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‐β) 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‐β 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.
Congenital oesophageal stricture was diagnosed via endoscopy in a 3-day-old Arabian filly suffering from nasal milk regurgitation. Vascular ring anomaly or other extramural, intramural or intraluminal causes were not identified on radiographs or on a computed tomography scan; thus a functional abnormality was suspected. The filly was treated with antibiotics for aspiration pneumonia and was fed milk through an indwelling nasoesophageal tube. Two sessions of balloon bougienage at the stenotic site, under sedation, resulted in marked clinical improvement and thereafter the filly was gradually reintroduced to suckling from the mare. The filly was discharged from the hospital after 17 days and on follow-up there were no reports of food regurgitation even after the introduction of solid food. The filly was still doing well in the latest follow-up at age 11 months.
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.
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.
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.
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