Characteristics and outcome of suspected cerebrovascular disease in dogs: 66 cases (2009-2016).

OBJECTIVES: To characterise the clinical signs of suspected cerebrovascular disease in dogs. MATERIALS AND METHODS: Medical records of one hospital were searched from November 2009 to December 2016 for dogs that suffered of cerebrovascular disease. We diagnosed cerebrovascular disease based on acute onset, clinical signs and magnetic resonance imaging findings. The medical history, clinical signs, concurrent disease, area of infarction, cerebrospinal fluid results, month at onset and outcome were investigated in the cerebrovascular disease group and in a control group (dogs with brain disorders other than cerebrovascular disease). RESULTS: A total of 122 CVD cases were extracted from the 5312 patients that visited during the study period. Of these 122 cases, 66 (1.2%) matched the subject selection criteria of our study and were included in the analysis. Forebrain infarction was observed in 51 of 66 cases, of which 24 (47.1%) suffered from seizures. The number of dogs diagnosed with cerebrovascular disease was disproportionately high in August (nine of 59 cases) and December (13 of 59 cases). In the outcome survey, deterioration was observed in 11 of 55 cases. CLINICAL SIGNIFICANCE: Seizure is an important clinical sign of cerebrovascular disease in dogs. There was a significant seasonal variation in the number of dogs diagnosed with cerebrovascular disease in Japan. Clinical features observed in this report differ from those of previous reports and highlight the need for additional research in this area.

Natural genetic variation in Stim1 creates stroke in the spontaneously hypertensive rat.

Similar to humans, the risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study, we show the involvement of genetic variation affecting the store-operated calcium signaling gene, Stim1, in the pathogenesis of stroke in SHR. Stim1 is a key lymphocyte activation signaling molecule and contains functional variation in SHR-A3 that diverges from stroke-resistant SHR-B2. We created a SHR-A3 congenic line in which Stim1 was substituted with the corresponding genomic segment from SHR-B2. Compared with SHR-A3 rats, Stim1 congenic SHR-A3 (SHR-A3(Stim1-B2)) have reduced cerebrovascular disease in response to salt loading including lower neurological deficit scores and cerebral edema. Microbleeds and major hemorrhages occurred in over half of SHR-A3 rats. These lesions were absent in SHR-A3(Stim1-B2) rats. Loss of Stim1 function in mice and humans is associated with antibody-mediated autoimmunity due to defects in T lymphocyte helper function to B cells. We investigated autoantibody formation using a high-density protein array to detect the presence of IgG and IgM autoantibodies in SHR-A3. Autoantibodies to key cerebrovascular stress proteins were detected that were reduced in the congenic line.

An Update on Cerebrovascular Disease in Dogs and Cats.

This article reviews definitions and normal anatomy and physiology of canine and feline cerebral vasculature. The pathophysiology of cerebrovascular disease (CVD), which results from disturbance of cerebral blood supply, is described, along with its common causes and correlative findings. The general clinical presentation of companion animals is described, although specific neurologic abnormalities depend on the neuroanatomic location of the disrupted blood supply. Current and future diagnostic approaches are described, including ancillary testing for predisposing factors. Acute and chronic management of patients with CVD is discussed. The prognosis for dogs and cats with acute CVD is generally considered good.

Extensive vascular mineralization in the brain of a chimpanzee (Pan troglodytes).

Spontaneous vascular mineralization (deposition of iron or calcium salts) has been observed in marble brain syndrome, mineralizing microangiopathy, hypothyroidism, Fahr syndrome, Sturge-Weber syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and calciphylaxis in humans and as an aging or idiopathic lesion in the brains of horses, cats, nonhuman primates, mice, rats, cattle, white-tailed deer, and dogs. Here we present a 27-y-old, adult male chimpanzee (Pan troglodytes) with spontaneous, extensive vascular mineralization localized solely to the brain. The chimpanzee exhibited tremors and weakness of the limbs, which progressed to paralysis before euthanasia. Magnetic resonance brain imaging in 2002 and 2010 (immediately before euthanasia) revealed multiple hypointense foci, suggestive of iron- and calcium-rich deposits. At necropsy, the brain parenchyma had occasional petechial hemorrhage, and microscopically, the cerebral, cerebellar and brain stem, gray and white matter had moderate to severe mural aggregates of a granular, basophilic material (mineral) in the blood vessels. In addition, these regions often had moderate to severe medial to transmural deposition of mature collagen in the blood vessels. We ruled out common causes of brain mineralization in humans and animals, but an etiology for the mineralization could not be determined. To our knowledge, mineralization in brain has been reported only once to occur in a chimpanzee, but its chronicity in our case makes it particularly interesting.

