gastrointestinal hypomotility and ascites were observed. Total protein of ascitic fluid was less than 2 g/dL, and the total nucleated cell count was 280, confirming a pure transudate. A small portal-vein diameter made it challenging to measure the blood flow velocity in the portal vein.

To resolve PANS, treatment with phenobarbital (Jeil Phenobarbital inj; Jeil Pharmaceutical, Seoul, South Korea) (2 mg/kg intravenously every 12 h [q 12 h]), levetiracetam (Keppra inj; UCB Pharma, Brussels, Belgium) (40 mg/kg intravenously q 8 h), and midazolam (Midazolam inj; Bukwang Pharma, Seoul, South Korea) (0.1-0.3 mg/kg/h constant rate infusion [CRI] for 3 days) were initiated, and CRI was discontinued on POD 10. Following the administration of midazolam CRI, no additional seizures were observed from POD 7. However, mental depression, tremors, and vocalization persisted. Therefore, CT and magnetic resonance imaging (MRI) scanning were performed without anesthesia on POD 11 to assess the brain and PHT.

CT revealed portal-vein hypoplasia, and no changes were observed in the diameter of the portal vein and shunt vessel. MRI was performed using a 1.5-T Vantage Elan system (Canon Medical Systems, Otawara, Japan). On the transverse plane of the T2-weighted image at the level of the interthalamic adhesion, extensive bilateral hyperintense lesions were observed (Fig. 2). Furthermore, a decrease in the height of the interthalamic adhesion, along with widened sulci, were observed. Based on these findings, a tentative diagnosis of hepatic encephalopathy with cerebral cortical necrosis and brain atrophy has been made.

Figure 2. Transverse plane magnetic resonance imaging of the interthalamic adhesion level in T2-weighted (A), T1-weighted (B), and fluid-attenuated inversion recovery sequences (C). Bilateral hyperintense lesions were observed in the cerebral cortex (red arrow), indicating overall brain atrophy (A). Widened sulci were also noted (yellow arrow), along with a decrease in the height of interthalamic adhesion (blue arrow), confirming the presence of brain atrophy (A, B, C).

After the administration of aforementioned antiepileptic drugs, the patient’s mental status returned to normal on POD 12 and tetraparesis resolved on POD 15. However peripheral edema and phlebectasia were identified and progressively worsened, indicating further exacerbation of PHT.

On POD 7, HCT decreased from 23 to 14.2 compared to the previous day. No visually suspected skin or urinary bleeding was confirmed, and no hematochezia or melena was observed. However, considering the overall clinical presentation of the patient and the extent of the decrease in HCT, secondary gastropathy due to portal hypertension was primarily considered. To manage portal hypertension-induced gastropathy, blood transfusion, almagate (Almagate suspension; Yuhan, Seoul, South Korea) (3 mL orally q 12 h), esomeprazole (Nexium inj.; AstraZeneca, Cambridge, UK) (1 mg/kg intravenously q 12 h), maropitant (Cerenia; Zoetis KR, Seoul, South Korea) (1 mg/kg intravenously q 24 h), metoclopramide (Meckool inj., Jeil Pharmaceutical) (0.04 mg/kg/h intravenously CRI for 5 days) were administered, and vitamin K1 (Vitamin K1 inj.; Daihan Pharma, Seoul, South Korea) (0.5 mg/kg subcutaneously q 12 h) and cyanocobalamin (Shin Poong Pharmaceutical, Seoul, South Korea) (25 μg/kg subcutaneously every week for 6 weeks) was added for supplementation. The quantity of ascitic fluid progressively increased, and on the POD 22, the dog showed respiratory distress, with an inhalation-to-exhalation ratio of approximately 3:1. To alleviate the respiratory distress, abdominocentesis was performed. To resolve hypoalbuminemia, dietary intake was increased. However, albumin levels remained at 1.5 g/dL with no improvement observed. Consequently, albumin transfusion was administered, but there was no significant improvement. Telmisartan (Ilyang Telmisartan Tab.; Il-Yang Pharmaceutical, Yongin, South Korea) (1 mg/kg orally q 24 h), spironolactone (Spirodactone Tab.; Guju Pharma Co., Seoul, South Korea) (0.5 mg/kg orally q 12 h), and carvedilol (Alvogen Carvedilol Tab.; Alvogen Korea, Seoul, South Korea) (0.3 mg/kg orally q 12 h) were added on postoperative days 12, 21, and 25, respectively (Fig. 3). Since spironolactone works slowly to mobilize fluid, it may take time to show its effects, and to prevent side effects due to overdosing, the dosage was maintained without any increases (2).

