Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations ...could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature. Unlike other brachycephalic dogs, these breeds also exhibit vertebral malformations that result in a truncated, kinked tail (screw tail). Whole genome sequencing of 100 dogs from 21 breeds identified 12.4 million bi-allelic variants that met inclusion criteria. Whole Genome Association of these variants with the breed defining phenotype of screw tail was performed using 10 cases and 84 controls and identified a frameshift mutation in the WNT pathway gene DISHEVELLED 2 (DVL2) (Chr5: 32195043_32195044del, p = 4.37 X 10-37) as the most strongly associated variant in the canine genome. This DVL2 variant was fixed in Bulldogs and French Bulldogs and had a high allele frequency (0.94) in Boston Terriers. The DVL2 variant segregated with thoracic and caudal vertebral column malformations in a recessive manner with incomplete and variable penetrance for thoracic vertebral malformations between different breeds. Importantly, analogous frameshift mutations in the human DVL1 and DVL3 genes cause Robinow syndrome, a congenital disorder characterized by similar craniofacial, limb and vertebral malformations. Analysis of the canine DVL2 variant protein showed that its ability to undergo WNT-induced phosphorylation is reduced, suggesting that altered WNT signaling may contribute to the Robinow-like syndrome in the screwtail breeds.
Choroid Plexus Tumors in 56 Dogs (1985-2007) Westworth, D.R.; Dickinson, P.J.; Vernau, W. ...
Journal of veterinary internal medicine,
September–October 2008, Letnik:
22, Številka:
5
Journal Article
Recenzirano
Background: Choroid plexus tumors (CPTs) comprise approximately 10% of all primary brain tumors in dogs. The clinical utility of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, ...or both in the presumptive diagnosis of CPTs has not been determined.
Objectives: To report MRI and CSF findings in dogs with CPT and determine if there are distinguishing features that allow clinical discrimination between the tumor grades.
Animals: Fifty‐six client‐owned dogs with naturally occurring CPT.
Methods: Retrospective case series. The inclusion criterion was histologically confirmed CPT. Blinded review of cranial MRI and cisternal CSF analysis was performed.
Results: Thirty‐six of 56 dogs had a choroid plexus carcinoma (CPC) and 20 had a choroid plexus papilloma (CPP). Golden Retrievers were overrepresented compared with the hospital population (frequency 3.7 times that expected, confidence interval 95%= 2.0–6.7, P < .0002). Median CSF protein concentration in CPCs (108 mg/dL, range 27–380 mg/dL) was significantly higher than in CPPs (34 mg/dL, range 32–80 mg/dL) (P= .002). Only dogs with CPCs had a CSF protein concentration >80 mg/dL. Cytological evidence of malignancy in CSF was seen in 7 of 15 CPCs. Only CPCs had evidence of intraventricular or subarachnoid metastases on MRI.
Conclusions and Clinical Importance: MRI, CSF analysis or both can help to differentiate between CPPs and CPCs, and may provide valuable prognostic and pretreatment information.
Background: Marked eosinophilic meningitis or meningoencephalomyelitis (EME) is rarely reported in dogs and the cause is usually undetermined. Long‐term prognosis for dogs with cerebrospinal fluid ...(CSF) eosinophilia is variable.
Animals: Twenty‐three client‐owned dogs.
Methods: Retrospective case series. Dogs with eosinophilic CSF, defined as total nucleated cell count (TNCC) >3 cells/μL with >20% eosinophils, were identified by a computerized search of all dogs having cisternal and/or lumbar CSF analyzed as part of the diagnostic workup between 1992 and 2007.
Results: TNCC in CSF ranged from 4 to 4,740 cells/μL (median 84 cells/μL, reference range ≤3 cells/μL), with 22 to 95% (median 78%) eosinophils in the differential count. An infectious agent was identified on necropsy in 4 of 23 (17%) dogs (Cryptococcus neoformans n = 2, Neospora caninum n = 1, and Baylisascaris procyonis n = 1). Each of these dogs had progressive neurologic deterioration. Sixteen dogs had idiopathic EME. Magnetic resonance imaging (MRI) findings were abnormal in 7 of 13 dogs with EME; 2 dogs had focal lesions and 5 dogs had multifocal lesions. Clinical signs in 12 of 16 (75%) dogs with idiopathic EME resolved with prednisone treatment. Three dogs with acute intervertebral disc herniations recovered after decompressive surgery alone.
