Susan P. Knowler

Hereditary aspects of occipital bone hypoplasia and syringomyelia (Chiari type I malformation) in cavalier King Charles spaniels

A database of over 1300 cavalier King Charles spaniels spanning 20 generations was established by obtaining pedigree information from 45 dogs with syringomyelia secondary to occipital bone hypoplasia. These data were supplemented with published information from the breed club. The incidence of syringomyelia was very high in certain families and lines which had been extensively inbred. The affected dogs could be traced back to one bitch born in 1956 and the two offspring from her single lifter. Four key dogs representing four major breeding lines consistently occurred within the individual pedigrees. If a dog had more than five of its eight great-grandparents descended from these four lines there was a greater chance of it having syringomyelia. The data from this preliminary study suggest that occipital bone hypoplasia is hereditary in the cavalier King Charles spaniel and that its inheritance is more likely to be autosomal recessive because both dam and sire must be inbred descendants from certain lines. However, the inheritance is more likely to be of variable penetrance or oligogenic than simple.

Prevalence of asymptomatic syringomyelia in Cavalier King Charles spaniels

The prevalence of syringomyelia was investigated in a sample population of 555 Cavalier King Charles spaniels. All dogs, which were declared by their owners to be showing no clinical signs of syringomyelia, underwent MRI to determine the presence or absence of the condition. Data were analysed by logistic regression to determine the effects of sex and age on the prevalence of syringomyelia. Only increased age was found to have a significant effect. The prevalence of syringomyelia was 25 per cent in dogs aged 12 months, increasing to a peak of 70 per cent in dogs aged 72 months or more.

Chiari-like malformation in the Griffon Bruxellois

OBJECTIVES This study describes Chiari-like malformation and syringomyelia in the Griffon Bruxellois and establishes if skull radiographs are useful for disease prediction. METHODS Magnetic resonance imaging from 56 Griffon Bruxellois dogs was assessed for Chiari-like malformation and cerebrospinal fluid pathway abnormalities. Skull radiographs were obtained in 33 dogs. Two rostrocaudal and two ventrodorsal measurements were made, and ratios of one length to another were compared. RESULTS In this selected sample, 60.7 per cent had Chiari-like malformation. Syringomyelia occurred with and without Chiari-like malformation (37.5 and 8.9 per cent study population, respectively). The radiographic study demonstrated that one measurement ratio could be used to predict Chiari-like malformation (sensitivity of 87 per cent and specificity of 78 per cent) and that there were significant interaction factors between sex and syringomyelia for two measurement ratios. CLINICAL SIGNIFICANCE The study suggests that Chiari-like malformation is characterised by a shortening of the basicranium and supra-occipital bone with a compensatory lengthening of the cranial vault, especially the parietal bone. We described a simple radiographic technique, which may be useful as a screening test until a more definite genetic test for Chiari-like malformation is available.

Feline orofacial pain syndrome (FOPS): A retrospective study of 113 cases

Feline orofacial pain syndrome (FOPS) is a pain disorder of cats with behavioural signs of oral discomfort and tongue mutilation. This report describes the findings from a case series of 113 cats including 100 Burmese. FOPS is suspected to be a neuropathic pain disorder and the predominance within the Burmese cat breed suggests an inherited disorder, possibly involving central and/or ganglion processing of sensory trigeminal information. The disease is characterised by an episodic, typically unilateral, discomfort with pain-free intervals. The discomfort is triggered, in many cases, by mouth movements. The disease is often recurrent and with time may become unremitting — 12% of cases in this series were euthanased as a consequence of the condition. Sensitisation of trigeminal nerve endings as a consequence of oral disease or tooth eruption appears to be an important factor in the aetiology — 63% of cases had a history of oral lesions and at least 16% experienced their first sign of discomfort during eruption of permanent teeth. External factors can also influence the disease as FOPS events could be directly linked to a situation causing anxiety in 20% of cats. FOPS can be resistant to traditional analgesics and in some cases successful management required anti-convulsants with an analgesic effect.

