Canine Distemper Encephalomyelitis Research Articles

Role of glial fibrillary acidic protein (GFAP) and neurofilament (NF) expression in the pathophysiology of canine distemper encephalomyelitis

Objectives: Canine distemper virus (CDV), a member of the genus Morbillivirus of the family Paramyxoviridae, is the causative agent of canine distemper, a fatal and highly contagious disease that affects dogs and other carnivores. This study aimed to investigate whether there is a correlation between glial fibrillary acidic protein (GFAP) and neurofilament (NF) expression in canine distemper encephalomyelitis (CDE) and the severe neuropathology that occurs.
 Materials and Methods: GFAP and NF expression levels in the brain tissue of 13 dogs diagnosed with CDE were investigated by immunohistochemical method.
 Results: The results of the study revealed that GFAP (P < 0.005) and NF (P < 0.005) expression levels in brain tissue were significantly increased in CDV-infected dogs compared to healthy, uninfected dogs. GFAP expression was mainly observed in endothelial cells and astrocytes, whereas NF expression was mainly found in neurons. In addition, it was found that the expression of both GFAP and NF was more pronounced in the areas with the most severe neuropathological findings.
 Conclusions: This study demonstrated pathological astrocyte reactivation and neuronal degeneration at the molecular level. These findings provide information about the stage of the disease. This study clearly demonstrated that detailed information about the prognosis of the disease can be obtained from GFAP and NF expression. Since GFAP/NF levels provide information about the severity of the disease, they can be used clinically. Therefore, further research into the involvement of GFAP and NF expression in the pathophysiology of CDE has great potential to improve our understanding of this complex neurological disorder.

Estimation of Myelin Basic Protein Levels in Natural Cases of Canine Distemper Encephalomyelitis

Background: Canine distemper virus (CDV) affects both white and grey matter in the central nervous system (CNS). It causes demyelination of white matter tracts, which releases myelin basic protein (MBP) into the cerebrospinal fluid (CSF). MBP levels in CSF could therefore indirectly indicate the extent of white matter damage. The objective of this study was to determine MBP levels in the CSF of dogs infected with natural cases of neurologic distemper. Methods: In this study samples from healthy dogs, clinical cases of CDV and stray dogs from in and around the institute were collected for investigation. The infection of the CNS was established by estimating the albumin quotient and, for 16 cases, by histopathology. CSF biochemical parameters were analysed for 35 sero-positive clinical cases of neurologic distemper. MBP levels in samples were estimated by quantitative ELISA. Stray dogs (6 cases) were also screened for this purpose. Result: MBP levels in CSF were significantly (p≤0.05) increased in natural cases of distemper encephalomyelitis and stray dogs relative to controls. Three of the neurologic distemper cases clinically recovered despite high MBP levels, and two stray dogs also had higher MBP concentrations. High CSF MBP may therefore not be a useful marker for predicting the outcome of neurologic distemper.

Relation of Clinical Signs to Pathological Changes in 19 Cases of Canine Distemper Encephalomyelitis

In an attempt to associate the clinical neurological syndromes with the neuropathological features of canine distemper (CD), 19 spontaneous cases with neurological involvement were examined, before and after euthanasia. Seventeen dogs were less than one year of age and all except two (89¶4%) were unvaccinated against CD. Various extraneural signs associated with CD encephalomyelitis (CDE) were seen in 15 dogs. Generalized or localized myoclonus was the most common sign observed (13/19). Seventeen of the dogs presented with signs suggestive of one neuroanatomical location of lesions. Of these animals, seven had signs of cerebral, two of cerebellar, four of cervical, one of cervicothoracic, two of thoracolumbar and two of lumbosacral syndrome. The diagnosis of CD was confirmed immunohistochemically (detection of CD viral antigen), serologically (neutralizing serum antibody titre →16) and histopathologically (CDV inclusion bodies, type of central nervous system lesions). An association of the neuroanatomical lesion location and the histopathological findings was noted in 14 out of 17 dogs (82¶3%). Myoclonus could be attributed to lower motor neuron damage in eight out of 13 dogs (61¶5%).

Immunohistochemical demonstration of canine distemper virus antigen as an aid in the diagnosis of canine distemper encephalomyelitis

Brain tissue from 33 dogs with non-suppurative encephalitis was examined for evidence of canine distemper virus (CDV) encephalitis. Sections were examined for lesions, inclusion bodies, syncytial cells and CDV antigen using a double bridge unlabelled antibody enzyme technique. Histopathological lesions considered to be typical of granulomatous meningoencephalomyelitis were found in seven dogs. They all lacked inclusion bodies, syncytial cells and CDV antigen. The remaining 26 dogs all had histopathological lesions typical of CDV encephalitis. Inclusion bodies were found in 24 dogs, four of which also had syncytial cells and CDV antigen was detected immunocytochemically in 25. One dog had no inclusion bodies or syncytial cells and was immunohistochemically negative. Syncytial cells have been found to be of limited diagnostic value for the diagnosis of CDV encephalitis. While inclusion bodies proved to be a good diagnostic criterion for the confirmation of CDV infection, the immunohistochemical demonstration of CDV antigen proved to be superior. CDV antigen was more prevalent than inclusion bodies in tissue sections and much more easily detectable.

