Chesapeake Bay retriever cross. ... The head tremor andquality of ataxia were unchanged ... dog (right) and the cerebellum from the dog with cerebellar cor-.
Cerebellar cortical degeneration in a Labrador retriever Rob J. Bildfell, Sally K. Mitchell, Alexander de Lahunta Cerebellar cortical degeneration (CCD) has been reported in various canine breeds. An inherited autosomal recessive mode of transmission has been demonstrated for Kerry blue terriers, Gordon setters, and rough-coated collies (1). In these breeds, the disease can be defined as an abiotrophy, which is a cellular degeneration resulting from an inborn metabolic defect (2). Although CCD has previously been reported in Labrador retrievers (1,3), an insufficient number of cases have been described to document abiotrophy in this breed. This report describes a degenerative cerebellar disease in a puppy of predominantely Labrador retriever lineage. A 9-week-old, male puppy with clinical signs of hindlimb ataxia was presented at the Small Animal Teaching Hospital of the Atlantic Veterinary College. The owner reported that the -animal had normal locomotion when it was acquired at 6 wk of age but seemed to have had poor balance during the past 2 wk. The puppy was from a litter of 1, from the breeding of a female purebred Labrador retriever with a male LabradorChesapeake Bay retriever cross. At least 1 other puppy from this litter had been euthanized due to neurologic disease. Examination revealed a bright, alert, and playful puppy with a wide-based stance and a mild hindlimb ataxia that worsened with activity. Postural reactions, muscle tone, and spinal reflexes were normal. At this examination, there was a suspicion of forelimb hypermetria, slight swaying of the trunk, and difficulty with balance. A serum chemistry profile and complete blood count were within normal limits. The owner declined further diagnostic tests and elected to observe the dog for any change in clinical signs. At presentation 3 wk later, ataxia had progressed to obvious involvement of the forelimbs. All limbs were remarkably hypermetric. The dog readily lost his balance and would fall in any direction. An intention tremor was prominent in the head and a generalized increase in muscle tone was noted. The remainder of the physical examination was normal. These signs reflected a progressive cerebellar disorder, possibly resulting from a degenerative or inflammatory process. The head tremor and quality of ataxia were unchanged when the dog was reexamined at 5 mo of age. The animal seemed less likely to fall over during ambulation, presumably due to a learned compensation. Seizurelike episodes lasting 30 s to I min were observed during this examination. During these episodes, the dog appeared Can Vet J 1995; 36: 570-572
Departments of Pathology/Microbiology (Bildfell) and Companion Animals (Mitchell), Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island C I A 4P3; Department of Anatomy, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA (de Lahunta). 570
I cm I
Figure 1. Ventrolateral view of the brain from the dog with cerebellar cortical degeneration. Note marked reduction in size of cerebellum.
Lcm l Figure 2. Dorsal view of a normal cerebellum from an adult dog (right) and the cerebellum from the dog with cerebellar cortical degeneration (left). Note retention of symmetry in the affected cerebellum. aware of his surroundings but became recumbent with opisthotonos and muscle rigidity. This behavior often occurred when the dog was excited or attempting to perform complex motor movements (climb stairs). At 10 mo of age, the only change in the dog's condition was a slightly increased frequency of these episodes. When the dog was I y old, he was euthanized at the owner's
request.
At necropsy, gross abnormal findings were restricted cerebellum, which was approximately 1/3 normal size (Figure 1) but bilaterally symmetrical (Figure 2). The folia were thin and the sulci appeared widened. Microscopically, both the cerebellar cortex and the cerebellar medulla were abnormal (Figure 3). The molecular layer was thinned and had a decreased staining density. The granular cell layer was hypocellular due to loss of neurons. The density of Purkinje cells throughout the cortex was markedly reduced. Typically, 0 to 3 Purkinje to the
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Figure 3. Photomicrograph of folium from the dog with cerebellar cortical degeneration. Note thinning of the molecular layer, hypocellularity of the granular cell layer, and the decreased number of Purkinje cells. Two surviving Purkinje cells with swollen dendritic processes are visible. Haematoxylin and eosin stain. Bar = 100 glm.