Quantitative Analysis of Chiari-Like Malformation and Syringomyelia in the Griffon Bruxellois Dog

This study aimed to develop a system of quantitative analysis of canine Chiari-like malformation and syringomyelia on variable quality MRI. We made a series of measurements from magnetic resonance DICOM images from Griffon Bruxellois dogs with and without Chiari-like malformation and syringomyelia and identified several significant variables. We found that in the Griffon Bruxellois dog, Chiari-like malformation is characterized by an apparent shortening of the entire cranial base and possibly by increased proximity of the atlas to the occiput. As a compensatory change, there appears to be an increased height of the rostral cranial cavity with lengthening of the dorsal cranial vault and considerable reorganization of the brain parenchyma including ventral deviation of the olfactory bulbs and rostral invagination of the cerebellum under the occipital lobes.

Effectiveness of breeding guidelines for reducing the prevalence of syringomyelia

Several toy breed dogs are predisposed to syringomyelia (SM), a spinal cord disorder, characterised by fluid-filled cavitation. SM is a complex trait with a moderately high heritability. Selective breeding against SM is confounded by its complex inheritance, its late onset nature and high prevalence in some breeds. This study investigated the early outcome of existing SM breeding guidelines. Six hundred and forty-three dogs, 550 Cavalier King Charles spaniels (CKCS) and 93 Griffon Bruxellois (GB), were identified as having either one (454 dogs) or both parents (189 dogs) with MRI-determined SM status. Offspring without SM were more common when the parents were both clear of SM (SM-free; CKCS 70 per cent, GB 73 per cent). Conversely, offspring with SM were more likely when both parents had SM (SM-affected; CKCS 92 per cent, GB 100 per cent). A mating of one SM-free parent with an SM-affected parent was risky for SM affectedness with 77 per cent of CKCS and 46 per cent of GB offspring being SM-affected. It is recommended that all breeding dogs from breeds susceptible to SM be MRI screened; that the SM status at five years old is established; and all results submitted to a central database that can be used by dog breeders to better enable mate selection based on estimated breeding values.

Craniometric Analysis of the Hindbrain and Craniocervical Junction of Chihuahua, Affenpinscher and Cavalier King Charles Spaniel Dogs With and Without Syringomyelia Secondary to Chiari-Like Malformation

Objectives To characterize and compare the phenotypic variables of the hindbrain and craniocervical junction associated with syringomyelia (SM) in the Chihuahua, Affenpinscher and Cavalier King Charles Spaniel (CKCS). Method Analysis of 273 T1-weighted mid-sagittal DICOM sequences of the hindbrain and craniocervical junction from 99 Chihuahuas, 42 Affenpinschers and 132 CKCSs. The study compared 22 morphometric features (11 lines, eight angles and three ratios) of dogs with and without SM using refined techniques based on previous studies of the Griffon Bruxellois (GB) using Discriminant Function Analysis and ANOVA with post-hoc corrections. Results The analysis identified 14/22 significant traits for SM in the three dog breeds, five of which were identical to those reported for the GB and suggest inclusion of a common aetiology. One ratio, caudal fossa height to the length of the skull base extended to an imaginary point of alignment between the atlas and supraoccipital bones, was common to all three breeds (p values 0.029 to <0.001). Associated with SM were a reduced occipital crest and two acute changes in angulation i) ‘sphenoid flexure’ at the spheno-occipital synchondrosis ii) ‘cervical flexure’ at the foramen magnum allied with medulla oblongata elevation. Comparing dogs with and without SM, each breed had a unique trait: Chihuahua had a smaller angle between the dens, atlas and basioccipital bone (p value < 0.001); Affenpinschers had a smaller distance from atlas to dens (p value 0.009); CKCS had a shorter distance between the spheno-occipital synchondrosis and atlas (p value 0.007). Conclusion The selected morphometries successfully characterised conformational changes in the brain and craniocervical junction that might form the basis of a diagnostic tool for all breeds. The severity of SM involved a spectrum of abnormalities, incurred by changes in both angulation and size that could alter neural parenchyma compliance and/or impede cerebrospinal fluid channels.

Inheritance of Chiari-Like Malformation: Can a Mixed Breeding Reduce the Risk of Syringomyelia?