Evidence of oligodendrocyte infection and degeneration in canine distemper encephalomyelitis

Canine distemper encephalomyelitis is an important neurological disease of the dog and is also of comparative medical interest. With some viral strains, demyelinating encephalomyelitis is seen; whether or not oligodendrocyte infection occurs has remained controversial. By examining very early white matter lesions unequivocal oligodendrocyte infection has been identified. Accordingly the direct effect of virus on oligodendrocyte viability must be weighed in considering the pathogenesis of this canine CNS infection.

Demyelination in canine distemper encephalomyelitis: an ultrastructural analysis.

SummaryA morphological study of selected white matter lesions was carried out in three dogs with canine distemper encephalomyelitis. Two dogs had experimental infections while the third was a spontaneous case. Two stages were identified in the process of demyelination. The earliest evidence of myelin injury was a ballooning change in myelin sheaths involving single or multiple axons. This was followed by a progressive stripping of compact sheaths by the cytoplasmic fingers of phagocytic cells which infiltrated and removed myelin lamellae. Some axonal necrosis also accompanied these changes. Where demyelination occurred, canine distemper viral nucleocapsids were found in astrocytes, macrophages, ependymal cells and infiltrating lymphocytes. In contrast, oligodendrocytes were conspicuous by their apparent lack of infection. Thus it seems that myelin loss cannot be ascribed to oligodendrocyte infection. Perturbed astrocyte function following canine distemper viral infection may cause oedema of myelin sheaths, leading to ballooning and primary demyelination. Cells which phagocytosed myelin were mainly identified as microglial cells with lesser involvement by astrocytes. Rarely, oligodendrocytes also acted as macrophages. Myelin debris was engulfed in bulk or as small droplets into coated pits. Remyelination was present in established plaques although not in great abundance, perhaps due to the diminished oligodendrocyte numbers and a relative increase in immature forms of these cells. These observations are compared to similar changes observed in other demyelinating diseases of animals and man.

Demyelinating canine distemper encephalomyelitis: measurement of myelin basic protein in cerebrospinal fluid

Beagle dogs were experimentally infected with the Cornell A75-17 strain of canine distemper virus. At three time points post-infection (PI), immunoreactive myelin basic protein (MBP) was measured in cerebrospinal fluid (CSF). Levels were correlated with neuropathological findings, interferon in CSF and virus isolation from the brain. CSF from animals inoculated with Cornell A75-17 strain often showed detectable immunoreactive MBO late in the disease course. As anticipated from earlier morphological studies, CSF drawn around day 20 PI lacked MBP while subsequent samples were positive. Dogs with severe demyelination had elevated values of immunoreactive MBP while dogs with only mild inflammation had little or none. Release of MBP or MBP peptides into CSF of dogs with canine distemper may be a valuable laboratory test in studies of the natural history of this disease and in assessing the response to treatment. Whether an immune response to MBP plays an immunopathogenic role in the chronic, demyelinating phase of canine distemper encephalitis remains to be determined.

Surgical conditions of the canine spine

There are various types of pathological change which can affect the spine of the dog. The approach to neurological diagnosis and localization of the lesion has been discussed previously ( Wheeler, 1985). Certain conditions are not considered to be ‘surgical’ in nature, for example, canine distemper encephalomyelitis ischaemic myelopathy and chronic degenerative radiculo myelopathy, and are thus not discussed here. However, their importance in differential diagnosis must not be ignored. Surgical treatments are described where applicable. The reader is referred to the list of further texts for details of technique.

Syncytia formation: An aid in the diagnosis of canine distemper encephalomyelitis

Syncytia formation has been observed in response to experimental Canine Distemper Virus (CDV) infection in specific-pathogen-free Beagle dogs. Multinucleated giant cells are most frequently found in white matter lesions of the brain and in the anterior uvea of the eye. Lymph nodes and the lung are occasionally positive, while the leptomeninges will also rarely harbour syncytia. The mechanism of syncytia formation and their possible importance in the pathogenesis of the disease are briefly discussed. Widespread tissue syncytia formation is a feature of CDV infection which should assist in identifying cases of non-suppurative encephalitis in the dog caused by this agent.

