A novel idiopathic superficial neocortical degeneration and atrophy in young adult dogs.

A diffuse, chronic, superficial neocortical degeneration that resulted in atrophy was detected in five 1 to 2-year-old-dogs. Presenting neurologic signs included ataxia, dysphagia, blindness, and mentation changes. Magnetic resonance imaging on brains from 2 dogs demonstrated severe bilateral cerebrocortical atrophy and enlarged lateral and third ventricles. Grossly, multifocal, bilaterally symmetrical, extensive areas of neocortical brownish discoloration associated with atrophy of gyri and sulcal widening were recorded in the dorsal and lateral cerebral hemispheres in 3 dogs. Microscopically, in all dogs there was subacute to chronic superficial neocortical degeneration affecting all cerebral lobes, ranging from loss of the molecular layer to less frequent larger and deeper cavitations of variable size. Clinical signs probably resulted from a combination of primary neocortical degeneration and secondary degeneration in the corticobulbar and corticospinal tracts. The distribution pattern of gross and histologic cerebrocortical lesions suggests that this is a novel degenerative canine cerebral disease.

Leukoencephalomyelopathy of mature captive cheetahs and other large felids: a novel neurodegenerative disease that came and went?

A novel leukoencephalomyelopathy was identified in 73 mature male and female large captive felids between 1994 and 2005. While the majority of identified cases occurred in cheetahs (Acinonyx jubatus), the disease was also found in members of 2 other subfamilies of Felidae: 1 generic tiger (Panthera tigris) and 2 Florida panthers (Puma concolor coryi). The median age at time of death was 12 years, and all but 1 cheetah were housed in the United States. Characteristic clinical history included progressive loss of vision leading to blindness, disorientation, and/or difficulty eating. Neurologic deficits progressed at a variable rate over days to years. Mild to severe bilateral degenerative lesions were present in the cerebral white matter and variably and to a lesser degree in the white matter of the brain stem and spinal cord. Astrocytosis and swelling of myelin sheaths progressed to total white matter degeneration and cavitation. Large, bizarre reactive astrocytes are a consistent histopathologic feature of this condition. The cause of the severe white matter degeneration in these captive felids remains unknown; the lesions were not typical of any known neurotoxicoses, direct effects of or reactions to infectious diseases, or nutritional deficiencies. Leukoencephalomyelopathy was identified in 70 cheetahs, 1 tiger, and 2 panthers over an 11-year period, and to our knowledge, cases have ceased without planned intervention. Given what is known about the epidemiology of the disease and morphology of the lesions, an environmental or husbandry-associated source of neurotoxicity is suspected.

Ventricular and extraventricular ependymal tumors in 18 cats.

Ependymal tumors are reported rarely in domestic animals. The aims of this study were to examine the clinical and pathologic features of ventricular and extraventricular ependymomas and subependymomas in 18 domestic cats examined between 1978 and 2011. Parameters examined included age, sex, breed, clinical signs, and macroscopic and histopathologic features. The mean age of affected cats was 9 years, 4 months; median age, 8.5 years. There were 8 female and 4 male cats, and 6 cats for which sex was not recorded. Breeds included 10 domestic shorthaired, 2 domestic longhaired, 1 Persian, and 1 Siamese. Clinical signs included altered mentation or behavior, seizures, circling, propulsive gait, generalized discomfort, and loss of condition. The tumors often formed intraventricular masses and usually arose from the lining of the lateral or third ventricles, followed by the fourth ventricle, mesencephalic aqueduct, and spinal cord central canal. Three tumors were extraventricular, forming masses within the cerebrum and adjacent subarachnoid space. Histologically, 15 tumors were classified as variants of ependymomas (classic, papillary, tanycytic, or clear cell) and 3 as subependymomas. Tumors were generally well demarcated; however, 6 ependymomas focally or extensively infiltrated the adjacent neural parenchyma. Characteristic perivascular pseudorosettes were observed in all ependymomas; true rosettes were less common. Some tumors had areas of necrosis, mineralization, cholesterol clefts, and/or hemorrhage. This cohort study of feline ependymal tumors includes subependymoma and primary extraventricular ependymoma, variants not previously described in the veterinary literature but well recognized in humans.

