Inflammatory disease of the central nervous system

Inflammatory diseases involving the central nervous system can be difficult to diagnose and frustrating to treat. The clinician can maximize successful treatment of these patients by recognizing the clinical signs in the early stages of disease, following a logical diagnostic plan to identify the specific etiologic agent involved, and formulating an appropriate and aggressive therapeutic plan. Treatment will not always be successful owing to lack of effective treatments and irreversible neurologic damage.     

Canine von Willebrand's disease. A heterogeneous group of bleeding disorders

The term "von Willebrand's disease," refers to a group of inherited bleeding disorders, all of which are caused by a deficiency of the multimeric plasma glycoprotein, von Willebrand factor. The various forms of canine von Willebrand's disease can be categorized into one of three major types: in type I canine von Willebrand's disease, all sizes of von Willebrand factor multimers can be detected in the plasma; in type II canine von Willebrand's disease, only the smaller von Willebrand factor multimers are found in the plasma (larger multimers are absent); and in type III canine von Willebrand's disease, von Willebrand factor is completely absent from the plasma or present in only trace amounts. Von Willebrand's disease is common in dogs, but some forms of the disease are so mild that they are of questionable clinical significance.     

猪中枢神经系统疾病的诊断方法

猪中枢神经系统疾病是临床常见病,通常由传染性疾病引起,也可能由先天性遗传或中毒所致.神经紊乱一般表现为步态异常、共济失调、瘫痪、肌肉震颤、角弓反张、抽搐、惊厥和眼球震颤等症状.     

von Willebrand's disease in Scottish Terriers in Australia

SUMMARY Over a 5-year period (1988–92), von Willebrand factor antigen (vWf:Ag) assays were performed on plasma samples from 207 Scottish Terriers. Based on these tests, 47 dogs (23%) had vWf:Ag concentrations < 50 canine units (CU)/dL and were classified as heterozygous carriers of the von Willebrand's disease (vWD) gene, while 9 (4%) had concentrations below the sensitivity of the assays and were classified as homozygous. There was thus an overall prevalence of 27% for the vWD gene in the Scottish Terriers tested. The homozygous dogs (median age 0.6 years at diagnosis) consisted of 7 males and 2 females. Eight of these had haemorrhage attributable to the disease, mostly spontaneous and from the oral mucosa. Other signs included haemorrhage induced by trauma or surgery, easy bruising and epistaxis. Many haemorrhagic episodes were severe enough to warrant therapeutic intervention and there was a single fatality. Pedigree analysis, possible in 7 of the dogs, revealed that each was the progeny of a mating between dogs with vWf:Ag concentrations < 50 CU/dL, which supported an autosomal recessive mode of inheritance. A single heterozygous carrier suffered haemorrhage after surgery that, in contrast to the homozygotes, was mild and did not require therapy. The data indicate that vWD is a significant problem in Scottish Terriers in Australia. Accordingly, we recommend that steps be taken to reduce the prevalence of the disease and thereby the number of clinically affected dogs, such as the establishment of a national testing scheme to determine the vWD status of all breeding dogs.     

von Willebrand's disease in Dobermann dogs in Australia

SUMMARY Over a 5-year period (1988–92), von Willebrand factor antigen (vWf:Ag) concentrations were determined on plasma samples from 614 Dobermanns. The vWf:Ag concentration was < 50 canine units (CU)/dL in 373 dogs (61%); these dogs were classified as carriers of the von Willebrand's disease (vWD) gene. In order to identify which dogs were at risk of haemorrhage due to vWD, we determined a cut-off vWf:Ag concentration below which dogs could be considered at risk. This cut-off was chosen in order to minimise the number of dogs genuinely at risk of haemorrhage, being wrongly classified as not at risk. This was done without sacrificing the specificity of the cut-off to any great extent. A vWf:Ag concentration of < 36 CU/dL was empirically chosen as the optimum cut-off concentration. In 282 dogs (76% of the carriers), the vWf:Ag concentration was below this cut-off and these dogs were, thus, classified as being at risk of haemorrhage due to vWD. Haemorrhage attributable to vWD was seen in 107 dogs (29% of the carriers, or 17% of all the dogs). Haemorrhage mostly followed trauma or surgery, but spontaneous genitourinary and gastrointestinal haemorrhages were also frequent. Of these dogs, 92 were of known age, with a median of 3 years, and 102 were of known sex, with 61% being female. In 89 dogs in which the severity of haemorrhage was subjectively assessed, mild and moderate bleeding occurred with similar frequency (48% and 43%, respectively). There were 8 cases of severe haemorrhage, with two deaths. The likelihood of haemorrhage was related to the vWf:Ag concentration: only 8% of 91 dogs with concentrations between 36 and 49 CU/dL had haemorrhage attributable to vWD, but 36% with concentrations < 36 CU/dL did so. Furthermore, dogs with haemorrhage attributable to vWD had significantly (P < 0.001) lower vWf:Ag concentrations (median 12 CU/dL, n = 107) than dogs with no such history (median 30 CU/dL, n = 132). The data indicate that vWD is a significant problem in the Dobermann breed in Australia and we accordingly recommend that steps be taken to reduce its prevalence, such as the establishment of a national testing scheme to determine the vWD status of all dogs used for breeding.     