Comparison of isoflurane and propofol for maintenance of anesthesia in dogs with intracranial disease undergoing magnetic resonance imaging.

OBJECTIVE: To compare isoflurane and propofol for maintenance of anesthesia and quality of recovery in client-owned dogs with intracranial disease undergoing magnetic resonance imaging (MRI). STUDY DESIGN: Prospective, randomized, clinical trial. ANIMALS: Twenty-five client-owned dogs with intracranial pathology, 13 females and 12 males, ages 11 months to 13 years, weighing between 3.0 and 48.0 kg. METHODS: Each dog was randomly assigned to receive propofol or isoflurane for maintenance of anesthesia. All dogs were not premedicated, were administered propofol intravenously to effect for induction, intubated and mechanically ventilated to maintain an end-tidal carbon dioxide tension 30-35 mmHg (4.0-4.7 kPa). Temperature and cardiac output were measured pre- and post-MRI. Scores for mentation, neurological status, ease of maintenance, and recovery were obtained pre- and post-anesthesia. Pulse oximetry, end-tidal gases, arterial blood pressure, heart rate (HR) and requirements for dopamine administration to maintain mean arterial pressure (MAP) >60 mmHg were recorded throughout anesthesia. RESULTS: End-tidal isoflurane concentration was 0.73 ± 0.35% and propofol infusion rate was 292 ± 119 µg kg(-1)  minute(-1) . Cardiac index was higher, while HR was lower, with propofol than isoflurane in dogs younger than 5 years, but not in older dogs. Dogs maintained with isoflurane were 14.7 times more likely to require dopamine than propofol dogs. Mentation and maintenance scores and temperature were not different. MAP and diastolic arterial pressure were higher in the propofol group. Recovery scores were better with propofol, although times to extubation were similar. Change in neurological score from pre- to post-anesthesia was not different between treatments. CONCLUSIONS: Dogs maintained with propofol during MRI had higher arterial pressures, decreased requirements for dopamine, and better recovery scores, compared to dogs maintained with isoflurane. CLINICAL RELEVANCE: Propofol anesthesia offered cardiovascular and recovery advantages over isoflurane during MRI in dogs with intracranial disease in this study.

Evaluation of standard magnetic resonance characteristics used to differentiate neoplastic, inflammatory, and vascular brain lesions in dogs.

Magnetic resonance (MR) imaging characteristics are commonly used to help predict intracranial disease categories in dogs, however, few large studies have objectively evaluated these characteristics. The purpose of this retrospective study was to evaluate MR characteristics that have been used to differentiate neoplastic, inflammatory, and vascular intracranial diseases in a large, multi-institutional population of dogs. Medical records from three veterinary teaching hospitals were searched over a 6-year period for dogs that had diagnostic quality brain MR scans and histologically confirmed intracranial disease. Three examiners who were unaware of histologic diagnosis independently evaluated 19 MR lesion characteristics totaling 57 possible responses. A total of 75 dogs with histologically confirmed intracranial disease were included in analyses: 51 with neoplasia, 18 with inflammatory disease, and six with cerebrovascular disease. Only strong contrast enhancement was more common in neoplasia than other disease categories. A multivariable statistical model suggested that extra-axial origin, T2-FLAIR mixed intensity, and defined lesion margins were also predictive of neoplasia. Meningeal enhancement, irregular lesion shape, and multifocal location distinguished inflammatory diseases from the other disease categories. No MR characteristics distinguished vascular lesions and these appeared most similar to neoplasia. These results differed from a previous report describing seven MR characteristics that were predictive of neoplasia in dogs and cats. Findings from the current study indicated that the high performance of MR for diagnosing canine intracranial diseases might be due to evaluator recognition of combinations of MR characteristics vs. relying on any one MR characteristic alone.

Feline cerebrovascular disease: clinical and histopathologic findings in 16 cats.

Sixteen cats with cerebrovascular disease confirmed via histology to be of nontraumatic and nonneoplastic origins are described. In addition, the anatomy of the arterial supply of the cat's brain is reviewed. It is suggested that this unique arterial design may influence the incidence of cerebrovascular accidents in this species. Of the 16 cats reviewed, seven cats had ischemic infarctions, five had hemorrhagic infarctions, and four were diagnosed with intracranial hemorrhage. The median age was 8 yr and 9.5 yr in cats with infarctions and intracranial hemorrhages, respectively. Clinical signs were severe, acute, consistent with the localization of the cerebrovascular lesion, and influenced by underlying pathology. Four cats with infarction showed lateralized neurologic signs. Four cats with infarctions were diagnosed with pulmonary disease antemortem and three cats had hyperthyroidism. Cerebrospinal fluid analysis and computed tomography scans were available in two cats. None of the infarctions were grossly visible. All cats with hemorrhagic infarcts had severe liver pathology and nephritis was identified in four cats. Hypoxia was a feature in four cats and one cat suffered cardiac failure. In conclusion, the clinical picture is influenced by the type of cerebrovascular disease, the localization of the intracranial lesions, and any underlying pathology.

