J. Vet. Med. B 39, 571-574 (1992) 0 1992 Paul Parey Scientific Publishers, Berlin and Hamburg ISSN 0931-1793
1Department of Pathology and 2Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas
Canine Distemper with Spinal Cord Lesions P. SCHONING'and C. E. LAY TON^ Corresponding author: Dr. POLLYSCHONING,Department of Pathology, Bldg. VCS, College of Veterinary Medicine, Kansas State University, Manhattan KS 66506
With 2 figures (Received for publication September 5, 1991)
Sum ma r y A case of distemper in a 6-month-old dog is described. The dog was presented with a history of tetraparesis suggestive of trauma. Neurological examination and clinical pathology findings of lymphopenia and pleocytosis suggested a viral cause. Microscopic findings of a nonsuppurative meningoencephalomyelitis with numerous intranuclear inclusions in the cerebellum, brain stem, and all parts of the spinal cord suggested a diagnosis of distemper.
Introduction Canine distemper is the most widespread, usually endemic, disease of dogs (3). It is caused by a paramyxovirus that is shed in all excretions of infected dogs. Transmission is by inhalation (3). The virus initially localizes in lymph nodes and then spreads to epithelial cells of most systems. The incubation period is approximately 5 days. Neurological signs occur in 1-5 weeks and may range from clonic muscle contractions to seizures. Macroscopic lesions are dependant on the system involved. If the disease has reached the neurological stage, macroscopic findings may be absent (3). A recent review article on canine distemper discussed pathogenesis, clinical signs, diagnosis, and treatment (7). This paper describes a case of distemper that illustrates the diagnostic challenge that this disease can pose.
Case Report A 6-month-old, 2.1 kg, female Poodle cross was referred to the Kansas State University (KSU) Teaching Hospital with a history of ataxia and proprioceptive defects. Two weeks earlier, the dog had either jumped or fallen off of a couch. Initially, the dog seemed unable to walk and was taken to the referring veterinarian. Corticosteroids and vitamin B complex were administered, with minimal improvement noted for 4-5 days. During this same initial examination, the dog was vaccinated for distemper, leptospirosis, hepatitis, parainfluenza, and parvovirus enteritis (Galaxy - 6@, Solvay Animal Health Inc., Mendota Heights, MN). The dog was referred to KSU, because of progression of the neurological signs. US.Copyright Clearance Center Code Statement:
0931- 1793/92/3908-0571$02.50/0
572
SCHONINGand LAYTON
Clinical Findings and Laboratory Tests O n admission, the dog was in lateral recumbency with flaccid tetraparesis. Neurological examination revealed normal cranial nerve signs, and the dog was alert and responsive. Proprioceptive deficits were present in all four legs, with the front legs less affected. Spinal reflexes in all four legs were assessed to be normal and a crossed extension was present in both hind legs. Fecal and urinary incontinence were not noted. Gentle manipulation of the neck caused pain. Increased resistance was felt, when the neck was flexed. A tentative diagnosis of cervical spinal cord disease was made, with differential diagnoses of trauma, vertebral fracture or subluxation, and aplastic or hypoplastic dens (odontoid process of axis). Radiographs of the cervical cord and a myelogram were normal. A complete blood count (CBC) revealed mild leukocytosis (20,200 cells/pl), characterized by a left shift (15,750 mature neutrophils/pl, 400 bands/&, a lymphopenia (1081 lymphocytedpl), and a monocytosis (1610 monocytes/pl). The serum chemical profile was within normal limits, with a mild hyperglycemia (137 mg/dl). Cerebrospinal fluid (CSF) analysis revealed a pleocytosis (increase of CSF lymphocytes) with 85 % lymphocytes, 15 % monocytes, and an occasional neutrophil. Protein was increased (185mg/dl). Etiologic agents were not seen. The CSF profile was highly suggestive of a viral meningitis/myelitis. Several days later, CSF titer results were received. Antibodies in the CSF were present for distemper and absent for toxoplasmosis. Because of progression of neurological signs and a loss of spinal nerve reflexes, the owners elected euthanasia. Pathological Findings At necropsy, there were no recognizable lesions. The brain and spinal cord were placed in 10 % neutral buffered formalin without segmental cutting. After fixation, the brain and cord were segmentally sectioned; lesions were not seen. Microscopic changes were limited to the cerebellum; brain stem; and cervical, thoracic, and lumbar spinal cord.