Canine Chiari-like malformation (CM) is a complex abnormality of the skull and craniocervical junction associated with miniaturization and brachycephaly which can result in the spinal cord disease syringomyelia (SM). This study investigated the inheritance of CM in a Griffon Bruxellois (GB) family and feasibility of crossbreeding a brachycephalic CM affected GB with a mesaticephalic normal Australian terrier and then backcrossing to produce individuals free of the malformation and regain GB breed characteristics. The study family cohort (n = 27) included five founder dogs from a previous baseline study of 155 GB which defined CM as a global malformation of the cranium and craniocervical junction with a shortened skull base and increased proximity of the cervical vertebrae to the skull. T1-weighted sagittal DICOM images of the brain and craniocervical junction were analysed for five significant traits (two angles, three lines) identified from the previous study and subsequent Qualitative Trait Loci analysis. Mean measurements for mixed breed, pure-breed and baseline study groups were compared. Results indicated that mixed breed traits posed less risk for CM and SM and were useful to distinguish the phenotype. Moreover on the MR images, the filial relationships displayed by the traits exhibited segregation and those presenting the greatest risk for CM appeared additive towards the severity of the condition. The external phenotypes revealed that by outcrossing breed types and with careful selection of appropriate conformation characteristics in the first generation, it is possible to regain the GB breed standard and reduce the degree of CM. The four GB affected with SM in the study all exhibited reduced caudal skull development compared to their relatives. The craniocervical traits may be useful for quantifying CM and assessing the possibility of SM thus assisting breeders with mate selection. However, such a system requires validation to ensure appropriateness for all breeds at risk.

Syringomyelia: determining risk and protective factors in the conformation of the Cavalier King Charles Spaniel dog

BackgroundSyringomyelia (SM) is a painful neurological condition, prevalent in brachycephalic toy breeds including the Cavalier King Charles Spaniel (CKCS). In these breeds, SM is typically secondary to Chiari-like Malformation (CM). There has been much debate in the scientific and veterinary communities to what extent head shape is indicative of either pathology, especially as certain craniosynostosis syndromes in humans (highly associated with CM) have characteristic facial and cranial morphologies. Elucidating a risk morphology would allow for selection away from these traits and proffer further breeding guidelines for the condition.Dogs were measured in multiple countries by means of a standardised bony landmark measuring protocol and photo analysis by blinded, trained researchers.ResultsThe results found two significant risk factors in the conformation of the CKCS: extent of brachycephaly and distribution of cranium. The study identified a greater amount of cranium distributed caudally (relative to the amount distributed rostrally) to be significantly protective against syrinx development at the levels of three years of age, five years of age and when comparing a sample of SM clear individuals over the age of five to those affected younger than three years of age. A decreased cephalic index (decreasing brachycephaly) was significantly protective at the latter level. Cephalic index and caudal cranium distribution exhibited a negative, linear relationship. Cephalic index demonstrated a positive linear relationship with the amount of doming of the head.ConclusionsThis study proposes a risk phenotype of brachycephaly with resulting rostrocaudal doming that is more rostrally distributed and hence sloping caudally.The results of this study may allow for selection against risk aspects of conformation in the CKCS in combination with the British Veterinary Association/Kennel Club CM/SM scheme to enable reduction in CM/SM incidence. Further research comparing this external risk phenotype to the internal presentation upon MRI would determine how these features are indicative of syrinx development. Utilising breeds in which CM free individuals are more available may allow for validation of this risk phenotype for CM or determine alternatives.

Progression of otitis media with effusion in the Cavalier King Charles spaniel

Hyperintense material is often detected within the tympanic bullae on T2-weighted MRI scans during screening schemes for Chiari-like malformation and syringomyelia (CMSM). This is frequently regarded as an incidental finding and is sometimes associated with hearing loss (Lu and others 2003, Owen and others 2004, Harcourt-Brown and others 2011). This may be analogous to otitis media with effusion (OME) in humans, which is informally referred to as ‘glue ear’. OME in humans is characterised by the presence of a middle ear effusion for three months or more, and the general absence of gross signs of infection (Kubba and others 2000). This is distinct from suppurative otitis media, which is associated with acute clinical signs. Previously, the term ‘Primary secretory otitis media’ (PSOM) has been used to describe an effusion present in the tympanic bullae of Cavalier King Charles Spaniels (CKCS) (Stern-Bertholtz and others 2003). All these cases were associated with moderate to severe pain and/or neurological signs. As no cases in our study had associated pain, and due to the chronicity of the condition, the authors have classified the condition described in this study as OME. It has recently been shown that the prevalence of OME in dogs is significantly associated with brachycephalic conformation, and that bilateral OME was associated with CKCS with more extreme nasopharyngeal conformation, than unaffected …