Dataset Information

Investigation of sensory thresholds in Cavalier King Charles Spaniels with and without Chiari-like malformations and syringomyelia.

ABSTRACT:

Background

Cavalier King Charles Spaniels (CKCS) suffer pain associated with Chiari-like malformation and syringomyelia (CMSM). People suffer from a similar condition and describe numerous sensory abnormalities. Sensory changes have not been quantified in affected CKCS.

Objectives

To use quantitative sensory testing (QST) to quantify thermal and mechanical thresholds in CKCS and to compare QST in dogs with and without syringomyelia (SM).

Animals

Forty-four CKCS.

Methods

Prospective study. Dogs underwent neurological examinations and craniocervical magnetic resonance imaging (MRI). Thermal testing was performed over the humerus and thorax (n?=?32); mechanical testing was performed on the paw and neck (n?=?44). Latencies, thresholds, and response rates were compared with presence and severity of SM on MRI, presence of pain reported by the owner and pain identified on examination.

Results

Thirty dogs had SM, 30 were painful on examination, 29 were owner-reported symptomatic. Thermal and mechanical variables were not significantly different based on presence or severity of SM. Dogs with pain on examination had decreased mechanical thresholds on the paw (0.38 kg, SD?= 0.18) and neck (2.05 kg, SD?= 0.74) compared to thresholds of dogs without pain on examination on the paw (0.60 kg, SD?= 0.30) and neck (2.72 kg, SD?= 0.57; P =?.021).

Conclusions and clinical importance

Mechanical and thermal sensitivity does not appear to be related to the presence of SM, but mechanical sensitivity appears to be related to the presence of pain and clinical signs. Mechanical testing may be useful for assessing sensory abnormalities during clinical trials.

SUBMITTER: Sparks CR

PROVIDER: S-EPMC6272044 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Investigation of sensory thresholds in Cavalier King Charles Spaniels with and without Chiari-like malformations and syringomyelia.

Sparks Courtney R CR Gorney Angela A Williams Kim K Griffith Emily H EH Cerda-Gonzalez Sofia S Lascelles B Duncan X BDX Olby Natasha J NJ

Journal of veterinary internal medicine 20181011 6

<h4>Background</h4>Cavalier King Charles Spaniels (CKCS) suffer pain associated with Chiari-like malformation and syringomyelia (CMSM). People suffer from a similar condition and describe numerous sensory abnormalities. Sensory changes have not been quantified in affected CKCS.<h4>Objectives</h4>To use quantitative sensory testing (QST) to quantify thermal and mechanical thresholds in CKCS and to compare QST in dogs with and without syringomyelia (SM).<h4>Animals</h4>Forty-four CKCS.<h4>Methods< ...[more]

PMID: 30307645

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Project description:BACKGROUND:Syringomyelia (SM) is a debilitating condition in the cavalier King Charles spaniel (CKCS) that results in neuropathic pain and diminished quality of life. Von Frey aesthesiometry (VFA) is a method of mechanical quantitative sensory testing that provides an objective sensory threshold (ST) value and can be used to quantify neuropathic pain (NP) and monitor response to therapy. The utility of VFA has been previously established in client-owned dogs with acute spinal cord injury but the technique has not been evaluated in dogs with SM. The goal of this study was to evaluate ST, as determined by VFA, in dogs with and without SM, to assess the utility of VFA in quantifying NP in SM-affected dogs. We hypothesized the SM-affected CKCS would have lower ST values, consistent with hyperesthesia, when compared to control CKCS. Additionally, we hypothesized that ST values in SM-affected dogs would be inversely correlated with syrinx size on MRI and with owner-derived clinical sign scores. RESULTS:ST values for the thoracic and pelvic limbs differed significantly between the SM-affected and control CKCS (p?=?0.027; p?=?0.0396 respectively). Median ST value (range) for the thoracic limbs was 184.1?g (120.9-552) for control dogs, and 139.9?g (52.6-250.9) for SM-affected dogs. The median ST value (range) for the pelvic limbs was 164.9?g (100.8-260.3) in control dogs and 129.8?g (57.95-168.4) in SM-affected dogs. The ST values in SM-affected dogs did not correlate with syrinx height on MRI (r?=?0.314; p?=?0.137). Owner-reported clinical sign scores showed an inverse correlation with pelvic limb ST values, where dogs with lower ST values (hyperesthesia) were reported by their owners to display more frequent and severe clinical signs (r?=?-?0.657; p?=?0.022). CONCLUSION:ST values were lower in SM-affected CKCS compared to control dogs, suggesting the presence of neuropathic pain. Dogs with lower ST pelvic limb values were perceived by their owners to have more severe clinical signs classically associated with SM. Our results suggest that VFA might offer quantitative assessment of neuropathic pain in SM-affected dogs and could be useful for monitoring response to therapy in future clinical studies.

Project description:BackgroundSyringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance.ResultsWe identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development.ConclusionsWe identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse diameter. The locus on CFA22 was significantly associated to SM secondary to CM in the CKCS dog breed strengthening its candidacy for this disease. This study will provide an entry point for identification of the genetic factors predisposing to this condition and its underlying pathogenic mechanisms.

Project description:Chiari-like malformation (CM), syringomyelia (SM) and middle ear effusion (also called PSOM) are three conditions that frequently occur in Cavalier King Charles Spaniels (CKCS). Both CM and SM are currently screened in the Netherlands prior to breeding and are graded according to the British Veterinary Association's Kennel Club (BVA/KC) scheme. This study evaluated the prevalence and estimated genetic parameter of CM, SM and middle ear effusion from 12 years of screening results. For SM, the classical method using the BVA/KC scheme, was compared with exact measuring of the central canal dilation. For CM, the BVA/KC scheme was compared with a more detailed scheme. Next to this the presence of microchip artifacts was assessed. 1249 screening of 1020 dogs were re-evaluated. Results indicated the presence of CM in all dogs, suggesting it has become a breed-specific characteristic. And although different grades of CM were observed, the condition did not deteriorate over time. SM was present in 39% of the dogs and a clear age effect was demonstrated, with SM increasing with age. This emphasizes the importance of screening at appropriate age, since SM can worsen with increasing age. One alternative is to promote repeated measures. The presence of middle ear effusion in this study was 19%-21% for dogs younger than 3 years, and 32%-38% for dogs older than 3 years. In as much as 60%, microchip artifacts were noticed, leading to the recommendation to place microchips in another location in breeds that are susceptible to developing SM. Finally, this study estimated the heritability of CM in this population, due to the lack of phenotypic variance, to be very low at 0.02-0.03. The heritability for SM central canal dilatation to be 0.30, compared to 0.13 for the classical BVA/KC method, using a model including the age effect and the combined effect of veterinary clinic and year of the evaluation. Genetic correlations were rather small, ranging from 0.16-0.33. As a conclusion, screening for SM and CM in the entire population should be maintained, and a selection scheme against SM should be based on estimated breeding values for the exact measurement of the central canal dilatation.

Project description:ObjectivesTo 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.MethodsThis 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.ResultsFourteen 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.ConclusionMorphometric 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.

Dataset Information

Investigation of sensory thresholds in Cavalier King Charles Spaniels with and without Chiari-like malformations and syringomyelia.

Background

Objectives

Animals

Methods

Results

Conclusions and clinical importance

Publications

Investigation of sensory thresholds in Cavalier King Charles Spaniels with and without Chiari-like malformations and syringomyelia.

Similar Datasets

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