Fig. 1. Demyelination and intranuclear inclusions (arrows) in the spinal cord of a dog with distemper. HE X850
Spinal Cord Lesions of Distemper
573
Fig. 2. Intranuclear viral nucleocapsids in the spinal cord. (Bar = .lkm)
The extent of change varied from section to section, but was most severe in the white matter of the cerebellum, brain stem, and cervical cord. Changes in the white matter of the cerebellum were characterized by many large vacuoles; some contained macrophages. Perivascular cuffing was marked, varying from 2 to 15 layers of cells, which were mainly lymphocytes with some plasma cells. Many astrocytes (5+ per high power field) in some areas, contained eosinophilic to amphophilic, intranuclear inclusions with margination of chromatin. Other changes includes Wallerian degeneration and diffuse gliosis. Additionally, the spinal cord was characterized by thickened meninges infiltrated by many lymphocytes; severely swollen, basophilic, granular nerve cell bodies; and in some areas, sheets of large active microglia (Gitter cells). Many nuclei had marginated chromatin and contained eosinophilic inclusions (Fig. 1). A diagnosis of chronic nonsuppurative meningoencephalomyelitis with eosinophilic intranuclear inclusions compatible with canine distemper was made. Formalin-fixed tissue was embedded, sectioned, and stained for transmission electron microscopy (TEM). Some nuclei contained virus particles (Fig. 2).
Discussion Because this dog had a history which included falling from a couch, trauma was the expected cause of the neurological signs. However, trauma was eliminated as a diagnosis, because radiographs and a myelogram were unremarkable. The blood and cerebrospinal fluid findings were similar to those for viral encephalitides described by others. Laboratory findings of lymphopenia, monocytosis, and slight neutrophilia are highly suggestive of a viral cause (4, 5). Pleocytosis, with an increase in lymphocytes and macrophages, also
5 74
SCHONING and LAYTON
supports a viral cause (2,4). Viral inclusions have been reported to occur in most types of circulating blood cells of dogs with distemper (6). Blood smears from this dog were not stained to identify inclusions, therefore we do not know if they were present. Canine distemper vaccination failure has been attributed to host factors, such as immunodeficiency, and to vaccination factors, such as improper storage and handling of vaccines (7). In this case, the dog was probably incubating distemper virus at the time of vaccination, because neurological signs were present at that time. Microscopic lesions, characterized by activated microglia, also indicated that the disease had been present at the time of vaccination. Retrospectively, the client recalled that the dog had shown mild signs compatible with an upper respiratory infection 4-5 weeks prior to presentation. Demyelination, which is usually most severe in the cerebellum, is the major lesion of the neurological form of distemper. A nonsuppurative meningitis is always present. This dog had pathognomonic lesions of distemper, such as demyelination, gliosis, and intranuclear inclusions. In this dog, the distribution of lesions was different from most cases, because the spinal cord was more severely involved than was the cerebellum. Lesions of the spinal cord included many intranuclear inclusions, demyelination and neuronal degeneration. Although electron microscopy was not necessary for a diagnosis, the TEM findings further assisted in the diagnosis since viral particles, arranged in a pattern typical for paramyxovirus, were present in some nuclei (2). Acknowledgement This paper is submitted as Contribution Number 92-103-J from the Kansas Agricultural Experiment Station.
References 1. C H E V I L LN~ ., F., 1983: Pathogenic intracellular microorganisms. In: Cell Pathology, 2nd ed., pp. 465-470, The Iowa State University Press, Ames, Iowa. 2. DUNCAN, J. R., and K. W. PRASE, 1986: Veterinary Laboratory Medicine, Clinical Pathology. 2nd ed., p. 211, The Iowa State University Press, Ames, Iowa. 3. DUNGWORTH, D. L., 1985: The respiratory system. In: Pathology of Domestic Animals, 3rd ed., vol. 2, ed. JUBB, K. V. F., P. C. KENNEDY, and N. PALMER pp. 476-481, Academic Press, Inc., New York. 4. FARROW,B.R.H., and D.N. L o n . , 1983: Bacterial, viral, and other infectious problems. In: Textbook of Veterinary Internal Medicine, Diseases of the Dog and Cat. 2nd ed., vol. 1, ed. S. J., pp. 269-273, W. B. Saunders, Philadelphia. ETTINGER, 5. GUY,J.S., 1986: Diagnosis of canine viral infections. Vet. Clin. North Am. 16 (6), 1145-1156. H.G., P.S. ADAMS,W.D. CORNELL, and A.D. ELKJNS, 1985: Canine distemper 6. MCLAUGHLIN, viral inclusions in blood cells of four vaccinated dogs. Can. Vet. J. 26, 368-372. 7. SHELL,L.G., 1990: Canine distemper. Compend. Contin. Educ. Pract. Vet. 12 ( 2 ) , 173-179.
1Department of Pathology and 2Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas
Canine Distemper with Spinal Cord Lesions P. SCHONING'and C. E. LAY TON^ Corresponding author: Dr. POLLYSCHONING,Department of Pathology, Bldg. VCS, College of Veterinary Medicine, Kansas State University, Manhattan KS 66506
With 2 figures (Received for publication September 5, 1991)
Sum ma r y A case of distemper in a 6-month-old dog is described. The dog was presented with a history of tetraparesis suggestive of trauma. Neurological examination and clinical pathology findings of lymphopenia and pleocytosis suggested a viral cause. Microscopic findings of a nonsuppurative meningoencephalomyelitis with numerous intranuclear inclusions in the cerebellum, brain stem, and all parts of the spinal cord suggested a diagnosis of distemper.
Introduction Canine distemper is the most widespread, usually endemic, disease of dogs (3). It is caused by a paramyxovirus that is shed in all excretions of infected dogs. Transmission is by inhalation (3). The virus initially localizes in lymph nodes and then spreads to epithelial cells of most systems. The incubation period is approximately 5 days. Neurological signs occur in 1-5 weeks and may range from clonic muscle contractions to seizures. Macroscopic lesions are dependant on the system involved. If the disease has reached the neurological stage, macroscopic findings may be absent (3). A recent review article on canine distemper discussed pathogenesis, clinical signs, diagnosis, and treatment (7). This paper describes a case of distemper that illustrates the diagnostic challenge that this disease can pose.
Case Report A 6-month-old, 2.1 kg, female Poodle cross was referred to the Kansas State University (KSU) Teaching Hospital with a history of ataxia and proprioceptive defects. Two weeks earlier, the dog had either jumped or fallen off of a couch. Initially, the dog seemed unable to walk and was taken to the referring veterinarian. Corticosteroids and vitamin B complex were administered, with minimal improvement noted for 4-5 days. During this same initial examination, the dog was vaccinated for distemper, leptospirosis, hepatitis, parainfluenza, and parvovirus enteritis (Galaxy - 6@, Solvay Animal Health Inc., Mendota Heights, MN). The dog was referred to KSU, because of progression of the neurological signs. US.Copyright Clearance Center Code Statement:
0931- 1793/92/3908-0571$02.50/0
572
SCHONINGand LAYTON
Clinical Findings and Laboratory Tests O n admission, the dog was in lateral recumbency with flaccid tetraparesis. Neurological examination revealed normal cranial nerve signs, and the dog was alert and responsive. Proprioceptive deficits were present in all four legs, with the front legs less affected. Spinal reflexes in all four legs were assessed to be normal and a crossed extension was present in both hind legs. Fecal and urinary incontinence were not noted. Gentle manipulation of the neck caused pain. Increased resistance was felt, when the neck was flexed. A tentative diagnosis of cervical spinal cord disease was made, with differential diagnoses of trauma, vertebral fracture or subluxation, and aplastic or hypoplastic dens (odontoid process of axis). Radiographs of the cervical cord and a myelogram were normal. A complete blood count (CBC) revealed mild leukocytosis (20,200 cells/pl), characterized by a left shift (15,750 mature neutrophils/pl, 400 bands/&, a lymphopenia (1081 lymphocytedpl), and a monocytosis (1610 monocytes/pl). The serum chemical profile was within normal limits, with a mild hyperglycemia (137 mg/dl). Cerebrospinal fluid (CSF) analysis revealed a pleocytosis (increase of CSF lymphocytes) with 85 % lymphocytes, 15 % monocytes, and an occasional neutrophil. Protein was increased (185mg/dl). Etiologic agents were not seen. The CSF profile was highly suggestive of a viral meningitis/myelitis. Several days later, CSF titer results were received. Antibodies in the CSF were present for distemper and absent for toxoplasmosis. Because of progression of neurological signs and a loss of spinal nerve reflexes, the owners elected euthanasia. Pathological Findings At necropsy, there were no recognizable lesions. The brain and spinal cord were placed in 10 % neutral buffered formalin without segmental cutting. After fixation, the brain and cord were segmentally sectioned; lesions were not seen. Microscopic changes were limited to the cerebellum; brain stem; and cervical, thoracic, and lumbar spinal cord.
Fig. 1. Demyelination and intranuclear inclusions (arrows) in the spinal cord of a dog with distemper. HE X850
Spinal Cord Lesions of Distemper
573
Fig. 2. Intranuclear viral nucleocapsids in the spinal cord. (Bar = .lkm)
The extent of change varied from section to section, but was most severe in the white matter of the cerebellum, brain stem, and cervical cord. Changes in the white matter of the cerebellum were characterized by many large vacuoles; some contained macrophages. Perivascular cuffing was marked, varying from 2 to 15 layers of cells, which were mainly lymphocytes with some plasma cells. Many astrocytes (5+ per high power field) in some areas, contained eosinophilic to amphophilic, intranuclear inclusions with margination of chromatin. Other changes includes Wallerian degeneration and diffuse gliosis. Additionally, the spinal cord was characterized by thickened meninges infiltrated by many lymphocytes; severely swollen, basophilic, granular nerve cell bodies; and in some areas, sheets of large active microglia (Gitter cells). Many nuclei had marginated chromatin and contained eosinophilic inclusions (Fig. 1). A diagnosis of chronic nonsuppurative meningoencephalomyelitis with eosinophilic intranuclear inclusions compatible with canine distemper was made. Formalin-fixed tissue was embedded, sectioned, and stained for transmission electron microscopy (TEM). Some nuclei contained virus particles (Fig. 2).
Discussion Because this dog had a history which included falling from a couch, trauma was the expected cause of the neurological signs. However, trauma was eliminated as a diagnosis, because radiographs and a myelogram were unremarkable. The blood and cerebrospinal fluid findings were similar to those for viral encephalitides described by others. Laboratory findings of lymphopenia, monocytosis, and slight neutrophilia are highly suggestive of a viral cause (4, 5). Pleocytosis, with an increase in lymphocytes and macrophages, also
5 74
SCHONING and LAYTON
supports a viral cause (2,4). Viral inclusions have been reported to occur in most types of circulating blood cells of dogs with distemper (6). Blood smears from this dog were not stained to identify inclusions, therefore we do not know if they were present. Canine distemper vaccination failure has been attributed to host factors, such as immunodeficiency, and to vaccination factors, such as improper storage and handling of vaccines (7). In this case, the dog was probably incubating distemper virus at the time of vaccination, because neurological signs were present at that time. Microscopic lesions, characterized by activated microglia, also indicated that the disease had been present at the time of vaccination. Retrospectively, the client recalled that the dog had shown mild signs compatible with an upper respiratory infection 4-5 weeks prior to presentation. Demyelination, which is usually most severe in the cerebellum, is the major lesion of the neurological form of distemper. A nonsuppurative meningitis is always present. This dog had pathognomonic lesions of distemper, such as demyelination, gliosis, and intranuclear inclusions. In this dog, the distribution of lesions was different from most cases, because the spinal cord was more severely involved than was the cerebellum. Lesions of the spinal cord included many intranuclear inclusions, demyelination and neuronal degeneration. Although electron microscopy was not necessary for a diagnosis, the TEM findings further assisted in the diagnosis since viral particles, arranged in a pattern typical for paramyxovirus, were present in some nuclei (2). Acknowledgement This paper is submitted as Contribution Number 92-103-J from the Kansas Agricultural Experiment Station.
References 1. C H E V I L LN~ ., F., 1983: Pathogenic intracellular microorganisms. In: Cell Pathology, 2nd ed., pp. 465-470, The Iowa State University Press, Ames, Iowa. 2. DUNCAN, J. R., and K. W. PRASE, 1986: Veterinary Laboratory Medicine, Clinical Pathology. 2nd ed., p. 211, The Iowa State University Press, Ames, Iowa. 3. DUNGWORTH, D. L., 1985: The respiratory system. In: Pathology of Domestic Animals, 3rd ed., vol. 2, ed. JUBB, K. V. F., P. C. KENNEDY, and N. PALMER pp. 476-481, Academic Press, Inc., New York. 4. FARROW,B.R.H., and D.N. L o n . , 1983: Bacterial, viral, and other infectious problems. In: Textbook of Veterinary Internal Medicine, Diseases of the Dog and Cat. 2nd ed., vol. 1, ed. S. J., pp. 269-273, W. B. Saunders, Philadelphia. ETTINGER, 5. GUY,J.S., 1986: Diagnosis of canine viral infections. Vet. Clin. North Am. 16 (6), 1145-1156. H.G., P.S. ADAMS,W.D. CORNELL, and A.D. ELKJNS, 1985: Canine distemper 6. MCLAUGHLIN, viral inclusions in blood cells of four vaccinated dogs. Can. Vet. J. 26, 368-372. 7. SHELL,L.G., 1990: Canine distemper. Compend. Contin. Educ. Pract. Vet. 12 ( 2 ) , 173-179.
