Adult onset thalamocerebellar degeneration in dogs associated to neuronal storage of ceroid lipopigment

Abstract

Late onset of hereditary cerebellar cortical abiotrophy has been described in a large variety of canine breeds. In some reported conditions, the cerebellar lesion is combined with degeneration of other systems. Here we describe a new hereditary cerebellar cortical degeneration in eight adult American Staffordshire and Pit Bull Terriers. The neuronal degeneration in these animals not only affects Purkinje cells of the cerebellum but also certain thalamic nuclei. In addition, nerve cell loss appears to be associated with a lysosomal storage disease, which is restricted to the affected cell populations. The stored material was histologically and ultrastructurally identified as fluorescent lipopigment. Since animals were euthanized at various stages of the disease, it could be shown that lysosomal storage preceded neuronal loss. Selective involvement of restricted neuronal populations is highly unusual in ceroid lipofuscinoses. It remains to be determined if the present neurodegenerative disease is caused by a primary or secondary neuronal ceroid lipofuscinosis.

Murine Cathepsin F Deficiency Causes Neuronal Lipofuscinosis and Late-Onset Neurological Disease

“…The heterogeneity of clinical presentations of late-onset disease suggests that more than one gene is likely involved (9). Several naturally occurring animal models exist that appear to represent late-onset NCLs, but thus far the underlying genetic defects have also not been identified in these (5,27,30,34). The present study has established another mouse model for late-onset NCL.…”

A canine Arylsulfatase G ( ARSG ) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis

“…E-mail: k9ncl@vet-alfort.fr. abiotrophy and remodeling with loss of Purkinje cells (15,16). Segregation analysis of ataxia in ASTs supports an autosomal recessive mode of inheritance with an alarming incidence of the deleterious allele, estimated at ∼40% (15).…”

Computer‐Assisted Magnetic Resonance Imaging Brain Morphometry in American Staffordshire Terriers with Cerebellar Cortical Degeneration

“…Cerebellar cortical degeneration in dogs has been reported in at least 27 different pure breeds and 1 mixed‐breed dog 1–40 . The onset of clinical signs differs among breeds but clinical signs usually start at <6 months of age 1,8,16–37,39 .…”

“…The onset of clinical signs differs among breeds but clinical signs usually start at <6 months of age 1,8,16–37,39 . Familial late‐onset cerebellar abiotrophies have been described in Gordon Setters, 2–4 Old English Sheepdogs, 5 Brittany Spaniels, 6,7 a Schnauzer‐Beagle dog, 9 Pit Bull Terriers, 15 Espagneul Bretons, 38 a Bernese Mountain dog, 40 and American Staffordshire Terriers 10–15 . Initially, clinical signs are very subtle, eg, an occasional sway of the body when making a sudden movement 13 .…”

“…Gross pathologic examination typically reveals diffuse atrophy of the cerebellum 4,8,12,13,19,22,31,33,39,40 . Histopathologic findings such as marked loss of Purkinje neurons, depletion of granular cell bodies, and shrinkage of the granular and molecular cell layer have been reported alone or in combination 2–40 . In breeds with familial late‐onset cerebellar abiotrophies, the mode of inheritance has been shown to be autosomal recessive in Old English Sheepdogs 5 and Gordon Setters 2,3 and it is suspected to be the same in American Staffordshire Terriers 13 .…”