Blood-brain barrier dysfunction and decreased transcription of tight junction proteins in epileptic dogs.

BACKGROUND: Epilepsy in dogs and humans is associated with blood-brain barrier (BBB) dysfunction (BBBD), which may involve dysfunction of tight junction (TJ) proteins, matrix metalloproteases, and astrocytes. Imaging techniques to assess BBB integrity, to identify potential treatment strategies, have not yet been evaluated in veterinary medicine. HYPOTHESIS: Some dogs with idiopathic epilepsy (IE) will exhibit BBBD. Identifying BBBD may improve antiepileptic treatment in the future. ANIMALS: Twenty-seven dogs with IE and 10 healthy controls. METHODS: Retrospective, prospective cohort study. Blood-brain barrier permeability (BBBP) scores were calculated for the whole brain and piriform lobe of all dogs by using dynamic contrast enhancement (DCE) magnetic resonance imaging (MRI) and subtraction enhancement analysis (SEA). Matrix metalloproteinase-9 (MMP9) activity in serum and cerebrospinal fluid (CSF) was measured and its expression in the piriform lobe was examined using immunofluorescent staining. Gene expression of TJ proteins and astrocytic transporters was analyzed in the piriform lobe. RESULTS: The DCE-MRI analysis of the piriform lobe identified higher BBBP score in the IE group when compared with controls (34.5% vs 26.5%; P = .02). Activity and expression of MMP9 were increased in the serum, CSF, and piriform lobe of IE dogs as compared with controls. Gene expression of Kir4.1 and claudin-5 in the piriform lobe of IE dogs was significantly lower than in control dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Our findings demonstrate BBBD in dogs with IE and were supported by increased MMP9 activity and downregulation of astrocytic potassium channels and some TJ proteins. Blood brain barrier dysfunction may be a novel antiepileptic therapy target.

Quantitative analysis of magnetic resonance images for characterization of blood-brain barrier dysfunction in dogs with brain tumors.

BACKGROUND: Blood-brain barrier (BBB) permeability can be assessed quantitatively using advanced imaging analysis. HYPOTHESIS/OBJECTIVES: Quantification and characterization of blood-brain barrier dysfunction (BBBD) patterns in dogs with brain tumors can provide useful information about tumor biology and assist in distinguishing between gliomas and meningiomas. ANIMALS: Seventy-eight hospitalized dogs with brain tumors and 12 control dogs without brain tumors. METHODS: In a 2-arm study, images from a prospective dynamic contrast-enhanced (DCE; n = 15) and a retrospective archived magnetic resonance imaging study (n = 63) were analyzed by DCE and subtraction enhancement analysis (SEA) to quantify BBB permeability in affected dogs relative to control dogs (n = 6 in each arm). For the SEA method, 2 ranges of postcontrast intensity differences, that is, high (HR) and low (LR), were evaluated as possible representations of 2 classes of BBB leakage. BBB score was calculated for each dog and was associated with clinical characteristics and tumor location and class. Permeability maps were generated, using the slope values (DCE) or intensity difference (SEA) of each voxel, and analyzed. RESULTS: Distinctive patterns and distributions of BBBD were identified for intra- and extra-axial tumors. At a cutoff of 0.1, LR/HR BBB score ratio yielded a sensitivity of 80% and specificity of 100% in differentiating gliomas from meningiomas. CONCLUSIONS AND CLINICAL IMPORTANCE: Blood-brain barrier dysfunction quantification using advanced imaging analyses has the potential to be used for assessment of brain tumor characteristics and behavior and, particularly, to help differentiating gliomas from meningiomas.

Detection of blood-brain barrier dysfunction using advanced imaging methods to predict seizures in dogs with meningoencephalitis of unknown origin.