Mapping of Purkinje neuron loss and polyglucosan body accumulation in hereditary cerebellar degeneration in Scottish terriers.

A hereditary cerebellar degenerative disorder has emerged in Scottish Terriers. The aims of this study were to describe and quantify polyglucosan body accumulation and quantify Purkinje neurons in the cerebellum of affected and control dogs. The brains of 6 affected Scottish Terriers ranging in age from 8 to 15 years and 8 age-matched control dogs were examined histopathologically. Counts of Purkinje neurons and polyglucosan bodies were performed in control and affected dogs on cerebellar sections stained with periodic acid-Schiff. Affected dogs showed a significant loss of Purkinje neurons compared with control dogs (vermis: P < .0001; hemisphere: P = .0104). The degeneration was significantly more pronounced dorsally than ventrally (P < .0001). There were significantly more polyglucosan bodies in the ventral half of the vermis when compared with the dorsal half (P < .0001) in affected dogs. In addition, there were more polyglucosan bodies in the ventral half of the vermis in affected dogs than in control dogs (P = .0005). Polyglucosan bodies in all affected dogs stained positively with toluidine blue and alcian blue. Immunohistochemically, polyglucosan bodies in affected dogs were positive for neurofilament 200 kD and ubiquitin and negative for glial fibrillary acidic protein, synaptophysin, neurospecific enolase, vimentin, and S100; the bodies were negative for all antigens in control dogs. Ultrastructurally, polyglucosan bodies in 1 affected dog were non-membrane-bound, amorphous structures with a dense core. This study demonstrates significant Purkinje cell loss and increased polyglucosan bodies in the cerebellum of affected Scottish Terriers.

Hereditary cerebellar degeneration in Scottish terriers.

BACKGROUND: Hereditary cerebellar degeneration is described in several dog breeds. This heterogeneous group of diseases causes cerebellar ataxia associated with cerebellar cortical degeneration. OBJECTIVE: To report the clinical and histopathological features, and describe the mode of inheritance of hereditary cerebellar degeneration in Scottish Terriers. ANIMALS: Sixty-two affected dogs recruited through the Scottish Terrier Club of America. MATERIALS AND METHODS: Prospective, observational study: Owners of affected dogs were contacted for a description of clinical signs, age of onset, and disease progression. Medical records, videotapes of gait, and brain imaging were evaluated. When possible, necropsy was performed and the brain examined histopathologically. Prevalence of the disease was estimated and a pedigree analysis was performed to determine mode of inheritance. RESULTS: Gait abnormalities were noted in the 1st year of life in 76% of dogs, and progressed slowly; only 1 of 27 dogs dead at time of writing was euthanized because of cerebellar degeneration. Clinical signs included wide based stance, dysmetria, intention tremor, and difficulty negotiating stairs and running. Cerebellar atrophy was detected on magnetic resonance imaging. On histopathological examination, there was segmental loss of Purkinje neurons, thinning of molecular and granular layers, and polyglucosan bodies in the molecular layer. Prevalence of disease was estimated at 1 in 1,335 American Kennel Club registered Scottish Terriers. Genetic analysis results are consistent with an autosomal recessive mode of inheritance. CONCLUSION AND CLINICAL IMPORTANCE: A hereditary cerebellar degenerative disorder with a relatively mild phenotype has emerged in the Scottish Terrier. Genetic studies are needed.

Four Cases of the Melanotic Variant of Malignant Nerve Sheath Tumour: a Rare, Aggressive Neoplasm in Young Dogs with a Predilection for the Spinal Cord.

Four cases of a rare melanotic variant of malignant nerve sheath tumour (MNST) in dogs are described. All four cases presented with neurological clinical signs due to multicentric, intradural, intra- and extraparenchymal neoplasms that surrounded the spinal and cranial nerves and infiltrated the adjacent spinal cord and brain. The dogs were young (3 months to 3 years of age), all were female and four different breeds were represented. Characteristic histological features were interweaving fascicles of spindle-shaped cells, sometimes with an architecture reminiscent of Antoni A and B patterns. Some spindle cells showed prominent cytoplasmic melanin pigmentation and such cells were positive by Masson-Fontana stain. Immunohistochemistry performed in three cases was positive for S100 and vimentin, strongly positive for melan A in the melanized cells and negative for glial fibrillary acidic protein and periaxin. Non-melanized cells did not express melan A. Transmission electron microscopy findings in one case were consistent with a peripheral nerve sheath tumour and demonstrated cytoplasmic pre-melanosomes and melanosomes. Melanotic variants of MNSTs are rare in animals with only a solitary report of two previous canine cases in the literature.

