Colin J. Driver

Relationship of brain parenchyma within the caudal cranial fossa and ventricle size to syringomyelia in cavalier King Charles spaniels.

OBJECTIVES To assess if the volumes of the caudal cranial fossa (CCF), parenchyma within the caudal cranial fossa (CCFP) or ventricles (V) are associated with syringomyelia (SM) in cavalier King Charles spaniels (CKCS) with Chiari-like malformation (CM). To evaluate if volumes are associated with transverse syrinx width. METHODS Magnetic resonance images of 59 CKCS with CM were retrospectively reviewed and grouped with or without SM. Three-dimensional images were created and volumes of the fossae, brain parenchyma and ventricular system were calculated from which percentages of CCF, CCFP and V were created. If present, syrinx size was measured from its maximal transverse width. The percentages were statistically compared between groups, and correlation between percentages and syrinx dimensions was made. RESULTS CKCS with SM had significantly higher CCFP (P=0.0001) and V (P=0.0002) to those without but no significant difference in CCF (P=0.925). There was a positive correlation between CCFP and syrinx width (Pearson r=0.437) and ventricle size to syrinx width (Spearman r=0.627). CLINICAL SIGNIFICANCE A more marked overcrowding of the CCF is associated with SM, which may explain the high incidence of SM in CKCS with CM. The association between ventricle and syrinx dimensions supports the theory that SM development is the result of altered cerebrospinal fluid dynamics.

Long-term outcome of Cavalier King Charles spaniel dogs with clinical signs associated with Chiari-like malformation and syringomyelia

The disease complex Chiari-like malformation (CM) and syringomyelia (SM) has been associated with the development of neuropathic pain (NeP), and commonly affects Cavalier King Charles spaniels (CKCS). This prospective cohort study followed 48 CKCSs with CM and/or SM and clinical signs suggestive of NeP for a period of 39 (±14.3) months from diagnosis. At the end of the study, 36 dogs were still alive; five dogs died of an unrelated or unknown cause, and seven were euthanased due to severe clinical signs suggestive of NeP. During the follow-up period, the clinical signs of scratching, facial rubbing behaviour, vocalisation and exercise ability were evaluated. Nine out of 48 dogs stopped scratching (P<0.001), but there was no statistically significant change in the number of dogs exhibiting exercise intolerance, vocalisation or facial rubbing behaviour. The overall severity of clinical signs based on a visual analogue scale (VAS) (0 mm: no clinical signs 100 mm: severe clinical signs) increased (from median 75 mm (interquartile ranges (IQR) 68–84) to 84 mm (IQR 71.5–91), P<0.001). A quarter of the dogs were static or improved. In general, the majority of the owners felt that the quality of life of their dogs was acceptable. Medical treatments received were gabapentin or pregabalin and/or intermittently, carprofen. The owners perception of their animals progress, and progress based on VAS, had strong positive correlation (Spearmans rank correlation (sr) 0.74, P<0.001). Overall, this study suggests that clinical signs suggestive of NeP progress in three-quarters of CKCSs with CM and/or SM.

Increase in Cerebellar Volume in Cavalier King Charles Spaniels with Chiari-like Malformation and Its Role in the Development of Syringomyelia

Previous research in Cavalier King Charles Spaniels (CKCS) has found that Chiari-like malformation and syringomyelia (CM/SM) are associated with a volume mismatch between the caudal cranial fossa (CCF) and the brain parenchyma contained within. The objectives of this study were to i) compare cerebellar volume in CKCS (a “high risk’ group which frequently develops CM/SM), small breed dogs (medium risk – occasionally develop CM/SM), and Labradors (low risk – CM/SM not reported); ii) evaluate a possible association between increased cerebellar volume and CM/SM in CKCS; iii) investigate the relationship between increased cerebellar volume and crowding of the cerebellum in the caudal part of the CCF (i.e. the region of the foramen magnum). Volumes of three-dimensional, magnetic resonance imaging derived models of the CCF and cerebellum were obtained from 75 CKCS, 44 small breed dogs, and 31 Labradors. As SM is thought to be a late onset disease process, two subgroups were formed for comparison: 18 CKCS younger than 2 years with SM (CM/SM group) and 13 CKCS older than 5 years without SM (CM group). Relative cerebellar volume was defined as the volume of the cerebellum divided by the total volume of brain parenchyma. Our results show that the CKCS has a relatively larger cerebellum than small breed dogs and Labradors and provide evidence that increased cerebellar volume in CKCS is associated with crowding of cerebellum in the caudal part of the CCF. In CKCS there is an association between increased cerebellar volume and SM. These findings have implications for the understanding of the pathological mechanisms of CM/SM, and support the hypothesis that it is a multifactorial disease process governed by increased cerebellar volume and failure of the CCF to reach a commensurate size.