BACKGROUND: The blood-brain barrier (BBB), which separates the intravascular and neuropil compartments, characterizes the vascular bed of the brain and is essential for its proper function. Recent advances in imaging techniques have driven the development of methods for quantitative assessment of BBB permeability. HYPOTHESIS/OBJECTIVES: Permeability of the BBB can be assessed quantitatively in dogs with meningoencephalitis of unknown origin (MUO) and its status is associated with the occurrence of seizures. ANIMALS: Forty dogs with MUO and 12 dogs without MUO. METHODS: Retrospective, prospective cohort study. Both dynamic contrast enhancement (DCE) and subtraction enhancement analysis (SEA) methods were used to evaluate of BBB permeability in affected (DCE, n = 8; SEA, n = 32) and control dogs (DCE, n = 6; SEA, n = 6). Association between BBB dysfunction (BBBD) score and clinical characteristics was examined. In brain regions where BBBD was identified by DCE or SEA magnetic resonance imaging (MRI) analysis, immunofluorescent staining for albumin, glial fibrillary acidic protein, ionized calcium binding adaptor molecule, and phosphorylated mothers against decapentaplegic homolog 2 were performed to detect albumin extravasation, reactive astrocytes, activated microglia, and transforming growth factor beta signaling, respectively. RESULTS: Dogs with BBBD had significantly higher seizure prevalence (72% vs 19%; P = .01) when compared to MUO dogs with no BBBD. The addition of SEA to routine MRI evaluation increased the identification rate of brain pathology in dogs with MUO from 50% to 72%. CONCLUSIONS AND CLINICAL IMPORTANCE: Imaging-based assessment of BBB integrity has the potential to predict risk of seizures in dogs with MUO.

CT findings and the prognostic value of the Koret CT score in cats with traumatic brain injury.

OBJECTIVES: The aims of this study were to evaluate associations between abnormal head CT findings and outcome, and to examine the prognostic value of the Koret CT score (KCTS) in cats sustaining acute traumatic brain injury (TBI). METHODS: The medical records of cats hospitalised with TBI that underwent head CT scans within 72 h of admission were retrospectively reviewed. CT scans were evaluated independently by a radiologist and a neurologist who were blinded to the outcome. A KCTS and modified Glasgow Coma Scale (MGCS) were assigned to each cat and the association between abnormal CT findings, KCTS, MGCS and outcome were analysed. RESULTS: Fourteen cats were included in the study: nine (64.2%) survivors and five (35.7%) non-survivors. Of the nine cats that were discharged, one was a short-term survivor (10 days) and eight (57.1%) were long-term survivors (⩾6 months). Abnormal CT findings included lateral ventricle asymmetry/midline shift (42.8%), intracranial haemorrhage (35.7%), caudotentorial lesions (14.2%) and cranial vault fractures (14.2%), all of which were depressed. Intracranial haemorrhage was found to be significantly and negatively associated with short-term (P = 0.005) and long-term (P = 0.023) survival. KCTS was significantly associated with short-term survival (P = 0.002) and long-term survival (P = 0.004). A KCTS cut-off value of 2 yielded a 100% sensitivity and 100% specificity for short-term survival and 100% sensitivity and 80% specificity for long-term survival. A MGCS cut-off value of ⩾13 was associated with a 100% sensitivity and 100% specificity for short-term survival, and with a 100% sensitivity and 80% specificity for long-term survival. CONCLUSIONS AND RELEVANCE: KCTS, performed up to 72 h from injury, can be used as an additional diagnostic tool for the prediction of survival in cats with TBI.

Comparison of three regional anaesthetic techniques for infraorbital or maxillary nerve block in cats: a cadaveric study.