Encephalomyelopathy and polyneuropathy associated with neuronal vacuolation in two Boxer littermates.

Neuronal vacuolation and spinocerebellar degeneration is a rare, presumably inherited condition that is reported only in Rottweilers and in crossbred dogs with known or potential Rottweiler heritage. Gross and histopathologic findings include laryngeal muscle atrophy, neuronal vacuolation, and a combined central and peripheral axonopathy. Two 6-month-old Boxer puppies from the same litter were referred for evaluation of progressive pelvic limb paresis and ataxia, upper airway stridor, and visual deficits. Examination of each dog suggested a combined myelopathy and peripheral neuropathy, as well as congenital ocular disease. Gross lesions were limited to atrophy of the intrinsic laryngeal muscles. Histopathologically, there was diffuse loss of axons and myelin in the dorsolateral and ventral funiculi throughout the spinal cord and extending into the caudal aspect of the brain stem. Vacuolation of scattered neuronal cell bodies was present in the spinal cord and selected brain stem nuclei. Multifocal axonal degeneration and demyelination was observed in the recurrent laryngeal nerve, sciatic nerve, and brachial plexus and was most severe in the recurrent laryngeal nerve. Ocular abnormalities included microphthalmia, cataracts, and retinal dysplasia. The findings in these Boxer dogs, unrelated to the Rottweiler breed, are analogous to the syndrome of neuronal vacuolation and spinocerebellar degeneration reported in Rottweilers.

Magnetic resonance imaging characteristics of necrotizing meningoencephalitis in Pug dogs.

BACKGROUND: The magnetic resonance imaging (MRI) characteristics of necrotizing meningoencephalitis (NME) are not well documented. OBJECTIVES: To describe common MRI features of NME, to compare the MRI features to histopathologic findings, and to determine whether or not MRI lesions are predictive of survival time. ANIMALS: Eighteen Pugs with NME. METHODS: Retrospective MRI case study of Pugs identified by a search of medical records at 6 veterinary institutions. Eighteen dogs met inclusion criteria of histopathologically confirmed NME and antemortem MRI exam. MRI lesions were characterized and compared with histopathology with the kappa statistic. Survival times were compared with MRI findings by use of Mann-Whitney U-tests and Spearman's rho. RESULTS: Twelve of 18 lesions were indistinctly marginated with mild parenchymal contrast enhancement. Prosencephalic (17/18) lesion distribution included the parietal (16/18), temporal (16/18), and occipital (16/18) lobes. There were cerebellar (4/18) and brainstem (3/18) lesions. Asymmetric lesions were present in both gray and white matter in all dogs. Falx cerebri shift was common (11/18), and 6 dogs had brain herniation. Leptomeningeal enhancement was present in 9/18 dogs. A moderate positive association was found between parenchymal contrast enhancement and both necrosis (kappa= 0.45; P= .045) and monocytic inflammation (kappa= 0.48; P= .025). Higher MRI lesion burden was correlated with longer time from disease onset to MRI (P= .045). MRI lesion burden did not correlate to survival time. CONCLUSIONS AND CLINICAL IMPORTANCE: Asymmetric prosencephalic grey and white matter lesions with variable contrast enhancement were consistent MRI changes in Pugs with confirmed NME. While not pathognomonic for NME, these MRI characteristics should increase confidence in a presumptive diagnosis of NME in young Pugs with acute signs of neurologic disease.

Cerebellar cortical abiotrophy in Lagotto Romagnolo dogs.

This case report documents two pathological variations of potentially inherited, cerebellar cortical abiotrophy in two unrelated Lagotto Romagnolo breed dogs. The first dog had an atypical lesion in the cerebellar cortex with depletion of cerebellar granular cell layer and sparing of the Purkinje cell layer. The second case had degenerative changes in both Purkinje and granular cell layers. The clinical picture was similar in both cases presented, although the severity of the signs of cerebellar dysfunction varied.