MRI of brain disease in veterinary patients part 2: Acquired brain disorders.

Magnetic resonance imaging (MRI) has revolutionized brain imaging in veterinary medicine, making possible improved characterization of intracranial pathologic processes. This article focuses on MRI features of acquired brain disorders, including infectious inflammatory, noninfectious inflammatory, cerebrovascular, metabolic, nutritional, toxic, degenerative, traumatic, and neoplastic causes. Congenital intracranial disorders are covered in a companion article.

Cerebrovascular disease in dogs and cats.

Cerebrovascular disease is defined as any abnormality of the brain resulting from a pathologic process affecting its blood supply. Stroke or cerebrovascular accident (CVA) is the most common clinical manifestation of cerebrovascular disease, and can be broadly divided into ischemic stroke and hemorrhagic stroke. Ischemic stroke results from occlusion of a cerebral blood vessel by a thrombus or embolism, depriving the brain of oxygen and glucose, whereas hemorrhagic stroke results from rupture of a blood vessel wall within the brain parenchyma or subarachnoid space. Previously considered uncommon, CVA is being recognized with greater frequency in veterinary medicine since magnetic resonance imaging has become more readily available. Once the diagnosis of ischemic or hemorrhagic stroke is confirmed, potential underlying causes should be sought after and treated accordingly.

Distribution of vascular amyloid in scrapie-affected sheep with different genotypes.

Vascular amyloidosis in the brain is a pathological feature of ovine scrapie. Its occurrence varies between sheep, but whether this variation reflects differences in the host or the infecting scrapie strain (or both) is not clear. To investigate whether amyloidosis, like vacuolation and PrPsc distribution, is associated with genotype, the brains from 131 sheep representing a range of genotypes commonly associated with scrapie were examined histologically and immunohistochemically. Vascular amyloidosis was absent in 66 sheep, 59 of which were of the ARQ/ARQ genotype and seven the ARQ/AHQ genotype. In contrast, it was found in four of 39 ARQ/VRQ sheep (10.2%) and in 10 of 26 VRQ/VRQ sheep (38.4%). The distribution of amyloid was highly variable, but the most severely affected areas were the lateral geniculate nuclei (five cases) and the ventral thalamic nuclei (four cases). No amyloidosis was found in the medulla or in the basal nuclei. From this preliminary study it was concluded that amyloidosis is relatively rare in sheep with scrapie. Moreover, its occurrence appeared to depend on the presence of at least one valine at codon 136.

Cerebrovascular disease.

Cerebrovascular disease may be secondary to various disorders including hypothyroidism, sepsis, neoplasia, hypertension, vascular malformation, and coagulopathy. Brain infarction or hemorrhage should be suspected in an animal with a sudden onset of a focal brain lesion. The recent availability of CT and MRI has improved our ability to diagnose cerebrovascular disease in animals. Treatment is directed at maintaining adequate oxygenation of the brain, controlling elevations of ICP, treating seizures, and identifying and treating any underlying disease. With appropriate care, many animals can recover.

[Age-related non-tumorous lesions in SPF C57BL/6 mice with special reference to amyloidosis].

Non-tumorous pathological changes in C57BL/6 CrSlc mice, which were reared under a barrier system and died spontaneously, were examined. At 3 months intervals 125 to 209 mice were purchased at 4 weeks of age and raised for the supply of aged animals. A large portion of the mice were used for various experiments between 3 and 30 months of age, while not a small number died spontaneously and were autopsied. The major non-neoplastic lesion was amyloidosis, with incidence of 55.5% and 74.4% for the autopsied female and male, respectively. The organs involved were the liver, kidneys, spleen, adrenal glands, ileum, heart and lungs. Skin ulceration and its scar, cerebral vascular calcification, glomerulosclerosis and sepsis in both sexes, distension of the seminal vesicles in males, fibroblast growth of the adrenal glands in females were commonly found. Incidence of spontaneous neoplastic lesions was 69.7% and 55.1% for the female and male, respectively.

Topographic relationship between senile plaques and cerebrovascular amyloidosis in the brain of aged dogs.