OBJECTIVES: The maxillary nerve courses very close to the globe, rendering cats - with their large eyes - at risk of globe penetration during infraorbital or maxillary nerve blocks. Therefore, the goals of the study were to compare the distribution and potential complications of three infraorbital or maxillary regional injection techniques. METHODS: Twenty-three bilateral maxillae of cat cadavers were used in a randomised blinded trial. Each maxilla was injected with a 0.2 ml 1:1 mixture of lidocaine 2% and a contrast medium by one of three injection techniques: infraorbital foramen (IOF; n = 14); infraorbital canal (IOC; n = 16); or maxillary foramen (MF; transpalpebral approach; n = 16) using a 25 G 1.6 cm needle. CT imaging of each cadaver head was performed before and after injections. A radiologist scored injectate distribution (none [0], mild [1], moderate [2], large [3]) in four locations: rostral, central and caudal IOC, and at the MF, for which the distribution side was also determined. Comparisons were performed with ordinal logistic mixed effects (P <0.05). RESULTS: The median (range) total distribution score of the IOC and MF technique were significantly higher compared with the IOF technique (6.5 [4-12], 4 [2-8] and 0 [0-10], respectively). The total IOC score was also significantly higher compared with the MF technique. Injectate distribution at the MF was significantly more central following IOC injection compared with MF injection, which distributed centrolaterally. None of the techniques resulted in intraocular injection. CONCLUSIONS AND RELEVANCE: The IOC and MF techniques produced a satisfactory spread of the mixture that could result in effective maxillary anaesthesia in cats. Further studies are required to determine the effectiveness and safety of these techniques.

Balloon expandable aortic stent-graft for the treatment of aortic aneurysm and rupture in a dog.

OBJECTIVE: To describe the successful placement of an aortic stent graft in a dog suffering from aortic aneurysm and rupture. CASE SUMMARY: A 4-year-old neutered female mixed breed dog weighing 25 kg was presented with a chief complaint of acute onset of weakness and respiratory distress. On presentation, the dog was lateral and unresponsive, hypothermic, tachycardic, and tachypneic. Pleural effusion was identified in the right hemi-thorax on thoracic-focused sonographic scan for trauma. Thoracic radiographs showed a fluid/soft tissue opacity in the cranial mediastinum and pleural effusion on the right side. Thoracocentesis yielded noncoagulating blood. Hematology revealed normal PCV and total plasma protein that decreased within 24 hours to 20% and 50 g/L (20%/5.0 g/dL), respectively. The dog was treated with IV fluids, tranexamic acid, and fresh frozen plasma. An aortic aneurysm with irregular mineralization of the right ventrolateral aortic wall was identified on computed tomography examination, which also demonstrated a peri-aortic hematoma. A decision was made to attempt treatment with a stent graft. Under general anesthesia, a marker catheter was inserted into the esophagus. A 10-Fr sheath was inserted into the right femoral artery, and an angiography catheter was advanced over a wire. After angiography, a stent graft (12-mm × 50-mm) was placed over the guide wire and deployed under fluoroscopic guidance. The dog recovered uneventfully, with no evidence of recurrent bleeding, and was discharged 2 days after the procedure with antimicrobials, anthelmintic, and antithrombotic treatment. At 90-day follow-up, the dog was doing well, and stent position was radiographically confirmed. NEW OR UNIQUE INFORMATION PROVIDED: This report describes successful management of aortic aneurysm and dissection, an uncommon and challenging pathology in the veterinary practice with few available treatment options. Stent graft placement is a minimally invasive procedure in which a covered stent is placed over the lesion to prevent rupture.

Ultrasonography is insensitive but specific for detecting aortic wall abnormalities in dogs infected with Spirocerca lupi.

BACKGROUND: Spirocercosis is caused by the nematode Spirocerca lupi (S lupi). The disease mainly affects dogs and is typically diagnosed by oesophagoscopy or faecal examination; however, these diagnostic tests may deliver false negative results during the migration phase of the nematode. The aim of the present prospective study was to evaluate whether ultrasonography could detect abnormalities in the abdominal aorta, celiac artery, and gastric wall structure as a diagnostic aid to detect S lupi infection in dogs. METHODS: Oesophagoscopy and a focused abdominal ultrasound scan were performed in 40 dogs that presented to the Koret School of Veterinary Medicine Teaching Hospital, Hebrew University of Jerusalem, with gastrointestinal complaints. Ultrasonography scan findings of 20 dogs with oesophageal nodules, indicating S lupi infection (study group), were compared with those of 20 control dogs. RESULTS: Vascular wall irregularity was significantly more common in the study group than in the control group (9/20 v 1/20, respectively; P=0.008). CONCLUSION: Ultrasonographic evaluation of the abdominal aorta, celiac artery, and gastric wall structure is not a sensitive diagnostic marker for spirocercosis in dogs. However, the presence of vascular wall irregularity of the abdominal aorta or celiac artery might indicate S lupi migration.

