A Novel Spongiform Leukoencephalomyelopathy in Border Terrier Puppies (original) (raw)
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Spongiform leukoencephalopathy in an adult mixed breed female dog
2020
Leukoencephalomyelopathy is a nonspecific lesion characterized by widespread vacuolation of central nervous system white matter. It is mainly of genetic basis, occurring in young pure breed dogs. This report describes a neurodegenerative disease associated to demyelination in an adult mixed breed female dog. After 20 days in a kennel with 12 other dogs, the dog showed progressive nervous signs with ataxia and inability to maintain balance. No other dog was affected. After 15 days, the animal was euthanized in extremis and necropsied. No macroscopic lesions of diagnostic relevance were present. Microscopically, status espongiosus was observed in white matter throughout the length of the neuroaxis, from frontal brain lobe to lumbar spinal cord. Specific stains of Kluver Barrera and immunohistochemistry for the detection of phosphorylated and non-phosphorylated neurofilaments, microglia, astrocytosis, oligodendrocytosis and myelin proteins in brain and spinal cord sections showed demyelination, axonal fragmentation and degeneration, microgliosis and decrease of oligodendrocytes. The anatomopathological study and epidemiological data suggests a primary demyelination due to decrease in number and function of oligodendrocytes, which is probably of genetic basis with late onset.
BMC Veterinary Research, 2013
Background: Leukoencephalomyelopathy is an inherited neurodegenerative disorder that affects the white matter of the spinal cord and brain and is known to occur in the Rottweiler breed. Due to the lack of a genetic test for this disorder, post mortem neuropathological examinations are required to confirm the diagnosis. Leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate levels is a rare, autosomal recessive disorder in humans that was recently described to have clinical features and magnetic resonance imaging (MRI) findings that are similar to the histopathologic lesions that define leukoencephalomyelopathy in Rottweilers. Leukoencephalopathy with brain stem and spinal cord involvement is caused by mutations in the DARS2 gene, which encodes a mitochondrial aspartyl-tRNA synthetase. The objective of this case report is to present the results of MRI and candidate gene analysis of a case of Rottweiler leukoencephalomyelopathy to investigate the hypothesis that leukoencephalomyelopathy in Rottweilers could serve as an animal model of human leukoencephalopathy with brain stem and spinal cord involvement. Case presentation: A two-and-a-half-year-old male purebred Rottweiler was evaluated for generalised progressive ataxia with hypermetria that was most evident in the thoracic limbs. MRI (T2-weighted) demonstrated wellcircumscribed hyperintense signals within both lateral funiculi that extended from the level of the first to the sixth cervical vertebral body. A neurodegenerative disorder was suspected based on the progressive clinical course and MRI findings, and Rottweiler leukoencephalomyelopathy was subsequently confirmed via histopathology. The DARS2 gene was investigated as a causative candidate, but a sequence analysis failed to identify any diseaseassociated variants in the DNA sequence.
MRI Findings in a Rottweiler with Leukoencephalomyelopathy
Journal of the American Animal Hospital Association, 2013
A 22 mo old male rottweiler presented with a 1 mo progressive history of general proprioceptive ataxia and upper motor neuron tetraparesis. Neurologic examination was consistent with a lesion affecting the first through fifth cervical spinal cord segments. MRI disclosed bilaterally symmetric hyperintensities on T2-weighted (T2W) images in the crus cerebri and pyramidal tracts of the brain and the dorsal portion of the lateral funiculi of the cervical spinal cord. Fifty days after initial presentation, the dog was euthanized due to disease progression. Pathologic examination of the central nervous system (CNS) revealed a bilaterally symmetric chronic leukoencephalomyelopathy (LEM) consistent with previous reports of LEM in rottweilers. To the authors' knowledge, this is the first report to describe the MRI characteristics of LEM in the rottweiler. The topography of the changes observed with MRI paralleled the pathologic changes, which were widespread loss of myelin, decreased axon numbers, and astroglial proliferation. Consequently, MRI of the CNS of affected rottweilers may aid in establishing a presumptive antemortem diagnosis of LEM.
Necrotizing Meningoencephalitis in Atypical Dog Breeds: A Case Series and Literature Review
Journal of Veterinary Internal Medicine, 2013
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 breedrestricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.
Journal of Veterinary Medical Science, 2013
To evaluate the ability of serum glial fibrillary acidic protein (GFAP) concentration as a diagnostic marker for canine central nervous system (CNS) disorders, sera from dogs with various CNS (n=47) and non-CNS (n=56) disorders were measured for GFAP by using an ELISA kit. Healthy Beagles (n=15) and Pug dogs (n=12) were also examined as controls. Interestingly, only Pug dogs with necrotizing meningoencephalitis (NME) showed elevated serum GFAP concentrations (<0.01 to 1.14 ng/ml), while other breeds of dogs with NME did not. Among the Pug dogs with NME, serum GFAP concentrations did not correlate with their clinical features, such as ages or survival times. Our data indicate the usefulness of serum GFAP as a novel marker for Pug dogs with NME.
Canine spongiform leukoencephalomyelopathy is associated with a missense mutation in cytochrome b
Neurobiology of Disease, 2006
Two families of dogs (Australian cattle dogs and Shetland sheepdogs) with an inherited ''spongiform leukoencephalomyelopathy'' were identified, with widespread vacuolation of white matter of the brain and spinal cord. Affected dogs of both breeds developed tremors at 2-9 weeks of age followed by progressive neurological worsening with ataxia, paresis, paralysis, spasticity, and cranial nerve dysfunction. The modes of inheritance of both families were most likely maternal. The cerebrospinal fluid (CSF) analysis showed elevated ratio of 3-OH butyrate to acetoacetic acid. Mitochondrial DNA sequencing showed a G to A transition at 14,474 nt (G14474A, GenBank accession no. NC _ 002008) that results in an amino acid change of valine-98 to methionine (V98M) of mitochondrial encoded cytochrome b. Western blot analysis showed increased levels of core I and core II but decreased level of cytochrome c 1 of the complex III and cytochrome c oxidase of the complex IV of the respiratory chain.
Journal of Veterinary Medical Science, 2019
A one-year-old male Maltese terrier presented with mild ataxia and disorientation for 4 months. Over time, clinical signs progressed from paraparesis to non-ambulatory tetraparesis, voice change and dysphagia. Histological examination revealed concurrent leukoencephalomyelitis and polyneuritis. Infectious etiologies, including dengue, Japanese encephalitis, Zika, canine distemper, pseudorabies, rabies, toxoplasmosis, neosporosis, leishmaniasis, and encephalitozoonosis, were ruled out by PCR and/or immunohistochemical (IHC) staining. IHC tested on neurological tissues highlighted a heterogeneous population of infiltrating T and B lymphocytes admixed macrophages. Therefore, this case was diagnosed with current leukoencephalomyelitis and polyneuritis, resembling combined central and peripheral demyelination (CCPD), an autoimmune inflammatory demyelinating disease affecting both the CNS and PNS in humans.
Globoid cell leukodystrophy in cairn and West Highland white terriers
The Journal of heredity
Krabbe disease or globoid cell leukodystrophy (GLD) is an autosomal recessive disorder resulting from the defective lysosomal hydrolysis of specific galactolipids found primarily in myelin. This leads to severe neurological symptoms including seizures, hypotonia, blindness, and death, usually before 2 years of age in human patients. In addition to human patients, several animals, including dog, mouse, and monkey, have the same disease caused by a deficiency of galactocerebrosidase (GALC) activity. In this article we describe studies in cairn and West Highland white terriers (WHWT) affected with GLD. Through a screening test based on the molecular defect found in these breeds, over 50 cairn terrier carriers have been identified and a colony of five carrier dogs has been established. Affected dogs from this colony plus an affected WHWT were available for study. An affected WHWT was evaluated by magnetic resonance imaging at 6 and 11 months of age and pronounced changes in the T-2 weig...