Neuroendodermal cyst in the fourth ventricle of a dog.

CASE REPORT: We describe the MRI appearance and surgical outcome of a rare neuroendodermal cyst in the fourth ventricle of a German Shorthaired Pointer. The dog presented with uncoordinated gait and occasional falling that increased when she became excited. The MRI appearance is shown and the surgical treatment described. Recurrence occurred on two occasions and the dog was euthanased. CONCLUSION: Recurrence of these cysts is highly likely unless there is complete surgical resection.

Hemifacial Microsomia in a Cat.

A 7-month-old domestic medium hair cat presented with facial asymmetry affecting the bony and soft tissue structures of the right side of the head including the maxilla, nose, eye and pinna of the ear. Additionally, neurological dysfunction of the facial and vestibulocochlear nerves on the affected side was present. A congenital malformation affecting the first and second embryologic pharyngeal arches was suspected. This is the first case of hemifacial microsomia of likely congenital origin reported in a cat.

Clinical and topographic magnetic resonance characteristics of suspected brain infarction in 40 dogs.

Medical records of 40 dogs presented for evaluation of acute-onset, nonprogressive, intracranial dysfunction by means of magnetic resonance imaging (MRI) diagnosis of brain infarction were reviewed. Location of the brain infarcts was: 11 of 38, telencephalic; 8 of 38, thalamic/midbrain; 18 of 38, cerebellar; and 3 of 38, multifocal. Telencephalic infarcts developed within the territory of the middle cerebral (4/11), rostral cerebral (2/11), and striate (5/11) arteries. Thalamic/midbrain infarcts developed within the territory of perforating arteries of the caudal portion of the thalamus and rostral portion of the brainstem (8/8). All cerebellar infarcts (18/38) were within the territory of the rostral cerebellar artery or one of its branches. All infarcts appeared nonhemorrhagic, with marked contrast enhancement observed in only 3 of 38 dogs, all of which were imaged more than 7 days after the onset of signs of neurologic dysfunction. Diffusion-weighted imaging (DWI) sequences were available from 6 dogs, all imaged within 5 days of the onset of signs of neurologic dysfunction. Suspected infarcts were hyperintense on DWI sequences and were hypointense on the apparent diffusion coefficient map. Telencephalic infarcts caused abnormal mental status, contralateral postural reaction deficit, contralateral nasal hypalgesia, contralateral menace deficit, and ipsilateral circling. Thalamic/midbrain infarcts caused contralateral or ipsilateral postural reaction deficit, contralateral menace deficit, ipsilateral head tilt or turn, nystagmus, ventrolateral strabismus, and anisocoria. Cerebellar infarcts caused ipsilateral asymmetric cerebellar quality ataxia, head tilt, intermittent opisthotonus, nystagmus, and ipsilateral menace deficit with apparent normal vision.

Results of diagnostic investigations and long-term outcome of 33 dogs with brain infarction (2000-2004).

Medical records of 33 dogs presented for acute onset, nonprogressive, intracranial dysfunction that had a magnetic resonance imaging diagnosis of brain infarction were reviewed. Postmortem confirmation of brain infarction was available in 10 dogs. All dogs were evaluated by CBC, serum biochemistry, thyroid and adrenal testing, urinalysis, thoracic and abdominal imaging, and cerebrospinal fluid analysis. Results of coagulation profile and arterial blood pressure were available in 32/33 and 28/33 dogs, respectively. On the basis of the imaging findings, infarcts were classified depending on their type (territorial or lacunar) and location within the brain (telencephalic, 10/33; thalamic/midbrain, 8/33; cerebellar, 15/33). No marked associations among location or type of infarct and patient age and sex, occurrence of systemic hypertension, and the presence or absence of a concurrent medical condition were identified. Small breed dogs (< or =15 kg) were significantly more likely to have territorial cerebellar infarcts, whereas large breed dogs (>15 kg) were significantly more likely to have lacunar thalamic or midbrain infarcts. A concurrent medical condition was detected in 18/33 dogs with brain infarcts, with chronic kidney disease (8/33) and hyperadrenocorticism (6/ 33) being most commonly encountered. Of 33 dogs, 10 were euthanized because of the severity and lack of improvement of their neurologic status or the severity of their concurrent medical condition. No association was identified between type or location of infarct and patient outcome. Dogs with concurrent medical conditions had significantly shorter survival times than those with no identifiable medical condition and were significantly more likely to suffer from recurrent neurologic signs because of subsequent infarcts.