Blood-brain barrier dysfunction in canine epileptic seizures detected by dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: Dogs with spontaneous or acquired epilepsy exhibit resemblance in etiology and disease course to humans, potentially offering a translational model of the human disease. Blood-brain barrier dysfunction (BBBD) has been shown to partake in epileptogenesis in experimental models of epilepsy. To test the hypothesis that BBBD can be detected in dogs with naturally occurring seizures, we developed a linear dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) analysis algorithm that was validated in clinical cases of seizing dogs and experimental epileptic rats. METHODS: Forty-six dogs with naturally occurring seizures of different etiologies and 12 induced epilepsy rats were imaged using DCE-MRI. Six healthy dogs and 12 naive rats served as control. DCE-MRI was analyzed by linear-dynamic method. BBBD scores were calculated in whole brain and in specific brain regions. Immunofluorescence analysis for transforming growth factor beta (TGF-ß) pathway proteins was performed on the piriform cortex of epileptic dogs. RESULTS: We found BBBD in 37% of dogs with seizures. A significantly higher cerebrospinal fluid to serum albumin ratio was found in dogs with BBBD relative to dogs with intact blood-brain barrier (BBB). A significant difference was found between epileptic and control rats when BBBD scores were calculated for the piriform cortex at 48 hours and 1 month after status epilepticus. Mean BBBD score of the piriform lobe in idiopathic epilepsy (IE) dogs was significantly higher compared to control. Immunohistochemistry results suggested active TGF-ß signaling and neuroinflammation in the piriform cortex of dogs with IE, showing increased levels of serum albumin colocalized with glial acidic fibrillary protein and pSMAD2 in an area where BBBD had been detected by linear DCE-MRI. SIGNIFICANCE: Detection of BBBD in dogs with naturally occurring epilepsy provides the ground for future studies for evaluation of novel treatment targeting the disrupted BBB. The involvement of the piriform lobe seen using our linear DCE-MRI protocol and algorithm emphasizes the possibility of using dogs as a translational model for the human disease.

Computed tomographic findings in dogs with head trauma and development of a novel prognostic computed tomography-based scoring system.

OBJECTIVE To characterize CT findings and outcomes in dogs with head trauma and design a prognostic scale. ANIMALS 27 dogs admitted to the Koret School Veterinary Teaching Hospital within 72 hours after traumatic head injury that underwent CT imaging of the head. PROCEDURES Data were extracted from medical records regarding dog signalment, history, physical and neurologic examination findings, and modified Glasgow coma scale scores. All CT images were retrospectively evaluated by a radiologist unaware of dog status. Short-term (10 days after trauma) and long-term (≥ 6 months after trauma) outcomes were determined, and CT findings and other variables were analyzed for associations with outcome. A prognostic CT-based scale was developed on the basis of the results. RESULTS Cranial vault fractures, parenchymal abnormalities, or both were identified via CT in 24 of 27 (89%) dogs. Three (11%) dogs had only facial bone fractures. Intracranial hemorrhage was identified in 16 (59%) dogs, cranial vault fractures in 15 (56%), midline shift in 14 (52%), lateral ventricle asymmetry in 12 (44%), and hydrocephalus in 7 (26%). Hemorrhage and ventricular asymmetry were significantly and negatively associated with short- and long-term survival, respectively. The developed 7-point prognostic scale included points for hemorrhage, midline shift or lateral ventricle asymmetry, cranial vault fracture, and depressed fracture (1 point each) and infratentorial lesion (3 points). CONCLUSIONS AND CLINICAL RELEVANCE The findings reported here may assist in determining prognoses for other dogs with head trauma. The developed scale may be useful for outcome assessment of dogs with head trauma; however, it must be validated before clinical application.