Postattenuation neurologic signs after surgical attenuation of congenital portosystemic shunts in dogs:A review

The development of postattenuation neurologic signs (PANS) is a poorly understood and potentially devastating complication after surgical attenuation of congenital portosystemic shunts in dogs. Postattenuation neurologic signs include seizures but also more subtle neurologic signs such as depression, behavioral changes, tremors, and twitching. They most commonly occur within 7 days postoperatively and are typically unrelated to hyperammonemia, hypoglycemia, or electrolyte disturbances. This narrative review summarizes the findings of 50 publications from 1988-2020 that report occurrence of PANS. While most published reports included only dogs affected by postattenuation seizures (PAS), others included dogs with any form of PANS. Overall, PANS (including PAS) affected 1.6%-27.3% of dogs, whereas incidence of PAS ranged from 0%-18.2%. The etiology of PANS remains unknown; however, several theories have been proposed. Risk factors include preoperative hepatic encephalopathy, increasing age, and possibly certain breeds and extrahepatic shunt morphology. There is increasing evidence that prophylactic antiepileptic drugs do not prevent PANS. Treatment is centered around controlling neurologic signs with antiepileptic drugs and providing supportive intensive care. The 30-day survival rate in studies that included a minimum of four dogs affected by PANS was 0%-100% (median, 50.0%) and 0%-75.0% (median, 37.5%) for those with PAS. Mortality associated with PANS was typically related to occurrence of generalized seizure activity. Prognostic factors positively associated with short-term survival included having a history of preoperative seizures and development of focal seizures only. If affected dogs survived to discharge, survival for several years was possible, and the majority of neurologic signs manifested as part of the phenomenon of PANS appeared to resolve

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

Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells.

C-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcation, as well as learning and memory. Several neurological disorders result in toxic concentrations of ammonia (hyperammonaemia), which can adversely affect astrocyte function. However, the relationship between CNP and hyperammonaemia is poorly understood. Here, we examine the molecular and pharmacological control of CNP in rat C6 glioma cells and rat GPNT brain endothelial cells, under conditions of hyperammonaemia. Concentration-dependent inhibition of C6 glioma cell proliferation by hyperammonaemia was unaffected by CNP co-treatment. Furthermore, hyperammonaemia pre-treatment (for 1 h and 24 h) caused a significant inhibition in subsequent CNP-stimulated cGMP accumulation in both C6 and GPNT cells, whereas nitric-oxide-dependent cGMP accumulation was not affected. CNP-stimulated cGMP efflux from C6 glioma cells was significantly reduced under conditions of hyperammonaemia, potentially via a mechanism involving changed in phosphodiesterase expression. Hyperammonaemia-stimulated ROS production was unaffected by CNP but enhanced by a nitric oxide donor in C6 cells. Extracellular vesicle production from C6 cells was enhanced by hyperammonaemia, and these vesicles caused impaired CNP-stimulated cGMP signalling in GPNT cells. Collectively, these data demonstrate functional interaction between CNP signalling and hyperammonaemia in C6 glioma and GPNT cells, but the exact mechanisms remain to be established

Prognostic factors for short‐term survival of dogs that experience postattenuation seizures after surgical correction of single congenital extrahepatic portosystemic shunts: 93 cases (2005‐2018)

© 2020 The American College of Veterinary Surgeons Objective: To identify prognostic factors for short-term survival of dogs that experience seizures within 7 days after surgical correction of single congenital extrahepatic portosystemic shunts (cEHPSS). Study design: Multi-institutional retrospective study. Sample population: Ninety-three client-owned dogs. Methods: Medical records at 14 veterinary institutions were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 1, 2005 through February 28, 2018 and experienced postattenuation seizures (PAS) within 7 days postoperatively. Logistic regression analysis was performed to identify factors associated with 1-month survival. Factors investigated included participating institution, signalment, shunt morphology, concurrent/historical conditions, presence of preoperative neurologic signs, presence of preoperative seizures, aspects of preoperative medical management, surgical details including method and degree of shunt attenuation, type of PAS (focal only or generalized ± focal), drugs administered as part of the treatment of PAS, and development of complications during treatment of PAS. Results: Thirty (32.3%) dogs survived to 30 days. Seventy-six (81.7%) dogs experienced generalized PAS. Factors positively associated with short-term survival included having a history of preoperative seizures (P =.004) and development of focal PAS only (P =.0003). Most nonsurvivors were humanely euthanized because of uncontrolled or recurrent seizures. Conclusion: Dogs that experienced PAS that had a history of preoperative seizures and those that experienced focal PAS only had significantly improved short-term survival. Clinical significance: The results of this study provide information that will help in the counseling of owners who seek treatment for PAS after surgical correction of cEHPSS. © 2020 The American College of Veterinary Surgeons

Incidence and risk factors for neurological signs after attenuation of a single congenital portosystemic shunt in 50 cats.

