Cerebellar degeneration is a common neurological problem in purebred and mixed breed dogs. The best described entity within this complex is cerebellar abiotrophy, or cerebellar cortical degeneration (CCD), which has been described in nearly 40 canine breeds so far. However, the underlying pathology and clinical course of the disease differ significantly between breeds. Affected breeds can be divided into 3 groups according to the onset of clinical signs: 1) neonatal onset: Beagle, Coton de Tulear, Dachshund mix, Irish Setter, Rhodesian Ridgeback, Samoyed; 2) juvenile onset at an age of 6 weeks to 6 months: Airedale Terrier, Australian Kelpie, Bavarian Mountain Dog, Bernese Mountain Dog, Border Collie, Chinese Crested Dog, English Bulldog, Finish Harrier, Italian Hound, Kerry Blue Terrier, Labrador Retriever, Portugese Podenco, Rough Coated Collie; 3) adult onset at an age of 1 to 8 years: American Pit Bull Terrier, American Staffordshire Terrier, Bernese Mountain Dog, Brittany Spaniel, Epagneul Breton, Gordon Setter, Italian Spinone, Old English Sheepdog, Scottish Terrier, Schnauzer Beagle mix. In the following breeds CCD has been described, but the time of first clinical signs is not well documented in the literature: Akita Inu, Chow Chow, Cairn terrier, Clumber Spaniel, Cocker Spaniel, Fox terrier and Great Dane.
Gross pathologic examination typically reveals diffuse atrophy of the cerebellum. The most common histopathological feature is a degeneration and loss of Purkinje cells of varying degree depending on the chronicity of the degenerative process. In acute cases, an ischemic type of Purkinje neurons may be seen, whereas in more chronic cases ongoing degeneration results in complete loss of Purkinje cells. The space formerly occupied by Purkinje neurons will be taken over by reactive astrocytes (Bergman astrocytes).1 The granule cell layer may be secondary depleted, since granule cells lack their synaptic interaction with Purkinje cells.
In some breeds the molecular or granule cell layers are affected selectively or loss of granule or molecular cells dominates the histological picture in combination with Purkinje cells loss (Bavarian Mountain Dog, Border Collie, Brittany Spaniel, Coton de Tulear, Italian Hound).2-6
Most breeds have no lesions in other brain areas. Sometimes however, cerebellar degeneration is combined with degenerative changes in other regions of the central nervous system, such as cerebral cortex, striatum or autonomic nervous system. In some American Staffordshire Terriers and in a Pit Bull Terrier additional lesions were found in certain thalamic nuclei.7 Neuronal degeneration in those dogs was associated with a lipopigment storage disease. In Kerry Blue terriers the olivary nucleus, caudate nucleus and substancia nigra may be affected during the late stage of the disease.8 A similar syndrome called canine multiple system degeneration has been observed in Chinese crested dogs.1
Functional deficits may precede histopathological changes, especially in breeds with the neonatal type of CCD.9
The underlying etiology has not been determined, and may indeed not be same in all breeds. In some canine breeds a storage disease has been suspected (i.e., Ceroid lipofuscinosis in American Staffordshire Terriers, Pit Bull Terrier)7, whereas in the fast majority of breeds the etiology is still completely unknown--even though an inherited intrinsic metabolic error is most likely. In Rhodesian Ridgebacks, the condition was linked with coat dilution, whereas it was seen in Bernese Mountain Dogs in association with hepatic fibrosis.10,11
The genetic basis has been established in American Staffordshire Terriers, whereas in other breeds such as Brittany Spaniel, Chow Chow, Coton de Tulear, Gordon Setter, Kerry Blue Terrier, Old English Sheepdog, and Rough Coated Collie a hereditary trait, which is usually autosomal recessive, has been identified.1,9,12-15
Clinical signs reflect the loss of function of inhibitory cerebellar cortical neurons. One of the first signs is a lack of coordination, which may initially become only obvious in certain situations such as turning around or negotiating stairs. With progression of the disease, permanent generalized ataxia, limb spasticity and dysmetria (inability to control range and force of movement) will develop. Dysmetria usually manifests as hypermetria, which results from loss of inhibition to limb flexion. In a standing position patients may have a wide based stance and they may experience truncal swaying from side to side (titubation). Patients may develop permanent head and neck tremor, which can be exacerbated by reaching for food, called intention tremor. Intention tremor can be interpreted as "dysmetria" of the head and neck. In cases of involvement of the flocculonodular lobe, vestibular signs, especially a broad based-staggering gait, tendency to fall to either side or backwards or forwards and nystagmus may be seen. Nystagmus may be permanent or more common positional (appears only after changing head position: head elevation or turning the patient on its back). However, nystagmus is not a consistent clinical sign of CCD. Vestibular signs, especially staggering gait and falling to the side, may be more obvious for some seconds after hyperextending the neck.