cells were visible in any 400X microscopic field in the vermis and hemisphere, compared with 6 to 7 Purkinje cells in the normal adult dog used as a control. The Purkinje cell layer of the flocculus was comparatively well populated (3 to 4 cells per 400X field). Degenerative changes were visible in a few of the remaining Purkinje cells; these included swelling of dendritic processes, cytoplasmic hypereosinophilia, and vacuolation. Necrotic Purkinje cells and eosinophilic axonal spheroids were also identified. This layer also contained increased numbers of Bergmann's astrocytes. Holmes' silver stain revealed very small numbers of "empty baskets" that no longer encircled intact Purkinje cells (4). Immunohistochemical staining for glial fibrillary acidic protein (GFAP reagent, Dako Corporation, Santa Barbara, California, USA) revealed increased numbers of astrocytes in the cerebellar white matter and also stained some of Bergmann's astrocytes. Mild degenerative changes were observed in several other foci. They included axonal spheroids in cerebellar nuclei, mild neuronal degeneration and axonal swelling in the olivary nucleus, and mild neuronal dropout in the vestibular nucleus. Swollen axons were visible in the vestibular nerve in the region of the cochlear nucleus. Most of these changes could be linked to Purkinje cell degeneration and subsequent transsynaptic loss of neurons communicating with the Purkinje cell population (1). Degenerative changes were not observed in other areas with cerebellar connections, including the thalamic and pontine nuclei and the white matter of the spinal cord. A gross postmortem observation of a poorly developed cerebellum in neonatal and juvenile animals often leads to a tentative diagnosis of cerebellar hypoplasia. However, CCD must also be considered, since the process of degeneration and atrophy can result in a small cerebellum. Cerebellar cortical degeneration can be the result of exogenous factors, such as viruses (e.g., murine C-type RNA virus) or toxins (e.g., Solanumfastigiatum toxicosis) (2). Demonstration of exposure to these agents is required to obtain a definitive diagnosis in such cases. However, many cases of CCD are abiotrophies and, therefore, not the result of an exogenous influence (2). Can Vet J Volume 36, September 1995
Abiotrophy may become apparent at any time between early organogenesis and old age. In contrast, cerebellar hypoplasia is a failure of proper development of the organ and is always the result of a problem during organogenesis (1). In many instances, fully differentiated cells are lost and thus a degree of atrophy also contributes to a decrease in organ size. Exogenous factors known to induce cerebellar hypoplasia or dysplasia in domestic animals include feline panleukopenia virus, bovine viral diarrhea virus, and bluetongue virus (1). An in utero viral disease causing hypoplasia or dysplasia of the canine cerebellum has not been identified, although postnatal canine herpesvirus infection can damage this tissue (5). The gross distinction between cerebellar hypoplasia and CCD can be difficult. Symmetrical damage may occur in both conditions but is more common in CCD. Microscopically, the cellular composition of a folium from a hypoplastic cerebellum is often normal, although foci of dysplasia may be present. Most cases of CCD are abiotrophies characterized by Purkinje cell dropout, with secondary loss of granular cell layer neurons that can no longer synapse with Purkinje cell dendrites (2). The demonstration of "empty baskets," which correspond to sites of Purkinje cell loss, may be necessary to confirm that a degenerative process has occurred. Degeneration of neurons in the granular cell layer, without Purkinje cell involvement, has also been reported in canine cerebellar abiotrophy (6). Ataxia developed at 9 to 17 wk of age in a previous report of CCD in 3 Labrador retriever littermates (3). These dogs required assistance to walk just 3 wk after the onset of clinical signs. Abnormal nystagmus was a notable feature in all 3 animals. In another case of CCD in this breed (1), the animal had signs of cerebellar ataxia from the time it first began to ambulate until it was euthanized at 3.5 mo of age. In contrast, the dog described here had a very slowly progressive neurologic disease and did not require assistance to walk, even at 1 y of age. He never exhibited abnormal nystagmus but did have seizure-like episodes, similar to those described for Gordon setters with CCD (7). These seizures appear to be a severe transient disturbance of cerebellar function and are likely initiated in the disorganized cerebellum. It is difficult to correlate the rate of disease progression or the degree of dysfunction with the lesions observed microscopically. The flocculus comprises much of the archicerebellum, the portion of the cerebellum concerned mainly with activity of the vestibular system (1). The less severe involvement of this area in our case may partially account for the animal's continued ambulation, despite marked loss of cerebellar tissue. On a phylogenetic basis, the archicerebellum is the most primitive portion of the cerebellum (8), so Purkinje cells of this region may have slight metabolic differences in comparison with more phylogenetically advanced areas. Variability in the degree of Purkinje cell loss between different cerebellar regions has been noted in other descriptions of canine CCD (9,10). Although all regions were affected, the rostral vermis was the most severely damaged area in the litter of Labrador retriever puppies with rapidly progressive CCD (3). This report documents a cerebellar cortical degeneration of unknown etiology in a dog of predominately 571
Labrador retriever breeding. Unfortunately, the breeding trials and pedigree analysis required to determine if this is a case of cerebellar abiotrophy were not possible.
Acknowledgment We thank Shelley Ebbett for photographic assistance. cvi
References 1. De Lahunta A. Veterinary Neuroanatomy and Clinical Neurology, 2nd ed. Philadelphia: WB Saunders, 1983: 255-278. 2. De Lahunta A. Abiotrophy in domestic animals: a review. Can J Vet Res 1990; 54: 65-76. 3. Perille AL, Baer K. Joseph RJ, et al. Postnatal cerebellar cortical degeneration in Labrador Retriever puppies. Can Vet J 1991; 32: 619-621.