Figure 3. Changes in HCT, TS, albumin, and glucose levels at different timepoints after medication administration. HCT, hematocrit; TS, total solid; POD, postoperative day.

On the CT scan performed on POD 28, an increase in the diameter of the portal vein and a decrease in the diameter of the shunt vessel were observed (Fig. 1). However, since ascites and phlebectasia still appeared severe, prednisolone (Solondo Tab. Yuhan Corp., Seoul, Korea) (0.5 mg/kg orally q 12 h) was added on the same day to further prolong the time until the alleviation of PHT, and was discharged (Fig. 3). On POD 43, the patient became even more alert than before the surgery and HCT (38.5%) and TS (6.7 g/dL) levels normalized (Fig. 3). Furthermore, the ascites, edema, and phlebectasia resolved on the same day. However, left-sided head tilt and ventrolateral positional strabismus of the left eye persisted. On POD 70, the albumin level was within the reference range (2.3 g/dL) (Fig. 3). Three months after surgery, CT did not reveal any evidence of acquired PSS, indicating successful management.

Discussion

In veterinary medicine, several risk factors for PANS have been reported in dogs, including increasing age, HE immediately before surgery, extrahepatic PSS morphology, and breed (7). In this case, the patient underwent PSS attenuation surgery at the age of 6. Considering that the dog presented clinical signs such as lethargy, hypersalivation, and vomiting a few years before the presentation, the prolonged presence of HE before surgery may have precipitated the development of PANS. In addition, the presence of a portoazyos shunt can serve as a risk factor for PANS, possibly because of its diagnosis at a later stage of life (7). These findings highlight the importance of identifying these factors in future studies.

In veterinary medicine, PHT is often indirectly assessed using ultrasonography (2). However, in cases such as this, where the portal vein is difficult to detect because of pre-existing hypoplasia, it may not be effective. In such cases, gastrointestinal hypomotility, gastropathy, protein-losing enteropathy (PLE), peripheral edema, ascites, or phlebectasia can be used to infer the possibility of PHT (2).

In the presence of PHT, there is general constriction of the blood vessels within the liver, while the splanchnic vasculature undergoes progressive vasodilation (7). Increased hydrostatic pressure in the portal vasculature leads to ascites, peripheral edema, and PLE. Furthermore, dogs with pre-existing hepatic disease are at an increased risk of gastrointestinal ulceration, which may be attributed to thrombosis of the mesenteric veins and alterations in gastrointestinal motility (4,11).

Currently, there are no well-established guidelines for the treatment of PHT in veterinary medicine. In this case, we successfully employed telmisartan, carvedilol and prednisolone that have not been widely reported for the management of secondary PHT.

First, telmisartan is a medication widely used in veterinary medicine for the treatment of systemic hypertension or proteinuria. Telmisartan but also effectively alleviates liver fibrosis and PHT while providing neuroprotection and may prevent the progression of chronic kidney disease (5,15). Secondly, in human medicine, the use of non-selective beta-blockers is often considered for PHT (2). However, propranolol was ineffective in some dogs (6,14). Carvedilol is 2-3 times more potent than propranolol and acts not only as a non-selective beta-blocker but also as an alpha-1 blocker, providing the additional benefit of reducing intrahepatic resistance (1,12). Third, in cases where other medications demonstrate limited efficacy, prednisolone has been reported as an effective treatment for PHT in humans (11). However, glucocorticoids can induce hypercoagulability in clinical settings (9). Therefore, the vigilant monitoring of coagulation systems is crucial. Other methods to treat PHT include abdominocentesis and albumin transfusion. Blood transfusion, almagate, esomeprazole, and maropitant should be considered for the treatment of portal hypertensive gastropathy. Moreover, the administration of metoclopramide, vitamin K1, and cyanocobalamin to compensate for the impaired liver and gastrointestinal function has been regarded as a successful therapeutic strategy in this dog.

