Editorial Type: Neurology
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Online Publication Date: 01 Jan 2002

Adult-Onset Cerebellar Cortical Abiotrophy and Retinal Degeneration in a Domestic Shorthair Cat

DVM,
DVM, PhD, and
DVM, PhD
Article Category: Other
Page Range: 51 – 54
DOI: 10.5326/0380051
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A 4-year-old, neutered male domestic shorthair cat presented for evaluation of ataxia and visual deficits. Neurological examination revealed severe cerebellar ataxia with symmetrical hypermetria and spasticity, a coarse whole-body tremor, positional vertical nystagmus, and frequent loss of balance. A menace response was absent bilaterally, and the pupils were widely dilated in room light. A funduscopic examination revealed markedly attenuated to absent retinal vessels and pronounced tapetal hyperreflectivity, findings consistent with end-stage retinal degeneration. Blood work evaluation included retroviral testing, a complete blood count, serum biochemistry analysis, taurine levels, and toxoplasma immunoglobulin G and immunoglobulin M titers. All were within reference ranges. The patient was euthanized, and a necropsy was performed. Microscopically, lesions of the nervous system were confined to the cerebellum and were consistent with cerebellar cortical abiotrophy. Selective photoreceptor degeneration was seen on histopathological examination of the retina with a reduction in the number of rods and cones. The combination of clinical findings and histopathological lesions seen here has not been previously reported in the cat.

Case Report

A 4-year-old, castrated male, black domestic shorthair cat presented to the Companion Animal Hospital at Cornell University with a 2.5-year history of a progressive gait disorder and a 1-year history of visual deficits. The cat had been examined and vaccinated at 1 year of age and was found to be clinically normal. Castration was performed at that time, and the surgical procedure and anesthetic episode proceeded without incident. At 2 years of age, the cat presented for signs associated with lower urinary tract disease. On physical examination, a mild cerebellar ataxia was noted. Vision was intact, and a funduscopic examination was within normal limits. The owner reported that the gait disorder had begun approximately 6 months earlier and seemed to be progressive, but declined any diagnostic workup at that time.

At presentation, the cat was alert and responsive and in good body condition. On neurological examination, the cat was severely ataxic with a base-wide stance and symmetrical hypermetria and spasticity, particularly in the thoracic limbs. A coarse whole-body tremor and intention tremors primarily affecting the head were noted. Postural reaction deficits were found in all four limbs, and the patient frequently lost his balance. A positional nystagmus, with vertical beats that were nearly pendulous, was evident on extension of the head. A menace response was absent in both eyes, and the pupils were widely dilated in room light. While both pupils would respond to a bright light, both direct and consensual, the pupillary light response (PLR) was judged to be diminished bilaterally. No other cranial nerve abnormalities were found. Funduscopic examination revealed end-stage retinal degeneration with diffuse tapetal hyperreflectivity and depigmentation of the nontapetal fundus. The optic discs were pale, and the retinal vessels were absent in the right eye and severely attenuated in the left eye [Figure 1].

Laboratory testing was performed and included a complete blood count (CBC), serum biochemistry profile, urinalysis, and retroviral testing. The CBC was within reference ranges. No leukocyte inclusions were seen. Serum biochemistries were within reference ranges, as were the results of the urinalysis. Tests for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) were both negative. Serum taurine levels were within reference ranges, and toxoplasma immunoglobulin G and immunoglobulin M titers were negative.

At this time, the authors’ differential diagnosis included lysosomal storage diseases such as GM1 and GM2 gangliosidosis, neuroaxonal dystrophy, and feline cerebellar cortical abiotrophy. Inflammatory diseases and neoplasia were considered unlikely because of the protracted clinical course and lack of supporting data. Feline panleukopenia virus was also considered unlikely based on the age of onset of signs and the progressive nature of the clinical course. Consideration was given concerning the possibility of the retinal disease being unrelated to the other neurological deficits.

Due to the poor prognosis, the cat was euthanized, and a necropsy was performed. Grossly, the cerebellum appeared to be approximately two-thirds the normal size. No other gross lesions were observed in the central nervous system (CNS). The only other gross lesion was in the left kidney, in which numerous cortical depressions were noted. These were found histopathologically to represent multifocal areas of chronic fibrosis and were considered to be unrelated to the neurological signs and of no clinical significance.