4. Jones TC, Hunt RD. Veterinary Pathology. 5th ed. Philadelphia: Lea & Febiger, 1983: 1657-1658. 5. Percy DH, Carmichael LE. Albert DM, et al. Lesions in puppies surviving infection with canine herpesvirus. Vet Pathol 1971; 8: 37-53. 6. Tatalick LM, Marks SL. Baszler TV. Cerebellar abiotrophy characterized by granular cell loss in a Brittany Spaniel. Vet Pathol 1993: 30: 385-388. 7. Steinberg HS, Troncoso JC, Cork LC, et al. Clinical features of inherited cerebellar degeneration in Gordon Setters. J Am Vet Med Assoc 1981; 179: 886-890. 8. Jenkins T. Functional Mammalian Neuroanatomy. Philadelphia: Lea & Febiger, 1978: 238-251. 9. Yasuba M, Okimoto K, lida M, et al. Cerebellar cortical degeneration in Beagle dogs. Vet Pathol 1988; 25: 315-317. 10. Cork LC, Troncoso JC, Price DL. Canine inherited ataxia. Ann Neurol 1981; 9: 492-499.
CROSS-CANADA DISEASE REPORT RAPPORT DES MALADIES DIAGNOSTIQUEES AU CANADA
Ontario Mechanobullous disease in a Belgian foal in eastern Ontario A mechanobullous disease with a suspected inherited etiology has been reported in Belgian foals in the United States (1). Affected foals develop bullae of the skin, and mucosal and mucocutaneous membranes that progress to irregular and asymmetrical erosions and ulcers following minor trauma. Corneal ulcers and dystrophic teeth are also described. Lesions may be present at birth or develop in the neonate. Death results from secondary bacterial infections and reduced feed intake due to oral lesions. Anecdotal reports of this disease have existed in Ontario for several years. In May 1992, formalin-fixed tissues from a 7-day-old, purebred, female, Belgian foal were submitted to the Kemptville Regional Veterinary Laboratory, Ontario Ministry of Agriculture, Food and Rural Affairs, for histological evaluation. The foal had been normal at birth and had nursed aggressively. By 2 d of age, large irregular erosions and ulcers of the skin over pressure points were observed; similar defects appeared at the oral mucocutaneous junction, and on the tongue, hard palate and mucosa over the erupted incisor teeth. Ulcers of the coronary band were present on both front feet, resulting in sloughing of 1 hoof wall by 6 d of age. A clinical diagnosis of mechanobullous disease of Belgian foals was made and the foal was euthanized at 7 d of age. Histopathology of the skin was characterized by subepidermal clefts. The basal cell layer was intact and attached to the epidermis, and there was intracellular edema of rare basal cells. Simple cleft formation was unaccompanied by inflammation; where this had progressed to epidermal sloughing and ulceration, the dermal surface consisted of granulation tissue covered
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with fibrin, neutrophils, and bacteria. At the periphery of ulcers, there was marked, irregular, epidermal hyperplasia; fibrin and neutrophils from the ulcer extended into the adjacent exposed subepidermal clefts, accompanied by an intense superficial dermal perivascular neutrophilic infiltrate. Lesions of the buccal, gingival, and glossal mucosae and the mucocutaneous junction were similar to those in the skin. In a published study (2), electron microscopic examination has shown that separation of the dermoepidermal junction occurs through the lamina lucida with destruction of basilar hemodesmosomes. This and other ultrastructural morphology was interpreted by the authors of that study as being similar to human epidermolysis bullosa of the junctional type. An autosomal recessive mode of inheritance is suspected. The histopathology of this case is being reported because anecdotal reports of mechanobullous disease of Belgian foals in eastern Ontario are rarely substantiated by laboratory tests; clinical signs are usually considered diagnostic.
References 1. Kohn CW. Johnson GC. Garry F. Johnson CW. Martin S. Mechanobullous disease in two Belgian foals. Equine Vet J 1989; 21: 297-301. 2. Johnson GC, Kohn CW. Johnson CW. Garry F, Scott D, Martin S. Ultrastructure of junctional epidermolysis bullosa in Belgian foals. J Comp Pathol 1988; 98: 329-336.
Janet Shapiro, Ontario Ministry of Agriculture, Food and Rural Affairs, Veterinary Laboratory Services, Mail Bag 2005, Kemptville, Ontario KOG IJO, and Beverly McEwen, Ontario Ministry of Agriculture, Food and Rural Affairs, Veterinary Laboratory Services, Box 3612, Guelph, Ontario NIH 6R8.
Can Vet J Volume 36, September 1995