The MRI findings in this patient such as brain atrophy, ventriculomegaly, widened sulci, and cerebrocortical necrosis were consistent with the characteristics observed in dogs with HE caused by PSS (10). In humans, significant HE can lead to irreversible cell damage, directly affecting astrocytes and neurons (8). Furthermore, in human patients with overt HE, damage to brain connectivity has been observed (8). The severity of such cellular damage is associated with profound cognitive impairment that may persist permanently (8). In the present case, the left-sided head tilt and ventrolateral positional strabismus persisted, indicating permanent brain damage. Therefore, in cases where portal-vein hypoplasia is present and PSS is diagnosed at a later age, continuous monitoring of various neurological clinical manifestations such as seizures is required.

Absence of a liver biopsy during the PSS ligation surgery may be considered a limitation of this case report. To assess potential precipitating factors for PHT, such as microvascular dysplasia, in addition to the suspected primary hypoplasia of the portal vein and congenital PSS ligation, liver biopsy would be required. Furthermore, observed improvement after administration of anti-inflammatory dose of prednisolone does not definitively rule out the possibility of glucocorticoid-responsive hepatopathy. However, considering the patient’s history and the diagnostic imaging results, this possibility is considered low. Another limitation could be the absence of endoscopy and biopsy results to confirm the cause of hypoalbuminemia such as lymphangiectasia. However, considering the overall condition of the patient, additional anesthesia would not be suitable. Furthermore, given the concurrent presence of panhypoproteinemia and hypocholesterolemia, PLE was strongly suspected as the main cause of hypoalbuminemia, indirectly indicating the presence of secondary portal hypertension.

Conclusions

It is important to recognize the risk factors of PANS and consider them before surgery. If gastrointestinal hypomotility, anemia, PLE, peripheral edema, ascites, and phlebectasia are observed after ligation of congenital extrahepatic PSS, PHT should be suspected. In such cases, telmisartan, carvedilol, and prednisolone may be considered as therapeutic options. Additionally, in situations in which chronic HE persists, continuous monitoring of neurological symptoms is necessary even after PSS attenuation.

Author Contributions

Conceptualization: Kim JY; Data curation: Song KH, Song JH; Writing - original draft: Kim JY; Writing - review & editing: Song KH, Song JH.

Source of Funding

This study was supported by the National Research Foundation of Korea and funded by a grant from the Korean Government (NRF-2022R1G1A10036821131482092640101), and the Basic Science Research Program through the NRF, funded by the Ministry of Education (RS-2023-0021971031482092640001).

Conflicts of Interest

The authors have no conflicting interests.

Fig 1.

Figure 1.Preoperative 3D reconstruction computed tomography (CT) images of the case dog (B), compared to a normal canine model (A), and postoperative transverse plane CT images showing the porta hepatis level (C, D) and splenic shunt level (E, F). In the patient, compared to a healthy dog, there is significant hypoplasia of the portal vein (highlighted in orange), making its structure nearly indiscernible. The extrahepatic portal vein is in pink, the gastroduodenal vein is in green, and the extrahepatic portoazygos shunt vessel is in white. The CT images on postoperative days 11 (C, E) and 28 (D, F) were compared. The red arrow indicates the shunt vessel, the blue arrow represents the portal vein, and the yellow arrow indicates the caudal vena cava. The shunt vessel diameter decreased from 5.0 mm preoperatively to 3.5 mm postoperatively, while the portal-vein diameter increased from 1.7 mm preoperatively to 3.7 mm postoperatively.
Journal of Veterinary Clinics 2024; 41: 95-100https://doi.org/10.17555/jvc.2024.41.2.95

Fig 2.

Figure 2.Transverse plane magnetic resonance imaging of the interthalamic adhesion level in T2-weighted (A), T1-weighted (B), and fluid-attenuated inversion recovery sequences (C). Bilateral hyperintense lesions were observed in the cerebral cortex (red arrow), indicating overall brain atrophy (A). Widened sulci were also noted (yellow arrow), along with a decrease in the height of interthalamic adhesion (blue arrow), confirming the presence of brain atrophy (A, B, C).
Journal of Veterinary Clinics 2024; 41: 95-100https://doi.org/10.17555/jvc.2024.41.2.95

Fig 3.

Figure 3.Changes in HCT, TS, albumin, and glucose levels at different timepoints after medication administration. HCT, hematocrit; TS, total solid; POD, postoperative day.
Journal of Veterinary Clinics 2024; 41: 95-100https://doi.org/10.17555/jvc.2024.41.2.95

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Vol.41 No.2 April 2024

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