Date Published: January 25, 2017
Publisher: Public Library of Science
Author(s): Susan P. Knowler, Chloe Cross, Sandra Griffiths, Angus K. McFadyen, Jelena Jovanovik, Anna Tauro, Zoha Kibar, Colin J. Driver, Roberto M. La Ragione, Clare Rusbridge, Claire Wade.
To characterise the symptomatic phenotype of Chiari-like malformation (CM), secondary syringomyelia (SM) and brachycephaly in the Cavalier King Charles Spaniel using morphometric measurements on mid-sagittal Magnetic Resonance images (MRI) of the brain and craniocervical junction.
This retrospective study, based on a previous quantitative analysis in the Griffon Bruxellois (GB), used 24 measurements taken on 130 T1-weighted MRI of hindbrain and cervical region. Associated brachycephaly was estimated using 26 measurements, including rostral forebrain flattening and olfactory lobe rotation, on 72 T2-weighted MRI of the whole brain. Both study cohorts were divided into three groups; Control, CM pain and SM and their morphometries compared with each other.
Fourteen significant traits were identified in the hindbrain study and nine traits in the whole brain study, six of which were similar to the GB and suggest a common aetiology. The Control cohort had the most elliptical brain (p = 0.010), least olfactory bulb rotation (p = 0.003) and a protective angle (p = 0.004) compared to the other groups. The CM pain cohort had the greatest rostral forebrain flattening (p = 0.007), shortest basioccipital (p = 0.019), but a greater distance between the atlas and basioccipital (p = 0.002) which was protective for SM. The SM cohort had two conformation anomalies depending on the severity of craniocervical junction incongruities; i) the proximity of the dens (p <0.001) ii) increased airorhynchy with a smaller, more ventrally rotated olfactory bulb (p <0.001). Both generated ‘concertina’ flexures of the brain and craniocervical junction. Morphometric mapping provides a diagnostic tool for quantifying symptomatic CM, secondary SM and their relationship with brachycephaly. It is hypothesized that CM pain is associated with increased brachycephaly and SM can result from different combinations of abnormalities of the forebrain, caudal fossa and craniocervical junction which compromise the neural parenchyma and impede cerebrospinal fluid flow.
Syringomyelia (SM) secondary to Chiari-like Malformation (CM) in the Cavalier King Charles Spaniel (CKCS) has been well documented over the last decade [1–3]. There is a high prevalence of SM in the breed for which CM is ubiquitous [4,5]. Canine CM is generally considered analogous to human Chiari-1 malformation and defined on the basis of the cerebellum being compacted into or herniated through the foramen magnum [6,7]. Aberrations of skull and brain morphology in CM can result in fluid cavitation of the spinal cord (syrinx or syringes) and this can develop progressively over time [8,9]. Reduced volume of the caudal fossa [10,11], cerebellar volume and herniation [12,13] medullary elevation (kinking) [13,14], jugular foramina [15,16], venous sinus volume  and atlanto-occipital overlapping [18,19] have all been shown to increase the risk of syringomyelia [20,21]. Evidence suggests that the early closure of skull bone sutures (craniosynostosis) in CKCS [9,22,23] and GB [15,24] reduces the size of the caudal fossa, alters the neuro-parenchymal morphology and disrupts cerebrospinal fluid (CSF) dynamics . Brachycephaly is a risk factor for SM and it is not fully understood how this and craniocervical junction abnormalities such as atlanto-occipital overlapping and medullary position interact with each other to contribute to the severity of CM and SM in the breed. Variable clinical signs are characterised by pain and / or sensory and motor neurological deficits depending on the site and extent of spinal cord damage [8,25,26]. However some dogs with CM alone exhibit behavioural signs of pain.
Inter-rater reliability was found to be very satisfactory with all ICC values in excess of 0.75. Average ICC value 0.86 for author SPK indicated a relatively high consistency maintained between the previous GB study and the CKCS study. Intra-observer results for author CC all exceeded 0.96 and 95% confidence intervals were considered narrow. Overall, 50 measurements, comprising 24 hindbrain (S1 Table) and 26 whole brain (S2 Table), were made to quantify the phenotypic differences CKCS with and without SM and with CM pain.
Morphometric mapping using a triangulation of lines, angles and circles is useful for defining SM and CM pain phenotypes. The results confirm that it is essential to consider the whole brain in the characterisation of CM which takes account of the brachycephaly and its additive effect on CM/SM. Through the standardisation of the ‘best fit’ circles and ellipse, it is possible to quantify differences in conformations associated with brachycephaly and the proximity of the cervical vertebrae to the skull that result in CM pain and SM. Linking the angles and lines to create a unique ‘signature ‘for each dog enables comparisons to be made relative to size and altered position of anatomical features. The Control cohort had the most natural, wolf-like, skull conformation in terms of ellipticity. The CM pain cohort was characterised by increased brachycephaly with greatest rostral forebrain flattening, shortest basicranium and compensatory cranial height. However, in this cohort, an increased distance between the occiput and atlas provided fewer impediments to CSF dynamics at the foramen magnum and reduced the risk for SM. The SM cohort exhibited two conformation anomalies. One phenotype variation was influenced by incongruities at the craniocervical junction and increased proximity of the dens producing a ‘concertina’ type flexure with medullary elevation. The other phenotypic variation was influenced by increased brachycephaly resulted in a ‘concertina’ type flexure similar to the CM pain cohort. However, both SM variations were characterised by an apparent reduction in caudal fossa volume which compromised the CSF dynamics in the spinal cord.