Risk factors associated with equine motor neuron disease: a possible model for human MND.

Equine motor neuron disease (EMND), a newly described neurodegenerative disease, bears a striking resemblance to progressive muscular atrophy (PMA) in humans. We present a comparison of the equine and human diseases and the results of a case-control study conducted to identify intrinsic factors associated with EMND. Cases included all horses with a confirmed diagnosis of EMND diagnosed in the United States since 1985 (32 cases). Controls included horses diagnosed with either cervical stenotic myelopathy, equine degenerative myeloencephalopathy, or protozoan myelitis at the Veterinary Teaching Hospital at the College of Veterinary Medicine, Cornell University (153 controls). Logistic regression analysis identified factors associated with the risk of EMND. Risk factors considered were age, sex, and breed of the horse. Most cases of EMND (30 of 32) have been sporadic. There was a breed association with the risk of EMND. Quarter horses were at a high risk for developing EMND (odds ratio [OR] = 12.7; 95% confidence interval, 3.3 to 49.6); thoroughbred horses were at increased risk (OR = 2.9, 0.8 to 10.4). There was also an age association with the risk of EMND. The risk increased with age, peaked at 16 years, and then declined, a pattern similar to that for amyotrophic lateral sclerosis in humans. There was no sex association with the disease. Despite the breed association, equine lymphocyte antigen studies have not revealed a systematic pattern, suggesting that genetic factors influencing susceptibility to EMND may be outside the major histocompatibility complex.

Tibetan terrier model of canine ceroid lipofuscinosis.

Over a 10-year period, we have studied the Tibetan terrier's visual electrophysiology, light and electron microscopic (EM) retinal characteristics of a slowly evolving inherited ceroid lipofuscinosis (CL). The retinal degeneration with CL inclusions (rdi) in the inner nuclear layer (bipolar cells) and nerve fiber layer (ganglion cells) has been called "rdi" to differentiate the visual abnormality from typical early retinal degeneration (erd) reported also in the Tibetan terrier. The unique "rdi" electroretinogram (ERG) gives a predominant P III wave at age 7 weeks but becomes more characteristically depressed in all phases over several years. Nyctalopia is the only functional abnormality for the first 5 to 6 year of life. Signs are remarkably few considering the pathology. Microscopic studies of the retina show accumulations, increasing with age, of autofluorescent dense inclusion particles which stain intensely by Luxol fast blue, PAS, and acid-fast procedures. Ultrastructural studies of the retina show the dense particles to be lamellar membranes repeating every 2 to 4 nm, consistent with ceroid lipofuscin. The inner retinal layers were always the target layer to be affected first and most severely. The ganglion cells were most frequently involved. The photoreceptors eventually degenerated but relatively few particles were found in this layer. The cytosomes in the cerebral cortex and brainstem neurons resemble lipofuscin, containing granular, lamellar, and globular components. Different pigment bodies were present in the cerebellar Purkinje cells. Neuronal loss which was moderate in the cerebellum and mild in the cerebrum was accompanied by astrogliosis and a striking presence of macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Canine X-linked muscular dystrophy as an animal model of Duchenne muscular dystrophy: a review.

Canine X-linked muscular dystrophy is a spontaneously occurring, progressive, degenerative myopathy of dogs that is clinically and pathologically similar to Duchenne muscular dystrophy in man. The molecular basis for the disease has been shown to be a lack of dystrophin, the protein product of the Duchenne muscular dystrophy gene. Breeding colonies of dystrophic dogs have been established. This report reviews the findings of genetic, clinical, pathologic, molecular biologic, and immunocytochemical studies of the canine model, and compares the features of the canine disease to those of Duchenne dystrophy in man.