Lesions observed on histopathological examination of the CNS were limited to the cerebellum. In all folia there was a marked reduction in the number of Purkinje cells, and the granule cell layer was severely attenuated [Figures 2, 3]. Replacing the Purkinje neurons was an increased number of astrocytes (i.e., Bergmann’s glia). Silver stain demonstrated the presence of “empty baskets” formed by the terminal branches of basket-cell axons [Figure 4]. This implies an advanced degenerative process. No lesions were observed in any of the brain-stem nuclei that projected to the cerebellum, nor in any of the cerebral extrapyramidal nuclei. Selective photoreceptor degeneration was seen on histopathological examination of the retina, with a marked reduction in the number of rods and cones [Figure 5]. All other cell layers of the retina appeared to be unaffected. The optic nerves, optic chiasm, and optic tracts were also evaluated and found to be within normal limits.

Discussion

Cerebellar cortical abiotrophies have been described in most domestic species, including cats, dogs, cattle, sheep, horses, and swine. When sufficient numbers of individuals have been studied, a hereditary basis (usually consistent with autosomal recessive transmission) has been proposed. In contrast to the dog, in which numerous breed-related abiotrophies are known,1 the condition is exceedingly rare in the cat. Sporadic anecdotal cases have been mentioned in the literature.2

Recently, the first report of late-onset cerebellar abiotrophy in the feline species was published.3 The patient, a Siamese, had a similar history to the cat in this report, with clinical signs beginning at 1.5 years of age and slowly progressing over a 2-year period. On necropsy, there was a profound loss of the Purkinje cell layer as well as depletion of the molecular and granule cell layers. However, no visual deficits and no retinal lesions were detected. The two cases also differed in that the CNS lesions in the Siamese were not limited to the cerebellum and included wallerian degeneration in the brain stem.

In addition, a single cat4 and a kindred,5 both from Japan, have been described. In these cats, an early-onset cerebellar abiotrophy characterized by cerebellar cortical degeneration (CCD) and pure cerebellar signs beginning at age 6 to 8 weeks of age were identified. The findings in CCD differ from the patient in this study in the age of onset and rate of progression, as well as the involvement of the olivary nuclei. Furthermore, the remarkable retinal degeneration seen in the patient of this study is not a feature of CCD.

Other conditions that are known to cause clinical cerebellar signs in the cat include in utero exposure to panleukopenia virus,6 feline neuroaxonal dystrophy,7–9 various lysosomal storage diseases including GM1 and GM2 gangliosidosis,10–12 sphingomyelin lipidosis (Niemann-Pick disease),1314 globoid cell leukodystrophy,15 mannosidosis,16–19 and neuronal ceroid-lipofuscin storage disease.20–23

In utero panleukopenia virus causes signs present at birth that are nonprogressive. In contrast, the cat described here was normal at birth and acquired signs at 1.5 years of age. Histopathologically, lesions in the cerebellum of this cat differ from the classic panleukopenia virus lesions that include failure of normal development of the granular cell layer and disorganization and loss of Purkinje cells in the folia.6 Feline neuroaxonal dystrophy is a degenerative disease that has been primarily seen in cats <1 year of age and has sometimes been linked to coat color dilution.7 It is characterized pathologically by spheroids within the CNS occurring in neuronal tracts and specific brain-stem nuclei.7–9 Cerebellar lesions, when present, include ballooning and loss of Purkinje cells primarily in the vermis, vacuolation of white matter, and spheroids in the granular layer. Lesions of this type were not observed in the present case.

Late-onset forms of lysosomal storage diseases have been described in humans, so these remained in the authors’ ante-mortem differential diagnoses. This category of disease was ruled out, however, based on the postmortem gross and histopathological presentation. Storage diseases typically present with no gross lesions of the brain, while this cat had a mild but noticeable atrophy of the cerebellum. Microscopic lesions typically seen in lysosomal storage diseases include abnormal accumulation of cell products in Purkinje and other neuronal cell populations as well as in visceral cells. The lesions in the CNS and retina of this patient were not consistent with a diagnosis of a lysosomal storage disorder.