An update on the pathogenesis of syringomyelia secondary to Chiari-like malformations in dogs

Syringomyelia (SM) is a spinal cord disease that can cause neuropathic pain in dogs. The pathogenesis of SM secondary to Chiari-like malformation (CM) has been the focus of intense research in recent years. The gulf in our understanding of CM/SM in dogs relative to the analogous human condition has progressively narrowed. CM is primarily a disease of abnormal geometric morphometry affecting the caudal cranial fossa and the brain parenchyma contained within it. This review describes how advanced imaging techniques have revealed a series of morphometric abnormalities associated with CM/SM. The series is presented in a logical order to help describe the pathogenesis of CM and the subsequent formation of syringes, with particular reference to the concepts of craniospinal compliance and cerebrospinal fluid pulse pressure timing.

Morphometric assessment of cranial volumes in age-matched Cavalier King Charles spaniels with and without syringomyelia

MORPHOLOGICAL abnormalities of the caudal cranial fossa (CCF) and craniocervical region, termed Chiari-like malformation (CM), are almost ubiquitous in Cavalier King Charles spaniels (CKCS) ([Cerda-Gonzalez and others 2009][1]). Syringomyelia is a painful condition that is commonly associated with

Changes over time in craniocerebral morphology and syringomyelia in cavalier King Charles spaniels with Chiari-like malformation.

BackgroundChiari-like malformation (CM) and syringomyelia is a neurological disease complex with high prevalence in cavalier King Charles spaniels (CKCS). The natural progression of this disease with time has not been described. The objectives of this study were to i) determine if syringomyelia progresses with time ii) determine if features of craniocrebral morphology previously associated with CM are progressive (including caudal cranial fossa volume, caudal cranial fossa parenchymal volume, ventricular dimensions, height of the foramen magnum and degree of cerebellar herniation). A retrospective morphometric analysis was undertaken in 12 CKCS with CM for which repeat magnetic resonance images were available without surgical intervention.ResultsThe maximal syrinx width, height of the foramen magnum, length of cerebellar herniation and caudal cranial fossa volume increased over time. Ventricular and caudal fossa parenchymal volumes were not significantly different between scans.ConclusionsThe results of this study suggest that syringomyelia progresses with time. Increased caudal cranial fossa volume may be associated with active resorption of the supraoccipital bone, which has previously been found in histology specimens from adult CKCS. We hypothesise that active resorption of the supraoccipital bone occurs due to pressure from the cerebellum. These findings have important implications for our understanding of the pathogenesis and variable natural clinical progression of CM and syringomyelia in CKCS.

Influence of head positioning on the assessment of Chiari-like malformation in Cavalier King Charles spaniels.

Chiari-like malformation (CM) is almost omnipresent in the Cavalier King Charles spaniels (CKCS), often leading to syringomyelia (SM). Morphometric studies have produced variable results concerning relationship between the brain parenchyma within the caudal cranial fossa (CCF) and SM. The present study assesses the effect of head position, one potential confounder. Magnetic resonance images of CKCS with CM were reviewed in extended and flexed head positions. Volumes were calculated from transverse T2-weighted brain images. Mid-sagittal images were used for measurement of cerebellar herniation and CSF space between cerebellum and brainstem. Fourteen CKCS were included into the study, seven dogs with CM and seven with CM/SM. There was no difference between the relative brain parenchyma within the CCF in extended position and flexed position, or the brain parenchyma within the rostral and middle cranial fossae proportion. Cerebellar herniation and CSF space between cerebellum and brainstem were significantly increased in the flexed position. Cerebellar herniation and CSF space differed significantly between CM and CM/SM in a flexed head position. Volumetric measurements did not vary with head position. Cerebellar herniation and CSF space between the cerebellum and the brainstem were larger in a flexed head position.