Dogs with CCD do not develop paresis or reduced muscle strength. The conscious proprioceptive reaction however, might be initiated with a slight delay followed by an exaggerated response. Segmental spinal reflexes are normal or hyperactive, but not decreased. Affected dogs do neither have mental or behavioral changes nor other cranial nerve deficits except a decreased menace response, despite normal vision and normal facial nerve function. The exact mechanism of how the cerebellum influences the menace response is not known, but it is assumed that either the pathway responsible for the menace response goes through the cerebellum or input occurs from the cerebellum to that pathway.1
The course of the disease is almost always chronic progressive. However, the rate of progression may vary significantly between breeds and dogs. In some breeds the clinical signs may progress rapidly resulting in complete inability to walk within months, whereas in other breeds, such as the American Staffordshire Terrier, the progression may take 3 to 8 years. In rare cases the disease may stabilize, as was observed in Collies at an age of 12 months. In cases of neonatal CCD the clinical signs might be static as seen in the Coton de Tulear.9
A few American Staffordshire Terriers with CCD have been reported experiencing seizures, even though it is not know if seizures are a manifestation of more generalized neurodegenerative changes or if those dogs have a seizure disorder in addition to CCD.16
Definite diagnosis requires histopathological evaluation of a brain tissue specimen. Therefore, in most cases final diagnosis is established on post-mortem examination, since cerebellar biopsies are rarely performed. A presumptive diagnosis is made by ruling out other cerebellar or vestibular diseases using cerebrospinal fluid (CSF) analysis, complete blood cell analysis, blood biochemistry, thyroid testing, urinalysis, brainstem auditory-evoked response, and computed tomography or magnetic resonance imaging (MRI) of the brain.
The amount of CSF between the cerebellar folia has been reported to appear to be increased in T2 weighted MR images in conjunction with an overall reduction in cerebellar size, which is more obvious on sagittal images.17 Mild cases or cases during the initial stage of the disease however, are difficult to diagnose that way. Therefore, more objective evaluation of cerebellar size using brain morphometry has been investigated more recently. It has been shown for American Staffordshire Terriers that the relative cerebellar size and the relative pericerebellar CSF space are significantly different between normal dogs and such affected by CCD based on measurements obtained from midsagittal T2 weighted brain MR images.18 The measurement of relative cerebellar size (ratio: area of the cerebellum/area of the entire brain x 100) could distinguish between affected and non affected dogs with a sensitivity and a specificity of 93 and 94%, respectively, using a cut-off of 13.3%. Using a cut-off of 12.8%, the measurement of relative CSF space (ratio: area of the cerebellum plus surrounding CSF/area of cerebellum without surrounding CSF x 100) could distinguish between both groups with a sensitivity of 93% and a specificity of 100%.
Another study has shown that similar measurements of relative cerebellar size based on MR images can be applied to other breeds in order to differentiate between dogs with CCD and normal dogs, even though the absolute cerebellar size is different in different breeds.19 In this study relative cerebellar size was not defined in relation to the size of the entire brain but in relation to the brain stem size. The brain stem/cerebellum ratio was 100% specific and sensitive using a cut off of 85.22% (values larger than this denoted affected status).
Even though MRI is an appropriate diagnostic tool to establish a presumptive diagnosis of CCD in patients showing neurological deficits, it is most likely not able to identify affected dogs before clinical signs develop. However, those diseases with presumably genetic background can only be eliminated by excluding carriers from breeding, which requires identification of affected dogs as early as possible. Therefore, possible marker genes are under investigation. As for the American Staffordshire Terrier, a genetic defect has been identified and a commercial test is available for screening. Applying this test it has been estimated that 30% of French American Staffordshire Terriers are carriers for CCD.
There is no known effective therapy for any of the conditions described above.
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