OBJECTIVE To determine the incidence, outcome, and risk factors for postattenuation neurological signs (PANS) in cats treated for single congenital portosystemic shunts (CPSS). STUDY DESIGN Retrospective cohort study. ANIMALS Cats (n = 50) with a single CPSS. METHODS Medical records of cats treated by surgical attenuation of a single CPSS between 2003 and 2017 were reviewed for signalment, surgical technique, preoperative management and postoperative clinical outcomes. Binary logistic regression was performed to investigate risk factors for occurrence of PANS and seizures. RESULTS Congenital portosystemic shunts in 50 cats included 40 extrahepatic and 10 intrahepatic shunts. Postattenuation neurological signs were recorded in 31 (62%) cats and graded as 1 in 10 cats, 2 in nine cats, and 3 in 12 cats. Postattenuation neurological signs included seizures in 11 cats. Five of 31 cats with PANS did not survive to discharge. No association was detected between PANS or seizures and the type of CPSS (intrahepatic or extrahepatic), degree of attenuation, age, or the use of perioperative levetiracetam or hepatic encephalopathy immediately preoperatively. Osmolality at a median 24 hours postoperatively was lower in cats with PANS (P < .049, Wald 3.867, odds ratio [Exp(B)] 0.855, CI 0.732-0.999). CONCLUSION Postattenuation neurological signs are common complications in cats treated for CPSS. Preoperative levetiracetam did not prevent the occurrence of PANS or seizures. The only risk factor for PANS detected was lower postoperative Osmolality in cats with PANS at 24 hours. CLINICAL SIGNIFICANCE Postattenuation neurological signs including seizures occur frequently in cats undergoing surgical attenuation of a CPSS. Preoperative levetiracetam did not protect against the development of PANS

A retrospective analysis of urethral rupture in 63 cats

The aim of this study was to investigate the short- and long-term morbidity and mortality associated with urethral rupture in cats. Medical records were reviewed from four veterinary hospitals. Diagnosis was made from retrograde urethrography or direct visualisation during surgery. Location of rupture was categorised as pre-, intra- or post-pelvic. Follow-up data were collected from referring veterinarians. Sixty-three cats were included in the study of which, males predominated (88.9%). Trauma was the most common cause (n = 35; 55.6%) with the remainder due to iatrogenic injury. Forty-eight cats (88.9%) were treated surgically and six (11.1%) managed conservatively. Significant differences between cats suffering traumatic versus iatrogenic injury included the presence of musculoskeletal injuries (P &lt;0.001); the location of rupture (P &lt;0.001); the degree of rupture (P &lt;0.001); definitive management (P &lt;0.001) and short-term complications (P = 0.026). Short-term complications were significantly associated with the following: musculoskeletal injuries (P = 0.012); uroabdomen/uroretroperitoneum (P = 0.004); azotaemia (P = 0.021); postoperative urinary diversion (P = 0.036) and &gt;1 surgery performed (P = 0.006). Forty-seven cats (74.6%) survived to discharge. Prognostic factors associated with survival to discharge included the presence of musculoskeletal injuries (P = 0.017); cause of rupture (P = 0.017); location of rupture (P = 0.039) and definitive management (P = 0.020). Twenty-four cats (57.1%) suffered short-term complications and 10 (27.0%) suffered long-term complications. Of those cats surviving to discharge 30 (71.4%) had a good outcome. Median follow-up was 16 months. Outcome was significantly associated with cause of rupture (P = 0.04); short-term complications (P = 0.03) and long-term complications (P &lt;0.001). In conclusion, a significantly greater proportion of cats with iatrogenic injuries survived to discharge and had a good outcome compared with those that suffered trauma

Percentage of dogs affected by BOAS by craniofacial ratio (CFR) category (a-d).

<p>Graphs (a) and (c) represent all dogs in populations 1 (n = 700) and 2 (n = 154), respectively. Graphs (b) and (d) only represent dogs of breeds and their crosses that were affected by BOAS in population 1 (n = 174) and 2 (n = 141), respectively. The breed-restricted population demonstrates the effects of conformation whilst keeping the genetic and environmental background as uniform as possible. The marked risk of CFRs <0.20 is clearly demonstrated in both studies, with >50% of dogs affected.</p

(a) (b) Predicted probability of brachycephalic dog breeds being affected by brachycephalic obstructive airway syndrome (BOAS) across relevant craniofacial ratio (CFR) and neck girth ranges.

<p>The risks across the CFR spectrum are calculated by breed using GLMM equations based on (a) Study 1 referral population data and (b) Study 2 non-referral population data. For each breed, the estimates are only plotted within the CFR ranges observed in the study populations. Dotted lines show breeds represented by <10 individuals. The breed mean neck girth is used for each breed (as stated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137496#pone.0137496.t002" target="_blank">Table 2</a>). In (b), the body condition score (BCS) = 5 (ideal bodyweight) and neuter status = neutered.</p

Synopsis of breeds affected by brachycephalic obstructive airway syndrome (BOAS), morphometric risk factors and modelled BOAS probabilities.

<p>Synopsis of breeds affected by brachycephalic obstructive airway syndrome (BOAS), morphometric risk factors and modelled BOAS probabilities.</p