Canine distemper encephalomyelitis: Variation with virus strain

Disease induced by 3 virulent strains of Canine Distemper Virus (CDV) was compared in specific pathogen-free Beagle dogs. All strains produced an encephalomyelitis but variation was observed in the severity, clinical course and resulting neuropathology. Infection with Snyder Hill strain of CDV was consistently acute; dogs either succumbed 14 to 19 days post-inoculation (PI) or recovered. Lesions in the neuraxis were those of a polioencephalomyelitis. In contrast, CDV strain A75-17 produced subacute to chronic disease in which demyelination was the predominant finding. Some dogs succumbed, generally around 28 to 42 days PI. Total recovery was again recorded for some members of the group. Others developed persistent central nervous system (CNS) infection but remained clinically stable until electively killed with barbiturate, up to 62 days PI. CDV strain R252 also induced delayed, predominantly white matter disease with a mixed pattern of mortalities, persistent infections and recoveries, similar to A75-17. Neutralizing antibody responses correlated with the disease course. Dogs which died had low serum titres or lacked serum antibody. Recovering dogs had the earliest and highest titres. A few dogs with persistent CNS infection had antibody in the cerebrospinal fluid also. Current concepts of the pathogenesis of canine distemper encephalomyelitis (CDE) are discussed and a basis for the strain-dependent clinical and pathological expression of CDE is proposed. Viral strain appears to be an important factor in this common disease of the canine CNS.

DOES VIRUS PERSIST IN THE UVEA IN MULTIPLE SCLEROSIS, AS IN CANINE DISTEMPER ENCEPHALOMYELITIS?

Epidemiological studies suggest that multiple sclerosis (MS) might be triggered by an infectious agent. Uveitis has been observed in a small percentage of MS patients. Dogs with canine distemper encephalomyelitis, another demyelinating disease of the central nervous system, have an anterior uveitis which is usually mild and asymptomatic, and dogs with persistent CNS infection and chronic distemper encephalomyelitis harbour virus persistently in the uvea. These observations in dogs suggest that pathological and virological studies of the uveitis associated with MS would be worth while.

Early events in canine distemper demyelinating encephalomyelitis

The early neuropathological development of demyelinating Canine Distemper Encephalomyelitis (CDE) was studied in SPF dogs. Neural tissues were examined up to 30 days post infection (PI). Three phases of activity were observed. The primary event (first observed 8 days PI) was a nonsuppurative encephalomyelitis associated with the initiation of central nervous system (CNS) infection by virus-laden lymphocytes. At 24 days PI noninflammatory demyelination occurred in well defined, subependymal foci. Cell fusion and syncytia formation accompanied this early demyelination. The third phase, found at day 30 PI in one dog showing signs of recovery, was a second wave of nonsuppurative inflammation. The initial encephalomyelitis was widely disseminated throughout the CNS but subsequent demyelination appeared to be initiated from within the ventricular system. Myelin was phagocytosed by endogeneous CNS macrophages often infected with Canine Distemper Virus (CDV). The possible importance of viral induced cell fusion as well as immune factors in the mechanism of demyelination are discussed.

On the development of CNS lesions in natural canine distemper encephalomyelitis

Acute lesions within spinal cord white matter have been studied by light and electron microscopy in 3 dogs suffering from the acute form of canine distemper encephalomyelitis (CDE). Prominent features of these lesions were viral inclusions, giant cell formation, cellular degeneration, myelin breakdown and phagocytic activity by cells believed to be derived from local glia. The viral inclusions occurred in giant cells, many astrocytes, macrophages and occasional oligodendroglia. Only suggestions of active viral replication from cell membranes were present. On the basis of the above features, these CDE lesions were classed as being acute. Perivascular inflammation and parenchymal invasion by haematogenous cells were lacking. However, older, gliotic, demyelinated lesions were always associated with inflammation. The pattern of demyelination in acute CDE lesions differed from those seen in other conditions, in particular the autoimmune demyelinating diseases. In acute CDE lesions, individual fibres became separated from others by rings of cells, the processes of which systematically stripped the myelin from the outer layers of the sheath inwards until a naked segment of axon remained. Some of the macrophages were recognisable as astroglia. Elsewhere, unequivocal astrocytes containing myelin debris were common. The results suggest that inflammation in acute CDE lesions is not a primary event, and that viral invasion causes breakdown of tissue which is accompanied pari passu by myelin destruction. The latter might be related to the non-specific release of host factors (viz. hydrolytic enzymes) or humoral factors during the cellular degeneration. Local cells appeared to participate in the process of myelin phagocytosis. Overt inflammation and damage by haematogenous cells were features only of chronic lesions and have been described previously in studies on chronic CDE lesions. The results are interpreted in terms of their relevance to the study of human subacute sclerosing panencephalitis, of which CDE is considered the animal analogue, and multiple sclerosis, the paradigm of the human demyelinating diseases.

The effects of canine distemper virus on explant tissue cultures of canine cerebellum.

Canine cerebellar explant cultures were employed as a model for studying the effects of the virus associated with demyelinating canine distemper encephalomyelitis. Cultures which were inoculated after four to seven days of growth with distemper virus (Lederle strain) had beginning cytopathic effect (CPE) in the peripheral outgrowth on the eighth post-inoculation day. The cells predominantly affected were astroglia and mesenchymal cells. The cellular lesions consisted of inclusion body development (intracytoplasmic and intranuclear), syncytial giant cell formation, and production of a reticular pattern in the outgrowth. Astrocytes subsequently became affected in the inner outgrowth and explant. Cellular degeneration was common, but a high degree of apparent coexistence of virus (inclusion bodies) and cells was a characteristic feature.