Cerebellar degenerative diseases in humans (i.e., spino-cerebellar ataxias) include at least seven distinct diseases with various spectra of related clinical presentations. Several of these have been genetically characterized as trinucleotide (Cytosine-Adenosine-Guanine; CAG) repeats and are related to expanded glutamine chains within mutant proteins. For neurodegenerative diseases associated with abnormally expanded CAG repeats, it has generally been shown that the length of expanded CAG repeats influences the age of onset and disease duration as well as the presenting features of the disease.2425 One type of spinocerebellar ataxia, type 7 (SCA 7), is defined clinically by a late-onset cerebellar degeneration accompanied by retinal lesions similar to those described in the authors’ patient.2627 It is possible that the cat described here has a disease that is analogous to SCA 7.

To the authors’ knowledge, the unique combination of clinical findings and histopathological lesions seen in the patient of this study has not been previously reported in the cat. The retinal degeneration present in this cat may be linked to or independent of the cerebellar lesions. Conditions known to cause retinal degeneration have been described in cats and include taurine deficiency, primary inherited rod/cone dysplasia and degeneration, inflammatory diseases, glaucoma, hypertension, and drug toxicity.2829 Taurine deficiency was considered unlikely since serum levels were within reference range and the cat had been maintained on a balanced commercial feline diet. Inflammatory disease was also considered highly improbable because of the diffuse and symmetrical nature of the lesions and the absence of obvious intraocular inflammation. Glaucoma was ruled out on the basis of normal intraocular pressure (measured by applanation tonometry). Although blood pressure was not measured in this patient, hypertension was not on the list of differential diagnoses because of the absence of predisposing factors, the absence of intraocular hemorrhage, and the slow progression of vision loss. Lastly, there was no history of drug administration or known toxin exposure that may have resulted in the clinical and histopathological findings.

While the retinal degeneration may be unrelated to the Purkinje cell loss, the authors speculate that there is an association between the neurological signs and the visual deficits in this cat. This suggests that an essential protein or process involved in neuronal pathways of the Purkinje cells is also critical in retinal pathways. Glutamic acid is an essential excitatory neurotransmitter in both the cerebellum and the visual system, and it has been proposed that alterations in the glutamic acid pathway are instrumental in the pathogenesis of the cerebellar abiotrophy seen in the Kerry blue terrier.30 It is possible that in this patient, a derangement of glutaminergic metabolism is expressed in both Purkinje cells and retinal neurons, although this is purely speculative. Confirmation of this hypothesis clearly requires further case studies and laboratory analysis.

Acknowledgment

The authors gratefully acknowledge Dr. Ronald Riis for his help in examining the patient and studying the slides of the retina.

Figure 1—. Funduscopic image in a 4-year-old domestic shorthair cat with ataxia and visual deficits. There is pallor of the optic disc and attenuation of retinal vessels. These findings are consistent with end-stage retinal degeneration.Figure 1—. Funduscopic image in a 4-year-old domestic shorthair cat with ataxia and visual deficits. There is pallor of the optic disc and attenuation of retinal vessels. These findings are consistent with end-stage retinal degeneration.Figure 1—. Funduscopic image in a 4-year-old domestic shorthair cat with ataxia and visual deficits. There is pallor of the optic disc and attenuation of retinal vessels. These findings are consistent with end-stage retinal degeneration.
Figure 1— Funduscopic image in a 4-year-old domestic shorthair cat with ataxia and visual deficits. There is pallor of the optic disc and attenuation of retinal vessels. These findings are consistent with end-stage retinal degeneration.

Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380051

Figure 2—. Histopathology of affected cerebellum from the cat in Figure 1. There is complete loss of Purkinje cells, a diminished molecular layer, and the presence of Bergmann’s glia (Hematoxylin and eosin stain; 10×).Figure 2—. Histopathology of affected cerebellum from the cat in Figure 1. There is complete loss of Purkinje cells, a diminished molecular layer, and the presence of Bergmann’s glia (Hematoxylin and eosin stain; 10×).Figure 2—. Histopathology of affected cerebellum from the cat in Figure 1. There is complete loss of Purkinje cells, a diminished molecular layer, and the presence of Bergmann’s glia (Hematoxylin and eosin stain; 10×).
Figure 2— Histopathology of affected cerebellum from the cat in Figure 1. There is complete loss of Purkinje cells, a diminished molecular layer, and the presence of Bergmann’s glia (Hematoxylin and eosin stain; 10×).

Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380051

Figure 3—. Section of cerebellar folia as seen in Figure 2 (Hematoxylin and eosin stain; 20×).Figure 3—. Section of cerebellar folia as seen in Figure 2 (Hematoxylin and eosin stain; 20×).Figure 3—. Section of cerebellar folia as seen in Figure 2 (Hematoxylin and eosin stain; 20×).
Figure 3— Section of cerebellar folia as seen in Figure 2 (Hematoxylin and eosin stain; 20×).

Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380051

Figure 4—. Silver-stained section of affected cerebellum (20×). Note the “empty baskets,” representing the site of Purkinje-cell destruction.Figure 4—. Silver-stained section of affected cerebellum (20×). Note the “empty baskets,” representing the site of Purkinje-cell destruction.Figure 4—. Silver-stained section of affected cerebellum (20×). Note the “empty baskets,” representing the site of Purkinje-cell destruction.
Figure 4— Silver-stained section of affected cerebellum (20×). Note the “empty baskets,” representing the site of Purkinje-cell destruction.

Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380051

Figure 5—. Section of tapetal retina from the cat in Figure 1. The numbers of rods and cones are markedly reduced. The separation between the pigmented retinal epithelium and the outer segment is artifactual.Figure 5—. Section of tapetal retina from the cat in Figure 1. The numbers of rods and cones are markedly reduced. The separation between the pigmented retinal epithelium and the outer segment is artifactual.Figure 5—. Section of tapetal retina from the cat in Figure 1. The numbers of rods and cones are markedly reduced. The separation between the pigmented retinal epithelium and the outer segment is artifactual.
Figure 5— Section of tapetal retina from the cat in Figure 1. The numbers of rods and cones are markedly reduced. The separation between the pigmented retinal epithelium and the outer segment is artifactual.

Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380051

Footnotes

    Doctor Barone’s current address is the Department of Neurology, School of Veterinary Medicine, University of Pennsylvania, 3850 Spruce Street, Philadelphia, Pennsylvania 19104. Doctor Foureman’s current address is the Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 3850 Spruce Street, Philadelphia, Pennsylvania 19104. The work described in the following manuscript was supported by a grant from the Zipporah S. Fleisher fund.

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Copyright: Copyright 2002 by The American Animal Hospital Association 2002
<bold> <italic toggle="yes">Figure 1</italic> — </bold>
Figure 1 —

Funduscopic image in a 4-year-old domestic shorthair cat with ataxia and visual deficits. There is pallor of the optic disc and attenuation of retinal vessels. These findings are consistent with end-stage retinal degeneration.

<bold> <italic toggle="yes">Figure 2</italic> — </bold>
Figure 2 —

Histopathology of affected cerebellum from the cat in Figure 1. There is complete loss of Purkinje cells, a diminished molecular layer, and the presence of Bergmann’s glia (Hematoxylin and eosin stain; 10×).

<bold> <italic toggle="yes">Figure 3</italic> — </bold>
Figure 3 —

Section of cerebellar folia as seen in Figure 2 (Hematoxylin and eosin stain; 20×).

<bold> <italic toggle="yes">Figure 4</italic> — </bold>
Figure 4 —

Silver-stained section of affected cerebellum (20×). Note the “empty baskets,” representing the site of Purkinje-cell destruction.

<bold> <italic toggle="yes">Figure 5</italic> — </bold>
Figure 5 —

Section of tapetal retina from the cat in Figure 1. The numbers of rods and cones are markedly reduced. The separation between the pigmented retinal epithelium and the outer segment is artifactual.

Contributor Notes

Address all reprint requests to Dr. Barone.
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