Conclusions: Idiopathic EME is a common cause of eosinophilic pleocytosis in dogs. MRI findings are variable. Infectious causes of EME were less common and had a poor prognosis.
Background: Cryptococcus spp. is a fungal pathogen with a predilection for the central nervous system (CNS). Objectives: To compare the clinical, advanced imaging, and neuropathologic findings in ...dogs and cats with CNS cryptococcosis, and to evaluate outcome of treatment in these animals. Animals: Twenty-six cats and 21 dogs with CNS cryptococcosis. Methods: Medical records were reviewed for clinical findings and results of CNS imaging. Archived cerebrospinal fluid and CNS tissue specimens were reviewed for pathology. Findings in cats were compared with those in dogs and the effects of variables on survival were determined by survival curve analysis. Results: When present, pain was localized to the cervical region in dogs and was generalized or localized to the thoracolumbar spine or pelvic limbs in cats. Magnetic resonance imaging (MRI) findings were variable but correlated with CNS histopathological findings of meningitis, meningitis with gelatinous pseudocyst formation, and granulomatous mass lesions. Peripherally enhancing brain lesions were seen only in cats. Histopathologically, the inflammatory response was milder in cats compared with dogs. Remissions of >or=1 year occurred in 32% of treated animals. Altered mentation was associated with negative outcome. Glucocorticoid use after diagnosis was associated with improved survival in the first 10 days. Conclusions and Clinical Importance: Lesions seen on MRI reflected neuropathological findings and were similar to those reported in human patients. The immune response to infection may differ between cats and dogs, or relate to the infecting cryptococcal species. Long-term (>6 month median survival time) survival may be possible in animals surviving ≥4 days after diagnosis.
Background: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic ...resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated.
Hypothesis: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics.
Animals: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma.
Methods: Retrospective observational study.
Results: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied.
Conclusions and Clinical Importance: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas.
Background: Cerebrospinal fluid (CSF) in dogs with Hansen type I intervertebral disc herniation (IVDH) is classically described as normal or mildly inflammatory with a predominance of large ...mononuclear cells or neutrophils in severe acute herniations. However, we have observed a moderate to marked pleocytosis with a predominance of lymphocytes in some dogs with IVDH.
Hypothesis: Moderate to marked CSF pleocytosis occurs more commonly in dogs with type I IVDH than is reported in the literature. Lymphocytic predominance is more common than nonlymphocytic pleocytosis in dogs with chronic IVDH.
Animals: Four hundred twenty‐three client‐owned dogs with type I IVDH.
Methods: Retrospective study. Lumbar CSF of dogs with surgically confirmed type I IVDH was evaluated cytologically. Information obtained from medical records included signalment, prior clinical history, time from onset of signs to presentation, neurologic status, and intraoperative findings. Dogs with prior history and/or intraoperative evidence consistent with chronic IVDH before an acute herniation were termed acute‐on‐chronic (AOC).
Results: Pleocytosis (> 5 cells/uL) was present in 51% of dogs, including 23% with cervical IVDH and 61% with thoracolumbar IVDH. Moderate or marked inflammation (≥ 20 cells/uL) was identified in the CSF of 51% of dogs with thoracolumbar IVDH and pleocytosis. A predominance of lymphocytes was significantly more common in dogs examined > 7 days from onset of signs (P= .032) and in dogs with AOC IVDH (P= .0013).
Conclusions and Clinical Importance: Moderate to marked CSF pleocytosis in dogs with type I IVDH is more common than previously reported. Lymphocytic pleocytosis is most common in dogs with chronic progression or AOC IVDH. Lymphocytic inflammation in the CSF of some dogs might suggest an immune‐mediated response to chronically herniated disc material.
BACKGROUND: Canine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led ...to the presumption that it is a breed‐restricted disorder. HYPOTHESIS/OBJECTIVES: Our objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported. ANIMALS: Four dogs with NME. METHODS: Archives from 3 institutions and from 1 author's (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated. RESULTS: Necrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate‐to‐severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents. CONCLUSIONS AND CLINICAL IMPORTANCE: Until now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed‐restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.
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