Mutation causing von Willebrand's disease in Scottish Terriers

Von Willebrand's Disease (vWD) in the Scottish Terrier breed is a serious, often fatal, hereditary bleeding disorder. Elimination of the mutated gene by selective breeding is an important goal for the health of this breed. Although the standard protein-based tests are accurate for identification of affected Scottish Terriers, they are not reliable for the identification of carriers of the mutant gene unless multiple replicate assays are performed. A simple, highly accurate test for carriers of the disease is needed so that veterinarians can counsel clients on which animals to use in their breeding programs. The complete coding region of von Willebrand factor (vWF) complementary DNA (cDNA) was sequenced from an affected animal, and a single base deletion in the codon for amino acid 85 of the prepro-vWF cDNA that leads to Scottish Terrier vWD was identified. A highly accurate polymerase chain reaction assay was developed that can distinguish homozygous normal animals from those that are homozygous affected or heterozygous. In a voluntary survey of 87 animals provided by Scottish Terrier owners, 15 were carriers and 4 were affected with vWD, 2 of which had previously been shown to have undetectable vWF. The determination of the complete canine vWF cDNA sequence should facilitate the identification of additional vWD alleles in other breeds and other species.     

Type 3 von Willebrand's disease in a Shetland sheepdog

A 3.75-year-old, spayed female, Shetland sheepdog was presented with excessive bleeding from a gingival surface. The dog's condition deteriorated over 24 h and whole fresh blood was transfused. Type 3 von Willebrand's disease was diagnosed. Coagulation was achieved and the dog was released with recommendations for a sedentary lifestyle and careful monitoring.     

Type III von Willebrand's disease in Dutch kooiker dogs

Summary

Type III von Willebrand's disease (vWD) was diagnosed in 38 Dutch kooiker dogs. Ten male and 9 female probands had been referred independently of each other to the Utrecht University Clinic for Companion Animals because of a moderate to severe bleeding tendency. Screening of 717 Dutch kooiker dogs, including 356 puppies, detected vWD in another 19 dogs. Diagnosis was based on non‐detectable amounts (< 1.6%) of von Willebrand factor antigen (vWF:Ag) in plasma by ELISA. Capillary bleeding time (CBT) was prolonged (> 10 min) and polybrene cofactor activity (vWF:PbCo) was not detectable in 11 dogs tested. No distinguishable protein bands were detected by multimer analysis. As in Scottish terriers with type III vWD, factor VIII clotting activity (F_VIII:C) in affected Dutch kooiker dogs was decreased but considerably less than in humans with type III vWD. A recessive mode of inheritance was indicated by the normal or subnormal but measurable amounts of vWF:Ag in the plasma of eight pairs of parents of affected dogs. The F₁ offspring resulting from the experimental mating of two affected dogs consisted of three affected males and four affected females. In 39 obligatory carriers vWF:Ag ranged from 30% to 114% with median and mean vWF values of 64% and 64.2%, respectively, and was subnormal (< 50%) in only 9 animals.     

Infectious diseases of the central nervous system.

Neurologic disease is seen commonly in cats, with infectious causes accounting for 30-45% of cases. However, since a specific infection cannot be identified in 12-40% of these cases, it is essential that we try to understand these cases better in the hope that we can eventually identify the cause(s), and so determine how best to treat and/or prevent them.     

