Cerebellar granuloprival and trans‐synaptic degeneration in a Chihuahua

Abstract

An unusual form of cerebellocortical degeneration called cerebellar granuloprival degeneration was diagnosed in a four-month-old Chihuahua. The dog had a two-week history of progressive signs of cerebellar dysfunction, including a wide-based stance, intention tremors and bilateral absence of menace response without visual impairment. On MRI of the encephalon, a reduction in cerebellar size was detected. On histopathological examination, depletion of the cerebellar granule cell layer was observed, in addition to neuronal degeneration in the vestibular nuclei, reticular formation, red nucleus and internal laminae of the parietal and temporal cortices. A diagnosis of cerebellar granuloprival degeneration with trans-synaptic degeneration was made. To the authors’ knowledge, this is the first case report of cerebellar granuloprival degeneration in a Chihuahua and the first report of cerebellar granuloprival degeneration with trans-synaptic degeneration in a dog.

Granuloprival cerebellar cortical degeneration in a Yorkshire Terrier and Lagotto Romagnolo dog

“…Granuloprival CCD is a relatively uncommon form of CCD and the exact etiology remains to be elucidated and might be multifactorial 1,5,9‐11 . Canine herpesvirus has been reported to cause granular cell depletion with associated Purkinje neuron loss along with foci of infiltrating mononuclear cells and malacia 13 .…”

“…The mechanisms underlying a genetically‐mediated selective loss of granule cell neurons also remain unclear 6,9‐11 . A channelopathy resulting in excitotoxicity and apoptosis of granule cell neurons as occurs in homozygous weaver mice has been postulated in dogs 6,19,20 .…”

“…Antemortem presumptive diagnosis of CCD involves ruling out anomalous, neoplastic, inflammatory (immune‐mediated and infectious), and metabolic causes as well as other degenerative causes 1 . Magnetic resonance imaging can be normal, usually early in the disease process, or can disclose a decreased cerebellar size with decreased thickness of the cerebellar folia, resulting in widening of the associated cerebellar fissures with cerebrospinal fluid 1,8,11 . Clinically, antemortem differentiation of CCD from cerebellar hypoplasia relies on criteria such as onset and progression of clinical signs 25 .…”

“…Because CCD is a degenerative condition with no known treatment, clinical signs progress until quality of life becomes compromised at which time euthanasia usually is performed 1 . All dogs with granuloprival CCD are reported to have been euthanized between 4 weeks and 6 months after the onset of clinical signs owing to compromised quality of life 2‐11 . In Case 1, euthanasia was performed 6 weeks after the onset of clinical signs, but in Case 2, euthanasia was performed 13 months after the onset of clinical signs, representing the longest reported survival time.…”

“…In the majority of dogs with CCD, the Purkinje neuron is the primary target with secondary retrograde degeneration of the granule cell neurons 1 . Sporadic cases of selective loss of granule cell neurons with relative sparing of the Purkinje neurons, called granuloprival degeneration, are also reported 2‐11 . These include reports of several puppies in a single litter being affected in the Border Collie, Labrador Retriever, Bavarian Mountain dog, and Coton de Tuléar breed, as well as single reported cases in the Australian Kelpie, Italian hound, and Lagotto Romagnolo breed 2‐11 …”