Short CommunicationsShort Communications

Short Communications

March 30, 2013 | Veterinary Record

Caudal cranial fossa partitioning in Cavalier King Charles spanielsT. A. Shaw, I. M. McGonnell, C. J. Driver, C. Rusbridge, H. A. Volk

Cavalier King Charles spaniels (CKCS) are notable among dog breeds for their high rate of Chiari-like malformation (CM—charac-terised 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), previ-ous 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 con-tained parenchyma that was disproportionately large (Cross and oth-ers 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 occipital region, in contrast with the other breeds in which caudal cerebellar crowding was independent of increased cerebellar volume. These are interesting findings as they suggest a multifactorial aetiology for CM/SM in CKCS, dependent on the cumulative effects of increased cerebellar volume and a CCF which does not reach a commensurate size. Here, we report that the morphology of the canine skull is affected by variation in hindbrain

volume. important differences exist between CKCS, SB and lD that are pertinent to the pathological mechanisms of CM/SM.

Our first hypothesis is that the caudal part of the CCF is relatively smaller in CKCS than in other breeds of dog, and there is an increase in the volume in other part(s) of the CCF. Our second hypothesis is that there is an association between SM in CKCS and reduced volume of the caudal part of the CCF. Our third hypothesis is that the volume of the caudal part of the CCF in CKCS is insensitive to variation in the relative hindbrain volume, and there is increased sensitivity in other part(s) of the CCF.

a retrospective study of Mri scans of CKCS, SB and lD was performed. Methods for selecting individuals, performing scans, con-structing 3D models of intracranial structures and partitioning the CCF and its contents are described in our previous study (Shaw and others 2012). However, in the present study, we partitioned the CCF into three compartments (pars rostralis, pars media and pars caudalis) for volumetric analysis (Fig 1). These parts were chosen to represent the volumes bounded by the occipital bones (pars caudalis), squamous portion of the temporal bone (pars media) and tentorium cerebelli (pars rostralis). The volumes were expressed as percentages of the total skull volume (the sum of the volumes of the CCF and the rostroten-torial compartment). Hindbrain volume (defined as the volume of parenchyma in the CCF) was expressed as a percentage of the overall brain volume (the sum of CCF parenchyma volume and rostrotento-rial parenchyma volume).

Subjects were divided into the following groups: 38 SB, 26 lD and 45 CKCS. SM is thought to be a late onset disease, and in order to dis-tinguish dogs that develop SM later in life from dogs that are unlikely to ever develop the condition, two further subgroups were selected from the individuals in the CKCS group. These groups were used in previous studies of CKCS (Driver and others 2010b, Shaw and others 2012), and were based on age cut-offs for CKCS breeding guidelines (Cappello and rusbridge 2007). They comprised 16 individuals under the age of 2 years with SM, all of which presented with clinical signs related to SM (the CM/SM group), and 11 individuals over the age of 5 years without SM, which presented for clinical signs unrelated to SM (the CM group). Breed group data (SB, lD and CKCS) was analysed with a one-way analysis of variance (aNOva), and if signifi-cant, followed by a Bonferroni-Dunn test. linear regression models and general linear models (GlM) were fitted to continuous data, and residuals were checked for normality by the Kolmogorov-Smirnov test and homoscedasticity by visual inspection. CM/SM and CM group

T. A. Shaw, BVetMed, MRCVSC. J. Driver, BSc, BVetMed (Hons), MVetMed, DipECVN, MRCVSH. A. Volk, PhD, DipECVN, PGCAP, FHEA, MRCVSDepartment of Veterinary Clinical Sciences, Royal Veterinary College, Hatfield AL9 7TA, UKI. M. McGonnell, PhDDepartment of Veterinary Basic Sciences, The Royal Veterinary College, Royal College Street, London, UK

C. Rusbridge, BVMS, PhD, DipECVN, MRCVSGoddard Veterinary Group, Stone Lion Veterinary Hospital, London, UK

Email for correspondence: hvolk@rvc.ac.uk

Provenance: Not commissioned; externally peer reviewed.