The distributions of senile plaques (SP) and cerebrovascular amyloidosis (CA) were studied by employing thioflavin S and modified Bielschowsky stains, and beta-protein immunohistochemistry on serial sections of the brains of aged dogs older than 10 years. Mature and perivascular plaques, both of which contained compact amyloid deposits, always showed a close topographic relationship to CA. In contrast, the majority of diffuse plaques showed no topographic relationship to CA. Cell bodies of neurons and/or glia were almost always involved in the diffuse plaques. In addition, beta-protein immunohistochemistry demonstrated amyloid deposits on the periphery of occasional neurons. These findings suggest that different mechanisms may be involved in the development of the different subtypes of SP in the brains of aged dogs.

Cerebral preamyloid deposits and congophilic angiopathy in aged dogs.

The brains of 7 dogs aged 6 to 18 years have been histochemically and immunohistochemically investigated at the light- and electron microscopy levels for preamyloid deposits and amyloid fibrils to verify the hypothesis that the accumulation of cleavage products of amyloid precursor protein is related not only to Alzheimer's disease but also to the normal aging of the brain. Preamyloid deposits were detected in the neuropil of the cerebral cortex and neostriatum, whereas amyloid fibrils were found in the walls of parenchimal and leptomeningeal vessels. The densities of preamyloid deposits in the neuropil and of deposits of amyloid fibrils in the vessel walls were higher in the brains of the most aged dogs. These findings suggest that aging of the canine brain is characterized by an accumulation of intermediate cleavage products of the amyloid precursor protein in both the neuropil and the vessel walls, and by processing of these products to amyloid fibrils in the vessel walls.

Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke.

Eight mares were infected with equid herpesvirus-1 subtype 1 isolated from a case of equine paresis. In two mares killed at 4 d.p.i. immunofluorescence showed endothelial cell infection together with thrombosis in the rete arteriosus of the nasal mucosa and also in the spinal cord of one of these mares. Circulating platelet counts in the other six mares fell as early as 2 d.p.i. and remained depressed for seven days. Circulating immune complexes started to appear at 2 d.p.i., reached maximum levels at 10 d.p.i., but were undetectable at 28 d.p.i. Three of the six remaining mares developed varying degrees of inco-ordination at 8 and 9 d.p.i. In the two inco-ordinate mares that were killed at 9 and 10 d.p.i. the haemorrhages in the spinal cord and brain were associated with extensive endothelial cell fluorescence and thrombus formation. Clinical paresis coincided with an increase in circulating complement fixing and neutralising antibodies which in all six mares were higher against the subtype 2 isolate than subtype 1. In five yearlings infected with a subtype 2 isolate of EHV-1 platelet counts remained normal and neither immune complexes nor viraemia, nor inco-ordination were detected.

Swine cerebrospinal angiopathy and demyelination and malacia.

In 15 pigs affected with cerebrospinal angiopathy accompanied by demyelination and malacia, the main symptoms were diarrhea and subsequent circling, spasms, sudden forward movements, ataxia, and inability to hold the head straight. Escherichia coli was isolated in a pure culture from the small intestine of pigs with diarrhea. The only gross change was a slight increase in cerebrospinal fluid. Histologic examination showed vascular lesions, demyelination, and malacia, most commonly located in the medulla oblongata, pons, and midbrain. The vascular lesions were degenerative and there were necrotic changes of the vessel walls and formation of periodic acid-Schiff positive perivascular eosinophilic droplets. Ultrastructurally, the swollen astrocytes around the vessels had many osmiophilic bodies in their cytoplasm with no limiting membrane. Demyelination and malacia, as well as vascular lesions, were considered to be the characteristic changes of cerebrospinal angiopathy. Our study suggests that E. coli may be a cause of cerebrospinal angiopathy.

Observations on vascular accidents in the central nervous system of neonatal foals.

A technique for the subarachnoid perfusion-fixation of the central nervous system was developed to help identify various significant vascular accidents (SVAs) in the central nervous system (CNS) of 24 neonatal foals submitted for necropsy. SVAs, comprising subarachnoid, parenchymal and nerve root haemorrhages, and oedema and necrosis, occurred in 17 foals, more frequently in the spinal cord than the brain. They occurred as frequently in premature foals as in those born at full term, in foals born dead as in foals born alive, and in foals born following dystocia with an assisted delivery as in foals born unassisted. Eight of the live foals showed neurological signs. Those with syndromes of cerebral disease tended to have brain SVAs, whilst all 3 with signs of spinal cord disease had SVAs restricted to the spinal cord. No association between the SVAs and other specific disease processes was detected in these foals although 2 premature foals born dead with equine herpesvirus-1 infection did have spinal cord SVAs only. A similar distribution of brain and/or spinal cord SVAs was detected in the foals born dead as in the live foals, but the lesions were more severe. It is concluded that the birth process itself may be a major factor in the development of SVAs and that some affected foals may exhibit a syndrome referable to spinal cord involvement.