Inheritance of von Willebrand's disease in a colony of Doberman Pinschers

OBJECTIVE: To determine the mode of inheritance of von Willebrand's disease (vWD) and perform linkage analysis between vWD and coat color or narcolepsy in a colony of Doberman Pinschers. ANIMALS: 159 Doberman Pinschers. PROCEDURE: von Willebrand factor antigen (vWF:Ag) concentration was measured by use of ELISA, and results were used to classify dogs as having low (< 20%), intermediate (20 to 65%), or high (> 65%) vWF:Ag concentration, compared with results of analysis of standard pooled plasma. Buccal bleeding time was measured, and mode of inheritance of vWD was assessed by pedigree analysis. RESULTS: von Willebrand's disease was transmitted as a single autosomal gene defect. Results suggested that 27.04% of dogs were homozygous for vWD, 62.26% were heterozygous, and 10.69% did not have the defect. Most homozygous and some heterozygous dogs had prolonged bleeding times. Dogs with diluted coat colors (blue and fawn) were significantly overrepresented in the homozygous group, compared with black and red dogs, but a significant link between vWD and coat color was not detected. CONCLUSIONS AND CLINICAL RELEVANCE: von Willebrand's disease is transmitted as an autosomal dominant trait with variable penetrance; most dogs in this colony (89.3%) were carriers of vWD. Homozygosity for vWD is not likely to be lethal. Some heterozygous dogs have prolonged bleeding times. An association between diluted coat colors and vWD may exist.     

Magnetic resonance imaging in two dogs with central nervous system disease

Accurate localization of the lesions in two dogs with progressive neurological disease was demonstrated with magnetic resonance imaging (MRI). The first dog had unilateral cerebellar signs with associated paradoxical vestibular symptoms. The CSF tap and clinical localization suggested a right-sided cerebellar tumour and this was confirmed with MRI scanning. The second dog had predominantly asymmetrical fore-brain signs with circling, personality changes, seizures and contralateral proprioceptive deficits. CSF analysis suggested an inflammatory or neoplastic condition. MRI showed a diffuse oedematous lesion of the left cerebral hemisphere which corresponded exactly with the lesions seen at necropsy. The advantages of MRI over CT scans are discussed.     

Plasma von Willebrand factor-collagen binding activity in normal dogs and in dogs with von Willebrand's disease.

A sensitive enzyme-linked immunosorbent assay was used for the simultaneous assessment of the amount of von Willebrand factor (vWF) in canine plasma and its ability to bind to canine collagen in vitro. In 60 normal dogs, there was close correlation between the concentration of vWF and its activity as determined by vWF-collagen binding. In 14 dogs with type I expressions of von Willebrand's disease, the ratio of vWF antigen to collagen binding activity was normal or only slightly increased. In 7 dogs with type II expressions of the disease, this ratio was consistently elevated suggesting a significant functional deficiency of the protein. Plasma from 3 dogs with type III von Willebrand's disease had little collagen binding activity because of the severe quantitative deficiency of the protein. The described assay permits the rapid assessment of both the quantity and quality of vWF in a dog. This information is necessary for the detection and characterization of canine von Willebrand's disease, particularly the type II expressions, which cannot be diagnosed by quantitative vWF assays alone.     

Hemorrhage from the cosmetic otoplasty of Doberman Pinschers with von Willebrand's disease

The hemorrhagic tendencies of 23 Doberman Pinscher pups were observed during cosmetic otoplasty and were ranked by a +1 to +4 grading system (+1 = least hemorrhage, and +4 = most hemorrhage). A second estimate of the hemostatic competencies of these dogs was made by counting the gauze sponges used in the otoplasties. Factor VIII-related antigen concentrations and coagglutinin cofactor concentrations were measured in plasma samples from blood drawn not more than 30 hours before the surgical procedures were done. The factor VIII-related antigen concentrations were between 9% and 147% of the concentration in a normal plasma pool, and the coagglutinin cofactor concentrations were between 1% and 165%, indicating that some of these dogs had von Willebrand's disease. The hemorrhagic tendencies of 12 pups were graded +1. This group had a mean antigen concentration of 75% (min-max, 38% to 147%) and a mean coagglutinin cofactor concentration of 89% (min-max, 42% to 165%). These were significantly greater than the antigen and cofactor concentrations of the grades +2 (n = 5), +3 (n = 3), or +4 (n = 3) dogs. Significant differences were not found when antigen concentrations of the grade +2 dogs (mean, 16%; min-max, 11% to 22%), grade +3 dogs (mean, 13%; 12% to 16%), and grade +4 dogs (mean, 11%; 9% to 12%) were compared with each other, nor were significant differences seen among the coagglutinin cofactor concentrations of the grade +2 dogs (mean, 7%; min-max, 1% to 11%), grade +3 dogs (mean, 6%, 4% to 8%), and grade +4 dogs (mean, 5%; 2% to 9%).(ABSTRACT TRUNCATED AT 250 WORDS)