Cerebellar Cortical Degeneration in Adult American Staffordshire Terriers

Abstract

Adult-onset cerebellar cortical degeneration recently has been reported in American Staffordshire Terriers. We describe the clinical and histopathologic features of this disease and examine its mode of inheritance in 63 affected dogs. The age at which neurologic deficits 1st were recognized varied from 18 months to 9 years, with the majority of dogs presented to veterinarians between 4 and 6 years of age. Time from onset of clinical signs to euthanasia varied from 6 months to 6.5 years, with the majority of affected dogs surviving from 2 to 4 years. Initial neurologic findings included stumbling, truncal sway, and ataxia exacerbated by lifting the head up and negotiating stairs. Signs progressed to obvious ataxia characterized by dysmetria, nystagmus, coarse intention tremor, variable loss of menace reaction, marked truncal sway, and falling with transient opisthotonus. With continued progression, dogs became unable to walk without falling repeatedly. Cerebellar atrophy was visible on magnetic resonance images and on gross pathology. Histopathologic findings included marked loss of Purkinje neurons with thinning of the molecular and granular layers and increased cellularity of the cerebellar nuclei. The closest common ancestor of the dogs was born in the 1950s and inheritance was most consistent with an autosomal recessive mode of transmission with a prevalence estimated at 1 in 400 dogs. This inherited disease is comparable to the group of diseases known as spinocerebellar ataxias in humans. Many spinocerebellar ataxias in humans are caused by nucleotide repeats, and this genetic aberration merits investigation as a potential cause of the disease in American Staffordshire Terriers.

Genome sequencing reveals a splice donor site mutation in the SNX14 gene associated with a novel cerebellar cortical degeneration in the Hungarian Vizsla dog breed

“…These changes fit well with previous reports of CCD or cerebellar abiotrophy, where primary Purkinje neuron loss and secondary granular cell degeneration are most commonly reported [7, 11, 13, 14, 16]. Similar to previous studies, the HVs also demonstrated a characteristic distribution of cerebellar folial atrophy, with the dorsal and rostral vermis predominantly affected whilst the caudoventral regions appeared spared [10, 12, 14, 17].…”

“…Although they remained ambulatory, both dogs demonstrated a progressive clinical course over a short period of around two months, to the point that their owners elected for euthanasia on humane grounds due to their poor quality of life. This history of progression to euthanasia is typical of CCD in most breeds, apart from those with an adult onset and slowly progressive CCD, whereby survival for years is possible [7, 12, 15]. …”

“…Histopathological examination most often reveals a primary diffuse loss of Purkinje neurons in the cerebellar cortex, in some cases with milder secondary neuronal depletion of the granular and molecular cell layers [7, 11, 13, 14, 16]. Less commonly there have also been reports of primary granular cell loss with sparing of the Purkinje neuron layer in some dog breeds, including the Border Collie and Bavarian Mountain Dog [6, 8], as well as an immune-mediated granuloprival degeneration in the Coton de Tulear [18].…”

Comparing the effects of first‐line antiepileptic drugs on the gait of dogs with idiopathic epilepsy

“…This method is easily implemented in a clinical setting and has been used to assess the recovery of dogs post spinal surgery successfully (Olby and others 2004). There are concerns, however, with reproducibility of rating scales due to their subjective nature (Gordon-Evans and others 2009), observer bias (Arkell and others 2006) and the influence of observer experience on the results (Keegan and others 1998, 2010).…”

Large Animal Models for Batten Disease

“…13,14 Progressive ataxia is the most obvious symptom, with initial disease onset occurring around 3 years to 5 years of age. Visual impairments are not reported and upon examination there is an absence of lipofuscin in the retina.…”