Accepted 14 January 2013

Veterinary Record (2013) doi: 10.1136/vr.101082

A

BC

FIG 1: Diagram of caudal cranial fossa (CCF) partitioning. (A) Pars rostralis (CCF), (B) pars media, (C) pars caudalis. The pars media and pars caudalis were divided by a plane orthogonal to the sagittal image, intersecting the base of the internal occipital protuberance and orientated perpendicular to the basioccipital bone (red line). The pars rostralis and pars media were divided by a plane orthogonal to the sagittal image, intersecting the sella turcica and base of the internal occipital protruberence. Green line—1 cm scale

on Septem

ber 7, 2020 by guest. Protected by copyright.

http://veterinaryrecord.bmj.com

/V

eterinary Record: first published as 10.1136/vr.101082 on 5 F

ebruary 2013. Dow

nloaded from

Short CommunicationsShort Communications

Veterinary Record | March 30, 2013

data was tested with an unpaired t test and F test of the equality of variances. a P value of 0.05 or below was considered significant.

We found that CKCS had a relatively large pars rostralis volume (3.21±0.14) and relatively small pars caudalis volume (3.59±0.10) when compared with lD and SB (lD: pars rostralis 2.49±0.11, P<0.001; pars caudalis 5.63±0.23, P<0.001, SB: pars rostralis 2.63±0.12, P=0.010; pars caudalis 4.28±0.22, P=0.016). These find-ings suggest that in CKCS there is a reduction in occipital skull volume and an increase in the volume bounded by the tentorium cerebelli. Furthermore, pars caudalis volume was reduced in the CM/SM group (3.43±0.14) compared with CM group (3.94±0.21, P=0.0463), which suggests an association between reduced volume in the caudal part of the CCF and the development of SM (Fig 2). The pars media of the SB group (6.77 (4.84–9.75)) was significantly smaller than the lD (8.16 (7.77–10.2), P<0.001) and CKCS groups (8.12 (6.33–9.67), P<0.001).

Our results also revealed important differences in the relation-ship between hindbrain volume and CCF morphology (Fig 3). in CKCS, pars rostralis volume was more sensitive than pars cauda-lis volume to variation in hindbrain volume (coef: pars rostralis 0.41±0.077 (P<0.0001), pars caudalis 0.105±0.073 (P=0.1538)). Conversely, in lD and SB, pars rostralis volume was less sensi-tive than pars caudalis volume to variation in hindbrain volume (pars rostralis coef: SB 0.13±0.065 (P=0.0519), lD 0.13±0.085 (P=0.1578), pars caudalis coef: SB 0.44±0.099 (P<0.0001), lD 0.59±0.18 (P=0.0027)). GlM analysis revealed a statistically sig-nificant difference in the gradient of the fitted lines in Fig 3 (pars rostralis: P=0.019, pars caudalis: P=0.013). These findings suggest that SB and lD compensate for variations in hindbrain volume by modifying the growth of the occipital skull, whereas in CKCS, occipital bone development is insensitive to changes in hindbrain

4% **

*** ***

****** * *

*

3%

2%

1%

0%

4%

3%

2%

1%

0%

10%

8%

6%

4%

2%

0%Labrador Small Breed Dogs CKCS

Labrador Small Breed Dogs CKCS

CM/SM

Cau

dal C

CF

Vol

ume

Cau

dal C

CF

Vol

ume

Mid

dle

CC

F V

olum

e

Mid

dle

CC

F V

olum

eR

ostr

al C

CF

Vol

ume

Ros

tral

CC

F V

olum

e

CM

Labrador Small Breed Dogs CKCS CM/SM CM

CM/SM CM

8%

6%

4%

2%

0%

8%

6%

4%

2%

0%

10%

8%

6%

4%

2%

0%

FIG 2: Caudal, middle and pars rostralis volumes comparing (1) labradors, small breed dogs and CKCS; (2) CM and CM/SM groups. CCF, caudal cranial fossa; CKCS, Cavalier King Charles spaniel; CM, CKCS with Chiari-like malformation; CM/SM, CKCS with CM and syringomyelia; *P<0.05, **P<0.01, ***P<0.001

on Septem

ber 7, 2020 by guest. Protected by copyright.

http://veterinaryrecord.bmj.com

/V

eterinary Record: first published as 10.1136/vr.101082 on 5 F

ebruary 2013. Dow

nloaded from

Short Communications

March 30, 2013 | Veterinary Record

volume. We infer from these results that increased hindbrain volume in CKCS causes the tentorium cerebelli to compensate by bulging in a rostral direction. a similar phenomenon, an increase in the angle of the tentorium, has been widely reported in humans with Chiari malformation i (Milhorat and others 1999, Karagoz and others 2002, Sekula and others 2005).

The data support the hypothesis that CM/SM in CKCS is a mul-tifactorial disease process governed by the effects of increased hind-brain volume and impaired occipital bone development. The present authors recently reported that CM/SM is linked to increased cerebellar volume (Shaw and others 2012). in view of this, the aetiopathogenesis of CM/SM may equivocally be mediated by conditions independently affecting the developing occipital bones and cerebellum, or by dys-regulation of a signalling mechanism coordinating the growth of the developing hindbrain and occipital skull.

ReferencesCaPPellO, r. & rUSBriDGe, C. (2007) report from the chiari-like malformation and

syringomyelia working group round table. Veterinary Surgery 36, 509–512Carrera, i., DeNNiS, r., MellOr, D. J., PeNDeriS, J. & SUllivaN, M. (2009)

Use of magnetic resonance imaging for morphometric analysis of the caudal cranial fossa in Cavalier King Charles Spaniels. American Journal of Veterinary Research 70, 340–345

CarrUTHerS, H., rUSBriDGe, C., DUBe, M. P., HOlMeS, M. & JeFFerY, N. (2009) association between cervical and intracranial dimensions and syringomyelia in the cavalier King Charles spaniel. Journal of Small Animal Practice 50, 394–398

CerDa-GONZaleZ, S., OlBY, N. J., MCCUllOUGH, S., PeaSe, a. P., BrOaDSTONe, r. & OSBOrNe, J. a. (2009) Morphology of the caudal fossa in Cavalier King Charles Spaniels. Veterinary Radiology & Ultrasound 50, 37–46

COUTUrier, J., raUlT, D. & CaUZiNille, l. (2008) Chiari-like malformation and syringomyelia in normal cavalier King Charles spaniels: a multiple diagnostic imaging approach. Journal of Small Animal Practice 49, 438–443

CrOSS, H. r., CaPPellO, r. & rUSBriDGe, C. (2009) Comparison of cerebral cra-nium volumes between cavalier King Charles spaniels with Chiari-like malformation, small breed dogs and labradors. Journal of Small Animal Practice 50, 399–405

DeWeY, C. W., BerG, J. M., STeFaNaCCi, J. D., BarONe, G. & MariNO, D. J. (2004) Caudal occipital malformation syndrome in dogs. Compendium on Continuing Education for the Practicing Veterinarian 26, 886–895

Driver, C. J., rUSBriDGe, C., CrOSS, H. r., MCGONNell, i. & vOlK, H. a. (2010a) relationship of brain parenchyma within the caudal cranial fossa and ventricle

size to syringomyelia in cavalier King Charles spaniels. Journal of Small Animal Practice 51, 382–386

Driver, C. J., rUSBriDGe, C., MCGONNell, i. M. & vOlK, H. a. (2010b) Morphometric assessment of cranial volumes in age-matched Cavalier King Charles spaniels with and without syringomyelia. Veterinary Record 167, 978–979

KaraGOZ, F., iZGi, N., KaPiJCiJOGlU SeNCer, S. (2002) Morphometric measure-ments of the cranium in patients with Chiari type i malformation and comparison with the normal population. Acta Neurochirurgia 144, 165–171

leviNe, D. N. (2004) The pathogenesis of syringomyelia associated with lesions at the foramen magnum: a critical review of existing theories and proposal of a new hypoth-esis. Journal of the Neurological Sciences 220, 3–21

leWiS, T., rUSBriDGe, C., KNOWler, P., BlOTT, S. & WOOlliaMS, J. a. (2010) Heritability of syringomyelia in Cavalier King Charles spaniels. The Veterinary Journal 183, 345–347

lU, D., laMB, C. r., PFeiFFer, D. U. & TarGeTT, M. P. (2003) Neurological signs and results of magnetic resonance imaging in 40 cavalier King Charles spaniels with Chiari type 1-like malformations. Veterinary Record 153, 260–263

MilHOraT, T. H., CHOU, M. W., TriNiDaD, e. M., KUla, r. W., MaNDell, M., WOlPerT, C., SPeer, M. C. (1999) Chiari i malformation redefined: clinical and radiographic findings for 364 symptomatic patients. Neurosurgery 44, 1005–1017

rUSBriDGe, C., GreiTZ, D. & iSKaNDar, B. J. (2006) Syringomyelia: current con-cepts in pathogenesis, diagnosis, and treatment. Journal of Veterinary Internal Medicine 20, 469–479

rUSBriDGe, C. & KNOWler, S. P. (2004) inheritance of occipital bone hypoplasia (Chiari type i malformation) in cavalier King Charles spaniels. Journal of Veterinary Internal Medicine 18, 673–678

rUSBriDGe, C. & KNOWler, S. P. (2006) Coexistence of occipital dysplasia and occipital hypoplasia/syringomyelia in the cavalier King Charles spaniel. Journal of Small Animal Practice 47, 603–606

rUSBriDGe, C., MaCSWeeNY, J. e., DavieS, J. v., CHaNDler, K., FiTZMaUriCe, S. N., DeNNiS, r., CaPPellO, r. & WHeeler, S. J. (2000) Syringohydromyelia in Cavalier King Charles spaniels. Journal of the American Animal Hospital Association 36, 34–41

SCHMiDT, M. J., Biel, M., KlUMPP, S., SCHNeiDer, M. & KraMer, M. (2009) evaluation of the volumes of cranial cavities in Cavalier King Charles Spaniels with Chiari-like malformation and other brachycephalic dogs as measured via computed tomography. American Journal of Veterinary Research 70, 508–512

SeKUla, r. F. Jr., JaNNeTTa, P. J., CaSeY, K. F., MarCHaN, e. M., SeKUla, l. K. & MCCraDY, C. S. (2005) Dimensions of the posterior fossa in patients sympto-matic for Chiari i malformation but without cerebellar tonsillar descent. Cerebrospinal Fluid Research 18, 11

SHaW, T. a., MCGONNell, i. M., Driver, C. J., rUSBriDGe, C. & vOlK, H. a. (2012) increase in cerebellar volume in Cavalier King Charles Spaniels with Chiari-like malformation and its role in the development of syringomyelia. PloS One 7, e33660

20

15

10

10

8

6

5 CKCSLDSD

CKCSLDSD

CKCSLDSD

CKCSLDSD

4

3

2

1

8

6

4

210 12 14

Hindbrain Volume16 10 12 14

Hindbrain Volume

Cau

dal C

CF

Vol

ume

Ros

tral

CC

F V

olum

e

Mid

dle

CC

F V

olum

eC

CF

Vol

ume

16

10 12 14Hindbrain Volume

1610 12 14Hindbrain Volume

16 18

FIG 3: Correlation of CCF volumes with hindbrain volume. CCF, caudal cranial fossa; CKCS, Cavalier King Charles spaniel; LD, labradors; SB, small breed dogs

on Septem

ber 7, 2020 by guest. Protected by copyright.

http://veterinaryrecord.bmj.com

/V

eterinary Record: first published as 10.1136/vr.101082 on 5 F

ebruary 2013. Dow

nloaded from