Clinical, imaging and histopathological characterization of a series of three cats with cerebellar cortical degeneration

Abstract

Background: Neurological inherited disorders are rare in domestic animals. Cerebellar cortical degeneration remains amongst the most common of these disorders. The condition is defined as the premature loss of fully differentiated cerebellar components due to genetic or metabolic defects. It has been studied in dogs and cats, and various genetic defects and diagnostic tests (including magnetic resonance imaging (MRI)) have been refined in these species. Cases in cats remain rare and mostly individual, and few diagnostic criteria, other than post-mortem exam, have been evaluated in reports with multiple cases. Here, we report three feline cases of cerebellar cortical degeneration with detailed clinical, diagnostic imaging and post-mortem findings.

Case presentation: The three cases were directly (siblings, case #1 and #2) or indirectly related (same farm, case #3) and showed early-onset of the disease, with clinical signs including cerebellar ataxia and tremors. Brain MRI was highly suggestive of cerebellar cortical degeneration on all three cases. The relative cerebrospinal fluid (CSF) space, relative cerebellum size, brainstem: cerebellum area ratio, and cerebellum: total brain area ratio, were measured and compared to a control group of cats and reference cut-offs for dogs in the literature. For the relative cerebellum size and cerebellum: total brain area ratio, all affected cases had a lower value than the control group. For the relative CSF space and brainstem: cerebellum area ratio, the more affected cases (#2 and #3) had higher values than the control group, while the least affected case (#3) had values within the ranges of the control group, but a progression was visible over time. Post-mortem examination confirmed the diagnosis of cerebellar cortical degeneration, with marked to complete loss of Purkinje cells and associated granular layer depletion and proliferation of Bergmann glia. One case also had Wallerian-like degeneration in the spinal cord, suggestive of spinocerebellar degeneration.

Conclusion: Our report further supports a potential genetic component for the disease in cats. For the MRI examination, the relative cerebellum size and cerebellum: total brain area ratio seem promising, but further studies are needed to establish specific feline cut-offs. Post-mortem evaluation of the cerebellum remains the gold standard for the final diagnosis.

Keywords: Cerebellar cortical degeneration; Genetic; Inherited; MRI; Purkinje cells.

Fig. 1

Mid-sagittal T2w FSE MRI images of the brain of three cats diagnosed with cerebellar cortical degeneration. (A) Case #1 at time of diagnosis, (B) Case #2, (C) Case #3 and D) unaffected feline brain for comparison. In the three cases, there is increased conspicuity of CSF space between cerebellar folia (arrows) of varying severity, considered subjectively moderate to marked in B) and C), and mild in A). There is also a mild distension of the fourth ventricle in B) and (C) (asterix)

Fig. 2

Mid-sagittal T2w FSE MRI images of the brain of case #1. (A) At time of imaging diagnosis with (B) close-up on the cerebellum. (C) Follow up 8 months later with (D) close-up on the cerebellum. There is moderate progression over time of the increased conspicuity of CSF space between cerebellar folia within both examinations (white arrows). The cerebellum has mildly decreased size and a mild progressive distension of the fourth ventricle is also noted at follow-up (asterix)

Fig. 3

Mid-sagittal T2w FSE MRI image of an unaffected cat illustrating the methodology of MRI measurements. The measurements used were described by Henke et al. [33] and Thames et al. [32] in dogs. (A) Three regions of interest (ROI) depicting the entire brain (white line), cerebellum (blue line) and the cerebellum plus cerebrospinal fluid (CSF) (yellow line). The relative cerebellar size was calculated as follows: area of the cerebellum x 100/area of the entire brain. The relative CSF space was calculated as follows: (area of the cerebellum plus CSF – area of the cerebellum) x 100/ area of the cerebellum plus CSF. (B) Three ROI depicting the forebrain (orange line), the brainstem (green line), and the cerebellum (blue line). The brainstem: cerebellum area ratio was calculated as follows: area of the brainstem / area of the cerebellum. The cerebellum: total brain area ratio was calculated as follows: cerebellum area / (forebrain area + brainstem area + cerebellum area)

Fig. 4

Gross and histopathological analyses of the brain/cerebellum of three cats diagnosed with cerebellar cortical degeneration. Case #1 (A, D, G), case #2 (B, E, H) and case #3 (C, F, I). On gross examination (A, B, C), there is decreased cerebellar size at different degree of severity between cases. The transverse cerebral fissure is prominent in case #3 (white arrow, C). At low magnification (D, E, F), histopathology revealed more prominent cerebellar sulci (black arrow, D) in all cases, along with marked pallor of cortical gray matter due to variable degrees of thinning of the granular layer. Bar = 2 mm. High magnification (G, H, I) shows complete loss of Purkinje cells with vacuolation and numerous empty spaces filled with eosinophilic granular material corresponding to Purkinje cell debris (black arrow, H). In the most severe case (I), the granular layer is thin, poorly cellular and pale (*). Bar = 200 μm

Fig. 5

Additional histological observations. (A, B) Immunohistochemical analysis using anti-GFAP marker shows an increased proliferation of Bergmann glia (orange) in a cerebellum section of case #2, compared to a less severely affected region of the same cat (internal control) (B). (C, D) Wallerian-like degeneration noted in the dorsal spinal cord white matter of case #1 (C), axonal spheroids and debris, digestion chambers and empty vacuoles, visible at high magnification (D). Bars = 100 μm