Caudal cranial fossa partitioning in Cavalier King Charles spaniels

Cavalier King Charles spaniels (CKCS) are notable among dog breeds for their high rate of Chiari-like malformation (CM-characterised by indentation of the cerebellum by the supraoccipital bone and/or herniation of a part of the cerebellum through the foramen magnum (Cappello and Rusbridge 2007)) and syringomyelia (SM-fluid-filled cavities within the spinal cord (syringes) (Rusbridge and others 2000, Lu and others 2003). The cause of this painful and heritable disease complex (Rusbridge and Knowler 2004, Lewis and others 2010) has been attributed to a volume mismatch between the caudal cranial fossa (CCF) and brain parenchyma contained within, mediated by crowding of hindbrain parenchyma and disturbance to cerebrospinal fluid flow dynamics in the caudal occipital region of the skull (Levine 2004, Rusbridge and others 2006). Although the occipital bones of CKCS appear to be malformed (Dewey and others 2004, Rusbridge and Knowler 2006, Carrera and others 2009), previous studies that investigated a possible association between reduced CCF volume and CM/SM yielded inconsistent results (Couturier and others 2008, Carrera and others 2009, Carruthers and others 2009, Cerda-Gonzalez and others 2009, Schmidt and others 2009, Driver and others 2010a, b). Furthermore, when CKCS were compared with other small breed dogs (SB), the CCF was appropriate in size but contained parenchyma that was disproportionately large (Cross and others 2009), suggesting that the aetiology of CM/SM in CKCS may be related to increased growth of the hindbrain. The authors of this communication recently reported that CKCS have a relatively larger cerebellum than SB and labradors (LD), and also found that in CKCS there is an association between the development of SM and increased cerebellar volume (Shaw and others 2012). However, this study also showed that increased cerebellar volume was associated with increased crowding in the caudal …

Assessment of cerebellar pulsation in dogs with and without Chiari-like malformation and syringomyelia using cardiac-gated cine magnetic resonance imaging

Canine Chiari-like malformation (CM) is characterised by herniation of part of the cerebellum through the foramen magnum. In humans with Chiari type I malformation (CM-I), abnormal pulsation of the cerebellum during the cardiac cycle has been documented and is pivotal to theories for the pathogenesis of syringomyelia (SM). In this retrospective study, cardiac-gated cine balanced fast field echo (bFEE) magnetic resonance imaging (MRI) was used to assess pulsation of the brain in dogs and to objectively measure the degree of cerebellar pulsation with the neck in a flexed position. Overall, 17 Cavalier King Charles Spaniels (CKCS) with CM, including eight with SM and nine without SM, were compared with six small breed control dogs. Linear regions of interest were generated for the length of cerebellar herniation from each phase of the cardiac cycle and the degree of cerebellar pulsation was subsequently calculated. Age, bodyweight and angle of neck flexion were also compared. CKCS with CM and SM had significantly greater pulsation of the cerebellum than control dogs (P=0.003) and CKCS with CM only (P=0.031). There was no significant difference in age, bodyweight and angle of neck flexion between the three groups. Cardiac-gated cine bFEE MRI permitted the dynamic visualisation of cerebellar pulsation in dogs. These findings support the current theories regarding the pathogenesis of SM secondary to CM and further highlight the similarities between canine CM and human CM-I.

The association between Chiari-like malformation, ventriculomegaly and seizures in cavalier King Charles spaniels.

Cavalier King Charles spaniels (CKCSs) with Chiari-like malformation (CM) and associated seizures are frequently diagnosed with idiopathic epilepsy. There could be an association between ventriculomegaly (V) or caudal fossa overcrowding (CCFP) and seizures. A retrospective case-control study was performed using MRI to investigate the possible association between these morphological abnormalities and seizures. Seizure semiology and, where possible, electroencephalographic (EEG) abnormalities were documented. Eighty-five CKCS with CM were included, 27 with seizures. There was no association between V or CCFP and seizures (P=0.10 and 0.71, respectively). Seizures were classified as having partial onset in 61% of individuals in the study population (95% CI 42.41-76.43%). Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported.