Morphometric Features of the Craniocervical Junction Region in Dogs with

Suspected Chiari-Like Malformation Based on Combined MR and CT

Imaging: 274 Cases (2007-2010)

Dominic J. Marino1, DVM, Diplomate ACVS, Diplomate, ACCT, CCRP

Catherine A. Loughin1, DVM, Diplomate ACVS, Diplomate, ACCT

Curtis W. Dewey1,2, DVM, MS, Diplomate ACVIM (Neurology), Diplomate ACVS, Leonard

J. Marino1, MD, FAAP, Joseph Sackman1, Martin L. Lesser1,3, PhD, EMT-CC, Meredith

Akerman3, MS

From The Canine Chiari Institute at Long Island Veterinary Specialists1, 163 South Service

Road, Plainview, NY 11803; the Department of Clinical Sciences2, College of Veterinary

Medicine, Cornell University, Ithaca, NY 14853; North Shore - LIJ Health System

Feinstein Institute for Medical Research3, Biostatistics Unit, 350 Community Drive,

Manhasset, NY 11030

Address correspondence to:

Dominic J. Marino, DVM, Diplomate ACVS, Diplomate, ACCT, CCRP

The Canine Chiari Institute at Long Island Veterinary Specialists,

163 South Service Road, Plainview, NY 11803

11

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

Abstract

Objective-To objectively describe morphometric features of the craniocervical junction

region of dogs with suspected Chiari-like malformation (CLM) and to investigate for

associations between these features and the occurrence of other malformations in this

region.

Design-Retrospective study.

Animals-274 dogs.

Procedures-Magnetic resonance (MR) and computed tomographic (CT) images from

patients evaluated for Chiari-like malformation (CLM) between 2007 and 2010 were

reviewed. Three regions of neural tissue compression were assessed: cerebellar

compression (CC); ventral compression at the level of the C1/C2 articulation, also

termed “medullary kinking” (MK); and dorsal compression (DC) at the level of the C1/C2

articulation. A compression index (CI) was calculated for all abnormal regions for each

dog. Multiple logistic regression analysis was performed (p<0.05) to ascertain whether

CI values for the different regions of compression were associated with the incidence of

other craniocervical junction abnormalities.

Results- All dogs had some level of CC. Approximately 68% of dogs had MK and 38% of

dogs had DC. Approximately 28% of dogs also had evidence of atlanto-occipital

overlapping (AOO). Breed and CC were the only significant predictors of AOO (p<0.0001

and p< 0.0092). CKCS had nearly a five-fold decrease in risk of AOO, and the risk of AOO

nearly doubled for every 10% increment in CC.

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

Conclusions and Clinical Relevance-A substantial percentage (28%) of suspected CLM

cases have AOO as the anatomic abnormality responsible for CC. Compression index

values may help differentiated subtypes of craniocervical junction abnormalities in dogs.

Introduction

Craniocervical junction abnormalities (CJAs) in small breed dogs are being

increasingly recognized as common and challenging disorders.1-5 In particular, Chiari-like

malformation (CLM), the canine analog of human Chiari type I malformation, has

emerged in recent years as the possible cause of major health problems in several small-

breed dogs, most notably the Cavalier King Charles spaniel (CKCS).6-15 The term CJA is

used in human medicine and serves as an “umbrella” term for a variety of

malformations that occur in the craniocervical region of small dogs. In veterinary

medicine, the term “Chiari-like malformation” or CLM has been widely used to describe

constrictive disorders at the cervicomedullary junction that are apparent on MR

imaging. Most definitions of CLM include the presence of an abnormally shaped

supraoccipital bone that leads to a rostrally directed compression of the caudal

cerebellum. It is often difficult to impossible to discern what specific structure or

structures cause the cerebellar compression on MR imaging, as bone is poorly visualized

on MR images. Rostral compression of the cerebellum evident on an MR image in dogs

is often assumed to be due to a malformed supraaoccipital bone, and such cases are

assigned a diagnosis of CLM. In a CJA disorder of humans known as basilar invagination

(BI), a rostrally displaced C1 dorsal arch can cause cerebellar compression.16,17 A similar

33

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

condition has been recently described in dogs and is referred to as atlanto-occipital

overlapping (AOO).2 Computed tomography is often performed along with MR imaging

in human cases of CJA in order to ascertain what specific structures are causing neural

compression. 16,17 Similarly, the authors have been routinely performing CT immediately

following the MR imaging of canine patients with CJA. Conditions included under CJA

include, but are not limited to: CLM5-11, atlantooccipital instability (AO)19, atlantoaxial

instability (AA)20,21, occipitoatlantoaxial malformations (OAA)22,23, atlantooccipital

overlapping (AOO)2 and dens abnormalities (DA).3,24,25

The wide variation in skull size and shape among small breed dogs presents

unique challenges when attempting to quantify morphologic abnormalities of the cranial

cavity as they relate to intracranial disease as well as diseases of the cervical spine.

Additionally, concurrent disease is commonly identified in dogs imaged for CLM

1,2,5,9,11,14,18 and in humans with Chiari type I malformation26,27 and is thought to be a

contributing factor in people experiencing a poor outcome after having a foramen

magnum decompression for the treatment of Chiari type 1 malformation.28,29

Techniques to develop objective assessment data relative to total brain volume,

total cranial volume, cranial and caudal fossa volumes using linear and 3 dimensional

measurements of MR and CT images have been reported.5,30-32 Results of some studies

have identified positive associations between the ratio of caudal fossa/total cranial

volume and neurologic signs5; volume ratios and linear measurements31 and decreased

caudal fossa volume; and the presence of syringomyelia30, while others found no

association between decreased caudal fossa volume and the presence of

44

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

syringomyelia.5,32 In the authors’ clinical experience, cerebellar compression (CC),

defined as an indentation of the cerebellum,15 medullary kinking (MK) defined as an

elevation of the medulla at the cervicomedullary junction by the dens3,8,15,24,25 , and

dorsal compression of the C1/C2 spinal cord (DC)5,9 are common findings on MR

screening images of dogs for suspected CLM. Several studies have attempted to

determine if an association between CC5,30,32,33, MK5,33, DC5,9 individually and the presence

of clinical signs or syringomyelia exists; however analysis proved difficult with low case

numbers resulting in conflicting results. To the authors’ knowledge associations among

CC, MK, and DC have not been examined individually or collectively in a large-scale

study. Furthermore, the presence of AOO as either a primary condition or a co-morbid

disease in dogs with suspected CLM has not been investigated. The purpose of this

study was to retrospectively evaluate objective measurements obtained as a

compression index of CC, MK, and DC in dogs imaged with MR and CT for suspected CLM

and to report any associations between CC, MK, DC and the presence of other CJAs.

Materials and Methods

Only dogs with CLM based on MRI (CC present) were included in this study. Cavalier

King Charles Spaniels were recruited from the general population in the United States by

advertising a low-cost screening program at The Canine Chiari Institute at Long Island

Veterinary Specialists. Additionally, dogs of breeds other than CKCS were included,

resulting in 274 dogs being enrolled in this study. All dogs had a neurologic examination,

complete blood count, and serum biochemistry panel within 14 days before

55

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

participating. A detailed history from the owner was recorded. All dogs had cervical

radiographs, 3.0 Tesla MR imaging of the brain and entire spinal cord, and multidetector

CT imaging of the skull from the nose through C3 and subsequent 3D reconstruction.

Each dog was premedicated with torbugesic (0.2 mg/kg IV), atropine (0.08 mg/kg IV),

followed by induction with propofol (11 mg/kg IV) and maintenance with isoflurane and

oxygen. Mean arterial blood pressure, end tidal CO2, ventilatory rate, temperature and

heart rate were maintained within physiologic limits during the testing period.

Imaging specifications

Each complete MRI study was performed with a Philips 3.0 Tesla magnet and consists of

T2-weighted sagittal views from the nose to the sacrum. Patients were placed in dorsal

recumbencey with the head in partial flexion (between 100 to 138 degrees) mimicking

the standing CKCS craniocervical angle. Imaging of the brain consisted of a T2-weighted

sagittal, T2-weighted axial, and a T1-weighted Flair axial, followed by T2-weighted axial

views of the cervical, thoracic and lumbar regions. With dogs in sternal recumbencey

with the head in partial flexion (between 100 to 138 degrees) mimicking the standing

CKCS craniocervical angle, CT (Marconi Mx8000, Marconi, Medical Systems Inc.,

Cleveland, OH) evaluation was performed at 140kV and 150mAs using a bone

reconstruction filter. Using helical acquisition, 1 mm collimated contiguous images were

collected. A bone algorithm of window width 3000 Hounsfield units and window length

of 500 Hounsfield units and 3-D reconstruction were used to interpret the images.

66

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

All images (CT and MR) were reviewed by two of the authors (DJM, CAL). Compression

was defined as indentation of the subarachnoid space and/or parenchyma by adjacent

soft tissue or bone. Objective measurements of each type of compression (CC, MK, DC)

were made by determining the compression length (CL) by measuring the distance from

the outer limit of the subarachnoid space to the greatest point of compression. A

compression index for MK and DC was used to take into account the different size dogs

included in the study and was calculated by dividing the CL by the diameter of the

adjacent normal portion of the cervical spinal cord with the subarachnoid space,

determined by measuring the distance between two parallel lines placed at the outer

limit of the subarachnoid space adjacent to the site of compression and multiplying by

100 (Figure 1 & 2). For the CC compression index, the CL was divided by the diameter of

the cerebellum determined by drawing a circle over the image of the cerebellar

perimeter and multiplied by 100 (Figure 3). The diagnosis of AOO was confirmed using

CT with 3-dimensional CT reconstruction as previously described (Figure 4a &b).2

Statistical methods

The primary statistical objective was to estimate the probability of other CJAs as a

function of one or more of the following four potential “predictors”: presence of DC,

presence of MK, CC compression index and breed of dog (CKCS vs. non-CKCS) in 274

dogs presenting with suspected CLM.

77

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

Multiple logistic regression was used to model the probability of other CJAs as a function

of breed and the specific factor (DC, MK, CC compression index). After fitting the logistic

models to the data, receiver operating characteristic (ROC) curves were computed for

each predictor separately for CKCS and non-CKCS. In order to find an “optimal” cutoff

point (e.g., above which the compression type would be classified as AOO), the

Euclidean distance from the “best” ROC point (0,1) to the ordered pair “(1-specificity,

sensitivity)” corresponding to each value of the selected predictor was calculated. The

value of the predictor corresponding to the shortest distance was taken as the “optimal”

cutoff point.34

A result was considered statistically significant if p<0.05.

Results

Two-hundred seventy four dogs were included in the study. Two hundred and

sixteen of 274 dogs (78.8%) were CKCS and 58 of 274 (21.2%) non-CKCS.

The following breeds were noted: CKCS (216), Yorkshire Terrier (15), Chihuahua (11),

Maltese (7), Pomeranian (4), Pug (3), Boston Terrier (3), Miniature Poodle (3), Mixed

Breed Dog (2), Shih-Tzu (2), Beagle (1), Affenpinscher (1), Brussels Griffon (1), French

Bull Dog (1), Maltipoo (1), Miniature Dachshund (1), Papillon (1), Tibetian Spaniel (1),

and. There were 119 males (43.4%) and 155 females (56.6%). The median age was 21

months, ranging from 5 to 132 months and the median weight was 7.3 kg, ranging from

1.4-16.8 kg.

88

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

Since this was a study of dogs with suspected CLM, all dogs had some degree of CC.

There were 187 of 274 dogs (68.2%) with concurrent MK, and 104 of 274 dogs (37.9%)

with concurrent DC. Based upon 3D reconstructed CT images, 76 of 274 dogs (27.7%)

with CC had AOO, rather than the typical CLM (i.e., cerebellar compression was from C1,

not supraoccipital bone).

Prior to conducting the primary statistical analyses, the investigators

estimated intra- and interobserver reliability of their measurements by randomly

selecting scans from 15 dogs and computing the appropriate intraclass correlations

(ICC). Each investigator (DM and CL) measured DC, MK, and CC in each dog on two

blinded occasions and blinded to each other. For measurements DC and MK, the

intraobserver variation ranged from 0.94 to 0.99, indicating outstanding repeat

reliability. For CC, the range was 0.51 to 0.74. Similarly, for interobserver variation, the

ICC ranged from 0.93 to 0.99 for DC and MK, but ranged lower, 0.52 to 0.70 for CC.

Univariable logistic regression was first applied to each of the variables. Breed

(p<0.0001) and CC compression index (p<0.0032) were significantly associated with

AOO, but DC (p<0.25) and MK (p<0.14) were not. When all four predictor variables

(breed, DC, MK and CC compression index) were included in one logistic regression

model, once again, only breed (p<0.0001) and CC compression index (p<0.0092) were

(jointly) significant as predictors of AOO. (See Table 1.) The final model was revised to

include only breed and AOO. Based on this model, CKCS had an approximately five-fold

reduction in the risk of AOO as compared to non-CKCS (p<0.0001, OR=0.208) and the

99

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

risk of AOO increased by a factor of 1.07 for every percentage unit increase in CC. An

alternative way to summarize the CC result is that for every 10 percentage unit increase

of CC, the risk of AOO nearly doubled (1.0710 = 1.97)).. This model was used to compute

predicted probabilities of AOO (Table 2).

An optimal cutoff point for CC to predict AOO was determined as described in the

Methods section. For CKCS, a dog would be classified as AOO if CC>16.1%; for Non-

CKCS, the cutoff is CC>12.3%.

DiscussionThe presence of more than one CJA in dogs with suspected CLM1-3,5,9,11,15,18 and people

with Chiari malformation26-29 has been reported; however, the high prevalence of

multiple areas of neural compression in dogs with CLM has not been reported in a large

scale study. There were 187 of 274 dogs (68.2%) with concurrent MK, and 104 of 274

dogs (37.9%) with concurrent DC. In addition, 76 of 274 dogs (27.7%) had CT-confirmed

AOO. These findings underscore the need for thorough diagnostic evaluation including

MRI and CT imaging to completely assess the magnitude and complexity of CJA in dogs

with suspected CLM. Failure to address concurrent CJAs in people having surgery for

Chiari malformation can lead to suboptimal results.28,29 The authors suspect that a

similar scenario may exist in dogs that are surgically treated for suspected CLM. Results

of a large-scale study of the effect on outcome of concurrent CJA in dogs having surgery

for CLM is currently underway. In the human literature, the relationship between

1010

195

196

197

198

199

200

201

202

203

204205

206

207

208

209

210

211

212

213

214

215

216

various CJA and Chiari malformation has been described in detail.17,28,35-37 In veterinary

medicine, several authors have speculated that a causal relationship between CC, MK,

DC, and AOO exists; 1-3,5 however, none has been documented. The breed distribution

and median weight (7.3 kg, ranging from 1.4-16.8 kg) of dogs in our study is consistent

with previous results reflecting CJAs are predominantly conditions affecting small breed

dogs. 2,5,7-9,11,14,38 The proportion of CKCS dogs versus non-CKCS dogs is disproportionately

high because the recruitment of clinical cases included CKCS breed clubs, thus the actual

prevalence of CKCS dogs cannot be determined.

Univariable logistic regression results indicate breed (p<0.0001) and CC compression

index (p<0.0032) were significantly associated with AOO. When all four predictor

variables (breed, DC, MK and CC compression index) were included in one logistic

regression model, once again, only breed (p<0.0001) and CC compression index

(p<0.0092) were (jointly) significant as predictors of AOO. Basilar invagination, the

human analogue to AOO in dogs, has been reported to further exacerbate the

overcrowding of the posterior fossa in human patients with Chiari malformation and

BI.39 The impact of AOO on the treatment of dogs having surgery for CLM is beyond the

scope of this study but consideration should be given to its effect on caudal fossa

overcrowding when generating a treatment plan. An optimal cutoff point for CC to

predict AOO for CKCS dog would be classified as AOO if CC>16.1%; for non-CKCS, the

cutoff is CC>12.3%.

1111

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

There were 187 of 274 dogs (68.2%) with concurrent MK. Dorsal position of the

dens resulting in spinal cord compression has been reported in dogs with CLM3,5 and was

found 66% of 64 dogs evaluated in a recent study.5 In human patients with Chiari

malformation, 26.4% had DA29 with females more commonly affected in one report.40

When MK was analyzed alone with univariable logistic regression and later with all four

predictor variables included in one logistic regression model, it was not significantly

associated with AOO. In human patients, kinking of the brain stem secondary to DA has

been reported to alter both cerbrospinal fluid (CSF) dynamics, local blood flow, and

cause compression myelopathy resulting in various clinical signs attributable to

brainstem compression.28,29,41 Recent reports stress the importance of stretch related

myelopathy in the development of clinical signs.42-45 Stretching of the axolemma may

result in several degrees of injury including the loss of microtubules and neurofilaments,

loss of axon transport, and accumulations of axoplasmic material called a retraction

ball.42-44,46-49 Axon retraction ball accumulation or axon bulbs are seen in stretch injury

associated with BI42-44,50 and “Shaken Baby Syndrome”.51,52 Current recommendations for

human patients with Chiari malformation and MK include decompression of the MK by

ventral cervical spinal fusion to restore the clivo-axial angle and thus lesson or eliminate

the tractional injury to the cervical spinal cord followed by a subsequent foramen

magnum decompression.53 Clinical studies are in progress to assess the results of ventral

decompression and stabilization with foramen magnum decompression with

cranioplasty in dogs with CLM and MK.

1212

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

There were 104 of 274 dogs (37.9%) with concurrent DC. Dorsal compression of

the spinal cord at the C1/C2 intervertebral space has been reported in dogs with

CJA.2,5,6,11,54,55 Although the exact etiology has not been established,

lymphocytic/plasmacytic inflammation, fibrosis and ossification of the soft tissues have

been reported on histopathology.5,6 In the author’s experience, the focal area of

compression is best visualized on sagittal T2-weighted images of the craniocervical

junction and may represent hypertrophy of the ligamentum flavum, dura or osseous

compression secondary to malformation or vertebral malarticulation. When DC was

analyzed alone with univariable logistic regression and later with all four predictor

variables included in one logistic regression model, it was not significantly associated

with AOO.

The formation of DC may be by differing mechanisms in CKCS dogs versus other

small breed dogs as it relates to dogs with AOO and CLM. The malarticulation between

the occipital condyles, atlas and axis appear to contribute to the formation of the dorsal

compression seen at the C1/C2 intervertebral space. The significance of DC and its

impact on clinical outcome is unknown at this time. It is reasonable to assume

significant dorsal compression can have detrimental effects by the same mechanisms

responsible for other CJA pathologic sequelae: disturbance of normal CSF flow patterns,

axonal compression and altered blood flow. Consideration should be given to further

diagnostics to assess for AOO and more robust treatment planning when DC is identified

in dogs with CLM.

1313

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

When the final logistic regression model was revised to include only breed and

AOO, CKCS had an approximately five-fold reduction in the risk of AOO as compared to

non-CKCS (p<0.0001, OR=0.208) and the risk of AOO increased by a factor of 1.07 for

every percentage unit increase in OH. Thus, for every 10 percentage unit increase of OH,

the risk of AOO nearly doubled (1.0710 = 1.97). Additional diagnostics including CT scan

have been recommended in dogs with AOO to best evaluate the extent of disease and

to formulate a comprehensive treatment plan.2

Because the CJA seen in dogs are typically dynamic lesions, changes in patient

position during imaging from mild extension and flexion are recommended for complete

assessment.2,17 Dogs in this study were placed in dorsal recumbencey with the head in

partial flexion (between 100 to 138 degrees) mimicking the standing CKCS craniocervical

angle for MR imaging. This limitation may affect the accurate determination of CJA. As

part of a larger study, imaging patients in multiple positions is in progress, however the

significant increase in imaging time may preclude clinical application.

In conclusion, objective measurements were successfully obtained in the form of

a CC, MK, and DC in dogs (CKCS and non CKCS) with suspected CLM. Only CC

compression index and breed were significant as predictors of AOO. The CKCS had an

approximately five-fold reduction in the risk of AOO as compared to non-CKCS and for

every 10 percentage unit increase of CC, the risk of AOO nearly doubled.

1414

280

281

282

283

284

285

286

287

288

289

290

291

292

293

294

295

296

297

298

299

300

301

1. Cerda-Gonzalez S, Dewey CW: Congenital Diseases of the Craniocervical Junction in the Dog. Vet Clin North Am Small Anim Pract 40:121-141, 2010

2. Cerda-Gonzalez S, Dewey CW, Scrivani PV, et al: Imaging features of atlanto-occipital overlapping in dogs. Vet Radiol Ultrasound 50:264-268, 2009

3. Bynevelt M, Rusbridge C, Britton J: Dorsal dens angulation and a Chiari type malformation in a Cavalier King Charles Spaniel. Vet Radiol Ultrasound 41:521-524, 2000

4. Gibson KL IS, Hogan PM: Severe Spinal Cord Compression Caused by a Dorsally Angulated Dens. Progress in Veterinary Neurology 6:55-57, 1995

5. Cerda-Gonzalez S, Olby NJ, McCullough S, et al: Morphology of the caudal fossa in Cavalier King Charles Spaniels. Vet Radiol Ultrasound 50:37-46, 2009

6. Dewey CW, Berg JM, Barone G, et al: Foramen magnum decompression for treatment of caudal occipital malformation syndrome in dogs. J Am Vet Med Assoc 227:1270-1275, 2005

7. Dewey CW, Marino DJ, Bailey KS, et al: Foramen magnum decompression with cranioplasty for treatment of caudal occipital malformation syndrome in dogs. Vet Surg 36:406-415, 2007

8. Dewey CW, Barone G, Stefanacci, JD, et al: Caudal occipital malformation syndrome in dogs. Compend Contin Educ Pract Vet 26:886-895, 2004

9. Dewey CW BJ, Barone G, et al: Treatment of caudal occipital malformation syndrome in dogs by foramen decompression. J Vet Intern Med 19:418, 2005

10. Rusbridge C: Persistent scratching in Cavalier King Charles spaniels. Vet Rec 141:179, 1997

11. Rusbridge C: Chiari-like malformation with syringomyelia in the Cavalier King Charles spaniel: long-term outcome after surgical management. Vet Surg 36:396-405, 2007

12. Rusbridge C, Jeffery ND: Pathophysiology and treatment of neuropathic pain associated with syringomyelia. Vet J 175:164-172, 2008

13. Rusbridge C, Knowler P, Rouleau GA, et al: Inherited occipital hypoplasia/syringomyelia in the cavalier King Charles spaniel:

1515

302

303304305306307308309310311312313314315316317318319320321322323324325326327328329330331332333334335336337338

experiences in setting up a worldwide DNA collection. J Hered 96:745-749, 2005

14. Rusbridge C, Knowler SP, Pieterse L, et al: Chiari-like malformation in the Griffon Bruxellois. J Small Anim Pract 50:386-393, 2009

15. Rusbridge C, MacSweeny JE, Davies JV, et al: Syringohydromyelia in Cavalier King Charles spaniels. J Am Anim Hosp Assoc 36:34-41, 2000

16. Botelho RV, Neto EB, Patriota GC, et al: Basilar invagination: craniocervical instability treated with cervical traction and occipitocervical fixation. Case report. J Neurosurg Spine 7:444-449, 2007

17. Goel A, Bhatjiwale M, Desai K: Basilar invagination: a study based on 190 surgically treated patients. J Neurosurg 88:962-968, 1998

18. Dewey CW, Scrivani PV, et al: Surgical stabilization of a craniocervical junction abnormality with atlanto-occipital overlapping in a dog. Comp Cont Educ Pract Vet( on line), E1-E6, 2009

19. McCarthy RJ LD, Hosgood G: Atlantoaxial subluxation in dogs. Compend Contin Educ Pract Vet 17:215-227, 1995

20. LeCouteur RA, McKeown D, Johnson J, et al: Stabilization of atlantoaxial subluxation in the dog, using the nuchal ligament. J Am Vet Med Assoc 177:1011-1017, 1980

21. Wheeler SJ: Atlantoaxial subluxation with absence of dens in a rottweiler. J Small Anim Pract 33:90-93, 1992

22. Petite A MF, De Stefani A, et al: Congenital occipito-atlanto-axial malformation in five dogs. Vet Radiol Ultrasound 50:118, 2009

23. Watson AG, de Lahunta A, Evans HE: Morphology and embryological interpretation of a congenital occipito-atlanto-axial malformation in a dog. Teratology 38:451-459, 1988

24. Ladds P, Guffy M, Blauch B, et al: Congenital odontoid process separation in two dogs. J Small Anim Pract 12:463-471, 1971

25. Parker AJ, Park RD, Cusick PK: Abnormal odontoid process angulation in a dog. Vet Rec 93:559-561, 1973

26. Schady W MR, Butler P: The Incidence of Craniocervical Bony Anomalies in the Adult Chiari Malformation. J Neurol Sci 82:193-203, 1987

27. Levy LJ ML, Hahn JF: Chiari Malformation Presenting in Adults: A Surgical Experience in 127 Cases. Neurosurgery 1983:377-389, 1983

1616

339340341342343344345346347348349350351352353354355356357358359360361362363364365366367368369370371372373374

28. Grabb PA, Mapstone TB, Oakes WJ: Ventral brain stem compression in pediatric and young adult patients with Chiari I malformations. Neurosurgery 44:520-527; discussion 527-528, 1999

29. Milhorat TH, Chou MW, Trinidad EM, et al: Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients. Neurosurgery 44:1005-1017, 1999

30. Carrera I DR, Mellor DJ, Penderis J, Sullivan M: Use of Magnetic Resonance Imaging for Morphometric Analysis of the Caudal Cranial Fossa in Cavalier King Charles Spaniels. AJVR 70:340-345, 2009

31. Garcia-Real I, Kass PH, Sturges BK, et al: Morphometric analysis of the cranial cavity and caudal cranial fossa in the dog: a computerized tomographic study. Vet Radiol Ultrasound 45:38-45, 2004

32. Schmidt MJ, Biel M, Klumpp S, et al: 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. Am J Vet Res 70:508-512, 2009

33. Lu D, Lamb CR, Pfeiffer DU, et al: Neurological signs and results of magnetic resonance imaging in 40 cavalier King Charles spaniels with Chiari type 1-like malformations. Vet Rec 153:260-263, 2003

34. Perkins NJ SE: The Inconsistency of ‘Optimal’ Cutpoints Obtained Using Two Criteria Based on the Receiver Operating Characteristic Curve. Amer J Epidemiology 163:670-675, 2006

35. Tassanawipas A, Mokkhavesa S, Chatchavong S, et al: Magnetic resonance imaging study of the craniocervical junction. J Orthop Surg (Hong Kong) 13:228-231, 2005

36. McGregor M: The significance of certain measurements of the skull in the diagnosis of basilar impression. Br J Radiol 21:171-181, 1948

37. Koenigsberg RA, Vakil N, Hong TA, et al: Evaluation of platybasia with MR imaging. AJNR Am J Neuroradiol 26:89-92, 2005

38. Rusbridge C, Carruthers H, Dube MP, et al: Syringomyelia in cavalier King Charles spaniels: the relationship between syrinx dimensions and pain. J Small Anim Pract 48:432-436, 2007

39. Nishikawa M, Sakamoto H, Hakuba A, et al: Pathogenesis of Chiari malformation: a morphometric study of the posterior cranial fossa. J Neurosurg 86:40-47, 1997

1717

375376377378379380381382383384385386387388389390391392393394395396397398399400401402403404405406407408409

40. Tubbs RS, Wellons JC, 3rd, Blount JP, et al: Inclination of the odontoid process in the pediatric Chiari I malformation. J Neurosurg 98:43-49, 2003

41. Menezes AH VJ: Transoral-Transpharyngeal Approach to the Anterior Craniocervical Junction. Ten-Year Experience with 72 Patients. J Neurosurg 69:895-903, 1988

42. Henderson F, Benzel E, Vaccaro AR: Stretch-related myelopathy. Seminars in Spine Surgery 17:2-7, 2005

43. Henderson F, Benzel EC, Kim D, et al: Pathophysiology of Cervical Myelopathy: Biomechanical Concepts, in Spine Surgery: techniques, complication avoidance, and management (ed 2nd)Elsevier Churchill Livingstone, 2005, pp 100-108

44. Henderson FC, Geddes JF, Vaccaro AR, et al: Stretch-associated injury in cervical spondylotic myelopathy: new concept and review. Neurosurgery 56:1101-1113; discussion 1101-1113, 2005

45. Henderson FC, Wilson W, Benzel EC: Pathophysiology of Cervical Myelopathy: Biomechanics and Deformative Stress, in Spine Surgery: techniques, complication avoidance, and management (ed 3rd)Elsevier Churchill Livingstone, 2010

46. Maxwell WL, Domleo A, McColl G, et al: Post-acute alterations in the axonal cytoskeleton after traumatic axonal injury. J Neurotrauma 20:151-168, 2003

47. Maxwell WL, Islam MN, Graham DI, et al: A qualitative and quantitative analysis of the response of the retinal ganglion cell soma after stretch injury to the adult guinea-pig optic nerve. J Neurocytol 23:379-392, 1994

48. Maxwell WL, Kosanlavit R, McCreath BJ, et al: Freeze-fracture and cytochemical evidence for structural and functional alteration in the axolemma and myelin sheath of adult guinea pig optic nerve fibers after stretch injury. J Neurotrauma 16:273-284, 1999

49. Henderson FC, Geddes JF, Crockard HA: Neuropathology of the brainstem and spinal cord in end stage rheumatoid arthritis: implications for treatment. Ann Rheum Dis 52:629-637, 1993

50. Bunge RP, Puckett WR, Becerra JL, et al: Observations on the pathology of human spinal cord injury. A review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination. Adv Neurol 59:75-89, 1993

1818

410411412413414415416417418419420421422423424425426427428429430431432433434435436437438439440441442443444445446

51. Geddes JF, Hackshaw AK, Vowles GH, et al: Neuropathology of inflicted head injury in children. I. Patterns of brain damage. Brain 124:1290-1298, 2001

52. Geddes JF, Vowles GH, Hackshaw AK, et al: Neuropathology of inflicted head injury in children. II. Microscopic brain injury in infants. Brain 124:1299-1306, 2001

53. Kubota M, Yamauchi T, Saeki N: Surgivcal Results of Foramen Magnum Decompression for Chiari Type 1 Malformation associated with Syringomyelia: A Retrospective Study on Neuroradiological Characters influencing Shrinkage of Syringes. Spinal Surgery 18:81-86, 2004

54. Tagaki S KT, Ohsaki T, et al: Hindbrain decompression in a dog with scoliosis associated with syringomyelia. J Am Vet Med Assoc 226:1359-1363, 2005

55. Vermeersch K, Van Ham L, Caemaert J, et al: Suboccipital craniectomy, dorsal laminectomy of C1, durotomy and dural graft placement as a treatment for syringohydromyelia with cerebellar tonsil herniation in Cavalier King Charles spaniels. Vet Surg 33:355-360, 2004

Figure Legend

Figure 1. Medullary Kink compression index.

Figure 2. Dorsal Compression index.

Figure 3. OH Compression index.

Figure 4. AOO as seen with 3D reconstruction. Position of C1 vertebral body residing

partially within the cranium.

Table 1: Results of Multiple Logistic Regression Model

1919

447448449450451452453454455456457458459460461462463464465

466467468469470471472473474475476477478479

480

Effect DF EstimateStandard

Error p-value

Odds Ratio (OR)

95% WaldConfidence

Limits

Intercept 1 -0.8938 0.5612 0.1113

CKCS vs .non-CKCS 1 -1.6530 0.3539 <.0001 0.191 (0.096, 0.383)

DC (Present vs. Absent) 1 -0.2859 0.3233 0.3765 0.751 (0.399, 1.416)

MK (Present vs. Absent) 1 0.1742 0.3241 0.5909 1.190 (0.631, 2.247)

OH compression index 1 0.0686 0.0263 0.0092 1.071 (1.017, 1.128)

Table 2: Predicted Probabilities of AOO for CKCS and non-CKCS Dogs at Varying Levels

of OH

OH Compression Index (%) CKCS Non-CKCS

5% 0.1037 0.3568

10% 0.1395 0.4374

20% 0.2415 0.6043

30% 0.3847 0.7500

40% 0.5511 0.8549

50% 0.7069 0.9204

2020

481

482

483

484